WorldWideScience

Sample records for bright ns lmxbs

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

    Science.gov (United States)

    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.

  2. Constraining the Dense Matter Equation of State with ATHENA-WFI observations of Neutron Stars in Quiescent LMXBs

    Science.gov (United States)

    Guillot, Sebastien; Oezel, F.

    2015-09-01

    The study of neutron star quiescent low-mass X-ray binaries (qLMXBs) will address one of the main science goals of the Athena x-ray observatory. The study of the soft X-ray thermal emission from the neutron star surface in qLMXBs is a crucial tool to place constrains on the dense matter equation of state. I will briefly review this method, its strength and current weaknesses and limitations, as well as the current constraints on the equation of state from qLMXBs. The superior sensitivity of Athena will permit the acquisition of unprecedentedly high signal-to-noise spectra from these sources. It has been demonstrated that a single qLMXB, even with high S/N, will not place useful constraints on the EoS. However, a combination of qLMXBs spectra has shown promises of obtaining tight constraints on the equation of state. I will discuss the expected prospects for observations of qLMXBs inside globular clusters -- those that Athena will be able to resolve. I will also present the constraints on the equation of state that Athena will be able to obtain from these qLMXBs and from a population of qLMXBs in the field of the Galaxy, with distance measurements provided by Gaia.

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

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Dacheng; Irwin, Jimmy A. [Department of Physics and Astronomy, University of Alabama, Box 870324, Tuscaloosa, AL 35487 (United States); Wong, Ka-Wah [Eureka Scientific, Inc., 2452 Delmer Street Suite 100, Oakland, CA 94602-3017 (United States); Jennings, Zachary G.; Romanowsky, Aaron J.; Brodie, Jean P. [University of California Observatories, Santa Cruz, CA 95064 (United States); Homan, Jeroen; Remillard, Ronald A. [MIT Kavli Institute for Astrophysics and Space Research, MIT, 70 Vassar Street, Cambridge, MA 02139-4307 (United States); Strader, Jay [Department of Physics and Astronomy, Michigan State University, East Lansing, Michigan, MI 48824 (United States); Sivakoff, Gregory R., E-mail: dacheng.lin@unh.edu [Department of Physics, University of Alberta, Edmonton, Alberta, T6G 2E1 (Canada)

    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.

  4. Quasi-periodic oscillations and noise in low-mass X-ray binaries

    International Nuclear Information System (INIS)

    Van der Klis, M.

    1989-01-01

    The phenomenology of quasi-periodic oscillations (QPOs) and noise in low-mass X-ray binaries (LMXBs) is discussed. Signal analysis aspects of QPO and noise are addressed along with the relationship between LMXBs and millisecond radio pulsars. The history and prehistory of QPOs and noise in LMXBs are examined. Universal noise components and normal and flaring branch QPOs in Z sources are described and the phenomenology of Z sources is discussed. Bright LMXBs known as atoll sources are considered, as are nonpersistently bright LMXBs accreting pulsars and black hole candidates. 162 refs

  5. The reflection component in NS LMXBs

    Directory of Open Access Journals (Sweden)

    D’Aí A.

    2014-01-01

    Full Text Available 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. Measurement of the Radius of Neutron Stars with High Signal-to-noise Quiescent Low-mass X-Ray Binaries in Globular Clusters

    Science.gov (United States)

    Guillot, Sebastien; Servillat, Mathieu; Webb, Natalie A.; Rutledge, Robert E.

    2013-07-01

    This paper presents the measurement of the neutron star (NS) radius using the thermal spectra from quiescent low-mass X-ray binaries (qLMXBs) inside globular clusters (GCs). Recent observations of NSs have presented evidence that cold ultra dense matter—present in the core of NSs—is best described by "normal matter" equations of state (EoSs). Such EoSs predict that the radii of NSs, R NS, are quasi-constant (within measurement errors, of ~10%) for astrophysically relevant masses (M NS>0.5 M ⊙). The present work adopts this theoretical prediction as an assumption, and uses it to constrain a single R NS value from five qLMXB targets with available high signal-to-noise X-ray spectroscopic data. Employing a Markov chain Monte-Carlo approach, we produce the marginalized posterior distribution for R NS, constrained to be the same value for all five NSs in the sample. An effort was made to include all quantifiable sources of uncertainty into the uncertainty of the quoted radius measurement. These include the uncertainties in the distances to the GCs, the uncertainties due to the Galactic absorption in the direction of the GCs, and the possibility of a hard power-law spectral component for count excesses at high photon energy, which are observed in some qLMXBs in the Galactic plane. Using conservative assumptions, we found that the radius, common to the five qLMXBs and constant for a wide range of masses, lies in the low range of possible NS radii, R_NS =9.1^{+ 1.3}_{- 1.5} \\,km (90%-confidence). Such a value is consistent with low-R NS equations of state. We compare this result with previous radius measurements of NSs from various analyses of different types of systems. In addition, we compare the spectral analyses of individual qLMXBs to previous works.

  7. MEASUREMENT OF THE RADIUS OF NEUTRON STARS WITH HIGH SIGNAL-TO-NOISE QUIESCENT LOW-MASS X-RAY BINARIES IN GLOBULAR CLUSTERS

    International Nuclear Information System (INIS)

    Guillot, Sebastien; Rutledge, Robert E.; Servillat, Mathieu; Webb, Natalie A.

    2013-01-01

    This paper presents the measurement of the neutron star (NS) radius using the thermal spectra from quiescent low-mass X-ray binaries (qLMXBs) inside globular clusters (GCs). Recent observations of NSs have presented evidence that cold ultra dense matter—present in the core of NSs—is best described by ''normal matter'' equations of state (EoSs). Such EoSs predict that the radii of NSs, R NS , are quasi-constant (within measurement errors, of ∼10%) for astrophysically relevant masses (M NS >0.5 M ☉ ). The present work adopts this theoretical prediction as an assumption, and uses it to constrain a single R NS value from five qLMXB targets with available high signal-to-noise X-ray spectroscopic data. Employing a Markov chain Monte-Carlo approach, we produce the marginalized posterior distribution for R NS , constrained to be the same value for all five NSs in the sample. An effort was made to include all quantifiable sources of uncertainty into the uncertainty of the quoted radius measurement. These include the uncertainties in the distances to the GCs, the uncertainties due to the Galactic absorption in the direction of the GCs, and the possibility of a hard power-law spectral component for count excesses at high photon energy, which are observed in some qLMXBs in the Galactic plane. Using conservative assumptions, we found that the radius, common to the five qLMXBs and constant for a wide range of masses, lies in the low range of possible NS radii, R NS =9.1 +1.3 -1.5 km (90%-confidence). Such a value is consistent with low-R NS equations of state. We compare this result with previous radius measurements of NSs from various analyses of different types of systems. In addition, we compare the spectral analyses of individual qLMXBs to previous works.

  8. Central-engine-powered Bright X-Ray Flares in Short Gamma-Ray Bursts: A Hint of a Black Hole–Neutron Star Merger?

    Science.gov (United States)

    Mu, Hui-Jun; Gu, Wei-Min; Mao, Jirong; Hou, Shu-Jin; Lin, Da-Bin; Liu, Tong

    2018-05-01

    Short gamma-ray bursts may originate from the merger of a double neutron star (NS) or the merger of a black hole (BH) and an NS. We propose that the bright X-ray flare related to the central engine reactivity may indicate a BH–NS merger, since such a merger can provide more fallback materials and therefore a more massive accretion disk than the NS–NS merger. Based on the 49 observed short bursts with the Swift/X-ray Telescope follow-up observations, we find that three bursts have bright X-ray flares, among which three flares from two bursts are probably related to the central engine reactivity. We argue that these two bursts may originate from the BH–NS merger rather than the NS–NS merger. Our suggested link between the central-engine-powered bright X-ray flare and the BH–NS merger event can be checked by future gravitational wave detections from advanced LIGO and Virgo.

  9. A study of the cross-correlation and time lag in black hole X-ray binary XTE J1859+226

    Science.gov (United States)

    Pei, Songpeng; Ding, Guoqiang; Li, Zhibing; Lei, Yajuan; Yuen, Rai; Qu, Jinlu

    2017-07-01

    With Rossi X-ray Timing Explorer (RXTE) data, we systematically study the cross-correlation and time lag in all spectral states of black hole X-ray binary (BHXB) XTE J1859+226 in detail during its entire 1999-2000 outburst that lasted for 166 days. Anti-correlations and positive correlations and their respective soft and hard X-ray lags are only detected in the first 100 days of the outburst when the luminosity is high. This suggests that the cross-correlations may be related to high luminosity. Positive correlations are detected in every state of XTE J1859+226, viz., hard state, hard-intermediate state (HIMS), soft-intermediate state (SIMS) and soft state. However, anti-correlations are only detected in HIMS and SIMS, anti-correlated hard lags are only detected in SIMS, while anti-correlated soft lags are detected in both HIMS and SIMS. Moreover, the ratio of the observations with anti-correlated soft lags to hard lags detected in XTE J1859+226 is significantly different from that in neutron star low-mass X-ray binaries (NS LMXBs). So far, anti-correlations are never detected in the soft state of BHXBs but detected in every branch or state of NS LMXBs. This may be due to the origin of soft seed photons in BHXBs is confined to the accretion disk and, for NS LMXBs, from both accretion disk and the surface of the NS. We notice that the timescale of anti-correlated time lags detected in XTE J1859+226 is similar with that of other BHXBs and NS LMXBs. We suggest that anti-correlated soft lag detected in BHXB may result from fluctuation in the accretion disk as well as NS LMXB.

  10. MEASUREMENT OF THE RADIUS OF NEUTRON STARS WITH HIGH SIGNAL-TO-NOISE QUIESCENT LOW-MASS X-RAY BINARIES IN GLOBULAR CLUSTERS

    Energy Technology Data Exchange (ETDEWEB)

    Guillot, Sebastien; Rutledge, Robert E. [Department of Physics, McGill University, 3600 rue University, Montreal, QC, H2X-3R4 (Canada); Servillat, Mathieu [Laboratoire AIM (CEA/DSM/IRFU/SAp, CNRS, Universite Paris Diderot), CEA Saclay, Bat. 709, F-91191 Gif-sur-Yvette (France); Webb, Natalie A., E-mail: guillots@physics.mcgill.ca, E-mail: rutledge@physics.mcgill.ca [Universite de Toulouse, UPS-OMP, IRAP, Toulouse (France)

    2013-07-20

    This paper presents the measurement of the neutron star (NS) radius using the thermal spectra from quiescent low-mass X-ray binaries (qLMXBs) inside globular clusters (GCs). Recent observations of NSs have presented evidence that cold ultra dense matter-present in the core of NSs-is best described by ''normal matter'' equations of state (EoSs). Such EoSs predict that the radii of NSs, R{sub NS}, are quasi-constant (within measurement errors, of {approx}10%) for astrophysically relevant masses (M{sub NS}>0.5 M{sub Sun }). The present work adopts this theoretical prediction as an assumption, and uses it to constrain a single R{sub NS} value from five qLMXB targets with available high signal-to-noise X-ray spectroscopic data. Employing a Markov chain Monte-Carlo approach, we produce the marginalized posterior distribution for R{sub NS}, constrained to be the same value for all five NSs in the sample. An effort was made to include all quantifiable sources of uncertainty into the uncertainty of the quoted radius measurement. These include the uncertainties in the distances to the GCs, the uncertainties due to the Galactic absorption in the direction of the GCs, and the possibility of a hard power-law spectral component for count excesses at high photon energy, which are observed in some qLMXBs in the Galactic plane. Using conservative assumptions, we found that the radius, common to the five qLMXBs and constant for a wide range of masses, lies in the low range of possible NS radii, R{sub NS}=9.1{sup +1.3}{sub -1.5} km (90%-confidence). Such a value is consistent with low-R{sub NS} equations of state. We compare this result with previous radius measurements of NSs from various analyses of different types of systems. In addition, we compare the spectral analyses of individual qLMXBs to previous works.

  11. COMPARING THE ACCRETION DISK EVOLUTION OF BLACK HOLE AND NEUTRON STAR X-RAY BINARIES FROM LOW TO SUPER-EDDINGTON LUMINOSITY

    International Nuclear Information System (INIS)

    Weng Shanshan; Zhang Shuangnan

    2011-01-01

    Low-mass X-ray binaries (LMXBs) are systems in which a low-mass companion transfers mass via Roche-lobe overflow onto a black hole (BH) or a weakly magnetized neutron star (NS). It is believed that both the solid surface and the magnetic field of an NS can affect the accretion flow and show some observable effects. Using the disk emission dominant data, we compare the disk evolution of the two types of systems from low luminosity to super-Eddington luminosity. As the luminosity decreases the disk in the NS LMXB 4U1608-522 begins to leave the innermost stable circular orbit (ISCO) at much higher luminosity (∼0.1 L Edd ), compared with BH LMXBs at much lower luminosity (∼0.03 L Edd ), due to the interaction between the NS magnetosphere and accretion flow. However, as the luminosity increases above a critical luminosity, the disks in BH and NS LMXBs trace the same evolutionary pattern, because the magnetosphere is restricted inside ISCO, and then both the NS surface emission and (dipole) magnetic field do not significantly affect the secular evolution of the accretion disk, which is driven by the increased radiation pressure in the inner region. We further suggest that the NS surface emission provides additional information about the accretion disk not available in BH systems. Through the observed NS surface emission, we argue that the disk thickness H/R is less than 0.3-0.4, and that the significant outflow from the inner disk edge exists at a luminosity close to Eddington luminosity.

  12. EVIDENCE FOR SIMULTANEOUS JETS AND DISK WINDS IN LUMINOUS LOW-MASS X-RAY BINARIES

    Energy Technology Data Exchange (ETDEWEB)

    Homan, Jeroen; Neilsen, Joseph; Allen, Jessamyn L.; Chakrabarty, Deepto; Remillard, Ronald A.; Schulz, Norbert [MIT Kavli Institute for Astrophysics and Space Research, 77 Massachusetts Avenue 37-582D, Cambridge, MA 02139 (United States); Fender, Rob [Astrophysics, Department of Physics, University of Oxford, Keble Road, Oxford OX1 3RH (United Kingdom); Fridriksson, Joel K., E-mail: jeroen@space.mit.edu [Anton Pannekoek Institute, University of Amsterdam, Postbus 94249, 1090 GE Amsterdam (Netherlands)

    2016-10-10

    Recent work on jets and disk winds in low-mass X-ray binaries (LMXBs) suggests that they are to a large extent mutually exclusive, with jets observed in spectrally hard states and disk winds observed in spectrally soft states. In this paper we use existing literature on jets and disk winds in the luminous neutron star (NS) LMXB GX 13+1, in combination with archival Rossi X-ray Timing Explorer data, to show that this source is likely able to produce jets and disk winds simultaneously. We find that jets and disk winds occur in the same location on the source’s track in its X-ray color–color diagram. A further study of literature on other luminous LMXBs reveals that this behavior is more common, with indications for simultaneous jets and disk winds in the black hole LMXBs V404 Cyg and GRS 1915+105 and the NS LMXBs Sco X-1 and Cir X-1. For the three sources for which we have the necessary spectral information, we find that simultaneous jets/winds all occur in their spectrally hardest states. Our findings indicate that in LMXBs with luminosities above a few tens of percent of the Eddington luminosity, jets and disk winds are not mutually exclusive, and the presence of disk winds does not necessarily result in jet suppression.

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

    International Nuclear Information System (INIS)

    Yu, Yun-Wei; Zhang, Bing; Gao, He

    2013-01-01

    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 m erger-nova ) 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

  14. Low-mass X-ray binary evolution and the origin of millisecond pulsars

    Science.gov (United States)

    Frank, Juhan; King, Andrew R.; Lasota, Jean-Pierre

    1992-01-01

    The evolution of low-mass X-ray binaries (LMXBs) is considered. It is shown that X-ray irradiation of the companion stars causes these systems to undergo episodes of rapid mass transfer followed by detached phases. The systems are visible as bright X-ray binaries only for a short part of each cycle, so that their space density must be considerably larger than previously estimated. This removes the difficulty in regarding LMXBs as the progenitors of low-mass binary pulsars. The low-accretion-rate phase of the cycle with the soft X-ray transients is identified. It is shown that 3 hr is likely to be the minimum orbital period for LMXBs with main-sequence companions and it is suggested that the evolutionary endpoint for many LMXBs may be systems which are the sites of gamma-ray bursts.

  15. An FFAG-ERL at Cornell University for eRHIC prototyping and bright-beam applications

    Energy Technology Data Exchange (ETDEWEB)

    Hoffstaetter, Georg [Cornell University, Ithaca, NY (United States)

    2016-07-01

    Cornell University has prototyped technology essential for any high-brightness electron ERL. This includes a DC gun and an SRF injector Linac with world-record current and normalized brightness in a bunch train, a high-current CW cryomodule for 70 MeV energy gain, a high-power beam stop, and several diagnostics tools for high-current and high-brightness beams, e.g. slid measurements for 6-D phase-space densities, a fast wire scanner for beam profiles, and beam loos diagnostics. All these are now available to equip a one-cryomodule ERL, and laboratory space has been cleared out and is radiation shielded to install this ERL at Cornell. BNL has designed a multi-turn ERL for eRHIC, where beam is transported more than 20 times around the RHIC tunnel. The number of transport lines is minimized by using two non-scaling (NS) FFAG arcs. A collaboration between BNL and Cornell has been formed to investigate the new NS-FFAG optics and the multi-turn eRHIC ERL design by building a 4-turn, one-cryomodule ERL at Cornell. It has a NS-FFAG return loop built with permanent magnets and is meant to accelerate 40 mA beam to 250 MeV.

  16. Interference of transcription across H-NS binding sites and repression by H-NS.

    Science.gov (United States)

    Rangarajan, Aathmaja Anandhi; Schnetz, Karin

    2018-05-01

    Nucleoid-associated protein H-NS represses transcription by forming extended DNA-H-NS complexes. Repression by H-NS operates mostly at the level of transcription initiation. Less is known about how DNA-H-NS complexes interfere with transcription elongation. In vitro H-NS has been shown to enhance RNA polymerase pausing and to promote Rho-dependent termination, while in vivo inhibition of Rho resulted in a decrease of the genome occupancy by H-NS. Here we show that transcription directed across H-NS binding regions relieves H-NS (and H-NS/StpA) mediated repression of promoters in these regions. Further, we observed a correlation of transcription across the H-NS-bound region and de-repression. The data suggest that the transcribing RNA polymerase is able to remodel the H-NS complex and/or dislodge H-NS from the DNA and thus relieve repression. Such an interference of transcription and H-NS mediated repression may imply that poorly transcribed AT-rich loci are prone to be repressed by H-NS, while efficiently transcribed loci escape repression. © 2018 John Wiley & Sons Ltd.

  17. Integrated performance of the LHC at 25 ns without and with Linac4

    International Nuclear Information System (INIS)

    Wenninger, J

    2014-01-01

    The performance of the LHC above 6.5 TeV will depend on many factors. The available beams and their brightness defines together with achievable beta* the potential peak luminosity. For some cases the peak luminosity and the associated event pile-up may degrade the quality of the data recorded by the experiments. Such cases will require luminosity leveling for which a number of options are available. The peak performance may also be limited by cooling capacities and other equipment related issues, including machine protection as well as UFOs. The 25 ns beams require in addition substantial periods of scrubbing. The performance of the LHC in terms of integrated luminosity will be evaluated for various scenarios involving 25 ns beams, taking into account potential limitations from the various sources

  18. Integrated performance of the LHC at 25 ns without and with Linac4

    CERN Document Server

    Wenninger, J

    2014-01-01

    The performance of the LHC above 6.5 TeV will depend on many factors. The available beams and their brightness defines together with achievable beta* the potential peak luminosity. For some cases the peak luminosity and the associated event pile-up may degrade the quality of the data recorded by the experiments. Such cases will require luminosity leveling for which a number of options are available. The peak performance may also be limited by cooling capacities and other equipment related issues, including machine protection as well as UFOs. The 25 ns beams require in addition substantial periods of scrubbing. The performance of the LHC in terms of integrated luminosity will be evaluated for various scenarios involving 25 ns beams, taking into account potential limitations from the various sources.

  19. NS19504

    DEFF Research Database (Denmark)

    Nausch, Bernhard; Rode, Frederik; Jørgensen, Susanne

    2014-01-01

    channel activators and identified a small-molecule positive modulator, NS19504 (5-[(4-bromophenyl)methyl]-1,3-thiazol-2-amine), which activated the BK channel with an EC50 value of 11.0 ± 1.4 µM. Hit validation was performed using high-throughput electrophysiology (QPatch), and further characterization......19504 activated BK channels in native smooth muscle cells from guinea pig urinary bladder. In guinea pig urinary bladder strips, NS19504 (1 µM) reduced spontaneous phasic contractions, an effect that was significantly inhibited by the specific BK channel blocker iberiotoxin. In contrast, NS19504 (1 µ......M) only modestly inhibited nerve-evoked contractions and had no effect on contractions induced by a high K(+) concentration consistent with a K(+) channel-mediated action. Collectively, these results show that NS19504 is a positive modulator of BK channels and provide support for the role of BK channels...

  20. 50 ns Backup Solution

    CERN Document Server

    Kain, V; Bartosik, H; Goddard, B; Höfle, W; Iadarola, G; Meddahi, M; Pieloni, T; Rumolo, G; Salvant, B; Wenninger, J

    2014-01-01

    The baseline bunch spacing for LHC high luminosity proton-proton operation after LS3 is 25 ns to maximize the integrated luminosity while keeping the pile-up low. The success of this mode of operation is not guaranteed. Electron cloud, UFOs, long-range beambeam, heating and other effects might make 25 ns operation in the LHC and/or the injectors difficult. This talk will review possible showstoppers in the LHC and injectors for 25 ns operation and discuss possible remedies. An alternative would be re-considering 50 ns operation. An estimate of the 50 ns performance will be given. The question of whether a different upgrade path would have to be chosen in case of 50 ns operation will also be addressed.

  1. 50 ns Backup Solution

    International Nuclear Information System (INIS)

    Kain, V; Arduini, G; Bartosik, H; Goddard, B; Höfle, W; Iadarola, G; Meddahi, M; Pieloni, T; Rumolo, G; Salvant, B; Wenninger, J

    2014-01-01

    The baseline bunch spacing for LHC high luminosity proton-proton operation after LS3 is 25 ns to maximize the integrated luminosity while keeping the pile-up low. The success of this mode of operation is not guaranteed. Electron cloud, UFOs, long-range beambeam, heating and other effects might make 25 ns operation in the LHC and/or the injectors difficult. This talk will review possible showstoppers in the LHC and injectors for 25 ns operation and discuss possible remedies. An alternative would be re-considering 50 ns operation. An estimate of the 50 ns performance will be given. The question of whether a different upgrade path would have to be chosen in case of 50 ns operation will also be addressed

  2. Radio emission from the X-ray pulsar Her X-1: a jet launched by a strong magnetic field neutron star?

    Science.gov (United States)

    van den Eijnden, J.; Degenaar, N.; Russell, T. D.; Miller-Jones, J. C. A.; Wijnands, R.; Miller, J. M.; King, A. L.; Rupen, M. P.

    2018-01-01

    Her X-1 is an accreting neutron star (NS) in an intermediate-mass X-ray binary. Like low-mass X-ray binaries (LMXBs), it accretes via Roche lobe overflow, but similar to many high-mass X-ray binaries containing a NS; Her X-1 has a strong magnetic field and slow spin. Here, we present the discovery of radio emission from Her X-1 with the Very Large Array. During the radio observation, the central X-ray source was partially obscured by a warped disc. We measure a radio flux density of 38.7 ± 4.8 μJy at 9 GHz but cannot constrain the spectral shape. We discuss possible origins of the radio emission, and conclude that coherent emission, a stellar wind, shocks and a propeller outflow are all unlikely explanations. A jet, as seen in LMXBs, is consistent with the observed radio properties. We consider the implications of the presence of a jet in Her X-1 on jet formation mechanisms and on the launching of jets by NSs with strong magnetic fields.

  3. Giant magnons under NS-NS and Melvin fields

    International Nuclear Information System (INIS)

    Huang, W.-H.

    2006-01-01

    The giant magnon is a rotating spiky string configuration which has the same dispersion relation between the energy and angular momentum as that of a spin magnon. In this paper we investigate the effects of the NS-NS and Melvin fields on the giant magnon. We first analyze the energy and angular momenta of the two-spin spiky D-string moving on the AdS 3 x S 1 with the NS-NS field. Due to the infinite boundary of the AdS spacetime the D-string solution will extend to infinity and it appears the divergences. After adding the counter terms we obtain the dispersion relation of the corresponding giant magnon. The result shows that there will appear a prefactor before the angular momentum, in addition to some corrections in the sine function. We also see that the spiky profile of a rotating D-string plays an important role in mapping it to a spin magnon. We next investigate the energy and angular momentum of the one-spin spiky fundamental string moving on the R x S 2 with the electric or magnetic Melvin field. The dispersion relation of the corresponding deformed giant magnon is also obtained. We discuss some properties of the correction terms and their relations to the spin chain with deformations

  4. Host cell killing by the West Nile Virus NS2B-NS3 proteolytic complex: NS3 alone is sufficient to recruit caspase-8-based apoptotic pathway

    International Nuclear Information System (INIS)

    Ramanathan, Mathura P.; Chambers, Jerome A.; Pankhong, Panyupa; Chattergoon, Michael; Attatippaholkun, Watcharee; Dang, Kesen; Shah, Neelima; Weiner, David B.

    2006-01-01

    The West Nile Virus (WNV) non-structural proteins 2B and 3 (NS2B-NS3) constitute the proteolytic complex that mediates the cleavage and processing of the viral polyprotein. NS3 recruits NS2B and NS5 proteins to direct protease and replication activities. In an effort to investigate the biology of the viral protease, we cloned cDNA encoding the NS2B-NS3 proteolytic complex from brain tissue of a WNV-infected dead crow, collected from the Lower Merion area (Merion strain). Expression of the NS2B-NS3 gene cassette induced apoptosis within 48 h of transfection. Electron microscopic analysis of NS2B-NS3-transfected cells revealed ultra-structural changes that are typical of apoptotic cells including membrane blebbing, nuclear disintegration and cytoplasmic vacuolations. The role of NS3 or NS2B in contributing to host cell apoptosis was examined. NS3 alone triggers the apoptotic pathways involving caspases-8 and -3. Experimental results from the use of caspase-specific inhibitors and caspase-8 siRNA demonstrated that the activation of caspase-8 was essential to initiate apoptotic signaling in NS3-expressing cells. Downstream of caspase-3 activation, we observed nuclear membrane ruptures and cleavage of the DNA-repair enzyme, PARP in NS3-expressing cells. Nuclear herniations due to NS3 expression were absent in the cells treated with a caspase-3 inhibitor. Expression of protease and helicase domains themselves was sufficient to trigger apoptosis generating insight into the apoptotic pathways triggered by NS3 from WNV

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

    Science.gov (United States)

    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.

  6. Enhanced brightness x-ray lasers

    International Nuclear Information System (INIS)

    Wan, A.S.; Cauble, R.C.; Da Silva, L.B.; Moreno, J.C.; Nilsen, J.

    1994-09-01

    We are developing short-pulsed, enhanced-brightness, and coherent x-ray lasers (XRLs) for applications in areas such as plasma imaging. In a traveling wave pump setup the optical laser creating the XRL plasma sweeps along the lasant axis at the same speed as the x-rays. This technique becomes increasingly important as the target length increases and the gain duration shortens. An order of magnitude increase in output energy was measured with vs without traveling wave pump. Using multiple pulse techniques and multilayer mirrors to inject the output of one pulse back into the plasma formed by a later pulse we have begun to develop the x-ray analog of a multi-pass amplifler. The use of multiple pulses separated by as much as 1.6 ns reduces multilayer mirror damage. This injection technique is demonstrated by imaging the near-field emission profiles of the XRL. The addition of multilayer beamsplitter will allow us to effectively produce a soft XRL cavity

  7. 100y DASCH Search for historical outbursts of Black Hole Low Mass X-ray Binaries

    Science.gov (United States)

    Grindlay, Jonathan E.; Miller, George; Gomez, Sebastian

    2018-01-01

    Black Hole Low mass X-ray binaries (BH-LMXBs) are all transients, although several (e.g. GRS1915+109 and GX339-4) are quasi-persistent. All of the now 22 dynamically confirmed BH-LMXBs were discovered by their luminous outbursts, reaching Lx ~10^37 ergs/s, with outburst durations of typically ~1-3 months. These systems then (with few exceptions) return to a deep quiescent state, with Lx reduced by factors ~10^5-6 and hard X-ray spectra. The X-ray outbursts are accompanied by optical outbursts (if not absorbed by Galactic extinction) with ~6-9 magnitude increases and similar lightcurve shapes and durations as the X-ray (discovery) outburst. Prior to this work, only 3 BH-LMXBs have had historical (before the X-ray discovery) outbursts found in the archival data: A0620-00, the first BH-LMXB to be so identified, V404 Cyg (discoverd as "Nova Cyg" in 1938 and regarded as a classical nova), and V4641-Sgr which was given its variable star name when first noted in 1975. We report on the historical outbursts now discovered from the DASCH (Digital Access to a Sky Century @ Harvard) data from scanning and digitizing the now ~210,000 glass plates in the northern Galactic Hemisphere. This was one of the primary motivations for the DASCH project: to use the detection (or lack threof) of historic outbursts to measure or constrain the Duty Cycle of the accreting black holes in these systems. This, in turn, allows the total population of BH-LMXBs to be estimated and compared with that for the very similar systems containing neutron stars as the accretor (NS-LMXBs). Whereas the ratio of BHs/NSs from stellar evolution and IMFs is expected to be <<1, the DASCH results on half the sky point to an excess of BH-LMXBs. This must constrain the formation process for these systems, of importance for understanding both BH formation and compact binary evolution.

  8. Introduction to Network Simulator NS2

    CERN Document Server

    Issariyakul, Teerawat

    2012-01-01

    "Introduction to Network Simulator NS2" is a primer providing materials for NS2 beginners, whether students, professors, or researchers for understanding the architecture of Network Simulator 2 (NS2) and for incorporating simulation modules into NS2. The authors discuss the simulation architecture and the key components of NS2 including simulation-related objects, network objects, packet-related objects, and helper objects. The NS2 modules included within are nodes, links, SimpleLink objects, packets, agents, and applications. Further, the book covers three helper modules: timers, ra

  9. Molecular dynamic simulation of complex NS2B-NS3 DENV2 ...

    African Journals Online (AJOL)

    Several vaccines have been developed against the disease, but they only ... a two component NS2B-NS3 protease that cleaves viral precursor proteins, and ... The results provide conformational changes of enzyme-inhibitor complex that is ...

