K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions

PubMed Central

Ostrem, Jonathan M.; Peters, Ulf; Sos, Martin L.; Wells, James A.; Shokat, Kevan M.

2014-01-01

Somatic mutations in the small GTPase K-Ras are the most common activating lesions found in human cancer, and are generally associated with poor response to standard therapies1–3. Efforts to target this oncogene directly have faced difficulties owing to its picomolar affinity for GTP/GDP4 and the absence of known allosteric regulatory sites. Oncogenic mutations result in functional activation of Ras family proteins by impairing GTP hydrolysis5,6. With diminished regulation by GTPase activity, the nucleotide state of Ras becomes more dependent on relative nucleotide affinity and concentration. This gives GTP an advantage over GDP7 and increases the proportion of active GTP-bound Ras. Here we report the development of small molecules that irreversibly bind to a common oncogenic mutant, K-Ras(G12C). These compounds rely on the mutant cysteine for binding and therefore do not affect the wild-type protein. Crystallographic studies reveal the formation of a new pocket that is not apparent in previous structures of Ras, beneath the effector binding switch-II region. Binding of these inhibitors to K-Ras(G12C) disrupts both switch-I and switch-II, subverting the native nucleotide preference to favour GDP over GTP and impairing binding to Raf. Our data provide structure-based validation of a new allosteric regulatory site on Ras that is targetable in a mutant-specific manner. PMID:24256730

The Strength of an Ig Switch Region is Determined by its Ability to Drive R-loop Formation and its Number of WGCW Sites

PubMed Central

Zhang, Zheng Z.; Pannunzio, Nicholas R.; Han, Li; Hsieh, Chih-Lin; Yu, Kefei; Lieber, Michael R.

2014-01-01

SUMMARY R-loops exist at the murine IgH switch regions and possibly other locations, but their functional importance is unclear. In biochemical systems, R-loop initiation requires DNA sequence regions containing clusters of G nucleotides, but cellular studies have not been done. Here, we vary the G-clustering, total switch region length, and the number of target sites (WGCW sites for the activation-induced deaminase) at synthetic switch regions in a murine B cell line to determine the effect on class switch recombination (CSR). G-clusters increase CSR, regardless of their immediate proximity to the WGCW sites. This increase is accompanied by an increase in R-loop formation. CSR efficiency correlates better with the absolute number of WGCW sites in the switch region rather than the total switch region length or density of WGCW sites. Thus, the overall strength of the switch region depends on G-clusters, which initiate R-loop formation, and on the number of WGCW sites. PMID:25017067

The beginning of kinesin's force-generating cycle visualized at 9-Å resolution

PubMed Central

Sindelar, Charles V.; Downing, Kenneth H.

2007-01-01

We have used cryo-electron microscopy of kinesin-decorated microtubules to resolve the structure of the motor protein kinesin's crucial nucleotide response elements, switch I and the switch II helix, in kinesin's poorly understood nucleotide-free state. Both of the switch elements undergo conformational change relative to the microtubule-free state. The changes in switch I suggest a role for it in “ejecting” adenosine diphosphate when kinesin initially binds to the microtubule. The switch II helix has an N-terminal extension, apparently stabilized by conserved microtubule contacts, implying a microtubule activation mechanism that could convey the state of the bound nucleotide to kinesin's putative force-delivering element (the “neck linker”). In deriving this structure, we have adapted an image-processing technique, single-particle reconstruction, for analyzing decorated microtubules. The resulting reconstruction visualizes the asymmetric seam present in native, 13-protofilament microtubules, and this method will provide an avenue to higher-resolution characterization of a variety of microtubule- binding proteins, as well as the microtubule itself. PMID:17470637

Rational modification of Corynebacterium glutamicum dihydrodipicolinate reductase to switch the nucleotide-cofactor specificity for increasing l-lysine production.

PubMed

Xu, Jian-Zhong; Yang, Han-Kun; Liu, Li-Ming; Wang, Ying-Yu; Zhang, Wei-Guo

2018-03-25

l-lysine is an important amino acid in animals and humans and NADPH is a vital cofactor for maximizing the efficiency of l-lysine fermentation. Dihydrodipicolinate reductase (DHDPR), an NAD(P)H-dependent enzyme, shows a variance in nucleotide-cofactor affinity in bacteria. In this study, we rationally engineered Corynebacterium glutamicum DHDPR (CgDHDPR) to switch its nucleotide-cofactor specificity resulting in an increase in final titer (from 82.6 to 117.3 g L -1 ), carbon yield (from 0.35 to 0.44 g [g glucose] -1 ) and productivity (from 2.07 to 2.93 g L -1  hr -1 ) of l-lysine in JL-6 ΔdapB::Ec-dapB C115G,G116C in fed-batch fermentation. To do this, we comparatively analyzed the characteristics of CgDHDPR and Escherichia coli DHDPR (EcDHDPR), indicating that hetero-expression of NADH-dependent EcDHDPR increased l-lysine production. Subsequently, we rationally modified the conserved structure of cofactor-binding motif, and results indicated that introducing the mutation K11A or R13A in CgDHDPR and introducing the mutation R16A or R39A in EcDHDPR modifies the nucleotide-cofactor affinity of DHDPR. Lastly, the effects of these mutated DHDPRs on l-lysine production were investigated. The highest increase (26.2%) in l-lysine production was observed for JL-6 ΔdapB::Ec-dapB C115G,G116C , followed by JL-6 Cg-dapB C37G,G38C (21.4%) and JL-6 ΔdapB::Ec-dapB C46G,G47C (15.2%). This is the first report of a rational modification of DHDPR that enhances the l-lysine production and yield through the modulation of nucleotide-cofactor specificity. © 2018 Wiley Periodicals, Inc.

Early stages of the recovery stroke in myosin II studied by molecular dynamics simulations

PubMed Central

Baumketner, Andrij; Nesmelov, Yuri

2011-01-01

The recovery stroke is a key step in the functional cycle of muscle motor protein myosin, during which pre-recovery conformation of the protein is changed into the active post-recovery conformation, ready to exersice force. We study the microscopic details of this transition using molecular dynamics simulations of atomistic models in implicit and explicit solvent. In more than 2 μs of aggregate simulation time, we uncover evidence that the recovery stroke is a two-step process consisting of two stages separated by a time delay. In our simulations, we directly observe the first stage at which switch II loop closes in the presence of adenosine triphosphate at the nucleotide binding site. The resulting configuration of the nucleotide binding site is identical to that detected experimentally. Distribution of inter-residue distances measured in the force generating region of myosin is in good agreement with the experimental data. The second stage of the recovery stroke structural transition, rotation of the converter domain, was not observed in our simulations. Apparently it occurs on a longer time scale. We suggest that the two parts of the recovery stroke need to be studied using separate computational models. PMID:21922589

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

NASA Astrophysics Data System (ADS)

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.

The switching mechanism of the mitochondrial ADP/ATP carrier explored by free-energy landscapes.

PubMed

Pietropaolo, Adriana; Pierri, Ciro Leonardo; Palmieri, Ferdinando; Klingenberg, Martin

2016-06-01

The ADP/ATP carrier (AAC) of mitochondria has been an early example for elucidating the transport mechanism alternating between the external (c-) and internal (m-) states (M. Klingenberg, Biochim. Biophys. Acta 1778 (2008) 1978-2021). An atomic resolution crystal structure of AAC is available only for the c-state featuring a three repeat transmembrane domain structure. Modeling of transport mechanism remained hypothetical for want of an atomic structure of the m-state. Previous molecular dynamics studies simulated the binding of ADP or ATP to the AAC remaining in the c-state. Here, a full description of the AAC switching from the c- to the m-state is reported using well-tempered metadynamics simulations. Free-energy landscapes of the entire translocation from the c- to the m-state, based on the gyration radii of the c- and m-gates and of the center of mass, were generated. The simulations revealed three free-energy basins attributed to the c-, intermediate- and m-states separated by activation barriers. These simulations were performed with the empty and with the ADP- and ATP-loaded AAC as well as with the poorly transported AMP and guanine nucleotides, showing in the free energy landscapes that ADP and ATP lowered the activation free-energy barriers more than the other substrates. Upon binding AMP and guanine nucleotides a deeper free-energy level stabilized the intermediate-state of the AAC2 hampering the transition to the m-state. The structures of the substrate binding sites in the different states are described producing a full picture of the translocation events in the AAC. Copyright © 2016 Elsevier B.V. All rights reserved.

Intrinsic K-Ras dynamics: A novel molecular dynamics data analysis method shows causality between residue pair motions

NASA Astrophysics Data System (ADS)

Vatansever, Sezen; Gümüş, Zeynep H.; Erman, Burak

2016-11-01

K-Ras is the most frequently mutated oncogene in human cancers, but there are still no drugs that directly target it in the clinic. Recent studies utilizing dynamics information show promising results for selectively targeting mutant K-Ras. However, despite extensive characterization, the mechanisms by which K-Ras residue fluctuations transfer allosteric regulatory information remain unknown. Understanding the direction of information flow can provide new mechanistic insights for K-Ras targeting. Here, we present a novel approach -conditional time-delayed correlations (CTC) - using the motions of all residue pairs of a protein to predict directionality in the allosteric regulation of the protein fluctuations. Analyzing nucleotide-dependent intrinsic K-Ras motions with the new approach yields predictions that agree with the literature, showing that GTP-binding stabilizes K-Ras motions and leads to residue correlations with relatively long characteristic decay times. Furthermore, our study is the first to identify driver-follower relationships in correlated motions of K-Ras residue pairs, revealing the direction of information flow during allosteric modulation of its nucleotide-dependent intrinsic activity: active K-Ras Switch-II region motions drive Switch-I region motions, while α-helix-3L7 motions control both. Our results provide novel insights for strategies that directly target mutant K-Ras.

Base Preferences in Non-Templated Nucleotide Incorporation by MMLV-Derived Reverse Transcriptases

PubMed Central

Zajac, Pawel; Islam, Saiful; Hochgerner, Hannah; Lönnerberg, Peter; Linnarsson, Sten

2013-01-01

Reverse transcriptases derived from Moloney Murine Leukemia Virus (MMLV) have an intrinsic terminal transferase activity, which causes the addition of a few non-templated nucleotides at the 3´ end of cDNA, with a preference for cytosine. This mechanism can be exploited to make the reverse transcriptase switch template from the RNA molecule to a secondary oligonucleotide during first-strand cDNA synthesis, and thereby to introduce arbitrary barcode or adaptor sequences in the cDNA. Because the mechanism is relatively efficient and occurs in a single reaction, it has recently found use in several protocols for single-cell RNA sequencing. However, the base preference of the terminal transferase activity is not known in detail, which may lead to inefficiencies in template switching when starting from tiny amounts of mRNA. Here, we used fully degenerate oligos to determine the exact base preference at the template switching site up to a distance of ten nucleotides. We found a strong preference for guanosine at the first non-templated nucleotide, with a greatly reduced bias at progressively more distant positions. Based on this result, and a number of careful optimizations, we report conditions for efficient template switching for cDNA amplification from single cells. PMID:24392002

Particle in cell simulation of peaking switch for breakdown evaluation

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

Umbarkar, Sachin B.; Bindu, S.; Mangalvedekar, H.A.

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 (withoutmore » 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)« less

Nucleotide-dependent conformational states of actin

PubMed Central

Pfaendtner, Jim; Branduardi, Davide; Parrinello, Michele; Pollard, Thomas D.; Voth, Gregory A.

2009-01-01

The influence of the state of the bound nucleotide (ATP, ADP-Pi, or ADP) on the conformational free-energy landscape of actin is investigated. Nucleotide-dependent folding of the DNase-I binding (DB) loop in monomeric actin and the actin trimer is carried out using all-atom molecular dynamics (MD) calculations accelerated with a multiscale implementation of the metadynamics algorithm. Additionally, an investigation of the opening and closing of the actin nucleotide binding cleft is performed. Nucleotide-dependent free-energy profiles for all of these conformational changes are calculated within the framework of metadynamics. We find that in ADP-bound monomer, the folded and unfolded states of the DB loop have similar relative free-energy. This result helps explain the experimental difficulty in obtaining an ordered crystal structure for this region of monomeric actin. However, we find that in the ADP-bound actin trimer, the folded DB loop is stable and in a free-energy minimum. It is also demonstrated that the nucleotide binding cleft favors a closed conformation for the bound nucleotide in the ATP and ADP-Pi states, whereas the ADP state favors an open confirmation, both in the monomer and trimer. These results suggest a mechanism of allosteric interactions between the nucleotide binding cleft and the DB loop. This behavior is confirmed by an additional simulation that shows the folding free-energy as a function of the nucleotide cleft width, which demonstrates that the barrier for folding changes significantly depending on the value of the cleft width. PMID:19620726

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

PubMed

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.

Structural Dynamics in Ras and Related Proteins upon Nucleotide Switching.

PubMed

Harrison, Rane A; Lu, Jia; Carrasco, Martin; Hunter, John; Manandhar, Anuj; Gondi, Sudershan; Westover, Kenneth D; Engen, John R

2016-11-20

Structural dynamics of Ras proteins contributes to their activity in signal transduction cascades. Directly targeting Ras proteins with small molecules may rely on the movement of a conserved structural motif, switch II. To understand Ras signaling and advance Ras-targeting strategies, experimental methods to measure Ras dynamics are required. Here, we demonstrate the utility of hydrogen-deuterium exchange (HDX) mass spectrometry (MS) to measure Ras dynamics by studying representatives from two branches of the Ras superfamily, Ras and Rho. A comparison of differential deuterium exchange between active (GMPPNP-bound) and inactive (GDP-bound) proteins revealed differences between the families, with the most notable differences occurring in the phosphate-binding loop and switch II. The P-loop exchange signature correlated with switch II dynamics observed in molecular dynamics simulations focused on measuring main-chain movement. HDX provides a means of evaluating Ras protein dynamics, which may be useful for understanding the mechanisms of Ras signaling, including activated signaling of pathologic mutants, and for targeting strategies that rely on protein dynamics. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bistability in a Metabolic Network Underpins the De Novo Evolution of Colony Switching in Pseudomonas fluorescens

PubMed Central

Gallie, Jenna; Libby, Eric; Bertels, Frederic; Remigi, Philippe; Jendresen, Christian B.; Ferguson, Gayle C.; Desprat, Nicolas; Buffing, Marieke F.; Sauer, Uwe; Beaumont, Hubertus J. E.; Martinussen, Jan; Kilstrup, Mogens; Rainey, Paul B.

2015-01-01

Phenotype switching is commonly observed in nature. This prevalence has allowed the elucidation of a number of underlying molecular mechanisms. However, little is known about how phenotypic switches arise and function in their early evolutionary stages. The first opportunity to provide empirical insight was delivered by an experiment in which populations of the bacterium Pseudomonas fluorescens SBW25 evolved, de novo, the ability to switch between two colony phenotypes. Here we unravel the molecular mechanism behind colony switching, revealing how a single nucleotide change in a gene enmeshed in central metabolism (carB) generates such a striking phenotype. We show that colony switching is underpinned by ON/OFF expression of capsules consisting of a colanic acid-like polymer. We use molecular genetics, biochemical analyses, and experimental evolution to establish that capsule switching results from perturbation of the pyrimidine biosynthetic pathway. Of central importance is a bifurcation point at which uracil triphosphate is partitioned towards either nucleotide metabolism or polymer production. This bifurcation marks a cell-fate decision point whereby cells with relatively high pyrimidine levels favour nucleotide metabolism (capsule OFF), while cells with lower pyrimidine levels divert resources towards polymer biosynthesis (capsule ON). This decision point is present and functional in the wild-type strain. Finally, we present a simple mathematical model demonstrating that the molecular components of the decision point are capable of producing switching. Despite its simple mutational cause, the connection between genotype and phenotype is complex and multidimensional, offering a rare glimpse of how noise in regulatory networks can provide opportunity for evolution. PMID:25763575

Unique Structural and Nucleotide Exchange Features of the Rho1 GTPase of Entamoeba histolytica

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

Bosch, Dustin E.; Wittchen, Erika S.; Qiu, Connie

The single-celled human parasite Entamoeba histolytica possesses a dynamic actin cytoskeleton vital for its intestinal and systemic pathogenicity. The E. histolytica genome encodes several Rho family GTPases known to regulate cytoskeletal dynamics. EhRho1, the first family member identified, was reported to be insensitive to the Rho GTPase-specific Clostridium botulinum C3 exoenzyme, raising the possibility that it may be a misclassified Ras family member. Here, we report the crystal structures of EhRho1 in both active and inactive states. EhRho1 is activated by a conserved switch mechanism, but diverges from mammalian Rho GTPases in lacking a signature Rho insert helix. EhRho1 engagesmore » a homolog of mDia, EhFormin1, suggesting a role in mediating serum-stimulated actin reorganization and microtubule formation during mitosis. EhRho1, but not a constitutively active mutant, interacts with a newly identified EhRhoGDI in a prenylation-dependent manner. Furthermore, constitutively active EhRho1 induces actin stress fiber formation in mammalian fibroblasts, thereby identifying it as a functional Rho family GTPase. EhRho1 exhibits a fast rate of nucleotide exchange relative to mammalian Rho GTPases due to a distinctive switch one isoleucine residue reminiscent of the constitutively active F28L mutation in human Cdc42, which for the latter protein, is sufficient for cellular transformation. Nonconserved, nucleotide-interacting residues within EhRho1, revealed by the crystal structure models, were observed to contribute a moderating influence on fast spontaneous nucleotide exchange. Collectively, these observations indicate that EhRho1 is a bona fide member of the Rho GTPase family, albeit with unique structural and functional aspects compared with mammalian Rho GTPases.« less

Modulation of mutagenesis in eukaryotes by DNA replication fork dynamics and quality of nucleotide pools

PubMed Central

Waisertreiger, Irina S.-R.; Liston, Victoria G.; Menezes, Miriam R.; Kim, Hyun-Min; Lobachev, Kirill S.; Stepchenkova, Elena I.; Tahirov, Tahir H.; Rogozin, Igor B.; Pavlov, Youri. I.

2014-01-01

The rate of mutations in eukaryotes depends on a plethora of factors and is not immediately derived from the fidelity of DNA polymerases (Pols). Replication of chromosomes containing the anti-parallel strands of duplex DNA occurs through the copying of leading and lagging strand templates by a trio of Pols α, δ and ε, with the assistance of Pol ζ and Y-family Pols at difficult DNA template structures or sites of DNA damage. The parameters of the synthesis at a given location are dictated by the quality and quantity of nucleotides in the pools, replication fork architecture, transcription status, regulation of Pol switches, and structure of chromatin. The result of these transactions is a subject of survey and editing by DNA repair. PMID:23055184

A Nucleotide-Driven Switch Regulates Flanking DNA Length Sensing by a Dimeric Chromatin Remodeler

PubMed Central

Leonard, John D.; Narlikar, Geeta J.

2015-01-01

SUMMARY The ATP-dependent chromatin assembly factor (ACF) is a dimeric motor that spaces nucleosomes to promote formation of silent chromatin. Two copies of its ATPase subunit SNF2h bind opposite sides of a nucleosome, but how these protomers avoid competition is unknown. SNF2h senses the length of DNA flanking a nucleosome via its HAND-SANT-SLIDE (HSS) domain, yet it is unclear how this interaction enhances remodeling. Using covalently connected SNF2h dimers we show that dimerization accelerates remodeling and that the HSS contributes to communication between protomers. We further identify a nucleotide-dependent conformational change in SNF2h. In one conformation the HSS binds flanking DNA, and in another conformation the HSS engages the nucleosome core. Based on these results, we propose a model in which DNA length sensing and translocation are performed by two distinct conformational states of SNF2h. Such separation of function suggests that these activities could be independently regulated to affect remodeling outcomes. PMID:25684208

Exact solution of a model DNA-inversion genetic switch with orientational control.

PubMed

Visco, Paolo; Allen, Rosalind J; Evans, Martin R

2008-09-12

DNA inversion is an important mechanism by which bacteria and bacteriophage switch reversibly between phenotypic states. In such switches, the orientation of a short DNA element is flipped by a site-specific recombinase enzyme. We propose a simple model for a DNA-inversion switch in which recombinase production is dependent on the switch state (orientational control). Our model is inspired by the fim switch in E. coli. We present an exact analytical solution of the chemical master equation for the model switch, as well as stochastic simulations. Orientational control causes the switch to deviate from Poissonian behavior: the distribution of times in the on state shows a peak and successive flip times are correlated.

The allosteric switching mechanism in bacteriophage MS2

NASA Astrophysics Data System (ADS)

Perkett, Matthew R.; Mirijanian, Dina T.; Hagan, Michael F.

2016-07-01

We use all-atom simulations to elucidate the mechanisms underlying conformational switching and allostery within the coat protein of the bacteriophage MS2. Assembly of most icosahedral virus capsids requires that the capsid protein adopts different conformations at precise locations within the capsid. It has been shown that a 19 nucleotide stem loop (TR) from the MS2 genome acts as an allosteric effector, guiding conformational switching of the coat protein during capsid assembly. Since the principal conformational changes occur far from the TR binding site, it is important to understand the molecular mechanism underlying this allosteric communication. To this end, we use all-atom simulations with explicit water combined with a path sampling technique to sample the MS2 coat protein conformational transition, in the presence and absence of TR-binding. The calculations find that TR binding strongly alters the transition free energy profile, leading to a switch in the favored conformation. We discuss changes in molecular interactions responsible for this shift. We then identify networks of amino acids with correlated motions to reveal the mechanism by which effects of TR binding span the protein. We find that TR binding strongly affects residues located at the 5-fold and quasi-sixfold interfaces in the assembled capsid, suggesting a mechanism by which the TR binding could direct formation of the native capsid geometry. The analysis predicts amino acids whose substitution by mutagenesis could alter populations of the conformational substates or their transition rates.

The allosteric switching mechanism in bacteriophage MS2

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

Perkett, Matthew R.; Mirijanian, Dina T.; Hagan, Michael F., E-mail: hagan@brandeis.edu

2016-07-21

We use all-atom simulations to elucidate the mechanisms underlying conformational switching and allostery within the coat protein of the bacteriophage MS2. Assembly of most icosahedral virus capsids requires that the capsid protein adopts different conformations at precise locations within the capsid. It has been shown that a 19 nucleotide stem loop (TR) from the MS2 genome acts as an allosteric effector, guiding conformational switching of the coat protein during capsid assembly. Since the principal conformational changes occur far from the TR binding site, it is important to understand the molecular mechanism underlying this allosteric communication. To this end, we usemore » all-atom simulations with explicit water combined with a path sampling technique to sample the MS2 coat protein conformational transition, in the presence and absence of TR-binding. The calculations find that TR binding strongly alters the transition free energy profile, leading to a switch in the favored conformation. We discuss changes in molecular interactions responsible for this shift. We then identify networks of amino acids with correlated motions to reveal the mechanism by which effects of TR binding span the protein. We find that TR binding strongly affects residues located at the 5-fold and quasi-sixfold interfaces in the assembled capsid, suggesting a mechanism by which the TR binding could direct formation of the native capsid geometry. The analysis predicts amino acids whose substitution by mutagenesis could alter populations of the conformational substates or their transition rates.« less

The allosteric switching mechanism in bacteriophage MS2

PubMed Central

Perkett, Matthew R.; Mirijanian, Dina T.

2016-01-01

We use all-atom simulations to elucidate the mechanisms underlying conformational switching and allostery within the coat protein of the bacteriophage MS2. Assembly of most icosahedral virus capsids requires that the capsid protein adopts different conformations at precise locations within the capsid. It has been shown that a 19 nucleotide stem loop (TR) from the MS2 genome acts as an allosteric effector, guiding conformational switching of the coat protein during capsid assembly. Since the principal conformational changes occur far from the TR binding site, it is important to understand the molecular mechanism underlying this allosteric communication. To this end, we use all-atom simulations with explicit water combined with a path sampling technique to sample the MS2 coat protein conformational transition, in the presence and absence of TR-binding. The calculations find that TR binding strongly alters the transition free energy profile, leading to a switch in the favored conformation. We discuss changes in molecular interactions responsible for this shift. We then identify networks of amino acids with correlated motions to reveal the mechanism by which effects of TR binding span the protein. We find that TR binding strongly affects residues located at the 5-fold and quasi-sixfold interfaces in the assembled capsid, suggesting a mechanism by which the TR binding could direct formation of the native capsid geometry. The analysis predicts amino acids whose substitution by mutagenesis could alter populations of the conformational substates or their transition rates. PMID:27448905

Temperature-Dependent Characterization, Modeling, and Switching Speed-Limitation Analysis of Third-Generation 10-kV SiC MOSFET

DOE PAGES

Ji, Shiqi; Zheng, Sheng; Wang, Fei; ...

2017-07-06

The temperature-dependent characteristics of the third-generation 10-kV/20-A SiC MOSFET including the static characteristics and switching performance are carried out in this paper. The steady-state characteristics, including saturation current, output characteristics, antiparallel diode, and parasitic capacitance, are tested. Here, a double pulse test platform is constructed including a circuit breaker and gate drive with >10-kV insulation and also a hotplate under the device under test for temperature-dependent characterization during switching transients. The switching performance is tested under various load currents and gate resistances at a 7-kV dc-link voltage from 25 to 125 C and compared with previous 10-kV MOSFETs. A simplemore » behavioral model with its parameter extraction method is proposed to predict the temperature-dependent characteristics of the 10-kV SiC MOSFET. The switching speed limitations, including the reverse recovery of SiC MOSFET's body diode, overvoltage caused by stray inductance, crosstalk, heat sink, and electromagnetic interference to the control are discussed based on simulations and experimental results.« less

Temperature-Dependent Characterization, Modeling, and Switching Speed-Limitation Analysis of Third-Generation 10-kV SiC MOSFET

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

Ji, Shiqi; Zheng, Sheng; Wang, Fei

The temperature-dependent characteristics of the third-generation 10-kV/20-A SiC MOSFET including the static characteristics and switching performance are carried out in this paper. The steady-state characteristics, including saturation current, output characteristics, antiparallel diode, and parasitic capacitance, are tested. Here, a double pulse test platform is constructed including a circuit breaker and gate drive with >10-kV insulation and also a hotplate under the device under test for temperature-dependent characterization during switching transients. The switching performance is tested under various load currents and gate resistances at a 7-kV dc-link voltage from 25 to 125 C and compared with previous 10-kV MOSFETs. A simplemore » behavioral model with its parameter extraction method is proposed to predict the temperature-dependent characteristics of the 10-kV SiC MOSFET. The switching speed limitations, including the reverse recovery of SiC MOSFET's body diode, overvoltage caused by stray inductance, crosstalk, heat sink, and electromagnetic interference to the control are discussed based on simulations and experimental results.« less

Magnetic domain wall engineering in a nanoscale permalloy junction

NASA Astrophysics Data System (ADS)

Wang, Junlin; Zhang, Xichao; Lu, Xianyang; Zhang, Jason; Yan, Yu; Ling, Hua; Wu, Jing; Zhou, Yan; Xu, Yongbing

2017-08-01

Nanoscale magnetic junctions provide a useful approach to act as building blocks for magnetoresistive random access memories (MRAM), where one of the key issues is to control the magnetic domain configuration. Here, we study the domain structure and the magnetic switching in the Permalloy (Fe20Ni80) nanoscale magnetic junctions with different thicknesses by using micromagnetic simulations. It is found that both the 90-° and 45-° domain walls can be formed between the junctions and the wire arms depending on the thickness of the device. The magnetic switching fields show distinct thickness dependencies with a broad peak varying from 7 nm to 22 nm depending on the junction sizes, and the large magnetic switching fields favor the stability of the MRAM operation.

Reactive molecular dynamics simulations of switching processes of azobenzene-based monolayer on surface

NASA Astrophysics Data System (ADS)

Tian, Ziqi; Wen, Jin; Ma, Jing

2013-07-01

It is a challenge to simulate the switching process of functional self-assembled monolayers (SAMs) on metal surfaces, since the systems consist of thousands of atoms and the switching is triggered by quantum-mechanical events. Herein a molecular dynamics simulation with a reactive rotation potential of N=N bond is implemented to investigate the dynamic conformational changes and packing effects on the stimuli-responsive isomerization of the terminally thiol functionalized azobiphenyls (AZOs), which are bound on the Au(111) surface. To, respectively, distinguish the time evolutions that start from cis and trans initial configurations, two different functions are established to model the potential energy curves for cis-to-trans and trans-to-cis transitions, instead of the only one cosine function used in the conventional non-reactive force fields. In order to simulate the conformation transitions of the AZO film on surface, a random switching function, depending on the N=N twisting angle, is constructed to consider both forward and backward cis/trans isomerization events and to trigger the reaction by changing the N atom types automatically. The factors that will influence the isomerization process, including the choice of ensembles and thermostat algorithms, the time intervals separating each switching, and the forms of the switching function, are systematically tested. Most AZO molecules switch from the cis to trans configuration with a coverage of 5.76 × 10-6 mol/m2 on a picosecond time scale, and a low coverage might make the switching irreversible, which is in agreement with the experiments.

The waiting time problem in a model hominin population.

PubMed

Sanford, John; Brewer, Wesley; Smith, Franzine; Baumgardner, John

2015-09-17

Functional information is normally communicated using specific, context-dependent strings of symbolic characters. This is true within the human realm (texts and computer programs), and also within the biological realm (nucleic acids and proteins). In biology, strings of nucleotides encode much of the information within living cells. How do such information-bearing nucleotide strings arise and become established? This paper uses comprehensive numerical simulation to understand what types of nucleotide strings can realistically be established via the mutation/selection process, given a reasonable timeframe. The program Mendel's Accountant realistically simulates the mutation/selection process, and was modified so that a starting string of nucleotides could be specified, and a corresponding target string of nucleotides could be specified. We simulated a classic pre-human hominin population of at least 10,000 individuals, with a generation time of 20 years, and with very strong selection (50% selective elimination). Random point mutations were generated within the starting string. Whenever an instance of the target string arose, all individuals carrying the target string were assigned a specified reproductive advantage. When natural selection had successfully amplified an instance of the target string to the point of fixation, the experiment was halted, and the waiting time statistics were tabulated. Using this methodology we tested the effect of mutation rate, string length, fitness benefit, and population size on waiting time to fixation. Biologically realistic numerical simulations revealed that a population of this type required inordinately long waiting times to establish even the shortest nucleotide strings. To establish a string of two nucleotides required on average 84 million years. To establish a string of five nucleotides required on average 2 billion years. We found that waiting times were reduced by higher mutation rates, stronger fitness benefits, and larger population sizes. However, even using the most generous feasible parameters settings, the waiting time required to establish any specific nucleotide string within this type of population was consistently prohibitive. We show that the waiting time problem is a significant constraint on the macroevolution of the classic hominin population. Routine establishment of specific beneficial strings of two or more nucleotides becomes very problematic.

Analysis of reliable sub-ns spin-torque switching under transverse bias magnetic fields

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

D'Aquino, M., E-mail: daquino@uniparthenope.it; Perna, S.; Serpico, C.

2015-05-07

The switching process of a magnetic spin-valve nanosystem subject to spin-polarized current pulses is considered. The dependence of the switching probability on the current pulse duration is investigated. The further application of a transverse field along the intermediate anisotropy axis of the particle is used to control the quasi-random relaxation of magnetization to the reversed magnetization state. The critical current amplitudes to realize the switching are determined by studying the phase portrait of the Landau-Lifshtz-Slonczewski dynamics. Macrospin numerical simulations are in good agreement with the theoretical prediction and demonstrate reliable switching even for very short (below 100 ps) current pulses.

Rho proteins of plants--functional cycle and regulation of cytoskeletal dynamics.

PubMed

Mucha, Elena; Fricke, Inka; Schaefer, Antje; Wittinghofer, Alfred; Berken, Antje

2011-11-01

Rho-related ROP proteins are molecular switches that essentially regulate a wide variety of processes. Of central interest is their influence on the plant cytoskeleton by which they affect vital processes like cell division, growth, morphogenesis, and pathogen defense. ROPs switch between GTP- and GDP-bound conformations by strictly regulated nucleotide exchange and GTP-hydrolysis, and only the active GTP-form interacts with downstream effectors to ultimately provoke a biological response. However, the mode of action of the engaged regulators and effectors as well as their upstream and downstream interaction partners have long been largely unknown. As opposed to analogous systems in animals and fungi, plants use specific GTPase activating proteins (RopGAPs) with a unique domain composition and novel guanine nucleotide exchange factors (RopGEFs) with a probable link to cell surface receptors. Moreover, plants comprise novel effector molecules and adapters connecting ROPs to mostly unknown downstream targets on the route to the cytoskeleton. This review aims to summarize recent knowledge on the molecular mechanisms and reaction cascades involved in ROP dependent cytoskeletal rearrangements, addressing the structure and function of the unusual RopGAPs, RopGEFs and effectors, and the upstream and downstream pathways linking ROPs to cell receptor-like kinases, actin filaments, and microtubules. Copyright © 2010 Elsevier GmbH. All rights reserved.

A p53-inducible microRNA-34a downregulates Ras signaling by targeting IMPDH

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

Kim, Hwa-Ryeon; Roe, Jae-Seok; Lee, Ji-Eun

2012-02-24

Highlights: Black-Right-Pointing-Pointer p53 downregulates IMPDH. Black-Right-Pointing-Pointer p53-dependent miR-34a transactivation inhibits IMPDH transcription. Black-Right-Pointing-Pointer miR-34a-mediated inhibition of IMPDH downregulates GTP-dependent Ras signal. -- Abstract: p53 is a well-known transcription factor that controls cell cycle arrest and cell death in response to a wide range of stresses. Moreover, p53 regulates glucose metabolism and its mutation results in the metabolic switch to the Warburg effect found in cancer cells. Nucleotide biosynthesis is also critical for cell proliferation and the cell division cycle. Nonetheless, little is known about whether p53 regulates nucleotide biosynthesis. Here we demonstrated that p53-inducible microRNA-34a (miR-34a) repressed inosine 5 Primemore » -monophosphate dehydrogenase (IMPDH), a rate-limiting enzyme of de novo GTP biosynthesis. Treatment with anti-miR-34a inhibitor relieved the expression of IMPDH upon DNA damage. Ultimately, miR-34a-mediated inhibition of IMPDH resulted in repressed activation of the GTP-dependent Ras signaling pathway. In summary, we suggest that p53 has a novel function in regulating purine biosynthesis, aided by miR-34a-dependent IMPDH repression.« less

Molecular Dynamics Simulations Reveal an Interplay between SHAPE Reagent Binding and RNA Flexibility.

PubMed

Mlýnský, Vojtěch; Bussi, Giovanni

2018-01-18

The function of RNA molecules usually depends on their overall fold and on the presence of specific structural motifs. Chemical probing methods are routinely used in combination with nearest-neighbor models to determine RNA secondary structure. Among the available methods, SHAPE is relevant due to its capability to probe all RNA nucleotides and the possibility to be used in vivo. However, the structural determinants for SHAPE reactivity and its mechanism of reaction are still unclear. Here molecular dynamics simulations and enhanced sampling techniques are used to predict the accessibility of nucleotide analogs and larger RNA structural motifs to SHAPE reagents. We show that local RNA reconformations are crucial in allowing reagents to reach the 2'-OH group of a particular nucleotide and that sugar pucker is a major structural factor influencing SHAPE reactivity.

The bioinformatics of nucleotide sequence coding for proteins requiring metal coenzymes and proteins embedded with metals

NASA Astrophysics Data System (ADS)

Tremberger, G.; Dehipawala, Sunil; Cheung, E.; Holden, T.; Sullivan, R.; Nguyen, A.; Lieberman, D.; Cheung, T.

2015-09-01

All metallo-proteins need post-translation metal incorporation. In fact, the isotope ratio of Fe, Cu, and Zn in physiology and oncology have emerged as an important tool. The nickel containing F430 is the prosthetic group of the enzyme methyl coenzyme M reductase which catalyzes the release of methane in the final step of methano-genesis, a prime energy metabolism candidate for life exploration space mission in the solar system. The 3.5 Gyr early life sulfite reductase as a life switch energy metabolism had Fe-Mo clusters. The nitrogenase for nitrogen fixation 3 billion years ago had Mo. The early life arsenite oxidase needed for anoxygenic photosynthesis energy metabolism 2.8 billion years ago had Mo and Fe. The selection pressure in metal incorporation inside a protein would be quantifiable in terms of the related nucleotide sequence complexity with fractal dimension and entropy values. Simulation model showed that the studied metal-required energy metabolism sequences had at least ten times more selection pressure relatively in comparison to the horizontal transferred sequences in Mealybug, guided by the outcome histogram of the correlation R-sq values. The metal energy metabolism sequence group was compared to the circadian clock KaiC sequence group using magnesium atomic level bond shifting mechanism in the protein, and the simulation model would suggest a much higher selection pressure for the energy life switch sequence group. The possibility of using Kepler 444 as an example of ancient life in Galaxy with the associated exoplanets has been proposed and is further discussed in this report. Examples of arsenic metal bonding shift probed by Synchrotron-based X-ray spectroscopy data and Zn controlled FOXP2 regulated pathways in human and chimp brain studied tissue samples are studied in relationship to the sequence bioinformatics. The analysis results suggest that relatively large metal bonding shift amount is associated with low probability correlation R-sq outcome in the bioinformatics simulation.

Kinetics of transient electroluminescence in organic light emitting diodes

NASA Astrophysics Data System (ADS)

Shukla, Manju; Kumar, Pankaj; Chand, Suresh; Brahme, Nameeta; Kher, R. S.; Khokhar, M. S. K.

2008-08-01

Mathematical simulation on the rise and decay kinetics of transient electroluminescence (EL) in organic light emitting diodes (OLEDs) is presented. The transient EL is studied with respect to a step voltage pulse. While rising, for lower values of time, the EL intensity shows a quadratic dependence on (t - tdel), where tdel is the time delay observed in the onset of EL, and finally attains saturation at a sufficiently large time. When the applied voltage is switched off, the initial EL decay shows an exponential dependence on (t - tdec), where tdec is the time when the voltage is switched off. The simulated results are compared with the transient EL performance of a bilayer OLED based on small molecular bis(2-methyl 8-hydroxyquinoline)(triphenyl siloxy) aluminium (SAlq). Transient EL studies have been carried out at different voltage pulse amplitudes. The simulated results show good agreement with experimental data. Using these simulated results the lifetime of the excitons in SAlq has also been calculated.

Ligand-Induced Stabilization of a Duplex-like Architecture Is Crucial for the Switching Mechanism of the SAM-III Riboswitch.

PubMed

Suresh, Gorle; Srinivasan, Harini; Nanda, Shivani; Priyakumar, U Deva

2016-06-21

Riboswitches are structured RNA motifs that control gene expression by sensing the concentrations of specific metabolites and make up a promising new class of antibiotic targets. S-Adenosylmethionine (SAM)-III riboswitch, mainly found in lactic acid bacteria, is involved in regulating methionine and SAM biosynthetic pathways. SAM-III riboswitch regulates the gene expression by switching the translation process on and off with respect to the absence and presence of the SAM ligand, respectively. In this study, an attempt is made to understand the key conformational transitions involved in ligand binding using atomistic molecular dynamics (MD) simulations performed in an explicit solvent environment. G26 is found to recognize the SAM ligand by forming hydrogen bonds, whereas the absence of the ligand leads to opening of the binding pocket. Consistent with experimental results, the absence of the SAM ligand weakens the base pairing interactions between the nucleobases that are part of the Shine-Dalgarno (SD) and anti-Shine-Dalgarno (aSD) sequences, which in turn facilitates recognition of the SD sequence by ribosomes. Detailed analysis reveals that a duplex-like structure formed by nucleotides from different parts of the RNA and the adenine base of the ligand is crucial for the stability of the completely folded state in the presence of the ligand. Previous experimental studies have shown that the SAM-III riboswitch exists in equilibrium between the unfolded and partially folded states in the absence of the ligand, which completely folds upon binding of the ligand. Comparison of the results presented here to the available experimental data indicates the structures obtained using the MD simulations resemble the partially folded state. Thus, this study provides a detailed understanding of the fully and partially folded structures of the SAM-III riboswitch in the presence and absence of the ligand, respectively. This study hypothesizes a dual role for the SAM ligand, which facilitates conformational switching between partially and fully folded states by forming a stable duplex-like structure and strengthening the interactions between SD and aSD nucleotides.

Kinetics and thermodynamics of exonuclease-deficient DNA polymerases

NASA Astrophysics Data System (ADS)

Gaspard, Pierre

2016-04-01

A kinetic theory is developed for exonuclease-deficient DNA polymerases, based on the experimental observation that the rates depend not only on the newly incorporated nucleotide, but also on the previous one, leading to the growth of Markovian DNA sequences from a Bernoullian template. The dependencies on nucleotide concentrations and template sequence are explicitly taken into account. In this framework, the kinetic and thermodynamic properties of DNA replication, in particular, the mean growth velocity, the error probability, and the entropy production are calculated analytically in terms of the rate constants and the concentrations. Theory is compared with numerical simulations for the DNA polymerases of T7 viruses and human mitochondria.

DRoP: a water analysis program identifies Ras-GTP-specific pathway of communication between membrane-interacting regions and the active site.

PubMed

Kearney, Bradley M; Johnson, Christian W; Roberts, Daniel M; Swartz, Paul; Mattos, Carla

2014-02-06

Ras GTPase mediates several cellular signal transduction pathways and is found mutated in a large number of cancers. It is active in the GTP-bound state, where it interacts with effector proteins, and at rest in the GDP-bound state. The catalytic domain is tethered to the membrane, with which it interacts in a nucleotide-dependent manner. Here we present the program Detection of Related Solvent Positions (DRoP) for crystallographic water analysis on protein surfaces and use it to study Ras. DRoP reads and superimposes multiple Protein Data Bank coordinates, transfers symmetry-related water molecules to the position closest to the protein surface, and ranks the waters according to how well conserved and tightly clustered they are in the set of structures. Coloring according to this rank allows visualization of the results. The effector-binding region of Ras is hydrated with highly conserved water molecules at the interface between the P-loop, switch I, and switch II, as well as at the Raf-RBD binding pocket. Furthermore, we discovered a new conserved water-mediated H-bonding network present in Ras-GTP, but not in Ras-GDP, that links the nucleotide sensor residues R161 and R164 on helix 5 to the active site. The double mutant RasN85A/N86A, where the final link between helix 5 and the nucleotide is not possible, is a severely impaired enzyme, while the single mutant RasN86A, with partial connection to the active site, has a wild-type hydrolysis rate. DRoP was instrumental in determining the water-mediated connectivity networks that link two lobes of the catalytic domain in Ras. Copyright © 2013 Elsevier Ltd. All rights reserved.

Structural Determinants at the Interface of the ARC2 and Leucine-Rich Repeat Domains Control the Activation of the Plant Immune Receptors Rx1 and Gpa21[C][W][OA

PubMed Central

Slootweg, Erik J.; Spiridon, Laurentiu N.; Roosien, Jan; Butterbach, Patrick; Pomp, Rikus; Westerhof, Lotte; Wilbers, Ruud; Bakker, Erin; Bakker, Jaap; Petrescu, Andrei-José; Smant, Geert; Goverse, Aska

2013-01-01

Many plant and animal immune receptors have a modular nucleotide-binding-leucine-rich repeat (NB-LRR) architecture in which a nucleotide-binding switch domain, NB-ARC, is tethered to a LRR sensor domain. The cooperation between the switch and sensor domains, which regulates the activation of these proteins, is poorly understood. Here, we report structural determinants governing the interaction between the NB-ARC and LRR in the highly homologous plant immune receptors Gpa2 and Rx1, which recognize the potato cyst nematode Globodera pallida and Potato virus X, respectively. Systematic shuffling of polymorphic sites between Gpa2 and Rx1 showed that a minimal region in the ARC2 and N-terminal repeats of the LRR domain coordinate the activation state of the protein. We identified two closely spaced amino acid residues in this region of the ARC2 (positions 401 and 403) that distinguish between autoactivation and effector-triggered activation. Furthermore, a highly acidic loop region in the ARC2 domain and basic patches in the N-terminal end of the LRR domain were demonstrated to be required for the physical interaction between the ARC2 and LRR. The NB-ARC and LRR domains dissociate upon effector-dependent activation, and the complementary-charged regions are predicted to mediate a fast reassociation, enabling multiple rounds of activation. Finally, we present a mechanistic model showing how the ARC2, NB, and N-terminal half of the LRR form a clamp, which regulates the dissociation and reassociation of the switch and sensor domains in NB-LRR proteins. PMID:23660837

Structural determinants at the interface of the ARC2 and leucine-rich repeat domains control the activation of the plant immune receptors Rx1 and Gpa2.

PubMed

Slootweg, Erik J; Spiridon, Laurentiu N; Roosien, Jan; Butterbach, Patrick; Pomp, Rikus; Westerhof, Lotte; Wilbers, Ruud; Bakker, Erin; Bakker, Jaap; Petrescu, Andrei-José; Smant, Geert; Goverse, Aska

2013-07-01

Many plant and animal immune receptors have a modular nucleotide-binding-leucine-rich repeat (NB-LRR) architecture in which a nucleotide-binding switch domain, NB-ARC, is tethered to a LRR sensor domain. The cooperation between the switch and sensor domains, which regulates the activation of these proteins, is poorly understood. Here, we report structural determinants governing the interaction between the NB-ARC and LRR in the highly homologous plant immune receptors Gpa2 and Rx1, which recognize the potato cyst nematode Globodera pallida and Potato virus X, respectively. Systematic shuffling of polymorphic sites between Gpa2 and Rx1 showed that a minimal region in the ARC2 and N-terminal repeats of the LRR domain coordinate the activation state of the protein. We identified two closely spaced amino acid residues in this region of the ARC2 (positions 401 and 403) that distinguish between autoactivation and effector-triggered activation. Furthermore, a highly acidic loop region in the ARC2 domain and basic patches in the N-terminal end of the LRR domain were demonstrated to be required for the physical interaction between the ARC2 and LRR. The NB-ARC and LRR domains dissociate upon effector-dependent activation, and the complementary-charged regions are predicted to mediate a fast reassociation, enabling multiple rounds of activation. Finally, we present a mechanistic model showing how the ARC2, NB, and N-terminal half of the LRR form a clamp, which regulates the dissociation and reassociation of the switch and sensor domains in NB-LRR proteins.

Switching LPV Control for High Performance Tactical Aircraft

NASA Technical Reports Server (NTRS)

Lu, Bei; Wu, Fen; Kim, SungWan

2004-01-01

This paper examines a switching Linear Parameter-Varying (LPV) control approach to determine if it is practical to use for flight control designs within a wide angle of attack region. The approach is based on multiple parameter-dependent Lyapunov functions. The full parameter space is partitioned into overlapping subspaces and a family of LPV controllers are designed, each suitable for a specific parameter subspace. The hysteresis switching logic is used to accomplish the transition among different parameter subspaces. The proposed switching LPV control scheme is applied to an F-16 aircraft model with different actuator dynamics in low and high angle of attack regions. The nonlinear simulation results show that the aircraft performs well when switching among different angle of attack regions.

Variability of multilevel switching in scaled hybrid RS/CMOS nanoelectronic circuits: theory

NASA Astrophysics Data System (ADS)

Heittmann, Arne; Noll, Tobias G.

2013-07-01

A theory is presented which describes the variability of multilevel switching in scaled hybrid resistive-switching/CMOS nanoelectronic circuits. Variability is quantified in terms of conductance variation using the first two moments derived from the probability density function (PDF) of the RS conductance. For RS, which are based on the electrochemical metallization effect (ECM), this variability is - to some extent - caused by discrete events such as electrochemical reactions, which occur on atomic scale and are at random. The theory shows that the conductance variation depends on the joint interaction between the programming circuit and the resistive switch (RS), and explicitly quantifies the impact of RS device parameters and parameters of the programming circuit on the conductance variance. Using a current mirror as an exemplary programming circuit an upper limit of 2-4 bits (dependent on the filament surface area) is estimated as the storage capacity exploiting the multilevel capabilities of an ECM cell. The theoretical results were verified by Monte Carlo circuit simulations on a standard circuit simulation environment using an ECM device model which models the filament growth by a Poisson process. Contribution to the Topical Issue “International Semiconductor Conference Dresden-Grenoble - ISCDG 2012”, Edited by Gérard Ghibaudo, Francis Balestra and Simon Deleonibus.

GDP-to-GTP exchange on the microtubule end can contribute to the frequency of catastrophe

PubMed Central

Piedra, Felipe-Andrés; Kim, Tae; Garza, Emily S.; Geyer, Elisabeth A.; Burns, Alexander; Ye, Xuecheng; Rice, Luke M.

2016-01-01

Microtubules are dynamic polymers of αβ-tubulin that have essential roles in chromosome segregation and organization of the cytoplasm. Catastrophe—the switch from growing to shrinking—occurs when a microtubule loses its stabilizing GTP cap. Recent evidence indicates that the nucleotide on the microtubule end controls how tightly an incoming subunit will be bound (trans-acting GTP), but most current models do not incorporate this information. We implemented trans-acting GTP into a computational model for microtubule dynamics. In simulations, growing microtubules often exposed terminal GDP-bound subunits without undergoing catastrophe. Transient GDP exposure on the growing plus end slowed elongation by reducing the number of favorable binding sites on the microtubule end. Slower elongation led to erosion of the GTP cap and an increase in the frequency of catastrophe. Allowing GDP-to-GTP exchange on terminal subunits in simulations mitigated these effects. Using mutant αβ-tubulin or modified GTP, we showed experimentally that a more readily exchangeable nucleotide led to less frequent catastrophe. Current models for microtubule dynamics do not account for GDP-to-GTP exchange on the growing microtubule end, so our findings provide a new way of thinking about the molecular events that initiate catastrophe. PMID:27146111

Merely two mutations switch a DNA-hydrolyzing deoxyribozyme from heterobimetallic (Zn2+/Mn2+) to monometallic (Zn2+-only) behavior

PubMed Central

Xiao, Ying; Allen, Emily C.

2012-01-01

A deoxyribozyme that hydrolyzes DNA phosphodiester linkages with a requirement for both Zn2+ and Mn2+ is switched by only two nucleotide mutations to require Zn2+ alone, demonstrating that DNA-catalyzed DNA hydrolysis can be achieved using only one metal ion cofactor. PMID:21125108

Switch junction sequences in PMS2-deficient mice reveal a microhomology-mediated mechanism of Ig class switch recombination

PubMed Central

Ehrenstein, Michael R.; Rada, Cristina; Jones, Anne-Marie; Milstein, César; Neuberger, Michael S.

2001-01-01

Isotype switching involves a region-specific, nonhomologous recombinational deletion that has been suggested to occur by nonhomologous joining of broken DNA ends. Here, we find increased donor/acceptor homology at switch junctions from PMS2-deficient mice and propose that class switching can occur by microhomology-mediated end-joining. Interestingly, although isotype switching and somatic hypermutation show many parallels, we confirm that PMS2 deficiency has no major effect on the pattern of nucleotide substitutions generated during somatic hypermutation. This finding is in contrast to MSH2 deficiency. With MSH2, the altered pattern of switch recombination and hypermutation suggests parallels in the mechanics of the two processes, whereas the fact that PMS2 deficiency affects only switch recombination may reflect differences in the pathways of break resolution. PMID:11717399

Mapping allosteric connections from the receptor to the nucleotide-binding pocket of heterotrimeric G proteins

PubMed Central

Oldham, William M.; Van Eps, Ned; Preininger, Anita M.; Hubbell, Wayne L.; Hamm, Heidi E.

2007-01-01

Heterotrimeric G proteins function as molecular relays that mediate signal transduction from heptahelical receptors in the cell membrane to intracellular effector proteins. Crystallographic studies have demonstrated that guanine nucleotide exchange on the Gα subunit causes specific conformational changes in three key “switch” regions of the protein, which regulate binding to Gβγ subunits, receptors, and effector proteins. In the present study, nitroxide side chains were introduced at sites within the switch I region of Gαi to explore the structure and dynamics of this region throughout the G protein cycle. EPR spectra obtained for each of the Gα(GDP), Gα(GDP)βγ heterotrimer and Gα(GTPγS) conformations are consistent with the local environment observed in the corresponding crystal structures. Binding of the heterotrimer to activated rhodopsin to form the nucleotide-free (empty) complex, for which there is no crystal structure, causes prominent changes relative to the heterotrimer in the structure of switch I and contiguous sequences. The data identify a putative pathway of allosteric changes triggered by receptor binding and, together with previously published data, suggest elements of a mechanism for receptor-catalyzed nucleotide exchange. PMID:17463080

Effects of polymerization and nucleotide identity on the conformational dynamics of the bacterial actin homolog MreB

PubMed Central

Colavin, Alexandre; Hsin, Jen; Huang, Kerwyn Casey

2014-01-01

The assembly of protein filaments drives many cellular processes, from nucleoid segregation, growth, and division in single cells to muscle contraction in animals. In eukaryotes, shape and motility are regulated through cycles of polymerization and depolymerization of actin cytoskeletal networks. In bacteria, the actin homolog MreB forms filaments that coordinate the cell-wall synthesis machinery to regulate rod-shaped growth and contribute to cellular stiffness through unknown mechanisms. Like actin, MreB is an ATPase and requires ATP to polymerize, and polymerization promotes nucleotide hydrolysis. However, it is unclear whether other similarities exist between MreB and actin because the two proteins share low sequence identity and have distinct cellular roles. Here, we use all-atom molecular dynamics simulations to reveal surprising parallels between MreB and actin structural dynamics. We observe that MreB exhibits actin-like polymerization-dependent structural changes, wherein polymerization induces flattening of MreB subunits, which restructures the nucleotide-binding pocket to favor hydrolysis. MreB filaments exhibited nucleotide-dependent intersubunit bending, with hydrolyzed polymers favoring a straighter conformation. We use steered simulations to demonstrate a coupling between intersubunit bending and the degree of flattening of each subunit, suggesting cooperative bending along a filament. Taken together, our results provide molecular-scale insight into the diversity of structural states of MreB and the relationships among polymerization, hydrolysis, and filament properties, which may be applicable to other members of the broad actin family. PMID:24550504

Effects of polymerization and nucleotide identity on the conformational dynamics of the bacterial actin homolog MreB.

PubMed

Colavin, Alexandre; Hsin, Jen; Huang, Kerwyn Casey

2014-03-04

The assembly of protein filaments drives many cellular processes, from nucleoid segregation, growth, and division in single cells to muscle contraction in animals. In eukaryotes, shape and motility are regulated through cycles of polymerization and depolymerization of actin cytoskeletal networks. In bacteria, the actin homolog MreB forms filaments that coordinate the cell-wall synthesis machinery to regulate rod-shaped growth and contribute to cellular stiffness through unknown mechanisms. Like actin, MreB is an ATPase and requires ATP to polymerize, and polymerization promotes nucleotide hydrolysis. However, it is unclear whether other similarities exist between MreB and actin because the two proteins share low sequence identity and have distinct cellular roles. Here, we use all-atom molecular dynamics simulations to reveal surprising parallels between MreB and actin structural dynamics. We observe that MreB exhibits actin-like polymerization-dependent structural changes, wherein polymerization induces flattening of MreB subunits, which restructures the nucleotide-binding pocket to favor hydrolysis. MreB filaments exhibited nucleotide-dependent intersubunit bending, with hydrolyzed polymers favoring a straighter conformation. We use steered simulations to demonstrate a coupling between intersubunit bending and the degree of flattening of each subunit, suggesting cooperative bending along a filament. Taken together, our results provide molecular-scale insight into the diversity of structural states of MreB and the relationships among polymerization, hydrolysis, and filament properties, which may be applicable to other members of the broad actin family.

Conformational dynamics of a G-protein α subunit is tightly regulated by nucleotide binding.

PubMed

Goricanec, David; Stehle, Ralf; Egloff, Pascal; Grigoriu, Simina; Plückthun, Andreas; Wagner, Gerhard; Hagn, Franz

2016-06-28

Heterotrimeric G proteins play a pivotal role in the signal-transduction pathways initiated by G-protein-coupled receptor (GPCR) activation. Agonist-receptor binding causes GDP-to-GTP exchange and dissociation of the Gα subunit from the heterotrimeric G protein, leading to downstream signaling. Here, we studied the internal mobility of a G-protein α subunit in its apo and nucleotide-bound forms and characterized their dynamical features at multiple time scales using solution NMR, small-angle X-ray scattering, and molecular dynamics simulations. We find that binding of GTP analogs leads to a rigid and closed arrangement of the Gα subdomain, whereas the apo and GDP-bound forms are considerably more open and dynamic. Furthermore, we were able to detect two conformational states of the Gα Ras domain in slow exchange whose populations are regulated by binding to nucleotides and a GPCR. One of these conformational states, the open state, binds to the GPCR; the second conformation, the closed state, shows no interaction with the receptor. Binding to the GPCR stabilizes the open state. This study provides an in-depth analysis of the conformational landscape and the switching function of a G-protein α subunit and the influence of a GPCR in that landscape.

Conformational dynamics of a G-protein α subunit is tightly regulated by nucleotide binding

PubMed Central

Goricanec, David; Stehle, Ralf; Egloff, Pascal; Grigoriu, Simina; Wagner, Gerhard; Hagn, Franz

2016-01-01

Heterotrimeric G proteins play a pivotal role in the signal-transduction pathways initiated by G-protein–coupled receptor (GPCR) activation. Agonist–receptor binding causes GDP-to-GTP exchange and dissociation of the Gα subunit from the heterotrimeric G protein, leading to downstream signaling. Here, we studied the internal mobility of a G-protein α subunit in its apo and nucleotide-bound forms and characterized their dynamical features at multiple time scales using solution NMR, small-angle X-ray scattering, and molecular dynamics simulations. We find that binding of GTP analogs leads to a rigid and closed arrangement of the Gα subdomain, whereas the apo and GDP-bound forms are considerably more open and dynamic. Furthermore, we were able to detect two conformational states of the Gα Ras domain in slow exchange whose populations are regulated by binding to nucleotides and a GPCR. One of these conformational states, the open state, binds to the GPCR; the second conformation, the closed state, shows no interaction with the receptor. Binding to the GPCR stabilizes the open state. This study provides an in-depth analysis of the conformational landscape and the switching function of a G-protein α subunit and the influence of a GPCR in that landscape. PMID:27298341

Fuel switching in the electricity sector under the EU ETS: Review and prospective

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

Delarue, E.; Voorspools, K.; D'haeseleer, W.

2008-06-15

The European Union has implemented the European Union emission trading scheme (EU ETS) as an instrument to facilitate greenhouse gas (GHG) emission abatement stipulated in the Kyoto protocol. Empirical data show that in the early stages of the EU ETS, the value of a ton of CO{sub 2} has already led to emission abatement through switching from coal to gas in the European electric power sector. In the second part of this paper, an electricity generation simulation model is used to perform simulations on the switching behavior in both the first and the second trading periods of the EU ETS.more » In 2005, the reduction in GHG emissions in the electric power sector due to EU ETS is estimated close to 88 Mton. For the second trading period, a European Union allowance (EUA) price dependent GHG reduction curve has been determined. The obtained switching potential turns out to be significant, up to 300 Mton/year, at sufficiently high EUA prices.« less

Conformational Smear Characterization and Binning of Single-Molecule Conductance Measurements for Enhanced Molecular Recognition.

PubMed

Korshoj, Lee E; Afsari, Sepideh; Chatterjee, Anushree; Nagpal, Prashant

2017-11-01

Electronic conduction or charge transport through single molecules depends primarily on molecular structure and anchoring groups and forms the basis for a wide range of studies from molecular electronics to DNA sequencing. Several high-throughput nanoelectronic methods such as mechanical break junctions, nanopores, conductive atomic force microscopy, scanning tunneling break junctions, and static nanoscale electrodes are often used for measuring single-molecule conductance. In these measurements, "smearing" due to conformational changes and other entropic factors leads to large variances in the observed molecular conductance, especially in individual measurements. Here, we show a method for characterizing smear in single-molecule conductance measurements and demonstrate how binning measurements according to smear can significantly enhance the use of individual conductance measurements for molecular recognition. Using quantum point contact measurements on single nucleotides within DNA macromolecules, we demonstrate that the distance over which molecular junctions are maintained is a measure of smear, and the resulting variance in unbiased single measurements depends on this smear parameter. Our ability to identify individual DNA nucleotides at 20× coverage increases from 81.3% accuracy without smear analysis to 93.9% with smear characterization and binning (SCRIB). Furthermore, merely 7 conductance measurements (7× coverage) are needed to achieve 97.8% accuracy for DNA nucleotide recognition when only low molecular smear measurements are used, which represents a significant improvement over contemporary sequencing methods. These results have important implications in a broad range of molecular electronics applications from designing robust molecular switches to nanoelectronic DNA sequencing.

Structural Dynamics as a Contributor to Error-prone Replication by an RNA-dependent RNA Polymerase*

PubMed Central

Moustafa, Ibrahim M.; Korboukh, Victoria K.; Arnold, Jamie J.; Smidansky, Eric D.; Marcotte, Laura L.; Gohara, David W.; Yang, Xiaorong; Sánchez-Farrán, María Antonieta; Filman, David; Maranas, Janna K.; Boehr, David D.; Hogle, James M.; Colina, Coray M.; Cameron, Craig E.

2014-01-01

RNA viruses encoding high- or low-fidelity RNA-dependent RNA polymerases (RdRp) are attenuated. The ability to predict residues of the RdRp required for faithful incorporation of nucleotides represents an essential step in any pipeline intended to exploit perturbed fidelity as the basis for rational design of vaccine candidates. We used x-ray crystallography, molecular dynamics simulations, NMR spectroscopy, and pre-steady-state kinetics to compare a mutator (H273R) RdRp from poliovirus to the wild-type (WT) enzyme. We show that the nucleotide-binding site toggles between the nucleotide binding-occluded and nucleotide binding-competent states. The conformational dynamics between these states were enhanced by binding to primed template RNA. For the WT, the occluded conformation was favored; for H273R, the competent conformation was favored. The resonance for Met-187 in our NMR spectra reported on the ability of the enzyme to check the correctness of the bound nucleotide. Kinetic experiments were consistent with the conformational dynamics contributing to the established pre-incorporation conformational change and fidelity checkpoint. For H273R, residues comprising the active site spent more time in the catalytically competent conformation and were more positively correlated than the WT. We propose that by linking the equilibrium between the binding-occluded and binding-competent conformations of the nucleotide-binding pocket and other active-site dynamics to the correctness of the bound nucleotide, faithful nucleotide incorporation is achieved. These studies underscore the need to apply multiple biophysical and biochemical approaches to the elucidation of the physical basis for polymerase fidelity. PMID:25378410

Adaptive Fuzzy Control Design for Stochastic Nonlinear Switched Systems With Arbitrary Switchings and Unmodeled Dynamics.

PubMed

Li, Yongming; Sui, Shuai; Tong, Shaocheng

2017-02-01

This paper deals with the problem of adaptive fuzzy output feedback control for a class of stochastic nonlinear switched systems. The controlled system in this paper possesses unmeasured states, completely unknown nonlinear system functions, unmodeled dynamics, and arbitrary switchings. A state observer which does not depend on the switching signal is constructed to tackle the unmeasured states. Fuzzy logic systems are employed to identify the completely unknown nonlinear system functions. Based on the common Lyapunov stability theory and stochastic small-gain theorem, a new robust adaptive fuzzy backstepping stabilization control strategy is developed. The stability of the closed-loop system on input-state-practically stable in probability is proved. The simulation results are given to verify the efficiency of the proposed fuzzy adaptive control scheme.

Monte Carlo simulation of a simple gene network yields new evolutionary insights.

PubMed

Andrecut, M; Cloud, D; Kauffman, S A

2008-02-07

Monte Carlo simulations of a genetic toggle switch show that its behavior can be more complex than analytic models would suggest. We show here that as a result of the interplay between frequent and infrequent reaction events, such a switch can have more stable states than an analytic model would predict, and that the number and character of these states depend to a large extent on the propensity of transcription factors to bind to and dissociate from promoters. The effects of gene duplications differ even more; in analytic models, these seem to result in the disappearance of bi-stability and thus a loss of the switching function, but a Monte Carlo simulation shows that they can result in the appearance of new stable states without the loss of old ones, and thus in an increase of the complexity of the switch's behavior which may facilitate the evolution of new cellular functions. These differences are of interest with respect to the evolution of gene networks, particularly in clonal lines of cancer cells, where the duplication of active genes is an extremely common event, and often seems to result in the appearance of viable new cellular phenotypes.

"Plug and play" logic gates based on fluorescence switching regulated by self-assembly of nucleotide and lanthanide ions.

PubMed

Pu, Fang; Ren, Jinsong; Qu, Xiaogang

2014-06-25

Molecular logic gates in response to chemical, biological, or optical input signals at a molecular level have received much interest over the past decade. Herein, we construct "plug and play" logic systems based on the fluorescence switching of guest molecules confined in coordination polymer nanoparticles generated from nucleotide and lanthanide ions. In the system, the addition of new modules directly enables new logic functions. PASS 0, YES, PASS 1, NOT, IMP, OR, and AND gates are successfully constructed in sequence. Moreover, different logic gates (AND, INH, and IMP) can be constructed using different guest molecules and the same input combinations. The work will be beneficial to the future logic design and expand the applications of coordination polymers.

Harnessing the polariton drag effect to design an electrically controlled optical switch.

PubMed

Berman, Oleg L; Kezerashvili, Roman Ya; Kolmakov, German V

2014-10-28

We propose a design of a Y-shaped electrically controlled optical switch based on the studies of propagation of an exciton-polariton condensate in a patterned optical microcavity with an embedded quantum well. The polaritons are driven by a time-independent force due to the microcavity wedge shape and by a time-dependent drag force owing to the interaction of excitons in a quantum well and the electric current running in a neighboring quantum well. It is demonstrated that by applying the drag force one can direct more than 90% of the polariton flow toward the desired branch of the switch with no hysteresis. By considering the transient dynamics of the polariton condensate, we estimate the response speed of the switch as 9.1 GHz. We also propose a design of the polariton switch in a flat microcavity based on the geometrically identical Y-shaped quantum wells where the polariton flow is only induced by the drag force. The latter setup enables one to design a multiway switch that can act as an electrically controlled optical transistor with on and off functions. Finally, we performed the simulations for a microcavity with an embedded gapped graphene layer and demonstrated that in this case the response speed of the switch can be increased up to 14 GHz for the same switch size. The simulations also show that the energy gap in the quasiparticle spectrum in graphene can be utilized as an additional parameter that controls the propagation of the signals in the switch.

Structure of the 26S proteasome with ATP-γS bound provides insights into the mechanism of nucleotide-dependent substrate translocation

PubMed Central

Śledź, Paweł; Unverdorben, Pia; Beck, Florian; Pfeifer, Günter; Schweitzer, Andreas; Förster, Friedrich; Baumeister, Wolfgang

2013-01-01

The 26S proteasome is a 2.5-MDa, ATP-dependent multisubunit proteolytic complex that processively destroys proteins carrying a degradation signal. The proteasomal ATPase heterohexamer is a key module of the 19S regulatory particle; it unfolds substrates and translocates them into the 20S core particle where degradation takes place. We used cryoelectron microscopy single-particle analysis to obtain insights into the structural changes of 26S proteasome upon the binding and hydrolysis of ATP. The ATPase ring adopts at least two distinct helical staircase conformations dependent on the nucleotide state. The transition from the conformation observed in the presence of ATP to the predominant conformation in the presence of ATP-γS induces a sliding motion of the ATPase ring over the 20S core particle ring leading to an alignment of the translocation channels of the ATPase and the core particle gate, a conformational state likely to facilitate substrate translocation. Two types of intersubunit modules formed by the large ATPase domain of one ATPase subunit and the small ATPase domain of its neighbor exist. They resemble the contacts observed in the crystal structures of ClpX and proteasome-activating nucleotidase, respectively. The ClpX-like contacts are positioned consecutively and give rise to helical shape in the hexamer, whereas the proteasome-activating nucleotidase-like contact is required to close the ring. Conformational switching between these forms allows adopting different helical conformations in different nucleotide states. We postulate that ATP hydrolysis by the regulatory particle ATPase (Rpt) 5 subunit initiates a cascade of conformational changes, leading to pulling of the substrate, which is primarily executed by Rpt1, Rpt2, and Rpt6. PMID:23589842

An intermediate along the recovery stroke of myosin VI revealed by X-ray crystallography and molecular dynamics.

