Science.gov

Sample records for bright ns lmxbs

  1. INTEGRAL long-term monitoring results on persistently bright NS LMXBs

    NASA Astrophysics Data System (ADS)

    Savolainen, P.; Hannikainen, D. C.; Paizis, A.; Farinelli, R.; Kuulkers, E.; Vilhu, O.

    2010-07-01

    We present long-term spectral and timing results from an INTEGRAL monitoring program of persistently bright neutron star Low-Mass X-ray Binaries, i.e. the three bright Atoll sources GX 3+1, GX 9+1 and GX 9+9, and the Z sources GX 5-1, GX 17+2, GX 340+0 and GX 349+2. From the available observing periods between 2003 and 2009, each lasting ~2 months, we have selected a few sample periods for each source, and analyzed all JEM-X and IBIS/ISGRI data with offsets <4 degrees. We seek an explanation for the dichotomy between the hard X-ray tails or lack thereof in the (otherwise very similar) X-ray spectra of Z sources and bright Atolls, respectively.

  2. Spectral evolution of bright NS LMXBs with INTEGRAL: an application of the thermal plus bulk Comptonization model

    NASA Astrophysics Data System (ADS)

    Mainardi, L. I.; Paizis, A.; Farinelli, R.; Kuulkers, E.; Rodriguez, J.; Hannikainen, D.; Savolainen, P.; Piraino, S.; Bazzano, A.; Santangelo, A.

    2010-03-01

    Aims: The aim of this work is to investigate in a physical and quantitative way the spectral evolution of bright neutron star low-mass X-ray binaries (NS LMXBs) with special regard to the transient hard X-ray tails. Methods: We analyzed INTEGRAL data for five sources (GX 5-1, GX 349+2, GX 13+1, GX 3+1, GX 9+1) and built broad-band X-ray spectra from JEM-X1 and IBIS/ISGRI data. For each source, X-ray spectra from different states were fitted with the recently proposed model compTB. Results: The spectra have been fit with a two-compTB model. In all cases the first compTB describes the dominant part of the spectrum that we interpret as thermal Comptonization of soft seed photons (<1 keV), likely from the accretion disk, by a 3-5 keV corona. In all cases, this component does not evolve much in terms of Comptonization efficiency, with the system converging to thermal equilibrium for an increasing accretion rate. The second compTB varies more dramatically, spanning from bulk plus thermal Comptonization of blackbody seed photons to the blackbody emission alone. These seed photons (R < 12 km, kTs > 1 keV), likely from the neutron star and the innermost part of the system, the transition layer, are Comptonized by matter in a converging flow. The presence and nature of this second compTB component (whether a pure blackbody or Comptonized) are related to the inner local accretion rate which can influence the transient behavior of the hard tail: high values of accretion rates correspond to an efficient bulk Comptonization process (bulk parameter δ≠0), while even higher values of accretion rates suppress the Comptonization, resulting in simple blackbody emission (δ=0). Conclusions: The spectral evolution of the sources has been successfully studied in terms of thermal and bulk Comptonization efficiency in relation to the physical conditions in the transition layer.

  3. A New Comptonization Model for Weakly Magnetized Accreting NS LMXBs

    NASA Astrophysics Data System (ADS)

    Paizis, A.; Farinelli, R.; Titarchuk, L.; Frontera, F.; Cocchi, M.; Ferrigno, C.

    2009-05-01

    We have developed a new Comptonization model to propose, for the first time, a self consistent physical interpretation of the complex spectral evolution seen in NS LMXBs. The model and its application to LMXBs are presented and compared to the Simbol-X expected capabilities.

  4. X-ray variability with spectral state transitions in NS-LMXBs observed with MAXI/GSC and Swift/BAT

    NASA Astrophysics Data System (ADS)

    Asai, Kazumi; Mihara, Tatehiro; Matsuoka, Masaru; Sugizaki, Mutsumi

    2015-10-01

    X-ray variabilities with spectral state transitions in bright low-mass X-ray binaries containing a neutron star are investigated by using the one-day bin light curves of MAXI/GSC (Gas Slit Camera) and Swift/BAT (Burst Alert Telescope). Four sources (4U 1636-536, 4U 1705-44, 4U 1608-52, and GS 1826-238) exhibited small-amplitude X-ray variabilities with spectral state transitions. Such "mini-outbursts" were characterized by smaller amplitudes (several times) and shorter duration (less than several tens of days) than those of "normal outbursts." A theoretical model of disk instability by Mineshige and Osaki (PASJ, 37, 1, 1985) predicts both large-amplitude outbursts and small-amplitude variabilities. We interpret the normal outbursts as the former prediction of this model, and the mini-outbursts as the latter. Here, we can also call the mini-outburst a "purr-type outburst" referring to the theoretical work. We suggest that similar variabilities lasting for several tens of days without spectral state transitions, which are often observed in the hard state, may be repeats of mini-outbursts.

  5. The reflection component in NS LMXBs

    NASA Astrophysics Data System (ADS)

    D'Aí, A.; Papitto, A.; Di Salvo, T.; Iaria, R.; Robba, N. R.; Egron, E.; Piraino, S.

    2014-01-01

    Thanks to the good spectral resolution and large effective area of the EPIC/PN instrument on board of XMM-Newton, we have at hand a large number of observations of accreting low-mass X-ray binaries, that allow for the fist time a comprehensive view on the characteristics of the reflection component at different accretion regimes and to probe the effects of a magnetosphere on its formation. We focus here on a comparative analysis of the reflection component from a series of spectroscopic studies on selected sources: 4U 1705-44, observed both in the soft and hard state, the pulsating ms pulsars SAX J1808.4-3658 and IGR J17511-3057, and the intermittent pulsar HETE J1900-2455. Although the sources can present very similar accretion rates and continuum shapes, the reflection parameters do not generally result the same, moreover the effect of a magnetosphere on the formation of the reflection component appears elusive.

  6. Dust Modeling of Si K Absorption in Galactic Bulge LMXBs with Chandra

    NASA Astrophysics Data System (ADS)

    Schulz, Norbert S.; Corrales, Lia; Canizares, Claude R.

    2016-04-01

    The Galactic Bulge hosts a large number of bright and highly absorbed low-mass X-ray binaries (LMXBs). Column densitiesbetween 1022 cm-2 and 5x1023 cm-2 offer the opportunity and contrast to study the Si K edge structure with very high spectral resolution. Recent models predict that the total extinction in X-ray spectra not only involves X-ray absorption from gas and dust along the line of sight, but also significant contributions from dust scattering. A survey with the Chandra HETG of about a dozen LMXBs yields a rich variety of spectral features, showing that the Si K edge structure is highly complex and variable, from source to source and with time for a given source. We find substructure from neutral atomic silicon, silicate dust absorption and scattering from the interstellar medium (ISM), and superimposed ionized absorption signatures from the circumstellar environment of the LMXBs.

  7. A Hard Look at NS LMXBs with NuSTAR

    NASA Astrophysics Data System (ADS)

    Ludlam, Renee; Miller, Jon M.; Cackett, Edward; Degenaar, Nathalie; Fabian, Andrew C.; Parker, Michael; Tomsick, John; Bachetti, Matteo; Barret, Didier; Natalucci, Lorenzo

    2017-08-01

    Through NuSTAR we have been able to perform inner disk measurements that are unbiased by pile-up effects. From these measurements we are able to infer different properties about the neutron star itself, such as magnetic field estimates, the extent of the boundary layer, and constraints to the equation of state. NuSTAR has observed a number of neutron stars over range of Eddington ratios, which has allowed us to probe the extent of the inner disk over a range of mass accretion rates. There does not appear to be a clear trend between mass accretion rate and the location of the inner disk radius. This affirms the results of several previous studies that were complicated by pile-up effects. We compare the magnetic field strengths from reflection modeling methods to those seen for accreting millisecond X-ray pulsars (AMXPs). We find the magnetic field strengths to be consistent with AMXP’s over comparable Eddington ratios, though coherent pulsations have not yet been detected for some of these sources. Additionally, we explore possible implications for the equation of state of neutron stars.

  8. Monitoring LMXBs with the Faulkes Telescope

    NASA Astrophysics Data System (ADS)

    Lewis, Fraser; Russell, D. M.; Fender, R. P.; Roche, P.

    The Faulkes Telescope Project is the educational arm of the Las Cumbres Observatory Global Telescope Network (LCOGT). It currently has two 2-metre robotic telescopes, located at Haleakala on Maui (FT North) and Siding Spring in Australia (FT South). It is planned to increase this to six 2-metre telescopes in the future, complemented by a network of 30-40 smaller (0.4 - 1 metre) telescopes providing 24 hour coverage of both northern and southern hemispheres. We are undertaking a monitoring project of 10 low-mass X-ray binaries (LMXBs) using FT North to study the optical continuum behaviour of X-ray transients in quiescence. The introduction of FT South in September 2006 allows us to extend this monitoring to include 17 southern hemisphere LMXBs. With new instrumentation, we also intend to expand this monitoring to include both infrared wavelengths and spectroscopy.

  9. Studies of Accreting Neutron Stars with RXTE Cycle 4 Observations: II: Too Observations of Transient LMXBs

    NASA Technical Reports Server (NTRS)

    Paciesas, William S.

    2002-01-01

    NASA Grant NAG 5-9045 provided funds for the research project 'TOO Observations of Transient LMxBs' approved under the Rossi X-ray Timing Explorer (RXTE) Guest Observer Program Cycle 4 and funded under the 1999 NASA Astrophysics Data Program. The principal investigator of the observing time proposal was Dr. M. Mendez (U. of Amsterdam). The grant was funded for one year beginning 3/1/2000. The original proposal was submitted by Prof. Jan van Paradijs, who passed away in 1999 before the funds were distributed. Prof. William S. Pauesas administered the grant during the period of performance. In spite of a wealth of observational data on the kHz QPO in low-mass X-ray binaries (LMXBs), the interpretation of this phenomenon is currently uncertain because the pairs of kHz QPO peaks and the oscillations seen in some Type I X-ray bursts are almost, but not quite, connected by a simple beat frequency relation. The proposal was intended to contribute to a solution to this confusion by making RXTE target-of-opportunity observations of two transient LMXBs, Aql X-1 and 4U 1608-52, if the sources became sufficiently bright.

  10. Unified view of the accretion corona in the LMXBs across the soft and the hard state

    NASA Astrophysics Data System (ADS)

    Ono, Ko; Nakazawa, Kazuhiro; Makishima, Kazuo; Sakurai, Soki; Zhang, Zhongli; Torii, Shunsuke

    A low-mass X-ray binary (LMXB) consists of a neutron star (NS) and a low-mass star (sim 1 M _{⊙}). It exhibits two typical spectral states, the soft state and the hard state, when the accretion rate is high and low, respectively. Using Suzaku, Sakurai et al. (2012, 2014) revealed that the spectra of Aql X-1 in both states can be explained by a blackbody emission from the NS surface Comptonized by an electron corona around the NS plus an optically thick disk emission, though with different parameters. To understand LMXBs in the two states in a unified way, we applied this model to broad-band Suzaku spectra of GS 1826-238 in the hard state and 4U 1608-52 in both states, and obtained successful fits to all the four spectra. As a result, we found that; (1) Comptonization plays an important role in both states; (2) a new parameter, Q equiv (electron temperature)/(seed photon temperature), can be regarded as a good state indicator, (3) multiple LMXBs draw a common locus on a (Q,y) plane, where y is the Compton y-parameter. This result suggests a continuous change of the comptonization across the two spectral states.

  11. THE X-RAY SPECTRA OF THE LUMINOUS LMXBs IN NGC 3379: FIELD AND GLOBULAR CLUSTER SOURCES

    SciTech Connect

    Brassington, N. J.; Fabbiano, G.; Zezas, A.; Kim, D.-W.; Blake, S.; Angelini, L.; Davies, R. L.; Gallagher, J.; Kalogera, V.; King, A. R.; Kundu, A.; Zepf, S.; Trinchieri, G.

    2010-12-20

    From a deep multi-epoch Chandra observation of the elliptical galaxy NGC 3379 we report the spectral properties of eight luminous LMXBs (L{sub X} >1.2 x 10{sup 38} erg s{sup -1}). We also present a set of spectral simulations, produced to aid the interpretation of low-count single-component spectral modeling. These simulations demonstrate that it is possible to infer the spectral states of X-ray binaries from these simple models and thereby constrain the properties of the source. Of the eight LMXBs studied, three reside within globular clusters (GCs) and one is a confirmed field source. Due to the nature of the luminosity cut, all sources are either neutron star (NS) binaries emitting at or above the Eddington luminosity or black hole (BH) binaries. The spectra from these sources are well described by single-component models, with parameters consistent with Galactic LMXB observations, where hard-state sources have a range in photon index of 1.5-1.9 and thermally dominant (TD) sources have inner-disk temperatures between {approx}0.7and1.55 keV. The large variability observed in the brightest GC source (L{sub X} >4 x 10{sup 38} erg s{sup -1}) suggests the presence of a BH binary. At its most luminous this source is observed in a TD state with kT{sub in} = 1.5 keV, consistent with a BH mass of {approx}4 M{sub sun}. This observation provides further evidence that GCs are able to retain such massive binaries. We also observed a source transitioning from a bright state (L{sub X} {approx}1 x 10{sup 39} erg s{sup -1}), with prominent thermal and non-thermal components, to a less luminous hard state (L{sub X} = 3.8 x 10{sup 38} erg s{sup -1}, {Gamma}= 1.85). In its high flux emission, this source exhibits a cool-disk component of {approx}0.14 keV, similar to spectra observed in some ultraluminous X-ray sources (ULXs). Such a similarity indicates a possible link between 'normal' stellar-mass BHs in a high accretion state and ULXs.

  12. Long-term optical/X-ray correlations in LMXBs

    NASA Astrophysics Data System (ADS)

    Russell, David

    We have been monitoring the long-term variability of ~30 low-mass X-ray binaries at optical wavelengths with the two 2-m Faulkes Telescopes. With six to eight years of light curves in several filters for most sources, the data provide a rich database of accretion history in samples of transient, quiescent and persistently accreting LMXBs. Here, we correlate the long-term optical evolution (on week to years timescales) of LMXBs with the hard X-ray flux evolution from Swift BAT, RXTE and INTEGRAL. For black hole LMXBs in the hard state, the optical and X-ray fluxes are highly correlated. In some sources, the clear hard X-ray drop/rise over the hard-to-soft/soft-to-hard state transition is replicated (to a lesser extent) in the optical light curves, and are associated with optical colour changes. Lags between optical and X-ray fluxes are apparent, in both the timing of the peak fluxes (e.g. the optical peak of some outbursts occur several days later than the hard X-ray flux peak) and the drop/rises over state transitions. Optical/X-ray cross-correlations have revealed X-ray lags of several days in some persistent sources, which are likely to represent the viscous timescale of the accretion disc. We demonstrate how the properties of the correlations (correlation index values, lag timescales, dependency on spectral state) can be used to infer the optical emission mechanisms. High amplitude optical drop/rises over state transitions are associated with synchrotron emission from jets, and we discuss whether the same is seen in transient, state changing neutron star LMXBs. We also search for optical correlations to the long-term (hundreds of days) X-ray variability timescales seen in some LMXBs.

  13. Probing the accretion disc structure by the twin kHz QPOs and spins of neutron stars in LMXBs

    NASA Astrophysics Data System (ADS)

    Wang, D. H.; Zhang, C. M.; Lei, Y. J.; Chen, L.; Qu, J. L.; Zhi, Q. J.

    2017-04-01

    We analyse the relation between the emission radii of twin kilohertz quasi-periodic oscillations (kHz QPOs) and the co-rotation radii of the 12 neutron star low-mass X-ray binaries (NS-LMXBs), which are simultaneously detected with the twin kHz QPOs and NS spins. We find that the average co-rotation radius of these sources is ∼ 32 km, and all the emission positions of twin kHz QPOs lie inside the co-rotation radii, indicating that the twin kHz QPOs are formed in the spin-up process. It is noticed that the upper frequency of twin kHz QPOs is higher than NS spin frequency by ≥10 per cent, which may account for a critical velocity difference between the Keplerian motion of accretion matter and NS spin that is corresponding to the production of twin kHz QPOs. In addition, we also find that ∼83 per cent of twin kHz QPOs cluster around the radius range of 15-20 km, which may be affected by the hard surface or the local strong magnetic field of the NS. As a special case, SAX J1808.4-3658 shows the larger emission radii of twin kHz QPOs of r ∼ 21-24 km, which may be due to its low accretion rate or small measured NS mass (<1.4 M⊙).

  14. Multi-wavelength coverage of outburst decays of LMXBs

    NASA Astrophysics Data System (ADS)

    Kalemci, Emrah; Tomsick, John; Bailyn, Charles; Dincer, Tolga

    2016-07-01

    Low mass X-ray binaries (LMXB) are dynamic laboratories that are powered by accretion, and under some conditions these systems create strong outflows in the form of highly collimated jets, or winds. Outburst decays of transient LMXBs provide additional information about compact jets and their relation to changes in timing properties. Our group characterizes the multi-wavelength evolution of Galactic black hole transients during their outburst decays using simultaneous X-ray (RXTE, Swift, and INTEGRAL), optical/infrared (SMARTS) and radio (VLA, ATCA, VLBI). By characterizing the X-ray spectral and timing evolution of these systems, and merging this information with the evolution in the near-infrared and radio, we obtain the conditions necessary to launch stable compact jets, and discuss how jets can be influencing and/or influenced by X-ray timing and spectral properties of these systems. In this presentation, I will summarize recent results regarding multi-wavelength observations of not only black hole systems, but also neutron star X-ray binaries during outburst decays, and discuss models that explain not only the broad spectral energy distribution, but also some of the timing properties of these systems.

  15. Helium-Rich Bursters Reveal the NS Interiors

    NASA Astrophysics Data System (ADS)

    Misanovic, Zdenka

    Thermonuclear bursts in LMXBs accreting pure helium are sensitive to the thermal proceses in the NS interiors, as the heat for burst ignition must come entirely from the pycnonuclear reactions in the crust. But for a small number of observed He-accretors, the measured burst recurrence times are significantly shorter than predicted and cannot be reconciled with any current realistic model. We propose to do the first systematic study of He-rich bursts by observing a sample of four He-accretor candidates and measure their accretion rates and burst recurrence times. (This proposal is companion to another requesting TOO observations of one additional target.)

  16. Soft X-ray Absorption Edges in LMXBs

    NASA Technical Reports Server (NTRS)

    2004-01-01

    The XMM observation of LMC X-2 is part of our program to study X-ray absorption in the interstellar medium (ISM). This program includes a variety of bright X-ray binaries in the Galaxy as well as the Magellanic Clouds (LMC and SMC). LMC X-2 is located near the heart of the LMC. Its very soft X-ray spectrum is used to determine abundance and ionization fractions of neutral and lowly ionized oxygen of the ISM in the LMC. The RGS spectrum so far allowed us to determine the O-edge value to be for atomic O, the EW of O-I in the ls-2p resonance absorption line, and the same for O-II. The current study is still ongoing in conjunction with other low absorption sources like Sco X-1 and the recently observed X-ray binary 4U 1957+11.

  17. A study of the population of LMXBs in the bulge of M 31

    NASA Astrophysics Data System (ADS)

    Voss, R.; Gilfanov, M.

    2007-06-01

    Aims: We explore the population of X-ray point sources in the bulge of M 31 to contrast properties of various subpopulations, such as persistent and transient sources and primordial LMXBs and dynamically formed ones. Methods: Based on the data from 26 archival Chandra observations we study the source content and properties of various subpopulations of X-ray sources to a maximum distance of 12´ from the centre of M 31. Results: To a limiting luminosity of ˜ 1035 erg s-1 we find 263 X-ray point sources, with ˜ 1/3 of these being background galaxies. A study of the spatial distribution and the luminosity function of the X-ray sources shows that the distribution of primordial LMXBs is consistent with the distribution of the K-band light and that their luminosity function flattens below ˜ 1037 erg s-1 to the dN/dL∝ L-1 law in agreement with the behaviour found earlier for LMXBs in the Milky Way and in Cen A. Within a radius of 12 arcmin, the luminosity function is independent of distance to the centre of M 31, in contrast to earlier Chandra studies. The LMXBs located in globular clusters and within ˜ 1 arcmin from the centre of M 31 are presumably created via dynamical interactions. The dynamical origin of the r< 1 arcmin sources is strongly suggested by their radial distribution which follows the ρ^2_{*} profile rather than the K-band light distribution. Their luminosity function shows a prominent fall-off below log(L_X)⪉ 36.5. Although the statistics is insufficient to claim a genuine low-luminosity cut-off in the luminosity function, the best fit powerlaw with a slope of -0.6±0.2 is significantly flatter than the dN/dL∝ L-1 law. We also searched for transients and found 28 sources that varied by a factor larger than 20. Their spatial distribution follows the distribution of the persistent LMXBs within the accuracy allowed by the limited number of transients. Full Table [see full text] is only available in electronic form at http://www.aanda.org

  18. Modeling the Spin Equilibrium of Neutron Stars in LMXBs Without Gravitational Radiation

    NASA Technical Reports Server (NTRS)

    Andersson, N.; Glampedakis, K.; Haskell, B.; Watts, A. L.

    2004-01-01

    In this paper we discuss the spin-equilibrium of accreting neutron stars in LMXBs. We demonstrate that, when combined with a naive spin-up torque, the observed data leads to inferred magnetic fields which are at variance with those of galactic millisecond radiopulsars. This indicates the need for either additional spin-down torques (eg. gravitational radiation) or an improved accretion model. We show that a simple consistent accretion model can be arrived at by accounting for radiation pressure in rapidly accreting systems (above a few percent of the Eddington accretion rate). In our model the inner disk region is thick and significantly sub-Keplerian, and the estimated equilibrium periods are such that the LMXB neutron stars have properties that accord well with the galactic millisecond radiopulsar sample. The implications for future gravitational-wave observations are also discussed briefly.

  19. Modeling the Spin Equilibrium of Neutron Stars in LMXBs Without Gravitational Radiation

    NASA Technical Reports Server (NTRS)

    Andersson, N.; Glampedakis, K.; Haskell, B.; Watts, A. L.

    2004-01-01

    In this paper we discuss the spin-equilibrium of accreting neutron stars in LMXBs. We demonstrate that, when combined with a naive spin-up torque, the observed data leads to inferred magnetic fields which are at variance with those of galactic millisecond radiopulsars. This indicates the need for either additional spin-down torques (eg. gravitational radiation) or an improved accretion model. We show that a simple consistent accretion model can be arrived at by accounting for radiation pressure in rapidly accreting systems (above a few percent of the Eddington accretion rate). In our model the inner disk region is thick and significantly sub-Keplerian, and the estimated equilibrium periods are such that the LMXB neutron stars have properties that accord well with the galactic millisecond radiopulsar sample. The implications for future gravitational-wave observations are also discussed briefly.

  20. Exploration of the Variety of Outburst Modes of Transient Neutron Star LMXBS

    NASA Astrophysics Data System (ADS)

    Bailyn, Charles

    Recent work on transient LMXBs containing neutron stars, particularly Aql X-1, has shown that outbursts are of three types. In addition to the traditional large outbursts, there are also low intensity outbursts, in which no high X-ray state occurs, and short "mini- outbursts" seen in the optical, which are not accompanied by any X-ray flux detectable by the RXTE/ASM. The absence of good triggers from the ASM means that little is known about the non-traditional outburst modes. Here we propose to use our ongoing optical monitoring to trigger PCA observations of ALL outbursts of Aql X-1 and Cen X-4, particularly those which do not evolve into strong X-ray outbursts.

  1. THE MEGASECOND CHANDRA X-RAY VISIONARY PROJECT OBSERVATION OF NGC 3115. III. LUMINOSITY FUNCTIONS OF LMXBS AND DEPENDENCE ON STELLAR ENVIRONMENTS

    SciTech Connect

    Lin, Dacheng; Irwin, Jimmy A.; Wong, Ka-Wah; Jennings, Zachary G.; Romanowsky, Aaron J.; Brodie, Jean P.; Homan, Jeroen; Remillard, Ronald A.; Strader, Jay; Sivakoff, Gregory R.

    2015-07-20

    We studied the X-ray luminosity function (XLF) of low-mass X-ray binaries (LMXBs) in the nearby lenticular galaxy NGC 3115, using the Megasecond Chandra X-ray Visionary Project Observation. With a total exposure time of ∼1.1 Ms, we constructed the XLF down to a limiting luminosity of ∼10{sup 36} erg s{sup −1}, which is much deeper than that typically reached for other early-type galaxies. We found significant flattening of the overall LMXB XLF from dN/dL ∝ L{sup −2.2±0.4} above 5.5 × 10{sup 37} erg s{sup −1} to dN/dL ∝ L{sup −1.0±0.1} below it, although we could not rule out a fit with a higher break at ∼1.6 × 10{sup 38} erg s{sup −1}. We also found evidence that the XLF of LMXBs in globular clusters (GCs) is overall flatter than that of field LMXBs. Thus, our results for this galaxy do not support the idea that all LMXBs are formed in GCs. The XLF of field LMXBs seems to show spatial variation, with the XLF in the inner region of the galaxy being flatter than that in the outer region, probably due to contamination of LMXBs from undetected and/or disrupted GCs in the inner region. The XLF in the outer region is probably the XLF of primordial field LMXBs, exhibiting dN/dL ∝ L{sup −1.2±0.1} up to a break close to the Eddington limit of neutron star LMXBs (∼1.7 × 10{sup 38} erg s{sup −1}). The break of the GC LMXB XLF is lower, at ∼1.1 × 10{sup 37} erg s{sup −1}. We also confirm previous findings that the metal-rich/red GCs are more likely to host LMXBs than the metal-poor/blue GCs, which is more significant for more luminous LMXBs, and that more massive GCs are more likely to host LMXBs.

  2. The XLF of LMXBs in the fields of early-type galaxies, their metal-rich, and metal-poor globular clusters

    NASA Astrophysics Data System (ADS)

    Peacock, Mark; Zepf, Steve E.

    2016-04-01

    The X-ray luminosity function (XLF) of extragalactic low mass X-ray binaries (LMXBs) can provide insights into their nature and origin. We present an analysis of seven early-type galaxies. These galaxies have deep Chandra observations, which detect X-ray sources down to 1037erg/s, and HST optical mosaics that enable the classification of these sources into field LMXBs, globular cluster (GC) LMXBs, and contaminating sources. At all luminosities, we find that the number of field LMXBs per stellar mass is similar in these galaxies. This sample therefore suggests that the GC specific frequency may not influence the field LMXB population. It also suggests that other parameters, such as the stellar IMF, are either similar across the galaxy sample or vary in a way that does not effect the LMXB population. The XLF of the field and GC LMXBs are significantly different (p-value of 3x10-6), with the latter having a flatter XLF. The XLFs of the metal-rich and metal-poor GC LMXBs are similar, although larger samples will be needed to provide sharper tests in the future.

  3. Bright Enceladus

    NASA Image and Video Library

    2011-02-14

    Saturn moon Enceladus reflects sunlight brightly while the planet and its rings fill the background in this view from NASA Cassini spacecraft. Enceladus is one of the most reflective bodies in the solar system.

  4. Brightness of Moonlight.

    ERIC Educational Resources Information Center

    Garstang, R. H.

    1985-01-01

    Measurement of the brightness of moonlight by comparison with lamp-light from a low wattage light bulb is an elementary project in astronomy which illustrates scientific principles for the freshman level. Two methods used for the comparison (shadow brightness method and grease spot method) are explained, with suggestions and expected answers. (DH)

  5. Characterization of Dengue Virus NS4A and NS4B Protein Interaction

    PubMed Central

    Zou, Jing; Xie, Xuping; Wang, Qing-Yin; Dong, Hongping; Lee, Michelle Yueqi; Kang, Congbao

    2015-01-01

    ABSTRACT Flavivirus replication is mediated by a membrane-associated replication complex where viral membrane proteins NS2A, NS2B, NS4A, and NS4B serve as the scaffold for the replication complex formation. Here, we used dengue virus serotype 2 (DENV-2) as a model to characterize viral NS4A-NS4B interaction. NS4A interacts with NS4B in virus-infected cells and in cells transiently expressing NS4A and NS4B in the absence of other viral proteins. Recombinant NS4A and NS4B proteins directly bind to each other with an estimated Kd (dissociation constant) of 50 nM. Amino acids 40 to 76 (spanning the first transmembrane domain, consisting of amino acids 50 to 73) of NS4A and amino acids 84 to 146 (also spanning the first transmembrane domain, consisting of amino acids 101 to 129) of NS4B are the determinants for NS4A-NS4B interaction. Nuclear magnetic resonance (NMR) analysis suggests that NS4A residues 17 to 80 form two amphipathic helices (helix α1, comprised of residues 17 to 32, and helix α2, comprised of residues 40 to 47) that associate with the cytosolic side of endoplasmic reticulum (ER) membrane and helix α3 (residues 52 to 75) that transverses the ER membrane. In addition, NMR analysis identified NS4A residues that may participate in the NS4A-NS4B interaction. Amino acid substitution of these NS4A residues exhibited distinct effects on viral replication. Three of the four NS4A mutations (L48A, T54A, and L60A) that affected the NS4A-NS4B interaction abolished or severely reduced viral replication; in contrast, two NS4A mutations (F71A and G75A) that did not affect NS4A-NS4B interaction had marginal effects on viral replication, demonstrating the biological relevance of the NS4A-NS4B interaction to DENV-2 replication. Taken together, the study has provided experimental evidence to argue that blocking the NS4A-NS4B interaction could be a potential antiviral approach. IMPORTANCE Flavivirus NS4A and NS4B proteins are essential components of the ER membrane

  6. Bright Patches on Ariel

    NASA Image and Video Library

    1998-12-05

    Distinct bright patches are visible on Ariel, the brightest of Uranus five largest satellites. NASA Voyager 2 obtained this image Jan. 22, 1986, from a distance of 2.52 million kilometers 1.56 million miles.

  7. Bright Lights, Green City

    NASA Image and Video Library

    2010-07-28

    Two extremely bright stars illuminate a greenish mist in this image from the new GLIMPSE360 survey from NASA Spitzer Space Telescope. The fog is comprised of hydrogen and carbon compounds called polycyclic aromatic hydrocarbons.

  8. Beyond Bright Rings

    NASA Image and Video Library

    2009-12-30

    The tiny moon Pandora appears beyond the bright disk of Saturn rings in this image taken by NASA Cassini spacecraft. Pandora orbits outside the F ring and, in this image, is farther from Cassini than the rings are.

  9. [Bright light therapy].

    PubMed

    Poirrier, R; Cambron, L

    2007-01-01

    Bright light therapy is a treatment that emerged in the eighties of the last century. It can be used in different pathologies such as seasonal affective disorders, major depressions, and many disorders of the wake-sleep rhythm, whether they are of primary or secondary origin. Important progress made at the basic neuroscience levels, allows today a sound understanding of the bright light mode of action. Moreover, the main indications are now the subject of consensus reports and meta-analyses which show good levels of evidence-based medicine. Bright light therapy constitutes a first choice indication in seasonal affective disorder. It is also perfectly possible to prescribe bright light therapy in the major depression disorders. It has been demonstrated that the effect size is the same as with antidepressants of reference. It is admitted nowadays that bright light therapy may be at least, an adjunct to pharmacotherapy, in order to accelerate the antidepressant effect onset, or to prolong this effect after withdrawal of the drug. Bright light therapy can also be viewed as an alternative to the pharmacological approach especially when this one is impossible, not tolerated or not accepted by the patient. The contraindications are rare.

  10. NS&T Management Observations

    SciTech Connect

    Gianotto, David

    2014-09-01

    The INL Management Observation Program (MOP) is designed to improve managers and supervisors understanding of work being performed by employees and the barriers impacting their success. The MOP also increases workers understanding of managements’ expectations as they relate to safety, security, quality, and work performance. Management observations (observations) are designed to improve the relationship and trust between employees and managers through increased engagement and interactions between managers and researchers in the field. As part of continuous improvement, NS&T management took initiative to focus on the participation and quality of observations in FY 14. This quarterly report is intended to (a) summarize the participation and quality of management’s observations, (b) assess observations for commonalities or trends related to facility or process barriers impacting research, and (c) provide feedback and make recommendations for improvements NS&T’s MOP.

  11. Bright Spokes, Dark Shadow

    NASA Image and Video Library

    2010-04-06

    Bright spokes and the shadow of a moon grace Saturn B ring in this NASA Cassini spacecraft image. Spokes are radial markings scientists continue to study, and they can be seen here stretching from the far left to upper right of the image.

  12. High Brightness OLED Lighting

    SciTech Connect

    Spindler, Jeffrey; Kondakova, Marina; Boroson, Michael; Hamer, John

    2016-05-25

    In this work we describe the technology developments behind our current and future generations of high brightness OLED lighting panels. We have developed white and amber OLEDs with excellent performance based on the stacking approach. Current products achieve 40-60 lm/W, while future developments focus on achieving 80 lm/W or higher.

  13. A Bright Shining Lesson

    ERIC Educational Resources Information Center

    Hurowitz, Amanda

    2010-01-01

    Sometimes students come up with crazy ideas. When this author first started teaching at Thomas Jefferson High School for Science and Technology in Virginia five years ago, she had a sophomore share such an idea with her. He wanted to put solar panels on the school's roof as a way to reduce the school's carbon footprint and set a bright clean…

  14. Bright Fireball Over Georgia

    NASA Image and Video Library

    A camera in Cartersville, Ga., captured this view of a bright fireball over Georgia on the night of Mar. 7, 2012, at approx. 10:19:11 EST. The meteor was first recorded at an altitude of 51.5 miles...

  15. A Bright Shining Lesson

    ERIC Educational Resources Information Center

    Hurowitz, Amanda

    2010-01-01

    Sometimes students come up with crazy ideas. When this author first started teaching at Thomas Jefferson High School for Science and Technology in Virginia five years ago, she had a sophomore share such an idea with her. He wanted to put solar panels on the school's roof as a way to reduce the school's carbon footprint and set a bright clean…

  16. Bright Streak on Amalthea

    NASA Technical Reports Server (NTRS)

    2000-01-01

    These two images of Jupiter's small, irregularly shaped moon Amalthea, obtained by the camera onboard NASA's Galileo spacecraft in August 1999(left) and November 1999 (right), form a 'stereo pair' that helps scientists determine this moon's shape and the topography of its surface features. Features as small as 3.8 kilometers (2.4 miles) across can be resolved in these images, making them among the highest-resolution images ever taken of Amalthea.

    The large impact crater visible in both images, near the right-hand edge of Amalthea's disk, is about 40 kilometers (about 29 miles) across; two ridges, tall enough to cast shadows, extend from the top of the crater in a V-shape reminiscent of a 'rabbit ears' television antenna. To the left of these ridges, in the top center portion of Amalthea's disk, is a second large impact crater similar in size to the first crater. To the left of this second crater is a linear 'streak' of relatively bright material about 50 kilometers (31 miles) long. In previous spacecraft images of Amalthea taken from other viewing directions, this bright feature was thought to be a small, round, bright 'spot' and was given the name Ida. These new images reveal for the first time that Ida is actually a long, linear 'streak.' This bright streak may represent material ejected during the formation of the adjacent impact crater, or it may just mark the crest of a local ridge. Other patches of relatively bright material can be seen elsewhere on Amalthea's disk, although none of these other bright spots has Ida's linear shape.

    In both images, sunlight is coming from the left and north is approximately up. Note that the north pole of Amalthea is missing in the right-hand image (it was cut off by the edge of the camera frame). The bright streak, Ida, is on the side of the moon that faces permanently away from Jupiter, and the crater near the right-hand edge of the disk is in the center of Amalthea's leading side (the side of the moon that 'leads

  17. Bright Streak on Amalthea

    NASA Technical Reports Server (NTRS)

    2000-01-01

    These two images of Jupiter's small, irregularly shaped moon Amalthea, obtained by the camera onboard NASA's Galileo spacecraft in August 1999(left) and November 1999 (right), form a 'stereo pair' that helps scientists determine this moon's shape and the topography of its surface features. Features as small as 3.8 kilometers (2.4 miles) across can be resolved in these images, making them among the highest-resolution images ever taken of Amalthea.

    The large impact crater visible in both images, near the right-hand edge of Amalthea's disk, is about 40 kilometers (about 29 miles) across; two ridges, tall enough to cast shadows, extend from the top of the crater in a V-shape reminiscent of a 'rabbit ears' television antenna. To the left of these ridges, in the top center portion of Amalthea's disk, is a second large impact crater similar in size to the first crater. To the left of this second crater is a linear 'streak' of relatively bright material about 50 kilometers (31 miles) long. In previous spacecraft images of Amalthea taken from other viewing directions, this bright feature was thought to be a small, round, bright 'spot' and was given the name Ida. These new images reveal for the first time that Ida is actually a long, linear 'streak.' This bright streak may represent material ejected during the formation of the adjacent impact crater, or it may just mark the crest of a local ridge. Other patches of relatively bright material can be seen elsewhere on Amalthea's disk, although none of these other bright spots has Ida's linear shape.

    In both images, sunlight is coming from the left and north is approximately up. Note that the north pole of Amalthea is missing in the right-hand image (it was cut off by the edge of the camera frame). The bright streak, Ida, is on the side of the moon that faces permanently away from Jupiter, and the crater near the right-hand edge of the disk is in the center of Amalthea's leading side (the side of the moon that 'leads

  18. Mapping the Interactions between the NS4B and NS3 Proteins of Dengue Virus

    PubMed Central

    Zou, Jing; Lee, Le Tian; Wang, Qing Yin; Xie, Xuping; Lu, Siyan; Yau, Yin Hoe; Yuan, Zhiming; Geifman Shochat, Susana; Kang, Congbao

    2015-01-01

    ABSTRACT Flavivirus RNA synthesis is mediated by a multiprotein complex associated with the endoplasmic reticulum membrane, named the replication complex (RC). Within the flavivirus RC, NS4B, an integral membrane protein with a role in virulence and regulation of the innate immune response, binds to the NS3 protease-helicase. NS4B modulates the RNA helicase activity of NS3, but the molecular details of their interaction remain elusive. Here, we used dengue virus (DENV) to map the determinants for the NS3-NS4B interaction. Coimmunoprecipitation and an in situ proximity ligation assay confirmed that NS3 colocalizes with NS4B in both DENV-infected cells and cells coexpressing both proteins. Surface plasmon resonance demonstrated that subdomains 2 and 3 of the NS3 helicase region and the cytoplasmic loop of NS4B are required for binding. Using nuclear magnetic resonance (NMR), we found that the isolated cytoplasmic loop of NS4B is flexible, with a tendency to form a three-turn α-helix and two short β-strands. Upon binding to the NS3 helicase, 12 amino acids within the cytoplasmic loop of NS4B exhibited line broadening, suggesting a participation in the interaction. Sequence alignment showed that 4 of these 12 residues are strictly conserved across different flaviviruses. Mutagenesis analysis showed that three (Q134, G140, and N144) of the four evolutionarily conserved NS4B residues are essential for DENV replication. The mapping of the NS3/NS4B-interacting regions described here can assist the design of inhibitors that disrupt their interface for antiviral therapy. IMPORTANCE NS3 and NS4B are essential components of the flavivirus RC. Using DENV as a model, we mapped the interaction between the viral NS3 and NS4B proteins. The subdomains 2 and 3 of NS3 helicase as well as the cytoplasmic loop of NS4B are critical for the interaction. Functional analysis delineated residues within the NS4B cytoplasmic loop that are crucial for DENV replication. Our findings reveal

  19. Bright Solar Flare

    NASA Image and Video Library

    2017-09-27

    A bright solar flare is captured by the EIT 195Å instrument on 1998 May 2. A solar flare (a sudden, rapid, and intense variation in brightness) occurs when magnetic energy that has built up in the solar atmosphere is suddenly released, launching material outward at millions of km per hour. The Sun’s magnetic fields tend to restrain each other and force the buildup of tremendous energy, like twisting rubber bands, so much that they eventually break. At some point, the magnetic lines of force merge and cancel in a process known as magnetic reconnection, causing plasma to forcefully escape from the Sun. Credit: NASA/GSFC/SOHO/ESA To learn more go to the SOHO website: sohowww.nascom.nasa.gov/home.html To learn more about NASA's Sun Earth Day go here: sunearthday.nasa.gov/2010/index.php

  20. Little Bright Spot

    NASA Image and Video Library

    2015-01-12

    A bright spot can be seen on the left side of Rhea in this image. The spot is the crater Inktomi, named for a Lakota spider spirit. Inktomi is believed to be the youngest feature on Rhea (949 miles or 1527 kilometers across). The relative youth of the feature is evident by its brightness. Material that is newly excavated from below the moon's surface and tossed across the surface by a cratering event, appears bright. But as the newly exposed surface is subjected to the harsh space environment, it darkens. This is one technique scientists use to date features on surfaces. This view looks toward the trailing hemisphere of Rhea. North on Rhea is up and rotated 21 degrees to the left. The image was taken in visible light with the Cassini spacecraft narrow-angle camera on July 29, 2013. The view was obtained at a distance of approximately 1.0 million miles (1.6 million kilometers) fro http://photojournal.jpl.nasa.gov/catalog/PIA18300

  1. Bright field illumination system

    NASA Technical Reports Server (NTRS)

    Huber, Edward D. (Inventor)

    1998-01-01

    A Bright Field Illumination system for inspecting a range of characteristically different kinds of defects, depressions, and ridges in a selected material surface. The system has an illumination source placed near a first focus of an elliptical reflector. In addition, a camera facing the inspected area is placed near the illumination source and the first focus. The second focus of the elliptical reflector is located at a distance approximately twice the elliptical reflector's distance above the inspected surface. The elliptical reflector directs the light from the source onto the inspected surface. Due to the shape of the elliptical reflector, light that is specularly reflected from the inspected surface is directed into the camera is which located at the position of the reflected second focus of the ellipse. This system creates a brightly lighted background field against which damage sites appear as high contrast dark objects which can be easily detected by a person or an automated inspection system. In addition, the Bright Field Illumination system and method can be used in combination with a vision inspection system providing for multiplexed illumination and data handling of multiple kinds of surface characteristics including abrupt and gradual surface variations and differences between measured characteristics of different kinds and prior instruments.

  2. Kiloamp high-brightness beams

    SciTech Connect

    Caporaso, G.J.

    1987-01-01

    Brightness preservation of high-current relativistic electron beams under two different types of transport is discussed. Recent progress in improving the brightness of laser-guided beams in the Advanced Test Accelerator is reviewed. A strategy for the preservation of the brightness of space-charge-dominated beams in a solenoidal transport system is presented.

  3. Low surface brightness galaxies

    NASA Technical Reports Server (NTRS)

    Vanderhulst, J. M.; Deblok, W. J. G.; Mcgaugh, S. S.; Bothun, G. D.

    1993-01-01

    A program to investigate the properties of low surface brightness (LSB) galaxies involving surface photometry in U, B, V, R, I, and H-alpha, HI imaging with the Westerbork Synthesis Radio Telescope (WSRT) and the very large array (VLA) and spectrophotometry of H2 regions in LSB galaxies is underway. The goal is to verify the idea that LSB galaxies have low star formation rates because the local gas density falls below the critical density for star formation, and to study the stellar population and abundances in LSB galaxies. Such information should help understanding the evolutionary history of LSB galaxies. Some preliminary results are reported.

  4. Bright Loops at 171

    NASA Technical Reports Server (NTRS)

    2007-01-01

    STEREO was able to capture bright loops in exquisite detail as they were arcing above an active region (May 26, 2007) over an 18 hour period. What we are actually seeing are charged particles spinning along magnetic field lines that extend above the Sun's surface. Active regions are areas of intense magnetic activity and often the source of solar storms. In fact, the clip ends with a flourish in which a small coronal mass ejection (CME) blows out into space. This is from the STEREO Ahead spacecraft at the 171 Angstroms wavelength in extreme ultraviolet light.

  5. Large, Bright Wind Ripples

    NASA Technical Reports Server (NTRS)

    2003-01-01

    MGS MOC Release No. MOC2-397, 20 June 2003

    This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows large, relatively bright ripples of windblown sediment in the Sinus Sabaeus region south of Schiaparelli Basin. The surrounding substrate is thickly mantled by very dark material, possibly windblown silt that settled out of the atmosphere. The picture is located near 7.1oS, 343.7oW. Sunlight illuminates the scene from the left.

  6. Large Bright Ripples

    NASA Technical Reports Server (NTRS)

    2004-01-01

    3 February 2004 Wind is the chief agent of change on Mars today. Wind blows dust and it can move coarser sediment such as sand and silt. This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows bright ripples or small dunes on the floors of troughs northeast of Isidis Planitia near 31.1oN, 244.6oW. The picture covers an area 3 km (1.9 mi) wide; sunlight illuminates the scene from the lower left.

  7. HI Surface brightness mapping

    NASA Astrophysics Data System (ADS)

    Pen, Ue-Li; Staveley-Smith, Lister; Chang, Tzu-Ching; Peterson, Jeff; Bandura, Kevin

    2008-04-01

    We propose to scan the 2dF survey field with Parkes multibeam in driftscan mode to make a map to cross correlate with galaxy redshifts. This allows a statistical detection of HI large scale structure out to z=0.15. In this cross correlation, the HI in ALL galaxies contributes, not only the bright ones, which significantly boosts the sensitivity. The proposed 40 hours on the fields result in a forecasted 20 sigma detection. The survey volume is 10 million cubic megaparsec, which contain 10^15 solar masses of hydrogen.

  8. Bright Loops at 171

    NASA Technical Reports Server (NTRS)

    2007-01-01

    STEREO was able to capture bright loops in exquisite detail as they were arcing above an active region (May 26, 2007) over an 18 hour period. What we are actually seeing are charged particles spinning along magnetic field lines that extend above the Sun's surface. Active regions are areas of intense magnetic activity and often the source of solar storms. In fact, the clip ends with a flourish in which a small coronal mass ejection (CME) blows out into space. This is from the STEREO Ahead spacecraft at the 171 Angstroms wavelength in extreme ultraviolet light.

  9. Optical and X-ray rebrightening in NS X-ray Nova Aql X-1

    NASA Astrophysics Data System (ADS)

    Meshcheryakov, A.; Bikmaev, I.; Irtuganov, E.; Sakhibullin, N.; Vlasyuk, V. V.; Spiridonova, O. I.; Khamitov, I.; Medvedev, P.; Pavlinsky, M. N.; Tsygankov, S. S.

    2017-06-01

    The current outburst in NS X-ray Nova Aql X-1 has started 28 May 2017, as it was reported earlier (see ATel#10441, #10450, #10452). During optical monitoring campaign of Aql X-1, performed at 1.5-m Russian-Turkish telescope (TUBITAK National Observatory) and 1-m SAO RAS optical telescope (Special Astrophysical Observatory) we report a substantial increase of optical brightness of Aql X-1 in the last few days.

  10. High brightness electron sources

    SciTech Connect

    Sheffield, R.L.

    1995-07-01

    High energy physics accelerators and free electron lasers put increased demands on the electron beam sources. This paper describes the present research on attaining intense bright electron beams using photoinjectors. Recent results from the experimental programs will be given. The performance advantages and difficulties presently faced by researchers will be discussed, and the following topics will be covered. Progress has been made in photocathode materials, both in lifetime and quantum efficiency. Cesium telluride has demonstrated significantly longer lifetimes than cesium antimonide at 10{sup {minus}8} torr. However, the laser system is more difficult because cesium telluride requires quadrupled YLF instead of the doubled YLF required for cesium antimonide. The difficulty in using photoinjectors is primarily the drive laser, in particular the amplitude stability. Finally, emittance measurements of photoinjector systems can be complicated by the non-thermal nature of the electron beam. An example of the difficulty in measuring beam emittance is given.

  11. High brightness electron accelerator

    DOEpatents

    Sheffield, Richard L.; Carlsten, Bruce E.; Young, Lloyd M.

    1994-01-01

    A compact high brightness linear accelerator is provided for use, e.g., in a free electron laser. The accelerator has a first plurality of acclerating cavities having end walls with four coupling slots for accelerating electrons to high velocities in the absence of quadrupole fields. A second plurality of cavities receives the high velocity electrons for further acceleration, where each of the second cavities has end walls with two coupling slots for acceleration in the absence of dipole fields. The accelerator also includes a first cavity with an extended length to provide for phase matching the electron beam along the accelerating cavities. A solenoid is provided about the photocathode that emits the electons, where the solenoid is configured to provide a substantially uniform magnetic field over the photocathode surface to minimize emittance of the electons as the electrons enter the first cavity.

  12. High brightness electron accelerator

    SciTech Connect

    Sheffield, R.L.; Carlsten, B.E.; Young, L.M.

    1992-12-31

    A compact high brightness linear accelerator is provided for use, e.g., in a free electron laser. The accelerator has a first plurality of acclerating cavities having end walls with four coupling slots for accelerating electrons to high velocities in the absence of quadrupole fields. A second plurality of cavities receives the high velocity electrons for further acceleration, where each of the second cavities has end walls with two coupling slots for acceleration in the absence of dipole fields. The accelerator also includes a first cavity with an extended length to provide for phase matching the electron beam along the accelerating cavities. A solenoid is provided about the photocathode that emits the electrons, where the solenoid is configured to provide a substantially uniform magnetic field over the photocathode surface to minimize emittance of the electrons as the electrons enter the first cavity.

  13. Bright Comet ISON

    NASA Image and Video Library

    2017-09-27

    Comet ISON shines brightly in this image taken on the morning of 19 Nov. 2013. This is a 10-second exposure taken with the Marshall Space Flight Center 20" telescope in New Mexico. The camera there is black and white, but the smaller field of view allows for a better "zoom in" on the comet's coma, which is essentially the head of the comet. Credit: NASA/MSFC/MEO/Cameron McCarty -------- More details on Comet ISON: Comet ISON began its trip from the Oort cloud region of our solar system and is now travelling toward the sun. The comet will reach its closest approach to the sun on Thanksgiving Day -- 28 Nov 2013 -- skimming just 730,000 miles above the sun's surface. If it comes around the sun without breaking up, the comet will be visible in the Northern Hemisphere with the naked eye, and from what we see now, ISON is predicted to be a particularly bright and beautiful comet. Catalogued as C/2012 S1, Comet ISON was first spotted 585 million miles away in September 2012. This is ISON's very first trip around the sun, which means it is still made of pristine matter from the earliest days of the solar system’s formation, its top layers never having been lost by a trip near the sun. Comet ISON is, like all comets, a dirty snowball made up of dust and frozen gases like water, ammonia, methane and carbon dioxide -- some of the fundamental building blocks that scientists believe led to the formation of the planets 4.5 billion years ago. NASA has been using a vast fleet of spacecraft, instruments, and space- and Earth-based telescope, in order to learn more about this time capsule from when the solar system first formed. The journey along the way for such a sun-grazing comet can be dangerous. A giant ejection of solar material from the sun could rip its tail off. Before it reaches Mars -- at some 230 million miles away from the sun -- the radiation of the sun begins to boil its water, the first step toward breaking apart. And, if it survives all this, the intense radiation

  14. Bluetongue Virus Nonstructural Protein NS3/NS3a Is Not Essential for Virus Replication

    PubMed Central

    van Gennip, René G. P.; van de Water, Sandra G. P.; van Rijn, Piet A.

    2014-01-01

    Orbiviruses form the largest genus of the family Reoviridae consisting of at least 23 different virus species. One of these is the bluetongue virus (BTV) and causes severe hemorrhagic disease in ruminants, and is transmitted by bites of Culicoides midges. BTV is a non-enveloped virus which is released from infected cells by cell lysis and/or a unique budding process induced by nonstructural protein NS3/NS3a encoded by genome segment 10 (Seg-10). Presence of both NS3 and NS3a is highly conserved in Culicoides borne orbiviruses which is suggesting an essential role in virus replication. We used reverse genetics to generate BTV mutants to study the function of NS3/NS3a in virus replication. Initially, BTV with small insertions in Seg-10 showed no CPE but after several passages these BTV mutants reverted to CPE phenotype comparable to wtBTV, and NS3/NS3a expression returned by repair of the ORF. These results show that there is a strong selection for functional NS3/NS3a. To abolish NS3 and/or NS3a expression, Seg-10 with one or two mutated start codons (mutAUG1, mutAUG2 and mutAUG1+2) were used to generate BTV mutants. Surprisingly, all three BTV mutants were generated and the respective AUGMet→GCCAla mutations were maintained. The lack of expression of NS3, NS3a, or both proteins was confirmed by westernblot analysis and immunostaining of infected cells with NS3/NS3a Mabs. Growth of mutAUG1 and mutAUG1+2 virus in BSR cells was retarded in both insect and mammalian cells, and particularly virus release from insect cells was strongly reduced. Our findings now enable research on the role of RNA sequences of Seg-10 independent of known gene products, and on the function of NS3/NS3a proteins in both types of cells as well as in the host and insect vector. PMID:24465709

  15. Spin Complicates Eccentric BH-NS Mergers

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2015-08-01

    When a neutron star (NS) has a glancing encounter with a black hole (BH), its spin has a significant effect on the outcome, according to new simulations run by William East of Stanford University and his collaborators. Spotting an Eccentric Merger. In a traditional BH-NS merger, the two objects orbit each other quasi-circularly as they spiral in. But there's another kind of merger that's possible in high-density environments like galactic nuclei or globular clusters: a dynamical capture merger, in which a NS and BH pass each other just close enough that the gravity of the black hole "catches" the NS, leading the two objects to merge with very eccentric orbits. During an eccentric merger, the NS can be torn apart -- at which point some fraction of the tidally-disrupted material will escape the system, while some fraction instead accretes back onto the BH. Knowing these fractions is important for being able to model the expected electromagnetic signatures for the merger: the unbound material can power transients like kilonovae, whereas the accreting material may be the cause of short gamma-ray bursts. The amount of material available for events like these would change their observable strengths. Testing the Effects of Spin. To see whether NS spin has an impact on the behavior of the merger, East and collaborators use a general-relativistic hydrodynamic code to simulate the glancing encounter of a BH and a NS with dimensionless spin between a=0 (non-spinning) and a=0.756 (rotation period of 1 ms). They also vary the separation of the first encounter. The group finds that changing the NS's spin can change a number of outcomes of the merger. To start with, it can affect whether the NS is captured by the BH, or if the encounter is glancing and then both objects carry on their merry way. And if the NS is trapped by the BH and torn apart, then the higher the NS's spin, the more matter outside of the BH ends up unbound, instead of getting trapped into an accretion disk

  16. How Bright Is the Sun?

    ERIC Educational Resources Information Center

    Berr, Stephen

    1991-01-01

    Presents a sequence of activities designed to allow eighth grade students to deal with one of the fundamental relationships that govern energy distribution. Activities guide students to measure light bulb brightness, discover the inverse square law, compare light bulb light to candle light, and measure sun brightness. (two references) (MCO)

  17. Bright Basin on Tethys

    NASA Image and Video Library

    2015-07-27

    With the expanded range of colors visible to Cassini's cameras, differences in materials and their textures become apparent that are subtle or unseen in natural color views. Here, the giant impact basin Odysseus on Saturn's moon Tethys stands out brightly from the rest of the illuminated icy crescent. This distinct coloration may result from differences in either the composition or structure of the terrain exposed by the giant impact. Odysseus (280 miles, or 450 kilometers, across) is one of the largest impact craters on Saturn's icy moons, and may have significantly altered the geologic history of Tethys. Tethys' dark side (at right) is faintly illuminated by reflected light from Saturn. Images taken using ultraviolet, green and infrared spectral filters were combined to create this color view. North on Tethys (660 miles or 1,062 kilometers across) is up in this view. The view was acquired on May 9, 2015 at a distance of approximately 186,000 miles (300,000 kilometers) from Tethys. Image scale is 1.1 mile (1.8 kilometers) per pixel. http://photojournal.jpl.nasa.gov/catalog/PIA18329

  18. Rationalizing meat consumption. The 4Ns.

    PubMed

    Piazza, Jared; Ruby, Matthew B; Loughnan, Steve; Luong, Mischel; Kulik, Juliana; Watkins, Hanne M; Seigerman, Mirra

    2015-08-01

    Recent theorizing suggests that the 4Ns - that is, the belief that eating meat is natural, normal, necessary, and nice - are common rationalizations people use to defend their choice of eating meat. However, such theorizing has yet to be subjected to empirical testing. Six studies were conducted on the 4Ns. Studies 1a and 1b demonstrated that the 4N classification captures the vast majority (83%-91%) of justifications people naturally offer in defense of eating meat. In Study 2, individuals who endorsed the 4Ns tended also to objectify (dementalize) animals and included fewer animals in their circle of moral concern, and this was true independent of social dominance orientation. Subsequent studies (Studies 3-5) showed that individuals who endorsed the 4Ns tend not to be motivated by ethical concerns when making food choices, are less involved in animal-welfare advocacy, less driven to restrict animal products from their diet, less proud of their animal-product decisions, tend to endorse Speciesist attitudes, tend to consume meat and animal products more frequently, and are highly committed to eating meat. Furthermore, omnivores who strongly endorsed the 4Ns tended to experience less guilt about their animal-product decisions, highlighting the guilt-alleviating function of the 4Ns. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Solution conformations of a linked construct of the Zika virus NS2B-NS3 protease.

    PubMed

    Mahawaththa, Mithun C; Pearce, Benjamin J G; Szabo, Monika; Graham, Bim; Klein, Christian D; Nitsche, Christoph; Otting, Gottfried

    2017-03-21

    The Zika virus presents a serious risk for global health. Crystal structures of different constructs of the Zika virus NS2B-NS3 protease (NS2B-NS3pro) have been determined with the aim to provide a basis for rational drug discovery. In these structures, the C-terminal β-hairpin of NS2B, NS2Bc, was observed to be either disordered (open conformation) or bound to NS3pro complementing the substrate binding site (closed conformation). Enzymatically active constructs of flaviviral NS2B-NS3 proteases commonly used for inhibitor testing contain a covalent peptide linker between NS2B and NS3pro. Using a linked construct of Zika virus NS2B-NS3pro, we studied the location of NS2Bc relative to NS3pro in solution by pseudocontact shifts generated by a paramagnetic lanthanide tag attached to NS3pro. Both closed and open conformations were observed with different inhibitors. As the NS2B co-factor is involved in substrate binding of flaviviral NS2B-NS3 proteases, the destabilization of the closed conformation in the linked construct makes it an attractive tool to search for inhibitors that interfere with the formation of the enzymatically active, closed conformation.

  20. Go with the (Bright) Flow

    NASA Image and Video Library

    2017-09-18

    NASA's Mars Reconnaissance Orbiter observes many slopes in the middle latitudes of Mars showing icy flows or glaciers. The region shown here, in the south-facing slope of a crater, is unusual because the flows have bright highlights. The color and brightness variations are likely due to surface coatings of bright dust and dark sand. There is no evidence that these flows are currently active, but they may have been active only millions of years ago. These flows may well contain ice today in their interiors, as confirmed in places by the subsurface radar experiment on MRO. https://photojournal.jpl.nasa.gov/catalog/PIA21953

  1. Notes on the Wess-Zumino-Witten-like structure: L ∞ triplet and NS-NS superstring field theory

    NASA Astrophysics Data System (ADS)

    Matsunaga, Hiroaki

    2017-05-01

    In the NS-NS sector of superstring field theory, there potentially exist three nilpotent generators of gauge transformations and two constraint equations: it makes the gauge algebra of type II theory somewhat complicated. In this paper, we show that every NS-NS actions have their WZW-like forms, and that a triplet of mutually commutative L ∞ products completely determines the gauge structure of NS-NS superstring field theory via its WZW-like structure. We give detailed analysis about it and present its characteristic properties by focusing on two NS-NS actions proposed by [1] and [2].

  2. The C-terminal 50 Amino Acid Residues of Dengue NS3 Protein Are Important for NS3-NS5 Interaction and Viral Replication*

    PubMed Central

    Tay, Moon Y. F.; Saw, Wuan Geok; Zhao, Yongqian; Chan, Kitti W. K.; Singh, Daljit; Chong, Yuwen; Forwood, Jade K.; Ooi, Eng Eong; Grüber, Gerhard; Lescar, Julien; Luo, Dahai; Vasudevan, Subhash G.

    2015-01-01

    Dengue virus multifunctional proteins NS3 protease/helicase and NS5 methyltransferase/RNA-dependent RNA polymerase form part of the viral replication complex and are involved in viral RNA genome synthesis, methylation of the 5′-cap of viral genome, and polyprotein processing among other activities. Previous studies have shown that NS5 residue Lys-330 is required for interaction between NS3 and NS5. Here, we show by competitive NS3-NS5 interaction ELISA that the NS3 peptide spanning residues 566–585 disrupts NS3-NS5 interaction but not the null-peptide bearing the N570A mutation. Small angle x-ray scattering study on NS3(172–618) helicase and covalently linked NS3(172–618)-NS5(320–341) reveals a rigid and compact formation of the latter, indicating that peptide NS5(320–341) engages in specific and discrete interaction with NS3. Significantly, NS3:Asn-570 to alanine mutation introduced into an infectious DENV2 cDNA clone did not yield detectable virus by plaque assay even though intracellular double-stranded RNA was detected by immunofluorescence. Detection of increased negative-strand RNA synthesis by real time RT-PCR for the NS3:N570A mutant suggests that NS3-NS5 interaction plays an important role in the balanced synthesis of positive- and negative-strand RNA for robust viral replication. Dengue virus infection has become a global concern, and the lack of safe vaccines or antiviral treatments urgently needs to be addressed. NS3 and NS5 are highly conserved among the four serotypes, and the protein sequence around the pinpointed amino acids from the NS3 and NS5 regions are also conserved. The identification of the functionally essential interaction between the two proteins by biochemical and reverse genetics methods paves the way for rational drug design efforts to inhibit viral RNA synthesis. PMID:25488659

  3. Progress on New Hepatitis C Virus Targets: NS2 and NS5A

    NASA Astrophysics Data System (ADS)

    Marcotrigiano, Joseph

    Hepatitis C virus (HCV) is a major global health problem, affecting about 170 million people worldwide. Chronic infection can lead to cirrhosis and liver cancer. The replication machine of HCV is a multi-subunit membrane associated complex, consisting of nonstructural proteins (NS2-5B), which replicate the viral RNA genome. The structures of NS5A and NS2 were recently determined. NS5A is an essential replicase component that also modulates numerous cellular processes ranging from innate immunity to cell growth and survival. The structure reveals a novel protein fold, a new zinc coordination motif, a disulfide bond and a dimer interface. Analysis of molecular surfaces suggests the location of the membrane interaction surface of NS5A, as well as hypothetical protein and RNA binding sites. NS2 is one of two virally encoded proteases that are required for processing the viral polyprotein into the mature nonstructural proteins. NS2 is a dimeric cysteine protease with two composite active sites. For each active site, the catalytic histidine and glutamate residues are contributed by one monomer and the nucleophilic cysteine by the other. The C-terminal residues remain coordinated in the two active sites, predicting an inactive post-cleavage form. The structure also reveals possible sites of membrane interaction, a rare cis-proline residue, and highly conserved dimer contacts. The novel features of both structures have changed the current view of HCV polyprotein replication and present new opportunities for antiviral drug design.

  4. Non-structural protein NS3/NS3a is required for propagation of bluetongue virus in Culicoides sonorensis

    USDA-ARS?s Scientific Manuscript database

    Background: Bluetongue virus (BTV) causes non-contagious haemorrhagic disease in ruminants and is transmitted by Culicoides spp. biting midges. BTV encodes four non-structural proteins of which NS3/NS3a is functional in virus release. NS3/NS3a is not essential for in vitro virus replication. However...

  5. Evolution of laser-produced Sn extreme ultraviolet source diameter for high-brightness source

    SciTech Connect

    Roy, Amitava E-mail: aroy@barc.gov.in; Arai, Goki; Hara, Hiroyuki; Higashiguchi, Takeshi; Ohashi, Hayato; Sunahara, Atsushi; Li, Bowen; Dunne, Padraig; O'Sullivan, Gerry; Miura, Taisuke; Mocek, Tomas; Endo, Akira

    2014-08-18

    We have investigated the effect of irradiation of solid Sn targets with laser pulses of sub-ns duration and sub-mJ energy on the diameter of the extreme ultraviolet (EUV) emitting region and source conversion efficiency. It was found that an in-band EUV source diameter as low as 18 μm was produced due to the short scale length of a plasma produced by a sub-ns laser. Most of the EUV emission occurs in a narrow region with a plasma density close to the critical density value. Such EUV sources are suitable for high brightness and high repetition rate metrology applications.

  6. High brightness picosecond electron gun

    SciTech Connect

    Merano, M.; Collin, S.; Renucci, P.; Gatri, M.; Sonderegger, S.; Crottini, A.; Ganiere, J.D.; Deveaud, B.

    2005-08-15

    We have developed a high brightness picosecond electron gun. We have used it to replace the thermionic electron gun of a commercial scanning electron microscope (SEM) in order to perform time-resolved cathodoluminescence experiments. Picosecond electron pulses are produced, at a repetition rate of 80.7 MHz, by femtosecond mode-locked laser pulses focused on a metal photocathode. This system has a normalized axial brightness of 93 A/cm{sup 2} sr kV, allowing for a spatial resolution of 50 nm in the secondary electron imaging mode of the SEM. The temporal width of the electron pulse is 12 ps.

  7. In Situ Mosaic Brightness Correction

    NASA Technical Reports Server (NTRS)

    Deen, Robert G.; Lorre, Jean J.

    2012-01-01

    In situ missions typically have pointable, mast-mounted cameras, which are capable of taking panoramic mosaics comprised of many individual frames. These frames are mosaicked together. While the mosaic software applies radiometric correction to the images, in many cases brightness/contrast seams still exist between frames. This is largely due to errors in the radiometric correction, and the absence of correction for photometric effects in the mosaic processing chain. The software analyzes the overlaps between adjacent frames in the mosaic and determines correction factors for each image in an attempt to reduce or eliminate these brightness seams.

  8. Absolute brightness of fluorescent microspheres.

    PubMed

    Finger, Isaac; Phillips, Scott; Mobley, Elizabeth; Tucker, Robert; Hess, Henry

    2009-02-07

    The absolute brightness of fluorescent particles, such as dye-containing nano- and microspheres or quantum dots, is a critical design parameter for many applications relying on fluorescence detection. The absolute brightness, defined as the ratio of radiant intensity of emission to illumination intensity of excitation, of nile-red fluorescent microspheres with a 1 micrometre diameter is measured to be 4.2 +/- 1 x 10(-16) m(2)/sr, and the implications for the design of kinesin motor protein-powered "smart dust" devices and the remote detection of fluorescence are discussed.

  9. Nonsmooth nonnegative matrix factorization (nsNMF).

    PubMed

    Pascual-Montano, Alberto; Carazo, J M; Kochi, Kieko; Lehmann, Dietrich; Pascual-Marqui, Roberto D

    2006-03-01

    We propose a novel nonnegative matrix factorization model that aims at finding localized, part-based, representations of nonnegative multivariate data items. Unlike the classical nonnegative matrix factorization (NMF) technique, this new model, denoted "nonsmooth nonnegative matrix factorization" (nsNMF), corresponds to the optimization of an unambiguous cost function designed to explicitly represent sparseness, in the form of nonsmoothness, which is controlled by a single parameter. In general, this method produces a set of basis and encoding vectors that are not only capable of representing the original data, but they also extract highly localized patterns, which generally lend themselves to improved interpretability. The properties of this new method are illustrated with several data sets. Comparisons to previously published methods show that the new nsNMF method has some advantages in keeping faithfulness to the data in the achieving a high degree of sparseness for both the estimated basis and the encoding vectors and in better interpretability of the factors.

  10. NS/EP Implications of Electronic Commerce

    DTIC Science & Technology

    1999-06-01

    electronic mail ( e -mail), computer bulletin boards, FAX, electronic funds transfer (EFT), and other similar technologies.3 In defining NS/EP...that are more accessible, efficient, and easy to use. Electronic commerce, e -mail, and electronic benefits funds transfer sensitive information within...several EC tools such as EDI, electronic funds transfer (EFT), e -mail, Internet technologies, computer bulletin boards, and other electronic means. DOD

  11. Bright Beginnings. WWC Intervention Report

    ERIC Educational Resources Information Center

    What Works Clearinghouse, 2009

    2009-01-01

    Bright Beginnings is an early childhood curriculum, based in part on High/Scope[R] and Creative Curriculum[R], with an additional emphasis on literacy skills. The curriculum consists of nine thematic units designed to enhance children's cognitive, social, emotional, and physical development, and each unit includes concept maps, literacy lessons,…

  12. Network based sky Brightness Monitor

    NASA Astrophysics Data System (ADS)

    McKenna, Dan; Pulvermacher, R.; Davis, D. R.

    2009-01-01

    We have developed and are currently testing an autonomous 2 channel photometer designed to measure the night sky brightness in the visual wavelengths over a multi-year campaign. The photometer uses a robust silicon sensor filtered with Hoya CM500 glass. The Sky brightness is measured every minute at two elevation angles typically zenith and 20 degrees to monitor brightness and transparency. The Sky Brightness monitor consists of two units, the remote photometer and a network interface. Currently these devices use 2.4 Ghz transceivers with a free space range of 100 meters. The remote unit is battery powered with day time recharging using a solar panel. Data received by the network interface transmits data via standard POP Email protocol. A second version is under development for radio sensitive areas using an optical fiber for data transmission. We will present the current comparison with the National Park Service sky monitoring camera. We will also discuss the calibration methods used for standardization and temperature compensation. This system is expected to be deployed in the next year and be operated by the International Dark Sky Association SKYMONITOR project.

  13. Bright Spot Locations on Ceres

    NASA Image and Video Library

    2015-12-10

    This map of Ceres, made from images taken by NASA's Dawn spacecraft, shows the locations of about 130 bright areas across the dwarf planet's surface, highlighted in blue. Most of these bright areas are associated with craters. Three insets zoom in on a few areas of interest. Occator Crater, containing the brightest area on Ceres, is shown at top left; Oxo Crater, the second-brightest feature on Ceres, is at top right. In a paper published in the Dec. 10, 2015, issue the journal Nature, Dawn mission scientists identify what they believe to be diffuse hazes at both Occator and Oxo. They believe the hazes appear when the sun shines on these craters, possibly from the sublimation of ice. A typical Ceres crater with bright material that does not appear to have remaining ice is shown at bottom. The bright material in this crater and others appears to originate from mineral salts that may have once been mixed with water ice, but dried up over time, scientists wrote in the same paper. http://photojournal.jpl.nasa.gov/catalog/PIA20183

  14. NetSim Project contributions to ns-3

    SciTech Connect

    2012-05-01

    ns-3 is an external (non-LLNL) open-source framework for modeling computer networks. The LLNL NetSim project uses the ns-3 framework to address specific questions in computer network design, operation, and security. As part of the NetSim work, we develop bug fixes, deature enhancements, and new capabilities for the ns-3 framework. The virtual package referenced here, ns-3-contrib, consists of those developments we have (or will) contribute back to the ns-3 project in source code form, for inclusion in future releases of ns-3.

  15. Identification of the sequence on NS4A required for enhanced cleavage of the NS5A/5B site by hepatitis C virus NS3 protease.

    PubMed Central

    Shimizu, Y; Yamaji, K; Masuho, Y; Yokota, T; Inoue, H; Sudo, K; Satoh, S; Shimotohno, K

    1996-01-01

    In addition to NS3 protease, the NS4A protein is required for efficient cleavage of the nonstructural protein region of the hepatitis C virus polyprotein. To investigate the function and the sequence of NS4A required for the enhancement of NS3 protease activity, we developed an in vitro NS3 protease assay system consisting of three purified viral elements: (i) a recombinant NS3 protease which was expressed in Escherichia coli as a maltose-binding protein-NS3 fusion protein (MBP-NS3), (ii) synthetic NS4A fragments, and (iii) a synthetic peptide substrate which mimics the NS5A/5B junction. We showed that the NS3 protease activity of MBP-NS3 was enhanced in a dose-dependent manner by 4A18-40, which is a peptide composed of amino acid residues 18 to 40 of NS4A. The optimal activity was observed at a 10-fold molar excess of 4A18-40 over MBP-NS3. The coefficient for proteolytic efficiency, kcat/Km, of NS3 protease was increased by about 40 times by the addition of a 10-fold molar excess of 4A18-40. Using a series of truncations of 4A18-40, we estimated that amino acid residues 22 to 31 in NS4A (SVVIVGRIIL) constituted the core sequence for the effector activity. Single-substitution experiments with 4A21-34, a peptide composed of amino acid residues 21 to 34 of NS4A, suggested the importance of several residues (Val-23, Ile-25, Gly-27, Arg-28, Ile-29, and Leu-31) for its activity. In addition, we found that some single-amino-acid substitutions in 4A21-34 were able to inhibit the enhancement of NS3 protease activity by 4A18-40. This approach has potential as a novel strategy for inhibiting the NS3 protease activity important for hepatitis C virus proliferation. PMID:8523516

  16. CONSECUTIVE BRIGHT PULSES IN THE VELA PULSAR

    SciTech Connect

    Palfreyman, Jim L.; Dickey, John M.; Hotan, Claire E.; Hotan, Aidan W.; Young, Timothy G.

    2011-07-01

    We report on the discovery of consecutive bright radio pulses from the Vela pulsar, a new phenomenon that may lead to a greater understanding of the pulsar emission mechanism. This results from a total of 345 hr worth of observations of the Vela pulsar using the University of Tasmania's 26 m radio telescope to study the frequency and statistics of abnormally bright pulses and sub-pulses. The bright pulses show a tendency to appear consecutively. The observations found two groups of six consecutive bright pulses and many groups of two to five bright pulses in a row. The strong radio emission process that produces the six bright pulses lasts between 0.4 and 0.6 s. The numbers of bright pulses in sequence far exceed what would be expected if individual bright pulses were independent random events. Consecutive bright pulses must be generated by an emission process that is long lived relative to the rotation period of the neutron star.