  10. Notes on the Wess-Zumino-Witten-like structure: L{sub ∞} triplet and NS-NS superstring field theory

    Energy Technology Data Exchange (ETDEWEB)

    Matsunaga, Hiroaki [Institute of Physics, the Czech Academy of Sciences,Na Slovance 2, Prague 8 (Czech Republic); Yukawa Institute for Theoretical Physics, Kyoto University,Kyoto 606-8502 (Japan)

    2017-05-17

    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{sub ∞} 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 https://www.doi.org/10.1007/JHEP01(2017)022 and https://www.doi.org/10.1007/JHEP08(2014)158.

  11. NMR analysis of the dynamic exchange of the NS2B cofactor between open and closed conformations of the West Nile virus NS2B-NS3 protease.

    Directory of Open Access Journals (Sweden)

    Xun-Cheng Su

    Full Text Available BACKGROUND: The two-component NS2B-NS3 proteases of West Nile and dengue viruses are essential for viral replication and established targets for drug development. In all crystal structures of the proteases to date, the NS2B cofactor is located far from the substrate binding site (open conformation in the absence of inhibitor and lining the substrate binding site (closed conformation in the presence of an inhibitor. METHODS: In this work, nuclear magnetic resonance (NMR spectroscopy of isotope and spin-labeled samples of the West Nile virus protease was used to investigate the occurrence of equilibria between open and closed conformations in solution. FINDINGS: In solution, the closed form of the West Nile virus protease is the predominant conformation irrespective of the presence or absence of inhibitors. Nonetheless, dissociation of the C-terminal part of the NS2B cofactor from the NS3 protease (open conformation occurs in both the presence and the absence of inhibitors. Low-molecular-weight inhibitors can shift the conformational exchange equilibria so that over 90% of the West Nile virus protease molecules assume the closed conformation. The West Nile virus protease differs from the dengue virus protease, where the open conformation is the predominant form in the absence of inhibitors. CONCLUSION: Partial dissociation of NS2B from NS3 has implications for the way in which the NS3 protease can be positioned with respect to the host cell membrane when NS2B is membrane associated via N- and C-terminal segments present in the polyprotein. In the case of the West Nile virus protease, discovery of low-molecular-weight inhibitors that act by breaking the association of the NS2B cofactor with the NS3 protease is impeded by the natural affinity of the cofactor to the NS3 protease. The same strategy can be more successful in the case of the dengue virus NS2B-NS3 protease.

  12. The bright-bright and bright-dark mode coupling-based planar metamaterial for plasmonic EIT-like effect

    Science.gov (United States)

    Yu, Wei; Meng, Hongyun; Chen, Zhangjie; Li, Xianping; Zhang, Xing; Wang, Faqiang; Wei, Zhongchao; Tan, Chunhua; Huang, Xuguang; Li, Shuti

    2018-05-01

    In this paper, we propose a novel planar metamaterial structure for the electromagnetically induced transparency (EIT)-like effect, which consists of a split-ring resonator (SRR) and a pair of metal strips. The simulated results indicate that a single transparency window can be realized in the symmetry situation, which originates from the bright-bright mode coupling. Further, a dual-band EIT-like effect can be achieved in the asymmetry situation, which is due to the bright-bright mode coupling and bright-dark mode coupling, respectively. Different EIT-like effect can be simultaneously achieved in the proposed structure with the different situations. It is of certain significance for the study of EIT-like effect.

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

    Directory of Open Access Journals (Sweden)

    Canard Bruno

    2011-10-01

    Full Text Available Abstract 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.

  14. Selection of high-brightness, laser-driven cathodes for electron accelerators and FELS

    International Nuclear Information System (INIS)

    Oettinger, P.E.

    1987-01-01

    Very intense, low emittance pulsed beams of electrons can be generated from laser-driven cathodes either by thermionic- or photo-emission. Several hundreds of amperes of electrons per square centimeter were observed for pulse lengths up to 50 ns. A normalized beam brightness of 10 7 A/cm 2 /rad 2 has been measured. These beams can be emission-gated at the cathode surface by modulating the laser-beam. Such beam bunching will generate picosecond-to-microsecond-long pulses at the source. A variety of cathodes are described, and a method of selection for specific applications is presented

  15. Globular cluster neutron stars and the determination of the dense matter equation of state

    Science.gov (United States)

    Guillot, Sebastien

    2016-09-01

    Combining measurements of the mass and radius of multiple neutron stars (NSs) represents the most promising way to determine the equation of state of dense NS matter. NSs in quiescent low-mass x-ray binaries (qLMXB) located in globular clusters have placed useful constraints on the equation of state. The statistical approaches combining measurements from multiple NSs can be further improved by the addition of more NS observations. We propose here to obtain a high signal to noise spectrum of the qLMXB in M30, the only low-absorption globular cluster qLMXBs that does not have deep X-ray observations, and which requires Chandra unmatched angular resolution. The 300 ks proposed observation will permit measurement of the NS radius with 12-15% uncertainties.

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

    DEFF Research Database (Denmark)

    Galli, Andrea; Scheel, Troels K H; Prentoe, Jannick C

    2013-01-01

    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 (c......LDs) 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...

  17. Computer Aided Screening of Phytochemicals from Garcinia against the Dengue NS2B/NS3 Protease.

    Science.gov (United States)

    Qamar, Tahir Ul; Mumtaz, Arooj; Ashfaq, Usman Ali; Azhar, Samia; Fatima, Tabeer; Hassan, Muhammad; Hussain, Syed Sajid; Akram, Waheed; Idrees, Sobia

    2014-01-01

    Dengue virus NS2/NS3 protease because of its ability to cleave viral proteins is considered as an attractive target to screen antiviral agents. Medicinal plants contain a variety of phytochemicals that can be used as drug against different diseases and infections. Therefore, this study was designed to uncover possible phytochemical of different classes (Aromatic, Carbohydrates, Lignin, Saponins, Steroids, Tannins, Terpenoids, Xanthones) that could be used as inhibitors against the NS2B/NS3 protease of DENV. With the help of molecular docking, Garcinia phytochemicals found to be bound deeply inside the active site of DENV NS2B/NS3 protease among all tested phytochemicals and had interactions with catalytic triad (His51, Asp75, Ser135). Thus, it can be concluded from the study that these Gracinia phytochemicals could serve as important inhibitors to inhibit the viral replication inside the host cell. Further in-vitro investigations require confirming their efficacy.

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

    International Nuclear Information System (INIS)

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

    1995-01-01

    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

  19. NS simulator for beginners

    CERN Document Server

    Altman, Eitan

    2012-01-01

    NS-2 is an open-source discrete event network simulator which is widely used by both the research community as well as by the people involved in the standardization protocols of IETF. The goal of this book is twofold: on one hand to learn how to use the NS-2 simulator, and on the other hand, to become acquainted with and to understand the operation of some of the simulated objects using NS-2 simulations. The book is intended to help students, engineers or researchers who need not have much background in programming or who want to learn through simple examples how to analyse some simulated obje

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

    Science.gov (United States)

    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

    2017-06-15

    The NS2A protein of dengue virus (DENV) has eight predicted transmembrane segments (pTMS1 to -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 explore the function of DENV NS2A by introducing a series of alanine substitutions into the N-terminal half (pTMS1 to -4) of the protein in the context of a DENV infectious clone or subgenomic replicon. Six NS2A mutants (NM5, -7, -9, and -17 to -19) around pTMS1 and -2 displayed a novel phenotype showing a >1,000-fold reduction in virus yield, an absence of plaque formation despite wild-type-like replicon activity, and infectious-virus-like particle yields. HEK-293 cells infected with the 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 pTMS7 of NS2A and isoleucine to threonine at codon 114 (I114T) within NS2B. The introduction of an 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 the NS2B-L114T mutation rescued the 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 the NS2A and NS2B proteins were also implicated. IMPORTANCE The characterization of the N-terminal (current study) and C-terminal halves of DENV NS2A is the most comprehensive mutagenesis study to date to investigate the function of NS2A during the flaviviral life cycle

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

    Science.gov (United States)

    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.

  2. In Vitro Evaluation of Novel Inhibitors against the NS2B-NS3 Protease of Dengue Fever Virus Type 4

    Directory of Open Access Journals (Sweden)

    Thi Thanh Hanh Nguyen

    2013-12-01

    Full Text Available The discovery of potent therapeutic compounds against dengue virus is urgently needed. The NS2B-NS3 protease (NS2B-NS3pro of dengue fever virus carries out all enzymatic activities needed for polyprotein processing and is considered to be amenable to antiviral inhibition by analogy. Virtual screening of 300,000 compounds using Autodock 3 on the GVSS platform was conducted to identify novel inhibitors against the NS2B-NS3pro. Thirty-six compounds were selected for in vitro assay against NS2B-NS3pro expressed in Pichia pastoris. Seven novel compounds were identified as inhibitors with IC50 values of 3.9 ± 0.6–86.7 ± 3.6 μM. Three strong NS2B-NS3pro inhibitors were further confirmed as competitive inhibitors with Ki values of 4.0 ± 0.4, 4.9 ± 0.3, and 3.4 ± 0.1 μM, respectively. Hydrophobic and hydrogen bond interactions between amino acid residues in the NS3pro active site with inhibition compounds were also identified.

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

    Energy Technology Data Exchange (ETDEWEB)

    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. (UIC); (NWU); (Novalex); (DNSK)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Miyazaki, Masaya [Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Nishihara, Hiroshi, E-mail: hnishihara@med.hokudai.ac.jp [Department of Translational Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Hasegawa, Hideki [Department of Pathology, National Institute of Infectious Diseases, Sinjuku-ku, Tokyo (Japan); Tashiro, Masato [Influenza Virus Research Center, National Institute of Infectious Diseases, Sinjuku-ku, Tokyo (Japan); Wang, Lei [Department of Translational Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Kimura, Taichi; Tanino, Mishie; Tsuda, Masumi [Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Tanaka, Shinya [Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Department of Translational Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan)

    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.

  5. 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

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yimeng; Zhou, Jianhong; Du, Yuchun, E-mail: ydu@uark.edu

    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.

  6. Assessment of Drug Binding Potential of Pockets in the NS2B/NS3 Dengue Virus Protein

    Science.gov (United States)

    Amelia, F.; Iryani; Sari, P. Y.; Parikesit, A. A.; Bakri, R.; Toepak, E. P.; Tambunan, U. S. F.

    2018-04-01

    Every year an endemic dengue fever estimated to affect over 390 million cases in over 128 countries occurs. However, the antigen types which stimulate the human immune response are variable, as a result, neither effective vaccines nor antiviral treatments have been successfully developed for this disease. The NS2B/NS3 protease of the dengue virus (DENV) responsible for viral replication is a potential drug target. The ligand-enzyme binding site determination is a key role in the success of virtual screening of new inhibitors. The NS2B/NS3 protease of DENV (PDB ID: 2FOM) has two pockets consisting of 37 (Pocket 1) and 27 (Pocket 2) amino acid residues in each pocket. In this research, we characterized the amino acid residues for binding sites in NS3/NS2B based on the hydrophobicity, the percentage of charged residues, volume, depth, ΔGbinding, hydrogen bonding and bond length. The hydrophobic percentages of both pockets are high, 59 % (Pocket 1) and 41% (Pocket 2) and the percentage of charged residues in Pocket 1 and 2 are 22% and 48%, and the pocket volume is less than 700 Å3. An interaction analysis using molecular docking showed that interaction between the ligand complex and protein in Pocket 1 is more negative than Pocket 2. As a result, Pocket 1 is the better potential target for a ligand to inhibit the action of NS2B/NS3 DENV.

  7. Boron tolerance in NS wheat lines

    Directory of Open Access Journals (Sweden)

    Brdar Milka

    2006-01-01

    Full Text Available Boron is an essential micronutrient for higher plants. Present in excessive amounts boron becomes toxic and can limit plant growth and yield. Suppression of root growth is one of the symptoms of boron toxicity in wheat. This study was undertaken to investigate the response of 10 perspective NS lines of wheat to high concentrations of boron. Analysis of root growth was done on young plants, germinated and grown in the presence of different concentrations of boric acid (0, 50,100 and 150 mg/1. Significant differences occurred between analyzed genotypes and treatments regarding root length. Average suppression of root growth was between 11,6 and 34,2%, for line NS 252/02 are even noted 61,4% longer roots at treatments in relation to the control. Lines with mean suppression of root growth less than 20% (NS 101/02, NS 138/01, NS 53/03 and NS 73/02 may be considered as boron tolerant. Spearmans coefficients showed high level of agreement regarding rang of root length for genotypes treated with 100 and 150 mg H3BO3/l.

  8. Docking, synthesis and bioassay studies of imine derivatives as potential inhibitors for dengue NS2B/ NS3 serine protease

    Directory of Open Access Journals (Sweden)

    Neni Frimayanti

    2017-11-01

    Full Text Available Objective: To search imine derivatives as new active agents against dengue type 2 NS2B/NS3 using molecular docking, since there is no effective vaccine against flaviviral infections. Methods: In this research, molecular docking was performed for a series of imine derivatives and the information obtained from the docking studies was used to explore the binding modes of these imine derivatives with dengue type 2 NS2B/NS3 serine protease. A set of imine were synthesized and bioassay study of the inhibitory activities of these compounds was then performed. Results: The results indicated that MY8 and MY4 have the ability to inhibit DEN2 NS2B/NS3 proteolytic activity. Conclusions: These two compounds were chosen as the reference for the next stage in drug design as new inhibitor agents against NS2B/NS3.

  9. Resistance Analyses of HCV NS3/4A Protease and NS5B Polymerase from Clinical Studies of Deleobuvir and Faldaprevir.

    Directory of Open Access Journals (Sweden)

    Kristi L Berger

    Full Text Available The resistance profile of anti-hepatitis C virus (HCV agents used in combination is important to guide optimal treatment regimens. We evaluated baseline and treatment-emergent NS3/4A and NS5B amino-acid variants among HCV genotype (GT-1a and -1b-infected patients treated with faldaprevir (HCV protease inhibitor, deleobuvir (HCV polymerase non-nucleoside inhibitor, and ribavirin in multiple clinical studies.HCV NS3/4A and NS5B population sequencing (Sanger method was performed on all baseline plasma samples (n = 1425 NS3; n = 1556 NS5B and on post-baseline plasma samples from patients with virologic failure (n = 113 GT-1a; n = 221 GT-1b. Persistence and time to loss of resistance-associated variants (RAVs was estimated using Kaplan-Meier analysis.Faldaprevir RAVs (NS3 R155 and D168 and deleobuvir RAVs (NS5B 495 and 496 were rare (90%. Virologic relapse was associated with RAVs in both NS3 and NS5B (53% GT-1b; 52% GT-1b; some virologic relapses had NS3 RAVs only (47% GT-1a; 17% GT-1b. Median time to loss of GT-1b NS5B P495 RAVs post-treatment (5 months was less than that of GT-1b NS3 D168 (8.5 months and GT-1a R155 RAVs (11.5 months.Faldaprevir and deleobuvir RAVs are more prevalent among virologic failures than at baseline. Treatment response was not compromised by common NS3 polymorphisms; however, alanine at NS5B amino acid 499 at baseline (wild-type in GT-1a, polymorphism in GT-1b may reduce response to this deleobuvir-based regimen.

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

    Energy Technology Data Exchange (ETDEWEB)

    D’Arcy, Allan, E-mail: allan.darcy@novartis.com; Chaillet, Maxime; Schiering, Nikolaus; Villard, Frederic [Novartis Institutes of Biomedical Research, Protease Platform, Klybeckstrasse 144, CH 4002 Basel (Switzerland); Lim, Siew Pheng [Novartis Institutes of Tropical Diseases (Singapore); Lefeuvre, Peggy [Novartis Institutes of Biomedical Research, Protease Platform, Klybeckstrasse 144, CH 4002 Basel (Switzerland); Erbel, Paul [Novartis Institutes of Biomedical Research, Protease Platform, Klybeckstrasse 144, CH 4002 Basel (Switzerland); Novartis Institutes of Tropical Diseases (Singapore)

    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.

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

    International Nuclear Information System (INIS)

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

    2006-01-01

    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

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

    Science.gov (United States)

    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

  13. Bright, water-soluble CeF{sub 3} photo-, cathodo-, and X-ray luminescent nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Clement, Sandhya; Deng, Wei; Drozdowicz-Tomsia, Krystyna; Liu, Deming [Macquarie University, Centre for Nanoscale BioPhotonics, Department of Physics and Astronomy (Australia); Zachreson, Cameron [University of Technology Sydney, School of Physics and Advanced Materials (Australia); Goldys, Ewa M., E-mail: ewa.goldys@mq.edu.au [Macquarie University, Centre for Nanoscale BioPhotonics, Department of Physics and Astronomy (Australia)

    2015-01-15

    Bright, water-soluble CeF{sub 3} 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 CeF{sub 3} 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.

  14. Circadian Phase-Shifting Effects of Bright Light, Exercise, and Bright Light + Exercise.

    Science.gov (United States)

    Youngstedt, Shawn D; Kline, Christopher E; Elliott, Jeffrey A; Zielinski, Mark R; Devlin, Tina M; Moore, Teresa A

    2016-02-26

    Limited research has compared the circadian phase-shifting effects of bright light and exercise and additive effects of these stimuli. The aim of this study was to compare the phase-delaying effects of late night bright light, late night exercise, and late evening bright light followed by early morning exercise. In a within-subjects, counterbalanced design, 6 young adults completed each of three 2.5-day protocols. Participants followed a 3-h ultra-short sleep-wake cycle, involving wakefulness in dim light for 2h, followed by attempted sleep in darkness for 1 h, repeated throughout each protocol. On night 2 of each protocol, participants received either (1) bright light alone (5,000 lux) from 2210-2340 h, (2) treadmill exercise alone from 2210-2340 h, or (3) bright light (2210-2340 h) followed by exercise from 0410-0540 h. Urine was collected every 90 min. Shifts in the 6-sulphatoxymelatonin (aMT6s) cosine acrophase from baseline to post-treatment were compared between treatments. Analyses revealed a significant additive phase-delaying effect of bright light + exercise (80.8 ± 11.6 [SD] min) compared with exercise alone (47.3 ± 21.6 min), and a similar phase delay following bright light alone (56.6 ± 15.2 min) and exercise alone administered for the same duration and at the same time of night. Thus, the data suggest that late night bright light followed by early morning exercise can have an additive circadian phase-shifting effect.

  15. Rationalizing meat consumption. The 4Ns.

    Science.gov (United States)

    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.

  16. XTE J1701-462 AND ITS IMPLICATIONS FOR THE NATURE OF SUBCLASSES IN LOW-MAGNETIC-FIELD NEUTRON STAR LOW-MASS X-RAY BINARIES

    International Nuclear Information System (INIS)

    Homan, Jeroen; Fridriksson, Joel K.; Remillard, Ronald A.; Lewin, Walter H. G.; Van der Klis, Michiel; Wijnands, Rudy; Altamirano, Diego; Mendez, Mariano; Lin Dacheng; Casella, Piergiorgio; Belloni, Tomaso M.

    2010-01-01

    We report on an analysis of Rossi X-Ray Timing Explorer data of the transient neutron star low-mass X-ray binary (NS-LMXB) XTE J1701-462, obtained during its 2006-2007 outburst. The X-ray properties of the source changed between those of various types of NS-LMXB subclasses. At high luminosities, the source switched between two types of Z source behavior and at low luminosities we observed a transition from Z source to atoll source behavior. These transitions between subclasses primarily manifest themselves as changes in the shapes of the tracks in X-ray color-color (CD) and hardness-intensity diagrams (HID), but they are accompanied by changes in the kHz quasi-periodic oscillations, broadband variability, burst behavior, and/or X-ray spectra. We find that for most of the outburst the low-energy X-ray flux is a good parameter to track the gradual evolution of the tracks in CD and HID, allowing us to resolve the evolution of the source in greater detail than before and relate the observed properties to other NS-LMXBs. We further find that during the transition from Z to atoll, characteristic behavior known as the atoll upper banana can equivalently be described as the final stage of a weakening Z source flaring branch, thereby blurring the line between the two subclasses. Our findings strongly suggest that the wide variety in behavior observed in NS-LXMBs with different luminosities can be linked through changes in a single variable parameter, namely the mass accretion rate, without the need for additional differences in the neutron star parameters or viewing angle. We briefly discuss the implications of our findings for the spectral changes observed in NS-LMXBs and suggest that, contrary to what is often assumed, the position along the color-color tracks of Z sources is not determined by the instantaneous mass accretion rate.

  17. Identification of drug resistance and immune-driven variations in hepatitis C virus (HCV) NS3/4A, NS5A and NS5B regions reveals a new approach toward personalized medicine.

    Science.gov (United States)

    Ikram, Aqsa; Obaid, Ayesha; Awan, Faryal Mehwish; Hanif, Rumeza; Naz, Anam; Paracha, Rehan Zafar; Ali, Amjad; Janjua, Hussnain Ahmed

    2017-01-01

    Cellular immune responses (T cell responses) during hepatitis C virus (HCV) infection are significant factors for determining the outcome of infection. HCV adapts to host immune responses by inducing mutations in its genome at specific sites that are important for HLA processing/presentation. Moreover, HCV also adapts to resist potential drugs that are used to restrict its replication, such as direct-acting antivirals (DAAs). Although DAAs have significantly reduced disease burden, resistance to these drugs is still a challenge for the treatment of HCV infection. Recently, drug resistance mutations (DRMs) observed in HCV proteins (NS3/4A, NS5A and NS5B) have heightened concern that the emergence of drug resistance may compromise the effectiveness of DAAs. Therefore, the NS3/4A, NS5A and NS5B drug resistance variations were investigated in this study, and their prevalence was examined in a large number of protein sequences from all HCV genotypes. Furthermore, potential CD4 + and CD8 + T cell epitopes were predicted and their overlap with genetic variations was explored. The findings revealed that many reported DRMs within NS3/4A, NS5A and NS5B are not drug-induced; rather, they are already present in HCV strains, as they were also detected in HCV-naïve patients. This study highlights several hot spots in which HLA and drug selective pressure overlap. Interestingly, these overlapping mutations were frequently observed among many HCV genotypes. This study implicates that knowledge of the host HLA type and HCV subtype/genotype can provide important information in defining personalized therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Kiloamp high-brightness beams

    International Nuclear Information System (INIS)

    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

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

    Science.gov (United States)

    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'.

  20. BrightFocus Foundation

    Science.gov (United States)

    ... About BrightFocus Foundation Featured Content BrightFocus: Investing in Science to Save Mind and Sight We're here to help. Explore ... recognition is very important. Monday, November 6, 2017 New Diagnosis? Managing a mind and sight disease is a journey. And you’ ...

  1. Localisation system in wireless sensor networks using ns-2

    CSIR Research Space (South Africa)

    Abu-Mahfouz, Adnan M

    2012-04-01

    Full Text Available -1 /************************************************************************** ********** * * File: readme.asn * * Author: Adnan Abu-Mahfouz * * Date: March 2012 * * Description: Localisation system in wireless sensor networks using ns-2... *************************************************************************** *********/ /************************************************************************** *************************************************************************** *****/ 1. Introduction: ns-2 contains several flexible features that encourage researchers to use ns-2 to investigate the characteristics of wireless sensor networks (WSNs). However, to implement and evaluate localisation algorithms, the current ns- 2...

  2. Functional investigation of grass carp reovirus nonstructural protein NS80

    Directory of Open Access Journals (Sweden)

    Shao Ling

    2011-04-01

    Full Text Available Abstract Background Grass Carp Reovirus (GCRV, a highly virulent agent of aquatic animals, has an eleven segmented dsRNA genome encased in a multilayered capsid shell, which encodes twelve proteins including seven structural proteins (VP1-VP7, and five nonstructural proteins (NS80, NS38, NS31, NS26, and NS16. It has been suggested that the protein NS80 plays an important role in the viral replication cycle that is similar to that of its homologous protein μNS in the genus of Orthoreovirus. Results As a step to understanding the basis of the part played by NS80 in GCRV replication and particle assembly, we used the yeast two-hybrid (Y2H system to identify NS80 interactions with proteins NS38, VP4, and VP6 as well as NS80 and NS38 self-interactions, while no interactions appeared in the four protein pairs NS38-VP4, NS38-VP6, VP4-VP4, and VP4-VP6. Bioinformatic analyses of NS80 with its corresponding proteins were performed with all currently available homologous protein sequences in ARVs (avian reoviruses and MRVs (mammalian reoviruses to predict further potential functional domains of NS80 that are related to VFLS (viral factory-like structures formation and other roles in viral replication. Two conserved regions spanning from aa (amino acid residues of 388 to 433, and 562 to 580 were discovered in this study. The second conserved region with corresponding conserved residues Tyr565, His569, Cys571, Asn573, and Glu576 located between the two coiled-coils regions (aa ~513-550 and aa ~615-690 in carboxyl-proximal terminus were supposed to be essential to form VFLS, so that aa residues ranging from 513 to 742 of NS80 was inferred to be the smallest region that is necessary for forming VFLS. The function of the first conserved region including Ala395, Gly419, Asp421, Pro422, Leu438, and Leu443 residues is unclear, but one-third of the amino-terminal region might be species specific, dominating interactions with other viral components. Conclusions Our

  3. A high brightness source for nano-probe secondary ion mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Smith, N.S. [Oregon Physics LLC, 2704 SE 39th Loop, Suite 109, Hillsboro, OR 97123 (United States)], E-mail: n.smith@oregon-physics.com; Tesch, P.P.; Martin, N.P.; Kinion, D.E. [Oregon Physics LLC, 2704 SE 39th Loop, Suite 109, Hillsboro, OR 97123 (United States)

    2008-12-15

    The two most prevalent ion source technologies in the field of surface analysis and surface machining are the Duoplasmatron and the liquid metal ion source (LMIS). There have been many efforts in this area of research to develop an alternative source [; N.S. Smith, W.P. Skoczylas, S.M. Kellogg, D.E. Kinion, P.P. Tesch, O. Sutherland, A. Aanesland, R.W. Boswell, J. Vac. Sci. Technol. B 24 (6) (2006) 2902-2906] with the brightness of a LMIS and yet the ability to produce secondary ion yield enhancing species such as oxygen. However, to date a viable alternative has not been realized. The high brightness and small virtual source size of the LMIS are advantageous for forming high resolution probes but a significant disadvantage when beam currents in excess of 100 nA are required, due to the effects of spherical aberration from the optical column. At these higher currents a source with a high angular intensity is optimal and in fact the relatively moderate brightness of today's plasma ion sources prevail in this operating regime. Both the LMIS and Duoplasmatron suffer from a large axial energy spread resulting in further limitations when forming focused beams at the chromatic limit where the figure-of-merit is inversely proportional to the square of the energy spread. Also, both of these ion sources operate with a very limited range of ion species. This article reviews some of the latest developments and some future potential in this area of instrument development. Here we present an approach to source development that could lead to oxygen ion beam SIMS imaging with 10 nm resolution, using a 'broad area' RF gas phase ion source.

  4. Differential Rotation via Tracking of Coronal Bright Points.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Intermittent episodes of bright light suppress myopia in the chicken more than continuous bright light.

    Directory of Open Access Journals (Sweden)

    Weizhong Lan

    Full Text Available 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 studies.

  7. Intermittent episodes of bright light suppress myopia in the chicken more than continuous bright light.

    Science.gov (United States)

    Lan, Weizhong; Feldkaemper, Marita; Schaeffel, Frank

    2014-01-01

    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. 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. 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. 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 studies.

  8. Identification and subcellular localization of porcine deltacoronavirus accessory protein NS6

    International Nuclear Information System (INIS)

    Fang, Puxian; Fang, Liurong; Liu, Xiaorong; Hong, Yingying; Wang, Yongle; Dong, Nan; Ma, Panpan; Bi, Jing; Wang, Dang; Xiao, Shaobo

    2016-01-01

    Porcine deltacoronavirus (PDCoV) is an emerging swine enteric coronavirus. Accessory proteins are genus-specific for coronavirus, and two putative accessory proteins, NS6 and NS7, are predicted to be encoded by PDCoV; however, this remains to be confirmed experimentally. Here, we identified the leader-body junction sites of NS6 subgenomic RNA (sgRNA) and found that the actual transcription regulatory sequence (TRS) utilized by NS6 is non-canonical and is located upstream of the predicted TRS. Using the purified NS6 from an Escherichia coli expression system, we obtained two anti-NS6 monoclonal antibodies that could detect the predicted NS6 in cells infected with PDCoV or transfected with NS6-expressing plasmids. Further studies revealed that NS6 is always localized in the cytoplasm of PDCoV-infected cells, mainly co-localizing with the endoplasmic reticulum (ER) and ER-Golgi intermediate compartments, as well as partially with the Golgi apparatus. Together, our results identify the NS6 sgRNA and demonstrate its expression in PDCoV-infected cells. -- Highlights: •The leader-body fusion site of NS6 sgRNA is identified. •NS6 sgRNA uses a non-canonical transcription regulatory sequence (TRS). •NS6 can be expressed in PDCoV-infected cell. •NS6 predominantly localize to the ER complex and ER-Golgi intermediate compartment.