PubMed

Blanc, Florian; Isabet, Tatiana; Benisty, Hannah; Sweeney, H Lee; Cecchini, Marco; Houdusse, Anne

2018-06-12

Myosins form a class of actin-based, ATPase motor proteins that mediate important cellular functions such as cargo transport and cell motility. Their functional cycle involves two large-scale swings of the lever arm: the force-generating powerstroke, which takes place on actin, and the recovery stroke during which the lever arm is reprimed into an armed configuration. Previous analyses of the prerecovery (postrigor) and postrecovery (prepowerstroke) states predicted that closure of switch II in the ATP binding site precedes the movement of the converter and the lever arm. Here, we report on a crystal structure of myosin VI, called pretransition state (PTS), which was solved at 2.2 Å resolution. Structural analysis and all-atom molecular dynamics simulations are consistent with PTS being an intermediate along the recovery stroke, where the Relay/SH1 elements adopt a postrecovery conformation, and switch II remains open. In this state, the converter appears to be largely uncoupled from the motor domain and explores an ensemble of partially reprimed configurations through extensive, reversible fluctuations. Moreover, we found that the free energy cost of hydrogen-bonding switch II to ATP is lowered by more than 10 kcal/mol compared with the prerecovery state. These results support the conclusion that closing of switch II does not initiate the recovery stroke transition in myosin VI. Rather, they suggest a mechanism in which lever arm repriming would be mostly driven by thermal fluctuations and eventually stabilized by the switch II interaction with the nucleotide in a ratchet-like fashion.

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

NASA Astrophysics Data System (ADS)

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. Possible explanations are discussed in the light of currently debated transport scenarios of ABC transporters.

True and apparent scaling: The proximity of the Markov-switching multifractal model to long-range dependence

NASA Astrophysics Data System (ADS)

Liu, Ruipeng; Di Matteo, T.; Lux, Thomas

2007-09-01

In this paper, we consider daily financial data of a collection of different stock market indices, exchange rates, and interest rates, and we analyze their multi-scaling properties by estimating a simple specification of the Markov-switching multifractal (MSM) model. In order to see how well the estimated model captures the temporal dependence of the data, we estimate and compare the scaling exponents H(q) (for q=1,2) for both empirical data and simulated data of the MSM model. In most cases the multifractal model appears to generate ‘apparent’ long memory in agreement with the empirical scaling laws.

Nucleotide synthetase ribozymes may have emerged first in the RNA world

PubMed Central

Ma, Wentao; Yu, Chunwu; Zhang, Wentao; Hu, Jiming

2007-01-01

Though the “RNA world” hypothesis has gained a central role in ideas concerning the origin of life, the scenario concerning its emergence remains uncertain. It has been speculated that the first scene may have been the emergence of a template-dependent RNA synthetase ribozyme, which catalyzed its own replication: thus, “RNA replicase.” However, the speculation remains uncertain, primarily because of the large sequence length requirement of such a replicase and the lack of a convincing mechanism to ensure its self-favoring features. Instead, we propose a nucleotide synthetase ribozyme as an alternative candidate, especially considering recent experimental evidence suggesting the possibility of effective nonenzymatic template-directed synthesis of RNA. A computer simulation was conducted to support our proposal. The conditions for the emergence of the nucleotide synthetase ribozyme are discussed, based on dynamic analysis on a computer. We suggest the template-dependent RNA synthetase ribozyme emerged later, perhaps after the emergence of protocells. PMID:17878321

Theoretical and experimental study of a laser-diode-pumped actively Q-switched Yb:NaY(WO4)2 laser with acoustic-optic modulator

NASA Astrophysics Data System (ADS)

Zhang, Haikun; Xia, Wei; Song, Peng; Wang, Jing; Li, Xin

2018-03-01

A laser-diode-pumped actively Q-switched Yb:NaY(WO4)2 laser operating at around 1040 nm is presented for the first time with acoustic-optic modulator. The dependence of pulse width on incident pump power for different pulse repetition rates is measured. By considering the Guassian spatial distribution of the intracavity photon density and the initial population-inversion density as well as the longitudinal distribution of the photon density along the cavity axis and the turn off time of the acoustic-optic Q-switch, the coupled equations of the actively Q-switched Yb:NaY(WO4)2 laser are given. The coupled rate equations are used to simulate the Q-switched process of laser, and the numerical solutions agree with the experimental results.

Characteristics of silicon-based Sagnac optical switches using magneto-optical micro-ring array

NASA Astrophysics Data System (ADS)

Ni, Shuang; Wu, Baojian; Liu, Yawen

2018-01-01

The miniaturization and integration of optical switches are necessary for photonic switching networks and the utilization of magneto optical effects is a promising candidate. We propose a Sagnac optical switch chip based on the principle of nonreciprocal phase shift (NPS) of the magneto-optical (MO) micro-ring (MOMR) array, composed of SiO2/Si/Ce:YIG/SGGG. The MO switching function is realized by controlling the drive current in the snake-like metal microstrip circuit layered on the MOMRs. The transmission characteristics of the Sagnac MO switch chip dependent on magnetization intensity, waveguide coupling coefficient and waveguide loss are simulated. By optimizing the coupling coefficients, we design an MO switch using two serial MOMRs with a circumference of 38.37 μm, and the 3dB bandwidth and the extinction ratio are respectively up to 1.6 nm and 50dB for the waveguide loss coefficient of ?. And the switching magnetization can be further reduced by increasing the number of parallel MOMRs. The frequency response of the MO Sagnac switch is analyzed as well.

Towards developing a compact model for magnetization switching in straintronics magnetic random access memory devices

NASA Astrophysics Data System (ADS)

Barangi, Mahmood; Erementchouk, Mikhail; Mazumder, Pinaki

2016-08-01

Strain-mediated magnetization switching in a magnetic tunneling junction (MTJ) by exploiting a combination of piezoelectricity and magnetostriction has been proposed as an energy efficient alternative to spin transfer torque (STT) and field induced magnetization switching methods in MTJ-based magnetic random access memories (MRAM). Theoretical studies have shown the inherent advantages of strain-assisted switching, and the dynamic response of the magnetization has been modeled using the Landau-Lifshitz-Gilbert (LLG) equation. However, an attempt to use LLG for simulating dynamics of individual elements in large-scale simulations of multi-megabyte straintronics MRAM leads to extremely time-consuming calculations. Hence, a compact analytical solution, predicting the flipping delay of the magnetization vector in the nanomagnet under stress, combined with a liberal approximation of the LLG dynamics in the straintronics MTJ, can lead to a simplified model of the device suited for fast large-scale simulations of multi-megabyte straintronics MRAMs. In this work, a tensor-based approach is developed to study the dynamic behavior of the stressed nanomagnet. First, using the developed method, the effect of stress on the switching behavior of the magnetization is investigated to realize the margins between the underdamped and overdamped regimes. The latter helps the designer realize the oscillatory behavior of the magnetization when settling along the minor axis, and the dependency of oscillations on the stress level and the damping factor. Next, a theoretical model to predict the flipping delay of the magnetization vector is developed and tested against LLG-based numerical simulations to confirm the accuracy of findings. Lastly, the obtained delay is incorporated into the approximate solutions of the LLG dynamics, in order to create a compact model to liberally and quickly simulate the magnetization dynamics of the MTJ under stress. Using the developed delay equation, the efficiency of the straintronics switching over the STT method is highlighted by analytically investigating the energy-delay trade-off of both methodologies.

Towards developing a compact model for magnetization switching in straintronics magnetic random access memory devices

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

Barangi, Mahmood, E-mail: barangi@umich.edu; Erementchouk, Mikhail; Mazumder, Pinaki

Strain-mediated magnetization switching in a magnetic tunneling junction (MTJ) by exploiting a combination of piezoelectricity and magnetostriction has been proposed as an energy efficient alternative to spin transfer torque (STT) and field induced magnetization switching methods in MTJ-based magnetic random access memories (MRAM). Theoretical studies have shown the inherent advantages of strain-assisted switching, and the dynamic response of the magnetization has been modeled using the Landau-Lifshitz-Gilbert (LLG) equation. However, an attempt to use LLG for simulating dynamics of individual elements in large-scale simulations of multi-megabyte straintronics MRAM leads to extremely time-consuming calculations. Hence, a compact analytical solution, predicting the flippingmore » delay of the magnetization vector in the nanomagnet under stress, combined with a liberal approximation of the LLG dynamics in the straintronics MTJ, can lead to a simplified model of the device suited for fast large-scale simulations of multi-megabyte straintronics MRAMs. In this work, a tensor-based approach is developed to study the dynamic behavior of the stressed nanomagnet. First, using the developed method, the effect of stress on the switching behavior of the magnetization is investigated to realize the margins between the underdamped and overdamped regimes. The latter helps the designer realize the oscillatory behavior of the magnetization when settling along the minor axis, and the dependency of oscillations on the stress level and the damping factor. Next, a theoretical model to predict the flipping delay of the magnetization vector is developed and tested against LLG-based numerical simulations to confirm the accuracy of findings. Lastly, the obtained delay is incorporated into the approximate solutions of the LLG dynamics, in order to create a compact model to liberally and quickly simulate the magnetization dynamics of the MTJ under stress. Using the developed delay equation, the efficiency of the straintronics switching over the STT method is highlighted by analytically investigating the energy-delay trade-off of both methodologies.« less

Optimization of spin-torque switching using AC and DC pulses

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

Dunn, Tom; Kamenev, Alex; Fine Theoretical Physics Institute, University of Minnesota, Minneapolis, Minnesota 55455

2014-06-21

We explore spin-torque induced magnetic reversal in magnetic tunnel junctions using combined AC and DC spin-current pulses. We calculate the optimal pulse times and current strengths for both AC and DC pulses as well as the optimal AC signal frequency, needed to minimize the Joule heat lost during the switching process. The results of this optimization are compared against numeric simulations. Finally, we show how this optimization leads to different dynamic regimes, where switching is optimized by either a purely AC or DC spin-current, or a combination AC/DC spin-current, depending on the anisotropy energies and the spin-current polarization.

Dynamic regulation of GDP binding to G proteins revealed by magnetic field-dependent NMR relaxation analyses

PubMed Central

Toyama, Yuki; Kano, Hanaho; Mase, Yoko; Yokogawa, Mariko; Osawa, Masanori; Shimada, Ichio

2017-01-01

Heterotrimeric guanine-nucleotide-binding proteins (G proteins) serve as molecular switches in signalling pathways, by coupling the activation of cell surface receptors to intracellular responses. Mutations in the G protein α-subunit (Gα) that accelerate guanosine diphosphate (GDP) dissociation cause hyperactivation of the downstream effector proteins, leading to oncogenesis. However, the structural mechanism of the accelerated GDP dissociation has remained unclear. Here, we use magnetic field-dependent nuclear magnetic resonance relaxation analyses to investigate the structural and dynamic properties of GDP bound Gα on a microsecond timescale. We show that Gα rapidly exchanges between a ground-state conformation, which tightly binds to GDP and an excited conformation with reduced GDP affinity. The oncogenic D150N mutation accelerates GDP dissociation by shifting the equilibrium towards the excited conformation. PMID:28223697

Dynamic regulation of GDP binding to G proteins revealed by magnetic field-dependent NMR relaxation analyses.

PubMed

Toyama, Yuki; Kano, Hanaho; Mase, Yoko; Yokogawa, Mariko; Osawa, Masanori; Shimada, Ichio

2017-02-22

Heterotrimeric guanine-nucleotide-binding proteins (G proteins) serve as molecular switches in signalling pathways, by coupling the activation of cell surface receptors to intracellular responses. Mutations in the G protein α-subunit (Gα) that accelerate guanosine diphosphate (GDP) dissociation cause hyperactivation of the downstream effector proteins, leading to oncogenesis. However, the structural mechanism of the accelerated GDP dissociation has remained unclear. Here, we use magnetic field-dependent nuclear magnetic resonance relaxation analyses to investigate the structural and dynamic properties of GDP bound Gα on a microsecond timescale. We show that Gα rapidly exchanges between a ground-state conformation, which tightly binds to GDP and an excited conformation with reduced GDP affinity. The oncogenic D150N mutation accelerates GDP dissociation by shifting the equilibrium towards the excited conformation.

Switch I-dependent allosteric signaling in a G-protein chaperone-B12 enzyme complex.

PubMed

Campanello, Gregory C; Lofgren, Michael; Yokom, Adam L; Southworth, Daniel R; Banerjee, Ruma

2017-10-27

G-proteins regulate various processes ranging from DNA replication and protein synthesis to cytoskeletal dynamics and cofactor assimilation and serve as models for uncovering strategies deployed for allosteric signal transduction. MeaB is a multifunctional G-protein chaperone, which gates loading of the active 5'-deoxyadenosylcobalamin cofactor onto methylmalonyl-CoA mutase (MCM) and precludes loading of inactive cofactor forms. MeaB also safeguards MCM, which uses radical chemistry, against inactivation and rescues MCM inactivated during catalytic turnover by using the GTP-binding energy to offload inactive cofactor. The conserved switch I and II signaling motifs used by G-proteins are predicted to mediate allosteric regulation in response to nucleotide binding and hydrolysis in MeaB. Herein, we targeted conserved residues in the MeaB switch I motif to interrogate the function of this loop. Unexpectedly, the switch I mutations had only modest effects on GTP binding and on GTPase activity and did not perturb stability of the MCM-MeaB complex. However, these mutations disrupted multiple MeaB chaperone functions, including cofactor editing, loading, and offloading. Hence, although residues in the switch I motif are not essential for catalysis, they are important for allosteric regulation. Furthermore, single-particle EM analysis revealed, for the first time, the overall architecture of the MCM-MeaB complex, which exhibits a 2:1 stoichiometry. These EM studies also demonstrate that the complex exhibits considerable conformational flexibility. In conclusion, the switch I element does not significantly stabilize the MCM-MeaB complex or influence the affinity of MeaB for GTP but is required for transducing signals between MeaB and MCM. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Kinetics and thermodynamics of DNA polymerases with exonuclease proofreading

NASA Astrophysics Data System (ADS)

Gaspard, Pierre

2016-04-01

Kinetic theory and thermodynamics are applied to DNA polymerases with exonuclease activity, taking into account the dependence of the rates on the previously incorporated nucleotide. The replication fidelity is shown to increase significantly thanks to this dependence at the basis of the mechanism of exonuclease proofreading. In particular, this dependence can provide up to a 100-fold lowering of the error probability under physiological conditions. Theory is compared with numerical simulations for the DNA polymerases of T7 viruses and human mitochondria.

Gene regulatory networks: a coarse-grained, equation-free approach to multiscale computation.

PubMed

Erban, Radek; Kevrekidis, Ioannis G; Adalsteinsson, David; Elston, Timothy C

2006-02-28

We present computer-assisted methods for analyzing stochastic models of gene regulatory networks. The main idea that underlies this equation-free analysis is the design and execution of appropriately initialized short bursts of stochastic simulations; the results of these are processed to estimate coarse-grained quantities of interest, such as mesoscopic transport coefficients. In particular, using a simple model of a genetic toggle switch, we illustrate the computation of an effective free energy Phi and of a state-dependent effective diffusion coefficient D that characterize an unavailable effective Fokker-Planck equation. Additionally we illustrate the linking of equation-free techniques with continuation methods for performing a form of stochastic "bifurcation analysis"; estimation of mean switching times in the case of a bistable switch is also implemented in this equation-free context. The accuracy of our methods is tested by direct comparison with long-time stochastic simulations. This type of equation-free analysis appears to be a promising approach to computing features of the long-time, coarse-grained behavior of certain classes of complex stochastic models of gene regulatory networks, circumventing the need for long Monte Carlo simulations.

The guanine nucleotide exchange factor Ric-8A induces domain separation and Ras domain plasticity in Gαi1

PubMed Central

Van Eps, Ned; Thomas, Celestine J.; Hubbell, Wayne L.; Sprang, Stephen R.

2015-01-01

Heterotrimeric G proteins are activated by exchange of GDP for GTP at the G protein alpha subunit (Gα), most notably by G protein-coupled transmembrane receptors. Ric-8A is a soluble cytoplasmic protein essential for embryonic development that acts as both a guanine nucleotide exchange factor (GEF) and a chaperone for Gα subunits of the i, q, and 12/13 classes. Previous studies demonstrated that Ric-8A stabilizes a dynamically disordered state of nucleotide-free Gα as the catalytic intermediate for nucleotide exchange, but no information was obtained on the structures involved or the magnitude of the structural fluctuations. In the present study, site-directed spin labeling (SDSL) together with double electron-electron resonance (DEER) spectroscopy is used to provide global distance constraints that identify discrete members of a conformational ensemble in the Gαi1:Ric-8A complex and the magnitude of structural differences between them. In the complex, the helical and Ras-like nucleotide-binding domains of Gαi1 pivot apart to occupy multiple resolved states with displacements as large as 25 Å. The domain displacement appears to be distinct from that observed in Gαs upon binding of Gs to the β2 adrenergic receptor. Moreover, the Ras-like domain exhibits structural plasticity within and around the nucleotide-binding cavity, and the switch I and switch II regions, which are known to adopt different conformations in the GDP- and GTP-bound states of Gα, undergo structural rearrangements. Collectively, the data show that Ric-8A induces a conformationally heterogeneous state of Gαi and provide insight into the mechanism of action of a nonreceptor Gα GEF. PMID:25605908

Electrical switching and oscillations in vanadium dioxide

NASA Astrophysics Data System (ADS)

Pergament, Alexander; Velichko, Andrey; Belyaev, Maksim; Putrolaynen, Vadim

2018-05-01

We have studied electrical switching with S-shaped I-V characteristics in two-terminal MOM devices based on vanadium dioxide thin films. The switching effect is associated with the metal-insulator phase transition. Relaxation oscillations are observed in circuits with VO2-based switches. Dependences of the oscillator critical frequency Fmax, threshold power and voltage, as well as the time of current rise, on the switching structure size are obtained by numerical simulation. The empirical dependence of the threshold voltage on the switching region dimensions and film thickness is found. It is shown that, for the VO2 channel sizes of 10 × 10 nm, Fmax can reach the value of 300 MHz at a film thickness of 20 nm. Next, it is shown that oscillatory neural networks can be implemented on the basis of coupled VO2 oscillators. For the weak capacitive coupling, we revealed the dependence of the phase difference upon synchronization on the coupling capacitance value. When the switches are scaled down, the limiting time of synchronization is reduced to Ts 13 μs, and the number of oscillation periods for the entering to the synchronization mode remains constant, Ns 17. In the case of weak thermal coupling in the synchronization mode, we observe in-phase behavior of oscillators, and there is a certain range of parameters of the supply current, in which the synchronization effect becomes possible. With a decrease in dimensions, a decrease in the thermal coupling action radius is observed, which can vary in the range from 0.5 to 50 μm for structures with characteristic dimensions of 0.1-5 μm, respectively. Thermal coupling may have a promising effect for realization of a 3D integrated oscillatory neural network.

Switch Panel wear loading - a parametric study regarding governing train operational factors

NASA Astrophysics Data System (ADS)

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.

Automated design of genetic toggle switches with predetermined bistability.

PubMed

Chen, Shuobing; Zhang, Haoqian; Shi, Handuo; Ji, Weiyue; Feng, Jingchen; Gong, Yan; Yang, Zhenglin; Ouyang, Qi

2012-07-20

Synthetic biology aims to rationally construct biological devices with required functionalities. Methods that automate the design of genetic devices without post-hoc adjustment are therefore highly desired. Here we provide a method to predictably design genetic toggle switches with predetermined bistability. To accomplish this task, a biophysical model that links ribosome binding site (RBS) DNA sequence to toggle switch bistability was first developed by integrating a stochastic model with RBS design method. Then, to parametrize the model, a library of genetic toggle switch mutants was experimentally built, followed by establishing the equivalence between RBS DNA sequences and switch bistability. To test this equivalence, RBS nucleotide sequences for different specified bistabilities were in silico designed and experimentally verified. Results show that the deciphered equivalence is highly predictive for the toggle switch design with predetermined bistability. This method can be generalized to quantitative design of other probabilistic genetic devices in synthetic biology.

Understanding the kinetic mechanism of RNA single base pair formation

PubMed Central

Xu, Xiaojun; Yu, Tao; Chen, Shi-Jie

2016-01-01

RNA functions are intrinsically tied to folding kinetics. The most elementary step in RNA folding is the closing and opening of a base pair. Understanding this elementary rate process is the basis for RNA folding kinetics studies. Previous studies mostly focused on the unfolding of base pairs. Here, based on a hybrid approach, we investigate the folding process at level of single base pairing/stacking. The study, which integrates molecular dynamics simulation, kinetic Monte Carlo simulation, and master equation methods, uncovers two alternative dominant pathways: Starting from the unfolded state, the nucleotide backbone first folds to the native conformation, followed by subsequent adjustment of the base conformation. During the base conformational rearrangement, the backbone either retains the native conformation or switches to nonnative conformations in order to lower the kinetic barrier for base rearrangement. The method enables quantification of kinetic partitioning among the different pathways. Moreover, the simulation reveals several intriguing ion binding/dissociation signatures for the conformational changes. Our approach may be useful for developing a base pair opening/closing rate model. PMID:26699466

Model for multishot all-thermal all-optical switching in ferromagnets

NASA Astrophysics Data System (ADS)

Gorchon, J.; Yang, Y.; Bokor, J.

2016-07-01

All-optical magnetic switching (AOS) is a recently observed rich and puzzling phenomenon that offers promising technological applications. However, a fundamental understanding of the underlying mechanisms remains elusive. Here we present a model for multishot helicity-dependent AOS in ferromagnetic materials based on a purely heat-driven mechanism in the presence of magnetic circular dichroism (MCD). We predict that AOS should be possible with as little as 0.5% of MCD, after a minimum number of laser shots heat the sample close to the Curie temperature. Finally, we qualitatively reproduce the all-optically switched domain patterns observed experimentally by numerically simulating the result of multiple laser shots on an FePtC granular ferromagnetic film.

Confinement and diffusion modulate bistability and stochastic switching in a reaction network with positive feedback

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

Mlynarczyk, Paul J.; Pullen, Robert H.; Abel, Steven M., E-mail: abel@utk.edu

2016-01-07

Positive feedback is a common feature in signal transduction networks and can lead to phenomena such as bistability and signal propagation by domain growth. Physical features of the cellular environment, such as spatial confinement and the mobility of proteins, play important but inadequately understood roles in shaping the behavior of signaling networks. Here, we use stochastic, spatially resolved kinetic Monte Carlo simulations to explore a positive feedback network as a function of system size, system shape, and mobility of molecules. We show that these physical properties can markedly alter characteristics of bistability and stochastic switching when compared with well-mixed simulations.more » Notably, systems of equal volume but different shapes can exhibit qualitatively different behaviors under otherwise identical conditions. We show that stochastic switching to a state maintained by positive feedback occurs by cluster formation and growth. Additionally, the frequency at which switching occurs depends nontrivially on the diffusion coefficient, which can promote or suppress switching relative to the well-mixed limit. Taken together, the results provide a framework for understanding how confinement and protein mobility influence emergent features of the positive feedback network by modulating molecular concentrations, diffusion-influenced rate parameters, and spatiotemporal correlations between molecules.« less

Development of Simulated Disturbing Source for Isolation Switch

NASA Astrophysics Data System (ADS)

Cheng, Lin; Liu, Xiang; Deng, Xiaoping; Pan, Zhezhe; Zhou, Hang; Zhu, Yong

2018-01-01

In order to simulate the substation in the actual scene of the harsh electromagnetic environment, and then research on electromagnetic compatibility testing of electronic instrument transformer, On the basis of the original isolation switch as a harassment source of the electronic instrument transformer electromagnetic compatibility test system, an isolated switch simulation source system was developed, to promote the standardization of the original test. In this paper, the circuit breaker is used to control the opening and closing of the gap arc to simulate the operating of isolating switch, and the isolation switch simulation harassment source system is designed accordingly. Comparison with the actual test results of the isolating switch, it is proved that the system can meet the test requirements, and the simulation harassment source system has good stability and high reliability.

A Histidine pH sensor regulates activation of the Ras-specific guanine nucleotide exchange factor RasGRP1.

PubMed

Vercoulen, Yvonne; Kondo, Yasushi; Iwig, Jeffrey S; Janssen, Axel B; White, Katharine A; Amini, Mojtaba; Barber, Diane L; Kuriyan, John; Roose, Jeroen P

2017-09-27

RasGRPs are guanine nucleotide exchange factors that are specific for Ras or Rap, and are important regulators of cellular signaling. Aberrant expression or mutation of RasGRPs results in disease. An analysis of RasGRP1 SNP variants led to the conclusion that the charge of His 212 in RasGRP1 alters signaling activity and plasma membrane recruitment, indicating that His 212 is a pH sensor that alters the balance between the inactive and active forms of RasGRP1. To understand the structural basis for this effect we compared the structure of autoinhibited RasGRP1, determined previously, to those of active RasGRP4:H-Ras and RasGRP2:Rap1b complexes. The transition from the autoinhibited to the active form of RasGRP1 involves the rearrangement of an inter-domain linker that displaces inhibitory inter-domain interactions. His 212 is located at the fulcrum of these conformational changes, and structural features in its vicinity are consistent with its function as a pH-dependent switch.

Nucleotide-dependent switch in proteasome assembly mediated by the Nas6 chaperone

PubMed Central

Li, Frances; Tian, Geng; Langager, Deanna; Sokolova, Vladyslava; Finley, Daniel; Park, Soyeon

2017-01-01

The proteasome is assembled via the nine-subunit lid, nine-subunit base, and 28-subunit core particle (CP). Previous work has shown that the chaperones Rpn14, Nas6, Hsm3, and Nas2 each bind a specific ATPase subunit of the base and antagonize base–CP interaction. Here, we show that the Nas6 chaperone also obstructs base–lid association. Nas6 alternates between these two inhibitory modes according to the nucleotide state of the base. When ATP cannot be hydrolyzed, Nas6 interferes with base–lid, but not base–CP, association. In contrast, under conditions of ATP hydrolysis, Nas6 obstructs base–CP, but not base–lid, association. Modeling of Nas6 into cryoelectron microscopy structures of the proteasome suggests that Nas6 controls both base–lid affinity and base–CP affinity through steric hindrance; Nas6 clashes with the lid in the ATP-hydrolysis–blocked proteasome, but clashes instead with the CP in the ATP-hydrolysis–competent proteasome. Thus, Nas6 provides a dual mechanism to control assembly at both major interfaces of the proteasome. PMID:28137839

Spin wave scattering and interference in ferromagnetic cross

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

Nanayakkara, Kasuni; Kozhanov, Alexander; Center for Nano Optics, Georgia State University, Atlanta, Georgia 30303

2015-10-28

Magnetostatic spin wave scattering and interference across a CoTaZr ferromagnetic spin wave waveguide cross junction were investigated experimentally and by micromagnetic simulations. It is observed that the phase of the scattered waves is dependent on the wavelength, geometry of the junction, and scattering direction. It is found that destructive and constructive interference of the spin waves generates switching characteristics modulated by the input phase of the spin waves. Micromagnetic simulations are used to analyze experimental data and simulate the spin wave scattering and interference.

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

PubMed Central

Krobath, Heinrich; Chan, Hue Sun

2016-01-01

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. PMID:27253392

Modeling of optical mirror and electromechanical behavior

NASA Astrophysics Data System (ADS)

Wang, Fang; Lu, Chao; Liu, Zishun; Liu, Ai Q.; Zhang, Xu M.

2001-10-01

This paper presents finite element (FE) simulation and theoretical analysis of novel MEMS fiber-optical switches actuated by electrostatic attraction. FE simulation for the switches under static and dynamic loading are first carried out to reveal the mechanical characteristics of the minimum or critical switching voltages, the natural frequencies, mode shapes and response under different levels of electrostatic attraction load. To validate the FE simulation results, a theoretical (or analytical) model is then developed for one specific switch, i.e., Plate_40_104. Good agreement is found between the FE simulation and the analytical results. From both FE simulation and theoretical analysis, the critical switching voltage for Plate_40_104 is derived to be 238 V for the switching angel of 12 degree(s). The critical switching on and off times are 431 microsecond(s) and 67 microsecond(s) , respectively. The present study not only develops good FE and analytical models, but also demonstrates step by step a method to simplify a real optical switch structure with reference to the FE simulation results for analytical purpose. With the FE and analytical models, it is easy to obtain any information about the mechanical behaviors of the optical switches, which are helpful in yielding optimized design.

Inherent conformational flexibility of F1-ATPase α-subunit.

PubMed

Hahn-Herrera, Otto; Salcedo, Guillermo; Barril, Xavier; García-Hernández, Enrique

2016-09-01

The core of F1-ATPase consists of three catalytic (β) and three noncatalytic (α) subunits, forming a hexameric ring in alternating positions. A wealth of experimental and theoretical data has provided a detailed picture of the complex role played by catalytic subunits. Although major conformational changes have only been seen in β-subunits, it is clear that α-subunits have to respond to these changes in order to be able to transmit information during the rotary mechanism. However, the conformational behavior of α-subunits has not been explored in detail. Here, we have combined unbiased molecular dynamics (MD) simulations and calorimetrically measured thermodynamic signatures to investigate the conformational flexibility of isolated α-subunits, as a step toward deepening our understanding of its function inside the α3β3 ring. The simulations indicate that the open-to-closed conformational transition of the α-subunit is essentially barrierless, which is ideal to accompany and transmit the movement of the catalytic subunits. Calorimetric measurements of the recombinant α-subunit from Geobacillus kaustophilus indicate that the isolated subunit undergoes no significant conformational changes upon nucleotide binding. Simulations confirm that the nucleotide-free and nucleotide-bound subunits show average conformations similar to that observed in the F1 crystal structure, but they reveal an increased conformational flexibility of the isolated α-subunit upon MgATP binding, which might explain the evolutionary conserved capacity of α-subunits to recognize nucleotides with considerable strength. Furthermore, we elucidate the different dependencies that α- and β-subunits show on Mg(II) for recognizing ATP. Copyright © 2016 Elsevier B.V. All rights reserved.

Persistent random walk of cells involving anomalous effects and random death

NASA Astrophysics Data System (ADS)

Fedotov, Sergei; Tan, Abby; Zubarev, Andrey

2015-04-01

The purpose of this paper is to implement a random death process into a persistent random walk model which produces sub-ballistic superdiffusion (Lévy walk). We develop a stochastic two-velocity jump model of cell motility for which the switching rate depends upon the time which the cell has spent moving in one direction. It is assumed that the switching rate is a decreasing function of residence (running) time. This assumption leads to the power law for the velocity switching time distribution. This describes the anomalous persistence of cell motility: the longer the cell moves in one direction, the smaller the switching probability to another direction becomes. We derive master equations for the cell densities with the generalized switching terms involving the tempered fractional material derivatives. We show that the random death of cells has an important implication for the transport process through tempering of the superdiffusive process. In the long-time limit we write stationary master equations in terms of exponentially truncated fractional derivatives in which the rate of death plays the role of tempering of a Lévy jump distribution. We find the upper and lower bounds for the stationary profiles corresponding to the ballistic transport and diffusion with the death-rate-dependent diffusion coefficient. Monte Carlo simulations confirm these bounds.

Aspect-ratio dependence of magnetization reversal in cylindrical ferromagnetic nanowires

NASA Astrophysics Data System (ADS)

Sultan, Musaab S.; Atkinson, Del

2016-05-01

The magnetization reversal behavior in isolated cylindrical and square cross-section Ni81Fe19 nanowires was systematically studied as a function of nanowire cross-section dimensions from 10 up to 200 nm using micromagnetic simulations. This approach provides access to the switching field, remanence ratio and most significantly the magnetization structures during reversal, which allows the evolution of magnetization processes to be studied with scaling of the cross-sectional dimensions. The dimensional trends in reversal behavior for both square and circular cross-section were comparable throughout the range of dimensions studied. The thinnest nanowires showed simple square switching and 100% remanence. With increasing diameter the switching field reduces and above 40 nm the reversal behavior shows an increasing rotational component prior to sharp switching of the magnetization. The magnitude of the reversible component increases with increasing dimensions up to 150 nm, above which the magnetization reversal process is more complicated and the hysteresis loops are no longer bistable. The micromagnetic structures evolve from simple uniform parallel single domain states in the thinnest wires through the formation of vortex-like end states in thicker wires to complex multidomain structures during the reversal of the thickest wires. In the later cases the reversal is not simple curling-like behavior, although the angular switching field dependence was comparable with curling.

LMI-based adaptive reliable H∞ static output feedback control against switched actuator failures

NASA Astrophysics Data System (ADS)

An, Liwei; Zhai, Ding; Dong, Jiuxiang; Zhang, Qingling

2017-08-01

This paper investigates the H∞ static output feedback (SOF) control problem for switched linear system under arbitrary switching, where the actuator failure models are considered to depend on switching signal. An active reliable control scheme is developed by combination of linear matrix inequality (LMI) method and adaptive mechanism. First, by exploiting variable substitution and Finsler's lemma, new LMI conditions are given for designing the SOF controller. Compared to the existing results, the proposed design conditions are more relaxed and can be applied to a wider class of no-fault linear systems. Then a novel adaptive mechanism is established, where the inverses of switched failure scaling factors are estimated online to accommodate the effects of actuator failure on systems. Two main difficulties arise: first is how to design the switched adaptive laws to prevent the missing of estimating information due to switching; second is how to construct a common Lyapunov function based on a switched estimate error term. It is shown that the new method can give less conservative results than that for the traditional control design with fixed gain matrices. Finally, simulation results on the HiMAT aircraft are given to show the effectiveness of the proposed approaches.

Nonlinear performance of asymmetric coupler based on dual-core photonic crystal fiber: Towards sub-nanojoule solitonic ultrafast all-optical switching

NASA Astrophysics Data System (ADS)

Curilla, L.; Astrauskas, I.; Pugzlys, A.; Stajanca, P.; Pysz, D.; Uherek, F.; Baltuska, A.; Bugar, I.

2018-05-01

We demonstrate ultrafast soliton-based nonlinear balancing of dual-core asymmetry in highly nonlinear photonic crystal fiber at sub-nanojoule pulse energy level. The effect of fiber asymmetry was studied experimentally by selective excitation and monitoring of individual fiber cores at different wavelengths between 1500 nm and 1800 nm. Higher energy transfer rate to non-excited core was observed in the case of fast core excitation due to nonlinear asymmetry balancing of temporal solitons, which was confirmed by the dedicated numerical simulations based on the coupled generalized nonlinear Schrödinger equations. Moreover, the simulation results correspond qualitatively with the experimentally acquired dependences of the output dual-core extinction ratio on excitation energy and wavelength. In the case of 1800 nm fast core excitation, narrow band spectral intensity switching between the output channels was registered with contrast of 23 dB. The switching was achieved by the change of the excitation pulse energy in sub-nanojoule region. The performed detailed analysis of the nonlinear balancing of dual-core asymmetry in solitonic propagation regime opens new perspectives for the development of ultrafast nonlinear all-optical switching devices.

Dual-bridge LLC-SRC with extended voltage range for deeply depleted PEV battery charging

NASA Astrophysics Data System (ADS)

Shahzad, M. Imran; Iqbal, Shahid; Taib, Soib

2017-11-01

This paper proposes a dual-bridge LLC series resonant converter with hybrid-rectifier for achieving extended charging voltage range of 50-420 V for on-board battery charger of plug-in electric vehicle for normal and deeply depleted battery charging. Depending upon the configuration of primary switching network and secondary rectifier, the proposed topology has three operating modes as half-bridge with bridge rectifier (HBBR), full-bridge with bridge rectifier (FBBR) and full-bridge with voltage doubler (FBVD). HBBR, FBBR and FBVD operating modes of converter achieve 50-125, 125-250 and 250-420 V voltage ranges, respectively. For voltage above 62 V, the converter operates below resonance frequency zero voltage switching region with narrow switching frequency range for soft commutation of secondary diodes and low turn-off current of MOSFETs to reduce switching losses. The proposed converter is simulated using MATLAB Simulink and a 1.5 kW laboratory prototype is also built to validate the operation of proposed topology. Simulation and experimental results show that the converter meets all the charging requirements for deeply depleted to fully charged battery using constant current-constant voltage charging method with fixed 400 V DC input and achieves 96.22% peak efficiency.

Sharp switches between regular and swinger mitochondrial replication: 16S rDNA systematically exchanging nucleotides A<->T+C<->G in the mitogenome of Kamimuria wangi.

PubMed

Seligmann, Hervé

2016-07-01

Swinger DNAs are sequences whose homology with known sequences is detected only by assuming systematic exchanges between nucleotides. Nine symmetric (X<->Y, i.e. A<->C) and fourteen asymmetric (X->Y->Z, i.e. A->C->G) exchanges exist. All swinger DNA previously detected in GenBank follow the A<->T+C<->G exchange, while mitochondrial swinger RNAs distribute among different swinger types. Here different alignment criteria detect 87 additional swinger mitochondrial DNAs (86 from insects), including the first swinger gene embedded within a complete genome, corresponding to the mitochondrial 16S rDNA of the stonefly Kamimuria wangi. Other Kamimuria mt genome regions are "regular", stressing unanswered questions on (a) swinger polymerization regulation; (b) swinger 16S rDNA functions; and (c) specificity to rDNA, in particular 16S rDNA. Sharp switches between regular and swinger replication, together with previous observations on swinger transcription, suggest that swinger replication might be due to a switch in polymerization mode of regular polymerases and the possibility of swinger-encoded information, predicted in primordial genes such as rDNA.

Phosphorylation decelerates conformational dynamics in bacterial translation elongation factors

PubMed Central

Talavera, Ariel; Hendrix, Jelle; Versées, Wim; Jurėnas, Dukas; Van Nerom, Katleen; Vandenberk, Niels; Singh, Ranjan Kumar; Konijnenberg, Albert; De Gieter, Steven; Castro-Roa, Daniel; Barth, Anders; De Greve, Henri; Sobott, Frank; Hofkens, Johan; Zenkin, Nikolay; Loris, Remy; Garcia-Pino, Abel

2018-01-01

Bacterial protein synthesis is intricately connected to metabolic rate. One of the ways in which bacteria respond to environmental stress is through posttranslational modifications of translation factors. Translation elongation factor Tu (EF-Tu) is methylated and phosphorylated in response to nutrient starvation upon entering stationary phase, and its phosphorylation is a crucial step in the pathway toward sporulation. We analyze how phosphorylation leads to inactivation of Escherichia coli EF-Tu. We provide structural and biophysical evidence that phosphorylation of EF-Tu at T382 acts as an efficient switch that turns off protein synthesis by decoupling nucleotide binding from the EF-Tu conformational cycle. Direct modifications of the EF-Tu switch I region or modifications in other regions stabilizing the β-hairpin state of switch I result in an effective allosteric trap that restricts the normal dynamics of EF-Tu and enables the evasion of the control exerted by nucleotides on G proteins. These results highlight stabilization of a phosphorylation-induced conformational trap as an essential mechanism for phosphoregulation of bacterial translation and metabolism. We propose that this mechanism may lead to the multisite phosphorylation state observed during dormancy and stationary phase. PMID:29546243

Stability analysis of switched cellular neural networks: A mode-dependent average dwell time approach.

PubMed

Huang, Chuangxia; Cao, Jie; Cao, Jinde

2016-10-01

This paper addresses the exponential stability of switched cellular neural networks by using the mode-dependent average dwell time (MDADT) approach. This method is quite different from the traditional average dwell time (ADT) method in permitting each subsystem to have its own average dwell time. Detailed investigations have been carried out for two cases. One is that all subsystems are stable and the other is that stable subsystems coexist with unstable subsystems. By employing Lyapunov functionals, linear matrix inequalities (LMIs), Jessen-type inequality, Wirtinger-based inequality, reciprocally convex approach, we derived some novel and less conservative conditions on exponential stability of the networks. Comparing to ADT, the proposed MDADT show that the minimal dwell time of each subsystem is smaller and the switched system stabilizes faster. The obtained results extend and improve some existing ones. Moreover, the validness and effectiveness of these results are demonstrated through numerical simulations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cavity length dependence of mode beating in passively Q-switched Nd-solid state lasers

NASA Astrophysics Data System (ADS)

Zameroski, Nathan D.; Wanke, Michael; Bossert, David

2013-03-01

The temporal intensity profile of pulse(s) from passively Q-switched and passively Q-switched mode locked (QSML) solid-state lasers is known to be dependent on cavity length. In this work, the pulse width, modulation depth, and beat frequencies of a Nd:Cr:GSGG laser using a Cr+4:YAG passive Q-switch are investigated as function cavity length. Measured temporal widths are linearly correlated with cavity length but generally 3-5 ns larger than theoretical predictions. Some cavity lengths exhibit pulse profiles with no modulation while other lengths exhibit complete amplitude modulation. The observed beat frequencies at certain cavity lengths cannot be accounted for with passively QSML models in which the pulse train repetition rate is τRT-1, τRT= round-trip time. They can be explained, however, by including coupled cavity mode-locking effects. A theoretical model developed for a two section coupled cavity semiconductor laser is adapted to a solid-state laser to interpret measured beat frequencies. We also numerically evaluate the temporal criterion required to achieve temporally smooth Q-switched pulses, versus cavity length and pump rate. We show that in flash lamp pumped systems, the difference in buildup time between longitudinal modes is largely dependent on the pump rate. In applications where short pulse delay is important, the pumping rate may limit the ability to achieve temporally smooth pulses in passively Q-switched lasers. Simulations support trends in experimental data. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

Effects of fundamentals acquisition and strategy switch on stock price dynamics

NASA Astrophysics Data System (ADS)

Wu, Songtao; He, Jianmin; Li, Shouwei

2018-02-01

An agent-based artificial stock market is developed to simulate trading behavior of investors. In the market, acquisition and employment of information about fundamentals and strategy switch are investigated to explain stock price dynamics. Investors could obtain the information from both market and neighbors resided on their social networks. Depending on information status and performances of different strategies, an informed investor may switch to the strategy of fundamentalist. This in turn affects the information acquisition process, since fundamentalists are more inclined to search and spread the information than chartists. Further investigation into price dynamics generated from three typical networks, i.e. regular lattice, small-world network and random graph, are conducted after general relation between network structures and price dynamics is revealed. In each network, integrated effects of different combinations of information efficiency and switch intensity are investigated. Results have shown that, along with increasing switch intensity, market and social information efficiency play different roles in the formation of price distortion, standard deviation and kurtosis of returns.

Possible repetitive pulse operation of diode-pumped alkali laser (DPAL)

NASA Astrophysics Data System (ADS)

Endo, Masamori

2017-01-01

A theoretical study has been conducted for investigating the possibility of a diode-pumped alkali laser (DPAL) operating in repetitive pulsed mode. A one-dimensional, time-dependent rate-equation simulation of a Cs DPAL was developed to calculate the dynamic behavior of the active medium when Q-switching or cavity dumping was applied. The simulation modeled our small-scale experimental apparatus. In the continuous-wave (CW) mode, the calculated output power was in good agreement with the experimental value. Q-switching was shown to be ineffective because of the short spontaneous lifetime of the active medium, on the order of 10 ns. On the other hand, cavity dumping was proven to be effective. In typical operational conditions, a 54 times increase in peak power with respect to the CW power was predicted.

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

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

Lu, Jia; Harrison, Rane A.; Li, Lianbo

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 basismore » 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.« less

A High-Throughput Assay for Rho Guanine Nucleotide Exchange Factors Based on the Transcreener GDP Assay.

PubMed

Reichman, Melvin; Schabdach, Amanda; Kumar, Meera; Zielinski, Tom; Donover, Preston S; Laury-Kleintop, Lisa D; Lowery, Robert G

2015-12-01

Ras homologous (Rho) family GTPases act as molecular switches controlling cell growth, movement, and gene expression by cycling between inactive guanosine diphosphate (GDP)- and active guanosine triphosphate (GTP)-bound conformations. Guanine nucleotide exchange factors (GEFs) positively regulate Rho GTPases by accelerating GDP dissociation to allow formation of the active, GTP-bound complex. Rho proteins are directly involved in cancer pathways, especially cell migration and invasion, and inhibiting GEFs holds potential as a therapeutic strategy to diminish Rho-dependent oncogenesis. Methods for measuring GEF activity suitable for high-throughput screening (HTS) are limited. We developed a simple, generic biochemical assay method for measuring GEF activity based on the fact that GDP dissociation is generally the rate-limiting step in the Rho GTPase catalytic cycle, and thus addition of a GEF causes an increase in steady-state GTPase activity. We used the Transcreener GDP Assay, which relies on selective immunodetection of GDP, to measure the GEF-dependent stimulation of steady-state GTP hydrolysis by small GTPases using Dbs (Dbl's big sister) as a GEF for Cdc42, RhoA, and RhoB. The assay is well suited for HTS, with a homogenous format and far red fluorescence polarization (FP) readout, and it should be broadly applicable to diverse Rho GEF/GTPase pairs. © 2015 Society for Laboratory Automation and Screening.

Molecular Mechanism of Processive 3' to 5' RNA Translocation in the Active Subunit of the RNA Exosome Complex.

PubMed

Vuković, Lela; Chipot, Christophe; Makino, Debora L; Conti, Elena; Schulten, Klaus

2016-03-30

Recent experimental studies revealed structural details of 3' to 5' degradation of RNA molecules, performed by the exosome complex. ssRNA is channeled through its multisubunit ring-like core into the active site tunnel of its key exonuclease subunit Rrp44, which acts both as an enzyme and a motor. Even in isolation, Rrp44 can pull and sequentially cleave RNA nucleotides, one at a time, without any external energy input and release a final 3-5 nucleotide long product. Using molecular dynamics simulations, we identify the main factors that control these processes. Our free energy calculations reveal that RNA transfer from solution into the active site of Rrp44 is highly favorable, but dependent on the length of the RNA strand. While RNA strands formed by 5 nucleotides or more correspond to a decreasing free energy along the translocation coordinate toward the cleavage site, a 4-nucleotide RNA experiences a free energy barrier along the same direction, potentially leading to incomplete cleavage of ssRNA and the release of short (3-5) nucleotide products. We provide new insight into how Rrp44 catalyzes a localized enzymatic reaction and performs an action distributed over several RNA nucleotides, leading eventually to the translocation of whole RNA segments into the position suitable for cleavage.

A novel dimerization interface of cyclic nucleotide binding domain, which is disrupted in presence of cAMP: implications for CNG channels gating.

PubMed

Gushchin, Ivan Y; Gordeliy, Valentin I; Grudinin, Sergei

2012-09-01

Cyclic nucleotide binding domain (CNBD) is a ubiquitous domain of effector proteins involved in signalling cascades of prokaryota and eukaryota. CNBD activation by cyclic nucleotide monophosphate (cNMP) is studied well in the case of several proteins. However, this knowledge is hardly applicable to cNMP-modulated cation channels. Despite the availability of CNBD crystal structures of bacterial cyclic nucleotide-gated (CNG) and mammalian hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels in presence and absence of the cNMP, the full understanding of CNBD conformational changes during activation is lacking. Here, we describe a novel CNBD dimerization interface found in crystal structures of bacterial CNG channel MlotiK1 and mammalian cAMP-activated guanine nucleotide-exchange factor Epac2. Molecular dynamics simulations show that the found interface is stable on the studied timescale of 100 ns, in contrast to the dimerization interface, reported previously. Comparisons with cN-bound structures of CNBD show that the dimerization is incompatible with cAMP binding. Thus, the cAMP-dependent monomerization of CNBD may be an alternative mechanism of the cAMP sensing. Based on these findings, we propose a model of the bacterial CNG channel modulation by cAMP.

High Ripples Reduction in DTC of Induction Motor by Using a New Reduced Switching Table

NASA Astrophysics Data System (ADS)

Mokhtari, Bachir; Benkhoris, Mohamed F.

2016-05-01

The direct torque and flux control (DTC) of electrical motors is characterized by ripples of torque and flux. Among the many solutions proposed to reduce them is to use modified switching tables which is very advantageous; because its implementation is easy and requires no additional cost compared to other solutions. This paper proposes a new reduced switching table (RST) to improve the DTC by reducing harmful ripples of torque and flux. This new switching table is smaller than the conventional one (CST) and depends principally at the flux error. This solution is studied by simulation under Matlab/Simulink and experimentally validated on a testbed with DSPACE1103. The results obtained of a DTC with RST applied to a three-phase induction motor (IM) show a good improvement and an effectiveness of proposed solution, the torque ripple decreases about 47% and 3% for the stator flux compared with a basic DTC.

Magneto-hydrodynamic modeling of gas discharge switches

NASA Astrophysics Data System (ADS)

Doiphode, P.; Sakthivel, N.; Sarkar, P.; Chaturvedi, S.

2002-12-01

We have performed one-dimensional, time-dependent magneto-hydrodynamic modeling of fast gas-discharge switches. The model has been applied to both high- and low-pressure switches, involving a cylindrical argon-filled cavity. It is assumed that the discharge is initiated in a small channel near the axis of the cylinder. Joule heating in this channel rapidly raises its temperature and pressure. This drives a radial shock wave that heats and ionizes the surrounding low-temperature region, resulting in progressive expansion of the current channel. Our model is able to reproduce this expansion. However, significant difference of detail is observed, as compared with a simple model reported in the literature. In this paper, we present details of our simulations, a comparison with results from the simple model, and a physical interpretation for these differences. This is a first step towards development of a detailed 2-D model for such switches.

A fully electric field driven scalable magnetoelectric switching element

NASA Astrophysics Data System (ADS)

Ahmed, R.; Victora, R. H.

2018-04-01

A technique for micromagnetic simulation of the magnetoelectric (ME) effect in Cr2O3 based structures has been developed. It has been observed that the microscopic ME susceptibility differs significantly from the experimentally measured values. The deviation between the two susceptibilities becomes more prominent near the Curie temperature, affecting the operation of the device at room temperature. A fully electric field controlled ME switching element has been proposed for use at technologically interesting densities: it employs quantum mechanical exchange at the boundaries instead of the applied magnetic field needed in traditional switching schemes. After establishing temperature dependent physics-based parameters, switching performances have been studied for different temperatures, applied electric fields, and Cr2O3 cross-sections. It has been found that our proposed use of quantum mechanical exchange favors reduced electric field operation and enhanced scalability while retaining reliable thermal stability.

A novel adaptive switching function on fault tolerable sliding mode control for uncertain stochastic systems.

PubMed

Zahiripour, Seyed Ali; Jalali, Ali Akbar

2014-09-01

A novel switching function based on an optimization strategy for the sliding mode control (SMC) method has been provided for uncertain stochastic systems subject to actuator degradation such that the closed-loop system is globally asymptotically stable with probability one. In the previous researches the focus on sliding surface has been on proportional or proportional-integral function of states. In this research, from a degree of freedom that depends on designer choice is used to meet certain objectives. In the design of the switching function, there is a parameter which the designer can regulate for specified objectives. A sliding-mode controller is synthesized to ensure the reachability of the specified switching surface, despite actuator degradation and uncertainties. Finally, the simulation results demonstrate the effectiveness of the proposed method. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

Evolutionary prisoner's dilemma games on the network with punishment and opportunistic partner switching

NASA Astrophysics Data System (ADS)

Takesue, H.

2018-02-01

Punishment and partner switching are two well-studied mechanisms that support the evolution of cooperation. Observation of human behaviour suggests that the extent to which punishment is adopted depends on the usage of alternative mechanisms, including partner switching. In this study, we investigate the combined effect of punishment and partner switching in evolutionary prisoner's dilemma games conducted on a network. In the model, agents are located on the network and participate in the prisoner's dilemma games with punishment. In addition, they can opportunistically switch interaction partners to improve their payoff. Our Monte Carlo simulation showed that a large frequency of punishers is required to suppress defectors when the frequency of partner switching is low. In contrast, cooperation is the most abundant strategy when the frequency of partner switching is high regardless of the strength of punishment. Interestingly, cooperators become abundant not because they avoid the cost of inflicting punishment and earn a larger average payoff per game but rather because they have more numerous opportunities to be referred to as a role agent by defectors. Our results imply that the fluidity of social relationships has a profound effect on the adopted strategy in maintaining cooperation.

Simulation study of a new inverse-pinch high Coulomb transfer switch

NASA Technical Reports Server (NTRS)

Choi, S. H.

1984-01-01

A simulation study of a simplified model of a high coulomb transfer switch is performed. The switch operates in an inverse pinch geometry formed by an all metal chamber, which greatly reduces hot spot formations on the electrode surfaces. Advantages of the switch over the conventional switches are longer useful life, higher current capability and lower inductance, which improves the characteristics required for a high repetition rate switch. The simulation determines the design parameters by analytical computations and comparison with the experimentally measured risetime, current handling capability, electrode damage, and hold-off voltages. The parameters of initial switch design can be determined for the anticipated switch performance. Results are in agreement with the experiment results. Although the model is simplified, the switch characteristics such as risetime, current handling capability, electrode damages, and hold-off voltages are accurately determined.

GDP-bound and nucleotide-free intermediates of the guanine nucleotide exchange in the Rab5·Vps9 system.

PubMed

Uejima, Tamami; Ihara, Kentaro; Goh, Tatsuaki; Ito, Emi; Sunada, Mariko; Ueda, Takashi; Nakano, Akihiko; Wakatsuki, Soichi

2010-11-19

Many GTPases regulate intracellular transport and signaling in eukaryotes. Guanine nucleotide exchange factors (GEFs) activate GTPases by catalyzing the exchange of their GDP for GTP. Here we present crystallographic and biochemical studies of a GEF reaction with four crystal structures of Arabidopsis thaliana ARA7, a plant homolog of Rab5 GTPase, in complex with its GEF, VPS9a, in the nucleotide-free and GDP-bound forms, as well as a complex with aminophosphonic acid-guanylate ester and ARA7·VPS9a(D185N) with GDP. Upon complex formation with ARA7, VPS9 wedges into the interswitch region of ARA7, inhibiting the coordination of Mg(2+) and decreasing the stability of GDP binding. The aspartate finger of VPS9a recognizes GDP β-phosphate directly and pulls the P-loop lysine of ARA7 away from GDP β-phosphate toward switch II to further destabilize GDP for its release during the transition from the GDP-bound to nucleotide-free intermediates in the nucleotide exchange reaction.

Time dependent and temperature dependent properties of the forward voltage characteristic of InGaN high power LEDs

NASA Astrophysics Data System (ADS)

Fulmek, P. L.; Haumer, P.; Wenzl, F. P.; Nemitz, W.; Nicolics, J.

2017-03-01

Estimating the junction temperature and its dynamic behavior in dependence of various operating conditions is an important issue, since these properties influence the optical characteristics as well as the aging processes of a light-emitting diode (LED). Particularly for high-power LEDs and pulsed operation, the dynamic behavior and the resulting thermal cycles are of interest. The forward voltage method relies on the existence of a time-independent unique triple of forward-voltage, forward-current, and junction temperature. These three figures should as well uniquely define the optical output power and spectrum, as well as the loss power of the LED, which is responsible for an increase of the junction temperature. From transient FEM-simulations one may expect an increase of the temperature of the active semiconductor layer of some 1/10 K within the first 10 μs. Most of the well-established techniques for junction temperature measurement via forward voltage method evaluate the measurement data several dozens of microseconds after switching on or switching off and estimate the junction temperature by extrapolation towards the time of switching. In contrast, the authors developed a measurement procedure with the focus on the first microseconds after switching. Besides a fast data acquisition system, a precise control of the switching process is required, i.e. a precisely defined current pulse amplitude with fast rise-time and negligible transient by-effects. We start with a short description of the measurement setup and the newly developed control algorithm for the generation of short current pulses. The thermal characterization of the LED chip during the measurement procedures is accomplished by an IR thermography system and transient finite element simulations. The same experimental setup is used to investigate the optical properties of the LED in an Ulbricht-sphere. Our experiments are performed on InGaN LED chips mounted on an Al based insulated metal substrate (IMS), giving a comprehensive picture of the transient behavior of the forward voltage of this type of high power LED.

Nanomechanical Optical Fiber with Embedded Electrodes Actuated by Joule Heating.

PubMed

Lian, Zhenggang; Segura, Martha; Podoliak, Nina; Feng, Xian; White, Nicholas; Horak, Peter

2014-07-31

Nanomechanical optical fibers with metal electrodes embedded in the jacket were fabricated by a multi-material co-draw technique. At the center of the fibers, two glass cores suspended by thin membranes and surrounded by air form a directional coupler that is highly temperature-dependent. We demonstrate optical switching between the two fiber cores by Joule heating of the electrodes with as little as 0.4 W electrical power, thereby demonstrating an electrically actuated all-fiber microelectromechanical system (MEMS). Simulations show that the main mechanism for optical switching is the transverse thermal expansion of the fiber structure.

Stem-Loop V of Varkud Satellite RNA Exhibits Characteristics of the Mg2+ Bound Structure in the Presence of Monovalent Ions

PubMed Central

2015-01-01

The Varkud Satellite RNA contains a self-cleaving ribozyme that has been shown to function independently of its surroundings. This 160 nucleotide ribozyme adopts a catalytically active tertiary structure that includes a kissing hairpin complex formed by stem-loop I and stem-loop V (SLV). The five-nucleotide 5′-rUGACU loop of the isolated SLV has been shown to adopt a Mg2+-dependent U-turn structure by solution NMR. This U-turn hairpin is examined here by molecular dynamics simulations in the presence of monovalent and divalent ions. Simulations confirm on an all-atom level the hypotheses for the role of the Mg2+ ions in stabilizing the loop, as well as the role of the solvent exposed U700 base. Additionally, these simulations suggest the Mg2+-free stem-loop adopts a wide range of structures, including energetically favorable structures similar to the Mg2+-bound loop structure. We propose this structure is a “gatekeeper” or precursor to Mg2+ binding when those ions are present. PMID:26328924

Detection of single-nucleotide polymorphisms using an ON-OFF switching of regenerated biosensor based on a locked nucleic acid-integrated and toehold-mediated strand displacement reaction.

PubMed

Gao, Zhong Feng; Ling, Yu; Lu, Lu; Chen, Ning Yu; Luo, Hong Qun; Li, Nian Bing

2014-03-04

Although various strategies have been reported for single-nucleotide polymorphisms (SNPs) detection, development of a time-saving, specific, and regenerated electrochemical sensing platform still remains a realistic goal. In this study, an ON-OFF switching of a regenerated biosensor based on a locked nucleic acid (LNA)-integrated and toehold-mediated strand displacement reaction technique is constructed for detection of SNPs. The LNA-integrated and methylene blue-labeled capture probe with an external toehold is designed to switch on the sensing system. The mutant-type DNA probe completes complementary with the capture probe to trigger the strand displacement reaction, which switches off the sensing system. However, when the single-base mismatched wild-type DNA probe is presented, the strand displacement reaction cannot be achieved; therefore, the sensing system still keeps the ON state. This DNA sensor is stable over five reuses. We further testify that the LNA-integrated sequence has better recognition ability for SNPs detection compared to the DNA-integrated sequence. Moreover, this DNA senor exhibits a remarkable discrimination capability of SNPs among abundant wild-type targets and 6000-fold (m/m) excess of genomic DNA. In addition, it is selective enough in complex and contaminant-ridden samples, such as human urine, soil, saliva, and beer. Overall, these results demonstrate that this reliable DNA sensor is easy to be fabricated, simple to operate, and stable enough to be readily regenerated.

Switch-on fluorescent/FRET probes to study human histidine triad nucleotide binding protein 1 (hHint1), a novel target for opioid tolerance and neuropathic pain.

PubMed

Shah, Rachit; Zhou, Andrew; Wagner, Carston R

2017-12-13

Histidine Triad Nucleotide Binding Protein 1 (Hint1) has emerged to be an important post-synaptic protein associated with a variety of central nervous system disorders such as pain, addiction, and schizophrenia. Recently, inhibition of histidine nucleotide binding protein 1 (Hint1) with a small nucleoside inhibitor has shown promise as a new therapeutic strategy for the treatment of neuropathic pain. Herein, we describe the first rationally designed small molecule switch-on probes with dual fluorescence and FRET properties to study Hint1. Two non-natural fluorescent nucleosides with a fluorescent lifetime of 20 and 25 ns were each coupled through a linker to the indole ring, i.e. probes 7 and 8. Both probes were found to be water soluble and quenched intramolecularly via photoinduced electron transfer (PET) resulting in minimal background fluorescence. Upon incubating with Hint1, compound 7 and 8 exhibited a 40- and 16-fold increase in the fluorescence intensity compared to the control. Compounds 7 and 8 bind Hint1 with a dissociation constant of 0.121 ± 0.02 and 2.2 ± 0.36 μM, respectively. We demonstrate that probe 8 exhibits a switch-on FRET property with an active site tryptophan residue (W123). We show the utility of probes in performing quantitative ligand displacement studies, as well as in selective detection of Hint1 in the cell lysates. These probes should be useful for studying the dynamics of the active site, as well as for the development of fluorescence lifetime based high throughput screening assay to identify novel inhibitors for Hint1 in future.

The small G-protein MglA connects to the MreB actin cytoskeleton at bacterial focal adhesions.

PubMed

Treuner-Lange, Anke; Macia, Eric; Guzzo, Mathilde; Hot, Edina; Faure, Laura M; Jakobczak, Beata; Espinosa, Leon; Alcor, Damien; Ducret, Adrien; Keilberg, Daniela; Castaing, Jean Philippe; Lacas Gervais, Sandra; Franco, Michel; Søgaard-Andersen, Lotte; Mignot, Tâm

2015-07-20

In Myxococcus xanthus the gliding motility machinery is assembled at the leading cell pole to form focal adhesions, translocated rearward to propel the cell, and disassembled at the lagging pole. We show that MglA, a Ras-like small G-protein, is an integral part of this machinery. In this function, MglA stimulates the assembly of the motility complex by directly connecting it to the MreB actin cytoskeleton. Because the nucleotide state of MglA is regulated spatially and MglA only binds MreB in the guanosine triphosphate-bound form, the motility complexes are assembled at the leading pole and dispersed at the lagging pole where the guanosine triphosphatase activating protein MglB disrupts the MglA-MreB interaction. Thus, MglA acts as a nucleotide-dependent molecular switch to regulate the motility machinery spatially. The function of MreB in motility is independent of its function in peptidoglycan synthesis, representing a coopted function. Our findings highlight a new function for the MreB cytoskeleton and suggest that G-protein-cytoskeleton interactions are a universally conserved feature. © 2015 Treuner-Lange et al.

The small G-protein MglA connects to the MreB actin cytoskeleton at bacterial focal adhesions

PubMed Central

Treuner-Lange, Anke; Macia, Eric; Guzzo, Mathilde; Hot, Edina; Faure, Laura M.; Jakobczak, Beata; Espinosa, Leon; Alcor, Damien; Ducret, Adrien; Keilberg, Daniela; Castaing, Jean Philippe; Lacas Gervais, Sandra; Franco, Michel

2015-01-01

In Myxococcus xanthus the gliding motility machinery is assembled at the leading cell pole to form focal adhesions, translocated rearward to propel the cell, and disassembled at the lagging pole. We show that MglA, a Ras-like small G-protein, is an integral part of this machinery. In this function, MglA stimulates the assembly of the motility complex by directly connecting it to the MreB actin cytoskeleton. Because the nucleotide state of MglA is regulated spatially and MglA only binds MreB in the guanosine triphosphate–bound form, the motility complexes are assembled at the leading pole and dispersed at the lagging pole where the guanosine triphosphatase activating protein MglB disrupts the MglA–MreB interaction. Thus, MglA acts as a nucleotide-dependent molecular switch to regulate the motility machinery spatially. The function of MreB in motility is independent of its function in peptidoglycan synthesis, representing a coopted function. Our findings highlight a new function for the MreB cytoskeleton and suggest that G-protein–cytoskeleton interactions are a universally conserved feature. PMID:26169353

Blast-induced phenotypic switching in cerebral vasospasm

PubMed Central

Alford, Patrick W.; Dabiri, Borna E.; Goss, Josue A.; Hemphill, Matthew A.; Brigham, Mark D.; Parker, Kevin Kit

2011-01-01

Vasospasm of the cerebrovasculature is a common manifestation of blast-induced traumatic brain injury (bTBI) reported among combat casualties in the conflicts in Afghanistan and Iraq. Cerebral vasospasm occurs more frequently, and with earlier onset, in bTBI patients than in patients with other TBI injury modes, such as blunt force trauma. Though vasospasm is usually associated with the presence of subarachnoid hemorrhage (SAH), SAH is not required for vasospasm in bTBI, which suggests that the unique mechanics of blast injury could potentiate vasospasm onset, accounting for the increased incidence. Here, using theoretical and in vitro models, we show that a single rapid mechanical insult can induce vascular hypercontractility and remodeling, indicative of vasospasm initiation. We employed high-velocity stretching of engineered arterial lamellae to simulate the mechanical forces of a blast pulse on the vasculature. An hour after a simulated blast, injured tissues displayed altered intracellular calcium dynamics leading to hypersensitivity to contractile stimulus with endothelin-1. One day after simulated blast, tissues exhibited blast force dependent prolonged hypercontraction and vascular smooth muscle phenotype switching, indicative of remodeling. These results suggest that an acute, blast-like injury is sufficient to induce a hypercontraction-induced genetic switch that potentiates vascular remodeling, and cerebral vasospasm, in bTBI patients. PMID:21765001

An Approach to Average Modeling and Simulation of Switch-Mode Systems

ERIC Educational Resources Information Center

Abramovitz, A.

2011-01-01

This paper suggests a pedagogical approach to teaching the subject of average modeling of PWM switch-mode power electronics systems through simulation by general-purpose electronic circuit simulators. The paper discusses the derivation of PSPICE/ORCAD-compatible average models of the switch-mode power stages, their software implementation, and…

Carbon Nanotube Switches for Communication and Memory Applications

NASA Technical Reports Server (NTRS)

Kaul, Anupama B.; Epp, Larry; Wong, Eric W.; Kowalczyk, Robert

2008-01-01

Lateral CNT Switches: a) dc CNT switches were demonstrated to operate at low voltages, low powers and high speeds. b) RF simulations of switch in series configuration with metallized tube yielded good RF performance 1) Isolation simulated to be approx. 20 dB at 100 GHz. 2) Insertion loss simulated to be < 0.5 dB at 100 GHz. Vertical CNT Switches: a) Thermal CVD was used to mechanically constrain tubes in nanopockets; tubes not self-supporting. b) Demonstrated growth of vertically aligned arrays and single-few MWNTs using dc PECVD with Ni catalyst using optical lithography.

The SAMHD1 dNTP Triphosphohydrolase Is Controlled by a Redox Switch.

PubMed

Mauney, Christopher H; Rogers, LeAnn C; Harris, Reuben S; Daniel, Larry W; Devarie-Baez, Nelmi O; Wu, Hanzhi; Furdui, Cristina M; Poole, Leslie B; Perrino, Fred W; Hollis, Thomas

2017-12-01

Proliferative signaling involves reversible posttranslational oxidation of proteins. However, relatively few molecular targets of these modifications have been identified. We investigate the role of protein oxidation in regulation of SAMHD1 catalysis. Here we report that SAMHD1 is a major target for redox regulation of nucleotide metabolism and cell cycle control. SAMHD1 is a triphosphate hydrolase, whose function involves regulation of deoxynucleotide triphosphate pools. We demonstrate that the redox state of SAMHD1 regulates its catalytic activity. We have identified three cysteine residues that constitute an intrachain disulfide bond "redox switch" that reversibly inhibits protein tetramerization and catalysis. We show that proliferative signals lead to SAMHD1 oxidation in cells and oxidized SAMHD1 is localized outside of the nucleus. Innovation and Conclusions: SAMHD1 catalytic activity is reversibly regulated by protein oxidation. These data identify a previously unknown mechanism for regulation of nucleotide metabolism by SAMHD1. Antioxid. Redox Signal. 27, 1317-1331.