  17. Antigenic variation of core, NS3, and NS5 proteins among genotypes of hepatitis C virus.

    PubMed Central

    Neville, J A; Prescott, L E; Bhattacherjee, V; Adams, N; Pike, I; Rodgers, B; El-Zayadi, A; Hamid, S; Dusheiko, G M; Saeed, A A; Haydon, G H; Simmonds, P

    1997-01-01

    Assays that detect antibody to hepatitis C virus (HCV) are used to screen blood donors and patients with hepatitis. Current enzyme-linked immunosorbent assay (ELISA)-based methods are invariably based upon antigens from expressed recombinant proteins or oligopeptides from HCV type 1. Some HCV antigens used in screening assays are coded by regions of the HCV genome that show extensive variability; therefore, HCV type 1-based assays may be less effective for the detection of antibody elicited by infection with other genotypes. In this study, we have measured antibody reactivity of sera from 110 hepatitis C patients infected with type 1b, 3a, or 4a to genotype-specific and cross-reactive epitopes present in recombinant proteins from HCV genotypes 1b (core, NS3, and NS5), 3a (NS3, NS5), and 4a (core, NS3), corresponding to those used in current third-generation screening ELISAs. By comparing the serological reactivities of sera to type-homologous and type-heterologous antigens, we detected a significant type-specific component to the reactivity to NS3 (61 to 77% of the total reactivity) and NS5 (60% of the total reactivity). Furthermore, despite the similarities in the amino acid sequences of the core antigens of type 1b and type 4a, we also found significantly greater reactivity to type-homologous antigens, with approximately 25% of reactivity being type specific. These findings are consistent with previous findings of fivefold weaker reactivity of sera from HCV type 2- and HCV type 3-infected blood donors in the currently used third-generation ELISAs and suggest that these assays are suboptimal for screening populations in which the predominant genotype is not type 1. PMID:9399495

  18. Investigation of high-temperature bright plasma X-ray sources produced in 5-MA X-pinch experiments.

    PubMed

    Sinars, D B; McBride, R D; Pikuz, S A; Shelkovenko, T A; Wenger, D F; Cuneo, M E; Yu, E P; Chittenden, J P; Harding, E C; Hansen, S B; Peyton, B P; Ampleford, D J; Jennings, C A

    2012-10-12

    Using solid, machined X-pinch targets driven by currents rising from 0 to 5-6 MA in 60 ns, we observed bright spots of 5-9-keV continuum radiation from 5±2-μm diameter regions. The >6-keV radiation is emitted in about 0.4 ns, and the bright spots are roughly 75 times brighter than the bright spots measured at 1 MA. A total x-ray power of 10 TW peak and yields of 165±20 kJ were emitted from a 3-mm height. The 3-5-keV continuum radiation had a 50-90-GW peak power and 0.15-0.35-kJ yield. The continuum is plausibly from a 1275±75-eV blackbody or alternatively from a 3500±500-eV bremsstrahlung source.

  19. High-Brightness Injector Modeling

    SciTech Connect

    Lewellen, John W.

    2004-12-07

    There are many aspects to the successful conception, design, fabrication, and operation of high-brightness electron beam sources. Accurate and efficient modeling of the injector are critical to all phases of the process, from evaluating initial ideas to successful diagnosis of problems during routine operation. The basic modeling tasks will vary from design to design, according to the basic nature of the injector (dc, rf, hybrid, etc.), the type of cathode used (thermionic, photo, field emitter, etc.), and 'macro' factors such as average beam current and duty factor, as well as the usual list of desired beam properties. The injector designer must be at least aware of, if not proficient at addressing, the multitude of issues that arise from these considerations; and, as high-brightness injectors continue to move out of the laboratory, the number of such issues will continue to expand.

  20. High-brightness injector modeling.

    SciTech Connect

    Lewellen, J. W.; Accelerator Systems Division

    2004-01-01

    There are many aspects to the successful conception, design, fabrication, and operation of high-brightness electron beam sources. Accurate and efficient modeling of the injector are critical to all phases of the process, from evaluating initial ideas to successful diagnosis of problems during routine operation. The basic modeling tasks will vary from design to design, according to the basic nature of the injector (dc, rf, hybrid, etc.), the type of cathode used (thermionic, photo, field emitter, etc.), and 'macro' factors such as average beam current and duty factor, as well as the usual list of desired beam properties. The injector designer must be at least aware of, if not proficient at addressing, the multitude of issues that arise from these considerations; and, as high-brightness injectors continue to move out of the laboratory, the number of such issues will continue to expand.

  1. Brightness-equalized quantum dots

    PubMed Central

    Lim, Sung Jun; Zahid, Mohammad U.; Le, Phuong; Ma, Liang; Entenberg, David; Harney, Allison S.; Condeelis, John; Smith, Andrew M.

    2015-01-01

    As molecular labels for cells and tissues, fluorescent probes have shaped our understanding of biological structures and processes. However, their capacity for quantitative analysis is limited because photon emission rates from multicolour fluorophores are dissimilar, unstable and often unpredictable, which obscures correlations between measured fluorescence and molecular concentration. Here we introduce a new class of light-emitting quantum dots with tunable and equalized fluorescence brightness across a broad range of colours. The key feature is independent tunability of emission wavelength, extinction coefficient and quantum yield through distinct structural domains in the nanocrystal. Precise tuning eliminates a 100-fold red-to-green brightness mismatch of size-tuned quantum dots at the ensemble and single-particle levels, which substantially improves quantitative imaging accuracy in biological tissue. We anticipate that these materials engineering principles will vastly expand the optical engineering landscape of fluorescent probes, facilitate quantitative multicolour imaging in living tissue and improve colour tuning in light-emitting devices. PMID:26437175

  2. Low-brightness quantum radar

    NASA Astrophysics Data System (ADS)

    Lanzagorta, Marco

    2015-05-01

    One of the major scientific thrusts from recent years has been to try to harness quantum phenomena to dramatically increase the performance of a wide variety of classical information processing devices. These advances in quantum information science have had a considerable impact on the development of standoff sensors such as quantum radar. In this paper we analyze the theoretical performance of low-brightness quantum radar that uses entangled photon states. We use the detection error probability as a measure of sensing performance and the interception error probability as a measure of stealthiness. We compare the performance of quantum radar against a coherent light sensor (such as lidar) and classical radar. In particular, we restrict our analysis to the performance of low-brightness standoff sensors operating in a noisy environment. We show that, compared to the two classical standoff sensing devices, quantum radar is stealthier, more resilient to jamming, and more accurate for the detection of low reflectivity targets.

  3. Brightness-equalized quantum dots.

    PubMed

    Lim, Sung Jun; Zahid, Mohammad U; Le, Phuong; Ma, Liang; Entenberg, David; Harney, Allison S; Condeelis, John; Smith, Andrew M

    2015-10-05

    As molecular labels for cells and tissues, fluorescent probes have shaped our understanding of biological structures and processes. However, their capacity for quantitative analysis is limited because photon emission rates from multicolour fluorophores are dissimilar, unstable and often unpredictable, which obscures correlations between measured fluorescence and molecular concentration. Here we introduce a new class of light-emitting quantum dots with tunable and equalized fluorescence brightness across a broad range of colours. The key feature is independent tunability of emission wavelength, extinction coefficient and quantum yield through distinct structural domains in the nanocrystal. Precise tuning eliminates a 100-fold red-to-green brightness mismatch of size-tuned quantum dots at the ensemble and single-particle levels, which substantially improves quantitative imaging accuracy in biological tissue. We anticipate that these materials engineering principles will vastly expand the optical engineering landscape of fluorescent probes, facilitate quantitative multicolour imaging in living tissue and improve colour tuning in light-emitting devices.

  4. Binary NS simulations using SpEC

    NASA Astrophysics Data System (ADS)

    Haas, Roland; Szilagyi, Bela; Kaplan, Jeffrey; Ott, Christian; Lippuner, Jonas; Scheel, Mark; Barkett, Kevin; Muhlberger, Curran; Foucart, Francois; Duez, Matthew

    2014-03-01

    NSNS binaries are expected to be one of the major sources of gravitational radiation detectable by Advanced LIGO. Together with neutrinos, gravitational waves are our only means to learn about the processes deep within a merging pair of NS, shedding light on the as yet poorly understood, equation of state governing matter at nuclear densities and beyond. We report on binary neutron star simulations using the Spectral Einstein Code (SpEC) developed by the Caltech-Cornell-CITA-WSU collaboration. We simulate the inspiral through many orbits, follow the post-merger evolution, and compute the full gravitational wave signal.

  5. Bright tunable ultraviolet squeezed light.

    PubMed

    Bell, A S; Riis, E; Ferguson, A I

    1997-04-15

    We have produced bright tunable squeezed light by second-harmonic generation in a singly resonant cavity. We have investigated the effect of input coupling and fundamental power on the squeezing. Up to 400 mW of continuous-wave mode-locked tunable squeezed light was produced at wavelengths as short as 389 nm, and more than 1.5 dB of squeezing was inferred.

  6. Iapetus Bright and Dark Terrains

    NASA Technical Reports Server (NTRS)

    1990-01-01

    Saturn's outermost large moon, Iapetus, has a bright, heavily cratered icy terrain and a dark terrain, as shown in this Voyager 2 image taken on August 22, 1981. Amazingly, the dark material covers precisely the side of Iapetus that leads in the direction of orbital motion around Saturn (except for the poles), whereas the bright material occurs on the trailing hemisphere and at the poles. The bright terrain is made of dirty ice, and the dark terrain is surfaced by carbonaceous molecules, according to measurements made with Earth-based telescopes. Iapetus' dark hemisphere has been likened to tar or asphalt and is so dark that no details within this terrain were visible to Voyager 2. The bright icy hemisphere, likened to dirty snow, shows many large impact craters. The closest approach by Voyager 2 to Iapetus was a relatively distant 600,000 miles, so that our best images, such as this, have a resolution of about 12 miles. The dark material is made of organic substances, probably including poisonous cyano compounds such as frozen hydrogen cyanide polymers. Though we know a little about the dark terrain's chemical nature, we do not understand its origin. Two theories have been developed, but neither is fully satisfactory--(1) the dark material may be organic dust knocked off the small neighboring satellite Phoebe and 'painted' onto the leading side of Iapetus as the dust spirals toward Saturn and Iapetus hurtles through the tenuous dust cloud, or (2) the dark material may be made of icy-cold carbonaceous 'cryovolcanic' lavas that were erupted from Iapetus' interior and then blackened by solar radiation, charged particles, and cosmic rays. A determination of the actual cause, as well as discovery of any other geologic features smaller than 12 miles across, awaits the Cassini Saturn orbiter to arrive in 2004.

  7. Iapetus Bright and Dark Terrains

    NASA Technical Reports Server (NTRS)

    1990-01-01

    Saturn's outermost large moon, Iapetus, has a bright, heavily cratered icy terrain and a dark terrain, as shown in this Voyager 2 image taken on August 22, 1981. Amazingly, the dark material covers precisely the side of Iapetus that leads in the direction of orbital motion around Saturn (except for the poles), whereas the bright material occurs on the trailing hemisphere and at the poles. The bright terrain is made of dirty ice, and the dark terrain is surfaced by carbonaceous molecules, according to measurements made with Earth-based telescopes. Iapetus' dark hemisphere has been likened to tar or asphalt and is so dark that no details within this terrain were visible to Voyager 2. The bright icy hemisphere, likened to dirty snow, shows many large impact craters. The closest approach by Voyager 2 to Iapetus was a relatively distant 600,000 miles, so that our best images, such as this, have a resolution of about 12 miles. The dark material is made of organic substances, probably including poisonous cyano compounds such as frozen hydrogen cyanide polymers. Though we know a little about the dark terrain's chemical nature, we do not understand its origin. Two theories have been developed, but neither is fully satisfactory--(1) the dark material may be organic dust knocked off the small neighboring satellite Phoebe and 'painted' onto the leading side of Iapetus as the dust spirals toward Saturn and Iapetus hurtles through the tenuous dust cloud, or (2) the dark material may be made of icy-cold carbonaceous 'cryovolcanic' lavas that were erupted from Iapetus' interior and then blackened by solar radiation, charged particles, and cosmic rays. A determination of the actual cause, as well as discovery of any other geologic features smaller than 12 miles across, awaits the Cassini Saturn orbiter to arrive in 2004.

  8. LSST Site: Sky Brightness Data

    NASA Astrophysics Data System (ADS)

    Burke, Jamison; Claver, Charles

    2015-01-01

    The Large Synoptic Survey Telescope (LSST) is an upcoming robotic survey telescope. At the telescope site on Cerro Pachon in Chile there are currently three photodiodes and a Canon camera with a fisheye lens, and both the photodiodes and Canon monitor the night sky continuously. The NIST-calibrated photodiodes directly measure the flux from the sky, and the sky brightness can also be obtained from the Canon images via digital aperture photometry. Organizing and combining the two data sets gives nightly information of the development of sky brightness across a swath of the electromagnetic spectrum, from blue to near infrared light, and this is useful for accurately predicting the performance of the LSST. It also provides data for models of moonlight and twilight sky brightness. Code to accomplish this organization and combination was successfully written in Python, but due to the backlog of data not all of the nights were processed by the end of the summer.Burke was supported by the NOAO/KPNO Research Experiences for Undergraduates (REU) Program which is funded by the National Science Foundation Research Experiences for Undergraduates Program (AST-1262829).

  9. Purification and crystallization of dengue and West Nile virus NS2B–NS3 complexes

    SciTech Connect

    D’Arcy, Allan Chaillet, Maxime; Schiering, Nikolaus; Villard, Frederic; Lim, Siew Pheng; Lefeuvre, Peggy; Erbel, Paul

    2006-02-01

    Crystals of dengue serotype 2 and West Nile virus NS2B–NS3 protease complexes have been obtained and the crystals of both diffract to useful resolution. Sample homogeneity was essential for obtaining X-ray-quality crystals of the dengue protease. Controlled proteolysis produced a crystallizable fragment of the apo West Nile virus NS2B–NS3 and crystals were also obtained in the presence of a peptidic inhibitor. Both dengue and West Nile virus infections are an increasing risk to humans, not only in tropical and subtropical areas, but also in North America and parts of Europe. These viral infections are generally transmitted by mosquitoes, but may also be tick-borne. Infection usually results in mild flu-like symptoms, but can also cause encephalitis and fatalities. Approximately 2799 severe West Nile virus cases were reported this year in the United States, resulting in 102 fatalities. With this alarming increase in the number of West Nile virus infections in western countries and the fact that dengue virus already affects millions of people per year in tropical and subtropical climates, there is a real need for effective medicines. A possible therapeutic target to combat these viruses is the protease, which is essential for virus replication. In order to provide structural information to help to guide a lead identification and optimization program, crystallizations of the NS2B–NS3 protease complexes from both dengue and West Nile viruses have been initiated. Crystals that diffract to high resolution, suitable for three-dimensional structure determinations, have been obtained.

  10. Discovery of novel cyclic peptide inhibitors of dengue virus NS2B-NS3 protease with antiviral activity.

    PubMed

    Takagi, Youhei; Matsui, Kouhei; Nobori, Haruaki; Maeda, Haruka; Sato, Akihiko; Kurosu, Takeshi; Orba, Yasuko; Sawa, Hirofumi; Hattori, Kazunari; Higashino, Kenichi; Numata, Yoshito; Yoshida, Yutaka

    2017-08-01

    NS2B-NS3 protease is an essential enzyme for the replication of dengue virus (DENV), which continues to be a serious threat to worldwide public health. We designed and synthesized a series of cyclic peptides mimicking the substrates of this enzyme, and assayed their activity against the DENV-2 NS2B-NS3 protease. The introduction of aromatic residues at the appropriate positions and conformational restriction generated the most promising cyclic peptide with an IC50 of 0.95μM against NS2B-NS3 protease. Cyclic peptides with proper positioning of additional arginines and aromatic residues exhibited antiviral activity against DENV. Furthermore, replacing the C-terminal amide bond of the polybasic amino acid sequence with an amino methylene moiety stabilized the cyclic peptides against hydrolysis by NS2B-NS3 protease, while maintaining their enzyme inhibitory activity and antiviral activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. High-brightness rf linear accelerators

    SciTech Connect

    Jameson, R.A.

    1986-01-01

    The issue of high brightness and its ramifications in linacs driven by radio-frequency fields is discussed. A history of the RF linacs is reviewed briefly. Some current applications are then examined that are driving progress in RF linacs. The physics affecting the brightness of RF linacs is then discussed, followed by the economic feasibility of higher brightness machines. (LEW)

  12. Conformational flexibility of DENV NS2B/NS3pro: from the inhibitor effect to the serotype influence

    NASA Astrophysics Data System (ADS)

    Piccirillo, Erika; Merget, Benjamin; Sotriffer, Christoph A.; do Amaral, Antonia T.

    2016-03-01

    The dengue virus (DENV) has four well-known serotypes, namely DENV1 to DENV4, which together cause 50-100 million infections worldwide each year. DENV NS2B/NS3pro is a protease recognized as a valid target for DENV antiviral drug discovery. However, NS2B/NS3pro conformational flexibility, involving in particular the NS2B region, is not yet completely understood and, hence, a big challenge for any virtual screening (VS) campaign. Molecular dynamics (MD) simulations were performed in this study to explore the DENV3 NS2B/NS3pro binding-site flexibility and obtain guidelines for further VS studies. MD simulations were done with and without the Bz-nKRR-H inhibitor, showing that the NS2B region stays close to the NS3pro core even in the ligand-free structure. Binding-site conformational states obtained from the simulations were clustered and further analysed using GRID/PCA, identifying four conformations of potential importance for VS studies. A virtual screening applied to a set of 31 peptide-based DENV NS2B/NS3pro inhibitors, taken from literature, illustrated that selective alternative pharmacophore models can be constructed based on conformations derived from MD simulations. For the first time, the NS2B/NS3pro binding-site flexibility was evaluated for all DENV serotypes using homology models followed by MD simulations. Interestingly, the number of NS2B/NS3pro conformational states differed depending on the serotype. Binding-site differences could be identified that may be crucial to subsequent VS studies.

  13. Determinants of Dengue Virus NS4A Protein Oligomerization

    PubMed Central

    Lee, Chia Min; Xie, Xuping; Zou, Jing; Li, Shi-Hua; Lee, Michelle Yue Qi; Dong, Hongping; Qin, Cheng-Feng; Kang, Congbao

    2015-01-01

    ABSTRACT Flavivirus NS4A protein induces host membrane rearrangement and functions as a replication complex component. The molecular details of how flavivirus NS4A exerts these functions remain elusive. Here, we used dengue virus (DENV) as a model to characterize and demonstrate the biological relevance of flavivirus NS4A oligomerization. DENV type 2 (DENV-2) NS4A protein forms oligomers in infected cells or when expressed alone. Deletion mutagenesis mapped amino acids 50 to 76 (spanning the first transmembrane domain [TMD1]) of NS4A as the major determinant for oligomerization, while the N-terminal 50 residues contribute only slightly to the oligomerization. Nuclear magnetic resonance (NMR) analysis of NS4A amino acids 17 to 80 suggests that residues L31, L52, E53, G66, and G67 could participate in oligomerization. Ala substitution for 15 flavivirus conserved NS4A residues revealed that these amino acids are important for viral replication. Among the 15 mutated NS4A residues, 2 amino acids (E50A and G67A) are located within TMD1. Both E50A and G67A attenuated viral replication, decreased NS4A oligomerization, and reduced NS4A protein stability. In contrast, NS4A oligomerization was not affected by the replication-defective mutations (R12A, P49A, and K80A) located outside TMD1. trans complementation experiments showed that expression of wild-type NS4A alone was not sufficient to rescue the replication-lethal NS4A mutants. However, the presence of DENV-2 replicons could partially restore the replication defect of some lethal NS4A mutants (L26A and K80A), but not others (L60A and E122A), suggesting an unidentified mechanism governing the outcome of complementation in a mutant-dependent manner. Collectively, the results have demonstrated the importance of TMD1-mediated NS4A oligomerization in flavivirus replication. IMPORTANCE We report that DENV NS4A forms oligomers. Such NS4A oligomerization is mediated mainly through amino acids 50 to 76 (spanning the first

  14. Photometric monitoring of bright supernovae

    NASA Astrophysics Data System (ADS)

    Tsvetkov, D. Yu.; Pavlyuk, N. N.; Volkov, I. M.; Shugarov, S. Yu.

    2014-03-01

    The program of CCD photometric monitoring of bright supernovae (SNe) is carried out at 0.4 — 1.0 meter telescopes of the Sternberg Astronomical Institute, Crimean Astrophysical Observatory and Stará Lesná Observatory since 1998. We have observed more than 250 SNe of different types. We present the results of observations of SNe Ia 2003du, 2009nr and 2011fe, type IIb SNe 2008ax, 2011dh, type II SNe 2004ek and 2005kd and discuss physical parameters of the explosions. %

  15. Exceptionally bright, compact starburst nucleus

    SciTech Connect

    Margon, B.; Anderson, S.F.; Mateo, M.; Fich, M.; Massey, P.

    1988-11-01

    Observations are reported of a remarkably bright (V about 13) starburst nucleus, 0833 + 652, which has been detected at radio, infrared, optical, ultraviolet, and X-ray wavelengths. Despite an observed flux at each of these wavelengths which is comparable to that of NGC 7714, often considered the 'prototypical' example of the starburst phenomenon, 0833 + 652 appears to be a previously uncataloged object. Its ease of detectability throughout the electromagnetic spectrum should make it useful for a variety of problems in the study of compact emission-line galaxies. 30 references.

  16. High brightness beams and applications

    SciTech Connect

    Sheffield, R.L.

    1995-09-01

    This paper describes the present research on attaining intense bright electron beams. Thermionic systems are briefly covered. Recent and past results from the photoinjector programs are given. The performance advantages and difficulties presently faced by researchers using photoinjectors is discussed. The progress that has been made in photocathode materials, both in lifetime and quantum efficiency, is covered. Finally, a discussion of emittance measurements of photoinjector systems and how the measurement is complicated by the non-thermal nature of the electron beam is presented.

  17. BRIGHT 'MERGER-NOVA' FROM THE REMNANT OF A NEUTRON STAR BINARY MERGER: A SIGNATURE OF A NEWLY BORN, MASSIVE, MILLISECOND MAGNETAR

    SciTech Connect

    Yu, Yun-Wei; Zhang, Bing; Gao, He E-mail: zhang@physics.unlv.edu

    2013-10-20

    A massive millisecond magnetar may survive the merger of a neutron star (NS) binary, which would continuously power the merger ejecta. We develop a generic dynamic model for the merger ejecta with energy injection from the central magnetar. The ejecta emission (the {sup m}erger-nova{sup )} powered by the magnetar peaks in the UV band and the peak of the light curve, progressively shifts to an earlier epoch with increasing frequency. A magnetar-powered merger-nova could have an optical peak brightness comparable to a supernova, which is a few tens or hundreds times brighter than the radioactive-powered merger-novae (the so-called macro-nova or kilo-nova). On the other hand, such a merger-nova would peak earlier and have a significantly shorter duration than that of a supernova. An early collapse of the magnetar could suppress the brightness of the optical emission and shorten its duration. Such millisecond-magnetar-powered merger-novae may be detected from NS-NS merger events without an observed short gamma-ray burst, and could be a bright electromagnetic counterpart for gravitational wave bursts due to NS-NS mergers. If detected, it suggests that the merger leaves behind a massive NS, which has important implications for the equation-of-state of nuclear matter.

  18. Binary NS simulations using SpEC

    NASA Astrophysics Data System (ADS)

    Haas, Roland; Kaplan, Jeffrey; Ott, Christian; Szilagyi, Bela; Scheel, Mark; Moesta, Philipp; Duez, Matthew; Foucart, Francois

    2012-03-01

    NSNS binaries are expected to be one of the major sources of gravitational radiation detectable by Advanced LIGO. Together with neutrinos, gravitational waves are our only means to learn about the processes deep within a merging pair of NS, shedding light on the as yet poorly understood, equation of state governing matter at nuclear densities and beyond. We report on binary neutron star simulations using the Spectral Einstein Code (SpEC) developed by the Caltech-Cornell-CITA-WSU collaboration. We simulate the inspiral through many orbits, follow the post-merger evolution, and compute the full gravitational wave signal. We provide estimates on the accuracy required for the LIGO scientific goals of constraining EOS parameters.

  19. Binary NS simulations using SpEC

    NASA Astrophysics Data System (ADS)

    Haas, Roland; Kaplan, Jeffrey; Szilagyi, Bela; Muhlberger, Curran; Foucart, Francois; Lippuner, Jonas; Scheel, Mark; Duez, Matthew; Ott, Christian

    2013-04-01

    NSNS binaries are expected to be one of the major sources of gravitational radiation detectable by Advanced LIGO. Together with neutrinos, gravitational waves are our only means to learn about the processes deep within a merging pair of NS, shedding light on the as yet poorly understood, equation of state governing matter at nuclear densities and beyond. We report on binary neutron star simulations using the Spectral Einstein Code (SpEC) developed by the Caltech-Cornell-CITA-WSU collaboration. We simulate the inspiral through many orbits, follow the post-merger evolution, and compute the full gravitational wave signal. We provide estimates on the accuracy required for the LIGO scientific goals of constraining EOS parameters.

  20. A Genetic Interaction between Hepatitis C Virus NS4B and NS3 Is Important for RNA Replication▿

    PubMed Central

    Paredes, Anne M.; Blight, Keril J.

    2008-01-01

    Hepatitis C virus (HCV) nonstructural protein 4B (NS4B), a poorly characterized integral membrane protein, is thought to function as a scaffold for replication complex assembly; however, functional interactions with the other HCV nonstructural proteins within this complex have not been defined. We report that a Con1 chimeric subgenomic replicon containing the NS4B gene from the closely related H77 isolate is defective for RNA replication in a transient assay, suggesting that H77 NS4B is unable to productively interact with the Con1 replication machinery. The H77 NS4B sequences that proved detrimental for Con1 RNA replication resided in the predicted N- and C-terminal cytoplasmic domains as well as the central transmembrane region. Selection for Con1 derivatives that could utilize the entire H77 NS4B or hybrid Con1-H77 NS4B proteins yielded mutants containing single amino acid substitutions in NS3 and NS4A. The second-site mutations in NS3 partially restored the replication of Con1 chimeras containing the N-terminal or transmembrane domains of H77 NS4B. In contrast, the deleterious H77-specific sequences in the C terminus of NS4B, which mapped to a cluster of four amino acids, were completely suppressed by second-site substitutions in NS3. Collectively, these results provide the first evidence for a genetic interaction between NS4B and NS3 important for productive HCV RNA replication. PMID:18715921

  1. High Brightness Accelerator for Warm Dense Matter Studies.

    NASA Astrophysics Data System (ADS)

    Henestroza, Enrique; Grote, David P.; Briggs, Richard J.

    2005-10-01

    A high brightness heavy ion accelerator for creating powerful beams to study warm dense matter is being designed at LBNL. The components are an injector that delivers 0.1 μC of sodium beam, and an accelerator that boosts the energy to about 20 MeV. Further beam manipulations will compress the beam to a final spot radius of 1 mm and a pulse length of 1 ns. In order to reach those final parameters, it is required to extract a high brightness beam and minimize the transverse and longitudinal emittance growth along the accelerator. The injector is based on the Accel-Decel concept which enables the extraction of a high line charge density beam from the ion source, and the accelerator is based on the Pulse Line Ion Accelerator concept, which uses a slow-wave structure based on a helical winding, on which a voltage pulse is launched and propagated to generate the accelerating fields. We will present numerical simulations of the beam dynamics in this system.

  2. Prevalence of Resistance-Associated Substitutions in HCV NS5A, NS5B, or NS3 and Outcomes of Treatment With Ledipasvir and Sofosbuvir.

    PubMed

    Sarrazin, Christoph; Dvory-Sobol, Hadas; Svarovskaia, Evguenia S; Doehle, Brian P; Pang, Phillip S; Chuang, Shu-Min; Ma, Julie; Ding, Xiao; Afdhal, Nezam H; Kowdley, Kris V; Gane, Edward J; Lawitz, Eric; Brainard, Diana M; McHutchison, John G; Miller, Michael D; Mo, Hongmei

    2016-09-01

    We evaluated the effects of baseline hepatitis C virus (HCV) NS5A, NS5B, and NS3 resistance-associated substitutions (RASs) on response to the combination of ledipasvir and sofosbuvir, with or without ribavirin, in patients with HCV genotype 1 infection. We analyzed data from 2144 participants in phase 2 and 3 studies of patients with HCV genotype 1a or b infection who received the combination of ledipasvir (90 mg) and sofosbuvir (400 mg) (ledipasvir/sofosbuvir) once daily, with or without ribavirin twice daily. Population and/or deep sequence analyses of the HCV NS3, NS5A, and NS5B genes were performed on blood samples collected at baseline. Overall, 16.0% of patients had detectable baseline RASs in NS5A. Among patients with HCV genotype 1b infection, there was no significant effect of baseline RASs in NS5A on sustained viral response 12 weeks after the end of treatment (SVR12) with ledipasvir/sofosbuvir and only a small effect in patients with HCV genotype 1a infection. RASs in NS5A that increased the half-maximal effective concentration to ledipasvir by more than 100-fold reduced the rate of SVR12 in treatment-naive patients given ledipasvir/sofosbuvir for 8 weeks (P = .011), but not for 12 weeks. These same baseline NS5A RASs reduced the percentage of treatment-experienced patients who achieved an SVR12 to 12 weeks (but not 24 weeks) ledipasvir/sofosbuvir (P < .001). These RASs had a small effect in patients given ledipasvir/sofosbuvir in combination with ribavirin for 12 weeks. Overall, 2.5% of patients had baseline NS5B nucleotide inhibitor RASs (L159F, N142T, S282G, or L320S) and all achieved an SVR12. Of patients previously treated with protease inhibitors, 53.7% had RASs in NS3 and 96.5% achieved an SVR12. Baseline RASs in NS5A have minimal effects on patient responses to ledipasvir/sofosbuvir therapy. When these RASs do have effects, they could be largely overcome by extending treatment duration or through treatment intensification. Copyright © 2016

  3. Solution conformations of Zika NS2B-NS3pro and its inhibition by natural products from edible plants.

    PubMed

    Roy, Amrita; Lim, Liangzhong; Srivastava, Shagun; Lu, Yimei; Song, Jianxing

    2017-01-01

    The recent Zika viral (ZIKV) epidemic has been associated with severe neurological pathologies such as neonatal microcephaly and Guillain-Barre syndrome but unfortunately no vaccine or medication is effectively available yet. Zika NS2B-NS3pro is essential for the proteolysis of the viral polyprotein and thereby viral replication. Thus NS2B-NS3pro represents an attractive target for anti-Zika drug discovery/design. Here, we have characterized the solution conformations and catalytic parameters of both linked and unlinked Zika NS2B-NS3pro complexes and found that the unlinked complex manifested well-dispersed NMR spectra. Subsequently with selective isotope-labeling using NMR spectroscopy, we demonstrated that C-terminal residues (R73-K100) of NS2B is highly disordered without any stable tertiary and secondary structures in the Zika NS2B-NS3pro complex in the free state. Upon binding to the well-characterized serine protease inhibitor, bovine pancreatic trypsin inhibitor (BPTI), only the extreme C-terminal residues (L86-K100) remain disordered. Additionally, we have identified five flavonoids and one natural phenol rich in edible plants including fruits and vegetables, which inhibit Zika NS2B-NS3pro in a non-competitive mode, with Ki ranging from 770 nM for Myricetin to 34.02 μM for Apigenin. Molecular docking showed that they all bind to a pocket on the back of the active site and their structure-activity relationship was elucidated. Our study provides valuable insights into the solution conformation of Zika NS2B-NS3pro and further deciphers its susceptibility towards allosteric inhibition by natural products. As these natural product inhibitors fundamentally differ from the currently-known active site inhibitors in terms of both inhibitory mode and chemical scaffold, our finding might open a new avenue for development of better allosteric inhibitors to fight ZIKV infection.

  4. Limb displacement and brightness seismology

    NASA Astrophysics Data System (ADS)

    Emilio, Marcelo; Cunnyngham, Ian; Kuhn, Jeff; Mehret, Leandro; Bush, Rock; Scholl, Isabelle

    2015-08-01

    The Helioseismic and Magnetic Imager (HMI) abord the Solar Dynamics Observatory (SDO) has been used to obtain the most sensitive spectrally resolved observation of individual p-modes at the extreme solar limb. Such oscillation observations of the limb displacement and brightness for some spatial and temporal regimes are even competitive in signal-to-noise to full-disk doppler measurements of the p-mode spectrum. Limb measurements of 5-min p-modes, while having many similarities to full-disk doppler observations, have significantly different sensitivities to the solar rotation and the 5-min mode solar atmospheric structure. These may provide information about the solar structure which is complementary to full-disk measurements. In this work we present results from Individual spherical harmonic p-modes that were detected around solar limb with amplitudes at the micro-arcsecond level.

  5. Bright diode laser light source.

    PubMed

    Lassila, Erkki; Hernberg, Rolf

    2006-05-20

    A simplified multiwavelength prototype of an axially symmetric diode laser device based on stacks made of single emitters has been made, and the performance of the device has been demonstrated experimentally. The results verify that kilowatt-level light power can be focused into a circular spot with a 1/e2 diameter of 360 microm, a focal length of 100 mm, and a numerical aperture of 0.24, thus producing an average power density in excess of 10 kW/mm2 and a brightness of 6x10(10) W m-2 sr-1. The experiments also predict that it will be possible to increase these values to more than 60 kW/mm2 and 3x10(11) W m-2 sr-1.

  6. How Bright Can Supernovae Get?

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-04-01

    Supernovae enormous explosions associated with the end of a stars life come in a variety of types with different origins. A new study has examined how the brightest supernovae in the Universe are produced, and what limits might be set on their brightness.Ultra-Luminous ObservationsRecent observations have revealed many ultra-luminous supernovae, which haveenergies that challenge our abilities to explain them usingcurrent supernova models. An especially extreme example is the 2015 discovery of the supernova ASASSN-15lh, which shone with a peak luminosity of ~2*1045 erg/s, nearly a trillion times brighter than the Sun. ASASSN-15lh radiated a whopping ~2*1052 erg in the first four months after its detection.How could a supernova that bright be produced? To explore the answer to that question, Tuguldur Sukhbold and Stan Woosley at University of California, Santa Cruz, have examined the different sources that could produce supernovae and calculated upper limits on the potential luminosities ofeach of these supernova varieties.Explosive ModelsSukhbold and Woosley explore multiple different models for core-collapse supernova explosions, including:Prompt explosionA stars core collapses and immediately explodes.Pair instabilityElectron/positron pair production at a massive stars center leads to core collapse. For high masses, radioactivity can contribute to delayed energy output.Colliding shellsPreviously expelled shells of material around a star collide after the initial explosion, providing additional energy release.MagnetarThe collapsing star forms a magnetar a rapidly rotating neutron star with an incredibly strong magnetic field at its core, which then dumps energy into the supernova ejecta, further brightening the explosion.They then apply these models to different types of stars.Setting the LimitThe authors show that the light curve of ASASSN-15lh (plotted in orange) can be described by a model (black curve) in which a magnetar with an initial spin period of 0.7 ms

  7. A Closer Look at the NS1 of Influenza Virus

    PubMed Central

    Dundon, William G.; Capua, Ilaria

    2009-01-01

    The Non-Structural 1 (NS1) protein is a multifactorial protein of type A influenza viruses that plays an important role in the virulence of the virus. A large amount of what we know about this protein has been obtained from studies using human influenza isolates and, consequently, the human NS1 protein. The current global interest in avian influenza, however, has highlighted a number of sequence and functional differences between the human and avian NS1. This review discusses these differences in addition to describing potential uses of NS1 in the management and control of avian influenza outbreaks. PMID:21994582

  8. Night sky brightness measurement at PERMATApintar observatory

    NASA Astrophysics Data System (ADS)

    Azhar, A. D.; Gopir, G.; Kamil, W. M. A. Wan Mohd; Mohamad, N. S.; Azmi, N. Che

    2016-11-01

    One of the quality parameter of an astronomical site testing is sky brightness. We measure the night sky brightness over PERMATApintar Observatory to obtain the first preliminary sky brightness reading. The measurement is done by using an Unihedron Sky Quality Meter (SQM-LU) with a position pointing zenith. Six measurements have been done during the period of January to March 2016. The measurement is taken between approximately 7 p.m. to 11 p.m. on each of the night. The best (darken) night sky brightness reading is 19.54 mag/arcsec2 obtained on March 11th, 2016. The preliminary average reading of sky brightness is 17.20 mag/arcsec2. Comparison with previous similar measurement for the same type of area (suburban area) shows that our data is within the range of the sky brightness for suburban area, which is 19.5 to 20.7 mag/arcsec2.

  9. Formation of the flavivirus envelope: role of the viral NS2B-NS3 protease.

    PubMed Central

    Yamshchikov, V F; Compans, R W

    1995-01-01

    One of the late processing events in the flavivirus replication cycle involves cleavage of the intracellular form of the flavivirus capsid protein (Cint) to the mature virion form (Cvir) lacking the carboxy-terminal stretch of hydrophobic amino acids which serves as a signal peptide for the downstream prM protein. This cleavage event was hypothesized to be effected by a viral protease and to be associated with virion formation. We have proposed a model of flavivirus virion formation in which processing of the C-prM precursor at the upstream signalase site is upregulated by interaction of the NS2B part of the protease with the prM signal peptide or with an adjacent carboxy-terminal region of the capsid protein in the precursor, and processing of Cint by the NS2B-NS3 protease follows the signalase cleavage. Recently, an alternative hypothesis was proposed which suggests a reverse order of these two cleavage events, namely, that cleavage of the C-prM precursor by the NS2B-NS3 protease at the Cint-->Cvir dibasic cleavage site is a prerequisite for the subsequent signalase cleavage of the prM signal peptide. To distinguish between these alternative models, we prepared a series of expression cassettes carrying mutations at the Cint-->Cvir dibasic cleavage site and investigated the effects of these mutations on signalase processing of C-prM and on formation and secretion of prM-E heterodimers. For certain mutated C-prM precursors, namely, for those with Lys-->Gly disruption of the dibasic site, efficient formation of prM was observed upon expression from larger cassettes encoding the viral protease, despite the absence of processing at the Cint-->Cvir cleavage site. Surprisingly, formation and secretion of prM-E heterodimers accompanied by late cleavage of prM was also observed for these cassettes, with an efficiency comparable to that of the wild-type expression cassette. These observations contradict the model in which cleavage of the C-prM precursor at the Cint

  10. Quantum communication with macroscopically bright nonclassical states.

    PubMed

    Usenko, Vladyslav C; Ruppert, Laszlo; Filip, Radim

    2015-11-30

    We analyze homodyne detection of macroscopically bright multimode nonclassical states of light and propose their application in quantum communication. We observe that the homodyne detection is sensitive to a mode-matching of the bright light to the highly intense local oscillator. Unmatched bright modes of light result in additional noise which technically limits detection of Gaussian entanglement at macroscopic level. When the mode-matching is sufficient, we show that multimode quantum key distribution with bright beams is feasible. It finally merges the quantum communication with classical optical technology of visible beams of light.

  11. Strong pollinator-mediated selection for increased flower brightness and contrast in a deceptive orchid.

    PubMed

    Sletvold, Nina; Trunschke, Judith; Smit, Mart; Verbeek, Jeffrey; Ågren, Jon

    2016-03-01

    Contrasting flower color patterns that putatively attract or direct pollinators toward a reward are common among angiosperms. In the deceptive orchid Anacamptis morio, the lower petal, which makes up most of the floral display, has a light central patch with dark markings. Within populations, there is pronounced variation in petal brightness, patch size, amount of dark markings, and contrast between patch and petal margin. We tested whether pollinators mediate selection on these color traits and on morphology (plant height, number of flowers, corolla size, spur length), and whether selection is consistent with facilitated or negative frequency-dependent pollination. Pollinators mediated strong selection for increased petal brightness (Δβpoll = 0.42) and contrast (Δβpoll = 0.51). Pollinators also tended to mediate stabilizing selection on brightness (Δγpoll = -0.27, n.s.) favoring the most common phenotype in the population. Selection for reduced petal brightness among hand-pollinated plants indicated a fitness cost associated with brightness. The results demonstrate that flower color traits influence pollination success and seed production in A. morio, indicating that they affect attractiveness to pollinators, efficiency of pollen transfer, or both. The documented selection is consistent with facilitated pollination and selection for color convergence toward cooccurring rewarding species.

  12. Simultaneous uncoupled expression and purification of the Dengue virus NS3 protease and NS2B co-factor domain.

    PubMed

    Shannon, A E; Chappell, K J; Stoermer, M J; Chow, S Y; Kok, W M; Fairlie, D P; Young, P R

    2016-03-01

    Dengue Virus (DENV) infection is responsible for the world's most significant insect-borne viral disease. Despite an increasing global impact, there are neither prophylactic nor therapeutic options available for the effective treatment of DENV infection. An attractive target for antiviral drugs is the virally encoded trypsin-like serine protease (NS3pro) and its associated cofactor (NS2B). The NS2B-NS3pro complex is responsible for cleaving the viral polyprotein into separate functional viral proteins, and is therefore essential for replication. Recombinant expression of an active NS2B-NS3 protease has primarily been based on constructs linking the C-terminus of the approximately 40 amino acid hydrophilic cofactor domain of NS2B to the N-terminus of NS3pro via a flexible glycine linker. The resulting complex can be expressed in high yield, is soluble and catalytically active and has been used for most in vitro screening, inhibitor, and X-ray crystallographic studies over the last 15 years. Despite extensive analysis, no inhibitor drug candidates have been identified yet. Moreover, the effect of the artificial linker introduced between the protease and its cofactor is unknown. Two alternate methods for bacterial expression of non-covalently linked, catalytically active, NS2B-NS3pro complex are described here along with a comparison of the kinetics of substrate proteolysis and binding affinities of substrate-based aldehyde inhibitors. Both expression methods produced high yields of soluble protein with improved substrate proteolysis kinetics and inhibitor binding compared to their glycine-linked equivalent. The non-covalent association between NS2B and NS3pro is predicted to be more relevant for examining inhibitors that target cofactor-protease interactions rather than the protease active site. Furthermore, these approaches offer alternative strategies for the high yield co-expression of other protein assemblies.

  13. Synergistic Activity of Combined NS5A Inhibitors

    PubMed Central

    Nower, Peter T.; Gao, Min; Fridell, Robert; Wang, Chunfu; Hewawasam, Piyasena; Lopez, Omar; Tu, Yong; Meanwell, Nicholas A.; Belema, Makonen; Roberts, Susan B.; Cockett, Mark; Sun, Jin-Hua

    2015-01-01

    Daclatasvir (DCV) is a first-in-class hepatitis C virus (HCV) nonstructural 5A replication complex inhibitor (NS5A RCI) that is clinically effective in interferon-free combinations with direct-acting antivirals (DAAs) targeting alternate HCV proteins. Recently, we reported NS5A RCI combinations that enhance HCV inhibitory potential in vitro, defining a new class of HCV inhibitors termed NS5A synergists (J. Sun, D. R. O’Boyle II, R. A. Fridell, D. R. Langley, C. Wang, S. Roberts, P. Nower, B. M. Johnson F. Moulin, M. J. Nophsker, Y. Wang, M. Liu, K. Rigat, Y. Tu, P. Hewawasam, J. Kadow, N. A. Meanwell, M. Cockett, J. A. Lemm, M. Kramer, M. Belema, and M. Gao, Nature 527:245–248, 2015, doi:10.1038/nature15711). To extend the characterization of NS5A synergists, we tested new combinations of DCV and NS5A synergists against genotype (gt) 1 to 6 replicons and gt 1a, 2a, and 3a viruses. The kinetics of inhibition in HCV-infected cells treated with DCV, an NS5A synergist (NS5A-Syn), or a combination of DCV and NS5A-Syn were distinctive. Similar to activity observed clinically, DCV caused a multilog drop in HCV, followed by rebound due to the emergence of resistance. DCV–NS5A-Syn combinations were highly efficient at clearing cells of viruses, in line with the trend seen in replicon studies. The retreatment of resistant viruses that emerged using DCV monotherapy with DCV–NS5A-Syn resulted in a multilog drop and rebound in HCV similar to the initial decline and rebound observed with DCV alone on wild-type (WT) virus. A triple combination of DCV, NS5A-Syn, and a DAA targeting the NS3 or NS5B protein cleared the cells of viruses that are highly resistant to DCV. Our data support the observation that the cooperative interaction of DCV and NS5A-Syn potentiates both the genotype coverage and resistance barrier of DCV, offering an additional DAA option for combination therapy and tools for explorations of NS5A function. PMID:26711745

  14. The interaction between the hepatitis C proteins NS4B and NS5A is involved in viral replication.

    PubMed

    David, Naama; Yaffe, Yakey; Hagoel, Lior; Elazar, Menashe; Glenn, Jeffrey S; Hirschberg, Koret; Sklan, Ella H

    2015-01-15

    Hepatitis C virus (HCV) replicates in membrane associated, highly ordered replication complexes (RCs). These complexes include viral and host proteins necessary for viral RNA genome replication. The interaction network among viral and host proteins underlying the formation of these RCs is yet to be thoroughly characterized. Here, we investigated the association between NS4B and NS5A, two critical RC components. We characterized the interaction between these proteins using fluorescence resonance energy transfer and a mammalian two-hybrid system. Specific tryptophan residues within the C-terminal domain (CTD) of NS4B were shown to mediate this interaction. Domain I of NS5A, was sufficient to mediate its interaction with NS4B. Mutations in the NS4B CTD tryptophan residues abolished viral replication. Moreover, one of these mutations also affected NS5A hyperphosphorylation. These findings provide new insights into the importance of the NS4B-NS5A interaction and serve as a starting point for studying the complex interactions between the replicase subunits.

  15. The interaction between the Hepatitis C proteins NS4B and NS5A is involved in viral replication

    PubMed Central

    David, Naama; Yaffe, Yakey; Hagoel, Lior; Elazar, Menashe; Glenn, Jeffrey S.; Hirschberg, Koret; Sklan, Ella H.

    2015-01-01

    Hepatitis C virus (HCV) replicates in membrane associated, highly ordered replication complexes (RCs). These complexes include viral and host proteins necessary for viral RNA genome replication. The interaction network among viral and host proteins underlying the formation of these RCs is yet to be thoroughly characterized. Here, we investigated the association between NS4B and NS5A, two critical RC components. We characterized the interaction between these proteins using fluorescence resonance energy transfer and a mammalian two-hybrid system. Specific tryptophan residues within the C-terminal domain (CTD) of NS4B were shown to mediate this interaction. Domain I of NS5A, was sufficient to mediate its interaction with NS4B. Mutations in the NS4B CTD tryptophan residues abolished viral replication. Moreover, one of these mutations also affected NS5A hyperphosphorylation. These findings provide new insights into the importance of the NS4B–NS5A interaction and serve as a starting point for studying the complex interactions between the replicase subunits. PMID:25462354

  16. Links between quasi-periodic oscillations and accretion states in neutron star low-mass X-ray binaries

    NASA Astrophysics Data System (ADS)

    Motta, S. E.; Rouco-Escorial, A.; Kuulkers, E.; Muñoz-Darias, T.; Sanna, A.

    2017-06-01

    We analysed the Rossi X-ray Timing Explorer data from a sample of bright accreting neutron star (NS) low-mass X-ray binaries (LMXBs). With the aim of studying the quasi-periodic variability as a function of the accretion regime, we carried out a systematic search of the quasi-periodic oscillations (QPOs) in the X-ray time series of these systems, using the integrated fractional variability as a tracker for the accretion states. We found that the three QPO types originally identified in the 1980s for the brightest LMXBs, the so-called Z sources, i.e. horizontal, normal and flaring branch oscillations (HBOs, NBOs and FBOs, respectively), are also identified in the slightly less bright NS LMXBs, the so-called atoll sources, where we see QPOs with a behaviour consistent with the HBOs and FBOs. We compared the quasi-periodic variability properties of our NS sample with those of a sample of black hole (BH) LMXBs. We confirm the association between HBOs, NBOs and FBOs observed in Z sources, with the type-C, type-B and type-A QPOs, respectively, observed in BH systems, and we extended the comparison to the HBO-like and FBO-like QPOs seen in atoll sources. We conclude that the variability properties of BH and weakly magnetized NS LMXBs show strong similarities, with QPOs only weakly sensitive to the nature of the central compact object in both classes of systems. We find that the historical association between kHz QPOs and high-frequency QPOs, seen around NSs and BHs, respectively, is not obvious when comparing similar accretion states in the two kinds of systems.

  17. Optimising the efficiency of pulsed diode pumped Yb:YAG laser amplifiers for ns pulse generation.

    PubMed

    Ertel, K; Banerjee, S; Mason, P D; Phillips, P J; Siebold, M; Hernandez-Gomez, C; Collier, J C

    2011-12-19

    We present a numerical model of a pulsed, diode-pumped Yb:YAG laser amplifier for the generation of high energy ns-pulses. This model is used to explore how optical-to-optical efficiency depends on factors such as pump duration, pump spectrum, pump intensity, doping concentration, and operating temperature. We put special emphasis on finding ways to achieve high efficiency within the practical limitations imposed by real-world laser systems, such as limited pump brightness and limited damage fluence. We show that a particularly advantageous way of improving efficiency within those constraints is operation at cryogenic temperature. Based on the numerical findings we present a concept for a scalable amplifier based on an end-pumped, cryogenic, gas-cooled multi-slab architecture.

  18. Hepatitis C Virus NS3 Inhibitors: Current and Future Perspectives

    PubMed Central

    Akimitsu, Nobuyoshi

    2013-01-01

    Currently, hepatitis C virus (HCV) infection is considered a serious health-care problem all over the world. A good number of direct-acting antivirals (DAAs) against HCV infection are in clinical progress including NS3-4A protease inhibitors, RNA-dependent RNA polymerase inhibitors, and NS5A inhibitors as well as host targeted inhibitors. Two NS3-4A protease inhibitors (telaprevir and boceprevir) have been recently approved for the treatment of hepatitis C in combination with standard of care (pegylated interferon plus ribavirin). The new therapy has significantly improved sustained virologic response (SVR); however, the adverse effects associated with this therapy are still the main concern. In addition to the emergence of viral resistance, other targets must be continually developed. One such underdeveloped target is the helicase portion of the HCV NS3 protein. This review article summarizes our current understanding of HCV treatment, particularly with those of NS3 inhibitors. PMID:24282816

  19. Spatial Brightness Perception of Trichromatic Stimuli

    SciTech Connect

    Royer, Michael P.; Houser, Kevin W.

    2012-11-16

    An experiment was conducted to examine the effect of tuning optical radiation on brightness perception for younger (18-25 years of age) and older (50 years of age or older) observers. Participants made forced-choice evaluations of the brightness of a full factorial of stimulus pairs selected from two groups of four metameric stimuli. The large-field stimuli were created by systematically varying either the red or the blue primary of an RGB LED mixture. The results indicate that light stimuli of equal illuminance and chromaticity do not appear equally bright to either younger or older subjects. The rank-order of brightness is not predicted by any current model of human vision or theory of brightness perception including Scotopic to Photopic or Cirtopic to Photopic ratio theory, prime color theory, correlated color temperature, V(λ)-based photometry, color quality metrics, linear brightness models, or color appearance models. Age may affect brightness perception when short-wavelength primaries are used, especially those with a peak wavelength shorter than 450 nm. The results suggest further development of metrics to predict brightness perception is warranted, and that including age as a variable in predictive models may be valuable.

  20. Bright Star Astrometry with URAT

    NASA Astrophysics Data System (ADS)

    Zacharias, N.

    2015-10-01

    The U.S. Naval Observatory Robotic Astrometric Telescope (URAT) is observing the northern sky since April 2012 for an astrometric survey. Multiple overlaps per year are performed in a single bandpass (680-750 nm) using the "redlens" 20 cm aperture astrograph and a mosaic of large CCDs. Besides the regular, deep survey to magnitude 18.5, short exposures with an objective grating are taken to access stars as bright as 3rd magnitude. A brief overview of the program, observing and reductions is given. Positions on the 8 to 20 mas level are obtained of 66,202 Hipparcos stars at current epochs. These are compared to the Hipparcos Catalog to investigate its accuracy. About 20% of the observed Hipparcos stars are found to have inconsistent positions with the Hipparcos Catalog prediction on the 3 sigma level or over (about 75 mas or more discrepant position offsets). Some stars are now seen at an arcsec (or 25 sigma) off their Hipparcos Catalog predicted position.

  1. Brightness alteration with interweaving contours

    PubMed Central

    Roncato, Sergio

    2012-01-01

    Chromatic induction is observed whenever the perceived colour of a target surface shifts towards the hue of a neighbouring surface. Some vivid manifestations may be seen in a white background where thin coloured lines have been drawn (assimilation) or when lines of different colours are collinear (neon effect) or adjacent (watercolour) to each other. This study examines a particular colour induction that manifests in concomitance with an opposite effect of colour saturation (or anti-spread). The two phenomena can be observed when a repetitive pattern is drawn in which outline thin contours intercept wider contours or surfaces, colour spreading appear to fill the surface occupied by surfaces or thick lines whereas the background traversed by thin lines is seen as brighter or filled of a saturated white. These phenomena were first observed by Bozzi (1975) and Kanizsa (1979) in figural conditions that did not allow them to document their conjunction. Here we illustrate various manifestations of this twofold phenomenon and compare its effects with the known effects of brightness and colour induction. Some conjectures on the nature of these effects are discussed. PMID:23483806

  2. Brightness alteration with interweaving contours.

    PubMed

    Roncato, Sergio

    2012-01-01

    Chromatic induction is observed whenever the perceived colour of a target surface shifts towards the hue of a neighbouring surface. Some vivid manifestations may be seen in a white background where thin coloured lines have been drawn (assimilation) or when lines of different colours are collinear (neon effect) or adjacent (watercolour) to each other. This study examines a particular colour induction that manifests in concomitance with an opposite effect of colour saturation (or anti-spread). The two phenomena can be observed when a repetitive pattern is drawn in which outline thin contours intercept wider contours or surfaces, colour spreading appear to fill the surface occupied by surfaces or thick lines whereas the background traversed by thin lines is seen as brighter or filled of a saturated white. These phenomena were first observed by Bozzi (1975) and Kanizsa (1979) in figural conditions that did not allow them to document their conjunction. Here we illustrate various manifestations of this twofold phenomenon and compare its effects with the known effects of brightness and colour induction. Some conjectures on the nature of these effects are discussed.

  3. Artificial NS4 mosaic antigen of hepatitis C virus.

    PubMed

    Chang, J C; Ruedinger, B; Cong, M; Lambert, S; Lopareva, E; Purdy, M; Holloway, B P; Jue, D L; Ofenloch, B; Fields, H A; Khudyakov, Y E

    1999-12-01

    An artificial antigen composed of 17 small antigenic regions derived from the NS4-protein of hepatitis C virus (HCV) genotypes 1 through 5 was designed and constructed. Eleven antigenic regions were derived from the 5-1-1 region, and 6 others were derived from the C-terminus of the NS4-protein of different genotypes. The gene encoding for this artificial antigen was assembled from synthetic oligonucleotides by a new approach designated as restriction enzyme-assisted ligation (REAL). The full-length synthetic gene was expressed in Escherichia coli as a fusion protein with glutathione S-transferase. By the use of site-specific antibodies raised against synthetic peptides, it was shown that all regions for which sequence-specific antibodies were obtained were accessible to antibody binding. The diagnostic relevance of the NS4 artificial antigen was demonstrated by testing this antigen with 4 HCV seroconversion panels and a panel of previously tested and stored serum specimens. The artificial antigen was found to specifically detect anti-NS4 antibodies in a number of specimens that were previously found to be anti-NS4 negative. Furthermore, this antigen detected anti-NS4 activity earlier in 2 of 4 seroconversion panels than did the antigen used in a commercially available supplemental assay. Equally important is the observation that the artificial NS4 antigen demonstrated equivalent anti-NS4 immunoreactivity with serum specimens obtained from patients infected with different HCV genotypes, whereas the NS4 recombinant protein derived from genotype 1, used in the commercial supplemental test, was less immunoreactive with serum specimens containing HCV genotypes 2, 3, and 4. Collectively, these data support the significant diagnostic potential of the NS4 mosaic antigen. The strategy employed in this study may be applied to the design and construction of other artificial antigens with improved diagnostically pertinent properties. J. Med. Virol. 59:437-450 1999. Copyright

  4. Cortical processing of a brightness illusion

    PubMed Central

    Roe, Anna Wang; Lu, Haidong D.; Hung, Chou P.

    2005-01-01

    Several brightness illusions indicate that borders can affect the perception of surfaces dramatically. In the Cornsweet illusion, two equiluminant surfaces appear to be different in brightness because of the contrast border between them. Here, we report the existence of cells in monkey visual cortex that respond to such an “illusory” brightness. We find that luminance responsive cells are located in color-activated regions (cytochrome oxidase blobs and bridges) of primary visual cortex (V1), whereas Cornsweet responsive cells are found preferentially in the color-activated regions (thin stripes) of second visual area (V2). This colocalization of brightness and color processing within V1 and V2 suggests a segregation of contour and surface processing in early visual pathways and a hierarchy of brightness information processing from V1 to V2 in monkeys. PMID:15738406

  5. Identification of novel small molecule inhibitors against NS2B/NS3 serine protease from Zika virus

    SciTech Connect

    Lee, Hyun; Ren, Jinhong; Nocadello, Salvatore; Rice, Amy J.; Ojeda, Isabel; Light, Samuel; Minasov, George; Vargas, Jason; Nagarathnam, Dhanapalan; Anderson, Wayne F.; Johnson, Michael E.

    2016-12-26

    Zika flavivirus infection during pregnancy appears to produce higher risk of microcephaly, and also causes multiple neurological problems such as Guillain–Barré syndrome. The Zika virus is now widespread in Central and South America, and is anticipated to become an increasing risk in the southern United States. With continuing global travel and the spread of the mosquito vector, the exposure is expected to accelerate, but there are no currently approved treatments against the Zika virus. The Zika NS2B/NS3 protease is an attractive drug target due to its essential role in viral replication. Our studies have identified several compounds with inhibitory activity (IC50) and binding affinity (KD) of ~5–10 μM against the Zika NS2B-NS3 protease from testing 71 HCV NS3/NS4A inhibitors that were initially discovered by high-throughput screening of 40,967 compounds. Competition surface plasmon resonance studies and mechanism of inhibition analyses by enzyme kinetics subsequently determined the best compound to be a competitive inhibitor with a Ki value of 9.5 μM. We also determined the X-ray structure of the Zika NS2B-NS3 protease in a “pre-open conformation”, a conformation never observed before for any flavivirus proteases. This provides the foundation for new structure-based inhibitor design.

  6. Identification of novel small molecule inhibitors against NS2B/NS3 serine protease from Zika virus.

    PubMed

    Lee, Hyun; Ren, Jinhong; Nocadello, Salvatore; Rice, Amy J; Ojeda, Isabel; Light, Samuel; Minasov, George; Vargas, Jason; Nagarathnam, Dhanapalan; Anderson, Wayne F; Johnson, Michael E

    2017-03-01

    Zika flavivirus infection during pregnancy appears to produce higher risk of microcephaly, and also causes multiple neurological problems such as Guillain-Barré syndrome. The Zika virus is now widespread in Central and South America, and is anticipated to become an increasing risk in the southern United States. With continuing global travel and the spread of the mosquito vector, the exposure is expected to accelerate, but there are no currently approved treatments against the Zika virus. The Zika NS2B/NS3 protease is an attractive drug target due to its essential role in viral replication. Our studies have identified several compounds with inhibitory activity (IC50) and binding affinity (KD) of ∼5-10 μM against the Zika NS2B-NS3 protease from testing 71 HCV NS3/NS4A inhibitors that were initially discovered by high-throughput screening of 40,967 compounds. Competition surface plasmon resonance studies and mechanism of inhibition analyses by enzyme kinetics subsequently determined the best compound to be a competitive inhibitor with a Ki value of 9.5 μM. We also determined the X-ray structure of the Zika NS2B-NS3 protease in a "pre-open conformation", a conformation never observed before for any flavivirus proteases. This provides the foundation for new structure-based inhibitor design.

  7. Novel Dengue Virus NS2B/NS3 Protease Inhibitors

    PubMed Central

    Wu, Hongmei; Bock, Stefanie; Snitko, Mariya; Berger, Thilo; Weidner, Thomas; Holloway, Steven; Kanitz, Manuel; Diederich, Wibke E.; Steuber, Holger; Walter, Christof; Hofmann, Daniela; Weißbrich, Benedikt; Spannaus, Ralf; Acosta, Eliana G.; Bartenschlager, Ralf; Engels, Bernd; Schirmeister, Tanja

    2014-01-01

    Dengue fever is a severe, widespread, and neglected disease with more than 2 million diagnosed infections per year. The dengue virus NS2B/NS3 protease (PR) represents a prime target for rational drug design. At the moment, there are no clinical PR inhibitors (PIs) available. We have identified diaryl (thio)ethers as candidates for a novel class of PIs. Here, we report the selective and noncompetitive inhibition of the serotype 2 and 3 dengue virus PR in vitro and in cells by benzothiazole derivatives exhibiting 50% inhibitory concentrations (IC50s) in the low-micromolar range. Inhibition of replication of DENV serotypes 1 to 3 was specific, since all substances influenced neither hepatitis C virus (HCV) nor HIV-1 replication. Molecular docking suggests binding at a specific allosteric binding site. In addition to the in vitro assays, a cell-based PR assay was developed to test these substances in a replication-independent way. The new compounds inhibited the DENV PR with IC50s in the low-micromolar or submicromolar range in cells. Furthermore, these novel PIs inhibit viral replication at submicromolar concentrations. PMID:25487800

  8. Bright Sparks of Our Future!

    NASA Astrophysics Data System (ADS)

    Riordan, Naoimh

    2016-04-01

    My name is Naoimh Riordan and I am the Vice Principal of Rockboro Primary School in Cork City, South of Ireland. I am a full time class primary teacher and I teach 4th class, my students are aged between 9-10 years. My passion for education has developed over the years and grown towards STEM (Science, Technology, Engineering and Mathematics) subjects. I believe these subjects are the way forward for our future. My passion and beliefs are driven by the unique after school programme that I have developed. It is titled "Sparks" coming from the term Bright Sparks. "Sparks" is an after school programme with a difference where the STEM subjects are concentrated on through lessons such as Science, Veterinary Science Computer Animation /Coding, Eco engineering, Robotics, Magical Maths, Chess and Creative Writing. All these subjects are taught through activity based learning and are one-hour long each week for a ten-week term. "Sparks" is fully inclusive and non-selective which gives all students of any level of ability an opportunity to engage into these subjects. "Sparks" is open to all primary students in County Cork. The "Sparks" after school programme is taught by tutors from the different Universities and Colleges in Cork City. It works very well because the tutor brings their knowledge, skills and specialised equipment from their respective universities and in turn the tutor gains invaluable teaching practise, can trial a pilot programme in a chosen STEM subject and gain an insight into what works in the physical classroom.

  9. Bright Streaks and Dark Fans

    NASA Technical Reports Server (NTRS)

    2007-01-01

    The south polar region of Mars is covered every year by a layer of carbon dioxide ice. In a region called the 'cryptic terrain,' the ice is translucent and sunlight can penetrate through the ice to warm the surface below.

    The ice layer sublimates (evaporates) from the bottom. The dark fans of dust seen in this image come from the surface below the layer of ice, carried to the top by gas venting from below. The translucent ice is 'visible' by virtue of the effect it has on the tone of the surface below, which would otherwise have the same color and reflectivity as the fans.

    Bright streaks in this image are fresh frost. The CRISM team has identified the composition of these streaks to be carbon dioxide.

    Observation Geometry Image PSP_003113_0940 was taken by the High Resolution Imaging Science Experiment (HiRISE) camera onboard the Mars Reconnaissance Orbiter spacecraft on 26-Mar-2007. The complete image is centered at -85.8 degrees latitude, 106.0 degrees East longitude. The range to the target site was 244.9 km (153.0 miles). At this distance the image scale is 49.0 cm/pixel (with 2 x 2 binning) so objects 147 cm across are resolved. The image shown here has been map-projected to 50 cm/pixel . The image was taken at a local Mars time of 06:20 PM and the scene is illuminated from the west with a solar incidence angle of 79 degrees, thus the sun was about 11 degrees above the horizon. At a solar longitude of 207.6 degrees, the season on Mars is Northern Autumn.

  10. Bright Streaks and Dark Fans

    NASA Technical Reports Server (NTRS)

    2007-01-01

    The south polar region of Mars is covered every year by a layer of carbon dioxide ice. In a region called the 'cryptic terrain,' the ice is translucent and sunlight can penetrate through the ice to warm the surface below.

    The ice layer sublimates (evaporates) from the bottom. The dark fans of dust seen in this image come from the surface below the layer of ice, carried to the top by gas venting from below. The translucent ice is 'visible' by virtue of the effect it has on the tone of the surface below, which would otherwise have the same color and reflectivity as the fans.

    Bright streaks in this image are fresh frost. The CRISM team has identified the composition of these streaks to be carbon dioxide.

    Observation Geometry Image PSP_003113_0940 was taken by the High Resolution Imaging Science Experiment (HiRISE) camera onboard the Mars Reconnaissance Orbiter spacecraft on 26-Mar-2007. The complete image is centered at -85.8 degrees latitude, 106.0 degrees East longitude. The range to the target site was 244.9 km (153.0 miles). At this distance the image scale is 49.0 cm/pixel (with 2 x 2 binning) so objects 147 cm across are resolved. The image shown here has been map-projected to 50 cm/pixel . The image was taken at a local Mars time of 06:20 PM and the scene is illuminated from the west with a solar incidence angle of 79 degrees, thus the sun was about 11 degrees above the horizon. At a solar longitude of 207.6 degrees, the season on Mars is Northern Autumn.

  11. Flavivirus NS3 and NS5 proteins interaction network: a high-throughput yeast two-hybrid screen

    PubMed Central

    2011-01-01

    Background The genus Flavivirus encompasses more than 50 distinct species of arthropod-borne viruses, including several major human pathogens, such as West Nile virus, yellow fever virus, Japanese encephalitis virus and the four serotypes of dengue viruses (DENV type 1-4). Each year, flaviviruses cause more than 100 million infections worldwide, some of which lead to life-threatening conditions such as encephalitis or haemorrhagic fever. Among the viral proteins, NS3 and NS5 proteins constitute the major enzymatic components of the viral replication complex and are essential to the flavivirus life cycle. Results We report here the results of a high-throughput yeast two-hybrid screen to identify the interactions between human host proteins and the flavivirus NS3 and NS5 proteins. Using our screen results and literature curation, we performed a global analysis of the NS3 and NS5 cellular targets based on functional annotation with the Gene Ontology features. We finally created the first flavivirus NS3 and NS5 proteins interaction network and analysed the topological features of this network. Our proteome mapping screen identified 108 human proteins interacting with NS3 or NS5 proteins or both. The global analysis of the cellular targets revealed the enrichment of host proteins involved in RNA binding, transcription regulation, vesicular transport or innate immune response regulation. Conclusions We proposed that the selective disruption of these newly identified host/virus interactions could represent a novel and attractive therapeutic strategy in treating flavivirus infections. Our virus-host interaction map provides a basis to unravel fundamental processes about flavivirus subversion of the host replication machinery and/or immune defence strategy. PMID:22014111

  12. Dengue virus NS1 triggers endothelial permeability and vascular leak that is prevented by NS1 vaccination.

    PubMed

    Beatty, P Robert; Puerta-Guardo, Henry; Killingbeck, Sarah S; Glasner, Dustin R; Hopkins, Kaycie; Harris, Eva

    2015-09-09

    The four dengue virus serotypes (DENV1 to DENV4) are mosquito-borne flaviviruses that cause up to ~100 million cases of dengue annually worldwide. Severe disease is thought to result from immunopathogenic processes involving serotype cross-reactive antibodies and T cells that together induce vasoactive cytokines, causing vascular leakage that leads to shock. However, no viral proteins have been directly implicated in triggering endothelial permeability, which results in vascular leakage. DENV nonstructural protein 1 (NS1) is secreted and circulates in patients' blood during acute infection; high levels of NS1 are associated with severe disease. We show that inoculation of mice with DENV NS1 alone induces both vascular leakage and production of key inflammatory cytokines. Furthermore, simultaneous administration of NS1 with a sublethal dose of DENV2 results in a lethal vascular leak syndrome. We also demonstrate that NS1 from DENV1, DENV2, DENV3, and DENV4 triggers endothelial barrier dysfunction, causing increased permeability of human endothelial cell monolayers in vitro. These pathogenic effects of physiologically relevant amounts of NS1 in vivo and in vitro were blocked by NS1-immune polyclonal mouse serum or monoclonal antibodies to NS1, and immunization of mice with NS1 from DENV1 to DENV4 protected against lethal DENV2 challenge. These findings add an important and previously overlooked component to the causes of dengue vascular leak, identify a new potential target for dengue therapeutics, and support inclusion of NS1 in dengue vaccines. Copyright © 2015, American Association for the Advancement of Science.

  13. Flavivirus NS3 and NS5 proteins interaction network: a high-throughput yeast two-hybrid screen.

    PubMed

    Le Breton, Marc; Meyniel-Schicklin, Laurène; Deloire, Alexandre; Coutard, Bruno; Canard, Bruno; de Lamballerie, Xavier; Andre, Patrice; Rabourdin-Combe, Chantal; Lotteau, Vincent; Davoust, Nathalie

    2011-10-20

    The genus Flavivirus encompasses more than 50 distinct species of arthropod-borne viruses, including several major human pathogens, such as West Nile virus, yellow fever virus, Japanese encephalitis virus and the four serotypes of dengue viruses (DENV type 1-4). Each year, flaviviruses cause more than 100 million infections worldwide, some of which lead to life-threatening conditions such as encephalitis or haemorrhagic fever. Among the viral proteins, NS3 and NS5 proteins constitute the major enzymatic components of the viral replication complex and are essential to the flavivirus life cycle. We report here the results of a high-throughput yeast two-hybrid screen to identify the interactions between human host proteins and the flavivirus NS3 and NS5 proteins. Using our screen results and literature curation, we performed a global analysis of the NS3 and NS5 cellular targets based on functional annotation with the Gene Ontology features. We finally created the first flavivirus NS3 and NS5 proteins interaction network and analysed the topological features of this network. Our proteome mapping screen identified 108 human proteins interacting with NS3 or NS5 proteins or both. The global analysis of the cellular targets revealed the enrichment of host proteins involved in RNA binding, transcription regulation, vesicular transport or innate immune response regulation. We proposed that the selective disruption of these newly identified host/virus interactions could represent a novel and attractive therapeutic strategy in treating flavivirus infections. Our virus-host interaction map provides a basis to unravel fundamental processes about flavivirus subversion of the host replication machinery and/or immune defence strategy.

  14. Influenza NS1 directly modulates Hedgehog signaling during infection

    PubMed Central

    Teijaro, John R.; Ganesan, Sundar; Zúñiga, Elina I.; Krug, Robert M.

    2017-01-01

    The multifunctional NS1 protein of influenza A viruses suppresses host cellular defense mechanisms and subverts other cellular functions. We report here on a new role for NS1 in modifying cell-cell signaling via the Hedgehog (Hh) pathway. Genetic epistasis experiments and FRET-FLIM assays in Drosophila suggest that NS1 interacts directly with the transcriptional mediator, Ci/Gli1. We further confirmed that Hh target genes are activated cell-autonomously in transfected human lung epithelial cells expressing NS1, and in infected mouse lungs. We identified a point mutation in NS1, A122V, that modulates this activity in a context-dependent fashion. When the A122V mutation was incorporated into a mouse-adapted influenza A virus, it cell-autonomously enhanced expression of some Hh targets in the mouse lung, including IL6, and hastened lethality. These results indicate that, in addition to its multiple intracellular functions, NS1 also modifies a highly conserved signaling pathway, at least in part via cell autonomous activities. We discuss how this new Hh modulating function of NS1 may influence host lethality, possibly through controlling cytokine production, and how these new insights provide potential strategies for combating infection. PMID:28837667

  15. Silencing by H-NS Potentiated the Evolution of Salmonella

    PubMed Central

    Rao, Chitong; Leung, Andrea S.; Ngai, David Hon-Man; Ensminger, Alexander W.; Navarre, William Wiley

    2014-01-01

    The bacterial H-NS protein silences expression from sequences with higher AT-content than the host genome and is believed to buffer the fitness consequences associated with foreign gene acquisition. Loss of H-NS results in severe growth defects in Salmonella, but the underlying reasons were unclear. An experimental evolution approach was employed to determine which secondary mutations could compensate for the loss of H-NS in Salmonella. Six independently derived S. Typhimurium hns mutant strains were serially passaged for 300 generations prior to whole genome sequencing. Growth rates of all lineages dramatically improved during the course of the experiment. Each of the hns mutant lineages acquired missense mutations in the gene encoding the H-NS paralog StpA encoding a poorly understood H-NS paralog, while 5 of the mutant lineages acquired deletions in the genes encoding the Salmonella Pathogenicity Island-1 (SPI-1) Type 3 secretion system critical to invoke inflammation. We further demonstrate that SPI-1 misregulation is a primary contributor to the decreased fitness in Salmonella hns mutants. Three of the lineages acquired additional loss of function mutations in the PhoPQ virulence regulatory system. Similarly passaged wild type Salmonella lineages did not acquire these mutations. The stpA missense mutations arose in the oligomerization domain and generated proteins that could compensate for the loss of H-NS to varying degrees. StpA variants most able to functionally substitute for H-NS displayed altered DNA binding and oligomerization properties that resembled those of H-NS. These findings indicate that H-NS was central to the evolution of the Salmonellae by buffering the negative fitness consequences caused by the secretion system that is the defining characteristic of the species. PMID:25375226

  16. Brightness of the solar F-corona

    NASA Astrophysics Data System (ADS)

    Kimura, Hiroshi; Mann, Ingrid

    1998-06-01

    We discuss our present knowledge about the brightness of the solar F-corona in the wavelength range from the visible to the middle infrared. From the general trend of the observational data, the F-corona is regarded as the continuous extension of the zodiacal light at smaller elongation of the line of sight. A contribution of thermal emission from dust is indicated by the increasing F-coronal brightness in comparison to the solar spectrum towards longer wavelength. As compared with the F-coronal brightness, the polarization and color in the visible regime are not well determined due to the high sensitivity of these quantities to the observational accuracy. Aside from observational problems, our present interpretation of the F-coronal brightness is also limited due to ambiguities in the inversion of the line of sight integral. Nevertheless, the measurements and model calculations of the brightness can be used to deduce some physical properties of dust grains. We show that the hump of the near-infrared brightness at 4 solar radii, which was sometimes observed in the corona, is related rather to the physical properties of dust grains along the line of sight than to the existence of a dust ring as previously discussed. We also show that the appearance or disappearance of the near-infrared peak in the coronal brightness cannot be described in any periodic cycle for each wavelength range.

  17. Galaxy Selection and the Surface Brightness Distribution

    NASA Astrophysics Data System (ADS)

    McGaugh, Stacy S.; Bothun, Gregory D.; Schombert, James M.