  9. Identification and subcellular localization of porcine deltacoronavirus accessory protein NS6

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Puxian; Fang, Liurong; Liu, Xiaorong; Hong, Yingying; Wang, Yongle; Dong, Nan; Ma, Panpan [State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070 (China); The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070 (China); Bi, Jing [State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070 (China); Department of Immunology and Aetology, College of Basic Medicine, Hubei University of Chinese Medicine, Wuhan 430065 (China); Wang, Dang [State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070 (China); The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070 (China); Xiao, Shaobo, E-mail: vet@mail.hzau.edu.cn [State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070 (China); The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070 (China)

    2016-12-15

    Porcine deltacoronavirus (PDCoV) is an emerging swine enteric coronavirus. Accessory proteins are genus-specific for coronavirus, and two putative accessory proteins, NS6 and NS7, are predicted to be encoded by PDCoV; however, this remains to be confirmed experimentally. Here, we identified the leader-body junction sites of NS6 subgenomic RNA (sgRNA) and found that the actual transcription regulatory sequence (TRS) utilized by NS6 is non-canonical and is located upstream of the predicted TRS. Using the purified NS6 from an Escherichia coli expression system, we obtained two anti-NS6 monoclonal antibodies that could detect the predicted NS6 in cells infected with PDCoV or transfected with NS6-expressing plasmids. Further studies revealed that NS6 is always localized in the cytoplasm of PDCoV-infected cells, mainly co-localizing with the endoplasmic reticulum (ER) and ER-Golgi intermediate compartments, as well as partially with the Golgi apparatus. Together, our results identify the NS6 sgRNA and demonstrate its expression in PDCoV-infected cells. -- Highlights: •The leader-body fusion site of NS6 sgRNA is identified. •NS6 sgRNA uses a non-canonical transcription regulatory sequence (TRS). •NS6 can be expressed in PDCoV-infected cell. •NS6 predominantly localize to the ER complex and ER-Golgi intermediate compartment.

  10. Bright Merger-nova Emission Powered by Magnetic Wind from a Newborn Black Hole

    Science.gov (United States)

    Ma, Shuai-Bing; Lei, Wei-Hua; Gao, He; Xie, Wei; Chen, Wei; Zhang, Bing; Wang, Ding-Xiong

    2018-01-01

    Mergers of neutron star–neutron star (NS–NS) or neutron star–black hole (NS–BH) binaries are candidate sources of gravitational waves (GWs). At least a fraction of the merger remnants should be a stellar mass BH with sub-relativistic ejecta. A collimated jet is launched via the Blandford–Znajek mechanism from the central BH to trigger a short gamma-ray burst (sGRB). At the same time, a near-isotropic wind may be driven by the Blandford–Payne mechanism (BP). In previous work, additional energy injection to the ejecta from the BP mechanism was ignored, and radioactive decay has long been thought to be the main source of the kilonova energy. In this Letter, we propose that the wind driven by the BP mechanism from the newborn BH’s disk can heat up and push the ejecta during the prompt emission phase or even at late times when there is fall-back accretion. Such a BP-powered merger-nova could be bright in the optical band even for a low-luminosity sGRB. The detection of a GW merger event with a BH clearly identified as a remnant, accompanied by a bright merger-nova, would provide robust confirmation of our model.

  11. Novel nucleotide and amino acid covariation between the 5'UTR and the NS2/NS3 proteins of hepatitis C virus: bioinformatic and functional analyses.

    Directory of Open Access Journals (Sweden)

    Hung-Yu Sun

    Full Text Available Molecular covariation of highly polymorphic viruses is thought to have crucial effects on viral replication and fitness. This study employs association rule data mining of hepatitis C virus (HCV sequences to search for specific evolutionary covariation and then tests functional relevance on HCV replication. Data mining is performed between nucleotides in the untranslated regions 5' and 3'UTR, and the amino acid residues in the non-structural proteins NS2, NS3 and NS5B. Results indicate covariance of the 243(rd nucleotide of the 5'UTR with the 14(th, 41(st, 76(th, 110(th, 211(th and 212(th residues of NS2 and with the 71(st, 175(th and 621(st residues of NS3. Real-time experiments using an HCV subgenomic system to quantify viral replication confirm replication regulation for each covariant pair between 5'UTR₂₄₃ and NS2-41, -76, -110, -211, and NS3-71, -175. The HCV subgenomic system with/without the NS2 region shows that regulatory effects vanish without NS2, so replicative modulation mediated by HCV 5'UTR₂₄₃ depends on NS2. Strong binding of the NS2 variants to HCV RNA correlates with reduced HCV replication whereas weak binding correlates with restoration of HCV replication efficiency, as determined by RNA-protein immunoprecipitation assay band intensity. The dominant haplotype 5'UTR₂₄₃-NS2-41-76-110-211-NS3-71-175 differs according to the HCV genotype: G-Ile-Ile-Ile-Gly-Ile-Met for genotype 1b and A-Leu-Val-Leu-Ser-Val-Leu for genotypes 1a, 2a and 2b. In conclusion, 5'UTR₂₄₃ co-varies with specific NS2/3 protein amino acid residues, which may have significant structural and functional consequences for HCV replication. This unreported mechanism involving HCV replication possibly can be exploited in the development of advanced anti-HCV medication.

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

    NARCIS (Netherlands)

    Nijboer, T.C.W.; Nys, G.M.S.; van der Smagt, M.J.; de Haan, E.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

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

    Directory of Open Access Journals (Sweden)

    Jihui Lin

    2017-08-01

    Full Text Available 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.

  14. COMMON PATTERNS IN THE EVOLUTION BETWEEN THE LUMINOUS NEUTRON STAR LOW-MASS X-RAY BINARY SUBCLASSES

    International Nuclear Information System (INIS)

    Fridriksson, Joel K.; Homan, Jeroen; Remillard, Ronald A.

    2015-01-01

    The X-ray transient XTE J1701–462 was the first source observed to evolve through all known subclasses of low-magnetic-field neutron star low-mass X-ray binaries (NS-LMXBs), as a result of large changes in its mass accretion rate. To investigate to what extent similar evolution is seen in other NS-LMXBs we have performed a detailed study of the color–color and hardness–intensity diagrams (CDs and HIDs) of Cyg X-2, Cir X-1, and GX 13+1—three luminous X-ray binaries, containing weakly magnetized neutron stars, known to exhibit strong secular changes in their CD/HID tracks. Using the full set of Rossi X-ray Timing Explorer Proportional Counter Array data collected for the sources over the 16 year duration of the mission, we show that Cyg X-2 and Cir X-1 display CD/HID evolution with close similarities to XTE J1701–462. Although GX 13+1 shows behavior that is in some ways unique, it also exhibits similarities to XTE J1701–462, and we conclude that its overall CD/HID properties strongly indicate that it should be classified as a Z source, rather than as an atoll source. We conjecture that the secular evolution of Cyg X-2, Cir X-1, and GX 13+1—illustrated by sequences of CD/HID tracks we construct—arises from changes in the mass accretion rate. Our results strengthen previous suggestions that within single sources Cyg-like Z source behavior takes place at higher luminosities and mass accretion rates than Sco-like Z behavior, and lend support to the notion that the mass accretion rate is the primary physical parameter distinguishing the various NS-LMXB subclasses

  15. COMMON PATTERNS IN THE EVOLUTION BETWEEN THE LUMINOUS NEUTRON STAR LOW-MASS X-RAY BINARY SUBCLASSES

    Energy Technology Data Exchange (ETDEWEB)

    Fridriksson, Joel K. [Anton Pannekoek Institute for Astronomy, University of Amsterdam, Science Park 904, 1098 XH Amsterdam (Netherlands); Homan, Jeroen; Remillard, Ronald A., E-mail: J.K.Fridriksson@uva.nl [Kavli Institute for Astrophysics and Space Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139 (United States)

    2015-08-10

    The X-ray transient XTE J1701–462 was the first source observed to evolve through all known subclasses of low-magnetic-field neutron star low-mass X-ray binaries (NS-LMXBs), as a result of large changes in its mass accretion rate. To investigate to what extent similar evolution is seen in other NS-LMXBs we have performed a detailed study of the color–color and hardness–intensity diagrams (CDs and HIDs) of Cyg X-2, Cir X-1, and GX 13+1—three luminous X-ray binaries, containing weakly magnetized neutron stars, known to exhibit strong secular changes in their CD/HID tracks. Using the full set of Rossi X-ray Timing Explorer Proportional Counter Array data collected for the sources over the 16 year duration of the mission, we show that Cyg X-2 and Cir X-1 display CD/HID evolution with close similarities to XTE J1701–462. Although GX 13+1 shows behavior that is in some ways unique, it also exhibits similarities to XTE J1701–462, and we conclude that its overall CD/HID properties strongly indicate that it should be classified as a Z source, rather than as an atoll source. We conjecture that the secular evolution of Cyg X-2, Cir X-1, and GX 13+1—illustrated by sequences of CD/HID tracks we construct—arises from changes in the mass accretion rate. Our results strengthen previous suggestions that within single sources Cyg-like Z source behavior takes place at higher luminosities and mass accretion rates than Sco-like Z behavior, and lend support to the notion that the mass accretion rate is the primary physical parameter distinguishing the various NS-LMXB subclasses.

  16. High-brightness rf linear accelerators

    International Nuclear Information System (INIS)

    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

  17. NS Pudarka: A new winter wheat cultivar

    Directory of Open Access Journals (Sweden)

    Hristov Nikola

    2014-01-01

    Full Text Available The high-yielding, medium late winter wheat cultivar NS Pudarka was developed by crossing genetic divergent parents: line NMNH-07 and cv. NS 40S and Simonida. In cultivar NS Pudarka genes responsible for high yield potential, very good technological quality, resistance to lodging, low temperature and diseases, were successfully combined. It was registered by Ministry of agriculture, forestry and water management of Serbia Republic in 2013. This cultivar has wide adaptability and stability of yield that enable growing in different environments with optimal agricultural practice. On the base of technological quality this cultivar belongs to the second quality class, A2 farinograph subgroup and second technological group.

  18. The interactomes of influenza virus NS1 and NS2 proteins identify new host factors and provide insights for ADAR1 playing a supportive role in virus replication.

    Science.gov (United States)

    de Chassey, Benoît; Aublin-Gex, Anne; Ruggieri, Alessia; Meyniel-Schicklin, Laurène; Pradezynski, Fabrine; Davoust, Nathalie; Chantier, Thibault; Tafforeau, Lionel; Mangeot, Philippe-Emmanuel; Ciancia, Claire; Perrin-Cocon, Laure; Bartenschlager, Ralf; André, Patrice; Lotteau, Vincent

    2013-01-01

    Influenza A NS1 and NS2 proteins are encoded by the RNA segment 8 of the viral genome. NS1 is a multifunctional protein and a virulence factor while NS2 is involved in nuclear export of viral ribonucleoprotein complexes. A yeast two-hybrid screening strategy was used to identify host factors supporting NS1 and NS2 functions. More than 560 interactions between 79 cellular proteins and NS1 and NS2 proteins from 9 different influenza virus strains have been identified. These interacting proteins are potentially involved in each step of the infectious process and their contribution to viral replication was tested by RNA interference. Validation of the relevance of these host cell proteins for the viral replication cycle revealed that 7 of the 79 NS1 and/or NS2-interacting proteins positively or negatively controlled virus replication. One of the main factors targeted by NS1 of all virus strains was double-stranded RNA binding domain protein family. In particular, adenosine deaminase acting on RNA 1 (ADAR1) appeared as a pro-viral host factor whose expression is necessary for optimal viral protein synthesis and replication. Surprisingly, ADAR1 also appeared as a pro-viral host factor for dengue virus replication and directly interacted with the viral NS3 protein. ADAR1 editing activity was enhanced by both viruses through dengue virus NS3 and influenza virus NS1 proteins, suggesting a similar virus-host co-evolution.

  19. The interactomes of influenza virus NS1 and NS2 proteins identify new host factors and provide insights for ADAR1 playing a supportive role in virus replication.

    Directory of Open Access Journals (Sweden)

    Benoît de Chassey

    Full Text Available Influenza A NS1 and NS2 proteins are encoded by the RNA segment 8 of the viral genome. NS1 is a multifunctional protein and a virulence factor while NS2 is involved in nuclear export of viral ribonucleoprotein complexes. A yeast two-hybrid screening strategy was used to identify host factors supporting NS1 and NS2 functions. More than 560 interactions between 79 cellular proteins and NS1 and NS2 proteins from 9 different influenza virus strains have been identified. These interacting proteins are potentially involved in each step of the infectious process and their contribution to viral replication was tested by RNA interference. Validation of the relevance of these host cell proteins for the viral replication cycle revealed that 7 of the 79 NS1 and/or NS2-interacting proteins positively or negatively controlled virus replication. One of the main factors targeted by NS1 of all virus strains was double-stranded RNA binding domain protein family. In particular, adenosine deaminase acting on RNA 1 (ADAR1 appeared as a pro-viral host factor whose expression is necessary for optimal viral protein synthesis and replication. Surprisingly, ADAR1 also appeared as a pro-viral host factor for dengue virus replication and directly interacted with the viral NS3 protein. ADAR1 editing activity was enhanced by both viruses through dengue virus NS3 and influenza virus NS1 proteins, suggesting a similar virus-host co-evolution.

  20. Silencing by H-NS potentiated the evolution of Salmonella.

    Directory of Open Access Journals (Sweden)

    Sabrina S Ali

    2014-11-01

    Full Text Available 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.

  1. Do Low Surface Brightness Galaxies Host Stellar Bars?

    International Nuclear Information System (INIS)

    Cervantes Sodi, Bernardo; Sánchez García, Osbaldo

    2017-01-01

    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.

  2. Do Low Surface Brightness Galaxies Host Stellar Bars?

    Energy Technology Data Exchange (ETDEWEB)

    Cervantes Sodi, Bernardo; Sánchez García, Osbaldo, E-mail: b.cervantes@irya.unam.mx, E-mail: o.sanchez@irya.unam.mx [Instituto de Radioastronomía y Astrofísica, Universidad Nacional Autónoma de México, Campus Morelia, A.P. 3-72, C.P. 58089 Michoacán, México (Mexico)

    2017-09-20

    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.

  3. Cleavage preference distinguishes the two-component NS2B-NS3 serine proteinases of Dengue and West Nile viruses.

    Science.gov (United States)

    Shiryaev, Sergey A; Kozlov, Igor A; Ratnikov, Boris I; Smith, Jeffrey W; Lebl, Michal; Strongin, Alex Y

    2007-02-01

    Regulated proteolysis of the polyprotein precursor by the NS2B-NS3 protease is required for the propagation of infectious virions. Unless the structural and functional parameters of NS2B-NS3 are precisely determined, an understanding of its functional role and the design of flaviviral inhibitors will be exceedingly difficult. Our objectives were to define the substrate recognition pattern of the NS2B-NS3 protease of West Nile and Dengue virises (WNV and DV respectively). To accomplish our goals, we used an efficient, 96-well plate format, method for the synthesis of 9-mer peptide substrates with the general P4-P3-P2-P1-P1'-P2'-P3'-P4'-Gly structure. The N-terminus and the constant C-terminal Gly of the peptides were tagged with a fluorescent tag and with a biotin tag respectively. The synthesis was followed by the proteolytic cleavage of the synthesized, tagged peptides. Because of the strict requirement for the presence of basic amino acid residues at the P1 and the P2 substrate positions, the analysis of approx. 300 peptide sequences was sufficient for an adequate representation of the cleavage preferences of the WNV and DV proteinases. Our results disclosed the strict substrate specificity of the WNV protease for which the (K/R)(K/R)R/GG amino acid motifs was optimal. The DV protease was less selective and it tolerated well the presence of a number of amino acid residue types at either the P1' or the P2' site, as long as the other position was occupied by a glycine residue. We believe that our data represent a valuable biochemical resource and a solid foundation to support the design of selective substrates and synthetic inhibitors of flaviviral proteinases.

  4. NS&T Management Observations

    Energy Technology Data Exchange (ETDEWEB)

    Gianotto, David [Idaho National Laboratory (INL), Idaho Falls, ID (United States)

    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.

  5. Recombinant HCV variants with NS5A from genotypes 1-7 have different sensitivities to an NS5A inhibitor but not interferon-a

    DEFF Research Database (Denmark)

    Scheel, Troels K H; Gottwein, Judith M; Mikkelsen, Lotte S

    2011-01-01

    Heterogeneity in the hepatitis C virus (HCV) protein NS5A influences its sensitivity to interferon-based therapy. Furthermore, NS5A is an important target for development of HCV-specific inhibitors. We aimed to develop recombinant infectious cell culture systems that express NS5A from isolates...

  6. Proxy magnetometry of the photosphere: why are G-band bright points so bright?

    NARCIS (Netherlands)

    Rutten, R.J.; Kiselman, Dan; Voort, Luc Rouppe van der; Plez, Bertrand

    2000-01-01

    We discuss the formation of G-band bright points in terms of standard uxtube modeling, in particular the 1D LTE models constructed by Solanki and coworkers. Combined with LTE spectral synthesis they explain observed G-band bright point contrasts quite well. The G-band contrast increase over the

  7. Role of nonstructural protein NS2A in flavivirus assembly

    NARCIS (Netherlands)

    Leung, J.Y.; Pijlman, G.P.; Kondratieva, N.; Hyde, J.; Mackenzie, J.M.; Khromykh, A.A.

    2008-01-01

    Flavivirus nonstructural (NS) proteins are involved in RNA replication and modulation of the host antiviral response; however, evidence is mounting that some NS proteins also have essential roles in virus assembly. Kunjin virus (KUN) NS2A is a small, hydrophobic, transmembrane protein that is part

  8. Dengue Virus NS2B/NS3 Protease Inhibitors Exploiting the Prime Side.

    Science.gov (United States)

    Lin, Kuan-Hung; Ali, Akbar; Rusere, Linah; Soumana, Djade I; Kurt Yilmaz, Nese; Schiffer, Celia A

    2017-05-15

    The mosquito-transmitted dengue virus (DENV) infects millions of people in tropical and subtropical regions. Maturation of DENV particles requires proper cleavage of the viral polyprotein, including processing of 8 of the 13 substrate cleavage sites by dengue virus NS2B/NS3 protease. With no available direct-acting antiviral targeting DENV, NS2/NS3 protease is a promising target for inhibitor design. Current design efforts focus on the nonprime side of the DENV protease active site, resulting in highly hydrophilic and nonspecific scaffolds. However, the prime side also significantly modulates DENV protease binding affinity, as revealed by engineering the binding loop of aprotinin, a small protein with high affinity for DENV protease. In this study, we designed a series of cyclic peptides interacting with both sides of the active site as inhibitors of dengue virus protease. The design was based on two aprotinin loops and aimed to leverage both key specific interactions of substrate sequences and the entropic advantage driving aprotinin's high affinity. By optimizing the cyclization linker, length, and amino acid sequence, the tightest cyclic peptide achieved a K i value of 2.9 μM against DENV3 wild-type (WT) protease. These inhibitors provide proof of concept that both sides of DENV protease active site can be exploited to potentially achieve specificity and lower hydrophilicity in the design of inhibitors targeting DENV. IMPORTANCE Viruses of the flaviviral family, including DENV and Zika virus transmitted by Aedes aegypti , continue to be a threat to global health by causing major outbreaks in tropical and subtropical regions, with no available direct-acting antivirals for treatment. A better understanding of the molecular requirements for the design of potent and specific inhibitors against flaviviral proteins will contribute to the development of targeted therapies for infections by these viruses. The cyclic peptides reported here as DENV protease inhibitors

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

    OpenAIRE

    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....

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

    Directory of Open Access Journals (Sweden)

    Matthew Brecher

    2017-05-01

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

  11. Modifying Cement Hydration with NS@PCE Core-Shell Nanoparticles

    Directory of Open Access Journals (Sweden)

    Yue Gu

    2017-01-01

    Full Text Available It is generally accepted that fine particles could accelerate cement hydration process, or, more specifically, this accelerating effect can be attributed to additional surface area introduced by fine particles. In addition to this view, the surface state of fine particles is also an important factor, especially for nanoparticles. In the previous study, a series of nano-SiO2-polycarboxylate superplasticizer core-shell nanoparticles (NS@PCE were synthesized, which have a similar particle size distribution but different surface properties. In this study, the impact of NS@PCE on cement hydration was investigated by heat flow calorimetry, mechanical property measurement, XRD, and SEM. Results show that, among a series of NS@PCE, NS@PCE-2 with a moderate shell-core ratio appeared to be more effective in accelerating cement hydration. As dosage increases, the efficiency of NS@PCE-2 would reach a plateau which is quantified by various characteristic values. Compressive strength results indicate that strength has a linear correlation with cumulative heat release. A hypothesis was proposed to explain the modification effect of NS@PCE, which highlights a balance between initial dispersion and pozzolanic reactivity. This paper provides a new understanding for the surface modification of supplementary cementitious materials and their application and also sheds a new light on nano-SiO2 for optimizing cement-based materials.

  12. BrightStat.com: free statistics online.

    Science.gov (United States)

    Stricker, Daniel

    2008-10-01

    Powerful software for statistical analysis is expensive. Here I present BrightStat, a statistical software running on the Internet which is free of charge. BrightStat's goals, its main capabilities and functionalities are outlined. Three different sample runs, a Friedman test, a chi-square test, and a step-wise multiple regression are presented. The results obtained by BrightStat are compared with results computed by SPSS, one of the global leader in providing statistical software, and VassarStats, a collection of scripts for data analysis running on the Internet. Elementary statistics is an inherent part of academic education and BrightStat is an alternative to commercial products.

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

    Science.gov (United States)

    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

  14. Dengue NS1 Antigen - for Early Detection of Dengue Virus Infection

    Directory of Open Access Journals (Sweden)

    Amol Hartalkar

    2015-08-01

    Full Text Available Objectives: To evaluate the efficacy of NS1 antigen assay for early diagnosis of dengue virus infection in a tertiary care hospital. Methods: This cross sectional study was carried out in department of Medicine from August to December 2013. Total 100 patients with dengue fever were included. Complete blood count, alanine aminotransferase (ALT, aspartate aminotransferase (AST, Dengue NS1 antigen and IgM and IgG antibodies of dengue virus were done in all cases. Results: Of the 100 sera tested, 75% were positive for dengue virus infection based on dengue NS1 antigen, IgM antibody and IgG antibody. Dengue NS1 antigen and IgM, IgG antibody were able to detect dengue virus infection between day 1 to day 8 in 92% of samples, 86.7% of samples and 82.6% of samples respectively. Sixty nine percent (69% were found positive for dengue NS1 antigen, 65% were IgM positive and 62% were IgG positive. Based on the dengue NS1 antigen and IgM antibody combination, 74% were positive for dengue virus infections. Sensitivity of Dengue NS1 antigen was 92.3% and specificity of 74.28% in comparison to IgM antibody. Detection rate increased to 75%, based on the antigen and IgG antibody combination. Sensitivity of dengue NS1 antigen was 90.3% and specificity of 65.8% in comparison to IgG antibody. Conclusion: Dengue NS1 antigen is a useful, sensitive and specific test for early diagnosis of dengue virus infection and it improves diagnostic efficiency in combination with antibody test. Key words: Dengue fever, NS1 antigen. Introduction: Dengue fever (DF is the most common arboviral illness in humans. Each year, an estimated 50-100 million cases of dengue fever and 500,000 cases of dengue hemorrhagic fever occur worldwide, with 30000 deaths (mainly in children. Globally 2.5-3 billion people in approximately 112 tropical and subtropical countries are at risk of dengue.of samples respectively. Sixty nine percent (69% were found positive for dengue NS1 antigen, 65% were Ig

  15. Brightness and transparency in the early visual cortex.

    Science.gov (United States)

    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.

  16. NS Otto Hahn

    International Nuclear Information System (INIS)

    Schafstall, H.G.

    1983-01-01

    For the bulk cargo ship had been chosen the advanced PWR, the secial characteristic of which is an integrated primary loop with automatic pressurisation. Altogether the Otto Hahn covered over half a million sea-miles. In-service inspections and examinations of the reactor plant were effected by control authorities every year. During the whole operating period the NS Otto Hahn showed a safe and reliable behaviour even from the view of radiation protection. (DG) [de

  17. Efficient hepatitis c virus genotype 1b core-NS5A recombinants permit efficacy testing of protease and NS5A inhibitors

    DEFF Research Database (Denmark)

    Pham, Long V.; Ramirez Almeida, Santseharay; Carlsen, Thomas H R

    2017-01-01

    Hepatitis C virus (HCV) strains belong to seven genotypes with numerous subtypes that respond differently to antiviral therapies. Genotype 1, and primarily subtype 1b, is the most prevalent genotype worldwide. The development of recombinant HCV infectious cell culture systems for different variants......, permitted by the high replication capacity of strain JFH1 (genotype 2a), has advanced efficacy and resistance testing of antivirals. However, efficient infectious JFH1-based cell cultures of subtype 1b are limited and comprise only the 5= untranslated region (5=UTR)-NS2, NS4A, or NS5A regions. Importantly...

  18. Increasing the Brightness of Light Sources

    OpenAIRE

    Fu, Ling

    2006-01-01

    In modern illumination systems, compact size and high brightness are important features. Light recycling allows an increase of the spectral radiance (brightness) emitted by a light source for the price of reducing the total radiant power. Light recycling means returning part of the emitted light to the source where part of it will escape absorption. As a result, the output brightness can be increased in a restricted phase space, ...

  19. Evolutionary dynamics of hepatitis C virus NS3 protease domain during and following treatment with narlaprevir, a potent NS3 protease inhibitor

    NARCIS (Netherlands)

    de Bruijne, J.; Thomas, X. V.; Rebers, S. P.; Weegink, C. J.; Treitel, M. A.; Hughes, E.; Bergmann, J. F.; de Knegt, R. J.; Janssen, H. L. A.; Reesink, H. W.; Molenkamp, R.; Schinkel, J.

    2013-01-01

    Narlaprevir, a hepatitis C virus (HCV) NS3/4A serine protease inhibitor, has demonstrated robust antiviral activity in a placebo-controlled phase 1 study. To study evolutionary dynamics of resistant variants, the NS3 protease sequence was clonally analysed in thirty-two HCV genotype 1-infected

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

    Directory of Open Access Journals (Sweden)

    Kazi Abdus Salam

    2013-01-01

    Full Text Available 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.

  1. Does low surface brightness mean low density?

    NARCIS (Netherlands)

    deBlok, WJG; McGaugh, SS

    1996-01-01

    We compare the dynamical properties of two galaxies at identical positions on the Tully-Fisher relation, but with different surface brightnesses. We find that the low surface brightness galaxy UGC 128 has a higher mass-to-light ratio, and yet has lower mass densities than the high surface brightness

  2. CIAE 600 kV ns pulse neutron generator

    International Nuclear Information System (INIS)

    Shen Guanren; Guan Xialing; Chen Hongtao

    2001-01-01

    The overall composition of CIAE 600 kV ns Pulse Neutron Generator (CPNG) are introduced, and its characteristic, main technological performance and application were also given. CPNG consists of high voltage power supply with highest output voltage 600 kV, direct current 15 mA, stability and ripple ≤0.1%, 2214 mm x 1604 mm x 1504 mm stainless steel high voltage electrode, built in head equipment uniform field accelerating tube, ns pulsed installation, turbomolecular vacuum pump system and drift pipes at 0 degree and 45 degree. Its characteristics are: (1) high current beam; (2) high current beam ns pulsed installation made use of low energy for chopper and high energy for buncher; (3) compactly laid out and simple in structure

  3. [11C]NS8880, a promising PET radiotracer targeting the norepinephrine transporter

    DEFF Research Database (Denmark)

    Vase, Karina Højrup; Peters, Dan; Nielsen, Elsebeth Ø

    2014-01-01

    -azabicyclo[3.2.1]octane (NS8880), targeting NET. NS8880 has an in vitro binding profile comparable to desipramine and is structurally not related to reboxetine. METHODS: Labeling of NS8880 with [11C] was achieved by a non-conventional technique: substitution of pyridinyl fluorine with [11C]methanolate...... yields with high purity. The PET in vivo evaluation in pig and rat revealed a rapid brain uptake of [11C]NS8880 and fast obtaining of equilibrium. Highest binding was observed in thalamic and hypothalamic regions. Pretreatment with desipramine efficiently reduced binding of [11C]NS8880. CONCLUSION: Based...... on the pre-clinical results obtained so far [11C]NS8880 displays promising properties for PET imaging of NET....

  4. Time-resolved brightness measurements by streaking

    Science.gov (United States)

    Torrance, Joshua S.; Speirs, Rory W.; McCulloch, Andrew J.; Scholten, Robert E.

    2018-03-01

    Brightness is a key figure of merit for charged particle beams, and time-resolved brightness measurements can elucidate the processes involved in beam creation and manipulation. Here we report on a simple, robust, and widely applicable method for the measurement of beam brightness with temporal resolution by streaking one-dimensional pepperpots, and demonstrate the technique to characterize electron bunches produced from a cold-atom electron source. We demonstrate brightness measurements with 145 ps temporal resolution and a minimum resolvable emittance of 40 nm rad. This technique provides an efficient method of exploring source parameters and will prove useful for examining the efficacy of techniques to counter space-charge expansion, a critical hurdle to achieving single-shot imaging of atomic scale targets.

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

    International Nuclear Information System (INIS)

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

    2008-01-01

    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

  6. AGILE Observations of the Gravitational-wave Source GW170817: Constraining Gamma-Ray Emission from an NS-NS Coalescence

    Science.gov (United States)

    Verrecchia, F.; Tavani, M.; Donnarumma, I.; Bulgarelli, A.; Evangelista, Y.; Pacciani, L.; Ursi, A.; Piano, G.; Pilia, M.; Cardillo, M.; Parmiggiani, N.; Giuliani, A.; Pittori, C.; Longo, F.; Lucarelli, F.; Minervini, G.; Feroci, M.; Argan, A.; Fuschino, F.; Labanti, C.; Marisaldi, M.; Fioretti, V.; Trois, A.; Del Monte, E.; Antonelli, L. A.; Barbiellini, G.; Caraveo, P.; Cattaneo, P. W.; Colafrancesco, S.; Costa, E.; D'Amico, F.; Ferrari, A.; Giommi, P.; Morselli, A.; Paoletti, F.; Pellizzoni, A.; Picozza, P.; Rappoldi, A.; Soffitta, P.; Vercellone, S.; Baroncelli, L.; Zollino, G.

    2017-12-01

    The LIGO-Virgo Collaboration (LVC) detected, on 2017 August 17, an exceptional gravitational-wave (GW) event temporally consistent within ˜ 1.7 {{s}} with the GRB 1708117A observed by Fermi-GBM and INTEGRAL. The event turns out to be compatible with a neutron star-neutron star (NS-NS) coalescence that subsequently produced a radio/optical/X-ray transient detected at later times. We report the main results of the observations by the AGILE satellite of the GW170817 localization region (LR) and its electromagnetic (EM) counterpart. At the LVC detection time T 0, the GW170817 LR was occulted by the Earth. The AGILE instrument collected useful data before and after the GW/GRB event because in its spinning observation mode it can scan a given source many times per hour. The earliest exposure of the GW170817 LR by the gamma-ray imaging detector started about 935 s after T 0. No significant X-ray or gamma-ray emission was detected from the LR that was repeatedly exposed over timescales of minutes, hours, and days before and after GW170817, also considering Mini-calorimeter and Super-AGILE data. Our measurements are among the earliest ones obtained by space satellites on GW170817 and provide useful constraints on the precursor and delayed emission properties of the NS-NS coalescence event. We can exclude with high confidence the existence of an X-ray/gamma-ray emitting magnetar-like object with a large magnetic field of {10}15 {{G}}. Our data are particularly significant during the early stage of evolution of the EM remnant.