A novel variant of DNA polymerase ζ, Rev3ΔC, highlights differential regulation of Pol32 as a subunit of polymerase δ versus ζ in Saccharomyces cerevisiae

PubMed Central

Siebler, Hollie M.; Lada, Artem G.; Baranovskiy, Andrey G.; Tahirov, Tahir H.; Pavlov, Youri I.

2014-01-01

Unrepaired DNA lesions often stall replicative DNA polymerases and are bypassed by translesion synthesis (TLS) to prevent replication fork collapse. Mechanisms of TLS are lesion- and species-specific, with a prominent role of specialized DNA polymerases with relaxed active sites. After nucleotide(s) are incorporated across from the altered base(s), the aberrant primer termini are typically extended by DNA polymerase ζ (pol ζ). As a result, pol ζ is responsible for most DNA damage-induced mutations. The mechanisms of sequential DNA polymerase switches in vivo remain unclear. The major replicative DNA polymerase δ (pol δ) shares two accessory subunits, called Pol31/Pol32 in yeast, with pol ζ. Inclusion of Pol31/Pol32 in the pol δ/pol ζ holoenzymes requires a [4Fe–4S] cluster in C-termini of the catalytic subunits. Disruption of this cluster in Pol ζ or deletion of POL32 attenuates induced mutagenesis. Here we describe a novel mutation affecting the catalytic subunit of pol ζ, rev3ΔC, which provides insight into the regulation of pol switches. Strains with Rev3ΔC, lacking the entire C-terminal domain and therefore the platform for Pol31/Pol32 binding, are partially proficient in Pol32-dependent UV-induced mutagenesis. This suggests an additional role of Pol32 in TLS, beyond being a pol ζ subunit, related to pol δ. In search for members of this regulatory pathway, we examined the effects of Maintenance of Genome Stability 1 (Mgs1) protein on mutagenesis in the absence of Rev3–Pol31/Pol32 interaction. Mgs1 may compete with Pol32 for binding to PCNA. Mgs1 overproduction suppresses induced mutagenesis, but had no effect on UV-mutagenesis in the rev3ΔC strain, suggesting that Mgs1 exerts its inhibitory effect by acting specifically on Pol32 bound to pol ζ. The evidence for differential regulation of Pol32 in pol δ and pol ζ emphasizes the complexity of polymerase switches. PMID:24819597

Comparative Analysis of the Flax Immune Receptors L6 and L7 Suggests an Equilibrium-Based Switch Activation Model

PubMed Central

Chen, Chunhong; Newell, Kim; Lawrence, Gregory J.; Ellis, Jeffrey G.; Anderson, Peter A.; Dodds, Peter N.

2016-01-01

NOD-like receptors (NLRs) are central components of the plant immune system. L6 is a Toll/interleukin-1 receptor (TIR) domain-containing NLR from flax (Linum usitatissimum) conferring immunity to the flax rust fungus. Comparison of L6 to the weaker allele L7 identified two polymorphic regions in the TIR and the nucleotide binding (NB) domains that regulate both effector ligand-dependent and -independent cell death signaling as well as nucleotide binding to the receptor. This suggests that a negative functional interaction between the TIR and NB domains holds L7 in an inactive/ADP-bound state more tightly than L6, hence decreasing its capacity to adopt the active/ATP-bound state and explaining its weaker activity in planta. L6 and L7 variants with a more stable ADP-bound state failed to bind to AvrL567 in yeast two-hybrid assays, while binding was detected to the signaling active variants. This contrasts with current models predicting that effectors bind to inactive receptors to trigger activation. Based on the correlation between nucleotide binding, effector interaction, and immune signaling properties of L6/L7 variants, we propose that NLRs exist in an equilibrium between ON and OFF states and that effector binding to the ON state stabilizes this conformation, thereby shifting the equilibrium toward the active form of the receptor to trigger defense signaling. PMID:26744216

NMR Structural Profiling of Transcriptional Intermediates Reveals Riboswitch Regulation by Metastable RNA Conformations.

PubMed

Helmling, Christina; Wacker, Anna; Wolfinger, Michael T; Hofacker, Ivo L; Hengesbach, Martin; Fürtig, Boris; Schwalbe, Harald

2017-02-22

Gene repression induced by the formation of transcriptional terminators represents a prime example for the coupling of RNA synthesis, folding, and regulation. In this context, mapping the changes in available conformational space of transcription intermediates during RNA synthesis is important to understand riboswitch function. A majority of riboswitches, an important class of small metabolite-sensing regulatory RNAs, act as transcriptional regulators, but the dependence of ligand binding and the subsequent allosteric conformational switch on mRNA transcript length has not yet been investigated. We show a strict fine-tuning of binding and sequence-dependent alterations of conformational space by structural analysis of all relevant transcription intermediates at single-nucleotide resolution for the I-A type 2'dG-sensing riboswitch from Mesoplasma florum by NMR spectroscopy. Our results provide a general framework to dissect the coupling of synthesis and folding essential for riboswitch function, revealing the importance of metastable states for RNA-based gene regulation.

The multifaceted influence of histone deacetylases on DNA damage signalling and DNA repair

PubMed Central

Roos, Wynand Paul; Krumm, Andrea

2016-01-01

Histone/protein deacetylases play multiple roles in regulating gene expression and protein activation and stability. Their deregulation during cancer initiation and progression cause resistance to therapy. Here, we review the role of histone deacetylases (HDACs) and the NAD+ dependent sirtuins (SIRTs) in the DNA damage response (DDR). These lysine deacetylases contribute to DNA repair by base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), non-homologous end joining (NHEJ), homologous recombination (HR) and interstrand crosslink (ICL) repair. Furthermore, we discuss possible mechanisms whereby these histone/protein deacetylases facilitate the switch between DNA double-strand break (DSB) repair pathways, how SIRTs play a central role in the crosstalk between DNA repair and cell death pathways due to their dependence on NAD+, and the influence of small molecule HDAC inhibitors (HDACi) on cancer cell resistance to genotoxin based therapies. Throughout the review, we endeavor to identify the specific HDAC targeted by HDACi leading to therapy sensitization. PMID:27738139

GDP-to-GTP exchange on the microtubule end can contribute to the frequency of catastrophe.

PubMed

Piedra, Felipe-Andrés; Kim, Tae; Garza, Emily S; Geyer, Elisabeth A; Burns, Alexander; Ye, Xuecheng; Rice, Luke M

2016-11-07

Microtubules are dynamic polymers of αβ-tubulin that have essential roles in chromosome segregation and organization of the cytoplasm. Catastrophe-the switch from growing to shrinking-occurs when a microtubule loses its stabilizing GTP cap. Recent evidence indicates that the nucleotide on the microtubule end controls how tightly an incoming subunit will be bound (trans-acting GTP), but most current models do not incorporate this information. We implemented trans-acting GTP into a computational model for microtubule dynamics. In simulations, growing microtubules often exposed terminal GDP-bound subunits without undergoing catastrophe. Transient GDP exposure on the growing plus end slowed elongation by reducing the number of favorable binding sites on the microtubule end. Slower elongation led to erosion of the GTP cap and an increase in the frequency of catastrophe. Allowing GDP-to-GTP exchange on terminal subunits in simulations mitigated these effects. Using mutant αβ-tubulin or modified GTP, we showed experimentally that a more readily exchangeable nucleotide led to less frequent catastrophe. Current models for microtubule dynamics do not account for GDP-to-GTP exchange on the growing microtubule end, so our findings provide a new way of thinking about the molecular events that initiate catastrophe. © 2016 Piedra et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Role of DNA conformation & energetic insights in Msx-1-DNA recognition as revealed by molecular dynamics studies on specific and nonspecific complexes.

PubMed

Kachhap, Sangita; Singh, Balvinder

2015-01-01

In most of homeodomain-DNA complexes, glutamine or lysine is present at 50th position and interacts with 5th and 6th nucleotide of core recognition region. Molecular dynamics simulations of Msx-1-DNA complex (Q50-TG) and its variant complexes, that is specific (Q50K-CC), nonspecific (Q50-CC) having mutation in DNA and (Q50K-TG) in protein, have been carried out. Analysis of protein-DNA interactions and structure of DNA in specific and nonspecific complexes show that amino acid residues use sequence-dependent shape of DNA to interact. The binding free energies of all four complexes were analysed to define role of amino acid residue at 50th position in terms of binding strength considering the variation in DNA on stability of protein-DNA complexes. The order of stability of protein-DNA complexes shows that specific complexes are more stable than nonspecific ones. Decomposition analysis shows that N-terminal amino acid residues have been found to contribute maximally in binding free energy of protein-DNA complexes. Among specific protein-DNA complexes, K50 contributes more as compared to Q50 towards binding free energy in respective complexes. The sequence dependence of local conformation of DNA enables Q50/Q50K to make hydrogen bond with nucleotide(s) of DNA. The changes in amino acid sequence of protein are accommodated and stabilized around TAAT core region of DNA having variation in nucleotides.

Magnetization switching process in a torus nanoring with easy-plane surface anisotropy

NASA Astrophysics Data System (ADS)

Alzate-Cardona, J. D.; Sabogal-Suárez, D.; Restrepo-Parra, E.

2017-11-01

We have studied the effects of surface shape anisotropy in the magnetization behavior of a torus nanoring by means of Monte Carlo simulations. Stable states (vortex and reverse vortex states) and metastable states (onion and asymmetric onion states) were found in the torus nanoring. The probability of occurrence of the metastable states (stable states) tends to decrease (increase) as the amount of Monte Carlo steps per spin, temperature steps and negative values of the anisotropy constant increase. We evaluated under which conditions it is possible to switch the magnetic state of the torus nanoring from a vortex to a reverse vortex state by applying a circular magnetic field at certain temperature interval. The switching probability (from a vortex to a reverse vortex state) depends on the value of the current intensity, which generates the circular magnetic field, and the temperature interval where the magnetic field is applied. There is a linear relationship between the current intensity and the minimum temperature interval above which the vortex state can be switched.

Detection of isotype switch rearrangement in bulk culture by PCR.

PubMed

Max, E E; Mills, F C; Chu, C

2001-05-01

When a B lymphocyte changes from synthesizing IgM to synthesizing IgG, IgA, or IgE, this isotype switch is generally accompanied by a unique DNA rearrangement. The protocols in this unit describe two polymerase chain reaction (PCR)-based strategies for detecting switch rearrangements in bulk culture. The first involves direct PCR across the switch junctions, providing the opportunity for characterizing the recombination products by nucleotide sequence analysis; however, because of characteristics inherent to the PCR methodology this strategy cannot easily be used as a quantitative assay for recombination. A support protocol details the preparation of the 5' Su PCR probe for this protocol. The second basic protocol describes a method known as digestion-circularization PCR (DCPCR) that is more amenable to quantitation but yields no information on structure of the recombination products. Both techniques should be capable of detecting reciprocal deletion circles as well as functional recombination products remaining on the expressed chromosome.

Optical properties of new wide heterogeneous waveguides with thermo optical shifters.

PubMed

De Leonardis, Francesco; Tsarev, Andrei V; Passaro, Vittorio M

2008-12-22

We present analysis and simulation of novel silicon-on-insulator (SOI) heterogeneous waveguides with thermo-optic phase shifters. New structure design contains a p-n junction on both sides of SOI ridge waveguide with 220 nm x 35 microm silicon core. Strongly mode-dependent optical losses (by additional free charge absorption) provide quasi-singe-mode behavior of wide waveguide with mode size approximately 10 microm. Local heater produces an efficient phase shifting by small temperature increase (DeltaT approximately 2K), switching power (< 40 mW) and switching time (< 10 micros). Mode optical losses are significantly decreased at high heating (DeltaT approximately 120 K).

Generalized Stoner-Wohlfarth model accurately describing the switching processes in pseudo-single ferromagnetic particles

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

Cimpoesu, Dorin, E-mail: cdorin@uaic.ro; Stoleriu, Laurentiu; Stancu, Alexandru

2013-12-14

We propose a generalized Stoner-Wohlfarth (SW) type model to describe various experimentally observed angular dependencies of the switching field in non-single-domain magnetic particles. Because the nonuniform magnetic states are generally characterized by complicated spin configurations with no simple analytical description, we maintain the macrospin hypothesis and we phenomenologically include the effects of nonuniformities only in the anisotropy energy, preserving as much as possible the elegance of SW model, the concept of critical curve and its geometric interpretation. We compare the results obtained with our model with full micromagnetic simulations in order to evaluate the performance and limits of our approach.

Robust pre-specified time synchronization of chaotic systems by employing time-varying switching surfaces in the sliding mode control scheme

NASA Astrophysics Data System (ADS)

Khanzadeh, Alireza; Pourgholi, Mahdi

2016-08-01

In the conventional chaos synchronization methods, the time at which two chaotic systems are synchronized, is usually unknown and depends on initial conditions. In this work based on Lyapunov stability theory a sliding mode controller with time-varying switching surfaces is proposed to achieve chaos synchronization at a pre-specified time for the first time. The proposed controller is able to synchronize chaotic systems precisely at any time when we want. Moreover, by choosing the time-varying switching surfaces in a way that the reaching phase is eliminated, the synchronization becomes robust to uncertainties and exogenous disturbances. Simulation results are presented to show the effectiveness of the proposed method of stabilizing and synchronizing chaotic systems with complete robustness to uncertainty and disturbances exactly at a pre-specified time.

Global tracking for a class of uncertain nonlinear systems with unknown sign-switching control direction by output feedback

NASA Astrophysics Data System (ADS)

Roux Oliveira, Tiago; Jacoud Peixoto, Alessandro; Hsu, Liu

2015-09-01

This paper addresses the design of a sliding mode controller for a class of high-order uncertain nonlinear plants with unmatched state-dependent nonlinearities and unknown sign of the high frequency gain, i.e., the control direction is assumed unknown. Differently from most previous studies, the control direction is allowed to switch its sign. We show that it is possible to obtain global exact tracking using only output-feedback by coupling a relay periodic switching function with a norm state observer. One significant advantage of the new scheme is its robustness and improved transient response under arbitrary changes of the control direction which have been theoretically demonstrated for jump variations and successfully tested by simulations. The proposed controller is also evaluated with a DC motor control experiment.

Modelling of creep hysteresis in ferroelectrics

NASA Astrophysics Data System (ADS)

He, Xuan; Wang, Dan; Wang, Linxiang; Melnik, Roderick

2018-05-01

In the current paper, a macroscopic model is proposed to simulate the hysteretic dynamics of ferroelectric ceramics with creep phenomenon incorporated. The creep phenomenon in the hysteretic dynamics is attributed to the rate-dependent characteristic of the polarisation switching processes induced in the materials. A non-convex Helmholtz free energy based on Landau theory is proposed to model the switching dynamics. The governing equation of single-crystal model is formulated by applying the Euler-Lagrange equation. The polycrystalline model is obtained by combining the single crystal dynamics with a density function which is constructed to model the weighted contributions of different grains with different principle axis orientations. In addition, numerical simulations of hysteretic dynamics with creep phenomenon are presented. Comparison of the numerical results and their experimental counterparts is also presented. It is shown that the creep phenomenon is captured precisely, validating the capability of the proposed model in a range of its potential applications.

Modeling of Solid State Transformer for the FREEDM System Demonstration

NASA Astrophysics Data System (ADS)

Jiang, Youyuan

The Solid State Transformer (SST) is an essential component in the FREEDM system. This research focuses on the modeling of the SST and the controller hardware in the loop (CHIL) implementation of the SST for the support of the FREEDM system demonstration. The energy based control strategy for a three-stage SST is analyzed and applied. A simplified average model of the three-stage SST that is suitable for simulation in real time digital simulator (RTDS) has been developed in this study. The model is also useful for general time-domain power system analysis and simulation. The proposed simplified av-erage model has been validated in MATLAB and PLECS. The accuracy of the model has been verified through comparison with the cycle-by-cycle average (CCA) model and de-tailed switching model. These models are also implemented in PSCAD, and a special strategy to implement the phase shift modulation has been proposed to enable the switching model simulation in PSCAD. The implementation of the CHIL test environment of the SST in RTDS is described in this report. The parameter setup of the model has been discussed in detail. One of the dif-ficulties is the choice of the damping factor, which is revealed in this paper. Also the grounding of the system has large impact on the RTDS simulation. Another problem is that the performance of the system is highly dependent on the switch parameters such as voltage and current ratings. Finally, the functionalities of the SST have been realized on the platform. The distributed energy storage interface power injection and reverse power flow have been validated. Some limitations are noticed and discussed through the simulation on RTDS.

Current induced incoherent magnetization dynamics in ferromagnetic/non-magnetic metallic multilayer nanowires

NASA Astrophysics Data System (ADS)

Al-Rashid, Md Mamun; Maqableh, Mazin; Stadler, Bethanie; Atulasimha, Jayasimha

High density arrays of electrodeposited nanowires consisting of ferromagnetic/non-magnetic (Co/Cu) multilayers are promising as magnetic memory devices. For individual nanowires containing multiple (Co/Cu) bilayers, the stable magnetization orientations of the Co layers (with respect to each other and the nanowire axis) are dependent on the Cu layer thickness, even when the Co layer dimensions are fixed. This dependence is a result of the competition between shape anisotropy, magneto-crystalline anisotropy and intra-wire dipole coupling. However, when the nanowires are closely packed in arrays, inter-wire dipole coupling can result in complex and tunable domain structures comprising segments of multiple nanowires. This work explores the dependence of these domain structures and their switching on the non-magnetic layer thickness and intra-wire spacing both experimentally and via rigorous micromagnetic simulation. These domain structures play a crucial role in determining the current and time required for STT switching. NSF CAREER Grant CCF-1253370.

Lipid-Loving ANTs: Molecular Simulations of Cardiolipin Interactions and the Organization of the Adenine Nucleotide Translocase in Model Mitochondrial Membranes.

PubMed

Hedger, George; Rouse, Sarah L; Domański, Jan; Chavent, Matthieu; Koldsø, Heidi; Sansom, Mark S P

2016-11-15

The exchange of ADP and ATP across the inner mitochondrial membrane is a fundamental cellular process. This exchange is facilitated by the adenine nucleotide translocase, the structure and function of which are critically dependent on the signature phospholipid of mitochondria, cardiolipin (CL). Here we employ multiscale molecular dynamics simulations to investigate CL interactions within a membrane environment. Using simulations at both coarse-grained and atomistic resolutions, we identify three CL binding sites on the translocase, in agreement with those seen in crystal structures and inferred from nuclear magnetic resonance measurements. Characterization of the free energy landscape for lateral lipid interaction via potential of mean force calculations demonstrates the strength of interaction compared to those of binding sites on other mitochondrial membrane proteins, as well as their selectivity for CL over other phospholipids. Extending the analysis to other members of the family, yeast Aac2p and mouse uncoupling protein 2, suggests a degree of conservation. Simulation of large patches of a model mitochondrial membrane containing multiple copies of the translocase shows that CL interactions persist in the presence of protein-protein interactions and suggests CL may mediate interactions between translocases. This study provides a key example of how computational microscopy may be used to shed light on regulatory lipid-protein interactions.

Single molecules can operate as primitive biological sensors, switches and oscillators.

PubMed

Hernansaiz-Ballesteros, Rosa D; Cardelli, Luca; Csikász-Nagy, Attila

2018-06-18

Switch-like and oscillatory dynamical systems are widely observed in biology. We investigate the simplest biological switch that is composed of a single molecule that can be autocatalytically converted between two opposing activity forms. We test how this simple network can keep its switching behaviour under perturbations in the system. We show that this molecule can work as a robust bistable system, even for alterations in the reactions that drive the switching between various conformations. We propose that this single molecule system could work as a primitive biological sensor and show by steady state analysis of a mathematical model of the system that it could switch between possible states for changes in environmental signals. Particularly, we show that a single molecule phosphorylation-dephosphorylation switch could work as a nucleotide or energy sensor. We also notice that a given set of reductions in the reaction network can lead to the emergence of oscillatory behaviour. We propose that evolution could have converted this switch into a single molecule oscillator, which could have been used as a primitive timekeeper. We discuss how the structure of the simplest known circadian clock regulatory system, found in cyanobacteria, resembles the proposed single molecule oscillator. Besides, we speculate if such minimal systems could have existed in an RNA world.

Inner surface flash-over of insulator of low-inductance high-voltage self-breakdown gas switch and its application

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

Zhang, Hong-bo, E-mail: walkman67@163.com; Liu, Jin-liang

2014-04-15

In this paper, the inner surface flash-over of high-voltage self-breakdown switch, which is used as a main switch of pulse modulator, is analyzed in theory by employing the method of distributed element equivalent circuit. Moreover, the field distortion of the switch is simulated by using software. The results of theoretical analysis and simulation by software show that the inner surface flash-over usually starts at the junction points among the stainless steel, insulator, and insulation gas in the switch. A switch with improved structure is designed and fabricated according to the theoretical analysis and simulation results. Several methods to avoid innermore » surface flash-over are used to improve the structure of switch. In experiment, the inductance of the switch is no more than 100 nH, the working voltage of the switch is about 600 kV, and the output voltage and current of the accelerator is about 500 kV and 50 kA, respectively. And the zero-to-peak rise time of output voltage at matched load is less than 30 ns due to the small inductance of switch. The original switch was broken-down after dozens of experiments, and the improved switch has been worked more than 200 times stably.« less

Analysis and Design of a Novel W-band SPST Switch by Employing Full-Wave EM Simulator

NASA Astrophysics Data System (ADS)

Xu, Zhengbin; Guo, Jian; Qian, Cheng; Dou, Wenbin

2011-12-01

In this paper, a W-band single pole single throw (SPST) switch based on a novel PIN diode model is presented. The PIN diode is modeled using a full-wave electromagnetic (EM) simulator and its parasitic parameters under both forward and reverse bias states are described by a T-network. By this approach, the measurement-based model, which is usually a must for high performance switch design, is no longer necessary. A compensation structure is optimized to obtain a high isolation of the switch. Accordingly, a W-band SPST switch is designed using a full wave EM simulator. Measurement results agree very well with simulated ones. Our measurements show that the developed switch has less than 1.5 dB insertion loss under the `on' state from 88 GHz to 98 GHz. Isolation greater than 30 dB over 2 GHz bandwidth and greater than 20 dB over 5 GHz bandwidth can be achieved at the center frequency of 94 GHz under the `off' state.

Quantum Point Contact Single-Nucleotide Conductance for DNA and RNA Sequence Identification.

PubMed

Afsari, Sepideh; Korshoj, Lee E; Abel, Gary R; Khan, Sajida; Chatterjee, Anushree; Nagpal, Prashant

2017-11-28

Several nanoscale electronic methods have been proposed for high-throughput single-molecule nucleic acid sequence identification. While many studies display a large ensemble of measurements as "electronic fingerprints" with some promise for distinguishing the DNA and RNA nucleobases (adenine, guanine, cytosine, thymine, and uracil), important metrics such as accuracy and confidence of base calling fall well below the current genomic methods. Issues such as unreliable metal-molecule junction formation, variation of nucleotide conformations, insufficient differences between the molecular orbitals responsible for single-nucleotide conduction, and lack of rigorous base calling algorithms lead to overlapping nanoelectronic measurements and poor nucleotide discrimination, especially at low coverage on single molecules. Here, we demonstrate a technique for reproducible conductance measurements on conformation-constrained single nucleotides and an advanced algorithmic approach for distinguishing the nucleobases. Our quantum point contact single-nucleotide conductance sequencing (QPICS) method uses combed and electrostatically bound single DNA and RNA nucleotides on a self-assembled monolayer of cysteamine molecules. We demonstrate that by varying the applied bias and pH conditions, molecular conductance can be switched ON and OFF, leading to reversible nucleotide perturbation for electronic recognition (NPER). We utilize NPER as a method to achieve >99.7% accuracy for DNA and RNA base calling at low molecular coverage (∼12×) using unbiased single measurements on DNA/RNA nucleotides, which represents a significant advance compared to existing sequencing methods. These results demonstrate the potential for utilizing simple surface modifications and existing biochemical moieties in individual nucleobases for a reliable, direct, single-molecule, nanoelectronic DNA and RNA nucleotide identification method for sequencing.

The C2'- and C3'-endo equilibrium for AMP molecules bound in the cystathionine-beta-synthase domain.

PubMed

Feng, Na; Qi, Chao; Hou, Yan-Jie; Zhang, Ying; Wang, Da-Cheng; Li, De-Feng

2018-03-04

The equilibrium between C2'- and C3'-endo conformations of nucleotides in solution, as well as their polymers DNA and RNA, has been well studied in previous work. However, this equilibrium of nucleotides in their binding state remains unclear. We observed two AMP molecules, in C3'- and C2'-endo conformations respectively, simultaneously bound to a cystathionine-beta-synthase (CBS) domain dimer of the magnesium and cobalt efflux protein CorC in the crystallographic study. The C2'-endo AMP molecule assumes the higher sugar pucker energy and one more hydrogen bond with the protein than the C3'-endo molecule does. The balance between the high sugar pucker energy and the low binding energy suggests an equilibrium or switch between C2'- and C3'-endo conformations of the bound nucleotides. Our work challenge the previous hypothesis that the ribose of the bound nucleotides would be locked in a fixed conformation. Copyright © 2018 Elsevier Inc. All rights reserved.

Multiscale contact mechanics model for RF-MEMS switches with quantified uncertainties

NASA Astrophysics Data System (ADS)

Kim, Hojin; Huda Shaik, Nurul; Xu, Xin; Raman, Arvind; Strachan, Alejandro

2013-12-01

We introduce a multiscale model for contact mechanics between rough surfaces and apply it to characterize the force-displacement relationship for a metal-dielectric contact relevant for radio frequency micro-electromechanicl system (MEMS) switches. We propose a mesoscale model to describe the history-dependent force-displacement relationships in terms of the surface roughness, the long-range attractive interaction between the two surfaces, and the repulsive interaction between contacting asperities (including elastic and plastic deformation). The inputs to this model are the experimentally determined surface topography and the Hamaker constant as well as the mechanical response of individual asperities obtained from density functional theory calculations and large-scale molecular dynamics simulations. The model captures non-trivial processes including the hysteresis during loading and unloading due to plastic deformation, yet it is computationally efficient enough to enable extensive uncertainty quantification and sensitivity analysis. We quantify how uncertainties and variability in the input parameters, both experimental and theoretical, affect the force-displacement curves during approach and retraction. In addition, a sensitivity analysis quantifies the relative importance of the various input quantities for the prediction of force-displacement during contact closing and opening. The resulting force-displacement curves with quantified uncertainties can be directly used in device-level simulations of micro-switches and enable the incorporation of atomic and mesoscale phenomena in predictive device-scale simulations.

Relationship Between Frequency and Deflection Angle in the DNA Prism

PubMed Central

Chen, Zhen; Dorfman, Kevin D.

2013-01-01

The DNA prism is a modification of the standard pulsed-field electrophoresis protocol to provide a continuous separation, where the DNA are deflected at an angle that depends on their molecular weight. The standard switchback model for the DNA prism predicts a monotonic increase in the deflection angle as a function of the frequency for switching the field until a plateau regime is reached. However, experiments indicate that the deflection angle achieves a maximum value before decaying to a size-independent value at high frequencies. Using Brownian dynamics simulations, we show that the maximum in the deflection angle is related to the reorientation time for the DNA and the decay in deflection angle at high frequencies is due to inadequate stretching. The generic features of the dependence of the deflection angle on molecular weight, switching frequency, and electric field strength explain a number of experimental phenomena. PMID:23410375

Numerical Simulation of Liquid Metal RF MEMS Switch Based on EWOD

NASA Astrophysics Data System (ADS)

Liu, Tingting; Gao, Yang; Yang, Tao; Guo, Huihui

2018-03-01

Conventional RF MEMS switches rely on metal-to-dielectric or metal-to-metal contacts. Some problems in the “solid-solid” contact, such as contact degradation, signal bounce and poor reliability, can be solved by using “liquid-solid” contact. The RF MEMS switch based on liquid metal is characterized by small contact resistance, no moving parts, high reliability and long life. Using electrowetting-on-dielectric (EWOD) way to control the movement of liquid metal in the RF MEMS switch, to achieve the “on” and “off” of the switch. In this paper, the electrical characteristics and RF characteristics of RF MEMS switches are simulated by fluid mechanics software FLUENT and electromagnetic simulation software HFSS. The effects of driving voltage, switching time, dielectric layer, hydrophobic layer material and thickness, switching channel height on the RF characteristics are studied. The results show that to increase the external voltage to the threshold voltage of 58V, the liquid metal began to move, and the switching time from “off” state to “on” state is 16ms. In the 0~20GHz frequency range, the switch insertion loss is less than 0.28dB, isolation is better than 23.32dB.

A finite element model of rigid body structures actuated by dielectric elastomer actuators

NASA Astrophysics Data System (ADS)

Simone, F.; Linnebach, P.; Rizzello, G.; Seelecke, S.

2018-06-01

This paper presents on finite element (FE) modeling and simulation of dielectric elastomer actuators (DEAs) coupled with articulated structures. DEAs have proven to represent an effective transduction technology for the realization of large deformation, low-power consuming, and fast mechatronic actuators. However, the complex dynamic behavior of the material, characterized by nonlinearities and rate-dependent phenomena, makes it difficult to accurately model and design DEA systems. The problem is further complicated in case the DEA is used to activate articulated structures, which increase both system complexity and implementation effort of numerical simulation models. In this paper, we present a model based tool which allows to effectively implement and simulate complex articulated systems actuated by DEAs. A first prototype of a compact switch actuated by DEA membranes is chosen as reference study to introduce the methodology. The commercially available FE software COMSOL is used for implementing and coupling a physics-based dynamic model of the DEA with the external structure, i.e., the switch. The model is then experimentally calibrated and validated in both quasi-static and dynamic loading conditions. Finally, preliminary results on how to use the simulation tool to optimize the design are presented.

SPMHD simulations of structure formation

NASA Astrophysics Data System (ADS)

Barnes, David J.; On, Alvina Y. L.; Wu, Kinwah; Kawata, Daisuke

2018-05-01

The intracluster medium of galaxy clusters is permeated by μ {G} magnetic fields. Observations with current and future facilities have the potential to illuminate the role of these magnetic fields play in the astrophysical processes of galaxy clusters. To obtain a greater understanding of how the initial seed fields evolve to the magnetic fields in the intracluster medium requires magnetohydrodynamic simulations. We critically assess the current smoothed particle magnetohydrodynamic (SPMHD) schemes, especially highlighting the impact of a hyperbolic divergence cleaning scheme and artificial resistivity switch on the magnetic field evolution in cosmological simulations of the formation of a galaxy cluster using the N-body/SPMHD code GCMHD++. The impact and performance of the cleaning scheme and two different schemes for the artificial resistivity switch is demonstrated via idealized test cases and cosmological simulations. We demonstrate that the hyperbolic divergence cleaning scheme is effective at suppressing the growth of the numerical divergence error of the magnetic field and should be applied to any SPMHD simulation. Although the artificial resistivity is important in the strong field regime, it can suppress the growth of the magnetic field in the weak field regime, such as galaxy clusters. With sufficient resolution, simulations with divergence cleaning can reproduce observed magnetic fields. We conclude that the cleaning scheme alone is sufficient for galaxy cluster simulations, but our results indicate that the SPMHD scheme must be carefully chosen depending on the regime of the magnetic field.

Electrostatic Switching in Vertically Oriented Nanotubes for Nonvolatile Memory Applications

NASA Technical Reports Server (NTRS)

Kaul, Anupama B.; Khan, Paul; Jennings, Andrew T.; Greer, Julia R.; Megerian, Krikor G.; Allmen, Paul von

2009-01-01

We have demonstrated electrostatic switching in vertically oriented nanotubes or nanofibers, where a nanoprobe was used as the actuating electrode inside an SEM. When the nanoprobe was manipulated to be in close proximity to a single tube, switching voltages between 10 V - 40 V were observed, depending on the geometrical parameters. The turn-on transitions appeared to be much sharper than the turn-off transitions which were limited by the tube-to-probe contact resistances. In many cases, stiction forces at these dimensions were dominant, since the tube appeared stuck to the probe even after the voltage returned to 0 V, suggesting that such structures are promising for nonvolatile memory applications. The stiction effects, to some extent, can be adjusted by engineering the switch geometry appropriately. Nanoscale mechanical measurements were also conducted on the tubes using a custom-built anoindentor inside an SEM, from which preliminary material parameters, such as the elastic modulus, were extracted. The mechanical measurements also revealed that the tubes appear to be well adhered to the substrate. The material parameters gathered from the mechanical measurements were then used in developing an electrostatic model of the switch using a commercially available finite-element simulator. The calculated pull-in voltages appeared to be in agreement to the experimentally obtained switching voltages to first order.

Clustering and Flow Conservation Monitoring Tool for Software Defined Networks.

PubMed

Puente Fernández, Jesús Antonio; García Villalba, Luis Javier; Kim, Tai-Hoon

2018-04-03

Prediction systems present some challenges on two fronts: the relation between video quality and observed session features and on the other hand, dynamics changes on the video quality. Software Defined Networks (SDN) is a new concept of network architecture that provides the separation of control plane (controller) and data plane (switches) in network devices. Due to the existence of the southbound interface, it is possible to deploy monitoring tools to obtain the network status and retrieve a statistics collection. Therefore, achieving the most accurate statistics depends on a strategy of monitoring and information requests of network devices. In this paper, we propose an enhanced algorithm for requesting statistics to measure the traffic flow in SDN networks. Such an algorithm is based on grouping network switches in clusters focusing on their number of ports to apply different monitoring techniques. Such grouping occurs by avoiding monitoring queries in network switches with common characteristics and then, by omitting redundant information. In this way, the present proposal decreases the number of monitoring queries to switches, improving the network traffic and preventing the switching overload. We have tested our optimization in a video streaming simulation using different types of videos. The experiments and comparison with traditional monitoring techniques demonstrate the feasibility of our proposal maintaining similar values decreasing the number of queries to the switches.

Finite-time synchronization of stochastic coupled neural networks subject to Markovian switching and input saturation.

PubMed

Selvaraj, P; Sakthivel, R; Kwon, O M

2018-06-07

This paper addresses the problem of finite-time synchronization of stochastic coupled neural networks (SCNNs) subject to Markovian switching, mixed time delay, and actuator saturation. In addition, coupling strengths of the SCNNs are characterized by mutually independent random variables. By utilizing a simple linear transformation, the problem of stochastic finite-time synchronization of SCNNs is converted into a mean-square finite-time stabilization problem of an error system. By choosing a suitable mode dependent switched Lyapunov-Krasovskii functional, a new set of sufficient conditions is derived to guarantee the finite-time stability of the error system. Subsequently, with the help of anti-windup control scheme, the actuator saturation risks could be mitigated. Moreover, the derived conditions help to optimize estimation of the domain of attraction by enlarging the contractively invariant set. Furthermore, simulations are conducted to exhibit the efficiency of proposed control scheme. Copyright © 2018 Elsevier Ltd. All rights reserved.

Dual-stage periodic event-triggered output-feedback control for linear systems.

PubMed

Ruan, Zhen; Chen, Wu-Hua; Lu, Xiaomei

2018-05-01

This paper proposes an event-triggered control framework, called dual-stage periodic event-triggered control (DSPETC), which unifies periodic event-triggered control (PETC) and switching event-triggered control (SETC). Specifically, two period parameters h 1 and h 2 are introduced to characterize the new event-triggering rule, where h 1 denotes the sampling period, while h 2 denotes the monitoring period. By choosing some specified values of h 2 , the proposed control scheme can reduce to PETC or SETC scheme. In the DSPETC framework, the controlled system is represented as a switched system model and its stability is analyzed via a switching-time-dependent Lyapunov functional. Both the cases with/without network-induced delays are investigated. Simulation and experimental results show that the DSPETC scheme is superior to the PETC scheme and the SETC scheme. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.

Illuminating light-dependent color shifts in core and veneer layers of dental all-ceramics.

PubMed

Lee, Yong-Keun; Cha, Hyun-Suk; Yu, Bin

2014-09-01

The color of an object is perceived differently depending on the ambient light conditions. Since dental all-ceramic restorations are fabricated by building up several layers to reproduce the tooth shade, the optical properties of each layer should be optimized for successful shade reproduction. This study aimed to determine the separate contributions of the color shifts in each of the core and veneer layers of all-ceramics by switching the illuminating lights on the color shifts of layered ceramics. Specimens of seven kinds of core ceramics and the corresponding veneer ceramics for each core were fabricated with a layered thickness of 1.5 mm. A sintering ceramic was used as a reference core material. The Commission Internationale de l’Eclairage (CIE) color coordinates of core, veneer, and layered specimens were measured with a spectroradiometer under the CIE illuminant D65 (daylight), A (incandescent lamp), and F9 (fluorescent lamp) simulating lights. Color shifts of the layered specimens were primarily determined by the CIE a shifts (D65 to A switch) or by the CIE b shifts (D65 to F9 switch) of the veneer layer. The color coordinates shifts in the constituent layers differentially influenced those of the layered specimens by the kind of switched lights. Therefore, the optical properties of the constituent layers of all-ceramics should be controlled to reflect these findings.

Illuminating light-dependent color shifts in core and veneer layers of dental all-ceramics

NASA Astrophysics Data System (ADS)

Lee, Yong-Keun; Cha, Hyun-Suk; Yu, Bin

2014-09-01

The color of an object is perceived differently depending on the ambient light conditions. Since dental all-ceramic restorations are fabricated by building up several layers to reproduce the tooth shade, the optical properties of each layer should be optimized for successful shade reproduction. This study aimed to determine the separate contributions of the color shifts in each of the core and veneer layers of all-ceramics by switching the illuminating lights on the color shifts of layered ceramics. Specimens of seven kinds of core ceramics and the corresponding veneer ceramics for each core were fabricated with a layered thickness of 1.5 mm. A sintering ceramic was used as a reference core material. The Commission Internationale de l'Eclairage (CIE) color coordinates of core, veneer, and layered specimens were measured with a spectroradiometer under the CIE illuminant D65 (daylight), A (incandescent lamp), and F9 (fluorescent lamp) simulating lights. Color shifts of the layered specimens were primarily determined by the CIE a* shifts (D65 to A switch) or by the CIE b* shifts (D65 to F9 switch) of the veneer layer. The color coordinates shifts in the constituent layers differentially influenced those of the layered specimens by the kind of switched lights. Therefore, the optical properties of the constituent layers of all-ceramics should be controlled to reflect these findings.

Stochastic simulation of enzyme-catalyzed reactions with disparate timescales.

PubMed

Barik, Debashis; Paul, Mark R; Baumann, William T; Cao, Yang; Tyson, John J

2008-10-01

Many physiological characteristics of living cells are regulated by protein interaction networks. Because the total numbers of these protein species can be small, molecular noise can have significant effects on the dynamical properties of a regulatory network. Computing these stochastic effects is made difficult by the large timescale separations typical of protein interactions (e.g., complex formation may occur in fractions of a second, whereas catalytic conversions may take minutes). Exact stochastic simulation may be very inefficient under these circumstances, and methods for speeding up the simulation without sacrificing accuracy have been widely studied. We show that the "total quasi-steady-state approximation" for enzyme-catalyzed reactions provides a useful framework for efficient and accurate stochastic simulations. The method is applied to three examples: a simple enzyme-catalyzed reaction where enzyme and substrate have comparable abundances, a Goldbeter-Koshland switch, where a kinase and phosphatase regulate the phosphorylation state of a common substrate, and coupled Goldbeter-Koshland switches that exhibit bistability. Simulations based on the total quasi-steady-state approximation accurately capture the steady-state probability distributions of all components of these reaction networks. In many respects, the approximation also faithfully reproduces time-dependent aspects of the fluctuations. The method is accurate even under conditions of poor timescale separation.

Controlled exciton transfer between quantum dots with acoustic phonons taken into account

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

Golovinski, P. A., E-mail: golovinski@bk.ru

2015-09-15

A system of excitons in two quantum dots coupled by the dipole–dipole interaction is investigated. The excitation transfer process controlled by the optical Stark effect at nonresonant frequencies is considered and the effect of the interaction between excitons and acoustic phonons in a medium on this process is taken into account. The system evolution is described using quantum Heisenberg equations. A truncated set of equations is obtained and the transfer dynamics is numerically simulated. High-efficiency picosecond switching of the excitation transfer by a laser pulse with a rectangular envelope is demonstrated. The dependence of picosecond switching on the quantum-dot parametersmore » and optical-pulse length is presented.« less

New results on anti-synchronization of switched neural networks with time-varying delays and lag signals.

PubMed

Cao, Yuting; Wen, Shiping; Chen, Michael Z Q; Huang, Tingwen; Zeng, Zhigang

2016-09-01

This paper investigates the problem of global exponential anti-synchronization of a class of switched neural networks with time-varying delays and lag signals. Considering the packed circuits, the controller is dependent on the output of the system as the inner states are very hard to measure. Therefore, it is necessary to investigate the controller based on the output of the neuron cell. Through theoretical analysis, it is obvious that the obtained ones improve and generalize the results derived in the previous literature. To illustrate the effectiveness, a simulation example with applications in image encryptions is also presented in the paper. Copyright © 2016 Elsevier Ltd. All rights reserved.

Non-equilibrium transport and spin dynamics in single-molecule magnets

NASA Astrophysics Data System (ADS)

Moldoveanu, V.; Dinu, I. V.; Tanatar, B.

2015-11-01

The time-dependent transport through single-molecule magnets (SMM) coupled to magnetic or non-magnetic electrodes is studied in the framework of the generalized Master equation (GME) method. We calculate the transient currents which develop when the molecule is smoothly coupled to the source and drain electrodes. The signature of the electrically induced magnetic switching on these transient currents is investigated. Our simulations show that the magnetic switching of the molecular spin can be read indirectly from the transient currents if one lead is magnetic and it is much faster if the leads have opposite spin polarizations. We identify effects of the transverse anisotropy on the dynamics of molecular states.

Evaluation of plasma-induced damage and bias temperature instability depending on type of antenna layer using current-starved ring oscillators

NASA Astrophysics Data System (ADS)

Kishida, Ryo; Furuta, Jun; Kobayashi, Kazutoshi

2018-04-01

Plasma-induced damage (PID) and bias temperature instability (BTI) are inevitable reliability issues that degrade the performance of transistors. In this study, PID and BTI, depending on the type of antenna layer, are evaluated in current-starved ring oscillators (ROs) to separate degradations in PMOS and NMOS transistors in a 65 nm silicon-on-insulator (SOI) process. Oscillation frequencies of ROs fluctuate with the performance of MOSFET switches between power/ground rails and virtual power/ground nodes. The initial frequencies of ROs with PMOS switches having antennas on upper layers decrease. However, those with NMOS switches become higher than those without PID because high-k dielectrics are damaged by positive charges. The degradation induced by negative BTI (NBTI) in PMOS is 1.5 times larger than that induced by positive BTI (PBTI) in NMOS. However, both NBTI- and PBTI-induced degradations are the same among different antenna layers. The frequency fluctuation caused by PID is converted to threshold voltage shifts by circuit simulations. Threshold voltages shift by 8.4 and 11% owing to PID in PMOS and NMOS transistors, respectively.

GTP Binding and Oncogenic Mutations May Attenuate Hypervariable Region (HVR)-Catalytic Domain Interactions in Small GTPase K-Ras4B, Exposing the Effector Binding Site*

PubMed Central

Lu, Shaoyong; Banerjee, Avik; Jang, Hyunbum; Zhang, Jian; Gaponenko, Vadim; Nussinov, Ruth

2015-01-01

K-Ras4B, a frequently mutated oncogene in cancer, plays an essential role in cell growth, differentiation, and survival. Its C-terminal membrane-associated hypervariable region (HVR) is required for full biological activity. In the active GTP-bound state, the HVR interacts with acidic plasma membrane (PM) headgroups, whereas the farnesyl anchors in the membrane; in the inactive GDP-bound state, the HVR may interact with both the PM and the catalytic domain at the effector binding region, obstructing signaling and nucleotide exchange. Here, using molecular dynamics simulations and NMR, we aim to figure out the effects of nucleotides (GTP and GDP) and frequent (G12C, G12D, G12V, G13D, and Q61H) and infrequent (E37K and R164Q) oncogenic mutations on full-length K-Ras4B. The mutations are away from or directly at the HVR switch I/effector binding site. Our results suggest that full-length wild-type GDP-bound K-Ras4B (K-Ras4BWT-GDP) is in an intrinsically autoinhibited state via tight HVR-catalytic domain interactions. The looser association in K-Ras4BWT-GTP may release the HVR. Some of the oncogenic mutations weaken the HVR-catalytic domain association in the K-Ras4B-GDP/-GTP bound states, which may facilitate the HVR disassociation in a nucleotide-independent manner, thereby up-regulating oncogenic Ras signaling. Thus, our results suggest that mutations can exert their effects in more than one way, abolishing GTP hydrolysis and facilitating effector binding. PMID:26453300

Switching synchronization in one-dimensional memristive networks

NASA Astrophysics Data System (ADS)

Slipko, Valeriy A.; Shumovskyi, Mykola; Pershin, Yuriy V.

2015-11-01

We report on a switching synchronization phenomenon in one-dimensional memristive networks, which occurs when several memristive systems with different switching constants are switched from the high- to low-resistance state. Our numerical simulations show that such a collective behavior is especially pronounced when the applied voltage slightly exceeds the combined threshold voltage of memristive systems. Moreover, a finite increase in the network switching time is found compared to the average switching time of individual systems. An analytical model is presented to explain our observations. Using this model, we have derived asymptotic expressions for memory resistances at short and long times, which are in excellent agreement with results of our numerical simulations.

Analysis of Duck Hepatitis B Virus Reverse Transcription Indicates a Common Mechanism for the Two Template Switches during Plus-Strand DNA Synthesis

PubMed Central

Havert, Michael B.; Ji, Lin; Loeb, Daniel D.

2002-01-01

The synthesis of the hepadnavirus relaxed circular DNA genome requires two template switches, primer translocation and circularization, during plus-strand DNA synthesis. Repeated sequences serve as donor and acceptor templates for these template switches, with direct repeat 1 (DR1) and DR2 for primer translocation and 5′r and 3′r for circularization. These donor and acceptor sequences are at, or near, the ends of the minus-strand DNA. Analysis of plus-strand DNA synthesis of duck hepatitis B virus (DHBV) has indicated that there are at least three other cis-acting sequences that make contributions during the synthesis of relaxed circular DNA. These sequences, 5E, M, and 3E, are located near the 5′ end, the middle, and the 3′ end of minus-strand DNA, respectively. The mechanism by which these sequences contribute to the synthesis of plus-strand DNA was unclear. Our aim was to better understand the mechanism by which 5E and M act. We localized the DHBV 5E element to a short sequence of approximately 30 nucleotides that is 100 nucleotides 3′ of DR2 on minus-strand DNA. We found that the new 5E mutants were partially defective for primer translocation/utilization at DR2. They were also invariably defective for circularization. In addition, examination of several new DHBV M variants indicated that they too were defective for primer translocation/utilization and circularization. Thus, this analysis indicated that 5E and M play roles in both primer translocation/utilization and circularization. In conjunction with earlier findings that 3E functions in both template switches, our findings indicate that the processes of primer translocation and circularization share a common underlying mechanism. PMID:11861843

The Characteristics of Binary Spike-Time-Dependent Plasticity in HfO2-Based RRAM and Applications for Pattern Recognition

NASA Astrophysics Data System (ADS)

Zhou, Zheng; Liu, Chen; Shen, Wensheng; Dong, Zhen; Chen, Zhe; Huang, Peng; Liu, Lifeng; Liu, Xiaoyan; Kang, Jinfeng

2017-04-01

A binary spike-time-dependent plasticity (STDP) protocol based on one resistive-switching random access memory (RRAM) device was proposed and experimentally demonstrated in the fabricated RRAM array. Based on the STDP protocol, a novel unsupervised online pattern recognition system including RRAM synapses and CMOS neurons is developed. Our simulations show that the system can efficiently compete the handwritten digits recognition task, which indicates the feasibility of using the RRAM-based binary STDP protocol in neuromorphic computing systems to obtain good performance.

Accuracy of MHD simulations: Effects of simulation initialization in GUMICS-4

NASA Astrophysics Data System (ADS)

Lakka, Antti; Pulkkinen, Tuija; Dimmock, Andrew; Osmane, Adnane; Palmroth, Minna; Honkonen, Ilja

2016-04-01

We conducted a study aimed at revealing how different global magnetohydrodynamic (MHD) simulation initialization methods affect the dynamics in different parts of the Earth's magnetosphere-ionosphere system. While such magnetosphere-ionosphere coupling codes have been used for more than two decades, their testing still requires significant work to identify the optimal numerical representation of the physical processes. We used the Grand Unified Magnetosphere-Ionosphere Coupling Simulation (GUMICS-4), the only European global MHD simulation being developed by the Finnish Meteorological Institute. GUMICS-4 was put to a test that included two stages: 1) a 10 day Omni data interval was simulated and the results were validated by comparing both the bow shock and the magnetopause spatial positions predicted by the simulation to actual measurements and 2) the validated 10 day simulation run was used as a reference in a comparison of five 3 + 12 hour (3 hour synthetic initialisation + 12 hour actual simulation) simulation runs. The 12 hour input was not only identical in each simulation case but it also represented a subset of the 10 day input thus enabling quantifying the effects of different synthetic initialisations on the magnetosphere-ionosphere system. The used synthetic initialisation data sets were created using stepwise, linear and sinusoidal functions. Switching the used input from the synthetic to real Omni data was immediate. The results show that the magnetosphere forms in each case within an hour after the switch to real data. However, local dissimilarities are found in the magnetospheric dynamics after formation depending on the used initialisation method. This is evident especially in the inner parts of the lobe.

Design and development of repetitive capacitor charging power supply based on series-parallel resonant converter topology.

PubMed

Patel, Ankur; Nagesh, K V; Kolge, Tanmay; Chakravarthy, D P

2011-04-01

LCL resonant converter based repetitive capacitor charging power supply (CCPS) is designed and developed in the division. The LCL converter acts as a constant current source when switching frequency is equal to the resonant frequency. When both resonant inductors' values of LCL converter are same, it results in inherent zero current switching (ZCS) in switches. In this paper, ac analysis with fundamental frequency approximation of LCL resonant tank circuit, frequency dependent of current gain converter followed by design, development, simulation, and practical result is described. Effect of change in switching frequency and resonant frequency and change in resonant inductors ratio on CCPS will be discussed. An efficient CCPS of average output power of 1.2 kJ/s, output voltage 3 kV, and 300 Hz repetition rate is developed in the division. The performance of this CCPS has been evaluated in the laboratory by charging several values of load capacitance at various repetition rates. These results indicate that this design is very feasible for use in capacitor-charging applications. © 2011 American Institute of Physics

Advanced EMT and Phasor-Domain Hybrid Simulation with Simulation Mode Switching Capability for Transmission and Distribution Systems

DOE PAGES

Huang, Qiuhua; Vittal, Vijay

2018-05-09

Conventional electromagnetic transient (EMT) and phasor-domain hybrid simulation approaches presently exist for trans-mission system level studies. Their simulation efficiency is generally constrained by the EMT simulation. With an increasing number of distributed energy resources and non-conventional loads being installed in distribution systems, it is imperative to extend the hybrid simulation application to include distribution systems and integrated transmission and distribution systems. Meanwhile, it is equally important to improve the simulation efficiency as the modeling scope and complexity of the detailed system in the EMT simulation increases. To meet both requirements, this paper introduces an advanced EMT and phasor-domain hybrid simulationmore » approach. This approach has two main features: 1) a comprehensive phasor-domain modeling framework which supports positive-sequence, three-sequence, three-phase and mixed three-sequence/three-phase representations and 2) a robust and flexible simulation mode switching scheme. The developed scheme enables simulation switching from hybrid simulation mode back to pure phasor-domain dynamic simulation mode to achieve significantly improved simulation efficiency. The proposed method has been tested on integrated transmission and distribution systems. In conclusion, the results show that with the developed simulation switching feature, the total computational time is significantly reduced compared to running the hybrid simulation for the whole simulation period, while maintaining good simulation accuracy.« less

Advanced EMT and Phasor-Domain Hybrid Simulation with Simulation Mode Switching Capability for Transmission and Distribution Systems

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

Huang, Qiuhua; Vittal, Vijay

Conventional electromagnetic transient (EMT) and phasor-domain hybrid simulation approaches presently exist for trans-mission system level studies. Their simulation efficiency is generally constrained by the EMT simulation. With an increasing number of distributed energy resources and non-conventional loads being installed in distribution systems, it is imperative to extend the hybrid simulation application to include distribution systems and integrated transmission and distribution systems. Meanwhile, it is equally important to improve the simulation efficiency as the modeling scope and complexity of the detailed system in the EMT simulation increases. To meet both requirements, this paper introduces an advanced EMT and phasor-domain hybrid simulationmore » approach. This approach has two main features: 1) a comprehensive phasor-domain modeling framework which supports positive-sequence, three-sequence, three-phase and mixed three-sequence/three-phase representations and 2) a robust and flexible simulation mode switching scheme. The developed scheme enables simulation switching from hybrid simulation mode back to pure phasor-domain dynamic simulation mode to achieve significantly improved simulation efficiency. The proposed method has been tested on integrated transmission and distribution systems. In conclusion, the results show that with the developed simulation switching feature, the total computational time is significantly reduced compared to running the hybrid simulation for the whole simulation period, while maintaining good simulation accuracy.« less

Brief Report: Long-Term (96-Week) Efficacy and Safety After Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in HIV-Infected, Virologically Suppressed Adults

PubMed Central

Raffi, François; Orkin, Chloe; Clarke, Amanda; Slama, Laurence; Gallant, Joel; Daar, Eric; Henry, Keith; Santana-Bagur, Jorge; Stein, David K.; Bellos, Nicholaos; Scarsella, Anthony; Yan, Mingjin; Abram, Michael E.; Cheng, Andrew

2017-01-01

Abstract: In a double-blind, phase 3 trial, 663 HIV-infected, virologically suppressed adults were randomized to switch to tenofovir alafenamide (TAF; n = 333) vs. remain on tenofovir disoproxil fumarate (TDF; n = 330), each coformulated with emtricitabine (FTC), while continuing their third agent (boosted protease inhibitor or unboosted third agent). At week 96, 88.6% on FTC/TAF and 89.1% on FTC/TDF had HIV-1 RNA <50 copies per milliliter [adjusted difference −0.5% (95% confidence interval: −5.3 to 4.4%)]. Proteinuria, albuminuria, proximal renal tubular function, and bone mineral density improved after switching to TAF- from TDF-containing regimens. These longer-term data support FTC/TAF as a safe, well-tolerated, and durable nucleotide reverse transcriptase inhibitor backbone. PMID:28272164

A critical switch in the enzymatic properties of the Cid1 protein deciphered from its product-bound crystal structure.

PubMed

Munoz-Tello, Paola; Gabus, Caroline; Thore, Stéphane

2014-03-01

The addition of uridine nucleotide by the poly(U) polymerase (PUP) enzymes has a demonstrated impact on various classes of RNAs such as microRNAs (miRNAs), histone-encoding RNAs and messenger RNAs. Cid1 protein is a member of the PUP family. We solved the crystal structure of Cid1 in complex with non-hydrolyzable UMPNPP and a short dinucleotide compound ApU. These structures revealed new residues involved in substrate/product stabilization. In particular, one of the three catalytic aspartate residues explains the RNA dependence of its PUP activity. Moreover, other residues such as residue N165 or the β-trapdoor are shown to be critical for Cid1 activity. We finally suggest that the length and sequence of Cid1 substrate RNA influence the balance between Cid1's processive and distributive activities. We propose that particular processes regulated by PUPs require the enzymes to switch between the two types of activity as shown for the miRNA biogenesis where PUPs can either promote DICER cleavage via short U-tail or trigger miRNA degradation by adding longer poly(U) tail. The enzymatic properties of these enzymes may be critical for determining their particular function in vivo.

A critical switch in the enzymatic properties of the Cid1 protein deciphered from its product-bound crystal structure

PubMed Central

Munoz-Tello, Paola; Gabus, Caroline; Thore, Stéphane

2014-01-01

The addition of uridine nucleotide by the poly(U) polymerase (PUP) enzymes has a demonstrated impact on various classes of RNAs such as microRNAs (miRNAs), histone-encoding RNAs and messenger RNAs. Cid1 protein is a member of the PUP family. We solved the crystal structure of Cid1 in complex with non-hydrolyzable UMPNPP and a short dinucleotide compound ApU. These structures revealed new residues involved in substrate/product stabilization. In particular, one of the three catalytic aspartate residues explains the RNA dependence of its PUP activity. Moreover, other residues such as residue N165 or the β-trapdoor are shown to be critical for Cid1 activity. We finally suggest that the length and sequence of Cid1 substrate RNA influence the balance between Cid1's processive and distributive activities. We propose that particular processes regulated by PUPs require the enzymes to switch between the two types of activity as shown for the miRNA biogenesis where PUPs can either promote DICER cleavage via short U-tail or trigger miRNA degradation by adding longer poly(U) tail. The enzymatic properties of these enzymes may be critical for determining their particular function in vivo. PMID:24322298

Lipid-Loving ANTs: Molecular Simulations of Cardiolipin Interactions and the Organization of the Adenine Nucleotide Translocase in Model Mitochondrial Membranes

PubMed Central

2016-01-01

The exchange of ADP and ATP across the inner mitochondrial membrane is a fundamental cellular process. This exchange is facilitated by the adenine nucleotide translocase, the structure and function of which are critically dependent on the signature phospholipid of mitochondria, cardiolipin (CL). Here we employ multiscale molecular dynamics simulations to investigate CL interactions within a membrane environment. Using simulations at both coarse-grained and atomistic resolutions, we identify three CL binding sites on the translocase, in agreement with those seen in crystal structures and inferred from nuclear magnetic resonance measurements. Characterization of the free energy landscape for lateral lipid interaction via potential of mean force calculations demonstrates the strength of interaction compared to those of binding sites on other mitochondrial membrane proteins, as well as their selectivity for CL over other phospholipids. Extending the analysis to other members of the family, yeast Aac2p and mouse uncoupling protein 2, suggests a degree of conservation. Simulation of large patches of a model mitochondrial membrane containing multiple copies of the translocase shows that CL interactions persist in the presence of protein–protein interactions and suggests CL may mediate interactions between translocases. This study provides a key example of how computational microscopy may be used to shed light on regulatory lipid–protein interactions. PMID:27786441

Statistical properties of the Jukes-Holmquist method of estimating the number of nucleotide substitutions: reply to Holmquist and Conroy's criticism.

PubMed

Nei, M; Tateno, Y

1981-01-01

Conducting computer simulations, Nei and Tateno (1978) have shown that Jukes and Holmquist's (1972) method of estimating the number of nucleotide substitutions tends to give an overestimate and the estimate obtained has a large variance. Holmquist and Conroy (1980) repeated some parts of our simulation and claim that the overestimation of nucleotide substitutions in our paper occurred mainly because we used selected data. Examination of Holmquist and Conroy's simulation indicates that their results are essentially the same as ours when the Jukes-Holmquist method is used, but since they used a different method of computation their estimates of nucleotide substitutions differed substantially from ours. Another problem in Holmquist and Conroy's Letter is that they confused the expected number of nucleotide substitution with the number in a sample. This confusion has resulted in a number of unnecessary arguments. They also criticized our X2 measure, but this criticism is apparently due to a misunderstanding of the assumptions of our method and a failure to use our method in the way we described. We believe that our earlier conclusions remain unchanged.

Numerical investigation of an all-optical switch in a graded nonlinear plasmonic grating.

PubMed

Wang, Guoxi; Lu, Hua; Liu, Xueming; Gong, Yongkang

2012-11-09

We have proposed and numerically investigated an all-optical switch based on a metal-insulator-metal waveguide with graded nonlinear plasmonic gratings. The influences of grating depth and refractive index of a Kerr nonlinear medium on the transmission of the switch are exactly analyzed by utilizing transmission line theory. The finite-difference time-domain simulation results show that the highly compact structure possesses excellent switch function by tuning the incident electric field intensity. In addition, the simulation results show that this all-optical switch has an ultrawide operating frequency regime and femtosecond-scale response time (~130 fs). Such a switch can find potential applications for all-optical signal processing and optical communication.

Influence of GTP/GDP and magnesium ion on the solvated structure of the protein FtsZ: a molecular dynamics study.

PubMed

Jamous, Carla; Basdevant, Nathalie; Ha-Duong, Tap

2014-01-01

We present here a structural analysis of ten extensive all-atom molecular dynamics simulations of the monomeric protein FtsZ in various binding states. Since the polymerization and GTPase activities of FtsZ depend on the nature of a bound nucleotide as well as on the presence of a magnesium ion, we studied the structural differences between the average conformations of the following five systems: FtsZ-Apo, FtsZ-GTP, FtsZ-GDP, FtsZ-GTP-Mg, and FtsZ-GDP-Mg. The in silico solvated average structure of FtsZ-Apo significantly differs from the crystallographic structure 1W59 of FtsZ which was crystallized in a dimeric form without nucleotide and magnesium. The simulated Apo form of the protein also clearly differs from the FtsZ structures when it is bound to its ligand, the most important discrepancies being located in the loops surrounding the nucleotide binding pocket. The three average structures of FtsZ-GTP, FtsZ-GDP, and FtsZ-GTP-Mg are overall similar, except for the loop T7 located at the opposite side of the binding pocket and whose conformation in FtsZ-GDP notably differs from the one in FtsZ-GTP and FtsZ-GTP-Mg. The presence of a magnesium ion in the binding pocket has no impact on the FtsZ conformation when it is bound to GTP. In contrast, when the protein is bound to GDP, the divalent cation causes a translation of the nucleotide outwards the pocket, inducing a significant conformational change of the loop H6-H7 and the top of helix H7.

(Invited) Comprehensive Assessment of Oxide Memristors As Post-CMOS Memory and Logic Devices

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

Gao, X.; Mamaluy, D.; Cyr, E. C.

As CMOS technology approaches the end of its scaling, oxide-based memristors have become one of the leading candidates for post-CMOS memory and logic devices. In orderTo facilitate the understanding of physical switching mechanisms and accelerate experimental development of memristors, we have developed a three-dimensional fully-coupled electrical and thermal transport model, which captures all the important processes that drive memristive switching and is applicable for simulating a wide range of memristors. Moreover, the model is applied to simulate the RESET and SET switching in a 3D filamentary TaOx memristor. Extensive simulations show that the switching dynamics of the bipolar device ismore » determined by thermally-activated field-dominant processes: with Joule heating, the raised temperature enables the movement of oxygen vacancies, and the field drift dominates the overall motion of vacancies. Simulated current-voltage hysteresis and device resistance profiles as a function of time and voltage during RESET and SET switching show good agreement with experimental measurement.« less

(Invited) Comprehensive Assessment of Oxide Memristors As Post-CMOS Memory and Logic Devices

DOE PAGES

Gao, X.; Mamaluy, D.; Cyr, E. C.; ...

2016-05-10

As CMOS technology approaches the end of its scaling, oxide-based memristors have become one of the leading candidates for post-CMOS memory and logic devices. In orderTo facilitate the understanding of physical switching mechanisms and accelerate experimental development of memristors, we have developed a three-dimensional fully-coupled electrical and thermal transport model, which captures all the important processes that drive memristive switching and is applicable for simulating a wide range of memristors. Moreover, the model is applied to simulate the RESET and SET switching in a 3D filamentary TaOx memristor. Extensive simulations show that the switching dynamics of the bipolar device ismore » determined by thermally-activated field-dominant processes: with Joule heating, the raised temperature enables the movement of oxygen vacancies, and the field drift dominates the overall motion of vacancies. Simulated current-voltage hysteresis and device resistance profiles as a function of time and voltage during RESET and SET switching show good agreement with experimental measurement.« less

The Hsp70 interdomain linker is a dynamic switch that enables allosteric communication between two structured domains.

PubMed

English, Charles A; Sherman, Woody; Meng, Wenli; Gierasch, Lila M

2017-09-08

Hsp70 molecular chaperones play key roles in cellular protein homeostasis by binding to exposed hydrophobic regions of incompletely folded or aggregated proteins. This crucial Hsp70 function relies on allosteric communication between two well-structured domains: an N-terminal nucleotide-binding domain (NBD) and a C-terminal substrate-binding domain (SBD), which are tethered by an interdomain linker. ATP or ADP binding to the NBD alters the substrate-binding affinity of the SBD, triggering functionally essential cycles of substrate binding and release. The interdomain linker is a well-structured participant in the interdomain interface in ATP-bound Hsp70s. By contrast, in the ADP-bound state, exemplified by the Escherichia coli Hsp70 DnaK, the interdomain linker is flexible. Hsp70 interdomain linker sequences are highly conserved; moreover, mutations in this region compromise interdomain allostery. To better understand the role of this region in Hsp70 allostery, we used molecular dynamics simulations to explore the conformational landscape of the interdomain linker in ADP-bound DnaK and supported our simulations by strategic experimental data. We found that while the interdomain linker samples many conformations, it behaves as three relatively ordered segments connected by hinges. As a consequence, the distances and orientations between the NBD and SBD are limited. Additionally, the C-terminal region of the linker forms previously unreported, transient interactions with the SBD, and the predominant linker-docking site is available in only one allosteric state, that with high affinity for substrate. This preferential binding implicates the interdomain linker as a dynamic allosteric switch. The linker-binding site on the SBD is a potential target for small molecule modulators of the Hsp70 allosteric cycle. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Synchronization of discrete-time neural networks with delays and Markov jump topologies based on tracker information.

PubMed

Yang, Xinsong; Feng, Zhiguo; Feng, Jianwen; Cao, Jinde

2017-01-01

In this paper, synchronization in an array of discrete-time neural networks (DTNNs) with time-varying delays coupled by Markov jump topologies is considered. It is assumed that the switching information can be collected by a tracker with a certain probability and transmitted from the tracker to controller precisely. Then the controller selects suitable control gains based on the received switching information to synchronize the network. This new control scheme makes full use of received information and overcomes the shortcomings of mode-dependent and mode-independent control schemes. Moreover, the proposed control method includes both the mode-dependent and mode-independent control techniques as special cases. By using linear matrix inequality (LMI) method and designing new Lyapunov functionals, delay-dependent conditions are derived to guarantee that the DTNNs with Markov jump topologies to be asymptotically synchronized. Compared with existing results on Markov systems which are obtained by separately using mode-dependent and mode-independent methods, our result has great flexibility in practical applications. Numerical simulations are finally given to demonstrate the effectiveness of the theoretical results. Copyright © 2016 Elsevier Ltd. All rights reserved.

Design and evaluation of a DAMQ multiprocessor network with self-compacting buffers

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

Park, J.; O`Krafka, B.W.O.; Vassiliadis, S.