    1995-08-01

    Optical surveys for galaxies are biased against the inclusion of low surface brightness (LSB) galaxies. Disney [Nature, 263,573(1976)] suggested that the constancy of disk central surface brightness noticed by Freeman [ApJ, 160,811(1970)] was not a physical result, but instead was an artifact of sample selection. Since LSB galaxies do exist, the pertinent and still controversial issue is if these newly discovered galaxies constitute a significant percentage of the general galaxy population. In this paper, we address this issue by determining the space density of galaxies as a function of disk central surface brightness. Using the physically reasonable assumption (which is motivated by the data) that central surface brightness is independent of disk scale length, we arrive at a distribution which is roughly flat (i.e., approximately equal numbers of galaxies at each surface brightness) faintwards of the Freeman (1970) value. Brightwards of this, we find a sharp decline in the distribution which is analogous to the turn down in the luminosity function at L^*^. An intrinsically sharply peaked "Freeman law" distribution can be completely ruled out, and no Gaussian distribution can fit the data. Low surface brightness galaxies (those with central surface brightness fainter than 22 B mag arcsec^-2^) comprise >~ 1/2 the general galaxy population, so a representative sample of galaxies at z = 0 does not really exist at present since past surveys have been insensitive to this component of the general galaxy population.

  18. Solution conformations of Zika NS2B-NS3pro and its inhibition by natural products from edible plants

    PubMed Central

    Srivastava, Shagun; Lu, Yimei

    2017-01-01

    The recent Zika viral (ZIKV) epidemic has been associated with severe neurological pathologies such as neonatal microcephaly and Guillain-Barre syndrome but unfortunately no vaccine or medication is effectively available yet. Zika NS2B-NS3pro is essential for the proteolysis of the viral polyprotein and thereby viral replication. Thus NS2B-NS3pro represents an attractive target for anti-Zika drug discovery/design. Here, we have characterized the solution conformations and catalytic parameters of both linked and unlinked Zika NS2B-NS3pro complexes and found that the unlinked complex manifested well-dispersed NMR spectra. Subsequently with selective isotope-labeling using NMR spectroscopy, we demonstrated that C-terminal residues (R73-K100) of NS2B is highly disordered without any stable tertiary and secondary structures in the Zika NS2B-NS3pro complex in the free state. Upon binding to the well-characterized serine protease inhibitor, bovine pancreatic trypsin inhibitor (BPTI), only the extreme C-terminal residues (L86-K100) remain disordered. Additionally, we have identified five flavonoids and one natural phenol rich in edible plants including fruits and vegetables, which inhibit Zika NS2B-NS3pro in a non-competitive mode, with Ki ranging from 770 nM for Myricetin to 34.02 μM for Apigenin. Molecular docking showed that they all bind to a pocket on the back of the active site and their structure-activity relationship was elucidated. Our study provides valuable insights into the solution conformation of Zika NS2B-NS3pro and further deciphers its susceptibility towards allosteric inhibition by natural products. As these natural product inhibitors fundamentally differ from the currently-known active site inhibitors in terms of both inhibitory mode and chemical scaffold, our finding might open a new avenue for development of better allosteric inhibitors to fight ZIKV infection. PMID:28700665

  19. High voltage high brightness electron accelerator with MITL voltage adder coupled to foilless diode

    SciTech Connect

    Mazarakis, M.G.; Poulkey, J.W.; Rovang, D.

    1995-12-31

    The design and analysis of a high brightness electron beam experiment under construction at Sandia National Laboratory is presented. The beam energy is 12 MeV, the current 35-40 kA, the rms radius 0.5 mm, and the pulse duration FWHM 40 ns. The accelerator is SABRE a pulsed inductive voltage adder, and the electron source is a magnetically immersed foilless diode. This experiment has as its goal to stretch the technology to the edge and produce the highest possible electron current in a submillimeter radius beam.

  20. Differential Rotation via Tracking of Coronal Bright Points.

    NASA Astrophysics Data System (ADS)

    McAteer, James; Boucheron, Laura E.; Osorno, Marcy

    2016-05-01

    The accurate computation of solar differential rotation is important both as a constraint for, and evidence towards, support of models of the solar dynamo. As such, the use of Xray and Extreme Ultraviolet bright points to elucidate differential rotation has been studied in recent years. In this work, we propose the automated detection and tracking of coronal bright points (CBPs) in a large set of SDO data for re-evaluation of solar differential rotation and comparison to other results. The big data aspects, and high cadence, of SDO data mitigate a few issues common to detection and tracking of objects in image sequences and allow us to focus on the use of CBPs to determine differential rotation. The high cadence of the data allows to disambiguate individual CBPs between subsequent images by allowing for significant spatial overlap, i.e., by the fact that the CBPs will rotate a short distance relative to their size. The significant spatial overlap minimizes the effects of incorrectly detected CBPs by reducing the occurrence of outlier values of differential rotation. The big data aspects of the data allows to be more conservative in our detection of CBPs (i.e., to err on the side of missing CBPs rather than detecting extraneous CBPs) while still maintaining statistically larger populations over which to study characteristics. The ability to compute solar differential rotation through the automated detection and tracking of a large population of CBPs will allow for further analyses such as the N-S asymmetry of differential rotation, variation of differential rotation over the solar cycle, and a detailed study of the magnetic flux underlying the CBPs.

  1. Subcellular Localization, Stability, and trans-Cleavage Competence of the Hepatitis C Virus NS3-NS4A Complex Expressed in Tetracycline-Regulated Cell Lines

    PubMed Central

    Wölk, Benno; Sansonno, Domenico; Kräusslich, Hans-Georg; Dammacco, Franco; Rice, Charles M.; Blum, Hubert E.; Moradpour, Darius

    2000-01-01

    A tetracycline-regulated gene expression system and a panel of novel monoclonal antibodies were used to examine the subcellular localization, stability, and trans-cleavage competence of the hepatitis C virus (HCV) NS3-NS4A complex in inducible cell lines. The NS3 serine protease domain and the full-length NS3 protein expressed in the absence of the NS4A cofactor were diffusely distributed in the cytoplasm and nucleus. Coexpression of NS4A, however, directed NS3 to the endoplasmic reticulum (ER) or an ER-like modified compartment, as demonstrated by colocalization with 3,3′-dihexyloxacarbocyanine iodide, protein disulfide isomerase, and calnexin, as well as subcellular fractionation analyses. In addition, coexpression with NS4A dramatically increased the intracellular stability of NS3 (mean protein half-life of 26 versus 3 h) and allowed for NS4A-dependent trans-cleavage at the NS4B-NS5A junction. Deletion analyses revealed that the hydrophobic amino-terminal domain of NS4A was required for ER targeting of NS3. These results demonstrate the importance of studying HCV proteins in their biological context and define a well-characterized cell culture system for further analyses of the NS3-NS4A complex and the evaluation of novel antiviral strategies against hepatitis C. PMID:10666260

  2. Tetrahydrobenzothiophene inhibitors of hepatitis C virus NS5B polymerase.

    PubMed

    Laporte, M G; Lessen, T A; Leister, L; Cebzanov, D; Amparo, E; Faust, C; Ortlip, D; Bailey, T R; Nitz, T J; Chunduru, S K; Young, D C; Burns, C J

    2006-01-01

    A novel series of selective HCV NS5B RNA dependent RNA polymerase inhibitors has been disclosed. These compounds contain an appropriately substituted tetrahydrobenzothiophene scaffold. This communication will detail the SAR and activities of this series.

  3. Mechanisms of HCV NS3 helicase monitored by optical tweezers.

    PubMed

    Cheng, Wei

    2015-01-01

    As one of the essential enzymes for viral genome replication, the hepatitis C virus NS3 helicase is one of the best characterized RNA helicases to date in understanding the mechanistic cycles in a helicase-catalyzed strand separation reaction. Recently, single-molecule studies on NS3, in particular the use of optical tweezers with sub-base pair spatial resolution, have allowed people to examine the potential elementary steps of NS3 in unwinding the double-stranded RNA fueled by ATP binding and hydrolysis. In this chapter, I detail the essential technical elements involved in conducting a high-resolution optical tweezers study of NS3 helicase, starting from the purification of the recombinant helicase protein from E. coli to setting up a high-resolution single-molecule experiment using optical tweezers.

  4. Mechanisms of HCV NS3 Helicase Monitored by Optical Tweezers

    PubMed Central

    Cheng, Wei

    2015-01-01

    As one of the essential enzymes for viral genome replication, the hepatitis C virus NS3 helicase is one of the best characterized RNA helicases to date in understanding the mechanistic cycles in a helicase-catalyzed strand separation reaction. Recently, single-molecule studies on NS3, in particular the use of optical tweezers with sub-base pair spatial resolution, have allowed people to examine the potential elementary steps of NS3 in unwinding the double-stranded RNA fueled by ATP binding and hydrolysis. In this chapter, I detail the essential technical elements involved in conducting a high-resolution optical tweezers study of NS3 helicase, starting from the purification of the recombinant helicase protein from E. coli to setting up a high-resolution single-molecule experiment using optical tweezers. PMID:25579590

  5. Just How Bright Is a Laser?

    ERIC Educational Resources Information Center

    Van Baak, David A.

    1995-01-01

    Attempts to quantify the subjective sensation of brightness of the spot projected by a helium-neon laser and compares this with conventional sources of light. Provides an exercise in using the blackbody radiation formulas. (JRH)

  6. Dark Lakes on a Bright Landscape

    NASA Image and Video Library

    2013-10-23

    Ultracold hydrocarbon lakes and seas dark shapes near the north pole of Saturn moon Titan can be seen embedded in some kind of bright surface material in this infrared mosaic from NASA Cassini mission.

  7. Just How Bright Is a Laser?

    ERIC Educational Resources Information Center

    Van Baak, David A.

    1995-01-01

    Attempts to quantify the subjective sensation of brightness of the spot projected by a helium-neon laser and compares this with conventional sources of light. Provides an exercise in using the blackbody radiation formulas. (JRH)

  8. Slow and Fast Transitions in the Rising Phase of Outbursts from NS-LMXB Transients, Aquila X-1 and 4U 1608-52

    NASA Astrophysics Data System (ADS)

    Asai, Kazumi; Matsuoka, Masaru; Mihara, Tatehiro; Sugizaki, Mutsumi; Serino, Motoko; Nakahira, Satoshi; Negoro, Hitoshi; Ueda, Yoshihiro; Yamaoka, Kazutaka

    2012-12-01

    We analyzed the initial rising behaviors of X-ray outbursts from two transient low-mass X-ray binaries (LMXBs) containing a neutron-star (NS), Aquila X-1 (Aql X-1) and 4U 1608-52, which are continuously being monitored by MAXI/GSC in 2-20 keV, RXTE/ASM in 2-10 keV, and Swift/BAT in 15-50 keV. We found that the observed ten outbursts can be classified into two types based on the patterns of the relative intensity evolutions in the two energy bands below/above 15 keV. One type behaves as the 15-50 keV intensity achieves the maximum during the initial hard-state period, and drops greatly at the hard-to-soft state transition. On the other hand, the other type does as both the 2-15 keV and 15-50 keV intensities achieve the maximums after the transition. The former have the longer initial hard-state (gtrsim 9 d) than the latter (lesssim 5 d). Therefore, we named them as slow-type (S-type) and fast-type (F-type), respectively. These two types also show differences in the luminosity at the hard-to-soft state transition as well as in the average luminosity before the outburst started, where the S-type are higher than the F-type in both. These results suggest that the X-ray radiation during the pre-outburst period, which heats up the accretion disk and delays the disk transition (i.e., from a geometrically thick disk to a thin one), would determine whether the following outburst becomes S-type or F-type. The luminosity when the hard-to-soft state transition occurs is higher than ˜8 × 1036 erg s-1 in the S-type, which corresponds to 4% of the Eddington luminosity for a 1.4 M⊙ NS.

  9. New Observations of Subarcsecond Photospheric Bright Points

    NASA Technical Reports Server (NTRS)

    Berger, T. E.; Schrijver, C. J.; Shine, R. A.; Tarbell, T. D.; Title, A. M.; Scharmer, G.

    1995-01-01

    We have used an interference filter centered at 4305 A within the bandhead of the CH radical (the 'G band') and real-time image selection at the Swedish Vacuum Solar Telescope on La Palma to produce very high contrast images of subarcsecond photospheric bright points at all locations on the solar disk. During the 6 day period of 1993 September 15-20 we observed active region NOAA 7581 from its appearance on the East limb to a near-disk-center position on September 20. A total of 1804 bright points were selected for analysis from the disk center image using feature extraction image processing techniques. The measured Full Width at Half Maximum (FWHM) distribution of the bright points in the image is lognormal with a modal value of 220 km (0 sec .30) and an average value of 250 km (0 sec .35). The smallest measured bright point diameter is 120 km (0 sec .17) and the largest is 600 km (O sec .69). Approximately 60% of the measured bright points are circular (eccentricity approx. 1.0), the average eccentricity is 1.5, and the maximum eccentricity corresponding to filigree in the image is 6.5. The peak contrast of the measured bright points is normally distributed. The contrast distribution variance is much greater than the measurement accuracy, indicating a large spread in intrinsic bright-point contrast. When referenced to an averaged 'quiet-Sun' area in the image, the modal contrast is 29% and the maximum value is 75%; when referenced to an average intergranular lane brightness in the image, the distribution has a modal value of 61% and a maximum of 119%. The bin-averaged contrast of G-band bright points is constant across the entire measured size range. The measured area of the bright points, corrected for pixelation and selection effects, covers about 1.8% of the total image area. Large pores and micropores occupy an additional 2% of the image area, implying a total area fraction of magnetic proxy features in the image of 3.8%. We discuss the implications of this

  10. New Observations of Subarcsecond Photospheric Bright Points

    NASA Technical Reports Server (NTRS)

    Berger, T. E.; Schrijver, C. J.; Shine, R. A.; Tarbell, T. D.; Title, A. M.; Scharmer, G.

    1995-01-01

    We have used an interference filter centered at 4305 A within the bandhead of the CH radical (the 'G band') and real-time image selection at the Swedish Vacuum Solar Telescope on La Palma to produce very high contrast images of subarcsecond photospheric bright points at all locations on the solar disk. During the 6 day period of 15-20 Sept. 1993 we observed active region NOAA 7581 from its appearance on the East limb to a near-disk-center position on 20 Sept. A total of 1804 bright points were selected for analysis from the disk center image using feature extraction image processing techniques. The measured FWHM distribution of the bright points in the image is lognormal with a modal value of 220 km (0.30 sec) and an average value of 250 km (0.35 sec). The smallest measured bright point diameter is 120 km (0.17 sec) and the largest is 600 km (O.69 sec). Approximately 60% of the measured bright points are circular (eccentricity approx. 1.0), the average eccentricity is 1.5, and the maximum eccentricity corresponding to filigree in the image is 6.5. The peak contrast of the measured bright points is normally distributed. The contrast distribution variance is much greater than the measurement accuracy, indicating a large spread in intrinsic bright-point contrast. When referenced to an averaged 'quiet-Sun' area in the image, the modal contrast is 29% and the maximum value is 75%; when referenced to an average intergranular lane brightness in the image, the distribution has a modal value of 61% and a maximum of 119%. The bin-averaged contrast of G-band bright points is constant across the entire measured size range. The measured area of the bright points, corrected for pixelation and selection effects, covers about 1.8% of the total image area. Large pores and micropores occupy an additional 2% of the image area, implying a total area fraction of magnetic proxy features in the image of 3.8%. We discuss the implications of this area fraction measurement in the context of

  11. Achieving Peak Brightness in an Atom Laser

    SciTech Connect

    Robins, N.P.; Figl, C.; Haine, S.A.; Morrison, A.K.; Jeppesen, M.; Hope, J.J.; Close, J.D.

    2006-04-14

    In this Letter we present experimental results and a simple analytic theory on the first continuous (long pulse) Raman atom laser. We analyze the flux and brightness of a generic two state atom laser with an analytic model that shows excellent agreement with our experiments. We show that, for the same source size, the brightness achievable with a Raman atom laser is at least 3 orders of magnitude greater than achievable in any other demonstrated continuously outcoupled atom laser.

  12. Apparent brightness distribution of GRB host galaxies

    NASA Astrophysics Data System (ADS)

    Bagoly, Zsolt; Racz, Istvan; Gyorgy Balazs, Lajos; Toth, Viktor; Horvath, Istvan

    2015-08-01

    We studied the relationship between the Swift GRB data and the optical brightness of the host galaxy measured by the Keck telescope. We calculated the unbiased distribution of the host's optical brightness by making use the survival analysis. Based on the sample obtained from merging the Swift GRB table and the Keck optical data we studied also the dependence of this distribution on the GRB's data.

  13. Observations and diagnostics in high brightness beams

    NASA Astrophysics Data System (ADS)

    Cianchi, A.; Anania, M. P.; Bisesto, F.; Castellano, M.; Chiadroni, E.; Pompili, R.; Shpakov, V.

    2016-09-01

    The brightness is a figure of merit largely used in the light sources, like FEL (Free Electron Lasers), but it is also fundamental in several other applications, as for instance Compton backscattering sources, beam driven plasma accelerators and THz sources. Advanced diagnostics are essential tools in the development of high brightness beams. 6D electron beam diagnostics will be reviewed with emphasis on emittance measurement.

  14. The analogy between stereo depth and brightness.

    PubMed

    Brookes, A; Stevens, K A

    1989-01-01

    Apparent depth in stereograms exhibits various simultaneous-contrast and induction effects analogous to those reported in the luminance domain. This behavior suggests that stereo depth, like brightness, is reconstructed, ie recovered from higher-order spatial derivatives or differences of the original signal. The extent to which depth is analogous to brightness is examined. There are similarities in terms of contrast effects but dissimilarities in terms of the lateral inhibition effects traditionally attributed to underlying spatial-differentiation operators.

  15. Adherent neural stem (NS) cells from fetal and adult forebrain.

    PubMed

    Pollard, Steven M; Conti, Luciano; Sun, Yirui; Goffredo, Donato; Smith, Austin

    2006-07-01

    Stable in vitro propagation of central nervous system (CNS) stem cells would offer expanded opportunities to dissect basic molecular, cellular, and developmental processes and to model neurodegenerative disease. CNS stem cells could also provide a source of material for drug discovery assays and cell replacement therapies. We have recently reported the generation of adherent, symmetrically expandable, neural stem (NS) cell lines derived both from mouse and human embryonic stem cells and from fetal forebrain (Conti L, Pollard SM, Gorba T, Reitano E, Toselli M, Biella G, Sun Y, Sanzone S, Ying QL, Cattaneo E, Smith A. 2005. Niche-independent symmetrical self-renewal of a mammalian tissue stem cell. PLoS Biol 3(9):e283). These NS cells retain neuronal and glial differentiation potential after prolonged passaging and are transplantable. NS cells are likely to comprise the resident stem cell population within heterogeneous neurosphere cultures. Here we demonstrate that similar NS cell cultures can be established from the adult mouse brain. We also characterize the growth factor requirements for NS cell derivation and self-renewal. We discuss our current understanding of the relationship of NS cell lines to physiological progenitor cells of fetal and adult CNS.

  16. The New High Resolution Crystal Structure of NS2B-NS3 Protease of Zika Virus

    PubMed Central

    Badshah, Syed Lal; Naeem, Abdul; Mabkhot, Yahia

    2017-01-01

    Zika virus (ZIKV) is the cause of a significant viral disease affecting humans, which has spread throughout many South American countries and has also become a threat to Southeastern Asia. This commentary discusses the article “Crystal structure of unlinked NS2B-NS3 protease from Zika virus” published recently in the journal Science by Zhang et al. of Nanyang Technological University, Singapore. They resolved a 1.58 Å resolution structure of the NS2B-NS3 protease of ZIKV and demonstrated how peptide and non-peptide inhibitors interact with this structure, along with the different conformational states that were observed. This protease crystal structure offers new opportunities for the design and development of novel antiviral drugs used for the treatment and control of ZIKV. PMID:28075376

  17. Structure of the NS2B-NS3 protease from Zika virus after self-cleavage

    PubMed Central

    Phoo, Wint Wint; Li, Yan; Zhang, Zhenzhen; Lee, Michelle Yueqi; Loh, Ying Ru; Tan, Yaw Bia; Ng, Elizabeth Yihui; Lescar, Julien; Kang, CongBao; Luo, Dahai

    2016-01-01

    The recent outbreak of Zika virus (ZIKV) infections in the Americas represents a serious threat to the global public health. The viral protease that processes viral polyproteins during infection appears as an attractive drug target. Here we report a crystal structure at 1.84 Å resolution of ZIKV non-structural protein NS2B-NS3 protease with the last four amino acids of the NS2B cofactor bound at the NS3 active site. This structure represents a post-proteolysis state of the enzyme during viral polyprotein processing and provides insights into peptide substrate recognition by the protease. Nuclear magnetic resonance (NMR) studies and protease activity assays unravel the protein dynamics upon binding the protease inhibitor BPTI in solution and confirm this finding. The structural and functional insights of the ZIKV protease presented here should advance our current understanding of flavivirus replication and accelerate structure-based antiviral drug discovery against ZIKV. PMID:27845325

  18. Red-emission phosphor's brightness deterioration by x-ray and brightness recovery phenomenon by heating.

    PubMed

    Nakamura, Masaaki; Chida, Koichi; Inaba, Yohei; Kobayashi, Ryota; Zuguchi, Masayuki

    2017-06-26

    There are no feasible real-time and direct skin dosimeters for interventional radiology. One would be available if there were x-ray phosphors that had no brightness change caused by x-ray irradiation, but the emission of the Y2O3:Eu, (Y, Gd, Eu)BO3, and YVO4:Eu phosphors investigated in our previous study was reduced by x-ray irradiation. We found that the brightness of those phosphors recovered, and the purpose of this study is to investigate their recovery phenomena. It is expected that more kinds of phosphors could be used in x-ray dosimeters if the brightness changes caused by x-rays are elucidated and prevented. Three kinds of phosphors-Y2O3:Eu, (Y, Gd, Eu)BO3, and YVO4:Eu-were irradiated by x-rays (2 Gy) to reduce their brightness. After the irradiation, brightness changes occurring at room temperature and at 80 °C were investigated. The irradiation reduced the brightness of all the phosphors by 5%-10%, but the brightness of each recovered immediately both at room temperature and at 80 °C. The recovery at 80 °C was faster than that at room temperature, and at both temperatures the recovered brightness remained at 95%-98% of the brightness before the x-ray irradiation. The brightness recovery phenomena of Y2O3:Eu, (Y, Gd, Eu)BO3, and YVO4:Eu phosphors occurring after brightness deterioration due to x-ray irradiation were found to be more significant at 80 °C than at room temperature. More kinds of phosphors could be used in x-ray scintillation dosimeters if the reasons for the brightness changes caused by x-rays were elucidated.

  19. Energy-exchange collisions of dark-bright-bright vector solitons.

    PubMed

    Radhakrishnan, R; Manikandan, N; Aravinthan, K

    2015-12-01

    We find a dark component guiding the practically interesting bright-bright vector one-soliton to two different parametric domains giving rise to different physical situations by constructing a more general form of three-component dark-bright-bright mixed vector one-soliton solution of the generalized Manakov model with nine free real parameters. Moreover our main investigation of the collision dynamics of such mixed vector solitons by constructing the multisoliton solution of the generalized Manakov model with the help of Hirota technique reveals that the dark-bright-bright vector two-soliton supports energy-exchange collision dynamics. In particular the dark component preserves its initial form and the energy-exchange collision property of the bright-bright vector two-soliton solution of the Manakov model during collision. In addition the interactions between bound state dark-bright-bright vector solitons reveal oscillations in their amplitudes. A similar kind of breathing effect was also experimentally observed in the Bose-Einstein condensates. Some possible ways are theoretically suggested not only to control this breathing effect but also to manage the beating, bouncing, jumping, and attraction effects in the collision dynamics of dark-bright-bright vector solitons. The role of multiple free parameters in our solution is examined to define polarization vector, envelope speed, envelope width, envelope amplitude, grayness, and complex modulation of our solution. It is interesting to note that the polarization vector of our mixed vector one-soliton evolves in sphere or hyperboloid depending upon the initial parametric choices.

  20. Replacement of the respiratory syncytial virus nonstructural proteins NS1 and NS2 by the V protein of parainfluenza virus 5

    SciTech Connect

    Tran, Kim C.; He, Biao; Teng, Michael N.

    2007-11-10

    Paramyxoviruses have been shown to produce proteins that inhibit interferon production and signaling. For human respiratory syncytial virus (RSV), the nonstructural NS1 and NS2 proteins have been shown to have interferon antagonist activity through an unknown mechanism. To understand further the functions of NS1 and NS2, we generated recombinant RSV in which both NS1 and NS2 were replaced by the PIV5 V protein, which has well-characterized IFN antagonist activities ({delta}NS1/2-V). Expression of V was able to partially inhibit IFN responses in {delta}NS1/2-V-infected cells. In addition, the replication kinetics of {delta}NS1/2-V were intermediate between {delta}NS1/2 and wild-type (rA2) in A549 cells. However, expression of V did not affect the ability of {delta}NS1/2-V to activate IRF3 nuclear translocation and IFN{beta} transcription. These data indicate that V was able to replace some of the IFN inhibitory functions of the RSV NS1 and NS2 proteins, but also that NS1 and NS2 have functions in viral replication beyond IFN antagonism.

  1. A Bright Neutron Source Driven by a Short Pulse Laser

    NASA Astrophysics Data System (ADS)

    Roth, Markus

    2012-10-01

    Neutrons are a unique tool to alter and diagnose material properties, and to exciting nuclear reactions, for many applications. Accelerator based spallation sources provide high neutron fluxes for research, but there is a growing need for more compact sources with higher peak brightness, whether fast or moderated neutrons. Intense lasers promise such as source, readily linkable to other experimental facilities, or deployable outside a laboratory setting. We present experimental results on the first short-pulse laser-driven neutron source powerful enough for radiography. A novel laser-driven ion acceleration mechanism (Breakout Afterburner), operating in the relativistic transparency regime, is used. Based on the mechanism's advantages, a laser-driven deuteron beam is used to achieve a new record in laser-neutron production, in numbers, energy and directionality. This neutron beam is a highly directional pulse < 1 ns at ˜ 1 cm from the target, with a flux > 40/2̂, and thus suitable for imaging applications with high temporal resolution. The beam contained, for the first time, neutrons with energies of up to 150 MeV. Thus using short pulse lasers, it is now possible to use the resulting hard x-rays and neutrons of different energies to radiograph an unknown object and to determine its material composition. Our data matches the simulated data for our test samples.

  2. NMR reveals the intrinsically disordered domain 2 of NS5A protein as an allosteric regulator of the hepatitis C virus RNA polymerase NS5B.

    PubMed

    Bessa, Luiza M; Launay, Hélène; Dujardin, Marie; Cantrelle, François-Xavier; Lippens, Guy; Landrieu, Isabelle; Schneider, Robert; Hanoulle, Xavier

    2017-09-14

    Non-structural protein 5B (NS5B) is the RNAdependent RNA polymerase that catalyses replication of the hepatitis C virus (HCV) RNA genome, and so is central for its life cycle. NS5B interacts with the intrinsically disordered domain 2 of NS5A (NS5A-D2), another essential multifunctional HCV protein that is required for RNA replication. As a result, these two proteins represent important targets for anti-HCV chemotherapies. Despite this importance and the existence of NS5B crystal structures, our understanding of the conformational and dynamic behaviour of NS5B in solution and its relationship with NS5A-D2 remain incomplete. To address these points, we report the first detailed NMR spectroscopic study of HCV NS5B lacking its membrane anchor (NS5BΔ21). Analysis of constructs with selective isotope labelling of the δ1 methyl groups of isoleucine side chains demonstrates that, in solution, NS5BΔ21 is highly dynamic, but predominantly adopts a closed conformation. Addition of NS5A-D2 leads to spectral changes indicative of binding to both allosteric thumb sites I and II of NS5BΔ21, and induces long range perturbations that affect the RNA-binding properties of the polymerase. We compared these modifications to the short- and long-range effects triggered in NS5BΔ21 upon binding of filibuvir, an allosteric inhibitor. We demonstrate that filibuvir-bound NS5BΔ21 is strongly impaired in the binding of both NS5A-D2 and RNA. NS5A-D2 induces conformational and functional perturbations in NS5B similar to those triggered by filibuvir. Thus, our work highlights NS5A-D2 as an allosteric regulator of the HCV polymerase and provides new insight into the dynamics of NS5B in solution. Copyright © 2017, The American Society for Biochemistry and Molecular Biology.

  3. Microwave Brightness Temperatures of Tilted Convective Systems

    NASA Technical Reports Server (NTRS)

    Hong, Ye; Haferman, Jeffrey L.; Olson, William S.; Kummerow, Christian D.

    1998-01-01

    Aircraft and ground-based radar data from the Tropical Ocean and Global Atmosphere Coupled-Ocean Atmosphere Response Experiment (TOGA COARE) show that convective systems are not always vertical. Instead, many are tilted from vertical. Satellite passive microwave radiometers observe the atmosphere at a viewing angle. For example, the Special Sensor Microwave/Imager (SSM/I) on Defense Meteorological Satellite Program (DMSP) satellites and the Tropical Rainfall Measurement Mission (TRMM) Microwave Imager (TMI) on the TRMM satellite have an incident angle of about 50deg. Thus, the brightness temperature measured from one direction of tilt may be different than that viewed from the opposite direction due to the different optical depth. This paper presents the investigation of passive microwave brightness temperatures of tilted convective systems. To account for the effect of tilt, a 3-D backward Monte Carlo radiative transfer model has been applied to a simple tilted cloud model and a dynamically evolving cloud model to derive the brightness temperature. The radiative transfer results indicate that brightness temperature varies when the viewing angle changes because of the different optical depth. The tilt increases the displacements between high 19 GHz brightness temperature (Tb(sub 19)) due to liquid emission from lower level of cloud and the low 85 GHz brightness temperature (Tb(sub 85)) due to ice scattering from upper level of cloud. As the resolution degrades, the difference of brightness temperature due to the change of viewing angle decreases dramatically. The dislocation between Tb(sub 19) and Tb(sub 85), however, remains prominent.

  4. The Sky Brightness Data Archive (SBDA)

    NASA Astrophysics Data System (ADS)

    Craine, Eric R.; Craine, Erin M.; Craine, Brian L.

    2011-05-01

    Although many astronomers have long been sensitive to issues of light pollution and deteriorating sky quality it is only in recent years that such interest has extended to other groups including, among others, ecologists, health professionals, and urban planners. Issues of light pollution and loss of dark skies are starting to appear in the scientific literature in the context of health and behavior impacts on both human and animal life. Nonetheless, a common deficiency in most such studies is the absence of historical or baseline data against which to compare sky brightness trends and temporal changes. To address this deficiency we have begun to collect a variety of types of quantitative sky brightness data for insertion in an international sky brightness archive that can be accessed for research projects which are dependent upon an understanding of the nature of local light pollution issues. To aid this process we have developed a mobile sky brightness meter which automatically logs sky brightness and observation location. The device can be stationary for long periods of time or can be easily transported for continuous sky brightness measurement from ground vehicles, boats, or aircraft. The sampling rate is typically about 0.25Hz. We present here examples of different modes of sky brightness measurement, various means of displaying and analyzing such data, ways to interpret natural astronomical phenomena apparent in the data, and suggest a number of complementary scientific projects that may capture the interest of both professional and amateur scientists. Finally, we discuss the status of the archive and ways that potential contributors may submit their observations for publication in the archive.

  5. Solar Cycle 23 in Coronal Bright Points

    NASA Astrophysics Data System (ADS)

    Sattarov, Isroil; Pevtsov, Alexei A.; Karachik, Nina V.; Sherdanov, Chori T.; Tillaboev, A. M.

    2010-04-01

    We describe an automatic routine to identify coronal bright points (CBPs) and apply this routine to SOHO/EIT observations taken in the 195 Å spectral range during solar cycle 23. We examine the total number of CBPs and its change in the course of this solar cycle. Unlike some other recent studies, we do find a modest ≈30% decrease in the number of CBPs associated with maximum of sunspot activity. Using the maximum brightness of CBPs as a criterion, we separate them on two categories: dim CBPs, associated with areas of a quiet Sun, and bright CBPs, associated with an active Sun. We find that the number of dim coronal bright points decreases at the maximum of sunspot cycle, while the number of bright CBPs increases. The latitudinal distributions suggest that dim CBPs are distributed uniformly over the solar disk. Active Sun CBPs exhibit a well-defined two-hump latitudinal profile suggestive of enhanced production of this type of CBPs in sunspot activity belts. Finally, we investigate the relative role of two mechanisms in cycle variations of CBP number, and conclude that a change in fraction of solar surface occupied by the quiet Sun’s magnetic field is the primary cause, with the visibility effect playing a secondary role.

  6. [Polyclonal antibodies against recombinant dengue virus NS3 protein].

    PubMed

    Morales, Liliana; Velandia, Myriam L; Calderon, María Angélica; Castellanos, Jaime E; Chaparro-Olaya, Jacqueline

    2017-01-24

    Dengue is a disease caused by one of four serotypes of the dengue virus (DENV) and is endemic in approximately 130 countries. The incidence of dengue has increased dramatically in recent decades, as well as the frequency and magnitude of outbreaks. Despite all efforts, there are no prophylactic or therapeutic treatments for the disease. Accordingly, research on the processes governing the DENV infection cycle is essential to develop vaccines or antiviral therapies. One of themost attractive DENV molecules to investigate is nonstructural protein 3 (NS3), which is essential for viral replication and a major immune target for infection. To produce antibodies to support future studies on NS3 and its cellular interactions with other proteins. Two recombinant proteins of the helicase domain of DENV NS3 serotype 2 were expressed, and used to immunize mice and produce polyclonal antibodies. The antibodies produced were useful in Western blot and immunofluorescence tests. We report an NS3 antibody that immunoprecipitates the viral protein and detects it in Western blot with no need to over-express it or use cell extracts with metabolic radiolabeling. The recombinant proteins expressed and the antibodies produced constitute valuable tools for studying DENV infectious processes involving NS3 and for evaluating tests designed to interfere with its functions.

  7. In silico evaluation of inhibitory potential of triterpenoids from Azadirachta indica against therapeutic target of dengue virus, NS2B-NS3 protease.

    PubMed

    Dwivedi, Vivek Dhar; Tripathi, Indra Prasad; Mishra, Sarad Kumar

    2016-01-01

    NS2B-NS3 protease (NS2B-NS3 pro ) of dengue virus (DENV) is the prime therapeutic target for the development of anti-dengue drug to combat the DENV infection, which is currently an increasing health problem in many countries. In the area of antiviral drug discovery, numerous reports on the antiviral activity of various medicinal plants against dengue viruses have been published. Neem plant (Azadirachta indica) is one among those medicinal plants which is reported to show potential antiviral activity against DENV. But active principle of neem plant extract which has inhibitory potential against DENV NS2B-NS3 pro is not yet reported. The aim of the present study was to explore the inhibitory potential of five triterpenoids from neem plant, viz. nimbin, desacetylnimbin, desacetylsalannin, azadirachtin and salannin, against DENV NS2B-NS3 pro. The molecular 3D structural data of DENV NS2B-NS3 pro and selected triterpenoids of neem plant were collected from protein databank (PDB ID: 2VBC) and PubChem database respectively. The molecular docking approach was employed to find out the in silico inhibitory potential of the five triterpenoids against DENV NS2B- NS3 pro. The molecular docking results showed that nimbin, desacetylnimbin and desacetylsalannin have good binding affinity with DENV NS2B-NS3 pro , while azadirachtin and salannin did not show any interaction with the target protein. It was observed that the DENV NS2B-NS3 pro binding energy for nimbin, desacetylnimbin and desacetylsalannin were -5.56, -5.24 and -3.43 kcal/mol, respectively. The findings attained through this study on the molecular interaction mode of three neem triterpenoids and DENV NS2B-NS3 pro can be considered for further in vitro and in vivo validation for designing new potential drugs for DENV infection.

  8. Discovering key residues of dengue virus NS2b-NS3-protease: New binding sites for antiviral inhibitors design.

    PubMed

    Aguilera-Pesantes, D; Robayo, L E; Méndez, P E; Mollocana, D; Marrero-Ponce, Y; Torres, F J; Méndez, M A

    2017-03-23

    The NS2B-NS3 protease is essential for the Dengue Virus (DENV) replication process. This complex constitutes a target for efficient antiviral discovery because a drug could inhibit the viral polyprotein processing. Furthermore, since the protease is highly conserved between the four Dengue virus serotypes, it is probable that a drug would be equally effective against all of them. In this article, a strategy is reported that allowed us to identify influential residues on the function of the Dengue NS2b-NS3 Protease. Moreover, this is a strategy that could be applied to virtually any protein for the search of alternative influential residues, and for non-competitive inhibitor development. First, we incorporated several features derived from computational alanine scanning mutagenesis, sequence, structure conservation, and other structure-based characteristics. Second, these features were used as variables to obtain a multilayer perceptron model to identify defined groups (clusters) of key residues as possible candidate pockets for binding sites of new leads on the DENV protease. The identified residues included: i) amino acids close to the beta sheet-loop-beta sheet known to be important in its closed conformation for NS2b ii) residues close to the active site, iii) several residues evenly spread on the NS2b-NS3 contact surface, and iv) some inner residues most likely related to the overall stability of the protease. In addition, we found concordance on our list of residues with previously identified amino acids part of a highly conserved peptide studied for vaccine development.

  9. Plasmonic EIT-like switching in bright-dark-bright plasmon resonators.

    PubMed

    Chen, Junxue; Wang, Pei; Chen, Chuncong; Lu, Yonghua; Ming, Hai; Zhan, Qiwen

    2011-03-28

    In this paper we report the study of the electromagnetically induced transparency (EIT)-like transmission in the bright-dark-bright plasmon resonators. It is demonstrated that the interferences between the dark plasmons excited by two bright plasmon resonators can be controlled by the incident light polarization. The constructive interference strengthens the coupling between the bright and dark resonators, leading to a more prominent EIT-like transparency window of the metamaterial. In contrary, destructive interference suppresses the coupling between the bright and dark resonators, destroying the interference pathway that forms the EIT-like transmission. Based on this observation, the plasmonic EIT switching can be realized by changing the polarization of incident light. This phenomenon may find applications in optical switching and plasmon-based information processing.

  10. A selective deficit in the appreciation and recognition of brightness: brightness agnosia?

    PubMed

    Nijboer, Tanja C W; Nys, Gudrun M S; van der Smagt, Maarten J; de Haan, Edward H F

    2009-01-01

    We report a patient with extensive brain damage in the right hemisphere who demonstrated a severe impairment in the appreciation of brightness. Acuity, contrast sensitivity as well as luminance discrimination were normal, suggesting her brightness impairment is not a mere consequence of low-level sensory impairments. The patient was not able to indicate the darker or the lighter of two grey squares, even though she was able to see that they differed. In addition, she could not indicate whether the lights in a room were switched on or off, nor was she able to differentiate between normal greyscale images and inverted greyscale images. As the patient recognised objects, colours, and shapes correctly, the impairment is specific for brightness. As low-level, sensory processing is normal, this specific deficit in the recognition and appreciation of brightness appears to be of a higher, cognitive level, the level of semantic knowledge. This appears to be the first report of 'brightness agnosia'.

  11. Brightness Discrimination in Budgerigars (Melopsittacus undulatus)

    PubMed Central

    Lind, Olle; Karlsson, Sandra; Kelber, Almut

    2013-01-01

    Birds have excellent spatial acuity and colour vision compared to other vertebrates while spatial contrast sensitivity is relatively poor for unknown reasons. Contrast sensitivity describes the detection of gratings of varying spatial frequency. It is unclear whether bird brightness discrimination between large uniform fields is poor as well. Here we show that budgerigars (Melopsittacus undulatus) need a Michelson contrast of 0.09 to discriminate between large spatially separated achromatic fields in bright light conditions. This is similar to the peak contrast sensitivity of 10.2 (0.098 Michelson contrast) for achromatic grating stimuli established in earlier studies. The brightness discrimination threshold described in Weber fractions is 0.18, which is modest compared to other vertebrates. PMID:23349946

  12. Dark Dunes Over-riding Bright Dunes

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Some martian sand dunes may be more active than others. In this picture, wind has caused the dark and somewhat crescent-shaped dunes to advance toward the lower left. While their movement cannot actually be seen in this April 1998snapshot, the location of their steepest slopes--their slip faces--on their southwestern sides indicates the direction of movement. Oddly, these dark dunes have moved across and partly cover sets of smaller, bright ridges that also formed by wind action.

    This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image illustrates an intriguing martian 'find.' Strangely, the two dune types have different shapes and a different relative brightness. There are two explanations for the relationship seen here, and neither can be distinguished as 'the answer'--(1) it is possible that the brighter dunes are old and cemented, and represent some ancient wind activity, whereas the dark dunes are modern and are marching across the older, 'fossilized' dune forms, or (2) the bright dunes are composed of grains that are much larger or more dense than those that compose the dark dunes. In the latter scenario, the bright dunes move more slowly and are over-taken by the dark dunes because their grains are harder to transport. An interpretation involving larger or denser grains is consistent with the small size and even-spacing of the bright dunes, as well, but usually on Earth such features occur on the surfaces of larger, finer-grained dunes, not under them. The actual composition of either the bright or dark materials are unknown. This example is located on the floor of an impact crater in western Arabia Terra at 10.7oN, 351.0oW. The picture is illuminated from the right.

  13. Richard Bright and his neurological studies.

    PubMed

    Pearce, J M S

    2009-01-01

    Richard Bright was one of the famous triumvirate of Guy's Hospital physicians in the Victorian era. Remembered for his account of glomerulonephritis (Bright's disease) he also made many important and original contributions to medicine and neurology. These included his work on cortical epileptogenesis, descriptions of simple partial (Jacksonian) seizures, infantile convulsions, and a variety of nervous diseases. Most notable were his reports of neurological studies including papers on traumatic tetanus, syringomyelia, arteries of the brain, contractures of spinal origin, tumours of the base of the brain, and narcolepsy. His career and these contributions are outlined.

  14. Diagnostics for high-brightness beams

    SciTech Connect

    Shafer, R.E.

    1990-01-01

    Special techniques are required for beam diagnostics on high-brightness particle beams. Examples of high-brightness beams include low-emittance proton linacs (either pulsed or CW), electron linacs suitable for free-electron-laser applications, and future linear colliders. Non-interceptive and minimally-interceptive techniques for measuring beam current, position, profile, and transverse and longitudinal emittance will be reviewed. Included will be stripline, wire scanner, laser neutralization, beam-beam scattering, interceptive microgratings, spontaneous emission, optical transition radiation, and other techniques. 24 refs.

  15. Comet brightness parameters: Definition, determination, and correlations

    NASA Technical Reports Server (NTRS)

    Meisel, D. D.; Morris, C. S.

    1976-01-01

    The power-law definition of comet brightness is reviewed and possible systematic influences are discussed that can affect the derivation of m sub o and n values from visual magnitude estimates. A rationale for the Bobrovnikoff aperture correction method is given and it is demonstrated that the Beyer extrafocal method leads to large systematic effects which if uncorrected by an instrumental relationship result in values significantly higher than those derived according to the Bobrovnikoff guidelines. A series of visual brightness parameter sets are presented which have been reduced to the same photometric system. Recommendations are given to insure that future observations are reduced to the same system.

  16. Kinematics of Low Surface Brightness Galaxies

    NASA Astrophysics Data System (ADS)

    Cardullo, A.; Pizzella, A.; Corsini, E. M.; Bertola, F.

    2008-10-01

    We analyzed the kinematic of 12 low surface-brightness (LSB) galaxies to study the correlation between the disk circular velocity V_{c} and the central velocity dispersion of the spheroidal component σ_{0}. This relation has been claimed to be either the same power-law relation tep{buy} or a different linear one tep{piz} with respect to high surface-brightness (HSB) galaxies. We confirm here that LSB and HSB galaxies follow two different linear V_{c}-σ_{0} relations.

  17. NS1-binding protein abrogates the elevation of cell viability by the influenza A virus NS1 protein in association with CRKL

    SciTech Connect

    Miyazaki, Masaya; Nishihara, Hiroshi; Hasegawa, Hideki; Tashiro, Masato; Wang, Lei; Kimura, Taichi; Tanino, Mishie; Tsuda, Masumi; Tanaka, Shinya

    2013-11-29

    Highlights: •NS1 induced excessive phosphorylation of ERK and elevated cell viability. •NS1-BP expression and CRKL knockdown abolished survival effect of NS1. •NS1-BP and NS1 formed the complex through the interaction with CRKL-SH3(N). -- Abstract: The influenza A virus non-structural protein 1 (NS1) is a multifunctional virulence factor consisting of an RNA binding domain and several Src-homology (SH) 2 and SH3 binding motifs, which promotes virus replication in the host cell and helps to evade antiviral immunity. NS1 modulates general host cell physiology in association with various cellular molecules including NS1-binding protein (NS1-BP) and signaling adapter protein CRK-like (CRKL), while the physiological role of NS1-BP during influenza A virus infection especially in association with NS1 remains unclear. In this study, we analyzed the intracellular association of NS1-BP, NS1 and CRKL to elucidate the physiological roles of these molecules in the host cell. In HEK293T cells, enforced expression of NS1 of A/Beijing (H1N1) and A/Indonesia (H5N1) significantly induced excessive phosphorylation of ERK and elevated cell viability, while the over-expression of NS1-BP and the abrogation of CRKL using siRNA abolished such survival effect of NS1. The pull-down assay using GST-fusion CRKL revealed the formation of intracellular complexes of NS1-BP, NS1 and CRKL. In addition, we identified that the N-terminus SH3 domain of CRKL was essential for binding to NS1-BP using GST-fusion CRKL-truncate mutants. This is the first report to elucidate the novel function of NS1-BP collaborating with viral protein NS1 in modulation of host cell physiology. In addition, an alternative role of adaptor protein CRKL in association with NS1 and NS1-BP during influenza A virus infection is demonstrated.

  18. hnRNP A2/B1 interacts with influenza A viral protein NS1 and inhibits virus replication potentially through suppressing NS1 RNA/protein levels and NS1 mRNA nuclear export

    SciTech Connect

    Wang, Yimeng; Zhou, Jianhong; Du, Yuchun

    2014-01-20

    The NS1 protein of influenza viruses is a major virulence factor and exerts its function through interacting with viral/cellular RNAs and proteins. In this study, we identified heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) as an interacting partner of NS1 proteins by a proteomic method. Knockdown of hnRNP A2/B1 by small interfering RNA (siRNA) resulted in higher levels of NS vRNA, NS1 mRNA, and NS1 protein in the virus-infected cells. In addition, we demonstrated that hnRNP A2/B1 proteins are associated with NS1 and NS2 mRNAs and that knockdown of hnRNP A2/B1 promotes transport of NS1 mRNA from the nucleus to the cytoplasm in the infected cells. Lastly, we showed that knockdown of hnRNP A2/B1 leads to enhanced virus replication. Our results suggest that hnRNP A2/B1 plays an inhibitory role in the replication of influenza A virus in host cells potentially through suppressing NS1 RNA/protein levels and NS1 mRNA nucleocytoplasmic translocation. - Highlights: • Cellular protein hnRNP A2/B1 interacts with influenza viral protein NS1. • hnRNP A2/B1 suppresses the levels of NS1 protein, vRNA and mRNA in infected cells. • hnRNP A2/B1 protein is associated with NS1 and NS2 mRNAs. • hnRNP A2/B1 inhibits the nuclear export of NS1 mRNAs. • hnRNP A2/B1 inhibits influenza virus replication.

  19. Further theoretical insight into the reaction mechanism of the hepatitis C NS3/NS4A serine protease

    NASA Astrophysics Data System (ADS)

    Martínez-González, José Ángel; Rodríguez, Alex; Puyuelo, María Pilar; González, Miguel; Martínez, Rodrigo

    2015-01-01

    The main reactions of the hepatitis C virus NS3/NS4A serine protease are studied using the second-order Møller-Plesset ab initio method and rather large basis sets to correct the previously reported AM1/CHARMM22 potential energy surfaces. The reaction efficiencies measured for the different substrates are explained in terms of the tetrahedral intermediate formation step (the rate-limiting process). The energies of the barrier and the corresponding intermediate are so close that the possibility of a concerted mechanism is open (especially for the NS5A/5B substrate). This is in contrast to the suggested general reaction mechanism of serine proteases, where a two-step mechanism is postulated.

  20. Co-refolding of a functional complex of Dengue NS3 protease and NS2B co-factor domain and backbone resonance assignment by solution NMR.

    PubMed

    Woestenenk, Esmeralda; Agback, Peter; Unnerståle, Sofia; Henderson, Ian; Agback, Tatiana

    2017-12-01

    A novel approach for separate expression of dengue virus NS3 protease and its NS2B cofactor domain is described in this paper. The two proteins are expressed in E.coli and purified separately and subsequently efficiently co-refolded to form a stable complex. This straightforward and robust method allows for separate isotope labeling of the two proteins, facilitating analysis by nuclear magnetic resonance (NMR) spectroscopy. Unlinked NS2B-NS3pro behaves better in NMR spectroscopy than linked NS2B-NS3pro, which has resulted in the backbone resonance assignment of the unlinked NS2B-NS3 complex bound to a peptidic boronic acid inhibitor. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Construction of plasmid, bacterial expression, purification, and assay of dengue virus type 2 NS5 methyltransferase.

    PubMed

    Boonyasuppayakorn, Siwaporn; Padmanabhan, Radhakrishnan

    2014-01-01

    Dengue virus (DENV), a member of mosquito-borne flavivirus, causes self-limiting dengue fever as well as life-threatening dengue hemorrhagic fever and dengue shock syndrome. Its positive sense RNA genome has a cap at the 5'-end and no poly(A) tail at the 3'-end. The viral RNA encodes a single polyprotein, C-prM-E-NS1-NS2A-NS2B-NS3-NS4A-NS4B-NS5. The polyprotein is processed into 3 structural proteins (C, prM, and E) and 7 nonstructural (NS) proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5). NS3 and NS5 are multifunctional enzymes performing various tasks in viral life cycle. The N-terminal domain of NS5 has distinct GTP and S-adenosylmethionine (SAM) binding sites. The role of GTP binding site is implicated in guanylyltransferase (GTase) activity of NS5. The SAM binding site is involved in both N-7 and 2'-O-methyltransferase (MTase) activities involved in formation of type I cap. The C-terminal domain of NS5 catalyzes RNA-dependent RNA polymerase (RdRp) activity involved in RNA synthesis. We describe the construction of the MTase domain of NS5 in an E. coli expression vector, purification of the enzyme, and conditions for enzymatic assays of N7- and 2'O-methyltransferase activities that yield the final type I 5'-capped RNA ((7Me)GpppA2'OMe-RNA).

  2. Brightness versus roughness: a multiscale approach

    NASA Astrophysics Data System (ADS)

    Bigerelle, M.; Marteau, J.; Paulin, C.

    2015-03-01

    A link between roughness and brightness is sought for brass specimens that were superfinished, sandblasted and brushed. Only the blasting conditions are varied in order to get different roughness and brightness. First, a relation between roughness and brightness is sought for specimens that were superfinished and sandblasted. The best relation is obtained using the mean height of the motifs, calculated using a low-pass filter and cut-off length equal to 30 μm, with a logarithmic-logarithmic model. Then, the same type of relation is determined after superfinishing sandblasting and brushing. The core material volume Vmc, computed using a high-pass filter with a cut-off length of 60 μm and a linear-logarithmic relationship, gives the best results. A relation between roughness and brightness that is common to both the pre-brushing state and post-brushing state is identified: the best roughness parameter is the arithmetic mean deviation Sa using a high-pass filter with a cut-off of 15 μm, with a logarithmic-logarithmic relationship. Finally, it is shown that the use of these filtering conditions enables us to verify the model of Beckmann and Spizzichino for the examined specimens. This scale corresponds to the end of the fractal regime and is close to the end of the signal correlation.

  3. Scattering amplitudes for dark and bright excitons

    NASA Astrophysics Data System (ADS)

    Shiau, Shiue-Yuan; Combescot, Monique; Combescot, Roland; Dubin, François; Chang, Yia-Chung

    2017-05-01

    Using the composite boson many-body formalism that takes single-exciton states rather than free carrier states as a basis, we derive the integral equation fulfilled by the exciton-exciton effective scattering from which the role of fermion exchanges can be unraveled. For excitons made of (+/-1/2) -spin electrons and (+/-3/2) -spin holes, as in GaAs heterostructures, one major result is that most spin configurations lead to brightness-conserving scatterings with equal amplitude Δ, despite differences in the carrier exchanges involved. A brightness-changing channel also exists when two opposite-spin excitons scatter: dark excitons (2,-2) can end either in the same dark states with an amplitude Δe , or in opposite-spin bright states (1,-1) , with a different amplitude Δo , the number of carrier exchanges involved in these scatterings being even or odd, respectively. Another major result is that these amplitudes are linked by a striking relation, Δ_e+Δ_o=Δ , which has decisive consequence on exciton Bose-Einstein condensation. By using Born values, we show that the exciton condensate can be optically observed through a bright part when excitons have large dipole only, that is, when the electrons and holes are in two well-separated layers, as in current experiments.

  4. Brightness and Darkness as Perceptual Dimensions

    PubMed Central

    Vladusich, Tony; Lucassen, Marcel P; Cornelissen, Frans W

    2007-01-01

    A common-sense assumption concerning visual perception states that brightness and darkness cannot coexist at a given spatial location. One corollary of this assumption is that achromatic colors, or perceived grey shades, are contained in a one-dimensional (1-D) space varying from bright to dark. The results of many previous psychophysical studies suggest, by contrast, that achromatic colors are represented as points in a color space composed of two or more perceptual dimensions. The nature of these perceptual dimensions, however, presently remains unclear. Here we provide direct evidence that brightness and darkness form the dimensions of a two-dimensional (2-D) achromatic color space. This color space may play a role in the representation of object surfaces viewed against natural backgrounds, which simultaneously induce both brightness and darkness signals. Our 2-D model generalizes to the chromatic dimensions of color perception, indicating that redness and greenness (blueness and yellowness) also form perceptual dimensions. Collectively, these findings suggest that human color space is composed of six dimensions, rather than the conventional three. PMID:18237226

  5. Surface brightness measurements for APM galaxies

    NASA Astrophysics Data System (ADS)

    Shao, Z.; Maddox, S. J.; Jones, J. B.; Coles, P.

    2003-01-01

    This paper considers some simple surface brightness (SB) estimates for galaxies in the Automated Plate Measuring machine (APM) catalogue in order to derive homogeneous SB data for a very large sample of faint galaxies. The isophotal magnitude and area are used to estimate the central surface brightness and total magnitude based on the assumption of an exponential SB profile. The SB measurements are corrected for field effects on each UK Schmidt plate and the zero-point of each plate is adjusted to give a uniform sample of SB and total magnitude estimates over the whole survey. Results are obtained for 2.4 million galaxies with blue photographic magnitudes brighter than bJ= 20.5 covering 4300 deg2 in the region of the South Galactic Cap. Almost all galaxies in our sample have central surface brightness in the range 20 to 24 bJ mag arcsec-2. The SB measurements we obtain are compared to previous SB measurements and we find an acceptable level of error of +/-0.2 bJ mag arcsec-2. The distribution of SB profiles is considered for different galaxy morphologies for the bright APM galaxies. We find that early-type galaxies have more centrally concentrated profiles.

  6. AMSR-E/Aqua Gridded Brightness Temperatures

    NASA Astrophysics Data System (ADS)

    Savoie, M.; Brodzik, M. J.; Knowles, K.

    2006-12-01

    Passive microwave brightness temperature data are a major component in many geophysical models and algorithms. For many researchers, a major difficulty in using these data is transforming the satellite swath data into a model-friendly, gridded format. Two new data sets and improvements to a toolkit at the National Snow and Ice Data Center (NSIDC) will help scientists incorporate these data into their research. We have produced "AMSR-E/Aqua Daily EASE-Grid Brightness Temperatures" from the Advanced Microwave Scanning Radiometer - Earth Observing System (AMSR-E) instrument aboard NASA's Earth Observing System (EOS) Aqua satellite. This data set will complement and extend NSIDC's existing EASE-grid brightness temperature data sets, with new data beginning June 2002 and continuing throughout the life-cycle of the instrument. Additionally, in order to respond to user demand for quarter-degree data, we are distributing "AMSR-E/Aqua Daily Global Quarter-Degree Gridded Brightness Temperatures" also spanning the AMSR-E time period. Researchers whose needs are not met by the above data sets can create customized grids with our AMSR-E Swath to Grid Toolkit. Recent improvements to the toolkit allow subsetted swath data as input, greatly reducing the initial data volume required to produce customized grids.

  7. Bright Meteor Lights Up Atlanta Skies

    NASA Image and Video Library

    This video shows a very bright meteor that streaked over the skies of Atlanta, Ga., on the night of Aug. 28, 2011. The view is from an all sky camera in Cartersville, Ga., operated by NASA’s Mars...

  8. Simultaneous brightness contrast of foraging Papilio butterflies.

    PubMed

    Kinoshita, Michiyo; Takahashi, Yuki; Arikawa, Kentaro

    2012-05-22

    This study focuses on the sense of brightness in the foraging Japanese yellow swallowtail butterfly, Papilio xuthus. We presented two red discs of different intensity on a grey background to butterflies, and trained them to select one of the discs. They were successfully trained to select either a high intensity or a low intensity disc. The trained butterflies were tested on their ability to perceive brightness in two different protocols: (i) two orange discs of different intensity presented on the same intensity grey background and (ii) two orange discs of the same intensity separately presented on a grey background that was either higher or lower in intensity than the training background. The butterflies trained to high intensity red selected the orange disc of high intensity in protocol 1, and the disc on the background of low intensity grey in protocol 2. We obtained similar results in another set of experiments with purple discs instead of orange discs. The choices of the butterflies trained to low intensity red were opposite to those just described. Taken together, we conclude that Papilio has the ability to learn brightness and darkness of targets independent of colour, and that they have the so-called simultaneous brightness contrast.

  9. Two Views of Vesta Bright and Dark

    NASA Image and Video Library

    2013-09-27

    These two maps of the giant asteroid Vesta show patterns of brightness from NASA Hubble Space Telescope top and NASA Dawn spacecraft bottom. Hubble view is from an orbit around Earth. Dawn went into orbit around Vesta from 2011 to 2012.

  10. Sky brightness during eclipses: a review.

    PubMed

    Silverman, S M; Mullen, E G

    1975-12-01

    This paper is abstracted from the introductory section of "Sky Brightness During Eclipses: A Compendium from the Literature," AFCRL-TR-74-0363, Special Reports 180, Air Force Cambridge Research Laboratories, Hanscom AFB, Massachusetts 01731. This report should be consulted for fuller details and tables.

  11. Venus: A Map of Its Brightness Temperature.

    PubMed

    Murray, B C; Wildey, R L; Westphal, J A

    1963-04-26

    The 200-inch Hale telescope has been used to make high-resolution maps of the brightness temperature of Venus at wavelengths 8 to 14 microns. Resolution of about 1/30 of the disk reveals a general symmetry about the plane of the orbit, no daynight temperature effects, and a transient temperature anomaly in the southern hemisphere.

  12. Brightness of synchrotron radiation from wigglers

    NASA Astrophysics Data System (ADS)

    Geloni, Gianluca; Kocharyan, Vitali; Saldin, Evgeni

    2016-01-01

    According to the literature, while calculating the brightness of synchrotron radiation from wigglers, one needs to account for the so-called 'depth-of-field' effects. In fact, the particle beam cross-section varies along the wiggler. It is usually stated that the effective photon source size increases accordingly, while the brightness is reduced. Here we claim that this is a misconception originating from an analysis of the wiggler source based on geometrical arguments, regarded as almost self-evident. According to electrodynamics, depth-of-field effects do not exist: we demonstrate this statement both theoretically and numerically, using a well-known first-principle computer code. This fact shows that under the usually accepted approximations, the description of the wiggler brightness turns out to be inconsistent even qualitatively. Therefore, there is a need for a well-defined procedure for computing the brightness from a wiggler source. We accomplish this task based on the use of a Wigner function formalism. We exemplify this formalism in simple limiting cases. We consider the problem of the calculation of the wiggler source size by means of numerical simulations alone, which play the same role of an experiment. We report a significant numerical disagreement between exact calculations and approximations currently used in the literature.

  13. Simultaneous brightness contrast of foraging Papilio butterflies

    PubMed Central

    Kinoshita, Michiyo; Takahashi, Yuki; Arikawa, Kentaro

    2012-01-01

    This study focuses on the sense of brightness in the foraging Japanese yellow swallowtail butterfly, Papilio xuthus. We presented two red discs of different intensity on a grey background to butterflies, and trained them to select one of the discs. They were successfully trained to select either a high intensity or a low intensity disc. The trained butterflies were tested on their ability to perceive brightness in two different protocols: (i) two orange discs of different intensity presented on the same intensity grey background and (ii) two orange discs of the same intensity separately presented on a grey background that was either higher or lower in intensity than the training background. The butterflies trained to high intensity red selected the orange disc of high intensity in protocol 1, and the disc on the background of low intensity grey in protocol 2. We obtained similar results in another set of experiments with purple discs instead of orange discs. The choices of the butterflies trained to low intensity red were opposite to those just described. Taken together, we conclude that Papilio has the ability to learn brightness and darkness of targets independent of colour, and that they have the so-called simultaneous brightness contrast. PMID:22179808

  14. A straightforward experimental approach to expression, purification, refolding, and enzymatic analysis of recombinant dengue virus NS2B(H)-NS3pro protease.

    PubMed

    Junaid, M; Angsuthanasombat, C; Wikberg, J E S; Ali, N; Katzenmeier, G

    2013-08-01

    Dengue virus threatens around 2.5 billion people worldwide; about 50 million become infected every year, and yet no vaccine or drug is available for prevention and/or treatment. The flaviviral NS2B-NS3pro complex is indispensable for flaviviral replication and is considered to be an important drug target. The aim of this study was to develop a simple and generally applicable experimental strategy to construct, purify, and assay a highly active recombinant NS2B(H)-NS3pro complex that would be useful for high-throughput screening of potential inhibitors. The sequence of NS2B(H)-NS3pro was generated by overlap extension PCR (SOE-PCR) and cloned into the pTrcHisA vector. Hexahistidine-tagged NS2B(H)-NS3pro complex was expressed in E. coli predominantly as insoluble protein and purified to >95% purity by single-step immobilized metal affinity chromatography. SDS-PAGE followed by immunoblotting of the purified enzyme demonstrated the presence of the NS2B(H)-NS3pro precursor and its autocleavage products, NS3pro and NS2B(H), as 37, 21, and 10 kDa bands, respectively. Kinetic parameters, Km, kcat, and kcat/Km for the fluorophore-linked protease model substrate Ac-nKRR-amc were obtained using inner-filter effect correction. The kinetic parameters Km, kcat, and kcat/Km for Ac-nKRR-amc substrate were 100 µM, 0.112 s(-1), and 1120 M(-1)·s(-1), respectively. A simplified procedure for the cloning, overexpression, and purification of the NS2B(H)-NS3pro complex was applied, and a highly active recombinant NS2B(H)-NS3pro complex was obtained that could be useful for the design of high-throughput assays aimed at flaviviral inhibitor discovery.

  15. Evolution, synthesis and SAR of tripeptide alpha-ketoacid inhibitors of the hepatitis C virus NS3/NS4A serine protease.

    PubMed

    Colarusso, Stefania; Gerlach, Benjamin; Koch, Uwe; Muraglia, Ester; Conte, Immacolata; Stansfield, Ian; Matassa, Victor G; Narjes, Frank

    2002-02-25

    N-terminal truncation of the hexapeptide ketoacid 1 gave rise to potent tripeptide inhibitors of the hepatitis C virus NS3 protease/NS4A cofactor complex. Optimization of these tripeptides led to ketoacid 30 with an IC50 of 0.38 microM. The SAR of these tripeptides is discussed in the light of the recently published crystal structures of a ternary tripetide/NS3/NS4A complexes.

  16. The nature of solar brightness variations

    NASA Astrophysics Data System (ADS)

    Shapiro, A. I.; Solanki, S. K.; Krivova, N. A.; Cameron, R. H.; Yeo, K. L.; Schmutz, W. K.

    2017-09-01

    Determining the sources of solar brightness variations1,2, often referred to as solar noise3, is important because solar noise limits the detection of solar oscillations3, is one of the drivers of the Earth's climate system4,5 and is a prototype of stellar variability6,7—an important limiting factor for the detection of extrasolar planets. Here, we model the magnetic contribution to solar brightness variability using high-cadence8,9 observations from the Solar Dynamics Observatory (SDO) and the Spectral And Total Irradiance REconstruction (SATIRE)10,11 model. The brightness variations caused by the constantly evolving cellular granulation pattern on the solar surface were computed with the Max Planck Institute for Solar System Research (MPS)/University of Chicago Radiative Magnetohydrodynamics (MURaM)12 code. We found that the surface magnetic field and granulation can together precisely explain solar noise (that is, solar variability excluding oscillations) on timescales from minutes to decades, accounting for all timescales that have so far been resolved or covered by irradiance measurements. We demonstrate that no other sources of variability are required to explain the data. Recent measurements of Sun-like stars by the COnvection ROtation and planetary Transits (CoRoT)13 and Kepler14 missions uncovered brightness variations similar to that of the Sun, but with a much wider variety of patterns15. Our finding that solar brightness variations can be replicated in detail with just two well-known sources will greatly simplify future modelling of existing CoRoT and Kepler as well as anticipated Transiting Exoplanet Survey Satellite16 and PLAnetary Transits and Oscillations of stars (PLATO)17 data.

  17. Mosquito densonucleosis virus non-structural protein NS2 is necessary for a productive infection

    SciTech Connect

    Azarkh, Eugene; Robinson, Erin; Hirunkanokpun, Supanee; Afanasiev, Boris; Kittayapong, Pattamaporn; Carlson, Jonathan Corsini, Joe

    2008-04-25

    Mosquito densonucleosis viruses synthesize two non-structural proteins, NS1 and NS2. While NS1 has been studied relatively well, little is known about NS2. Antiserum was raised against a peptide near the N-terminus of NS2, and used to conduct Western blot analysis and immuno-fluorescence assays. Western blots revealed a prominent band near the expected size (41 kDa). Immuno-fluorescence studies of mosquito cells transfected with AeDNV indicate that NS2 has a wider distribution pattern than does NS1, and the distribution pattern appears to be a function of time post-infection. Nuclear localization of NS2 requires intact C-terminus but does not require additional viral proteins. Mutations ranging from complete NS2 knock-out to a single missense amino acid substitution in NS2 can significantly reduce viral replication and production of viable progeny.

  18. RNA unwinding by NS3 helicase: a statistical approach.

    PubMed

    Arunajadai, Srikesh G

    2009-09-22

    The study of double-stranded RNA unwinding by helicases is a problem of basic scientific interest. One such example is provided by studies on the hepatitis C virus (HCV) NS3 helicase using single molecule mechanical experiments. HCV currently infects nearly 3% of the world population and NS3 is a protein essential for viral genome replication. The objective of this study is to model the RNA unwinding mechanism based on previously published data and study its characteristics and their dependence on force, ATP and NS3 protein concentration. In this work, RNA unwinding by NS3 helicase is hypothesized to occur in a series of discrete steps and the steps themselves occurring in accordance with an underlying point process. A point process driven change point model is employed to model the RNA unwinding mechanism. The results are in large agreement with findings in previous studies. A gamma distribution based renewal process was found to model well the point process that drives the unwinding mechanism. The analysis suggests that the periods of constant extension observed during NS3 activity can indeed be classified into pauses and subpauses and that each depend on the ATP concentration. The step size is independent of external factors and seems to have a median value of 11.37 base pairs. The steps themselves are composed of a number of substeps with an average of about 4 substeps per step and an average substep size of about 3.7 base pairs. An interesting finding pertains to the stepping velocity. Our analysis indicates that stepping velocity may be of two kinds- a low and a high velocity.

  19. Priming and stimulation of hepatitis C virus-specific CD4+ and CD8+ T cells against HCV antigens NS4, NS5a or NS5b from HCV-naive individuals: implications for prophylactic vaccine.

    PubMed

    Li, Wen; Krishnadas, Deepa K; Kumar, Rakesh; Tyrrell, D Lorne J; Agrawal, Babita

    2008-01-01

    Hepatitis C virus (HCV) is a devastating human pathogen, yet there is no vaccine available for this virus. From studies with acute or chronic HCV-infected humans and chimpanzees, T-cell responses against HCV-derived conserved non-structural antigens have been correlated with viral clearance. In this study, recombinant adenoviral vectors containing HCV-derived NS4, NS5a or NS5b genes were employed to endogenously express the HCV antigens in human dendritic cells (DCs). The DCs expressing these HCV antigens exhibited normal phenotype and function. Intriguingly, we found that the DCs expressing HCV NS4, NS5a or NS5b antigens were able to significantly stimulate autologous T cells obtained from uninfected healthy individuals. These T cells produced various cytokines and proliferated in an HCV antigen-dependent manner. Evidence of both CD4(+) and CD8(+) T-cell responses generated in vitro against HCV NS4, NS5a or NS5b were obtained. HCV NS4 was much less stimulatory for CD4(+) and CD8(+) T cells than NS5. Further, in secondary assays, the CD4(+) T cells primed in vitro exhibited HCV antigen-specific proliferative responses against recombinant protein antigens. In summary, we provide conclusive evidence of in vitro stimulation of CD4(+) and CD8(+) T cells from HCV-naive individuals against HCV antigens NS4, NS5a and NS5b. The studies with naive T cells represent early events in the induction of cellular immune responses, which most likely govern the outcome of HCV infection. These studies have significant implications in designing vaccines for HCV infection in both prophylactic and therapeutic settings.

  20. Cortical brightness adaptation when darkness and brightness produce different dynamical states in the visual cortex

    PubMed Central

    Xing, Dajun; Yeh, Chun-I; Gordon, James; Shapley, Robert M.

    2014-01-01

    Darkness and brightness are very different perceptually. To understand the neural basis for the visual difference, we studied the dynamical states of populations of neurons in macaque primary visual cortex when a spatially uniform area (8° × 8°) of the visual field alternated between black and white. Darkness evoked sustained nerve-impulse spiking in primary visual cortex neurons, but bright stimuli evoked only a transient response. A peak in the local field potential (LFP) γ band (30–80 Hz) occurred during darkness; white-induced LFP fluctuations were of lower amplitude, peaking at 25 Hz. However, the sustained response to white in the evoked LFP was larger than for black. Together with the results on spiking, the LFP results imply that, throughout the stimulus period, bright fields evoked strong net sustained inhibition. Such cortical brightness adaptation can explain many perceptual phenomena: interocular speeding up of dark adaptation, tonic interocular suppression, and interocular masking. PMID:24398523

  1. Cortical brightness adaptation when darkness and brightness produce different dynamical states in the visual cortex.

    PubMed

    Xing, Dajun; Yeh, Chun-I; Gordon, James; Shapley, Robert M

    2014-01-21

    Darkness and brightness are very different perceptually. To understand the neural basis for the visual difference, we studied the dynamical states of populations of neurons in macaque primary visual cortex when a spatially uniform area (8° × 8°) of the visual field alternated between black and white. Darkness evoked sustained nerve-impulse spiking in primary visual cortex neurons, but bright stimuli evoked only a transient response. A peak in the local field potential (LFP) γ band (30-80 Hz) occurred during darkness; white-induced LFP fluctuations were of lower amplitude, peaking at 25 Hz. However, the sustained response to white in the evoked LFP was larger than for black. Together with the results on spiking, the LFP results imply that, throughout the stimulus period, bright fields evoked strong net sustained inhibition. Such cortical brightness adaptation can explain many perceptual phenomena: interocular speeding up of dark adaptation, tonic interocular suppression, and interocular masking.

  2. Dengue virus-specific CD4+ and CD8+ T lymphocytes target NS1, NS3 and NS5 in infected Indian rhesus macaques.

    PubMed

    Mladinich, Katherine M; Piaskowski, Shari M; Rudersdorf, Richard; Eernisse, Christopher M; Weisgrau, Kim L; Martins, Mauricio A; Furlott, Jessica R; Partidos, Charalambos D; Brewoo, Joseph N; Osorio, Jorge E; Wilson, Nancy A; Rakasz, Eva G; Watkins, David I

    2012-02-01

    Every year, Dengue virus (DENV) infects approximately 100 million people. There are currently several vaccines undergoing clinical studies, but most target the induction of neutralizing antibodies. Unfortunately, DENV infection can be enhanced by subneutralizing levels of antibodies that bind virions and deliver them to cells of the myeloid lineage, thereby increasing viral replication (termed antibody-dependent enhancement [ADE]). T lymphocyte-based vaccines may offer an alternative that avoids ADE. The goal of our study was to describe the cellular immune response generated after primary DENV infection in Indian rhesus macaques. We infected eight rhesus macaques with 10⁵ plaque-forming units (PFU) of DENV serotype 2 (DENV2) New Guinea C (NGC) strain, and monitored viral load and the cellular immune response to the virus. Viral replication peaked at day 4 post-infection and was resolved by day 10. DENV-specific CD4+ and CD8+ T lymphocytes targeted nonstructural (NS) 1, NS3 and NS5 proteins after resolution of peak viremia. DENV-specific CD4+ cells expressed interferon-gamma (IFN-γ) along with tumor necrosis factor-alpha (TNF-α), interleukin-2 (IL-2), and macrophage inflammatory protein-1 beta (MIP-1β). In comparison, DENV-specific CD8+ cells expressed IFN-γ in addition to MIP-1β and TNF-α and were positive for the degranulation marker CD107a. Interestingly, a fraction of the DENV-specific CD4+ cells also stained for CD107a, suggesting that they might be cytotoxic. Our results provide a more complete understanding of the cellular immune response during DENV infection in rhesus macaques and contribute to the development of rhesus macaques as an animal model for DENV vaccine and pathogenicity studies.

  3. TFaNS-Tone Fan Noise Design/Prediction System: Users' Manual TFaNS Version 1.5

    NASA Technical Reports Server (NTRS)

    Topol, David A.; Huff, Dennis L. (Technical Monitor)

    2003-01-01

    TFaNS is the Tone Fan Noise Design/Prediction System developed by Pratt & Whitney under contract to NASA Glenn. The purpose of this system is to predict tone noise emanating from a fan stage including the effects of reflection and transmission by the rotor and stator and by the duct inlet and nozzle. The first version of this design system was developed under a previous NASA contract. Several improvements have been made to TFaNS. This users' manual shows how to run this new system. TFaNS consists of the codes that compute the acoustic properties (reflection and transmission coefficients) of the various elements and writes them to files, CUP3D Fan Noise Coupling Code that reads these files, solves the coupling problem, and outputs the desired noise predictions, and AWAKEN CFD/Measured Wake Postprocessor which reformats CFD wake predictions and/or measured wake data so they can be used by the system. This report provides information on code input and file structure essential for potential users of TFaNS.