  7. Electromagnetically induced transparency control in terahertz metasurfaces based on bright-bright mode coupling

    Science.gov (United States)

    Yahiaoui, R.; Burrow, J. A.; Mekonen, S. M.; Sarangan, A.; Mathews, J.; Agha, I.; Searles, T. A.

    2018-04-01

    We demonstrate a classical analog of electromagnetically induced transparency (EIT) in a highly flexible planar terahertz metamaterial (MM) comprised of three-gap split-ring resonators. The keys to achieve EIT in this system are the frequency detuning and hybridization processes between two bright modes coexisting in the same unit cell as opposed to bright-dark modes. We present experimental verification of two bright modes coupling for a terahertz EIT-MM in the context of numerical results and theoretical analysis based on a coupled Lorentz oscillator model. In addition, a hybrid variation of the EIT-MM is proposed and implemented numerically to dynamically tune the EIT window by incorporating photosensitive silicon pads in the split gap region of the resonators. As a result, this hybrid MM enables the active optical control of a transition from the on state (EIT mode) to the off state (dipole mode).

  8. Unexpected Functional Divergence of Bat Influenza Virus NS1 Proteins.

    Science.gov (United States)

    Turkington, Hannah L; Juozapaitis, Mindaugas; Tsolakos, Nikos; Corrales-Aguilar, Eugenia; Schwemmle, Martin; Hale, Benjamin G

    2018-03-01

    Recently, two influenza A virus (FLUAV) genomes were identified in Central and South American bats. These sequences exhibit notable divergence from classical FLUAV counterparts, and functionally, bat FLUAV glycoproteins lack canonical receptor binding and destroying activity. Nevertheless, other features that distinguish these viruses from classical FLUAVs have yet to be explored. Here, we studied the viral nonstructural protein NS1, a virulence factor that modulates host signaling to promote efficient propagation. Like all FLUAV NS1 proteins, bat FLUAV NS1s bind double-stranded RNA and act as interferon antagonists. Unexpectedly, we found that bat FLUAV NS1s are unique in being unable to bind host p85β, a regulatory subunit of the cellular metabolism-regulating enzyme, phosphoinositide 3-kinase (PI3K). Furthermore, neither bat FLUAV NS1 alone nor infection with a chimeric bat FLUAV efficiently activates Akt, a PI3K effector. Structure-guided mutagenesis revealed that the bat FLUAV NS1-p85β interaction can be reengineered (in a strain-specific manner) by changing two to four NS1 residues (96L, 99M, 100I, and 145T), thereby creating a hydrophobic patch. Notably, ameliorated p85β-binding is insufficient for bat FLUAV NS1 to activate PI3K, and a chimeric bat FLUAV expressing NS1 with engineered hydrophobic patch mutations exhibits cell-type-dependent, but species-independent, propagation phenotypes. We hypothesize that bat FLUAV hijacking of PI3K in the natural bat host has been selected against, perhaps because genes in this metabolic pathway were differentially shaped by evolution to suit the unique energy use strategies of this flying mammal. These data expand our understanding of the enigmatic functional divergence between bat FLUAVs and classical mammalian and avian FLUAVs. IMPORTANCE The potential for novel influenza A viruses to establish infections in humans from animals is a source of continuous concern due to possible severe outbreaks or pandemics. The

  9. NIGHT SKY BRIGHTNESS ABOVE ZAGREB 2012.-2017.

    Directory of Open Access Journals (Sweden)

    Željko Andreić

    2018-01-01

    Full Text Available The night sky brightness at the RGN site (near the centre of Zagreb, Croatia was monitored form January 2012. to December 2017. The gathered data show that the average night sky brightness in this period did not change significantly, apart from differences caused by yearly variations in meteorological parameters. The nightly minima, maxima and mean values of the sky brightness do change considerably due to changes in meteorological conditions, often being between 2 and 3 magnitudes. The seasonal probability curves and histograms are constructed and are used to obtain additional information on the light pollution at the RGN site. They reveal that the night sky brightness clutters around two peaks, at about 15.0 mag/arcsec2 and at about 18.2 mag/arcsec2. The tendency to slightly lower brightness values in spring and summer can also be seen in the data. Two peaks correspond to cloudy and clear nights respectively, the difference in brightness between them being about 3 magnitudes. A crude clear/cloudy criterion can be defined too: the minimum between two peaks is around 16.7 mag/arcsec2. The brightness values smaller than thisare attributed to clear nights and vice-versa. Comparison with Vienna and Hong-Kong indicates that the light pollution of Zagreb is a few times larger.

  10. Electron beam brightness with field immersed emission

    International Nuclear Information System (INIS)

    Boyd, J.K.; Neil, V.K.

    1985-01-01

    The beam quality or brightness of an electron beam produced with field immersed emission is studied with two models. First, an envelope formulation is used to determine the scaling of brightness with current, magnetic field and cathode radius, and examine the equilibrium beam radius. Second, the DPC computer code is used to calculate the brightness of two electron beam sources

  11. [Clinical significance of NS1-BP expression in esophageal squamous cell carcinoma].

    Science.gov (United States)

    Ren, K; Qian, D; Wang, Y W; Pang, Q S; Zhang, W C; Yuan, Z Y; Wang, P

    2018-01-23

    Objective: To investigate the clinical significance of NS1-BP expression in patients with esophageal squamous cell carcinoma (ESCC), and to study the roles of NS1-BP in proliferation and apoptosis of ESCC cells. Methods: A total of 98 tumor tissues and 30 adjacent normal tissues from 98 ESCC patients were used as study group and control group, and these samples were collected in Sun Yat-Sen University Cancer Center between 2002 and 2008. In addition, 46 ESCC tissues which were collected in Cancer Institute and Hospital of Tianjin Medical University were used as validation group. Expression of mucosal NS1-BP was detected by immunohistochemistry. Kaplan-Meier curve and log-rank test were used to analyze the survival rate. Multivariate Cox proportional hazard model was used to analyze the prognostic factors. Furthermore, NS1-BP was over expressed or knocked down in ESCC cells by transient transfection. Protein levels of c-Myc were detected by western blot. Cell viability and apoptosis was analyzed by MTT assay and flow cytometry. Results: Among all of tested samples, NS1-BP were down-regulated in 9 out of 30 non-tumorous normal esophageal tissues (30.0%) and 85 out of 144 ESCC tissues (59.0%), respectively, showing a statistically significant difference ( P =0.012). In the study group, three-year disease-free survival rate of NS1-BP high expression group (53.2%) was significantly higher than that of NS1-BP low expression group (27.6%; P =0.009). In the validation group, the three-year disease-free survival rates were 57.8% and 25.5% in NS1-BP high and low levels groups, respectively, showing a similar results ( P =0.016). Importantly, multivariate analyses showed that low expression of NS1-BP was an independent predictor for chemoradiotherapy sensitivity and shorter disease-free survival time in ESCC patients( P <0.05 for all). Furthermore, overexpressed NS1-BP in TE-1 cells repressed c-Myc expression, inhibited cell proliferation and promoted apoptosis. In contrast

  12. Teradiode's high brightness semiconductor lasers

    Science.gov (United States)

    Huang, Robin K.; Chann, Bien; Burgess, James; Lochman, Bryan; Zhou, Wang; Cruz, Mike; Cook, Rob; Dugmore, Dan; Shattuck, Jeff; Tayebati, Parviz

    2016-03-01

    TeraDiode is manufacturing multi-kW-class ultra-high brightness fiber-coupled direct diode lasers for industrial applications. A fiber-coupled direct diode laser with a power level of 4,680 W from a 100 μm core diameter, BPP) of 3.5 mm-mrad and is the lowest BPP multi-kW-class direct diode laser yet reported. This laser is suitable for industrial materials processing applications, including sheet metal cutting and welding. This 4-kW fiber-coupled direct diode laser has comparable brightness to that of industrial fiber lasers and CO2 lasers, and is over 10x brighter than state-of-the-art direct diode lasers. We have also demonstrated novel high peak power lasers and high brightness Mid-Infrared Lasers.

  13. Structure-based discovery of clinically approved drugs as Zika virus NS2B-NS3 protease inhibitors that potently inhibit Zika virus infection in vitro and in vivo.

    Science.gov (United States)

    Yuan, Shuofeng; Chan, Jasper Fuk-Woo; den-Haan, Helena; Chik, Kenn Ka-Heng; Zhang, Anna Jinxia; Chan, Chris Chung-Sing; Poon, Vincent Kwok-Man; Yip, Cyril Chik-Yan; Mak, Winger Wing-Nga; Zhu, Zheng; Zou, Zijiao; Tee, Kah-Meng; Cai, Jian-Piao; Chan, Kwok-Hung; de la Peña, Jorge; Pérez-Sánchez, Horacio; Cerón-Carrasco, José Pedro; Yuen, Kwok-Yung

    2017-09-01

    Zika virus (ZIKV) infection may be associated with severe complications in fetuses and adults, but treatment options are limited. We performed an in silico structure-based screening of a large chemical library to identify potential ZIKV NS2B-NS3 protease inhibitors. Clinically approved drugs belonging to different drug classes were selected among the 100 primary hit compounds with the highest predicted binding affinities to ZIKV NS2B-NS3-protease for validation studies. ZIKV NS2B-NS3 protease inhibitory activity was validated in most of the selected drugs and in vitro anti-ZIKV activity was identified in two of them (novobiocin and lopinavir-ritonavir). Molecular docking and molecular dynamics simulations predicted that novobiocin bound to ZIKV NS2B-NS3-protease with high stability. Dexamethasone-immunosuppressed mice with disseminated ZIKV infection and novobiocin treatment had significantly (P < 0.05) higher survival rate (100% vs 0%), lower mean blood and tissue viral loads, and less severe histopathological changes than untreated controls. This structure-based drug discovery platform should facilitate the identification of additional enzyme inhibitors of ZIKV. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Astronomy in Denver: Spatial distributions of dust properties via far-IR broadband map with HerPlaNS

    Science.gov (United States)

    Asano, Kentaro; Ueta, Toshiya; Ladjal, Djazia; Exter, Katrina; Otsuka, Masaaki; HerPlaNS Consortium

    2018-06-01

    We present the results of our analyses on dust properties in all of Galactic planetary nebulae based on 5-band broadband images in the far-IR taken with the Herschel Space Observatory.By fitting surface brightness distributions of dust thermal emission at 70, 160, 250, 350 and 500 microns with a single-temperature modified black body function, we derive spatially resolved maps of the dust emissivity power-law index (beta) and dust temperature (Td), as well as the column density.We find that circumstellar dust grains in PNe occupy a specific region in the beta-Td space, which is distinct from that occupied by dust grains in the Interstellar Matter (ISM) and star forming regions (SFRs). Unlike those in the ISM and SFRs, dust grains in PNe exhibit little variation in beta while a large spread in Td, suggesting rather homogeneous dust properties.This work is part of the Herschel Planetary Nebula Survey Plus (HerPlaNS+) supported by the NASA Astrophysics Data Analysis Program.

  15. Antiviral Activity and Resistance Analysis of NS3/4A Protease Inhibitor Grazoprevir and NS5A Inhibitor Elbasvir in Hepatitis C Virus GT4 Replicons.

    Science.gov (United States)

    Asante-Appiah, Ernest; Curry, Stephanie; McMonagle, Patricia; Ingravallo, Paul; Chase, Robert; Nickle, David; Qiu, Ping; Howe, Anita; Lahser, Frederick C

    2017-07-01

    Although genotype 4 (GT4)-infected patients represent a minor overall percentage of the global hepatitis C virus (HCV)-infected population, the high prevalence of the genotype in specific geographic regions coupled with substantial sequence diversity makes it an important genotype to study for antiviral drug discovery and development. We evaluated two direct-acting antiviral agents-grazoprevir, an HCV NS3/4A protease inhibitor, and elbasvir, an HCV NS5A inhibitor-in GT4 replicons prior to clinical studies in this genotype. Following a bioinformatics analysis of available GT4 sequences, a set of replicons bearing representative GT4 clinical isolates was generated. For grazoprevir, the 50% effective concentration (EC 50 ) against the replicon bearing the reference GT4a (ED43) NS3 protease and NS4A was 0.7 nM. The median EC 50 for grazoprevir against chimeric replicons encoding NS3/4A sequences from GT4 clinical isolates was 0.2 nM (range, 0.11 to 0.33 nM; n = 5). The difficulty in establishing replicons bearing NS3/4A resistance-associated substitutions was substantially overcome with the identification of a G162R adaptive substitution in NS3. Single NS3 substitutions D168A/V identified from de novo resistance selection studies reduced grazoprevir antiviral activity by 137- and 47-fold, respectively, in the background of the G162R replicon. For elbasvir, the EC 50 against the replicon bearing the reference full-length GT4a (ED43) NS5A gene was 0.0002 nM. The median EC 50 for elbasvir against chimeric replicons bearing clinical isolates from GT4 was 0.0007 nM (range, 0.0002 to 34 nM; n = 14). De novo resistance selection studies in GT4 demonstrated a high propensity to suppress the emergence of amino acid substitutions that confer high-potency reductions to elbasvir. Phenotypic characterization of the NS5A amino acid substitutions identified (L30F, L30S, M31V, and Y93H) indicated that they conferred 15-, 4-, 2.5-, and 7.5-fold potency losses, respectively, to elbasvir

  16. Epitope Sequences in Dengue Virus NS1 Protein Identified by Monoclonal Antibodies

    Directory of Open Access Journals (Sweden)

    Leticia Barboza Rocha

    2017-10-01

    Full Text Available Dengue nonstructural protein 1 (NS1 is a multi-functional glycoprotein with essential functions both in viral replication and modulation of host innate immune responses. NS1 has been established as a good surrogate marker for infection. In the present study, we generated four anti-NS1 monoclonal antibodies against recombinant NS1 protein from dengue virus serotype 2 (DENV2, which were used to map three NS1 epitopes. The sequence 193AVHADMGYWIESALNDT209 was recognized by monoclonal antibodies 2H5 and 4H1BC, which also cross-reacted with Zika virus (ZIKV protein. On the other hand, the sequence 25VHTWTEQYKFQPES38 was recognized by mAb 4F6 that did not cross react with ZIKV. Lastly, a previously unidentified DENV2 NS1-specific epitope, represented by the sequence 127ELHNQTFLIDGPETAEC143, is described in the present study after reaction with mAb 4H2, which also did not cross react with ZIKV. The selection and characterization of the epitope, specificity of anti-NS1 mAbs, may contribute to the development of diagnostic tools able to differentiate DENV and ZIKV infections.

  17. Study of Three-Dimensional Image Brightness Loss in Stereoscopy

    Directory of Open Access Journals (Sweden)

    Hsing-Cheng Yu

    2015-10-01

    Full Text Available When viewing three-dimensional (3D images, whether in cinemas or on stereoscopic televisions, viewers experience the same problem of image brightness loss. This study aims to investigate image brightness loss in 3D displays, with the primary aim being to quantify the image brightness degradation in the 3D mode. A further aim is to determine the image brightness relationship to the corresponding two-dimensional (2D images in order to adjust the 3D-image brightness values. In addition, the photographic principle is used in this study to measure metering values by capturing 2D and 3D images on television screens. By analyzing these images with statistical product and service solutions (SPSS software, the image brightness values can be estimated using the statistical regression model, which can also indicate the impact of various environmental factors or hardware on the image brightness. In analysis of the experimental results, comparison of the image brightness between 2D and 3D images indicates 60.8% degradation in the 3D image brightness amplitude. The experimental values, from 52.4% to 69.2%, are within the 95% confidence interval

  18. The effect of glycosylation on cytotoxicity of Ibaraki virus nonstructural protein NS3

    Science.gov (United States)

    URATA, Maho; WATANABE, Rie; IWATA, Hiroyuki

    2015-01-01

    The cytotoxicity of Ibaraki virus nonstructural protein NS3 was confirmed, and the contribution of glycosylation to this activity was examined by using glycosylation mutants of NS3 generated by site-directed mutagenesis. The expression of NS3 resulted in leakage of lactate dehydrogenase to the culture supernatant, suggesting the cytotoxicity of this protein. The lack of glycosylation impaired the transport of NS3 to the plasma membrane and resulted in reduced cytotoxicity. Combined with the previous observation that NS3 glycosylation was specifically observed in mammalian cells (Urata et al., Virus Research 2014), it was suggested that the alteration of NS3 cytotoxicity through modulating glycosylation is one of the strategies to achieve host specific pathogenisity of Ibaraki virus between mammals and vector arthropods. PMID:26178820

  19. The lowest surface brightness disc galaxy known

    International Nuclear Information System (INIS)

    Davies, J.I.; Phillipps, S.; Disney, M.J.

    1988-01-01

    The discovery of a galaxy with a prominent bulge and a dominant extremely low surface brightness disc component is reported. The profile of this galaxy is very similar to the recently discovered giant low surface brightness galaxy Malin 1. The disc central surface brightness is found to be ∼ 26.4 Rμ, some 1.5 mag fainter than Malin 1 and thus by far the lowest yet observed. (author)

  20. Brightness masking is modulated by disparity structure.

    Science.gov (United States)

    Pelekanos, Vassilis; Ban, Hiroshi; Welchman, Andrew E

    2015-05-01

    The luminance contrast at the borders of a surface strongly influences surface's apparent brightness, as demonstrated by a number of classic visual illusions. Such phenomena are compatible with a propagation mechanism believed to spread contrast information from borders to the interior. This process is disrupted by masking, where the perceived brightness of a target is reduced by the brief presentation of a mask (Paradiso & Nakayama, 1991), but the exact visual stage that this happens remains unclear. In the present study, we examined whether brightness masking occurs at a monocular-, or a binocular-level of the visual hierarchy. We used backward masking, whereby a briefly presented target stimulus is disrupted by a mask coming soon afterwards, to show that brightness masking is affected by binocular stages of the visual processing. We manipulated the 3-D configurations (slant direction) of the target and mask and measured the differential disruption that masking causes on brightness estimation. We found that the masking effect was weaker when stimuli had a different slant. We suggest that brightness masking is partly mediated by mid-level neuronal mechanisms, at a stage where binocular disparity edge structure has been extracted. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Brightness and darkness as perceptual dimensions

    NARCIS (Netherlands)

    Vladusich, T.; Lucassen, M.P.; Cornelissen, F.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

  2. The Future of HCV Therapy: NS4B as an Antiviral Target

    Directory of Open Access Journals (Sweden)

    Hadas Dvory-Sobol

    2010-11-01

    Full Text Available Chronic hepatitis C virus (HCV infection is a major worldwide cause of liver disease, including cirrhosis and hepatocellular carcinoma. It is estimated that more than 170 million individuals are infected with HCV, with three to four million new cases each year. The current standard of care, combination treatment with interferon and ribavirin, eradicates the virus in only about 50% of chronically infected patients. Notably, neither of these drugs directly target HCV. Many new antiviral therapies that specifically target hepatitis C (e.g. NS3 protease or NS5B polymerase inhibitors are therefore in development, with a significant number having advanced into clinical trials. The nonstructural 4B (NS4B protein, is among the least characterized of the HCV structural and nonstructural proteins and has been subjected to few pharmacological studies. NS4B is an integral membrane protein with at least four predicted transmembrane (TM domains. A variety of functions have been postulated for NS4B, such as the ability to induce the membranous web replication platform, RNA binding and NTPase activity. This review summarizes potential targets within the nonstructural protein NS4B, with a focus on novel classes of NS4B inhibitors.

  3. Effect of evening exposure to bright or dim light after daytime bright light on absorption of dietary carbohydrates the following morning.

    Science.gov (United States)

    Hirota, Naoko; Sone, Yoshiaki; Tokura, Hiromi

    2010-01-01

    We had previously reported on the effect of exposure to light on the human digestive system: daytime bright light exposure has a positive effect, whereas, evening bright light exposure has a negative effect on the efficiency of dietary carbohydrate absorption from the evening meal. These results prompted us to examine whether the light intensity to which subjects are exposed in the evening affects the efficiency of dietary carbohydrate absorption the following morning. In this study, subjects were exposed to either 50 lux (dim light conditions) or 2,000 lux (bright light conditions) in the evening for 9 h (from 15:00 to 24:00) after staying under bright light in the daytime (under 2,000 lux from 07:00 to 15:00). We measured unabsorbed dietary carbohydrates using the breath-hydrogen test the morning after exposure to either bright light or dim light the previous evening. Results showed that there was no significant difference between the two conditions in the amount of breath hydrogen. This indicates that evening exposure to bright or dim light after bright light exposure in the daytime has no varying effect on digestion or absorption of dietary carbohydrates in the following morning's breakfast.

  4. Uncoupling of Protease trans-Cleavage and Helicase Activities in Pestivirus NS3.

    Science.gov (United States)

    Zheng, Fengwei; Lu, Guoliang; Li, Ling; Gong, Peng; Pan, Zishu

    2017-11-01

    The nonstructural protein NS3 from the Flaviviridae family is a multifunctional 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 a 2.35-Å resolution. The structure reveals a previously unidentified ∼2,200-Å 2 intramolecular 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 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 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 through different

  5. Unperturbed moderator brightness in pulsed neutron sources

    International Nuclear Information System (INIS)

    Batkov, K.; Takibayev, A.; Zanini, L.; Mezei, F.

    2013-01-01

    The unperturbed neutron brightness of a moderator can be defined from the number of neutrons leaving the surface of a moderator completely surrounded by a reflector. Without openings for beam extraction, it is the maximum brightness that can be theoretically achieved in a moderator. The unperturbed brightness of a cylindrical cold moderator filled with pure para-H 2 was calculated using MCNPX; the moderator dimensions were optimised, for a fixed target and reflector geometry corresponding to the present concept for the ESS spallation source. This quantity does not depend on openings for beam extraction and therefore can be used for a first-round optimisation of a moderator, before effects due to beam openings are considered. We find that such an optimisation yields to a factor of 2 increase with respect to a conventional volume moderator, large enough to accommodate a viewed surface of 12×12 cm 2 : the unperturbed neutron brightness is maximum for a disc-shaped moderator of 15 cm diameter, 1.4 cm height. The reasons for this increase can be related to the properties of the scattering cross-section of para-H 2 , to the added reflector around the exit surface in the case of a compact moderator, and to a directionality effect. This large optimisation gain in the unperturbed brightness hints towards similar potentials for the perturbed neutron brightness, in particular in conjunction with advancing the optical quality of neutron delivery from the moderator to the sample, where by Liouville theorem the brightness is conserved over the beam trajectory, except for absorption and similar type losses

  6. The effects of non-synonymous single nucleotide polymorphisms (nsSNPs) on protein-protein interactions.

    Science.gov (United States)

    Yates, Christopher M; Sternberg, Michael J E

    2013-11-01

    Non-synonymous single nucleotide polymorphisms (nsSNPs) are single base changes leading to a change to the amino acid sequence of the encoded protein. Many of these variants are associated with disease, so nsSNPs have been well studied, with studies looking at the effects of nsSNPs on individual proteins, for example, on stability and enzyme active sites. In recent years, the impact of nsSNPs upon protein-protein interactions has also been investigated, giving a greater insight into the mechanisms by which nsSNPs can lead to disease. In this review, we summarize these studies, looking at the various mechanisms by which nsSNPs can affect protein-protein interactions. We focus on structural changes that can impair interaction, changes to disorder, gain of interaction, and post-translational modifications before looking at some examples of nsSNPs at human-pathogen protein-protein interfaces and the analysis of nsSNPs from a network perspective. © 2013.

  7. Nodding syndrome (NS) and Onchocerca Volvulus (OV) in Northern Uganda.

    Science.gov (United States)

    Lagoro, David Kitara; Arony, Denis Anywar

    2017-01-01

    Nodding Syndrome (NS) is a childhood neurological disorder characterized by atonic seizures, cognitive decline, school dropout, muscle weakness, thermal dysfunction, wasting and stunted growth. There are recent published information suggesting associations between Nodding Syndrome (NS) with cerebrospinal fluid (CSF) VGKC antibodies and serum leiomidin-1 antibody cross reacting with Onchocerca Volvulus ( OV ). These findings suggest a neuro-inflammatory cause of NS and they are important findings in the search for the cause of Nodding Syndrome. These observations perhaps provide further, the unique explanation for the association between Nodding Syndrome and Onchocerca Volvulus . Many clinical and epidemiological studies had shown a significant correlation between NS and infestation with a nematode, Onchocerca volvulus which causes a disease, Onchocerciasis , some of which when left untreated can develop visual defect ("River Blindness"). While these studies conducted in Northern Uganda and Southern Sudan indicate a statistically significant association with ( OV infection (using positive skin snips), we observe that ( OV is generally endemic in many parts of Sub Saharan Africa and Latin America and that to date, no NS cases have been recorded in those regions. This letter to the Editor is to provide additional information on the current view about the relationship between Nodding Syndrome and Onchocerca Volvulus as seen in Northern Uganda.

  8. Genetic Defects Underlie the Non-syndromic Autosomal Recessive Intellectual Disability (NS-ARID

    Directory of Open Access Journals (Sweden)

    Saleha Shamim

    2017-05-01

    Full Text Available Intellectual disability (ID is a neurodevelopmental disorder which appears frequently as the result of genetic mutations and may be syndromic (S-ID or non-syndromic (NS-ID. ID causes an important economic burden, for patient's family, health systems, and society. Identifying genes that cause S-ID can easily be evaluated due to the clinical symptoms or physical anomalies. However, in the case of NS-ID due to the absence of co-morbid features, the latest molecular genetic techniques can be used to understand the genetic defects that underlie it. Recent studies have shown that non-syndromic autosomal recessive (NS-ARID is extremely heterogeneous and contributes much more than X-linked ID. However, very little is known about the genes and loci involved in NS-ARID relative to X-linked ID, and whose complete genetic etiology remains obscure. In this review article, the known genetic etiology of NS-ARID and possible relationships between genes and the associated molecular pathways of their encoded proteins has been reviewed which will enhance our understanding about the underlying genes and mechanisms in NS-ARID.

  9. The brightness of colour.

    Directory of Open Access Journals (Sweden)

    David Corney

    Full Text Available The perception of brightness depends on spatial context: the same stimulus can appear light or dark depending on what surrounds it. A less well-known but equally important contextual phenomenon is that the colour of a stimulus can also alter its brightness. Specifically, stimuli that are more saturated (i.e. purer in colour appear brighter than stimuli that are less saturated at the same luminance. Similarly, stimuli that are red or blue appear brighter than equiluminant yellow and green stimuli. This non-linear relationship between stimulus intensity and brightness, called the Helmholtz-Kohlrausch (HK effect, was first described in the nineteenth century but has never been explained. Here, we take advantage of the relative simplicity of this 'illusion' to explain it and contextual effects more generally, by using a simple Bayesian ideal observer model of the human visual ecology. We also use fMRI brain scans to identify the neural correlates of brightness without changing the spatial context of the stimulus, which has complicated the interpretation of related fMRI studies.Rather than modelling human vision directly, we use a Bayesian ideal observer to model human visual ecology. We show that the HK effect is a result of encoding the non-linear statistical relationship between retinal images and natural scenes that would have been experienced by the human visual system in the past. We further show that the complexity of this relationship is due to the response functions of the cone photoreceptors, which themselves are thought to represent an efficient solution to encoding the statistics of images. Finally, we show that the locus of the response to the relationship between images and scenes lies in the primary visual cortex (V1, if not earlier in the visual system, since the brightness of colours (as opposed to their luminance accords with activity in V1 as measured with fMRI.The data suggest that perceptions of brightness represent a robust

  10. Production of recombinant dengue non-structural 1 (NS1) proteins from clinical virus isolates.

    Science.gov (United States)

    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.

  11. Gelatin nanoparticles enhance delivery of hepatitis C virus recombinant NS2 gene.

    Science.gov (United States)

    Sabet, Salwa; George, Marina A; El-Shorbagy, Haidan M; Bassiony, Heba; Farroh, Khaled Y; Youssef, Tareq; Salaheldin, Taher A

    2017-01-01

    Development of an effective non-viral vaccine against hepatitis C virus infection is of a great importance. Gelatin nanoparticles (Gel.NPs) have an attention and promising approach as a viable carrier for delivery of vaccine, gene, drug and other biomolecules in the body. The present study aimed to develop stable Gel.NPs conjugated with nonstructural protein 2 (NS2) gene of Hepatitis C Virus genotype 4a (HCV4a) as a safe and an efficient vaccine delivery system. Gel.NPs were synthesized and characterized (size: 150±2 nm and zeta potential +17.6 mv). NS2 gene was successfully cloned and expressed into E. coli M15 using pQE-30 vector. Antigenicity of the recombinant NS2 protein was confirmed by Western blotting to verify the efficiency of NS2 as a possible vaccine. Then NS2 gene was conjugated to gelatin nanoparticles and a successful conjugation was confirmed by labeling and imaging using Confocal Laser Scanning Microscope (CLSM). Interestingly, the transformation of the conjugated NS2/Gel.NPs complex into E. coli DH5-α was 50% more efficient than transformation with the gene alone. In addition, conjugated NS2/Gel.NPs with ratio 1:100 (w/w) showed higher transformation efficiency into E. coli DH5-α than the other ratios (1:50 and 2:50). Gel.NPs effectively enhanced the gene delivery in bacterial cells without affecting the structure of NS2 gene and could be used as a safe, easy, rapid, cost-effective and non-viral vaccine delivery system for HCV.

  12. D-Branes in the Background of NS Fivebranes

    CERN Document Server

    Elitzur, Shmuel; Rabinovici, Eliezer; Sarkisian, G; Kutasov, D; Elitzur, Shmuel; Giveon, Amit; Kutasov, David; Rabinovici, Eliezer; Sarkissian, Gor

    2000-01-01

    We study the dynamics of $D$-branes in the near-horizon geometry of $NS$ fivebranes. This leads to a holographically dual description of the physics of $D$-branes ending on and/or intersecting $NS5$-branes. We use it to verify some properties of such $D$-branes which were deduced indirectly in the past, and discuss some instabilities of non-supersymmetric brane configurations. Our construction also describes vacua of Little String Theory which are dual to open plus closed string theory in asymptotically linear dilaton spacetimes.