1994-12-31

This paper describes a new approach to implement Dynamically Allocated Multi-Queue (DAMQ) switching elements using a technique called ``self-compacting buffers``. This technique is efficient in that the amount of hardware required to manage the buffers is relatively small; it offers high performance since it is an implementation of a DAMQ. The first part of this paper describes the self-compacting buffer architecture in detail, and compares it against a competing DAMQ switch design. The second part presents extensive simulation results comparing the performance of a self compacting buffer switch against an ideal switch including several examples of k-ary n-cubes and deltamore » networks. In addition, simulation results show how the performance of an entire network can be quickly and accurately approximated by simulating just a single switching element.« less

Microsecond Simulations of DNA and Ion Transport in Nanopores with Novel Ion-Ion and Ion-Nucleotides Effective Potentials

PubMed Central

De Biase, Pablo M.; Markosyan, Suren; Noskov, Sergei

2014-01-01

We developed a novel scheme based on the Grand-Canonical Monte-Carlo/Brownian Dynamics (GCMC/BD) simulations and have extended it to studies of ion currents across three nanopores with the potential for ssDNA sequencing: solid-state nanopore Si3N4, α-hemolysin, and E111N/M113Y/K147N mutant. To describe nucleotide-specific ion dynamics compatible with ssDNA coarse-grained model, we used the Inverse Monte-Carlo protocol, which maps the relevant ion-nucleotide distribution functions from an all-atom MD simulations. Combined with the previously developed simulation platform for Brownian Dynamic (BD) simulations of ion transport, it allows for microsecond- and millisecond-long simulations of ssDNA dynamics in nanopore with a conductance computation accuracy that equals or exceeds that of all-atom MD simulations. In spite of the simplifications, the protocol produces results that agree with the results of previous studies on ion conductance across open channels and provide direct correlations with experimentally measured blockade currents and ion conductances that have been estimated from all-atom MD simulations. PMID:24738152

FPGA Based Reconfigurable ATM Switch Test Bed

NASA Technical Reports Server (NTRS)

Chu, Pong P.; Jones, Robert E.

1998-01-01

Various issues associated with "FPGA Based Reconfigurable ATM Switch Test Bed" are presented in viewgraph form. Specific topics include: 1) Network performance evaluation; 2) traditional approaches; 3) software simulation; 4) hardware emulation; 5) test bed highlights; 6) design environment; 7) test bed architecture; 8) abstract sheared-memory switch; 9) detailed switch diagram; 10) traffic generator; 11) data collection circuit and user interface; 12) initial results; and 13) the following conclusions: Advances in FPGA make hardware emulation feasible for performance evaluation, hardware emulation can provide several orders of magnitude speed-up over software simulation; due to the complexity of hardware synthesis process, development in emulation is much more difficult than simulation and requires knowledge in both networks and digital design.

Electron Nuclear Dynamics Simulations of Proton Cancer Therapy Reactions: Water Radiolysis and Proton- and Electron-Induced DNA Damage in Computational Prototypes.

PubMed

Teixeira, Erico S; Uppulury, Karthik; Privett, Austin J; Stopera, Christopher; McLaurin, Patrick M; Morales, Jorge A

2018-05-06

Proton cancer therapy (PCT) utilizes high-energy proton projectiles to obliterate cancerous tumors with low damage to healthy tissues and without the side effects of X-ray therapy. The healing action of the protons results from their damage on cancerous cell DNA. Despite established clinical use, the chemical mechanisms of PCT reactions at the molecular level remain elusive. This situation prevents a rational design of PCT that can maximize its therapeutic power and minimize its side effects. The incomplete characterization of PCT reactions is partially due to the health risks associated with experimental/clinical techniques applied to human subjects. To overcome this situation, we are conducting time-dependent and non-adiabatic computer simulations of PCT reactions with the electron nuclear dynamics (END) method. Herein, we present a review of our previous and new END research on three fundamental types of PCT reactions: water radiolysis reactions, proton-induced DNA damage and electron-induced DNA damage. These studies are performed on the computational prototypes: proton + H₂O clusters, proton + DNA/RNA bases and + cytosine nucleotide, and electron + cytosine nucleotide + H₂O. These simulations provide chemical mechanisms and dynamical properties of the selected PCT reactions in comparison with available experimental and alternative computational results.

Electro-Thermal Transient Simulation of Silicon Carbide Power Mosfet

DTIC Science & Technology

2013-06-01

ionization rate than electron in silicon carbide , the breakdown voltage almost remains constant even at elevated temperatures . This is due to the positive... temperature coefficient of holes in case of silicon carbide as discussed in [7, 8]. The higher ambient temperature influences the leakage current...in the RLC ring down circuit . E. Power Dissipation and Lattice Temperature The power dissipation for any switching device is dependent on the

Improved silica-PLC Mach-Zehnder interferometer type optical switches with error dependence compensation of directional coupler

NASA Astrophysics Data System (ADS)

Wang, Jun; Yi, Jia; Guo, Lijun; Liu, Peng; Hall, Trevor J.; Sun, DeGui

2017-03-01

For the most popular structure of planer lightwave circuit (PLC) 2×2 thermo-optic switches, Mach-Zehnder interferometer (MZI), a full range of splitting ratio errors of directional coupler (DC) are investigated. All the parameters determining the splitting ratio are the dimensions and the refractive indices of the waveguide core and cladding layers. In this work, the coherent relationships between the waveguide size and the refractive indices are analyzed and then the error compensation between the width and the refractive index of waveguide core, and the controllable effect of over clad layer refractive index error upon the MZI-type optical switch are all discovered with numerical calculation and BPM simulations. Then, an MZI-type 2×2 thermo-optic switch having a higher error tolerance is established with the efficient optimizations of all the 3 dB-DC parameters. As a result, for the symmetric MZI switch, an insertion loss of 1.5 dB and optical extinction ratio of over 20 dB are realized for the average tolerance of±5.0%. An asymmetric arm optical phase and unequal arm lengths is also employed to improve the uniformities of insertion loss. The agreements between the designs and the experiments are recognized, leading to a wide adoption of practical silica-PLC optical switch products.

Clustering and Flow Conservation Monitoring Tool for Software Defined Networks

PubMed Central

Puente Fernández, Jesús Antonio

2018-01-01

Prediction systems present some challenges on two fronts: the relation between video quality and observed session features and on the other hand, dynamics changes on the video quality. Software Defined Networks (SDN) is a new concept of network architecture that provides the separation of control plane (controller) and data plane (switches) in network devices. Due to the existence of the southbound interface, it is possible to deploy monitoring tools to obtain the network status and retrieve a statistics collection. Therefore, achieving the most accurate statistics depends on a strategy of monitoring and information requests of network devices. In this paper, we propose an enhanced algorithm for requesting statistics to measure the traffic flow in SDN networks. Such an algorithm is based on grouping network switches in clusters focusing on their number of ports to apply different monitoring techniques. Such grouping occurs by avoiding monitoring queries in network switches with common characteristics and then, by omitting redundant information. In this way, the present proposal decreases the number of monitoring queries to switches, improving the network traffic and preventing the switching overload. We have tested our optimization in a video streaming simulation using different types of videos. The experiments and comparison with traditional monitoring techniques demonstrate the feasibility of our proposal maintaining similar values decreasing the number of queries to the switches. PMID:29614049

Mechanical switching of ferroelectric domains beyond flexoelectricity

NASA Astrophysics Data System (ADS)

Chen, Weijin; Liu, Jianyi; Ma, Lele; Liu, Linjie; Jiang, G. L.; Zheng, Yue

2018-02-01

The resurgence of interest in flexoelectricity has prompted discussions on the feasibility of switching ferroelectric domains 'non-electrically'. In this work, we perform three-dimensional thermodynamic simulations in combination with ab initio calculations and effective Hamiltonian simulations to demonstrate the great effects of surface screening and surface bonding on ferroelectric domain switching triggered by local tip loading. A three-dimensional simulation scheme has been developed to capture the tip-induced domain switching behavior in ferroelectric thin films by adequately taking into account the surface screening effect and surface bonding effect of the ferroelectric film, as well as the finite elastic stiffness of the substrate and the electrode layers. The major findings are as follows. (i) Compared with flexoelectricity, surface effects can be overwhelming and lead to much more efficient mechanical switching caused by tip loading. (ii) The surface-assisted mechanical switching can be bi-directional without the necessity of reversing strain gradients. (iii) A mode transition from local to propagating domain switching occurs when the screening below a critical value. A ripple effect of domain switching appears with the formation of concentric loop domains. (iv) The ripple effect can lead to 'domain interference' and a deterministic writing of confined loop domain patterns by local excitations. Our study reveals the hidden switching mechanisms of ferroelectric domains and the possible roles of surface in mechanical switching. The ripple effect of domain switching, which is believed to be general in dipole systems, broadens our current knowledge of domain engineering.

Strong light illumination on gain-switched semiconductor lasers helps the eavesdropper in practical quantum key distribution systems

NASA Astrophysics Data System (ADS)

Fei, Yang-yang; Meng, Xiang-dong; Gao, Ming; Yang, Yi; Wang, Hong; Ma, Zhi

2018-07-01

The temperature of the semiconductor diode increases under strong light illumination whether thermoelectric cooler is installed or not, which changes the output wavelength of the laser (Lee et al., 2017). However, other characteristics also vary as temperature increases. These variations may help the eavesdropper in practical quantum key distribution systems. We study the effects of temperature increase on gain-switched semiconductor lasers by simulating temperature dependent rate equations. The results show that temperature increase may cause large intensity fluctuation, decrease the output intensity and lead the signal state and decoy state distinguishable. We also propose a modified photon number splitting attack by exploiting the effects of temperature increase. Countermeasures are also proposed.

Role of the dorsolateral prefrontal cortex in context-dependent motor performance.

PubMed

Lee, Y-Y; Winstein, C J; Fisher, B E

2016-04-01

Context-dependent motor performance is a phenomenon in which people perform better in the environmental context where they originally practised a task. Some animal and computer simulation studies have suggested that context-dependent performance may be associated with neural activation of the dorsolateral prefrontal cortex (DLPFC). This study aimed to determine the role of the DLPFC in context-dependent motor performance by perturbing the neural processing of the DLPFC with repetitive transcranial magnetic stimulation (rTMS) in healthy adults. Thirty healthy adults were recruited into the Control, rTMS DLPFC and rTMS Vertex groups. The participants practised three finger sequences associated with a specific incidental context (a coloured circle and a location on the computer screen). One day following practice, the rTMS groups received 1 Hz rTMS prior to the testing conditions in which the sequence-context associations remained the same as practice (SAME) or changed (SWITCH). All three groups improved significantly over practice on day 1. The second day testing results showed that the DLPFC group had a significantly lower decrease in motor performance under the SWITCH condition than the Control and Vertex groups. This finding suggests a specific role of the DLPFC in context-dependent motor performance. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Shape-dependent control of cell growth, differentiation, and apoptosis: switching between attractors in cell regulatory networks

NASA Technical Reports Server (NTRS)

Huang, S.; Ingber, D. E.

2000-01-01

Development of characteristic tissue patterns requires that individual cells be switched locally between different phenotypes or "fates;" while one cell may proliferate, its neighbors may differentiate or die. Recent studies have revealed that local switching between these different gene programs is controlled through interplay between soluble growth factors, insoluble extracellular matrix molecules, and mechanical forces which produce cell shape distortion. Although the precise molecular basis remains unknown, shape-dependent control of cell growth and function appears to be mediated by tension-dependent changes in the actin cytoskeleton. However, the question remains: how can a generalized physical stimulus, such as cell distortion, activate the same set of genes and signaling proteins that are triggered by molecules which bind to specific cell surface receptors. In this article, we use computer simulations based on dynamic Boolean networks to show that the different cell fates that a particular cell can exhibit may represent a preprogrammed set of common end programs or "attractors" which self-organize within the cell's regulatory networks. In this type of dynamic network model of information processing, generalized stimuli (e.g., mechanical forces) and specific molecular cues elicit signals which follow different trajectories, but eventually converge onto one of a small set of common end programs (growth, quiescence, differentiation, apoptosis, etc.). In other words, if cells use this type of information processing system, then control of cell function would involve selection of preexisting (latent) behavioral modes of the cell, rather than instruction by specific binding molecules. Importantly, the results of the computer simulation closely mimic experimental data obtained with living endothelial cells. The major implication of this finding is that current methods used for analysis of cell function that rely on characterization of linear signaling pathways or clusters of genes with common activity profiles may overlook the most critical features of cellular information processing which normally determine how signal specificity is established and maintained in living cells. Copyright 2000 Academic Press.

Dynamical mechanical characteristic simulation and analysis of the low voltage switch under vibration and shock conditions

NASA Astrophysics Data System (ADS)

Miao, Xiaodan; Han, Feng

2017-04-01

The low voltage switch has widely application especially in the hostile environment such as large vibration and shock conditions. In order to ensure the validity of the switch in the hostile environment, it is necessary to predict its mechanical characteristic. In traditional method, the complex and expensive testing system is build up to verify its validity. This paper presented a method based on finite element analysis to predict the dynamic mechanical characteristic of the switch by using ANSYS software. This simulation could provide the basis for the design and optimization of the switch to shorten the design process to improve the product efficiency.

Coherent Multimodal Sensory Information Allows Switching between Gravitoinertial Contexts

PubMed Central

Barbiero, Marie; Rousseau, Célia; Papaxanthis, Charalambos; White, Olivier

2017-01-01

Whether the central nervous system is capable to switch between contexts critically depends on experimental details. Motor control studies regularly adopt robotic devices to perturb the dynamics of a certain task. Other approaches investigate motor control by altering the gravitoinertial context itself as in parabolic flights and human centrifuges. In contrast to conventional robotic experiments, where only the hand is perturbed, these gravitoinertial or immersive settings coherently plunge participants into new environments. However, radically different they are, perfect adaptation of motor responses are commonly reported. In object manipulation tasks, this translates into a good matching of the grasping force or grip force to the destabilizing load force. One possible bias in these protocols is the predictability of the forthcoming dynamics. Here we test whether the successful switching and adaptation processes observed in immersive environments are a consequence of the fact that participants can predict the perturbation schedule. We used a short arm human centrifuge to decouple the effects of space and time on the dynamics of an object manipulation task by adding an unnatural explicit position-dependent force. We created different dynamical contexts by asking 20 participants to move the object at three different paces. These contextual sessions were interleaved such that we could simulate concurrent learning. We assessed adaptation by measuring how grip force was adjusted to this unnatural load force. We found that the motor system can switch between new unusual dynamical contexts, as reported by surprisingly well-adjusted grip forces, and that this capacity is not a mere consequence of the ability to predict the time course of the upcoming dynamics. We posit that a coherent flow of multimodal sensory information born in a homogeneous milieu allows switching between dynamical contexts. PMID:28553233

Relationship between Ni(II) and Zn(II) Coordination and Nucleotide Binding by the Helicobacter pylori [NiFe]-Hydrogenase and Urease Maturation Factor HypB*

PubMed Central

Sydor, Andrew M.; Lebrette, Hugo; Ariyakumaran, Rishikesh; Cavazza, Christine; Zamble, Deborah B.

2014-01-01

The pathogen Helicobacter pylori requires two nickel-containing enzymes, urease and [NiFe]-hydrogenase, for efficient colonization of the human gastric mucosa. These enzymes possess complex metallocenters that are assembled by teams of proteins in multistep pathways. One essential accessory protein is the GTPase HypB, which is required for Ni(II) delivery to [NiFe]-hydrogenase and participates in urease maturation. Ni(II) or Zn(II) binding to a site embedded in the GTPase domain of HypB modulates the enzymatic activity, suggesting a mechanism of regulation. In this study, biochemical and structural analyses of H. pylori HypB (HpHypB) revealed an intricate link between nucleotide and metal binding. HpHypB nickel coordination, stoichiometry, and affinity were modulated by GTP and GDP, an effect not observed for zinc, and biochemical evidence suggests that His-107 coordination to nickel toggles on and off in a nucleotide-dependent manner. These results are consistent with the crystal structure of HpHypB loaded with Ni(II), GDP, and Pi, which reveals a nickel site distinct from that of zinc-loaded Methanocaldococcus jannaschii HypB as well as subtle changes to the protein structure. Furthermore, Cys-142, a metal ligand from the Switch II GTPase motif, was identified as a key component of the signal transduction between metal binding and the enzymatic activity. Finally, potassium accelerated the enzymatic activity of HpHypB but had no effect on the other biochemical properties of the protein. Altogether, this molecular level information about HpHypB provides insight into its cellular function and illuminates a possible mechanism of metal ion discrimination. PMID:24338018

Relationship between Ni(II) and Zn(II) coordination and nucleotide binding by the Helicobacter pylori [NiFe]-hydrogenase and urease maturation factor HypB.

PubMed

Sydor, Andrew M; Lebrette, Hugo; Ariyakumaran, Rishikesh; Cavazza, Christine; Zamble, Deborah B

2014-02-14

The pathogen Helicobacter pylori requires two nickel-containing enzymes, urease and [NiFe]-hydrogenase, for efficient colonization of the human gastric mucosa. These enzymes possess complex metallocenters that are assembled by teams of proteins in multistep pathways. One essential accessory protein is the GTPase HypB, which is required for Ni(II) delivery to [NiFe]-hydrogenase and participates in urease maturation. Ni(II) or Zn(II) binding to a site embedded in the GTPase domain of HypB modulates the enzymatic activity, suggesting a mechanism of regulation. In this study, biochemical and structural analyses of H. pylori HypB (HpHypB) revealed an intricate link between nucleotide and metal binding. HpHypB nickel coordination, stoichiometry, and affinity were modulated by GTP and GDP, an effect not observed for zinc, and biochemical evidence suggests that His-107 coordination to nickel toggles on and off in a nucleotide-dependent manner. These results are consistent with the crystal structure of HpHypB loaded with Ni(II), GDP, and Pi, which reveals a nickel site distinct from that of zinc-loaded Methanocaldococcus jannaschii HypB as well as subtle changes to the protein structure. Furthermore, Cys-142, a metal ligand from the Switch II GTPase motif, was identified as a key component of the signal transduction between metal binding and the enzymatic activity. Finally, potassium accelerated the enzymatic activity of HpHypB but had no effect on the other biochemical properties of the protein. Altogether, this molecular level information about HpHypB provides insight into its cellular function and illuminates a possible mechanism of metal ion discrimination.

Switching speeds in NCAP displays: dependence on collection angle and wavelength

NASA Astrophysics Data System (ADS)

Reamey, Robert H.; Montoya, Wayne; Wartenberg, Mark

1991-06-01

The on and off switching speeds of nematic droplet-polymer films (NCAP) are shown to depend on the collection angle (f/#) and the wavelength of the light used in the measurement. Conventional twisted nematic liquid crystal displays have switching speeds which depend little on these factors. The switching speed dependence on collection angle (f/#) and wavelength for nematic droplet-polymer films is inherent to the mechanism by which light is modulated in these films. This mechanism is the scattering of light by the nematic droplets. The on times become faster and the off times become slower as the collection angle of detection is increased. The overall change in switching speed can be large. Greater than 100X changes in off time have been observed. As the wavelength of the light used to interrogate the sample is increased (blue yields green yields red) the on times become faster and the off times become slower. This dependence of switching speed on wavelength is apparent at all collection angles. An awareness of these effects is necessary when developing nematic droplet-polymer films for display applications and when comparing switching speed data from different sources.

ATP hydrolysis in Eg5 kinesin involves a catalytic two-water mechanism.

PubMed

Parke, Courtney L; Wojcik, Edward J; Kim, Sunyoung; Worthylake, David K

2010-02-19

Motor proteins couple steps in ATP binding and hydrolysis to conformational switching both in and remote from the active site. In our kinesin.AMPPPNP crystal structure, closure of the active site results in structural transformations appropriate for microtubule binding and organizes an orthosteric two-water cluster. We conclude that a proton is shared between the lytic water, positioned for gamma-phosphate attack, and a second water that serves as a general base. To our knowledge, this is the first experimental detection of the catalytic base for any ATPase. Deprotonation of the second water by switch residues likely triggers subsequent large scale structural rearrangements. Therefore, the catalytic base is responsible for initiating nucleophilic attack of ATP and for relaying the positive charge over long distances to initiate mechanotransduction. Coordination of switch movements via sequential proton transfer along paired water clusters may be universal for nucleotide triphosphatases with conserved active sites, such as myosins and G-proteins.

Negative differential electrolyte resistance in a solid-state nanopore resulting from electroosmotic flow bistability.

PubMed

Luo, Long; Holden, Deric A; White, Henry S

2014-03-25

A solid-state nanopore separating two aqueous solutions containing different concentrations of KCl is demonstrated to exhibit negative differential resistance (NDR) when a constant pressure is applied across the nanopore. NDR refers to a decrease in electrical current when the voltage applied across the nanopore is increased. NDR results from the interdependence of solution flow (electroosmotic and pressure-engendered) with the distributions of K+ and Cl- within the nanopore. A switch from a high-conductivity state to a low-conductivity state occurs over a very narrow voltage window (<2 mV) that depends on the nanopore geometry, electrolyte concentration, and nanopore surface charge density. Finite element simulations based on a simultaneous solution of the Navier-Stokes, Poisson, and Nernst-Planck equations demonstrate that NDR results from a positive feedback mechanism between the ion distributions and electroosmotic flow, yielding a true bistability in fluid flow and electrical current at a critical applied voltage, i.e., the NDR "switching potential". Solution pH and Ca2+ were separately employed as chemical stimuli to investigate the dependence of the NDR on the surface charge density. The NDR switching potential is remarkably sensitive to the surface charge density, and thus to pH and the presence of Ca2+, suggesting possible applications in chemical sensing.

Dynamics of vortex domain walls in ferromagnetic nanowires - A possible method for chirality manipulation

NASA Astrophysics Data System (ADS)

Li, Y.; Lu, Z.; Chen, C.; Cheng, M.; Yin, H.; Wang, W.; Li, C.; Liu, Y.; Xiong, R.; Shi, J.

2018-06-01

The dynamic behaviors of vortex domain walls (VDWs) in ferromagnetic nanowires driven by a magnetic field above Walker breakdown field (Hw) were investigated using micromagnetic simulation. It was found when nanowire has proper geometrical dimensions, the VDW may oscillate in a chirality invariant mode or a chirality switching mode depending on applied field and damping constant. At fixed damping constant, the oscillation mode can be controlled by applied field - with the increase of applied field, the oscillation of VDW change from a chirality invariant mode to a variant one. As the oscillation of VDW changes from chirality invariant regime to chirality switching regime, the oscillation frequency and amplification will undergo an abnormal change, which may offer a fingerprint for the switch of oscillation mode. Our finding proposes a simple way to control the chirality of a VDW by properly manipulating nanowire geometry and applied field, which may have important applications in VDW-based devices.

A phenylalanine rotameric switch for signal-state control in bacterial chemoreceptors

NASA Astrophysics Data System (ADS)

Ortega, Davi R.; Yang, Chen; Ames, Peter; Baudry, Jerome; Parkinson, John S.; Zhulin, Igor B.

2013-12-01

Bacterial chemoreceptors are widely used as a model system for elucidating the molecular mechanisms of transmembrane signalling and have provided a detailed understanding of how ligand binding by the receptor modulates the activity of its associated kinase CheA. However, the mechanisms by which conformational signals move between signalling elements within a receptor dimer and how they control kinase activity remain unknown. Here, using long molecular dynamics simulations, we show that the kinase-activating cytoplasmic tip of the chemoreceptor fluctuates between two stable conformations in a signal-dependent manner. A highly conserved residue, Phe396, appears to serve as the conformational switch, because flipping of the stacked aromatic rings of an interacting F396-F396‧ pair in the receptor homodimer takes place concomitantly with the signal-related conformational changes. We suggest that interacting aromatic residues, which are common stabilizers of protein tertiary structure, might serve as rotameric molecular switches in other biological processes as well.

Effects of the shape anisotropy and biasing field on the magnetization reversal process of the diamond-shaped NiFe nano films

NASA Astrophysics Data System (ADS)

Xu, Sichen; Yin, Jianfeng; Tang, Rujun; Zhang, Wenxu; Peng, Bin; Zhang, Wanli

2017-11-01

The effects of the planar shape anisotropy and biasing field on the magnetization reversal process (MRP) of the diamond-shaped NiFe nano films have been investigated by micromagnetic simulations. Results show that when the length to width ratio (LWR) of the diamond-shaped film is small, the MRP of the diamond-shaped films are sensitive to LWR. But when LWR is larger than 2, a stable domain switching mode is observed which nucleates from the center of the diamond and then expands to the edges. At a fixed LWR, the magnitude of the switching fields decrease with the increase of the biasing field, but the domain switching mode is not affected by the biasing field. Further analysis shows that demagnetization energy dominates over the MRP of the diamond-shaped films. The above LWR dependence of MRP can be well explained by a variation of the shape anisotropic factor with LWR.

Multiscale modeling of current-induced switching in magnetic tunnel junctions using ab initio spin-transfer torques

NASA Astrophysics Data System (ADS)

Ellis, Matthew O. A.; Stamenova, Maria; Sanvito, Stefano

2017-12-01

There exists a significant challenge in developing efficient magnetic tunnel junctions with low write currents for nonvolatile memory devices. With the aim of analyzing potential materials for efficient current-operated magnetic junctions, we have developed a multi-scale methodology combining ab initio calculations of spin-transfer torque with large-scale time-dependent simulations using atomistic spin dynamics. In this work we introduce our multiscale approach, including a discussion on a number of possible schemes for mapping the ab initio spin torques into the spin dynamics. We demonstrate this methodology on a prototype Co/MgO/Co/Cu tunnel junction showing that the spin torques are primarily acting at the interface between the Co free layer and MgO. Using spin dynamics we then calculate the reversal switching times for the free layer and the critical voltages and currents required for such switching. Our work provides an efficient, accurate, and versatile framework for designing novel current-operated magnetic devices, where all the materials details are taken into account.

Ion manipulations in structures for lossless ion manipulations (SLIM): computational evaluation of a 90° turn and a switch

DOE PAGES

Garimella, Sandilya V. B.; Ibrahim, Yehia. M.; Webb, Ian K.; ...

2015-08-19

The process of redirecting ions through 90° turns and ‘tee’ switches utilizing Structures for Lossless Ion Manipulations (SLIM) was evaluated using theoretical and simulation methods at 4 Torr pressure. SIMION simulations were used to optimize and evaluate conditions for performing turns without loss of signal intensity or ion mobility resolving power. Fundamental considerations indicated that the “race track” effect during ion turns may incur only small losses to the ion mobility resolving power at 4 Torr pressure for the typical plume widths predicted in an optimized SLIM ‘tee’ switch design. The dynamic switching of ions into orthogonal channels was alsomore » evaluated using SIMION ion trajectory simulations, and achieved similar performance. Simulation results were in close agreement with experimental results and were used to refine SLIM designs and applied potentials for their use.« less

Heat-transfer resistance at solid-liquid interfaces: a tool for the detection of single-nucleotide polymorphisms in DNA.

PubMed

van Grinsven, Bart; Vanden Bon, Natalie; Strauven, Hannelore; Grieten, Lars; Murib, Mohammed; Monroy, Kathia L Jiménez; Janssens, Stoffel D; Haenen, Ken; Schöning, Michael J; Vermeeren, Veronique; Ameloot, Marcel; Michiels, Luc; Thoelen, Ronald; De Ceuninck, Ward; Wagner, Patrick

2012-03-27

In this article, we report on the heat-transfer resistance at interfaces as a novel, denaturation-based method to detect single-nucleotide polymorphisms in DNA. We observed that a molecular brush of double-stranded DNA grafted onto synthetic diamond surfaces does not notably affect the heat-transfer resistance at the solid-to-liquid interface. In contrast to this, molecular brushes of single-stranded DNA cause, surprisingly, a substantially higher heat-transfer resistance and behave like a thermally insulating layer. This effect can be utilized to identify ds-DNA melting temperatures via the switching from low- to high heat-transfer resistance. The melting temperatures identified with this method for different DNA duplexes (29 base pairs without and with built-in mutations) correlate nicely with data calculated by modeling. The method is fast, label-free (without the need for fluorescent or radioactive markers), allows for repetitive measurements, and can also be extended toward array formats. Reference measurements by confocal fluorescence microscopy and impedance spectroscopy confirm that the switching of heat-transfer resistance upon denaturation is indeed related to the thermal on-chip denaturation of DNA. © 2012 American Chemical Society

Safety Assessment of TACOM’s Crew Station/Turret Motion Base Simulator

DTIC Science & Technology

1992-04-01

mode. The power ON switch is interlocked with the system hydraulic pressure switch so that the electronics can not be turned off while the system...analog) "o Oil Temperature Transducer (analog) "o Facility Pressure Switch o Pressure Critical Switch "o Six Supply Solenoid Valves "O Three Accumulator...Relief Solenoid Valves o Return Pressure Switch o Return Valve Switch o Six Filter Clogged Switches (one per filter) The Facility Pressure switch detects

High accuracy switched-current circuits using an improved dynamic mirror

NASA Technical Reports Server (NTRS)

Zweigle, G.; Fiez, T.

1991-01-01

The switched-current technique, a recently developed circuit approach to analog signal processing, has emerged as an alternative/compliment to the well established switched-capacitor circuit technique. High speed switched-current circuits offer potential cost and power savings over slower switched-capacitor circuits. Accuracy improvements are a primary concern at this stage in the development of the switched-current technique. Use of the dynamic current mirror has produced circuits that are insensitive to transistor matching errors. The dynamic current mirror has been limited by other sources of error including clock-feedthrough and voltage transient errors. In this paper we present an improved switched-current building block using the dynamic current mirror. Utilizing current feedback the errors due to current imbalance in the dynamic current mirror are reduced. Simulations indicate that this feedback can reduce total harmonic distortion by as much as 9 dB. Additionally, we have developed a clock-feedthrough reduction scheme for which simulations reveal a potential 10 dB total harmonic distortion improvement. The clock-feedthrough reduction scheme also significantly reduces offset errors and allows for cancellation with a constant current source. Experimental results confirm the simulated improvements.

Study on Frequency Dependency of ON-Resistance and Pulse-Loss Calculation of MOSFETs for Switch Mode Power Supply

NASA Astrophysics Data System (ADS)

Yamamura, Hideho; Sato, Ryohei; Iwata, Yoshiharu

Global efforts toward energy conservation, increasing data centers, and the increasing use of IT equipments are leading to a demand in reduced power consumption of equipments, and power efficiency improvement of power supply units is becoming a necessity. MOSFETs are widely used for their low ON-resistances. Power efficiency is designed using time-domain circuit simulators, except for transformer copper-loss, which has frequency dependency which is calculated separately using methods based on skin and proximity effects. As semiconductor technology reduces the ON-resistance of MOSFETs, frequency dependency due to the skin effect or proximity effect is anticipated. In this study, ON-resistance of MOSFETs are measured and frequency dependency is confirmed. Power loss against rectangular current pulse is calculated. The calculation method for transformer copper-loss is expanded to MOSFETs. A frequency function for the resistance model is newly developed and parametric calculation is enabled. Acceleration of calculation is enabled by eliminating summation terms. Using this method, it is shown that the frequency dependent component of the measured MOSFETs increases the dissipation from 11% to 32% at a switching frequency of 100kHz. From above, this paper points out the importance of the frequency dependency of MOSFETs' ON-resistance, provides means of calculating its pulse losses, and improves loss calculation accuracy of SMPSs.

A Genetic Variant Ameliorates β-Thalassemia Severity by Epigenetic-Mediated Elevation of Human Fetal Hemoglobin Expression.

PubMed

Chen, Diyu; Zuo, Yangjin; Zhang, Xinhua; Ye, Yuhua; Bao, Xiuqin; Huang, Haiyan; Tepakhan, Wanicha; Wang, Lijuan; Ju, Junyi; Chen, Guangfu; Zheng, Mincui; Liu, Dun; Huang, Shuodan; Zong, Lu; Li, Changgang; Chen, Yajun; Zheng, Chenguang; Shi, Lihong; Zhao, Quan; Wu, Qiang; Fucharoen, Supan; Zhao, Cunyou; Xu, Xiangmin

2017-07-06

A delayed fetal-to-adult hemoglobin (Hb) switch ameliorates the severity of β-thalassemia and sickle cell disease. The molecular mechanism underlying the epigenetic dysregulation of the switch is unclear. To explore the potential cis-variants responsible for the Hb switching, we systematically analyzed an 80-kb region spanning the β-globin cluster using capture-based next-generation sequencing of 1142 Chinese β-thalassemia persons and identified 31 fetal hemoglobin (HbF)-associated haplotypes of the selected 28 tag regulatory single-nucleotide polymorphisms (rSNPs) in seven linkage disequilibrium (LD) blocks. A Ly1 antibody reactive (LYAR)-binding motif disruptive rSNP rs368698783 (G/A) from LD block 5 in the proximal promoter of hemoglobin subunit gamma 1 (HBG1) was found to be a significant predictor for β-thalassemia clinical severity by epigenetic-mediated variant-dependent HbF elevation. We found this rSNP accounted for 41.6% of β-hemoglobinopathy individuals as an ameliorating factor in a total of 2,738 individuals from southern China and Thailand. We uncovered that the minor allele of the rSNP triggers the attenuation of LYAR and two repressive epigenetic regulators DNA methyltransferase 3 alpha (DNMT3A) and protein arginine methyltransferase 5 (PRMT5) from the HBG promoters, mediating allele-biased γ-globin elevation by facilitating demethylation of HBG core promoter CpG sites in erythroid progenitor cells from β-thalassemia persons. The present study demonstrates that this common rSNP in the proximal A γ-promoter is a major genetic modifier capable of ameliorating the severity of thalassemia major through the epigenetic-mediated regulation of the delayed fetal-to-adult Hb switch and provides potential targets for the treatment of β-hemoglobinopathy. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

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

PubMed

Filchtinski, Daniel; Sharabi, Oz; Rüppel, Alma; Vetter, Ingrid R; Herrmann, Christian; Shifman, Julia M

2010-06-11

Ras is a small GTP-binding protein that is an essential molecular switch for a wide variety of signaling pathways including the control of cell proliferation, cell cycle progression and apoptosis. In the GTP-bound state, Ras can interact with its effectors, triggering various signaling cascades in the cell. In the GDP-bound state, Ras looses its ability to bind to known effectors. The interaction of the GTP-bound Ras (Ras(GTP)) with its effectors has been studied intensively. However, very little is known about the much weaker interaction between the GDP-bound Ras (Ras(GDP)) and Ras effectors. We investigated the factors underlying the nucleotide-dependent differences in Ras interactions with one of its effectors, Raf kinase. Using computational protein design, we generated mutants of the Ras-binding domain of Raf kinase (Raf) that stabilize the complex with Ras(GDP). Most of our designed mutations narrow the gap between the affinity of Raf for Ras(GTP) and Ras(GDP), producing the desired shift in binding specificity towards Ras(GDP). A combination of our best designed mutation, N71R, with another mutation, A85K, yielded a Raf mutant with a 100-fold improvement in affinity towards Ras(GDP). The Raf A85K and Raf N71R/A85K mutants were used to obtain the first high-resolution structures of Ras(GDP) bound to its effector. Surprisingly, these structures reveal that the loop on Ras previously termed the switch I region in the Ras(GDP).Raf mutant complex is found in a conformation similar to that of Ras(GTP) and not Ras(GDP). Moreover, the structures indicate an increased mobility of the switch I region. This greater flexibility compared to the same loop in Ras(GTP) is likely to explain the natural low affinity of Raf and other Ras effectors to Ras(GDP). Our findings demonstrate that an accurate balance between a rigid, high-affinity conformation and conformational flexibility is required to create an efficient and stringent molecular switch. Copyright 2010 Elsevier Ltd. All rights reserved.

Application of a time-dependent coalescence process for inferring the history of population size changes from DNA sequence data.

PubMed

Polanski, A; Kimmel, M; Chakraborty, R

1998-05-12

Distribution of pairwise differences of nucleotides from data on a sample of DNA sequences from a given segment of the genome has been used in the past to draw inferences about the past history of population size changes. However, all earlier methods assume a given model of population size changes (such as sudden expansion), parameters of which (e.g., time and amplitude of expansion) are fitted to the observed distributions of nucleotide differences among pairwise comparisons of all DNA sequences in the sample. Our theory indicates that for any time-dependent population size, N(tau) (in which time tau is counted backward from present), a time-dependent coalescence process yields the distribution, p(tau), of the time of coalescence between two DNA sequences randomly drawn from the population. Prediction of p(tau) and N(tau) requires the use of a reverse Laplace transform known to be unstable. Nevertheless, simulated data obtained from three models of monotone population change (stepwise, exponential, and logistic) indicate that the pattern of a past population size change leaves its signature on the pattern of DNA polymorphism. Application of the theory to the published mtDNA sequences indicates that the current mtDNA sequence variation is not inconsistent with a logistic growth of the human population.

Computational Simulation of the Activation Cycle of Gα Subunit in the G Protein Cycle Using an Elastic Network Model

PubMed Central

Kim, Min Hyeok; Kim, Young Jin; Kim, Hee Ryung; Jeon, Tae-Joon; Choi, Jae Boong; Chung, Ka Young; Kim, Moon Ki

2016-01-01

Agonist-activated G protein-coupled receptors (GPCRs) interact with GDP-bound G protein heterotrimers (Gαβγ) promoting GDP/GTP exchange, which results in dissociation of Gα from the receptor and Gβγ. The GTPase activity of Gα hydrolyzes GTP to GDP, and the GDP-bound Gα interacts with Gβγ, forming a GDP-bound G protein heterotrimer. The G protein cycle is allosterically modulated by conformational changes of the Gα subunit. Although biochemical and biophysical methods have elucidated the structure and dynamics of Gα, the precise conformational mechanisms underlying the G protein cycle are not fully understood yet. Simulation methods could help to provide additional details to gain further insight into G protein signal transduction mechanisms. In this study, using the available X-ray crystal structures of Gα, we simulated the entire G protein cycle and described not only the steric features of the Gα structure, but also conformational changes at each step. Each reference structure in the G protein cycle was modeled as an elastic network model and subjected to normal mode analysis. Our simulation data suggests that activated receptors trigger conformational changes of the Gα subunit that are thermodynamically favorable for opening of the nucleotide-binding pocket and GDP release. Furthermore, the effects of GTP binding and hydrolysis on mobility changes of the C and N termini and switch regions are elucidated. In summary, our simulation results enabled us to provide detailed descriptions of the structural and dynamic features of the G protein cycle. PMID:27483005

Push or Pull? -- Cryo-Electron Microscopy of Microtubule's Dynamic Instability and Its Roles in the Kinetochore

NASA Astrophysics Data System (ADS)

Wang, Hong-Wei

2009-03-01

Microtubule is a biopolymer made up of alpha-beta-tubulin heterodimers. The tubulin dimers assemble head-to-tail as protofilaments and about 13 protofilaments interact laterally to form a hollow cylindrical structure which is the microtubule. As the major cytoskeleton in all eukaryotic cells, microtubules have the intrinsic property to switch stochastically between growth and shrinkage phases, a phenomenon termed as their dynamic instability. Microtubule's dynamic instability is closely related to the types of nucleotide (GTP or GDP) that binds to the beta-tubulin. We have biochemically trapped two types of assembly states of tubulin with GTP or GDP bound representing the polymerizing and depolymerizing ends of microtubules respectively. Using cryo-electron microscopy, we have elucidated the structures of these intermediate assemblies, showing that tubulin protofilaments demonstrate various curvatures and form different types of lateral interactions depending on the nucleotide states of tubulin and the temperature. Our work indicates that during the microtubule's dynamic cycle, tubulin undergoes various assembly states. These states, different from the straight microtubule, lend the highly dynamic and complicated behavior of microtubules. Our study of microtubule's interaction with certain kinetochore complexes suggests that the intermediate assemblies are responsible for specific mechanical forces that are required during the mitosis or meiosis. Our discoveries strongly suggest that a microtubule is a molecular machine rather than a simple cellular scaffold.

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

NASA Astrophysics Data System (ADS)

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.

Multistage switching hardware and software implementations for student experiment purpose

NASA Astrophysics Data System (ADS)

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.

Thermal Simulation of a Silicon Carbide (SiC) Insulated-Gate Bipolar Transistor (IGBT) in Continuous Switching Mode

DTIC Science & Technology

operation in a DC-DC power converter switching at a frequency of up to 15 kHz. Calculations also estimated the effect of solder layers on temperature in the device....Thermal simulations were used to calculate temperatures in a silicon carbide (SiC) Insulated -Gate Bipolar Transistor (IGBT),simulating device

Preliminary testing for the Markov property of the fifteen chromatin states of the Broad Histone Track.

PubMed

Lee, Kyung-Eun; Park, Hyun-Seok

2015-01-01

Epigenetic computational analyses based on Markov chains can integrate dependencies between regions in the genome that are directly adjacent. In this paper, the BED files of fifteen chromatin states of the Broad Histone Track of the ENCODE project are parsed, and comparative nucleotide frequencies of regional chromatin blocks are thoroughly analyzed to detect the Markov property in them. We perform various tests to examine the Markov property embedded in a frequency domain by checking for the presence of the Markov property in the various chromatin states. We apply these tests to each region of the fifteen chromatin states. The results of our simulation indicate that some of the chromatin states possess a stronger Markov property than others. We discuss the significance of our findings in statistical models of nucleotide sequences that are necessary for the computational analysis of functional units in noncoding DNA.

Thickness-dependent resistance switching in Cr-doped SrTiO3

NASA Astrophysics Data System (ADS)

Kim, TaeKwang; Du, Hyewon; Kim, Minchang; Seo, Sunae; Hwang, Inrok; Kim, Yeonsoo; Jeon, Jihoon; Lee, Sangik; Park, Baeho

2012-09-01

The thickness-dependent bipolar resistance-switching behavior was investigated for epitaxiallygrown Cr-doped SrTiO3 (Cr-STO). All the pristine devices of different thickness showed polarity-independent symmetric current-voltage characteristic and the same space-charge-limited conduction mechanism. However, after a forming process, the resultant conduction and switching phenomena were significantly different depending on the thickness of Cr-STO. The forming process itself was highly influenced by resistance value of each pristine device. Based on our results, we suggest that the resistance-switching mechanism in Cr-STO depends not only on the insulating material's composition or the contact metal as previously reported but also on the initial resistance level determined by the geometry and the quality of the insulating material. The bipolar resistance-switching behaviors in oxide materials of different thicknesses exhibit mixed bulk and interface switching. This indicates that efforts in resistance-based memory research should be focused on scalability or process method to control a given oxide material in addition to material type and device structure.

Simulation of switching overvoltages in the mine electric power supply system

NASA Astrophysics Data System (ADS)

Ivanchenko, D. I.; Novozhilov, N. G.

2017-02-01

Overvoltages occur in mine power supply systems during switching off consumers with high inductive load, such as transformers, reactors and electrical machines. Overvoltages lead to an increase of insulation degradation rate and may cause electric faults, power outage, fire and explosion of methane and coal dust. This paper is dedicated to simulation of vacuum circuit breaker switching overvoltages in a mine power supply system by means of Simulink MATLAB. The model of the vacuum circuit breaker implements simulation of transient recovery voltage, current chopping and an electric arc. Obtained results were compared to available experimental data.

Molecular Simulations of Mutually Exclusive Folding in a Two-Domain Protein Switch

PubMed Central

Mills, Brandon M.; Chong, Lillian T.

2011-01-01

A major challenge with testing designs of protein conformational switches is the need for experimental probes that can independently monitor their individual protein domains. One way to circumvent this issue is to use a molecular simulation approach in which each domain can be directly observed. Here we report what we believe to be the first molecular simulations of mutually exclusive folding in an engineered two-domain protein switch, providing a direct view of how folding of one protein drives unfolding of the other in a barnase-ubiquitin fusion protein. These simulations successfully capture the experimental effects of interdomain linker length and ligand binding on the extent of unfolding in the less stable domain. In addition, the effect of linker length on the potential for oligomerization, which eliminates switch activity, is in qualitative agreement with analytical ultracentrifugation experiments. We also perform what we believe to be the first study of protein unfolding via progressive localized compression. Finally, we are able to explore the kinetics of mutually exclusive folding by determining the effect of linker length on rates of unfolding and refolding of each protein domain. Our results demonstrate that molecular simulations can provide seemingly novel biological insights on the behavior of individual protein domains, thereby aiding in the rational design of bifunctional switches. PMID:21281591

Maraviroc, as a Switch Option, in HIV-1–infected Individuals With Stable, Well-controlled HIV Replication and R5-tropic Virus on Their First Nucleoside/Nucleotide Reverse Transcriptase Inhibitor Plus Ritonavir-boosted Protease Inhibitor Regimen: Week 48 Results of the Randomized, Multicenter MARCH Study

PubMed Central

Pett, Sarah Lilian; Amin, Janaki; Horban, Andrejz; Andrade-Villanueva, Jaime; Losso, Marcelo; Porteiro, Norma; Sierra Madero, Juan; Belloso, Waldo; Tu, Elise; Silk, David; Kelleher, Anthony; Harrigan, Richard; Clark, Andrew; Sugiura, Wataru; Wolff, Marcelo; Gill, John; Gatell, Jose; Fisher, Martin; Clarke, Amanda; Ruxrungtham, Kiat; Prazuck, Thierry; Kaiser, Rolf; Woolley, Ian; Arnaiz, Juan Alberto; Cooper, David; Rockstroh, Jürgen K.; Mallon, Patrick; Emery, Sean; Kelleher, Anthony; Merlin, Kate; Yeung, Julie; Fsadni, Bertha; Marks, Kat; Suzuki, Kazuo; Rismanto, Nick; Salomon, Horacio; Rubio, Andrea E.; Chibo, Doris; Birch, Chris; Harrigan, Richard; Swenson, Luke; Chan, Dennison; Berg, Thomas; Obermeier, Martin; Kaiser, Rolf; Schuelter, Eugen; Sierra Aragon, Saleta; Luebke, Nadine; Coughlan, Suzie; Dean, Jonathan; Sugiura, Wataru; Iwatani, Yasumasa; Reyes Teran, Gustavo; Avila, Santiago; Ruxrungtham, Kiat; Sirivichayakul, Sunee; Naphassanant, May; Ubolyam, Sasiwimol; Kaye, Steve; Land, Sally; Walker, Sarah; Haubrich, Richard; DeJesus, Edwin; Emery, Sean; Pett, Sarah L.; Tu, Elise; Silk, David; Berthon-Jones, Nisha; Amin, Janaki; Espinosa, Natalie; Courtney-Vega, Kymme; Absar, Noorul; Haskelberg, Hila; Robson, Rose; Donaldson, Anna; Losso, Marcelo; Belloso, Waldo; Guelman, Daniel; Gambardella, Luciana; Valdovinos, Mariana; Gatell, Jose; Arnaiz, Juan; Beleta, Helena; Ramos, Nuria; Targa, Marta; Rockstroh, Jurgen; Späth, Brigitta; Boesecke, Christoph; Engelhardt, Angelika; Fisher, Martin; Perry, Nicky; Clarke, Amanda; Gill, John; Beckthold, Brenda; Clark, Andrew; Drummond, Fraser; Lefevre, Eric; Corr, Sharon; Grant, Carol; Lupo, Sergio; Peroni, Luciana; Italiano, Hospital; Sanchez, Marisa; De Paz Sierra, Mariana; Mejia, Ramos; Losso, Marcelo; Viloria, Guillermo; Parlante, Angel; Bissio, Emiliano; Luchetti, Pablo; Warley, Eduardo; Vieni, Ines; Porteiro, Norma; Vilas, Cecilia; Zarate, Abel; Mayer, Gabriela; Elliot, Julian; Hagenauer, Michelle; Kelley, Mark; Rowling, Diane; Gibson, Abby; Latch, Ngaire; Tabrett, Chantal; Warzywoda, Elizabeth; Cooper, David; Pett, Sarah; MacRae, Karen; Sinclair, Brett; Sinn, Kate; Bloch, Mark; Franic, Teo; Vincent, Trina; Stewart, Natasha; Jayewardene, Avindra; Dwyer, Dominic; Kok, Jennifer; Assam, Delene; Taylor, Janette; King, Patricia; Orth, David; Youds, David; Sowden, David; Johnston, Colleen; Murray, Suzanne; Hehir, Jennifer; Wadham, Samantha; Donohue, William; Thompson, Jill; Garsia, Roger; Turnham, Geoffrey; Madden, Tracey; Woolley, Ian; Gillies, Ainsley; Bryant, Mellissa; Gill, John; Beckthold, Brenda; Walmsley, Sharon; Chan, Warmond; LeBlanc, Roger; Lanteigne, Francois; Mouawad, Rima; Rahal, Ines; Guber, Sergio; Ozturk, Sefika; Smith, Graham; Halpenny, Roberta; Reko, Tatjana; Robinette Hills, Jennifer; Wolff, Marcelo; Prazuck, Thierry; Laurent Hocqueloux, Francois; Wolfgang, Johann; Stephan, Christoph; Ebeling, Franziska; Rockstroh, Juergen; Boesecke, Christoph; Spath, Brigitta; Engelhardt, Angelika; Ole Jensen, Bjorn-Erik; Feind, Cecilie; Meyer-Olson, Dirk; Stoll, Matthias; Hoeper, Kirsten; Beider, Renata; Faetkenheur, Gerd; Thomas Baumgarten, Ellen; Baumgarten, Axel; Ingiliz, Patrick; Wienbreyer, Andreas; Behrendt, Daniela; Nienkarken, Tanja; Stein, Jessen; Jessen, Heiko; Zedlack, Carmen; Mallon, Paddy; Simelane, Sibongile; Assmann, Jennifer; Ghavami-Kia, Bijan; Sugiura, Wataru; Imahashi, Mayumi; Tanabe, Kazue; Yokomaku, Yoshiyuki; Imamura, Junji; Andrade-Villanueva, Jaime; Montes de Oca, Melva; Gonzalez, Lucero; Ponce, David; Mendoza, Andrea; Sierra-Madero, Juan; Sanchez Hernandez, Jesus Eduardo; Jaime Ruiz Ballesteros, Eduardo; del Moral Ponce, Sergio; Mosqueda, Luis; Lopez, Monica; Horban, Andrzej; Ignatowska, Anna; Bakowska, Elzbieta; Pulik, Piotr; Sanz-Moreno, Jose; Paredes, Roger; Puig, Jordi; Domingo, Pere; Gutierrez, Mar; Gatell, Jose; González-Cordón, Ana; Callau, Pili; Lopez Aldeguer, Jose; Cuellar Tovar, Sandra; Leal Noval, Manuel; Rivas, Inmaculada; Delgado-Fernandez, Marcial; Ramon Arribas, Jose; Miguel Castro, Juan; Ruxrungtham, Kiat; Avihingsanon, Anchalee; Maek-a-nantawat, Wirach; Intasan, Jintana; Charoenporn, Walairat; Cuprasitrut, Thidarat; Jaisomkom, Pachuen; Pruksakaew, Kanchana; Winston, Alan; Mullaney, Scott; Fisher, Martin; Clarke, Amanda; Barbour, Lisa; Perry, Nicky; Richardson, Celia; Fox, Julie; Murray, Tammy; Leen, Clifford; Morris, Shelia; Satyajit, Das; Sandhu, Rumun; Tucker, James

2016-01-01

Abstract Background. Alternative combination antiretroviral therapies in virologically suppressed human immunodeficiency virus (HIV)–infected patients experiencing side effects and/or at ongoing risk of important comorbidities from current therapy are needed. Maraviroc (MVC), a chemokine receptor 5 antagonist, is a potential alternative component of therapy in those with R5-tropic virus. Methods. The Maraviroc Switch Study is a randomized, multicenter, 96-week, open-label switch study in HIV type 1–infected adults with R5-tropic virus, virologically suppressed on a ritonavir-boosted protease inhibitor (PI/r) plus double nucleoside/nucleotide reverse transcriptase inhibitor (2 N(t)RTI) backbone. Participants were randomized 1:2:2 to current combination antiretroviral therapy (control), or replacing the protease inhibitor (MVC + 2 N(t)RTI arm) or the nucleoside reverse transcriptase inhibitor backbone (MVC + PI/r arm) with twice-daily MVC. The primary endpoint was the difference (switch minus control) in proportion with plasma viral load (VL) <200 copies/mL at 48 weeks. The switch arms were judged noninferior if the lower limit of the 95% confidence interval (CI) for the difference in the primary endpoint was < −12% in the intention-to-treat (ITT) population. Results. The ITT population comprised 395 participants (control, n = 82; MVC + 2 N(t)RTI, n = 156; MVC + PI/r, n = 157). Baseline characteristics were well matched. At week 48, noninferior rates of virological suppression were observed in those switching away from a PI/r (93.6% [95% CI, −9.0% to 2.2%] and 91.7% [95% CI, −9.6% to 3.8%] with VL <200 and <50 copies/mL, respectively) compared to the control arm (97.6% and 95.1% with VL <200 and <50 copies/mL, respectively). In contrast, MVC + PI/r did not meet noninferiority bounds and was significantly inferior (84.1% [95% CI, −19.8% to −5.8%] and 77.7% [95% CI, −24.9% to −8.4%] with VL <200 and <50 copies/mL, respectively) to the control arm in the ITT analysis. Conclusions. These data support MVC as a switch option for ritonavir-boosted PIs when partnered with a 2-N(t)RTI backbone, but not as part of N(t)RTI-sparing regimens comprising MVC with PI/r. Clinical Trials Registration. NCT01384682. PMID:27048747

Two nucleotide binding sites modulate ( sup 3 H) glyburide binding to rat cortex membranes

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

Johnson, D.E.; Gopalakrishnan, M.; Triggle, D.J.

1991-03-11

The effects of nucleotides on the binding of the ATP-dependent K{sup +}-channel antagonist ({sup 3}H)glyburide (GLB) to rat cortex membranes were examined. Nucleotide triphosphates (NTPs) and nucleotide diphosphate (NDPs) inhibited the binding of GLB. This effect was dependent on the presence of dithiothreitol (DTT). Inhibition of binding by NTPs, with the exception of ATP{gamma}S, was dependent on the presence of Mg{sup 2+}. GLB binding showed a biphasic response to ADP: up to 3 mM, ADP inhibited binding, and above this concentration GLB binding increased rapidly, and was restored to normal levels by 10 mM ADP. In the presence of Mg{supmore » 2+}, ADP did not stimulate binding. Saturation analysis in the presence of Mg{sup 2+} and increasing concentrations of ADP showed that ADP results primarily in a change of the B{sub max} for GLB binding. The differential effects of NTPS and NDPs indicate that two nucleotide binding sites regulate GLB binding.« less

NONLINEAR OPTICAL PHENOMENA Intracavity SRS conversion in diode-pumpedmultifunctional Nd3+:SrMoO4 laser crystal

NASA Astrophysics Data System (ADS)

Basiev, Tasoltan T.; Smetanin, Sergei N.; Fedin, Aleksandr V.; Shurygin, Anton S.

2010-10-01

Lasing of a miniature all-solid-state SRS laser based on a Nd3+:SrMoO4 crystal with a LiF:F2--passive Q-switch is studied. The dependences of the laser and SRS self-conversion parameters on the initial transmission of the passive Q-switch are studied experimentally and theoretically. Simulation of the lasing kinetics has shown the possibility of nonlinear cavity dumping upon highly efficient SRS self-conversion of laser radiation. An increase in the active medium length from 1 to 3mm resulted in an increase in the energy of the output 1.17-μm SRS radiation from 20 μJ to record-high 60 μJ at the absorbed multimode diode pump energy of 3.7 mJ.

Structure-dependent magnetoresistance and spin-transfer torque in antiferromagnetic Fe |MgO |FeMn |Cu tunnel junctions

NASA Astrophysics Data System (ADS)

Jia, Xingtao; Tang, Huimin; Wang, Shizhuo; Qin, Minghui

2017-02-01

We predict large magnetoresistance (MR) and spin transfer torque (STT) in antiferromagnetic Fe |MgO |FeMn |Cu tunnel junctions based on first-principles scattering theory. MR as large as ˜100 % is found in one junction. Magnetic dynamic simulations show that STT acting on the antiferromagnetic order parameter dominates the spin dynamics, and an electronic bias of order 10-1mV and current density of order 105Acm-2 can switches a junction of three-layer MgO, they are about one order smaller than that in Fe |MgO |Fe junction with the same barrier thickness, respectively. The multiple scattering in the antiferromagnetic region is considered to be responsible for the enhanced spin torque and smaller switching current density.

Filtering of Discrete-Time Switched Neural Networks Ensuring Exponential Dissipative and $l_{2}$ - $l_{\\infty }$ Performances.

PubMed

Choi, Hyun Duck; Ahn, Choon Ki; Karimi, Hamid Reza; Lim, Myo Taeg

2017-10-01

This paper studies delay-dependent exponential dissipative and l 2 - l ∞ filtering problems for discrete-time switched neural networks (DSNNs) including time-delayed states. By introducing a novel discrete-time inequality, which is a discrete-time version of the continuous-time Wirtinger-type inequality, we establish new sets of linear matrix inequality (LMI) criteria such that discrete-time filtering error systems are exponentially stable with guaranteed performances in the exponential dissipative and l 2 - l ∞ senses. The design of the desired exponential dissipative and l 2 - l ∞ filters for DSNNs can be achieved by solving the proposed sets of LMI conditions. Via numerical simulation results, we show the validity of the desired discrete-time filter design approach.

pH Wave-Front Propagation in the Urea-Urease Reaction

PubMed Central

Wrobel, Magdalena M.; Bánsági, Tamás; Scott, Stephen K.; Taylor, Annette F.; Bounds, Chris O.; Carranza, Arturo; Pojman, John A.

2012-01-01

The urease-catalyzed hydrolysis of urea displays feedback that results in a switch from acid (pH ∼3) to base (pH ∼9) after a controllable period of time (from 10 to >5000 s). Here we show that the spatially distributed reaction can support pH wave fronts propagating with a speed of the order of 0.1−1 mm min−1. The experimental results were reproduced qualitatively in reaction-diffusion simulations including a Michaelis-Menten expression for the urease reaction with a bell-shaped rate-pH dependence. However, this model fails to predict that at lower enzyme concentrations, the unstirred reaction does not always support fronts when the well-stirred reaction still rapidly switches to high pH. PMID:22947878

Fast simulation techniques for switching converters

NASA Technical Reports Server (NTRS)

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.

Simulation and characterization of a laterally-driven inertial micro-switch

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

Chen, Wenguo; Wang, Yang; Wang, Huiying

2015-04-15

A laterally-driven inertial micro-switch was designed and fabricated using surface micromachining technology. The dynamic response process was simulated by ANSYS software, which revealed the vibration process of movable electrode when the proof mass is shocked by acceleration in sensitive direction. The test results of fabricated inertial micro-switches with and without anti-shock beams indicated that the contact process of micro-switch with anti-shock beams is more reliable than the one without anti-shock beams. The test results indicated that three contact signals had been observed in the contact process of the inertial switch without anti-shock beams, and only one contact signal in themore » inertial switch with anti-shock beams, which demonstrated that the anti-shock beams can effectively constrain the vibration in non-sensitive direction.« less

Bio-mimicked atomic-layer-deposited iron oxide-based memristor with synaptic potentiation and depression functions

NASA Astrophysics Data System (ADS)

Wan, Xiang; Gao, Fei; Lian, Xiaojuan; Ji, Xincun; Hu, Ertao; He, Lin; Tong, Yi; Guo, Yufeng

2018-06-01

In this study, an iron oxide (FeO x )-based memristor was investigated for the realization of artificial synapses. An FeO x resistive switching layer was prepared by self-limiting atomic layer deposition (ALD). The movement of oxygen vacancies enabled the device to have history-dependent synaptic functions, which was further demonstrated by device modeling and simulation. Analog synaptic potentiation/depression in conductance was emulated by applying consecutive voltage pulses in the simulation. Our results suggest that the ALD FeO x -based memristor can be used as the basic building block for neural networks, neuromorphic systems, and brain-inspired computers.

Verifying different-modality properties for concepts produces switching costs.

PubMed

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.

Effects of AEA Cell-Bypass-Switch Closure on Charged EOS-Aqua NiH2 Cell

NASA Technical Reports Server (NTRS)

Keys, Denney; Rao, Gopalakrishna M.; Sullivan, David; Wannemacher, Harry

2001-01-01

The nominal performance of AEA CBPD under simulated EOS-Aqua/Aura flight hardware configuration has been demonstrated. There is no evidence of cell rupture or excessive heat production during or after CBPD switch activation under simulated high cell impedance (open-circuit cell failure mode). Inadvertent CBPD switch activation with a charged cell (low impedance path) intermittently closes and opens up the switch, therefore the device may or may not provide protection against future open-circuit cell failure. Further testing with switches F01 and F02 may provide clarification. The formation of a continuous low impedance path (a homogeneous low melting point alloy), has been confirmed - which is the expected mode of operation.

3D RNA and functional interactions from evolutionary couplings

PubMed Central

Weinreb, Caleb; Riesselman, Adam; Ingraham, John B.; Gross, Torsten; Sander, Chris; Marks, Debora S.

2016-01-01

Summary Non-coding RNAs are ubiquitous, but the discovery of new RNA gene sequences far outpaces research on their structure and functional interactions. We mine the evolutionary sequence record to derive precise information about function and structure of RNAs and RNA-protein complexes. As in protein structure prediction, we use maximum entropy global probability models of sequence co-variation to infer evolutionarily constrained nucleotide-nucleotide interactions within RNA molecules, and nucleotide-amino acid interactions in RNA-protein complexes. The predicted contacts allow all-atom blinded 3D structure prediction at good accuracy for several known RNA structures and RNA-protein complexes. For unknown structures, we predict contacts in 160 non-coding RNA families. Beyond 3D structure prediction, evolutionary couplings help identify important functional interactions, e.g., at switch points in riboswitches and at a complex nucleation site in HIV. Aided by accelerating sequence accumulation, evolutionary coupling analysis can accelerate the discovery of functional interactions and 3D structures involving RNA. PMID:27087444

Switching Between Menthol and Nonmenthol Cigarettes: Findings From the U.S. Cohort of the International Tobacco Control Four Country Survey

PubMed Central

Hyland, Andrew J.; Bansal-Travers, Maansi; Vogl, Lisa M.; Chen, Jiping; Evans, Sarah E.; Fong, Geoffrey T.; Cummings, Kenneth Michael; O’Connor, Richard J.

2014-01-01

Introduction: This article examines trends in switching between menthol and nonmenthol cigarettes, smoker characteristics associated with switching, and associations among switching, indicators of nicotine dependence, and quitting activity. Methods: Participants were 5,932 U.S. adult smokers who were interviewed annually as part of the International Tobacco Control Four Country Survey between 2002 and 2011. Generalized estimating equations (GEEs) were used to examine the prevalence of menthol cigarette use and switching between menthol and nonmenthol cigarettes (among 3,118 smokers who participated in at least 2 consecutive surveys). We also evaluated characteristics associated with menthol cigarette use and associations among switching, indicators of nicotine dependence, and quitting activity using GEEs. Results: Across the entire study period, 27% of smokers smoked menthol cigarettes; prevalence was highest among Blacks (79%), young adults (36%), and females (30%). Prevalence of switching between menthol and nonmenthol cigarettes was low (3% switched to menthol and 8% switched to nonmenthol), and switchers tended to revert back to their previous type. Switching types was not associated with indicators of nicotine dependence or quit attempts. However, those who switched cigarette brands within cigarette types were more likely to attempt to quit smoking. Conclusions: While overall switching rates were low, the percentage who switched from menthol to nonmenthol was significantly higher than the percentage who switched from nonmenthol to menthol. An asymmetry was seen in patterns of switching such that reverting back to menthol was more common than reverting back to nonmenthol, particularly among Black smokers. PMID:24984878

Relatively slow stochastic gene-state switching in the presence of positive feedback significantly broadens the region of bimodality through stabilizing the uninduced phenotypic state.

PubMed

Ge, Hao; Wu, Pingping; Qian, Hong; Xie, Xiaoliang Sunney

2018-03-01

Within an isogenic population, even in the same extracellular environment, individual cells can exhibit various phenotypic states. The exact role of stochastic gene-state switching regulating the transition among these phenotypic states in a single cell is not fully understood, especially in the presence of positive feedback. Recent high-precision single-cell measurements showed that, at least in bacteria, switching in gene states is slow relative to the typical rates of active transcription and translation. Hence using the lac operon as an archetype, in such a region of operon-state switching, we present a fluctuating-rate model for this classical gene regulation module, incorporating the more realistic operon-state switching mechanism that was recently elucidated. We found that the positive feedback mechanism induces bistability (referred to as deterministic bistability), and that the parameter range for its occurrence is significantly broadened by stochastic operon-state switching. We further show that in the absence of positive feedback, operon-state switching must be extremely slow to trigger bistability by itself. However, in the presence of positive feedback, which stabilizes the induced state, the relatively slow operon-state switching kinetics within the physiological region are sufficient to stabilize the uninduced state, together generating a broadened parameter region of bistability (referred to as stochastic bistability). We illustrate the opposite phenotype-transition rate dependence upon the operon-state switching rates in the two types of bistability, with the aid of a recently proposed rate formula for fluctuating-rate models. The rate formula also predicts a maximal transition rate in the intermediate region of operon-state switching, which is validated by numerical simulations in our model. Overall, our findings suggest a biological function of transcriptional "variations" among genetically identical cells, for the emergence of bistability and transition between phenotypic states.

Variable sequences outside the SAM-binding core critically influence the conformational dynamics of the SAM-III/SMK box riboswitch

PubMed Central

Lu, Changrui; Smith, Angela M; Ding, Fang; Chowdhury, Anirban; Henkin, Tina M; Ke, Ailong

2012-01-01

The SMK box (SAM-III) translational riboswitches were identified in S-adenosyl-L-methionine (SAM) synthetase metK genes in members of the Lactobacillales. This riboswitch switches between two alternative conformations in response to the intracellular SAM concentration and controls metK expression at the level of translation initiation. We previously reported the crystal structure of the SAM-bound SMK box riboswitch. In this study we combined SHAPE chemical probing with mutagenesis to probe the ligand-induced conformational switching mechanism. We revealed that while the majority of the apo SMK box RNA molecules exist in an alternatively base paired (ON) conformation, a subset of them pre-organize into a SAM-bound-like (READY) conformation, which upon SAM exposure is selectively stabilized into the SAM-bound (OFF) conformation through an induced-fit mechanism. Mutagenesis showed that the ON state is only slightly more stable than the READY state, as several single-nucleotide substitutions in a hypervariable region outside the SAM-binding core can alter the folding landscape to favor the READY state. Such SMK variants display a “constitutively-OFF” behavior both in vitro and in vivo. Time-resolved and temperature-dependent SHAPE analyses revealed adaptation of the SMK box RNA to its mesothermal working environment. The latter analysis revealed that the SAM-bound SMK box RNA follows a two-step folding/unfolding process. PMID:21549712

Minimal determinants for binding activated G-alpha from the structure of a G-alpha-i1/peptide dimer†

PubMed Central

Johnston, Christopher A.; Lobanova, Ekaterina S.; Shavkunov, Alexander S.; Low, Justin; Ramer, J. Kevin; Blaesius, Rainer; Fredericks, Zoey; Willard, Francis S.; Kuhlman, Brian; Arshavsky, Vadim Y.; Siderovski, David P.