  4. Effects of NS2B-NS3 protease and furin inhibition on West Nile and Dengue virus replication.

    PubMed

    Kouretova, Jenny; Hammamy, M Zouhir; Epp, Anton; Hardes, Kornelia; Kallis, Stephanie; Zhang, Linlin; Hilgenfeld, Rolf; Bartenschlager, Ralf; Steinmetzer, Torsten

    2017-12-01

    West Nile virus (WNV) and Dengue virus (DENV) replication depends on the viral NS2B-NS3 protease and the host enzyme furin, which emerged as potential drug targets. Modification of our previously described WNV protease inhibitors by basic phenylalanine analogs provided compounds with reduced potency against the WNV and DENV protease. In a second series, their decarboxylated P1-trans-(4-guanidino)cyclohexylamide was replaced by an arginyl-amide moiety. Compound 4-(guanidinomethyl)-phenylacetyl-Lys-Lys-Arg-NH2 inhibits the NS2B-NS3 protease of WNV with an inhibition constant of 0.11 µM. Due to the similarity in substrate specificity, we have also tested the potency of our previously described multibasic furin inhibitors. Their further modification provided chimeric inhibitors with additional potency against the WNV and DENV proteases. A strong inhibition of WNV and DENV replication in cell culture was observed for the specific furin inhibitors, which reduced virus titers up to 10,000-fold. These studies reveal that potent inhibitors of furin can block the replication of DENV and WNV.

  5. Novel antiviral activity and mechanism of bromocriptine as a Zika virus NS2B-NS3 protease inhibitor.

    PubMed

    Chan, Jasper Fuk-Woo; Chik, Kenn Ka-Heng; Yuan, Shuofeng; Yip, Cyril Chik-Yan; Zhu, Zheng; Tee, Kah-Meng; Tsang, Jessica Oi-Ling; Chan, Chris Chung-Sing; Poon, Vincent Kwok-Man; Lu, Gang; Zhang, Anna Jinxia; Lai, Kin-Kui; Chan, Kwok-Hung; Kao, Richard Yi-Tsun; Yuen, Kwok-Yung

    2017-02-07

    Zika virus (ZIKV) infection is associated with congenital malformations in infected fetuses and severe neurological and other systemic complications in adults. There are currently limited anti-ZIKV treatment options that are readily available and safe for use in pregnancy. In this drug repurposing study, bromocriptine was found to have inhibitory effects on ZIKV replication in cytopathic effect inhibition, virus yield reduction, and plaque reduction assays. Time-of-drug-addition assay showed that bromocriptine exerted anti-ZIKV activity between 0 and 12 h post-ZIKV inoculation, corroborating with post-entry events in the virus replication cycle prior to budding. Our docking model showed that bromocriptine interacted with several active site residues of the proteolytic cavity involving H51 and S135 in the ZIKV-NS2B-NS3 protease protein, and might occupy the active site and inhibit the protease activity of the ZIKV-NS2B-NS3 protein. A fluorescence-based protease inhibition assay confirmed that bromocriptine inhibited ZIKV protease activity. Moreover, bromocriptine exhibited synergistic effect with interferon-α2b against ZIKV replication in cytopathic effect inhibition assay. The availability of per vagina administration of bromocriptine as suppositories or vaginoadhesive discs and the synergistic anti-ZIKV activity between bromocriptine and type I interferon may make bromocriptine a potentially useful and readily available treatment option for ZIKV infection. The anti-ZIKV effects of bromocriptine should be evaluated in a suitable animal model.

  6. Increased activity of unlinked Zika virus NS2B/NS3 protease compared to linked Zika virus protease.

    PubMed

    Kuiper, Benjamin D; Slater, Kristin; Spellmon, Nicholas; Holcomb, Joshua; Medapureddy, Prasanna; Muzzarelli, Kendall M; Yang, Zhe; Ovadia, Reuben; Amblard, Franck; Kovari, Iulia A; Schinazi, Raymond F; Kovari, Ladislau C

    2017-03-22

    Zika virus (ZIKV) is a flavivirus spread by daytime-active Aedes spp. mosquitoes such as A. aegypti and A. albopictus. Previously thought to be a mild infection, the latest ZIKV outbreak in the Americas is causally associated with more severe symptoms as well as severe birth defects, such as microcephaly. Currently no vaccine or antiviral exists. However, recent progress has demonstrated the viral NS2B/NS3 protease may be a suitable target for the development of small-molecule antiviral agents. To better understand the ZIKV protease, we expressed, purified, and characterized unlinked and linked NS2B/NS3 protease corresponding to an isolate from the recent outbreak in Puerto Rico. Unlinked ZIKV protease is more active and binds substrate with greater affinity than linked ZIKV protease. Therefore, we propose that unlinked ZIKV protease be used when evaluating or designing ZIKV protease inhibitors. Additionally, potent inhibitors of related viral proteases, like West Nile Virus and Dengue virus, may serve as advanced starting points to identify and develop ZIKV protease inhibitors.

  7. Intermittent Episodes of Bright Light Suppress Myopia in the Chicken More than Continuous Bright Light

    PubMed Central

    Lan, Weizhong; Feldkaemper, Marita; Schaeffel, Frank

    2014-01-01

    Purpose Bright light has been shown a powerful inhibitor of myopia development in animal models. We studied which temporal patterns of bright light are the most potent in suppressing deprivation myopia in chickens. Methods Eight-day-old chickens wore diffusers over one eye to induce deprivation myopia. A reference group (n = 8) was kept under office-like illuminance (500 lux) at a 10∶14 light∶dark cycle. Episodes of bright light (15 000 lux) were super-imposed on this background as follows. Paradigm I: exposure to constant bright light for either 1 hour (n = 5), 2 hours (n = 5), 5 hours (n = 4) or 10 hours (n = 4). Paradigm II: exposure to repeated cycles of bright light with 50% duty cycle and either 60 minutes (n = 7), 30 minutes (n = 8), 15 minutes (n = 6), 7 minutes (n = 7) or 1 minute (n = 7) periods, provided for 10 hours. Refraction and axial length were measured prior to and immediately after the 5-day experiment. Relative changes were analyzed by paired t-tests, and differences among groups were tested by one-way ANOVA. Results Compared with the reference group, exposure to continuous bright light for 1 or 2 hours every day had no significant protective effect against deprivation myopia. Inhibition of myopia became significant after 5 hours of bright light exposure but extending the duration to 10 hours did not offer an additional benefit. In comparison, repeated cycles of 1∶1 or 7∶7 minutes of bright light enhanced the protective effect against myopia and could fully suppress its development. Conclusions The protective effect of bright light depends on the exposure duration and, to the intermittent form, the frequency cycle. Compared to the saturation effect of continuous bright light, low frequency cycles of bright light (1∶1 min) provided the strongest inhibition effect. However, our quantitative results probably might not be directly translated into humans, but rather need further amendments in clinical

  8. Serotype-specific interactions among functional domains of Dengue virus 2 non-structural proteins (NS) 5 and NS3 are crucial for viral RNA replication.

    PubMed

    Teramoto, Tadahisa; Balasubramanian, Anuradha; Choi, Kyung H; Padmanabhan, Radhakrishnan

    2017-04-10

    Four serotypes of mosquito-borne Dengue virus (DENV), evolved from a common ancestor, are human pathogens of global significance, and there is no vaccine or antiviral drug available. The N-terminal domain of DENV NS5 has guanylyltransferase and methyltransferase (MTase) and the C-terminal region has the polymerase (POL) which are important for 5'-capping and RNA replication. The crystal structure of NS5 showed it as a dimer but the functional evidence for NS5 dimer is lacking. The results of our studies show that the substitution of DENV2 NS5 MTase or POL with that of DENV4 NS5 within DENV2 RNA resulted in severe attenuation of replication in the transfected BHK-21 cells. A replication competent species evolved with acquired mutations in the DENV2 and DENV4 NS5 MTase or POL domain or in DENV2 NS3 helicase domain in the DENV2 chimera RNAs by repeated passaging of infected BHK-21 or mosquito cells. The linker region of seven residues in NS5, rich in serotype-specific residues, is important for recovery of replication fitness in the chimera RNA. Our results, taken together, provide genetic evidence for serotype-specific interaction between NS3 and NS5 as well as specific inter-domain interaction within NS5 required for RNA replication. Genome-wide RNAseq analysis revealed the distribution of adaptive mutations in RNA quasispecies. Those within NS3 and NS5 are located at the surface and/or within the NS5 dimer interface providing a functional significance to the crystal structure NS5 dimer.

  9. Performance of commercial dengue NS1 ELISA and molecular analysis of NS1 gene of dengue viruses obtained during surveillance in Indonesia.

    PubMed

    Aryati, Aryati; Trimarsanto, Hidayat; Yohan, Benediktus; Wardhani, Puspa; Fahri, Sukmal; Sasmono, R Tedjo

    2013-12-29

    Early diagnosis of dengue infection is crucial for better management of the disease. Diagnostic tests based on the detection of dengue virus (DENV) Non Structural Protein 1 (NS1) antigen are commercially available with different sensitivities and specificities observed in various settings. Dengue is endemic in Indonesia and clinicians are increasingly using the NS1 detection for dengue confirmation. This study described the performance of Panbio Dengue Early NS1 and IgM Capture ELISA assays for dengue detection during our surveillance in eight cities in Indonesia as well as the genetic diversity of DENV NS1 genes and its relationship with the NS1 detection. The NS1 and IgM/IgG ELISA assays were used for screening and confirmation of dengue infection during surveillance in 2010-2012. Collected serum samples (n = 440) were subjected to RT-PCR and virus isolation, in which 188 samples were confirmed for dengue infection. The positivity of the ELISA assays were correlated with the RT-PCR results to obtain the sensitivity of the assays. The NS1 genes of 48 Indonesian virus isolates were sequenced and their genetic characteristics were studied. Using molecular data as gold standard, the sensitivity of NS1 ELISA assay for samples from Indonesia was 56.4% while IgM ELISA was 73.7%. When both NS1 and IgM results were combined, the sensitivity increased to 89.4%. The NS1 sensitivity varied when correlated with city/geographical origins and DENV serotype, in which the lowest sensitivity was observed for DENV-4 (19.0%). NS1 sensitivity was higher in primary (67.6%) compared to secondary infection (48.2%). The specificity of NS1 assay for non-dengue samples were 100%. The NS1 gene sequence analysis of 48 isolates revealed the presence of polymorphisms of the NS1 genes which apparently did not influence the NS1 sensitivity. We observed a relatively low sensitivity of NS1 ELISA for dengue detection on RT-PCR-positive dengue samples. The detection rate increased significantly

  10. hnRNP A2/B1 interacts with influenza A viral protein NS1 and inhibits virus replication potentially through suppressing NS1 RNA/protein levels and NS1 mRNA nuclear export.

    PubMed

    Wang, Yimeng; Zhou, Jianhong; Du, Yuchun

    2014-01-20

    The NS1 protein of influenza viruses is a major virulence factor and exerts its function through interacting with viral/cellular RNAs and proteins. In this study, we identified heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) as an interacting partner of NS1 proteins by a proteomic method. Knockdown of hnRNP A2/B1 by small interfering RNA (siRNA) resulted in higher levels of NS vRNA, NS1 mRNA, and NS1 protein in the virus-infected cells. In addition, we demonstrated that hnRNP A2/B1 proteins are associated with NS1 and NS2 mRNAs and that knockdown of hnRNP A2/B1 promotes transport of NS1 mRNA from the nucleus to the cytoplasm in the infected cells. Lastly, we showed that knockdown of hnRNP A2/B1 leads to enhanced virus replication. Our results suggest that hnRNP A2/B1 plays an inhibitory role in the replication of influenza A virus in host cells potentially through suppressing NS1 RNA/protein levels and NS1 mRNA nucleocytoplasmic translocation.

  11. The Hepatitis C Virus NS5A Stimulates NS5B During In Vitro RNA Synthesis in a Template Specific Manner

    PubMed Central

    Quezada, Elizabeth M; Kane, Caroline M

    2009-01-01

    The hepatitis C virus (HCV) NS5B protein contains the RNA dependent RNA polymerase (RdRp) activity that catalyzes the synthesis of the viral genome with other host and viral factors. NS5A is an HCV-encoded protein previously shown to localize to the replisome and be necessary for viral replication. However, its role in replication has not been defined. Using an in vitro biochemical assay, we detected a stimulatory effect of NS5A on the NS5B replication reaction with minimal natural templates. NS5A stimulates replication by NS5B on two templates derived from the 3’ end of the RNA genome (4 fold ± 1.3 fold). A pre-incubation step with the two proteins prior to the replication reaction and substoichiometric levels of NS5A are required for detecting stimulation. With a template derived from the 3’end complementary to the RNA genome (the negative strand) no stimulation was observed. Furthermore, with a synthetic template that allows studying different phases of replication, NS5A stimulates NS5B during elongation. These findings suggest that NS5A stimulates NS5B during synthesis of the complementary (i.e., negative) strand of the RNA genome. PMID:19590581

  12. Lyso-myristoyl phosphatidylcholine micelles sustain the activity of Dengue non-structural (NS) protein 3 protease domain fused with the full-length NS2B.

    PubMed

    Huang, Qiwei; Li, Qingxin; Joy, Joma; Chen, Angela Shuyi; Ruiz-Carrillo, David; Hill, Jeffrey; Lescar, Julien; Kang, Congbao

    2013-12-01

    Dengue virus (DENV), a member of the flavivirus genus, affects 50-100 million people in tropical and sub-tropical regions. The DENV protease domain is located at the N-terminus of the NS3 protease and requires for its enzymatic activity a hydrophilic segment of the NS2B that acts as a cofactor. The protease is an important antiviral drug target because it plays a crucial role in virus replication by cleaving the genome-coded polypeptide into mature functional proteins. Currently, there are no drugs to inhibit DENV protease activity. Most structural and functional studies have been conducted using protein constructs containing the NS3 protease domain connected to a soluble segment of the NS2B membrane protein via a nine-residue linker. For in vitro structural and functional studies, it would be useful to produce a natural form of the DENV protease containing the NS3 protease domain and the full-length NS2B protein. Herein, we describe the expression and purification of a natural form of DENV protease (NS2BFL-NS3pro) containing the full-length NS2B protein and the protease domain of NS3 (NS3pro). The protease was expressed and purified in detergent micelles necessary for its folding. Our results show that this purified protein was active in detergent micelles such as lyso-myristoyl phosphatidylcholine (LMPC). These findings should facilitate further structural and functional studies of the protease and will facilitate drug discovery targeting DENV.

  13. Do Low Surface Brightness Galaxies Host Stellar Bars?

    NASA Astrophysics Data System (ADS)

    Cervantes Sodi, Bernardo; Sánchez García, Osbaldo

    2017-09-01

    With the aim of assessing if low surface brightness galaxies host stellar bars and by studying the dependence of the occurrence of bars as a function of surface brightness, we use the Galaxy Zoo 2 data set to construct a large volume-limited sample of galaxies and then segregate these galaxies as having low or high surface brightness in terms of their central surface brightness. We find that the fraction of low surface brightness galaxies hosting strong bars is systematically lower than that found for high surface brightness galaxies. The dependence of the bar fraction on the central surface brightness is mostly driven by a correlation of the surface brightness with the spin and the gas richness of the galaxies, showing only a minor dependence on the surface brightness. We also find that the length of the bars is strongly dependent on the surface brightness, and although some of this dependence is attributed to the gas content, even at a fixed gas-to-stellar mass ratio, high surface brightness galaxies host longer bars than their low surface brightness counterparts, which we attribute to an anticorrelation of the surface brightness with the spin.

  14. TURBULENT PAIR DISPERSION OF PHOTOSPHERIC BRIGHT POINTS

    SciTech Connect

    Lepreti, F.; Carbone, V.; Capparelli, V.; Vecchio, A.

    2012-11-01

    Observations of solar granulation obtained with the New Solar Telescope of Big Bear Solar Observatory are used to study the turbulent pair dispersion of photospheric bright points in a quiet-Sun area, a coronal hole, and an active region plage. In all the three magnetic environments, it is found that the pair mean-squared separation {Delta}{sup 2}(t) follows a power-law timescaling {Delta}{sup 2}(t) {approx} t {sup {eta}} in the range 10 s {approx}< t {approx}< 400 s. The power-law index is found to be {eta} {approx_equal} 1.5 for all the three investigated regions. It is shown that these results can be explained in the same framework as the classical Batchelor theory, under the hypothesis that the observed range of timescales corresponds to a non-asymptotic regime in which the photospheric bright points keep the memory of their initial separations.

  15. Bright Feature Appears in Titan Kraken Mare

    NASA Image and Video Library

    2014-11-10

    Two Synthetic Aperture Radar (SAR) images from the radar experiment on NASA's Cassini spacecraft show that, between May 2013 and August 2014, a bright feature appeared in Kraken Mare, the largest hydrocarbon sea on Saturn's moon Titan. Researchers think the bright feature is likely representative of something on the hydrocarbon sea's surface, such as waves or floating debris. A similar feature appeared in Ligea Mare, another Titan sea, and was seen to evolve in appearance between 2013 and 2014 (see PIA18430). The image at left was taken on May 23, 2013 at an incidence angle of 56 degrees; the image at right was taken on August 21, 2014 at an incidence angle of 5 degrees. Incidence angle refers to the angle at which the radar beam strikes the surface. http://photojournal.jpl.nasa.gov/catalog/PIA19047

  16. Image mosaic with color and brightness correction

    NASA Astrophysics Data System (ADS)

    Zhao, Yili; Xu, Dan; Pan, Zhigeng

    2004-03-01

    Image mosaic is comprised of building a large field of view from a sequence of smaller images. It can be performed by registering, projective warping, resampling and compositing a serials of images. Due to the many possible factors for color and brightness variations when taking images, it is possible to lead to misalignment and obtain poor stitching result. Despite image mosaic can be manually adjusted using some photo editors like PhotoShop, this is not only tedious but also requires skills, knowledge and experience. Automatic adjustment is therefore desirable. By converting images to lαβ space and applying a special statistical analysis, color and brightness correction can be done automatically and improved image mosaic can be obtained.

  17. Extreme Ultraviolet Explorer Bright Source List

    NASA Technical Reports Server (NTRS)

    Malina, Roger F.; Marshall, Herman L.; Antia, Behram; Christian, Carol A.; Dobson, Carl A.; Finley, David S.; Fruscione, Antonella; Girouard, Forrest R.; Hawkins, Isabel; Jelinsky, Patrick

    1994-01-01

    Initial results from the analysis of the Extreme Ultraviolet Explorer (EUVE) all-sky survey (58-740 A) and deep survey (67-364 A) are presented through the EUVE Bright Source List (BSL). The BSL contains 356 confirmed extreme ultraviolet (EUV) point sources with supporting information, including positions, observed EUV count rates, and the identification of possible optical counterparts. One-hundred twenty-six sources have been detected longward of 200 A.

  18. UV-bright stars in globular clusters

    NASA Technical Reports Server (NTRS)

    Landsman, Wayne B.

    1994-01-01

    This paper highlights globular cluster studies with Ultraviolet Imaging Telescope (UIT) in three areas: the discrepancy between observed ultraviolet HB magnitudes and predictions of theoretical HB models; the discovery of two hot subdwarfs in NGC 1851, a globular not previously known to contain such stars; and spectroscopic follow up of newly identified UV-bright stars in M79 and w Cen. I also present results of a recent observation of NGC 6397 with the Voyager ultraviolet spectrometer.

  19. Modular Zero Energy. BrightBuilt Home

    SciTech Connect

    Aldrich, Robb; Butterfield, Karla

    2016-03-01

    With funding from the Building America Program, part of the U.S. Department of Energy Building Technologies Office, the Consortium for Advanced Residential Buildings (CARB) worked with BrightBuilt Home (BBH) to evaluate and optimize building systems. CARB’s work focused on a home built by Black Bros. Builders in Lincolnville, Maine (International Energy Conservation Code Climate Zone 6). As with most BBH projects to date, modular boxes were built by Keiser Homes in Oxford, Maine.

  20. Nonlinear Brightness Optimization in Compton Scattering

    NASA Astrophysics Data System (ADS)

    Hartemann, Fred V.; Wu, Sheldon S. Q.

    2013-07-01

    In Compton scattering light sources, a laser pulse is scattered by a relativistic electron beam to generate tunable x and gamma rays. Because of the inhomogeneous nature of the incident radiation, the relativistic Lorentz boost of the electrons is modulated by the ponderomotive force during the interaction, leading to intrinsic spectral broadening and brightness limitations. These effects are discussed, along with an optimization strategy to properly balance the laser bandwidth, diffraction, and nonlinear ponderomotive force.

  1. Spectral Characterization of Bright Materials on Vesta

    NASA Technical Reports Server (NTRS)

    Capaccioni, Fabrizio; DeSanctis, M. C.; Ammannito, E.; Li, Jian-Yang; Longobardo, A.; Mittlefehldt, David W.; Palomba, E.; Pieters, C. M.; Schroeder, S. E.; Tosi, F.; hide

    2012-01-01

    The surface of Vesta, as observed by the camera and imaging spectrometer onboard the Dawn spacecraft, displays large surface diversity in terms of its geology and mineralogy with noticeably dark and bright areas on the surface often associated with various geological features and showing remarkably different forms. Here we report our initial attempt to spectrally characterize the areas that are distinctively brighter than their surroundings.

  2. Australia 31-GHz brightness temperature exceedance statistics

    NASA Technical Reports Server (NTRS)

    Gary, B. L.

    1988-01-01

    Water vapor radiometer measurements were made at DSS 43 during an 18 month period. Brightness temperatures at 31 GHz were subjected to a statistical analysis which included correction for the effects of occasional water on the radiometer radome. An exceedance plot was constructed, and the 1 percent exceedance statistics occurs at 120 K. The 5 percent exceedance statistics occurs at 70 K, compared with 75 K in Spain. These values are valid for all of the three month groupings that were studied.

  3. iPTF report of bright transients

    NASA Astrophysics Data System (ADS)

    Cannella, Chris; Kuesters, Daniel; Ferretti, Raphael; Blagorodnova, Nadejda; Adams, Scott; Kupfer, Thomas; Neill, James D.; Walters, Richard; Yan, Lin; Kulkarni, Shri

    2017-02-01

    The intermediate Palomar Transient Factory (iPTF; ATel #4807) reports the following bright ( Our automated candidate vetting to distinguish a real astrophysical source (1.0) from bogus artifacts (0.0) is powered by three generations of machine learning algorithms: RB2 (Brink et al. 2013MNRAS.435.1047B), RB4 (Rebbapragada et al. 2015AAS...22543402R), and RB5 (Wozniak et al. 2013AAS...22143105W).

  4. Nonlinear Brightness Optimization in Compton Scattering

    SciTech Connect

    Hartemann, Fred V.; Wu, Sheldon S. Q.

    2013-07-26

    In Compton scattering light sources, a laser pulse is scattered by a relativistic electron beam to generate tunable x and gamma rays. Because of the inhomogeneous nature of the incident radiation, the relativistic Lorentz boost of the electrons is modulated by the ponderomotive force during the interaction, leading to intrinsic spectral broadening and brightness limitations. We discuss these effects, along with an optimization strategy to properly balance the laser bandwidth, diffraction, and nonlinear ponderomotive force.

  5. Nonlinear brightness optimization in compton scattering.

    PubMed

    Hartemann, Fred V; Wu, Sheldon S Q

    2013-07-26

    In Compton scattering light sources, a laser pulse is scattered by a relativistic electron beam to generate tunable x and gamma rays. Because of the inhomogeneous nature of the incident radiation, the relativistic Lorentz boost of the electrons is modulated by the ponderomotive force during the interaction, leading to intrinsic spectral broadening and brightness limitations. These effects are discussed, along with an optimization strategy to properly balance the laser bandwidth, diffraction, and nonlinear ponderomotive force.

  6. Human VAP-B is involved in hepatitis C virus replication through interaction with NS5A and NS5B.

    PubMed

    Hamamoto, Itsuki; Nishimura, Yorihiro; Okamoto, Toru; Aizaki, Hideki; Liu, Minyi; Mori, Yoshio; Abe, Takayuki; Suzuki, Tetsuro; Lai, Michael M C; Miyamura, Tatsuo; Moriishi, Kohji; Matsuura, Yoshiharu

    2005-11-01

    The hepatitis C virus (HCV) nonstructural protein (NS) 5A is a phosphoprotein that associates with various cellular proteins and participates in the replication of the HCV genome. Human vesicle-associated membrane protein-associated protein (VAP) subtype A (VAP-A) is known to be a host factor essential for HCV replication by binding to both NS5A and NS5B. To obtain more information on the NS5A protein in HCV replication, we screened human brain and liver libraries by a yeast two-hybrid system using NS5A as bait and identified VAP-B as an NS5A-binding protein. Immunoprecipitation and mutation analyses revealed that VAP-B binds to both NS5A and NS5B in mammalian cells and forms homo- and heterodimers with VAP-A. VAP-A interacts with VAP-B through the transmembrane domain. NS5A interacts with the coiled-coil domain of VAP-B via 70 residues in the N-terminal and 341 to 344 amino acids in the C-terminal polyproline cluster region. NS5A was colocalized with VAP-B in the endoplasmic reticulum and Golgi apparatus. The specific antibody to VAP-B suppressed HCV RNA replication in a cell-free assay. Overexpression of VAP-B, but not of a mutant lacking its transmembrane domain, enhanced the expression of NS5A and NS5B and the replication of HCV RNA in Huh-7 cells harboring a subgenomic replicon. In the HCV replicon cells, the knockdown of endogenous VAP-B by small interfering RNA decreased expression of NS5B, but not of NS5A. These results suggest that VAP-B, in addition to VAP-A, plays an important role in the replication of the HCV genome.

  7. Identification of Residues in the Dengue Virus Type 2 NS2B Cofactor That Are Critical for NS3 Protease Activation

    PubMed Central

    Niyomrattanakit, Pornwaratt; Winoyanuwattikun, Pakorn; Chanprapaph, Santad; Angsuthanasombat, Chanan; Panyim, Sakol; Katzenmeier, Gerd

    2004-01-01

    Proteolytic processing of the dengue virus polyprotein is mediated by host cell proteases and the virus-encoded NS2B-NS3 two-component protease. The NS3 protease represents an attractive target for the development of antiviral inhibitors. The three-dimensional structure of the NS3 protease domain has been determined, but the structural determinants necessary for activation of the enzyme by the NS2B cofactor have been characterized only to a limited extent. To test a possible functional role of the recently proposed Φx3Φ motif in NS3 protease activation, we targeted six residues within the NS2B cofactor by site-specific mutagenesis. Residues Trp62, Ser71, Leu75, Ile77, Thr78, and Ile79 in NS2B were replaced with alanine, and in addition, an L75A/I79A double mutant was generated. The effects of these mutations on the activity of the NS2B(H)-NS3pro protease were analyzed in vitro by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of autoproteolytic cleavage at the NS2B/NS3 site and by assay of the enzyme with the fluorogenic peptide substrate GRR-AMC. Compared to the wild type, the L75A, I77A, and I79A mutants demonstrated inefficient autoproteolysis, whereas in the W62A and the L75A/I79A mutants self-cleavage appeared to be almost completely abolished. With exception of the S71A mutant, which had a kcat/Km value for the GRR-AMC peptide similar to that of the wild type, all other mutants exhibited drastically reduced kcat values. These results indicate a pivotal function of conserved residues Trp62, Leu75, and Ile79 in the NS2B cofactor in the structural activation of the dengue virus NS3 serine protease. PMID:15564480

  8. Bright Ray Craters in Ganymede's Northern Hemisphere

    NASA Technical Reports Server (NTRS)

    1979-01-01

    GANYMEDE COLOR PHOTOS: This color picture as acquired by Voyager 1 during its approach to Ganymede on Monday afternoon (the 5th of March). At ranges between about 230 to 250 thousand km. The images show detail on the surface with a resolution of four and a half km. This picture is of a region in the northern hemisphere near the terminator. It shows a variety of impact structures, including both razed and unrazed craters, and the odd, groove-like structures discovered by Voyager in the lighter regions. The most striking features are the bright ray craters which have a distinctly 'bluer' color appearing white against the redder background. Ganymede's surface is known to contain large amounts of surface ice and it appears that these relatively young craters have spread bright fresh ice materials over the surface. Likewise, the lighter color and reflectivity of the grooved areas suggests that here, too, there is cleaner ice. We see ray craters with all sizes of ray patterns, ranging from extensive systems of the crater in the southern part of this picture, which has rays at least 300-500 kilometers long, down to craters which have only faint remnants of bright ejects patterns (such as several of the craters in the southern half of PIA01516; P21262). This variation suggests that, as on the Moon, there are processes which act to darken ray material, probably 'gardening' by micrometeoroid impact. JPL manages and controls the Voyager project for NASA's Office of Space Science.

  9. Search for bright stars with infrared excess

    SciTech Connect

    Raharto, Moedji

    2014-03-24

    Bright stars, stars with visual magnitude smaller than 6.5, can be studied using small telescope. In general, if stars are assumed as black body radiator, then the color in infrared (IR) region is usually equal to zero. Infrared data from IRAS observations at 12 and 25μm (micron) with good flux quality are used to search for bright stars (from Bright Stars Catalogues) with infrared excess. In magnitude scale, stars with IR excess is defined as stars with IR color m{sub 12}−m{sub 25}>0; where m{sub 12}−m{sub 25} = −2.5log(F{sub 12}/F{sub 25})+1.56, where F{sub 12} and F{sub 25} are flux density in Jansky at 12 and 25μm, respectively. Stars with similar spectral type are expected to have similar color. The existence of infrared excess in the same spectral type indicates the existence of circum-stellar dust, the origin of which is probably due to the remnant of pre main-sequence evolution during star formation or post AGB evolution or due to physical process such as the rotation of those stars.

  10. Dark and Bright Terrains of Pluto

    NASA Image and Video Library

    2015-07-10

    These circular maps shows the distribution of Pluto's dark and bright terrains as revealed by NASA's New Horizons mission prior to July 4, 2015. Each map is an azimuthal equidistant projection centered on the north pole, with latitude and longitude indicated. Both a gray-scale and color version are shown. The gray-scale version is based on 7 days of panchromatic imaging from the Long Range Reconnaissance Imager (LORRI), whereas the color version uses the gray-scale base and incorporates lower-resolution color information from the Multi-spectral Visible Imaging Camera (MVIC), part of the Ralph instrument. The color version is also shown in a simple cylindrical projection in PIA19700. In these maps, the polar bright terrain is surrounded by a somewhat darker polar fringe, one whose latitudinal position varies strongly with longitude. Especially striking are the much darker regions along the equator. A broad dark swath ("the whale") stretches along the equator from approximately 20 to 160 degrees of longitude. Several dark patches appear in a regular sequence centered near 345 degrees of longitude. A spectacular bright region occupies Pluto's mid-latitudes near 180 degrees of longitude, and stretches southward over the equator. New Horizons' closest approach to Pluto will occur near this longitude, which will permit high-resolution visible imaging and compositional mapping of these various regions. http://photojournal.jpl.nasa.gov/catalog/PIA19706

  11. Bright and Dark Slopes on Ganymede

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Ridges on the edge of Ganymede's north polar cap show bright east-facing slopes and dark west-facing slopes with troughs of darker material below the larger ridges. North is to the top. The bright slopes may be due to grain size differences, differences in composition between the original surface and the underlying material, frost deposition, or illumination effects. The large 2.4 kilometer (1.5 mile) diameter crater in this image shows frost deposits located on the north-facing rim slope, away from the sun. A smaller 675 meter (2200 foot) diameter crater in the center of the image is surrounded by a bright deposit which may be ejecta from the impact. Ejecta deposits such as this are uncommon for small craters on Ganymede. This image measures 18 by 19 kilometers (11 by 12 miles) and has a resolution of 45 meters (148 feet) per pixel. NASA's Galileo spacecraft obtained this image on September 6, 1996 during its second orbit around Jupiter.

    The Jet Propulsion Laboratory, Pasadena, CA manages the Galileo mission for NASA's Office of Space Science, Washington, DC. JPL is an operating division of California Institute of Technology (Caltech).

    This image and other images and data received from Galileo are posted on the World Wide Web, on the Galileo mission home page at URL http://galileo.jpl.nasa.gov. Background information and educational context for the images can be found at URL http://www.jpl.nasa.gov/galileo/sepo

  12. Brightness Changes in Sun-like Stars

    NASA Technical Reports Server (NTRS)

    Henry, Stephen M.; Henry, Gregory W.

    1998-01-01

    Does the Sun's energy output vary with time? Are observable climatic changes on the earth caused by changes in the Sun? Can we gain greater insight into this relation-ship by studying other stars with properties similar to the Sun's? In recent years, satellite observations have shown that the solar irradiance varies in phase with the 1 l-year sunspot cycle. The Sun is brighter by about O.l% at the peak of the sunspot cycle when solar magnetic activity is at its maximum. Over longer intervals, changes in the cart h's climate and solar magnetic activity seem to be correlated. We are using automatic photoelectric telescopes to measure brightness changes in a sample of 150 Sun-like stars. Lowell Observatory astronomers have also observed about 30 of these same stars with a manual telescope in a program that began 10 years before ours. Since these two data sets were acquired with different instruments and so have significant systematic differences, we developed software to combine them accurately and, therefore, extend our observational time coverage. We show sample results of brightness variations over 14 years in several Sun-like stars with different ages. Longitudinal studies like these, combined with cross-sectional studies of the larger sample of stars, may eventually allow us to infer with confidence the Sun's long-term brightness history and its impact on the earth's climate.

  13. Bright and Dark Slopes on Ganymede

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Ridges on the edge of Ganymede's north polar cap show bright east-facing slopes and dark west-facing slopes with troughs of darker material below the larger ridges. North is to the top. The bright slopes may be due to grain size differences, differences in composition between the original surface and the underlying material, frost deposition, or illumination effects. The large 2.4 kilometer (1.5 mile) diameter crater in this image shows frost deposits located on the north-facing rim slope, away from the sun. A smaller 675 meter (2200 foot) diameter crater in the center of the image is surrounded by a bright deposit which may be ejecta from the impact. Ejecta deposits such as this are uncommon for small craters on Ganymede. This image measures 18 by 19 kilometers (11 by 12 miles) and has a resolution of 45 meters (148 feet) per pixel. NASA's Galileo spacecraft obtained this image on September 6, 1996 during its second orbit around Jupiter.

    The Jet Propulsion Laboratory, Pasadena, CA manages the Galileo mission for NASA's Office of Space Science, Washington, DC. JPL is an operating division of California Institute of Technology (Caltech).

    This image and other images and data received from Galileo are posted on the World Wide Web, on the Galileo mission home page at URL http://galileo.jpl.nasa.gov. Background information and educational context for the images can be found at URL http://www.jpl.nasa.gov/galileo/sepo

  14. Personal audio with a planar bright zone.

    PubMed

    Coleman, Philip; Jackson, Philip J B; Olik, Marek; Pedersen, Jan Abildgaard

    2014-10-01

    Reproduction of multiple sound zones, in which personal audio programs may be consumed without the need for headphones, is an active topic in acoustical signal processing. Many approaches to sound zone reproduction do not consider control of the bright zone phase, which may lead to self-cancellation problems if the loudspeakers surround the zones. Conversely, control of the phase in a least-squares sense comes at a cost of decreased level difference between the zones and frequency range of cancellation. Single-zone approaches have considered plane wave reproduction by focusing the sound energy in to a point in the wavenumber domain. In this article, a planar bright zone is reproduced via planarity control, which constrains the bright zone energy to impinge from a narrow range of angles via projection in to a spatial domain. Simulation results using a circular array surrounding two zones show the method to produce superior contrast to the least-squares approach, and superior planarity to the contrast maximization approach. Practical performance measurements obtained in an acoustically treated room verify the conclusions drawn under free-field conditions.

  15. Brightness illusion in the guppy (Poecilia reticulata).

    PubMed

    Agrillo, Christian; Miletto Petrazzini, Maria Elena; Bisazza, Angelo

    2016-02-01

    A long-standing debate surrounds the issue of whether human and nonhuman species share similar perceptual mechanisms. One experimental strategy to compare visual perception of vertebrates consists in assessing how animals react in the presence of visual illusions. To date, this methodological approach has been widely used with mammals and birds, while few studies have been reported in distantly related species, such as fish. In the present study we investigated whether fish perceive the brightness illusion, a well-known illusion occurring when 2 objects, identical in physical features, appear to be different in brightness. Twelve guppies (Poecilia reticulata) were initially trained to discriminate which rectangle was darker or lighter between 2 otherwise identical rectangles. Three different conditions were set up: neutral condition between rectangle and background (same background used for both darker and lighter rectangle); congruent condition (darker rectangle in a darker background and lighter rectangle in a lighter background); and incongruent condition (darker rectangle in a lighter background and lighter rectangle in a darker background). After reaching the learning criterion, guppies were presented with the illusory pattern: 2 identical rectangles inserted in 2 different backgrounds. Guppies previously trained to select the darker rectangle showed a significant choice of the rectangle that appears to be darker by human observers (and vice versa). The human-like performance exhibited in the presence of the illusory pattern suggests the existence of similar perceptual mechanisms between humans and fish to elaborate the brightness of objects.

  16. NS&T Management Observations - 3rd Quarter

    SciTech Connect

    Gianotto, David

    2014-07-01

    The INL Management Observation Program (MOP) is designed to improve managers and supervisors understanding of work being performed by employees and the barriers impacting their success. The MOP also increases workers understanding of managements’ expectations as they relate to safety, security, quality, and work performance. Management observations are designed to improve the relationship and trust between employees and managers through increased engagement and interactions between managers and researchers in the field. As part of continuous improvement, NS&T management took initiative to focus on the participation and quality of observations in FY 14. This quarterly report is intended to (a) summarize the participation and quality of management’s observations, (b) assess observations for commonalities or trends related to facility or process barriers impacting research, and (c) provide feedback and make recommendations for improvements NS&T’s MOP.

  17. NS&T Management Observations: Quarterly Performance Analysis

    SciTech Connect

    Gianotto, David

    2014-09-01

    The INL Management Observation Program (MOP) is designed to improve managers and supervisors understanding of work being performed by employees and the barriers impacting their success. The MOP also increases workers understanding of managements’ expectations as they relate to safety, security, quality, and work performance. Management observations (observations) are designed to improve the relationship and trust between employees and managers through increased engagement and interactions between managers and researchers in the field. As part of continuous improvement, NS&T management took initiative to focus on the participation and quality of observations in FY-14. This quarterly report is intended to (a) summarize the participation and quality of management’s observations, (b) assess observations for commonalities or trends related to facility or process barriers impacting research, and (c) provide feedback and make recommendations for improvements NS&T’s MOP.

  18. NS&T Managment Observations - 1st Quarter

    SciTech Connect

    David Gianotto

    2014-06-01

    The INL Management Observation Program (MOP) is designed to improve managers and supervisors understanding of work being performed by employees and the barriers impacting their success. The MOP also increases workers understanding of managements’ expectations as they relate to safety, security, quality, and work performance. Management observations (observations) are designed to improve the relationship and trust between employees and managers through increased engagement and interactions between managers and researchers in the field. As part of continuous improvement, NS&T management took initiative to focus on the participation and quality of observations in FY 14. This quarterly report is intended to (a) summarize the participation and quality of management’s observations, (b) assess observations for commonalities or trends related to facility or process barriers impacting research, and (c) provide feedback and make recommendations for improvements NS&T’s MOP.

  19. Process Performances of 2 ns Pulsed Discharge Plasma

    NASA Astrophysics Data System (ADS)

    Matsumoto, Takao; Wang, Douyan; Namihira, Takao; Akiyama, Hidenori

    2011-08-01

    Pulsed discharge plasmas have been used to treat exhaust gases. Since pulse duration and the rise time of applied voltage to the discharge electrode has a strong influence on the energy efficiency of pollutant removal, the development of a short-pulse generator is of paramount importance for practical applications. In this work, it is demonstrated that the non thermal plasma produced by the 2 ns pulsed discharge has a higher energy efficiency than the 5 ns pulsed discharge plasma for NO removal and ozone generation. Typically, the NO removal efficiency was 1.0 mol kW-1 h-1 for 70% NO removal (initial NO concentration = 200 ppm, gas flow = 10 L/min). Meanwhile, the ozone yield was 500 g kW-1 h-1 for 20 g/m3 ozone concentration in the case of oxygen feeding. These energy efficiencies are the highest in the literature.

  20. Bright and Dark at West Rim of Marcia Crater

    NASA Image and Video Library

    2012-03-21

    The interplay of bright and dark material at the rim of Marcia crater on Vesta is visible in this image mosaic taken by NASA Dawn spacecraft. The bright and dark material appear to be exposed from weathering.

  1. Apparent Brightness and Topography Images of Calpurnia and Minucia

    NASA Image and Video Library

    2012-03-13

    Located in the Marcia quadrangle, the left-hand image from NASA Dawn spacecraft shows the apparent brightness of asteroid Vesta surface. The right-hand image is based on this apparent brightness image.

  2. Discovery of an irreversible HCV NS5B polymerase inhibitor.

    PubMed

    Zeng, Qingbei; Nair, Anilkumar G; Rosenblum, Stuart B; Huang, Hsueh-Cheng; Lesburg, Charles A; Jiang, Yueheng; Selyutin, Oleg; Chan, Tin-Yau; Bennett, Frank; Chen, Kevin X; Venkatraman, Srikanth; Sannigrahi, Mousumi; Velazquez, Francisco; Duca, Jose S; Gavalas, Stephen; Huang, Yuhua; Pu, Haiyan; Wang, Li; Pinto, Patrick; Vibulbhan, Bancha; Agrawal, Sony; Ferrari, Eric; Jiang, Chuan-kui; Li, Cheng; Hesk, David; Gesell, Jennifer; Sorota, Steve; Shih, Neng-Yang; Njoroge, F George; Kozlowski, Joseph A

    2013-12-15

    The discovery of lead compound 2e was described. Its covalent binding to HCV NS5B polymerase enzyme was investigated by X-ray analysis. The results of distribution, metabolism and pharmacokinetics were reported. Compound 2e was demonstrated to be potent (replicon GT-1b EC50 = 0.003 μM), highly selective, and safe in in vitro and in vivo assays.

  3. Membrane Interacting Regions of Dengue Virus NS2A Protein

    PubMed Central

    2015-01-01

    The Dengue virus (DENV) NS2A protein, essential for viral replication, is a poorly characterized membrane protein. NS2A displays both protein/protein and membrane/protein interactions, yet neither its functions in the viral cycle nor its active regions are known with certainty. To highlight the different membrane-active regions of NS2A, we characterized the effects of peptides derived from a peptide library encompassing this protein’s full length on different membranes by measuring their membrane leakage induction and modulation of lipid phase behavior. Following this initial screening, one region, peptide dens25, had interesting effects on membranes; therefore, we sought to thoroughly characterize this region’s interaction with membranes. This peptide presents an interfacial/hydrophobic pattern characteristic of a membrane-proximal segment. We show that dens25 strongly interacts with membranes that contain a large proportion of lipid molecules with a formal negative charge, and that this effect has a major electrostatic contribution. Considering its membrane modulating capabilities, this region might be involved in membrane rearrangements and thus be important for the viral cycle. PMID:25119664

  4. Coupling translocation with nucleic acid unwinding by NS3 helicase.

    PubMed

    Yu, Jin; Cheng, Wei; Bustamante, Carlos; Oster, George

    2010-12-03

    We present a semiquantitative model for translocation and unwinding activities of monomeric nonstructural protein 3 (NS3) helicase. The model is based on structural, biochemical, and single-molecule measurements. The model predicts that the NS3 helicase actively unwinds duplex by reducing more than 50% the free energy that stabilizes base pairing/stacking. The unwinding activity slows the movement of the helicase in a sequence-dependent manner, lowering the average unwinding efficiency to less than 1 bp per ATP cycle. When bound with ATP, the NS3 helicase can display significant translocational diffusion. This increases displacement fluctuations of the helicase, decreases the average unwinding efficiency, and enhances the sequence dependence. Also, interactions between the helicase and the duplex stabilize the helicase at the junction, facilitating the helicase's unwinding activity while preventing it from dissociating. In the presence of translocational diffusion during active unwinding, the dissociation rate of the helicase also exhibits sequence dependence. Based on unwinding velocity fluctuations measured from single-molecule experiments, we estimate the diffusion rate to be on the order of 10 s(-1). The generic features of coupling single-stranded nucleic acid translocation with duplex unwinding presented in this work may apply generally to a class of helicases.

  5. Active Processes: Bright Streaks and Dark Fans

    NASA Technical Reports Server (NTRS)

    2007-01-01

    [figure removed for brevity, see original site] [figure removed for brevity, see original site] Figure 1Figure 2

    In a region of the south pole known informally as 'Ithaca' numerous fans of dark frost form every spring. HiRISE collected a time lapse series of these images, starting at Ls = 185 and culminating at Ls = 294. 'Ls' is the way we measure time on Mars: at Ls = 180 the sun passes the equator on its way south; at Ls = 270 it reaches its maximum subsolar latitude and summer begins.

    In the earliest image (figure 1) fans are dark, but small narrow bright streaks can be detected. In the next image (figure 2), acquired at Ls = 187, just 106 hours later, dramatic differences are apparent. The dark fans are larger and the bright fans are more pronounced and easily detectable. The third image in the sequence shows no bright fans at all.

    We believe that the bright streaks are fine frost condensed from the gas exiting the vent. The conditions must be just right for the bright frost to condense.

    Observation Geometry Image PSP_002622_0945 was taken by the High Resolution Imaging Science Experiment (HiRISE) camera onboard the Mars Reconnaissance Orbiter spacecraft on 16-Feb-2007. The complete image is centered at -85.2 degrees latitude, 181.5 degrees East longitude. The range to the target site was 246.9 km (154.3 miles). At this distance the image scale is 49.4 cm/pixel (with 2 x 2 binning) so objects 148 cm across are resolved. The image shown here has been map-projected to 50 cm/pixel . The image was taken at a local Mars time of 05:46 PM and the scene is illuminated from the west with a solar incidence angle of 88 degrees, thus the sun was about 2 degrees above the horizon. At a solar longitude of 185.1 degrees, the season on Mars is Northern Autumn.

  6. Active Processes: Bright Streaks and Dark Fans

    NASA Technical Reports Server (NTRS)

    2007-01-01

    [figure removed for brevity, see original site] [figure removed for brevity, see original site] Figure 1Figure 2

    In a region of the south pole known informally as 'Ithaca' numerous fans of dark frost form every spring. HiRISE collected a time lapse series of these images, starting at Ls = 185 and culminating at Ls = 294. 'Ls' is the way we measure time on Mars: at Ls = 180 the sun passes the equator on its way south; at Ls = 270 it reaches its maximum subsolar latitude and summer begins.

    In the earliest image (figure 1) fans are dark, but small narrow bright streaks can be detected. In the next image (figure 2), acquired at Ls = 187, just 106 hours later, dramatic differences are apparent. The dark fans are larger and the bright fans are more pronounced and easily detectable. The third image in the sequence shows no bright fans at all.

    We believe that the bright streaks are fine frost condensed from the gas exiting the vent. The conditions must be just right for the bright frost to condense.

    Observation Geometry Image PSP_002622_0945 was taken by the High Resolution Imaging Science Experiment (HiRISE) camera onboard the Mars Reconnaissance Orbiter spacecraft on 16-Feb-2007. The complete image is centered at -85.2 degrees latitude, 181.5 degrees East longitude. The range to the target site was 246.9 km (154.3 miles). At this distance the image scale is 49.4 cm/pixel (with 2 x 2 binning) so objects 148 cm across are resolved. The image shown here has been map-projected to 50 cm/pixel . The image was taken at a local Mars time of 05:46 PM and the scene is illuminated from the west with a solar incidence angle of 88 degrees, thus the sun was about 2 degrees above the horizon. At a solar longitude of 185.1 degrees, the season on Mars is Northern Autumn.

  7. 7 CFR 51.2000 - Clean and bright.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 2 2013-01-01 2013-01-01 false Clean and bright. 51.2000 Section 51.2000 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing....2000 Clean and bright. Clean and bright means that the individual filbert and the lot as a whole...

  8. 7 CFR 51.2000 - Clean and bright.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 2 2014-01-01 2014-01-01 false Clean and bright. 51.2000 Section 51.2000 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing....2000 Clean and bright. Clean and bright means that the individual filbert and the lot as a whole...

  9. Two types of coronal bright points their characteristics, and evolution

    NASA Astrophysics Data System (ADS)

    Sattarov, Isroil; Karachik, Nina V.; Sherdanov, Chori T.; Tillaboev, Azlarxon M.; Pevtsov, Alexei A.

    2011-08-01

    Using maximum brightness of coronal bright point's (CBP) as a criterion, we separate them on two categories: dim CBPs, associated with areas of a quiet Sun, and bright CBPs, associated with an active Sun. This study reports on characteristics of two types of CBPs and their evolution.

  10. Discovery of Dengue Virus NS4B Inhibitors

    PubMed Central

    Wang, Qing-Yin; Dong, Hongping; Zou, Bin; Karuna, Ratna; Wan, Kah Fei; Zou, Jing; Susila, Agatha; Yip, Andy; Shan, Chao; Yeo, Kim Long; Xu, Haoying; Ding, Mei; Chan, Wai Ling; Gu, Feng; Seah, Peck Gee; Liu, Wei; Lakshminarayana, Suresh B.; Kang, CongBao; Lescar, Julien; Blasco, Francesca; Smith, Paul W.

    2015-01-01

    ABSTRACT The four serotypes of dengue virus (DENV-1 to -4) represent the most prevalent mosquito-borne viral pathogens in humans. No clinically approved vaccine or antiviral is currently available for DENV. Here we report a spiropyrazolopyridone compound that potently inhibits DENV both in vitro and in vivo. The inhibitor was identified through screening of a 1.8-million-compound library by using a DENV-2 replicon assay. The compound selectively inhibits DENV-2 and -3 (50% effective concentration [EC50], 10 to 80 nM) but not DENV-1 and -4 (EC50, >20 μM). Resistance analysis showed that a mutation at amino acid 63 of DENV-2 NS4B (a nonenzymatic transmembrane protein and a component of the viral replication complex) could confer resistance to compound inhibition. Genetic studies demonstrate that variations at amino acid 63 of viral NS4B are responsible for the selective inhibition of DENV-2 and -3. Medicinal chemistry improved the physicochemical properties of the initial “hit” (compound 1), leading to compound 14a, which has good in vivo pharmacokinetics. Treatment of DENV-2-infected AG129 mice with compound 14a suppressed viremia, even when the treatment started after viral infection. The results have proven the concept that inhibitors of NS4B could potentially be developed for clinical treatment of DENV infection. Compound 14a represents a potential preclinical candidate for treatment of DENV-2- and -3-infected patients. IMPORTANCE Dengue virus (DENV) threatens up to 2.5 billion people and is now spreading in many regions in the world where it was not previously endemic. While there are several promising vaccine candidates in clinical trials, approved vaccines or antivirals are not yet available. Here we describe the identification and characterization of a spiropyrazolopyridone as a novel inhibitor of DENV by targeting the viral NS4B protein. The compound potently inhibits two of the four serotypes of DENV (DENV-2 and -3) both in vitro and in vivo. Our

  11. Detection of dengue NS1 and NS3 proteins in placenta and umbilical cord in fetal and maternal death.

    PubMed

    Nunes, Priscila Conrado Guerra; Paes, Marciano Viana; de Oliveira, Carlos Alberto Basilio; Soares, Ana Carla Gomes; de Filippis, Ana Maria Bispo; Lima, Monique da Rocha Queiroz; de Barcelos Alves, Ada Maria; da Silva, Juliana Fernandes Amorim; de Oliveira Coelho, Janice Mery Chicarino; de Carvalho Rodrigues, Francisco das Chagas; Nogueira, Rita Maria Ribeiro; Dos Santos, Flávia Barreto

    2016-08-01

    In Brazil, dengue is a public health problem with the occurrence of explosive epidemics. This study reports maternal and fetal deaths due to dengue and which tissues of placenta and umbilical cord were analyzed by molecular methods and immunohistochemistry. The dengue NS3 and NS1 detection revealed the viral presence in different cells from placenta and umbilical cord. In the latter, DENV-2 was detected at a viral titer of 1,02 × 10(4) amounts of viral RNA. It was shown that the DENV markers analyzed here may be an alternative approach for dengue fatal cases investigation, especially involving maternal and fetal death. J. Med. Virol. 88:1448-1452, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  12. Miniature bovine pancreatic trypsin inhibitors (m-BPTIs) of the West Nile virus NS2B-NS3 protease.

    PubMed

    Ang, Melgious J Y; Lim, Huichang A; Poulsen, Anders; Wee, John Liang Kuan; Ng, Fui Mee; Joy, Joma; Hill, Jeffrey; Chia, C S Brian

    2016-01-01

    The mosquito-borne West Nile virus (WNV) causes a wide range of symptoms ranging from fever to the often fatal viral encephalitis. To date, no vaccine or drug therapy is available. The trypsin-like WNV NS2B-NS3 protease is deemed a plausible drug target and was shown to be inhibited by bovine pancreatic trypsin inhibitor (BPTI), a 58-residue protein isolated from bovine lung. Herein, we report a protein truncation study that resulted in a novel 14-residue cyclic peptide with equipotent inhibitory activity to native BPTI. We believe our truncation strategy can be further applied in the development of peptide-based inhibitors targeting trypsin-like proteases.

  13. Identification and analysis of truncated and elongated species of the flavivirus NS1 protein.

    PubMed

    Blitvich, B J; Scanlon, D; Shiell, B J; Mackenzie, J S; Hall, R A

    1999-03-01

    The flavivirus non-structural glycoprotein NS1 is often detected in Western blots as a heterogeneous cluster of bands due to glycosylation variations, precursor-product relationships and/or alternative cleavage sites in the viral polyprotein. In this study, we determined the basis of structural heterogeneity of the NS1 protein of Murray Valley encephalitis virus (MVE) by glycosylation analysis, pulse-chase experiments and terminal amino acid sequencing. Inhibition of N-linked glycosylation by tunicamycin revealed that NS1 synthesised in MVE-infected C6/36 cells was derived from two polypeptide backbones of 39 kDa (NS1(o)) and 47 kDa (NS1'). Pulse-chase experiments established that no precursor-product relationship existed between NS1(o) and NS1' and that both were stable end products. Terminal sequencing revealed that the N- and C-termini of NS1(o) were located at amino acid positions 714 and 1145 in the polyprotein respectively, consistent with the predicted sites based upon sequence homology with other flaviviruses. Expression of the NS1 gene alone or in conjunction with NS2A by recombinant baculoviruses demonstrated that the production of NS1' was dependent on the presence of NS2A, indicating that the C-terminus of the larger protein was generated within NS2A. A smaller form (31 kDa) of NS1 (deltaNS1) was also identified in MVE-infected Vero cultures, and amino acid sequencing revealed a 120-residue truncation at the N-terminus of this protein. This corresponds closely with the in-frame 121-codon deletion at the 5' end of the NS1 gene of defective MVE viral RNA (described by Lancaster et al. in 1998), suggesting that deltaNS1 may be a translation product of defective viral RNA.

  14. Conformer and pharmacophore based identification of peptidomimetic inhibitors of chikungunya virus nsP2 protease.

    PubMed

    Dhindwal, Sonali; Kesari, Pooja; Singh, Harvijay; Kumar, Pravindra; Tomar, Shailly

    2016-12-02

    Chikungunya virus nsP2 replication protein is a cysteine protease, which cleaves the nonstructural nsP1234 polyprotein into functional replication components. The cleavage and processing of nsP1234 by nsP2 protease is essential for the replication and proliferation of the virus. Thus, ChikV nsP2 protease is a promising target for antiviral drug discovery. In this study, the crystal structure of the C-terminal domain of ChikV nsP2 protease (PDB ID: 4ZTB) was used for structure based identification and rational designing of peptidomimetic inhibitors against nsP2 protease. The interactions of the junction residues of nsP3/4 polyprotein in the active site of nsP2 protease have been mimicked to identify and design potential inhibitory molecules. Molecular docking of the nsP3/4 junction peptide in the active site of ChikV nsP2 protease provided the structural insight of the probable binding mode of nsP3/4 peptide and pigeonholed the molecular interactions critical for the substrate binding. Further, the shape and pharmacophoric properties of the viral nsP3/4 substrate peptide were taken into consideration and the mimetic molecules were identified and designed. The designed mimetic compounds were then analyzed by docking and their binding affinity was assessed by molecular dynamics simulations.

  15. Calculation of gyrosynchrotron radiation brightness temperature for outer bright loop of ICME

    NASA Astrophysics Data System (ADS)

    Sun, Weiying; Wu, Ji; Wang, C. B.; Wang, S.

    :Solar polar orbit radio telescope (SPORT) is proposed to detect the high density plasma clouds of outer bright loop of ICMEs from solar orbit with large inclination. Of particular interest is following the propagation of the plasma clouds with remote sensor in radio wavelength band. Gyrosynchrotron emission is a main radio radiation mechanism of the plasma clouds and can provide information of interplanetary magnetic field. In this paper, we statistically analyze the electron density, electron temperature and magnetic field of background solar wind in time of quiet sun and ICMEs propagation. We also estimate the fluctuation range of the electron density, electron temperature and magnetic field of outer bright loop of ICMEs. Moreover, we calculate and analyze the emission brightness temperature and degree of polarization on the basis of the study of gyrosynchrotron emission, absorption and polarization characteristics as the optical depth is less than or equal to 1.

  16. Dark and Bright Ridges on Europa

    NASA Technical Reports Server (NTRS)

    1998-01-01

    This high-resolution image of Jupiter's moon Europa, taken by NASA's Galileo spacecraft camera, shows dark, relatively smooth region at the lower right hand corner of the image which may be a place where warm ice has welled up from below. The region is approximately 30 square kilometers in area. An isolated bright hill stands within it. The image also shows two prominent ridges which have different characteristics; youngest ridge runs from left to top right and is about 5 kilometers in width (about 3.1 miles). The ridge has two bright, raised rims and a central valley. The rims of the ridge are rough in texture. The inner and outer walls show bright and dark debris streaming downslope, some of it forming broad fans. This ridge overlies and therefore must be younger than a second ridge running from top to bottom on the left side of the image. This dark 2 km wide ridge is relatively flat, and has smaller-scale ridges and troughs along its length.

    North is to the top of the picture, and the sun illuminates the surface from the upper left. This image, centered at approximately 14 degrees south latitude and 194 degrees west longitude, covers an area approximately 15 kilometers by 20 kilometers (9 miles by 12 miles). The resolution is 26 meters (85 feet) per picture element. This image was taken on December 16, 1997 at a range of 1300 kilometers (800 miles) by Galileo's solid state imaging system.

    The Jet Propulsion Laboratory, Pasadena, CA manages the Galileo mission for NASA's Office of Space Science, Washington, DC. JPL is an operating division of California Institute of Technology (Caltech).

    This image and other images and data received from Galileo are posted on the World Wide Web, on the Galileo mission home page at URL http://www.jpl.nasa.gov/ galileo.

  17. Dark and Bright Ridges on Europa

    NASA Technical Reports Server (NTRS)

    1998-01-01

    This high-resolution image of Jupiter's moon Europa, taken by NASA's Galileo spacecraft camera, shows dark, relatively smooth region at the lower right hand corner of the image which may be a place where warm ice has welled up from below. The region is approximately 30 square kilometers in area. An isolated bright hill stands within it. The image also shows two prominent ridges which have different characteristics; youngest ridge runs from left to top right and is about 5 kilometers in width (about 3.1 miles). The ridge has two bright, raised rims and a central valley. The rims of the ridge are rough in texture. The inner and outer walls show bright and dark debris streaming downslope, some of it forming broad fans. This ridge overlies and therefore must be younger than a second ridge running from top to bottom on the left side of the image. This dark 2 km wide ridge is relatively flat, and has smaller-scale ridges and troughs along its length.

    North is to the top of the picture, and the sun illuminates the surface from the upper left. This image, centered at approximately 14 degrees south latitude and 194 degrees west longitude, covers an area approximately 15 kilometers by 20 kilometers (9 miles by 12 miles). The resolution is 26 meters (85 feet) per picture element. This image was taken on December 16, 1997 at a range of 1300 kilometers (800 miles) by Galileo's solid state imaging system.

    The Jet Propulsion Laboratory, Pasadena, CA manages the Galileo mission for NASA's Office of Space Science, Washington, DC. JPL is an operating division of California Institute of Technology (Caltech).

    This image and other images and data received from Galileo are posted on the World Wide Web, on the Galileo mission home page at URL http://www.jpl.nasa.gov/ galileo.

  18. Rotation and macroturbulence in bright giants

    SciTech Connect

    Gray, D.F.; Toner, C.G.

    1986-11-01

    Spectral line profiles of 35 F, G, and K bright giants were analyzed to obtain rotation rates, v sin i, and macroturbulence dispersion. This sample indicates that rotation rates of cool class II giants is less than 11 km/s, in contrast with some recent periodicity measurements. Macroturbulence dispersion generally increases with effective temperature, but the range of values at a given effective temperature is much larger than seen for lower luminosity classes; this is interpreted in terms of red-giant and blue-loop evolution. No evidence is found for angular momentum dissipation on the first crossing of the H-R diagram. 57 references.

  19. Raman beam combining for laser brightness enhancement

    DOEpatents

    Dawson, Jay W.; Allen, Graham S.; Pax, Paul H.; Heebner, John E.; Sridharan, Arun K.; Rubenchik, Alexander M.; Barty, Chrisopher B. J.

    2015-10-27

    An optical source capable of enhanced scaling of pulse energy and brightness utilizes an ensemble of single-aperture fiber lasers as pump sources, with each such fiber laser operating at acceptable pulse energy levels. Beam combining involves stimulated Raman scattering using a Stokes' shifted seed beam, the latter of which is optimized in terms of its temporal and spectral properties. Beams from fiber lasers can thus be combined to attain pulses with peak energies in excess of the fiber laser self-focusing limit of 4 MW while retaining the advantages of a fiber laser system of high average power with good beam quality.

  20. Two-color bright squeezed vacuum

    SciTech Connect

    Agafonov, Ivan N.; Chekhova, Maria V.

    2010-07-15

    In a strongly pumped nondegenerate traveling-wave optical parametric amplifier, we produce a two-color squeezed vacuum with up to millions of photons per pulse. Our approach to registering this macroscopic quantum state is direct detection of a large number of transverse and longitudinal modes, which is achieved by making the detection time and area much larger than the coherence time and area, respectively. Using this approach, we obtain a record value of twin-beam squeezing for direct detection of bright squeezed vacuum. This makes direct detection of macroscopic squeezed vacuum a practical tool for quantum information applications.

  1. Apparent brightness distribution of GRB host galaxies

    NASA Astrophysics Data System (ADS)

    Bagoly, Zsolt; Rácz, István I.; Balázs, Lajos G.; Horváth, István; Tóth, L. Viktor

    We studied the unbiased optical brightness distribution which was calculated from the survival analysis of host galaxies (HGs) data and its relationship with the Swift GRB data of the host galaxies observed by the Keck telescope. Based on the sample obtained from merging the Swift GRB table and the Keck optical data we also studied the dependence of this distribution on the GRB's data. Finally, we compared the HGs distribution with standard galaxies distribution of the DEEP2 redshift survey and checked the result with the VIPERS catalogue too.

  2. Mutagenesis of Dengue Virus Protein NS2A Revealed a Novel Domain Responsible for Virus-Induced Cytopathic Effect and Interactions Between NS2A and NS2B Transmembrane Segments.

    PubMed

    Wu, Ren-Huang; Tsai, Ming-Han; Tsai, Kuen-Nan; Tian, Jia Ni; Wu, Jian-Sung; Wu, Su-Ying; Chern, Jyh-Haur; Chen, Chun-Hong; Yueh, Andrew

    2017-04-05

    The NS2A protein of Dengue virus (DENV) has eight predicted transmembrane segments (pTMS1-8) and participates in RNA replication, virion assembly, and host antiviral response. However, the roles of specific amino acid residues within the pTMS regions of NS2A during the viral life cycle are not clear. Here, we explored the function of DENV NS2A by introducing a series of alanine substitutions into the N-terminal half (pTMS1-4) of the protein in the context of a DENV infectious clone or subgenomic replicon. Six NS2A mutants (NM5, 7, 9, and 17-19) around pTMS1-2 displayed a novel phenotype showing a >1000-fold reduction in virus yield, an absence of plaque formation despite wild-type-like replicon activity, and infectious virus-like particle yields. The HEK293 cells infected with those six NS2A mutant viruses failed to cause a virus-induced cytopathic effect (CPE) by MitoCapture staining, cell proliferation, and lactate dehydrogenase release assays. Sequencing analyses of pseudorevertant viruses derived from lethal mutant viruses revealed two consensus reversion mutations, leucine-to-phenylalanine at codon 181 (L181F) within the pTMS7 of NS2A and isoleucine-to-threonine at codon 114 (I114T) within NS2B. The introduction of NS2A-L181F mutation into the lethal (NM15, 16, 25, and 33) and CPE-defective (NM7, 9, and 19) mutants substantially rescued virus infectivity and virus-induced CPE, respectively, whereas NS2B-L114T mutation rescued NM16, 25, and 33 mutants. In conclusion, the results revealed the essential roles of the N-terminal half of NS2A in RNA replication and virus-induced CPE. Intramolecular interactions between pTMSs of NS2A and intermolecular interactions between NS2A and NS2B protein were also implicated.Importance: The characterization of the N-terminal (current study) and C-terminal half of DENV NS2A is the most comprehensive mutagenesis study to date to investigate the function of NS2A during the flaviviral life cycle. A novel region responsible for

  3. The NS3 and NS4A genes as the targets of RNA interference inhibit replication of Japanese encephalitis virus in vitro and in vivo.

    PubMed

    Yuan, Lei; Wu, Rui; Liu, Hanyang; Wen, Xintian; Huang, Xiaobo; Wen, Yiping; Ma, Xiaoping; Yan, Qigui; Huang, Yong; Zhao, Qin; Cao, Sanjie

    2016-12-15

    Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that can cause acute encephalitis with a high fatality rate. RNA interference (RNAi) is a powerful tool to silence gene expression and a potential therapy for virus infection. In this study, the antiviral ability of eight shRNA expression plasmids targeting different sites of the NS3 and NS4A genes of JEV was determined in BHK21 cells and mice. The pGP-NS3-3 and pGP-NS4A-4 suppressed 93.9% and 82.0% of JEV mRNA in cells, respectively. The virus titer in cells was reduced approximately 950-fold by pretreating with pGP-NS3-4, and 640-fold by pretreating with pGP-NS4A-4. The results of western blot and immunofluorescence analysis showed JEV E protein and viral load in cells were remarkably inhibited by shRNA expression plasmids. The viral load in brains of mice pretreated with pGP-NS3-4 or pGP-NS4A-4 were reduced approximately 2400-fold and 800-fold, respectively, and the survival rate of mice challenged with JEV were 70% and 50%, respectively. However, the antiviral ability of shRNA expression plasmids was decreased over time. This study indicates that RNAi targeting of the NS3 and NS4A genes of JEV can sufficiently inhibit the replication of JEV in vitro and in vivo, and NS3 and NS4A genes might be potential targets of molecular therapy for JEV infection.

  4. Human Bocavirus NS1 and NS1-70 Proteins Inhibit TNF-α-Mediated Activation of NF-κB by targeting p65

    PubMed Central

    Liu, Qingshi; Zhang, Zhenfeng; Zheng, Zhenhua; Zheng, Caishang; Liu, Yan; Hu, Qinxue; Ke, Xianliang; Wang, Hanzhong

    2016-01-01

    Human bocavirus (HBoV), a parvovirus, is a single-stranded DNA etiologic agent causing lower respiratory tract infections in young children worldwide. Nuclear factor kappa B (NF-κB) transcription factors play crucial roles in clearance of invading viruses through activation of many physiological processes. Previous investigation showed that HBoV infection could significantly upregulate the level of TNF-α which is a strong NF-κB stimulator. Here we investigated whether HBoV proteins modulate TNF-α–mediated activation of the NF-κB signaling pathway. We showed that HBoV NS1 and NS1-70 proteins blocked NF-κB activation in response to TNF-α. Overexpression of TNF receptor-associated factor 2 (TRAF2)-, IκB kinase alpha (IKKα)-, IκB kinase beta (IKKβ)-, constitutively active mutant of IKKβ (IKKβ SS/EE)-, or p65-induced NF-κB activation was inhibited by NS1 and NS1-70. Furthermore, NS1 and NS1-70 didn’t interfere with TNF-α-mediated IκBα phosphorylation and degradation, nor p65 nuclear translocation. Coimmunoprecipitation assays confirmed the interaction of both NS1 and NS1-70 with p65. Of note, NS1 but not NS1-70 inhibited TNF-α-mediated p65 phosphorylation at ser536. Our findings together indicate that HBoV NS1 and NS1-70 inhibit NF-κB activation. This is the first time that HBoV has been shown to inhibit NF-κB activation, revealing a potential immune-evasion mechanism that is likely important for HBoV pathogenesis. PMID:27329558

  5. Rab5 Enhances Classical Swine Fever Virus Proliferation and Interacts with Viral NS4B Protein to Facilitate Formation of NS4B Related Complex.

    PubMed

    Lin, Jihui; Wang, Chengbao; Zhang, Longxiang; Wang, Tao; Zhang, Jing; Liang, Wulong; Li, Cheng; Qian, Gui; Ouyang, Yueling; Guo, Kangkang; Zhang, Yanming

    2017-01-01

    Classical swine fever virus (CSFV) is a fatal pig pestivirus and causes serious financial losses to the pig industry. CSFV NS4B protein is one of the most important viral replicase proteins. Rab5, a member of the small Rab GTPase family, is involved in infection and replication of numerous viruses including hepatitis C virus and dengue virus. Until now, the effects of Rab5 on the proliferation of CSFV are poorly defined. In the present study, we showed that Rab5 could enhance CSFV proliferation by utilizing lentivirus-mediated constitutive overexpression and eukaryotic plasmid transient overexpression approaches. On the other hand, lentivirus-mediated short hairpin RNA knockdown of Rab5 dramatically inhibited virus production. Co-immunoprecipitation, glutathione S-transferase pulldown and laser confocal microscopy assays further confirmed the interaction between Rab5 and CSFV NS4B protein. In addition, intracellular distribution of NS4B-Red presented many granular fluorescent signals (GFS) in CSFV infected PK-15 cells. Inhibition of basal Rab5 function with Rab5 dominant negative mutant Rab5S34N resulted in disruption of the GFS. These results indicate that Rab5 plays a critical role in facilitating the formation of the NS4B related complexes. Furthermore, it was observed that NS4B co-localized with viral NS3 and NS5A proteins in the cytoplasm, suggesting that NS3 and NS5A might be components of the NS4B related complex. Taken together, these results demonstrate that Rab5 positively modulates CSFV propagation and interacts with NS4B protein to facilitate the NS4B related complexes formation.

  6. Rab5 Enhances Classical Swine Fever Virus Proliferation and Interacts with Viral NS4B Protein to Facilitate Formation of NS4B Related Complex

    PubMed Central

    Lin, Jihui; Wang, Chengbao; Zhang, Longxiang; Wang, Tao; Zhang, Jing; Liang, Wulong; Li, Cheng; Qian, Gui; Ouyang, Yueling; Guo, Kangkang; Zhang, Yanming

    2017-01-01

    Classical swine fever virus (CSFV) is a fatal pig pestivirus and causes serious financial losses to the pig industry. CSFV NS4B protein is one of the most important viral replicase proteins. Rab5, a member of the small Rab GTPase family, is involved in infection and replication of numerous viruses including hepatitis C virus and dengue virus. Until now, the effects of Rab5 on the proliferation of CSFV are poorly defined. In the present study, we showed that Rab5 could enhance CSFV proliferation by utilizing lentivirus-mediated constitutive overexpression and eukaryotic plasmid transient overexpression approaches. On the other hand, lentivirus-mediated short hairpin RNA knockdown of Rab5 dramatically inhibited virus production. Co-immunoprecipitation, glutathione S-transferase pulldown and laser confocal microscopy assays further confirmed the interaction between Rab5 and CSFV NS4B protein. In addition, intracellular distribution of NS4B-Red presented many granular fluorescent signals (GFS) in CSFV infected PK-15 cells. Inhibition of basal Rab5 function with Rab5 dominant negative mutant Rab5S34N resulted in disruption of the GFS. These results indicate that Rab5 plays a critical role in facilitating the formation of the NS4B related complexes. Furthermore, it was observed that NS4B co-localized with viral NS3 and NS5A proteins in the cytoplasm, suggesting that NS3 and NS5A might be components of the NS4B related complex. Taken together, these results demonstrate that Rab5 positively modulates CSFV propagation and interacts with NS4B protein to facilitate the NS4B related complexes formation. PMID:28848503

  7. Full length and protease domain activity of chikungunya virus nsP2 differ from other alphavirus nsP2 proteases in recognition of small peptide substrates

    PubMed Central

    Saisawang, Chonticha; Sillapee, Pornpan; Sinsirimongkol, Kwanhathai; Ubol, Sukathida; Smith, Duncan R.; Ketterman, Albert J.

    2015-01-01

    Alphavirus nsP2 proteins are multifunctional and essential for viral replication. The protease role of nsP2 is critical for virus replication as only the virus protease activity is used for processing of the viral non-structural polypeptide. Chikungunya virus is an emerging disease problem that is becoming a world-wide health issue. We have generated purified recombinant chikungunya virus nsP2 proteins, both full length and a truncated protease domain from the C-terminus of the nsP2 protein. Enzyme characterization shows that the protease domain alone has different properties compared with the full length nsP2 protease. We also show chikungunya nsP2 protease possesses different substrate specificity to the canonical alphavirus nsP2 polyprotein cleavage specificity. Moreover, the chikungunya nsP2 also appears to differ from other alphavirus nsP2 in its distinctive ability to recognize small peptide substrates. PMID:26182358

  8. Full length and protease domain activity of chikungunya virus nsP2 differ from other alphavirus nsP2 proteases in recognition of small peptide substrates.