  13. Predicting deleterious nsSNPs: an analysis of sequence and structural attributes

    Directory of Open Access Journals (Sweden)

    Saqi Mansoor AS

    2006-04-01

    Full Text Available Abstract Background There has been an explosion in the number of single nucleotide polymorphisms (SNPs within public databases. In this study we focused on non-synonymous protein coding single nucleotide polymorphisms (nsSNPs, some associated with disease and others which are thought to be neutral. We describe the distribution of both types of nsSNPs using structural and sequence based features and assess the relative value of these attributes as predictors of function using machine learning methods. We also address the common problem of balance within machine learning methods and show the effect of imbalance on nsSNP function prediction. We show that nsSNP function prediction can be significantly improved by 100% undersampling of the majority class. The learnt rules were then applied to make predictions of function on all nsSNPs within Ensembl. Results The measure of prediction success is greatly affected by the level of imbalance in the training dataset. We found the balanced dataset that included all attributes produced the best prediction. The performance as measured by the Matthews correlation coefficient (MCC varied between 0.49 and 0.25 depending on the imbalance. As previously observed, the degree of sequence conservation at the nsSNP position is the single most useful attribute. In addition to conservation, structural predictions made using a balanced dataset can be of value. Conclusion The predictions for all nsSNPs within Ensembl, based on a balanced dataset using all attributes, are available as a DAS annotation. Instructions for adding the track to Ensembl are at http://www.brightstudy.ac.uk/das_help.html

  14. Oncolytic effects of a novel influenza A virus expressing interleukin-15 from the NS reading frame.

    Directory of Open Access Journals (Sweden)

    Marijke van Rikxoort

    Full Text Available Oncolytic influenza A viruses with deleted NS1 gene (delNS1 replicate selectively in tumour cells with defective interferon response and/or activated Ras/Raf/MEK/ERK signalling pathway. To develop a delNS1 virus with specific immunostimulatory properties, we used an optimised technology to insert the interleukin-15 (IL-15 coding sequence into the viral NS gene segment (delNS1-IL-15. DelNS1 and delNS1-IL-15 exerted similar oncolytic effects. Both viruses replicated and caused caspase-dependent apoptosis in interferon-defective melanoma cells. Virus replication was required for their oncolytic activity. Cisplatin enhanced the oncolytic activity of delNS1 viruses. The cytotoxic drug increased delNS1 replication and delNS1-induced caspase-dependent apoptosis. Interference with MEK/ERK signalling by RNAi-mediated depletion or the MEK inhibitor U0126 did not affect the oncolytic effects of the delNS1 viruses. In oncolysis sensitive melanoma cells, delNS1-IL-15 (but not delNS1 infection resulted in the production of IL-15 levels ranging from 70 to 1140 pg/mL in the cell culture supernatants. The supernatants of delNS1-IL-15-infected (but not of delNS1-infected melanoma cells induced primary human natural killer cell-mediated lysis of non-infected tumour cells. In conclusion, we constructed a novel oncolytic influenza virus that combines the oncolytic activity of delNS1 viruses with immunostimulatory properties through production of functional IL-15. Moreover, we showed that the oncolytic activity of delNS1 viruses can be enhanced in combination with cytotoxic anti-cancer drugs.

  15. Identification of specific regions in hepatitis C virus core, NS2 and NS5A that genetically interact with p7 and co-ordinate infectious virus production.

    Science.gov (United States)

    Gouklani, H; Beyer, C; Drummer, H; Gowans, E J; Netter, H J; Haqshenas, G

    2013-04-01

    The p7 protein of hepatitis C virus (HCV) is a small, integral membrane protein that plays a critical role in virus replication. Recently, we reported two intergenotypic JFH1 chimeric viruses encoding the partial or full-length p7 protein of the HCV-A strain of genotype 1b (GT1b; Virology; 2007; 360:134). In this study, we determined the consensus sequences of the entire polyprotein coding regions of the wild-type JFH1 and the revertant chimeric viruses and identified predominant amino acid substitutions in core (K74M), NS2 (T23N, H99P) and NS5A (D251G). Forward genetic analysis demonstrated that all single mutations restored the infectivity of the defective chimeric genomes suggesting that the infectious virus production involves the association of p7 with specific regions in core, NS2 and NS5A. In addition, it was demonstrated that the NS2 T23N facilitated the generation of infectious intergenotypic chimeric virus encoding p7 from GT6 of HCV. © 2012 Blackwell Publishing Ltd.

  16. The ZTF Bright Transient Survey

    Science.gov (United States)

    Fremling, C.; Sharma, Y.; Kulkarni, S. R.; Miller, A. A.; Taggart, K.; Perley, D. A.; Gooba, A.

    2018-06-01

    As a supplement to the Zwicky Transient Facility (ZTF; ATel #11266) public alerts (ATel #11685) we plan to report (following ATel #11615) bright probable supernovae identified in the raw alert stream from the ZTF Northern Sky Survey ("Celestial Cinematography"; see Bellm & Kulkarni, 2017, Nature Astronomy 1, 71) to the Transient Name Server (https://wis-tns.weizmann.ac.il) on a daily basis; the ZTF Bright Transient Survey (BTS; see Kulkarni et al., 2018; arXiv:1710.04223).

  17. The night sky brightness at McDonald Observatory

    Science.gov (United States)

    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.

  18. Selection effects in the bivariate brightness distribution for spiral galaxies

    International Nuclear Information System (INIS)

    Phillipps, S.; Disney, M.

    1986-01-01

    The joint distribution of total luminosity and characteristic surface brightness (the bivariate brightness distribution) is investigated for a complete sample of spiral galaxies in the Virgo cluster. The influence of selection and physical limits of various kinds on the apparent distribution are detailed. While the distribution of surface brightness for bright galaxies may be genuinely fairly narrow, faint galaxies exist right across the (quite small) range of accessible surface brightnesses so no statement can be made about the true extent of the distribution. The lack of high surface brightness bright galaxies in the Virgo sample relative to an overall RC2 sample (mostly field galaxies) supports the contention that the star-formation rate is reduced in the inner region of the cluster for environmental reasons. (author)

  19. Dark-Bright Soliton Dynamics Beyond the Mean-Field Approximation

    Science.gov (United States)

    Katsimiga, Garyfallia; Koutentakis, Georgios; Mistakidis, Simeon; Kevrekidis, Panagiotis; Schmelcher, Peter; Theory Group of Fundamental Processes in Quantum Physics Team

    2017-04-01

    The dynamics of dark bright solitons beyond the mean-field approximation is investigated. We first examine the case of a single dark-bright soliton and its oscillations within a parabolic trap. Subsequently, we move to the setting of collisions, comparing the mean-field approximation to that involving multiple orbitals in both the dark and the bright component. Fragmentation is present and significantly affects the dynamics, especially in the case of slower solitons and in that of lower atom numbers. It is shown that the presence of fragmentation allows for bipartite entanglement between the distinguishable species. Most importantly the interplay between fragmentation and entanglement leads to the decay of each of the initial mean-field dark-bright solitons into fast and slow fragmented dark-bright structures. A variety of excitations including dark-bright solitons in multiple (concurrently populated) orbitals is observed. Dark-antidark states and domain-wall-bright soliton complexes can also be observed to arise spontaneously in the beyond mean-field dynamics. Deutsche Forschungsgemeinschaft (DFG) in the framework of the SFB 925 ``Light induced dynamics and control of correlated quantum systems''.

  20. A Model of H-NS Mediated Compaction of Bacterial DNA

    NARCIS (Netherlands)

    Joyeux, M.; Vreede, J.

    2013-01-01

    The histone-like nucleoid structuring protein (H-NS) is a nucleoid-associated protein, which is involved in both gene regulation and DNA compaction. H-NS can bind to DNA in two different ways: in trans, by binding to two separate DNA duplexes, or in cis, by binding to different sites on the same

  1. Diagnostics for high-brightness beams

    International Nuclear Information System (INIS)

    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

  2. Supersymmetric non-singular fractional D2-branes and NS-NS 2-branes

    International Nuclear Information System (INIS)

    Cvetic, M.; Gibbons, G.W.; Lue, H.; Pope, C.N.

    2001-01-01

    We obtain regular deformed D2-brane solutions with fractional D2-branes arising as wrapped D4-branes. The space transverse to the D2-brane is a complete Ricci-flat 7-manifold of G 2 holonomy, which is asymptotically conical with principal orbits that are topologically CP 3 or the flag manifold SU(3)/(U(1)xU(1)). We obtain the solution by first constructing an L 2 normalisable harmonic 3-form. We also review a previously-obtained regular deformed D2-brane whose transverse space is a different 7-manifold of G 2 holonomy, with principal orbits that are topologically S 3 xS 3 . This describes D2-branes with fractional NS-NS 2-branes coming from the wrapping of 5-branes, which is supported by a non-normalisable harmonic 3-form on the 7-manifold. We prove that both types of solutions are supersymmetric, preserving 1/16 of the maximal supersymmetry and hence that they are dual to N=1 three-dimensional gauge theories. In each case, the spectrum for minimally-coupled scalars is discrete, indicating confinement in the infrared region of the dual gauge theories. We examine resolutions of other branes, and obtain necessary conditions for their regularity. The resolution of many of these seems to lie beyond supergravity. In the process of studying these questions, we construct new explicit examples of complete Ricci-flat metrics

  3. High brightness semiconductor lasers with reduced filamentation

    DEFF Research Database (Denmark)

    McInerney, John; O'Brien, Peter.; Skovgaard, Peter M. W.

    1999-01-01

    High brightness semiconductor lasers have applications in spectroscopy, fiber lasers, manufacturing and materials processing, medicine and free space communication or energy transfer. The main difficulty associated with high brightness is that, because of COD, high power requires a large aperture...

  4. Measuring energy conservation on Nova Scotia (NS) farms: A 2004 to 2011 comparison

    International Nuclear Information System (INIS)

    Bailey, J.A.; Duinker, P.; Amyotte, P.; Adams, M.; Khan, F.

    2016-01-01

    Many jurisdictions, including Nova Scotia (NS), have implemented policies and programs around energy. The NS government has targeted energy efficiency and more renewable energy as two main policy areas. The NS Department of Agriculture has taken initiative to provide support to implement energy conservation, energy efficiency and renewable energy opportunities in recent years but have these programs and policies been effective? A baseline energy use survey was conducted in 2005 and responses from mail surveys in 2012 (n = 273, 11.4% response rate) were used to measure the change in NS farm energy use data reported for 2004 and 2011. There have been significant reductions in energy use on NS farms. On average, NS farmers spent $8790 on energy expenses in 2011 compared to $11,228 in 2004. Adjusting for inflation, this is a 32% decrease, despite energy commodity pricing increases beyond the inflation rate. This is likely due to a decrease in energy use and a shift from gasoline use to diesel use. By the end of 2012, 36.0% of NS farmers (more than 860) had received some level of support to evaluate their energy options. This includes 410 energy audits compared to only 36 by the end of 2005. - Highlights: • Nova Scotia farmers decreased their energy costs by 32% between 2004 and 2011. • Energy reductions were likely due to decreased energy use and a shift in fuel use. • An estimated 374 NS farms had an energy audit between 2005 and 2012.

  5. Expression of NS1 of PPV in E.coli%猪细小病毒NS1基因的原核表达

    Institute of Scientific and Technical Information of China (English)

    冉旭华; 闻晓波; 孟凡; 周恩民

    2007-01-01

    根据GenBank发表的猪细小病毒(porcine parvovirus, PPV)中国株基因序列设计引物,通过PCR方法扩增到了PPV LJL12株NS1全长基因,将其克隆到原核表达载pET30a(+)上,成功构建原核表达载体pET30a-NS1,将其转化到大肠杆菌BL21(DE3)感受态细胞.经IPTG诱导表达后,进行SDS-PAGE和Western blot分析.SDS-PAGE电泳显示NS1在大肠杆菌中得到成功表达,重组蛋白大小约为86 ku,与预期大小相符;Western blot分析表明,该蛋白能与PPV阳性血清发生特异性反应,证明该蛋白具有良好生物学活性.NS1在大肠杆菌中成功表达,具有免疫原性,可作为鉴别诊断抗原用于PPV的临床检测.

  6. Construction and analysis of a plant non-specific lipid transfer protein database (nsLTPDB).

    Science.gov (United States)

    Wang, Nai-Jyuan; Lee, Chi-Ching; Cheng, Chao-Sheng; Lo, Wei-Cheng; Yang, Ya-Fen; Chen, Ming-Nan; Lyu, Ping-Chiang

    2012-01-01

    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. 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/. 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. 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.

  7. Construction and analysis of a plant non-specific lipid transfer protein database (nsLTPDB

    Directory of Open Access Journals (Sweden)

    Wang Nai-Jyuan

    2012-01-01

    Full Text Available Abstract 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.

  8. Burkina Faso - BRIGHT II

    Data.gov (United States)

    Millennium Challenge Corporation — Millennium Challenge Corporation hired Mathematica Policy Research to conduct an independent evaluation of the BRIGHT II program. The three main research questions...

  9. LHC experience with different bunch spacings in 2011 (25, 50 and 75 ns)

    International Nuclear Information System (INIS)

    Rumolo, G.; Iadarola, G.; Dominguez, O.; Arduini, G.; Bartosik, H.; Claudet, S.; Esteban-Mueller, J.; Roncarolo, F.; Shaposhnikova, E.; Tavian, L.

    2012-01-01

    LHC operation in 2011 had a smooth start in March with 75 ns beams and only one month later moved to 50 ns beam, after a successful dedicated scrubbing run. Several observables, such as pressure rise, heat load in the arcs, beam instability, emittance growth and synchronous phase shift, clearly pointed to the presence of an electron cloud inside the machine during the first days of operation with 50 ns beams. The gradual reduction of all these effects, and their eventual disappearance, over the days of the scrubbing run, indicated electron cloud mitigation and allowed physics production to shift to 50 ns beams. Up to the end of the run the quality of the 50 ns beams was increased by regular stages (first lower transverse emittances, then higher intensities), so that these beams could provide steadily improving peak luminosities. Furthermore, five MD sessions with 25 ns beams took place in the period June-October, but the quality of these beams was always deteriorated by severe electron cloud effects. However, a clear improvement was noticed also with the 25 ns runs. An estimation of the present state of conditioning of the machine and the required scrubbing time can be inferred from electron cloud simulations compared with measured data. (authors)

  10. Utility of dengue NS1 antigen rapid diagnostic test for use in difficult to reach areas and its comparison with dengue NS1 ELISA and qRT-PCR.

    Science.gov (United States)

    Shukla, Mohan K; Singh, Neeru; Sharma, Ravendra K; Barde, Pradip V

    2017-07-01

    The objective of this study was to demonstrate the utility of dengue virus (DENV) non structural protein 1 (NS1) based rapid diagnostic test (RDT) for use in tribal and difficult to reach areas for early dengue (DEN) diagnosis in acute phase patients and evaluate its sensitivity and specificity against DENV NS1 enzyme linked immune sorbent assay (ELISA) and real time reverse transcriptase polymerase chain reaction (qRT-PCR). The DENV NS1 RDT was used for preliminary diagnosis during outbreaks in difficult to reach rural and tribal areas. The diagnosis was confirmed by DENV NS1 ELISA in the laboratory. The samples were also tested and serotyped by qRT-PCR. The results were evaluated using statistical tests. The DENV NS1 RDT showed 99.2% sensitivity and 96.0% specificity when analyzed using DENV NS1 ELISA as standard. The specificity and sensitivity of the RDT when compared with qRT-PCR was 93.6% and 91.1%, respectively. The serotype specific evaluation showed more than 90% sensitivity and specificity for DENV-1, 2, and 3. The RDT proved a good diagnostic tool in difficult to reach rural and tribal areas. Further evaluation studies with different commercially available RDTs in different field conditions are essential, that will help clinicians and patients for treatment and programme managers for timely intervention. © 2017 Wiley Periodicals, Inc.

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

    Directory of Open Access Journals (Sweden)

    Koichi Higashi

    2016-01-01

    Full Text Available 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.

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

    Science.gov (United States)

    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. ns-2 extension to simulate localization system in wireless sensor networks

    CSIR Research Space (South Africa)

    Abu-Mahfouz, Adnan M

    2011-09-01

    Full Text Available The ns-2 network simulator is one of the most widely used tools by researchers to investigate the characteristics of wireless sensor networks. Academic papers focus on results and rarely include details of how ns-2 simulations are implemented...

  14. Spiky strings on AdS3 x S3 with NS-NS flux

    CERN Document Server

    Banerjee, Aritra; Pradhan, Pabitra M.

    2014-01-01

    We study rigidly rotating strings in the background of AdS3 x S3 with Neveu-Schwarz (NS) fluxes. We find two interesting limiting cases corresponding to the known giant magnon and the new single spike solution of strings in the above background and write down the dispersion relations among various conserved charges. We use proper regularization to find the correct relations among them. We further study the circular and infinite spiky strings on AdS and study their properties.

  15. Adapted J6/JFH1-based Hepatitis C virus recombinants with genotype-specific NS4A show similar efficacies against lead protease inhibitors, alpha interferon, and a putative NS4A inhibitor

    DEFF Research Database (Denmark)

    Gottwein, Judith M; Jensen, Sanne B; Serre, Stéphanie B N

    2013-01-01

    To facilitate studies of hepatitis C virus (HCV) NS4A, we aimed at developing J6/JFH1-based recombinants with genotype 1- to 7-specific NS4A proteins. We developed efficient culture systems expressing NS4A proteins of genotypes (isolates) 1a (H77 and TN), 1b (J4), 2a (J6), 4a (ED43), 5a (SA13), 6a...... (HK6a), and 7a (QC69), with peak infectivity titers of ∼3.5 to 4.5 log10 focus-forming units per ml. Except for genotype 2a (J6), growth depended on adaptive mutations identified in long-term culture. Genotype 1a, 1b, and 4a recombinants were adapted by amino acid substitutions F772S (p7) and V1663A...... (NS4A), while 5a, 6a, and 7a recombinants required additional substitutions in the NS3 protease and/or NS4A. We demonstrated applicability of the developed recombinants for study of antivirals. Genotype 1 to 7 NS4A recombinants showed similar responses to the protease inhibitors telaprevir (VX-950...

  16. Increasing the brightness of light sources

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Ling

    2006-11-16

    In this work the principle of light recycling is applied to artificial light sources in order to achieve brightness enhancement. Firstly, the feasibilities of increasing the brightness of light sources via light recycling are examined theoretically, based on the fundamental laws of thermodynamics including Kirchhoff's law on radiation, Planck's law, Lambert-Beer's law, the etendue conservation and the brightness theorem. From an experimental viewpoint, the radiation properties of three different kinds of light sources including short-arc lamps, incandescent lamps and LEDs characterized by their light-generating mechanisms are investigated. These three types of sources are used in light recycling experiments, for the purpose of 1. validating the intrinsic light recycling effect in light sources, e. g. the intrinsic light recycling effect in incandescent lamps stemming from the coiled filament structure. 2. acquiring the required parameters for establishing physical models, e.g. the emissivity/absorptivity of the short-arc lamps, the intrinsic reflectivity and the external quantum efficiency of LEDs. 3. laying the foundations for designing optics aimed at brightness enhancement according to the characteristics of the sources and applications. Based on the fundamental laws and experiments, two physical models for simulating the radiance distribution of light sources are established, one for thermal filament lamps, the other for luminescent sources, LEDs. As validation of the theoretical and experimental investigation of the light recycling effect, an optical device, the Carambola, is designed for achieving deterministic and multiple light recycling. The Carambola has the function of a concentrator. In order to achieve the maximum possible brightness enhancement with the Carambola, several combinations of sources and Carambolas are modelled in ray-tracing simulations. Sources with different light-emitting mechanisms and different radiation properties

  17. Electron paramagnetic resonance of the ns1 centers in crystals

    International Nuclear Information System (INIS)

    Nistor, S.V.; Ursu, I.

    1993-05-01

    The results of the EPR studies concerning the paramagnetic centers with ns 1 (N=n>2) outer electronic configuration contained in crystals are reviewed. Such centers, with 2 S 1/2 ground state, are produced by electron trapping at impurities of the IB and IIB group or by hole trapping at impurities of the IIIB and IV group of elements. The production and structural properties of such centers consisting of ns 1 ions (atoms) at various sites in the crystal lattice with different configurations of neighbouring defects are discussed in connection with their EPR characteristics. Tables containing the spin Hamiltonian parameters of all ns 1 centers reported in the literature until the end of year 1992 are given. (author). 146 refs, 14 tabs

  18. Life-threatening motor vehicle crashes in bright sunlight

    OpenAIRE

    Redelmeier, Donald A.; Raza, Sheharyar

    2017-01-01

    Abstract Bright sunlight may create visual illusions that lead to driver error, including fallible distance judgment from aerial perspective. We tested whether the risk of a life-threatening motor vehicle crash was increased when driving in bright sunlight. This longitudinal, case-only, paired-comparison analysis evaluated patients hospitalized because of a motor vehicle crash between January 1, 1995 and December 31, 2014. The relative risk of a crash associated with bright sunlight was estim...

  19. High-brightness fiber-coupled pump laser development

    Science.gov (United States)

    Price, Kirk; Karlsen, Scott; Leisher, Paul; Martinsen, Robert

    2010-02-01

    We report on the continued development of high brightness laser diode modules at nLIGHT Photonics. These modules, based on nLIGHT's PearlTM product platform, demonstrate excellence in output power, brightness, wavelength stabilization, and long wavelength performance. This system, based on 14 single emitters, is designed to couple diode laser light into a 105 μm fiber at an excitation NA of under 0.14. We demonstrate over 100W of optical power at 9xx nm with a diode brightness exceeding 20 MW/cm2-str with an operating efficiency of approximately 50%. Additional results show over 70W of optical coupled at 8xx nm. Record brilliance at wavelengths 14xx nm and longer will also be demonstrated, with over 15 W of optical power with a beam quality of 7.5 mm-mrad. These results of high brightness, high efficiency, and wavelength stabilization demonstrate the pump technology required for next generation solid state and fiber lasers.

  20. Identification of Hydroxyanthraquinones as Novel Inhibitors of Hepatitis C Virus NS3 Helicase

    Science.gov (United States)

    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. Identification of Hydroxyanthraquinones as Novel Inhibitors of Hepatitis C Virus NS3 Helicase

    Directory of Open Access Journals (Sweden)

    Atsushi Furuta

    2015-08-01

    Full Text Available 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.

  2. Decreasing the infusion rate reduces the proarrhythmic risk of NS-7

    DEFF Research Database (Denmark)

    Detre, Elke; Thomsen, Morten Bækgaard; Beekman, Jet D

    2005-01-01

    1 The rate of infusion has been suggested to be important for drug-induced torsades de pointes (TdP) arrhythmias. We investigated the repolarisation-prolonging effects and proarrhythmic properties of NS-7, a neuroprotective drug in development, using two different infusion rates. 2 A fast (5 min...... intravenously (i.v.)) escalating dosing regimen (0.3 and 3.0 mg kg(-1), n=4) of NS-7 was investigated in anaesthetised control dogs in sinus rhythm (SR). This was compared to a slow infusion (60 min i.v.) of one dose (3.0 mg kg(-1), n=4) NS-7. The similar dosing regimens were investigated in anaesthetised dogs...... with chronic, complete AV block (CAVB), an animal model of TdP (n=6). 3 No electrophysiological effects were seen after 0.3 mg kg(-1) NS-7. Fast infusion of 3.0 mg kg(-1) caused prolongation of repolarisation, for example, heart rate corrected QT interval (QT(c)): in SR: 6+/-1%; in CAVB: 10+/-7%, which...

  3. Hepatitis C virus NS4B carboxy terminal domain is a membrane binding domain

    Directory of Open Access Journals (Sweden)

    Spaan Willy JM

    2009-05-01

    Full Text Available Abstract Background 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. Results 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. Conclusion Together these data show that NS4B-CTD is associated to membranes, similar to the prokaryotic d-LDH MBD, and is important for replication.

  4. Characterization of Pressure Transients Generated by Nanosecond Electrical Pulse (nsEP) Exposure

    Science.gov (United States)

    Roth, Caleb C.; Barnes Jr., Ronald A.; Ibey, Bennett L.; Beier, Hope T.; Christopher Mimun, L.; Maswadi, Saher M.; Shadaram, Mehdi; Glickman, Randolph D.

    2015-01-01

    The mechanism(s) responsible for the breakdown (nanoporation) of cell plasma membranes after nanosecond pulse (nsEP) exposure remains poorly understood. Current theories focus exclusively on the electrical field, citing electrostriction, water dipole alignment and/or electrodeformation as the primary mechanisms for pore formation. However, the delivery of a high-voltage nsEP to cells by tungsten electrodes creates a multitude of biophysical phenomena, including electrohydraulic cavitation, electrochemical interactions, thermoelastic expansion, and others. To date, very limited research has investigated non-electric phenomena occurring during nsEP exposures and their potential effect on cell nanoporation. Of primary interest is the production of acoustic shock waves during nsEP exposure, as it is known that acoustic shock waves can cause membrane poration (sonoporation). Based on these observations, our group characterized the acoustic pressure transients generated by nsEP and determined if such transients played any role in nanoporation. In this paper, we show that nsEP exposures, equivalent to those used in cellular studies, are capable of generating high-frequency (2.5 MHz), high-intensity (>13 kPa) pressure transients. Using confocal microscopy to measure cell uptake of YO-PRO®-1 (indicator of nanoporation of the plasma membrane) and changing the electrode geometry, we determined that acoustic waves alone are not responsible for poration of the membrane. PMID:26450165

  5. Characterization of Pressure Transients Generated by Nanosecond Electrical Pulse (nsEP) Exposure.

    Science.gov (United States)

    Roth, Caleb C; Barnes, Ronald A; Ibey, Bennett L; Beier, Hope T; Christopher Mimun, L; Maswadi, Saher M; Shadaram, Mehdi; Glickman, Randolph D

    2015-10-09

    The mechanism(s) responsible for the breakdown (nanoporation) of cell plasma membranes after nanosecond pulse (nsEP) exposure remains poorly understood. Current theories focus exclusively on the electrical field, citing electrostriction, water dipole alignment and/or electrodeformation as the primary mechanisms for pore formation. However, the delivery of a high-voltage nsEP to cells by tungsten electrodes creates a multitude of biophysical phenomena, including electrohydraulic cavitation, electrochemical interactions, thermoelastic expansion, and others. To date, very limited research has investigated non-electric phenomena occurring during nsEP exposures and their potential effect on cell nanoporation. Of primary interest is the production of acoustic shock waves during nsEP exposure, as it is known that acoustic shock waves can cause membrane poration (sonoporation). Based on these observations, our group characterized the acoustic pressure transients generated by nsEP and determined if such transients played any role in nanoporation. In this paper, we show that nsEP exposures, equivalent to those used in cellular studies, are capable of generating high-frequency (2.5 MHz), high-intensity (>13 kPa) pressure transients. Using confocal microscopy to measure cell uptake of YO-PRO®-1 (indicator of nanoporation of the plasma membrane) and changing the electrode geometry, we determined that acoustic waves alone are not responsible for poration of the membrane.

  6. Discovery of Dengue Virus NS4B Inhibitors

    Science.gov (United States)

    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

  7. The surface brightness of spiral galaxies

    International Nuclear Information System (INIS)

    Phillipps, S.; Disney, M.

    1983-01-01

    It is proposed that Freeman's discovery that the extrapolated central surface brightness of spiral galaxies is approximately constant can be simply explained if the galaxies contain a spheroidal component which dominates the light in their outer isophotes. Calculations of an effective central surface brightness indicate a wide spread of values. This requires either a wide spread in disc properties or significant spheroidal components or, most probably, both. (author)

  8. Improved Bunch Splitting for the 75ns LHC Beam

    CERN Document Server

    Damerau, H

    2011-01-01

    The 75ns variant was added to the PS arsenal of LHC-type beams by adapting the 20MHz cavity used to produce the 25 and 50ns variants to operate at a switchable 13MHz. This permitted splitting from harmonic 14 to 28, but at a cost in adiabaticity compared with the h=2142 splitting of the other two cases. Consequently, a delicate empirical optimization was necessary to bring the 75ns beam inside specification. More recently the speed at which the bunches, once fully distinct, are moved apart has been revisited and further optimization achieved. As a by-product, deliberately degrading the splitting by moving the bunches apart too quickly led to sufficient coherent motion in the resultant bunch pair to permit a voltage calibration of the 13MHz cavity by means of the influence on convergence of the rf voltage input into the iterative algorithm of the Tomoscope [1,2].

  9. Experimental voyages of N.S. Mutsu

    International Nuclear Information System (INIS)

    Ochiai, Masaaki

    1993-01-01

    The first Japanese nuclear ship, N.S. MUTSU was commissioned by the Government on February 14 1991, after power up test and official sea trial with much success. Four experimental voyages of the ship were taken in the Pacific Ocean from March to December 1991 to study the performance of the nuclear power plant when it was influenced by marine conditions. In such an environment, incessant ship motion and load changes due to wave, wind, maneuvering, etc. are experienced. The ship sailed for a total of 110 days, a total distance of 64,180 km and for a total reactor operating time of 2,321 hours. Integrated reactor power was about 2,250 efph (effective full power hour) including that during the power up test. Zero power experiments were done again in Jan. 1992 to measure the core characteristics after finishing all the N.S. MUTSU plant operation program. Thus the most essential parts in the R ampersand D program on N.S. MUTSU was completed. The voyages demonstrated that the nuclear power plant worked well in any case and that the plant system had excellent capability as a marine engine. The data acquired through the experiments will contribute to the research and development program of the advanced marine reactor in Japan Atomic Energy Research Institute. This paper describes the technical informations obtained through the experimental voyages, such as load following abilities, system performances during the high sea sailing and the tropical sea sailing and behavior of system parameters accompanied with steering. The latest technical results yielded by the program are also summarized here

  10. New NS varieties of six-rowed winter barley

    Directory of Open Access Journals (Sweden)

    Pržulj Novo

    2009-01-01

    Full Text Available The paper describes the characteristics of several new NS varieties of winter six-rowed barley released in Serbia between 2004 and 2007. These are Somborac, Ozren, Javor, Novosadski 773, Sremac and Leotar. In the official variety trials in the country, all six of these varieties outyielded the check variety, and the margins were as follows: Somborac - 3.4%, Ozren - 5.0%, Javor - 7.3%, Novosadski 773 - 3.4%, Sremac - 7.4%, and Leotar - 7.2%. Yield levels in absolute terms depended on the variety as well as year. All six-rowed NS varieties headed earlier than the check and had better resistance to lodging than the check has. The test weight of the new varieties was 70.2-73.8 kg/hl and the 1000-grain weight 33.4-50.2 g. The cellulose content was 4.4-4.8%, the fat content 1.4%, and the protein content 13.3-14.6%. The high variability of the new NS varieties of winter six-rowed barley makes it possible to choose the most suitable genotype for each barley-growing area in the country. .