2008-01-01

G-proteins cycle between an inactive GDP-bound state and active GTP-bound state, serving as molecular switches that coordinate cellular signaling. We recently used phage-display to identify a series of peptides that bind Gα subunits in a nucleotide-dependent manner [Johnston, C. A., Willard, F. S., Jezyk, M. R., Fredericks, Z., Bodor, E. T., Jones, M. B., Blaesius, R., Watts, V. J., Harden, T. K., Sondek, J., Ramer, J. K., and Siderovski, D. P. (2005) Structure 13, 1069–1080]. Here we describe the structural features and functions of KB-1753, a peptide that binds selectively to GDP·AlF4−- and GTPγS-bound states of Gαi subunits. KB-1753 blocks interaction of Gαtransducin with its effector, cGMP phosphodiesterase, and inhibits transducin-mediated activation of cGMP degradation. Additionally, KB-1753 interferes with RGS protein binding and resultant GAP activity. A fluorescent KB-1753 variant was found to act as a sensor for activated Gα in vitro. The crystal structure of KB-1753 bound to Gαi1·GDP·AlF4− reveals binding to a conserved hydrophobic groove between switch II and α3 helices, and, along with supporting biochemical data and previous structural analyses, supports the notion that this is the site of effector interactions for Gαi subunits. PMID:16981699

Perceived color shift of ceramics according to the change of illuminating light with spectroradiometer

PubMed Central

Cha, Hyun-Suk; Yu, Bin

2013-01-01

PURPOSE Perceived color of ceramics changes by the spectral power distribution of ambient light. This study aimed to quantify the amount of shifts in color and color coordinates of clinically simulated seven all-ceramics due to the switch of three ambient light sources using a human vision simulating spectroradiometer. MATERIALS AND METHODS CIE color coordinates, such as L*, a* and b*,of ceramic specimens were measured under three light sources, which simulate the CIE standard illuminant D65 (daylight), A (incandescent lamp), and F9 (fluorescent lamp). Shifts in color and color coordinate by the switch of lights were determined. Influence of the switched light (D65 to A, or D65 to F9), shade of veneer ceramics (A2 or A3), and brand of ceramics on the shifts was analyzed by a three-way ANOVA. RESULTS Shifts in color and color coordinates were influenced by three factors (P<.05). Color shifts by the switch to A were in the range of 5.9 to 7.7 ΔE*abunits, and those by the switch to F9 were 7.7 to 10.2; all of which were unacceptable (ΔE*ab > 5.5). When switched to A, CIE a* increased (Δa*: 5.6 to 7.6), however, CIE b* increased (Δb*: 4.9 to 7.8) when switched to F9. CONCLUSION Clinically simulated ceramics demonstrated clinically unacceptable color shifts according to the switches in ambient lights based on spectroradiometric readings. Therefore, shade matching and compatibility evaluation should be performed considering ambient lighting conditions and should be done under most relevant lighting condition. PMID:24049567

Ultrafast Beam Switching Using Coupled VCSELs

NASA Technical Reports Server (NTRS)

Ning, Cun-Zheng; Goorjian, Peter

2001-01-01

We propose a new approach to performing ultrafast beam switching using two coupled Vertical-Cavity Surface-Emitting Lasers (VCSELs). The strategy is demonstrated by numerical simulation, showing a beam switching of 10 deg at 42 GHz.

Generic products of antiepileptic drugs: a perspective on bioequivalence, bioavailability, and formulation switches using Monte Carlo simulations.

PubMed

Karalis, Vangelis; Macheras, Panos; Bialer, Meir

2014-01-01

Generic products of antiepileptic drugs (AEDs) are currently a controversial topic as neurologists and patients are reluctant to switch from brand products to generics and to switch between generics. The aim of this study was to provide enlightenment on issues of bioequivalence (BE) and interchangeability of AED products. Monte Carlo simulations of the classic 2 × 2 BE studies were performed to study the effect of sample size, within-subject variability, and the true difference in pharmacokinetic values of the products under comparison on BE acceptance of generic AED products. Simulations were extended to study the comparative performance of two generic AED products against the same innovative product. The simulated results are compared with literature data on AEDs. The question with regard to bioavailability (BA) is whether two formulations are different, while for BE the question is whether two formulations are sufficiently similar in terms of extent and rate of absorption. Therefore, the criteria for BA and BE and the statistical analysis involved in their analysis are different. Two generic formulations that meet regulatory approval requirements for generics by being bioequivalent to the same innovative AED may not be bioequivalent to one another and therefore should not be regarded as equal or as therapeutically equivalent products. A switch from a standard or an immediate-release formulation to a modified-release product, which comprises extended-release or delayed-release formulations, should not be regarded as a switch between generics, but rather as a switch between different formulation types. Switches between bioequivalent generic AED products could potentially lead to larger changes in plasma levels and exposure than the brand-to-generic switch. The simulation work verified the clinical findings that not all generic AED products bioequivalent to the same innovative product are bioequivalent to one another. Two generic formulations that meet regulatory approval requirements for generics, by being bioequivalent to the innovative AED, may not be bioequivalent to one another. Additional BE criteria are needed for a formulation switch, particularly in epilepsy, where a breakthrough seizure may change a patient's status from seizure-free to refractory.

Circuit-Switched Memory Access in Photonic Interconnection Networks for High-Performance Embedded Computing

DTIC Science & Technology

2010-07-22

dependent , providing a natural bandwidth match between compute cores and the memory subsystem. • High Bandwidth Dcnsity. Waveguides crossing the chip...simulate this memory access architecture on a 2S6-core chip with a concentrated 64-node network lIsing detailed traces of high-performance embedded...memory modulcs, wc placc memory access poi nts (MAPs) around the pcriphery of the chip connected to thc nctwork. These MAPs, shown in Figure 4, contain

Comparative simulation of switching regimes of magnetic explosion generators by copper and aluminum magnetodynamic current breakers taking into account elastoplastic properties of materials

NASA Astrophysics Data System (ADS)

Bazanov, A. A.; Ivanovskii, A. V.; Panov, A. I.; Samodolov, A. V.; Sokolov, S. S.; Shaidullin, V. Sh.

2017-06-01

We report on the results of the computer simulation of the operation of magnetodynamic break switches used as the second stage of current pulse formation in magnetic explosion generators. The simulation was carried out under the conditions when the magnetic field energy density on the surface of the switching conductor as a function of the current through it was close to but still did not exceed the critical value typical of the beginning of electric explosion. In the computational model, we used the parameters of experimentally tested sample of a coil magnetic explosion generator that can store energy of up to 2.7 MJ in the inductive storage circuit and equipped with a primary explosion stage of the current pulse formation. It has been shown that the choice of the switching conductor material, as well as its elastoplastic properties, considerably affects the breaker speed. Comparative results of computer simulation for copper and aluminum have been considered.

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

NASA Technical Reports Server (NTRS)

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.

Measuring technical and mathematical investigation of multiple reignitions at the switching of a motor using vacuum circuit breakers

NASA Astrophysics Data System (ADS)

Luxa, Andreas

The necessary conditions in switching system and vacuum circuit breaker for the occurrence of multiple re-ignitions and accompanying effects were examined. The shape of the occurring voltages was determined in relationship to other types of overvoltage. A phenomenological model of the arc, based on an extension of the Mayr equation for arcs was used with the simulation program NETOMAC for the switching transients. Factors which affect the arc parameters were analyzed. The results were statistically verified by 3000 three-phase switching tests on 3 standard vacuum circuit breakers under realistic systems conditions; the occurring overvoltage level was measured. Dimensioning criteria for motor simulation circuits in power plants were formulated on the basis of a theoretical equivalence analysis and experimental studies. The simulation model allows a sufficiently correct estimation of all effects.

Nucleotide Selectivity in Abiotic RNA Polymerization Reactions.

PubMed

Coari, Kristin M; Martin, Rebecca C; Jain, Kopal; McGown, Linda B

2017-09-01

In order to establish an RNA world on early Earth, the nucleotides must form polymers through chemical rather than biochemical reactions. The polymerization products must be long enough to perform catalytic functions, including self-replication, and to preserve genetic information. These functions depend not only on the length of the polymers, but also on their sequences. To date, studies of abiotic RNA polymerization generally have focused on routes to polymerization of a single nucleotide and lengths of the homopolymer products. Less work has been done the selectivity of the reaction toward incorporation of some nucleotides over others in nucleotide mixtures. Such information is an essential step toward understanding the chemical evolution of RNA. To address this question, in the present work RNA polymerization reactions were performed in the presence of montmorillonite clay catalyst. The nucleotides included the monophosphates of adenosine, cytosine, guanosine, uridine and inosine. Experiments included reactions of mixtures of an imidazole-activated nucleotide (ImpX) with one or more unactivated nucleotides (XMP), of two or more ImpX, and of XMP that were activated in situ in the polymerization reaction itself. The reaction products were analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to identify the lengths and nucleotide compositions of the polymerization products. The results show that the extent of polymerization, the degree of heteropolymerization vs. homopolymerization, and the composition of the polymeric products all vary among the different nucleotides and depend upon which nucleotides and how many different nucleotides are present in the mixture.

Nucleotide Selectivity in Abiotic RNA Polymerization Reactions

NASA Astrophysics Data System (ADS)

Coari, Kristin M.; Martin, Rebecca C.; Jain, Kopal; McGown, Linda B.

2017-09-01

In order to establish an RNA world on early Earth, the nucleotides must form polymers through chemical rather than biochemical reactions. The polymerization products must be long enough to perform catalytic functions, including self-replication, and to preserve genetic information. These functions depend not only on the length of the polymers, but also on their sequences. To date, studies of abiotic RNA polymerization generally have focused on routes to polymerization of a single nucleotide and lengths of the homopolymer products. Less work has been done the selectivity of the reaction toward incorporation of some nucleotides over others in nucleotide mixtures. Such information is an essential step toward understanding the chemical evolution of RNA. To address this question, in the present work RNA polymerization reactions were performed in the presence of montmorillonite clay catalyst. The nucleotides included the monophosphates of adenosine, cytosine, guanosine, uridine and inosine. Experiments included reactions of mixtures of an imidazole-activated nucleotide (ImpX) with one or more unactivated nucleotides (XMP), of two or more ImpX, and of XMP that were activated in situ in the polymerization reaction itself. The reaction products were analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to identify the lengths and nucleotide compositions of the polymerization products. The results show that the extent of polymerization, the degree of heteropolymerization vs. homopolymerization, and the composition of the polymeric products all vary among the different nucleotides and depend upon which nucleotides and how many different nucleotides are present in the mixture.

First principles investigation of the unipolar resistive switching mechanism in an interfacial phase change memory based on a GeTe/Sb2Te3 superlattice

NASA Astrophysics Data System (ADS)

Shirakawa, Hiroki; Araidai, Masaaki; Shiraishi, Kenji

2018-04-01

The interfacial phase change memory (iPCM) based on a GeTe/Sb2Te3 superlattice is one of the candidates for future storage class memories. However, the atomic structures of the high and low resistance states (HRS/LRS) remain unclear and the resistive switching mechanism is still under debate. Clarifying the switching mechanism is essential for developing further high-reliability and low-power-consumption iPCM. We propose, on the basis of the results of first-principles molecular dynamics simulations, a mechanism for resistive switching, and describe the atomic structures of the high and low resistance states of iPCM for unipolar switching. Our simulations indicated that switching from HRS to LRS occurs with Joule heating only, while that from LRS to HRS occurs with both hole injection and Joule heating.

Design and analysis of compact MMIC switches utilising GaAs pHEMTs in 3D multilayer technology

NASA Astrophysics Data System (ADS)

Haris, Norshakila; Kyabaggu, Peter B. K.; Alim, Mohammad A.; Rezazadeh, Ali A.

2017-05-01

In this paper, we demonstrate for the first time the implementation of three-dimensional multilayer technology on GaAs-based pseudomorphic high electron mobility transistor (pHEMT) switches. Two types of pHEMT switches are considered, namely single-pole single-throw (SPST) and single-pole double-throw (SPDT). The design and analysis of the devices are demonstrated first through a simulation of the industry-recognised standard model, TriQuint’s Own Model—Level 3, developed by TriQuint Semiconductor, Inc. From the simulation analysis, three optimised SPST and SPDT pHEMT switches which can address applications ranging from L to X bands, are fabricated and tested. The performance of the pHEMT switches using multilayer technology are comparable to those of the current state-of-the-art pHEMT switches, while simultaneously offering compact circuits with the advantages of integration with other MMIC components.

The association between fasting hypoglycemia and methylated mercaptopurine metabolites in children with acute lymphoblastic leukemia.

PubMed

Melachuri, Samyuktha; Gandrud, Laura; Bostrom, Bruce

2014-06-01

Symptomatic fasting hypoglycemia has been reported as an unusual side effect in patients with acute lymphoblastic leukemia (ALL) on maintenance therapy. We evaluated the relation of the red cell 6-mercaptopurine (6-MP) metabolite 6-methyl-mercaptopurine (6MMP) with hypoglycemia. We retrospectively reviewed charts of three patients with ALL and symptomatic hypoglycemia while fasting who were noted to have high levels of 6MMP. All patients had an empiric trial of switching from evening to morning 6-MP administration, and two patients were subsequently switched to twice daily dosing. Patients also received complex carbohydrates at bedtime. Switching 6-MP from evening to morning administration reduced 6MMP levels yet preserved adequate levels of the active metabolite red cell 6-thioguanine nucleotide (6TGN). All patients had decreased hypoglycemic events when changed from evening to morning dosing. Two patients showed a rebound in 6MMP levels with return of hypoglycemic symptoms. Both were then switched to twice daily 6-MP dosing with one having a decrease in 6MMP and hypoglycemic symptoms. High levels of 6MMP are associated with symptomatic hypoglycemia which may be mitigated by switching to morning or twice daily 6-MP dose administration. © 2014 Wiley Periodicals, Inc.

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

DTIC Science & Technology

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

DISCRETE EVENT SIMULATION OF OPTICAL SWITCH MATRIX PERFORMANCE IN COMPUTER NETWORKS

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

Imam, Neena; Poole, Stephen W

2013-01-01

In this paper, we present application of a Discrete Event Simulator (DES) for performance modeling of optical switching devices in computer networks. Network simulators are valuable tools in situations where one cannot investigate the system directly. This situation may arise if the system under study does not exist yet or the cost of studying the system directly is prohibitive. Most available network simulators are based on the paradigm of discrete-event-based simulation. As computer networks become increasingly larger and more complex, sophisticated DES tool chains have become available for both commercial and academic research. Some well-known simulators are NS2, NS3, OPNET,more » and OMNEST. For this research, we have applied OMNEST for the purpose of simulating multi-wavelength performance of optical switch matrices in computer interconnection networks. Our results suggest that the application of DES to computer interconnection networks provides valuable insight in device performance and aids in topology and system optimization.« less

A Model for the Epigenetic Switch Linking Inflammation to Cell Transformation: Deterministic and Stochastic Approaches

PubMed Central

Gérard, Claude; Gonze, Didier; Lemaigre, Frédéric; Novák, Béla

2014-01-01

Recently, a molecular pathway linking inflammation to cell transformation has been discovered. This molecular pathway rests on a positive inflammatory feedback loop between NF-κB, Lin28, Let-7 microRNA and IL6, which leads to an epigenetic switch allowing cell transformation. A transient activation of an inflammatory signal, mediated by the oncoprotein Src, activates NF-κB, which elicits the expression of Lin28. Lin28 decreases the expression of Let-7 microRNA, which results in higher level of IL6 than achieved directly by NF-κB. In turn, IL6 can promote NF-κB activation. Finally, IL6 also elicits the synthesis of STAT3, which is a crucial activator for cell transformation. Here, we propose a computational model to account for the dynamical behavior of this positive inflammatory feedback loop. By means of a deterministic model, we show that an irreversible bistable switch between a transformed and a non-transformed state of the cell is at the core of the dynamical behavior of the positive feedback loop linking inflammation to cell transformation. The model indicates that inhibitors (tumor suppressors) or activators (oncogenes) of this positive feedback loop regulate the occurrence of the epigenetic switch by modulating the threshold of inflammatory signal (Src) needed to promote cell transformation. Both stochastic simulations and deterministic simulations of a heterogeneous cell population suggest that random fluctuations (due to molecular noise or cell-to-cell variability) are able to trigger cell transformation. Moreover, the model predicts that oncogenes/tumor suppressors respectively decrease/increase the robustness of the non-transformed state of the cell towards random fluctuations. Finally, the model accounts for the potential effect of competing endogenous RNAs, ceRNAs, on the dynamics of the epigenetic switch. Depending on their microRNA targets, the model predicts that ceRNAs could act as oncogenes or tumor suppressors by regulating the occurrence of cell transformation. PMID:24499937

Time and spatial evolution of spin-orbit torque-induced magnetization switching in W/CoFeB/MgO structures with various sizes

NASA Astrophysics Data System (ADS)

Zhang, Chaoliang; Fukami, Shunsuke; DuttaGupta, Samik; Sato, Hideo; Ohno, Hideo

2018-04-01

We study spin-orbit torque (SOT) switching in W/CoFeB/MgO structures with various dot sizes (120-3500 nm) using pulsed current of various widths τ (800 ps-100 ms) to examine the time and spatial evolution of magnetization switching. We show that the switching behavior and the resultant threshold switching current density J th strongly depend on device size and pulse width. The switching mode in a 3500 nm dot device changes from probabilistic switching to reproducible partial switching as τ decreases. At τ = 800 ps, J th becomes more than 3 times larger than that in the long-pulse regime. A decrease in dot size to 700 nm does not significantly change the switching characteristics, suggesting that domain-wall propagation among the nucleated multiple domains governs switching. In contrast, devices with further reduced size (120 nm) show normal full switching with increasing probability with current and insignificant dependence of J th on τ, indicating that nucleation governs switching.

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

NASA Astrophysics Data System (ADS)

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.

Functional asymmetry in the lysyl-tRNA synthetase explored by molecular dynamics, free energy calculations and experiment

PubMed Central

Hughes, Samantha J; Tanner, Julian A; Hindley, Alison D; Miller, Andrew D; Gould, Ian R

2003-01-01

Background Charging of transfer-RNA with cognate amino acid is accomplished by the aminoacyl-tRNA synthetases, and proceeds through an aminoacyl adenylate intermediate. The lysyl-tRNA synthetase has evolved an active site that specifically binds lysine and ATP. Previous molecular dynamics simulations of the heat-inducible Escherichia coli lysyl-tRNA synthetase, LysU, have revealed differences in the binding of ATP and aspects of asymmetry between the nominally equivalent active sites of this dimeric enzyme. The possibility that this asymmetry results in different binding affinities for the ligands is addressed here by a parallel computational and biochemical study. Results Biochemical experiments employing isothermal calorimetry, steady-state fluorescence and circular dichroism are used to determine the order and stoichiometries of the lysine and nucleotide binding events, and the associated thermodynamic parameters. An ordered mechanism of substrate addition is found, with lysine having to bind prior to the nucleotide in a magnesium dependent process. Two lysines are found to bind per dimer, and trigger a large conformational change. Subsequent nucleotide binding causes little structural rearrangement and crucially only occurs at a single catalytic site, in accord with the simulations. Molecular dynamics based free energy calculations of the ATP binding process are used to determine the binding affinities of each site. Significant differences in ATP binding affinities are observed, with only one active site capable of realizing the experimental binding free energy. Half-of-the-sites models in which the nucleotide is only present at one active site achieve their full binding potential irrespective of the subunit choice. This strongly suggests the involvement of an anti-cooperative mechanism. Pathways for relaying information between the two active sites are proposed. Conclusions The asymmetry uncovered here appears to be a common feature of oligomeric aminoacyl-tRNA synthetases, and may play an important functional role. We suggest a manner in which catalytic efficiency could be improved by LysU operating in an alternating sites mechanism. PMID:12787471

When should irrigators invest in more water-efficient technologies as an adaptation to climate change?

NASA Astrophysics Data System (ADS)

Malek, K.; Adam, J. C.; Stockle, C.; Brady, M.; Yoder, J.

2015-12-01

The western US is expected to experience more frequent droughts with higher magnitudes and persistence due to the climate change, with potentially large impacts on agricultural productivity and the economy. Irrigated farmers have many options for minimizing drought impacts including changing crops, engaging in water markets, and switching irrigation technologies. Switching to more efficient irrigation technologies, which increase water availability in the crop root zone through reduction of irrigation losses, receives significant attention because of the promise of maintaining current production with less. However, more efficient irrigation systems are almost always more capital-intensive adaptation strategy particularly compared to changing crops or trading water. A farmer's decision to switch will depend on how much money they project to save from reducing drought damages. The objective of this study is to explore when (and under what climate change scenarios) it makes sense economically for farmers to invest in a new irrigation system. This study was performed over the Yakima River Basin (YRB) in Washington State, although the tools and information gained from this study are transferable to other watersheds in the western US. We used VIC-CropSyst, a large-scale grid-based modeling framework that simulates hydrological processes while mechanistically capturing crop water use, growth and development. The water flows simulated by VIC-CropSyst were used to run the RiverWare river system and water management model (YAK-RW), which simulates river processes and calculates regional water availability for agricultural use each day (i.e., the prorationing ratio). An automated computational platform has been developed and programed to perform the economic analysis for each grid cell, crop types and future climate projections separately, which allows us to explore whether or not implementing a new irrigation system is economically viable. Results of this study indicate that climate change could justify the investment in new irrigation systems during this century, but the timing of a farmer's response is likely to depend on a variety of factors, including changes in the frequency and magnitude of drought events, current irrigation systems, climatological characteristics within the basin, and crop type.

Simulating Chemical Kinetics Without Differential Equations: A Quantitative Theory Based on Chemical Pathways.

PubMed

Bai, Shirong; Skodje, Rex T

2017-08-17

A new approach is presented for simulating the time-evolution of chemically reactive systems. This method provides an alternative to conventional modeling of mass-action kinetics that involves solving differential equations for the species concentrations. The method presented here avoids the need to solve the rate equations by switching to a representation based on chemical pathways. In the Sum Over Histories Representation (or SOHR) method, any time-dependent kinetic observable, such as concentration, is written as a linear combination of probabilities for chemical pathways leading to a desired outcome. In this work, an iterative method is introduced that allows the time-dependent pathway probabilities to be generated from a knowledge of the elementary rate coefficients, thus avoiding the pitfalls involved in solving the differential equations of kinetics. The method is successfully applied to the model Lotka-Volterra system and to a realistic H 2 combustion model.

Structural Basis for Nucleotide Exchange in Heterotrimeric G Proteins

PubMed Central

Dror, Ron O.; Mildorf, Thomas J.; Hilger, Daniel; Manglik, Aashish; Borhani, David W.; Arlow, Daniel H.; Philippsen, Ansgar; Villanueva, Nicolas; Yang, Zhongyu; Lerch, Michael T.; Hubbell, Wayne L.; Kobilka, Brian K.; Sunahara, Roger K.; Shaw, David E.

2016-01-01

G protein–coupled receptors (GPCRs) relay diverse extracellular signals into cells by catalyzing nucleotide release from heterotrimeric G proteins, but the mechanism underlying this quintessential molecular signaling event has remained unclear. Here we use atomic-level simulations to elucidate the nucleotide-release mechanism. We find that the G protein α subunit Ras and helical domains—previously observed to separate widely upon receptor binding to expose the nucleotide-binding site—separate spontaneously and frequently even in the absence of a receptor. Domain separation is necessary but not sufficient for rapid nucleotide release. Rather, receptors catalyze nucleotide release by favoring an internal structural rearrangement of the Ras domain that weakens its nucleotide affinity. We use double electron-electron resonance spectroscopy and protein engineering to confirm predictions of our computationally determined mechanism. PMID:26089515

Negative voltage modulated multi-level resistive switching by using a Cr/BaTiOx/TiN structure and quantum conductance through evidence of H2O2 sensing mechanism.

PubMed

Chakrabarti, Somsubhra; Ginnaram, Sreekanth; Jana, Surajit; Wu, Zong-Yi; Singh, Kanishk; Roy, Anisha; Kumar, Pankaj; Maikap, Siddheswar; Qiu, Jian-Tai; Cheng, Hsin-Ming; Tsai, Ling-Na; Chang, Ya-Ling; Mahapatra, Rajat; Yang, Jer-Ren

2017-07-05

Negative voltage modulated multi-level resistive switching with quantum conductance during staircase-type RESET and its transport characteristics in Cr/BaTiO x /TiN structure have been investigated for the first time. The as-deposited amorphous BaTiO x film has been confirmed by high-resolution transmission electron microscopy. X-ray photo-electron spectroscopy shows different oxidation states of Ba in the switching material, which is responsible for tunable more than 10 resistance states by varying negative stop voltage owing to slow decay value of RESET slope (217.39 mV/decade). Quantum conductance phenomenon has been observed in staircase RESET cycle of the memory devices. By inspecting the oxidation states of Ba + and Ba 2+ through measuring H 2 O 2 with a low concentration of 1 nM in electrolyte/BaTiO x /SiO 2 /p-Si structure, the switching mechanism of each HRS level as well as the multi-level phenomenon has been explained by gradual dissolution of oxygen vacancy filament. Along with negative stop voltage modulated multi-level, current compliance dependent multi-level has also been demonstrated and resistance ratio up to 2000 has been achieved even for a thin (<5 nm) switching material. By considering oxidation-reduction of the conducting filaments, the current-voltage switching curve has been simulated as well. Hence, multi-level resistive switching of Cr/BaTiO x /TiN structure implies the promising applications in high dense, multistate non-volatile memories in near future.

Generalized semiparametric varying-coefficient models for longitudinal data

NASA Astrophysics Data System (ADS)

Qi, Li

In this dissertation, we investigate the generalized semiparametric varying-coefficient models for longitudinal data that can flexibly model three types of covariate effects: time-constant effects, time-varying effects, and covariate-varying effects, i.e., the covariate effects that depend on other possibly time-dependent exposure variables. First, we consider the model that assumes the time-varying effects are unspecified functions of time while the covariate-varying effects are parametric functions of an exposure variable specified up to a finite number of unknown parameters. The estimation procedures are developed using multivariate local linear smoothing and generalized weighted least squares estimation techniques. The asymptotic properties of the proposed estimators are established. The simulation studies show that the proposed methods have satisfactory finite sample performance. ACTG 244 clinical trial of HIV infected patients are applied to examine the effects of antiretroviral treatment switching before and after HIV developing the 215-mutation. Our analysis shows benefit of treatment switching before developing the 215-mutation. The proposed methods are also applied to the STEP study with MITT cases showing that they have broad applications in medical research.

Intra-wire coupling in segmented Ni/Cu nanowires deposited by electrodeposition

NASA Astrophysics Data System (ADS)

Sergelius, Philip; Lee, Ji Hyun; Fruchart, Olivier; Shaker Salem, Mohamed; Allende, Sebastian; Alejandro Escobar, Roberto; Gooth, Johannes; Zierold, Robert; Toussaint, Jean-Christophe; Schneider, Sebastian; Pohl, Darius; Rellinghaus, Bernd; Martin, Sylvain; Garcia, Javier; Reith, Heiko; Spende, Anne; Toimil-Molares, Maria-Eugenia; Altbir, Dora; Cowburn, Russel; Görlitz, Detlef; Nielsch, Kornelius

2017-02-01

Segmented magnetic nanowires are a promising route for the development of three dimensional data storage techniques. Such devices require a control of the coercive field and the coupling mechanisms between individual magnetic elements. In our study, we investigate electrodeposited nanomagnets within host templates using vibrating sample magnetometry and observe a strong dependence between nanowire length and coercive field (25 nm-5 μm) and diameter (25-45 nm). A transition from a magnetization reversal through coherent rotation to domain wall propagation is observed at an aspect ratio of approximately 2. Our results are further reinforced via micromagnetic simulations and angle dependent hysteresis loops. The found behavior is exploited to create nanowires consisting of a fixed and a free segment in a spin-valve like structure. The wires are released from the membrane and electrically contacted, displaying a giant magnetoresistance effect that is attributed to individual switching of the coupled nanomagnets. We develop a simple analytical model to describe the observed switching phenomena and to predict stable and unstable regimes in coupled nanomagnets of certain geometries.

Observer-based robust finite time H∞ sliding mode control for Markovian switching systems with mode-dependent time-varying delay and incomplete transition rate.

PubMed

Gao, Lijun; Jiang, Xiaoxiao; Wang, Dandan

2016-03-01

This paper investigates the problem of robust finite time H∞ sliding mode control for a class of Markovian switching systems. The system is subjected to the mode-dependent time-varying delay, partly unknown transition rate and unmeasurable state. The main difficulty is that, a sliding mode surface cannot be designed based on the unknown transition rate and unmeasurable state directly. To overcome this obstacle, the set of modes is firstly divided into two subsets standing for known transition rate subset and unknown one, based on which a state observer is established. A component robust finite-time sliding mode controller is also designed to cope with the effect of partially unknown transition rate. It is illustrated that the reachability, finite-time stability, finite-time boundedness, finite-time H∞ state feedback stabilization of sliding mode dynamics can be ensured despite the unknown transition rate. Finally, the simulation results verify the effectiveness of robust finite time control problem. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

Modeling of Semiconductor Optical Amplifier Gain Characteristics for Amplification and Switching

NASA Astrophysics Data System (ADS)

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.

Self-consistent radiation-based simulation of electric arcs: II. Application to gas circuit breakers

NASA Astrophysics Data System (ADS)

Iordanidis, A. A.; Franck, C. M.

2008-07-01

An accurate and robust method for radiative heat transfer simulation for arc applications was presented in the previous paper (part I). In this paper a self-consistent mathematical model based on computational fluid dynamics and a rigorous radiative heat transfer model is described. The model is applied to simulate switching arcs in high voltage gas circuit breakers. The accuracy of the model is proven by comparison with experimental data for all arc modes. The ablation-controlled arc model is used to simulate high current PTFE arcs burning in cylindrical tubes. Model accuracy for the lower current arcs is evaluated using experimental data on the axially blown SF6 arc in steady state and arc resistance measurements close to current zero. The complete switching process with the arc going through all three phases is also simulated and compared with the experimental data from an industrial circuit breaker switching test.

Quantum dot spin-V(E)CSELs: polarization switching and periodic oscillations

NASA Astrophysics Data System (ADS)

Li, Nianqiang; Alexandropoulos, Dimitris; Susanto, Hadi; Henning, Ian; Adams, Michael

2017-09-01

Spin-polarized vertical (external) cavity surface-emitting lasers [Spin-V(E)CSELs] using quantum dot (QD) material for the active region, can display polarization switching between the right- and left-circularly polarized fields via control of the pump polarization. In particular, our previous experimental results have shown that the output polarization ellipticity of the spin-V(E)CSEL emission can exhibit either the same handedness as that of the pump polarization or the opposite, depending on the experimental operating conditions. In this contribution, we use a modified version of the spin-flip model in conjunction with combined time-independent stability analysis and direct time integration. With two representative sets of parameters our simulation results show good agreement with experimental observations. In addition periodic oscillations provide further insight into the dynamic properties of spin-V(E)CSELs.

Interplay of multiple synaptic plasticity features in filamentary memristive devices for neuromorphic computing

NASA Astrophysics Data System (ADS)

La Barbera, Selina; Vincent, Adrien F.; Vuillaume, Dominique; Querlioz, Damien; Alibart, Fabien

2016-12-01

Bio-inspired computing represents today a major challenge at different levels ranging from material science for the design of innovative devices and circuits to computer science for the understanding of the key features required for processing of natural data. In this paper, we propose a detail analysis of resistive switching dynamics in electrochemical metallization cells for synaptic plasticity implementation. We show how filament stability associated to joule effect during switching can be used to emulate key synaptic features such as short term to long term plasticity transition and spike timing dependent plasticity. Furthermore, an interplay between these different synaptic features is demonstrated for object motion detection in a spike-based neuromorphic circuit. System level simulation presents robust learning and promising synaptic operation paving the way to complex bio-inspired computing systems composed of innovative memory devices.

All-optical transistors and logic gates using a parity-time-symmetric Y-junction: Design and simulation

NASA Astrophysics Data System (ADS)

Ding, Shulin; Wang, Guo Ping

2015-09-01

Classical nonlinear or quantum all-optical transistors are dependent on the value of input signal intensity or need extra co-propagating beams. In this paper, we present a kind of all-optical transistors constructed with parity-time (PT)-symmetric Y-junctions, which perform independently on the value of signal intensity in an unsaturated gain case and can also work after introducing saturated gain. Further, we show that control signal can switch the device from amplification of peaks in time to transformation of peaks to amplified troughs. By using these PT-symmetric Y-junctions with currently available materials and technologies, we can implement interesting logic functions such as NOT and XOR (exclusive OR) gates, implying potential applications of such structures in designing optical logic gates, optical switches, and signal transformations or amplifications.

A dual switch controls bacterial enhancer-dependent transcription

PubMed Central

Wiesler, Simone C.; Burrows, Patricia C.; Buck, Martin

2012-01-01

Bacterial RNA polymerases (RNAPs) are targets for antibiotics. Myxopyronin binds to the RNAP switch regions to block structural rearrangements needed for formation of open promoter complexes. Bacterial RNAPs containing the major variant σ54 factor are activated by enhancer-binding proteins (bEBPs) and transcribe genes whose products are needed in pathogenicity and stress responses. We show that (i) enhancer-dependent RNAPs help Escherichia coli to survive in the presence of myxopyronin, (ii) enhancer-dependent RNAPs partially resist inhibition by myxopyronin and (iii) ATP hydrolysis catalysed by bEBPs is obligatory for functional interaction of the RNAP switch regions with the transcription start site. We demonstrate that enhancer-dependent promoters contain two barriers to full DNA opening, allowing tight regulation of transcription initiation. bEBPs engage in a dual switch to (i) allow propagation of nucleated DNA melting from an upstream DNA fork junction and (ii) complete the formation of the transcription bubble and downstream DNA fork junction at the RNA synthesis start site, resulting in switch region-dependent RNAP clamp closure and open promoter complex formation. PMID:22965125

Highly-dispersive electromagnetic induced transparency in planar symmetric metamaterials.

PubMed

Lu, Xiqun; Shi, Jinhui; Liu, Ran; Guan, Chunying

2012-07-30

We propose, design and experimentally demonstrate highly-dispersive electromagnetically induced transparency (EIT) in planar symmetric metamaterials actively switched and controlled by angles of incidence. Full-wave simulation and measurement results show EIT phenomena, trapped-mode excitations and the associated local field enhancement of two symmetric metamaterials consisting of symmetrically split rings (SSR) and a fishscale (FS) metamaterial pattern, respectively, strongly depend on angles of incidence. The FS metamaterial shows much broader spectral splitting than the SSR metamaterial due to the surface current distribution variation.

A conserved tripeptide in CNG and HCN channels regulates ligand gating by controlling C-terminal oligomerization.

PubMed

Zhou, Lei; Olivier, Nelson B; Yao, Huan; Young, Edgar C; Siegelbaum, Steven A

2004-12-02

Cyclic nucleotides directly enhance the opening of the tetrameric CNG and HCN channels, although the mechanism remains unclear. We examined why HCN and certain CNG subunits form functional homomeric channels, whereas other CNG subunits only function in heteromeric channels. The "defect" in the CNGA4 subunit that prevents its homomeric expression was localized to its C-linker, which connects the transmembrane domain to the binding domain and contains a tripeptide that decreases the efficacy of ligand gating. Remarkably, replacement of the homologous HCN tripeptide with the CNGA4 sequence transformed cAMP into an inverse agonist that inhibits HCN channel opening. Using analytical ultracentrifugation, we identified the structural basis for this gating switch: whereas cAMP normally enhances the assembly of HCN C-terminal domains into a tetrameric gating ring, inclusion of the CNGA4 tripeptide reversed this action so that cAMP now causes gating ring disassembly. Thus, ligand gating depends on the dynamic oligomerization of C-terminal binding domains.

Track Detection in Railway Sidings Based on MEMS Gyroscope Sensors

PubMed Central

Broquetas, Antoni; Comerón, Adolf; Gelonch, Antoni; Fuertes, Josep M.; Castro, J. Antonio; Felip, Damià; López, Miguel A.; Pulido, José A.

2012-01-01

The paper presents a two-step technique for real-time track detection in single-track railway sidings using low-cost MEMS gyroscopes. The objective is to reliably know the path the train has taken in a switch, diverted or main road, immediately after the train head leaves the switch. The signal delivered by the gyroscope is first processed by an adaptive low-pass filter that rejects noise and converts the temporal turn rate data in degree/second units into spatial turn rate data in degree/meter. The conversion is based on the travelled distance taken from odometer data. The filter is implemented to achieve a speed-dependent cut-off frequency to maximize the signal-to-noise ratio. Although direct comparison of the filtered turn rate signal with a predetermined threshold is possible, the paper shows that better detection performance can be achieved by processing the turn rate signal with a filter matched to the rail switch curvature parameters. Implementation aspects of the track detector have been optimized for real-time operation. The detector has been tested with both simulated data and real data acquired in railway campaigns. PMID:23443376

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

NASA Technical Reports Server (NTRS)

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.

Molecular dynamics simulations of viral RNA polymerases link conserved and correlated motions of functional elements to fidelity

PubMed Central

Moustafa, Ibrahim M.; Shen, Hujun; Morton, Brandon; Colina, Coray M.; Cameron, Craig E.

2011-01-01

The viral RNA-dependent RNA polymerase (RdRp) is essential for multiplication of all RNA viruses. The sequence diversity of an RNA virus population contributes to its ability to infect the host. This diversity emanates from errors made by the RdRp during RNA synthesis. The physical basis for RdRp fidelity is unclear but is linked to conformational changes occurring during the nucleotide-addition cycle. To understand RdRp dynamics that might influence RdRp function, we have analyzed all-atom molecular dynamics (MD) simulations on the nanosecond timescale of four RdRps from the picornavirus family that exhibit 30–74% sequence identity. Principal component analysis showed that the major motions observed during the simulations derived from conserved structural motifs and regions of known function. Dynamics of residues participating in the same biochemical property, for example RNA binding, nucleotide binding or catalysis, were correlated even when spatially distant on the RdRp structure. The conserved and correlated dynamics of functional, structural elements suggest co-evolution of dynamics with structure and function of the RdRp. Crystal structures of all picornavirus RdRps exhibit a template-nascent RNA duplex channel too small to fully accommodate duplex RNA. Simulations revealed opening and closing motions of the RNA and NTP channels, which might be relevant to NTP entry, PPi exit and translocation. A role for nanosecond timescale dynamics in RdRp fidelity is supported by altered dynamics of the high-fidelity G64S derivative of PV RdRp relative to wild-type enzyme. PMID:21575642

Fault handling schemes in electronic systems with specific application to radiation tolerance and VLSI design

NASA Technical Reports Server (NTRS)

Attia, John Okyere

1993-01-01

Naturally occurring space radiation particles can produce transient and permanent changes in the electrical properties of electronic devices and systems. In this work, the transient radiation effects on DRAM and CMOS SRAM were considered. In addition, the effect of total ionizing dose radiation of the switching times of CMOS logic gates were investigated. Effects of transient radiation on the column and cell of MOS dynamic memory cell was simulated using SPICE. It was found that the critical charge of the bitline was higher than that of the cell. In addition, the critical charge of the combined cell-bitline was found to be dependent on the gate voltage of the access transistor. In addition, the effect of total ionizing dose radiation on the switching times of CMOS logic gate was obtained. The results of this work indicate that, the rise time of CMOS logic gates increases, while the fall time decreases with an increase in total ionizing dose radiation. Also, by increasing the size of the P-channel transistor with respect to that of the N-channel transistor, the propagation delay of CMOS logic gate can be made to decrease with, or be independent of an increase in total ionizing dose radiation. Furthermore, a method was developed for replacing polysilicon feedback resistance of SRAMs with a switched capacitor network. A switched capacitor SRAM was implemented using MOS Technology. The critical change of the switched capacitor SRAM has a very large critical charge. The results of this work indicate that switched capacitor SRAM is a viable alternative to SRAM with polysilicon feedback resistance.

Magnetization Reversal of Nanoscale Islands: How Size and Shape Affect the Arrhenius Prefactor

NASA Astrophysics Data System (ADS)

Krause, S.; Herzog, G.; Stapelfeldt, T.; Berbil-Bautista, L.; Bode, M.; Vedmedenko, E. Y.; Wiesendanger, R.

2009-09-01

The thermal switching behavior of individual in-plane magnetized Fe/W(110) nanoislands is investigated by a combined study of variable-temperature spin-polarized scanning tunneling microscopy and Monte Carlo simulations. Even for islands consisting of less than 100 atoms the magnetization reversal takes place via nucleation and propagation. The Arrhenius prefactor is found to strongly depend on the individual island size and shape, and based on the experimental results a simple model is developed to describe the magnetization reversal in terms of metastable states. Complementary Monte Carlo simulations confirm the model and provide new insight into the microscopic processes involved in magnetization reversal of smallest nanomagnets.

Ab Initio Molecular-Dynamics Simulation of Neuromorphic Computing in Phase-Change Memory Materials.

PubMed

Skelton, Jonathan M; Loke, Desmond; Lee, Taehoon; Elliott, Stephen R

2015-07-08

We present an in silico study of the neuromorphic-computing behavior of the prototypical phase-change material, Ge2Sb2Te5, using ab initio molecular-dynamics simulations. Stepwise changes in structural order in response to temperature pulses of varying length and duration are observed, and a good reproduction of the spike-timing-dependent plasticity observed in nanoelectronic synapses is demonstrated. Short above-melting pulses lead to instantaneous loss of structural and chemical order, followed by delayed partial recovery upon structural relaxation. We also investigate the link between structural order and electrical and optical properties. These results pave the way toward a first-principles understanding of phase-change physics beyond binary switching.

Mapping Flexibility and the Assembly Switch of Cell Division Protein FtsZ by Computational and Mutational Approaches*♦

PubMed Central

Martín-Galiano, Antonio J.; Buey, Rubén M.; Cabezas, Marta; Andreu, José M.

2010-01-01

The molecular switch for nucleotide-regulated assembly and disassembly of the main prokaryotic cell division protein FtsZ is unknown despite the numerous crystal structures that are available. We have characterized the functional motions in FtsZ with a computational consensus of essential dynamics, structural comparisons, sequence conservation, and networks of co-evolving residues. Employing this information, we have constructed 17 mutants, which alter the FtsZ functional cycle at different stages, to modify FtsZ flexibility. The mutant phenotypes ranged from benign to total inactivation and included increased GTPase, reduced assembly, and stabilized assembly. Six mutations clustering at the long cleft between the C-terminal β-sheet and core helix H7 deviated FtsZ assembly into curved filaments with inhibited GTPase, which still polymerize cooperatively. These mutations may perturb the predicted closure of the C-terminal domain onto H7 required for switching between curved and straight association modes and for GTPase activation. By mapping the FtsZ assembly switch, this work also gives insight into FtsZ druggability because the curved mutations delineate the putative binding site of the promising antibacterial FtsZ inhibitor PC190723. PMID:20472561

Mapping flexibility and the assembly switch of cell division protein FtsZ by computational and mutational approaches.

PubMed

Martín-Galiano, Antonio J; Buey, Rubén M; Cabezas, Marta; Andreu, José M

2010-07-16

The molecular switch for nucleotide-regulated assembly and disassembly of the main prokaryotic cell division protein FtsZ is unknown despite the numerous crystal structures that are available. We have characterized the functional motions in FtsZ with a computational consensus of essential dynamics, structural comparisons, sequence conservation, and networks of co-evolving residues. Employing this information, we have constructed 17 mutants, which alter the FtsZ functional cycle at different stages, to modify FtsZ flexibility. The mutant phenotypes ranged from benign to total inactivation and included increased GTPase, reduced assembly, and stabilized assembly. Six mutations clustering at the long cleft between the C-terminal beta-sheet and core helix H7 deviated FtsZ assembly into curved filaments with inhibited GTPase, which still polymerize cooperatively. These mutations may perturb the predicted closure of the C-terminal domain onto H7 required for switching between curved and straight association modes and for GTPase activation. By mapping the FtsZ assembly switch, this work also gives insight into FtsZ druggability because the curved mutations delineate the putative binding site of the promising antibacterial FtsZ inhibitor PC190723.

Combining Reaction Time and Accuracy: The Relationship Between Working Memory Capacity and Task Switching as a Case Example.

PubMed

Draheim, Christopher; Hicks, Kenny L; Engle, Randall W

2016-01-01

It is generally agreed upon that the mechanisms underlying task switching heavily depend on working memory, yet numerous studies have failed to show a strong relationship between working memory capacity (WMC) and task-switching ability. We argue that this relationship does indeed exist but that the dependent variable used to measure task switching is problematic. To support our claim, we reanalyzed data from two studies with a new scoring procedure that combines reaction time (RT) and accuracy into a single score. The reanalysis revealed a strong relationship between task switching and WMC that was not present when RT-based switch costs were used as the dependent variable. We discuss the theoretical implications of this finding along with the potential uses and limitations of the scoring procedure we used. More broadly, we emphasize the importance of using measures that incorporate speed and accuracy in other areas of research, particularly in comparisons of subjects differing in cognitive and developmental levels. © The Author(s) 2015.

Improved nucleic acid descriptors for siRNA efficacy prediction.

PubMed

Sciabola, Simone; Cao, Qing; Orozco, Modesto; Faustino, Ignacio; Stanton, Robert V

2013-02-01

Although considerable progress has been made recently in understanding how gene silencing is mediated by the RNAi pathway, the rational design of effective sequences is still a challenging task. In this article, we demonstrate that including three-dimensional descriptors improved the discrimination between active and inactive small interfering RNAs (siRNAs) in a statistical model. Five descriptor types were used: (i) nucleotide position along the siRNA sequence, (ii) nucleotide composition in terms of presence/absence of specific combinations of di- and trinucleotides, (iii) nucleotide interactions by means of a modified auto- and cross-covariance function, (iv) nucleotide thermodynamic stability derived by the nearest neighbor model representation and (v) nucleic acid structure flexibility. The duplex flexibility descriptors are derived from extended molecular dynamics simulations, which are able to describe the sequence-dependent elastic properties of RNA duplexes, even for non-standard oligonucleotides. The matrix of descriptors was analysed using three statistical packages in R (partial least squares, random forest, and support vector machine), and the most predictive model was implemented in a modeling tool we have made publicly available through SourceForge. Our implementation of new RNA descriptors coupled with appropriate statistical algorithms resulted in improved model performance for the selection of siRNA candidates when compared with publicly available siRNA prediction tools and previously published test sets. Additional validation studies based on in-house RNA interference projects confirmed the robustness of the scoring procedure in prospective studies.

Incremental passivity and output regulation for switched nonlinear systems

NASA Astrophysics Data System (ADS)

Pang, Hongbo; Zhao, Jun

2017-10-01

This paper studies incremental passivity and global output regulation for switched nonlinear systems, whose subsystems are not required to be incrementally passive. A concept of incremental passivity for switched systems is put forward. First, a switched system is rendered incrementally passive by the design of a state-dependent switching law. Second, the feedback incremental passification is achieved by the design of a state-dependent switching law and a set of state feedback controllers. Finally, we show that once the incremental passivity for switched nonlinear systems is assured, the output regulation problem is solved by the design of global nonlinear regulator controllers comprising two components: the steady-state control and the linear output feedback stabilising controllers, even though the problem for none of subsystems is solvable. Two examples are presented to illustrate the effectiveness of the proposed approach.

Analysis of a minimal Rho-GTPase circuit regulating cell shape

NASA Astrophysics Data System (ADS)

Holmes, William R.; Edelstein-Keshet, Leah

2016-08-01

Networks of Rho-family GTPases regulate eukaryotic cell polarization and motility by controlling assembly and contraction of the cytoskeleton. The mutually inhibitory Rac-Rho circuit is emerging as a central, regulatory hub that can affect the shape and motility phenotype of eukaryotic cells. Recent experimental manipulation of the amounts of Rac and Rho or their regulators (guanine nucleotide-exchange factors, GTPase-activating proteins, guanine nucleotide dissociation inhibitors) have been shown to bias the prevalence of these different states and promote transitions between them. Here we show that part of this data can be understood in terms of inherent Rac-Rho mutually inhibitory dynamics. We analyze a spatio-temporal mathematical model of Rac-Rho dynamics to produce a detailed set of predictions of how parameters such as GTPase rates of activation and total amounts affect cell decisions (such as Rho-dominated contraction, Rac-dominated spreading, and spatially segregated Rac-Rho polarization). We find that in some parameter regimes, a cell can take on any of these three fates depending on its environment or stimuli. We also predict how experimental manipulations (corresponding to parameter variations) can affect cell shapes observed. Our methods are based on local perturbation analysis (a kind of nonlinear stability analysis), and an approximation of nonlinear feedback by sharp switches. We compare the Rac-Rho model to an even simpler single-GTPase (‘wave-pinning’) model and demonstrate that the overall behavior is inherent to GTPase properties, rather than stemming solely from network topology.

Thermal coupling and effect of subharmonic synchronization in a system of two VO2 based oscillators

NASA Astrophysics Data System (ADS)

Velichko, Andrey; Belyaev, Maksim; Putrolaynen, Vadim; Perminov, Valentin; Pergament, Alexander

2018-03-01

We explore a prototype of an oscillatory neural network (ONN) based on vanadium dioxide switching devices. The model system under study represents two oscillators based on thermally coupled VO2 switches. Numerical simulation shows that the effective action radius RTC of coupling depends both on the total energy released during switching and on the average power. It is experimentally and numerically proved that the temperature change ΔT commences almost synchronously with the released power peak and T-coupling reveals itself up to a frequency of about 10 kHz. For the studied switching structure configuration, the RTC value varies over a wide range from 4 to 45 μm, depending on the external circuit capacitance C and resistance Ri, but the variation of Ri is more promising from the practical viewpoint. In the case of a "weak" coupling, synchronization is accompanied by attraction effect and decrease of the main spectra harmonics width. In the case of a "strong" coupling, the number of effects increases, synchronization can occur on subharmonics resulting in multilevel stable synchronization of two oscillators. An advanced algorithm for synchronization efficiency and subharmonic ratio calculation is proposed. It is shown that of the two oscillators the leading one is that with a higher main frequency, and, in addition, the frequency stabilization effect is observed. Also, in the case of a strong thermal coupling, the limit of the supply current parameters, for which the oscillations exist, expands by ∼10%. The obtained results have a universal character and open up a new kind of coupling in ONNs, namely, T-coupling, which allows for easy transition from 2D to 3D integration. The effect of subharmonic synchronization hold promise for application in classification and pattern recognition.

All-optical spin switching: A new frontier in femtomagnetism — A short review and a simple theory

NASA Astrophysics Data System (ADS)

Zhang, G. P.; Latta, T.; Babyak, Z.; Bai, Y. H.; George, Thomas F.

2016-08-01

Using an ultrafast laser pulse to manipulate the spin degree of freedom has broad technological appeal. It allows one to control the spin dynamics on a femtosecond time scale. The discipline, commonly called femtomagnetism, started with the pioneering experiment by Beaurepaire and coworkers in 1996, who showed subpicosecond demagnetization occurs in magnetic Ni thin films. This finding has motivated extensive research worldwide. All-optical helicity-dependent spin switching (AO-HDS) represents a new frontier in femtomagnetism, where a single ultrafast laser pulse can permanently switch spin without any assistance from a magnetic field. This review summarizes some of the crucial aspects of this new discipline: key experimental findings, leading mechanisms, controversial issues, and possible future directions. The emphasis is on our latest investigation. We first develop the all-optical spin switching (AOS) rule that determines how the switchability depends on the light helicity. This rule allows one to understand microscopically how the spin is reversed and why the circularly polarized light appears more powerful than the linearly polarized light. Then we invoke our latest spin-orbit coupled harmonic oscillator model to simulate single spin reversal. We consider both continuous wave (cw) excitation and pulsed laser excitation. The results are in a good agreement with the experimental result (a MatLab code is available upon request from the author). We then extend the code to include the exchange interaction among different spin sites. We show where the “inverse-Faraday field” comes from and how the laser affects the spin reversal nonlinearly. Our hope is that this review will motivate new experimental and theoretical investigations and discussions.

Maraviroc, as a Switch Option, in HIV-1-infected Individuals With Stable, Well-controlled HIV Replication and R5-tropic Virus on Their First Nucleoside/Nucleotide Reverse Transcriptase Inhibitor Plus Ritonavir-boosted Protease Inhibitor Regimen: Week 48 Results of the Randomized, Multicenter MARCH Study.

PubMed

Pett, Sarah Lilian; Amin, Janaki; Horban, Andrejz; Andrade-Villanueva, Jaime; Losso, Marcelo; Porteiro, Norma; Sierra Madero, Juan; Belloso, Waldo; Tu, Elise; Silk, David; Kelleher, Anthony; Harrigan, Richard; Clark, Andrew; Sugiura, Wataru; Wolff, Marcelo; Gill, John; Gatell, Jose; Fisher, Martin; Clarke, Amanda; Ruxrungtham, Kiat; Prazuck, Thierry; Kaiser, Rolf; Woolley, Ian; Arnaiz, Juan Alberto; Cooper, David; Rockstroh, Jürgen K; Mallon, Patrick; Emery, Sean

2016-07-01

Alternative combination antiretroviral therapies in virologically suppressed human immunodeficiency virus (HIV)-infected patients experiencing side effects and/or at ongoing risk of important comorbidities from current therapy are needed. Maraviroc (MVC), a chemokine receptor 5 antagonist, is a potential alternative component of therapy in those with R5-tropic virus. The Maraviroc Switch Study is a randomized, multicenter, 96-week, open-label switch study in HIV type 1-infected adults with R5-tropic virus, virologically suppressed on a ritonavir-boosted protease inhibitor (PI/r) plus double nucleoside/nucleotide reverse transcriptase inhibitor (2 N(t)RTI) backbone. Participants were randomized 1:2:2 to current combination antiretroviral therapy (control), or replacing the protease inhibitor (MVC + 2 N(t)RTI arm) or the nucleoside reverse transcriptase inhibitor backbone (MVC + PI/r arm) with twice-daily MVC. The primary endpoint was the difference (switch minus control) in proportion with plasma viral load (VL) <200 copies/mL at 48 weeks. The switch arms were judged noninferior if the lower limit of the 95% confidence interval (CI) for the difference in the primary endpoint was < -12% in the intention-to-treat (ITT) population. The ITT population comprised 395 participants (control, n = 82; MVC + 2 N(t)RTI, n = 156; MVC + PI/r, n = 157). Baseline characteristics were well matched. At week 48, noninferior rates of virological suppression were observed in those switching away from a PI/r (93.6% [95% CI, -9.0% to 2.2%] and 91.7% [95% CI, -9.6% to 3.8%] with VL <200 and <50 copies/mL, respectively) compared to the control arm (97.6% and 95.1% with VL <200 and <50 copies/mL, respectively). In contrast, MVC + PI/r did not meet noninferiority bounds and was significantly inferior (84.1% [95% CI, -19.8% to -5.8%] and 77.7% [95% CI, -24.9% to -8.4%] with VL <200 and <50 copies/mL, respectively) to the control arm in the ITT analysis. These data support MVC as a switch option for ritonavir-boosted PIs when partnered with a 2-N(t)RTI backbone, but not as part of N(t)RTI-sparing regimens comprising MVC with PI/r. NCT01384682. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Microfluidic T-form mixer utilizing switching electroosmotic flow.

PubMed

Lin, Che-Hsin; Fu, Lung-Ming; Chien, Yu-Sheng

2004-09-15

This paper presents a microfluidic T-form mixer utilizing alternatively switching electroosmotic flow. The microfluidic device is fabricated on low-cost glass slides using a simple and reliable fabrication process. A switching DC field is used to generate an electroosmotic force which simultaneously drives and mixes the fluid samples. The proposed design eliminates the requirements for moving parts within the microfluidic device and delicate external control systems. Two operation modes, namely, a conventional switching mode and a novel pinched switching mode, are presented. Computer simulation is employed to predict the mixing performance attainable in both operation modes. The simulation results are then compared to those obtained experimentally. It is shown that a mixing performance as high as 97% can be achieved within a mixing distance of 1 mm downstream from the T-junction when a 60 V/cm driving voltage and a 2-Hz switching frequency are applied in the pinched switching operation mode. This study demonstrates how the driving voltage and switching frequency can be optimized to yield an enhanced mixing performance. The novel methods presented in this study provide a simple solution to mixing problems in the micro-total-analysis-systems field.

Conformational Spread in the Flagellar Motor Switch: A Model Study

PubMed Central

Maini, Philip K.; Berry, Richard M.; Bai, Fan

2012-01-01

The reliable response to weak biological signals requires that they be amplified with fidelity. In E. coli, the flagellar motors that control swimming can switch direction in response to very small changes in the concentration of the signaling protein CheY-P, but how this works is not well understood. A recently proposed allosteric model based on cooperative conformational spread in a ring of identical protomers seems promising as it is able to qualitatively reproduce switching, locked state behavior and Hill coefficient values measured for the rotary motor. In this paper we undertook a comprehensive simulation study to analyze the behavior of this model in detail and made predictions on three experimentally observable quantities: switch time distribution, locked state interval distribution, Hill coefficient of the switch response. We parameterized the model using experimental measurements, finding excellent agreement with published data on motor behavior. Analysis of the simulated switching dynamics revealed a mechanism for chemotactic ultrasensitivity, in which cooperativity is indispensable for realizing both coherent switching and effective amplification. These results showed how cells can combine elements of analog and digital control to produce switches that are simultaneously sensitive and reliable. PMID:22654654

A novel fast optical switch based on two cascaded Terahertz Optical Asymmetric Demultiplexers (TOAD).

PubMed

Wang, Bing; Baby, Varghese; Tong, Wilson; Xu, Lei; Friedman, Michelle; Runser, Robert; Glesk, Ivan; Prucnal, Paul

2002-01-14

A novel optical switch based on cascading two terahertz optical asymmetric demultiplexers (TOAD) is presented. By utilizing the sharp edge of the asymmetric TOAD switching window profile, two TOAD switching windows are overlapped to produce a narrower aggregate switching window, not limited by the pulse propagation time in the SOA of the TOAD. Simulations of the cascaded TOAD switching window show relatively constant window amplitude for different window sizes. Experimental results on cascading two TOADs, each with a switching window of 8ps, but with the SOA on opposite sides of the fiber loop, show a minimum switching window of 2.7ps.

Simulation and test of the thermal behavior of pressure switch

NASA Astrophysics Data System (ADS)

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.

Fabrication and analysis of radiofrequency MEMS series capacitive single-pole double-throw switch

NASA Astrophysics Data System (ADS)

Bansal, Deepak; Bajpai, Anuroop; Kumar, Prem; Kaur, Maninder; Rangra, Kamaljit

2016-10-01

A compact radiofrequency (RF) MEMS single-pole double-throw (SPDT) switch based on series capacitive configuration is proposed. The critical process parameters are analyzed to improve the fabrication process. A technique of cold-hot thermal shock for lift-off method is explored. The residual stress in the structure is quantified by lancet test structures that come out to be 51 MPa. Effect of residual stress on actuation voltage is explored, which changes its value from 24 to 22 V. Resonance frequency and switching speed of the switch are 11 kHz and 44 μs, respectively, measured using laser Doppler vibrometer. Measured bandwidth of the SPDT switch is 20 GHz (5 to 25 GHz), which is verified with finite element method simulations in high frequency structure simulator©; and an equivalent LCR circuit in advanced design system©;. Insertion loss of the switch lies in -0.1 to -0.5 dB with isolation better than -20 dB for the above-mentioned bandwidth.

Toward a Probabilistic Automata Model of Some Aspects of Code-Switching.

ERIC Educational Resources Information Center

Dearholt, D. W.; Valdes-Fallis, G.

1978-01-01

The purpose of the model is to select either Spanish or English as the language to be used; its goals at this stage of development include modeling code-switching for lexical need, apparently random code-switching, dependency of code-switching upon sociolinguistic context, and code-switching within syntactic constraints. (EJS)

Structural outline of the detailed mechanism for elongation factor Ts-mediated guanine nucleotide exchange on elongation factor Tu.

PubMed

Thirup, Søren S; Van, Lan Bich; Nielsen, Tine K; Knudsen, Charlotte R

2015-07-01

Translation elongation factor EF-Tu belongs to the superfamily of guanine-nucleotide binding proteins, which play key cellular roles as regulatory switches. All G-proteins require activation via exchange of GDP for GTP to carry out their respective tasks. Often, guanine-nucleotide exchange factors are essential to this process. During translation, EF-Tu:GTP transports aminoacylated tRNA to the ribosome. GTP is hydrolyzed during this process, and subsequent reactivation of EF-Tu is catalyzed by EF-Ts. The reaction path of guanine-nucleotide exchange is structurally poorly defined for EF-Tu and EF-Ts. We have determined the crystal structures of the following reaction intermediates: two structures of EF-Tu:GDP:EF-Ts (2.2 and 1.8Å resolution), EF-Tu:PO4:EF-Ts (1.9Å resolution), EF-Tu:GDPNP:EF-Ts (2.2Å resolution) and EF-Tu:GDPNP:pulvomycin:Mg(2+):EF-Ts (3.5Å resolution). These structures provide snapshots throughout the entire exchange reaction and suggest a mechanism for the release of EF-Tu in its GTP conformation. An inferred sequence of events during the exchange reaction is presented. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Back-Hopping in Spin-Transfer-Torque Devices: Possible Origin and Countermeasures

NASA Astrophysics Data System (ADS)

Abert, Claas; Sepehri-Amin, Hossein; Bruckner, Florian; Vogler, Christoph; Hayashi, Masamitsu; Suess, Dieter

2018-05-01

The effect of undesirable high-frequency free-layer switching in magnetic multilayer systems, referred to as back-hopping, is investigated by means of the spin-diffusion model. A possible origin of the back-hopping effect is found to be the destabilization of the pinned layer, which leads to the perpetual switching of both layers. While the presented mechanism is not claimed to be the only possible reason for back-hopping, we show that it is a fundamental effect that will occur in any spin-transfer-torque device when exceeding a critical current. The influence of different material parameters on the critical switching currents for the free and pinned layer is obtained by micromagnetic simulations. The spin-diffusion model enables an accurate description of the torque on both layers, depending on various material parameters. It is found that the choice of a free-layer material with low polarization β and saturation magnetization Ms and a pinned-layer material with high β and Ms leads to a low free-layer critical current and a high pinned-layer critical current and hence reduces the likelihood of back-hopping. While back-hopping has been observed in various types of devices, there are only a few experiments that exhibit this effect in perpendicularly magnetized systems. However, our simulations suggest that the described effect will also gain importance in perpendicular systems due to the loss of pinned-layer anisotropy for decreasing device sizes.

Switching by Domain-Wall Automotion in Asymmetric Ferromagnetic Rings

NASA Astrophysics Data System (ADS)

Mawass, Mohamad-Assaad; Richter, Kornel; Bisig, Andre; Reeve, Robert M.; Krüger, Benjamin; Weigand, Markus; Stoll, Hermann; Krone, Andrea; Kronast, Florian; Schütz, Gisela; Kläui, Mathias

2017-04-01

Spintronic applications based on magnetic domain-wall (DW) motion, such as magnetic data storage, sensors, and logic devices, require approaches to reliably manipulate the magnetization in nanowires. In this paper, we report the direct dynamic experimental visualization of reliable switching from the onion to the vortex state by DW automotion at zero field in asymmetric ferromagnetic rings using a uniaxial field pulse. Employing time-resolved x-ray microscopy, we demonstrate that depending on the detailed spin structure of the DWs and the size and geometry of the rings, the automotive propagation can be tailored during the DW relaxation from the higher-energy onion state to the energetically favored vortex state, where both DWs annihilate. Our measurements show DW automotion with an average velocity of about 60 m /s , which is a significant speed for spintronic devices. Such motion is mostly governed by local forces resulting from the geometry variations in the device. A closer study of the annihilation process via micromagnetic simulations reveals that a new vortex is nucleated in between the two initial walls. We demonstrate that the annihilation of DWs through automotion in our scheme always occurs with the detailed topological nature of the walls influencing only the DW dynamics on a local scale. The simulations show good quantitative agreement with our experimental results. These findings shed light on a robust and reliable switching process of the onion state in ferromagnetic rings, which paves the way for further optimization of these devices.

Structural Basis of Tonic Inhibition by Dimers of Dimers in Hyperpolarization-Activated Cyclic-Nucleotide-Modulated (HCN) Ion Channels.

PubMed

VanSchouwen, Bryan; Melacini, Giuseppe

2016-10-03

The hyperpolarization-activated cyclic-nucleotide-modulated (HCN) ion channels control rhythmicity in neurons and cardiomyocytes. Cyclic AMP (cAMP) modulates HCN activity through cAMP-dependent formation of a tetrameric gating ring spanning the intracellular region (IR) of HCN. In the absence of cAMP, the IR cAMP-binding domain (CBD) mainly samples its inactive conformation, resulting in steric clashes that destabilize the IR tetramer. Although these clashes with the inactive CBD are released through tetramer dissociation into monomers, functional mutagenesis suggests that the apo IR is not fully monomeric. To investigate the inhibitory non-monomeric IR species, we performed molecular dynamics simulations starting from "hybrid" structures that are tetrameric, but contain inactive apo-state CBD conformations. The ensemble of simulated trajectories reveals that full dissociation of the tetramer into monomers is not necessary to release the steric hindrance with the inactive CBD. Specifically, we found that partial dissociation of the tetramer into dimers is sufficient to accommodate four inactive CBDs, while reduction of the quaternary symmetry of the non-dissociated tetramer from four- to two-fold permits accommodation of two inactive CBDs. Our findings not only rationalize available electrophysiological, fluorometry and sedimentation equilibrium data, but they also provide unprecedented structural insight into previously elusive non-monomeric auto-inhibitory HCN species.

Temperature dependence of carrier transport and resistance switching in Pt/SrTi1-xNbxO3 Schottky junctions

NASA Astrophysics Data System (ADS)

Li, Jianyong; Ohashi, Naoki; Okushi, Hideyo; Haneda, Hajime

2011-03-01

We investigated the temperature dependence of carrier transport and resistance switching of Pt/SrTi1-xNbxO3 Schottky junctions in the temperature range 80-400 K by measuring the current-voltage (I-V) characteristics and the frequency dependence of the capacitance-voltage (C-V) characteristics. The I-V curves displayed a high degree of hysteresis, known as the colossal electroresistance (CER) effect, and their temperature dependence showed an anomalous behavior, i.e., the magnitude of the hysteresis increased with decreasing T. The experimental results were analyzed by taking into account the temperature and electric-field dependence of the relative permittivity of SrTi1-xNbxO3 as well as the inhomogeneity of the Schottky barrier height (SBH) (a model in which two parallel current paths coexist in the Schottky barrier). It was confirmed that the observed I-V and C-V curves were well simulated by this model, thus indicating that the CER effects originated in the field emission current through different SBHs and at different locations of the Schottky junctions. Based on these results, we explain the mechanism of the CER effect qualitatively in terms of this model. For this purpose, we take into account the pinched-off effect caused by the small-scale inhomogeneity of SBH and the existence of deep levels as a result of defects and unintentional impurities in the depletion layer of the Pt/SrTi1-xNbxO3 Schottky junctions.

A fast multipole method combined with a reaction field for long-range electrostatics in molecular dynamics simulations: The effects of truncation on the properties of water

NASA Astrophysics Data System (ADS)

Mathias, Gerald; Egwolf, Bernhard; Nonella, Marco; Tavan, Paul

2003-06-01

We present a combination of the structure adapted multipole method with a reaction field (RF) correction for the efficient evaluation of electrostatic interactions in molecular dynamics simulations under periodic boundary conditions. The algorithm switches from an explicit electrostatics evaluation to a continuum description at the maximal distance that is consistent with the minimum image convention, and, thus, avoids the use of a periodic electrostatic potential. A physically motivated switching function enables charge clusters interacting with a given charge to smoothly move into the solvent continuum by passing through the spherical dielectric boundary surrounding this charge. This transition is complete as soon as the cluster has reached the so-called truncation radius Rc. The algorithm is used to examine the dependence of thermodynamic properties and correlation functions on Rc in the three point transferable intermolecular potential water model. Our test simulations on pure liquid water used either the RF correction or a straight cutoff and values of Rc ranging from 14 Å to 40 Å. In the RF setting, the thermodynamic properties and the correlation functions show convergence for Rc increasing towards 40 Å. In the straight cutoff case no such convergence is found. Here, in particular, the dipole-dipole correlation functions become completely artificial. The RF description of the long-range electrostatics is verified by comparison with the results of a particle-mesh Ewald simulation at identical conditions.

The wiring diagram for plant G signaling

DOE PAGES

Colaneri, Alejandro C.; Jones, Alan M.