    PubMed

    Saisawang, Chonticha; Sillapee, Pornpan; Sinsirimongkol, Kwanhathai; Ubol, Sukathida; Smith, Duncan R; Ketterman, Albert J

    2015-04-22

    Alphavirus nsP2 proteins are multifunctional and essential for viral replication. The protease role of nsP2 is critical for virus replication as only the virus protease activity is used for processing of the viral non-structural polypeptide. Chikungunya virus is an emerging disease problem that is becoming a world-wide health issue. We have generated purified recombinant chikungunya virus nsP2 proteins, both full length and a truncated protease domain from the C-terminus of the nsP2 protein. Enzyme characterization shows that the protease domain alone has different properties compared with the full length nsP2 protease. We also show chikungunya nsP2 protease possesses different substrate specificity to the canonical alphavirus nsP2 polyprotein cleavage specificity. Moreover, the chikungunya nsP2 also appears to differ from other alphavirus nsP2 in its distinctive ability to recognize small peptide substrates.

  9. 16th International Conference on Nuclear Structure: NS2016

    DOE PAGES

    Galindo-Uribarri, Alfredo

    2016-10-28

    Every two years the Nuclear Structure (NS) conference series brings together researchers from an international community of experimental and theoretical nuclear physicists to present and discuss their latest results in nuclear structure. This biennial conference covered the latest results on experimental and theoretical research into the structure of nuclei at the extremes of isospin, excitation energy, mass, and angular momentum. Topics included many of the most exciting areas of modern nuclear structure research such as transitional behavior, nuclear structure and its evolution across the nuclear landscape, shell structure, collectivity, nuclear structure with radioactive beams, and macroscopic and microscopic approaches tomore » nuclear structure.« less

  10. 16th International Conference on Nuclear Structure: NS2016

    SciTech Connect

    Galindo-Uribarri, Alfredo

    2016-10-28

    Every two years the Nuclear Structure (NS) conference series brings together researchers from an international community of experimental and theoretical nuclear physicists to present and discuss their latest results in nuclear structure. This biennial conference covered the latest results on experimental and theoretical research into the structure of nuclei at the extremes of isospin, excitation energy, mass, and angular momentum. Topics included many of the most exciting areas of modern nuclear structure research such as transitional behavior, nuclear structure and its evolution across the nuclear landscape, shell structure, collectivity, nuclear structure with radioactive beams, and macroscopic and microscopic approaches to nuclear structure.

  11. Strong HCV NS3/4a, NS4b, NS5a, NS5b-specific cellular immune responses induced in Rhesus macaques by a novel HCV genotype 1a/1b consensus DNA vaccine.

    PubMed

    Latimer, Brian; Toporovski, Roberta; Yan, Jian; Pankhong, Panyupa; Morrow, Matthew P; Khan, Amir S; Sardesai, Niranjan Y; Welles, Seth L; Jacobson, Jeffrey M; Weiner, David B; Kutzler, Michele A

    2014-01-01

    Chronic HCV is a surreptitious disease currently affecting approximately 3% of the world's population that can lead to liver failure and cancer decades following initial infection. However, there are currently no vaccines available for the prevention of chronic HCV. From patients who acutely resolve HCV infection, it is apparent that a strong and broad cytotoxic T lymphocyte (CTL) response is important in HCV clearance. DNA vaccines are naked plasmid DNA molecules that encode pathogen antigens to induce a pathogen-specific immune response. They are inexpensive to produce and have an excellent safety profile in animals and humans. Additionally, DNA vaccines are able to induce strong CTL responses, making them well-suited for an HCV vaccine. We aimed to maximize vaccine recipients' opportunity to induce a broad T cell response with a novel antigenic sequence, multi-antigen vaccine strategy. We have generated DNA plasmids encoding consensus sequences of HCV genotypes 1a and 1b non-structural proteins NS3/4a, NS4b, NS5a, and NS5b. Rhesus macaques were used to study the immunogenicity of these constructs. Four animals were immunized 3 times, 6 weeks apart, at a dose of 1.0mg per antigen construct, as an intramuscular injection followed by in vivo electroporation, which greatly increases DNA uptake by local cells. Immune responses were measured 2 weeks post-immunization regimen (PIR) in immunized rhesus macaques and showed a broad response to multiple HCV nonstructural antigens, with up to 4680 spot-forming units per million peripheral blood mononuclear cells (PBMCs) as measured by Interferon-γ ELISpot. In addition, multiparametric flow cytometry detected HCV-specific CD4+ and CD8+ T cell responses by intracellular cytokine staining and detected HCV-specific CD107a+/GrzB+ CD8+ T cells indicating an antigen specific cytolytic response 2 weeks PIR compared with baseline measurements. At the final study time point, 6 weeks PIR, HCV-specific CD45RA- memory-like T cells

  12. Bright, water-soluble CeF3 photo-, cathodo-, and X-ray luminescent nanoparticles

    NASA Astrophysics Data System (ADS)

    Clement, Sandhya; Deng, Wei; Drozdowicz-Tomsia, Krystyna; Liu, Deming; Zachreson, Cameron; Goldys, Ewa M.

    2015-01-01

    Bright, water-soluble CeF3 nanoparticles with small size and narrow size distribution have been synthesized using a simple co-precipitation method without any ligands. Size control of nanoparticles from 13 ± 2 to 9 ± 2 nm was achieved by varying the reaction time. Colloidal properties have been found to vary with pH and, independently, with dilution. The photoluminescence of the as-synthesized nanoparticles shows a highly photostable UV/Visible fluorescence band due to allowed 5d-4f transitions, also observed in the X-ray luminescence spectrum. This band is suitable for X-ray excitation of a range of photosensitizers. The photoluminescence quantum yield of nanoparticles was also determined to be 31 %. Using the measured fluorescence decay time of 25 ns, the radiative lifetime of Ce in CeF3 was found to be 80.6 ns. Both photoluminescence and cathodoluminescence emission are affected by the reaction time and measurement temperature. Electron-beam-induced defect annealing is also observed.

  13. Adaptive brightness transfer functions in echocardiography.

    PubMed

    Zwirn, Gil; Akselrod, Solange

    2005-05-01

    Despite the clear advantages of echocardiography as a diagnostic tool, its images tend to be noisy and unclear. This paper presents an innovative algorithm, called ABTF (adaptive brightness transfer function), designed to optimally adjust the gray-levels used in echocardiography. The algorithm is aimed at aiding in visual tissue classification and texture-based visual tissue tracking in echocardiographic images. The ABTF method is based on fitting the cine-loop's gray-level histogram to a sum of three Gaussian functions, each of which relates to a different region within the image, the left ventricular cavity, the relatively dark regions within the cardiac muscle and the bright regions within the cardiac muscle. The procedure's feasibility has been supported by a test-set, including 23 echocardiographic cine-loops from 10 different patients. The resulting image quality appears to be superior to that of the original images, tending to show better contrast and a higher dynamic range of gray-levels within the cardiac muscle. According to two expert cardiologists, who have blindly ranked the image quality of each cine-loop on a scale from 1 to 10, where 10 corresponds to the highest possible image quality, the mean score of the original cine-loops is 7.1 +/- 1.1, while the mean score of the cine-loops to which ABTF has been applied is 8.0 +/- 1.2.

  14. A high brightness field emission display

    SciTech Connect

    Palevsky, A.

    1996-12-31

    The military requirement for avionics display performance requires that displays be legible with 10,000 foot-candles (fc) bright light shining into the pilot`s eyes, or 10,000 fc shining directly on the display. The contrast ratio under these conditions must be at least 4.66:1. In addition, instant-on operation is sought for temperatures as low as {minus}54 C. Currently these specifications can barely be met by monochrome CRTs whose use is counter-indicated by other factors. No color display can achieve optimum performance in the areas mentioned, nor do any current contenders, primarily AMLCD`s, have any prospects of achieving full compliance. The FED being developed by Raytheon shows strong promise of being able to achieve the brightness and contrast ratios desired. The FED is also inherently able to provide instant-on functionality at any terrestrial temperature and does not require any heating at low temperatures. The technical objective of the Raytheon development program is to develop a high performance, full color, FED Panel that meets the performance and environmental operating condition requirements specified for military and other high performance display applications.

  15. At Bright Band Inside Victoria Crater

    NASA Technical Reports Server (NTRS)

    2007-01-01

    A layer of light-toned rock exposed inside Victoria Crater in the Meridiani Planum region of Mars appears to mark where the surface was at the time, many millions of years ago, when an impact excavated the crater. NASA's Mars Exploration Rover Opportunity drove to this bright band as the science team's first destination for the rover during investigations inside the crater.

    Opportunity's left front hazard-identification camera took this image just after the rover finished a drive of 2.25 meters (7 feet, 5 inches) during the rover's 1,305th Martian day, or sol, (Sept. 25, 2007). The rocks beneath the rover and its extended robotic arm are part of the bright band.

    Victoria Crater has a scalloped shape of alternating alcoves and promontories around the crater's circumference. Opportunity descended into the crater two weeks earlier, within an alcove called 'Duck Bay.' Counterclockwise around the rim, just to the right of the arm in this image, is a promontory called 'Cabo Frio.'

  16. Sublimation in bright spots on (1) Ceres.

    PubMed

    Nathues, A; Hoffmann, M; Schaefer, M; Le Corre, L; Reddy, V; Platz, T; Cloutis, E A; Christensen, U; Kneissl, T; Li, J-Y; Mengel, K; Schmedemann, N; Schaefer, T; Russell, C T; Applin, D M; Buczkowski, D L; Izawa, M R M; Keller, H U; O'Brien, D P; Pieters, C M; Raymond, C A; Ripken, J; Schenk, P M; Schmidt, B E; Sierks, H; Sykes, M V; Thangjam, G S; Vincent, J-B

    2015-12-10

    The dwarf planet (1) Ceres, the largest object in the main asteroid belt with a mean diameter of about 950 kilometres, is located at a mean distance from the Sun of about 2.8 astronomical units (one astronomical unit is the Earth-Sun distance). Thermal evolution models suggest that it is a differentiated body with potential geological activity. Unlike on the icy satellites of Jupiter and Saturn, where tidal forces are responsible for spewing briny water into space, no tidal forces are acting on Ceres. In the absence of such forces, most objects in the main asteroid belt are expected to be geologically inert. The recent discovery of water vapour absorption near Ceres and previous detection of bound water and OH near and on Ceres (refs 5-7) have raised interest in the possible presence of surface ice. Here we report the presence of localized bright areas on Ceres from an orbiting imager. These unusual areas are consistent with hydrated magnesium sulfates mixed with dark background material, although other compositions are possible. Of particular interest is a bright pit on the floor of crater Occator that exhibits probable sublimation of water ice, producing haze clouds inside the crater that appear and disappear with a diurnal rhythm. Slow-moving condensed-ice or dust particles may explain this haze. We conclude that Ceres must have accreted material from beyond the 'snow line', which is the distance from the Sun at which water molecules condense.

  17. Coronal Bright Points Associated with Minifilament Eruptions

    NASA Astrophysics Data System (ADS)

    Hong, Junchao; Jiang, Yunchun; Yang, Jiayan; Bi, Yi; Li, Haidong; Yang, Bo; Yang, Dan

    2014-12-01

    Coronal bright points (CBPs) are small-scale, long-lived coronal brightenings that always correspond to photospheric network magnetic features of opposite polarity. In this paper, we subjectively adopt 30 CBPs in a coronal hole to study their eruptive behavior using data from the Atmospheric Imaging Assembly (AIA) and the Helioseismic and Magnetic Imager (HMI) on board the Solar Dynamics Observatory. About one-quarter to one-third of the CBPs in the coronal hole go through one or more minifilament eruption(s) (MFE(s)) throughout their lifetimes. The MFEs occur in temporal association with the brightness maxima of CBPs and possibly result from the convergence and cancellation of underlying magnetic dipoles. Two examples of CBPs with MFEs are analyzed in detail, where minifilaments appear as dark features of a cool channel that divide the CBPs along the neutral lines of the dipoles beneath. The MFEs show the typical rising movements of filaments and mass ejections with brightenings at CBPs, similar to large-scale filament eruptions. Via differential emission measure analysis, it is found that CBPs are heated dramatically by their MFEs and the ejected plasmas in the MFEs have average temperatures close to the pre-eruption BP plasmas and electron densities typically near 109 cm-3. These new observational results indicate that CBPs are more complex in dynamical evolution and magnetic structure than previously thought.

  18. Coronal bright points associated with minifilament eruptions

    SciTech Connect

    Hong, Junchao; Jiang, Yunchun; Yang, Jiayan; Bi, Yi; Li, Haidong; Yang, Bo; Yang, Dan

    2014-12-01

    Coronal bright points (CBPs) are small-scale, long-lived coronal brightenings that always correspond to photospheric network magnetic features of opposite polarity. In this paper, we subjectively adopt 30 CBPs in a coronal hole to study their eruptive behavior using data from the Atmospheric Imaging Assembly (AIA) and the Helioseismic and Magnetic Imager (HMI) on board the Solar Dynamics Observatory. About one-quarter to one-third of the CBPs in the coronal hole go through one or more minifilament eruption(s) (MFE(s)) throughout their lifetimes. The MFEs occur in temporal association with the brightness maxima of CBPs and possibly result from the convergence and cancellation of underlying magnetic dipoles. Two examples of CBPs with MFEs are analyzed in detail, where minifilaments appear as dark features of a cool channel that divide the CBPs along the neutral lines of the dipoles beneath. The MFEs show the typical rising movements of filaments and mass ejections with brightenings at CBPs, similar to large-scale filament eruptions. Via differential emission measure analysis, it is found that CBPs are heated dramatically by their MFEs and the ejected plasmas in the MFEs have average temperatures close to the pre-eruption BP plasmas and electron densities typically near 10{sup 9} cm{sup –3}. These new observational results indicate that CBPs are more complex in dynamical evolution and magnetic structure than previously thought.

  19. Inverse relationship between surface brightness and polarization

    NASA Astrophysics Data System (ADS)

    Egan, Walter G.

    1999-10-01

    There is an inverse relationship between surface brightness and polarization in the wavelength range from the ultraviolet to the near infrared. This relationship was first observed by the French astronomers B. Lyot and A. Dollfus in the early 20th century for planetary surfaces and laboratory models. The relationship was later confirmed principally by Egan and his coworkers in the Grumman Research Department in lunar simulation experiments prior to the Lunar Module landing. The observations indicate that the percent polarization (The percent polarization is the ratio of the difference between two orthogonal polarized measurements ratioed to the sum multiplied by 100) is an inverse function of the surface brightness (albedo). The Grumman instrument was a unique large scale polarimeter/photometer that allowed measurements not only of coated surfaces, but of particulates or structural surfaces up to 10 centimeters in diameter. It was found that, for instance, a diffuse surface having a reflectance of 2% could have a percent polarization of nearly 100%. The polarization was found to be a function of the optical complex index of refraction of the surface and the surface structure, and the relationship was found to be true for farm soils, agricultural and forested areas and was useful to characterize them. Astronomical and recent laboratory data will be presented to illustrate the relationship. More recent polarimeters will be discussed that permit polarization measurements accurate to plus or minus 0.1% from 0 to 100%.

  20. At Bright Band Inside Victoria Crater

    NASA Technical Reports Server (NTRS)

    2007-01-01

    A layer of light-toned rock exposed inside Victoria Crater in the Meridiani Planum region of Mars appears to mark where the surface was at the time, many millions of years ago, when an impact excavated the crater. NASA's Mars Exploration Rover Opportunity drove to this bright band as the science team's first destination for the rover during investigations inside the crater.

    Opportunity's left front hazard-identification camera took this image just after the rover finished a drive of 2.25 meters (7 feet, 5 inches) during the rover's 1,305th Martian day, or sol, (Sept. 25, 2007). The rocks beneath the rover and its extended robotic arm are part of the bright band.

    Victoria Crater has a scalloped shape of alternating alcoves and promontories around the crater's circumference. Opportunity descended into the crater two weeks earlier, within an alcove called 'Duck Bay.' Counterclockwise around the rim, just to the right of the arm in this image, is a promontory called 'Cabo Frio.'

  1. Synchrotron brightness distribution of turbulent radio jets

    NASA Technical Reports Server (NTRS)

    Henriksen, R. N.; Bridle, A. H.; Chan, K. L.

    1981-01-01

    Radio jets are considered as turbulent mixing regions and it is proposed that the essential small scale viscous dissipation in these jets is by emission of MHD waves and by their subsequent strong damping due, at least partly, to gyro-resonant acceleration of supra-thermal particles. A formula relating the synchrotron surface brightness of a radio jet to the turbulent power input is deduced from physical postulates, and is tested against the data for NGC315 and 3C31 (NGC383). The predicted brightness depends essentially on the collimation behavior of the jet, and, to a lesser extent, on the CH picture of a 'high' nozzle with accelerating flow. The conditions for forming a large scale jet at a high nozzle from a much smaller scale jet are discussed. The effect of entrainment on the prediction is discussed with the use of similarity solutions. Although entrainment is inevitably associated with the turbulent jet, it may or may not be a dominant factor depending on the ambient density profile.

  2. Sublimation in bright spots on (1) Ceres

    NASA Astrophysics Data System (ADS)

    Nathues, A.; Hoffmann, M.; Schaefer, M.; Le Corre, L.; Reddy, V.; Platz, T.; Cloutis, E. A.; Christensen, U.; Kneissl, T.; Li, J.-Y.; Mengel, K.; Schmedemann, N.; Schaefer, T.; Russell, C. T.; Applin, D. M.; Buczkowski, D. L.; Izawa, M. R. M.; Keller, H. U.; O'Brien, D. P.; Pieters, C. M.; Raymond, C. A.; Ripken, J.; Schenk, P. M.; Schmidt, B. E.; Sierks, H.; Sykes, M. V.; Thangjam, G. S.; Vincent, J.-B.

    2015-12-01

    The dwarf planet (1) Ceres, the largest object in the main asteroid belt with a mean diameter of about 950 kilometres, is located at a mean distance from the Sun of about 2.8 astronomical units (one astronomical unit is the Earth-Sun distance). Thermal evolution models suggest that it is a differentiated body with potential geological activity. Unlike on the icy satellites of Jupiter and Saturn, where tidal forces are responsible for spewing briny water into space, no tidal forces are acting on Ceres. In the absence of such forces, most objects in the main asteroid belt are expected to be geologically inert. The recent discovery of water vapour absorption near Ceres and previous detection of bound water and OH near and on Ceres (refs 5, 6, 7) have raised interest in the possible presence of surface ice. Here we report the presence of localized bright areas on Ceres from an orbiting imager. These unusual areas are consistent with hydrated magnesium sulfates mixed with dark background material, although other compositions are possible. Of particular interest is a bright pit on the floor of crater Occator that exhibits probable sublimation of water ice, producing haze clouds inside the crater that appear and disappear with a diurnal rhythm. Slow-moving condensed-ice or dust particles may explain this haze. We conclude that Ceres must have accreted material from beyond the ‘snow line’, which is the distance from the Sun at which water molecules condense.

  3. Analysis of hepatitis C virus core/NS5A protein co-localization using novel cell culture systems expressing core-NS2 and NS5A of genotypes 1-7.

    PubMed

    Galli, Andrea; Scheel, Troels K H; Prentoe, Jannick C; Mikkelsen, Lotte S; Gottwein, Judith M; Bukh, Jens

    2013-10-01

    Hepatitis C virus (HCV) is an important human pathogen infecting hepatocytes. With the advent of infectious cell culture systems, the HCV particle assembly and release processes are finally being uncovered. The HCV core and NS5A proteins co-localize on cytoplasmic lipid droplets (cLDs) or on the endoplasmic reticulum (ER) at different stages of particle assembly. Current knowledge on assembly and release is primarily based on studies in genotype 2a cell culture systems; however, given the high genetic heterogeneity of HCV, variations might exist among genotypes. Here, we developed novel HCV strain JFH1-based recombinants expressing core-NS2 and NS5A from genotypes 1-7, and analysed core and NS5A co-localization in infected cells. Huh7.5 cells were transfected with RNA of core-NS2/NS5A recombinants and putative adaptive mutations were analysed by reverse genetics. Adapted core-NS2/NS5A recombinants produced infectivity titres of 10(2.5)-10(4.5) f.f.u. ml(-1). Co-localization analysis demonstrated that the core and NS5A proteins from all genotypes co-localized extensively, and there was no significant difference in protein co-localization among genotypes. In addition, we found that the core and NS5A proteins were highly associated with cLDs at 12 h post-infection but became mostly ER associated at later stages. Finally, we found that different genotypes showed varying levels of core/cLD co-localization, with a possible effect on viral assembly/release. In summary, we developed a panel of HCV genotype 1-7 core-NS2/NS5A recombinants producing infectious virus, and an immunostaining protocol detecting the core and NS5A proteins from seven different genotypes. These systems will allow, for the first time, investigation of core/NS5A interactions during assembly and release of HCV particles of all major genotypes.

  4. LARGER PLANET RADII INFERRED FROM STELLAR ''FLICKER'' BRIGHTNESS VARIATIONS OF BRIGHT PLANET-HOST STARS

    SciTech Connect

    Bastien, Fabienne A.; Stassun, Keivan G.; Pepper, Joshua

    2014-06-10

    Most extrasolar planets have been detected by their influence on their parent star, typically either gravitationally (the Doppler method) or by the small dip in brightness as the planet blocks a portion of the star (the transit method). Therefore, the accuracy with which we know the masses and radii of extrasolar planets depends directly on how well we know those of the stars, the latter usually determined from the measured stellar surface gravity, log g. Recent work has demonstrated that the short-timescale brightness variations ({sup f}licker{sup )} of stars can be used to measure log g to a high accuracy of ∼0.1-0.2 dex. Here, we use flicker measurements of 289 bright (Kepmag < 13) candidate planet-hosting stars with T {sub eff} = 4500-6650 K to re-assess the stellar parameters and determine the resulting impact on derived planet properties. This re-assessment reveals that for the brightest planet-host stars, Malmquist bias contaminates the stellar sample with evolved stars: nearly 50% of the bright planet-host stars are subgiants. As a result, the stellar radii, and hence the radii of the planets orbiting these stars, are on average 20%-30% larger than previous measurements had suggested.

  5. Does Stevens's Power Law for Brightness Extend to Perceptual Brightness Averaging?

    ERIC Educational Resources Information Center

    Bauer, Ben

    2009-01-01

    Stevens's power law ([Psi][infinity][Phi][beta]) captures the relationship between physical ([Phi]) and perceived ([Psi]) magnitude for many stimulus continua (e.g., luminance and brightness, weight and heaviness, area and size). The exponent ([beta]) indicates whether perceptual magnitude grows more slowly than physical magnitude ([beta] less…

  6. Does Stevens's Power Law for Brightness Extend to Perceptual Brightness Averaging?

    ERIC Educational Resources Information Center

    Bauer, Ben

    2009-01-01

    Stevens's power law ([Psi][infinity][Phi][beta]) captures the relationship between physical ([Phi]) and perceived ([Psi]) magnitude for many stimulus continua (e.g., luminance and brightness, weight and heaviness, area and size). The exponent ([beta]) indicates whether perceptual magnitude grows more slowly than physical magnitude ([beta] less…

  7. Larger Planet Radii Inferred from Stellar "Flicker" Brightness Variations of Bright Planet-host Stars

    NASA Astrophysics Data System (ADS)

    Bastien, Fabienne A.; Stassun, Keivan G.; Pepper, Joshua

    2014-06-01

    Most extrasolar planets have been detected by their influence on their parent star, typically either gravitationally (the Doppler method) or by the small dip in brightness as the planet blocks a portion of the star (the transit method). Therefore, the accuracy with which we know the masses and radii of extrasolar planets depends directly on how well we know those of the stars, the latter usually determined from the measured stellar surface gravity, log g. Recent work has demonstrated that the short-timescale brightness variations ("flicker") of stars can be used to measure log g to a high accuracy of ~0.1-0.2 dex. Here, we use flicker measurements of 289 bright (Kepmag < 13) candidate planet-hosting stars with T eff = 4500-6650 K to re-assess the stellar parameters and determine the resulting impact on derived planet properties. This re-assessment reveals that for the brightest planet-host stars, Malmquist bias contaminates the stellar sample with evolved stars: nearly 50% of the bright planet-host stars are subgiants. As a result, the stellar radii, and hence the radii of the planets orbiting these stars, are on average 20%-30% larger than previous measurements had suggested.

  8. SIMULATION, GENERATION, AND CHARACTERIZATION OF HIGH BRIGHTNESS ELECTRON SOURCE AT 1GV/M GRADIENT.

    SciTech Connect

    SRINIVASAN-RAO,T.; SCHILL,J.; BEN-ZVI,I.; BATCHELOR,K.; FARRELL,J.P.; SMEDLEY,J.; LIN,X.E.; ODIAN,A.

    1999-03-29

    This paper describes computer simulations and measurements on an electron bunch from a pulsed, high gradient gap. MAFIA and PBGUNS were used to calculate the emittance, brightness and energy spread of the electron beam for peak currents ranging from 10A to 1 kA and pulse durations ranging from 0.3 ps to 10 ps. Under optimum conditions, normalized emittance of 10{sup -7} {pi} m-rad, beam brightness of 3 x 10{sup 15} A/(m-rad){sup 2} and energy spread of 0.15% were obtained. A pulsed high voltage with 1 MV amplitude, and {approx}1 ns duration was applied to the diode with an interelectrode gap ranging from 2 mm to 0.5 mm. Copper cathodes with three different surface preparations; diamond polished, diamond turned and chemically cleaned, have been tested for their voltage hold-off properties under this high gradient and the Fowler-Nordheim plots were generated. The diamond polished OFC class II copper was shown to consistently produce lower dark current and higher hold-off voltage. Photoemission studies have been made using light from a KrF excimer. The field enhancement factor for photoemission was calculated to be 5, an order of magnitude smaller than the dark current beta for a similar surface.

  9. Generation and propagation of high-brightness electron beams from a magnetically crowbarred injector

    NASA Astrophysics Data System (ADS)

    Humphries, S., Jr.; Len, L. K.; Allen, C. B.

    1987-05-01

    Tests of a 300-keV electrostatic electron beam injector with a magnetic crowbar switch are described. The saturable ferrite core switch allows generation of a constant voltage, 80-ns pulse directly from a Marx generator. Inductive isolation in the switch permits direct access to the high-voltage electrode for thermionic or active plasma cathode experiments. The pulse modulator can drive a 1.5-kA load. A high brightness 290-A beam from a felt plasma-emission cathode was extracted and propagated in vacuum. Because of the reliability of the magnetic crowbar switch, more than 500 shots were accumulated on the cathode at over 1 kA/sq cm with no degradation of the output. The output beam had a normalized brightness of 2.6 x 10 to the 8th A/(m rad) sq. A solenoidal lens was used to match the space-charge-dominated beam into a 1-m-long periodic focusing system with 25 reversing solenoidal coils. A beam current of 150 A was successfully transported through the 1.7-cm radius tube.

  10. Magnetic Piston Propagation in a 100-ns Plasma Opening Switch

    NASA Astrophysics Data System (ADS)

    Weingarten, A.; Grabowski, C.; Chakrabarti, N.; Maron, Y.; Fruchtman, A.

    1998-11-01

    The propagation of a magnetic piston through the plasma of a 90-ns, 170-kA POS is observed by studying the electron density, magnetic field, and ion velocity evolution. For the prefilled plasma n_e=(2.2± 0.5)× 10^14 cm-3, and T_e=5.5± 1 eV. The plasma composition is studied from absolute line intensities and collisional-radiative calculations. Most of the plasma ions are protons (90% near the cathode) with the rest being mainly CIV. The Hall-MHD conditions are not fulfilled for our experiment and ion motion is significant. The 3D-resolved ne evolution during the current pulse is studied from the line intensities of ions doped in the plasma using laser evaporation, and the magnetic field from Zeeman splitting. A diagonal magnetic piston propagates from the generator towards the load at about half the proton Alfven velocity. The protons are specularly reflected by the piston, while the heavy ions cross the potential hill in the piston, acquiring a lower velocity. The proton reflection causes an increase of ne ahead of the piston, followed by a sharp (10-20 ns) and substantial drop in ne (to 10-50% from the initial value). The magnetic field distribution studied using chordal observation, and theoretical analysis of ne and the magnetic field evolution are presented.

  11. Autonomous Magnetoexplosive Generator of Megavolt, 100 NS Pulses

    NASA Astrophysics Data System (ADS)

    Gurin, V. Ye.; Kataev, V. N.; Korolev, P. V.; Kargin, V. I.; Makartsev, G. F.; Nudikov, V. N.; Pikar, A. S.; Popkov, N. F.; Saratov, A. F.

    2004-11-01

    Here we present the results of the work carried out at different stages aimed at the development of autonomous magnetocumulative generators having 100 ns megavolt pulses. This generator is meant to replace the PIRIT-01 stationary facility by a magnetocumulative energy source. Using a generator with permanent magnets as a source of initial energy and multiplying this energy by a cascade of magnetoexplosive generators allows 100 kJ of energy accumulation in a contour. The generator that has a permanent magnet does not need an additional energy source for its operation. It is convenient to operate and is always available for service. Shortening the MC generator current pulse up to 1 μs is implemented using a high-voltage explosive driven opening switch. In the first sharpening cascade, the voltage increases up to 500 kV. Further shortening of the current pulse duration up to 100 ns and the voltage rise up to 1 MV are performed using plasma opening switches according to the two-stage formation scheme. Such a scheme allows the decrease of electric field strength on the insulator surface and the use of magnetic insulation in the high-voltage section of the facility.

  12. Assessing ubiquitination of viral proteins: Lessons from flavivirus NS5.

    PubMed

    Taylor, R Travis; Best, Sonja M

    2011-10-01

    Ubiquitin (Ub) conjugation to a substrate protein is a widely used cellular mechanism for control of protein stability and function, modulation of signal transduction pathways and antiviral responses. Identification and characterization of ubiquitinated viral proteins is an important step in understanding novel mechanisms of viral protein regulation as well as elucidating cellular antiviral strategies. Here we describe a protocol to easily detect and characterize the ubiquitination status of a viral substrate protein expressed either during infection or ectopically expressed as a fusion with a biotinylatable epitope tag. This tag provides advantages over current immunoprecipitation techniques by making use of the extremely tight biotin-streptavidin interaction. We provide an example of this protocol using the nonstructural protein 5 (NS5) from Langat virus (LGTV), a member of the tick-borne encephalitis virus (TBEV) serocomplex within the Flavivirus genus. Using the protocols outlined here, we describe some of the pitfalls inherent in determination of Ub linkage and demonstrate that NS5 is modified by at least two distinct ubiquitination types, multiubiquitination and K48-linked polyubiquitin chains.

  13. Assessing ubiquitination of viral proteins: lessons from flavivirus NS5

    PubMed Central

    Taylor, R. Travis; Best, Sonja M.

    2011-01-01

    Ubiquitin (Ub) conjugation to a substrate protein is a widely used cellular mechanism for control of protein stability and function, modulation of signal transduction pathways and antiviral responses. Identification and characterization of ubiquitinated viral proteins is an important step in understanding novel mechanisms of viral protein regulation as well as elucidating cellular antiviral strategies. Here we describe a protocol to easily detect and characterize the ubiquitination status of a viral substrate protein expressed either during infection or ectopically expressed as a fusion with a biotinylatable epitope tag. This tag provides advantages over current immunoprecipitation techniques by making use of the extremely tight biotin-streptavidin interaction. We provide an example of this protocol using the nonstructural protein 5 (NS5) from Langat virus (LGTV), a member of the tick-borne encephalitis virus (TBEV) serocomplex within the Flavivirus genus. Using the protocols outlined here, we describe some of the pitfalls inherent in determination of Ub linkage and demonstrate that NS5 is modified by at least two distinct ubiquitination types, multiubiquitination and K48-linked polyubiquitin chains. PMID:21855635

  14. Turbulent Mixing Layer Control using Ns-DBD Plasma Actuators

    NASA Astrophysics Data System (ADS)

    Singh, Ashish; Little, Jesse

    2016-11-01

    A low speed turbulent mixing layer (Reθo =1282, U1 /U2 = 0 . 28 and U2 = 11 . 8 m / s) is subject to nanosecond pulse driven dielectric barrier discharge (ns-DBD) plasma actuation. The forcing frequency corresponds to a Strouhal number (St) of 0.032 which is the most amplified frequency based on stability theory. Flow response is studied as a function of the pulse energy, the energy input time scale (carrier frequency) and the duration of actuation (duty cycle). It is found that successful actuation requires a combination of forcing parameters. An evaluation of the forcing efficacy is achieved by examining different flow quantities such as momentum thickness, vorticity and velocity fluctuations. In accordance with past work, a dependence is found between the initial shear layer thickness and the energy coupled to the flow. More complex relationships are also revealed such as a limitation on the maximum pulse energy which yields control. Also, the pulse energy and the carrier frequency (inverse of period between successive pulses) are interdependent whereby an optimum exists between them and extreme values of either parameter is inconsonant with the control desired. These observations establish a rich and complex process behind ns-DBD plasma actuation. Air Force Office of Scientific Research (FA9550-12-1-0044).

  15. Cyclosporine Inhibits a Direct Interaction between Cyclophilins and Hepatitis C NS5A

    PubMed Central

    Striker, Rob

    2010-01-01

    Background Hepatitis C Virus (HCV) infection is a leading indication for liver transplantation. HCV infection reoccurs almost universally post transplant, decreasing both graft longevity and patient survival. The immunosuppressant, cyclosporine A (CsA) has potent anti-HCV activity towards both HCV replicons and the genotype 2a cell culture infectious virus. Previously, we isolated mutations in the 1bN replicon with less sensitivity to CsA that mapped to both NS5A and NS5B regions of the virus. Mutations in NS5A alone conferred decreased CsA susceptibility regardless of NS5B mutations. Methodology/Principal Findings We examined the mechanisms by which NS5A mutations contribute to CsA resistance and if they are strain dependent. Using in vitro mutagenesis, the amino acid position 321 mutation of NS5A was restored to the wild-type tyrosine residue conferring partial CsA susceptibility on the mutant replicon. The 321 mutation also alters CsA susceptibility of the JFH cell culture virus. Additionally, we demonstrated a novel CsA-sensitive interaction between NS5A and both cyclophilin A and B. Both the mutant NS5A and wild type NS5A bind cyclophilin in vitro. The NS5A: cyclophilin interaction requires both the NS5A region identified by the resistance mutants and cyclophilin catalytic residues. In cell culture, NS5A from CsA resistant mutant has an enhanced interaction with cyclophilin B. Additionally; NS5B facilitates a stronger binding of mutant NS5A to endogenous cyclophilin B than wild-type in cell culture. Conclusions/Significance Collectively, this data suggests direct interactions between cyclophilins and NS5A are critical to understand for optimal use of cyclophilin inhibitors in anti-HCV therapy. PMID:20352119

  16. Cyclosporine inhibits a direct interaction between cyclophilins and hepatitis C NS5A.

    PubMed

    Fernandes, Fiona; Ansari, Israr-ul H; Striker, Rob

    2010-03-23

    Hepatitis C Virus (HCV) infection is a leading indication for liver transplantation. HCV infection reoccurs almost universally post transplant, decreasing both graft longevity and patient survival. The immunosuppressant, cyclosporine A (CsA) has potent anti-HCV activity towards both HCV replicons and the genotype 2a cell culture infectious virus. Previously, we isolated mutations in the 1bN replicon with less sensitivity to CsA that mapped to both NS5A and NS5B regions of the virus. Mutations in NS5A alone conferred decreased CsA susceptibility regardless of NS5B mutations. We examined the mechanisms by which NS5A mutations contribute to CsA resistance and if they are strain dependent. Using in vitro mutagenesis, the amino acid position 321 mutation of NS5A was restored to the wild-type tyrosine residue conferring partial CsA susceptibility on the mutant replicon. The 321 mutation also alters CsA susceptibility of the JFH cell culture virus. Additionally, we demonstrated a novel CsA-sensitive interaction between NS5A and both cyclophilin A and B. Both the mutant NS5A and wild type NS5A bind cyclophilin in vitro. The NS5A: cyclophilin interaction requires both the NS5A region identified by the resistance mutants and cyclophilin catalytic residues. In cell culture, NS5A from CsA resistant mutant has an enhanced interaction with cyclophilin B. Additionally; NS5B facilitates a stronger binding of mutant NS5A to endogenous cyclophilin B than wild-type in cell culture. Collectively, this data suggests direct interactions between cyclophilins and NS5A are critical to understand for optimal use of cyclophilin inhibitors in anti-HCV therapy.

  17. Activity of purified hepatitis C virus protease NS3 on peptide substrates.

    PubMed Central

    Steinkühler, C; Urbani, A; Tomei, L; Biasiol, G; Sardana, M; Bianchi, E; Pessi, A; De Francesco, R

    1996-01-01

    The protease domain of the hepatitis C virus (HCV) protein NS3 was expressed in Escherichia coli, purified to homogeneity, and shown to be active on peptides derived from the sequence of the NS4A-NS4B junction. Experiments were carried out to optimize protease activity. Buffer requirements included the presence of detergent, glycerol, and dithiothreitol, pH between 7.5 and 8.5, and low ionic strength. C- and N-terminal deletion experiments defined a peptide spanning from the P6 to the P4' residue as a suitable substrate. Cleavage kinetics were subsequently measured by using decamer P6-P4' peptides corresponding to all intermolecular cleavage sites of the HCV polyprotein. The following order of cleavage efficiency, in terms of kcat/Km, was determined: NS5A-NS5B > NS4A-NS4B >> NS4B-NS5A. A 14-mer peptide containing residues 21 to 34 of the protease cofactor NS4A (Pep4A 21-34), when added in stoichiometric amounts, was shown to increase cleavage rates of all peptides, the largest effect (100-fold) being observed on the hydrolysis of the NS4B-NS5A decamer. From the kinetic analysis of cleavage data, we conclude that (i) primary structure is an important determinant of the efficiency with which each site is cleaved during polyprotein processing, (ii) slow cleavage of the NS4B-NS5A site in the absence of NS4A is due to low binding affinity of the enzyme for this site, and (iii) formation of a 1:1 complex between the protease and Pep4A 21-34 is sufficient and required for maximum activation. PMID:8794305

  18. Hyperthymic temperament and rapid reaction time in brightness preference.

    PubMed

    Kodama, Kensuke; Harada, Mayu; Terao, Takeshi; Hatano, Koji; Kohno, Kentaro; Araki, Yasuo; Mizokami, Yoshinori; Hoaki, Nobuhiko; Shimomura, Tsuyoshi; Fujiki, Minoru; Kochiyama, Takanori

    2013-12-01

    It is well-known that Type A behavior pattern is characterized by hard-driving, competitive behavior and time urgency. Also, people with hyperthymic temperament are known to have high energy levels and are full of plans. It is therefore hypothesized that hyperthymic temperament is associated with rapid processing and fast reaction time in making decisions. Using data from our previous experimental studies (N=58) examining brightness judgment and brightness preference, reaction time (RT) was investigated in relation to hyperthymic temperament scores and fMRI signal changes of the left inferior orbitofrontal cortex during brightness judgment. RT for brightness judgment was significantly shorter than RT for brightness preference. Significant associations were found between RT for brightness preference and hyperthymic temperament scores, and RT for brightness preference and fMRI signal changes of the left inferior orbitofrontal cortex whilst performing brightness preference task. Multiple regression analysis revealed that RT for brightness preference task was significantly and negatively associated with hyperthymic temperament scores, and significantly and positively associated with fMRI signal changes of the left inferior orbitofrontal cortex. It is uncertain whether the findings of RT (around 1s) can be extrapolated to routine life (around 24h) and whether RT for brightness preference can be generalized to a variety of daily activities. The present findings suggest that hyperthymic temperament is associated with rapid processing. Further studies are required to overcome the above limitations. © 2013 Elsevier B.V. All rights reserved.

  19. Brightness and transparency in the early visual cortex.

    PubMed

    Salmela, Viljami R; Vanni, Simo

    2013-06-24

    Several psychophysical studies have shown that transparency can have drastic effects on brightness and lightness. However, the neural processes generating these effects have remained unresolved. Several lines of evidence suggest that the early visual cortex is important for brightness perception. While single cell recordings suggest that surface brightness is represented in the primary visual cortex, the results of functional magnetic resonance imaging (fMRI) studies have been discrepant. In addition, the location of the neural representation of transparency is not yet known. We investigated whether the fMRI responses in areas V1, V2, and V3 correlate with brightness and transparency. To dissociate the blood oxygen level-dependent (BOLD) response to brightness from the response to local border contrast and mean luminance, we used variants of White's brightness illusion, both opaque and transparent, in which luminance increments and decrements cancel each other out. The stimuli consisted of a target surface and a surround. The surround luminance was always sinusoidally modulated at 0.5 Hz to induce brightness modulation to the target. The target luminance was constant or modulated in counterphase to null brightness modulation. The mean signal changes were calculated from the voxels in V1, V2, and V3 corresponding to the retinotopic location of the target surface. The BOLD responses were significantly stronger for modulating brightness than for stimuli with constant brightness. In addition, the responses were stronger for transparent than for opaque stimuli, but there was more individual variation. No interaction between brightness and transparency was found. The results show that the early visual areas V1-V3 are sensitive to surface brightness and transparency and suggest that brightness and transparency are represented separately.

  20. Multiple determinants influence complex formation of the hepatitis C virus NS3 protease domain with its NS4A cofactor peptide.

    PubMed

    Urbani, A; Biasiol, G; Brunetti, M; Volpari, C; Di Marco, S; Sollazzo, M; Orrú, S; Piaz, F D; Casbarra, A; Pucci, P; Nardi, C; Gallinari, P; De Francesco, R; Steinkühler, C

    1999-04-20

    The interaction of the hepatitis C virus (HCV) NS3 protease domain with its NS4A cofactor peptide (Pep4AK) was investigated at equilibrium and at pre-steady state under different physicochemical conditions. Equilibrium dissociation constants of the NS3-Pep4AK complex varied by several orders of magnitude depending on buffer additives. Glycerol, NaCl, detergents, and peptide substrates were found to stabilize this interaction. The extent of glycerol-induced stabilization varied in an HCV strain-dependent way with at least one determinant mapping to an NS3-NS4A interaction site. Conformational transitions affecting at least the first 18 amino acids of NS3 were the main energy barriers for both the association and the dissociation reactions of the complex. However, deletion of this N-terminal portion of the protease molecule only slightly influenced equilibrium dissociation constants determined under different physicochemical conditions. Limited proteolysis experiments coupled with mass spectrometric identification of cleavage fragments suggested a high degree of conformational flexibility affecting at least the first 21 residues of NS3. The accessibility of this region of the protease to limited chymotryptic digestion did not significantly change in any condition tested, whereas a significant reduction of chymotryptic cleavages within the NS3 core was detected under conditions of high NS3-Pep4AK complex affinity. We conclude the following: (1) The N-terminus of the NS3 protease that, according to the X-ray crystal structure, makes extensive contacts with the cofactor peptide is highly flexible in solution and contributes only marginally to the thermodynamic stability of the complex. (2) Affinity enhancement is accomplished by several factors through a general stabilization of the fold of the NS3 molecule.

  1. In vitro Splicing of Influenza Viral NS1 mRNA and NS1-β -globin Chimeras: Possible Mechanisms for the Control of Viral mRNA Splicing

    NASA Astrophysics Data System (ADS)

    Plotch, Stephen J.; Krug, Robert M.

    1986-08-01

    In influenza virus-infected cells, the splicing of the viral NS1 mRNA catalyzed by host nuclear enzymes is controlled so that the steady-state amount of the spliced NS2 mRNA is only 5-10% of that of the unspliced NS1 mRNA. Here we examine the splicing of NS1 mRNA in vitro, using nuclear extracts from HeLa cells. We show that in addition to its consensus 5' and 3' splice sites, NS1 mRNA has an intron branch-point adenosine residue that was functional in lariat formation. Nonetheless, this RNA was not detectably spliced in vitro under conditions in which a human β -globin precursor was efficiently spliced. Using chimeric RNA precursors containing both NS1 and β -globin sequences, we show that the NS1 5' splice site was effectively utilized by the β -globin branch-point sequence and 3' splice site to form a spliced RNA, whereas the NS1 3' splice site did not function in detectable splicing in vitro, even in the presence of the β -globin branch-point sequence or in the presence of both the branch-point sequence and 5' exon and splice site from β -globin With the chimeric precursors that were not detectably spliced, as with NS1 mRNA itself, a low level of a lariat structure containing only intron and not 3' exon sequences was formed. The inability of the consensus 3' splice site of NS1 mRNA to function effectively in in vitro splicing suggests that this site is structurally inaccessible to components of the splicing machinery. Based on these results, we propose two mechanisms whereby NS1 mRNA splicing in infected cells is controlled via the accessibility of its 3' splice site.

  2. Characterization of Naturally Occurring NS5A and NS5B Polymorphisms in Patients Infected with HCV Genotype 3a Treated with Direct-Acting Antiviral Agents.

    PubMed

    Bartolini, Barbara; Giombini, Emanuela; Taibi, Chiara; Lionetti, Raffaella; Montalbano, Marzia; Visco-Comandini, Ubaldo; D'Offizi, Gianpiero; Capobianchi, Maria Rosaria; McPhee, Fiona; Garbuglia, Anna Rosa

    2017-08-07

    Hepatitis C virus (HCV) genotype (GT)3 is associated with increased risk of steatosis, development of cirrhosis and hepatocellular carcinoma. Limited data are available regarding genetic variability and use of direct-acting antiviral agents in these patients. non-structural protein 5A (NS5A) and non-structural protein 5B (NS5B) sequencing was performed on 45 HCV GT3-infected Italian patients subsequently treated with sofosbuvir ± daclatasvir (SOF ± DCV). Novel GT3a polymorphisms were observed by Sanger sequencing in three NS5A (T79S, T107K, and T107S) and three NS5B (G166R, Q180K, and C274W) baseline sequences in patients who achieved sustained virological response (SVR). Baseline NS5A resistance-associated substitutions A30K and Y93H were detected in 9.5% of patients; one patient with A30K did not achieve SVR. Phylogenetic analyses of sequences showed no distinct clustering. Genetic heterogeneity of NS5A and NS5B was evaluated using ultra-deep pyrosequencing (UDPS) in samples longitudinally collected in patients not achieving SVR. Some novel NS5A and NS5B polymorphisms detected at baseline may not impact treatment outcome, as they were not enriched in post-failure samples. In contrast, the novel L31F NS5A variant emerged in one treatment failure, and I184T, G188D and N310S, located on the same NS5B haplotype, became predominant after failure. These findings suggest a potential impact of these novel substitutions on the treatment outcome; however, their significance requires further investigation.

  3. Surface brightness and intrinsic luminosity of ellipticals

    NASA Astrophysics Data System (ADS)

    Dhar, Barun Kumar; Williams, Liliya L. R.

    2012-11-01

    We show that the surface brightness profiles of elliptical galaxies can be parametrized using a linear superposition of two or three components, each of which is described by functions developed in Dhar & Williams as the 2D projections of a 3D Einasto density profile. For a sample of 23 ellipticals in and around the Virgo Cluster with total absolute V magnitude -24 < MVT < -15, our multicomponent models span a dynamic range up to 106 in surface brightness and up to 105 in radius down to the resolution limit of the Hubble Space Telescope, have a median rms of 0.032 mag arcsec-2 consistent with the rms of 0.03 from random errors of the data, and are statistically justified at >3σ. Our models indicate that (i) the central component is more concentrated than the outer component; and (ii) the central component of massive shallow-cusp ('core') galaxies is much more luminous, extended and concentrated than that of steep-cusp ('cuspy') galaxies, with their near exponential central profiles indicating disc-like systems, whose existence must be verified spectroscopically. Galaxy structure can thus be modelled extremely well with a central mass excess for all galaxies. This is not necessarily contrary to the notion of a mass deficit in 'core' galaxies, since mass ejection due to core scouring by a supermassive black hole (SMBH) binary could have affected the shape of the central components. However, we show that the existence, amount, radial extent and sign of such deficits disagree substantially in the literature, both for a given galaxy and on an average over a sample. We discuss possible implications and suggest that SMBH binaries are unlikely to be the sole mechanism for producing the large 'cores' of massive galaxies. Using results from the SAURON survey, we deduce that under certain conditions of symmetry, inclination angles and degree of triaxiality, the intrinsic (3D) density of light can be well described with a multicomponent Einasto model for both steep- and

  4. Hepatitis C virus NS5A inhibitors and drug resistance mutations.

    PubMed

    Nakamoto, Shingo; Kanda, Tatsuo; Wu, Shuang; Shirasawa, Hiroshi; Yokosuka, Osamu

    2014-03-21

    Some direct-acting antiviral agents for hepatitis C virus (HCV), such as telaprevir and boceprevir have been available since 2011. It was reported that HCV NS5A is associated with interferon signaling related to HCV replication and hepatocarcinogenesis. HCV NS5A inhibitors efficiently inhibited HCV replication in vitro. Human studies showed that dual, triple and quad regimens with HCV NS5A inhibitors, such as daclatasvir and ledipasvir, in combination with other direct-acting antiviral agents against other regions of HCV with or without peginterferon/ribavirin, could efficiently inhibit HCV replication according to HCV genotypes. These combinations might be a powerful tool for "difficult-to-treat" HCV-infected patients. "First generation" HCV NS5A inhibitors such as daclatasvir, ledipasvir and ABT-267, which are now in phase III clinical trials, could result in resistance mutations. "Second generation" NS5A inhibitors such as GS-5816, ACH-3102, and MK-8742, have displayed improvements in the genetic barrier while maintaining potency. HCV NS5A inhibitors are safe at low concentrations, which make them attractive for use despite low genetic barriers, although, in fact, HCV NS5A inhibitors should be used with HCV NS3/4A inhibitors, HCV NS5B inhibitors or peginterferon plus ribavirin. This review article describes HCV NS5A inhibitor resistance mutations and recommends that HCV NS5A inhibitors be used in combination regimens potent enough to prevent the emergence of resistant variants.

  5. The 2NS Translocation from Aegilops ventricosa Confers Resistance to the Triticum Pathotype of Magnaporthe oryzae

    PubMed Central

    Cruz, C.D.; Peterson, G.L.; Bockus, W.W.; Kankanala, P.; Dubcovsky, J.; Jordan, K.W.; Akhunov, E.; Chumley, F.; Baldelomar, F.D.; Valent, B.

    2016-01-01

    Wheat blast is a serious disease caused by the fungus Magnaporthe oryzae (Triticum pathotype) (MoT). The objective of this study was to determine the effect of the 2NS translocation from Aegilops ventricosa (Zhuk.) Chennav on wheat head and leaf blast resistance. Disease phenotyping experiments were conducted in growth chamber, greenhouse, and field environments. Among 418 cultivars of wheat (Triticum aestivum L.), those with 2NS had 50.4 to 72.3% less head blast than those without 2NS when inoculated with an older MoT isolate under growth chamber conditions. When inoculated with recently collected isolates, cultivars with 2NS had 64.0 to 80.5% less head blast. Under greenhouse conditions when lines were inoculated with an older MoT isolate, those with 2NS had a significant head blast reduction. With newer isolates, not all lines with 2NS showed a significant reduction in head blast, suggesting that the genetic background and/or environment may influence the expression of any resistance conferred by 2NS. However, when near-isogenic lines (NILs) with and without 2NS were planted in the field, there was strong evidence that 2NS conferred resistance to head blast. Results from foliar inoculations suggest that the resistance to head infection that is imparted by the 2NS translocation does not confer resistance to foliar disease. In conclusion, the 2NS translocation was associated with significant reductions in head blast in both spring and winter wheat. PMID:27814405

  6. The 2NS Translocation from Aegilops ventricosa Confers Resistance to the Triticum Pathotype of Magnaporthe oryzae.

    PubMed

    Cruz, C D; Peterson, G L; Bockus, W W; Kankanala, P; Dubcovsky, J; Jordan, K W; Akhunov, E; Chumley, F; Baldelomar, F D; Valent, B

    2016-01-01

    Wheat blast is a serious disease caused by the fungus Magnaporthe oryzae (Triticum pathotype) (MoT). The objective of this study was to determine the effect of the 2NS translocation from Aegilops ventricosa (Zhuk.) Chennav on wheat head and leaf blast resistance. Disease phenotyping experiments were conducted in growth chamber, greenhouse, and field environments. Among 418 cultivars of wheat (Triticum aestivum L.), those with 2NS had 50.4 to 72.3% less head blast than those without 2NS when inoculated with an older MoT isolate under growth chamber conditions. When inoculated with recently collected isolates, cultivars with 2NS had 64.0 to 80.5% less head blast. Under greenhouse conditions when lines were inoculated with an older MoT isolate, those with 2NS had a significant head blast reduction. With newer isolates, not all lines with 2NS showed a significant reduction in head blast, suggesting that the genetic background and/or environment may influence the expression of any resistance conferred by 2NS. However, when near-isogenic lines (NILs) with and without 2NS were planted in the field, there was strong evidence that 2NS conferred resistance to head blast. Results from foliar inoculations suggest that the resistance to head infection that is imparted by the 2NS translocation does not confer resistance to foliar disease. In conclusion, the 2NS translocation was associated with significant reductions in head blast in both spring and winter wheat.

  7. High brightness angled cavity quantum cascade lasers

    SciTech Connect

    Heydari, D.; Bai, Y.; Bandyopadhyay, N.; Slivken, S.; Razeghi, M.

    2015-03-02

    A quantum cascade laser (QCL) with an output power of 203 W is demonstrated in pulsed mode at 283 K with an angled cavity. The device has a ridge width of 300 μm, a cavity length of 5.8 mm, and a tilt angle of 12°. The back facet is high reflection coated, and the front facet is anti-reflection coated. The emitting wavelength is around 4.8 μm. In distinct contrast to a straight cavity broad area QCL, the lateral far field is single lobed with a divergence angle of only 3°. An ultrahigh brightness value of 156 MW cm{sup −2 }sr{sup −1} is obtained, which marks the brightest QCL to date.

  8. Visualizing individual microtubules by bright field microscopy

    NASA Astrophysics Data System (ADS)

    Gutiérrez-Medina, Braulio; Block, Steven M.

    2010-11-01

    Microtubules are slender (˜25 nm diameter), filamentous polymers involved in cellular structure and organization. Individual microtubules have been visualized via fluorescence imaging of dye-labeled tubulin subunits and by video-enhanced, differential interference-contrast microscopy of unlabeled polymers using sensitive CCD cameras. We demonstrate the imaging of unstained microtubules using a microscope with conventional bright field optics in conjunction with a webcam-type camera and a light-emitting diode illuminator. The light scattered by microtubules is image-processed to remove the background, reduce noise, and enhance contrast. The setup is based on a commercial microscope with a minimal set of inexpensive components, suitable for implementation in a student laboratory. We show how this approach can be used in a demonstration motility assay, tracking the gliding motions of microtubules driven by the motor protein kinesin.

  9. Bright Solitonic Matter-Wave Interferometer

    NASA Astrophysics Data System (ADS)

    McDonald, G. D.; Kuhn, C. C. N.; Hardman, K. S.; Bennetts, S.; Everitt, P. J.; Altin, P. A.; Debs, J. E.; Close, J. D.; Robins, N. P.

    2014-07-01

    We present the first realization of a solitonic atom interferometer. A Bose-Einstein condensate of 1×104 atoms of rubidium-85 is loaded into a horizontal optical waveguide. Through the use of a Feshbach resonance, the s-wave scattering length of the Rb85 atoms is tuned to a small negative value. This attractive atomic interaction then balances the inherent matter-wave dispersion, creating a bright solitonic matter wave. A Mach-Zehnder interferometer is constructed by driving Bragg transitions with the use of an optical lattice colinear with the waveguide. Matter-wave propagation and interferometric fringe visibility are compared across a range of s-wave scattering values including repulsive, attractive and noninteracting values. The solitonic matter wave is found to significantly increase fringe visibility even compared with a noninteracting cloud.

  10. Dark Skies, Bright Kids Year 8

    NASA Astrophysics Data System (ADS)

    Bittle, Lauren E.; Wenger, Trey; Johnson, Kelsey E.; Angell, Dylan; Burkhardt, Andrew; Davis, Blair; Firebaugh, Ariel; Hancock, Danielle; Richardson, Whitney; Rochford Hayes, Christian; Linden, Sean; Liss, Sandra; Matthews, Allison; McNair, Shunlante; Prager, Brian; Pryal, Matthew; Troup, Nicholas William

    2017-01-01

    We present activities from the eighth year of Dark Skies Bright Kids (DSBK), an entirely volunteer-run outreach organization based out of the Department of Astronomy at the University of Virginia. Our core mission is to enhance elementary science education and literacy in Central Virginia through fun, hands-on activities that introduce basic Astronomy concepts. Over the past seven years, our primary focus has been hosting an 8-10 week after-school astronomy club at underserved elementary and middle schools, and over the past several years, we have partnered with local businesses to host our Annual Central Virginia Star Party, a free event open to the community featuring star-gazing and planetarium shows. This past summer we expanded our reach through a new initiative to bring week-long summer day camps to south and southwest Virginia, home to some of the most underserved communities in the commonwealth.

  11. High brightness angled cavity quantum cascade lasers

    NASA Astrophysics Data System (ADS)

    Heydari, D.; Bai, Y.; Bandyopadhyay, N.; Slivken, S.; Razeghi, M.

    2015-03-01

    A quantum cascade laser (QCL) with an output power of 203 W is demonstrated in pulsed mode at 283 K with an angled cavity. The device has a ridge width of 300 μm, a cavity length of 5.8 mm, and a tilt angle of 12°. The back facet is high reflection coated, and the front facet is anti-reflection coated. The emitting wavelength is around 4.8 μm. In distinct contrast to a straight cavity broad area QCL, the lateral far field is single lobed with a divergence angle of only 3°. An ultrahigh brightness value of 156 MW cm-2 sr-1 is obtained, which marks the brightest QCL to date.

  12. Infrared Sky Brightness Monitors for Antarctica

    NASA Astrophysics Data System (ADS)

    Storey, J. W. V.; Ashley, M. C. B.; Boccas, M.; Phillips, M. A.; Schinckel, A. E. T.

    1999-06-01

    Two sky brightness monitors-one for the near-infrared and one for the mid-infrared-have been developed for site survey work in Antarctica. The instruments, which we refer to as the NISM (Near-Infrared Sky Monitor) and the MISM (Mid-Infrared Sky Monitor), are part of a suite of instruments being deployed in the Automated Astrophysical Site-Testing Observatory (AASTO). The chief design constraints include reliable, autonomous operation, low power consumption, and of course the ability to operate under conditions of extreme cold. The instruments are currently operational at the Amundsen-Scott South Pole Station, prior to deployment at remote, unattended sites on the high antarctic plateau.

  13. Dark Skies, Bright Kids Year 7

    NASA Astrophysics Data System (ADS)

    Bittle, Lauren E.; Johnson, Kelsey E.; Borish, H. Jacob; Burkhardt, Andrew; Firebaugh, Ariel; Hancock, Danielle; Rochford Hayes, Christian; Linden, Sean; Liss, Sandra; Matthews, Allison; Prager, Brian; Pryal, Matthew; Sokal, Kimberly R.; Troup, Nicholas William; Wenger, Trey

    2016-01-01

    We present updates from our seventh year of operation including new club content, continued assessments, and our fifth annual Star Party. Dark Skies, Bright Kids (DSBK) is an entirely volunteer-run outreach organization based out of the Department of Astronomy at the University of Virginia. Our core mission is to enhance elementary science education and literacy in Central Virginia through fun, hands-on activities that introduce basic Astronomy concepts. Our primary focus is hosting an 8-10 week after-school astronomy club at underserved elementary and middle schools. Each week, DSBK volunteers take the role of coaches to introduce astronomy-related concepts ranging from the Solar System to galaxies to astrobiology, and to lead students in interactive learning activities. Another hallmark of DSBK is hosting our Annual Central Virginia Star Party, a free event open to the community featuring star-gazing and planetarium shows.

  14. Extinction and Sky Brightness at Dome C

    NASA Astrophysics Data System (ADS)

    Faurobert, M.; Arnaud, J.; Vernisse, Y.

    2012-06-01

    We have installed a small telescope to monitor the sky brightness around the sun at the French-Italian station Concordia at Dome C in Antarctica. Previous campaigns have been performed with the same instrument at Haleakala in Hawai and Sunspot in New Mexico. We compare here the results of the first year of the campaign at Dome C (2008) to the purest sky observed at Haleakala. We show that Dome C is an outstanding site for coronal observations. Compared to Haleaka, it appears to be more transparent, and to contain less aerosols. Its water vapour content is also significantly smaller. These results still have to be confirmed by the analysis of the 2009 and 2010 data.

  15. Bioinspired bright noniridescent photonic melanin supraballs

    PubMed Central

    Xiao, Ming; Hu, Ziying; Wang, Zhao; Li, Yiwen; Tormo, Alejandro Diaz; Le Thomas, Nicolas; Wang, Boxiang; Gianneschi, Nathan C.; Shawkey, Matthew D.; Dhinojwala, Ali

    2017-01-01

    Structural colors enable the creation of a spectrum of nonfading colors without pigments, potentially replacing toxic metal oxides and conjugated organic pigments. However, significant challenges remain to achieve the contrast needed for a complete gamut of colors and a scalable process for industrial application. We demonstrate a feasible solution for producing structural colors inspired by bird feathers. We have designed core-shell nanoparticles using high–refractive index (RI) (~1.74) melanin cores and low-RI (~1.45) silica shells. The design of these nanoparticles was guided by finite-difference time-domain simulations. These nanoparticles were self-assembled using a one-pot reverse emulsion process, which resulted in bright and noniridescent supraballs. With the combination of only two ingredients, synthetic melanin and silica, we can generate a full spectrum of colors. These supraballs could be directly added to paints, plastics, and coatings and also used as ultraviolet-resistant inks or cosmetics. PMID:28929137

  16. Bioinspired bright noniridescent photonic melanin supraballs.

    PubMed

    Xiao, Ming; Hu, Ziying; Wang, Zhao; Li, Yiwen; Tormo, Alejandro Diaz; Le Thomas, Nicolas; Wang, Boxiang; Gianneschi, Nathan C; Shawkey, Matthew D; Dhinojwala, Ali

    2017-09-01

    Structural colors enable the creation of a spectrum of nonfading colors without pigments, potentially replacing toxic metal oxides and conjugated organic pigments. However, significant challenges remain to achieve the contrast needed for a complete gamut of colors and a scalable process for industrial application. We demonstrate a feasible solution for producing structural colors inspired by bird feathers. We have designed core-shell nanoparticles using high-refractive index (RI) (~1.74) melanin cores and low-RI (~1.45) silica shells. The design of these nanoparticles was guided by finite-difference time-domain simulations. These nanoparticles were self-assembled using a one-pot reverse emulsion process, which resulted in bright and noniridescent supraballs. With the combination of only two ingredients, synthetic melanin and silica, we can generate a full spectrum of colors. These supraballs could be directly added to paints, plastics, and coatings and also used as ultraviolet-resistant inks or cosmetics.

  17. Modelling Solar and Stellar Brightness Variabilities

    NASA Astrophysics Data System (ADS)

    Yeo, K. L.; Shapiro, A. I.; Krivova, N. A.; Solanki, S. K.

    2016-04-01

    Total and spectral solar irradiance, TSI and SSI, have been measured from space since 1978. This is accompanied by the development of models aimed at replicating the observed variability by relating it to solar surface magnetism. Despite significant progress, there remains persisting controversy over the secular change and the wavelength-dependence of the variation with impact on our understanding of the Sun's influence on the Earth's climate. We highlight the recent progress in TSI and SSI modelling with SATIRE. Brightness variations have also been observed for Sun-like stars. Their analysis can profit from knowledge of the solar case and provide additional constraints for solar modelling. We discuss the recent effort to extend SATIRE to Sun-like stars.

  18. A conserved predicted pseudoknot in the NS2A-encoding sequence of West Nile and Japanese encephalitis flaviviruses suggests NS1' may derive from ribosomal frameshifting

    PubMed Central

    Firth, Andrew E; Atkins, John F

    2009-01-01

    Japanese encephalitis, West Nile, Usutu and Murray Valley encephalitis viruses form a tight subgroup within the larger Flavivirus genus. These viruses utilize a single-polyprotein expression strategy, resulting in ~10 mature proteins. Plotting the conservation at synonymous sites along the polyprotein coding sequence reveals strong conservation peaks at the very 5' end of the coding sequence, and also at the 5' end of the sequence encoding the NS2A protein. Such peaks are generally indicative of functionally important non-coding sequence elements. The second peak corresponds to a predicted stable pseudoknot structure whose biological importance is supported by compensatory mutations that preserve the structure. The pseudoknot is preceded by a conserved slippery heptanucleotide (Y CCU UUU), thus forming a classical stimulatory motif for -1 ribosomal frameshifting. We hypothesize, therefore, that the functional importance of the pseudoknot is to stimulate a portion of ribosomes to shift -1 nt into a short (45 codon), conserved, overlapping open reading frame, termed foo. Since cleavage at the NS1-NS2A boundary is known to require synthesis of NS2A in cis, the resulting transframe fusion protein is predicted to be NS1-NS2AN-term-FOO. We hypothesize that this may explain the origin of the previously identified NS1 'extension' protein in JEV-group flaviviruses, known as NS1'. PMID:19196463

  19. HTS identifies novel and specific uncompetitive inhibitors of the two-component NS2B-NS3 proteinase of West Nile virus.

    PubMed

    Johnston, Paul A; Phillips, Jennifer; Shun, Tong Ying; Shinde, Sunita; Lazo, John S; Huryn, Donna M; Myers, Michael C; Ratnikov, Boris I; Smith, Jeffrey W; Su, Ying; Dahl, Russell; Cosford, Nicholas D P; Shiryaev, Sergey A; Strongin, Alex Y

    2007-12-01

    West Nile virus (WNV), a member of the Flavividae family, is a mosquito-borne, emerging pathogen. In addition to WNV, the family includes dengue, yellow fever, and Japanese encephalitis viruses, which affect millions of individuals worldwide. Because countermeasures are currently unavailable, flaviviral therapy is urgently required. The flaviviral two-component nonstructural NS2B-NS3 proteinase (protease [pro]) is essential for viral life cycle and, consequently, is a promising drug target. We report here the results of the miniaturization of an NS2B-NS3pro activity assay, followed by high-throughput screening of the National Institutes of Health's 65,000 compound library and identification of novel, uncompetitive inhibitors of WNV NS2B-NS3pro that appear to interfere with the productive interactions of the NS2B cofactor with the NS3pro domain. We anticipate that following structure optimization, the identified probes could form the foundation for the design of novel and specific therapeutics for WNV infection. We also provide the structural basis for additional species-selective allosteric inhibitors of flaviviruses.

  20. Nucleoprotein filament formation is the structural basis for bacterial protein H-NS gene silencing

    NASA Astrophysics Data System (ADS)

    Lim, Ci Ji; Lee, Sin Yi; Kenney, Linda J.; Yan, Jie

    2012-07-01

    H-NS is an abundant nucleoid-associated protein in bacteria that globally silences genes, including horizontally-acquired genes related to pathogenesis. Although it has been shown that H-NS has multiple modes of DNA-binding, which mode is employed in gene silencing is still unclear. Here, we report that in H-NS mutants that are unable to silence genes, are unable to form a rigid H-NS nucleoprotein filament. These results indicate that the H-NS nucleoprotein filament is crucial for its gene silencing function, and serves as the fundamental structural basis for gene silencing by H-NS and likely other H-NS-like bacterial proteins.

  1. Trailed Spectra of Bright Spectrophotometric Standard Stars

    NASA Astrophysics Data System (ADS)

    Pitts, Ronald E.

    The IUE archives is an extensive and growing database of UV spectra of a wide variety of astronomical objects. The usefulness of the archives will be greatly enhanced by the presence of a number of wellobserved standard stars including those which define the visual wavelength absolute flux calibrations. Observation of ground-based spectrophotometric standards by IUE will be useful for providing a selfconsistent flux calibration for bright stars and for permitting direct comparisons with fainter standards for future missions, already in the archives, on the IUE system. New observing techniques now make it possible for IUE to obtain well-exposed spectra of these bright stars. However, this observing method is one of the few which may not be possible if IUE were to lose another gyro and the backup control mode, now under development, were used. We propose to obtain short and long wavelength spectra for four of the brightest spectrophotometric standard stars which have either not been observed with with IUE or are poorly represented in the IUE archives. Over a number of years these stars have been observed and defined as standards by a number of ground based observers including Oke(1964), Breger (1976), Stone(1977), Oke and Gunn (1983), and Taylor (1984). The primary standard has been Vega with 109 Vir as an alternate (Davis Philip and Hayes 1984). By combining trailed and point source spectra, ultraviolet absolute flux distributions will be obtained for the 1200-3200 A interval. A comparison will be made of Alpha Lyr and 109 Vir with the nearby star Alpha CMA A, which has a well-determined distance and measured radius. The suspected low-level intermittent variability of Alpha Lyr is not believed to pose major problems for our analysis.

  2. Statistical Properties of Solar Coronal Bright Points

    NASA Astrophysics Data System (ADS)

    Alipour, N.; Safari, H.

    2015-07-01

    Here, we aim to study the statistical properties (i.e., spatial, temporal, and magnetic structures) of extreme ultraviolet coronal bright points (CBPs) observed by SDO during a 4.4 yr period (2010 June 1 to 2014 October 31). We developed the automatic detection method for CBPs based on the machine-learning technique and Zernike image moments. The average number and the mean density of CBPs are estimated to be about 572 (per full disk image taken at 193 Å) and 1.9× {10}-4 Mm-2, respectively. There is a negative correlation (-0.7) between the number of CBPs and the number of sunspots. The size and lifetime frequency distribution of CBPs show the lognormal and power-law (exponent equal to -1.6) behaviors, respectively. The relationship between the lifetime and size of CBPs is clearly treated by a power-law function with an exponent equal to 0.13. Around 1.3% of the solar surface is covered by the bright cores of CBPs and 2.6% of that is covered by their total area. About 52% of CBPs have lifetimes of less than 20 minutes and the remaining 48% have mean lifetimes of 6 hr. More than 95% of CBPs with lifetimes of less than 20 hr and nine CBPs with lifetimes of more than 72 hr are detected. The average number of the new CBPs emerging every 45 s in the whole of the Sun is about 27 ± 3. The temporal self-affinity of the time series of CBPs that emerged, indexed by the Hurst exponent determined using both detrended fluctuation analysis and R/S analysis, is 0.78. This long-temporal correlation suggests that CBPs form a system of self-organized criticality.

  3. The GPM Common Calibrated Brightness Temperature Product

    NASA Technical Reports Server (NTRS)

    Stout, John; Berg, Wesley; Huffman, George; Kummerow, Chris; Stocker, Erich

    2005-01-01

    The Global Precipitation Measurement (GPM) project will provide a core satellite carrying the GPM Microwave Imager (GMI) and will use microwave observations from a constellation of other satellites. Each partner with a satellite in the constellation will have a calibration that meets their own requirements and will decide on the format to archive their brightness temperature (Tb) record in GPM. However, GPM multi-sensor precipitation algorithms need to input intercalibrated Tb's in order to avoid differences among sensors introducing artifacts into the longer term climate record of precipitation. The GPM Common Calibrated Brightness Temperature Product is intended to address this problem by providing intercalibrated Tb data, called "Tc" data, where the "c" stands for common. The precipitation algorithms require a Tc file format that is both generic and flexible enough to accommodate the different passive microwave instruments. The format will provide detailed information on the processing history in order to allow future researchers to have a record of what was done. The format will be simple, including the main items of scan time, latitude, longitude, and Tc. It will also provide spacecraft orientation, spacecraft location, orbit, and instrument scan type (cross-track or conical). Another simplification is to store data in real numbers, avoiding the ambiguity of scaled data. Finally, units and descriptions will be provided in the product. The format is built on the concept of a swath, which is a series of scans that have common geolocation and common scan geometry. Scan geometry includes pixels per scan, sensor orientation, scan type, and incidence angles. The Tc algorithm and data format are being tested using the pre-GPM Precipitation Processing System (PPS) software to generate formats and 1/0 routines. In the test, data from SSM/I, TMI, AMSR-E, and WindSat are being processed and written as Tc products.

  4. The GPM Common Calibrated Brightness Temperature Product

    NASA Technical Reports Server (NTRS)

    Stout, John; Berg, Wesley; Huffman, George; Kummerow, Chris; Stocker, Erich

    2005-01-01

    The Global Precipitation Measurement (GPM) project will provide a core satellite carrying the GPM Microwave Imager (GMI) and will use microwave observations from a constellation of other satellites. Each partner with a satellite in the constellation will have a calibration that meets their own requirements and will decide on the format to archive their brightness temperature (Tb) record in GPM. However, GPM multi-sensor precipitation algorithms need to input intercalibrated Tb's in order to avoid differences among sensors introducing artifacts into the longer term climate record of precipitation. The GPM Common Calibrated Brightness Temperature Product is intended to address this problem by providing intercalibrated Tb data, called "Tc" data, where the "c" stands for common. The precipitation algorithms require a Tc file format that is both generic and flexible enough to accommodate the different passive microwave instruments. The format will provide detailed information on the processing history in order to allow future researchers to have a record of what was done. The format will be simple, including the main items of scan time, latitude, longitude, and Tc. It will also provide spacecraft orientation, spacecraft location, orbit, and instrument scan type (cross-track or conical). Another simplification is to store data in real numbers, avoiding the ambiguity of scaled data. Finally, units and descriptions will be provided in the product. The format is built on the concept of a swath, which is a series of scans that have common geolocation and common scan geometry. Scan geometry includes pixels per scan, sensor orientation, scan type, and incidence angles. The Tc algorithm and data format are being tested using the pre-GPM Precipitation Processing System (PPS) software to generate formats and 1/0 routines. In the test, data from SSM/I, TMI, AMSR-E, and WindSat are being processed and written as Tc products.

  5. In Silico Screening, Alanine Mutation, and DFT Approaches for Identification of NS2B/NS3 Protease Inhibitors

    PubMed Central

    Balajee, R.; Srinivasadesikan, V.; Sakthivadivel, M.; Gunasekaran, P.