  11. Direct binding of ledipasvir to HCV NS5A: mechanism of resistance to an HCV antiviral agent.

    Directory of Open Access Journals (Sweden)

    Hyock Joo Kwon

    Full Text Available Ledipasvir, a direct acting antiviral agent (DAA targeting the Hepatitis C Virus NS5A protein, exhibits picomolar activity in replicon cells. While its mechanism of action is unclear, mutations that confer resistance to ledipasvir in HCV replicon cells are located in NS5A, suggesting that NS5A is the direct target of ledipasvir. To date co-precipitation and cross-linking experiments in replicon or NS5A transfected cells have not conclusively shown a direct, specific interaction between NS5A and ledipasvir. Using recombinant, full length NS5A, we show that ledipasvir binds directly, with high affinity and specificity, to NS5A. Ledipasvir binding to recombinant NS5A is saturable with a dissociation constant in the low nanomolar range. A mutant form of NS5A (Y93H that confers resistance to ledipasvir shows diminished binding to ledipasvir. The current study shows that ledipasvir inhibits NS5A through direct binding and that resistance to ledipasvir is the result of a reduction in binding affinity to NS5A mutants.

  12. The effect of bright lines in environmental risk communication

    International Nuclear Information System (INIS)

    Wilson, K.N.; Desvousges, W.H.; Smith, K.V.; Payne, J.

    1993-01-01

    Bright lines in environmental risk communication refer to the specific levels at which an environmental risk becomes a serious health threat and action should be taken to mitigate its effects. This study examined the effect of ''bright lines'' in risk communication by emphasizing the radon exposure threshold level of 4 picocuries per liter. Specifically, the authors developed a computer-assisted interview containing bright-line versions of risk information. The bright-line version contained a range of possible radon levels, the corresponding number of estimated lung cancer cases, the relative health risk from radon compared to other health risks, and the EPA guidelines for mitigating levels above 4 picocuries in the home. The non-bright line version was identical to the bright-line version, except it did not include the EPA's mitigation recommendations. Effect measures included respondents' change in perceived risk after reading their materials, intended testing behavior, and advice to their neighbor for a specified radon level either above or below the 4 picocury threshold level. This paper discusses broader policy implications for designing effective risk communication programs

  13. Bright boys the making of information technology

    CERN Document Server

    Green, Tom

    2010-01-01

    Everything has a beginning. None was more profound-and quite as unexpected-than Information Technology. Here for the first time is the untold story of how our new age came to be and the bright boys who made it happen. What began on the bare floor of an old laundry building eventually grew to rival in size the Manhattan Project. The unexpected consequence of that journey was huge---what we now know as Information Technology. For sixty years the bright boys have been totally anonymous while their achievements have become a way of life for all of us. "Bright Boys" brings them home. By 1950 they'd

  14. Designing cyclopentapeptide inhibitor as potential antiviral drug for dengue virus ns5 methyltransferase.

    Science.gov (United States)

    Idrus, Syarifuddin; Tambunan, Usman Sumo Friend; Zubaidi, Ahmad Ardilla

    2012-01-01

    NS5 methyltransferase (Mtase) has a crucial role in the replication of dengue virus. There are two active sites on NS5 Mtase i.e., SAM and RNA-cap binding sites. Inhibition of the NS5 Mtase activity is expected to prevent the propagation of dengue virus. This study was conducted to design cyclic peptide ligands as enzyme inhibitors of dengue virus NS5 Mtase through computational approach. Cyclopentapeptides were designed as ligand of SAM binding site as much as 1635 and 736 cyclopentpeptides were designed as ligand of RNA-cap binding site. Interaction between ligand and NS5 Mtase has been conducted on the Docking simulation. The result shows that cyclopentapeptide CTWYC was the best peptide candidate on SAM binding site, with estimated free binding energy -30.72 kca/mol. Cyclopentapeptide CYEFC was the best peptide on RNA-cap binding site with estimated free binding energy -22.89 kcal/mol. Both peptides did not have tendency toward toxicity properties. So it is expected that both CTWYC and CYEFC ligands could be used as a potential antiviral drug candidates, which can inhibit the SAM and RNA-cap binding sites of dengue virus NS5 Mtase.

  15. Star formation and the surface brightness of spiral galaxies

    International Nuclear Information System (INIS)

    Phillipps, S.; Disney, M.

    1985-01-01

    The (blue) surface brightness of spiral galaxies is significantly correlated with their Hα linewidth. This can be most plausibly interpreted as a correlation of surface brightness with star formation rate. There is also a significant difference in surface brightness between galaxies forming stars in a grand design spiral pattern and those with floc star formation regions. (author)

  16. Electron Cloud Observations during LHC Operation with 25 ns Beams

    CERN Document Server

    Li, Kevin; Iadarola, Giovanni; Mether, Lotta; Romano, Annalisa; Rumolo, Giovanni; Schenk, Michael

    2016-01-01

    While during the Run 1 (2010-2012) of the Large Hadron Collider (LHC) most of the integrated luminosity was produced with 50 ns bunch spacing, for the Run 2 start-up (2015) it was decided to move to the nominal bunch spacing of 25 ns. As expected, with this beam configuration strong electron cloud effects were observed in the machine, which had to be mitigated with dedicated 'scrubbing' periods at injection energy. This enabled to start the operation with 25 ns beams at 6.5 TeV, but e-cloud effects continued to pose challenges while gradually increasing the number of circulating bunch trains. This contribution will review the encountered limitations and the mitigation measures that where put in place and will discuss possible strategies for further performance gain.

  17. Naturally occurring mutations associated with resistance to HCV NS5B polymerase and NS3 protease inhibitors in treatment-naïve patients with chronic hepatitis C.

    Science.gov (United States)

    Costantino, Angela; Spada, Enea; Equestre, Michele; Bruni, Roberto; Tritarelli, Elena; Coppola, Nicola; Sagnelli, Caterina; Sagnelli, Evangelista; Ciccaglione, Anna Rita

    2015-11-14

    The detection of baseline resistance mutations to new direct-acting antivirals (DAAs) in HCV chronically infected treatment-naïve patients could be important for their management and outcome prevision. In this study, we investigated the presence of mutations, which have been previously reported to be associated with resistance to DAAs in HCV polymerase (NS5B) and HCV protease (NS3) regions, in sera of treatment-naïve patients. HCV RNA from 152 naïve patients (84 % Italian and 16 % immigrants from various countries) infected with different HCV genotypes (21,1a; 21, 1b; 2, 2a; 60, 2c; 22, 3a; 25, 4d and 1, 4k) was evaluated for sequence analysis. Amplification and sequencing of fragments in the NS5B (nt 8256-8640) and NS3 (nt 3420-3960) regions of HCV genome were carried out for 152 and 28 patients, respectively. The polymorphism C316N/H in NS5B region, associated with resistance to sofosbuvir, was detected in 9 of the 21 (43 %) analysed sequences from genotype 1b-infected patients. Naturally occurring mutations V36L, and M175L in the NS3 protease region were observed in 100 % of patients infected with subtype 2c and 4. A relevant proportion of treatment naïve genotype 1b infected patients evaluated in this study harboured N316 polymorphism and might poorly respond to sofosbuvir treatment. As sofosbuvir has been approved for treatment of HCV chronic infection in USA and Europe including Italy, pre-treatment testing for N316 polymorphism on genotype 1b naïve patients should be considered for this drug.

  18. The surface brightness of spiral galaxies

    International Nuclear Information System (INIS)

    Disney, M.; Phillipps, S.

    1985-01-01

    The intrinsic surface brightness Ssub(e) of 500 disc galaxies (0<=T<=9) drawn from the Second Reference Catalogue is computed and it is shown that Ssub(e) does not correlate significantly with Msub(B), (B-V) or type. This is consistent with the notion that there is a heavy selection bias in favour of disc galaxies with that particular surface brightness which allows inclusion in the catalogue over the largest volume of space. (author)

  19. SURFACE PHOTOMETRY OF LOW SURFACE BRIGHTNESS GALAXIES

    NARCIS (Netherlands)

    DEBLOK, WJG; VANDERHULST, JM; BOTHUN, GD

    1995-01-01

    Low surface brightness (LSB) galaxies are galaxies dominated by an exponential disc whose central surface brightness is much fainter than the value of mu(B)(0) = 21.65 +/- 0.30 mag arcsec(-2) found by Freeman. In this paper we present broadband photometry of a sample of 21 late-type LSB galaxies.

  20. X-ray structure of the pestivirus NS3 helicase and its conformation in solution.

    Science.gov (United States)

    Tortorici, M Alejandra; Duquerroy, Stéphane; Kwok, Jane; Vonrhein, Clemens; Perez, Javier; Lamp, Benjamin; Bricogne, Gerard; Rümenapf, Till; Vachette, Patrice; Rey, Félix A

    2015-04-01

    Pestiviruses form a genus in the Flaviviridae family of small enveloped viruses with a positive-sense single-stranded RNA genome. Viral replication in this family requires the activity of a superfamily 2 RNA helicase contained in the C-terminal domain of nonstructural protein 3 (NS3). NS3 features two conserved RecA-like domains (D1 and D2) with ATPase activity, plus a third domain (D3) that is important for unwinding nucleic acid duplexes. We report here the X-ray structure of the pestivirus NS3 helicase domain (pNS3h) at a 2.5-Å resolution. The structure deviates significantly from that of NS3 of other genera in the Flaviviridae family in D3, as it contains two important insertions that result in a narrower nucleic acid binding groove. We also show that mutations in pNS3h that rescue viruses from which the core protein is deleted map to D3, suggesting that this domain may be involved in interactions that facilitate particle assembly. Finally, structural comparisons of the enzyme in different crystalline environments, together with the findings of small-angle X-ray-scattering studies in solution, show that D2 is mobile with respect to the rest of the enzyme, oscillating between closed and open conformations. Binding of a nonhydrolyzable ATP analog locks pNS3h in a conformation that is more compact than the closest apo-form in our crystals. Together, our results provide new insight and bring up new questions about pNS3h function during pestivirus replication. Although pestivirus infections impose an important toll on the livestock industry worldwide, little information is available about the nonstructural proteins essential for viral replication, such as the NS3 helicase. We provide here a comparative structural and functional analysis of pNS3h with respect to its orthologs in other viruses of the same family, the flaviviruses and hepatitis C virus. Our studies reveal differences in the nucleic acid binding groove that could have implications for understanding the

  1. Effects of NS lactobacillus strains on lipid metabolism of rats fed a high-cholesterol diet

    Science.gov (United States)

    2013-01-01

    Background Elevated serum cholesterol level is generally considered to be a risk factor for the development of cardiovascular diseases which seriously threaten human health. The cholesterol-lowering effects of lactic acid bacteria have recently become an area of great interest and controversy for many researchers. In this study, we investigated the effects of two NS lactobacillus strains, Lactobacillus plantarum NS5 and Lactobacillus delbrueckii subsp. bulgaricus NS12, on lipid metabolism of rats fed a high cholesterol diet. Methods Thirty-two SD rats were assigned to four groups and fed either a normal or a high-cholesterol diet. The NS lactobacillus treated groups received the high-cholesterol diet supplemented with Lactobacillus plantarum NS5 or Lactobacillus delbrueckii subsp. bulgaricus NS12 in drinking water. The rats were sacrificed after a 6-week feeding period. Body weights, visceral organ and fat weights, serum and liver cholesterol and lipid levels, intestinal microbiota and liver mRNA expression levels related to cholesterol metabolism were analyzed. Liver lipid deposition and adipocyte size were evaluated histologically. Results Compared with rats fed a high cholesterol diet, serum total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B and free fatty acids levels were decreased and apolipoprotein A-I level was increased in NS5 or NS12 strain treated rats, and with no significant change in high-density lipoprotein cholesterol level. Liver cholesterol and triglyceride levels were also significantly decreased in NS lactobacillus strains treated groups. Meanwhile, the NS lactobacillus strains obviously alleviated hepatic injuries, decreased liver lipid deposition and reduced adipocyte size of high cholesterol diet fed rats. NS lactobacillus strains restored the changes in intestinal microbiota compositions, such as the increase in Bacteroides and the decrease in Clostridium. NS lactobacillus strains also regulated the mRNA expression

  2. Low mass X-ray binaries in the Inner Galaxy: implications for millisecond pulsars and the GeV excess

    Energy Technology Data Exchange (ETDEWEB)

    Haggard, Daryl; Heinke, Craig; Hooper, Dan; Linden, Tim

    2017-05-01

    If millisecond pulsars (MSPs) are responsible for the excess gamma-ray emission observed from the region surrounding the Galactic Center, the same region should also contain a large population of low-mass X-ray binaries (LMXBs). In this study, we compile and utilize a sizable catalog of LMXBs observed in the the Milky Way's globular cluster system and in the Inner Galaxy, as well as the gamma-ray emission observed from globular clusters, to estimate the flux of gamma rays predicted from MSPs in the Inner Galaxy. From this comparison, we conclude that only up to $\\sim$4-23% of the observed gamma-ray excess is likely to originate from MSPs. This result is consistent with, and more robust than, previous estimates which utilized smaller samples of both globular clusters and LMXBs. If MSPs had been responsible for the entirety of the observed excess, INTEGRAL should have detected $\\sim$$10^3$ LMXBs from within a $10^{\\circ}$ radius around the Galactic Center, whereas only 42 LMXBs (and 46 additional LMXB candidates) have been observed.

  3. Simultaneous removal of chlorothalonil and nitrate by Bacillus cereus strain NS1

    International Nuclear Information System (INIS)

    Zhang Yiqiang; Lu Jianhang; Wu Laosheng; Chang, Andrew; Frankenberger, William T.

    2007-01-01

    Elevated NO 3 - and chlorothalonil (CTN) have been found in production nursery recycling ponds. Bacillus cereus strain NS1 isolated from nursery recycling pond sediment was assessed for its ability to reduce NO 3 - and degrade CTN in a mineral medium. The results showed that the efficiency of NO 3 - reduction and CTN degradation by B. cereus strain NS1 were related to the nature of organic carbon sources added to the medium. In the medium amended with 100 mg/L yeast extract, 86% of NO 3 - (100 mg/L) and 99% of CTN (78 μg/L) were simultaneously removed by B. cereus strain NS1 during the first day of the experiment. It took 6 days for the removal of 82-93% of NO 3 - and 87-91% of CTN in the media containing glucose and acetate. B. cereus strain NS1 needed organic carbon as energy sources and electron donors to respire NO 3 - , and simultaneously degrade CTN. These results suggest that B. cereus strain NS1 may have great potential to remediate NO 3 - and CTN contaminated water in nursery recycling ponds

  4. The N-Terminal of Aquareovirus NS80 Is Required for Interacting with Viral Proteins and Viral Replication.

    Directory of Open Access Journals (Sweden)

    Jie Zhang

    Full Text Available Reovirus replication and assembly occurs within viral inclusion bodies that formed in specific intracellular compartments of cytoplasm in infected cells. Previous study indicated that aquareovirus NS80 is able to form inclusion bodies, and also can retain viral proteins within its inclusions. To better understand how NS80 performed in viral replication and assembly, the functional regions of NS80 associated with other viral proteins in aquareovirus replication were investigated in this study. Deletion mutational analysis and rotavirus NSP5-based protein association platform were used to detect association regions. Immunofluorescence images indicated that different N-terminal regions of NS80 could associate with viral proteins VP1, VP4, VP6 and NS38. Further co-immunoprecipitation analysis confirmed the interaction between VP1, VP4, VP6 or NS38 with different regions covering the N-terminal amino acid (aa, 1-471 of NS80, respectively. Moreover, removal of NS80 N-terminal sequences required for interaction with proteins VP1, VP4, VP6 or NS38 not only prevented the capacity of NS80 to support viral replication in NS80 shRNA-based replication complementation assays, but also inhibited the expression of aquareovirus proteins, suggesting that N-terminal regions of NS80 are necessary for viral replication. These results provided a foundational basis for further understanding the role of NS80 in viral replication and assembly during aquareovirus infection.

  5. A STRANGE STAR SCENARIO FOR THE FORMATION OF ECCENTRIC MILLISECOND PULSAR/HELIUM WHITE DWARF BINARIES

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Long; Li, Xiang-Dong [Department of Astronomy, Nanjing University, Nanjing 210046 (China); Dey, Jishnu; Dey, Mira, E-mail: lixd@nju.edu.cn [Department of Physics, Presidency University, 86/1, College Street, Kolkata 700 073 (India)

    2015-07-01

    According to the recycling scenario, millisecond pulsars (MSPs) have evolved from low-mass X-ray binaries (LMXBs). Their orbits are expected to be circular due to tidal interactions during binary evolution, as observed in most binary MSPs. There are some peculiar systems that do not fit this picture. Three recent examples are the PSRs J2234+06, J1946+3417, and J1950+2414, all of which are MSPs in eccentric orbits but with mass functions compatible with expected He white dwarf (WD) companions. It has been suggested these MSPs may have formed from delayed accretion-induced collapse of massive WDs, or the eccentricity may be induced by dynamical interaction between the binary and a circumbinary disk. Assuming that the core density of accreting neutron stars (NSs) in LMXBs may reach the density of quark deconfinement, which can lead to phase transition from NSs to strange quark stars, we show that the resultant MSPs are likely to have an eccentric orbit, due to the sudden loss of the gravitational mass of the NS during the transition. The eccentricities can be reproduced with a reasonable estimate of the mass loss. This scenario might also account for the formation of the youngest known X-ray binary Cir X–1, which also possesses a low-field compact star in an eccentric orbit.

  6. NS&T Management Observations - 3rd Quarter

    Energy Technology Data Exchange (ETDEWEB)

    Gianotto, David [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    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.

  7. NS&T Management Observations: Quarterly Performance Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Gianotto, David [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    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.

  8. NS&T Managment Observations - 1st Quarter

    Energy Technology Data Exchange (ETDEWEB)

    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.

  9. NS OTTO HAHN - the first German nuclear ship

    International Nuclear Information System (INIS)

    1981-01-01

    The NS OTTO HAHN is the first and only European nuclear propelled cargo and research vessel. She entered service in 1968 and was operated for 11 years without any technical failure. The essential experience and know-how about the nuclear propulsion unit is available now. Therefore the ship was decommissioned in 1979. Until the end of 1981 all activated and contaminated components will be removed and decontaminated. The ship can then be released for conventional utilization. In this book the NS OTTO HAHN is described in detail and the experiences of operation as well as research and development activities are reported. All earlier publications of GKSS on the same subject are listed. (orig.) [de

  10. The surface brightness of spiral galaxies: Pt. 4

    International Nuclear Information System (INIS)

    Phillipps, S.; Disney, M.; Ohio State Univ., Columbus

    1988-01-01

    Using measurements from IRAS correlations are found between optical surface brightness and both infrared-to-optical flux ratio and infrared colour temperature, in the sense that galaxies with high surface brightness have higher FIR emission and higher temperatures. (author)

  11. Bright point study

    International Nuclear Information System (INIS)

    Tang, F.; Harvey, K.; Bruner, M.; Kent, B.; Antonucci, E.

    1982-01-01

    Transition region and coronal observations of bright points by instruments aboard the Solar Maximum Mission and high resolution photospheric magnetograph observations on September 11, 1980 are presented. A total of 31 bipolar ephemeral regions were found in the photosphere from birth in 9.3 hours of combined magnetograph observations from three observatories. Two of the three ephemeral regions present in the field of view of the Ultraviolet Spectrometer-Polarimeter were observed in the C IV 1548 line. The unobserved ephemeral region was determined to be the shortest-lived (2.5 hr) and lowest in magnetic flux density (13G) of the three regions. The Flat Crystal Spectrometer observed only low level signals in the O VIII 18.969 A line, which were not statistically significant to be positively identified with any of the 16 ephemeral regions detected in the photosphere. In addition, the data indicate that at any given time there lacked a one-to-one correspondence between observable bright points and photospheric ephemeral regions, while more ephemeral regions were observed than their counterparts in the transition region and the corona

  12. Hepatitis C virus NS3/4A protease inhibits complement activation by cleaving complement component 4.

    Directory of Open Access Journals (Sweden)

    Seiichi Mawatari

    Full Text Available BACKGROUND: It has been hypothesized that persistent hepatitis C virus (HCV infection is mediated in part by viral proteins that abrogate the host immune response, including the complement system, but the precise mechanisms are not well understood. We investigated whether HCV proteins are involved in the fragmentation of complement component 4 (C4, composed of subunits C4α, C4β, and C4γ, and the role of HCV proteins in complement activation. METHODS: Human C4 was incubated with HCV nonstructural (NS 3/4A protease, core, or NS5. Samples were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and then subjected to peptide sequencing. The activity of the classical complement pathway was examined using an erythrocyte hemolysis assay. The cleavage pattern of C4 in NS3/4A-expressing and HCV-infected cells, respectively, was also examined. RESULTS: HCV NS3/4A protease cleaved C4γ in a concentration-dependent manner, but viral core and NS5 did not. A specific inhibitor of NS3/4A protease reduced C4γ cleavage. NS3/4A protease-mediated cleavage of C4 inhibited classical pathway activation, which was abrogated by a NS3/4A protease inhibitor. In addition, co-transfection of cells with C4 and wild-type NS3/4A, but not a catalytic-site mutant of NS3/4A, produced cleaved C4γ fragments. Such C4 processing, with a concomitant reduction in levels of full-length C4γ, was also observed in HCV-infected cells expressing C4. CONCLUSIONS: C4 is a novel cellular substrate of the HCV NS3/4A protease. Understanding disturbances in the complement system mediated by NS3/4A protease may provide new insights into the mechanisms underlying persistent HCV infection.

  13. Giant Low Surface Brightness Galaxies

    Science.gov (United States)

    Mishra, Alka; Kantharia, Nimisha G.; Das, Mousumi

    2018-04-01

    In this paper, we present radio observations of the giant low surface brightness (LSB) galaxies made using the Giant Metrewave Radio Telescope (GMRT). LSB galaxies are generally large, dark matter dominated spirals that have low star formation efficiencies and large HI gas disks. Their properties suggest that they are less evolved compared to high surface brightness galaxies. We present GMRT emission maps of LSB galaxies with an optically-identified active nucleus. Using our radio data and archival near-infrared (2MASS) and near-ultraviolet (GALEX) data, we studied morphology and star formation efficiencies in these galaxies. All the galaxies show radio continuum emission mostly associated with the centre of the galaxy.

  14. Helmholtz bright and boundary solitons

    International Nuclear Information System (INIS)

    Christian, J M; McDonald, G S; Chamorro-Posada, P

    2007-01-01

    We report, for the first time, exact analytical boundary solitons of a generalized cubic-quintic nonlinear Helmholtz (NLH) equation. These solutions have a linked-plateau topology that is distinct from conventional dark soliton solutions; their amplitude and intensity distributions are spatially delocalized and connect regions of finite and zero wave-field disturbances (suggesting also the classification as 'edge solitons'). Extensive numerical simulations compare the stability properties of recently derived Helmholtz bright solitons, for this type of polynomial nonlinearity, to those of the new boundary solitons. The latter are found to possess a remarkable stability characteristic, exhibiting robustness against perturbations that would otherwise lead to the destabilizing of their bright-soliton counterparts

  15. Brightness waves of electroluminescence in ZnO:La electroluminor

    International Nuclear Information System (INIS)

    Bhushan, S.; Pandey, A.N.; Kaza, Balakrishna Rao

    1979-01-01

    A cryostat for the measurement of different luminescent characteristics from liquid N 2 temperature to above has been fabricated. Using this cryostat brightness waves due to sinusoidal excitations for ZnO:La electroluminor (EL) has been studied at different temperatures from -168deg C. Brightness waves for this system consist of two primary peaks during each cycle of excitation. Each primary peak is associated with a secondary peak. This secondary peak at -168deg C exists at the left arm of the primary peak. As the temperature is increased to 18deg C it moves towards the right arm of the primary peak. At an intermediate temperature the secondary peaks are most pronounced. Possible mechanism for these phenomena have been discussed. Temperature dependence of time averaged EL brightness for this system has also been studied and three peaks have been found. The results of brightness waves have also been discussed in the light of temperature dependence of time averaged EL brightness. (auth.)

  16. Intrinsic brightness temperatures of blazar jets at 15 GHz

    Directory of Open Access Journals (Sweden)

    Hovatta Talvikki

    2013-12-01

    Full Text Available We have developed a new Bayesian Markov Chain Monte Carlo method to deconvolve light curves of blazars into individual flares, including proper estimation of the fit errors. We use the method to fit 15GHzlight curves obtained within the OVRO 40-m blazar monitoring program where a large number of AGN have been monitored since 2008 in support of the Fermi Gamma-Ray Space Telescope mission. The time scales obtained from the fitted models are used to calculate the variability brightness temperature of the sources. Additionally, we have calculated brightness temperatures of a sample of these objects using Very Long Baseline Array data from the MOJAVE survey. Combining these two data sets enables us to study the intrinsic brightness temperature distribution in these blazars at 15 GHz. Our preliminary results indicate that the mean intrinsic brightness temperature in a sample of 14 sources is near the equipartition brightness temperature of ~ 1011K.

  17. Crystal structure of full-length Zika virus NS5 protein reveals a conformation similar to Japanese encephalitis virus NS5

    Energy Technology Data Exchange (ETDEWEB)

    Upadhyay, Anup K.; Cyr, Matthew; Longenecker, Kenton; Tripathi, Rakesh; Sun, Chaohong; Kempf, Dale J. (AbbVie)

    2017-02-21

    The rapid spread of the recentZika 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 ofZika 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 groupP21212 and containing two protein molecules in the asymmetric unit. The structure is similar to that reported for the NS5 protein fromJapanese encephalitis virusand suggests opportunities for structure-based drug design targeting either its MTase or RdRp domain.

  18. High-brightness injector modeling

    International Nuclear Information System (INIS)

    Lewellen, J.W.

    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.

  19. Selective susceptibility to nanosecond pulsed electric field (nsPEF) across different human cell types.

    Science.gov (United States)

    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 LD 50 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.

  20. Characterization of purified Sindbis virus nsP4 RNA-dependent RNA polymerase activity in vitro

    International Nuclear Information System (INIS)

    Rubach, Jon K.; Wasik, Brian R.; Rupp, Jonathan C.; Kuhn, Richard J.; Hardy, Richard W.; Smith, Janet L.

    2009-01-01

    The Sindbis virus RNA-dependent RNA polymerase (nsP4) is responsible for the replication of the viral RNA genome. In infected cells, nsP4 is localized in a replication complex along with the other viral non-structural proteins. nsP4 has been difficult to homogenously purify from infected cells due to its interactions with the other replication proteins and the fact that its N-terminal residue, a tyrosine, causes the protein to be rapidly turned over in cells. We report the successful expression and purification of Sindbis nsP4 in a bacterial system, in which nsP4 is expressed as an N-terminal SUMO fusion protein. After purification the SUMO tag is removed, resulting in the isolation of full-length nsP4 possessing the authentic N-terminal tyrosine. This purified enzyme is able to produce minus-strand RNA de novo from plus-strand templates, as well as terminally add adenosine residues to the 3' end of an RNA substrate. In the presence of the partially processed viral replicase polyprotein, P123, purified nsP4 is able to synthesize discrete template length minus-strand RNA products. Mutations in the 3' CSE or poly(A) tail of viral template RNA prevent RNA synthesis by the replicase complex containing purified nsP4, consistent with previously reported template requirements for minus-strand RNA synthesis. Optimal reaction conditions were determined by investigating the effects of time, pH, and the concentrations of nsP4, P123 and magnesium on the synthesis of RNA

  1. A novel cell-based assay to measure activity of Venezuelan equine encephalitis virus nsP2 protease

    International Nuclear Information System (INIS)

    Campos-Gomez, Javier; Ahmad, Fahim; Rodriguez, Efrain; Saeed, Mohammad F.

    2016-01-01

    The encephalitic alphaviruses encode nsP2 protease (nsP2pro), which because of its vital role in virus replication, represents an attractive target for therapeutic intervention. To facilitate the discovery of nsP2 inhibitors we have developed a novel assay for quantitative measurement of nsP2pro activity in a cell-based format. The assay is based on a substrate fusion protein consisting of eGFP and Gaussia luciferase (Gluc) linked together by a small peptide containing a VEEV nsp2pro cleavage sequence. The expression of the substrate protein in cells along with recombinant nsP2pro results in cleavage of the substrate protein resulting in extracellular release of free Gluc. The Gluc activity in supernatants corresponds to intracellular nsP2pro-mediated substrate cleavage; thus, providing a simple and convenient way to quantify nsP2pro activity. Here, we demonstrate potential utility of the assay in identification of nsP2pro inhibitors, as well as in investigations related to molecular characterization of nsP2pro. - Highlights: • A novel cell-based assay to measure VEEV nsP2 protease activity was developed. • Assay utility was demonstrated for antiviral screening. • .The assay also proved to be useful in basic mechanistic studies of nsP2 protease.

  2. A novel cell-based assay to measure activity of Venezuelan equine encephalitis virus nsP2 protease

    Energy Technology Data Exchange (ETDEWEB)

    Campos-Gomez, Javier; Ahmad, Fahim; Rodriguez, Efrain; Saeed, Mohammad F., E-mail: saeed@southernresearch.org

    2016-09-15

    The encephalitic alphaviruses encode nsP2 protease (nsP2pro), which because of its vital role in virus replication, represents an attractive target for therapeutic intervention. To facilitate the discovery of nsP2 inhibitors we have developed a novel assay for quantitative measurement of nsP2pro activity in a cell-based format. The assay is based on a substrate fusion protein consisting of eGFP and Gaussia luciferase (Gluc) linked together by a small peptide containing a VEEV nsp2pro cleavage sequence. The expression of the substrate protein in cells along with recombinant nsP2pro results in cleavage of the substrate protein resulting in extracellular release of free Gluc. The Gluc activity in supernatants corresponds to intracellular nsP2pro-mediated substrate cleavage; thus, providing a simple and convenient way to quantify nsP2pro activity. Here, we demonstrate potential utility of the assay in identification of nsP2pro inhibitors, as well as in investigations related to molecular characterization of nsP2pro. - Highlights: • A novel cell-based assay to measure VEEV nsP2 protease activity was developed. • Assay utility was demonstrated for antiviral screening. • .The assay also proved to be useful in basic mechanistic studies of nsP2 protease.