2014-10-01

Like electronic circuits, the modular arrangement of cell-signaling networks decides how inputs produce outputs. Animal heterotrimeric guanine nucleotide binding proteins (G-proteins) operate as switches in the circuits that signal between extracellular agonists and intracellular effectors. There still is no biochemical evidence for a receptor or its agonist in the plant G-protein pathways. Plant G-proteins deviate in many important ways from the animal paradigm. This paper covers important discoveries from the last two years that enlighten these differences and ends describing alternative wiring diagrams for the plant signaling circuits regulated by G-proteins. Finally, we propose that plant G-proteins are integrated inmore » the signaling circuits as variable resistor rather than switches, controlling the flux of information in response to the cell's metabolic state.« less

45° sign switching of effective exchange bias due to competing anisotropies in fully epitaxial Co3FeN/MnN bilayers.

PubMed

Hajiri, T; Yoshida, T; Filianina, M; Jaiswal, S; Borie, B; Asano, H; Zabel, H; Kläui, M

2017-12-05

We report an unusual angular-dependent exchange bias effect in ferromagnet/antiferromagnet bilayers, where both ferromagnet and antiferromagnet are epitaxially grown. Numerical model calculations predict an approximately 45° period for the sign switching of the exchange-bias field, depending on the ratio between magnetocrystalline anisotropy and exchange-coupling constant. The switching of the sign is indicative of a competition between a fourfold magnetocrystalline anisotropy of the ferromagnet and a unidirectional anisotropy field of the exchange coupling. This predicted unusual angular-dependent exchange bias and its magnetization switching process are confirmed by measurements on fully epitaxial Co 3 FeN/MnN bilayers by longitudinal and transverse magneto-optic Kerr effect magnetometry. These results provide a deeper understanding of the exchange coupling phenomena in fully epitaxial bilayers with tailored materials and open up a complex switching energy landscape engineering by anisotropies.

45° sign switching of effective exchange bias due to competing anisotropies in fully epitaxial Co3FeN/MnN bilayers

NASA Astrophysics Data System (ADS)

Hajiri, T.; Yoshida, T.; Filianina, M.; Jaiswal, S.; Borie, B.; Asano, H.; Zabel, H.; Kläui, M.

2018-01-01

We report an unusual angular-dependent exchange bias effect in ferromagnet/antiferromagnet bilayers, where both ferromagnet and antiferromagnet are epitaxially grown. Numerical model calculations predict an approximately 45° period for the sign switching of the exchange-bias field, depending on the ratio between magnetocrystalline anisotropy and exchange-coupling constant. The switching of the sign is indicative of a competition between a fourfold magnetocrystalline anisotropy of the ferromagnet and a unidirectional anisotropy field of the exchange coupling. This predicted unusual angular-dependent exchange bias and its magnetization switching process are confirmed by measurements on fully epitaxial Co3FeN/MnN bilayers by longitudinal and transverse magneto-optic Kerr effect magnetometry. These results provide a deeper understanding of the exchange coupling phenomena in fully epitaxial bilayers with tailored materials and open up a complex switching energy landscape engineering by anisotropies.

Structural Basis for Conserved Regulation and Adaptation of the Signal Recognition Particle Targeting Complex.

PubMed

Wild, Klemens; Bange, Gert; Motiejunas, Domantas; Kribelbauer, Judith; Hendricks, Astrid; Segnitz, Bernd; Wade, Rebecca C; Sinning, Irmgard

2016-07-17

The signal recognition particle (SRP) is a ribonucleoprotein complex with a key role in targeting and insertion of membrane proteins. The two SRP GTPases, SRP54 (Ffh in bacteria) and FtsY (SRα in eukaryotes), form the core of the targeting complex (TC) regulating the SRP cycle. The architecture of the TC and its stimulation by RNA has been described for the bacterial SRP system while this information is lacking for other domains of life. Here, we present the crystal structures of the GTPase heterodimers of archaeal (Sulfolobus solfataricus), eukaryotic (Homo sapiens), and chloroplast (Arabidopsis thaliana) SRP systems. The comprehensive structural comparison combined with Brownian dynamics simulations of TC formation allows for the description of the general blueprint and of specific adaptations of the quasi-symmetric heterodimer. Our work defines conserved external nucleotide-binding sites for SRP GTPase activation by RNA. Structural analyses of the GDP-bound, post-hydrolysis states reveal a conserved, magnesium-sensitive switch within the I-box. Overall, we provide a general model for SRP cycle regulation by RNA. Copyright © 2016 Elsevier Ltd. All rights reserved.

Output regulation control for switched stochastic delay systems with dissipative property under error-dependent switching

NASA Astrophysics Data System (ADS)

Li, L. L.; Jin, C. L.; Ge, X.

2018-01-01

In this paper, the output regulation problem with dissipative property for a class of switched stochastic delay systems is investigated, based on an error-dependent switching law. Under the assumption that none subsystem is solvable for the problem, a sufficient condition is derived by structuring multiple Lyapunov-Krasovskii functionals with respect to multiple supply rates, via designing error feedback regulators. The condition is also established when dissipative property reduces to passive property. Finally, two numerical examples are given to demonstrate the feasibility and efficiency of the present method.

Determination of pulse energy dependence for skin denaturation from 585nm fibre laser

NASA Astrophysics Data System (ADS)

Mujica-Ascencio, S.; Velazquez-Gonzalez, J. S.; Mujica-Ascencio, C.; Alvarez-Chavez, J. A.

2014-05-01

In this paper, simulation and mathematical analysis for the determination of pulse energy from a Q-switched Yb3+-doped fibre laser is required in Port Wine Stain (PWS) treatment. The pulse energy depends on average power, gain, volume, repetition rate and pulse duration. In some treatments such as Selective Photothermolysis (SP), the peak power at the end of the optical fibre and pulse duration can be obtained and modified via a cavity design. For that purpose, a 585nm optical fibre laser full design which considers all of the above besides the average losses through the optical devices proposed for the design and the Ytterbium optical fibre overall gain will be presented.

Zampanolide Binding to Tubulin Indicates Cross-Talk of Taxane Site with Colchicine and Nucleotide Sites.

PubMed

Field, Jessica J; Pera, Benet; Gallego, Juan Estévez; Calvo, Enrique; Rodríguez-Salarichs, Javier; Sáez-Calvo, Gonzalo; Zuwerra, Didier; Jordi, Michel; Andreu, José M; Prota, Andrea E; Ménchon, Grégory; Miller, John H; Altmann, Karl-Heinz; Díaz, J Fernando

2018-03-23

The marine natural product zampanolide and analogues thereof constitute a new chemotype of taxoid site microtubule-stabilizing agents with a covalent mechanism of action. Zampanolide-ligated tubulin has the switch-activation loop (M-loop) in the assembly prone form and, thus, represents an assembly activated state of the protein. In this study, we have characterized the biochemical properties of the covalently modified, activated tubulin dimer, and we have determined the effect of zampanolide on tubulin association and the binding of tubulin ligands at other binding sites. Tubulin activation by zampanolide does not affect its longitudinal oligomerization but does alter its lateral association properties. The covalent binding of zampanolide to β-tubulin affects both the colchicine site, causing a change of the quantum yield of the bound ligand, and the exchangeable nucleotide binding site, reducing the affinity for the nucleotide. While these global effects do not change the binding affinity of 2-methoxy-5-(2,3,4-trimethoxyphenyl)-2,4,6-cycloheptatrien-1-one (MTC) (a reversible binder of the colchicine site), the binding affinity of a fluorescent analogue of GTP (Mant-GTP) at the nucleotide E-site is reduced from 12 ± 2 × 10 5 M -1 in the case of unmodified tubulin to 1.4 ± 0.3 × 10 5 M -1 in the case of the zampanolide tubulin adduct, indicating signal transmission between the taxane site and the colchicine and nucleotide sites of β-tubulin.

Reconfigurable optofluidic switch for generation of optical pulse width modulation based on tunable reflective interface.

PubMed

Mansuori, M; Zareei, G H; Hashemi, H

2015-10-01

We present a numerical method for generation of optical pulse width modulation (PWM) based on tunable reflective interface by using a microfluidic droplet. We demonstrate a single layer, planar, optofluidic PWM switch that is driven by excited alternating microbubbles. The main parameters of generation of this PWM such as frequency and speed of switching can be controlled by the mass flow rates of input fluids, and the shape of plug or droplet. Advantages of this design are the reconfigurability in design and the easy control of the switching parameters. The validation of the proposed design is carried out by employing the finite element method (FEM) for the mechanical simulation and the finite-difference time-domain (FDTD) for the optical simulation.

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

NASA Astrophysics Data System (ADS)

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

2014-02-01

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.

A scalable silicon photonic chip-scale optical switch for high performance computing systems.

PubMed

Yu, Runxiang; Cheung, Stanley; Li, Yuliang; Okamoto, Katsunari; Proietti, Roberto; Yin, Yawei; Yoo, S J B

2013-12-30

This paper discusses the architecture and provides performance studies of a silicon photonic chip-scale optical switch for scalable interconnect network in high performance computing systems. The proposed switch exploits optical wavelength parallelism and wavelength routing characteristics of an Arrayed Waveguide Grating Router (AWGR) to allow contention resolution in the wavelength domain. Simulation results from a cycle-accurate network simulator indicate that, even with only two transmitter/receiver pairs per node, the switch exhibits lower end-to-end latency and higher throughput at high (>90%) input loads compared with electronic switches. On the device integration level, we propose to integrate all the components (ring modulators, photodetectors and AWGR) on a CMOS-compatible silicon photonic platform to ensure a compact, energy efficient and cost-effective device. We successfully demonstrate proof-of-concept routing functions on an 8 × 8 prototype fabricated using foundry services provided by OpSIS-IME.

The temperature dependence of the pressure switching of Jahn Teller deformation in the deuterated ammonium copper Tutton salt

NASA Astrophysics Data System (ADS)

Augustyniak, Maria A.; Krupski, Marcin

1999-09-01

The pressure switch of the Jahn-Teller deformation direction in (ND 4) 2Cu(SO 4) 2·6D 2O was investigated in the temperature range 130-320 K. Below 295 K, the new, pressure-induced phase, is stable under ambient pressure. Switching back is observed on heating to above 297 K. In the range 150-295 K a strong temperature dependence of the switching pressure (from 24 to 450 MPa) is observed. Below 150 K, the switching process is slow and a coexistence of two phases is observed. We conclude that the switch of the Cu(D 2O) 6 complex deformation direction is the Jahn-Teller response to the changes in the hydrogen bond system.

Fully parameterized model of a voltage-driven capacitive coupled micromachined ohmic contact switch for RF applications

NASA Astrophysics Data System (ADS)

Heeb, Peter; Tschanun, Wolfgang; Buser, Rudolf

2012-03-01

A comprehensive and completely parameterized model is proposed to determine the related electrical and mechanical dynamic system response of a voltage-driven capacitive coupled micromechanical switch. As an advantage over existing parameterized models, the model presented in this paper returns within few seconds all relevant system quantities necessary to design the desired switching cycle. Moreover, a sophisticated and detailed guideline is given on how to engineer a MEMS switch. An analytical approach is used throughout the modelling, providing representative coefficients in a set of two coupled time-dependent differential equations. This paper uses an equivalent mass moving along the axis of acceleration and a momentum absorption coefficient. The model describes all the energies transferred: the energy dissipated in the series resistor that models the signal attenuation of the bias line, the energy dissipated in the squeezed film, the stored energy in the series capacitor that represents a fixed separation in the bias line and stops the dc power in the event of a short circuit between the RF and dc path, the energy stored in the spring mechanism, and the energy absorbed by mechanical interaction at the switch contacts. Further, the model determines the electrical power fed back to the bias line. The calculated switching dynamics are confirmed by the electrical characterization of the developed RF switch. The fabricated RF switch performs well, in good agreement with the modelled data, showing a transition time of 7 µs followed by a sequence of bounces. Moreover, the scattering parameters exhibit an isolation in the off-state of >8 dB and an insertion loss in the on-state of <0.6 dB up to frequencies of 50 GHz. The presented model is intended to be integrated into standard circuit simulation software, allowing circuit engineers to design the switch bias line, to minimize induced currents and cross actuation, as well as to find the mechanical structure dimensions necessary for the desired switching time and actuation voltage waveform. Moreover, process related design rules can be automatically verified.

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

NASA Astrophysics Data System (ADS)

Zhengang, Lu; Hongyang, Yu; Xi, Yang

2017-05-01

The Modular Multilevel Converter (MMC) is one of the most attractive topologies in recent years for medium or high voltage industrial applications, such as high voltage dc transmission (HVDC) and medium voltage varying speed motor drive. The wide adoption of MMCs in industry is mainly due to its flexible expandability, transformer-less configuration, common dc bus, high reliability from redundancy, and so on. But, when the sub module number of MMC is more, the test of MMC controller will cost more time and effort. Hardware in the loop test based on real time simulator will save a lot of time and money caused by the MMC test. And due to the flexible of HIL, it becomes more and more popular in the industry area. The MMC modelling method remains an important issue for the MMC HIL test. Specifically, the VSC model should realistically reflect the nonlinear device switching characteristics, switching and conduction losses, tailing current, and diode reverse recovery behaviour of a realistic converter. In this paper, an IGBT switching characteristic curve embedded half-bridge MMC modelling method is proposed. This method is based on the switching curve referring and sample circuit calculation, and it is sample for implementation. Based on the proposed method, a FPGA real time simulation is carried out with 200ns sample time. The real time simulation results show the proposed method is correct.

Global exponential stability for switched memristive neural networks with time-varying delays.

PubMed

Xin, Youming; Li, Yuxia; Cheng, Zunshui; Huang, Xia

2016-08-01

This paper considers the problem of exponential stability for switched memristive neural networks (MNNs) with time-varying delays. Different from most of the existing papers, we model a memristor as a continuous system, and view switched MNNs as switched neural networks with uncertain time-varying parameters. Based on average dwell time technique, mode-dependent average dwell time technique and multiple Lyapunov-Krasovskii functional approach, two conditions are derived to design the switching signal and guarantee the exponential stability of the considered neural networks, which are delay-dependent and formulated by linear matrix inequalities (LMIs). Finally, the effectiveness of the theoretical results is demonstrated by two numerical examples. Copyright © 2016 Elsevier Ltd. All rights reserved.

All-optical transistors and logic gates using a parity-time-symmetric Y-junction: Design and simulation

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

Ding, Shulin; Wang, Guo Ping, E-mail: gpwang@szu.edu.cn; College of Electronic Science and Technology, Shenzhen University, Shenzhen 518060

Classical nonlinear or quantum all-optical transistors are dependent on the value of input signal intensity or need extra co-propagating beams. In this paper, we present a kind of all-optical transistors constructed with parity-time (PT)-symmetric Y-junctions, which perform independently on the value of signal intensity in an unsaturated gain case and can also work after introducing saturated gain. Further, we show that control signal can switch the device from amplification of peaks in time to transformation of peaks to amplified troughs. By using these PT-symmetric Y-junctions with currently available materials and technologies, we can implement interesting logic functions such as NOTmore » and XOR (exclusive OR) gates, implying potential applications of such structures in designing optical logic gates, optical switches, and signal transformations or amplifications.« less

Mass removal modes in the laser ablation of silicon by a Q-switched diode-pumped solid-state laser (DPSSL)

NASA Astrophysics Data System (ADS)

Lim, Daniel J.; Ki, Hyungson; Mazumder, Jyoti

2006-06-01

A fundamental study on the Q-switched diode-pumped solid-state laser interaction with silicon was performed both experimentally and numerically. Single pulse drilling experiments were conducted on N-type silicon wafers by varying the laser intensity from 108-109 W cm-2 to investigate how the mass removal mechanism changes depending on the laser intensity. Hole width and depth were measured and surface morphology was studied using scanning electron microscopy. For the numerical model study, Ki et al's self-consistent continuous-wave laser drilling model (2001 J. Phys. D: Appl. Phys. 34 364-72) was modified to treat the solidification phenomenon between successive laser pulses. The model has the capabilities of simulating major interaction physics, such as melt flow, heat transfer, evaporation, homogeneous boiling, multiple reflections and surface evolution. This study presents some interesting results on how the mass removal mode changes as the laser intensity increases.

Computer analysis of the negative differential resistance switching phenomenon of double-injection devices

NASA Technical Reports Server (NTRS)

Shieh, Tsay-Jiu

1989-01-01

By directly solving the semiconductor differential equations for the double-injection (DI) devices involving two interacting deep levels, the authors studied the negative differential resistance switching characteristic and its relationship with the device dimension, doping level, and dependence on the deep impurity profile. Computer simulation showed that although one can increase the threshold voltage by increasing the device length, the excessive holding voltage that would follow would put this device in a very limited application such as pulse power source. The excessive leakage current in the low conductance state also jeopardizes the attempt to use the device for any practical purpose. Unless there are new materials and deep impurities found that have a great differential hole and electron capture cross sections and a reasonable energy bandgap for low intrinsic carrier concentration, no big improvement in the fate of DI devices is expected in the near future.

Electrical model of dielectric barrier discharge homogenous and filamentary modes

NASA Astrophysics Data System (ADS)

López-Fernandez, J. A.; Peña-Eguiluz, R.; López-Callejas, R.; Mercado-Cabrera, A.; Valencia-Alvarado, R.; Muñoz-Castro, A.; Rodríguez-Méndez, B. G.

2017-01-01

This work proposes an electrical model that combines homogeneous and filamentary modes of an atmospheric pressure dielectric barrier discharge cell. A voltage controlled electric current source has been utilized to implement the power law equation that represents the homogeneous discharge mode, which starts when the gas breakdown voltage is reached. The filamentary mode implies the emergence of electric current conducting channels (microdischarges), to add this phenomenon an RC circuit commutated by an ideal switch has been proposed. The switch activation occurs at a higher voltage level than the gas breakdown voltage because it is necessary to impose a huge electric field that contributes to the appearance of streamers. The model allows the estimation of several electric parameters inside the reactor that cannot be measured. Also, it is possible to appreciate the modes of the DBD depending on the applied voltage magnitude. Finally, it has been recognized a good agreement between simulation outcomes and experimental results.

How to turn a genetic circuit into a synthetic tunable oscillator, or a bistable switch.

PubMed

Marucci, Lucia; Barton, David A W; Cantone, Irene; Ricci, Maria Aurelia; Cosma, Maria Pia; Santini, Stefania; di Bernardo, Diego; di Bernardo, Mario

2009-12-07

Systems and Synthetic Biology use computational models of biological pathways in order to study in silico the behaviour of biological pathways. Mathematical models allow to verify biological hypotheses and to predict new possible dynamical behaviours. Here we use the tools of non-linear analysis to understand how to change the dynamics of the genes composing a novel synthetic network recently constructed in the yeast Saccharomyces cerevisiae for In-vivo Reverse-engineering and Modelling Assessment (IRMA). Guided by previous theoretical results that make the dynamics of a biological network depend on its topological properties, through the use of simulation and continuation techniques, we found that the network can be easily turned into a robust and tunable synthetic oscillator or a bistable switch. Our results provide guidelines to properly re-engineering in vivo the network in order to tune its dynamics.

Fast simulation of packet loss rates in a shared buffer communications switch

NASA Technical Reports Server (NTRS)

Chang, Cheng-Shang; Heidelberger, Philip; Shahabuddin, Perwez

1993-01-01

This paper describes an efficient technique for estimating, via simulation, the probability of buffer overflows in a queueing model that arises in the analysis of ATM (Asynchronous Transfer Mode) communication switches. There are multiple streams of (autocorrelated) traffic feeding the switch that has a buffer of finite capacity. Each stream is designated as either being of high or low priority. When the queue length reaches a certain threshold, only high priority packets are admitted to the switch's buffer. The problem is to estimate the loss rate of high priority packets. An asymptotically optimal importance sampling approach is developed for this rare event simulation problem. In this approach, the importance sampling is done in two distinct phases. In the first phase, an importance sampling change of measure is used to bring the queue length up to the threshold at which low priority packets get rejected. In the second phase, a different importance sampling change of measure is used to move the queue length from the threshold to the buffer capacity.

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

NASA Astrophysics Data System (ADS)

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.

DNA Replication Origins in Immunoglobulin Switch Regions Regulate Class Switch Recombination in an R-Loop-Dependent Manner.

PubMed

Wiedemann, Eva-Maria; Peycheva, Mihaela; Pavri, Rushad

2016-12-13

Class switch recombination (CSR) at the immunoglobulin heavy chain (IgH) locus generates antibody isotypes. CSR depends on double-strand breaks (DSBs) induced by activation-induced cytidine deaminase (AID). Although DSB formation and repair machineries are active in G1 phase, efficient CSR is dependent on cell proliferation and S phase entry; however, the underlying mechanisms are obscure. Here, we show that efficient CSR requires the replicative helicase, the Mcm complex. Mcm proteins are enriched at IgH switch regions during CSR, leading to assembly of facultative replication origins that require Mcm helicase function for productive CSR. Assembly of CSR-associated origins is facilitated by R loops and promotes the physical proximity (synapsis) of recombining switch regions, which is reduced by R loop inhibition or Mcm complex depletion. Thus, R loops contribute to replication origin specification that promotes DSB resolution in CSR. This suggests a mechanism for the dependence of CSR on S phase and cell division. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Size dependence of spin-torque induced magnetic switching in CoFeB-based perpendicular magnetization tunnel junctions (invited)

NASA Astrophysics Data System (ADS)

Sun, J. Z.; Trouilloud, P. L.; Gajek, M. J.; Nowak, J.; Robertazzi, R. P.; Hu, G.; Abraham, D. W.; Gaidis, M. C.; Brown, S. L.; O'Sullivan, E. J.; Gallagher, W. J.; Worledge, D. C.

2012-04-01

CoFeB-based magnetic tunnel junctions with perpendicular magnetic anisotropy are used as a model system for studies of size dependence in spin-torque-induced magnetic switching. For integrated solid-state memory applications, it is important to understand the magnetic and electrical characteristics of these magnetic tunnel junctions as they scale with tunnel junction size. Size-dependent magnetic anisotropy energy, switching voltage, apparent damping, and anisotropy field are systematically compared for devices with different materials and fabrication treatments. Results reveal the presence of sub-volume thermal fluctuation and reversal, with a characteristic length-scale of the order of approximately 40 nm, depending on the strength of the perpendicular magnetic anisotropy and exchange stiffness. To have the best spin-torque switching efficiency and best stability against thermal activation, it is desirable to optimize the perpendicular anisotropy strength with the junction size for intended use. It also is important to ensure strong exchange-stiffness across the magnetic thin film. These combine to give an exchange length that is comparable or larger than the lateral device size for efficient spin-torque switching.

All-optical switch consisting of two-stage interferometers controlled by using saturable absorption of monolayer graphene.

PubMed

Oya, Masayuki; Kishikawa, Hiroki; Goto, Nobuo; Yanagiya, Shin-ichiro

2012-11-19

At routing nodes in future photonic networks, pico-second switching will be a key function. We propose an all-optical switch consisting of two-stage Mach-Zehnder interferometers, whose arms contain graphene saturable absorption films. Optical amplitudes along the interferometers are controlled to perform switching between two output ports instead of phase control used in conventional switches. Since only absorption is used for realizing complete switching, insertion loss of 10.2 dB is accompanied in switching. Picosecond response can be expected because of the fast response of saturable absorption of graphene. The switching characteristics are theoretically analyzed and numerically simulated by the finite-difference beam propagation method (FD-BPM).

Interaction-induced conducting-non-conducting transition of ultra-cold atoms in one-dimensional optical lattices

NASA Astrophysics Data System (ADS)

Chien, Chih-Chun; Gruss, Daniel; Di Ventra, Massimiliano; Zwolak, Michael

2013-06-01

The study of time-dependent, many-body transport phenomena is increasingly within reach of ultra-cold atom experiments. We show that the introduction of spatially inhomogeneous interactions, e.g., generated by optically controlled collisions, induce negative differential conductance in the transport of atoms in one-dimensional optical lattices. Specifically, we simulate the dynamics of interacting fermionic atoms via a micro-canonical transport formalism within both a mean-field and a higher-order approximation, as well as with a time-dependent density-matrix renormalization group (DMRG). For weakly repulsive interactions, a quasi-steady-state atomic current develops that is similar to the situation occurring for electronic systems subject to an external voltage bias. At the mean-field level, we find that this atomic current is robust against the details of how the interaction is switched on. Further, a conducting-non-conducting transition exists when the interaction imbalance exceeds some threshold from both our approximate and time-dependent DMRG simulations. This transition is preceded by the atomic equivalent of negative differential conductivity observed in transport across solid-state structures.

Density-dependent liquid nitromethane decomposition: molecular dynamics simulations based on ReaxFF.

PubMed

Rom, Naomi; Zybin, Sergey V; van Duin, Adri C T; Goddard, William A; Zeiri, Yehuda; Katz, Gil; Kosloff, Ronnie

2011-09-15

The decomposition mechanism of hot liquid nitromethane at various compressions was studied using reactive force field (ReaxFF) molecular dynamics simulations. A competition between two different initial thermal decomposition schemes is observed, depending on compression. At low densities, unimolecular C-N bond cleavage is the dominant route, producing CH(3) and NO(2) fragments. As density and pressure rise approaching the Chapman-Jouget detonation conditions (∼30% compression, >2500 K) the dominant mechanism switches to the formation of the CH(3)NO fragment via H-transfer and/or N-O bond rupture. The change in the decomposition mechanism of hot liquid NM leads to a different kinetic and energetic behavior, as well as products distribution. The calculated density dependence of the enthalpy change correlates with the change in initial decomposition reaction mechanism. It can be used as a convenient and useful global parameter for the detection of reaction dynamics. Atomic averaged local diffusion coefficients are shown to be sensitive to the reactions dynamics, and can be used to distinguish between time periods where chemical reactions occur and diffusion-dominated, nonreactive time periods. © 2011 American Chemical Society

Two‐phase designs for joint quantitative‐trait‐dependent and genotype‐dependent sampling in post‐GWAS regional sequencing

PubMed Central

Espin‐Garcia, Osvaldo; Craiu, Radu V.

2017-01-01

ABSTRACT We evaluate two‐phase designs to follow‐up findings from genome‐wide association study (GWAS) when the cost of regional sequencing in the entire cohort is prohibitive. We develop novel expectation‐maximization‐based inference under a semiparametric maximum likelihood formulation tailored for post‐GWAS inference. A GWAS‐SNP (where SNP is single nucleotide polymorphism) serves as a surrogate covariate in inferring association between a sequence variant and a normally distributed quantitative trait (QT). We assess test validity and quantify efficiency and power of joint QT‐SNP‐dependent sampling and analysis under alternative sample allocations by simulations. Joint allocation balanced on SNP genotype and extreme‐QT strata yields significant power improvements compared to marginal QT‐ or SNP‐based allocations. We illustrate the proposed method and evaluate the sensitivity of sample allocation to sampling variation using data from a sequencing study of systolic blood pressure. PMID:29239496

Glucose inhibits cardiac muscle maturation through nucleotide biosynthesis.

PubMed

Nakano, Haruko; Minami, Itsunari; Braas, Daniel; Pappoe, Herman; Wu, Xiuju; Sagadevan, Addelynn; Vergnes, Laurent; Fu, Kai; Morselli, Marco; Dunham, Christopher; Ding, Xueqin; Stieg, Adam Z; Gimzewski, James K; Pellegrini, Matteo; Clark, Peter M; Reue, Karen; Lusis, Aldons J; Ribalet, Bernard; Kurdistani, Siavash K; Christofk, Heather; Nakatsuji, Norio; Nakano, Atsushi

2017-12-12

The heart switches its energy substrate from glucose to fatty acids at birth, and maternal hyperglycemia is associated with congenital heart disease. However, little is known about how blood glucose impacts heart formation. Using a chemically defined human pluripotent stem-cell-derived cardiomyocyte differentiation system, we found that high glucose inhibits the maturation of cardiomyocytes at genetic, structural, metabolic, electrophysiological, and biomechanical levels by promoting nucleotide biosynthesis through the pentose phosphate pathway. Blood glucose level in embryos is stable in utero during normal pregnancy, but glucose uptake by fetal cardiac tissue is drastically reduced in late gestational stages. In a murine model of diabetic pregnancy, fetal hearts showed cardiomyopathy with increased mitotic activity and decreased maturity. These data suggest that high glucose suppresses cardiac maturation, providing a possible mechanistic basis for congenital heart disease in diabetic pregnancy.

Glucose inhibits cardiac muscle maturation through nucleotide biosynthesis

PubMed Central

Nakano, Haruko; Minami, Itsunari; Braas, Daniel; Pappoe, Herman; Wu, Xiuju; Sagadevan, Addelynn; Vergnes, Laurent; Fu, Kai; Morselli, Marco; Dunham, Christopher; Ding, Xueqin; Stieg, Adam Z; Gimzewski, James K; Pellegrini, Matteo; Clark, Peter M; Reue, Karen; Lusis, Aldons J; Ribalet, Bernard; Kurdistani, Siavash K; Christofk, Heather; Nakatsuji, Norio

2017-01-01

The heart switches its energy substrate from glucose to fatty acids at birth, and maternal hyperglycemia is associated with congenital heart disease. However, little is known about how blood glucose impacts heart formation. Using a chemically defined human pluripotent stem-cell-derived cardiomyocyte differentiation system, we found that high glucose inhibits the maturation of cardiomyocytes at genetic, structural, metabolic, electrophysiological, and biomechanical levels by promoting nucleotide biosynthesis through the pentose phosphate pathway. Blood glucose level in embryos is stable in utero during normal pregnancy, but glucose uptake by fetal cardiac tissue is drastically reduced in late gestational stages. In a murine model of diabetic pregnancy, fetal hearts showed cardiomyopathy with increased mitotic activity and decreased maturity. These data suggest that high glucose suppresses cardiac maturation, providing a possible mechanistic basis for congenital heart disease in diabetic pregnancy. PMID:29231167

Hyperpolarization-activated current (I(h)) in vestibular calyx terminals: characterization and role in shaping postsynaptic events.

PubMed

Meredith, Frances L; Benke, Tim A; Rennie, Katherine J

2012-12-01

Calyx afferent terminals engulf the basolateral region of type I vestibular hair cells, and synaptic transmission across the vestibular type I hair cell/calyx is not well understood. Calyces express several ionic conductances, which may shape postsynaptic potentials. These include previously described tetrodotoxin-sensitive inward Na(+) currents, voltage-dependent outward K(+) currents and a K(Ca) current. Here, we characterize an inwardly rectifying conductance in gerbil semicircular canal calyx terminals (postnatal days 3-45), sensitive to voltage and to cyclic nucleotides. Using whole-cell patch clamp, we recorded from isolated calyx terminals still attached to their type I hair cells. A slowly activating, noninactivating current (I(h)) was seen with hyperpolarizing voltage steps negative to the resting potential. External Cs(+) (1-5 mM) and ZD7288 (100 μM) blocked the inward current by 97 and 83 %, respectively, confirming that I(h) was carried by hyperpolarization-activated, cyclic nucleotide gated channels. Mean half-activation voltage of I(h) was -123 mV, which shifted to -114 mV in the presence of cAMP. Activation of I(h) was well described with a third order exponential fit to the current (mean time constant of activation, τ, was 190 ms at -139 mV). Activation speeded up significantly (τ=136 and 127 ms, respectively) when intracellular cAMP and cGMP were present, suggesting that in vivo I(h) could be subject to efferent modulation via cyclic nucleotide-dependent mechanisms. In current clamp, hyperpolarizing current steps produced a time-dependent depolarizing sag followed by either a rebound afterdepolarization or an action potential. Spontaneous excitatory postsynaptic potentials (EPSPs) became larger and wider when I(h) was blocked with ZD7288. In a three-dimensional mathematical model of the calyx terminal based on Hodgkin-Huxley type ionic conductances, removal of I(h) similarly increased the EPSP, whereas cAMP slightly decreased simulated EPSP size and width.

Bone and kidney toxicity induced by nucleotide analogues in patients affected by HBV-related chronic hepatitis: a longitudinal study.

PubMed

Maggi, Paolo; Montinaro, Vincenzo; Leone, Armando; Fasano, Massimo; Volpe, Anna; Bellacosa, Chiara; Grattagliano, Vito; Coladonato, Laura; Lapadula, Giovanni; Santantonio, Teresa; Angarano, Gioacchino

2015-04-01

Nucleotide analogues may promote renal and bone toxicity. The aim of the present study was to evaluate markers of osteorenal toxicity in patients affected by hepatitis B virus-related chronic hepatitis treated with lamivudine plus adefovir who were switched to tenofovir. We evaluated 60 consecutive patients at the time of the switch of treatment and after 1, 3, 6, 9 and 12 months. The mean baseline estimated glomerular filtration rate (eGFR) was 89.3 ± 19.0 mL/min/1.73 m(2). During the study period we observed a reduction in mean eGFR up to 6 months after switching to tenofovir, and this remained stable for the last two timepoints. At the end of study, the mean eGFR was 82.6 ± 21.5 mL/min/1.73 m(2), a reduction of 7.5%. The mean baseline proteinuria was 202.6 ± 237.6 mg/24 h. Microhaematuria was observed in 22.6% of patients and hypophosphataemia in 18.6%. After 1 month of tenofovir, we observed a worsening of serum phosphate and parathyroid hormone levels, haemoglobinuria and 24 h proteinuria. After 3 and 12 months of tenofovir, these data tended to recover to baseline levels. A total of 92.6% of patients at baseline had hypovitaminosis D. After supplementation with cholecalciferol, this percentage decreased significantly. We observed a reduced bone mineral density (BMD) in 52.7% of patients at baseline; this increased to 77.8% after 6 months of tenofovir, but at the last timepoint the percentage of patients with a reduced BMD had fallen to a level above the baseline. In conclusion, patients exposed to lamivudine plus adefovir showed relevant osteorenal damage. The switch to tenofovir provoked a slight reduction in eGFR that stabilized after 6 months. The reduced BMD at baseline did not worsen under tenofovir treatment. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

SELECTED ANNOTATED BIBLIOGRAPHY ON SYSTEMS OF THEORETICAL DEVICES,

DTIC Science & Technology

BIONICS, BIBLIOGRAPHIES), (*BIBLIOGRAPHIES, BIONICS), (*CYBERNETICS, BIBLIOGRAPHIES), MATHEMATICS, COMPUTER LOGIC, NETWORKS, NERVOUS SYSTEM , THEORY , SEQUENCE SWITCHES, SWITCHING CIRCUITS, REDUNDANT COMPONENTS, LEARNING, MATHEMATICAL MODELS, BEHAVIOR, NERVES, SIMULATION, NERVE CELLS

Activation of the Cph1-Dependent MAP Kinase Signaling Pathway Induces White-Opaque Switching in Candida albicans

PubMed Central

Ramírez-Zavala, Bernardo; Weyler, Michael; Gildor, Tsvia; Schmauch, Christian; Kornitzer, Daniel; Arkowitz, Robert; Morschhäuser, Joachim

2013-01-01

Depending on the environmental conditions, the pathogenic yeast Candida albicans can undergo different developmental programs, which are controlled by dedicated transcription factors and upstream signaling pathways. C. albicans strains that are homozygous at the mating type locus can switch from the normal yeast form (white) to an elongated cell type (opaque), which is the mating-competent form of this fungus. Both white and opaque cells use the Ste11-Hst7-Cek1/Cek2 MAP kinase signaling pathway to react to the presence of mating pheromone. However, while opaque cells employ the transcription factor Cph1 to induce the mating response, white cells recruit a different downstream transcription factor, Tec1, to promote the formation of a biofilm that facilitates mating of opaque cells in the population. The switch from the white to the opaque cell form is itself induced by environmental signals that result in the upregulation of the transcription factor Wor1, the master regulator of white-opaque switching. To get insight into the upstream signaling pathways controlling the switch, we expressed all C. albicans protein kinases from a tetracycline-inducible promoter in a switching-competent strain. Screening of this library of strains showed that a hyperactive form of Ste11 lacking its N-terminal domain (Ste11ΔN467) efficiently stimulated white cells to switch to the opaque phase, a behavior that did not occur in response to pheromone. Ste11ΔN467-induced switching specifically required the downstream MAP kinase Cek1 and its target transcription factor Cph1, but not Cek2 and Tec1, and forced expression of Cph1 also promoted white-opaque switching in a Wor1-dependent manner. Therefore, depending on the activation mechanism, components of the pheromone-responsive MAP kinase pathway can be reconnected to stimulate an alternative developmental program, switching of white cells to the mating-competent opaque phase. PMID:24130492

Cyclic nucleotide binding proteins in the Arabidopsis thaliana and Oryza sativa genomes

PubMed Central

Bridges, Dave; Fraser, Marie E; Moorhead, Greg BG

2005-01-01

Background Cyclic nucleotides are ubiquitous intracellular messengers. Until recently, the roles of cyclic nucleotides in plant cells have proven difficult to uncover. With an understanding of the protein domains which can bind cyclic nucleotides (CNB and GAF domains) we scanned the completed genomes of the higher plants Arabidopsis thaliana (mustard weed) and Oryza sativa (rice) for the effectors of these signalling molecules. Results Our analysis found that several ion channels and a class of thioesterases constitute the possible cyclic nucleotide binding proteins in plants. Contrary to some reports, we found no biochemical or bioinformatic evidence for a plant cyclic nucleotide regulated protein kinase, suggesting that cyclic nucleotide functions in plants have evolved differently than in mammals. Conclusion This paper provides a molecular framework for the discussion of cyclic nucleotide function in plants, and resolves a longstanding debate about the presence of a cyclic nucleotide dependent kinase in plants. PMID:15644130

Statistical electric field and switching time distributions in PZT 1Nb2Sr ceramics: Crystal- and microstructure effects

NASA Astrophysics Data System (ADS)

Zhukov, Sergey; Kungl, Hans; Genenko, Yuri A.; von Seggern, Heinz

2014-01-01

Dispersive polarization response of ferroelectric PZT ceramics is analyzed assuming the inhomogeneous field mechanism of polarization switching. In terms of this model, the local polarization switching proceeds according to the Kolmogorov-Avrami-Ishibashi scenario with the switching time determined by the local electric field. As a result, the total polarization reversal is dominated by the statistical distribution of the local field magnitudes. Microscopic parameters of this model (the high-field switching time and the activation field) as well as the statistical field and consequent switching time distributions due to disorder at a mesoscopic scale can be directly determined from a set of experiments measuring the time dependence of the total polarization switching, when applying electric fields of different magnitudes. PZT 1Nb2Sr ceramics with Zr/Ti ratios 51.5/48.5, 52.25/47.75, and 60/40 with four different grain sizes each were analyzed following this approach. Pronounced differences of field and switching time distributions were found depending on the Zr/Ti ratios. Varying grain size also affects polarization reversal parameters, but in another way. The field distributions remain almost constant with grain size whereas switching times and activation field tend to decrease with increasing grain size. The quantitative changes of the latter parameters with grain size are very different depending on composition. The origin of the effects on the field and switching time distributions are related to differences in structural and microstructural characteristics of the materials and are discussed with respect to the hysteresis loops observed under bipolar electrical cycling.

Single Active Switch PV Inverter

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

Ramanan, V. R.; Pan, Zhiguo

This report presents a new PV inverter topology that uses only one active switch instead of 7 active switches in a conventional PV inverter. It has a buck boost converter and operates at discontinuous current control mode, which can reduce the output stage from an active switch bridge to a thyristor bridge. This concept, if successfully demonstrated, may have great cost and size/weight benefits over conventional solutions. Since the proposed topology is completely different from the traditional boost converter plus voltage source inverter approach, there is no existing control/modulation scheme available. A new modulation scheme for both the main switchmore » and the thyristors has been developed. An active clamping circuit has also been proposed to reduce switching losses and voltage spike during the switching transient. A simulation model has been set up to validate the control algorithm and clamping circuit. Simulated results show that a proposed 10 kW PV inverter can reach 5% total harmonic distortion (THD), 98.8% peak efficiency with only one main active switch, and an inductor weighing less than 3 kg. Based on that, a 10 kW prototype converter has been designed and built.« less

Neural network for control of rearrangeable Clos networks.

PubMed

Park, Y K; Cherkassky, V

1994-09-01

Rapid evolution in the field of communication networks requires high speed switching technologies. This involves a high degree of parallelism in switching control and routing performed at the hardware level. The multistage crossbar networks have always been attractive to switch designers. In this paper a neural network approach to controlling a three-stage Clos network in real time is proposed. This controller provides optimal routing of communication traffic requests on a call-by-call basis by rearranging existing connections, with a minimum length of rearrangement sequence so that a new blocked call request can be accommodated. The proposed neural network controller uses Paull's rearrangement algorithm, along with the special (least used) switch selection rule in order to minimize the length of rearrangement sequences. The functional behavior of our model is verified by simulations and it is shown that the convergence time required for finding an optimal solution is constant, regardless of the switching network size. The performance is evaluated for random traffic with various traffic loads. Simulation results show that applying the least used switch selection rule increases the efficiency in switch rearrangements, reducing the network convergence time. The implementation aspects are also discussed to show the feasibility of the proposed approach.

Photonics in Switching. Organization of the 1993 Photonics Science Topical Meetings Held in Palm Springs, California on March 15 - 17, 1993. Technical Digest

DTIC Science & Technology

1993-03-17

placed on the number of inputs and outputs. For the TeO2 material used in this design, the TB is approximately 1000. Due to the over-resolved...Design of the acoustooptic crossbar switch Figure 2 shows a numerical simulation of the momentum space of an 8 by 8 switch in TeO2 . This switch...results Figure 4 shows switching results from a preliminary demonstration of a three by three switch in a beam-steered flint glass cell. The scope trace

A dynamic structural model of expanded RNA CAG repeats: A refined X-ray structure and computational investigations using molecular dynamics and umbrella sampling simulations

PubMed Central

Yildirim, Ilyas; Park, Hajeung; Disney, Matthew D.; Schatz, George C.

2013-01-01

One class of functionally important RNA is repeating transcripts that cause disease through various mechanisms. For example, expanded r(CAG) repeats can cause Huntington’s and other disease through translation of toxic proteins. Herein, crystal structure of r[5ʹUUGGGC(CAG)3GUCC]2, a model of CAG expanded transcripts, refined to 1.65 Å resolution is disclosed that show both anti-anti and syn-anti orientations for 1×1 nucleotide AA internal loops. Molecular dynamics (MD) simulations using Amber force field in explicit solvent were run for over 500 ns on model systems r(5ʹGCGCAGCGC)2 (MS1) and r(5ʹCCGCAGCGG)2 (MS2). In these MD simulations, both anti-anti and syn-anti AA base pairs appear to be stable. While anti-anti AA base pairs were dynamic and sampled multiple anti-anti conformations, no syn-anti↔anti-anti transformations were observed. Umbrella sampling simulations were run on MS2, and a 2D free energy surface was created to extract transformation pathways. In addition, over 800 ns explicit solvent MD simulation was run on r[5ʹGGGC(CAG)3GUCC]2, which closely represents the refined crystal structure. One of the terminal AA base pairs (syn-anti conformation), transformed to anti-anti conformation. The pathway followed in this transformation was the one predicted by umbrella sampling simulations. Further analysis showed a binding pocket near AA base pairs in syn-anti conformations. Computational results combined with the refined crystal structure show that global minimum conformation of 1×1 nucleotide AA internal loops in r(CAG) repeats is anti-anti but can adopt syn-anti depending on the environment. These results are important to understand RNA dynamic-function relationships and develop small molecules that target RNA dynamic ensembles. PMID:23441937

Structural Evidence for a Sequential Release Mechanism for Activation of Heterotrimeric G Proteins

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

Kapoor, Neeraj; Menon, Santosh T.; Chauhan, Radha

2010-01-12

Heptahelical G-protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptors couple to heterotrimeric G proteins to relay extracellular signals to intracellular signaling networks, but the molecular mechanism underlying guanosine 5'-diphosphate (GDP) release by the G protein {alpha}-subunit is not well understood. Amino acid substitutions in the conserved {alpha}5 helix of Gi, which extends from the C-terminal region to the nucleotide-binding pocket, cause dramatic increases in basal (receptor-independent) GDP release rates. For example, mutant G{alpha}{sub i1}-T329A shows an 18-fold increase in basal GDP release rate and, when expressed in culture, it causes a significant decrease in forskolin-stimulated cAMP accumulation. The crystal structure of G{alpha}{submore » i1}-T329A {center_dot} GDP shows substantial conformational rearrangement of the switch I region and additional striking alterations of side chains lining the catalytic pocket that disrupt the Mg{sup +2} coordination sphere and dislodge bound Mg{sup +2}. We propose a 'sequential release' mechanism whereby a transient conformational change in the {alpha}5 helix alters switch I to induce GDP release. Interestingly, this mechanistic model for heterotrimeric G protein activation is similar to that suggested for the activation of the plant small G protein Rop4 by RopGEF8.« less

Learning Switching Control: A Tank Level-Control Exercise

ERIC Educational Resources Information Center

Pasamontes, M.; Alvarez, J. D.; Guzman, J. L.; Berenguel, M.

2012-01-01

A key topic in multicontroller strategies is the mechanism for switching between controllers, depending on the current operating point. The objective of the switching mechanism is to keep the control action coherent. To help students understand the switching strategy involved in multicontroller schema and the relationship between the system…

Inactivation of the first nucleotide-binding fold of the sulfonylurea receptor, and familial persistent hyperinsulinemic hypoglycemia of infancy

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

Thomas, P.M.; Wohllk, N.; Huang, E.

1996-09-01

Familial persistent hyperinsulinemic hypoglycemia of infancy is a disorder of glucose homeostasis and is characterized by unregulated insulin secretion and profound hypoglycemia. Loss-of-function mutations in the second nucleotide-binding fold of the sulfonylurea receptor, a subunit of the pancreatic-islet {beta}-cell ATP-dependent potassium channel, has been demonstrated to be causative for persistent hyperinsulinemic hypoglycemia of infancy. We now describe three additional mutations in the first nucleotide-binding fold of the sulfonylurea-receptor gene. One point mutation disrupts the highly conserved Walker A motif of the first nucleotide-binding-fold region. The other two mutations occur in noncoding sequences required for RNA processing and are predicted tomore » disrupt the normal splicing pathway of the sulfonylurea-receptor mRNA precursor. These data suggest that both nucleotide-binding-fold regions of the sulfortylurea receptor are required for normal regulation of {beta}-cell ATP-dependent potassium channel activity and insulin secretion. 32 refs., 4 figs., 1 tab.« less

Theoretical proposal for determining angular momentum compensation in ferrimagnets

NASA Astrophysics Data System (ADS)

Zhu, Zhifeng; Fong, Xuanyao; Liang, Gengchiau

2018-05-01

This work demonstrates that the magnetization and angular momentum compensation temperatures (TMC and TAMC) in ferrimagnets can be unambiguously determined by performing two sets of temperature-dependent current switching, with the symmetry reversals at TMC and TAMC, respectively. A theoretical model based on the modified Landau-Lifshitz-Bloch equation is developed to systematically study the spin torque effect under different temperatures, and numerical simulations are performed to corroborate our proposal. Furthermore, we demonstrate that the recently reported linear relation between TAMC and TMC can be explained using the Curie-Weiss theory.

Stability phase diagram of a perpendicular magnetic tunnel junction in noncollinear geometry

NASA Astrophysics Data System (ADS)

Strelkov, N.; Timopheev, A.; Sousa, R. C.; Chshiev, M.; Buda-Prejbeanu, L. D.; Dieny, B.

2017-05-01

Experimental measurements performed on MgO-based perpendicular magnetic tunnel junctions show a strong dependence of the stability voltage-field diagrams as a function of the direction of the magnetic field with respect to the plane of the sample. When the magnetic field is applied in-plane, systematic nonlinear phase boundaries are observed for various lateral sizes. The simulation results based on the phenomenological Landau-Lifshitz-Gilbert equation including the in-plane and out-of-plane spin transfer torques are consistent with the measurements if a second-order anisotropy contribution is considered. Furthermore, performing the stability analysis in linear approximation allowed us to analytically extract the critical switching voltage at zero temperature in the presence of an in-plane field. This study indicates that in the noncollinear geometry investigations are suitable to detect the presence of the second-order term in the anisotropy. Such higher order anisotropy term can yield an easy-cone anisotropy which reduces the thermal stability factor but allows for more reproducible spin transfer torque switching due to a reduced stochasticity of the switching. As a result, the energy per write event decreases much faster than the thermal stability factor as the second-order anisotropy becomes more negative. Easy-cone anisotropy can be useful for fast-switching spin transfer torque magnetic random access memories provided the thermal stability can be maintained above the required value for a given memory specification.

RNA polymerase II trigger loop residues stabilize and position the incoming nucleotide triphosphate in transcription

PubMed Central

Huang, Xuhui; Wang, Dong; Weiss, Dahlia R.; Bushnell, David A.; Kornberg, Roger D.; Levitt, Michael

2010-01-01

A structurally conserved element, the trigger loop, has been suggested to play a key role in substrate selection and catalysis of RNA polymerase II (pol II) transcription elongation. Recently resolved X-ray structures showed that the trigger loop forms direct interactions with the β-phosphate and base of the matched nucleotide triphosphate (NTP) through residues His1085 and Leu1081, respectively. In order to understand the role of these two critical residues in stabilizing active site conformation in the dynamic complex, we performed all-atom molecular dynamics simulations of the wild-type pol II elongation complex and its mutants in explicit solvent. In the wild-type complex, we found that the trigger loop is stabilized in the “closed” conformation, and His1085 forms a stable interaction with the NTP. Simulations of point mutations of His1085 are shown to affect this interaction; simulations of alternative protonation states, which are inaccessible through experiment, indicate that only the protonated form is able to stabilize the His1085-NTP interaction. Another trigger loop residue, Leu1081, stabilizes the incoming nucleotide position through interaction with the nucleotide base. Our simulations of this Leu mutant suggest a three-component mechanism for correctly positioning the incoming NTP in which (i) hydrophobic contact through Leu1081, (ii) base stacking, and (iii) base pairing work together to minimize the motion of the incoming NTP base. These results complement experimental observations and provide insight into the role of the trigger loop on transcription fidelity. PMID:20798057

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

PubMed

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.

Folding behavior of a T-shaped, ribosome-binding translation enhancer implicated in a wide-spread conformational switch

PubMed Central

Le, My-Tra; Kasprzak, Wojciech K; Kim, Taejin; Gao, Feng; Young, Megan YL; Yuan, Xuefeng; Shapiro, Bruce A; Seog, Joonil; Simon, Anne E

2017-01-01

Turnip crinkle virus contains a T-shaped, ribosome-binding, translation enhancer (TSS) in its 3’UTR that serves as a hub for interactions throughout the region. The viral RNA-dependent RNA polymerase (RdRp) causes the TSS/surrounding region to undergo a conformational shift postulated to inhibit translation. Using optical tweezers (OT) and steered molecular dynamic simulations (SMD), we found that the unusual stability of pseudoknotted element H4a/Ψ3 required five upstream adenylates, and H4a/Ψ3 was necessary for cooperative association of two other hairpins (H5/H4b) in Mg2+. SMD recapitulated the TSS unfolding order in the absence of Mg2+, showed dependence of the resistance to pulling on the 3D orientation and gave structural insights into the measured contour lengths of the TSS structure elements. Adenylate mutations eliminated one-site RdRp binding to the 3’UTR, suggesting that RdRp binding to the adenylates disrupts H4a/Ψ3, leading to loss of H5/H4b interaction and promoting a conformational switch interrupting translation and promoting replication. DOI: http://dx.doi.org/10.7554/eLife.22883.001 PMID:28186489

Modeling of patient's blood pressure variation during ambulance transportation

NASA Astrophysics Data System (ADS)

Sakatani, Kenji; Ono, Takahiko; Kobayasi, Yasuhide; Hikita, Shinichi; Saito, Mitsuyuki

2007-12-01

In an emergency transportation by ambulance, a patient is transported in a supine position. In this position, a patient's blood pressure (BP) variation depending on an inertial force which occurs when an ambulance accelerates or decelerates. This BP variation causes a critical damage for a patent with brain disorder. In order to keep a patient stable during transportation, it is required to maintain small BP variation. To analyze the BP variation during transportation, a model of the BP variation has so far been made. But, it can estimate the BP variation only in braking. The purpose of this paper is to make a dynamical model of the BP variation which can simulate it in both braking and accelerating. First, to obtain the data to construct the model, we used a tilting bed to measure a head-to-foot acceleration and BP of fingertip. Based on this data, we build a mathematical model whose input is the head-to-foot acceleration and output is the Mean BP variation. It is a switched model which switches two models depending on the jerk. We add baroreceptor reflex to the model as a offset value.

Role of Dynamics in the Autoinhibition and Activation of the Hyperpolarization-activated Cyclic Nucleotide-modulated (HCN) Ion Channels*♦

PubMed Central

VanSchouwen, Bryan; Akimoto, Madoka; Sayadi, Maryam; Fogolari, Federico; Melacini, Giuseppe

2015-01-01

The hyperpolarization-activated cyclic nucleotide-modulated (HCN) ion channels control rhythmicity in neurons and cardiomyocytes. Cyclic AMP allosterically modulates HCN through the cAMP-dependent formation of a tetrameric gating ring spanning the intracellular region (IR) of HCN, to which cAMP binds. Although the apo versus holo conformational changes of the cAMP-binding domain (CBD) have been previously mapped, only limited information is currently available on the HCN IR dynamics, which have been hypothesized to play a critical role in the cAMP-dependent gating of HCN. Here, using molecular dynamics simulations validated and complemented by experimental NMR and CD data, we comparatively analyze HCN IR dynamics in the four states of the thermodynamic cycle arising from the coupling between cAMP binding and tetramerization equilibria. This extensive set of molecular dynamics trajectories captures the active-to-inactive transition that had remained elusive for other CBDs, and it provides unprecedented insight on the role of IR dynamics in HCN autoinhibition and its release by cAMP. Specifically, the IR tetramerization domain becomes more flexible in the monomeric states, removing steric clashes that the apo-CDB structure would otherwise impose. Furthermore, the simulations reveal that the active/inactive structural transition for the apo-monomeric CBD occurs through a manifold of pathways that are more divergent than previously anticipated. Upon cAMP binding, these pathways become disallowed, pre-confining the CBD conformational ensemble to a tetramer-compatible state. This conformational confinement primes the IR for tetramerization and thus provides a model of how cAMP controls HCN channel gating. PMID:25944904

Performance of Single Nucleotide Polymorphisms versus Haplotypes for Genome-Wide Association Analysis in Barley

PubMed Central

Jannink, Jean-Luc

2010-01-01

Genome-wide association studies (GWAS) may benefit from utilizing haplotype information for making marker-phenotype associations. Several rationales for grouping single nucleotide polymorphisms (SNPs) into haplotype blocks exist, but any advantage may depend on such factors as genetic architecture of traits, patterns of linkage disequilibrium in the study population, and marker density. The objective of this study was to explore the utility of haplotypes for GWAS in barley (Hordeum vulgare) to offer a first detailed look at this approach for identifying agronomically important genes in crops. To accomplish this, we used genotype and phenotype data from the Barley Coordinated Agricultural Project and constructed haplotypes using three different methods. Marker-trait associations were tested by the efficient mixed-model association algorithm (EMMA). When QTL were simulated using single SNPs dropped from the marker dataset, a simple sliding window performed as well or better than single SNPs or the more sophisticated methods of blocking SNPs into haplotypes. Moreover, the haplotype analyses performed better 1) when QTL were simulated as polymorphisms that arose subsequent to marker variants, and 2) in analysis of empirical heading date data. These results demonstrate that the information content of haplotypes is dependent on the particular mutational and recombinational history of the QTL and nearby markers. Analysis of the empirical data also confirmed our intuition that the distribution of QTL alleles in nature is often unlike the distribution of marker variants, and hence utilizing haplotype information could capture associations that would elude single SNPs. We recommend routine use of both single SNP and haplotype markers for GWAS to take advantage of the full information content of the genotype data. PMID:21124933

Formation of template-switching artifacts by linear amplification.

PubMed

Chakravarti, Dhrubajyoti; Mailander, Paula C

2008-07-01

Linear amplification is a method of synthesizing single-stranded DNA from either a single-stranded DNA or one strand of a double-stranded DNA. In this protocol, molecules of a single primer DNA are extended by multiple rounds of DNA synthesis at high temperature using thermostable DNA polymerases. Although linear amplification generates the intended full-length single-stranded product, it is more efficient over single-stranded templates than double-stranded templates. We analyzed linear amplification over single- or double-stranded mouse H-ras DNA (exon 1-2 region). The single-stranded H-ras template yielded only the intended product. However, when the double-stranded template was used, additional artifact products were observed. Increasing the concentration of the double-stranded template produced relatively higher amounts of these artifact products. One of the artifact DNA bands could be mapped and analyzed by sequencing. It contained three template-switching products. These DNAs were formed by incomplete DNA strand extension over the template strand, followed by switching to the complementary strand at a specific Ade nucleotide within a putative hairpin sequence, from which DNA synthesis continued over the complementary strand.

Switched-beam radiometer front-end network analysis

NASA Technical Reports Server (NTRS)

Trew, R. J.; Bilbro, G. L.

1994-01-01

The noise figure performance of various delay-line networks fabricated from microstrip lines with varying number of elements was investigated using a computer simulation. The effects of resistive losses in both the transmission lines and power combiners were considered. In general, it is found that an optimum number of elements exists, depending upon the resistive losses present in the network. Small resistive losses are found to have a significant degrading effect upon the noise figure performance of the array. Extreme stability in switching characteristics is necessary to minimize the nondeterministic noise of the array. For example, it is found that a 6 percent tolerance on the delay-line lengths will produce a 0.2 db uncertainty in the noise figure which translates into a 13.67 K temperature uncertainty generated by the network. If the tolerance can be held to 2 percent, the uncertainty in noise figure and noise temperature will be 0.025 db and 1.67 K, respectively. Three phase shift networks fabricated using a commercially available PIN diode switch were investigated. Loaded-line phase shifters are found to have desirable RF and noise characteristics and are attractive components for use in phased-array networks.

45^○ sign switching of effective exchange bias due to competing anisotropies in fully epitaxial Co₃FeN/MnN bilayers.

PubMed

Hajiri, Tetsuya; Yoshida, Takuya; Filianina, Mariia; Jaiswal, Samridh; Borie, Benjamin; Asano, H; Zabel, Hartmut; Klaui, Mathias

2017-11-20

We report an unusual angular-dependent exchange bias effect in ferromagnet/antiferromagnet bilayers, where both ferromagnet and antiferromagnet are epitaxially grown. Numerical model calculations predict an approximately 45$^\\circ$ period for the sign switching of the exchange-bias field, depending on the ratio between magnetocrystalline anisotropy and exchange-coupling constant. The switching of the sign is indicative of a competition between a fourfold magnetocrystalline anisotropy of the ferromagnet and a unidirectional anisotropy field of the exchange coupling. This predicted unusual angular-dependent exchange bias and its magnetization switching process are confirmed by measurements on fully epitaxial Co$_3$FeN/MnN bilayers by longitudinal and transverse magneto-optic Kerr effect magnetometry. These results provide a deeper understanding of the exchange coupling phenomena in fully epitaxial bilayers with tailored materials and open up a complex switching energy landscape engineering by anisotropies. © 2017 IOP Publishing Ltd.

Ultrasensitive Silicon Photonic-Crystal Nanobeam Electro-Optical Modulator (Preprint)

DTIC Science & Technology

2013-10-01

and simulation results are presented for an ultralow switching energy, resonator based silicon-on-insulator (SOI) electro-optical modulator. The...joshua.hendrickson@wpafb.af.mil Abstract: Design and simulation results are presented for an ultralow switching energy, resonator based silicon-on...S. Fegadolli, J. E. B. Oliveira, V. R. Almeida, and A. Scherer, “Compact and low power consumption tunable photonic crystal nanobeam cavity,” 21

Rapid switching of TFIIH between RNA polymerase I and II transcription and DNA repair in vivo.

PubMed

Hoogstraten, Deborah; Nigg, Alex L; Heath, Helen; Mullenders, Leon H F; van Driel, Roel; Hoeijmakers, Jan H J; Vermeulen, Wim; Houtsmuller, Adriaan B

2002-11-01

The transcription/repair factor TFIIH operates as a DNA helix opener in RNA polymerase II (RNAP2) transcription and nucleotide excision repair. To study TFIIH in vivo, we generated cell lines expressing functional GFP-tagged TFIIH. TFIIH was homogeneously distributed throughout the nucleus with nucleolar accumulations. We provide in vivo evidence for involvement of TFIIH in RNA polymerase I (RNAP1) transcription. Photobleaching revealed that TFIIH moves freely and gets engaged in RNAP1 and RNAP2 transcription for approximately 25 and approximately 6 s, respectively. TFIIH readily switches between transcription and repair sites (where it is immobilized for approximately 4 min) without large-scale alterations in composition. Our findings support a model of diffusion and random collision of individual components that permits a quick and versatile response to changing conditions.

Scaling Effect on Unipolar and Bipolar Resistive Switching of Metal Oxides

PubMed Central

Yanagida, Takeshi; Nagashima, Kazuki; Oka, Keisuke; Kanai, Masaki; Klamchuen, Annop; Park, Bae Ho; Kawai, Tomoji

2013-01-01

Electrically driven resistance change in metal oxides opens up an interdisciplinary research field for next-generation non-volatile memory. Resistive switching exhibits an electrical polarity dependent “bipolar-switching” and a polarity independent “unipolar-switching”, however tailoring the electrical polarity has been a challenging issue. Here we demonstrate a scaling effect on the emergence of the electrical polarity by examining the resistive switching behaviors of Pt/oxide/Pt junctions over 8 orders of magnitudes in the areas. We show that the emergence of two electrical polarities can be categorised as a diagram of an electric field and a cell area. This trend is qualitatively common for various oxides including NiOx, CoOx, and TiO2-x. We reveal the intrinsic difference between unipolar switching and bipolar switching on the area dependence, which causes a diversity of an electrical polarity for various resistive switching devices with different geometries. This will provide a foundation for tailoring resistive switching behaviors of metal oxides. PMID:23584551

Code-Switching in Persian-English and Telugu-English Conversations: With a Focus on Light Verb Constructions

ERIC Educational Resources Information Center

Moradi, Hamzeh

2014-01-01

Depending on the demands of a particular communicative situation, bilingual or multilingual speakers ("bilingualism-multilingualism") will switch between language varieties. Code-switching is the practice of moving between variations of languages in different contexts. In an educational context, code-switching is defined as the practice…

Amplification of a bi-phase shift-key modulated signal by a mm-wave FEL

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

Prosnitz, D.; Scharlemann, E.T.; Sheaffer, M.K.

Bi-phase shift keying (BPSK) is a modulation scheme used in communications and radar in which the phase of a transmitted rf signal is switched in a coded pattern between discrete values differing by {pi} radians. The transmitted information rate (in communications) or resolution (in imaging radar) depends on the rate at which the transmitted signal can be modulated. Modulation rates of greater than 1 GHz are generally desired. Although the instantaneous gain bandwidth of a mm-wave FEL amplifier can be much greater than 10 GHz, slippage may limit the BPSK modulation rate that can be amplified. Qualitative slippage arguments wouldmore » limit the modulation rate to relatively low values; nevertheless, simulations with a time-dependent FEL code (GINGER) indicate that rates of 2 GHz or more are amplified without much loss in modulation integrity. In this paper we describe the effects of slippage in the simulations and discuss the limits of simple arguments.« less

Nucleotide Interdependency in Transcription Factor Binding Sites in the Drosophila Genome.

PubMed

Dresch, Jacqueline M; Zellers, Rowan G; Bork, Daniel K; Drewell, Robert A

2016-01-01

A long-standing objective in modern biology is to characterize the molecular components that drive the development of an organism. At the heart of eukaryotic development lies gene regulation. On the molecular level, much of the research in this field has focused on the binding of transcription factors (TFs) to regulatory regions in the genome known as cis-regulatory modules (CRMs). However, relatively little is known about the sequence-specific binding preferences of many TFs, especially with respect to the possible interdependencies between the nucleotides that make up binding sites. A particular limitation of many existing algorithms that aim to predict binding site sequences is that they do not allow for dependencies between nonadjacent nucleotides. In this study, we use a recently developed computational algorithm, MARZ, to compare binding site sequences using 32 distinct models in a systematic and unbiased approach to explore nucleotide dependencies within binding sites for 15 distinct TFs known to be critical to Drosophila development. Our results indicate that many of these proteins have varying levels of nucleotide interdependencies within their DNA recognition sequences, and that, in some cases, models that account for these dependencies greatly outperform traditional models that are used to predict binding sites. We also directly compare the ability of different models to identify the known KRUPPEL TF binding sites in CRMs and demonstrate that a more complex model that accounts for nucleotide interdependencies performs better when compared with simple models. This ability to identify TFs with critical nucleotide interdependencies in their binding sites will lead to a deeper understanding of how these molecular characteristics contribute to the architecture of CRMs and the precise regulation of transcription during organismal development.

Nucleotide Interdependency in Transcription Factor Binding Sites in the Drosophila Genome

PubMed Central

Dresch, Jacqueline M.; Zellers, Rowan G.; Bork, Daniel K.; Drewell, Robert A.

2016-01-01

A long-standing objective in modern biology is to characterize the molecular components that drive the development of an organism. At the heart of eukaryotic development lies gene regulation. On the molecular level, much of the research in this field has focused on the binding of transcription factors (TFs) to regulatory regions in the genome known as cis-regulatory modules (CRMs). However, relatively little is known about the sequence-specific binding preferences of many TFs, especially with respect to the possible interdependencies between the nucleotides that make up binding sites. A particular limitation of many existing algorithms that aim to predict binding site sequences is that they do not allow for dependencies between nonadjacent nucleotides. In this study, we use a recently developed computational algorithm, MARZ, to compare binding site sequences using 32 distinct models in a systematic and unbiased approach to explore nucleotide dependencies within binding sites for 15 distinct TFs known to be critical to Drosophila development. Our results indicate that many of these proteins have varying levels of nucleotide interdependencies within their DNA recognition sequences, and that, in some cases, models that account for these dependencies greatly outperform traditional models that are used to predict binding sites. We also directly compare the ability of different models to identify the known KRUPPEL TF binding sites in CRMs and demonstrate that a more complex model that accounts for nucleotide interdependencies performs better when compared with simple models. This ability to identify TFs with critical nucleotide interdependencies in their binding sites will lead to a deeper understanding of how these molecular characteristics contribute to the architecture of CRMs and the precise regulation of transcription during organismal development. PMID:27330274

All-optical 4-bit binary to binary coded decimal converter with the help of semiconductor optical amplifier-assisted Sagnac switch

NASA Astrophysics Data System (ADS)

Bhattachryya, Arunava; Kumar Gayen, Dilip; Chattopadhyay, Tanay

2013-04-01

All-optical 4-bit binary to binary coded decimal (BCD) converter has been proposed and described, with the help of semiconductor optical amplifier (SOA)-assisted Sagnac interferometric switches in this manuscript. The paper describes all-optical conversion scheme using a set of all-optical switches. BCD is common in computer systems that display numeric values, especially in those consisting solely of digital logic with no microprocessor. In many personal computers, the basic input/output system (BIOS) keep the date and time in BCD format. The operations of the circuit are studied theoretically and analyzed through numerical simulations. The model accounts for the SOA small signal gain, line-width enhancement factor and carrier lifetime, the switching pulse energy and width, and the Sagnac loop asymmetry. By undertaking a detailed numerical simulation the influence of these key parameters on the metrics that determine the quality of switching is thoroughly investigated.

Strong Orientation-Dependent Spin-Orbit Torque in Thin Films of the Antiferromagnet Mn2Au

NASA Astrophysics Data System (ADS)

Zhou, X. F.; Zhang, J.; Li, F.; Chen, X. Z.; Shi, G. Y.; Tan, Y. Z.; Gu, Y. D.; Saleem, M. S.; Wu, H. Q.; Pan, F.; Song, C.