    2016-01-01

    To identify the ligand that binds to a target protein with high affinity is a nontrivial task in computer-assisted approaches. Antiviral drugs have been identified for NS2B/NS3 protease enzyme on the mechanism to cleave the viral protein using the computational tools. The consequence of the molecular docking, free energy calculations, and simulation protocols explores the better ligand. It provides in-depth structural insights with the catalytic triad of His51, Asp75, Ser135, and Gly133. The MD simulation was employed here to predict the stability of the complex. The alanine mutation has been performed and its stability was monitored by using the molecular dynamics simulation. The minimal RMSD value suggests that the derived complexes are close to equilibrium. The DFT outcome reveals that the HOMO-LUMO gap of Ligand19 is 2.86 kcal/mol. Among the considered ligands, Ligand19 shows the lowest gap and it is suggested that the HOMO of Ligand19 may transfer the electrons to the LUMO in the active regions. The calculated binding energy of Ligand19 using the DFT method is in good agreement with the docking studies. The pharmacological activity of ligand was performed and satisfies Lipinski rule of 5. Moreover, the computational results are compared with the available IC50 values of experimental results. PMID:27057355

  6. Suitable technological conditions for enzymatic hydrolysis of waste paper by Novozymes® enzymes NS50013 and NS50010.

    PubMed

    Brummer, Vladimir; Skryja, Pavel; Jurena, Tomas; Hlavacek, Viliam; Stehlik, Petr

    2014-10-01

    Waste paper belongs to a group of quantitatively the most produced waste types. Enzymatic hydrolysis is becoming a suitable way to treat this type of waste and at the same time, to produce a valuable liquid biofuel, because reducing sugars solutions that are formed during the process of saccharification can be a precursor for following or simultaneous fermentation. If it will be possible to make the enzymatic hydrolysis of the waste paper economically viable, it could serve as one of the new ways to lower the dependence of the transport sector on oil in the future. Only several studies comparing the enzymatic hydrolysis of different waste papers were performed in the past; they are summarized in this manuscript. In our experimental trials, suitable technological conditions for waste paper enzymatic hydrolysis using enzymes from Novozymes® biomass kit: enzymes NS50013 and NS50010 were investigated. The following enzymatic hydrolysis parameters in laboratory scale trials were verified on high cellulose content substrates-filter paper and cellulose pulp: type of buffer, pH, temperature, concentration of the substrate, loading of the enzyme and rate of stirring.

  7. Note: A rectangular pulse generator for 50 kV voltage, 0.8 ns rise time, and 10 ns pulse width based on polymer-film switch

    NASA Astrophysics Data System (ADS)

    Wu, Hanyu; Zhang, Xinjun; Sun, Tieping; Zeng, Zhengzhong; Cong, Peitian; Zhang, Shaoguo

    2015-10-01

    In this article, we describe a rectangular pulse generator, consisting of a polymer-film switch, a tri-plate transmission line, and parallel post-shaped ceramic resistor load, for 50-kV voltage, 0.8-ns rise time, and 10-ns width. The switch and resistors are arranged in atmospheric air and the transmission line can work in atmospheric air or in transformer oil to change the pulse width from 6.7 ns to 10 ns. The fast switching and low-inductance characteristics of the polymer-film switch ensure the fast rising wavefront of <1 ns. This generator can be applied in the calibration of nanosecond voltage dividers and used for electromagnetic pulse tests as a fast-rising current injection source.

  8. The night sky brightness at McDonald Observatory

    NASA Technical Reports Server (NTRS)

    Kalinowski, J. K.; Roosen, R. G.; Brandt, J. C.

    1975-01-01

    Baseline observations of the night sky brightness in B and V are presented for McDonald Observatory. In agreement with earlier work by Elvey and Rudnick (1937) and Elvey (1943), significant night-to-night and same-night variations in sky brightness are found. Possible causes for these variations are discussed. The largest variation in sky brightness found during a single night is approximately a factor of two, a value which corresponds to a factor-of-four variation in airglow brightness. The data are used to comment on the accuracy of previously published surface photometry of M 81.

  9. Investigation of the moving structures in a coronal bright point

    SciTech Connect

    Ning, Zongjun; Guo, Yang

    2014-10-10

    We have explored the moving structures in a coronal bright point (CBP) observed by the Solar Dynamic Observatory Atmospheric Imaging Assembly (AIA) on 2011 March 5. This CBP event has a lifetime of ∼20 minutes and is bright with a curved shape along a magnetic loop connecting a pair of negative and positive fields. AIA imaging observations show that a lot of bright structures are moving intermittently along the loop legs toward the two footpoints from the CBP brightness core. Such moving bright structures are clearly seen at AIA 304 Å. In order to analyze their features, the CBP is cut along the motion direction with a curved slit which is wide enough to cover the bulk of the CBP. After integrating the flux along the slit width, we get the spacetime slices at nine AIA wavelengths. The oblique streaks starting from the edge of the CBP brightness core are identified as moving bright structures, especially on the derivative images of the brightness spacetime slices. They seem to originate from the same position near the loop top. We find that these oblique streaks are bi-directional, simultaneous, symmetrical, and periodic. The average speed is about 380 km s{sup –1}, and the period is typically between 80 and 100 s. Nonlinear force-free field extrapolation shows the possibility that magnetic reconnection takes place during the CBP, and our findings indicate that these moving bright structures could be the observational outflows after magnetic reconnection in the CBP.

  10. The C. U. Ariëns Kappers brain collection.

    PubMed

    Hofman, Michel A; Johnson, John I

    2011-05-01

    The C. U. Ariëns Kappers brain collection, at the Netherlands Institute for Neuroscience in Amsterdam, is one of the largest and oldest of the world's catalogued repositories of specimens that reveal the course of brain evolution and the resulting panoply of neural biodiversity. Established a century ago, it has served since then as the basis of the encyclopedic texts authored by its founder, as well as research publications into the current time. It consists of 726 specimens: these include 309 mammals, 134 birds, 81 reptiles, 21 amphibians, and 179 "pisces"--a grouping of bony fish, sharks, and cyclostomes. We present here accounts of the history and contents of this treasure trove of research materials. © 2011 New York Academy of Sciences.

  11. N-->S phosphoryl migration in phosphoryl glutathion.

    PubMed

    Yang, H J; Liu, J; Zhao, Y F

    1993-07-01

    It was found that in the case of N-(diisopropylphosphoryl) glutathion (reduced form), 2, N-->S phosphoryl migration took place, but not for N,N-bis(diisopropylphosphoryl) glutathion (oxidized form) or N-diisopropylphosphoryl cysteine. These results were deduced by 31P-NMR tracing experiments. It was shown that phosphoryl migration was catalyzed by an intramolecular carboxyl group, and a mechanism involving a mixed carboxyl-phosphoric anhydride was proposed. A competitive reaction between the amino and thiol group toward diisopropyl phosphite indicated that the phospho-thiol derived from N-(diisopropylphosphoryl) glutathion (reduced form), 2, did not result from direct phosphorylation of the thiol group. N,S-Bis(diisopropylphosphoryl) glutathion provides an authentic sample to confirm the migrated phosphoryl thiol product.

  12. Effects of Early Bright, Late Bright and Dim Illumination upon Circadian Neuroendocrine, Electrophysiological and Behavioral Responses

    DTIC Science & Technology

    1992-07-29

    Electrophysiological and Behavioral Measures. 19. on the Stanford Sleep Scale from 2400 hrs through 0500 hrs (light x time, F= 2.595, p=.02 3...scores on the Stanford Sleep Scale from 2400 hrs through 0500 hrs (light x time, F= 2.595, p=.023). Subjects under the bright light conditions performed...serious safety problem. Night shift personnel and task managers (eg. military officers and skilled military labor) who manage their sleep schedule

  13. Nonstructural protein 3 of the hepatitis C virus encodes a serine-type proteinase required for cleavage at the NS3/4 and NS4/5 junctions.

    PubMed Central

    Bartenschlager, R; Ahlborn-Laake, L; Mous, J; Jacobsen, H

    1993-01-01

    We have studied processing of the nonstructural (NS) polyprotein of the hepatitis C virus. A series of cDNAs corresponding to predicted NS2/3/4 or NS3/4 regions were constructed, and processing of the polyproteins was studied in an in vitro transcription-translation system. We report that a catalytically active serine-type proteinase is encoded by the NS3 region. Substitution of the serine residue of the putative catalytic triad (H, D, and S) by alanine blocked cleavage at the NS3/4 junction, while processing between NS2 and NS3 was not affected. Thus, cleavage at the NS2/3 junction is mediated either by cellular enzymes or by an NS-2 inherent proteinase activity. Deletion analysis of an NS3/4 cDNA construct mapped the amino terminus of the enzymatically active proteinase between amino acids 1049 and 1065 of the polyprotein. As internal deletions of variable segments of the presumed helicase domain prevented processing at the NS314 junction, a continuous NS3 region appears to be required for processing at this site. To analyze hepatitis C virus polyprotein cleavage in vivo, recombinant vaccinia viruses expressing NS2/3/4 or NS3/4/5 proteins were generated. In agreement with the in vitro data, cleavage between NS2 and NS3 was independent of a catalytically active NS3 proteinase, whereas substitution of the active-site serine residue by the amino acid alanine completely blocked processing at the NS3/4 and NS4/5 junctions. These results demonstrate that NS3 encodes the viral proteinase essential for generating the amino termini of NS4 and NS5. Images PMID:8389908

  14. The relation between isolated tree brightness temperature and grass background brightness temperature

    NASA Astrophysics Data System (ADS)

    Krusinger, A. E.

    1983-08-01

    This study involves thermal infrared measurement for the determination of the diurnal and seasonal aspects of the relations between isolated evergreen tress and a cut grass background and between a large truck brightness temperature and cut grass, uncut grass, and bare soil backgrounds. Seasonal changes in the tree brightness temperature-background brightness temperature contrast ranged from 4 to 5 C in February and March to 1 to 2 C in July. At night, the thermal contrast between trees and background was found to vary inversely with long wave incoming radiation, which is a measure of cloudiness. A study of the change in the thermal contrast during the night showed that, during clear weather, the contrast was at a peak a few hours after sundown and decreased the rest of the night. In overcast conditions, a reduced contrast peak occurred at sundown and very gradually diminished through the night. Isothermal conditions were found to occur in the early mornings, and the time of these occurrences changed seasonally, in a systematic manner.

  15. The role of nuclear NS1 protein in highly pathogenic H5N1 influenza viruses.

    PubMed

    Mok, Bobo Wing-Yee; Liu, Honglian; Chen, Pin; Liu, Siwen; Lau, Siu-Ying; Huang, Xiaofeng; Liu, Yen-Chin; Wang, Pui; Yuen, Kwok-Yung; Chen, Honglin

    2017-09-10

    The non-structural protein (NS1) of influenza A viruses (IAV) performs multiple functions during viral infection. NS1 contains two nuclear localization signals (NLS): NLS1 and NLS2. The NS1 protein is located predominantly in the nucleus during the early stages of infection and subsequently exported to the cytoplasm. A nonsense mutation that results in a large deletion in the carboxy-terminal region of the NS1 protein that contains the NLS2 domain was found in some IAV subtypes, including highly pathogenic avian influenza (HPAI) H7N9 and H5N1 viruses. We introduced different mutations into the NLS domains of NS1 proteins in various strains of IAV, and demonstrated that mutation of the NLS2 region in the NS1 protein of HPAI H5N1 viruses severely affects its nuclear localization pattern. H5N1 viruses expressing NS1 protein that is unable to localize to the nucleus are less potent in antagonizing cellular antiviral responses than viruses expressing wild-type NS1. However, no significant difference was observed with respect to viral replication and pathogenesis. In contrast, the replication and antiviral defenses of H1N1 viruses are greatly attenuated when nuclear localization of the NS1 protein is blocked. Our data reveals a novel functional plasticity for NS1 proteins among different IAV subtypes. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  16. High Brightness Neutron Source for Radiography

    SciTech Connect

    Cremer, J. T.; Piestrup, Melvin, A.; Gary, Charles, K.; Harris, Jack, L. Williams, David, J.; Jones, Glenn, E.; Vainionpaa, J. , H.; Fuller, Michael, J.; Rothbart, George, H.; Kwan, J., W.; Ludewigt, B., A.; Gough, R.., A..; Reijonen, Jani; Leung, Ka-Ngo

    2008-12-08

    This research and development program was designed to improve nondestructive evaluation of large mechanical objects by providing both fast and thermal neutron sources for radiography. Neutron radiography permits inspection inside objects that x-rays cannot penetrate and permits imaging of corrosion and cracks in low-density materials. Discovering of fatigue cracks and corrosion in piping without the necessity of insulation removal is possible. Neutron radiography sources can provide for the nondestructive testing interests of commercial and military aircraft, public utilities and petrochemical organizations. Three neutron prototype neutron generators were designed and fabricated based on original research done at the Lawrence Berkeley National Laboratory (LBNL). The research and development of these generators was successfully continued by LBNL and Adelphi Technology Inc. under this STTR. The original design goals of high neutron yield and generator robustness have been achieved, using new technology developed under this grant. In one prototype generator, the fast neutron yield and brightness was roughly 10 times larger than previously marketed neutron generators using the same deuterium-deuterium reaction. In another generator, we integrate a moderator with a fast neutron source, resulting in a high brightness thermal neutron generator. The moderator acts as both conventional moderator and mechanical and electrical support structure for the generator and effectively mimics a nuclear reactor. In addition to the new prototype generators, an entirely new plasma ion source for neutron production was developed. First developed by LBNL, this source uses a spiral antenna to more efficiently couple the RF radiation into the plasma, reducing the required gas pressure so that the generator head can be completely sealed, permitting the possible use of tritium gas. This also permits the generator to use the deuterium-tritium reaction to produce 14-MeV neutrons with increases

  17. Discovery of a bright eclipsing cataclysmic variable

    NASA Astrophysics Data System (ADS)

    Sing, D. K.; Green, E. M.; Howell, S. B.; Holberg, J. B.; Lopez-Morales, M.; Shaw, J. S.; Schmidt, G. D.

    2007-11-01

    Aims:We report on the discovery of J0644+3344, a bright, deeply-eclipsing cataclysmic variable (CV) binary. Methods: Optical photometric and spectroscopic observations were obtained to determine the nature and characteristics of this CV. Results: Spectral signatures of both binary components and an accretion disk can be seen at optical wavelengths. The optical spectrum shows broad H I, He I, and He II accretion disk emission lines with deep narrow absorption components from H I, He I, Mg II, and Ca II. The absorption lines are seen throughout the orbital period, disappearing only during primary eclipse. These absorption lines are either the result of an optically-thick inner accretion disk or from the photosphere of the primary star. Radial velocity measurements show that the H I, He I, and Mg II absorption lines phase with the primary star, while weak absorption features in the continuum, between Hα and Hβ, phase with the secondary star. Radial velocity solutions give a 150±4 km s-1 semi-amplitude for the primary star and 192.8±5.6 km s-1 for the secondary, resulting in a primary to secondary mass ratio of q = 1.285. The individual stellar masses are 0.63-0.69 M⊙ for the primary and 0.49-0.54 M⊙ for the secondary, with the uncertainty largely due to the inclination. Conclusions: The bright eclipsing nature of this binary has helped provide masses for both components with an accuracy rarely achieved for CVs. This binary most closely resembles a nova-like UX UMa or SW Sex type of CV. J0644+3344, however, has a longer orbital period than most UX UMa or SW Sex stars. Assuming an evolution toward shorter orbital periods, J0644+3344 is therefore likely to be a young interacting binary. The secondary star is consistent with the size and spectral type of a K8 star, but has the mass of a M0.

  18. The effect of classical swine fever virus NS5A and NS5A mutants on oxidative stress and inflammatory response in swine testicular cells.

    PubMed

    Dong, Wang; Lv, Huifang; Wang, Yifan; Li, Xiaomeng; Li, Cheng; Wang, Lu; Wang, Chengbao; Guo, Kangkang; Zhang, Yanming

    2017-06-01

    Infection with classical swine fever virus (CSFV) results in highly significant economic losses; this infection is characterized by being highly contagious and accompanied by hyperthermia and systemic bleeding. Oxidative stress (OS) plays a critical role in the pathological process of viral infection. The function of the nonstructural protein 5A (NS5A) in the pathogenesis of CSFV has not been completely understood. Here, OS and the inflammatory response were studied with NS5A and substitution mutants in swine testicular (ST) cells. ST cell lines stably expressing CSFV NS5A or substitution mutants were established. Reactive oxygen species (ROS) production, antioxidant protein expression and inflammatory response were analyzed by quantitative real-time PCR (qRT-PCR), ELISA and flow cytometry analysis. The results showed that CSFV NS5A did not increase ROS production or the antioxidant protein (Trx, HO-1 and PRDX-6) expression in ST cells. However, NS5A inhibited cyclooxygenase-2 (COX-2) expression, a pro-inflammatory protein related to OS. Further studies have shown that NS5A mutants S15A and S92A increased ROS production and inhibited antioxidant protein expression. S15A, S81A and T274A affected the inflammatory response. This study suggested that CSFV NS5A did not induce OS, and amino acids Ser15 and Ser92 of CSFV NS5A were essential for inhibiting OS. Additionally, Ser15, Ser81 and Thr274 played important roles in the inflammatory response in ST cells. These observations provided insight into the function of CSFV NS5A and the mechanism of CSFV persistent infection in ST cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Dengue Virus NS1 Protein Modulates Cellular Energy Metabolism by Increasing Glyceraldehyde-3-Phosphate Dehydrogenase Activity

    PubMed Central

    Allonso, Diego; Andrade, Iamara S.; Conde, Jonas N.; Coelho, Diego R.; Rocha, Daniele C. P.; da Silva, Manuela L.; Ventura, Gustavo T.

    2015-01-01

    ABSTRACT Dengue is one of the main public health concerns worldwide. Recent estimates indicate that over 390 million people are infected annually with the dengue virus (DENV), resulting in thousands of deaths. Among the DENV nonstructural proteins, the NS1 protein is the only one whose function during replication is still unknown. NS1 is a 46- to 55-kDa glycoprotein commonly found as both a membrane-associated homodimer and a soluble hexameric barrel-shaped lipoprotein. Despite its role in the pathogenic process, NS1 is essential for proper RNA accumulation and virus production. In the present study, we identified that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) interacts with intracellular NS1. Molecular docking revealed that this interaction occurs through the hydrophobic protrusion of NS1 and the hydrophobic residues located at the opposite side of the catalytic site. Moreover, addition of purified recombinant NS1 enhanced the glycolytic activity of GAPDH in vitro. Interestingly, we observed that DENV infection promoted the relocalization of GAPDH to the perinuclear region, where NS1 is commonly found. Both DENV infection and expression of NS1 itself resulted in increased GAPDH activity. Our findings indicate that the NS1 protein acts to increase glycolytic flux and, consequently, energy production, which is consistent with the recent finding that DENV induces and requires glycolysis for proper replication. This is the first report to propose that NS1 is an important modulator of cellular energy metabolism. The data presented here provide new insights that may be useful for further drug design and the development of alternative antiviral therapies against DENV. IMPORTANCE Dengue represents a serious public health problem worldwide and is caused by infection with dengue virus (DENV). Estimates indicate that half of the global population is at risk of infection, with almost 400 million cases occurring per year. The NS1 glycoprotein is found in both the

  20. Dengue Virus NS1 Protein Modulates Cellular Energy Metabolism by Increasing Glyceraldehyde-3-Phosphate Dehydrogenase Activity.

    PubMed

    Allonso, Diego; Andrade, Iamara S; Conde, Jonas N; Coelho, Diego R; Rocha, Daniele C P; da Silva, Manuela L; Ventura, Gustavo T; Silva, Emiliana M; Mohana-Borges, Ronaldo

    2015-12-01

    Dengue is one of the main public health concerns worldwide. Recent estimates indicate that over 390 million people are infected annually with the dengue virus (DENV), resulting in thousands of deaths. Among the DENV nonstructural proteins, the NS1 protein is the only one whose function during replication is still unknown. NS1 is a 46- to 55-kDa glycoprotein commonly found as both a membrane-associated homodimer and a soluble hexameric barrel-shaped lipoprotein. Despite its role in the pathogenic process, NS1 is essential for proper RNA accumulation and virus production. In the present study, we identified that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) interacts with intracellular NS1. Molecular docking revealed that this interaction occurs through the hydrophobic protrusion of NS1 and the hydrophobic residues located at the opposite side of the catalytic site. Moreover, addition of purified recombinant NS1 enhanced the glycolytic activity of GAPDH in vitro. Interestingly, we observed that DENV infection promoted the relocalization of GAPDH to the perinuclear region, where NS1 is commonly found. Both DENV infection and expression of NS1 itself resulted in increased GAPDH activity. Our findings indicate that the NS1 protein acts to increase glycolytic flux and, consequently, energy production, which is consistent with the recent finding that DENV induces and requires glycolysis for proper replication. This is the first report to propose that NS1 is an important modulator of cellular energy metabolism. The data presented here provide new insights that may be useful for further drug design and the development of alternative antiviral therapies against DENV. Dengue represents a serious public health problem worldwide and is caused by infection with dengue virus (DENV). Estimates indicate that half of the global population is at risk of infection, with almost 400 million cases occurring per year. The NS1 glycoprotein is found in both the intracellular and the

  1. 7 CFR 51.2000 - Clean and bright.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Clean and bright. 51.2000 Section 51.2000 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Standards for Grades of Filberts in the Shell 1 Definitions § 51.2000 Clean and bright. Clean and...

  2. 7 CFR 51.2000 - Clean and bright.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 2 2011-01-01 2011-01-01 false Clean and bright. 51.2000 Section 51.2000 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Standards for Grades of Filberts in the Shell 1 Definitions § 51.2000 Clean and bright. Clean and...

  3. 7 CFR 51.2000 - Clean and bright.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 2 2012-01-01 2012-01-01 false Clean and bright. 51.2000 Section 51.2000 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Standards for Grades of Filberts in the Shell 1 Definitions § 51.2000 Clean and bright. Clean and...

  4. Analysis of Bright Harvest Remote Analysis for Residential Solar Installations

    SciTech Connect

    Nangle, John; Simon, Joseph

    2015-06-17

    Bright Harvest provides remote shading analysis and design products for residential PV system installers. The National Renewable Energy Laboratory (NREL) through the NREL Commercialization Assistance Program, completed comparative assessments between on-site measurements and remotely calculated values to validate the accuracy of Bright Harvest’s remote shading and power generation.

  5. Spatial Model of Sky Brightness Magnitude in Langkawi Island, Malaysia

    NASA Astrophysics Data System (ADS)

    Redzuan Tahar, Mohammad; Kamarudin, Farahana; Umar, Roslan; Khairul Amri Kamarudin, Mohd; Sabri, Nor Hazmin; Ahmad, Karzaman; Rahim, Sobri Abdul; Sharul Aikal Baharim, Mohd

    2017-03-01

    Sky brightness is an essential topic in the field of astronomy, especially for optical astronomical observations that need very clear and dark sky conditions. This study presents the spatial model of sky brightness magnitude in Langkawi Island, Malaysia. Two types of Sky Quality Meter (SQM) manufactured by Unihedron are used to measure the sky brightness on a moonless night (or when the Moon is below the horizon), when the sky is cloudless and the locations are at least 100 m from the nearest light source. The selected locations are marked by their GPS coordinates. The sky brightness data obtained in this study were interpolated and analyzed using a Geographic Information System (GIS), thus producing a spatial model of sky brightness that clearly shows the dark and bright sky areas in Langkawi Island. Surprisingly, our results show the existence of a few dark sites nearby areas of high human activity. The sky brightness of 21.45 mag arcsec{}-2 in the Johnson-Cousins V-band, as the average of sky brightness equivalent to 2.8 × {10}-4{cd} {{{m}}}-2 over the entire island, is an indication that the island is, overall, still relatively dark. However, the amount of development taking place might reduce the number in the near future as the island is famous as a holiday destination.

  6. Spain 31-GHz observations of sky brightness temperatures

    NASA Technical Reports Server (NTRS)

    Gary, B. L.

    1988-01-01

    A water vapor radiometer was deployed at DSS 63 for 3 months of sky brightness temperature measurements at 31 GHz. An exceedance plot was derived from this data showing the fraction of time that 31 GHz 30 degree elevation angle brightness temperature exceeds specified values. The 5 percent exceedance statistics occurs at 75 K, compared with 70 K in Australia.

  7. Spatial Model of Sky Brightness Magnitude in Langkawi Island, Malaysia

    NASA Astrophysics Data System (ADS)

    Redzuan Tahar, Mohammad; Kamarudin, Farahana; Umar, Roslan; Khairul Amri Kamarudin, Mohd; Hazmin Sabri, Nor; Ahmad, Karzaman; Rahim, Sobri Abdul; Sharul Aikal Baharim, Mohd

    2017-03-01

    Sky brightness is an essential topic in the field of astronomy, especially for optical astronomical observations that need very clear and dark sky conditions. This study presents the spatial model of sky brightness magnitude in Langkawi Island, Malaysia. Two types of Sky Quality Meter (SQM) manufactured by Unihedron are used to measure the sky brightness on a moonless night (or when the Moon is below the horizon), when the sky is cloudless and the locations are at least 100 m from the nearest light source. The selected locations are marked by their GPS coordinates. The sky brightness data obtained in this study were interpolated and analyzed using a Geographic Information System (GIS), thus producing a spatial model of sky brightness that clearly shows the dark and bright sky areas in Langkawi Island. Surprisingly, our results show the existence of a few dark sites nearby areas of high human activity. The sky brightness of 21.45 mag arcsec{}-2 in the Johnson-Cousins V-band, as the average of sky brightness equivalent to 2.8 × {10}-4{cd} {{{m}}}-2 over the entire island, is an indication that the island is, overall, still relatively dark. However, the amount of development taking place might reduce the number in the near future as the island is famous as a holiday destination.

  8. Challenging Exceptionally Bright Children in Early Childhood Classrooms

    ERIC Educational Resources Information Center

    Gadzikowski, Ann

    2013-01-01

    Nearly every group of children includes at least one exceptionally bright child. From the especially creative child to the child who has already mastered learning outcomes to the "twice exceptional" child, exceptionally bright children have a wide range of talents and behaviors. This book will help you understand what it means to be…

  9. Challenging Exceptionally Bright Children in Early Childhood Classrooms

    ERIC Educational Resources Information Center

    Gadzikowski, Ann

    2013-01-01

    Nearly every group of children includes at least one exceptionally bright child. From the especially creative child to the child who has already mastered learning outcomes to the "twice exceptional" child, exceptionally bright children have a wide range of talents and behaviors. This book will help you understand what it means to be…

  10. The Two Intelligences of Bright, Average, and Retarded Children.

    ERIC Educational Resources Information Center

    DeVries, Rheta

    This study attempted to determine if performance on Piagetian tasks can be predicted from Stanford-Binet mental age or IQ. Subjects were 143 children of bright, average, and retarded abilities as measured by performance on the Stanford-Binet Intelligence Test. Bright and average children were chronologically aged five to seven years; retarded…

  11. Apparent Brightness and Topography Images of Vibidia Crater

    NASA Image and Video Library

    2012-03-09

    The left-hand image from NASA Dawn spacecraft shows the apparent brightness of asteroid Vesta surface. The right-hand image is based on this apparent brightness image, with a color-coded height representation of the topography overlain onto it.

  12. Broken Surface Brightness Profiles in Dwarf Galaxies

    NASA Astrophysics Data System (ADS)

    Herrmann, Kimberly A.; Hunter, D. A.; Zhang, H. X.; LITTLE THINGS Team

    2011-01-01

    Recently it has been well shown that there are three different surface brightness profile types in spiral galaxies: (I) the minority, where the light falls off with a single exponential; (II) truncated, the majority, where the light falls off with one exponential to a break radius and then falls off more steeply; and (III) anti-truncated, where the light falls off with a more shallow exponential beyond the break radius. Additionally, Bakos, Trujillo, & Pohlen (2008) showed that each type has a characteristic color trend with respect to the break location. In dwarf disk galaxies, however, there is a fourth type which is perhaps a special Type II case: the light profile is flat on the inside and then falls off exponentially beyond the break radius. We will show the different color trends for these four profile types from a large photometric study of dwarf disk galaxies and explore the ramifications of the differences between spirals and dwarfs. We gratefully acknowledge funding for this research from the National Science Foundation (AST-0707563).

  13. Modular Zero Energy. BrightBuilt Home

    SciTech Connect

    Aldrich, Robb; Butterfield, Karla

    2016-03-01

    Kaplan Thompson Architects (KTA) has specialized in sustainable, energy-efficient buildings, and they have designed several custom, zero-energy homes in New England. These zero-energy projects have generally been high-end, custom homes with budgets that could accommodate advanced energy systems. In an attempt to make zero energy homes more affordable and accessible to a larger demographic, KTA explored modular construction as way to provide high-quality homes at lower costs. In the mid-2013, KTA formalized this concept when they launched BrightBuilt Home (BBH). The BBH mission is to offer a line of architect-designed, high-performance homes that are priced to offer substantial savings off the lifetime cost of a typical home and can be delivered in less time. For the past two years, CARB has worked with BBH and Keiser Homes (the primary modular manufacturer for BBH) to discuss challenges related to wall systems, HVAC, and quality control. In Spring of 2014, CARB and BBH began looking in detail on a home to be built in Lincolnville, ME by Black Bros. Builders. This report details the solution package specified for this modular plan and the challenges that arose during the project.

  14. Bright visible light emission from graphene

    NASA Astrophysics Data System (ADS)

    Kim, Young Duck; Kim, Hakseong; Cho, Yujin; Ryoo, Ji Hoon; Park, Cheol-Hwan; Kim, Pilkwang; Kim, Yong Seung; Lee, Sunwoo; Li, Yilei; Park, Seung-Nam; Shim Yoo, Yong; Yoon, Duhee; Dorgan, Vincent E.; Pop, Eric; Heinz, Tony F.; Hone, James; Chun, Seung-Hyun; Cheong, Hyeonsik; Lee, Sang Wook; Bae, Myung-Ho; Park, Yun Daniel

    2015-08-01

    Graphene and related two-dimensional materials are promising candidates for atomically thin, flexible and transparent optoelectronics. In particular, the strong light-matter interaction in graphene has allowed for the development of state-of-the-art photodetectors, optical modulators and plasmonic devices. In addition, electrically biased graphene on SiO2 substrates can be used as a low-efficiency emitter in the mid-infrared range. However, emission in the visible range has remained elusive. Here, we report the observation of bright visible light emission from electrically biased suspended graphene devices. In these devices, heat transport is greatly reduced. Hot electrons (˜2,800 K) therefore become spatially localized at the centre of the graphene layer, resulting in a 1,000-fold enhancement in thermal radiation efficiency. Moreover, strong optical interference between the suspended graphene and substrate can be used to tune the emission spectrum. We also demonstrate the scalability of this technique by realizing arrays of chemical-vapour-deposited graphene light emitters. These results pave the way towards the realization of commercially viable large-scale, atomically thin, flexible and transparent light emitters and displays with low operation voltage and graphene-based on-chip ultrafast optical communications.

  15. Intercomparisons of nine sky brightness detectors.

    PubMed

    den Outer, Peter; Lolkema, Dorien; Haaima, Marty; van der Hoff, Rene; Spoelstra, Henk; Schmidt, Wim

    2011-01-01

    Nine Sky Quality Meters (SQMs) have been intercompared during a night time measurement campaign held in the Netherlands in April 2011. Since then the nine SQMs have been distributed across The Netherlands and form the Dutch network for monitoring night sky brightness. The goal of the intercomparison was to infer mutual calibration factors and obtain insight into the variability of the SQMs under different meteorological situations. An ensemble average is built from the individual measurements and used as a reference to infer the mutual calibration factors. Data required additional synchronization prior to the calibration determination, because the effect of moving clouds combined with small misalignments emerges as time jitter in the measurements. Initial scatter of the individual instruments lies between ±14%. Individual night time sums range from -16% to +20%. Intercalibration reduces this to 0.5%, and -7% to +9%, respectively. During the campaign the smallest luminance measured was 0.657 ± 0.003 mcd/m(2) on 12 April, and the largest value was 5.94 ± 0.03 mcd/m(2) on 2 April. During both occurrences interfering circumstances like snow cover or moonlight were absent.

  16. The Bright Future of Gravitational Wave Astronomy

    NASA Astrophysics Data System (ADS)

    Gonzalez, Gabriela

    2008-04-01

    These are exciting times in the search for gravitational waves. Gravitational waves are expected from many different astrophysical sources: brief transients from violent events like supernova explosions and collisions of neutron stars and black holes, coalescence of compact binary systems, continuous waves from rotating systems, and stochastic signals from cosmological origin or unresolved transients. The LIGO gravitational wave detectors have achieved unprecedented sensitivity to gravitational waves, and other detectors around the world are expected to reach similar sensitivities. The LIGO Scientific Collaboration (LSC) has recently completed their most sensitive observation run to date with LIGO and GEO detectors, including several months of joint observations with the European VIRGO detector. The LIGO Laboratory and the LSC, as well as the Virgo Collaboration, are actively preparing for operating enhanced detectors in the very near future. The next decade will see the construction and commissioning of Advanced LIGO and VIRGO, and quite possibly the launch of the space-based LISA mission, starting for sure then, if not earlier, a new era for gravitational wave astronomy. Plans for a world-wide network of ground based detectors involving more detectors in Europe, Japan and Australia are becoming more concrete. The future of gravitational wave astronomy is bright indeed! In this talk, will briefly describe the present status of the ground and space based detector projects and discuss the science we may expect to do with the detectors (and detections!) we will have in the upcoming era of gravitational wave astronomy.

  17. NuSTAR Observations of Bright AGNs

    NASA Astrophysics Data System (ADS)

    Elvis, Martin; Ballantyne, D. R.; Blandford, R. D.; Boggs, S.; Boydstun, K.; Brenneman, L.; Cappi, M.; Christensen, F.; Craig, W.; Fabian, A.; Fuerst, F.; Guainazzi, M.; Hailey, C. J.; Harrison, F.; Madejski, G. M.; Marinucci, A.; Matt, G.; Nandra, K.; Reynolds, C. S.; Stern, D.; Walton, D.; Zhang, W.; NuSTAR Team

    2013-01-01

    The dramatically improved signal-to-noise provided by NuSTAR up to ~80 keV allows a qualitative change in our understanding of the X-ray emission of Active Galactic Nuclei (AGNs). Despite intensive investigation for over 30 years, during which the 0.1-10 keV spectra and variability of AGNs have been mapped out in detail, we do not know the origin of the X-ray source in AGNs. The "standard model" of supermassive black hole, accretion disk and relativistic jet does not predict an X-ray source in a straightforward way. It is usually assumed that the X-rays were UV photons from the accretion disk that have been Compton up-scattered in a "hot corona", but the temperature, optical depth and geometry of this corona are unknown - if it exists. NuSTAR enables the measurement of the high energy cut-off of the X-ray spectrum, and so the corona temperature, to be measured precisely for the first time, and tests the relativistic Fe-K line and Compton reflection models. If this model is correct then, with Suzaku and XMM-Newton, NuSTAR can measure black hole spins to high accuracy. We outline the NuSTAR GTO program on bright, unobscured, AGNs including simultaneous observations with Suzaku and XMM-Newton, and show early data.

  18. High output lamp with high brightness

    DOEpatents

    Kirkpatrick, Douglas A.; Bass, Gary K.; Copsey, Jesse F.; Garber, Jr., William E.; Kwong, Vincent H.; Levin, Izrail; MacLennan, Donald A.; Roy, Robert J.; Steiner, Paul E.; Tsai, Peter; Turner, Brian P.

    2002-01-01

    An ultra bright, low wattage inductively coupled electrodeless aperture lamp is powered by a solid state RF source in the range of several tens to several hundreds of watts at various frequencies in the range of 400 to 900 MHz. Numerous novel lamp circuits and components are disclosed including a wedding ring shaped coil having one axial and one radial lead, a high accuracy capacitor stack, a high thermal conductivity aperture cup and various other aperture bulb configurations, a coaxial capacitor arrangement, and an integrated coil and capacitor assembly. Numerous novel RF circuits are also disclosed including a high power oscillator circuit with reduced complexity resonant pole configuration, parallel RF power FET transistors with soft gate switching, a continuously variable frequency tuning circuit, a six port directional coupler, an impedance switching RF source, and an RF source with controlled frequency-load characteristics. Numerous novel RF control methods are disclosed including controlled adjustment of the operating frequency to find a resonant frequency and reduce reflected RF power, controlled switching of an impedance switched lamp system, active power control and active gate bias control.

  19. Dark Skies, Bright Kids Year 6

    NASA Astrophysics Data System (ADS)

    Liss, Sandra; Troup, Nicholas William; Johnson, Kelsey E.; Barcos-Munoz, Loreto D.; Beaton, Rachael; Bittle, Lauren; Borish, Henry J.; Burkhardt, Andrew; Corby, Joanna; Dean, Janice; Hancock, Danielle; King, Jennie; Prager, Brian; Romero, Charles; Sokal, Kimberly R.; Stierwalt, Sabrina; Wenger, Trey; Zucker, Catherine

    2015-01-01

    Now entering our sixth year of operation, Dark Skies, Bright Kids (DSBK) is an entirely volunteer-run outreach organization based out of the Department of Astronomy at the University of Virginia. Our core mission is to enhance elementary science education and literacy in central Virginia through fun, hands-on activities that introduce basic Astronomy concepts beyond Virginia's Standards of Learning. Our primary focus is hosting an 8-10 week after-school astronomy club at underserved elementary and middle schools. Each week, DSBK volunteers take the role of coaches to introduce astronomy-related concepts ranging from the Solar System to galaxies to astrobiology, and to lead students in interactive learning activities. Another hallmark of DSBK is hosting our Annual Central Virginia Star Party, a free event open to the community featuring star-gazing and planetarium shows.DSBK has amassed over 15,000 contact hours since 2009 and we continue to broaden our impact. One important step we have taken in the past year is to establish a graduate student led assessment program to identify and implement directed learning goals for DSBK outreach. The collection of student workbooks, observations, and volunteer surveys indicates broad scale success for the program both in terms of student learning and their perception of science. The data also reveal opportunities to improve our organizational and educational practices to maximize student achievement and overall volunteer satisfaction for DSBK's future clubs and outreach endeavors.

  20. MAGNETIC BRIGHT POINTS IN THE QUIET SUN

    SciTech Connect

    Sanchez Almeida, J.; Bonet, J. A.; Viticchie, B.

    2010-05-20

    We present a visual determination of the number of bright points (BPs) existing in the quiet Sun, which are structures though to trace intense kG magnetic concentrations. The measurement is based on a 0.''1 angular resolution G-band movie obtained with the Swedish Solar Telescope at the solar disk center. We find 0.97 BPs Mm{sup -2}, which is a factor 3 larger than any previous estimate. It corresponds to 1.2 BPs per solar granule. Depending on the details of the segmentation, the BPs cover between 0.9% and 2.2% of the solar surface. Assuming their field strength to be 1.5 kG, the detected BPs contribute to the solar magnetic flux with an unsigned flux density between 13 G and 33 G. If network and inter-network regions are counted separately, they contain 2.2 BPs Mm{sup -2} and 0.85 BPs Mm{sup -2}, respectively.

  1. VP2 Exchange and NS3/NS3a Deletion in African Horse Sickness Virus (AHSV) in Development of Disabled Infectious Single Animal Vaccine Candidates for AHSV

    PubMed Central

    van de Water, Sandra G. P.; van Gennip, René G. P.; Potgieter, Christiaan A.; Wright, Isabel M.

    2015-01-01

    ABSTRACT African horse sickness virus (AHSV) is a virus species in the genus Orbivirus of the family Reoviridae. There are nine serotypes of AHSV showing different levels of cross neutralization. AHSV is transmitted by species of Culicoides biting midges and causes African horse sickness (AHS) in equids, with a mortality rate of up to 95% in naive horses. AHS has become a serious threat for countries outside Africa, since endemic Culicoides species in moderate climates appear to be competent vectors for the related bluetongue virus (BTV). To control AHS, live-attenuated vaccines (LAVs) are used in Africa. We used reverse genetics to generate “synthetic” reassortants of AHSV for all nine serotypes by exchange of genome segment 2 (Seg-2). This segment encodes VP2, which is the serotype-determining protein and the dominant target for neutralizing antibodies. Single Seg-2 AHSV reassortants showed similar cytopathogenic effects in mammalian cells but displayed different growth kinetics. Reverse genetics for AHSV was also used to study Seg-10 expressing NS3/NS3a proteins. We demonstrated that NS3/NS3a proteins are not essential for AHSV replication in vitro. NS3/NS3a of AHSV is, however, involved in the cytopathogenic effect in mammalian cells and is very important for virus release from cultured insect cells in particular. Similar to the concept of the bluetongue disabled infectious single animal (BT DISA) vaccine platform, an AHS DISA vaccine platform lacking NS3/NS3a expression was developed. Using exchange of genome segment 2 encoding VP2 protein (Seg-2[VP2]), we will be able to develop AHS DISA vaccine candidates for all current AHSV serotypes. IMPORTANCE African horse sickness virus is transmitted by species of Culicoides biting midges and causes African horse sickness in equids, with a mortality rate of up to 95% in naive horses. African horse sickness has become a serious threat for countries outside Africa, since endemic Culicoides species in moderate

  2. Infection of Common Marmosets with GB Virus B Chimeric Virus Encoding the Major Nonstructural Proteins NS2 to NS4A of Hepatitis C Virus.

    PubMed

    Zhu, Shaomei; Li, Tingting; Liu, Bochao; Xu, Yuxia; Sun, Yachun; Wang, Yilin; Wang, Yuanzhan; Shuai, Lifang; Chen, Zixuan; Allain, Jean-Pierre; Li, Chengyao

    2016-09-15

    A lack of immunocompetent-small-primate models has been an obstacle for developing hepatitis C virus (HCV) vaccines and affordable antiviral drugs. In this study, HCV/GB virus B (GBV-B) chimeric virus carrying the major nonstructural proteins NS2 to NS4A (HCV NS2 to -4A chimera) was produced and used to infect common marmosets, since HCV NS2 to NS4A proteins are critical proteases and major antigens. Seven marmosets were inoculated intrahepatically with HCV NS2 to -4A chimera RNA for primary infection or intravenously injected with chimera-containing serum for passage infection. Three animals used as controls were injected with phosphate-buffered saline (PBS) or GBV-B, respectively. Six of seven HCV NS2 to -4A chimera-infected marmosets exhibited consistent viremia and one showed transient viremia during the course of follow-up detection. All six infected animals with persistent circulating viremia presented characteristics typical of viral hepatitis, including viral RNA and proteins in hepatocytes and histopathological changes in liver tissue. Viremia was consistently detected for 5 to 54 weeks of follow-up. FK506 immunosuppression facilitated the establishment of persistent chimera infection in marmosets. An animal with chimera infection spontaneously cleared the virus in blood 7 weeks following the first inoculation, but viral-RNA persistence, low-level viral protein, and mild necroinflammation remained in liver tissue. The specific antibody and T-cell response to HCV NS3 in this viremia-resolved marmoset was boosted by rechallenging, but no viremia was detected during 57 weeks of follow-up. The chimera-infected marmosets described can be used as a suitable small-primate animal model for studying novel antiviral drugs and T-cell-based vaccines against HCV infection. HCV infection causes approximately 70% of chronic hepatitis and is frequently associated with primary liver cancer globally. Chimpanzees have been used as a reliable primate model for HCV infection

  3. Quantitative Proteomic Analysis of the Influenza A Virus Nonstructural Proteins NS1 and NS2 during Natural Cell Infection Identifies PACT as an NS1 Target Protein and Antiviral Host Factor

    PubMed Central

    Tawaratsumida, Kazuki; Phan, Van; Hrincius, Eike R.; High, Anthony A.; Webby, Richard; Redecke, Vanessa

    2014-01-01

    ABSTRACT Influenza A virus (IAV) replication depends on the interaction of virus proteins with host factors. The viral nonstructural protein 1 (NS1) is essential in this process by targeting diverse cellular functions, including mRNA splicing and translation, cell survival, and immune defense, in particular the type I interferon (IFN-I) response. In order to identify host proteins targeted by NS1, we established a replication-competent recombinant IAV that expresses epitope-tagged forms of NS1 and NS2, which are encoded by the same gene segment, allowing purification of NS proteins during natural cell infection and analysis of interacting proteins by quantitative mass spectrometry. We identified known NS1- and NS2-interacting proteins but also uncharacterized proteins, including PACT, an important cofactor for the IFN-I response triggered by the viral RNA-sensor RIG-I. We show here that NS1 binds PACT during virus replication and blocks PACT/RIG-I-mediated activation of IFN-I, which represents a critical event for the host defense. Protein interaction and interference with IFN-I activation depended on the functional integrity of the highly conserved RNA binding domain of NS1. A mutant virus with deletion of NS1 induced high levels of IFN-I in control cells, as expected; in contrast, shRNA-mediated knockdown of PACT compromised IFN-I activation by the mutant virus, but not wild-type virus, a finding consistent with the interpretation that PACT (i) is essential for IAV recognition and (ii) is functionally compromised by NS1. Together, our data describe a novel approach to identify virus-host protein interactions and demonstrate that NS1 interferes with PACT, whose function is critical for robust IFN-I production. IMPORTANCE Influenza A virus (IAV) is an important human pathogen that is responsible for annual epidemics and occasional devastating pandemics. Viral replication and pathogenicity depends on the interference of viral factors with components of the host

  4. Inhibition of Hepatitis C Virus NS5B Polymerase by S-Trityl-L-Cysteine Derivatives

    PubMed Central

    Nichols, Daniel B.; Fournet, Guy; Gurukumar, K. R.; Basu, Amartya; Lee, Jin-Ching; Sakamoto, Naoya; Kozielski, Frank; Musmuca, Ira; Joseph, Benoît; Ragno, Rino; Kaushik-Basu, Neerja

    2012-01-01

    Structure-based studies led to the identification of a constrained derivative of S-trityl-L-cysteine (STLC) scaffold as a candidate inhibitor of hepatitis C virus (HCV) NS5B polymerase. A panel of STLC derivatives were synthesized and investigated for their activity against HCV NS5B. Three STLC derivatives, 9, F-3070, and F-3065, were identified as modest HCV NS5B inhibitors with IC50 values between 22.3 to 39.7 μM. F-3070 and F-3065 displayed potent inhibition of intracellular NS5B activity in the BHK-NS5B-FRLuc reporter and also inhibited HCV RNA replication in the Huh7/Rep-Feo1b reporter system. Binding mode investigations suggested that the STLC scaffold can be used to develop new NS5B inhibitors by further chemical modification at one of the trityl phenyl group. PMID:22280819

  5. Structure of NS1A effector domain from the influenza A/Udorn/72 virus

    SciTech Connect

    Xia, Shuangluo; Monzingo, Arthur F.; Robertus, Jon D.

    2009-01-01

    The structure of the effector domain of the influenza protein NS1, a validated antiviral drug target, has been solved in two space groups. The nonstructural protein NS1A from influenza virus is a multifunctional virulence factor and a potent inhibitor of host immunity. It has two functional domains: an N-terminal 73-amino-acid RNA-binding domain and a C-terminal effector domain. Here, the crystallographic structure of the NS1A effector domain of influenza A/Udorn/72 virus is presented. Structure comparison with the NS1 effector domain from mouse-adapted influenza A/Puerto Rico/8/34 (PR8) virus strain reveals a similar monomer conformation but a different dimer interface. Further analysis and evaluation shows that the dimer interface observed in the structure of the PR8 NS1 effector domain is likely to be a crystallographic packing effect. A hypothetical model of the intact NS1 dimer is presented.

  6. Characterization of Bombyx mori parvo-like virus non-structural protein NS1.

    PubMed

    Li, Guohui; Sun, Chen; Zhang, Junhong; He, Yuanqing; Chen, Huiqing; Kong, Jie; Huang, Guoping; Chen, Keping; Yao, Qin

    2009-12-01

    NS1 gene of Bombyx mori parvo-like virus (China Zhenjiang isolate, BmDNV-Z) codes a predicted 316-amino acid protein, but its function remains unknown. Results of the current study showed that purified recombinant 6 x His-NS1 protein possesses ATP binding, ATPase, DNA binding, and helicase activities. Only one protein was captured in infected Bombyx mori midgut cells against NS1 target protein by employing co-immunoprecipitation, which was identified to be a viral protein by mass spectrometry. The NS1-interacting protein is encoded by BmDNV-Z ORF4 and its molecular is about 100 kD. Analysis of His pull-down confirmed that binding of identified viral protein to purified recombinant 6 x His-NS1 protein in vitro. Taken together, our results indicated that BmDNV-Z NS1 was a multifunctional protein, which may be involved with virus replication.

  7. Intracellular degradation and localization of NS1 of TBEV affects its protective properties.

    PubMed

    Kuzmenko, Yulia; Starodubova, Elizaveta; Shevtsova, Anastasia; Chernokhaeva, Lubov; Latanova, Anastasia; Preobrazhenskaia, Olga; Timofeev, Andrey; Karganova, Galina; Karpov, Vadim

    2016-12-30

    Currently many DNA vaccines against infectious diseases are in clinical trials however their efficacy is needed to be improved. Potency of DNA immunogen can be optimized by targeting technologies. In a current study to increase the efficacy of NS1encoded by plasmid the proteasome targeting was applied. NS1 variants with or without translocation sequence and with signal of proteasomal degradation of ornithine decarboxylase were tested for expression, localization, protein turnover, proteasomal degradation and protection properties. Deletion of translocation signal abrogated presentation of NS1 on the cell surface and increased proteasomal processing of NS1. Fusion with ODC signal led to increase of protein turnover and proteasome degradation rate of NS1. Immunization with NS1 variants with increased proteasome processing protected mice from viral challenge only partially, however, the survival time of infected mice was prolonged in these groups. This data can give a presupposition for formulation of specific immune therapy for infected individuals.

  8. The changing photoionized plasma in the bright Low-Mass X-ray binary GX 13+1

    NASA Astrophysics Data System (ADS)

    Diaz Trigo, Maria

    2006-10-01

    We propose five 10 ks XMM-Newton observations of GX13+1, the brightest low-mass X-ray binary (LMXB) which exhibits strong X-ray absorption features. Such features have been observed in a number of LMXBs and are identified with ions such as Fe XXV and Fe XXVI. GX13+1 is the best source to study the variations in the lines with the intensity of the source due to its both high and strongly variable luminosity. We will test whether the absorption lines detected in GX13+1 by XMM-Newton and Chandra are consistent with the presence of a highly-ionized absorber located around the accretion disk, similar to other LMXBs and study the changes of such absorber. This reveals dynamics of the disk wind, which commonly exists in high luminosity accretion-disk systems as galactic binaries and AGNs.

  9. The NS5A protein of hepatitis C virus is a zinc metalloprotein.

    PubMed

    Tellinghuisen, Timothy L; Marcotrigiano, Joseph; Gorbalenya, Alexander E; Rice, Charles M

    2004-11-19

    The NS5A protein of hepatitis C virus is believed to be an integral part of the viral replicase. Despite extensive investigation, the role of this protein remains elusive. Only limited biochemical characterization of NS5A has been performed, with most research to date involving the myriad of host proteins and signaling cascades that interact with NS5A. The need for better characterization of NS5A is paramount for elucidating the role of this protein in the virus life cycle. Examination of NS5A using bioinformatics tools suggested the protein consisted of three domains and contained an unconventional zinc binding motif within the N-terminal domain. We have developed a method to produce NS5A and performed limited proteolysis to confirm the domain organization model. The zinc content of purified NS5A and the N-terminal domain of NS5A was determined, and each of these proteins was found to coordinate one zinc atom per protein. The predicted zinc binding motif consists of four cysteine residues, conserved among the Hepacivirus and Pestivirus genera, fitting the formula of CX17CXCX20C. Mutation of any of the four cysteine components of this motif reduced NS5A zinc coordination and led to a lethal phenotype for HCV RNA replication, whereas mutation of other potential metal coordination residues in the N-terminal domain of NS5A, but outside the zinc binding motif, had little effect on zinc binding and, aside from one exception, were tolerated for replication. Collectively, these results indicate that NS5A is a zinc metalloprotein and that zinc coordination is likely required for NS5A function in the hepatitis C replicase.

  10. Daclatasvir inhibits hepatitis C virus NS5A motility and hyper-accumulation of phosphoinositides

    PubMed Central

    Chukkapalli, Vineela; Berger, Kristi L.; Kelly, Sean M.; Thomas, Meryl; Deiters, Alexander; Randall, Glenn

    2014-01-01

    Combinations of direct-acting antivirals (DAAs) against the hepatitis C virus (HCV) have the potential to revolutionize the HCV therapeutic regime. An integral component of DAA combination therapies are HCV NS5A inhibitors. It has previously been proposed that NS5A DAAs inhibit two functions of NS5A: RNA replication and virion assembly. In this study, we characterize the impact of a prototype NS5A DAA, daclatasvir (DCV), on HCV replication compartment formation. DCV impaired HCV replicase localization and NS5A motility. In order to characterize the mechanism behind altered HCV replicase localization, we examined the impact of DCV on the interaction of NS5A with its essential cellular cofactor, phosphatidylinositol-4-kinase III α (PI4KA). We observed that DCV does not inhibit PI4KA directly, nor does it impair early events of the NS5A-PI4KA interaction that can occur when NS5A is expressed alone. NS5A functions that are unaffected by DCV include PI4KA binding, as determined by co-immunoprecipitation, and a basal accumulation of the PI4KA product, PI4P. However, DCV impairs late steps in PI4KA activation that requires NS5A expressed in the context of the HCV polyprotein. These NS5A functions include hyper-stimulation of PI4P levels and appropriate replication compartment formation. The data are most consistent with a model wherein DCV inhibits conformational changes in the NS5A protein or protein complex formations that occur in the context of HCV polyprotein expression and stimulate PI4P hyper-accumulation and replication compartment formation. PMID:25546252

  11. H-NS Facilitates Sequence Diversification of Horizontally Transferred DNAs during Their Integration in Host Chromosomes

    PubMed Central

    Higashi, Koichi; Tobe, Toru; Kanai, Akinori; Uyar, Ebru; Ishikawa, Shu; Suzuki, Yutaka; Ogasawara, Naotake; Kurokawa, Ken; Oshima, Taku

    2016-01-01

    Bacteria can acquire new traits through horizontal gene transfer. Inappropriate expression of transferred genes, however, can disrupt the physiology of the host bacteria. To reduce this risk, Escherichia coli expresses the nucleoid-associated protein, H-NS, which preferentially binds to horizontally transferred genes to control their expression. Once expression is optimized, the horizontally transferred genes may actually contribute to E. coli survival in new habitats. Therefore, we investigated whether and how H-NS contributes to this optimization process. A comparison of H-NS binding profiles on common chromosomal segments of three E. coli strains belonging to different phylogenetic groups indicated that the positions of H-NS-bound regions have been conserved in E. coli strains. The sequences of the H-NS-bound regions appear to have diverged more so than H-NS-unbound regions only when H-NS-bound regions are located upstream or in coding regions of genes. Because these regions generally contain regulatory elements for gene expression, sequence divergence in these regions may be associated with alteration of gene expression. Indeed, nucleotide substitutions in H-NS-bound regions of the ybdO promoter and coding regions have diversified the potential for H-NS-independent negative regulation among E. coli strains. The ybdO expression in these strains was still negatively regulated by H-NS, which reduced the effect of H-NS-independent regulation under normal growth conditions. Hence, we propose that, during E. coli evolution, the conservation of H-NS binding sites resulted in the diversification of the regulation of horizontally transferred genes, which may have facilitated E. coli adaptation to new ecological niches. PMID:26789284

  12. H-NS Facilitates Sequence Diversification of Horizontally Transferred DNAs during Their Integration in Host Chromosomes.

    PubMed

    Higashi, Koichi; Tobe, Toru; Kanai, Akinori; Uyar, Ebru; Ishikawa, Shu; Suzuki, Yutaka; Ogasawara, Naotake; Kurokawa, Ken; Oshima, Taku

    2016-01-01

    Bacteria can acquire new traits through horizontal gene transfer. Inappropriate expression of transferred genes, however, can disrupt the physiology of the host bacteria. To reduce this risk, Escherichia coli expresses the nucleoid-associated protein, H-NS, which preferentially binds to horizontally transferred genes to control their expression. Once expression is optimized, the horizontally transferred genes may actually contribute to E. coli survival in new habitats. Therefore, we investigated whether and how H-NS contributes to this optimization process. A comparison of H-NS binding profiles on common chromosomal segments of three E. coli strains belonging to different phylogenetic groups indicated that the positions of H-NS-bound regions have been conserved in E. coli strains. The sequences of the H-NS-bound regions appear to have diverged more so than H-NS-unbound regions only when H-NS-bound regions are located upstream or in coding regions of genes. Because these regions generally contain regulatory elements for gene expression, sequence divergence in these regions may be associated with alteration of gene expression. Indeed, nucleotide substitutions in H-NS-bound regions of the ybdO promoter and coding regions have diversified the potential for H-NS-independent negative regulation among E. coli strains. The ybdO expression in these strains was still negatively regulated by H-NS, which reduced the effect of H-NS-independent regulation under normal growth conditions. Hence, we propose that, during E. coli evolution, the conservation of H-NS binding sites resulted in the diversification of the regulation of horizontally transferred genes, which may have facilitated E. coli adaptation to new ecological niches.

  13. Molecular dynamics simulations of Zika virus NS3 helicase: Insights into RNA binding site activity.

    PubMed

    Mottin, Melina; Braga, Rodolpho C; da Silva, Roosevelt A; Silva, Joao H Martins da; Perryman, Alexander L; Ekins, Sean; Andrade, Carolina Horta

    2017-03-21

    America is still suffering with the outbreak of Zika virus (ZIKV) infection. Congenital ZIKV syndrome has already caused a public health emergency of international concern. However, there are still no vaccines to prevent or drugs to treat the infection caused by ZIKV. The ZIKV NS3 helicase (NS3h) protein is a promising target for drug discovery due to its essential role in viral genome replication. NS3h unwinds the viral RNA to enable the replication of the viral genome by the NS5 protein. NS3h contains two important binding sites: the NTPase binding site and the RNA binding site. Here, we used molecular dynamics (MD) simulations to study the molecular behavior of ZIKV NS3h in the presence and absence of ssRNA and the potential implications for NS3h activity and inhibition. Although there is conformational variability and poor electron densities of the RNA binding loop in various apo flaviviruses NS3h crystallographic structures, the MD trajectories of NS3h-ssRNA demonstrated that the RNA binding loop becomes more stable when NS3h is occupied by RNA. Our results suggest that the presence of RNA generates important interactions with the RNA binding loop, and these interactions stabilize the loop sufficiently that it remains in a closed conformation. This closed conformation likely keeps the ssRNA bound to the protein for a sufficient duration to enable the unwinding/replication activities of NS3h to occur. In addition, conformational changes of this RNA binding loop can change the nature and location of the optimal ligand binding site, according to ligand binding site prediction results. These are important findings to help guide the design and discovery of new inhibitors of NS3h as promising compounds to treat the ZIKV infection.

  14. Functional differences in hepatitis C virus nonstructural (NS) 3/4A- and 5A-specific T cell responses

    PubMed Central

    Holmström, Fredrik; Chen, Margaret; Balasiddaiah, Anangi; Sällberg, Matti; Ahlén, Gustaf; Frelin, Lars

    2016-01-01

    The hepatitis C virus nonstructural (NS) 3/4A and NS5A proteins are major targets for the new direct-acting antiviral compounds. Both viral proteins have been suggested as modulators of the response to the host cell. We have shown that NS3/4A- and NS5A-specific T cell receptors confer different effector functions, and that killing of NS3/4A-expressing hepatocytes is highly dependent on IFN-γ. We here characterize the functional differences in the T cell responses to NS3/4A and NS5A. NS3/4A- and NS5A-specific T cells could be induced at various frequencies in wild-type-, NS3/4A-, and NS5A-transgenic mice. Priming of NS5A-specific T cells required a high DNA dose, and was unlike NS3/4A dependent on both CD4+ and CD8+ T cells, but less influenced by CD25+/GITR+ regulatory T cells. The presence of IL-12 greatly improved specific CD8+ T cell priming by NS3/4A but not by NS5A, suggesting a less dependence of IFN-γ for NS5A. This notion was supported by the observation that NS5A-specific T cells could eliminate NS5A-expressing hepatocytes also in the absence of IFN-γ-receptor-2. This supports that NS3/4A- and NS5A-specific T cells become activated and eliminate antigen expressing, or infected hepatocytes, by distinct mechanisms, and that NS5A-specific T cells show an overall less dependence of IFN-γ. PMID:27141891

  15. Artefactual cleavage of E coli H-NS by OmpT.

    PubMed

    Goldberg, M D; Canvin, J R; Freestone, P; Andersen, C; Laoudj, D; Williams, P H; Holland, I B; Norris, V

    1997-06-01

    In the bacterium Escherichia coli, H-NS-(H1, H1a) is a heat-stable protein with a molecular mass of 15.5 kDa involved in nucleoid organisation and gene regulation linked to certain signal transduction pathways. We have shown that, following addition of preparations of everted inner membrane vesicles, heat-stable cleavage products of approximately 10 kDa of H-NS are formed in vitro from newly synthesised, radio-labelled H-NS and from purified H-NS. The 15.5 kDa protein and its cleavage products were also recovered from a minicell system. These results raised the possibility that cleavage of H-NS is physiologically significant. However, the cleavage of H-NS observed appears to occur during cell breakage and to depend on the method of protein extraction and the presence of the outer membrane protease, OmpT. Nevertheless, the results indicate that H-NS may contain at least two separate domains with cleavage occurring between these domains at a preferred OmpT site. Failure to take account of H-NS cleavage in sample preparation and analysis can lead to serious underestimation of H-NS levels.

  16. Production of recombinant dengue non-structural 1 (NS1) proteins from clinical virus isolates.

    PubMed

    Yohan, Benediktus; Wardhani, Puspa; Aryati; Trimarsanto, Hidayat; Sasmono, R Tedjo

    2017-01-01

    Dengue is a febrile disease caused by infection of dengue virus (DENV). Early diagnosis of dengue infection is important for better management of the disease. The DENV Non-Structural Protein 1 (NS1) antigen has been routinely used for the early dengue detection. In dengue epidemic countries such as Indonesia, clinicians are increasingly relying on the NS1 detection for confirmation of dengue infection. Various NS1 diagnostic tests are commercially available, however different sensitivities and specificities were observed in various settings. This study was aimed to generate dengue NS1 recombinant protein for the development of dengue diagnostic tests. Four Indonesian DENV isolates were used as the source of the NS1 gene cloning, expression, and purification in bacterial expression system. Recombinant NS1 proteins were successfully purified and their antigenicities were assessed. Immunization of mice with recombinant proteins observed the immunogenicity of the NS1 protein. The generated recombinant proteins can be potentially used in the development of NS1 diagnostic test. With minimal modifications, this method can be used for producing NS1 recombinant proteins from isolates obtained from other geographical regions. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Approaches to hepatitis C treatment and cure using NS5A inhibitors

    PubMed Central

    Kohler, James J; Nettles, James H; Amblard, Franck; Hurwitz, Selwyn J; Bassit, Leda; Stanton, Richard A; Ehteshami, Maryam; Schinazi, Raymond F

    2014-01-01

    Recent progress in the understanding of hepatitis C virus (HCV) biology and the availability of in vitro models to study its replication have facilitated the development of direct-acting antiviral agents (DAAs) that target specific steps in the viral replication cycle. Currently, there are three major classes of DAA in clinical development: NS3/4A protease inhibitors, NS5B polymerase inhibitors, and NS5A directed inhibitors. Several compounds thought to bind directly with NS5A are now in various clinical trial phases, including the most advanced, daclatasvir (BMS-790052), ledipasvir (GS-5885), and ABT-267. While many NS5A-targeted compounds demonstrate picomolar potency, the exact mechanism(s) of their action is still unclear. In the clinic, NS5A HCV inhibitors show promise as important components in DAA regimens and have multifunctionality. In addition to inhibiting viral replication, they may synergize with other DAAs, possibly by modulating different viral proteins, to help suppress the emergence of resistant viruses. Structure-based models have identified target interaction domains and spatial interactions that explain drug resistance for mutations at specific positions (eg, residues 93 and 31) within NS5A and potential binding partners. This review provides, insights into the unique complexity of NS5A as a central platform for multiple viral/host protein interactions, and possible mechanism(s) for the NS5A inhibitors currently undergoing clinical trials that target this nonstructural viral protein. PMID:24623983

  18. Attenuation of equine influenza viruses through truncations of the NS1 protein.

    PubMed

    Quinlivan, Michelle; Zamarin, Dmitriy; García-Sastre, Adolfo; Cullinane, Ann; Chambers, Thomas; Palese, Peter

    2005-07-01

    Equine influenza is a common disease of the horse, causing significant morbidity worldwide. Here we describe the establishment of a plasmid-based reverse genetics system for equine influenza virus. Utilizing this system, we generated three mutant viruses encoding carboxy-terminally truncated NS1 proteins. We have previously shown that a recombinant human influenza virus lacking the NS1 gene (delNS1) could only replicate in interferon (IFN)-incompetent systems, suggesting that the NS1 protein is responsible for IFN antagonist activity. Contrary to previous findings with human influenza virus, we found that in the case of equine influenza virus, the length of the NS1 protein did not correlate with the level of attenuation of that virus. With equine influenza virus, the mutant virus with the shortest NS1 protein turned out to be the least attenuated. We speculate that the basis for attenuation of the equine NS1 mutant viruses generated is related to their level of NS1 protein expression. Our findings show that the recombinant mutant viruses are impaired in their ability to inhibit IFN production in vitro and they do not replicate as efficiently as the parental recombinant strain in embryonated hen eggs, in MDCK cells, or in vivo in a mouse model. Therefore, these attenuated mutant NS1 viruses may have potential as candidates for a live equine influenza vaccine.

  19. Expression of dengue virus NS3 protein in Drosophila alters its susceptibility to infection

    PubMed Central

    Querenet, Matthieu; Danjoy, Marie-Laure; Mollereau, Bertrand; Davoust, Nathalie

    2015-01-01

    We developed a Drosophila model in which the dengue virus NS3 protein is expressed in a tissue specific and inducible manner. Dengue virus NS3 is a multifunctional protein playing a major role during viral replication. Both protease and helicase domains of NS3 are interacting with human and insect host proteins including innate immune components of the host machinery. We characterized the NS3 transgenic flies showing that NS3 expression did not affect fly development. To further study the links between NS3 and the innate immune response, we challenge the flies with gram-positive and gram-negative bacteria. Interestingly, the Drosophila transgenic flies expressing NS3 were more susceptible to bacterial infections than control flies. However ubiquitous or immune-specific NS3 expression affected neither the life span nor the response to a non-infectious stress of the flies. In conclusion, we generated a new in vivo system to study the functional impact of DENV NS3 protein on the innate immune response. PMID:26267447

  20. Time stamping of single optical photons with 10 ns resolution

    NASA Astrophysics Data System (ADS)

    Chakaberia, Irakli; Cotlet, Mircea; Fisher-Levine, Merlin; Hodges, Diedra R.; Nguyen, Jayke; Nomerotski, Andrei

    2017-05-01

    High spatial and temporal resolution are key features for many modern applications, e.g. mass spectrometry, probing the structure of materials via neutron scattering, studying molecular structure, etc.1-5 Fast imaging also provides the capability of coincidence detection, and the further addition of sensitivity to single optical photons with the capability of timestamping them further broadens the field of potential applications. Photon counting is already widely used in X-ray imaging,6 where the high energy of the photons makes their detection easier. TimepixCam is a novel optical imager,7 which achieves high spatial resolution using an array of 256×256 55 μm × 55μm pixels which have individually controlled functionality. It is based on a thin-entrance-window silicon sensor, bump-bonded to a Timepix ASIC.8 TimepixCam provides high quantum efficiency in the optical wavelength range (400-1000 nm). We perform the timestamping of single photons with a time resolution of 20 ns, by coupling TimepixCam to a fast image-intensifier with a P47 phosphor screen. The fast emission time of the P479 allows us to preserve good time resolution while maintaining the capability to focus the optical output of the intensifier onto the 256×256 pixel Timepix sensor area. We demonstrate the capability of the (TimepixCam + image intensifier) setup to provide high-resolution single-photon timestamping, with an effective frame rate of 50 MHz.

  1. Nitrogen oxide removal dynamic process through 15 Ns DBD technique

    NASA Astrophysics Data System (ADS)

    Wang, Xiaojun; Zhang, Lianshui; Lai, Weidong; Liu, Fengliang

    2015-05-01

    Nitrogen oxides exhaust gas assumes the important responsibility on air pollution by forming acid rain. This paper discusses the NO removal mechanism in 15 ns pulse dielectric barrier discharge (DBD) plasma through experimental and simulating method. Emission spectra collected from plasma are evaluated as sourced from N+ and O(3P). The corresponding zero-dimensional model is established and verified through comparing the simulated concentration evolution and the experimental time-resolved spectra of N+. The electron impact ionization plays major role on NO removal and the produced NO+ are further decomposed into N+ and O(3P) through electron impact dissociative excitation rather than the usual reported dissociative recombination process. Simulation also indicates that the removal process can be accelerated by NO inputted at lower initial concentration or electrons streamed at higher concentration, due to the heightened electron impact probability on NO molecules. The repetitive pulse discharge is a benefit for improving the NO removal efficiency by effectively utilizing the radicals generated from the previous pulse under the condition that the pulse period should be shorter enough to ignore the spatial diffusion of radicals. Finally, slight attenuation on NO removal has been experimentally and simulatively observed after N2 mixed, due to the competitive consumption of electrons.

  2. Comments on D-brane dynamics near NS5-branes

    NASA Astrophysics Data System (ADS)

    Sahakyan, David A.

    2004-10-01

    We study the properties of a D-brane in the presence of k NS5 branes. The Dirac-Born-Infeld action describing the dynamics of this D-brane is very similar to that of a non-BPS D-brane in ten dimensions. As the D-brane approaches the fivebranes, its equation of state approaches that of a pressureless fluid. In non-BPS D-brane case this is considered as an evidence for the decay of the D-brane into ``tachyon matter''. We show that in our case similar behavior is the consequence of the motion of the D-brane. In particular in the rest frame of the moving D-brane the equation of state is that of a usual D-brane, for which the pressure is equal to the energy density. We also compute the total cross-section for the decay of the D-brane into closed string modes and show that the emitted energy has a power like divergence for D0, D1 and D2 branes, while converges for higher dimensional D-branes. We also speculate on the possibility that the infalling D-brane describes a decaying defect in six dimensional Little String Theory.

  3. Dark Skies, Bright Kids! Year 3

    NASA Astrophysics Data System (ADS)

    Whelan, David G.; Johnson, K. E.; Barcos-Munoz, L. D.; Beaton, R. L.; Borish, J.; Corby, J. F.; Dorsey, G.; Gugliucci, N. E.; Prager, B. J.; Ries, P. A.; Romero, C. E.; Sokal, K. R.; Tang, X.; Walker, L. M.; Yang, A. J.; Zasowski, G.

    2012-01-01

    Dark Skies, Bright Kids! (DSBK) is a program that brings astronomy education to elementary schools throughout central Virginia. In a relaxed, out-of-classroom atmosphere, we are able to foster the innate curiosity that young students have about science and the world around them. We target schools that are under-served due to their rural locale or special needs students, demonstrating that science is a fun and creative process to a segment of the population that might not otherwise be exposed to astronomy. Families are included in the learning experience during semi-annual `star parties'. Since last January, we have expanded the breadth and depth of our educational capabilities. We have developed new programs for use in our digital planetarium. We held the first Central Virginia Star Party, providing an atmosphere where local children from multiple schools were able to share their love for astronomy. Local government and University officials were also invited so that they could experience our focused science outreach. Most recently, we have become part of Ivy Creek School's Club Day activities, bringing our program to a new segment of the elementary school system in Albemarle County: those that have `low-incidence' disabilities, requiring special attention. We continue to develop a curriculum for after-school programs that functions as either a series of one-time activities or several months of focused outreach at one school. Many of these activities are provided on our website, http://www.astro.virginia.edu/dsbk/, for the wider astronomical community, including the new planetarium work. We have extended our book project to include two bilingual astronomy books called `Snapshots of the Universe,' one in Spanish and English, the other in French and English. These books introduce young people to some of the many wonders of the Universe through art and captions developed by DSBK volunteers.

  4. Dark Skies, Bright Kids! Year 4

    NASA Astrophysics Data System (ADS)

    Sokal, Kimberly R.; Johnson, K. E.; Barcos-Munoz, L. D.; Beaton, R.; Borish, J.; Crawford, S. B.; Corby, J.; Damke, G.; Dean, J.; Dorsey, G.; Jackson, L.; Liss, S.; Oza, A.; Peacock, S.; Prager, B.; Romero, C.; Sivakoff, G. R.; Walker, L.; Whelan, D. G.; Zucker, C.

    2013-01-01

    Aiming to engage young children's natural excitement and curiosity, the outreach group Dark Skies, Bright Kids (DSBK) brings a hands-on approach to astronomy to elementary schools in Virginia. We hope to enhance children's view and understanding of science while exploring the Universe using fun activities. DSBK focuses on rural and underserved schools in Albemarle County and offers a semester-long astronomy club for third through fifth grade students. We believe regular interactions foster personal relationships between students and volunteers that encourage a life-long interest in science. In our fourth year of hosting clubs, we returned to Ivy Creek Elementary School, where we saw wonderful responses from a special group of students with `low-incidence' disabilities. DSBK has grown to realize a broader reach beyond local astronomy clubs; we hope to ignite a spark of interest in astronomy and science more widely- in more children, their families, and their teachers. We also hosted the Second Annual Central Virginia Star Party with an open invitation to the community to encourage families to enjoy astronomy together. Throughout the year, DSBK now holds 'one-off' programs (akin to astronomy field days) for elementary schools and children's groups throughout Virginia. Furthermore, we are in the final stages of a project to create two bilingual astronomy books called "Snapshots of the Universe", in Spanish and French with English translations. This art book will be made available online and we are working to get a copy in every elementary school in the state. DSBK has begun to reach out to elementary school teachers in order to provide them with useful and engaging classroom material. We have adapted our volunteer-created activities into useful and ready-to-use lessons, available online. After improvements based on research through interactions and feedback from teachers, we have explicitly identified the learning goals in terms of Virginia's Standards of Learning

  5. Bright Times for an Ancient Star

    NASA Astrophysics Data System (ADS)

    Fuhrmann, K.; Chini, R.

    2017-01-01

    Field stars of Population II are among the oldest sources in the Galaxy. Most of their solar-type dwarfs are non-single and, given their extreme age, a significant fraction is accompanied by stellar remnants. Here we report the discovery of the bright F7V star 49 Lib as a massive and very metal-rich Population II field blue straggler, along with evidence for a white dwarf as its dark and unseen companion. 49 Lib is known as a relatively fast-rotating, single-lined spectroscopic binary in a 3 year orbit and with an apparent age of about τ ≃ 2.3 Gyr. Its chemistry and kinematics, however, both consistently imply that 49 Lib must be an ancient Population II star at τ ≃ 12 Gyr. With reference to the inclination from the astrometric orbit, leading to a {M}{WD}={0.50}-0.04+0.03 M⊙ low-mass white dwarf, and in view of the {M}{BS}={1.55}-0.13+0.07 M⊙ massive, evolved F-type blue straggler star, we demonstrate that 49 Lib must have been the subject of a mostly conservative mass transfer with a near-equal-mass M ≃ 1.06 + 1.00 M⊙ G-type binary at birth. For its future evolution, we point to the possibility as a progenitor system toward a type Ia supernova. Most importantly, however, we note that the remarkable metal enrichment of 49 Lib at [Mg/H] = +0.23 and [Fe/H] = ‑0.11 has principally very relevant implications for the early epoch when the Milky Way came into being.