  3. Analysis of the PDZ binding specificities of Influenza A Virus NS1 proteins

    Directory of Open Access Journals (Sweden)

    Nagasaka Kazunori

    2011-01-01

    Full Text Available Abstract The Influenza A virus non-structural protein 1 (NS1 is a multifunctional virulence factor with several protein-protein interaction domains, involved in preventing apoptosis of the infected cell and in evading the interferon response. In addition, the majority of influenza A virus NS1 proteins have a class I PDZ-binding motif at the C-terminus, and this itself has been shown to be a virulence determinant. In the majority of human influenza NS1 proteins the consensus motif is RSxV: in avian NS1 it is ESxV. Of the few human strains that have the avian motif, all were from very high mortality outbreaks of the disease. Previous work has shown that minor differences in PDZ-binding motifs can have major effects on the spectrum of cellular proteins targeted. In this study we analyse the effect of these differences upon the binding of Influenza A virus NS1 protein to a range of cellular proteins involved in polarity and signal transduction.

  4. A new approach to dengue fatal cases diagnosis: NS1 antigen capture in tissues.

    Directory of Open Access Journals (Sweden)

    Monique da Rocha Queiroz Lima

    Full Text Available UNLABELLED: / BACKGROUND: Dengue is the most important arthropod borne viral disease worldwide in terms of morbidity and mortality and is caused by any of the four serotypes of dengue virus (DENV-1 to 4. Brazil is responsible for approximately 80% of dengue cases in the Americas, and since the introduction of dengue in 1986, a total of 5,944,270 cases have been reported including 21,596 dengue hemorrhagic fever and 874 fatal cases. DENV can infect many cell types and cause diverse clinical and pathological effects. The goal of the study was to investigate the usefulness of NS1 capture tests as an alternative tool to detect DENV in tissue specimens from previously confirmed dengue fatal cases (n = 23 that occurred in 2002 in Brazil. METHODOLOGY/PRINCIPAL FINDINGS: A total of 74 tissue specimens were available: liver (n = 23, lung (n = 14, kidney (n = 04, brain (n = 10, heart (n = 02, skin (n = 01, spleen (n = 15, thymus (n = 03 and lymph nodes (n = 02. We evaluated three tests for NS1 antigen capture: first generation Dengue Early ELISA (PanBio Diagnostics, Platelia NS1 (BioRad Laboratories and the rapid test NS1 Ag Strip (BioRad Laboratories. The overall dengue fatal case diagnosis based on the tissues analyzed by Dengue Early ELISA, Platelia NS1 and the NS1 Ag Strip was 34.7% (08/23, 60.8% (14/23 and 91.3% (21/23, respectively. The Dengue Early ELISA detected NS1 in 22.9% (17/74 of the specimens analyzed and the Platelia NS1 in 45.9% (34/74. The highest sensitivity (78.3%; 58/74 was achieved by the NS1 Ag Strip, and the differences in the sensitivities were statistically significant (p<0.05. The NS1 Ag Strip was the most sensitive in liver (91.3%; 21/23, lung (71.4%; 10/14, kidney (100%; 4/4, brain (80%; 8/10, spleen (66.6%, 10/15 and thymus (100%, 3/3 when compared to the other two ELISA assays. CONCLUSIONS/SIGNIFICANCE: This study shows the DENV NS1 capture assay as a rapid and valuable approach to postmortem dengue confirmation. With an

  5. Stunningly bright optical emission

    Science.gov (United States)

    Heinke, Craig O.

    2017-12-01

    The detection of bright, rapid optical pulsations from pulsar PSR J1023+0038 have provided a surprise for researchers working on neutron stars. This discovery poses more questions than it answers and will spur on future work and instrumentation.

  6. Broadband Fan Noise Prediction System for Turbofan Engines. Volume 2; BFaNS User's Manual and Developer's Guide

    Science.gov (United States)

    Morin, Bruce L.

    2010-01-01

    Pratt & Whitney has developed a Broadband Fan Noise Prediction System (BFaNS) for turbofan engines. This system computes the noise generated by turbulence impinging on the leading edges of the fan and fan exit guide vane, and noise generated by boundary-layer turbulence passing over the fan trailing edge. BFaNS has been validated on three fan rigs that were tested during the NASA Advanced Subsonic Technology Program (AST). The predicted noise spectra agreed well with measured data. The predicted effects of fan speed, vane count, and vane sweep also agreed well with measurements. The noise prediction system consists of two computer programs: Setup_BFaNS and BFaNS. Setup_BFaNS converts user-specified geometry and flow-field information into a BFaNS input file. From this input file, BFaNS computes the inlet and aft broadband sound power spectra generated by the fan and FEGV. The output file from BFaNS contains the inlet, aft and total sound power spectra from each noise source. This report is the second volume of a three-volume set documenting the Broadband Fan Noise Prediction System: Volume 1: Setup_BFaNS User s Manual and Developer s Guide; Volume 2: BFaNS User s Manual and Developer s Guide; and Volume 3: Validation and Test Cases. The present volume begins with an overview of the Broadband Fan Noise Prediction System, followed by step-by-step instructions for installing and running BFaNS. It concludes with technical documentation of the BFaNS computer program.

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

    International Nuclear Information System (INIS)

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

    2014-01-01

    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 ( f licker ) 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. Quantification of NS1 dengue biomarker in serum via optomagnetic nanocluster detection

    DEFF Research Database (Denmark)

    Antunes, Paula Soares Martins; Watterson, Daniel; Parmvi, Mattias

    2015-01-01

    Dengue is a tropical vector-borne disease without cure or vaccine that progressively spreads into regions with temperate climates. Diagnostic tools amenable to resource-limited settings would be highly valuable for epidemiologic control and containment during outbreaks. Here, we present a novel low......-cost automated biosensing platform for detection of dengue fever biomarker NS1 and demonstrate it on NS1 spiked in human serum. Magnetic nanoparticles (MNPs) are coated with high-affinity monoclonal antibodies against NS1 via bio-orthogonal Cu-free 'click' chemistry on an anti-fouling surface molecular...... method. The resulting automated dengue fever assay takes just 8 minutes, requires 6 μL of serum sample and shows a limit of detection of 25 ng/mL with an upper detection range of 20000 ng/mL. The technology holds a great potential to be applied to NS1 detection in patient samples. As the assay...

  9. Beam brightness calculation for analytical and empirical distribution functions

    International Nuclear Information System (INIS)

    Myers, T.J.; Boulais, K.A.; O, Y.S.; Rhee, M.J.

    1992-01-01

    The beam brightness, a figure of merit for a beam quality useful for high-current low-emittance beams, was introduced by van Steenbergen as B = I/V 4 , where I is the beam current and V 4 is the hypervolume in the four-dimensional trace space occupied by the beam particles. Customarily, the brightness is expressed in terms of the product of emittances ε x ε y as B = ηI/(π 2 ε x ε y ), where η is a form factor of order unity which depends on the precise definition of emittance and hypervolume. Recently, a refined definition of the beam brightness based on the arithmetic mean value defined in statistics is proposed. The beam brightness is defined as B triple-bond 4 > = I -1 ∫ ρ 4 2 dxdydx'dy', where I is the beam current given by I ∫ ρ 4 dxdydx'dy'. Note that in this definition, neither the hypervolume V 4 nor the emittance, are explicitly used; the brightness is determined solely by the distribution function. Brightnesses are unambiguously calculated and expressed analytically in terms of the respective beam current and effective emittance for a few commonly used distribution functions, including Maxwellian and water-bag distributions. Other distributions of arbitrary shape frequently encountered in actual experiments are treated numerically. The resulting brightnesses are expressed in the form B = ηI/(π 2 ε x ε y ), and η is found to be weakly dependent on the form of velocity distribution as well as spatial distribution

  10. Color and emotion: effects of hue, saturation, and brightness.

    Science.gov (United States)

    Wilms, Lisa; Oberfeld, Daniel

    2017-06-13

    Previous studies on emotional effects of color often failed to control all the three perceptual dimensions of color: hue, saturation, and brightness. Here, we presented a three-dimensional space of chromatic colors by independently varying hue (blue, green, red), saturation (low, medium, high), and brightness (dark, medium, bright) in a factorial design. The 27 chromatic colors, plus 3 brightness-matched achromatic colors, were presented via an LED display. Participants (N = 62) viewed each color for 30 s and then rated their current emotional state (valence and arousal). Skin conductance and heart rate were measured continuously. The emotion ratings showed that saturated and bright colors were associated with higher arousal. The hue also had a significant effect on arousal, which increased from blue and green to red. The ratings of valence were the highest for saturated and bright colors, and also depended on the hue. Several interaction effects of the three color dimensions were observed for both arousal and valence. For instance, the valence ratings were higher for blue than for the remaining hues, but only for highly saturated colors. Saturated and bright colors caused significantly stronger skin conductance responses. Achromatic colors resulted in a short-term deceleration in the heart rate, while chromatic colors caused an acceleration. The results confirm that color stimuli have effects on the emotional state of the observer. These effects are not only determined by the hue of a color, as is often assumed, but by all the three color dimensions as well as their interactions.

  11. Quantitative Brightness Analysis of Fluorescence Intensity Fluctuations in E. Coli.

    Directory of Open Access Journals (Sweden)

    Kwang-Ho Hur

    Full Text Available The brightness measured by fluorescence fluctuation spectroscopy specifies the average stoichiometry of a labeled protein in a sample. Here we extended brightness analysis, which has been mainly applied in eukaryotic cells, to prokaryotic cells with E. coli serving as a model system. The small size of the E. coli cell introduces unique challenges for applying brightness analysis that are addressed in this work. Photobleaching leads to a depletion of fluorophores and a reduction of the brightness of protein complexes. In addition, the E. coli cell and the point spread function of the instrument only partially overlap, which influences intensity fluctuations. To address these challenges we developed MSQ analysis, which is based on the mean Q-value of segmented photon count data, and combined it with the analysis of axial scans through the E. coli cell. The MSQ method recovers brightness, concentration, and diffusion time of soluble proteins in E. coli. We applied MSQ to measure the brightness of EGFP in E. coli and compared it to solution measurements. We further used MSQ analysis to determine the oligomeric state of nuclear transport factor 2 labeled with EGFP expressed in E. coli cells. The results obtained demonstrate the feasibility of quantifying the stoichiometry of proteins by brightness analysis in a prokaryotic cell.

  12. The CENNS-10 liquid argon detector to measure CEvNS at the Spallation Neutron Source

    Science.gov (United States)

    Tayloe, R.

    2018-04-01

    The COHERENT collaboration is deploying a suite of low-energy detectors in a low-background corridor of the ORNL Spallation Neutron Source (SNS) to measure coherent elastic neutrino-nucleus scattering (CEvNS) on an array of nuclear targets employing different detector technologies. A measurement of CEvNS on different nuclei will test the N2-dependence of the CEvNS cross section and further the physics reach of the COHERENT effort. The first step of this program has been realized recently with the observation of CEvNS in a 14.6 kg CsI detector. Operation and deployment of Ge and NaI detectors are also underway. A 22 kg, single-phase, liquid argon detector (CENNS-10) started data-taking in Dec. 2016 and will provide results on CEvNS from a lighter nucleus. Initial results indicate that light output, pulse-shape discrimination, and background suppression are sufficient for a measurement of CEvNS on argon.

  13. Nucleolar localization of influenza A NS1: striking differences between mammalian and avian cells

    Directory of Open Access Journals (Sweden)

    Mazel-Sanchez Beryl

    2010-03-01

    Full Text Available Abstract In mammalian cells, nucleolar localization of influenza A NS1 requires the presence of a C-terminal nucleolar localization signal. This nucleolar localization signal is present only in certain strains of influenza A viruses. Therefore, only certain NS1 accumulate in the nucleolus of mammalian cells. In contrast, we show that all NS1 tested in this study accumulated in the nucleolus of avian cells even in the absence of the above described C-terminal nucleolar localization signal. Thus, nucleolar localization of NS1 in avian cells appears to rely on a different nucleolar localization signal that is more conserved among influenza virus strains.

  14. Lamp spectrum and spatial brightness at photopic levels

    DEFF Research Database (Denmark)

    Fotios, Steve; Atli, Deniz; Cheal, Chris

    2015-01-01

    Light sources are available in a variety of spectral power distributions (SPDs) and this affects spatial brightness in a manner not predicted by quantities such as illuminance. Tuning light source SPD to better match the sensitivity of visual perception may allow the same spatial brightness but a...

  15. Pomegranate ( Punica granatum L.) expresses several nsLTP isoforms characterized by different immunoglobulin E-binding properties.

    Science.gov (United States)

    Bolla, Michela; Zenoni, Sara; Scheurer, Stephan; Vieths, Stefan; San Miguel Moncin, Maria Del Mar; Olivieri, Mario; Antico, Andrea; Ferrer, Marta; Berroa, Felicia; Enrique, Ernesto; Avesani, Linda; Marsano, Francesco; Zoccatelli, Gianni

    2014-01-01

    Pomegranate allergy is associated with sensitization to non-specific lipid transfer proteins (nsLTPs). Our aim was to identify and characterize the non-specific nsLTPs expressed in pomegranate at the molecular level and to study their allergenic properties in terms of immunoglobulin E (IgE)-binding and cross-reactivity with peach nsLTP (Pru p 3). A non-equilibrium two-dimensional (2-D) electrophoretic approach based on acid-urea PAGE and sodium dodecyl sulfate PAGE was set up to separate pomegranate nsLTPs. Their immunoreactivity was tested by immunoblotting carried out with anti-Pru p 3 polyclonal antibodies and sera from pomegranate-allergic patients. For final identification, pomegranate nsLTPs were purified by chromatography and subjected to trypsin digestion and mass spectrometry (MS) analysis. For this purpose, the sequences obtained by cDNA cloning of three pomegranate nsLTPs were integrated in the database that was subsequently searched for MS data interpretation. Four nsLTPs were identified by 2-D immunoblotting. The detected proteins showed different IgE-binding capacity and partial cross-reactivity with Pru p 3. cDNA cloning and MS analyses led to the identification of three nsLTP isoforms with 66-68% amino acid sequence identity named Pun g 1.0101, Pun g 1.0201 and Pun g 1.0301. By 2-D electrophoresis, we could separate different nsLTP isoforms possessing different IgE-binding properties, which might reflect peculiar allergenic potencies. The contribution of Pru p 3 to prime sensitization is not central as in other plant nsLTPs. © 2014 S. Karger AG, Basel.

  16. Visible Color and Photometry of Bright Materials on Vesta

    Science.gov (United States)

    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].

  17. Helmholtz bright and boundary solitons

    Energy Technology Data Exchange (ETDEWEB)

    Christian, J M [Joule Physics Laboratory, School of Computing, Science and Engineering, Institute for Materials Research, University of Salford, Salford M5 4WT (United Kingdom); McDonald, G S [Joule Physics Laboratory, School of Computing, Science and Engineering, Institute for Materials Research, University of Salford, Salford M5 4WT (United Kingdom); Chamorro-Posada, P [Departmento de TeorIa de la Senal y Comunicaciones e IngenierIa Telematica, Universidad de Valladolid, ETSI Telecomunicacion, Campus Miguel Delibes s/n, 47011 Valladolid (Spain)

    2007-02-16

    We report, for the first time, exact analytical boundary solitons of a generalized cubic-quintic nonlinear Helmholtz (NLH) equation. These solutions have a linked-plateau topology that is distinct from conventional dark soliton solutions; their amplitude and intensity distributions are spatially delocalized and connect regions of finite and zero wave-field disturbances (suggesting also the classification as 'edge solitons'). Extensive numerical simulations compare the stability properties of recently derived Helmholtz bright solitons, for this type of polynomial nonlinearity, to those of the new boundary solitons. The latter are found to possess a remarkable stability characteristic, exhibiting robustness against perturbations that would otherwise lead to the destabilizing of their bright-soliton counterparts.

  18. Detergent-resistant membrane association of NS2 and E2 during hepatitis C virus replication.

    Science.gov (United States)

    Shanmugam, Saravanabalaji; Saravanabalaji, Dhanaranjani; Yi, MinKyung

    2015-04-01

    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. 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 targeted to these

  19. On the meaning of NS comparisons in Israel-critical discourse

    Directory of Open Access Journals (Sweden)

    Wilhelm Kempf

    2017-04-01

    Full Text Available Apart from Holocaust denial, probably nothing outrages Israelis and Jews around the world more than comparisons of Israeli Palestinian policy with National Socialist Jewish policy. Particularly, if Germans make such comparisons, the obvious suspicion is that they are an expression of secondary anti-Semitism. On the other hand, in Western democracies it is virtually part of political culture to fall back on NS comparisons whenever one wants to dramatize precarious human rights situations and justify the need for action to change them. Based on new analyses of survey data published in Kempf (2015a,b, this study shows that NS comparisons can constitute not only anti-Semitic demonization of Jews but also anti-Zionist dramatization of the Palestinian human rights situation. People who work consequently and without reservation for human rights, however, indeed see a strong need for action to change Israeli policy, but strictly refuse to equate it with NS policy.

  20. Human CD56bright NK Cells

    DEFF Research Database (Denmark)

    Michel, Tatiana; Poli, Aurélie; Cuapio, Angelica

    2016-01-01

    Human NK cells can be subdivided into various subsets based on the relative expression of CD16 and CD56. In particular, CD56(bright)CD16(-/dim) NK cells are the focus of interest. They are considered efficient cytokine producers endowed with immunoregulatory properties, but they can also become c...... NK cell subsets is not fully defined, nor is their precise hematopoietic origin. In this article, we summarize recent studies about CD56(bright) NK cells in health and disease and briefly discuss the current controversies surrounding them....

  1. Time-resolved energy spectrum of a pseudospark-produced high-brightness electron beam

    International Nuclear Information System (INIS)

    Myers, T.J.; Ding, B.N.; Rhee, M.J.

    1992-01-01

    The pseudospark, a fast low-pressure gas discharge between a hollow cathode and a planar anode, is found to be an interesting high-brightness electron beam source. Typically, all electron beam produced in the pseudospark has the peak current of ∼1 kA, pulse duration of ∼50 ns, and effective emittance of ∼100 mm-mrad. The energy information of this electron beam, however, is least understood due to the difficulty of measuring a high-current-density beam that is partially space-charge neutralized by the background ions produced in the gas. In this paper, an experimental study of the time-resolved energy spectrum is presented. The pseudospark produced electron beam is injected into a vacuum through a small pinhole so that the electrons without background ions follow single particle motion; the beam is sent through a negative biased electrode and the only portion of beam whose energy is greater than the bias voltage can pass through the electrode and the current is measured by a Faraday cup. The Faraday cup signals with various bias voltage are recorded in a digital oscilloscope. The recorded waveforms are then numerically analyzed to construct a time-resolved energy spectrum. Preliminary results are presented

  2. Music for a Brighter World: Brightness Judgment Bias by Musical Emotion.

    Science.gov (United States)

    Bhattacharya, Joydeep; Lindsen, Job P

    2016-01-01

    A prevalent conceptual metaphor is the association of the concepts of good and evil with brightness and darkness, respectively. Music cognition, like metaphor, is possibly embodied, yet no study has addressed the question whether musical emotion can modulate brightness judgment in a metaphor consistent fashion. In three separate experiments, participants judged the brightness of a grey square that was presented after a short excerpt of emotional music. The results of Experiment 1 showed that short musical excerpts are effective emotional primes that cross-modally influence brightness judgment of visual stimuli. Grey squares were consistently judged as brighter after listening to music with a positive valence, as compared to music with a negative valence. The results of Experiment 2 revealed that the bias in brightness judgment does not require an active evaluation of the emotional content of the music. By applying a different experimental procedure in Experiment 3, we showed that this brightness judgment bias is indeed a robust effect. Altogether, our findings demonstrate a powerful role of musical emotion in biasing brightness judgment and that this bias is aligned with the metaphor viewpoint.

  3. Evolution of Bacterial Global Modulators: Role of a Novel H-NS Paralogue in the Enteroaggregative Escherichia coli Strain 042.

    Science.gov (United States)

    Prieto, A; Bernabeu, M; Aznar, S; Ruiz-Cruz, S; Bravo, A; Queiroz, M H; Juárez, A

    2018-01-01

    Bacterial genomes sometimes contain genes that code for homologues of global regulators, the function of which is unclear. In members of the family Enterobacteriaceae , cells express the global regulator H-NS and its paralogue StpA. In Escherichia coli , out of providing a molecular backup for H-NS, the role of StpA is poorly characterized. The enteroaggregative E. coli strain 042 carries, in addition to the hns and stpA genes, a third gene encoding an hns paralogue ( hns2 ). We present in this paper information about its biological function. Transcriptomic analysis has shown that the H-NS2 protein targets a subset of the genes targeted by H-NS. Genes targeted by H-NS2 correspond mainly with horizontally transferred (HGT) genes and are also targeted by the Hha protein, a fine-tuner of H-NS activity. Compared with H-NS, H-NS2 expression levels are lower. In addition, H-NS2 expression exhibits specific features: it is sensitive to the growth temperature and to the nature of the culture medium. This novel H-NS paralogue is widespread within the Enterobacteriaceae . IMPORTANCE Global regulators such as H-NS play key relevant roles enabling bacterial cells to adapt to a changing environment. H-NS modulates both core and horizontally transferred (HGT) genes, but the mechanism by which H-NS can differentially regulate these genes remains to be elucidated. There are several instances of bacterial cells carrying genes that encode homologues of the global regulators. The question is what the roles of these proteins are. We noticed that the enteroaggregative E. coli strain 042 carries a new hitherto uncharacterized copy of the hns gene. We decided to investigate why this pathogenic E. coli strain requires an extra H-NS paralogue, termed H-NS2. In our work, we show that H-NS2 displays specific expression and regulatory properties. H-NS2 targets a subset of H-NS-specific genes and may help to differentially modulate core and HGT genes by the H-NS cellular pool.

  4. Suppression of Rac1 Signaling by Influenza A Virus NS1 Facilitates Viral Replication

    Science.gov (United States)

    Jiang, Wei; Sheng, Chunjie; Gu, Xiuling; Liu, Dong; Yao, Chen; Gao, Shijuan; Chen, Shuai; Huang, Yinghui; Huang, Wenlin; Fang, Min

    2016-01-01

    Influenza A virus (IAV) is a major human pathogen with the potential to become pandemic. IAV contains only eight RNA segments; thus, the virus must fully exploit the host cellular machinery to facilitate its own replication. In an effort to comprehensively characterize the host machinery taken over by IAV in mammalian cells, we generated stable A549 cell lines with over-expression of the viral non-structural protein (NS1) to investigate the potential host factors that might be modulated by the NS1 protein. We found that the viral NS1 protein directly interacted with cellular Rac1 and facilitated viral replication. Further research revealed that NS1 down-regulated Rac1 activity via post-translational modifications. Therefore, our results demonstrated that IAV blocked Rac1-mediated host cell signal transduction through the NS1 protein to facilitate its own replication. Our findings provide a novel insight into the mechanism of IAV replication and indicate new avenues for the development of potential therapeutic targets. PMID:27869202

  5. NS maize hybrids in production regions of Serbia

    Directory of Open Access Journals (Sweden)

    Stojaković Milisav

    2010-01-01

    Full Text Available Fifteen NS maize hybrids of FAO 300-700 maturity groups were evaluated in strip trials (plot size 1,120 m2 at 30 locations in Serbia. In all locations including all production regions, the most yielding hybrid was NS 6030 with average yield of 10.9 t ha-1. The additive Main Effects and Multiplicative Interaction (AMMI and the sites regression (SREG models were used to study basic structure of G x E interactions and the possible existence of different mega-environments in Serbian maize growing regions in 2009. The results of the 15 hybrids x 10 locations for grain yield in maize showed by biplot technique indicate several specific location-hybrid deviations (the AMMI biplot, and possible existence of at least one mega-environment (the GGE biplot. .

  6. Simultaneous brightness contrast of foraging Papilio butterflies

    Science.gov (United States)

    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

  7. Low surface brightness galaxies in the Fornax Cluster: automated galaxy surface photometry

    International Nuclear Information System (INIS)

    Davies, J.I.; Phillipps, S.; Disney, M.J.

    1988-01-01

    A sample is presented of low surface brightness galaxies (with extrapolated central surface brightness fainter than 22.0 Bμ) in the Fornax Cluster region which has been measured by the APM machine. Photometric parameters, namely profile shape, scale length, central brightness and total magnitude, are derived for the sample galaxies and correlations between the parameters of low surface brightness dwarf galaxies are discussed, with particular reference to the selection limits. Contrary to previous authors we find no evidence for a luminosity-surface brightness correlation in the sense of lower surface brightness galaxies having lower luminosities and scale sizes. In fact, the present data suggest that it is the galaxies with the largest scale lengths which are more likely to be of very low surface brightness. In addition, the larger scale length galaxies occur preferentially towards the centre of the Cluster. (author)

  8. StpA and Hha stimulate pausing by RNA polymerase by promoting DNA-DNA bridging of H-NS filaments.

    Science.gov (United States)

    Boudreau, Beth A; Hron, Daniel R; Qin, Liang; van der Valk, Ramon A; Kotlajich, Matthew V; Dame, Remus T; Landick, Robert

    2018-06-20

    In enterobacteria, AT-rich horizontally acquired genes, including virulence genes, are silenced through the actions of at least three nucleoid-associated proteins (NAPs): H-NS, StpA and Hha. These proteins form gene-silencing nucleoprotein filaments through direct DNA binding by H-NS and StpA homodimers or heterodimers. Both linear and bridged filaments, in which NAPs bind one or two DNA segments, respectively, have been observed. Hha can interact with H-NS or StpA filaments, but itself lacks a DNA-binding domain. Filaments composed of H-NS alone can inhibit transcription initiation and, in the bridged conformation, slow elongating RNA polymerase (RNAP) by promoting backtracking at pause sites. How the other NAPs modulate these effects of H-NS is unknown, despite evidence that they help regulate subsets of silenced genes in vivo (e.g. in pathogenicity islands). Here we report that Hha and StpA greatly enhance H-NS-stimulated pausing by RNAP at 20°C. StpA:H-NS or StpA-only filaments also stimulate pausing at 37°C, a temperature at which Hha:H-NS or H-NS-only filaments have much less effect. In addition, we report that both Hha and StpA greatly stimulate DNA-DNA bridging by H-NS filaments. Together, these observations indicate that Hha and StpA can affect H-NS-mediated gene regulation by stimulating bridging of H-NS/DNA filaments.

  9. Potential of plant alkaloids as dengue ns3 protease inhibitors: Molecular docking and simulation approach

    Directory of Open Access Journals (Sweden)

    Muhammad Tahir ul Qamar

    2014-08-01

    Full Text Available Dengue infection has become a worldwide health problem and infection rate is increasing each year. Alkaloids are important phytochemicals of medicinal plant and can be used as vaccine candidates for viruses. Therefore, present study was designed to find potential alkaloids inhibitors against the Dengue virus NS2B/NS3 protease which can inhibit the viral replication inside the host cell. Through molecular docking it was investigated that most of the alkaloids bound deeply in the binding pocket of Dengue virus NS2B/NS3 protease and had potential interactions with catalytic triad. Five alkaloids (6’-desmethylthalifaboramin; 3,5-dihydroxythalifaboramine; Betanin; Reserpic acid and Tubulosine successfully blocked the catalytic triad of NS2B/NS3 protease and these alkaloids can serve as a potential drug candidate to stop viral replication. It can be concluded from this study that these alkaloids could serve as important inhibitors to inhibit the replication of DENV and need further in-vitro investigations to confirm their efficacy and drug ability.

  10. The ASAS-SN bright supernova catalogue - III. 2016

    DEFF Research Database (Denmark)

    Holoien, T. W. -S.; Brown, J. S.; Stanek, K. Z.

    2017-01-01

    This catalogue summarizes information for all supernovae discovered by the All-Sky Automated Survey for SuperNovae (ASAS-SN) and all other bright (m(peak)d......This catalogue summarizes information for all supernovae discovered by the All-Sky Automated Survey for SuperNovae (ASAS-SN) and all other bright (m(peak)d...

  11. Comparative Analysis of Disruption Tolerant Network Routing Simulations in the One and NS-3

    Science.gov (United States)

    2017-12-01

    The added levels of simulation increase the processing required by a simulation . ns-3’s simulation of other layers of the network stack permits...NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS COMPARATIVE ANALYSIS OF DISRUPTION TOLERANT NETWORK ROUTING SIMULATIONS IN THE ONE AND NS-3...Thesis 03-23-2016 to 12-15-2017 4. TITLE AND SUBTITLE COMPARATIVE ANALYSIS OF DISRUPTION TOLERANT NETWORK ROUTING SIMULATIONS IN THE ONE AND NS-3 5

  12. Bright THz Instrument and Nonlinear THz Science

    Science.gov (United States)

    2017-10-30

    Report: Bright THz Instrument and Nonlinear THz Science The views, opinions and/or findings contained in this report are those of the author(s) and...Number: W911NF-16-1-0436 Organization: University of Rochester Title: Bright THz Instrument and Nonlinear THz Science Report Term: 0-Other Email: xi...exploring new cutting-edge research and broader applications, following the significant development of THz science and technology in the late 80’s, is the

  13. [Advances in Parvovirus Non-structural Protein NS1 Induced Apoptosis].

    Science.gov (United States)

    Tu, Mengyu; Liu, Fei; Chen, Shun; Wang, Mingshu; Cheng, Anchun

    2015-11-01

    Until now, more than seventeen parvovirus have been reported which can infect mammals and poultries. The infected cells appeared different properties of apoptosis and death, present a typical cytopathic effect. NS1 is a major nonstructural protein of parvovirus, with a conservative structure and function, which plays an important role in the viral life cycle. In addition to the influence on viral replication, the NS1 also participates in apoptosis induced by viruses. Parvovirus induced apoptosis which is mainly mediated by mitochondrial pathway, this review summarized the latest research progresses of parvovirus induced apoptosis.