2018-05-01

Antiferromagnets with zero net magnetic moment, strong anti-interference, and ultrafast switching speed are potentially competitive in high-density information storage. The body-centered tetragonal antiferromagnet Mn2Au with opposite-spin sublattices is a unique metallic material for Néel-order spin-orbit-torque (SOT) switching. We investigate the SOT switching in quasiepitaxial (103), (101) and (204) Mn2Au films prepared by a simple magnetron sputtering method. We demonstrate current-induced antiferromagnetic moment switching in all of the prepared Mn2Au films by using a short current pulse at room temperature, whereas differently oriented films exhibit distinguished switching characters. A direction-independent reversible switching is attained in Mn2Au (103) films due to negligible magnetocrystalline anisotropy energy, while for Mn2Au (101) and (204) films, the switching is invertible with the current applied along the in-plane easy axis and its vertical axis, but it becomes attenuated seriously during initial switching circles when the current is applied along the hard axis because of the existence of magnetocrystalline anisotropy energy. Besides the fundamental significance, the strong orientation-dependent SOT switching, which is not realized, irrespective of ferromagnet and antiferromagnet, provides versatility for spintronics.

Ranking of Prokaryotic Genomes Based on Maximization of Sortedness of Gene Lengths

PubMed Central

Bolshoy, A; Salih, B; Cohen, I; Tatarinova, T

2014-01-01

How variations of gene lengths (some genes become longer than their predecessors, while other genes become shorter and the sizes of these factions are randomly different from organism to organism) depend on organismal evolution and adaptation is still an open question. We propose to rank the genomes according to lengths of their genes, and then find association between the genome rank and variousproperties, such as growth temperature, nucleotide composition, and pathogenicity. This approach reveals evolutionary driving factors. The main purpose of this study is to test effectiveness and robustness of several ranking methods. The selected method of evaluation is measuring of overall sortedness of the data. We have demonstrated that all considered methods give consistent results and Bubble Sort and Simulated Annealing achieve the highest sortedness. Also, Bubble Sort is considerably faster than the Simulated Annealing method. PMID:26146586

Ranking of Prokaryotic Genomes Based on Maximization of Sortedness of Gene Lengths.

PubMed

Bolshoy, A; Salih, B; Cohen, I; Tatarinova, T

How variations of gene lengths (some genes become longer than their predecessors, while other genes become shorter and the sizes of these factions are randomly different from organism to organism) depend on organismal evolution and adaptation is still an open question. We propose to rank the genomes according to lengths of their genes, and then find association between the genome rank and variousproperties, such as growth temperature, nucleotide composition, and pathogenicity. This approach reveals evolutionary driving factors. The main purpose of this study is to test effectiveness and robustness of several ranking methods. The selected method of evaluation is measuring of overall sortedness of the data. We have demonstrated that all considered methods give consistent results and Bubble Sort and Simulated Annealing achieve the highest sortedness. Also, Bubble Sort is considerably faster than the Simulated Annealing method.

Dual-cycle dielectrophoretic collection rates for probing the dielectric properties of nanoparticles

PubMed Central

Bakewell, David J; Holmes, David

2013-01-01

A new DEP spectroscopy method and supporting theoretical model is developed to systematically quantify the dielectric properties of nanoparticles using continuously pulsed DEP collection rates. Initial DEP collection rates, that are dependent on the nanoparticle dielectric properties, are an attractive alternative to the crossover frequency method for determining dielectric properties. The new method introduces dual-cycle amplitude modulated and frequency-switched DEP (dual-cycle DEP) where the first collection rate with a fixed frequency acts as a control, and the second collection rate frequency is switched to a chosen value, such that, it can effectively probe the dielectric properties of the nanoparticles. The application of the control means that measurement variation between DEP collection experiments is reduced so that the frequency-switched probe collection is more effective. A mathematical model of the dual-cycle method is developed that simulates the temporal dynamics of the dual-cycle DEP nanoparticle collection system. A new statistical method is also developed that enables systematic bivariate fitting of the multifrequency DEP collection rates to the Clausius–Mossotti function, and is instrumental for determining dielectric properties. A Monte-Carlo simulation validates that collection rates improve estimation of the dielectric properties, compared with the crossover method, by exploiting a larger number of independent samples. Experiments using 200 nm diameter latex nanospheres suspended in 0.2 mS/m KCl buffer yield a nanoparticle conductivity of 26 mS/m that lies within 8% of the expected value. The results show that the dual-frequency method has considerable promise particularly for automated DEP investigations and associated technologies. PMID:23172363

Design and simulation of RF MEMS SPST shunt and SPDT shunt-shunt switches for X-band and Ku-band applications

NASA Astrophysics Data System (ADS)

Lenka, Manas K.; Sharma, Amit; Sharma, Jaibir; DasGupta, Amitava

2012-10-01

This paper describes the design and simulation of RF MEMS SPST shunt and SPDT shunt-shunt switches with modified coplanar waveguide (CPW) configuration for X-band and Ku-band applications exhibiting high isolation and low insertion loss. By modifying the basic CPW structure for a six-strip membrane having length 720 μm, the resonant frequency can be reduced from 33.5 GHz to 13.5 GHz with isolation as high as -30 dB(-63 dB at resonant frequency) in Ku-band. Similar results are also found in case SPST and SPDT switches with other membrane types.

Ultrafast fragmentation dynamics of triply charged carbon dioxide: Vibrational-mode-dependent molecular bond breakage

NASA Astrophysics Data System (ADS)

Yang, HongJiang; Wang, Enliang; Dong, WenXiu; Gong, Maomao; Shen, Zhenjie; Tang, Yaguo; Shan, Xu; Chen, Xiangjun

2018-05-01

The a b i n i t i o molecular dynamics (MD) simulations using an atom-centered density matrix propagation method have been carried out to investigate the fragmentation of the ground-state triply charged carbon dioxide, CO23 +→C+ + Oa+ + Ob+ . Ten thousands of trajectories have been simulated. By analyzing the momentum correlation of the final fragments, it is demonstrated that the sequential fragmentation dominates in the three-body dissociation, consistent with our experimental observations which were performed by electron collision at impact energy of 1500 eV. Furthermore, the MD simulations allow us to have detailed insight into the ultrafast evolution of the molecular bond breakage at a very early stage, within several tens of femtoseconds, and the result shows that the initial nuclear vibrational mode plays a decisive role in switching the dissociation pathways.

Temporal sequence learning in winner-take-all networks of spiking neurons demonstrated in a brain-based device.

PubMed

McKinstry, Jeffrey L; Edelman, Gerald M

2013-01-01

Animal behavior often involves a temporally ordered sequence of actions learned from experience. Here we describe simulations of interconnected networks of spiking neurons that learn to generate patterns of activity in correct temporal order. The simulation consists of large-scale networks of thousands of excitatory and inhibitory neurons that exhibit short-term synaptic plasticity and spike-timing dependent synaptic plasticity. The neural architecture within each area is arranged to evoke winner-take-all (WTA) patterns of neural activity that persist for tens of milliseconds. In order to generate and switch between consecutive firing patterns in correct temporal order, a reentrant exchange of signals between these areas was necessary. To demonstrate the capacity of this arrangement, we used the simulation to train a brain-based device responding to visual input by autonomously generating temporal sequences of motor actions.

The indispensable role of the transversal spin fluctuations mechanism in laser-induced demagnetization of Co/Pt multilayers with nanoscale magnetic domains.

PubMed

Zhang, Wei; He, Wei; Peng, Li-Cong; Zhang, Ying; Cai, Jian-Wang; Evans, Richard F L; Zhang, Xiang-Qun; Cheng, Zhao-Hua

2018-07-06

The switching of magnetic domains induced by an ultrashort laser pulse has been demonstrated in nanostructured ferromagnetic films. This leads to the dawn of a new era in breaking the ultimate physical limit for the speed of magnetic switching and manipulation, which is relevant to current and future information storage. However, our understanding of the interactions between light and spins in magnetic heterostructures with nanoscale domain structures is still lacking. Here, both time-resolved magneto-optical Kerr effect experiments and atomistic simulations are carried out to investigate the dominant mechanism of laser-induced ultrafast demagnetization in [Co/Pt] 20 multilayers with nanoscale magnetic domains. It is found that the ultrafast demagnetization time remains constant with various magnetic configurations, indicating that the domain structures play a minor role in laser-induced ultrafast demagnetization. In addition, both in experiment and atomistic simulations, we find a dependence of ultrafast demagnetization time τ M on the laser fluence, which is in contrast to the observations of spin transport within magnetic domains. The remarkable agreement between experiment and atomistic simulations indicates that the local dissipation of spin angular momentum is the dominant demagnetization mechanism in this system. More interestingly, we made a comparison between the atomistic spin dynamic simulation and the longitudinal spin flip model, highlighting that the transversal spin fluctuations mechanism is responsible for the ultrafast demagnetization in the case of inhomogeneous magnetic structures. This is a significant advance in clarifying the microscopic mechanism underlying the process of ultrafast demagnetization in inhomogeneous magnetic structures.

AEA Cell-Bypass-Switch Activation: An Update

NASA Technical Reports Server (NTRS)

Keys, Denney; Rao, Gopalakrishna M.; Wannemacher, Harry

2002-01-01

The objectives of this project included the following: (1) verify the performance of AEA cell bypass protection device (CBPD) under simulated EOS-Aqua/Aura flight hardware configuration; (2) assess the safety of the hardware under an inadvertent firing of CBPD switch, as well as the closing of CBPD; and (3) confirm that the mode of operation of CBPD switch is the formation of a continuous low impedance path (a homogeneous low melting point alloy). The nominal performance of AEA CBPD under flight operating conditions (vacuum except zero-G, and high impedance cell) has been demonstrated. There is no evidence of cell rupture or excessive heat production during or after CBPD switch activation under simulated high cell impedance (open-circuit cell failure mode). The formation of a continuous low impedance path (a homogeneous low melting point alloy) has been confirmed.

Effect of damping on the laser induced ultrafast switching in rare earth-transition metal alloys

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

Oniciuc, Eugen; Stoleriu, Laurentiu; Cimpoesu, Dorin

2014-06-02

In this paper, we present simulations of thermally induced magnetic switching in ferrimagnetic systems performed with a Landau-Lifshitz-Bloch (LLB) equation for damping constant in a wide range of values. We have systematically studied the GdFeCo ferrimagnet with various concentrations of Gd and compared for some values of parameters the LLB results with atomistic simulations. The agreement is remarkably good, which shows that the dynamics described by the ferrimagnetic LLB is a reasonable approximation of this complex physical phenomenon. As an important element, we show that the LLB is able to also describe the intermediate formation of a ferromagnetic state whichmore » seems to be essential to understand laser induced ultrafast switching. The study reveals the fundamental role of damping during the switching process.« less

Synthesis, physical properties and simulation of thermo-optic switch based on azo benzothiazole heterocyclic polymer

NASA Astrophysics Data System (ADS)

Qiu, Fengxian; Chen, Caihong; Zhou, Qiaolan; Cao, Zhijuan; Cao, Guorong; Guan, Yijun; Yang, Dongya

2014-05-01

A chromophore molecule 4-[(benzothiazole-2-yl)diazenyl]phenyl-1,3-diamine (BTPD) was prepared with 2-amino benzothiazole and m-phenylenediamine by diazo-coupling reaction. Then, the BTPD was polymerized with polyether polyol (NJ-220) and isophorone diisocyanate (IPDI) to obtain novel azo benzothiazole polyurethane-urea (BTPUU). The chemical structures of BTPD and BTPUU were characterized by FT-IR and UV-visible spectroscopy. The thermal and mechanical properties of BTPUU film were investigated. The refractive index and transmission loss of BTPUU film were measured at different temperatures and different laser wavelengths (532 nm, 650 nm and 850 nm) by an attenuated total reflection (ATR) technique and CCD digital imaging devices. The thermo-optic coefficients of BTPUU are -4.7086 × 10-4 °C-1 (532 nm), -6.5257 × 10-4 °C-1 (650 nm) and -5.1029 × 10-4 °C-1 (850 nm), respectively. A Y-branch switch and Mach-Zehnder interferometer (MZI) thermo-optic switches based on thermo-optic effect were proposed and the performances of the switches were simulated, respectively. The results show that the power consumption of the Y-branch thermo-optic switch is only 3.28 mW. The response times of Y-branch and MZI switches are 8.0 ms and 2.0 ms, respectively. The results indicate that the prepared BTPUU has high potential for the applications of the Y-branch digital optical switch (DOS), MZI thermo-optic switch, directional coupler (DC) switch and optical modulators.

Low Cost Embedded Controlled Full Bridge LC Parallel Resonant Converter

NASA Astrophysics Data System (ADS)

Chandrasekhar, P.; Reddy, S.

2009-01-01

In this paper the converter requirements for an optimum control of an electrolyser linked with a DC bus are analyzed and discussed. An electrolyser is a part of renewable energy system which generates hydrogen from water electrolysis. The hydrogen generating device is part of a complex system constituted by a supplying photovoltaic plant, the grid and a fuel cell battery. The characterization in several operative conditions of an actual industrial electrolyser is carried out in order to design and optimize the DC/DC converter. A dedicated zero voltage switching DC/DC converter is presented and simulated inside the context of the distributed energy production and storage system. The proposed supplying converter gives a stable output voltage and high circuit efficiency in all the proposed simulated scenarios. The adopted DC/DC converter is realized in a full-bridge topology technique in order to achieve zero voltage switching for the power switches and to regulate the output voltage. This converter has advantages like high power density, low EMI and reduced switching stresses. The simulation results are verified with the experimental results.

Exploring Modality Switching Effects in Negated Sentences: Further Evidence for Grounded Representations

PubMed Central

Hald, Lea A.; Hocking, Ian; Vernon, David; Marshall, Julie-Ann; Garnham, Alan

2013-01-01

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 et al., 2003). Similarly, modality switching costs lead to a modulation of the N400 effect in event-related potentials (ERPs; Collins et al., 2011; Hald et al., 2011). This effect of modality switching has also been shown to interact with the veracity of the sentence (Hald et al., 2011). The current ERP study 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. PMID:23450002

Design of a digital, ultra-broadband electro-optic switch for reconfigurable optical networks-on-chip.

PubMed

Van Campenhout, Joris; Green, William M J; Vlasov, Yurii A

2009-12-21

We present a novel design for a noise-tolerant, ultra-broadband electro-optic switch, based on a Mach-Zehnder lattice (MZL) interferometer. We analyze the switch performance through rigorous optical simulations, for devices implemented in silicon-on-insulator with carrier-injection-based phase shifters. We show that such a MZL switch can be designed to have a step-like switching response, resulting in improved tolerance to drive-voltage noise and temperature variations as compared to a single-stage Mach-Zehnder switch. Furthermore, we show that degradation in switching crosstalk and insertion loss due to free-carrier absorption can be largely overcome by a MZL switch design. Finally, MZL switches can be designed for having an ultra-wide, temperature-insensitive optical bandwidth of more than 250 nm. The proposed device shows good potential as a broadband optical switch in reconfigurable optical networks-on-chip.

Tests of a low-pressure switch protected by a saturating inductor

NASA Astrophysics Data System (ADS)

Lauer, E. J.; Birx, D. L.

1981-10-01

A triggered low-pressure switch was tested switching a charged capacitor across a damping resistor simulating a transformer. A series saturating inductor protected the switch from electron beam anode damage. The capacitor was 15 micro F and charge voltages up to 50 kV were used. The time to current maximum was 5 to 8 micro S. The current terminated at about 50 micro S and voltage could be reapplied at about 100 micro S.

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

NASA Astrophysics Data System (ADS)

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.

Switching control of an R/C hovercraft: stabilization and smooth switching.

PubMed

Tanaka, K; Iwasaki, M; Wang, H O

2001-01-01

This paper presents stable switching control of an radio-controlled (R/C) hovercraft that is a nonholonomic (nonlinear) system. To exactly represent its nonlinear dynamics, more importantly, to maintain controllability of the system, we newly propose a switching fuzzy model that has locally Takagi-Sugeno (T-S) fuzzy models and switches them according to states, external variables, and/or time. A switching fuzzy controller is constructed by mirroring the rule structure of the switching fuzzy model of an R/C hovercraft. We derive linear matrix inequality (LMI) conditions for ensuring the stability of the closed-loop system consisting of a switching fuzzy model and controller. Furthermore, to guarantee smooth switching of control input at switching boundaries, we also derive a smooth switching condition represented in terms of LMIs. A stable switching fuzzy controller satisfying the smooth switching condition is designed by simultaneously solving both of the LMIs. The simulation and experimental results for the trajectory control of an R/C hovercraft show the validity of the switching fuzzy model and controller design, particularly, the smooth switching condition.

Design of photonic phased array switches using nano electromechanical systems on silicon-on-insulator integration platform

NASA Astrophysics Data System (ADS)

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 array switch elements is demonstrated in this chapter. An executive summary and conclusions sections are also included in the thesis.

Mental states inside out: switching costs for emotional and nonemotional sentences that differ in internal and external focus.

PubMed

Oosterwijk, Suzanne; Winkielman, Piotr; Pecher, Diane; Zeelenberg, René; Rotteveel, Mark; Fischer, Agneta H

2012-01-01

Mental states-such as thinking, remembering, or feeling angry, happy, or dizzy-have a clear internal component. We feel a certain way when we are in these states. These internal experiences may be simulated when people understand conceptual references to mental states. However, mental states can also be described from an "external" perspective, for example when referring to "smiling." In those cases, simulation of visible outside features may be more relevant for understanding. In a switching costs paradigm, we presented semantically unrelated sentences describing emotional and nonemotional mental states while manipulating their internal or external focus. The results show that switching costs occur when participants shift between sentences with an internal and an external focus. This suggests that different forms of simulation underlie understanding these sentences. In addition, these effects occurred for emotional and nonemotional mental states, suggesting that they are grounded in a similar way-through the process of simulation.

Free-energy simulations reveal molecular mechanism for functional switch of a DNA helicase

PubMed Central

Ma, Wen; Whitley, Kevin D; Schulten, Klaus

2018-01-01

Helicases play key roles in genome maintenance, yet it remains elusive how these enzymes change conformations and how transitions between different conformational states regulate nucleic acid reshaping. Here, we developed a computational technique combining structural bioinformatics approaches and atomic-level free-energy simulations to characterize how the Escherichia coli DNA repair enzyme UvrD changes its conformation at the fork junction to switch its function from unwinding to rezipping DNA. The lowest free-energy path shows that UvrD opens the interface between two domains, allowing the bound ssDNA to escape. The simulation results predict a key metastable 'tilted' state during ssDNA strand switching. By simulating FRET distributions with fluorophores attached to UvrD, we show that the new state is supported quantitatively by single-molecule measurements. The present study deciphers key elements for the 'hyper-helicase' behavior of a mutant and provides an effective framework to characterize directly structure-function relationships in molecular machines. PMID:29664402

Free-energy simulations reveal molecular mechanism for functional switch of a DNA helicase.

PubMed

Ma, Wen; Whitley, Kevin D; Chemla, Yann R; Luthey-Schulten, Zaida; Schulten, Klaus

2018-04-17

Helicases play key roles in genome maintenance, yet it remains elusive how these enzymes change conformations and how transitions between different conformational states regulate nucleic acid reshaping. Here, we developed a computational technique combining structural bioinformatics approaches and atomic-level free-energy simulations to characterize how the Escherichia coli DNA repair enzyme UvrD changes its conformation at the fork junction to switch its function from unwinding to rezipping DNA. The lowest free-energy path shows that UvrD opens the interface between two domains, allowing the bound ssDNA to escape. The simulation results predict a key metastable 'tilted' state during ssDNA strand switching. By simulating FRET distributions with fluorophores attached to UvrD, we show that the new state is supported quantitatively by single-molecule measurements. The present study deciphers key elements for the 'hyper-helicase' behavior of a mutant and provides an effective framework to characterize directly structure-function relationships in molecular machines. © 2018, Ma et al.

Simulation model for a seven-phase BLDCM drive system

NASA Astrophysics Data System (ADS)

Park, Sang-Hoon; Lee, Won-Cheol; Lee, Jung-Hyo; Yu, Jae-Sung; Kim, Gyu-Sik; Won, Chung-Yuen

2007-12-01

BLDC motors have many advantages over brushed DC motors and induction motors. So, BLDC motors extend their application to many industrial fields. In this paper, the digital simulation and modeling of a 7-phase brushless DC motor have been presented. The 14-switch inverter and a 7-phase brushless DC motor drive system are simulated using hysteresis current controller and logic of switching pattern with the Boolean¡s function. Through some simulations, we found that our modeling and analysis of a 7-phase BLDCM with PWM inverter would be helpful for the further studies of the multi-phase BLDCM drive systems.

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

NASA Technical Reports Server (NTRS)

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.

Geant4-DNA simulation of DNA damage caused by direct and indirect radiation effects and comparison with biological data.

NASA Astrophysics Data System (ADS)

Villagrasa, Carmen; Meylan, Sylvain; Gonon, Geraldine; Gruel, Gaëtan; Giesen, Ulrich; Bueno, Marta; Rabus, Hans

2017-09-01

In this work we present results obtained in the frame of the BioQuaRT project. The objective of the study was the correlation between the number of radiation-induced double strand breaks (DSB) of the DNA molecule and the probability of detecting nuclear foci after targeted microbeam irradiation of cells with protons and alpha particles of different LET. The former were obtained by simulation with new methods integrated into Geant4-DNA that permit calculating the number of DSB in a DNA target model induced by direct and indirect radiation effects. A particular focus was laid in this work on evaluating the influence of different criteria applied to the simulated results for predicting the formation of a direct SSB. Indeed, these criteria have an important impact on the predicted number of DSB per particle track and its dependence with LET. Among the criteria tested in this work, the case that a direct radiation interaction leads to a strand break if the cumulative energy deposited in the backbone part of one nucleotide exceeds a threshold of 17.5 eV leads to the best agreement with the relative LET dependence of number of radiation induced foci. Further calculations and experimental data are nevertheless needed in order to fix the simulation parameters and to help interpreting the biological experimental data observed by immunofluorescence in terms of the DSB complexity.

Effects of transcriptional start site sequence and position on nucleotide-sensitive selection of alternative start sites at the pyrC promoter in Escherichia coli.

PubMed Central

Liu, J; Turnbough, C L

1994-01-01

In Escherichia coli, expression of the pyrC gene is regulated primarily by a translational control mechanism based on nucleotide-sensitive selection of transcriptional start sites at the pyrC promoter. When intracellular levels of CTP are high, pyrC transcripts are initiated predominantly with CTP at a site 7 bases downstream of the Pribnow box. These transcripts form a stable hairpin at their 5' ends that blocks ribosome binding. When the CTP level is low and the GTP level is high, conditions found in pyrimidine-limited cells, transcripts are initiated primarily with GTP at a site 9 bases downstream of the Pribnow box. These shorter transcripts are unable to form a hairpin at their 5' ends and are readily translated. In this study, we examined the effects of nucleotide sequence and position on the selection of transcriptional start sites at the pyrC promoter. We characterized promoter mutations that systematically alter the sequence at position 7 or 9 downstream of the Pribnow box or vary the spacing between the Pribnow box and wild-type transcriptional initiation region. The results reveal preferences for particular initiating nucleotides (ATP > or = GTP > UTP >> CTP) and for starting positions downstream of the Pribnow box (7 >> 6 and 8 > 9 > 10). The results indicate that optimal nucleotide-sensitive start site switching at the wild-type pyrC promoter is the result of competition between the preferred start site (position 7) that uses the poorest initiating nucleotide (CTP) and a weak start site (position 9) that uses a good initiating nucleotide (GTP). The sequence of the pyrC promoter also minimizes the synthesis of untranslatable transcripts and provides for maximum stability of the regulatory transcript hairpin. In addition, the results show that the effects of the mutations on pyrC expression and regulation are consistent with the current model for translational control. Possible effects of preferences for initiating nucleotides and start sites on the expression and regulation of other genes are discussed. Images PMID:7910603

Molecular dynamics studies on the interaction and encapsulation processes of the nucleotide and peptide chains inside of a carbon nanotube matrix with inclusion of gold nanoparticles

NASA Astrophysics Data System (ADS)

Kholmurodov, Kholmirzo; Dushanov, Eric; Khusenov, Mirzoaziz; Rahmonov, Khaiyom; Zelenyak, Tatyana; Doroshkevich, Alexander; Majumder, Subrata

2017-05-01

Studying of molecular systems as single nucleotides, nucleotide and peptide chains, RNA and DNA interacting with metallic nanoparticles within a carbon nanotube matrix represents a great interest in modern research. In this respect it is worth mentioning the development of the electronics diagnostic apparatus, the biochemical and biotechnological application tools (nanorobotic design, facilities of drug delivery in a living cell), so on. In the present work using molecular dynamics (MD) simulation method the interaction process of small nucleotide chains (NCs) and elongated peptide chains with different sets of metallic nanoparticles (NPs) on a matrix from carbon nanotube (CNT) were simulated to study their mechanisms of encapsulation and folding processes. We have performed a series of the MD calculations with different NC,peptides-NP-CNT models that were aimed on the investigation of the peculiarities of NC,peptide-NP interactions, the formation of bonds and structures in the system, as well as the dynamical behavior in an environment confined by the CNT matrix.

Highly efficient temperature-dependent chiral separation with a nucleotide-based coordination polymer.

PubMed

Bruno, Rosaria; Marino, Nadia; Bartella, Lucia; Di Donna, Leonardo; De Munno, Giovanni; Pardo, Emilio; Armentano, Donatella

2018-06-05

We report a new chiral coordination polymer, prepared from the cytidine 5'-monophosphate (CMP) nucleotide, capable of separating efficiently (enantiomeric excess of ca. 100%) racemic mixtures of l- and d-Asp in a temperature-dependent manner. The crystal structure of the host-guest adsorbate, with the d-Asp guest molecules loaded within its channels, could be solved allowing a direct visualization of the chiral recognition process.

Localization of palmitoylated and activated G protein α-subunit in Dictyostelium discoideum.

PubMed

Alamer, Sarah; Kageyama, Yusuke; Gundersen, Robert E

2018-06-01

Guanine nucleotide-binding proteins (G proteins) act as molecular switches to regulate many fundamental cellular processes. The lipid modification, palmitoylation, can be considered as a key factor for proper G protein function and plasma membrane localization. In Dictyostelium discoidum, Gα2 is essential for the chemotactic response to cAMP in their developmental life cycle. However, the regulation of Gα2 with respect to palmitoylation, activation and Gβγ association is less clear. In this study, Gα2 is shown to be palmitoylated on Cys-4 by [ 3 H]palmitate labeling. Loss of this palmitoylation site results in redistribution of Gα2 within the cell and poor D. discoideum development. Cellular re-localization is also observed for activated Gα2. In the membrane fraction, Gα2-wt (YFP) is highly enriched in a low-density membrane fraction, which is palmitoylation-dependent. Activated Gα2 monomer and heterotrimer are shifted to two different higher-density fractions. These results broaden our understanding of how G protein localization and function are regulated inside the cells. © 2018 Wiley Periodicals, Inc.

Energy loss in spark gap switches

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

Oreshkin, V. I., E-mail: oreshkin@ovpe.hcei.tsc.ru; Lavrinovich, I. V.; National Research Tomsk Polytechnic University, Lenin Avenue 30, 634050 Tomsk

2014-04-15

The paper reports on numerical study of the energy loss in spark gap switches. The operation of the switches is analyzed using the Braginsky model which allows calculation of the time dependence of the spark channel resistance. The Braginsky equation is solved simultaneously with generator circuit equations for different load types. Based on the numerical solutions, expressions which determine both the energy released in a spark gap switch and the switching time are derived.

Defining the mRNA recognition signature of a bacterial toxin protein

DOE PAGES

Schureck, Marc A.; Dunkle, Jack A.; Maehigashi, Tatsuya; ...

2015-10-27

Bacteria contain multiple type II toxins that selectively degrade mRNAs bound to the ribosome to regulate translation and growth and facilitate survival during the stringent response. Ribosome-dependent toxins recognize a variety of three-nucleotide codons within the aminoacyl (A) site, but how these endonucleases achieve substrate specificity remains poorly understood. In this paper, we identify the critical features for how the host inhibition of growth B (HigB) toxin recognizes each of the three A-site nucleotides for cleavage. X-ray crystal structures of HigB bound to two different codons on the ribosome illustrate how HigB uses a microbial RNase-like nucleotide recognition loop tomore » recognize either cytosine or adenosine at the second A-site position. Strikingly, a single HigB residue and 16S rRNA residue C1054 form an adenosine-specific pocket at the third A-site nucleotide, in contrast to how tRNAs decode mRNA. Finally, our results demonstrate that the most important determinant for mRNA cleavage by ribosome-dependent toxins is interaction with the third A-site nucleotide.« less

Defining the mRNA recognition signature of a bacterial toxin protein

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

Schureck, Marc A.; Dunkle, Jack A.; Maehigashi, Tatsuya

Bacteria contain multiple type II toxins that selectively degrade mRNAs bound to the ribosome to regulate translation and growth and facilitate survival during the stringent response. Ribosome-dependent toxins recognize a variety of three-nucleotide codons within the aminoacyl (A) site, but how these endonucleases achieve substrate specificity remains poorly understood. In this paper, we identify the critical features for how the host inhibition of growth B (HigB) toxin recognizes each of the three A-site nucleotides for cleavage. X-ray crystal structures of HigB bound to two different codons on the ribosome illustrate how HigB uses a microbial RNase-like nucleotide recognition loop tomore » recognize either cytosine or adenosine at the second A-site position. Strikingly, a single HigB residue and 16S rRNA residue C1054 form an adenosine-specific pocket at the third A-site nucleotide, in contrast to how tRNAs decode mRNA. Finally, our results demonstrate that the most important determinant for mRNA cleavage by ribosome-dependent toxins is interaction with the third A-site nucleotide.« less

Numerical and experimental investigations of dependence of photoacoustic signals from gold nanoparticles on the optical properties

NASA Astrophysics Data System (ADS)

Okawa, Shinpei; Hirasawa, Takeshi; Sato, Ryota; Kushibiki, Toshihiro; Ishihara, Miya; Teranishi, Toshiharu

2018-06-01

Gold nanoparticles (AuNPs) are used as a contrast agent of the photoacoustic (PA) imaging. The efficiency of AuNPs has been discussed with the absorption cross section. However, the effects of the scattering of the light by AuNPs and surrounding medium on the PA signal from AuNPs have not been discussed. The PA signals from the aqueous solution of AuNPs were examined in the numerical simulation and the experiment. In the numerical simulation, the absorption and scattering cross sections of spherical and polyhedral AuNPs were calculated by Mie theory and discrete dipole approximation. Monte Carlo simulation calculated the absorbed light energy in the aqueous solution of AuNPs. Based on the PA wave equation, the PA signals were simulated. In the experiment, the PA signal from the aqueous solution of AuNP was measured by use of a piezoelectric film and a Q-switched Nd:YAG laser operated at 532 nm. The results of the numerical simulation and the experiment agreed well. In the numerical simulation and the experiment, a single Au nanocube with 50-nm edge generated the peak value of the PA signal significantly. It was approximately 350 times and twice as large as the peak values of the spherical AuNPs with 10- and 50-nm diameters, respectively. The peak value of the PA signal depended on both the absorption and scattering coefficients of the AuNPs and the surrounding medium. The peak value increased with the scattering coefficient in a quadratic manner. The character of the temporal profile of the PA signal such as full width at half maximum depended on the scattering coefficient of the AuNPs.

Numerical and experimental investigations of dependence of photoacoustic signals from gold nanoparticles on the optical properties

NASA Astrophysics Data System (ADS)

Okawa, Shinpei; Hirasawa, Takeshi; Sato, Ryota; Kushibiki, Toshihiro; Ishihara, Miya; Teranishi, Toshiharu

2018-04-01

Gold nanoparticles (AuNPs) are used as a contrast agent of the photoacoustic (PA) imaging. The efficiency of AuNPs has been discussed with the absorption cross section. However, the effects of the scattering of the light by AuNPs and surrounding medium on the PA signal from AuNPs have not been discussed. The PA signals from the aqueous solution of AuNPs were examined in the numerical simulation and the experiment. In the numerical simulation, the absorption and scattering cross sections of spherical and polyhedral AuNPs were calculated by Mie theory and discrete dipole approximation. Monte Carlo simulation calculated the absorbed light energy in the aqueous solution of AuNPs. Based on the PA wave equation, the PA signals were simulated. In the experiment, the PA signal from the aqueous solution of AuNP was measured by use of a piezoelectric film and a Q-switched Nd:YAG laser operated at 532 nm. The results of the numerical simulation and the experiment agreed well. In the numerical simulation and the experiment, a single Au nanocube with 50-nm edge generated the peak value of the PA signal significantly. It was approximately 350 times and twice as large as the peak values of the spherical AuNPs with 10- and 50-nm diameters, respectively. The peak value of the PA signal depended on both the absorption and scattering coefficients of the AuNPs and the surrounding medium. The peak value increased with the scattering coefficient in a quadratic manner. The character of the temporal profile of the PA signal such as full width at half maximum depended on the scattering coefficient of the AuNPs.

Develop a Model Component

NASA Technical Reports Server (NTRS)

Ensey, Tyler S.

2013-01-01

During my internship at NASA, I was a model developer for Ground Support Equipment (GSE). The purpose of a model developer is to develop and unit test model component libraries (fluid, electrical, gas, etc.). The models are designed to simulate software for GSE (Ground Special Power, Crew Access Arm, Cryo, Fire and Leak Detection System, Environmental Control System (ECS), etc. .) before they are implemented into hardware. These models support verifying local control and remote software for End-Item Software Under Test (SUT). The model simulates the physical behavior (function, state, limits and 110) of each end-item and it's dependencies as defined in the Subsystem Interface Table, Software Requirements & Design Specification (SRDS), Ground Integrated Schematic (GIS), and System Mechanical Schematic.(SMS). The software of each specific model component is simulated through MATLAB's Simulink program. The intensiv model development life cycle is a.s follows: Identify source documents; identify model scope; update schedule; preliminary design review; develop model requirements; update model.. scope; update schedule; detailed design review; create/modify library component; implement library components reference; implement subsystem components; develop a test script; run the test script; develop users guide; send model out for peer review; the model is sent out for verifictionlvalidation; if there is empirical data, a validation data package is generated; if there is not empirical data, a verification package is generated; the test results are then reviewed; and finally, the user. requests accreditation, and a statement of accreditation is prepared. Once each component model is reviewed and approved, they are intertwined together into one integrated model. This integrated model is then tested itself, through a test script and autotest, so that it can be concluded that all models work conjointly, for a single purpose. The component I was assigned, specifically, was a fluid component, a discrete pressure switch. The switch takes a fluid pressure input, and if the pressure is greater than a designated cutoff pressure, the switch would stop fluid flow.

On-line Monitoring Device for High-voltage Switch Cabinet Partial Discharge Based on Pulse Current Method

NASA Astrophysics Data System (ADS)

Y Tao, S.; Zhang, X. Z.; Cai, H. W.; Li, P.; Feng, Y.; Zhang, T. C.; Li, J.; Wang, W. S.; Zhang, X. K.

2017-12-01

The pulse current method for partial discharge detection is generally applied in type testing and other off-line tests of electrical equipment at delivery. After intensive analysis of the present situation and existing problems of partial discharge detection in switch cabinets, this paper designed the circuit principle and signal extraction method for partial discharge on-line detection based on a high-voltage presence indicating systems (VPIS), established a high voltage switch cabinet partial discharge on-line detection circuit based on the pulse current method, developed background software integrated with real-time monitoring, judging and analyzing functions, carried out a real discharge simulation test on a real-type partial discharge defect simulation platform of a 10KV switch cabinet, and verified the sensitivity and validity of the high-voltage switch cabinet partial discharge on-line monitoring device based on the pulse current method. The study presented in this paper is of great significance for switch cabinet maintenance and theoretical study on pulse current method on-line detection, and has provided a good implementation method for partial discharge on-line monitoring devices for 10KV distribution network equipment.

Conformational switching between protein substates studied with 2D IR vibrational echo spectroscopy and molecular dynamics simulations.

PubMed

Bagchi, Sayan; Thorpe, Dayton G; Thorpe, Ian F; Voth, Gregory A; Fayer, M D

2010-12-30

Myoglobin is an important protein for the study of structure and dynamics. Three conformational substates have been identified for the carbonmonoxy form of myoglobin (MbCO). These are manifested as distinct peaks in the IR absorption spectrum of the CO stretching mode. Ultrafast 2D IR vibrational echo chemical exchange experiments are used to observed switching between two of these substates, A(1) and A(3), on a time scale of <100 ps for two mutants of wild-type Mb. The two mutants are a single mutation of Mb, L29I, and a double mutation, T67R/S92D. Molecular dynamics (MD) simulations are used to model the structural differences between the substates of the two MbCO mutants. The MD simulations are also employed to examine the substate switching in the two mutants as a test of the ability of MD simulations to predict protein dynamics correctly for a system in which there is a well-defined transition over a significant potential barrier between two substates. For one mutant, L29I, the simulations show that translation of the His64 backbone may differentiate the two substates. The simulations accurately reproduce the experimentally observed interconversion time for the L29I mutant. However, MD simulations exploring the same His64 backbone coordinate fail to display substate interconversion for the other mutant, T67R/S92D, thus pointing to the likely complexity of the underlying protein interactions. We anticipate that understanding conformational dynamics in MbCO via ultrafast 2D IR vibrational echo chemical exchange experiments can help to elucidate fast conformational switching processes in other proteins.

User’s Manual for the Ride Motion Simulator

DTIC Science & Technology

1989-08-01

1800 psi). Step 16. Pressurize the system by moving the main pressure switch to "ON." Wait for the roll, pitch, and yaw error signals to go to "Zero...Carefully, help the test subject dismount. Step 41. Flip the main pressure switch on the hydraulic control panel to "OFF." This will block hydraulic...1.13, thus lowering the seat. Release the "Low Limit Override" switch. Step 5. Dismount the test subject. Step 6. Move the main pressure switch to the

Setting the Delay of the LTD Switch Firing Using Trigger Inductors

NASA Astrophysics Data System (ADS)

Alexeenko, V. M.; Sinebryukhov, V. A.; Kondratiev, S. S.; Volkov, S. N.; Kim, A. A.; Yakovlev, V. Yu.

2018-01-01

Simulation results are compared with experimental data to define the integral breakdown criterion for the spark gaps of the switches of the LTDs with oil insulation and to determine the influence of the inductance of the trigger inductor on the delay of the switch firing. The results confirm that the shape of the output square pulse produced by the oil-insulated LTDs can be corrected as required if the trigger inductors are used to trigger the cavity switches.

Manufacture of radio frequency micromachined switches with annealing.

PubMed

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.

Manufacture of Radio Frequency Micromachined Switches with Annealing

PubMed Central

Lin, Cheng-Yang; Dai, Ching-Liang

2014-01-01

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. PMID:24445415

Label-free technology for the amplified detection of microRNA based on the allosteric hairpin DNA switch and hybridization chain reaction.

PubMed

Cai, Sheng; Cao, Zhijuan; Lau, Choiwan; Lu, Jianzhong

2014-11-21

By using the allosteric hairpin DNA switch, a novel assay for the detection of microRNA (miRNA) let-7a via a hybridization chain reaction (HCR) was introduced. Briefly, the hairpin DNA switch probe is a single-stranded DNA consisting of a streptavidin (SA) aptamer sequence, a target binding sequence and a certain sequence that acts as a trigger of the HCR. In the presence of target let-7a, the hairpin DNA switch would open and expose the stem region sequences, where a part of this sequence acts as initiator sequence strands for the HCR and triggers a cascade of hybridization events that yields nicked double helices analogous to alternating copolymers, another part is the SA aptamer sequence which activates its binding affinity to SA on SA-coated magnetic particles. The hybridization event could be sensitively detected via an instantaneous derivatization reaction between a special chemiluminescence (CL) reagent, 3,4,5-trimethoxylphenylglyoxal (TMPG) and the guanine nucleotides within the target, the hairpin DNA switch probe, and HCR helices to form an unstable CL intermediate for the generation of light. Our results show that the coupling of the hairpin DNA switch probe and the HCR for the amplified detection of let-7a achieves a better performance (e.g. wide linear response range: 0.1-1000 fmol, low detection limit: 0.1 fmol, and high specificity). Furthermore, this approach could be easily applied to the detection of let-7a in human lung cells, and extended to detect other types of miRNA and proteins such as PDGF based on aptamers. We believe such advancements will represent a significant step towards improved diagnostics and more personalized medical treatment.

Unveiling Stability Criteria of DNA-Carbon Nanotubes Constructs by Scanning Tunneling Microscopy and Computational Modeling

DOE PAGES

Kilina, Svetlana; Yarotski, Dzmitry A.; Talin, A. Alec; ...

2011-01-01

We present a combined approach that relies on computational simulations and scanning tunneling microscopy (STM) measurements to reveal morphological properties and stability criteria of carbon nanotube-DNA (CNT-DNA) constructs. Application of STM allows direct observation of very stable CNT-DNA hybrid structures with the well-defined DNA wrapping angle of 63.4 ° and a coiling period of 3.3 nm. Using force field simulations, we determine how the DNA-CNT binding energy depends on the sequence and binding geometry of a single strand DNA. This dependence allows us to quantitatively characterize the stability of a hybrid structure with an optimal π-stacking between DNA nucleotides and themore » tube surface and better interpret STM data. Our simulations clearly demonstrate the existence of a very stable DNA binding geometry for (6,5) CNT as evidenced by the presence of a well-defined minimum in the binding energy as a function of an angle between DNA strand and the nanotube chiral vector. This novel approach demonstrates the feasibility of CNT-DNA geometry studies with subnanometer resolution and paves the way towards complete characterization of the structural and electronic properties of drug-delivering systems based on DNA-CNT hybrids as a function of DNA sequence and a nanotube chirality.« less

Proposal of optical mode switch

NASA Astrophysics Data System (ADS)

Takakura, Ryuta; Jizodo, Makoto; Fujino, Asuka; Tanaka, Tatsushi; Hamamoto, Kiichi

2014-08-01

Here, we propose a novel optical mode switch, which is a new concept of the optical switch. It can overcome the matrix size limitation issue, which has been a general issue for the waveguide optical space switch, because of its simple fiber coupling configuration. In addition, it contributes to the lossless mux/demux function such as wavelength multiplexing with powerless mode conversion unlike wavelength conversion. In this paper, we propose the principle of the optical mode switch. The simulation results showed less than -30 dB mode crosstalk, with less than only 0.1 dB excess loss for a two-mode optical switch. Moreover, the scalable configuration up to four modes is also proposed in this paper.

Optimal wavelength-space crossbar switches for supercomputer optical interconnects.

PubMed

Roudas, Ioannis; Hemenway, B Roe; Grzybowski, Richard R; Karinou, Fotini

2012-08-27

We propose a most economical design of the Optical Shared MemOry Supercomputer Interconnect System (OSMOSIS) all-optical, wavelength-space crossbar switch fabric. It is shown, by analysis and simulation, that the total number of on-off gates required for the proposed N × N switch fabric can scale asymptotically as N ln N if the number of input/output ports N can be factored into a product of small primes. This is of the same order of magnitude as Shannon's lower bound for switch complexity, according to which the minimum number of two-state switches required for the construction of a N × N permutation switch is log2 (N!).

High Efficiency Single Output ZVS-ZCS Voltage Doubled Flyback Converter

NASA Astrophysics Data System (ADS)

Kaliyaperumal, Deepa; Saju, Hridya Merin; Kumar, M. Vijaya

2016-06-01

A switch operating at high switching frequency increases the switching losses of the converter resulting in lesser efficiency. Hence this paper proposes a new topology which has resonant switches [zero voltage switching (ZVS)] in the primary circuit to eliminate the above said disadvantages, and voltage doubler zero current switching (ZCS) circuit in the secondary to double the output voltage, and hence the output power, power density and efficiency. The design aspects of the proposed topology for a single output of 5 V at 50 kHz, its simulation and hardware results are discussed in detail. The analysis of the results obtained from a 2.5 W converter reveals the superiority of the proposed converter.

Evidence for thermally assisted threshold switching behavior in nanoscale phase-change memory cells

NASA Astrophysics Data System (ADS)

Le Gallo, Manuel; Athmanathan, Aravinthan; Krebs, Daniel; Sebastian, Abu

2016-01-01

In spite of decades of research, the details of electrical transport in phase-change materials are still debated. In particular, the so-called threshold switching phenomenon that allows the current density to increase steeply when a sufficiently high voltage is applied is still not well understood, even though there is wide consensus that threshold switching is solely of electronic origin. However, the high thermal efficiency and fast thermal dynamics associated with nanoscale phase-change memory (PCM) devices motivate us to reassess a thermally assisted threshold switching mechanism, at least in these devices. The time/temperature dependence of the threshold switching voltage and current in doped Ge2Sb2Te5 nanoscale PCM cells was measured over 6 decades in time at temperatures ranging from 40 °C to 160 °C. We observe a nearly constant threshold switching power across this wide range of operating conditions. We also measured the transient dynamics associated with threshold switching as a function of the applied voltage. By using a field- and temperature-dependent description of the electrical transport combined with a thermal feedback, quantitative agreement with experimental data of the threshold switching dynamics was obtained using realistic physical parameters.

Redefining the Speed Limit of Phase Change Memory Revealed by Time-resolved Steep Threshold-Switching Dynamics of AgInSbTe Devices

NASA Astrophysics Data System (ADS)

Shukla, Krishna Dayal; Saxena, Nishant; Durai, Suresh; Manivannan, Anbarasu

2016-11-01

Although phase-change memory (PCM) offers promising features for a ‘universal memory’ owing to high-speed and non-volatility, achieving fast electrical switching remains a key challenge. In this work, a correlation between the rate of applied voltage and the dynamics of threshold-switching is investigated at picosecond-timescale. A distinct characteristic feature of enabling a rapid threshold-switching at a critical voltage known as the threshold voltage as validated by an instantaneous response of steep current rise from an amorphous off to on state is achieved within 250 picoseconds and this is followed by a slower current rise leading to crystallization. Also, we demonstrate that the extraordinary nature of threshold-switching dynamics in AgInSbTe cells is independent to the rate of applied voltage unlike other chalcogenide-based phase change materials exhibiting the voltage dependent transient switching characteristics. Furthermore, numerical solutions of time-dependent conduction process validate the experimental results, which reveal the electronic nature of threshold-switching. These findings of steep threshold-switching of ‘sub-50 ps delay time’, opens up a new way for achieving high-speed non-volatile memory for mainstream computing.

Low-Loss, High-Isolation Microwave Microelectromechanical Systems (MEMS) Switches Being Developed

NASA Technical Reports Server (NTRS)

Ponchak, George E.

2002-01-01

Switches, electrical components that either permit or prevent the flow of electricity, are the most important and widely used electrical devices in integrated circuits. In microwave systems, switches are required for switching between the transmitter and receiver; in communication systems, they are needed for phase shifters in phased-array antennas, for radar and communication systems, and for the new class of digital or software definable radios. Ideally, switches would be lossless devices that did not depend on the electrical signal's frequency or power, and they would not consume electrical power to change from OFF to ON or to maintain one of these two states. Reality is quite different, especially at microwave frequencies. Typical switches in microwave integrated circuits are pin diodes or gallium arsenide (GaAs) field-effect transistors that are nonlinear, with characteristics that depend on the power of the signal. In addition, they are frequency-dependent, lossy, and require electrical power to maintain a certain state. A new type of component has been developed that overcomes most of these technical difficulties. Microelectromechanical (MEMS) switches rely on mechanical movement as a response to an applied electrical force to either transmit or reflect electrical signal power. The NASA Glenn Research Center has been actively developing MEMS for microwave applications for over the last 5 years. Complete fabrication procedures have been developed so that the moving parts of the switch can be released with near 100-percent yield. Moreover, the switches fabricated at Glenn have demonstrated state-of-the-art performance. A typical MEMS switch is shown. The switch extends over the signal and ground lines of a finite ground coplanar waveguide, a commonly used microwave transmission line. In the state shown, the switch is in the UP state and all the microwave power traveling along the transmission line proceeds unimpeded. When a potential difference is applied between the cantilever and the transmission line, the cantilever is pulled downward until it connects the signal line to the ground planes, creating a short circuit. In this state, all the microwave power is reflected. The graph shows the measured performance of the switch, which has less than 0.1 dB of insertion loss and greater than 30dB of isolation. These switches consume negligible electrical power and are extremely linear. Additional research is required to address reliability and to increase the switching speed.

Improved treatment of nucleosides and nucleotides in the OPLS-AA force field

NASA Astrophysics Data System (ADS)

Robertson, Michael J.; Tirado-Rives, Julian; Jorgensen, William L.

2017-09-01

DFT calculations have been used to develop improved descriptions of the torsional energetics for nucleosides and nucleotides in the OPLS-AA force field. Scans of nucleotide dihedral angles (γ, χ, and β) and methyl phosphates provided the bases for the new torsional parameters. In addition, the angle-bending parameters of phosphodiesters and ribose were updated, and adjustments were made to existing carbohydrate torsions to better capture the sugar puckering landscape of ribose. MD simulations of nucleosides with the new parameters demonstrate a significant improvement in the ribose sugar puckering and χ angle distributions. Additionally, energy-minimization of protein-nucleotide crystal structures with the new parameters produced accurate poses.

A study on the temperature dependence of the threshold switching characteristics of Ge2Sb2Te5

NASA Astrophysics Data System (ADS)

Lee, Suyoun; Jeong, Doo Seok; Jeong, Jeung-hyun; Zhe, Wu; Park, Young-Wook; Ahn, Hyung-Woo; Cheong, Byung-ki

2010-01-01

We investigated the temperature dependence of the threshold switching characteristics of a memory-type chalcogenide material, Ge2Sb2Te5. We found that the threshold voltage (Vth) decreased linearly with temperature, implying the existence of a critical conductivity of Ge2Sb2Te5 for its threshold switching. In addition, we investigated the effect of bias voltage and temperature on the delay time (tdel) of the threshold switching of Ge2Sb2Te5 and described the measured relationship by an analytic expression which we derived based on a physical model where thermally activated hopping is a dominant transport mechanism in the material.

Polarization-dependent photon switch in a one-dimensional coupled-resonator waveguide.

PubMed

Zhang, Zhe-Yong; Dong, Yu-Li; Zhang, Sheng-Li; Zhu, Shi-Qun

2013-09-09

Polarization-dependent photon switch is one of the most important ingredients in building future large-scale all-optical quantum network. We present a scheme for a single-photon switch in a one-dimensional coupled-resonator waveguide, where N(a) Λ-type three-level atoms are individually embedded in each of the resonator. By tuning the interaction between atom and field, we show that an initial incident photon with a certain polarization can be transformed into its orthogonal polarization state. Finally, we use the fidelity as a figure of merit and numerically evaluate the performance of our photon switch scheme in varieties of system parameters, such as number of atoms, energy detuning and dipole couplings.

NASA Tech Briefs, October 2003

NASA Technical Reports Server (NTRS)

2003-01-01

Topics covered include: Cryogenic Temperature-Gradient Foam/Substrate Tensile Tester; Flight Test of an Intelligent Flight-Control System; Slat Heater Boxes for Thermal Vacuum Testing; System for Testing Thermal Insulation of Pipes; Electrical-Impedance-Based Ice-Thickness Gauges; Simulation System for Training in Laparoscopic Surgery; Flasher Powered by Photovoltaic Cells and Ultracapacitors; Improved Autoassociative Neural Networks; Toroidal-Core Microinductors Biased by Permanent Magnets; Using Correlated Photons to Suppress Background Noise; Atmospheric-Fade-Tolerant Tracking and Pointing in Wireless Optical Communication; Curved Focal-Plane Arrays Using Back-Illuminated High-Purity Photodetectors; Software for Displaying Data from Planetary Rovers; Software for Refining or Coarsening Computational Grids; Software for Diagnosis of Multiple Coordinated Spacecraft; Software Helps Retrieve Information Relevant to the User; Software for Simulating a Complex Robot; Software for Planning Scientific Activities on Mars; Software for Training in Pre-College Mathematics; Switching and Rectification in Carbon-Nanotube Junctions; Scandia-and-Yttria-Stabilized Zirconia for Thermal Barriers; Environmentally Safer, Less Toxic Fire-Extinguishing Agents; Multiaxial Temperature- and Time-Dependent Failure Model; Cloverleaf Vibratory Microgyroscope with Integrated Post; Single-Vector Calibration of Wind-Tunnel Force Balances; Microgyroscope with Vibrating Post as Rotation Transducer; Continuous Tuning and Calibration of Vibratory Gyroscopes; Compact, Pneumatically Actuated Filter Shuttle; Improved Bearingless Switched-Reluctance Motor; Fluorescent Quantum Dots for Biological Labeling; Growing Three-Dimensional Corneal Tissue in a Bioreactor; Scanning Tunneling Optical Resonance Microscopy; The Micro-Arcsecond Metrology Testbed; Detecting Moving Targets by Use of Soliton Resonances; and Finite-Element Methods for Real-Time Simulation of Surgery.

Mixed H∞ and passive control for linear switched systems via hybrid control approach

NASA Astrophysics Data System (ADS)

Zheng, Qunxian; Ling, Youzhu; Wei, Lisheng; Zhang, Hongbin

2018-03-01

This paper investigates the mixed H∞ and passive control problem for linear switched systems based on a hybrid control strategy. To solve this problem, first, a new performance index is proposed. This performance index can be viewed as the mixed weighted H∞ and passivity performance. Then, the hybrid controllers are used to stabilise the switched systems. The hybrid controllers consist of dynamic output-feedback controllers for every subsystem and state updating controllers at the switching instant. The design of state updating controllers not only depends on the pre-switching subsystem and the post-switching subsystem, but also depends on the measurable output signal. The hybrid controllers proposed in this paper can include some existing ones as special cases. Combine the multiple Lyapunov functions approach with the average dwell time technique, new sufficient conditions are obtained. Under the new conditions, the closed-loop linear switched systems are globally uniformly asymptotically stable with a mixed H∞ and passivity performance index. Moreover, the desired hybrid controllers can be constructed by solving a set of linear matrix inequalities. Finally, a numerical example and a practical example are given.

Low-temperature plasma simulations with the LSP PIC code

NASA Astrophysics Data System (ADS)

Carlsson, Johan; Khrabrov, Alex; Kaganovich, Igor; Keating, David; Selezneva, Svetlana; Sommerer, Timothy

2014-10-01

The LSP (Large-Scale Plasma) PIC-MCC code has been used to simulate several low-temperature plasma configurations, including a gas switch for high-power AC/DC conversion, a glow discharge and a Hall thruster. Simulation results will be presented with an emphasis on code comparison and validation against experiment. High-voltage, direct-current (HVDC) power transmission is becoming more common as it can reduce construction costs and power losses. Solid-state power-electronics devices are presently used, but it has been proposed that gas switches could become a compact, less costly, alternative. A gas-switch conversion device would be based on a glow discharge, with a magnetically insulated cold cathode. Its operation is similar to that of a sputtering magnetron, but with much higher pressure (0.1 to 0.3 Torr) in order to achieve high current density. We have performed 1D (axial) and 2D (axial/radial) simulations of such a gas switch using LSP. The 1D results were compared with results from the EDIPIC code. To test and compare the collision models used by the LSP and EDIPIC codes in more detail, a validation exercise was performed for the cathode fall of a glow discharge. We will also present some 2D (radial/azimuthal) LSP simulations of a Hall thruster. The information, data, or work presented herein was funded in part by the Advanced Research Projects Agency-Energy (ARPA-E), U.S. Department of Energy, under Award Number DE-AR0000298.

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

NASA Technical Reports Server (NTRS)

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.

Magnetization switching in nanoscale ferromagnetic grains: MFM observables from Monte Carlo simulations

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

Richards, H.L.; Sides, S.W.; Novotny, M.A.

1996-12-31

Recently experimental techniques, such as magnetic force microscopy (MFM), have enabled the magnetic state of individual sub-micron particles to be resolved. Motivated by these experimental developments, the authors use Monte Carlo simulations of two-dimensional kinetic Ising ferromagnets to study the magnetic relaxation in a negative applied field of a grain with an initial magnetization m{sub 0} = + 1. They use classical droplet theory to predict the functional forms for some quantities which can be observed by MFM. An example is the probability that the magnetization is positive, which is a function of time, field, grain size, and grain dimensionality.more » The qualitative agreement between experiments and their simulations of switching in individual single-domain ferromagnets indicates that the switching mechanism in such particles may involve local nucleation and subsequent growth of droplets of the stable phase.« less

Mechanism for verification of mismatched and homoduplex DNAs by nucleotides-bound MutS analyzed by molecular dynamics simulations.

PubMed

Ishida, Hisashi; Matsumoto, Atsushi

2016-09-01

In order to understand how MutS recognizes mismatched DNA and induces the reaction of DNA repair using ATP, the dynamics of the complexes of MutS (bound to the ADP and ATP nucleotides, or not) and DNA (with mismatched and matched base-pairs) were investigated using molecular dynamics simulations. As for DNA, the structure of the base-pairs of the homoduplex DNA which interacted with the DNA recognition site of MutS was intermittently disturbed, indicating that the homoduplex DNA was unstable. As for MutS, the disordered loops in the ATPase domains, which are considered to be necessary for the induction of DNA repair, were close to (away from) the nucleotide-binding sites in the ATPase domains when the nucleotides were (not) bound to MutS. This indicates that the ATPase domains changed their structural stability upon ATP binding using the disordered loop. Conformational analysis by principal component analysis showed that the nucleotide binding changed modes which have structurally solid ATPase domains and the large bending motion of the DNA from higher to lower frequencies. In the MutS-mismatched DNA complex bound to two nucleotides, the bending motion of the DNA at low frequency modes may play a role in triggering the formation of the sliding clamp for the following DNA-repair reaction step. Moreover, MM-PBSA/GBSA showed that the MutS-homoduplex DNA complex bound to two nucleotides was unstable because of the unfavorable interactions between MutS and DNA. This would trigger the ATP hydrolysis or separation of MutS and DNA to continue searching for mismatch base-pairs. Proteins 2016; 84:1287-1303. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

A network of molecular switches controls the activation of the two-component response regulator NtrC

NASA Astrophysics Data System (ADS)

Vanatta, Dan K.; Shukla, Diwakar; Lawrenz, Morgan; Pande, Vijay S.

2015-06-01

Recent successes in simulating protein structure and folding dynamics have demonstrated the power of molecular dynamics to predict the long timescale behaviour of proteins. Here, we extend and improve these methods to predict molecular switches that characterize conformational change pathways between the active and inactive state of nitrogen regulatory protein C (NtrC). By employing unbiased Markov state model-based molecular dynamics simulations, we construct a dynamic picture of the activation pathways of this key bacterial signalling protein that is consistent with experimental observations and predicts new mutants that could be used for validation of the mechanism. Moreover, these results suggest a novel mechanistic paradigm for conformational switching.

Structural and Functional Analysis of BipA, a Regulator of Virulence in Enteropathogenic Escherichia coli

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

Fan, Haitian; Hahm, Joseph; Diggs, Stephen

The translational GTPase BipA regulates the expression of virulence and pathogenicity factors in several eubacteria. BipA-dependent expression of virulence factors occurs under starvation conditions, such as encountered during infection of a host. Under these conditions, BipA associates with the small ribosomal subunit. BipA also has a second function to promote the efficiency of late steps in biogenesis of large ribosomal subunits at low temperatures, presumably while bound to the ribosome. During starvation, the cellular concentration of stress alarmone guanosine-3', 5'-bis pyrophosphate (ppGpp) is increased. This increase allows ppGpp to bind to BipA and switch its binding specificity from ribosomes tomore » small ribosomal subunits. A conformational change of BipA upon ppGpp binding could explain the ppGpp regulation of the binding specificity of BipA. Here, we present the structures of the full-length BipA from Escherichia coli in apo, GDP-, and ppGpp-bound forms. The crystal structure and small-angle x-ray scattering data of the protein with bound nucleotides, together with a thermodynamic analysis of the binding of GDP and of ppGpp to BipA, indicate that the ppGpp-bound form of BipA adopts the structure of the GDP form. This suggests furthermore, that the switch in binding preference only occurs when both ppGpp and the small ribosomal subunit are present. Finally, this molecular mechanism would allow BipA to interact with both the ribosome and the small ribosomal subunit during stress response.« less

Structural and Functional Analysis of BipA, a Regulator of Virulence in Enteropathogenic Escherichia coli

DOE PAGES

Fan, Haitian; Hahm, Joseph; Diggs, Stephen; ...

2015-07-10

The translational GTPase BipA regulates the expression of virulence and pathogenicity factors in several eubacteria. BipA-dependent expression of virulence factors occurs under starvation conditions, such as encountered during infection of a host. Under these conditions, BipA associates with the small ribosomal subunit. BipA also has a second function to promote the efficiency of late steps in biogenesis of large ribosomal subunits at low temperatures, presumably while bound to the ribosome. During starvation, the cellular concentration of stress alarmone guanosine-3', 5'-bis pyrophosphate (ppGpp) is increased. This increase allows ppGpp to bind to BipA and switch its binding specificity from ribosomes tomore » small ribosomal subunits. A conformational change of BipA upon ppGpp binding could explain the ppGpp regulation of the binding specificity of BipA. Here, we present the structures of the full-length BipA from Escherichia coli in apo, GDP-, and ppGpp-bound forms. The crystal structure and small-angle x-ray scattering data of the protein with bound nucleotides, together with a thermodynamic analysis of the binding of GDP and of ppGpp to BipA, indicate that the ppGpp-bound form of BipA adopts the structure of the GDP form. This suggests furthermore, that the switch in binding preference only occurs when both ppGpp and the small ribosomal subunit are present. Finally, this molecular mechanism would allow BipA to interact with both the ribosome and the small ribosomal subunit during stress response.« less

Comprehensive thermodynamic analysis of 3′ double-nucleotide overhangs neighboring Watson–Crick terminal base pairs

PubMed Central

O'Toole, Amanda S.; Miller, Stacy; Haines, Nathan; Zink, M. Coleen; Serra, Martin J.

2006-01-01

Thermodynamic parameters are reported for duplex formation of 48 self-complementary RNA duplexes containing Watson–Crick terminal base pairs (GC, AU and UA) with all 16 possible 3′ double-nucleotide overhangs; mimicking the structures of short interfering RNAs (siRNA) and microRNAs (miRNA). Based on nearest-neighbor analysis, the addition of a second dangling nucleotide to a single 3′ dangling nucleotide increases stability of duplex formation up to 0.8 kcal/mol in a sequence dependent manner. Results from this study in conjunction with data from a previous study [A. S. O'Toole, S. Miller and M. J. Serra (2005) RNA, 11, 512.] allows for the development of a refined nearest-neighbor model to predict the influence of 3′ double-nucleotide overhangs on the stability of duplex formation. The model improves the prediction of free energy and melting temperature when tested against five oligomers with various core duplex sequences. Phylogenetic analysis of naturally occurring miRNAs was performed to support our results. Selection of the effector miR strand of the mature miRNA duplex appears to be dependent upon the identity of the 3′ double-nucleotide overhang. Thermodynamic parameters for 3′ single terminal overhangs adjacent to a UA pair are also presented. PMID:16820533

In What Ways Do Synthetic Nucleotides and Natural Base Lesions Alter the Structural Stability of G-Quadruplex Nucleic Acids?

PubMed Central

2017-01-01

Synthetic analogs of natural nucleotides have long been utilized for structural studies of canonical and noncanonical nucleic acids, including the extensively investigated polymorphic G-quadruplexes (GQs). Dependence on the sequence and nucleotide modifications of the folding landscape of GQs has been reviewed by several recent studies. Here, an overview is compiled on the thermodynamic stability of the modified GQ folds and on how the stereochemical preferences of more than 70 synthetic and natural derivatives of nucleotides substituting for natural ones determine the stability as well as the conformation. Groups of nucleotide analogs only stabilize or only destabilize the GQ, while the majority of analogs alter the GQ stability in both ways. This depends on the preferred syn or anti N-glycosidic linkage of the modified building blocks, the position of substitution, and the folding architecture of the native GQ. Natural base lesions and epigenetic modifications of GQs explored so far also stabilize or destabilize the GQ assemblies. Learning the effect of synthetic nucleotide analogs on the stability of GQs can assist in engineering a required stable GQ topology, and exploring the in vitro action of the single and clustered natural base damage on GQ architectures may provide indications for the cellular events. PMID:29181193

Electrical detection and quantification of single and mixed DNA nucleotides in suspension

NASA Astrophysics Data System (ADS)

Ahmad, Mahmoud Al; Panicker, Neena G.; Rizvi, Tahir A.; Mustafa, Farah

2016-09-01

High speed sequential identification of the building blocks of DNA, (deoxyribonucleotides or nucleotides for short) without labeling or processing in long reads of DNA is the need of the hour. This can be accomplished through exploiting their unique electrical properties. In this study, the four different types of nucleotides that constitute a DNA molecule were suspended in a buffer followed by performing several types of electrical measurements. These electrical parameters were then used to quantify the suspended DNA nucleotides. Thus, we present a purely electrical counting scheme based on the semiconductor theory that allows one to determine the number of nucleotides in a solution by measuring their capacitance-voltage dependency. The nucleotide count was observed to be similar to the multiplication of the corresponding dopant concentration and debye volume after de-embedding the buffer contribution. The presented approach allows for a fast and label-free quantification of single and mixed nucleotides in a solution.

Prohibitin as the Molecular Binding Switch in the Retinal Pigment Epithelium.

PubMed

Sripathi, Srinivas R; Sylvester, O'Donnell; He, Weilue; Moser, Trevor; Um, Ji-Yeon; Lamoke, Folami; Ramakrishna, Wusirika; Bernstein, Paul S; Bartoli, Manuela; Jahng, Wan Jin

2016-02-01

Previously, our molecular binding study showed that prohibitin interacts with phospholipids, including phosphatidylinositide and cardiolipin. Under stress conditions, prohibitin interacts with cardiolipin as a retrograde response to activate mitochondrial proliferation. The lipid-binding switch mechanism of prohibitin with phosphatidylinositol-3,4,5-triphosphate and cardiolipin may suggest the role of prohibitin effects on energy metabolism and age-related diseases. The current study examined the region-specific expressions of prohibitin with respect to the retina and retinal pigment epithelium (RPE) in age-related macular degeneration (AMD). A detailed understanding of prohibitin binding with lipids, nucleotides, and proteins shown in the current study may suggest how molecular interactions control apoptosis and how we can intervene against the apoptotic pathway in AMD. Our data imply that decreased prohibitin in the peripheral RPE is a significant step leading to mitochondrial dysfunction that may promote AMD progression.

Prohibitin as the Molecular Binding Switch in the Retinal Pigment Epithelium

PubMed Central

Sripathi, Srinivasa R.; Sylvester, O’Donnell; He, Weilue; Moser, Trevor; Um, Ji-Yeon; Lamoke, Folami; Ramakrishna, Wusirika; Bernstein, Paul S.; Bartoli, Manuela; Jahng, Wan Jin

2016-01-01

Previously, our study showed that prohibitin interacts with phospholipids, including phosphatidylinositide and cardiolipin. Under stress conditions, prohibitin interacts with cardiolipin as a retrograde response to activate mitochondrial proliferation. The lipid-binding switch mechanism of prohibitin with phosphatidylinositol-3,4,5-triphosphate (PIP3) and cardiolipin may suggest the role of prohibitin effects on energy metabolism and age-related diseases. The current study examined the region-specific expressions of prohibitin with respect to the retina and retinal pigment epithelium (RPE) in age-related macular degeneration (AMD). A detailed understanding of prohibitin binding with lipids, nucleotides, and proteins shown in the current study may suggest how molecular interactions control apoptosis and how we can intervene against the apoptotic pathway in AMD. Our data imply that decreased prohibitin in the peripheral RPE is a significant step leading to mitochondrial dysfunction that may promote AMD progression. PMID:26661103

Hybrid colored noise process with space-dependent switching rates

NASA Astrophysics Data System (ADS)

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.