  6. Dark Skies, Bright Kids! Year 5

    NASA Astrophysics Data System (ADS)

    Prager, Brian; Johnson, K. E.; Barcos-Munoz, L. D.; Beaton, R.; Bittle, L.; Borish, H.; Burkhardt, A.; Corby, J.; Damke, G.; Dean, J.; Dorsey, G.; Graninger, D.; Lauck, T.; Liss, S.; Oza, A.; Peacock, S.; Romero, C.; Sokal, K. R.; Stierwalt, S.; Walker, L.; Wenger, T.; Zucker, C.

    2014-01-01

    Our public outreach group Dark Skies, Bright Kids! (DSBK) fosters science literacy in Virginia by bringing a hands-on approach to astronomy that engages children's natural excitement and curiosity. We are an entirely volunteer-run group based out of the Department of Astronomy at the University of Virginia and we enthusiastically utilize astronomy as a 'gateway science.' We create long-term relationships with students during an 8 to 10 week long, after-school astronomy club at under served elementary schools in neighboring counties, and we visited 3 different schools in 2013. Additionally, we organize and participate in science events throughout the community. The fifth year of DSBK was marked by surpassing 10,000 contact hours in Spring 2013 Semester and by ringing in the fall semester with our biggest, most successful star party to date. We hosted the Third Annual Central Virginia Star Party, free and open to the community to encourage families to enjoy astronomy together. Nearly four hundred people of all ages attended, double the number from previous years. Joining with local astronomical societies, we offered an enlightening and exciting night with resources rarely accessible to the public, such as an IR camera and a portable planetarium. With numerous telescopes pointed at the sky, and a beautifully clear night with views of the Milky Way, the International Space Station, and numerous meteors, the star party was a fantastic opportunity to introduce many of our guests to the natural wonders of our night sky and enjoy some of the darkest skies on the eastern seaboard.

  7. CO observations towards bright-rimmed clouds

    NASA Astrophysics Data System (ADS)

    Morgan, L. K.; Urquhart, J. S.; Thompson, M. A.

    2009-12-01

    Bright-rimmed clouds (BRCs) appear to be sites of triggered star formation induced through the propagation of shocks initiated by the expansion of nearby HII regions. Our main aim is to establish support for observations of star-forming activity within a sample of BRCs. A secondary aim is to establish a plausible link between such star formation and observed external influences. We have conducted CO (J = 2-1) observations using the James Clerk Maxwell Telescope to probe the environments of a sample of star-forming BRCs associated with embedded protostellar cores. Local thermodynamic equilibrium analysis allows the determination of the physical properties of these protostars and investigation of the structure and kinematic motions within the molecular gas. Using a combination of archival radio and mid-infrared data, and submillimeter observations, we have refined the Sugitani, Fukui and Ogura (SFO) catalogue, excluding 18 BRCs that do not show any evidence of photoionization induced collapse. Of the remaining 26 clouds that are being photoionized, we find 20 that are associated with embedded protostars. These 20 clouds are excellent candidates with which to further investigate the radiatively driven implosion mode of triggered star formation. Comparing the physical parameters of the triggered and untriggered samples, we find that the surface temperatures of the potentially triggered clouds are significantly higher (by ~10 K) than those in which triggering is considered unlikely. The higher surface temperatures found towards the sample of potentially triggered clouds are consistent with the hypothesis that these clouds are being externally heated through their exposure to the HII region.

  8. MAGNETIC FLUX SUPPLEMENT TO CORONAL BRIGHT POINTS

    SciTech Connect

    Mou, Chaozhou; Huang, Zhenghua; Xia, Lidong; Li, Bo; Fu, Hui; Jiao, Fangran; Hou, Zhenyong; Madjarska, Maria S.

    2016-02-10

    Coronal bright points (BPs) are associated with magnetic bipolar features (MBFs) and magnetic cancellation. Here we investigate how BP-associated MBFs form and how the consequent magnetic cancellation occurs. We analyze longitudinal magnetograms from the Helioseismic and Magnetic Imager to investigate the photospheric magnetic flux evolution of 70 BPs. From images taken in the 193 Å passband of the Atmospheric Imaging Assembly (AIA) we dermine that the BPs’ lifetimes vary from 2.7 to 58.8 hr. The formation of the BP MBFs is found to involve three processes, namely, emergence, convergence, and local coalescence of the magnetic fluxes. The formation of an MBF can involve more than one of these processes. Out of the 70 cases, flux emergence is the main process of an MBF buildup of 52 BPs, mainly convergence is seen in 28, and 14 cases are associated with local coalescence. For MBFs formed by bipolar emergence, the time difference between the flux emergence and the BP appearance in the AIA 193 Å passband varies from 0.1 to 3.2 hr with an average of 1.3 hr. While magnetic cancellation is found in all 70 BPs, it can occur in three different ways: (I) between an MBF and small weak magnetic features (in 33 BPs); (II) within an MBF with the two polarities moving toward each other from a large distance (34 BPs); (III) within an MBF whose two main polarities emerge in the same place simultaneously (3 BPs). While an MBF builds up the skeleton of a BP, we find that the magnetic activities responsible for the BP heating may involve small weak fields.

  9. Chromospheric evaporation in sympathetic coronal bright points

    NASA Astrophysics Data System (ADS)

    Zhang, Q. M.; Ji, H. S.

    2013-09-01

    Context. Chromospheric evaporation is a key process in solar flares that has been extensively investigated using spectroscopic observations. However, direct soft X-ray (SXR) imaging of the process is rare, especially in remote brightenings associated with the primary flares that have recently attracted a great deal of attention. Aims: We intend to find the evidence for chromospheric evaporation and figure out the cause of the process in sympathetic coronal bright points (CBPs), i.e., remote brightenings induced by the primary CBP. Methods: We utilised the high-cadence and high-resolution SXR observations of CBPs from the X-ray Telescope (XRT) aboard the Hinode spacecraft on 2009 August 23. Results: We discovered a thermal conduction front propagating from the primary CBP (hereafter BP1) to the first of the sympathetic CBPs (hereafter BP2) that is 60″ away from BP1. The apparent velocity of the thermal conduction is ~138 km s-1. Afterwards, hot plasma flowed upwards into the loop connecting BP1 and BP2 at a speed of ~76 km s-1, a clear signature of chromospheric evaporation. Similar upflow was also observed in the loop connecting BP1 and the other sympathetic CBP (hereafter BP3) that is 80″ away from BP1, though less significant than BP2. The apparent velocity of the upflow is ~47 km s-1. The thermal conduction front propagating from BP1 to BP3 was not well identified except for the jet-like motion also originating from BP1. Conclusions: We propose that the gentle chromospheric evaporation in the sympathetic CBPs were caused by thermal conduction originating from the primary CBP.

  10. [Bright light therapy in seasonal bipolar depressions].

    PubMed

    Geoffroy, P A; Fovet, T; Micoulaud-Franchi, J-A; Boudebesse, C; Thomas, P; Etain, B; Amad, A

    2015-12-01

    Bipolar disorders (BD) are frequent mood disorders associated with a poor prognosis mainly due to a high relapse rate. Depressive relapses may follow a seasonal cyclicality, and bright-light therapy (BLT) has been established as the treatment of choice for seasonal affective disorder (SAD). The use of BLT for seasonal unipolar depression is well known, but the scientific literature is much poorer on the management of seasonal depressive episodes in BD. In addition, some specificities related to BD must be taken into account. We conducted a comprehensive review using Medline and Google Scholar databases up to August 2014 using the following keywords combination: "bipolar disorder" and "light therapy" or "phototherapy". Papers were included in the review if (a) they were published in an English or French-language peer-reviewed journal; (b) the study enrolled patients with BD and SAD; and (c) the diagnosis was made according to the DSM or ICD criteria. BLT was considered among the first-line treatments for SAD with a size effect similar to antidepressants. Most of the studies did not distinguish between patients with unipolar and bipolar disorders. However, it has been demonstrated that the most significant risk of BLT in patients with BD is the mood shift. Thus, the most important therapeutic adaptation corresponds to the use of an effective mood stabilizer, as with any antidepressant. Another therapeutic adaptation in first intention is that the times of exposure to light should be shifted from morning to midday. This review also includes therapeutic guidelines regarding the management of BLT in seasonal bipolar depressive episodes. There are very few specific data on seasonal bipolar depressive episodes. This literature review has highlighted that BLT should be handled as a regular antidepressant treatment in patients suffering from seasonal bipolar depressive episodes. Copyright © 2015 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

  11. Magnetic Flux Supplement to Coronal Bright Points

    NASA Astrophysics Data System (ADS)

    Mou, Chaozhou; Huang, Zhenghua; Xia, Lidong; Madjarska, Maria S.; Li, Bo; Fu, Hui; Jiao, Fangran; Hou, Zhenyong

    2016-02-01

    Coronal bright points (BPs) are associated with magnetic bipolar features (MBFs) and magnetic cancellation. Here we investigate how BP-associated MBFs form and how the consequent magnetic cancellation occurs. We analyze longitudinal magnetograms from the Helioseismic and Magnetic Imager to investigate the photospheric magnetic flux evolution of 70 BPs. From images taken in the 193 Å passband of the Atmospheric Imaging Assembly (AIA) we dermine that the BPs’ lifetimes vary from 2.7 to 58.8 hr. The formation of the BP MBFs is found to involve three processes, namely, emergence, convergence, and local coalescence of the magnetic fluxes. The formation of an MBF can involve more than one of these processes. Out of the 70 cases, flux emergence is the main process of an MBF buildup of 52 BPs, mainly convergence is seen in 28, and 14 cases are associated with local coalescence. For MBFs formed by bipolar emergence, the time difference between the flux emergence and the BP appearance in the AIA 193 Å passband varies from 0.1 to 3.2 hr with an average of 1.3 hr. While magnetic cancellation is found in all 70 BPs, it can occur in three different ways: (I) between an MBF and small weak magnetic features (in 33 BPs); (II) within an MBF with the two polarities moving toward each other from a large distance (34 BPs); (III) within an MBF whose two main polarities emerge in the same place simultaneously (3 BPs). While an MBF builds up the skeleton of a BP, we find that the magnetic activities responsible for the BP heating may involve small weak fields.

  12. All Bright Cold Classical KBOs are Binary

    NASA Astrophysics Data System (ADS)

    Noll, Keith S.; Parker, Alex H.; Grundy, William M.

    2014-11-01

    When sorted by absolute magnitude as seen in ground based observations, an extremely high fraction of the brightest Cold Classical (CC) Kuiper Belt objects (KBO) are, in fact resolved as binaries when observed at higher angular resolution. Of the 22 CCs brighter than H=6.1 observed by HST, 16 have been found to be binary yielding a binary fraction of 73±10%. When low inclination interlopers from the hot population and close binaries are considered, this very high fraction is consistent with 100% of bright CCs being binary. At fainter absolute magnitudes, this fraction drops to ~20%. Such a situation is a natural outcome of a broken size distribution with a steep drop-off in the number of CCs with individual component diameters larger than 150 km (for an assumed albedo of 0.15). A sharp cutoff in the size distribution for CCs is consistent with formation models that suggest that most planetesimals form at a preferred modal size of order 100 km.The very high fraction of binaries among the largest CCs also serves to limit the separation distribution of KBO binaries. At most, 27% of the brightest CCs are possible unresolved binaries. The apparent power law distribution of binary separation must cut off near the current observational limits of HST ( 1800 km at 43 AU). It is worth noting, however, that this observation does not constrain how many components of resolved binaries may themselves be unresolved multiples like 47171 1999 TC36. Finally, it is important to point out that, when sorted by the size of the primary rather than absolute magnitude of the unresolved pair, the fraction of binaries is relatively constant with size (Nesvorny et al. 2011, AJ 141, 159) eliminating observational bias as cause of the pile up of binaries among the brightest Cold Classical Kuiper Belt objects.The very high fraction of binaries among the brightest CCs appears to be an effect of the underlying CC size distribution.

  13. Impact of snow on surface brightness

    NASA Astrophysics Data System (ADS)

    Kukla, George J.; Brown, Jeffrey A.

    The snow-covered land surface has different albedo than the snow-free surface, depending primarily on the type and density of the vegetation, the relief, and the continuity and age of the snow blanket. This is clearly demonstrated by the winter mosaic of east central Asia shown on the front cover. It is a section of a larger composite assembled from cloud-free satellite images to portray the land surface under continuous snow cover. The mosaic is a valuable tool for distinguishing (from remote positions) snow from clouds and for charting snow cover where illumination is poor. It also can be used to determine relative sensitivity of surface albedo to the occurrence of snow.Segments with a minimum of clouds along the orbital subtrack were selected from the transparencies of the Defense Meteorological Satellite Program (DMSP). Satellite sensors record in the spectral band 0.4-1.2 µm. The satellite is in polar orbit at a mean altitude of 830 km (450 nm) and crosses the equator at approximately local noon. The spatial resolution along the orbital subtrack is about 0.6 km [Dickinson et al., 1974]. The mosaic is assembled from imagery taken between mid-January and mid-February of 1979. The original hard-copy transparencies (on loan from the DMSP library) were reproduced as contact negatives to preserve detail.The snow cover marks the land surface with a characteristic signature that depends on the distribution, density, and type of vegetation; relief; presence of water bodies; distribution and type of land use, etc. This signature can be readily utilized, among others, to distinguish snow-covered land from clouds and from snow-free land [Barnes et al., 1974; Lillesand et al., 1982]. We have compared the brightness fields in the imagery with the vegetation density and land-use patterns charted in the World Forestry Atlas [Wiebecke, 1971].

  14. Dark Skies, Bright Kids: Year 2

    NASA Astrophysics Data System (ADS)

    Carlberg, Joleen K.; Johnson, K.; Lynch, R.; Walker, L.; Beaton, R.; Corby, J.; de Messieres, G.; Drosback, M.; Gugliucci, N.; Jackson, L.; Kingery, A.; Layman, S.; Murphy, E.; Richardson, W.; Ries, P.; Romero, C.; Sivakoff, G.; Sokal, K.; Trammell, G.; Whelan, D.; Yang, A.; Zasowski, G.

    2011-01-01

    The Dark Skies, Bright Kids (DSBK) outreach program brings astronomy education into local elementary schools in central Virginia's Southern Albemarle County through an after-school club. Taking advantage of the unusually dark night skies in the rural countryside, DSBK targets economically disadvantaged schools that tend to be underserved due to their rural locale. The goals of DSBK are to foster children's natural curiosity, demonstrate that science is a fun and creative process, challenge students' conceptions of what a scientist is and does, and teach some basic astronomy. Furthermore, DSBK works to assimilate families into students' education by holding family observing nights at the school. Now in its third semester, DSBK has successfully run programs at two schools with very diverse student populations. Working with these students has helped us to revise our activities and to create new ones. A by-product of our work has been the development of lesson plans, complete with learning goals and detailed instructions, that we make publically available on our website. This year we are expanding our repertoire with our new planetarium, which allows us to visualize topics in novel ways and supplements family observing on cloudy nights. The DSBK volunteers have also created a bilingual astronomy artbook --- designed, written, and illustrated by UVa students --- that we will publish and distribute to elementary schools in Virginia. Our book debuted at the last AAS winter meeting, and since then it has been extensively revised and updated with input from many individuals, including parents, professional educators, and a children's book author. Because the club is currently limited to serving a few elementary schools, this book will be part of our efforts to broaden our impact by bringing astronomy to schools we cannot go to ourselves and reaching out to Spanish-speaking communities at the same time.

  15. Design, structure-based focusing and in silico screening of combinatorial library of peptidomimetic inhibitors of Dengue virus NS2B-NS3 protease.

    PubMed

    Frecer, Vladimir; Miertus, Stanislav

    2010-03-01

    Serine protease activity of the NS3 protein of Dengue virus is an important target of antiviral agents that interfere with the viral polyprotein precursor processing catalyzed by the NS3 protease (NS3pro), which is important for the viral replication and maturation. Recent studies showed that substrate-based peptidomimetics carrying an electrophilic warhead inhibit the NS2B-NS3pro cofactor-protease complex with inhibition constants in the low micromolar concentration range when basic amino acid residues occupy P(1) and P(2) positions of the inhibitor, and an aldehyde warhead is attached to the P(1). We have used computer-assisted combinatorial techniques to design, focus using the NS2B-NS3pro receptor 3D structure, and in silico screen a virtual library of more than 9,200 peptidomimetic analogs targeted around the template inhibitor Bz-Nle-Lys-Arg-Arg-H (Bz-benzoyl) that are composed mainly of unusual amino acid residues in all positions P(1)-P(4). The most promising virtual hits were analyzed in terms of computed enzyme-inhibitor interactions and Adsorption, Distribution, Metabolism and Excretion (ADME) related physico-chemical properties. Our study can direct the interest of medicinal chemists working on a next generation of antiviral chemotherapeutics against the Dengue Fever towards the explored subset of the chemical space that is predicted to contain peptide aldehydes with NS3pro inhibition potencies in nanomolar range which display ADME-related properties comparable to the training set inhibitors.

  16. The Putative Metal Coordination Motif in the Endonuclease Domain of Human Parvovirus B19 NS1 Is Critical for NS1 Induced S Phase Arrest and DNA Damage

    PubMed Central

    Kivovich, Violetta; Gilbert, Leona; Vuento, Matti; Naides, Stanley J.

    2012-01-01

    The non-structural proteins (NS) of the parvovirus family are highly conserved multi-functional molecules that have been extensively characterized and shown to be integral to viral replication. Along with NTP-dependent helicase activity, these proteins carry within their sequences domains that allow them to bind DNA and act as nucleases in order to resolve the concatameric intermediates developed during viral replication. The parvovirus B19 NS1 protein contains sequence domains highly similar to those previously implicated in the above-described functions of NS proteins from adeno-associated virus (AAV), minute virus of mice (MVM) and other non-human parvoviruses. Previous studies have shown that transient transfection of B19 NS1 into human liver carcinoma (HepG2) cells initiates the intrinsic apoptotic cascade, ultimately resulting in cell death. In an effort to elucidate the mechanism of mammalian cell demise in the presence of B19 NS1, we undertook a mutagenesis analysis of the protein's endonuclease domain. Our studies have shown that, unlike wild-type NS1, which induces an accumulation of DNA damage, S phase arrest and apoptosis in HepG2 cells, disruptions in the metal coordination motif of the B19 NS1 protein reduce its ability to induce DNA damage and to trigger S phase arrest and subsequent apoptosis. These studies support our hypothesis that, in the absence of replicating B19 genomes, NS1-induced host cell DNA damage is responsible for apoptotic cell death observed in parvoviral infection of non-permissive mammalian cells. PMID:22211107

  17. The putative metal coordination motif in the endonuclease domain of human Parvovirus B19 NS1 is critical for NS1 induced S phase arrest and DNA damage.

    PubMed

    Kivovich, Violetta; Gilbert, Leona; Vuento, Matti; Naides, Stanley J

    2012-01-01

    The non-structural proteins (NS) of the parvovirus family are highly conserved multi-functional molecules that have been extensively characterized and shown to be integral to viral replication. Along with NTP-dependent helicase activity, these proteins carry within their sequences domains that allow them to bind DNA and act as nucleases in order to resolve the concatameric intermediates developed during viral replication. The parvovirus B19 NS1 protein contains sequence domains highly similar to those previously implicated in the above-described functions of NS proteins from adeno-associated virus (AAV), minute virus of mice (MVM) and other non-human parvoviruses. Previous studies have shown that transient transfection of B19 NS1 into human liver carcinoma (HepG2) cells initiates the intrinsic apoptotic cascade, ultimately resulting in cell death. In an effort to elucidate the mechanism of mammalian cell demise in the presence of B19 NS1, we undertook a mutagenesis analysis of the protein's endonuclease domain. Our studies have shown that, unlike wild-type NS1, which induces an accumulation of DNA damage, S phase arrest and apoptosis in HepG2 cells, disruptions in the metal coordination motif of the B19 NS1 protein reduce its ability to induce DNA damage and to trigger S phase arrest and subsequent apoptosis. These studies support our hypothesis that, in the absence of replicating B19 genomes, NS1-induced host cell DNA damage is responsible for apoptotic cell death observed in parvoviral infection of non-permissive mammalian cells.

  18. Design, structure-based focusing and in silico screening of combinatorial library of peptidomimetic inhibitors of Dengue virus NS2B-NS3 protease

    NASA Astrophysics Data System (ADS)

    Frecer, Vladimir; Miertus, Stanislav

    2010-03-01

    Serine protease activity of the NS3 protein of Dengue virus is an important target of antiviral agents that interfere with the viral polyprotein precursor processing catalyzed by the NS3 protease (NS3pro), which is important for the viral replication and maturation. Recent studies showed that substrate-based peptidomimetics carrying an electrophilic warhead inhibit the NS2B-NS3pro cofactor-protease complex with inhibition constants in the low micromolar concentration range when basic amino acid residues occupy P1 and P2 positions of the inhibitor, and an aldehyde warhead is attached to the P1. We have used computer-assisted combinatorial techniques to design, focus using the NS2B-NS3pro receptor 3D structure, and in silico screen a virtual library of more than 9,200 peptidomimetic analogs targeted around the template inhibitor Bz-Nle-Lys-Arg-Arg- H (Bz—benzoyl) that are composed mainly of unusual amino acid residues in all positions P1-P4. The most promising virtual hits were analyzed in terms of computed enzyme-inhibitor interactions and Adsorption, Distribution, Metabolism and Excretion (ADME) related physico-chemical properties. Our study can direct the interest of medicinal chemists working on a next generation of antiviral chemotherapeutics against the Dengue Fever towards the explored subset of the chemical space that is predicted to contain peptide aldehydes with NS3pro inhibition potencies in nanomolar range which display ADME-related properties comparable to the training set inhibitors.

  19. Extended substrate specificity and first potent irreversible inhibitor/activity-based probe design for Zika virus NS2B-NS3 protease.

    PubMed

    Rut, Wioletta; Zhang, Linlin; Kasperkiewicz, Paulina; Poreba, Marcin; Hilgenfeld, Rolf; Drąg, Marcin

    2017-03-01

    Zika virus is spread by Aedes mosquitoes and is linked to acute neurological disorders, especially to microcephaly in newborn children and Guillan-Barré Syndrome. The NS2B-NS3 protease of this virus is responsible for polyprotein processing and therefore considered an attractive drug target. In this study, we have used the Hybrid Combinatorial Substrate Library (HyCoSuL) approach to determine the substrate specificity of ZIKV NS2B-NS3 protease in the P4-P1 positions using natural and a large spectrum of unnatural amino acids. Obtained data demonstrate a high level of specificity of the S3-S1 subsites, especially for basic amino acids. However, the S4 site exhibits a very broad preference toward natural and unnatural amino acids with selected D-amino acids being favored over L enantiomers. This information was used for the design of a very potent phosphonate inhibitor/activity-based probe of ZIKV NS2B-NS3 protease.

  20. Easy way to estimate meteor brightness on TV frames

    NASA Astrophysics Data System (ADS)

    Leonov, V. A.; Bagrov, A. V.

    2016-01-01

    The traditional method of the meteor brightness measurements claims that the meteor brightness is equal to the stellar magnitude of a star that looks like a meteor in the brightest point of its track. This rule was convenient for the comparison of meteor observations by different observers and for the analysis of the brightness distributions of meteors from observed showers. This traditional method suffers from systematic errors, particularly those that arise from using stellar brightness measured in specific spectral wave bands different from the observer's ones, but mainly due to neglecting the influence of the meteor angular velocity on the real meteor brightness. To get a proper estimate of the meteor brightness that is a measure of the ground meteor illumination in the non-systematic units, an observer must take into account that the effective exposition of a meteor image in any resolution element of its track is a few times shorter than the corresponding exposition of a star image in the same frame. We propose a very simple method for improved estimations of meteor brightness by applying a correction to the meteor stellar magnitude obtained within the traditional framework.

  1. The lowest spatial frequency channel determines brightness perception.

    PubMed

    Perna, A; Morrone, M C

    2007-05-01

    This study investigates the role played by individual spatial scales in determining the apparent brightness of greyscale patterns. We measured the perceived difference in brightness across an edge in the presence of notch filtering and high-pass filtering for two stimulus configurations, one that elicits the perception of transparency and one that appears opaque. For both stimulus configurations, the apparent brightness of the surfaces delimited by the border decreased monotonically with progressive (ideal) high-pass filtering, with a critical cut-off at 1 c/deg. Using two octave ideal notch filtering, the maximum detrimental effect on apparent brightness was observed at about 1c/deg. Critical frequencies for apparent brightness did not vary with contrast, viewing distance, or surface size, suggesting that apparent brightness is determined by the channel tuned at 1 c/deg. Modelling the data with the local energy model [Morrone, M. C., & Burr, D. C. (1988). Feature detection in human vision: a phase dependent energy model. Proceedings of the Royal Society (London), B235, 221-245] at 1c/deg confirmed the suggestion that this channel mediates apparent brightness for both opaque and transparent borders, with no need for pooling or integration across spatial channels.

  2. Perceived brightness of incandescent and LED aviation signal lights.

    PubMed

    Bullough, John D; Yuan, Zongjie; Rea, Mark S

    2007-09-01

    Aviation signal lights using light emitting diodes (LEDs) are commonly perceived as brighter than those using incandescent sources, even at the same measured intensity. In general, saturated colors, like those produced by LEDs, appear brighter than less saturated lights, like those produced by incandescent sources. We describe a series of experiments quantifying the brightness of simulated blue, white, and green LED signal lights relative to incandescent signal lights of the same hue. Simulated signal lights and arrays were compared against dark and against dimly lighted backgrounds, and through simulated fog. The results confirm that LED signal lights are brighter than incandescent signals at matched luminous intensities. Brightness relationships were unaffected by background light level, and by the number of signals viewed, but the simulated fog reduced the brightness difference between the incandescent and LED signal lights. The present results could not be accurately predicted by several previously published models of brightness appearance, probably because of differences in experimental conditions. We present a new model that can be used to predict signal light brightness for blue, white, and green signal colors. Except for very short-wavelength blue signal lights, the model was able to accurately predict the present brightness data as well as those from previously published independent experiments. This validation lends confidence to the generality of the model for predicting blue, white, and green signal light brightness, but different colors (e.g., yellow or red) remain to be tested and modeled using this approach.

  3. DNA Binding and Cleavage by the Human Parvovirus B19 NS1 Nuclease Domain.

    PubMed

    Sanchez, Jonathan L; Romero, Zachary; Quinones, Angelica; Torgeson, Kristiane R; Horton, Nancy C

    2016-11-29

    Infection with human parvovirus B19 (B19V) has been associated with a myriad of illnesses, including erythema infectiosum (Fifth disease), hydrops fetalis, arthropathy, hepatitis, and cardiomyopathy, and also possibly the triggering of any number of different autoimmune diseases. B19V NS1 is a multidomain protein that plays a critical role in viral replication, with predicted nuclease, helicase, and gene transactivation activities. Herein, we investigate the biochemical activities of the nuclease domain (residues 2-176) of B19V NS1 (NS1-nuc) in sequence-specific DNA binding of the viral origin of replication sequences, as well as those of promoter sequences, including the viral p6 and the human p21, TNFα, and IL-6 promoters previously identified in NS1-dependent transcriptional transactivation. NS1-nuc was found to bind with high cooperativity and with multiple (five to seven) copies to the NS1 binding elements (NSBE) found in the viral origin of replication and the overlapping viral p6 promoter DNA sequence. NS1-nuc was also found to bind cooperatively with at least three copies to the GC-rich Sp1 binding sites of the human p21 gene promoter. Only weak or nonspecific binding of NS1-nuc to the segments of the TNFα and IL-6 promoters was found. Cleavage of DNA by NS1-nuc occurred at the expected viral sequence (the terminal resolution site), but only in single-stranded DNA, and NS1-nuc was found to covalently attach to the 5' end of the DNA at the cleavage site. Off-target cleavage by NS1-nuc was also identified.

  4. Discovery of New Scaffolds for Rational Design of HCV NS5B Polymerase Inhibitors

    PubMed Central

    Golub, Andriy G.; Gurukumar, K. R.; Basu, Amartya; Bdzhola, Volodymyr G.; Bilokin, Yaroslav; Yarmoluk, Sergiy M.; Lee, Jin-Ching; Talele, Tanaji T.; Nichols, Daniel B.; Kaushik-Basu, Neerja

    2012-01-01

    Hepatitis C virus (HCV) NS5B polymerase is a key target for the development of anti-HCV drugs. Here we report on the identification of novel allosteric inhibitors of HCV NS5B through a combination of structure-based virtual screening and in vitro NS5B inhibition assays. One hundred and sixty thousand compounds from the Otava database were virtually screened against the thiazolone inhibitor binding site on NS5B (thumb pocket-2, TP-2), resulting in a sequential down-sizing of the library by 2.7 orders of magnitude to yield 59 NS5B non-nucleoside inhibitor (NNI) candidates. In vitro evaluation of the NS5B inhibitory activity of the 59 selected compounds resulted in a 14% hit rate, yielding 8 novel structural scaffolds. Of these, compound 1 bearing a 4-hydrazinoquinazoline scaffold was the most active (IC50 = 16.0 µM). The binding site of all 8 NNIs was mapped to TP-2 of NS5B as inferred by a decrease in their inhibition potency against the M423T NS5B mutant, employed as a screen for TP-2 site binders. At 100 µM concentration, none of the eight compounds exhibited any cytotoxicity, and all except compound 8 exhibited between 40–60% inhibition of intracellular NS5B polymerase activity in BHK-NS5B-FRLuc reporter cells. These inhibitor scaffolds will form the basis for future optimization and development of more potent NS5B inhibitors. PMID:23127989

  5. Novel ATP-Independent RNA Annealing Activity of the Dengue Virus NS3 Helicase

    PubMed Central

    Gebhard, Leopoldo G.; Kaufman, Sergio B.; Gamarnik, Andrea V.

    2012-01-01

    The flavivirus nonstructural protein 3 (NS3) bears multiple enzymatic activities and represents an attractive target for antiviral intervention. NS3 contains the viral serine protease at the N-terminus and ATPase, RTPase, and helicase activities at the C-terminus. These activities are essential for viral replication; however, the biological role of RNA remodeling by NS3 helicase during the viral life cycle is still unclear. Secondary and tertiary RNA structures present in the viral genome are crucial for viral replication. Here, we used the NS3 protein from dengue virus to investigate functions of NS3 associated to changes in RNA structures. Using different NS3 variants, we characterized a domain spanning residues 171 to 618 that displays ATPase and RNA unwinding activities similar to those observed for the full-length protein. Interestingly, we found that, besides the RNA unwinding activity, dengue virus NS3 greatly accelerates annealing of complementary RNA strands with viral or non-viral sequences. This new activity was found to be ATP-independent. It was determined that a mutated NS3 lacking ATPase activity retained full-RNA annealing activity. Using an ATP regeneration system and different ATP concentrations, we observed that NS3 establishes an ATP-dependent steady state between RNA unwinding and annealing, allowing modulation of the two opposing activities of this enzyme through ATP concentration. In addition, we observed that NS3 enhanced RNA-RNA interactions between molecules representing the ends of the viral genome that are known to be necessary for viral RNA synthesis. We propose that, according to the ATP availability, NS3 could function regulating the folding or unfolding of viral RNA structures. PMID:22558403

  6. Cosmological models and the brightness profile of distant galaxies

    NASA Astrophysics Data System (ADS)

    Olivares-Salaverri, I.; Ribeiro, Marcelo B.

    2010-11-01

    This work aims to determine the feasibility of an assumed cosmological model by means of a detailed analysis of the brightness profiles of distant galaxies. Starting from the theory of Ellis & Perry (1979) connecting the angular diameter distance obtained from a relativistic cosmological model and the detailed photometry of galaxies, we assume the presently most accepted cosmology with Λ ¬ = 0 and seek to predict the brightness profile of a galaxy in a given redshift z. To do so, we have to make assumptions concerning the galactic brightness structure and evolution, assuming a scenario where the specific emitted surface brightness Be,νe can be characterized as, Be,νe (r,z) = B0(z)J(νe,z)f[r(z)/a(z)]. Here r is the intrinsic galactic radius, νe the emitted frequency, B0(z) the central surface brightness, J(νe,z) the spectral energy distribution (SED), f[r(z)/a(z)] characterizes the shape of the surface profile distribution and a(z) is the scaling radius. The dependence on z is due to the galactic evolution. As spacetime curvature affects the received surface brightness, the reciprocity theorem (Ellis 1971) allows us to predict the theoretical received surface brightness. So, we are able to compare the theoretical surface brightness with its equivalent observational data already available for high redshift galaxies in order to test the consistency of the assumed cosmological model. The function f[r(z)/a(z)] is represented in the literature by various different shapes, like the Hubble, Hubble-Oemler and Abell-Mihalas single parameter profiles, characterizing the galactic surface brightness quite well when the disk or bulge dependence is dominant. Sérsic and core-Sérsic profiles use two or more parameters and reproduce the galactic profile almost exactly (Trujillo et al. 2004). If we consider all wavelengths, the theory tells us that the total intensity is equal to the surface brightness, so the chosen bandwidth should include most of the SED. In order to

  7. High-speed CuBr brightness amplifier beam profile

    NASA Astrophysics Data System (ADS)

    Evtushenko, G. S.; Torgaev, S. N.; Trigub, M. V.; Shiyanov, D. V.; Evtushenko, T. G.; Kulagin, A. E.

    2017-01-01

    This paper addresses the experimental study of the beam profile of the CuBr brightness amplifier operating at a wide range of pulse repetition frequencies. The use of a medium-size gas discharge tube (2 cm) ensures the operation of the brightness amplifier both at typical PRFs (520 kHz) and at higher PRFs (up to 100 kHz), either with or without HBr additive. The effect of the active additive on the beam profile is demonstrated. The testing results on kinetic modeling of radial processes in the laser (brightness amplifier) plasma are also discussed.

  8. Bright single photons for light-matter interaction

    NASA Astrophysics Data System (ADS)

    Wu, Chih-Hsiang; Wu, Tsung-Yao; Yeh, Yung-Chin; Liu, Po-Hui; Chang, Chin-Hsuan; Liu, Chiao-Kai; Cheng, Ting; Chuu, Chih-Sung

    2017-08-01

    Single photons of subnatural linewidth and high spectral brightness are necessary for efficient light-matter interaction at the single-photon level, which lies at the heart of many quantum photonic technologies. Here we demonstrate a bright source of single photons with subnatural linewidth, controllable waveforms, and a high spectral brightness of 3.67 ×105 s -1mW -1MHz -1. The interaction between the single photons and atoms is demonstrated by the controlled absorption of the single photons in an atomic vapor. Our work has potential applications in quantum information technologies.

  9. The 'Brightness Rules' alternative conception for light bulb circuits

    NASA Astrophysics Data System (ADS)

    Bryan, Joel A.; Stuessy, Carol

    2006-11-01

    An alternative conception for the observed differences in light bulb brightness was revealed during an unguided inquiry investigation in which prospective elementary teachers placed identical bulbs in series, parallel, and combination direct current circuits. Classroom observations, document analyses, and video and audio transcriptions led to the discovery of this alternative conception, appropriately christened 'Brightness Rules'. Assessments administered three weeks after the activity confirmed that several prospective teachers maintained the 'Brightness Rules' conception even after instructor-led intervention. Implications of the discovery of this alternative conception are discussed with respect to a previously administered assessment question that could not identify the presence of this alternative conception.

  10. ECR Ion Source for a High-Brightness Cyclotron

    NASA Astrophysics Data System (ADS)

    Comeaux, Justin; McIntyre, Peter; Assadi, Saeed

    2011-10-01

    New technology is being developed for high-brightness, high-current cyclotrons with performance benefits for accelerator-driven subcritical fission power, medical isotope production, and proton beam cancer therapy. This paper describes the design for a 65 kV electron cyclotron resonance (ECR) ion source that will provide high-brightness beam for injection into the cyclotron. The ion source is modeled closely upon the one that is used at the Paul Scherrer Institute. Modifications are being made to provide enhanced brightness and compatibility for higher-current operation.

  11. HUBBLE FINDS MANY BRIGHT CLOUDS ON URANUS

    NASA Technical Reports Server (NTRS)

    2002-01-01

    A recent Hubble Space Telescope view reveals Uranus surrounded by its four major rings and by 10 of its 17 known satellites. This false-color image was generated by Erich Karkoschka using data taken on August 8, 1998, with Hubble's Near Infrared Camera and Multi-Object Spectrometer. Hubble recently found about 20 clouds - nearly as many clouds on Uranus as the previous total in the history of modern observations. The orange-colored clouds near the prominent bright band circle the planet at more than 300 mph (500 km/h), according to team member Heidi Hammel (MIT). One of the clouds on the right-hand side is brighter than any other cloud ever seen on Uranus. The colors in the image indicate altitude. Team member Mark Marley (New Mexico State University) reports that green and blue regions show where the atmosphere is clear and sunlight can penetrate deep into Uranus. In yellow and grey regions the sunlight reflects from a higher haze or cloud layer. Orange and red colors indicate very high clouds, such as cirrus clouds on Earth. The Hubble image is one of the first images revealing the precession of the brightest ring with respect to a previous image [LINK to PRC97-36a]. Precession makes the fainter part of the ring (currently on the upper right-hand side) slide around Uranus once every nine months. The fading is caused by ring particles crowding and hiding each other on one side of their eight-hour orbit around Uranus. The blue, green and red components of this false-color image correspond to exposures taken at near-infrared wavelengths of 0.9, 1.1, and 1.7 micrometers. Thus, regions on Uranus appearing blue, for example, reflect more sunlight at 0.9 micrometer than at the longer wavelengths. Apparent colors on Uranus are caused by absorption of methane gas in its atmosphere, an effect comparable to absorption in our atmosphere which can make distant clouds appear red. Credit: Erich Karkoschka (University of Arizona) and NASA

  12. Structure and Function of Flavivirus NS5 Methyltransferase

    SciTech Connect

    Zhou,Y.; Ray, D.; Zhao, Y.; Dong, H.; Ren, S.; Li, Z.; Guo, Y.; Bernard, K.; Shi, P.; Li, H.

    2007-01-01

    The plus-strand RNA genome of flavivirus contains a 5' terminal cap 1 structure (m{sup 7}GpppAmG). The flaviviruses encode one methyltransferase, located at the N-terminal portion of the NS5 protein, to catalyze both guanine N-7 and ribose 2'-OH methylations during viral cap formation. Representative flavivirus methyltransferases from dengue, yellow fever, and West Nile virus (WNV) sequentially generate GpppA {yields} m{sup 7}GpppA {yields} m{sup 7}GpppAm. The 2'-O methylation can be uncoupled from the N-7 methylation, since m{sup 7}GpppA-RNA can be readily methylated to m{sup 7}GpppAm-RNA. Despite exhibiting two distinct methylation activities, the crystal structure of WNV methyltransferase at 2.8 {angstrom} resolution showed a single binding site for S-adenosyl-L-methionine (SAM), the methyl donor. Therefore, substrate GpppA-RNA should be repositioned to accept the N-7 and 2'-O methyl groups from SAM during the sequential reactions. Electrostatic analysis of the WNV methyltransferase structure showed that, adjacent to the SAM-binding pocket, is a highly positively charged surface that could serve as an RNA binding site during cap methylations. Biochemical and mutagenesis analyses show that the N-7 and 2'-O cap methylations require distinct buffer conditions and different side chains within the K{sub 61}-D{sub 146}-K{sub 182}-E{sub 218} motif, suggesting that the two reactions use different mechanisms. In the context of complete virus, defects in both methylations are lethal to WNV; however, viruses defective solely in 2'-O methylation are attenuated and can protect mice from later wild-type WNV challenge. The results demonstrate that the N-7 methylation activity is essential for the WNV life cycle and, thus, methyltransferase represents a novel target for flavivirus therapy.

  13. Synergistic hemolysins of coagulase-negative staphylococci (CoNS).

    PubMed

    Różalska, Małgorzata; Derczyńska, Anna; Maszewska, Agnieszka

    2015-01-01

    A total of 104 coagulase negative staphylococci, belonging to S. capitis, S. hominis, S. haemolyticus and S. warneri, originating from the collection of the Department of Pharmaceutical Microbiology (ZMF), Medical University of Lodz, Poland, were tested for their synergistic hemolytic activity. 83% of strains produced δ-hemolysin, however, the percentage of positive strains of S. haemolyticus, S. warneri, S. capitis and S. hominis was different - 98%, 78%, 75% and 68%, respectively. Highly pure hemolysins were obtained from culture supernatants by protein precipitation with ammonium sulphate (0-70% of saturation) and extraction by using a mixture of organic solvents. The purity and molecular mass of hemolysins was determined by TRIS/Tricine PAGE. All CoNS hemolysins were small peptides with a molar mass of about 3.5 kDa; they possessed cytotoxic activity against the line of human foreskin fibroblasts ATCC Hs27 and lysed red cells from different mammalian species, however, the highest activity was observed when guinea pig, dog and human red blood cells were used. The cytotoxic effect on fibroblasts occurred within 30 minutes. The S. cohnii ssp. urealyticus strain was used as a control. The antimicrobial activity was examined using hemolysins of S. capitis, S. hominis, S. cohnii ssp. cohnii and S. cohnii ssp. urealyticus. Hemolysins of the two S. cohnii subspecies did not demonstrate antimicrobial activity. Cytolysins of S. capitis and S. hominis had a very narrow spectrum of action; out of 37 examined strains, the growth of only Micrococcus luteus, Corynebacterium diphtheriae and Pasteurella multocida was inhibited.

  14. Modulation of cell growth by the hepatitis C virus nonstructural protein NS5A.

    PubMed

    Arima, N; Kao, C Y; Licht, T; Padmanabhan, R; Sasaguri, Y; Padmanabhan, R

    2001-04-20

    Hepatitis C virus nonstructural protein, NS5A, is a phosphoprotein produced from the processing of the viral polyprotein precursor. NS5A associates with several cellular proteins in mammalian cells, and the biological consequences of this interaction are currently unknown. To this end, five stable NS5A-expressing murine and human cell lines were established. Tetracycline-regulated NIH3T3 cells and rat liver epithelial cells as well as the constitutive, NS5A-expressing, human Chang liver, HeLa, and NIH3T3 cells all exhibited cell growth retardation compared with the control cells. Cell cycle analysis by flow cytometry indicated that the NS5A-expressing human epitheloid tumor cells had a reduced S phase and an increase in the G(2)/M phase, which could be explained by a p53-dependent induction of p21(Waf1/Cip1) protein and mRNA levels. NS5A interacts with Cdk1 in vivo and in vitro, and a significant portion of the p21(Waf1/Cip1) was found to be in a complex with Cdk2 in the NS5A-expressing human hepatic cell line. Cdk1 and cyclin B1 proteins were also reduced in human Chang liver cells consistent with the increase in G(2)/M phase. Our results suggest that the NS5A protein causes growth inhibition and cell cycle perturbations by targeting the Cdk1/2-cyclin complexes.

  15. Identification of an NTPase motif in classical swine fever virus NS4B protein

    USDA-ARS?s Scientific Manuscript database

    Classical swine fever (CSF) is a highly contagious and often fatal disease of swine caused by CSF virus (CSFV), a positive sense single-stranded RNA virus in the genus Pestivirus of the Flaviviridae family. Here, we have identified, within CSFV non-structural (NS) protein NS4B, conserved sequence el...

  16. Structure and sequence based functional annotation of Zika virus NS2b protein: Computational insights.

    PubMed

    Aguilera-Pesantes, Daniel; Méndez, Miguel A

    2017-02-08

    While Zika virus (ZIKV) outbreaks are a growing concern for global health, a deep understanding about the virus is lacking. Here we report a contribution to the basic science on the virus- a detailed computational analysis of the non structural protein NS2b. This protein acts as a cofactor for the NS3 protease (NS3Pro) domain that is important on the viral life cycle, and is an interesting target for drug development. We found that ZIKV NS2b cofactor is highly similar to other virus within the Flavivirus genus, especially to West Nile Virus, suggesting that it is completely necessary for the protease complex activity. Furthermore, the ZIKV NS2b has an important role to the function and stability of the ZIKV NS3 protease domain even when presents a low conservation score. In addition, ZIKV NS2b is mostly rigid, which could imply a non dynamic nature in substrate recognition. Finally, by performing a computational alanine scanning mutagenesis, we found that residues Gly 52 and Asp 83 in the NS2b could be important in substrate recognition.

  17. Mutations in the classical swine fever virus NS4B protein affects virulence in swine

    USDA-ARS?s Scientific Manuscript database

    NS4B is one of the non-structural proteins of Classical Swine Fever Virus (CSFV), the etiological agent of a severe, highly lethal disease of swine. Protein domain analysis of the predicted amino acid sequence of the NS4B protein of highly pathogenic CSFV strain Brescia (BICv) identified a Toll/Inte...

  18. Experimental evidence and molecular modeling of the interaction between hRSV-NS1 and quercetin.

    PubMed

    Gomes, Deriane Elias; Caruso, Ícaro Putinhon; de Araujo, Gabriela Campos; de Lourenço, Isabella Otenio; de Melo, Fernando Alves; Cornélio, Marinônio Lopes; Fossey, Marcelo Andrés; de Souza, Fátima Pereira

    2016-04-01

    Human Respiratory Syncytial Virus is one of the major causes of acute respiratory infections in children, causing bronchiolitis and pneumonia. Non-Structural Protein 1 (NS1) is involved in immune system evasion, a process that contributes to the success of hRSV replication. This protein can act by inhibiting or neutralizing several steps of interferon pathway, as well as by silencing the hRSV ribonucleoproteic complex. There is evidence that quercetin can reduce the infection and/or replication of several viruses, including RSV. The aims of this study include the expression and purification of the NS1 protein besides experimental and computational assays of the NS1-quercetin interaction. CD analysis showed that NS1 secondary structure composition is 30% alpha-helix, 21% beta-sheet, 23% turn and 26% random coils. The melting temperature obtained through DSC analysis was around 56°C. FRET analysis showed a distance of approximately 19Å between the NS1 and quercetin. Fluorescence titration results showed that the dissociation constant of the NS1-quercetin interaction was around 10(-6)M. In thermodynamic analysis, the enthalpy and entropy balanced forces indicated that the NS1-quercetin interaction presented both hydrophobic and electrostatic contributions. The computational results from the molecular modeling for NS1 structure and molecular docking regarding its interaction with quercetin corroborate the experimental data.

  19. Canine parvovirus NS1 protein exhibits anti-tumor activity in a mouse mammary tumor model.

    PubMed

    Gupta, Shishir Kumar; Yadav, Pavan Kumar; Gandham, Ravi Kumar; Sahoo, A P; Harish, D R; Singh, Arvind Kumar; Tiwari, A K

    2016-02-02

    Many viral proteins have the ability to kill tumor cells specifically without harming the normal cells. These proteins, on ectopic expression, cause lysis or induction of apoptosis in the target tumor cells. Parvovirus NS1 is one of such proteins, which is known to kill high proliferating tumor cells. In the present study, we assessed the apoptosis inducing ability of canine parvovirus type 2 NS1 protein (CPV2.NS1) in vitro in 4T1 cells, and found it to cause significant cell death due to induction of apoptosis through intrinsic or mitochondrial pathway. Further, we also evaluated the oncolytic activity of CPV2.NS1 protein in a mouse mammary tumor model. The results suggested that CPV2.NS1 was able to inhibit the growth of 4T1 induced mouse mammary tumor as indicated by significantly reduced tumor volume, mitotic, AgNOR and PCNA indices. Further, inhibition of tumor growth was found to be because of induction of apoptosis in the tumor cells, which was evident by a significant increase in the number of TUNEL positive cells. Further, CPV2.NS1 was also able to stimulate the immune cells against the tumor antigens as indicated by the increased CD4+ and CD8+ counts in the blood of CVP2.NS1 treated mice. Further optimization of the delivery of NS1 protein and use of an adjuvant may further enhance its anti-tumor activity.

  20. NS1-mediated delay of type I interferon induction contributes to influenza A virulence in ferrets.

    PubMed

    Meunier, Isabelle; von Messling, Veronika

    2011-07-01

    Interference of the influenza A virus non-structural protein NS1 with type I interferon (IFN) signalling has been characterized extensively in vitro. To assess the contribution of NS1 to the virulence of a specific strain, we generated recombinant USSR/90/77 viruses bearing the NS1 proteins of the attenuated strain PR/8/34 or the highly pathogenic strain 1918 'Spanish flu', all belonging to the H1N1 subtype. In vitro, the extent of interference with type I IFN production exerted by the different NS1 proteins correlated with the reported virulence of the respective strain. Infection of ferrets with the recombinant viruses revealed that the presence of the 1918 NS1 resulted in a slightly more severe disease with generally higher clinical scores and increased lung pathology. Analysis of mRNA from nasal wash cells revealed that viruses carrying the 1918 and, to a lesser extent, USSR/90/77 NS1 proteins caused a delay in upregulation of type I IFNs compared with the NS1 PR/8/34-expressing virus, demonstrating the importance of NS1 for early host-response control and virulence.

  1. The mechanism underlying Ler-mediated alleviation of gene repression by H-NS.

    PubMed

    Shin, Minsang

    2017-01-29

    Secretion of effector proteins in Enteropathogeneic Escherichia coli (EPEC) and Enterohemorrhagic Escherichia coli (EHEC) is mediated by a specialized type III secretion system, components of which are encoded in the LEE operons 1 to 5. H-NS, a global repressor in E. coli, silences the expression of LEE operons. Ler, a master regulator in LEE operons, shares 24% amnio acid identity and 44% amino acid similarity to H-NS. Interestingly, rather than a gene silencer, its main role has been characterized as an antagonizing protein that relieves H-NS-mediated transcriptional silencing. In the previous study we reported molecular mechanism for the repression of LEE5 promoter in EPEC and EHEC by H-NS as a protein interaction between upstream DNA-bound H-NS and the αCTD of promoter-bound RNA polymerase. The mechanism underlying Ler-mediated alleviation of the genes repression by H-NS is largely unknown. We examined regulatory effect of these proteins on LEE5p activity using various in vitro tools. Our results revealed that binding affinity of Ler to the LEE5p DNA is about 40 folds greater than that of H-NS as determined by surface plasmon resonance. We verified that Ler binding removed H-NS bound to the same stretch of DNA on LEE5 promoter resulting in a derepression. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Introduction to Cognitive and Affective Skills (NS 127): Competency-Based Course Syllabus.

    ERIC Educational Resources Information Center

    Brady, Marilyn H.; Wells, Tanya G.

    "Introduction to Cognitive and Affective Skills" (NS 127) is an associate degree nursing course offered at Chattanooga State Technical Community College to help students develop competencies in decision making, communication, teaching-learning, and management. The course syllabus for NS 127 begins with information on class, laboratory, and credit…

  3. Identification and characterization of coumestans as novel HCV NS5B polymerase inhibitors

    PubMed Central

    Kaushik-Basu, Neerja; Bopda-Waffo, Alain; Talele, Tanaji T.; Basu, Amartya; Costa, Paulo R. R.; da Silva, Alcides J. M.; Sarafianos, Stefan G.; Noël, François

    2008-01-01

    The hepatitis C virus (HCV) NS5B is essential for viral RNA replication and is therefore a prime target for development of HCV replication inhibitors. Here, we report the identification of a new class of HCV NS5B inhibitors belonging to the coumestan family of phytoestrogens. Based on the in vitro NS5B RNA-dependent RNA polymerase (RdRp) inhibition in the low micromolar range by wedelolactone, a naturally occurring coumestan, we evaluated the anti-NS5B activity of four synthetic coumestan analogues bearing different patterns of substitutions in their A and D rings, and observed a good structure-activity correlation. Kinetic characterization of coumestans revealed a noncompetitive mode of inhibition with respect to nucleoside triphosphate (rNTP) substrate and a mixed mode of inhibition towards the nucleic acid template, with a major competitive component. The modified order of addition experiments with coumestans and nucleic acid substrates affected the potencies of the coumestan inhibitors. Coumestan interference at the step of NS5B–RNA binary complex formation was confirmed by cross-linking experiments. Molecular docking of coumestans within the allosteric site of NS5B yielded significant correlation between their calculated binding energies and IC50 values. Coumestans thus add to the diversifying pool of anti-NS5B agents and provide a novel scaffold for structural refinement and development of potent NS5B inhibitors. PMID:18203743

  4. Introduction to Cognitive and Affective Skills (NS 127): Competency-Based Course Syllabus.

    ERIC Educational Resources Information Center

    Brady, Marilyn H.; Wells, Tanya G.

    "Introduction to Cognitive and Affective Skills" (NS 127) is an associate degree nursing course offered at Chattanooga State Technical Community College to help students develop competencies in decision making, communication, teaching-learning, and management. The course syllabus for NS 127 begins with information on class, laboratory, and credit…

  5. Structural analysis and insight into Zika virus NS5 mediated interferon inhibition.

    PubMed

    Dar, Hamza Arshad; Zaheer, Tahreem; Paracha, Rehan Zafar; Ali, Amjad

    2017-03-30

    The Zika virus outbreak in 2015-2016 is the largest of its kind for which WHO declared a Public Health Emergency of International Concerns. No FDA approved drug is available for the treatment of the viral infection. The interaction of flavivirus NS5 protein with SIAH2 ubiquitin ligase has been previously known. NS5 of Zika virus has been implicated in the degradation of STAT2 protein, which activates interferon-stimulated antiviral activity. Based on our proposition that NS5 utilizes SIAH2-mediated proteasomal degradation of STAT2, an in-silico study was carried out to characterize the protein-protein interactions between NS5, SIAH2 and STAT2 proteins. The aim of our study was to identify the amino acid residues of NS5 involved in IFN antagonism as well as to find the association between NS5, SIAH2 and STAT2 to predict the interaction pattern of these proteins. Analysis proposed that NS5 recruits SIAH2 for the ubiquitination-dependent degradation of STAT2. NS5 residues involved in interaction with SIAH2 and/or STAT2 were found to be mostly conserved across related flaviviruses. These are novel findings regarding the Zika virus and require confirmation through experimental approaches.

  6. Mutations in classical swine fever virus NS4B affect virulence in swine

    USDA-ARS?s Scientific Manuscript database

    NS4B is one of the non-structural proteins of Classical Swine Fever Virus (CSFV), a virus causing a severe disease in swine. Protein domain analysis of the predicted amino acid sequence of NS4B in highly pathogenic CSFV strain Brescia (BICv) identified a Toll/Interleukin-1 receptor like domain (TIR...

  7. 76 FR 65542 - N.S. Savannah; Exemption From Certain Security Requirements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-21

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION N.S. Savannah; Exemption From Certain Security Requirements 1.0 Background The U.S. Department of...-1 issued for the N.S. Savannah (NSS) currently located in the Port of Baltimore, Maryland. The NSS...

  8. Structural basis for substrate specificity of alphavirus nsP2 proteases.

    PubMed

    Russo, Andrew T; Malmstrom, Robert D; White, Mark A; Watowich, Stanley J

    2010-08-24

    The alphavirus nsP2 protease is essential for correct processing of the alphavirus nonstructural polyprotein (nsP1234) and replication of the viral genome. We have combined molecular dynamics simulations with our structural studies to reveal features of the nsP2 protease catalytic site and S1'-S4 subsites that regulate the specificity of the protease. The catalytic mechanism of the nsP2 protease appears similar to the papain-like cysteine proteases, with the conserved catalytic dyad forming a thiolate-imidazolium ion pair in the nsP2-activated state. Substrate binding likely stabilizes this ion pair. Analysis of bimolecular complexes of Venezuelan equine encephalitis virus (VEEV) nsP2 protease with each of the nsP1234 cleavage sites identified protease residues His(510), Ser(511), His(546) and Lys(706) as critical for cleavage site recognition. Homology modelling and molecular dynamics simulations of diverse alphaviruses and their cognate cleavage site sequences revealed general features of substrate recognition that operate across alphavirus strains as well as strain specific covariance between binding site and cleavage site residues. For instance, compensatory changes occurred in the P3 and S3 subsite residues to maintain energetically favourable complementary binding surfaces. These results help explain how alphavirus nsP2 proteases recognize different cleavage sites within the nonstructural polyprotein and discriminate between closely related cleavage targets.

  9. Identifying Bright X-Ray Beasts

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2017-10-01

    Ultraluminous X-ray sources (ULXs) are astronomical sources of X-rays that, while dimmer than active galactic nuclei, are nonetheless brighter than any known stellar process. What are these beasts and why do they shine so brightly?Exceeding the LimitFirst discovered in the 1980s, ULXs are rare sources that have nonetheless been found in all types of galaxies. Though the bright X-ray radiation seems likely to be coming from compact objects accreting gas, theres a problem with this theory: ULXs outshine the Eddington luminosity for stellar-mass compact objects. This means that a stellar-mass object couldnt emit this much radiation isotropically without blowing itself apart.There are two alternative explanations commonly proposed for ULXs:Rather than being accreting stellar-mass compact objects, they are accreting intermediate-mass black holes. A hypothetical black hole of 100 solar masses or more would have a much higher Eddington luminosity than a stellar-mass black hole, making the luminosities that we observe from ULXs feasible.An example of one of the common routes the authors find for a binary system to become a ULX. In this case, the binary begins as two main sequence stars. As one star evolves off the main sequence, the binary undergoes a common envelope phase and a stage of mass transfer. The star ends its life as a supernova, and the resulting neutron star then accretes matter from the main sequence star as a ULX. [Wiktorowicz et al. 2017]They are ordinary X-ray binaries (a stellar-mass compact object accreting matter from a companion star), but they are undergoing a short phase of extreme accretion. During this time, their emission is beamed into jets, making them appear brighter than the Eddington luminosity.Clues from a New DiscoveryA few years ago, a new discovery shed some light on ULXs: M82 X-2, a pulsing ULX. Two more pulsing ULXs have been discovered since then, demonstrating that at least some ULXs contain pulsars i.e., neutron stars as the

  10. BOREAS Level-2 NS001 TMS Imagery: Reflectance and Temperature in BSQ Format

    NASA Technical Reports Server (NTRS)

    Lobitz, Brad; Spanner, Michael; Hall, Forrest G. (Editor); Newcomer, Jeffrey A. (Editor); Strub, Richard

    2000-01-01

    For BOREAS, the NS001 TMS images, along with the other remotely sensed data, were collected to provide spatially extensive information over the primary study areas. This information includes detailed land cover and biophysical parameter maps such as fPAR and LAI. Collection of the NS001 images occurred over the study areas during the 1994 field campaigns. The level-2 NS001 data are atmospherically corrected versions of some of the best original NS001 imagery and cover the dates of 19-Apr-1994, 07-Jun-1994, 21-Jul-1994, 08-Aug-1994, and 16-Sep-1994. The data are not geographically/geometrically corrected; however, files of relative X and Y coordinates for each image pixel were derived by using the C130 INS data in an NS001 scan model. The data are provided in binary image format files.

  11. H-NS, Its Family Members and Their Regulation of Virulence Genes in Shigella Species

    PubMed Central

    Picker, Michael A.; Wing, Helen J.

    2016-01-01

    The histone-like nucleoid structuring protein (H-NS) has played a key role in shaping the evolution of Shigella spp., and provides the backdrop to the regulatory cascade that controls virulence by silencing many genes found on the large virulence plasmid. H-NS and its paralogue StpA are present in all four Shigella spp., but a second H-NS paralogue, Sfh, is found in the Shigella flexneri type strain 2457T, which is routinely used in studies of Shigella pathogenesis. While StpA and Sfh have been proposed to serve as “molecular backups” for H-NS, the apparent redundancy of these proteins is questioned by in vitro studies and work done in Escherichia coli. In this review, we describe the current understanding of the regulatory activities of the H-NS family members, the challenges associated with studying these proteins and their role in the regulation of virulence genes in Shigella. PMID:27916940

  12. NsLTP1 and NsLTP2 isoforms in soft wheat (Triticum aestivum Cv. Centauro) and farro (Triticum dicoccon Schrank) bran.

    PubMed

    Capocchi, Antonella; Fontanini, Debora; Muccilli, Vera; Cunsolo, Vincenzo; Saviozzi, Franco; Saletti, Rosaria; Lorenzi, Roberto; Foti, Salvatore; Galleschi, Luciano

    2005-10-05

    Isoforms of nonspecific lipid-transfer protein 1 (nsLTP1) and nonspecific lipid-transfer protein 2 (nsLTP2) were investigated in bran tissues isolated from caryopses of two cereal crops quite relevant for the Italian market, the cultivar Centauro of soft wheat (Triticum aestivum) and Italian emmer or farro (Triticum dicoccon Schrank). By sequential separation of the bran extracts on cation-exchange and gel filtration chromatographies, fractions containing only proteins belonging to the nsLTP1 and nsLTP2 classes were obtained. The proteins were roughly identified by SDS-PAGE and by immunoreactions in Western blotting experiments. By MALDI-MS and RP-HPLC/ESI-MS analyses we were able to show the presence of several LTP1 and LTP2 isoforms in the investigated species. Bioinformatic searches based on the determined Mr indicated that (i) two nsLTP1s already identified in T. aestivum have Mr and number of Cys residues identical to that of a 9.6 kDa protein present both in soft wheat cv. Centauro and in farro; (ii) two isoforms of nsLTP2 detected in T. aestivum have the same Mr and number of Cys residues of two 7 kDa proteins found in Centauro; and (iii) a nsLTP1 detected in Ambrosia artemisiifolia has Mr and number of Cys residues coincident to that of a 9.9 kDa protein found both in soft wheat cv. Centauro and in farro.

  13. Detail of Bright Angel stone vault, containing condenser, Hoffman condensation ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Detail of Bright Angel stone vault, containing condenser, Hoffman condensation pump, Jennings vacuum heating pump, and misc. pipes and valves. - Grand Canyon Village Utilities, Grand Canyon National Park, Grand Canyon Village, Coconino County, AZ

  14. Western Edge of Cape York, with Bright Vein

    NASA Image and Video Library

    2011-12-07

    NASA Mars Exploration Rover Opportunity recorded this view of the western edge of Cape York, a segment of the rim of Endeavour Crater. A bright vein, informally named Homestake, is visible on the right side of the image.

  15. Significant increase in the optical brightness of V2492 Cyg

    NASA Astrophysics Data System (ADS)

    Ibryamov, Sunay; Semkov, Evgeni

    2017-03-01

    We observed a recent increase in the optical brightness of the young eruptive star V2492 Cyg using the 2-m and the 50/70-cm Schmidt telescopes administered by National Astronomical Observatory Rozhen in Bulgaria.

  16. Dark Murky Clouds in the Bright Milky Way

    NASA Image and Video Library

    2011-08-24

    This infrared image from NASA Wide-field Infrared Survey Explorer shows exceptionally cold, dense cloud cores seen in silhouette against the bright diffuse infrared glow of the plane of the Milky Way galaxy.

  17. Yellow steam and electrical pipes across from Bright Angel Lodge. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Yellow steam and electrical pipes across from Bright Angel Lodge. Note control valve to right of control box, view E. - Grand Canyon Village Utilities, Grand Canyon National Park, Grand Canyon Village, Coconino County, AZ

  18. South and west elevations of Bright Angel boiler house. Red ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    South and west elevations of Bright Angel boiler house. Red Horse log cabin visible in background. - Grand Canyon Village Utilities, Grand Canyon National Park, Grand Canyon Village, Coconino County, AZ

  19. Perspective of Bright Angel stone vault, view south, with HAER ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Perspective of Bright Angel stone vault, view south, with HAER field team measuring (Michael Lee and Dominic Duran foreground, Christopher Marston rear). - Grand Canyon Village Utilities, Grand Canyon National Park, Grand Canyon Village, Coconino County, AZ

  20. Bright Angel stone vault, with HAER field team members Dominic ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Bright Angel stone vault, with HAER field team members Dominic Duran, Christopher Marston, and Michael Lee (l to r). - Grand Canyon Village Utilities, Grand Canyon National Park, Grand Canyon Village, Coconino County, AZ

  1. Zernike analysis of all-sky night brightness maps.

    PubMed

    Bará, Salvador; Nievas, Miguel; Sánchez de Miguel, Alejandro; Zamorano, Jaime

    2014-04-20

    All-sky night brightness maps (calibrated images of the night sky with hemispherical field-of-view (FOV) taken at standard photometric bands) provide useful data to assess the light pollution levels at any ground site. We show that these maps can be efficiently described and analyzed using Zernike circle polynomials. The relevant image information can be compressed into a low-dimensional coefficients vector, giving an analytical expression for the sky brightness and alleviating the effects of noise. Moreover, the Zernike expansions allow us to quantify in a straightforward way the average and zenithal sky brightness and its variation across the FOV, providing a convenient framework to study the time course of these magnitudes. We apply this framework to analyze the results of a one-year campaign of night sky brightness measurements made at the UCM observatory in Madrid.

  2. Bright Particle in Hole Dug by Scooping of Martian Soil

    NASA Image and Video Library

    2012-10-18

    The mission science team assessed the bright particles in this scooped pit to be native Martian material rather than spacecraft debris as seen in this image from NASA Mars rover Curiosity as it collected its second scoop of Martian soil.

  3. Female butterflies prefer males bearing bright iridescent ornamentation

    PubMed Central

    Kemp, Darrell J

    2007-01-01

    Butterflies are among nature's most colourful animals, and provide a living showcase for how extremely bright, chromatic and iridescent coloration can be generated by complex optical mechanisms. The gross characteristics of male butterfly colour patterns are understood to function for species and/or sex recognition, but it is not known whether female mate choice promotes visual exaggeration of this coloration. Here I show that females of the sexually dichromatic species Hypolimnas bolina prefer conspecific males that possess bright iridescent blue/ultraviolet dorsal ornamentation. In separate field and enclosure experiments, using both dramatic and graded wing colour manipulations, I demonstrate that a moderate qualitative reduction in signal brightness and chromaticity has the same consequences as removing the signal entirely. These findings validate a long-held hypothesis, and argue for the importance of intra- versus interspecific selection as the driving force behind the exaggeration of bright, iridescent butterfly colour patterns. PMID:17284412

  4. Proposal for a High-Brightness Pulsed Electron Source

    SciTech Connect

    Zolotorev, Max; Commins, Eugene D.; Heifets, Sam; Sannibale,Fernando

    2006-03-15

    We propose a novel scheme for a high-brightness pulsedelectron source, which has the potential for many useful applications inelectron microscopy, inverse photo-emission, low energy electronscattering experiments, and electron holography. A description of theproposed scheme is presented.

  5. Brightness differences influence the evaluation of affective pictures.

    PubMed

    Lakens, Daniël; Fockenberg, Daniel A; Lemmens, Karin P H; Ham, Jaap; Midden, Cees J H

    2013-01-01

    We explored the possibility of a general brightness bias: brighter pictures are evaluated more positively, while darker pictures are evaluated more negatively. In Study 1 we found that positive pictures are brighter than negative pictures in two affective picture databases (the IAPS and the GAPED). Study 2 revealed that because researchers select affective pictures on the extremity of their affective rating without controlling for brightness differences, pictures used in positive conditions of experiments were on average brighter than those used in negative conditions. Going beyond correlational support for our hypothesis, Studies 3 and 4 showed that brighter versions of neutral pictures were evaluated more positively than darker versions of the same picture. Study 5 revealed that people categorised positive words more quickly than negative words after a bright picture prime, and vice versa for negative pictures. Together, these studies provide strong support for the hypotheses that picture brightness influences evaluations.

  6. A model function for ocean microwave brightness temperatures

    NASA Technical Reports Server (NTRS)

    Wentz, F. J.

    1983-01-01

    A relatively simple, yet accurate, relationship between the microwave brightness temperature of the ocean and conventional oceanographic and meteorological parameters is derived. The equation for the brightness temperature upwelling from the sea surface through the intervening atmosphere is obtained, considering radiative emission and scattering by the sea surface along with radiative absorption and emission by the atmosphere. A number of approximations are applied to the integral brightness temperature equation and its supporting equations in order to obtain a simple equation for the brightness temperature that does not contain integrals. Values for a number of atmospheric parameters are determined, including temperature sensitivities, oxygen opacity, water vapor and liquid water normalized absorption coefficients, and effective columnar height. The sea surface emissivity model is then considered, modelling the sea surface as a composite of foam-free rough water and foam patches.

  7. Visible Color and Photometry of Bright Materials on Vesta

    NASA Technical Reports Server (NTRS)

    Schroder, S. E.; Li, J. Y.; Mittlefehldt, D. W.; Pieters, C. M.; De Sanctis, M. C.; Hiesinger, H.; Blewett, D. T.; Russell, C. T.; Raymond, C. A.; Keller, H. U.

    2012-01-01

    The Dawn Framing Camera (FC) collected images of the surface of Vesta at a pixel scale of 70 m in the High Altitude Mapping Orbit (HAMO) phase through its clear and seven color filters spanning from 430 nm to 980 nm. The surface of Vesta displays a large diversity in its brightness and colors, evidently related to the diverse geology [1] and mineralogy [2]. Here we report a detailed investigation of the visible colors and photometric properties of the apparently bright materials on Vesta in order to study their origin. The global distribution and the spectroscopy of bright materials are discussed in companion papers [3, 4], and the synthesis results about the origin of Vestan bright materials are reported in [5].

  8. THE RELATION BETWEEN VISUAL ACUITY AND BRIGHTNESS DISCRIMINATION

    PubMed Central

    Hendley, Charles D.

    1948-01-01

    1. Visual acuity depends on the brightness contrast between test object and background; and conversely, brightness discrimination depends on the target size. Both functions vary with the brightness of the background. Measurements with rectangular targets of length-width ratio 2 were made over a range of sizes, contrasts, and brightnesses sufficient to determine the relations among these three variables. The rectangles were from 2' to 50' wide; the contrast fraction, ΔI/I, ranged from 0.01 to 40; the background brightness varied from 0.0001 to 2500 millilamberts. 2. When ΔI/I or visual acuity is plotted as a function of brightness the data do, in general, follow Hecht's equation. The departure from a simple photochemical theory which the larger targets show is probably due to changes in the functional retinal mosaic with changing brightness. 3. In general also, the relation between visual acuity and brightness, at selected contrasts, fits Hecht's derivation. At low contrasts, as the brightness is reduced a point is reached at which the test object becomes invisible at any size. 4. No simple relation emerges from the data relating visual acuity to contrast, at set levels of illumination. Over only a very short range are visual acuity and contrast directly related. At high contrasts, visual acuity reaches a maximum, whereas at low visual acuity, ΔI/I reaches a minimum which cannot be passed regardless of size. 5. The shape of the curves relating ΔI/I to brightness is not significantly altered by changing the exposure time. There is some evidence to show that a 3 second exposure of the target is equivalent to two looks of 0.2 second each. 6. In all these studies the thresholds were determined by a frequency of seeing method, and the data have been considered in terms of a quantum theory of threshold seeing. It was found that a threshold response involves between four and eight independent critical events, which are largely independent of size, brightness, and

  9. Hepatitis C virus NS4B carboxy terminal domain is a membrane binding domain.

    PubMed

    Liefhebber, Jolanda M P; Brandt, Bernd W; Broer, Rene; Spaan, Willy J M; van Leeuwen, Hans C

    2009-05-25

    Hepatitis C virus (HCV) induces membrane rearrangements during replication. All HCV proteins are associated to membranes, pointing out the importance of membranes for HCV. Non structural protein 4B (NS4B) has been reported to induce cellular membrane alterations like the membranous web. Four transmembrane segments in the middle of the protein anchor NS4B to membranes. An amphipatic helix at the amino-terminus attaches to membranes as well. The carboxy-terminal domain (CTD) of NS4B is highly conserved in Hepaciviruses, though its function remains unknown. A cytosolic localization is predicted for the NS4B-CTD. However, using membrane floatation assays and immunofluorescence, we now show targeting of the NS4B-CTD to membranes. Furthermore, a profile-profile search, with an HCV NS4B-CTD multiple sequence alignment, indicates sequence similarity to the membrane binding domain of prokaryotic D-lactate dehydrogenase (d-LDH). The crystal structure of E. coli d-LDH suggests that the region similar to NS4B-CTD is located in the membrane binding domain (MBD) of d-LDH, implying analogy in membrane association. Targeting of d-LDH to membranes occurs via electrostatic interactions of positive residues on the outside of the protein with negative head groups of lipids. To verify that anchorage of d-LDH MBD and NS4B-CTD is analogous, NS4B-CTD mutants were designed to disrupt these electrostatic interactions. Membrane association was confirmed by swopping the membrane contacting helix of d-LDH with the corresponding domain of the 4B-CTD. Furthermore, the functionality of these residues was tested in the HCV replicon system. Together these data show that NS4B-CTD is associated to membranes, similar to the prokaryotic d-LDH MBD, and is important for replication.

  10. Dengue Virus NS1 Disrupts the Endothelial Glycocalyx, Leading to Hyperpermeability

    PubMed Central

    Puerta-Guardo, Henry; Glasner, Dustin R.; Harris, Eva

    2016-01-01

    Dengue is the most prevalent arboviral disease in humans and a major public health problem worldwide. Systemic plasma leakage, leading to hypovolemic shock and potentially fatal complications, is a critical determinant of dengue severity. Recently, we and others described a novel pathogenic effect of secreted dengue virus (DENV) non-structural protein 1 (NS1) in triggering hyperpermeability of human endothelial cells in vitro and systemic vascular leakage in vivo. NS1 was shown to activate toll-like receptor 4 signaling in primary human myeloid cells, leading to secretion of pro-inflammatory cytokines and vascular leakage. However, distinct endothelial cell-intrinsic mechanisms of NS1-induced hyperpermeability remained to be defined. The endothelial glycocalyx layer (EGL) is a network of membrane-bound proteoglycans and glycoproteins lining the vascular endothelium that plays a key role in regulating endothelial barrier function. Here, we demonstrate that DENV NS1 disrupts the EGL on human pulmonary microvascular endothelial cells, inducing degradation of sialic acid and shedding of heparan sulfate proteoglycans. This effect is mediated by NS1-induced expression of sialidases and heparanase, respectively. NS1 also activates cathepsin L, a lysosomal cysteine proteinase, in endothelial cells, which activates heparanase via enzymatic cleavage. Specific inhibitors of sialidases, heparanase, and cathepsin L prevent DENV NS1-induced EGL disruption and endothelial hyperpermeability. All of these effects are specific to NS1 from DENV1-4 and are not induced by NS1 from West Nile virus, a related flavivirus. Together, our data suggest an important role for EGL disruption in DENV NS1-mediated endothelial dysfunction during severe dengue disease. PMID:27416066

  11. Raman spectroscopy based discrimination of NS1 positive and negative dengue virus infected serum

    NASA Astrophysics Data System (ADS)

    Bilal, M.; Saleem, M.; Bilal, Maria; Khurram, M.; Khan, Saranjam; Ullah, Rahat; Ali, Hina; Ahmed, M.