Effect of the nucleotides surrounding the start codon on the translation of foot-and-mouth disease virus RNA.

PubMed

Ma, X X; Feng, Y P; Gu, Y X; Zhou, J H; Ma, Z R

2016-06-01

As for the alternative AUGs in foot-and-mouth disease virus (FMDV), nucleotide bias of the context flanking the AUG(2nd) could be used as a strong signal to initiate translation. To determine the role of the specific nucleotide context, dicistronic reporter constructs were engineered to contain different versions of nucleotide context linking between internal ribosome entry site (IRES) and downstream gene. The results indicate that under FMDV IRES-dependent mechanism, the nucleotide contexts flanking start codon can influence the translation initiation efficiencies. The most optimal sequences for both start codons have proved to be UUU AUG(1st) AAC and AAG AUG(2nd) GAA.

"Off-on" electrochemical hairpin-DNA-based genosensor for cancer diagnostics.

PubMed

Farjami, Elaheh; Clima, Lilia; Gothelf, Kurt; Ferapontova, Elena E

2011-03-01

A simple and robust "off-on" signaling genosensor platform with improved selectivity for single-nucleotide polymorphism (SNP) detection based on the electronic DNA hairpin molecular beacons has been developed. The DNA beacons were immobilized onto gold electrodes in their folded states through the alkanethiol linker at the 3'-end, while the 5'-end was labeled with a methylene blue (MB) redox probe. A typical "on-off" change of the electrochemical signal was observed upon hybridization of the 27-33 nucleotide (nt) long hairpin DNA to the target DNA, in agreement with all the hitherto published data. Truncation of the DNA hairpin beacons down to 20 nts provided improved genosensor selectivity for SNP and allowed switching of the electrochemical genosensor response from the on-off to the off-on mode. Switching was consistent with the variation in the mechanism of the electron transfer reaction between the electrode and the MB redox label, for the folded beacon being characteristic of the electrochemistry of adsorbed species, while for the "open" duplex structure being formally controlled by the diffusion of the redox label within the adsorbate layer. The relative current intensities of both processes were governed by the length of the formed DNA duplex, potential scan rate, and apparent diffusion coefficient of the redox species. The off-on genosensor design used for detection of a cancer biomarker TP53 gene sequence favored discrimination between the healthy and SNP-containing DNA sequences, which was particularly pronounced at short hybridization times.

Structure of the protein core of translation initiation factor 2 in apo, GTP-bound and GDP-bound forms

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

Simonetti, Angelita; Marzi, Stefano; Fabbretti, Attilio

2013-06-01

The crystal structures of the eubacterial translation initiation factor 2 in apo form and with bound GDP and GTP reveal conformational changes upon nucleotide binding and hydrolysis, notably of the catalytically important histidine in the switch II region. Translation initiation factor 2 (IF2) is involved in the early steps of bacterial protein synthesis. It promotes the stabilization of the initiator tRNA on the 30S initiation complex (IC) and triggers GTP hydrolysis upon ribosomal subunit joining. While the structure of an archaeal homologue (a/eIF5B) is known, there are significant sequence and functional differences in eubacterial IF2, while the trimeric eukaryotic IF2more » is completely unrelated. Here, the crystal structure of the apo IF2 protein core from Thermus thermophilus has been determined by MAD phasing and the structures of GTP and GDP complexes were also obtained. The IF2–GTP complex was trapped by soaking with GTP in the cryoprotectant. The structures revealed conformational changes of the protein upon nucleotide binding, in particular in the P-loop region, which extend to the functionally relevant switch II region. The latter carries a catalytically important and conserved histidine residue which is observed in different conformations in the GTP and GDP complexes. Overall, this work provides the first crystal structure of a eubacterial IF2 and suggests that activation of GTP hydrolysis may occur by a conformational repositioning of the histidine residue.« less

Single-pixel computational ghost imaging with helicity-dependent metasurface hologram.

PubMed

Liu, Hong-Chao; Yang, Biao; Guo, Qinghua; Shi, Jinhui; Guan, Chunying; Zheng, Guoxing; Mühlenbernd, Holger; Li, Guixin; Zentgraf, Thomas; Zhang, Shuang

2017-09-01

Different optical imaging techniques are based on different characteristics of light. By controlling the abrupt phase discontinuities with different polarized incident light, a metasurface can host a phase-only and helicity-dependent hologram. In contrast, ghost imaging (GI) is an indirect imaging modality to retrieve the object information from the correlation of the light intensity fluctuations. We report single-pixel computational GI with a high-efficiency reflective metasurface in both simulations and experiments. Playing a fascinating role in switching the GI target with different polarized light, the metasurface hologram generates helicity-dependent reconstructed ghost images and successfully introduces an additional security lock in a proposed optical encryption scheme based on the GI. The robustness of our encryption scheme is further verified with the vulnerability test. Building the first bridge between the metasurface hologram and the GI, our work paves the way to integrate their applications in the fields of optical communications, imaging technology, and security.

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

Wang, Yujie; Gong, Sha; Wang, Zhen

The thermodynamic and kinetic parameters of an RNA base pair were obtained through a long-time molecular dynamics simulation of the opening-closing switch process of the base pair near its melting temperature. The thermodynamic parameters were in good agreement with the nearest-neighbor model. The opening rates showed strong temperature dependence, however, the closing rates showed only weak temperature dependence. The transition path time was weakly temperature dependent and was insensitive to the energy barrier. The diffusion constant exhibited super-Arrhenius behavior. The free energy barrier of breaking a single base stack results from the enthalpy increase, ΔH, caused by the disruption ofmore » hydrogen bonding and base-stacking interactions. The free energy barrier of base pair closing comes from the unfavorable entropy loss, ΔS, caused by the restriction of torsional angles. These results suggest that a one-dimensional free energy surface is sufficient to accurately describe the dynamics of base pair opening and closing, and the dynamics are Brownian.« less

Single-pixel computational ghost imaging with helicity-dependent metasurface hologram

PubMed Central

Liu, Hong-Chao; Yang, Biao; Guo, Qinghua; Shi, Jinhui; Guan, Chunying; Zheng, Guoxing; Mühlenbernd, Holger; Li, Guixin; Zentgraf, Thomas; Zhang, Shuang

2017-01-01

Different optical imaging techniques are based on different characteristics of light. By controlling the abrupt phase discontinuities with different polarized incident light, a metasurface can host a phase-only and helicity-dependent hologram. In contrast, ghost imaging (GI) is an indirect imaging modality to retrieve the object information from the correlation of the light intensity fluctuations. We report single-pixel computational GI with a high-efficiency reflective metasurface in both simulations and experiments. Playing a fascinating role in switching the GI target with different polarized light, the metasurface hologram generates helicity-dependent reconstructed ghost images and successfully introduces an additional security lock in a proposed optical encryption scheme based on the GI. The robustness of our encryption scheme is further verified with the vulnerability test. Building the first bridge between the metasurface hologram and the GI, our work paves the way to integrate their applications in the fields of optical communications, imaging technology, and security. PMID:28913433

Distinguishing between the partial-mapping preparation hypothesis and the failure-to-engage hypothesis of residual switch costs.

PubMed

Lindsen, Job P; de Jong, Ritske

2010-10-01

Lien, Ruthruff, Remington, & Johnston (2005) reported residual switch cost differences between stimulus-response (S-R) pairs and proposed the partial-mapping preparation (PMP) hypothesis, which states that advance preparation will typically be limited to a subset of S-R pairs because of structural capacity limitations, to account for these differences. Alternatively, the failure-to-engage (FTE) hypothesis does not allow for differences in probability of advance preparation between S-R pairs within a set; it accounts for residual switch cost differences by assuming that benefits of advance preparation may differ between S-R pairs. Three Experiments were designed to test between these hypotheses. No capacity limitations of the type assumed by the PMP hypothesis were found for many participants in Experiment 1. In Experiments 2 and 3, no evidence was found for the dependency of residual switch cost differences between S-R pairs on response-stimulus interval that is predicted by the PMP hypothesis. Mixture-model analysis of reaction times distributions in Experiment 3 provided strong support for the FTE hypothesis over the PMP hypothesis. Simulation studies with a computational implementation of the FTE hypothesis showed that it is able to account in great detail for the results of the present study. Together, these results provide strong evidence against the PMP hypothesis and support the FTE hypothesis that advance preparation probabilistically fails or succeeds at the level of the task set. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

Effects of Switching Behavior for the Attraction on Pedestrian Dynamics

PubMed Central

Kwak, Jaeyoung; Jo, Hang-Hyun; Luttinen, Tapio; Kosonen, Iisakki

2015-01-01

Walking is a fundamental activity of our daily life not only for moving to other places but also for interacting with surrounding environment. While walking on the streets, pedestrians can be aware of attractions like shopping windows. They can be influenced by the attractions and some of them might shift their attention towards the attractions, namely switching behavior. As a first step to incorporate the switching behavior, this study investigates collective effects of switching behavior for an attraction by developing a behavioral model. Numerical simulations exhibit different patterns of pedestrian behavior depending on the strength of the social influence and the average length of stay. When the social influence is strong along with a long length of stay, a saturated phase can be defined at which all the pedestrians have visited the attraction. If the social influence is not strong enough, an unsaturated phase appears where one can observe that some pedestrians head for the attraction while others walk in their desired direction. These collective patterns of pedestrian behavior are summarized in a phase diagram by comparing the number of pedestrians who visited the attraction to the number of passersby near the attraction. Measuring the marginal benefits with respect to the strength of the social influence and the average length of stay enables us to identify under what conditions enhancing these variables would be more effective. The findings from this study can be understood in the context of the pedestrian facility management, for instance, for retail stores. PMID:26218430

Effects of Switching Behavior for the Attraction on Pedestrian Dynamics.

PubMed

Kwak, Jaeyoung; Jo, Hang-Hyun; Luttinen, Tapio; Kosonen, Iisakki

2015-01-01

Walking is a fundamental activity of our daily life not only for moving to other places but also for interacting with surrounding environment. While walking on the streets, pedestrians can be aware of attractions like shopping windows. They can be influenced by the attractions and some of them might shift their attention towards the attractions, namely switching behavior. As a first step to incorporate the switching behavior, this study investigates collective effects of switching behavior for an attraction by developing a behavioral model. Numerical simulations exhibit different patterns of pedestrian behavior depending on the strength of the social influence and the average length of stay. When the social influence is strong along with a long length of stay, a saturated phase can be defined at which all the pedestrians have visited the attraction. If the social influence is not strong enough, an unsaturated phase appears where one can observe that some pedestrians head for the attraction while others walk in their desired direction. These collective patterns of pedestrian behavior are summarized in a phase diagram by comparing the number of pedestrians who visited the attraction to the number of passersby near the attraction. Measuring the marginal benefits with respect to the strength of the social influence and the average length of stay enables us to identify under what conditions enhancing these variables would be more effective. The findings from this study can be understood in the context of the pedestrian facility management, for instance, for retail stores.

A sweep algorithm for massively parallel simulation of circuit-switched networks

NASA Technical Reports Server (NTRS)

Gaujal, Bruno; Greenberg, Albert G.; Nicol, David M.

1992-01-01

A new massively parallel algorithm is presented for simulating large asymmetric circuit-switched networks, controlled by a randomized-routing policy that includes trunk-reservation. A single instruction multiple data (SIMD) implementation is described, and corresponding experiments on a 16384 processor MasPar parallel computer are reported. A multiple instruction multiple data (MIMD) implementation is also described, and corresponding experiments on an Intel IPSC/860 parallel computer, using 16 processors, are reported. By exploiting parallelism, our algorithm increases the possible execution rate of such complex simulations by as much as an order of magnitude.

Phytoplankton Assemblage Characteristics in Recurrently Fluctuating Environments

PubMed Central

Roelke, Daniel L.; Spatharis, Sofie

2015-01-01

Annual variations in biogeochemical and physical processes can lead to nutrient variability and seasonal patterns in phytoplankton productivity and assemblage structure. In many coastal systems river inflow and water exchange with the ocean varies seasonally, and alternating periods can arise where the nutrient most limiting to phytoplankton growth switches. Transitions between these alternating periods can be sudden or gradual and this depends on human activities, such as reservoir construction and interbasin water transfers. How such activities might influence phytoplankton assemblages is largely unknown. Here, we employed a multispecies, multi-nutrient model to explore how nutrient loading switching mode might affect characteristics of phytoplankton assemblages. The model is based on the Monod-relationship, predicting an instantaneous growth rate from ambient inorganic nutrient concentrations whereas the limiting nutrient at any given time was determined by Liebig’s Law of the Minimum. Our simulated phytoplankton assemblages self-organized from species rich pools over a 15-year period, and only the surviving species were considered as assemblage members. Using the model, we explored the interactive effects of complementarity level in trait trade-offs within phytoplankton assemblages and the amount of noise in the resource supply concentrations. We found that the effect of shift from a sudden resource supply transition to a gradual one, as observed in systems impacted by watershed development, was dependent on the level of complementarity. In the extremes, phytoplankton species richness and relative overyielding increased when complementarity was lowest, and phytoplankton biomass increased greatly when complementarity was highest. For low-complementarity simulations, the persistence of poorer-performing phytoplankton species of intermediate R*s led to higher richness and relative overyielding. For high-complementarity simulations, the formation of phytoplankton species clusters and niche compression enabled higher biomass accumulation. Our findings suggest that an understanding of factors influencing the emergence of life history traits important to complementarity is necessary to predict the impact of watershed development on phytoplankton productivity and assemblage structure. PMID:25799563

Assessment of Zr-Fe-V getter alloy for gas-gap heat switches

NASA Technical Reports Server (NTRS)

Prina, M.; Kulleck, J. G.; Bowman, R. C., Jr.

2000-01-01

A commercial Zr-V-Fe alloy (i.e., SAES Getters trade name alloy St-172) has been assessed as reversible hydrogen storage material for use in actuators of gas gap heat switches. Two prototype actuators containing the SAES St-172 material were built and operated for several thousand cycles to evaluate performance of the metal hydride system under conditions simulating heat switch operation.

Capacitance of Nanoporous Carbon-Based Supercapacitors Is a Trade-Off between the Concentration and the Separability of the Ions.

PubMed

Burt, Ryan; Breitsprecher, Konrad; Daffos, Barbara; Taberna, Pierre-Louis; Simon, Patrice; Birkett, Greg; Zhao, X S; Holm, Christian; Salanne, Mathieu

2016-10-06

Nanoporous carbon-based supercapacitors store electricity through adsorption of ions from the electrolyte at the surface of the electrodes. Room temperature ionic liquids, which show the largest ion concentrations among organic liquid electrolytes, should in principle yield larger capacitances. Here, we show by using electrochemical measurements that the capacitance is not significantly affected when switching from a pure ionic liquid to a conventional organic electrolyte using the same ionic species. By performing additional molecular dynamics simulations, we interpret this result as an increasing difficulty of separating ions of opposite charges when they are more concentrated, that is, in the absence of a solvent that screens the Coulombic interactions. The charging mechanism consistently changes with ion concentration, switching from counterion adsorption in the diluted organic electrolyte to ion exchange in the pure ionic liquid. Contrarily to the capacitance, in-pore diffusion coefficients largely depend on the composition, with a noticeable slowing of the dynamics in the pure ionic liquid.

Adaptive tracking control of leader-following linear multi-agent systems with external disturbances

NASA Astrophysics Data System (ADS)

Lin, Hanquan; Wei, Qinglai; Liu, Derong; Ma, Hongwen

2016-10-01

In this paper, the consensus problem for leader-following linear multi-agent systems with external disturbances is investigated. Brownian motions are used to describe exogenous disturbances. A distributed tracking controller based on Riccati inequalities with an adaptive law for adjusting coupling weights between neighbouring agents is designed for leader-following multi-agent systems under fixed and switching topologies. In traditional distributed static controllers, the coupling weights depend on the communication graph. However, coupling weights associated with the feedback gain matrix in our method are updated by state errors between neighbouring agents. We further present the stability analysis of leader-following multi-agent systems with stochastic disturbances under switching topology. Most traditional literature requires the graph to be connected all the time, while the communication graph is only assumed to be jointly connected in this paper. The design technique is based on Riccati inequalities and algebraic graph theory. Finally, simulations are given to show the validity of our method.

Theoretical Modeling of the Plasma Erosion Opening Switch for Inductive Storage Applications.

DTIC Science & Technology

1983-10-27

instantaneous and depends on the switch and load characteristics. In general T is finite and T >T >0. Thus energy will be lost to switch heatings s op - as...Top, then the switch opening time is the dominant factor and T T Clearly T must be small compared with the decay time of the load S op 5 current, T_

Ultra High-Speed Radio Frequency Switch Based on Photonics.

PubMed

Ge, Jia; Fok, Mable P

2015-11-26

Microwave switches, or Radio Frequency (RF) switches have been intensively used in microwave systems for signal routing. Compared with the fast development of microwave and wireless systems, RF switches have been underdeveloped particularly in terms of switching speed and operating bandwidth. In this paper, we propose a photonics based RF switch that is capable of switching at tens of picoseconds speed, which is hundreds of times faster than any existing RF switch technologies. The high-speed switching property is achieved with the use of a rapidly tunable microwave photonic filter with tens of gigahertz frequency tuning speed, where the tuning mechanism is based on the ultra-fast electro-optics Pockels effect. The RF switch has a wide operation bandwidth of 12 GHz and can go up to 40 GHz, depending on the bandwidth of the modulator used in the scheme. The proposed RF switch can either work as an ON/OFF switch or a two-channel switch, tens of picoseconds switching speed is experimentally observed for both type of switches.

Ovonic switching in tin selenide thin films. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Baxter, C. R.

1974-01-01

Amorphous tin selenide thin films which possess Ovonic switching properties were fabricated using vacuum deposition techniques. Results obtained indicate that memory type Ovonic switching does occur in these films the energy density required for switching from a high impedance to a low impedance state is dependent on the spacing between the electrodes of the device. The switching is also function of the magnitude of the applied voltage pulse. A completely automated computer controlled testing procedure was developed which allows precise control over the shape of the applied voltage switching pulse. A survey of previous experimental and theoretical work in the area of Ovonic switching is also presented.

A homogeneous quenching resonance energy transfer assay for the kinetic analysis of the GTPase nucleotide exchange reaction.

PubMed

Kopra, Kari; Ligabue, Alessio; Wang, Qi; Syrjänpää, Markku; Blaževitš, Olga; Veltel, Stefan; van Adrichem, Arjan J; Hänninen, Pekka; Abankwa, Daniel; Härmä, Harri

2014-07-01

A quenching resonance energy transfer (QRET) assay for small GTPase nucleotide exchange kinetic monitoring is demonstrated using nanomolar protein concentrations. Small GTPases are central signaling proteins in all eukaryotic cells acting as a "molecular switches" that are active in the GTP-state and inactive in the GDP-state. GTP-loading is highly regulated by guanine nucleotide exchange factors (GEFs). In several diseases, most prominently cancer, this process in misregulated. The kinetics of the nucleotide exchange reaction reports on the enzymatic activity of the GEF reaction system and is, therefore, of special interest. We determined the nucleotide exchange kinetics using europium-labeled GTP (Eu-GTP) in the QRET assay for small GTPases. After GEF catalyzed GTP-loading of a GTPase, a high time-resolved luminescence signal was found to be associated with GTPase bound Eu-GTP, whereas the non-bound Eu-GTP fraction was quenched by soluble quencher. The association kinetics of the Eu-GTP was measured after GEF addition, whereas the dissociation kinetics could be determined after addition of unlabeled GTP. The resulting association and dissociation rates were in agreement with previously published values for H-Ras(Wt), H-Ras(Q61G), and K-Ras(Wt), respectively. The broader applicability of the QRET assay for small GTPases was demonstrated by determining the kinetics of the Ect2 catalyzed RhoA(Wt) GTP-loading. The QRET assay allows the use of nanomolar protein concentrations, as more than 3-fold signal-to-background ratio was achieved with 50 nM GTPase and GEF proteins. Thus, small GTPase exchange kinetics can be efficiently determined in a HTS compatible 384-well plate format.

Bistability and delay-induced stability switches in a cancer network with the regulation of microRNA

NASA Astrophysics Data System (ADS)

Song, Yongli; Cao, Xin; Zhang, Tonghua

2018-01-01

In this paper, we are concerned with a cancer network including a protein module and a corresponding microRNA cluster that inhibits the synthesis of proteins. The existence of multiple steady states and their stability depending on the parameters are firstly determined. Bistability and dependency on the parameters, Hopf bifurcations and the corresponding properties like direction and stability of Hopf bifurcations are determined by computing the normal form on the center manifold. Then, the role of the delay in the process of synthesis of the protein is investigated. We show that the delay can stabilize the unstable equilibrium and destabilize the stable equilibrium. Some simulations are carried out to numerically illustrate the obtained theoretical results. Finally, the biological interpretation of the theoretical results is discussed.

Observer-based H∞ resilient control for a class of switched LPV systems and its application

NASA Astrophysics Data System (ADS)

Yang, Dong; Zhao, Jun

2016-11-01

This paper deals with the issue of observer-based H∞ resilient control for a class of switched linear parameter-varying (LPV) systems by utilising a multiple parameter-dependent Lyapunov functions method. First, attention is focused upon the design of a resilient observer, an observer-based resilient controller and a parameter and estimate state-dependent switching signal, which can stabilise and achieve the disturbance attenuation for the given systems. Then, a solvability condition of the H∞ resilient control problem is given in terms of matrix inequality for the switched LPV systems. This condition allows the H∞ resilient control problem for each individual subsystem to be unsolvable. The observer, controller, and switching signal are explicitly computed by solving linear matrix inequalities (LMIs). Finally, the effectiveness of the proposed control scheme is illustrated by its application to a turbofan engine, which can hardly be handled by the existing approaches.

Two-phase designs for joint quantitative-trait-dependent and genotype-dependent sampling in post-GWAS regional sequencing.

PubMed

Espin-Garcia, Osvaldo; Craiu, Radu V; Bull, Shelley B

2018-02-01

We evaluate two-phase designs to follow-up findings from genome-wide association study (GWAS) when the cost of regional sequencing in the entire cohort is prohibitive. We develop novel expectation-maximization-based inference under a semiparametric maximum likelihood formulation tailored for post-GWAS inference. A GWAS-SNP (where SNP is single nucleotide polymorphism) serves as a surrogate covariate in inferring association between a sequence variant and a normally distributed quantitative trait (QT). We assess test validity and quantify efficiency and power of joint QT-SNP-dependent sampling and analysis under alternative sample allocations by simulations. Joint allocation balanced on SNP genotype and extreme-QT strata yields significant power improvements compared to marginal QT- or SNP-based allocations. We illustrate the proposed method and evaluate the sensitivity of sample allocation to sampling variation using data from a sequencing study of systolic blood pressure. © 2017 The Authors. Genetic Epidemiology Published by Wiley Periodicals, Inc.

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

NASA Astrophysics Data System (ADS)

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.

Simulation of the Plasma Density Evolution during Electron Cyclotron Resonance Heating at the T-10 Tokamak

NASA Astrophysics Data System (ADS)

Dnestrovskij, Yu. N.; Vershkov, V. A.; Danilov, A. V.; Dnestrovskij, A. Yu.; Zenin, V. N.; Lysenko, S. E.; Melnikov, A. V.; Shelukhin, D. A.; Subbotin, G. F.; Cherkasov, S. V.

2018-01-01

In ohmically heated (OH) plasma with low recycling, an improved particle confinement (IPC) mode is established during gas puffing. However, after gas puffing is switched off, this mode is retained only for about 100 ms, after which an abrupt phase transition into the low particle confinement (LPC) mode occurs in the entire plasma cross section. During such a transition, energy transport due to heat conduction does not change. The phase transition in OH plasma is similar to the effect of density pump-out from the plasma core, which occurs after electron cyclotron heating (ECH) is switched on. Analysis of the measured plasma pressure profiles in the T-10 tokamak shows that, after gas puffing in the OH mode is switched off, the plasma pressure profile in the IPC stage becomes more peaked and, after the peakedness exceeds a certain critical value, the IPC-LPC transition occurs. Similar processes are also observed during ECH. If the pressure profile is insufficiently peaked during ECH, then the density pump-out effect comes into play only after the critical peakedness of the pressure profile is reached. In the plasma core, the density and pressure profiles are close to the corresponding canonical profiles. This allows one to derive an expression for the particle flux within the canonical profile model and formulate a criterion for the IPC-LPC transition. The time evolution of the plasma density profile during phase transitions was simulated for a number of T-10 shots with ECH and high recycling. The particle transport coefficients in the IPC and LPC phases, as well as the dependences of these coefficients on the ECH power, are determined.

Switch-on Shock and Nonlinear Kink Alfvén Waves in Solar Polar Jets

NASA Astrophysics Data System (ADS)

DeVore, C. Richard; Karpen, Judith T.; Antiochos, Spiro K.; Uritsky, Vadim

2016-05-01

It is widely accepted that solar polar jets are produced by fast magnetic reconnection in the low corona, whether driven directly by flux emergence from below or indirectly by instability onset above the photosphere. In either scenario, twisted flux on closed magnetic field lines reconnects with untwisted flux on nearby open field lines. Part of the twist is inherited by the newly reconnected open flux, which rapidly relaxes due to magnetic tension forces that transmit the twist impulsively into the outer corona and heliosphere. We propose that this transfer of twist launches switch-on MHD shock waves, which propagate parallel to the ambient coronal magnetic field ahead of the shock and convect a perpendicular component of magnetic field behind the shock. In the frame moving with the shock front, the post-shock flow is precisely Alfvénic in all three directions, whereas the pre-shock flow is super-Alfvénic along the ambient magnetic field, yielding a density enhancement at the shock front. Nonlinear kink Alfvén waves are exact solutions of the time-dependent MHD equations in the post-shock region when the ambient corona is uniform and the magnetic field is straight. We have performed and analyzed 3D Cartesian and spherical simulations of polar jets driven by instability onset in the corona. The results of both simulations are consistent with the generation of MHD switch-on shocks trailed predominantly by incompressible kink Alfvén waves. It is noteworthy that the kink waves are irrotational, in sharp contrast to the vorticity-bearing torsional waves reported from previous numerical studies. We will discuss the implications of the results for understanding solar polar jets and predicting their heliospheric signatures. Our research was supported by NASA’s LWS TR&T and H-SR programs.

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

NASA Astrophysics Data System (ADS)

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.

Novel switching method for single-phase NPC three-level inverter with neutral-point voltage control

NASA Astrophysics Data System (ADS)

Lee, June-Seok; Lee, Seung-Joo; Lee, Kyo-Beum

2018-02-01

This paper proposes a novel switching method with the neutral-point voltage control in a single-phase neutral-point-clamped three-level inverter (SP-NPCI) used in photovoltaic systems. A proposed novel switching method for the SP-NPCI improves the efficiency. The main concept is to fix the switching state of one leg. As a result, the switching loss decreases and the total efficiency is improved. In addition, it enables the maximum power-point-tracking operation to be performed by applying the proposed neutral-point voltage control algorithm. This control is implemented by modifying the reference signal. Simulation and experimental results provide verification of the performance of a novel switching method with the neutral-point voltage control.

Ultra-fast all-optical plasmonic switching in near infra-red spectrum using a Kerr nonlinear ring resonator

NASA Astrophysics Data System (ADS)

Nurmohammadi, Tofiq; Abbasian, Karim; Yadipour, Reza

2018-03-01

In this paper, an all-optical plasmonic switch based on metal-insulator-metal (MIM) nanoplasmonic waveguide with a Kerr nonlinear ring resonator is introduced and studied. Two-dimensional simulations utilizing the finite-difference time-domain algorithm are used to demonstrate an apparent optical bistability and significant switching mechanisms (in enabled-low condition: T(ON/OFF) =21.9 and in enabled-high condition: T(ON/OFF) =24.9) of the signal light arisen by altering the pump-light intensity. The proposed all-optical switching demonstrates femtosecond-scale feedback time (90 fs) and then ultra-fast switching can be achieved. The offered all-optical switch may recognize potential significant applications in integrated optical circuits.

Switches in Genomic GC Content Drive Shifts of Optimal Codons under Sustained Selection on Synonymous Sites

PubMed Central

Sun, Yu; Tamarit, Daniel

2017-01-01

Abstract The major codon preference model suggests that codons read by tRNAs in high concentrations are preferentially utilized in highly expressed genes. However, the identity of the optimal codons differs between species although the forces driving such changes are poorly understood. We suggest that these questions can be tackled by placing codon usage studies in a phylogenetic framework and that bacterial genomes with extreme nucleotide composition biases provide informative model systems. Switches in the background substitution biases from GC to AT have occurred in Gardnerella vaginalis (GC = 32%), and from AT to GC in Lactobacillus delbrueckii (GC = 62%) and Lactobacillus fermentum (GC = 63%). We show that despite the large effects on codon usage patterns by these switches, all three species evolve under selection on synonymous sites. In G. vaginalis, the dramatic codon frequency changes coincide with shifts of optimal codons. In contrast, the optimal codons have not shifted in the two Lactobacillus genomes despite an increased fraction of GC-ending codons. We suggest that all three species are in different phases of an on-going shift of optimal codons, and attribute the difference to a stronger background substitution bias and/or longer time since the switch in G. vaginalis. We show that comparative and correlative methods for optimal codon identification yield conflicting results for genomes in flux and discuss possible reasons for the mispredictions. We conclude that switches in the direction of the background substitution biases can drive major shifts in codon preference patterns even under sustained selection on synonymous codon sites. PMID:27540085

SwiSpot: modeling riboswitches by spotting out switching sequences.

PubMed

Barsacchi, Marco; Novoa, Eva Maria; Kellis, Manolis; Bechini, Alessio

2016-11-01

Riboswitches are cis-regulatory elements in mRNA, mostly found in Bacteria, which exhibit two main secondary structure conformations. Although one of them prevents the gene from being expressed, the other conformation allows its expression, and this switching process is typically driven by the presence of a specific ligand. Although there are a handful of known riboswitches, our knowledge in this field has been greatly limited due to our inability to identify their alternate structures from their sequences. Indeed, current methods are not able to predict the presence of the two functionally distinct conformations just from the knowledge of the plain RNA nucleotide sequence. Whether this would be possible, for which cases, and what prediction accuracy can be achieved, are currently open questions. Here we show that the two alternate secondary structures of riboswitches can be accurately predicted once the 'switching sequence' of the riboswitch has been properly identified. The proposed SwiSpot approach is capable of identifying the switching sequence inside a putative, complete riboswitch sequence, on the basis of pairing behaviors, which are evaluated on proper sets of configurations. Moreover, it is able to model the switching behavior of riboswitches whose generated ensemble covers both alternate configurations. Beyond structural predictions, the approach can also be paired to homology-based riboswitch searches. SwiSpot software, along with the reference dataset files, is available at: http://www.iet.unipi.it/a.bechini/swispot/Supplementary information: Supplementary data are available at Bioinformatics online. a.bechini@ing.unipi.it. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Abrupt current switching in graphene bilayer tunnel transistors enabled by van Hove singularities.

PubMed

Alymov, Georgy; Vyurkov, Vladimir; Ryzhii, Victor; Svintsov, Dmitry

2016-04-21

In a continuous search for the energy-efficient electronic switches, a great attention is focused on tunnel field-effect transistors (TFETs) demonstrating an abrupt dependence of the source-drain current on the gate voltage. Among all TFETs, those based on one-dimensional (1D) semiconductors exhibit the steepest current switching due to the singular density of states near the band edges, though the current in 1D structures is pretty low. In this paper, we propose a TFET based on 2D graphene bilayer which demonstrates a record steep subthreshold slope enabled by van Hove singularities in the density of states near the edges of conduction and valence bands. Our simulations show the accessibility of 3.5 × 10(4) ON/OFF current ratio with 150 mV gate voltage swing, and a maximum subthreshold slope of (20 μV/dec)(-1) just above the threshold. The high ON-state current of 0.8 mA/μm is enabled by a narrow (~0.3 eV) extrinsic band gap, while the smallness of the leakage current is due to an all-electrical doping of the source and drain contacts which suppresses the band tailing and trap-assisted tunneling.

Abrupt current switching in graphene bilayer tunnel transistors enabled by van Hove singularities

PubMed Central

Alymov, Georgy; Vyurkov, Vladimir; Ryzhii, Victor; Svintsov, Dmitry

2016-01-01

In a continuous search for the energy-efficient electronic switches, a great attention is focused on tunnel field-effect transistors (TFETs) demonstrating an abrupt dependence of the source-drain current on the gate voltage. Among all TFETs, those based on one-dimensional (1D) semiconductors exhibit the steepest current switching due to the singular density of states near the band edges, though the current in 1D structures is pretty low. In this paper, we propose a TFET based on 2D graphene bilayer which demonstrates a record steep subthreshold slope enabled by van Hove singularities in the density of states near the edges of conduction and valence bands. Our simulations show the accessibility of 3.5 × 104 ON/OFF current ratio with 150 mV gate voltage swing, and a maximum subthreshold slope of (20 μV/dec)−1 just above the threshold. The high ON-state current of 0.8 mA/μm is enabled by a narrow (~0.3 eV) extrinsic band gap, while the smallness of the leakage current is due to an all-electrical doping of the source and drain contacts which suppresses the band tailing and trap-assisted tunneling. PMID:27098051

Effect of reaction-step-size noise on the switching dynamics of stochastic populations

NASA Astrophysics Data System (ADS)

Be'er, Shay; Heller-Algazi, Metar; Assaf, Michael

2016-05-01

In genetic circuits, when the messenger RNA lifetime is short compared to the cell cycle, proteins are produced in geometrically distributed bursts, which greatly affects the cellular switching dynamics between different metastable phenotypic states. Motivated by this scenario, we study a general problem of switching or escape in stochastic populations, where influx of particles occurs in groups or bursts, sampled from an arbitrary distribution. The fact that the step size of the influx reaction is a priori unknown and, in general, may fluctuate in time with a given correlation time and statistics, introduces an additional nondemographic reaction-step-size noise into the system. Employing the probability-generating function technique in conjunction with Hamiltonian formulation, we are able to map the problem in the leading order onto solving a stationary Hamilton-Jacobi equation. We show that compared to the "usual case" of single-step influx, bursty influx exponentially decreases the population's mean escape time from its long-lived metastable state. In particular, close to bifurcation we find a simple analytical expression for the mean escape time which solely depends on the mean and variance of the burst-size distribution. Our results are demonstrated on several realistic distributions and compare well with numerical Monte Carlo simulations.

Modified Dual Three-Pulse Modulation technique for single-phase inverter topology

NASA Astrophysics Data System (ADS)

Sree Harsha, N. R.; Anitha, G. S.; Sreedevi, A.

2016-01-01

In a recent paper, a new modulation technique called Dual Three Pulse Modulation (DTPM) was proposed to improve the efficiency of the power converters of the Electric/Hybrid/Fuel-cell vehicles. It was simulated in PSIM 9.0.4 and uses analog multiplexers to generate the modulating signals for the DC/DC converter and inverter. The circuit used is complex and many other simulation softwares do not support the analog multiplexers as well. Also, the DTPM technique produces modulating signals for the converter, which are essentially needed to produce the modulating signals for the inverter. Hence, it cannot be used efficiently to switch the valves of a stand-alone inverter. We propose a new method to generate the modulating signals to switch MOSFETs of a single phase Dual-Three pulse Modulation based stand-alone inverter. The circuits proposed are simulated in Multisim 12.0. We also show an alternate way to switch a DC/DC converter in a way depicted by DTPM technique both in simulation (MATLAB/Simulink) and hardware. The circuitry is relatively simple and can be used for the further investigations of DTPM technique.

A novel MEMS inertial switch with a reinforcing rib structure and electrostatic power assist to prolong the contact time

NASA Astrophysics Data System (ADS)

Li, Jian; Wang, Yan; Yang, Zhuoqing; Ding, Guifu; Zhao, Xiaolin; Wang, Hong

2018-03-01

The MEMS inertial switch is widely used in various industries owing to its advantage of small size, high integration, low power consumption and low costs, especially in the timing of Internet of things, such as toys, handheld devices, accessories and vibration testing. This paper provided a novel inertial switch with a reinforcing rib structure and electrostatic power assist. The designed inertial switch can reduce the complexity of the post-processing circuit and broaden its application prospect. The continuous electrostatic force can extend the contact time of the designed inertia switch before the leakage of electricity ends. The moving electrode with a reinforcing rib structure can effectively restrain the bending of the lower surface of moving electrode caused by residual stress. The array-type fixed electrode can ensure stable contact between the electrodes when the device is sensitive to external shocks. The dynamic displacement-time curve can be simulated by the COMSOL finite element simulation software. The laminated plating process is used to produce the designed inertial switch and the drop hammer acceleration monitoring system is used to test the fabricated device. The results indicate that, compared with the traditional design, the bouncing phenomenon can be prevented and extend the contact time to 336μs.

Thermo-optic characteristics and switching power limit of slow-light photonic crystal structures on a silicon-on-insulator platform.

PubMed

Chahal, Manjit; Celler, George K; Jaluria, Yogesh; Jiang, Wei

2012-02-13

Employing a semi-analytic approach, we study the influence of key structural and optical parameters on the thermo-optic characteristics of photonic crystal waveguide (PCW) structures on a silicon-on-insulator (SOI) platform. The power consumption and spatial temperature profile of such structures are given as explicit functions of various structural, thermal and optical parameters, offering physical insight not available in finite-element simulations. Agreement with finite-element simulations and experiments is demonstrated. Thermal enhancement of the air-bridge structure is analyzed. The practical limit of thermo-optic switching power in slow light PCWs is discussed, and the scaling with key parameters is analyzed. Optical switching with sub-milliwatt power is shown viable.

Different threshold and bipolar resistive switching mechanisms in reactively sputtered amorphous undoped and Cr-doped vanadium oxide thin films

NASA Astrophysics Data System (ADS)

Rupp, Jonathan A. J.; Querré, Madec; Kindsmüller, Andreas; Besland, Marie-Paule; Janod, Etienne; Dittmann, Regina; Waser, Rainer; Wouters, Dirk J.

2018-01-01

This study investigates resistive switching in amorphous undoped and Cr-doped vanadium oxide thin films synthesized by sputtering deposition at low oxygen partial pressure. Two different volatile threshold switching characteristics can occur as well as a non-volatile bipolar switching mechanism, depending on device stack symmetry and Cr-doping. The two threshold switching types are associated with different crystalline phases in the conduction filament created during an initial forming step. The first kind of threshold switching, observed for undoped vanadium oxide films, was, by its temperature dependence, proven to be associated with a thermally triggered insulator-to-metal transition in a crystalline VO2 phase, whereas the threshold switch observed in chromium doped films is stable up to 90 °C and shows characteristics of an electronically induced Mott transition. This different behaviour for undoped versus doped films has been attributed to an increased stability of V3+ due to the Cr3+ doping (as evidenced by X-ray photoelectron spectroscopy analysis), probably favouring the creation of a crystalline Cr-doped V2O3 phase (rather than a Cr-doped VO2 phase) during the energetic forming step. The symmetric Pt/a-(VCr)Ox/Pt device showing high temperature stable threshold switching may find interesting applications as a possible new selector device for resistive switching memory (ReRAM) crossbar arrays.

Influence of hydrostatic pressure on the switching time and switching coefficient of NiZnCo ferrites

NASA Astrophysics Data System (ADS)

Romanowski, S.; Goldberg, S.

1980-04-01

Results of the investigation of the effect of hydrostatic pressure on the pulse performance of NiZnCo ferrites with square hysteresis loop are given. It is stated that with increasing hydrostatic pressure, the threshold field strength increases, the switching coefficient value decreases, while the switching time value may increase monotonically or reach a maximum depending on the magnetizing field strength.

Compact wavelength-selective optical switch based on digital optical phase conjugation.

PubMed

Li, Zhiyang; Claver, Havyarimana

2013-11-15

In this Letter, we show that digital optical phase conjugation might be utilized to construct a new kind of wavelength-selective switches. When incorporated with a multimode interferometer, these switches have wide bandwidth, high tolerance for fabrication error, and low polarization dependency. They might help to build large-scale multiwavelength nonblocking switching systems, or even to fabricate an optical cross-connecting or routing system on a chip.

Evidence for thermally assisted threshold switching behavior in nanoscale phase-change memory cells

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

Le Gallo, Manuel; Athmanathan, Aravinthan; Krebs, Daniel

2016-01-14

In spite of decades of research, the details of electrical transport in phase-change materials are still debated. In particular, the so-called threshold switching phenomenon that allows the current density to increase steeply when a sufficiently high voltage is applied is still not well understood, even though there is wide consensus that threshold switching is solely of electronic origin. However, the high thermal efficiency and fast thermal dynamics associated with nanoscale phase-change memory (PCM) devices motivate us to reassess a thermally assisted threshold switching mechanism, at least in these devices. The time/temperature dependence of the threshold switching voltage and current inmore » doped Ge{sub 2}Sb{sub 2}Te{sub 5} nanoscale PCM cells was measured over 6 decades in time at temperatures ranging from 40 °C to 160 °C. We observe a nearly constant threshold switching power across this wide range of operating conditions. We also measured the transient dynamics associated with threshold switching as a function of the applied voltage. By using a field- and temperature-dependent description of the electrical transport combined with a thermal feedback, quantitative agreement with experimental data of the threshold switching dynamics was obtained using realistic physical parameters.« less

Resistive switching characteristics of thermally oxidized TiN thin films

NASA Astrophysics Data System (ADS)

Biju, K. P.

2018-04-01

Resistive switching characteristics of thermally oxidized TiN thin films and mechanisms were investigated.XPS results indicates Ti-O content decreases with sputter etching and Ti 2p peak shift towards lower binding energy due to formation of Ti-O-N and Ti-N. Pt/TiO2/TiON/TiN stack exhibits both clockwise switching (CWS) and counter clockwise switching(CCWS) characteristic depending on polarity of the applied voltage. However the transition from CCWS to CWS is irreversible. Two stable switching modes with opposite switching polarity and different electrical characteristics are found to coexist in the same memory cell. Clockwise switching shows filamentary characteristics that lead to faster switching with excellent retention at high temperature. Counter-clockwise switching exhibits homogeneous conduction with slower switching and moderate retention. The field-induced switching in both CCWS and CWS might be due to inhomogeneous defect distribution due to thermal oxidation.

Voltage-controlled low-energy switching of nanomagnets through Ruderman-Kittel-Kasuya-Yosida interactions for magnetoelectric device applications

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

Ghosh, Bahniman, E-mail: bghosh@utexas.edu; Dey, Rik; Register, Leonard F.

2016-07-21

In this article, we consider through simulation low-energy switching of nanomagnets via electrostatically gated inter-magnet Ruderman-Kittel-Kasuya-Yosida (RKKY) interactions on the surface of three-dimensional topological insulators, for possible memory and nonvolatile logic applications. We model the possibility and dynamics of RKKY-based switching of one nanomagnet by coupling to one or more nanomagnets of set orientation. Potential applications to both memory and nonvolatile logic are illustrated. Sub-attojoule switching energies, far below conventional spin transfer torque (STT)-based memories and even below CMOS logic appear possible. Switching times on the order of a few nanoseconds, comparable to times for STT switching, are estimated formore » ferromagnetic nanomagnets, but the approach also appears compatible with the use of antiferromagnets which may allow for faster switching.« less

Sweet taste transduction in hamster: sweeteners and cyclic nucleotides depolarize taste cells by reducing a K+ current.

PubMed

Cummings, T A; Daniels, C; Kinnamon, S C

1996-03-01

1. The gigaseal voltage-clamp technique was used to record responses of hamster taste receptor cells to synthetic sweeteners and cyclic nucleotides. Voltage-dependent currents and steady-state currents were monitored during bath exchanges of saccharin, two high-potency sweeteners, 8-chlorophenylthio-adenosine 3',5'-cyclic monophosphate (8cpt-cAMP), and dibutyryl-guanosine 3',5'-cyclic monophosphate (db-cGMP). 2. Of the 237 fungiform taste cells studied, only one in eight was sweet responsive. Outward currents, both voltage-dependent and resting, were reduced by all of the sweeteners tested in sweet-responsive taste cells, whereas these currents were unaffected by sweeteners in sweet-unresponsive taste cells. 3. In every sweet-responsive cell tested, 8cpt-cAMP and db-cGMP mimicked the response to the sweeteners, but neither nucleotide elicited responses in sweet-unresponsive cells. Thus there was a one-to-one correlation between sweet responsivity and cyclic nucleotide responsivity. 4. Sweet responses showed cross adaptation with cyclic nucleotide responses. This indicates that the same ion channel is modulated by sweeteners and cyclic nucleotides. 5. The sweetener- and cyclic nucleotide-blocked current had an apparent reversal potential of -50 mV, which was close to the potassium reversal potential in these experiments. In addition, there was no effect of sweeteners and cyclic nucleotides in the presence of the K+ channel blocker tetraethylammonium bromide (TEA). These data suggest that block of a resting, TEA-sensitive K+ current is the final common step leading to taste cell depolarization during sweet transduction. 6. These data, together with data from a previous study (Cummings et al. 1993), suggest that both synthetic sweeteners and sucrose utilize second-messenger pathways that block a resting K+ conductance to depolarize the taste cell membrane.

Development and simulation study of a new inverse-pinch high Coulomb transfer switch

NASA Technical Reports Server (NTRS)

Choi, Sang H.

1989-01-01

The inverse-pinch plasma switch was studied using a computer simulation code. The code was based on a 2-D, 2-temperature magnetohydrodynamic (MHD) model. The application of this code was limited to the disk-type inverse-pinch plasma switch. The results of the computer analysis appear to be in agreement with the experimental results when the same parameters are used. An inverse-pinch plasma switch for closing has been designed and tested for high-power switching requirements. An azimuthally uniform initiation of breakdown is a key factor in achieving an inverse-pinch current path in the switch. Thus, various types of triggers, such as trigger pins, wire-brush, ring trigger, and hypocycloidal-pinch (HCP) devices have been tested for uniform breakdown. Recently, triggering was achieved by injection of a plasma-ring (plasma puff) that is produced separately with hypocycloidal-pinch electrodes placed under the cathode of the main gap. The current paths at switch closing, initiated by the injection of a plasma-ring from the HCP trigger are azimuthally uniform, and the local current density is significantly reduced, so that damage to the electrodes and the insulator surfaces is minimized. The test results indicate that electron bombardment on the electrodes and the insulator surfaces is minimized. The test results indicate that electron bombardment on the electrodes is four orders of magnitude less than that of a spark-gap switch for the same switching power. Indeed, a few thousand shots with peak current exceeding a mega-ampere and with hold-off voltage up to 20 kV have been conducted without showing measurable damage to the electrodes and insulators.

Studies of ZVS soft switching of dual-active-bridge isolated bidirectional DC-DC converters

NASA Astrophysics Data System (ADS)

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.

The HILDA Complex Coordinates a Conditional Switch in the 3′-Untranslated Region of the VEGFA mRNA

PubMed Central

Yao, Peng; Potdar, Alka A.; Ray, Partho Sarothi; Eswarappa, Sandeepa M.; Flagg, Andrew C.; Willard, Belinda; Fox, Paul L.

2013-01-01

Cell regulatory circuits integrate diverse, and sometimes conflicting, environmental cues to generate appropriate, condition-dependent responses. Here, we elucidate the components and mechanisms driving a protein-directed RNA switch in the 3′UTR of vascular endothelial growth factor (VEGF)-A. We describe a novel HILDA (hypoxia-inducible hnRNP L–DRBP76–hnRNP A2/B1) complex that coordinates a three-element RNA switch, enabling VEGFA mRNA translation during combined hypoxia and inflammation. In addition to binding the CA-rich element (CARE), heterogeneous nuclear ribonucleoprotein (hnRNP) L regulates switch assembly and function. hnRNP L undergoes two previously unrecognized, condition-dependent posttranslational modifications: IFN-γ induces prolyl hydroxylation and von Hippel-Lindau (VHL)-mediated proteasomal degradation, whereas hypoxia stimulates hnRNP L phosphorylation at Tyr359, inducing binding to hnRNP A2/B1, which stabilizes the protein. Also, phospho-hnRNP L recruits DRBP76 (double-stranded RNA binding protein 76) to the 3′UTR, where it binds an adjacent AU-rich stem-loop (AUSL) element, “flipping” the RNA switch by disrupting the GAIT (interferon-gamma-activated inhibitor of translation) element, preventing GAIT complex binding, and driving robust VEGFA mRNA translation. The signal-dependent, HILDA complex coordinates the function of a trio of neighboring RNA elements, thereby regulating translation of VEGFA and potentially other mRNA targets. The VEGFA RNA switch might function to ensure appropriate angiogenesis and tissue oxygenation during conflicting signals from combined inflammation and hypoxia. We propose the VEGFA RNA switch as an archetype for signal-activated, protein-directed, multi-element RNA switches that regulate posttranscriptional gene expression in complex environments. PMID:23976881

A lightweight thermal heat switch for redundant cryocooling on satellites

NASA Astrophysics Data System (ADS)

Dietrich, M.; Euler, A.; Thummes, G.

2017-04-01

A previously designed cryogenic thermal heat switch for space applications has been optimized for low mass, high structural stability, and reliability. The heat switch makes use of the large linear thermal expansion coefficient (CTE) of the thermoplastic UHMW-PE for actuation. A structure model, which includes the temperature dependent properties of the actuator, is derived to be able to predict the contact pressure between the switch parts. This pressure was used in a thermal model in order to predict the switch performance under different heat loads and operating temperatures. The two models were used to optimize the mass and stability of the switch. Its reliability was proven by cyclic actuation of the switch and by shaker tests.

Low-cost fabrication and polar-dependent switching uniformity of memory devices using alumina interfacial layer and Ag nanoparticle monolayer

NASA Astrophysics Data System (ADS)

Xia, Peng; Li, Luman; Wang, Pengfei; Gan, Ying; Xu, Wei

2017-11-01

A facile and low-cost process was developed for fabricating write-once-read-many-times (WORM) Cu/Ag NPs/Alumina/Al memory devices, where the alumina passivation layer formed naturally in air at room temperature, whereas the Ag nanoparticle monolayer was in situ prepared through thermal annealing of a 4.5 nm Ag film in air at 150°C. The devices exhibit irreversible transition from initial high resistance (OFF) state to low resistance (ON) state, with ON/OFF ratio of 107, indicating the introduction of Ag nanoparticle monolayer greatly improves ON/OFF ratio by four orders of magnitude. The uniformity of threshold voltages exhibits a polar-dependent behavior, and a narrow range of threshold voltages of 0.40 V among individual devices was achieved upon the forward voltage. The memory device can be regarded as two switching units connected in series. The uniform alumina interfacial layer and the non-uniform distribution of local electric fields originated from Ag nanoparticles might be responsible for excellent switching uniformity. Since silver ions in active layer can act as fast ion conductor, a plausible mechanism relating to the formation of filaments sequentially among the two switching units connected in series is suggested for the polar-dependent switching behavior. Furthermore, we demonstrate both alumina layer and Ag NPs monolayer play essential roles in improving switching parameters based on comparative experiments.

Analysis of non-destructive current simulators of flux compression generators.

PubMed

O'Connor, K A; Curry, R D

2014-06-01

Development and evaluation of power conditioning systems and high power microwave components often used with flux compression generators (FCGs) requires repeated testing and characterization. In an effort to minimize the cost and time required for testing with explosive generators, non-destructive simulators of an FCG's output current have been developed. Flux compression generators and simulators of FCGs are unique pulsed power sources in that the current waveform exhibits a quasi-exponential increasing rate at which the current rises. Accurately reproducing the quasi-exponential current waveform of a FCG can be important in designing electroexplosive opening switches and other power conditioning components that are dependent on the integral of current action and the rate of energy dissipation. Three versions of FCG simulators have been developed that include an inductive network with decreasing impedance in time. A primary difference between these simulators is the voltage source driving them. It is shown that a capacitor-inductor-capacitor network driving a constant or decreasing inductive load can produce the desired high-order derivatives of the load current to replicate a quasi-exponential waveform. The operation of the FCG simulators is reviewed and described mathematically for the first time to aid in the design of new simulators. Experimental and calculated results of two recent simulators are reported with recommendations for future designs.

Simulator design for advanced ISDN satellite design and experiments

NASA Technical Reports Server (NTRS)

Pepin, Gerald R.

1992-01-01

This simulation design task completion report documents the simulation techniques associated with the network models of both the Interim Service ISDN (integrated services digital network) Satellite (ISIS) and the Full Service ISDN Satellite (FSIS) architectures. The ISIS network model design represents satellite systems like the Advanced Communication Technology Satellite (ACTS) orbiting switch. The FSIS architecture, the ultimate aim of this element of the Satellite Communications Applications Research (SCAR) program, moves all control and switching functions on-board the next generation ISDN communication satellite. The technical and operational parameters for the advanced ISDN communications satellite design will be obtained from the simulation of ISIS and FSIS engineering software models for their major subsystems. Discrete events simulation experiments will be performed with these models using various traffic scenarios, design parameters and operational procedures. The data from these simulations will be used to determine the engineering parameters for the advanced ISDN communications satellite.

Organic solid state optical switches and method for producing organic solid state optical switches

DOEpatents

Wasielewski, M.R.; Gaines, G.L.; Niemczyk, M.P.; Johnson, D.G.; Gosztola, D.J.; O`Neil, M.P.

1993-01-01

This invention consists of a light-intensity dependent molecular switch comprised of a compound which shuttles an electron or a plurality of electrons from a plurality of electron donors to an electron acceptor upon being stimulated with light of predetermined wavelengths, and a method for making said compound.

Junction size dependence of ferroelectric properties in e-beam patterned BaTiO{sub 3} ferroelectric tunnel junctions

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

Singh, A. V.; Gupta, A.; Althammer, M.

We investigate the switching characteristics in BaTiO{sub 3}-based ferroelectric tunnel junctions patterned in a capacitive geometry with circular Ru top electrode with diameters ranging from ∼430 to 2300 nm. Two different patterning schemes, viz., lift-off and ion-milling, have been employed to examine the variations in the ferroelectric polarization, switching, and tunnel electro-resistance resulting from differences in the pattering processes. The values of polarization switching field are measured and compared for junctions of different diameter in the samples fabricated using both patterning schemes. We do not find any specific dependence of polarization switching bias on the size of junctions in both samplemore » stacks. The junctions in the ion-milled sample show up to three orders of resistance change by polarization switching and the polarization retention is found to improve with increasing junction diameter. However, similar switching is absent in the lift-off sample, highlighting the effect of patterning scheme on the polarization retention.« less

Static magnetism and thermal switching in randomly oriented L10 FePt thin films

NASA Astrophysics Data System (ADS)

Lisfi, A.; Pokharel, S.; Alqarni, A.; Akioya, O.; Morgan, W.; Wuttig, M.

2018-05-01

Static magnetism and thermally activated magnetic relaxation were investigated in granular FePt films (20 nm-200 nm thick) with random magnetic anisotropy through hysteresis loop, torque curve and magnetization time dependence measurements. While the magnetism of thicker film (200 nm thick) is dominated by a single switching of the ordered L10 phase, thinner film (20 nm) displays a double switching, which is indicative of the presence of the disordered cubic phase. The pronounced behavior of double switching in thinner film suggests that the film grain boundary is composed of soft cubic magnetic phase. The magnetic relaxation study reveals that magnetic viscosity S of the films is strongly dependent on the external applied field and exhibits a maximum value (12 kAm) around the switching field and a vanishing behavior at low (1 kOe) and large (12 kOe) fields. The activation volume of the thermal switching was found to be much smaller than the physical volume of the granular structure due to the incoherent rotation mode of the magnetization reversal mechanism, which is established to be domain wall nucleation.

Crystal Structure And Mutagenisis of the Metallochaperone MeaB: Insight Into the Causes of the Methylmalonic Aciduria

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

Hubbard, P.A.; Padovani, D.; Labunska, T.

MeaB is an auxiliary protein that plays a crucial role in the protection and assembly of the B{sub 12}-dependent enzyme methylmalonyl-CoA mutase. Impairments in the human homologue of MeaB, MMAA, lead to methylmalonic aciduria, an inborn error of metabolism. To explore the role of this metallochaperone, its structure was solved in the nucleotide-free form, as well as in the presence of product, GDP. MeaB is a homodimer, with each subunit containing a central {alpha}/{beta}-core G domain that is typical of the GTPase family, as well as a-helical extensions at the N and C termini that are not found in othermore » metalloenzyme chaperone GTPases. The C-terminal extension appears to be essential for nucleotide-independent dimerization, and the N-terminal region is implicated in protein-protein interaction with its partner protein, methylmalonyl-CoA mutase. The structure of MeaB confirms that it is a member of the G3E family of P-loop GTPases, which contains other putative metallochaperones HypB, CooC, and UreG. Interestingly, the so-called switch regions, responsible for signal transduction following GTP hydrolysis, are found at the dimer interface of MeaB instead of being positioned at the surface of the protein where its partner protein methylmalonyl-CoA mutase should bind. This observation suggests a large conformation change of MeaB must occur between the GDP- and GTP-bound forms of this protein. Because of their high sequence homology, the missense mutations in MMAA that result in methylmalonic aciduria have been mapped onto MeaB and, in conjunction with mutagenesis data, provide possible explanations for the pathology of this disease.« less

Ovonic type switching in tin selenide thin films

NASA Technical Reports Server (NTRS)

Baxter, C. R.; Mclennan, W. D.

1975-01-01

Amorphous tin selenide thin films which possess Ovonic type switching properties are fabricated using vacuum deposition techniques. The devices are fabricated in a planar configuration and consist of amorphous tin selenide deposited over silver contacts. Results obtained indicate that Ovonic type memory switching does occur in these films with the energy density required for switching from a high impedance to a low impedance state being dependent on the spacing between the electrodes of the device. There is also a strong implication that the switching is a function of the magnitude of the applied voltage pulse.

Investigating the origins of high multilevel resistive switching in forming free Ti/TiO2-x-based memory devices through experiments and simulations

NASA Astrophysics Data System (ADS)

Bousoulas, P.; Giannopoulos, I.; Asenov, P.; Karageorgiou, I.; Tsoukalas, D.

2017-03-01

Although multilevel capability is probably the most important property of resistive random access memory (RRAM) technology, it is vulnerable to reliability issues due to the stochastic nature of conducting filament (CF) creation. As a result, the various resistance states cannot be clearly distinguished, which leads to memory capacity failure. In this work, due to the gradual resistance switching pattern of TiO2-x-based RRAM devices, we demonstrate at least six resistance states with distinct memory margin and promising temporal variability. It is shown that the formation of small CFs with high density of oxygen vacancies enhances the uniformity of the switching characteristics in spite of the random nature of the switching effect. Insight into the origin of the gradual resistance modulation mechanisms is gained by the application of a trap-assisted-tunneling model together with numerical simulations of the filament formation physical processes.

Investigation of a compact coaxially fed switched oscillator.

PubMed

Wang, Yuwei; Chen, Dongqun; Zhang, Jiande; Cao, Shengguang; Li, Da; Liu, Chebo

2013-09-01

To generate a relative high frequency mesoband microwave, a compact coaxially fed transmission line switched oscillator with high voltage capability is investigated. The characteristic impedance and voltage capability of the low impedance transmission line (LITL) have been analyzed. It is shown that the working voltage of the oscillator can reach up to 200 kV when it is filled by pressurized nitrogen and charged by a nanosecond driving source. By utilizing a commercial electromagnetic simulation code, the transient performance of the switched oscillator with a lumped resistance load is simulated. It is illustrated that the center frequency of the output signal reaches up to ~0.6 GHz when the spark gap practically closes with a single channel. Besides, the influence of the closing mode and rapidity of the spark gap, the permittivity of the insulator at the output end of the LITL, and the load impedance on the transient performance of the designed oscillator has been analyzed in quantification. Finally, the good transient performance of the switched oscillator has been preliminarily proved by the experiment.

A Computer for Low Context-Switch Time

DTIC Science & Technology

1990-03-01

Results To find out how an implementation performs, we use a set of programs that make up a simulation system. These programs compile C language programs ...have worse relative context-switch performance: the time needed to switch contexts has not de- creased as much as the time to run programs . Much of...this study is: How seriously is throughput performance im- paired by this approach to computer architecture? Reasonable estimates are possible only

Modelling and properties of a nonlinear autonomous switching system in fed-batch culture of glycerol

NASA Astrophysics Data System (ADS)

Wang, Juan; Sun, Qingying; Feng, Enmin

2012-11-01

A nonlinear autonomous switching system is proposed to describe the coupled fed-batch fermentation with the pH as the feedback parameter. We prove the non-Zeno behaviors of the switching system and some basic properties of its solution, including the existence, uniqueness, boundedness and regularity. Numerical simulation is also carried out, which reveals that the proposed system can describe the factual fermentation process properly.

Bistability in dual-frequency nematic liquid crystals

NASA Astrophysics Data System (ADS)

Palto, S. P.; Barnik, M. I.

2007-03-01

Different modes of bistable switching in liquid crystals with frequency inversion of the dielectric anisotropy sign are discussed. The study is performed by numerical simulation and experimentally. It is shown that dual frequency driving can be effectively used to control switching between topologically equivalent and non-equivalent director field distributions. The experimental results on temperature performance of the dual-frequency switching and possible driving methods for energy consumption and expanding the temperature range are presented.

Conductance Switching Phenomena and H-Like Aggregates in Squarylium-Dye Langmuir-Blodgett Films

NASA Astrophysics Data System (ADS)

Kushida, Masahito; Inomata, Hisao; Tanaka, Yuichiro; Harada, Kieko; Saito, Kyoichi; Sugita, Kazuyuki

2002-03-01

The current-voltage characteristics of sandwich devices with the structure of top gold electrode/squarylium-dye Langmuir-Blodgett (SQ LB) films/bottom aluminum electrode indicated four kinds of conductivity depending on the evaporation conditions of the top gold electrode. The current densities of two, which showed conductance switching, of the four samples were 30-40 μA/cm2 and 20-30 mA/cm2 in the ON state. In the former case, the dependence of conductance switching voltage on the number of SQ LB films and ultraviolet-visible absorption spectra were studied. The results revealed that conductance switching phenomena were induced at the interface between the top gold electrode and SQ LB films, and caused by the presence of H-like aggregates in SQ LB films.

What is the Best Way to Reduce Unintended Pregnancies? A Micro Simulation of Contraceptive Switching, Discontinuation and Failure Patterns in France

PubMed Central

Diamond-Smith, Nadia; Moreau, Caroline; Bishai, David

2015-01-01

Despite high rates of contraceptive use in France, over a third of pregnancies are unintended. We built a dynamic micro simulation model which applies data from the French COCON study on method switching, discontinuation, and failure rates to a hypothetical population of 20,000 women, followed for 5 years. We use the model to estimate the adjustment factor needed to make the survey data fit the demographic profile of France, by adjusting for underreporting of contraceptive non-use and abortions. We then test three behavior change scenarios which would aim to reduce unintended pregnancies: decreasing method failure, increasing time spent on effective methods, and increasing switching from less to more effective methods. Our model suggests that decreasing method failure is the most effective strategy for reducing unintended pregnancies, but all scenarios reduced unintended pregnancies by at least 25%. Dynamic micro simulations such as this may be useful for policy makers. PMID:25469928

Phase-change memory: A continuous multilevel compact model of subthreshold conduction and threshold switching

NASA Astrophysics Data System (ADS)

Pigot, Corentin; Gilibert, Fabien; Reyboz, Marina; Bocquet, Marc; Zuliani, Paola; Portal, Jean-Michel

2018-04-01

Phase-change memory (PCM) compact modeling of the threshold switching based on a thermal runaway in Poole–Frenkel conduction is proposed. Although this approach is often used in physical models, this is the first time it is implemented in a compact model. The model accuracy is validated by a good correlation between simulations and experimental data collected on a PCM cell embedded in a 90 nm technology. A wide range of intermediate states is measured and accurately modeled with a single set of parameters, allowing multilevel programing. A good convergence is exhibited even in snapback simulation owing to this fully continuous approach. Moreover, threshold properties extraction indicates a thermally enhanced switching, which validates the basic hypothesis of the model. Finally, it is shown that this model is compliant with a new drift-resilient cell-state metric. Once enriched with a phase transition module, this compact model is ready to be implemented in circuit simulators.

Effect of Electronegativity on Bipolar Resistive Switching in a WO3-Based Asymmetric Capacitor Structure.

PubMed

Kim, Jongmin; Inamdar, Akbar I; Jo, Yongcheol; Woo, Hyeonseok; Cho, Sangeun; Pawar, Sambhaji M; Kim, Hyungsang; Im, Hyunsik

2016-04-13

This study investigates the transport and switching time of nonvolatile tungsten oxide based resistive-switching (RS) memory devices. These devices consist of a highly resistive tungsten oxide film sandwiched between metal electrodes, and their RS characteristics are bipolar in the counterclockwise direction. The switching voltage, retention, endurance, and switching time are strongly dependent on the type of electrodes used, and we also find quantitative and qualitative evidence that the electronegativity (χ) of the electrodes plays a key role in determining the RS properties and switching time. We also propose an RS model based on the role of the electronegativity at the interface.

Membrane microdomain switching: a regulatory mechanism of amyloid precursor protein processing.

PubMed

Sakurai, Takashi; Kaneko, Kumi; Okuno, Misako; Wada, Koji; Kashiyama, Taku; Shimizu, Hideaki; Akagi, Takumi; Hashikawa, Tsutomu; Nukina, Nobuyuki

2008-10-20

Neuronal activity has an impact on beta cleavage of amyloid precursor protein (APP) by BACE1 to generate amyloid-beta peptide (Abeta). However, the molecular mechanisms underlying this effect remain to be elucidated. Cholesterol dependency of beta cleavage prompted us to analyze immunoisolated APP-containing detergent-resistant membranes from rodent brains. We found syntaxin 1 as a key molecule for activity-dependent regulation of APP processing in cholesterol-dependent microdomains. In living cells, APP associates with syntaxin 1-containing microdomains through X11-Munc18, which inhibits the APP-BACE1 interaction and beta cleavage via microdomain segregation. Phosphorylation of Munc18 by cdk5 causes a shift of APP to BACE1-containing microdomains. Neuronal hyperactivity, implicated in Abeta overproduction, promotes the switching of APP microdomain association as well as beta cleavage in a partially cdk5-dependent manner. We propose that microdomain switching is a mechanism of cholesterol- and activity-dependent regulation of APP processing in neurons.

Membrane microdomain switching: a regulatory mechanism of amyloid precursor protein processing

PubMed Central

Sakurai, Takashi; Kaneko, Kumi; Okuno, Misako; Wada, Koji; Kashiyama, Taku; Shimizu, Hideaki; Akagi, Takumi; Hashikawa, Tsutomu; Nukina, Nobuyuki

2008-01-01

Neuronal activity has an impact on β cleavage of amyloid precursor protein (APP) by BACE1 to generate amyloid-β peptide (Aβ). However, the molecular mechanisms underlying this effect remain to be elucidated. Cholesterol dependency of β cleavage prompted us to analyze immunoisolated APP-containing detergent-resistant membranes from rodent brains. We found syntaxin 1 as a key molecule for activity-dependent regulation of APP processing in cholesterol-dependent microdomains. In living cells, APP associates with syntaxin 1–containing microdomains through X11–Munc18, which inhibits the APP–BACE1 interaction and β cleavage via microdomain segregation. Phosphorylation of Munc18 by cdk5 causes a shift of APP to BACE1-containing microdomains. Neuronal hyperactivity, implicated in Aβ overproduction, promotes the switching of APP microdomain association as well as β cleavage in a partially cdk5-dependent manner. We propose that microdomain switching is a mechanism of cholesterol- and activity-dependent regulation of APP processing in neurons. PMID:18936252

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

NASA Astrophysics Data System (ADS)

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.