    2016-09-01

    This study is intended to develop a multivariate statistical model for the prediction of nonstructural protein 1 (NS1) in dengue virus (DENV) infected blood serum in humans. The model has been developed on the basis of partial least squares regression using the Raman spectra of NS1 positive and NS1 negative samples. Human blood sera of 218 subjects is included in this study, of which 95 were NS1 positive and 123 were NS1 negative, which was confirmed with the enzyme linked immunosorbent assay method. For model development, 80 NS1 positive and 98 NS1 negative samples were used, while 40 DENV suspected samples were used for double blind testing of the model. This selection of samples was performed by the code in an automatic manner to avoid biasing. A laser at 785 nm was used as the excitation source to acquire Raman spectra of samples with an integration time of 15 s. The multivariate model yields coefficients of regression at corresponding Raman shifts. These coefficients represent changes in the molecular structures associated with NS1 positive and negative samples. The analysis of the regression coefficients which differentiate NS1 positive and NS1 negative groups shows an increasing trend for phosphatidylinositol, ceramide, and amide-III, and a decreasing trend for thiocyanate in the DENV infected serum. The R-squared value of the model was found to be 0.91, which is clinically acceptable. The blind testing of 40 suspected samples yields an accuracy, sensitivity, and specificity of about 100% each.

  12. The uncoupling of protease trans-cleavage and helicase activities in the pestivirus NS3.

    PubMed

    Zheng, Fengwei; Lu, Guoliang; Li, Ling; Gong, Peng; Pan, Zishu

    2017-08-23

    The nonstructural protein NS3 from the Flaviviridae family is a multi-functional protein that contains an N-terminal protease and a C-terminal helicase, playing essential roles in viral polyprotein processing and genome replication. Here we report a full-length crystal structure of the Classical swine fever virus (CSFV) NS3 in complex with its NS4A protease cofactor segment (PCS) at 2.35 Å resolution. The structure reveals a previously unidentified ∼2200-Å(2) intra-molecular protease-helicase interface comprising three clusters of interactions, representing a "closed" global conformation related to the NS3-NS4A cis-cleavage event. Although this conformation is incompatible with protease trans-cleavage, it appears to be functionally important and beneficial to the helicase activity, as the mutations designed to perturb this conformation impaired both the helicase activities in vitro and virus production in vivo Collectively, our work reveals important features of protease-helicase coordination in pestivirus NS3, and provides a key basis for how different conformational states may explicitly contribute to certain functions of this natural protease-helicase fusion protein.IMPORTANCE Many RNA viruses encode helicases to aid their RNA genome replication and transcription by unwinding structured RNA. Being naturally fused to a protease participating in viral polyprotein processing, the NS3 helicases encoded by the Flaviviridae family viruses are quite unique. Therefore, how these two enzyme modules coordinate in a single polypeptide is of particular interest. Here we report a previously unidentified conformation of pestivirus NS3 in complex with its NS4A protease cofactor segment (PCS). This conformational state is related to the protease cis-cleavage event and is optimal for the function of helicase. This work provides an important basis to understand how different enzymatic activities of NS3 may be achieved by the coordination between the protease and helicase

  13. Dengue NS1 antigen contributes to disease severity by inducing interleukin (IL)-10 by monocytes.

    PubMed

    Adikari, T N; Gomes, L; Wickramasinghe, N; Salimi, M; Wijesiriwardana, N; Kamaladasa, A; Shyamali, N L A; Ogg, G S; Malavige, G N

    2016-04-01

    Both dengue NS1 antigen and serum interleukin (IL)-10 levels have been shown to associate with severe clinical disease in acute dengue infection, and IL-10 has also been shown to suppress dengue-specific T cell responses. Therefore, we proceeded to investigate the mechanisms by which dengue NS1 contributes to disease pathogenesis and if it is associated with altered IL-10 production. Serum IL-10 and dengue NS1 antigen levels were assessed serially in 36 adult Sri Lankan individuals with acute dengue infection. We found that the serum IL-10 levels correlated positively with dengue NS1 antigen levels (Spearman's r = 0·47, P < 0·0001), and NS1 also correlated with annexin V expression by T cells in acute dengue (Spearman's r = 0·63, P = 0·001). However, NS1 levels did not associate with the functionality of T cell responses or with expression of co-stimulatory molecules. Therefore, we further assessed the effect of dengue NS1 on monocytes and T cells by co-culturing primary monocytes and peripheral blood mononuclear cells (PBMC), with varying concentrations of NS1 for up to 96 h. Monocytes co-cultured with NS1 produced high levels of IL-10, with the highest levels seen at 24 h, and then declined gradually. Therefore, our data show that dengue NS1 appears to contribute to pathogenesis of dengue infection by inducing IL-10 production by monocytes. © 2016 British Society for Immunology.

  14. NS5ATP13 Promotes Liver Fibrogenesis via Activation of Hepatic Stellate Cells.

    PubMed

    Li, Yaru; Liu, Shunai; Han, Ming; Lu, Hongping; Wang, Qi; Zhang, Yu; Tursun, Kelbinur; Li, Zhongshu; Feng, Shenghu; Cheng, Jun

    2017-01-29

    Liver fibrosis is a reversible wound-healing response to any etiology of chronic hepatic injuries. Activation of hepatic stellate cells (HSCs) is the key event in liver fibrogenesis. Generally, persistent activation and proliferation of HSCs results in liver fibrosis progression, while primary mechanisms of liver fibrosis resolution are apoptosis and reversion to a quiescent phenotype of activated HSCs. NS5ATP13 (HCV NS5A-transactivated protein 13) is involved in nucleologenesis and tumorigenesis, but its role in liver fibrosis and HSC activation remains unclear. This study found that NS5ATP13 was upregulated in both fibrotic liver tissues and activated human HSCs induced by TGF-β1. Moreover, NS5ATP13 enhanced extracellular matrix (ECM) production and HSC activation, with or without TGF-β1 treatment, likely involving the TGF-β1/Smad3 signaling pathway. Additionally, NS5ATP13 boosted HSC proliferation by inhibiting cell apoptosis. Furthermore, HCV NS5A promoted the profibrogenic effect of NS5ATP13 partly through TGF-β1 and NF-κB p65 (RelA) upregulation. Meanwhile, NS5ATP13 was required for the pro-fibrogenic effect of NF-κB. Moreover, NS5ATP13 and NF-κB phosphorylation as well as HSC activation were reduced by CX-4945, a CK2 specific inhibitor. These findings indicated that NS5ATP13 acts as a profibrogenic factor, providing a potential target for antifibrotic therapies. This article is protected by copyright. All rights reserved.

  15. The sonographic "bright band sign" of splenic infarction.

    PubMed

    Llewellyn, Michael E; Jeffrey, R Brooke; DiMaio, Michael A; Olcott, Eric W

    2014-06-01

    To evaluate the frequency of the "bright band sign" in patients with splenic infarcts as well as control patients and to thereby assess whether the bright band sign has potential utility as a sonographic sign of splenic infarction. Using an electronic search engine and image review, 37 patients were retrospectively identified with noncystic parenchymal splenic infarcts on sonography. Nineteen abnormal control patients with noninfarcted splenic lesions on sonography and 100 normal control patients with sonographically normal spleens were also identified. The sonographic appearance of each splenic lesion was evaluated by 2 reviewers and assessed for the bright band sign, defined as thin specular reflectors perpendicular to the sound beam within hypoechoic parenchymal lesions, and for the presence or absence of the classic sonographic appearance of splenic infarction. Possible histologic counterparts of the bright band sign were assessed in archival infarct specimens. The bright band sign was present in 34 (91.9%; 95% confidence interval [CI], 78.1%-98.3%) of 37 patients with splenic infarcts on sonography, including 12 (85.7%; 95% CI, 57.2%-98.2%) of 14 with classic and 22 (95.7%; 95% CI, 78.1%-99.9%) of 23 with nonclassic infarct appearances. No normal or abnormal control patients had the bright band sign. Histologic sections suggested that preserved splenic trabeculae within infarcts may generate the bright band sign. The bright band sign is a potentially useful sonographic sign of splenic infarction, which may confer additional sensitivity and specificity and may be particularly helpful with infarcts having nonclassic appearances. © 2014 by the American Institute of Ultrasound in Medicine.

  16. Sky Brightness During Eclipses: A Compendium from the Literature

    DTIC Science & Technology

    1974-08-05

    Sky Brightness 90 Tables 29. Optical Dimensions o. 30. Data on Apparatus 31. Intensity of Emissions 32. Recordings Made During Eclipse and...Compendium From The Literature i. a:\\KR\\i. The brightness of the sky represents the optical ambient field in which objects are imbedded. Thus detection...instrument used was Pyranometer A. P. O. No. 5 (see 19) partially rebuilt by inserting a new thermopile, consisting of four tellurium-platinum thermo

  17. Sky Brightness Analysis using a Million GEODSS Observations

    NASA Astrophysics Data System (ADS)

    Mandeville, W. Jody; McLaughlin, Tim; Six, Steve; Hollm, Rick

    2012-09-01

    Brightness of the sky background due to lunar phase and location can dramatically affect the limiting magnitude of astronomical detectors. Formerly, theoretical models have attained limited data sets with 10-20% differences between model and observation. This paper compares and contrasts previous investigations with over a million data points collected from various GEODSS sites located around the world and attempts to refine predictive modeling of sky brightness for use in scheduling as well as modeling and simulation tools.

  18. Catalogue of Galactic globular-cluster surface-brightness profiles

    NASA Technical Reports Server (NTRS)

    Trager, S. C.; King, Ivan R.; Djorgovski, S.

    1995-01-01

    We present a catalogue of surface-brightness profiles (SBPs) of 125 Galactic globular clusters, the largest such collection ever gathered. The SPBs are constructed from generally inhomogeneous data, but are based heavily on the Berkeley Global Cluster Survey of Djorgovski & King. All but four of the SBPs have photometric zero points. We derive central surface brightness, King-model concentrations, core radii, half-light, and other fraction-of-light radii where data permit, and we briefly discuss their use.

  19. Laser-heated X-ray flashlamp brightness measurements

    SciTech Connect

    Matthews, D.L.; Campbell, E.M.; Hagelstein, P.; Halsey, W.; Kauffman, R.L.; Koppel, L.; Phillion, D.; Price, R.; Toor, A.

    1983-12-01

    The authors present measurements of the X-ray emission characteristics of laser-irradiated flashlamp foils which are candidates to produce by resonant photoexcitation a population inversion in either a neon or fluorine lasant gas. Using the Shiva 1.06 ..mu.. laser, the authors heated Fe, Cr, and Ni foils to study the brightness and centroid energies of X-ray lines stemming from L-M transitions. Results indicate that appropriately bright and uniform sources can be produced.

  20. Global View of the Bright Material on Vesta

    NASA Technical Reports Server (NTRS)

    Zambon, F.; DeSanctis, C.; Schroeder, S.; Tosi, F.; Li, J.-Y.; Longobardo, A.; Ammannito, E.; Blewett, D. T.; Palomba, E.; Capaccioni, F.; hide

    2014-01-01

    At 525 km in mean diameter, Vesta is the second-most massive and one of the brightest asteroids of the main-belt. Here we give a global view of the bright material (BM) units on Vesta. We classified the BMs according to the normal visual albedo. The global albedo map of Vesta allows to be divided the surface into three principal types of terrains: bright regions, dark regions and intermediate regions. The distribution of bright regions is not uniform. The mid-southern latitudes contain the most bright areas, while the northern hemisphere is poor in bright regions. The analysis of the spectral parameters and the normal visual albedo show a dependence between albedo and the strength (depth) of ferrous iron absorption bands, strong bands correspond with high albedo units. Vesta's average albedo is 0.38, but there are bright material whose albedo can exceed 0.50. Only the E-Type asteroids have albedos comparable to those of the BMs on Vesta. The Dawn mission observed a large fraction of Vesta's surface at high spatial resolution, allowing a detailed study of the morphology and mineralogy of it. In particular, reflectance spectra provided by the Visible and InfraRed spectrometer (VIR), confirmed that Vesta's mineralogy is dominated by pyroxenes. All Vesta spectra show two strong absorption bands at approx 0.9 and 1.9 micron, typical of the pyroxenes and associated with the howardite, eucrite and diogenite (HED) meteorites.

  1. An observational correlation between stellar brightness variations and surface gravity.

    PubMed

    Bastien, Fabienne A; Stassun, Keivan G; Basri, Gibor; Pepper, Joshua

    2013-08-22

    Surface gravity is a basic stellar property, but it is difficult to measure accurately, with typical uncertainties of 25 to 50 per cent if measured spectroscopically and 90 to 150 per cent if measured photometrically. Asteroseismology measures gravity with an uncertainty of about 2 per cent but is restricted to relatively small samples of bright stars, most of which are giants. The availability of high-precision measurements of brightness variations for more than 150,000 stars provides an opportunity to investigate whether the variations can be used to determine surface gravities. The Fourier power of granulation on a star's surface correlates physically with surface gravity: if brightness variations on timescales of hours arise from granulation, then such variations should correlate with surface gravity. Here we report an analysis of archival data that reveals an observational correlation between surface gravity and root mean squared brightness variations on timescales of less than eight hours for stars with temperatures of 4,500 to 6,750 kelvin, log surface gravities of 2.5 to 4.5 (cgs units) and overall brightness variations of less than three parts per thousand. A straightforward observation of optical brightness variations therefore allows a determination of the surface gravity with a precision of better than 25 per cent for inactive Sun-like stars at main-sequence to giant stages of evolution.

  2. The Influence of Microphysical Cloud Parameterization on Microwave Brightness Temperatures

    NASA Technical Reports Server (NTRS)

    Skofronick-Jackson, Gail M.; Gasiewski, Albin J.; Wang, James R.; Zukor, Dorothy J. (Technical Monitor)

    2000-01-01

    The microphysical parameterization of clouds and rain-cells plays a central role in atmospheric forward radiative transfer models used in calculating passive microwave brightness temperatures. The absorption and scattering properties of a hydrometeor-laden atmosphere are governed by particle phase, size distribution, aggregate density., shape, and dielectric constant. This study identifies the sensitivity of brightness temperatures with respect to the microphysical cloud parameterization. Cloud parameterizations for wideband (6-410 GHz observations of baseline brightness temperatures were studied for four evolutionary stages of an oceanic convective storm using a five-phase hydrometeor model in a planar-stratified scattering-based radiative transfer model. Five other microphysical cloud parameterizations were compared to the baseline calculations to evaluate brightness temperature sensitivity to gross changes in the hydrometeor size distributions and the ice-air-water ratios in the frozen or partly frozen phase. The comparison shows that, enlarging the rain drop size or adding water to the partly Frozen hydrometeor mix warms brightness temperatures by up to .55 K at 6 GHz. The cooling signature caused by ice scattering intensifies with increasing ice concentrations and at higher frequencies. An additional comparison to measured Convection and Moisture LA Experiment (CAMEX 3) brightness temperatures shows that in general all but, two parameterizations produce calculated T(sub B)'s that fall within the observed clear-air minima and maxima. The exceptions are for parameterizations that, enhance the scattering characteristics of frozen hydrometeors.

  3. Synthesizing SMOS Zero-Baselines with Aquarius Brightness Temperature Simulator

    NASA Technical Reports Server (NTRS)

    Colliander, A.; Dinnat, E.; Le Vine, D.; Kainulainen, J.

    2012-01-01

    SMOS [1] and Aquarius [2] are ESA and NASA missions, respectively, to make L-band measurements from the Low Earth Orbit. SMOS makes passive measurements whereas Aquarius measures both passive and active. SMOS was launched in November 2009 and Aquarius in June 2011.The scientific objectives of the missions are overlapping: both missions aim at mapping the global Sea Surface Salinity (SSS). Additionally, SMOS mission produces soil moisture product (however, Aquarius data will eventually be used for retrieving soil moisture too). The consistency of the brightness temperature observations made by the two instruments is essential for long-term studies of SSS and soil moisture. For resolving the consistency, the calibration of the instruments is the key. The basis of the SMOS brightness temperature level is the measurements performed with the so-called zero-baselines [3]; SMOS employs an interferometric measurement technique which forms a brightness temperature image from several baselines constructed by combination of multiple receivers in an array; zero-length baseline defines the overall brightness temperature level. The basis of the Aquarius brightness temperature level is resolved from the brightness temperature simulator combined with ancillary data such as antenna patterns and environmental models [4]. Consistency between the SMOS zero-baseline measurements and the simulator output would provide a robust basis for establishing the overall comparability of the missions.

  4. Dominant recognition by human CD8+ cytotoxic T lymphocytes of dengue virus nonstructural proteins NS3 and NS1.2a.

    PubMed Central

    Mathew, A; Kurane, I; Rothman, A L; Zeng, L L; Brinton, M A; Ennis, F A

    1996-01-01

    A severe complication of dengue virus infection, dengue hemorrhagic fever (DHF), is hypothesized to be immunologically mediated and virus-specific cytotoxic T lymphocytes (CTLs) may trigger DHF. It is also likely that dengue virus-specific CTLs are important for recovery from dengue virus infections. There is little available information on the human CD8+ T cell responses to dengue viruses. Memory CD8+CTL responses were analyzed to determine the diversity of the T cell response to dengue virus and to identify immunodominant proteins using PBMC from eight healthy adult volunteers who had received monovalent, live-attenuated candidate vaccines of the four dengue serotypes. All the donors had specific T cell proliferation to dengue and to other flaviviruses that we tested. CTLs were generated from the stimulated PBMC of all donors, and in the seven donors tested, dengue virus-specific CD8+CTL activity was demonstrated. The nonstructural (NS3 and NS1.2a) and envelope (E) proteins were recognized by CD8+CTLs from six, five, and three donors, respectively. All donors recognized either NS3 or NS1.2a. In one donor who received a dengue 4 vaccine, CTL killing was seen in bulk culture against the premembrane protein (prM). This is the first demonstration of a CTL response against the prM protein. The CTL responses using the PBMC of two donors were serotype specific, whereas all other donors had serotype-cross-reactive responses. For one donor, CTLs specific for E, NS1.2a, and NS3 proteins were all HLA-B44 restricted. For three other donors tested, the potential restricting alleles for recognition of NS3 were B38, A24, and/or B62 and B35.These results indicate that the CD8+CTL responses of humans after immunization with one serotype of dengue virus are diverse and directed against a variety of proteins. The NS3 and NS1.2a proteins should be considered when designing subunit vaccines for dengue. PMID:8833919

  5. The NS4A Cofactor Dependent Enhancement of HCV NS3 Protease Activity Correlates with a 4D Geometrical Measure of the Catalytic Triad Region

    PubMed Central

    Hamad, Hamzah A.; Thurston, Jeremy; Teague, Thomas; Ackad, Edward; Yousef, Mohammad S.

    2016-01-01

    We are developing a 4D computational methodology, based on 3D structure modeling and molecular dynamics simulation, to analyze the active site of HCV NS3 proteases, in relation to their catalytic activity. In our previous work, the 4D analyses of the interactions between the catalytic triad residues (His57, Asp81, and Ser139) yielded divergent, gradual and genotype-dependent, 4D conformational instability measures, which strongly correlate with the known disparate catalytic activities among genotypes. Here, the correlation of our 4D geometrical measure is extended to intra-genotypic alterations in NS3 protease activity, due to sequence variations in the NS4A activating cofactor. The correlation between the 4D measure and the enzymatic activity is qualitatively evident, which further validates our methodology, leading to the development of an accurate quantitative metric to predict protease activity in silico. The results suggest plausible “communication” pathways for conformational propagation from the activation subunit (the NS4A cofactor binding site) to the catalytic subunit (the catalytic triad). The results also strongly suggest that the well-sampled (via convergence quantification) structural dynamics are more connected to the divergent catalytic activity observed in HCV NS3 proteases than to rigid structures. The method could also be applicable to predict patients’ responses to interferon therapy and better understand the innate interferon activation pathway. PMID:27936126

  6. Antibiotic susceptibility of coagulase-negative staphylococci (CoNS): emergence of teicoplanin-non-susceptible CoNS strains with inducible resistance to vancomycin.

    PubMed

    Ma, Xiao Xue; Wang, En Hua; Liu, Yong; Luo, En Jie

    2011-11-01

    Coagulase-negative staphylococci (CoNS) have become increasingly recognized as important agents of nosocomial infection. One of the characteristics of CoNS is their resistance to multiple antimicrobial agents commonly used for the treatment of staphylococcal infections. CoNS strains (n = 745) isolated from a university teaching hospital in China between 2004 and 2009 were tested for antibiotic resistance. The antibiotics were placed into three categories based on resistance levels of the CoNS strains to these antibiotics: high resistance (resistance rate >70 %), including penicillin G, oxacillin and erythromycin; medium resistance (resistance rate between 30 and 70 %), including tetracycline, clindamycin, ciprofloxacin, trimethoprim/sulfamethoxazole and chloramphenicol; and low resistance (resistance rate <30 %), including rifampicin, ceftizoxime and gentamicin. We also found that the prevalence of strains non-susceptible to teicoplanin increased from 4.5 to 6.7 % between 2008 and 2009. A one-step vancomycin agar selection experiment and subsequent population analysis revealed potentially vancomycin-resistant subpopulations that have been selected from the teicoplanin-non-susceptible strains. Vigilant surveillance of nosocomial isolates of CoNS is needed to determine their resistance to glycopeptides.

  7. Virtual screening of commercial cyclic peptides as NS2B-NS3 protease inhibitor of dengue virus serotype 2 through molecular docking simulation

    NASA Astrophysics Data System (ADS)

    Nasution, M. A. F.; Aini, R. N.; Tambunan, U. S. F.

    2017-04-01

    A disease caused by dengue virus infection has become one of the major health problems in the world, particularly in Asia, Africa, and South America. This disease has become endemic in more than 100 countries, and approximately 100 million cases occur each year with 2.5 billion people or 40% of the world population at risk of having this virus infection. Therefore, we need an antiviral drug that can inhibit the activity of the enzymes that involved in the virus replication in the body. Lately, the peptide-based drug design has been developed and proved to have interesting pharmacological properties. This study uses commercially cyclic peptides that have already marketed. The purpose of this study is to screen the commercial cyclic peptides that can be used as an inhibitor of the NS2B-NS3 protease of dengue virus serotype 2 (DENV-2) through molecular docking simulations. Inhibition of NS3 protease enzyme can lead to enzymatic inhibition activity so the formed polyprotein from the translation of RNA cannot be cut into pieces and remain in the long strand form. Consequently, proteins that are vital for the sustainability of dengue virus replication cannot be formed. This research resulted in [alpha]-ANF (1-28), rat, Brain Natriuretic Peptide, porcine, Atrial Natriuretic Factor (3-28) (human) and Atrial Natriuretic Peptide (126-150) (rat) as the best drug candidate for inhibiting the NS2B-NS3 protease of DENV-2.

  8. Nucleolin interacts with the feline calicivirus 3' untranslated region and the protease-polymerase NS6 and NS7 proteins, playing a role in virus replication.

    PubMed

    Cancio-Lonches, Clotilde; Yocupicio-Monroy, Martha; Sandoval-Jaime, Carlos; Galvan-Mendoza, Iván; Ureña, Luis; Vashist, Surender; Goodfellow, Ian; Salas-Benito, Juan; Gutiérrez-Escolano, Ana Lorena

    2011-08-01

    Cellular proteins play many important roles during the life cycle of all viruses. Specifically, host cell nucleic acid-binding proteins interact with viral components of positive-stranded RNA viruses and regulate viral translation, as well as RNA replication. Here, we report that nucleolin, a ubiquitous multifunctional nucleolar shuttling phosphoprotein, interacts with the Norwalk virus and feline calicivirus (FCV) genomic 3' untranslated regions (UTRs). Nucleolin can also form a complex in vitro with recombinant Norwalk virus NS6 and -7 (NS6/7) and can be copurified with the analogous protein from feline calicivirus (p76 or NS6/7) from infected feline kidney cells. Nucleolin RNA levels or protein were not modified during FCV infection; however, as a consequence of the infection, nucleolin was seen to relocalize from the nucleoli to the nucleoplasm, as well as to the perinuclear area where it colocalizes with the feline calicivirus NS6/7 protein. In addition, antibodies to nucleolin were able to precipitate viral RNA from feline calicivirus-infected cells, indicating a direct or indirect association of nucleolin with the viral RNA during virus replication. Small interfering RNA (siRNA)-mediated knockdown of nucleolin resulted in a reduction of the cytopathic effect and virus yield in CrFK cells. Taken together, these results demonstrate that nucleolin is a nucleolar component that interacts with viral RNA and NS6/7 and is required for feline calicivirus replication.

  9. Nucleolin Interacts with the Feline Calicivirus 3′ Untranslated Region and the Protease-Polymerase NS6 and NS7 Proteins, Playing a Role in Virus Replication ▿

    PubMed Central

    Cancio-Lonches, Clotilde; Yocupicio-Monroy, Martha; Sandoval-Jaime, Carlos; Galvan-Mendoza, Iván; Ureña, Luis; Vashist, Surender; Goodfellow, Ian; Salas-Benito, Juan; Gutiérrez-Escolano, Ana Lorena

    2011-01-01

    Cellular proteins play many important roles during the life cycle of all viruses. Specifically, host cell nucleic acid-binding proteins interact with viral components of positive-stranded RNA viruses and regulate viral translation, as well as RNA replication. Here, we report that nucleolin, a ubiquitous multifunctional nucleolar shuttling phosphoprotein, interacts with the Norwalk virus and feline calicivirus (FCV) genomic 3′ untranslated regions (UTRs). Nucleolin can also form a complex in vitro with recombinant Norwalk virus NS6 and -7 (NS6/7) and can be copurified with the analogous protein from feline calicivirus (p76 or NS6/7) from infected feline kidney cells. Nucleolin RNA levels or protein were not modified during FCV infection; however, as a consequence of the infection, nucleolin was seen to relocalize from the nucleoli to the nucleoplasm, as well as to the perinuclear area where it colocalizes with the feline calicivirus NS6/7 protein. In addition, antibodies to nucleolin were able to precipitate viral RNA from feline calicivirus-infected cells, indicating a direct or indirect association of nucleolin with the viral RNA during virus replication. Small interfering RNA (siRNA)-mediated knockdown of nucleolin resulted in a reduction of the cytopathic effect and virus yield in CrFK cells. Taken together, these results demonstrate that nucleolin is a nucleolar component that interacts with viral RNA and NS6/7 and is required for feline calicivirus replication. PMID:21680514

  10. Epitope mapping and functional analysis of sigma A and sigma NS proteins of avian reovirus

    SciTech Connect

    Huang, Pi H.; Li, Ying J.; Su, Yu P.; Lee, Long H.; Liu, Hung J. . E-mail: hjliu@mail.npust.edu.tw

    2005-02-20

    We have previously shown that avian reovirus (ARV) {sigma}A and {sigma}NS proteins possess dsRNA and ssRNA binding activity and suggested that there are two epitopes on {sigma}A (I and II) and three epitopes (A, B, and C) on {sigma}NS. To further define the location of epitopes on {sigma}A and {sigma}NS proteins and to further elucidate the biological functions of these epitopes by using monoclonal antibodies (MAbs) 62, 1F9, H1E1, and 4A123 against the ARV S1133 strain, the full-length and deletion fragments of S2 and S4 genes of ARV generated by polymerase chain reaction (PCR) were cloned into pET32 expression vectors and the fusion proteins were overexpressed in Escherichia coli BL21 strain. Epitope mapping using MAbs and E. coli-expressed deletion fragments of {sigma}A and {sigma}NS of the ARV S1133 strain, synthetic peptides, and the cross reactivity of MAbs to heterologous ARV strains demonstrated that epitope II on {sigma}A was located at amino acid residues {sup 340}QWVMAGLVSAA{sup 350} and epitope B on {sigma}NS at amino acid residues {sup 180}MLDMVDGRP{sup 188}. The MAbs (62, 1F9, and H1E1) directed against epitopes II and B did not require the native conformation of {sigma}A and {sigma}NS, suggesting that their binding activities were conformation-independent. On the other hand, MAb 4A123 only reacted with complete {sigma}NS but not with truncated {sigma}NS fusion proteins in Western blot, suggesting that the binding activity of MAb to epitope A on {sigma}NS was conformation-dependent. Amino acid sequence analysis and the binding assays of MAb 62 to heterologous ARV strains suggested that epitope II on {sigma}A was highly conserved among ARV strains and that this epitope is suitable as a serological marker for the detection of ARV antibodies following natural infection in chickens. On the contrary, an amino acid substitution at position 183 (M to V) in epitope B of ARV could hinder the reactivity of the {sigma}NS with MAb 1F9. The {sigma}NS of ARV with ss

  11. Construction and analysis of a plant non-specific lipid transfer protein database (nsLTPDB)

    PubMed Central

    2012-01-01

    Background Plant non-specific lipid transfer proteins (nsLTPs) are small and basic proteins. Recently, nsLTPs have been reported involved in many physiological functions such as mediating phospholipid transfer, participating in plant defence activity against bacterial and fungal pathogens, and enhancing cell wall extension in tobacco. However, the lipid transfer mechanism of nsLTPs is still unclear, and comprehensive information of nsLTPs is difficult to obtain. Methods In this study, we identified 595 nsLTPs from 121 different species and constructed an nsLTPs database -- nsLTPDB -- which comprises the sequence information, structures, relevant literatures, and biological data of all plant nsLTPs http://nsltpdb.life.nthu.edu.tw/. Results Meanwhile, bioinformatics and statistics methods were implemented to develop a classification method for nsLTPs based on the patterns of the eight highly-conserved cysteine residues, and to suggest strict Prosite-styled patterns for Type I and Type II nsLTPs. The pattern of Type I is C X2 V X5-7 C [V, L, I] × Y [L, A, V] X8-13 CC × G X12 D × [Q, K, R] X2 CXC X16-21 P X2 C X13-15C, and that of Type II is C X4 L X2 C X9-11 P [S, T] X2 CC X5 Q X2-4 C[L, F]C X2 [A, L, I] × [D, N] P X10-12 [K, R] X4-5 C X3-4 P X0-2 C. Moreover, we referred the Prosite-styled patterns to the experimental mutagenesis data that previously established by our group, and found that the residues with higher conservation played an important role in the structural stability or lipid binding ability of nsLTPs. Conclusions Taken together, this research has suggested potential residues that might be essential to modulate the structural and functional properties of plant nsLTPs. Finally, we proposed some biologically important sites of the nsLTPs, which are described by using a new Prosite-styled pattern that we defined. PMID:22369214

  12. Detergent-Resistant Membrane Association of NS2 and E2 during Hepatitis C Virus Replication

    PubMed Central

    Shanmugam, Saravanabalaji; Saravanabalaji, Dhanaranjani

    2015-01-01

    ABSTRACT Previously, we demonstrated that the efficiency of hepatitis C virus (HCV) E2-p7 processing regulates p7-dependent NS2 localization to putative virus assembly sites near lipid droplets (LD). In this study, we have employed subcellular fractionations and membrane flotation assays to demonstrate that NS2 associates with detergent-resistant membranes (DRM) in a p7-dependent manner. However, p7 likely plays an indirect role in this process, since only the background level of p7 was detectable in the DRM fractions. Our data also suggest that the p7-NS2 precursor is not involved in NS2 recruitment to the DRM, despite its apparent targeting to this location. Deletion of NS2 specifically inhibited E2 localization to the DRM, indicating that NS2 regulates this process. Treatment of cells with methyl-β-cyclodextrin (MβCD) significantly reduced the DRM association of Core, NS2, and E2 and reduced infectious HCV production. Since disruption of the DRM localization of NS2 and E2, either due to p7 and NS2 defects, respectively, or by MβCD treatment, inhibited infectious HCV production, these proteins' associations with the DRM likely play an important role during HCV assembly. Interestingly, we detected the HCV replication-dependent accumulation of ApoE in the DRM fractions. Taking into consideration the facts that ApoE was shown to be a major determinant for infectious HCV particle production at the postenvelopment step and that the HCV Core protein strongly associates with the DRM, recruitment of E2 and ApoE to the DRM may allow the efficient coordination of Core particle envelopment and postenvelopment events at the DRM to generate infectious HCV production. IMPORTANCE The biochemical nature of HCV assembly sites is currently unknown. In this study, we investigated the correlation between NS2 and E2 localization to the detergent-resistant membranes (DRM) and HCV particle assembly. We determined that although NS2's DRM localization is dependent on p7, p7 was not

  13. NMR and MD Studies Reveal That the Isolated Dengue NS3 Protease Is an Intrinsically Disordered Chymotrypsin Fold Which Absolutely Requests NS2B for Correct Folding and Functional Dynamics

    PubMed Central

    Gupta, Garvita; Lim, Liangzhong; Song, Jianxing

    2015-01-01

    Dengue genome encodes a two component protease complex (NS2B-NS3pro) essential for the viral maturation/infectivity, thus representing a key drug target. Previously, due to its “complete insolubility”, the isolated NS3pro could not be experimentally studied and it remains elusive what structure it adopts without NS2B and why NS2B is indispensable. Here as facilitated by our previous discovery, the isolated NS3pro has been surprisingly deciphered by NMR to be the first intrinsically-disordered chymotrypsin-like fold, which exists in a loosely-packed state with non-native long-range interactions as revealed by paramagnetic relaxation enhancement (PRE). The disordered NS3pro appears to be needed for binding a human host factor to trigger the membrane remodeling. Moreover, we have in vitro refolded the NS3pro in complex with either NS2B (48–100) or the full-length NS2B (1–130) anchored into the LMPC micelle, and the two complexes have similar activities but different dynamics. We also performed molecular dynamics (MD) simulations and the results revealed that NS2B shows the highest structural fluctuations in the complex, thus providing the dynamic basis for the observation on its conformational exchange between open and closed states. Remarkably, the NS2B cofactor plays a central role in maintaining the correlated motion network required for the catalysis as we previously decoded for the SARS 3CL protease. Indeed, a truncated NS2B (48–100;Δ77–84) with the flexible loop deleted is able to trap the NS2B-NS3pro complex in a highly dynamic and catalytically-impotent state. Taken together, our study implies potential strategies to perturb the NS2B-NS3pro interface for design of inhibitors for treating dengue infection. PMID:26258523

  14. Results of Satellite Brightness Modeling Using Kringing Optimized Interpolation

    NASA Astrophysics Data System (ADS)

    Weeden, C.; Hejduk, M.

    At the 2005 AMOS conference, Kriging Optimized Interpolation (KOI) was presented as a tool to model satellite brightness as a function of phase angle and solar declination angle (J.M Okada and M.D. Hejduk). Since November 2005, this method has been used to support the tasking algorithm for all optical sensors in the Space Surveillance Network (SSN). The satellite brightness maps generated by the KOI program are compared to each sensor's ability to detect an object as a function of the brightness of the background sky and angular rate of the object. This will determine if the sensor can technically detect an object based on an explicit calculation of the object's probability of detection. In addition, recent upgrades at Ground-Based Electro Optical Deep Space Surveillance Sites (GEODSS) sites have increased the amount and quality of brightness data collected and therefore available for analysis. This in turn has provided enough data to study the modeling process in more detail in order to obtain the most accurate brightness prediction of satellites. Analysis of two years of brightness data gathered from optical sensors and modeled via KOI solutions are outlined in this paper. By comparison, geo-stationary objects (GEO) were tracked less than non-GEO objects but had higher density tracking in phase angle due to artifices of scheduling. A statistically-significant fit to a deterministic model was possible less than half the time in both GEO and non-GEO tracks, showing that a stochastic model must often be used alone to produce brightness results, but such results are nonetheless serviceable. Within the Kriging solution, the exponential variogram model was the most frequently employed in both GEO and non-GEO tracks, indicating that monotonic brightness variation with both phase and solar declination angle is common and testifying to the suitability to the application of regionalized variable theory to this particular problem. Finally, the average nugget value, or

  15. Coming to terms with lightness and brightness: effects of stimulus configuration and instructions on brightness and lightness judgments.

    PubMed

    Blakeslee, Barbara; Reetz, Daniel; McCourt, Mark E

    2008-08-06

    To recover surface reflectance and illuminance from the raw luminance signal, the visual system must use prior assumptions and strategies that make use of additional sources of information. Indeed, it has been found that depending on experimental conditions, lightness (apparent reflectance) may refer to judgments that are similar to brightness judgments (apparent luminance), that are similar to local brightness-contrast judgments, or that represent an independent third dimension of achromatic experience which exists only when the illumination across regions of the display is visibly non-uniform (L. E. Arend & B. Spehar, 1993a, 1993b). This means that lightness data generated in one experimental condition may not be comparable to lightness data measured in other conditions. We investigate this problem with regard to a history of data on simultaneous brightness-contrast by measuring brightness, brightness-contrast, and lightness in stimuli similar to those used in Gilchrist's edge-substitution studies (A. Gilchrist, S. Delman, & A. Jacobsen, 1983) and in stimuli similar to those used to test Gilchrist's intrinsic-image model against his newer anchoring model (A. Gilchrist, 2006). Our results clarify confusions that appear to stem from comparing different types of lightness judgments and from inadvertently using brightness as an index of lightness under conditions where independent lightness judgments are possible.

  16. Antagonism of the complement component C4 by flavivirus nonstructural protein NS1

    PubMed Central

    Avirutnan, Panisadee; Fuchs, Anja; Hauhart, Richard E.; Somnuke, Pawit; Youn, Soonjeon

    2010-01-01

    The complement system plays an essential protective role in the initial defense against many microorganisms. Flavivirus NS1 is a secreted nonstructural glycoprotein that accumulates in blood, is displayed on the surface of infected cells, and has been hypothesized to have immune evasion functions. Herein, we demonstrate that dengue virus (DENV), West Nile virus (WNV), and yellow fever virus (YFV) NS1 attenuate classical and lectin pathway activation by directly interacting with C4. Binding of NS1 to C4 reduced C4b deposition and C3 convertase (C4b2a) activity. Although NS1 bound C4b, it lacked intrinsic cofactor activity to degrade C4b, and did not block C3 convertase formation or accelerate decay of the C3 and C5 convertases. Instead, NS1 enhanced C4 cleavage by recruiting and activating the complement-specific protease C1s. By binding C1s and C4 in a complex, NS1 promotes efficient degradation of C4 to C4b. Through this mechanism, NS1 protects DENV from complement-dependent neutralization in solution. These studies define a novel immune evasion mechanism for restricting complement control of microbial infection. PMID:20308361

  17. Raising the avermectins production in Streptomyces avermitilis by utilizing nanosecond pulsed electric fields (nsPEFs)

    NASA Astrophysics Data System (ADS)

    Guo, Jinsong; Ma, Ruonan; Su, Bo; Li, Yinglong; Zhang, Jue; Fang, Jing

    2016-05-01

    Avermectins, a group of anthelmintic and insecticidal agents produced from Streptomyces avermitilis, are widely used in agricultural, veterinary, and medical fields. This study presents the first report on the potential of using nanosecond pulsed electric fields (nsPEFs) to improve avermectin production in S. avermitilis. The results of colony forming units showed that 20 pulses of nsPEFs at 10 kV/cm and 20 kV/cm had a significant effect on proliferation, while 100 pulses of nsPEFs at 30 kV/cm exhibited an obvious effect on inhibition of agents. Ultraviolet spectrophotometry assay revealed that 20 pulses of nsPEFs at 15 kV/cm increased avermectin production by 42% and reduced the time for reaching a plateau in fermentation process from 7 days to 5 days. In addition, the decreased oxidation reduction potential (ORP) and increased temperature of nsPEFs-treated liquid were evidenced to be closely associated with the improved cell growth and fermentation efficiency of avermectins in S. avermitilis. More importantly, the real-time RT-PCR analysis showed that nsPEFs could remarkably enhance the expression of aveR and malE in S. avermitilis during fermentation, which are positive regulator for avermectin biosynthesis. Therefore, the nsPEFs technology presents an alternative strategy to be developed to increase avermectin output in fermentation industry.

  18. Structure of the catalytic domain of the hepatitis C virus NS2-3 protease

    SciTech Connect

    Lorenz,I.; Marcotrigiano, J.; Dentzer, T.; Rice, C.

    2006-01-01

    Hepatitis C virus is a major global health problem affecting an estimated 170 million people worldwide. Chronic infection is common and can lead to cirrhosis and liver cancer. There is no vaccine available and current therapies have met with limited success. The viral RNA genome encodes a polyprotein that includes two proteases essential for virus replication. The NS2-3 protease mediates a single cleavage at the NS2/NS3 junction, whereas the NS3-4A protease cleaves at four downstream sites in the polyprotein. NS3-4A is characterized as a serine protease with a chymotrypsin-like fold, but the enzymatic mechanism of the NS2-3 protease remains unresolved. Here we report the crystal structure of the catalytic domain of the NS2-3 protease at 2.3 Angstroms resolution. The structure reveals a dimeric cysteine protease with two composite active sites. For each active site, the catalytic histidine and glutamate residues are contributed by one monomer, and the nucleophilic cysteine by the other. The carboxy-terminal residues remain coordinated in the two active sites, predicting an inactive post-cleavage form. Proteolysis through formation of a composite active site occurs in the context of the viral polyprotein expressed in mammalian cells. These features offer unexpected insights into polyprotein processing by hepatitis C virus and new opportunities for antiviral drug design.

  19. Molecular Modeling and Docking Study to Elucidate Novel Chikungunya Virus nsP2 Protease Inhibitors.

    PubMed

    Agarwal, T; Asthana, Somya; Bissoyi, A

    2015-01-01

    Chikungunya is one of the tropical viral infections that severely affect the Asian and African countries. Absence of any suitable drugs or vaccines against Chikungunya virus till date makes it essential to identify and develop novel leads for the same. Recently, nsP2 cysteine protease has been classified as a crucial drug target to combat infections caused by Alphaviruses including Chikungunya virus due to its involvement viral replication. Here in, we investigated the structural aspects of the nsP2 protease through homology modeling based on nsP2 protease from Venezuelan equine encephalitis virus. Further, the ligands were virtually screened based on various pharmacological, ADME/Tox filters and subjected to docking with the modeled Chikungunya nsP2 protease using AutoDock4.2. The interaction profiling of ligand with the protein was carried out using LigPlot(+). The results demonstrated that the ligand with PubChem Id (CID_5808891) possessed highest binding affinity towards Chikungunya nsP2 protease with a good interaction profile with the active site residues. We hereby propose that these compounds could inhibit the nsP2 protease by binding to its active site. Moreover, they may provide structural scaffold for the design of novel leads with better efficacy and specificity for the nsP2 protease.

  20. Identification of Hydroxyanthraquinones as Novel Inhibitors of Hepatitis C Virus NS3 Helicase

    PubMed Central

    Furuta, Atsushi; Tsubuki, Masayoshi; Endoh, Miduki; Miyamoto, Tatsuki; Tanaka, Junichi; Abdus Salam, Kazi; Akimitsu, Nobuyoshi; Tani, Hidenori; Yamashita, Atsuya; Moriishi, Kohji; Nakakoshi, Masamichi; Sekiguchi, Yuji; Tsuneda, Satoshi; Noda, Naohiro

    2015-01-01

    Hepatitis C virus (HCV) is an important etiological agent of severe liver diseases, including cirrhosis and hepatocellular carcinoma. The HCV genome encodes nonstructural protein 3 (NS3) helicase, which is a potential anti-HCV drug target because its enzymatic activity is essential for viral replication. Some anthracyclines are known to be NS3 helicase inhibitors and have a hydroxyanthraquinone moiety in their structures; mitoxantrone, a hydroxyanthraquinone analogue, is also known to inhibit NS3 helicase. Therefore, we hypothesized that the hydroxyanthraquinone moiety alone could also inhibit NS3 helicase. Here, we performed a structure–activity relationship study on a series of hydroxyanthraquinones by using a fluorescence-based helicase assay. Hydroxyanthraquinones inhibited NS3 helicase with IC50 values in the micromolar range. The inhibitory activity varied depending on the number and position of the phenolic hydroxyl groups, and among different hydroxyanthraquinones examined, 1,4,5,8-tetrahydroxyanthraquinone strongly inhibited NS3 helicase with an IC50 value of 6 µM. Furthermore, hypericin and sennidin A, which both have two hydroxyanthraquinone-like moieties, were found to exert even stronger inhibition with IC50 values of 3 and 0.8 µM, respectively. These results indicate that the hydroxyanthraquinone moiety can inhibit NS3 helicase and suggest that several key chemical structures are important for the inhibition. PMID:26262613

  1. Evaluation of an Enzyme Immunoassay for Detection of Dengue Virus NS1 Antigen in Human Serum▿

    PubMed Central

    Dussart, Philippe; Labeau, Bhety; Lagathu, Gisèle; Louis, Philippe; Nunes, Marcio R. T.; Rodrigues, Sueli G.; Storck-Herrmann, Cécile; Cesaire, Raymond; Morvan, Jacques; Flamand, Marie; Baril, Laurence

    2006-01-01

    We evaluated a one-step sandwich-format microplate enzyme immunoassay for detecting dengue virus NS1 antigen (Ag) in human serum by use of Platelia Dengue NS1 Ag kits (Bio-Rad Laboratories, Marnes La Coquette, France). We collected 299 serum samples from patients with dengue disease and 50 serum samples from patients not infected with dengue virus. For the 239 serum samples from patients with acute infections testing positive by reverse transcription-PCR and/or virus isolation for one of the four dengue virus serotypes, the sensitivity of the Platelia Dengue NS1 Ag kit was 88.7% (95% confidence interval, 84.0% to 92.4%). None of the serum samples from patients not infected with dengue virus tested positive with the Platelia Dengue NS1 Ag kit. A diagnostic strategy combining the Platelia Dengue NS1 Ag test for acute-phase sera and immunoglobulin M capture enzyme-linked immunosorbent assay for early-convalescent-phase sera increased sensitivity only from 88.7% to 91.9%. Thus, NS1 antigen detection with the Platelia Dengue NS1 Ag kit could be used for first-line testing for acute dengue virus infection in clinical diagnostic laboratories. PMID:16988003

  2. Detection of damaging nsSNPs on human caspase-cascades related to apoptotic signalling pathway.

    PubMed

    Tomar, Jinny; Gera, V K; Chakraborty, Chiranjib

    2013-09-01

    In tumorigenesis, cancer genetics and the related mutations have been the main topic of study these days. Caspases have been found to be actively involved in the process of apoptosis. Malfunction of apoptosis is one of the causes for cancerous tumors and different caspase mutations are related to that process. It has been found that two groups of caspases involved in this process apoptosis which are initiator caspases and executioner caspases. SNPs have been extensively studied over the last decade, due to their association with a number of genetic diseases. Human SNPs have always been a source of information related to the complex changes associated with their origin. SNPs which can change the resulting amino acid i.e., nonsynonymous SNPs (nsSNPs) are of prime concern these days because of their direct relation with the disease or the respective individual. In this study our focus is not only to detect the nsSNPs available in the human caspase data but to further evaluate the potentially damaging nsSNPs. Using the computational approach we have been able to obtain almost seventy eight nsSNPs, among these few of the nsSNPs seem to have serious consequences, as they have been cross verified from a variety of SNP prediction tools. The functional as well as structural impact of the nsSNPs is determined and discussed. Our predicted nsSNPs on human caspases may be associated with cancer risk.

  3. Selective susceptibility to nanosecond pulsed electric field (nsPEF) across different human cell types.

    PubMed

    Gianulis, Elena C; Labib, Chantelle; Saulis, Gintautas; Novickij, Vitalij; Pakhomova, Olga N; Pakhomov, Andrei G

    2017-05-01

    Tumor ablation by nanosecond pulsed electric fields (nsPEF) is an emerging therapeutic modality. We compared nsPEF cytotoxicity for human cell lines of cancerous (IMR-32, Hep G2, HT-1080, and HPAF-II) and non-cancerous origin (BJ and MRC-5) under strictly controlled and identical conditions. Adherent cells were uniformly treated by 300-ns PEF (0-2000 pulses, 1.8 kV/cm, 50 Hz) on indium tin oxide-covered glass coverslips, using the same media and serum. Cell survival plotted against the number of pulses displayed three distinct regions (initial resistivity, logarithmic survival decline, and residual resistivity) for all tested cell types, but with differences in LD50 spanning as much as nearly 80-fold. The non-cancerous cells were less sensitive than IMR-32 neuroblastoma cells but more vulnerable than the other cancers tested. The cytotoxic efficiency showed no apparent correlation with cell or nuclear size, cell morphology, metabolism level, or the extent of membrane disruption by nsPEF. Increasing pulse duration to 9 µs (0.75 kV/cm, 5 Hz) produced a different selectivity pattern, suggesting that manipulation of PEF parameters can, at least for certain cancers, overcome their resistance to nsPEF ablation. Identifying mechanisms and cell markers of differential nsPEF susceptibility will critically contribute to the proper choice and outcome of nsPEF ablation therapies.

  4. Efficacy of NS-718, a novel lipid nanosphere-encapsulated amphotericin B, against Cryptococcus neoformans.

    PubMed

    Hossain, M A; Maesaki, S; Kakeya, H; Noda, T; Yanagihara, K; Sasaki, E; Hirakata, Y; Tomono, K; Tashiro, T; Kohno, S

    1998-07-01

    In vitro and in vivo efficacies of NS-718, a lipid nanosphere-encapsulated amphotericin B (AMPH-B), have been studied. Of the tested AMPH-B formulations, NS-718 had the lowest MIC for Cryptococcus neoformans. In a murine model, low-dose therapy (0.8 mg/kg of body weight) with NS-718 showed higher efficacy than that with AmBisome. High-dose therapy (2.0 mg/kg) with NS-718 was much more effective than those with Fungizone and AmBisome. In mice treated with a high dose of NS-718, only a few yeast cells had grown in lung by 7 days after inoculation. A pharmacokinetic study showed higher concentrations of AMPH-B in lung following administration of NS-718 than after administration of AmBisome. Our results indicated that NS-718, a new AMPH-B formulation, is a promising antifungal agent for treatment of pulmonary cryptococcosis and could be the most effective antifungal agent against C. neoformans infections.

  5. Purification and characterization of the major nonstructural protein (NS-1) of Aleutian mink disease parvovirus.

    PubMed Central

    Christensen, J; Pedersen, M; Aasted, B; Alexandersen, S

    1995-01-01

    We have previously described the expression of the major nonstructural protein (NS-1) of Aleutian mink disease parvovirus (ADV) in insect cells by using a baculovirus vector (J. Christensen, T. Storgaard, B. Bloch, S. Alexandersen, and B. Aasted, J. Virol. 67:229-238, 1993). To study its biochemical properties, ADV NS-1 was expressed in Sf9 insect cells and purified to apparent homogeneity with a combination of nuclear extraction, Zn2+ ion chromatography, and immunoaffinity chromatography on monoclonal antibodies. The purified protein showed ATP binding and ATPase- and ATP- or dATP-dependent helicase activity requiring either Mg2+ or Mn2+ as a cofactor. The ATPase activity of NS-1 was efficiently stimulated by single-stranded DNA and, to a lesser extent, double-stranded DNA. We also describe the expression, purification, and characterization of a mutant NS-1 protein, in which a lysine in the putative nucleotide binding consensus sequence of the molecule was replaced with serine. The mutated NS-1 was expressed at 10-fold higher levels than wild-type NS-1, but it exhibited no ATP binding. ATPase, or helicase activity. The availability of large amounts of purified functional NS-1 protein will facilitate studies of the biochemistry of ADV replication and gene regulation leading to disease in mink. PMID:7853520

  6. Zika-Virus-Encoded NS2A Disrupts Mammalian Cortical Neurogenesis by Degrading Adherens Junction Proteins.

    PubMed

    Yoon, Ki-Jun; Song, Guang; Qian, Xuyu; Pan, Jianbo; Xu, Dan; Rho, Hee-Sool; Kim, Nam-Shik; Habela, Christa; Zheng, Lily; Jacob, Fadi; Zhang, Feiran; Lee, Emily M; Huang, Wei-Kai; Ringeling, Francisca Rojas; Vissers, Caroline; Li, Cui; Yuan, Ling; Kang, Koeun; Kim, Sunghan; Yeo, Junghoon; Cheng, Yichen; Liu, Sheng; Wen, Zhexing; Qin, Cheng-Feng; Wu, Qingfeng; Christian, Kimberly M; Tang, Hengli; Jin, Peng; Xu, Zhiheng; Qian, Jiang; Zhu, Heng; Song, Hongjun; Ming, Guo-Li

    2017-09-07

    Zika virus (ZIKV) directly infects neural progenitors and impairs their proliferation. How ZIKV interacts with the host molecular machinery to impact neurogenesis in vivo is not well understood. Here, by systematically introducing individual proteins encoded by ZIKV into the embryonic mouse cortex, we show that expression of ZIKV-NS2A, but not Dengue virus (DENV)-NS2A, leads to reduced proliferation and premature differentiation of radial glial cells and aberrant positioning of newborn neurons. Mechanistically, in vitro mapping of protein-interactomes and biochemical analysis suggest interactions between ZIKA-NS2A and multiple adherens junction complex (AJ) components. Functionally, ZIKV-NS2A, but not DENV-NS2A, destabilizes the AJ complex, resulting in impaired AJ formation and aberrant radial glial fiber scaffolding in the embryonic mouse cortex. Similarly, ZIKA-NS2A, but not DENV-NS2A, reduces radial glial cell proliferation and causes AJ deficits in human forebrain organoids. Together, our results reveal pathogenic mechanisms underlying ZIKV infection in the developing mammalian brain. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Current Drug Discovery for Anti-hepatitis C Virus Targeting NS4B.

    PubMed

    Wang, Zhenya; Chen, Xinli; Wu, Chunli; Xu, Haiwei; Liu, Hongmin

    2016-01-01

    Hepatitis C virus (HCV) infection is a major worldwide epidemic disease. It is estimated that more than 170 million individuals are infected with HCV and with three to four million new cases each year. Many new direct-acting antiviral (DAA) agents that specifically target HCV NS3 protease or NS5B polymerase inhibitors are therefore in development, with a significant effect for the patient and for the market recently. The non-structural 4B (NS4B) protein, is among the least characterized of the HCV proteins. A variety of functions have been recognized for NS4B, such as the ability to induce the membranous web replication platform, RNA binding and NTPase activity. In order to maximize antiviral efficacy and prevent the emergence of resistance, novel NS4B inhibitors have been subjected to pharmacological studies. In this review, we discussed current understanding of the structure and function of NS4B, and novel drug discoveries targeting NS4B as anti-hepatitis C virus such as sulfonamide, piperidine, carboxamide, piperazinone and quinoline derivatives within the last three years.

  8. Candidate nsSNPs that can affect the functions and interactions of cell cycle proteins.

    PubMed

    Savas, Sevtap; Ahmad, M Farhan; Shariff, Mehjabeen; Kim, David Y; Ozcelik, Hilmi

    2005-02-15

    Nonsynonymous single nucleotide polymorphisms (nsSNPs) alter the encoded amino acid sequence, and are thus likely to affect the function of the proteins, and represent potential disease-modifiers. There is an enormous number of nsSNPs in the human population, and the major challenge lies in distinguishing the functionally significant and potentially disease-related ones from the rest. In this study, we analyzed the genetic variations that can alter the functions and the interactions of a group of cell cycle proteins (n = 60) and the proteins interacting with them (n = 26) using computational tools. As a result, we extracted 249 nsSNPs from 77 cell cycle proteins and their interaction partners from public SNP databases. Only 31 (12.4%) of the nsSNPs were validated. The majority (64.5%) of the validated SNPs were rare (minor allele frequencies < 5%). Evolutionary conservation analysis using the SIFT tool suggested that 16.1% of the validated nsSNPs may disrupt the protein function. In addition, 58% of the validated nsSNPs were located in functional protein domains/motifs, which together with the evolutionary conservation analysis enabled us to infer possible biological consequences of the nsSNPs in our set. Our study strongly suggests the presence of naturally occurring genetic variations in the cell cycle proteins that may affect their interactions and functions with possible roles in complex human diseases, such as cancer.

  9. Raising the avermectins production in Streptomyces avermitilis by utilizing nanosecond pulsed electric fields (nsPEFs)

    PubMed Central

    Guo, Jinsong; Ma, Ruonan; Su, Bo; Li, Yinglong; Zhang, Jue; Fang, Jing

    2016-01-01

    Avermectins, a group of anthelmintic and insecticidal agents produced from Streptomyces avermitilis, are widely used in agricultural, veterinary, and medical fields. This study presents the first report on the potential of using nanosecond pulsed electric fields (nsPEFs) to improve avermectin production in S. avermitilis. The results of colony forming units showed that 20 pulses of nsPEFs at 10 kV/cm and 20 kV/cm had a significant effect on proliferation, while 100 pulses of nsPEFs at 30 kV/cm exhibited an obvious effect on inhibition of agents. Ultraviolet spectrophotometry assay revealed that 20 pulses of nsPEFs at 15 kV/cm increased avermectin production by 42% and reduced the time for reaching a plateau in fermentation process from 7 days to 5 days. In addition, the decreased oxidation reduction potential (ORP) and increased temperature of nsPEFs-treated liquid were evidenced to be closely associated with the improved cell growth and fermentation efficiency of avermectins in S. avermitilis. More importantly, the real-time RT-PCR analysis showed that nsPEFs could remarkably enhance the expression of aveR and malE in S. avermitilis during fermentation, which are positive regulator for avermectin biosynthesis. Therefore, the nsPEFs technology presents an alternative strategy to be developed to increase avermectin output in fermentation industry. PMID:27181521

  10. Molecular Modeling and Docking Study to Elucidate Novel Chikungunya Virus nsP2 Protease Inhibitors

    PubMed Central

    Agarwal, T.; Asthana, Somya; Bissoyi, A.

    2015-01-01

    Chikungunya is one of the tropical viral infections that severely affect the Asian and African countries. Absence of any suitable drugs or vaccines against Chikungunya virus till date makes it essential to identify and develop novel leads for the same. Recently, nsP2 cysteine protease has been classified as a crucial drug target to combat infections caused by Alphaviruses including Chikungunya virus due to its involvement viral replication. Here in, we investigated the structural aspects of the nsP2 protease through homology modeling based on nsP2 protease from Venezuelan equine encephalitis virus. Further, the ligands were virtually screened based on various pharmacological, ADME/Tox filters and subjected to docking with the modeled Chikungunya nsP2 protease using AutoDock4.2. The interaction profiling of ligand with the protein was carried out using LigPlot+. The results demonstrated that the ligand with PubChem Id (CID_5808891) possessed highest binding affinity towards Chikungunya nsP2 protease with a good interaction profile with the active site residues. We hereby propose that these compounds could inhibit the nsP2 protease by binding to its active site. Moreover, they may provide structural scaffold for the design of novel leads with better efficacy and specificity for the nsP2 protease. PMID:26664062

  11. The Dengue Virus NS5 Protein Intrudes in the Cellular Spliceosome and Modulates Splicing

    PubMed Central

    Shah, Priya; Pozzi, Berta; Gebhard, Leopoldo G.; Mammi, Pablo; Yanovsky, Marcelo J.; Andino, Raul; Krogan, Nevan; Srebrow, Anabella; Gamarnik, Andrea V.

    2016-01-01

    Dengue virus NS5 protein plays multiple functions in the cytoplasm of infected cells, enabling viral RNA replication and counteracting host antiviral responses. Here, we demonstrate a novel function of NS5 in the nucleus where it interferes with cellular splicing. Using global proteomic analysis of infected cells together with functional studies, we found that NS5 binds spliceosome complexes and modulates endogenous splicing as well as minigene-derived alternative splicing patterns. In particular, we show that NS5 alone, or in the context of viral infection, interacts with core components of the U5 snRNP particle, CD2BP2 and DDX23, alters the inclusion/exclusion ratio of alternative splicing events, and changes mRNA isoform abundance of known antiviral factors. Interestingly, a genome wide transcriptome analysis, using recently developed bioinformatics tools, revealed an increase of intron retention upon dengue virus infection, and viral replication was improved by silencing specific U5 components. Different mechanistic studies indicate that binding of NS5 to the spliceosome reduces the efficiency of pre-mRNA processing, independently of NS5 enzymatic activities. We propose that NS5 binding to U5 snRNP proteins hijacks the splicing machinery resulting in a less restrictive environment for viral replication. PMID:27575636

  12. NS1619-induced vasodilation is enhanced and differentially mediated in chronically hypoxic lungs.

    PubMed

    McCullough, Danielle J; Vang, Alexander; Choudhary, Gaurav

    2014-10-01

    To identify the effect of the benzimidazalone derivative, NS1619, on modulating pulmonary vascular tone in lungs from rats exposed to normoxia (21% FiO2) or chronic hypoxia (10% FiO2) for three weeks. Isolated perfused lungs were preconstricted (U46619), and dose-dependent vasodilation to NS1619 was assessed. To elucidate the mechanisms responsible, NS1619 vasodilatory responses were assessed following inhibition of large-conductance Ca(2+)-activated (BKCa; iberiotoxin and paxilline), L-type Ca2+ (nifedipine), K+ (tetraethylammonium), Cl- (niflumic acid), and cation/TRP (lanthanum) channels, as well as nitric oxide synthase (L-NAME). Compared to normoxia, NS1619-induced vasodilation was significantly greater following hypoxia; however, NO-dependent vasodilation and BKCa-mediated vasodilation, in response to NS1619, were similar in the normoxic and hypoxic lungs. In contrast, direct activation of L-type Ca2+ and non-BKCa K+ channel was involved in the NS1619-induced vasodilation only in hypoxic lungs. NS1619 causes pulmonary vasodilation by affecting multiple complementary pathways, including stimulation of NO production, activation of BKCa channels, other TEA-sensitive K+ channels, and L-type Ca2+ channels, and could be considered as a therapeutic agent in hypoxic PH.

  13. Crystal structure of full-length Zika virus NS5 protein reveals a conformation similar to Japanese encephalitis virus NS5.

    PubMed

    Upadhyay, Anup K; Cyr, Matthew; Longenecker, Kenton; Tripathi, Rakesh; Sun, Chaohong; Kempf, Dale J

    2017-03-01

    The rapid spread of the recent Zika virus (ZIKV) epidemic across various countries in the American continent poses a major health hazard for the unborn fetuses of pregnant women. To date, there is no effective medical intervention. The nonstructural protein 5 of Zika virus (ZIKV-NS5) is critical for ZIKV replication through the 5'-RNA capping and RNA polymerase activities present in its N-terminal methyltransferase (MTase) and C-terminal RNA-dependent RNA polymerase (RdRp) domains, respectively. The crystal structure of the full-length ZIKV-NS5 protein has been determined at 3.05 Å resolution from a crystal belonging to space group P21212 and containing two protein molecules in the asymmetric unit. The structure is similar to that reported for the NS5 protein from Japanese encephalitis virus and suggests opportunities for structure-based drug design targeting either its MTase or RdRp domain.

  14. Plasma Membrane Permeabilization by 60- and 600-ns Electric Pulses Is Determined by the Absorbed Dose

    PubMed Central

    Ibey, Bennett L.; Xiao, Shu; Schoenbach, Karl H.; Murphy, Michael R.; Pakhomov, Andrei G.

    2008-01-01

    We explored how the effect of plasma membrane permeabilization by nanosecond-duration electric pulses (nsEP) depends on the physical characteristics of exposure. The resting membrane resistance (Rm) and membrane potential (MP) were measured in cultured GH3 and CHO cells by conventional whole-cell patch-clamp technique. Intact cells were exposed to a single nsEP (60 or 600 ns duration, 0-22 kV/cm), followed by patch-clamp measurements after a 2-3 min delay. Consistent with earlier findings, nsEP caused long-lasting Rm decrease, accompanied by the loss of MP. The threshold for these effects was about 6 kV/cm for 60 ns pulses, and about 1 kV/cm for 600 ns pulses. Further analysis established that it was neither pulse duration nor the E-field amplitude per se, but the absorbed dose that determined the magnitude of the biological effect. In other words, exposure to nsEP at either pulse duration caused equal effects if the absorbed doses were equal. The threshold absorbed dose to produce plasma membrane effects in either GH3 or CHO cells at either pulse duration was found to be at or below 10 mJ/g. Despite being determined by the dose, the nsEP effect clearly is not thermal, as the maximum heating at the threshold dose is less than 0.01 °C. The use of the absorbed dose as a universal exposure metric may help to compare and quantify nsEP sensitivity of different cell types and of cells in different physiological conditions. The absorbed dose may also prove to be a more useful metric than the incident E-field in determining safety limits for high peak, lowaverage power EMF emissions. PMID:18839412

  15. Dynamic Imaging of the Hepatitis C Virus NS5A Protein during a Productive Infection

    PubMed Central

    Eyre, Nicholas S.; Fiches, Guillaume N.; Aloia, Amanda L.; Helbig, Karla J.; McCartney, Erin M.; McErlean, Christopher S. P.; Li, Kui; Aggarwal, Anupriya; Turville, Stuart G.

    2014-01-01

    ABSTRACT Hepatitis C virus (HCV) NS5A is essential for viral genome replication within cytoplasmic replication complexes and virus assembly at the lipid droplet (LD) surface, although its definitive functions are poorly understood. We developed approaches to investigate NS5A dynamics during a productive infection. We report here that NS5A motility and efficient HCV RNA replication require the microtubule network and the cytoplasmic motor dynein and demonstrate that both motile and relatively static NS5A-positive foci are enriched with host factors VAP-A and Rab5A. Pulse-chase imaging revealed that newly synthesized NS5A foci are small and distinct from aged foci, while further studies using a unique dual fluorescently tagged infectious HCV chimera showed a relatively stable association of NS5A foci with core-capped LDs. These results reveal new details about the dynamics and maturation of NS5A and the nature of potential sites of convergence of HCV replication and assembly pathways. IMPORTANCE Hepatitis C virus (HCV) is a major cause of serious liver disease worldwide. An improved understanding of the HCV replication cycle will enable development of novel and improved antiviral strategies. Here we have developed complementary fluorescent labeling and imaging approaches to investigate the localization, traffic and interactions of the HCV NS5A protein in living, virus-producing cells. These studies reveal new details as to the traffic, composition and biogenesis of NS5A foci and the nature of their association with putative sites of virus assembly. PMID:24429364

  16. Recombinant Dengue virus protein NS2B alters membrane permeability in different membrane models.

    PubMed

    León-Juárez, Moisés; Martínez-Castillo, Macario; Shrivastava, Gaurav; García-Cordero, Julio; Villegas-Sepulveda, Nicolás; Mondragón-Castelán, Mónica; Mondragón-Flores, Ricardo; Cedillo-Barrón, Leticia

    2016-01-04

    One of the main phenomena occurring in cellular membranes during virus infection is a change in membrane permeability. It has been observed that numerous viral proteins can oligomerize and form structures known as viroporins that alter the permeability of membranes. Previous findings have identified such proteins in cells infected with Japanese encephalitis virus (JEV), a member of the same family that Dengue virus (DENV) belongs to (Flaviviridae). In the present work, we investigated whether the small hydrophobic DENV protein NS2B serves a viroporin function. We cloned the DENV NS2B sequence and expressed it in a bacterial expression system. Subsequently, we evaluated the effect of DENV NS2B on membranes when NS2B was overexpressed, measured bacterial growth restriction, and evaluated changes of permeability to hygromycin. The NS2B protein was purified by affinity chromatography, and crosslinking assays were performed to determine the presence of oligomers. Hemolysis assays and transmission electron microscopy were performed to identify structures involved in permeability changes. The DENV-2 NS2B protein showed similitude with the JEV viroporin. The DENV-2 NS2B protein possessed the ability to change the membrane permeability in bacteria, to restrict bacterial cell growth, and to enable membrane permeability to hygromycin B. The NS2B protein formed trimers that could participate in cell lysis and generate organized structures on eukaryotes membranes. Our data suggest that the DENV-2 NS2B viral protein is capable of oligomerizing and organizing to form pore-like structures in different lipid environments, thereby modifying the permeability of cell membranes.

  17. [Preparation of reactive bright blue praseodymium dyestuff and its spectral properties].

    PubMed

    Liu, Xiao-Zhen; Yuan, Ya-Qin; Cai, Yu; Zhu, Xian; Wang, Yan-Hong

    2004-08-01

    Reactive bright blue praseodymium dyestuff was prepared by using reactive bright blue and praseodymium oxide. The spectra of reactive bright blue praseodymium and dyed silk cloth by reactive bright blue praseodymium dyestuff were studied by UV-Vis and IR spectra respectively. In the range of 200-800 nm, reactive bright blue has four absorption peaks, and lambda(max) is 259 nm; reactive bright blue praseodymium has three absorption peaks, while lambda(max), is 264.00 nm. In the range of 420-760 nm, reactive bright blue has two absorption peaks at 661.50 and 625.50 nm, respectively, and lambda(max) is 661.50 nm; reactive bright blue praseodymium has only one absorption peak at 618.00 nm. Coordinate bond links reactive bright blue to praseodymium ion. Reactive bright blue praseodymium increases linking radicals as compared with reactive bright blue.

  18. FORCAST Observations of a Bright ToO Comet

    NASA Astrophysics Data System (ADS)

    Wooden, Diane

    2013-10-01

    We propose to measure the dust and organics of a bright unknown comet or comet outburst with this CY2 Target-of-Opportunity (ToO) proposal. A 5-39 micron spectrum of a ToO bright comet with FORCAST will address our two primary goals: 1) characterize the coma dust mineralogy; and 2) identify organics in the critical 5-8 micron region. The crystalline fraction of comet dust has become a benchmark for models of heating and radial transport in our protoplanetary disk. In addition, by measuring the wavelengths, relative intensities, and feature asymmetries of crystalline peaks at 11.2, 19, 23.5, 27.5, and 33 micron, the shapes of forsterite crystals can be constrained and their condensation temperatures inferred by comparison with theoretical and experimental data. Observations of cometary organics probe the unknown precursor materials that were transformed by heat into 'macromolecular carbon' found ubiquitously in carbonaceous chondrite samples from primitive asteroids. Thermal models fitted to FORCAST observations of a bright ToO comet determine the dust properties and the comet's dust properties links to the physical and chemical conditions in the solar nebula, and help to fulfill the SOFIA Science Case for Evolution of Our Solar System. We define a CY2 ToO bright comet as an unpredictable cometary outburst event or a comet discovered after the CY2 submission deadline that produces a naked-eye comet that is observable within CY2. From 1995 through 2013, there are eight bright comet apparitions where five out of eight are ToO comets. For CY1, the likelihood was low for a ToO bright comet but comet ISON was discovered and activated. FORCAST 5-39 micron observations of a bright comet will enable the study of dust mineral compositions and organic materials, will enable the search for controversial species including PAHs, phyllosilicates and carbonates, and will add to 17 comets with known silicate crystalline fractions.

  19. Brightness of synchrotron radiation from undulators and bending magnets.

    PubMed

    Geloni, Gianluca; Kocharyan, Vitali; Saldin, Evgeni

    2015-03-01

    The maximum of the Wigner distribution (WD) of synchrotron radiation (SR) fields is considered as a possible definition of SR source brightness. Such a figure of merit was originally introduced in the SR community by Kim [(1986), Nucl. Instrum. Methods Phys. Res. A, 246, 71-76]. The brightness defined in this way is always positive and, in the geometrical optics limit, can be interpreted as the maximum density of photon flux in phase space. For undulator and bending magnet radiation from a single electron, the WD function can be explicitly calculated. In the case of an electron beam with a finite emittance the brightness is given by the maximum of the convolution of a single electron WD function and the probability distribution of the electrons in phase space. In the particular case when both electron beam size and electron beam divergence dominate over the diffraction size and the diffraction angle, one can use a geometrical optics approach. However, there are intermediate regimes when only the electron beam size or the electron beam divergence dominate. In these asymptotic cases the geometrical optics approach is still applicable, and the brightness definition used here yields back once more to the maximum photon flux density in phase space. In these intermediate regimes a significant numerical disagreement is found between exact calculations and the approximation for undulator brightness currently used in the literature. The WD formalism is extended to a satisfactory theory for the brightness of a bending magnet. It is found that in the intermediate regimes the usually accepted approximation for bending magnet brightness turns out to be inconsistent even parametrically.

  20. Genome-wide analysis of the rice and Arabidopsis non-specific lipid transfer protein (nsLtp) gene families and identification of wheat nsLtp genes by EST data mining.

    PubMed

    Boutrot, Freddy; Chantret, Nathalie; Gautier, Marie-Françoise

    2008-02-21

    Plant non-specific lipid transfer proteins (nsLTPs) are encoded by multigene families and possess physiological functions that remain unclear. Our objective was to characterize the complete nsLtp gene family in rice and arabidopsis and to perform wheat EST database mining for nsLtp gene discovery. In this study, we carried out a genome-wide analysis of nsLtp gene families in Oryza sativa and Arabidopsis thaliana and identified 52 rice nsLtp genes and 49 arabidopsis nsLtp genes. Here we present a complete overview of the genes and deduced protein features. Tandem duplication repeats, which represent 26 out of the 52 rice nsLtp genes and 18 out of the 49 arabidopsis nsLtp genes identified, support the complexity of the nsLtp gene families in these species. Phylogenetic analysis revealed that rice and arabidopsis nsLTPs are clustered in nine different clades. In addition, we performed comparative analysis of rice nsLtp genes and wheat (Triticum aestivum) EST sequences indexed in the UniGene database. We identified 156 putative wheat nsLtp genes, among which 91 were found in the 'Chinese Spring' cultivar. The 122 wheat non-redundant nsLTPs were organized in eight types and 33 subfamilies. Based on the observation that seven of these clades were present in arabidopsis, rice and wheat, we conclude that the major functional diversification within the nsLTP family predated the monocot/dicot divergence. In contrast, there is no type VII nsLTPs in arabidopsis and type IX nsLTPs were only identified in arabidopsis. The reason for the larger number of nsLtp genes in wheat may simply be due to the hexaploid state of wheat but may also reflect extensive duplication of gene clusters as observed on rice chromosomes 11 and 12 and arabidopsis chromosome 5. Our current study provides fundamental information on the organization of the rice, arabidopsis and wheat nsLtp gene families. The multiplicity of nsLTP types provide new insights on arabidopsis, rice and wheat nsLtp gene families