  14. Micro Coronal Bright Points Observed in the Quiet Magnetic Network by SOHO/EIT

    Science.gov (United States)

    Falconer, D. A.; Moore, R. L.; Porter, J. G.

    1997-01-01

    When one looks at SOHO/EIT Fe XII images of quiet regions, one can see the conventional coronal bright points (> 10 arcsec in diameter), but one will also notice many smaller faint enhancements in brightness (Figure 1). Do these micro coronal bright points belong to the same family as the conventional bright points? To investigate this question we compared SOHO/EIT Fe XII images with Kitt Peak magnetograms to determine whether the micro bright points are in the magnetic network and mark magnetic bipoles within the network. To identify the coronal bright points, we applied a picture frame filter to the Fe XII images; this brings out the Fe XII network and bright points (Figure 2) and allows us to study the bright points down to the resolution limit of the SOHO/EIT instrument. This picture frame filter is a square smoothing function (hlargelyalf a network cell wide) with a central square (quarter of a network cell wide) removed so that a bright point's intensity does not effect its own background. This smoothing function is applied to the full disk image. Then we divide the original image by the smoothed image to obtain our filtered image. A bright point is defined as any contiguous set of pixels (including diagonally) which have enhancements of 30% or more above the background; a micro bright point is any bright point 16 pixels or smaller in size. We then analyzed the bright points that were fully within quiet regions (0.6 x 0.6 solar radius) centered on disk center on six different days.

  15. Music for a Brighter World: Brightness Judgment Bias by Musical Emotion.

    Directory of Open Access Journals (Sweden)

    Joydeep Bhattacharya

    Full Text Available A prevalent conceptual metaphor is the association of the concepts of good and evil with brightness and darkness, respectively. Music cognition, like metaphor, is possibly embodied, yet no study has addressed the question whether musical emotion can modulate brightness judgment in a metaphor consistent fashion. In three separate experiments, participants judged the brightness of a grey square that was presented after a short excerpt of emotional music. The results of Experiment 1 showed that short musical excerpts are effective emotional primes that cross-modally influence brightness judgment of visual stimuli. Grey squares were consistently judged as brighter after listening to music with a positive valence, as compared to music with a negative valence. The results of Experiment 2 revealed that the bias in brightness judgment does not require an active evaluation of the emotional content of the music. By applying a different experimental procedure in Experiment 3, we showed that this brightness judgment bias is indeed a robust effect. Altogether, our findings demonstrate a powerful role of musical emotion in biasing brightness judgment and that this bias is aligned with the metaphor viewpoint.

  16. Molecular models of NS3 protease variants of the Hepatitis C virus

    Directory of Open Access Journals (Sweden)

    Mello Isabel MVGC

    2005-01-01

    Full Text Available Abstract Background Hepatitis C virus (HCV currently infects approximately three percent of the world population. In view of the lack of vaccines against HCV, there is an urgent need for an efficient treatment of the disease by an effective antiviral drug. Rational drug design has not been the primary way for discovering major therapeutics. Nevertheless, there are reports of success in the development of inhibitor using a structure-based approach. One of the possible targets for drug development against HCV is the NS3 protease variants. Based on the three-dimensional structure of these variants we expect to identify new NS3 protease inhibitors. In order to speed up the modeling process all NS3 protease variant models were generated in a Beowulf cluster. The potential of the structural bioinformatics for development of new antiviral drugs is discussed. Results The atomic coordinates of crystallographic structure 1CU1 and 1DY9 were used as starting model for modeling of the NS3 protease variant structures. The NS3 protease variant structures are composed of six subdomains, which occur in sequence along the polypeptide chain. The protease domain exhibits the dual beta-barrel fold that is common among members of the chymotrypsin serine protease family. The helicase domain contains two structurally related beta-alpha-beta subdomains and a third subdomain of seven helices and three short beta strands. The latter domain is usually referred to as the helicase alpha-helical subdomain. The rmsd value of bond lengths and bond angles, the average G-factor and Verify 3D values are presented for NS3 protease variant structures. Conclusions This project increases the certainty that homology modeling is an useful tool in structural biology and that it can be very valuable in annotating genome sequence information and contributing to structural and functional genomics from virus. The structural models will be used to guide future efforts in the structure

  17. Richard Bright and his neurological studies.

    Science.gov (United States)

    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. Copyright 2009 S. Karger AG, Basel.

  18. Sky brightness and twilight measurements at Jogyakarta city, Indonesia

    International Nuclear Information System (INIS)

    Herdiwijaya, Dhani

    2016-01-01

    The sky brightness measurements were performed using a portable photometer. A pocket-sized and low-cost photometer has 20 degree area measurement, and spectral ranges between 320-720 nm with output directly in magnitudes per arc second square (mass) unit. The sky brightness with 3 seconds temporal resolutions was recorded at Jogyakarta city (110° 25’ E; 70° 52’ S; elevation 100 m) within 136 days in years from 2014 to 2016. The darkest night could reach 22.61 mpass only in several seconds, with mean value 18.8±0.7 mpass and temperature variation 23.1±1.2 C. The difference of mean sky brightness between before and after midnight was about -0.76 mpass or 2.0 times brighter. Moreover, the sky brightness and temperature fluctuations were more stable in after midnight than in before midnight. It is suggested that city light pollution affects those variations, and subsequently duration of twilight. By comparing twilight brightness for several places, we also suggest a 17° solar dip or about 66 minutes before sunrise for new time of Fajr prayer. (paper)

  19. Low dimensional neutron moderators for enhanced source brightness

    DEFF Research Database (Denmark)

    Mezei, Ferenc; Zanini, Luca; Takibayev, Alan

    2014-01-01

    In a recent numerical optimization study we have found that liquid para-hydrogen coupled cold neutron moderators deliver 3–5 times higher cold neutron brightness at a spallation neutron source if they take the form of a flat, quasi 2-dimensional disc, in contrast to the conventional more voluminous...... for cold neutrons. This model leads to the conclusions that the optimal shape for high brightness para-hydrogen neutron moderators is the quasi 1-dimensional tube and these low dimensional moderators can also deliver much enhanced cold neutron brightness in fission reactor neutron sources, compared...... to the much more voluminous liquid D2 or H2 moderators currently used. Neutronic simulation calculations confirm both of these theoretical conclusions....

  20. Raising the avermectins production in Streptomyces avermitilis by utilizing nanosecond pulsed electric fields (nsPEFs)

    Science.gov (United States)

    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.

  1. Broadband Fan Noise Prediction System for Turbofan Engines. Volume 1; Setup_BFaNS User's Manual and Developer's Guide

    Science.gov (United States)

    Morin, Bruce L.

    2010-01-01

    Pratt & Whitney has developed a Broadband Fan Noise Prediction System (BFaNS) for turbofan engines. This system computes the noise generated by turbulence impinging on the leading edges of the fan and fan exit guide vane, and noise generated by boundary-layer turbulence passing over the fan trailing edge. BFaNS has been validated on three fan rigs that were tested during the NASA Advanced Subsonic Technology Program (AST). The predicted noise spectra agreed well with measured data. The predicted effects of fan speed, vane count, and vane sweep also agreed well with measurements. The noise prediction system consists of two computer programs: Setup_BFaNS and BFaNS. Setup_BFaNS converts user-specified geometry and flow-field information into a BFaNS input file. From this input file, BFaNS computes the inlet and aft broadband sound power spectra generated by the fan and FEGV. The output file from BFaNS contains the inlet, aft and total sound power spectra from each noise source. This report is the first volume of a three-volume set documenting the Broadband Fan Noise Prediction System: Volume 1: Setup_BFaNS User s Manual and Developer s Guide; Volume 2: BFaNS User's Manual and Developer s Guide; and Volume 3: Validation and Test Cases. The present volume begins with an overview of the Broadband Fan Noise Prediction System, followed by step-by-step instructions for installing and running Setup_BFaNS. It concludes with technical documentation of the Setup_BFaNS computer program.

  2. Spatially single-mode source of bright squeezed vacuum

    OpenAIRE

    Pérez, A. M.; Iskhakov, T. Sh.; Sharapova, P.; Lemieux, S.; Tikhonova, O. V.; Chekhova, M. V.; Leuchs, G.

    2014-01-01

    Bright squeezed vacuum, a macroscopic nonclassical state of light, can be obtained at the output of a strongly pumped non-seeded traveling-wave optical parametric amplifier (OPA). By constructing the OPA of two consecutive crystals separated by a large distance we make the squeezed vacuum spatially single-mode without a significant decrease in the brightness or squeezing.

  3. H-NS represses transcription of the flagellin gene lafA of lateral flagella in Vibrio parahaemolyticus.

    Science.gov (United States)

    Wang, Yan; Zhang, Yiquan; Yin, Zhe; Wang, Jie; Zhu, Yongzhe; Peng, Haoran; Zhou, Dongsheng; Qi, Zhongtian; Yang, Wenhui

    2018-01-01

    Swarming motility is ultimately mediated by the proton-powered lateral flagellar (laf) system in Vibrio parahaemolyticus. Expression of laf genes is tightly regulated by a number of environmental conditions and regulatory factors. The nucleoid-associated DNA-binding protein H-NS is a small and abundant protein that is widely distributed in bacteria, and H-NS-like protein-dependent expression of laf genes has been identified in Vibrio cholerae and V. parahaemolyticus. The data presented here show that H-NS acts as a repressor of the swarming motility in V. parahaemolyticus. A single σ 28 -dependent promoter was detected for lafA encoding the flagellin of the lateral flagella, and its activity was directly repressed by H-NS. Thus, H-NS represses swarming motility by directly acting on lafA. Briefly, this work revealed a novel function for H-NS as a repressor of the expression of lafA and swarming motility in V. parahaemolyticus.

  4. Mosquito Rasputin interacts with chikungunya virus nsP3 and determines the infection rate in Aedes albopictus.

    Science.gov (United States)

    Fros, Jelke J; Geertsema, Corinne; Zouache, Karima; Baggen, Jim; Domeradzka, Natalia; van Leeuwen, Daniël M; Flipse, Jacky; Vlak, Just M; Failloux, Anna-Bella; Pijlman, Gorben P

    2015-09-17

    Chikungunya virus (CHIKV) is an arthritogenic alphavirus (family Togaviridae), transmitted by Aedes species mosquitoes. CHIKV re-emerged in 2004 with multiple outbreaks worldwide and recently reached the Americas where it has infected over a million individuals in a rapidly expanding epidemic. While alphavirus replication is well understood in general, the specific function (s) of non-structural protein nsP3 remain elusive. CHIKV nsP3 modulates the mammalian stress response by preventing stress granule formation through sequestration of G3BP. In mosquitoes, nsP3 is a determinant of vector specificity, but its functional interaction with mosquito proteins is unclear. In this research we studied the domains required for localization of CHIKV nsP3 in insect cells and demonstrated its molecular interaction with Rasputin (Rin), the mosquito homologue of G3BP. The biological involvement of Rin in CHIKV infection was investigated in live Ae. albopictus mosquitoes. In insect cells, nsP3 localized as cytoplasmic granules, which was dependent on the central domain and the C-terminal variable region but independent of the N-terminal macrodomain. Ae. albopictus Rin displayed a diffuse, cytoplasmic localization, but was effectively sequestered into nsP3-granules upon nsP3 co-expression. Site-directed mutagenesis showed that the Rin-nsP3 interaction involved the NTF2-like domain of Rin and two conserved TFGD repeats in the C-terminal variable domain of nsP3. Although in vitro silencing of Rin did not impact nsP3 localization or CHIKV replication in cell culture, Rin depletion in vivo significantly decreased the CHIKV infection rate and transmissibility in Ae.albopictus. We identified the nsP3 hypervariable C-terminal domain as a critical factor for granular localization and sequestration of mosquito Rin. Our study offers novel insight into a conserved virus-mosquito interaction at the molecular level, and reveals a strong proviral role for G3BP homologue Rin in live mosquitoes

  5. In vivo effects of the IKr agonist NS3623 on cardiac electrophysiology of the guinea pig

    DEFF Research Database (Denmark)

    Hansen, Rie Schultz; Olesen, Søren-Peter; Rønn, Lars Christian B

    2008-01-01

    to examining the in vivo effects of NS3623. Injection of 30 mg/kg NS3623 shortened the corrected QT interval by 25 +/- 4% in anaesthetized guinea pigs. Accordingly, 50 mg/kg of NS3623 shortened the QT interval by 30 +/- 6% in conscious guinea pigs. Finally, pharmacologically induced QT prolongation by a h......ERG channel antagonist (0.15 mg/kg E-4031) could be reverted by injection of NS3623 (50 mg/kg) in conscious guinea pigs. In conclusion, the present in vivo study demonstrates that injection of the hERG channel agonist NS3623 results in shortening of the QTc interval as well as reversal of a pharmacologically...... induced QT prolongation in both anaesthetized and conscious guinea pigs....

  6. A New Sky Brightness Monitor

    Science.gov (United States)

    Crawford, David L.; McKenna, D.

    2006-12-01

    A good estimate of sky brightness and its variations throughout the night, the months, and even the years is an essential bit of knowledge both for good observing and especially as a tool in efforts to minimize sky brightness through local action. Hence a stable and accurate monitor can be a valuable and necessary tool. We have developed such a monitor, with the financial help of Vatican Observatory and Walker Management. The device is now undergoing its Beta test in preparation for production. It is simple, accurate, well calibrated, and automatic, sending its data directly to IDA over the internet via E-mail . Approximately 50 such monitors will be ready soon for deployment worldwide including most major observatories. Those interested in having one should enquire of IDA about details.

  7. Observation of near-infrared surface brightness of the large Magellanic cloud

    International Nuclear Information System (INIS)

    Hayakawa, Satio; Koizumi, Yutaka; Matsumoto, Toshio; Murakami, Hiroshi; Uyama, Kiichiro.

    1981-01-01

    The near-infrared surface brightness of the large Magellanic cloud was observed by an infrared telescope carried by a balloon. The balloon flight was made at Australian Balloon Launching Station. The brightness distribution of 2.4 Mu m radiation was obtained. A part of Bar was bright, and the expansion of the contour at the east end of Bar corresponded to the 30 Dor region. Many near-infrared sources distribute in this region. Discussions on the color and brightness of the center of Bar and the 30 Dor region are presented. (Kato, T.)

  8. Measuring brightness temperature distributions of plasma bunches

    International Nuclear Information System (INIS)

    Kirko, V.I.; Stadnichenko, I.A.

    1981-01-01

    The possibility of restoration of brightness temperature distribution along plasma jet on the base of a simple ultra high- speed photography and subsequent photometric treatment is shown. The developed technique has been applied for finding spectral radiation intensity and brightness temperature of plasma jets of a tubular gas-cumulative charge and explosive plasma compressor. The problem of shock wave front has been successfully solved and thus distribution of above parameters beginning from the region preceeding the shock wave has been obtained [ru

  9. Hepatitis C virus expressing reporter tagged NS5A protein

    DEFF Research Database (Denmark)

    2014-01-01

    Hepatitis C reporter viruses containing Core through NS2 of prototype isolates of all major HCV genotypes and the remaining genes of isolate JFH1, by insertion of reporter genes in domain III of HCV NS5A were developed. A deletion upstream of the inserted reporter gene sequence conferred favorable...... growth kinetics in Huh7.5 cells to these viruses. These reporter viruses can be used for high throughput analysis of drug and vaccine candidates as well as patient samples. JFH1-based intergenotypic recombinants with genotype specific homotypic 5'UTR, or heterotypic 5'UTR (either of genotype 1a (strain H...

  10. Edge integration and the perception of brightness and darkness

    NARCIS (Netherlands)

    Vladusich, T.; Lucassen, M.P.; Cornelissen, F.W.

    2006-01-01

    How do induced brightness and darkness signals from local and remote surfaces interact to determine the final achromatic color percept of a target surface? An emerging theory of achromatic color perception posits that brightness and darkness percepts are computed by weighting and summing the

  11. High Brightness OLED Lighting

    Energy Technology Data Exchange (ETDEWEB)

    Spindler, Jeffrey [OLEDWorks LLC; Kondakova, Marina [OLEDWorks LLC; Boroson, Michael [OLEDWorks LLC; Hamer, John [OLEDWorks LLC

    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.

  12. The μs and ns mode modulation system for grid controlled gun of the HESYRL linac

    International Nuclear Information System (INIS)

    Wang, Guicheng; Hong, Jun; Pei, Yuanji

    1988-01-01

    A μs and ns mode modulation system has been developed for the grid-controlled gun in the HESYRL. The gun drived by this system generated 1A and 500 MA pulse current for μs and ns mode respectively. In the ns mode modulation pulse formulation system, the sharper was built up using one transistor 3DA87D as avalanche switch and a shortcircuit coaxal cable as waveform sharp element. Outline of the μs mode system and details of the ns mode system are presented. (author)

  13. STARS4ALL Night Sky Brightness Photometer

    Directory of Open Access Journals (Sweden)

    Jaime Zamorano

    2017-06-01

    Full Text Available We present the main features of TESS-W, the first version of a series of inexpensive but reliable photometers that will be used to measure night sky brightness. The bandpass is extended to the red with respect of that of the Sky Quality Meter (SQM. TESS-W connects to a router via WIFI and it sends automatically the brightness values to a data repository using Internet of Things protocols. The device includes an infrared sensor to estimate the cloud coverage. It is designed for fixed stations to monitor the evolution of the sky brightness. The photometer could also be used in local mode connected to a computer or tablet to gather data from a moving vehicle. The photometer is being developed within STARS4ALL project, a collective awareness platform for promoting dark skies in Europe, funded by the EU. We intend to extend the existing professional networks to a citizen-based network of photometers. 

  14. 76 FR 59174 - Environmental Assessment and Finding of No Significant Impact for the N.S. Savannah; License NS-1...

    Science.gov (United States)

    2011-09-23

    ... of Federal Regulations (10 CFR) part 73 and 10 CFR 50.54(p) for the N.S. Savannah (NSS). This... security requirements from the 10 CFR Part 50 licensed site because the NSS spent fuel elements were... Carolina. There is no longer any special nuclear material (SNM) located within the NSS other than that...

  15. Bright environments vision of the Intelligent Lighting Institute (ILI)

    NARCIS (Netherlands)

    Özçelebi, T.

    2014-01-01

    The Bright Environments research program of the Eindhoven University of Technology Intelligent Lighting Institute aims to find new methods of intelligent lighting control and human interaction. We present a summary of the institute’s work on this research field and the research vision of the Bright

  16. Process Performances of 2 ns Pulsed Discharge Plasma

    Science.gov (United States)

    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.

  17. Data center network performance evaluation in ns3

    DEFF Research Database (Denmark)

    Andrus, Bogdan-Mihai; Vegas Olmos, Juan José

    2015-01-01

    In the following paper we present the analysis of highly interconnected topologies like hypercube and torus and how they can be implemented in data centers in order to cope with the rapid increase and demands for performance of the internal traffic. By replicating the topologies in NS3 and subjec......In the following paper we present the analysis of highly interconnected topologies like hypercube and torus and how they can be implemented in data centers in order to cope with the rapid increase and demands for performance of the internal traffic. By replicating the topologies in NS3...... and subjecting them to uniformly distributed traffic routed by shortest path algorithms we are able to extract statistics related to average throughput, latency and loss rate that show the decrease in the average throughput per connection is only about 5% for the hypercube compared to 16% for the 3D torus when...

  18. Evaluation of dengue NS1 antigen rapid tests and ELISA kits using clinical samples.

    Directory of Open Access Journals (Sweden)

    Subhamoy Pal

    Full Text Available Early diagnosis of dengue virus (DENV infection can improve clinical outcomes by ensuring close follow-up, initiating appropriate supportive therapies and raising awareness to the potential of hemorrhage or shock. Non-structural glycoprotein-1 (NS1 has proven to be a useful biomarker for early diagnosis of dengue. A number of rapid diagnostic tests (RDTs and enzyme-linked immunosorbent assays (ELISAs targeting NS1 antigen (Ag are now commercially available. Here we evaluated these tests using a well-characterized panel of clinical samples to determine their effectiveness for early diagnosis.Retrospective samples from South America were used to evaluate the following tests: (i "Dengue NS1 Ag STRIP" and (ii "Platelia Dengue NS1 Ag ELISA" (Bio-Rad, France, (iii "Dengue NS1 Detect Rapid Test (1st Generation" and (iv "DENV Detect NS1 ELISA" (InBios International, United States, (v "Panbio Dengue Early Rapid (1st generation" (vi "Panbio Dengue Early ELISA (2nd generation" and (vii "SD Bioline Dengue NS1 Ag Rapid Test" (Alere, United States. Overall, the sensitivity of the RDTs ranged from 71.9%-79.1% while the sensitivity of the ELISAs varied between 85.6-95.9%, using virus isolation as the reference method. Most tests had lower sensitivity for DENV-4 relative to the other three serotypes, were less sensitive in detecting secondary infections, and appeared to be most sensitive on Day 3-4 post symptom onset. The specificity of all evaluated tests ranged from 95%-100%.ELISAs had greater overall sensitivity than RDTs. In conjunction with other parameters, the performance data can help determine which dengue diagnostics should be used during the first few days of illness, when the patients are most likely to present to a clinic seeking care.

  19. Resistance Patterns Associated with HCV NS5A Inhibitors Provide Limited Insight into Drug Binding

    Directory of Open Access Journals (Sweden)

    Moheshwarnath Issur

    2014-11-01

    Full Text Available Direct-acting antivirals (DAAs have significantly improved the treatment of infection with the hepatitis C virus. A promising class of novel antiviral agents targets the HCV NS5A protein. The high potency and broad genotypic coverage are favorable properties. NS5A inhibitors are currently assessed in advanced clinical trials in combination with viral polymerase inhibitors and/or viral protease inhibitors. However, the clinical use of NS5A inhibitors is also associated with new challenges. HCV variants with decreased susceptibility to these drugs can emerge and compromise therapy. In this review, we discuss resistance patterns in NS5A with focus prevalence and implications for inhibitor binding.

  20. In-Silico Computing of the Most Deleterious nsSNPs in HBA1 Gene.

    Directory of Open Access Journals (Sweden)

    Sayed AbdulAzeez

    Full Text Available α-Thalassemia (α-thal is a genetic disorder caused by the substitution of single amino acid or large deletions in the HBA1 and/or HBA2 genes.Using modern bioinformatics tools as a systematic in-silico approach to predict the deleterious SNPs in the HBA1 gene and its significant pathogenic impact on the functions and structure of HBA1 protein was predicted.A total of 389 SNPs in HBA1 were retrieved from dbSNP database, which includes: 201 non-coding synonymous (nsSNPs, 43 human active SNPs, 16 intronic SNPs, 11 mRNA 3' UTR SNPs, 9 coding synonymous SNPs, 9 5' UTR SNPs and other types. Structural homology-based method (PolyPhen and sequence homology-based tool (SIFT, SNPs&Go, PROVEAN and PANTHER revealed that 2.4% of the nsSNPs are pathogenic.A total of 5 nsSNPs (G60V, K17M, K17T, L92F and W15R were predicted to be responsible for the structural and functional modifications of HBA1 protein. It is evident from the deep comprehensive in-silico analysis that, two nsSNPs such as G60V and W15R in HBA1 are highly deleterious. These "2 pathogenic nsSNPs" can be considered for wet-lab confirmatory analysis.

  1. Dynamics of bright-bright solitons in Bose-Einstein condensate with Raman-induced one-dimensional spin-orbit coupling

    Science.gov (United States)

    Wen, Lin; Zhang, Xiao-Fei; Hu, Ai-Yuan; Zhou, Jing; Yu, Peng; Xia, Lei; Sun, Qing; Ji, An-Chun

    2018-03-01

    We investigate the dynamics of bright-bright solitons in one-dimensional two-component Bose-Einstein condensates with Raman-induced spin-orbit coupling, via the variational approximation and the numerical simulation of Gross-Pitaevskii equations. For the uniform system without trapping potential, we obtain two population balanced stationary solitons. By performing the linear stability analysis, we find a Goldstone eigenmode and an oscillation eigenmode around these stationary solitons. Moreover, we derive a general dynamical solution to describe the center-of-mass motion and spin evolution of the solitons under the action of spin-orbit coupling. The effects of a harmonic trap have also been discussed.

  2. Activation of ERG2 potassium channels by the diphenylurea NS1643

    DEFF Research Database (Denmark)

    Elmedyb, Pernille; Olesen, Søren-Peter; Grunnet, Morten

    2007-01-01

    Three members of the ERG potassium channel family have been described (ERG1-3 or Kv 11.1-3). ERG1 is by far the best characterized subtype and it constitutes the molecular component of the cardiac I(Kr) current. All three channel subtypes are expressed in neurons but their function remains unclear....... The lack of functional information is at least partly due to the lack of specific pharmacological tools. The compound NS1643 has earlier been reported as an ERG1 channel activator. We found that NS1643 also activates the ERG2 channel; however, the molecular mechanism of the activation differs between...... the ERG1 and ERG2 channels. This is surprising since ERG1 and ERG2 channels have very similar biophysical and structural characteristics. For ERG2, NS1643 causes a left-ward shift of the activation curve, a faster time-constant of activation and a slower time-constant of inactivation as well...

  3. Quantitative Analysis of Hepatitis C NS5A Viral Protein Dynamics on the ER Surface

    Directory of Open Access Journals (Sweden)

    Markus M. Knodel

    2018-01-01

    Full Text Available Exploring biophysical properties of virus-encoded components and their requirement for virus replication is an exciting new area of interdisciplinary virological research. To date, spatial resolution has only rarely been analyzed in computational/biophysical descriptions of virus replication dynamics. However, it is widely acknowledged that intracellular spatial dependence is a crucial component of virus life cycles. The hepatitis C virus-encoded NS5A protein is an endoplasmatic reticulum (ER-anchored viral protein and an essential component of the virus replication machinery. Therefore, we simulate NS5A dynamics on realistic reconstructed, curved ER surfaces by means of surface partial differential equations (sPDE upon unstructured grids. We match the in silico NS5A diffusion constant such that the NS5A sPDE simulation data reproduce experimental NS5A fluorescence recovery after photobleaching (FRAP time series data. This parameter estimation yields the NS5A diffusion constant. Such parameters are needed for spatial models of HCV dynamics, which we are developing in parallel but remain qualitative at this stage. Thus, our present study likely provides the first quantitative biophysical description of the movement of a viral component. Our spatio-temporal resolved ansatz paves new ways for understanding intricate spatial-defined processes central to specfic aspects of virus life cycles.

  4. Quantitative Analysis of Hepatitis C NS5A Viral Protein Dynamics on the ER Surface.

    Science.gov (United States)

    Knodel, Markus M; Nägel, Arne; Reiter, Sebastian; Vogel, Andreas; Targett-Adams, Paul; McLauchlan, John; Herrmann, Eva; Wittum, Gabriel

    2018-01-08

    Exploring biophysical properties of virus-encoded components and their requirement for virus replication is an exciting new area of interdisciplinary virological research. To date, spatial resolution has only rarely been analyzed in computational/biophysical descriptions of virus replication dynamics. However, it is widely acknowledged that intracellular spatial dependence is a crucial component of virus life cycles. The hepatitis C virus-encoded NS5A protein is an endoplasmatic reticulum (ER)-anchored viral protein and an essential component of the virus replication machinery. Therefore, we simulate NS5A dynamics on realistic reconstructed, curved ER surfaces by means of surface partial differential equations (sPDE) upon unstructured grids. We match the in silico NS5A diffusion constant such that the NS5A sPDE simulation data reproduce experimental NS5A fluorescence recovery after photobleaching (FRAP) time series data. This parameter estimation yields the NS5A diffusion constant. Such parameters are needed for spatial models of HCV dynamics, which we are developing in parallel but remain qualitative at this stage. Thus, our present study likely provides the first quantitative biophysical description of the movement of a viral component. Our spatio-temporal resolved ansatz paves new ways for understanding intricate spatial-defined processes central to specfic aspects of virus life cycles.

  5. Quantitative Analysis of Hepatitis C NS5A Viral Protein Dynamics on the ER Surface

    Science.gov (United States)

    Nägel, Arne; Reiter, Sebastian; Vogel, Andreas; McLauchlan, John; Herrmann, Eva; Wittum, Gabriel

    2018-01-01

    Exploring biophysical properties of virus-encoded components and their requirement for virus replication is an exciting new area of interdisciplinary virological research. To date, spatial resolution has only rarely been analyzed in computational/biophysical descriptions of virus replication dynamics. However, it is widely acknowledged that intracellular spatial dependence is a crucial component of virus life cycles. The hepatitis C virus-encoded NS5A protein is an endoplasmatic reticulum (ER)-anchored viral protein and an essential component of the virus replication machinery. Therefore, we simulate NS5A dynamics on realistic reconstructed, curved ER surfaces by means of surface partial differential equations (sPDE) upon unstructured grids. We match the in silico NS5A diffusion constant such that the NS5A sPDE simulation data reproduce experimental NS5A fluorescence recovery after photobleaching (FRAP) time series data. This parameter estimation yields the NS5A diffusion constant. Such parameters are needed for spatial models of HCV dynamics, which we are developing in parallel but remain qualitative at this stage. Thus, our present study likely provides the first quantitative biophysical description of the movement of a viral component. Our spatio-temporal resolved ansatz paves new ways for understanding intricate spatial-defined processes central to specfic aspects of virus life cycles. PMID:29316722

  6. Quantitative Analysis of Hepatitis C NS5A Viral Protein Dynamics on the ER Surface

    KAUST Repository

    Knodel, Markus

    2018-01-08

    Exploring biophysical properties of virus-encoded components and their requirement for virus replication is an exciting new area of interdisciplinary virological research. To date, spatial resolution has only rarely been analyzed in computational/biophysical descriptions of virus replication dynamics. However, it is widely acknowledged that intracellular spatial dependence is a crucial component of virus life cycles. The hepatitis C virus-encoded NS5A protein is an endoplasmatic reticulum (ER)-anchored viral protein and an essential component of the virus replication machinery. Therefore, we simulate NS5A dynamics on realistic reconstructed, curved ER surfaces by means of surface partial differential equations (sPDE) upon unstructured grids. We match the in silico NS5A diffusion constant such that the NS5A sPDE simulation data reproduce experimental NS5A fluorescence recovery after photobleaching (FRAP) time series data. This parameter estimation yields the NS5A diffusion constant. Such parameters are needed for spatial models of HCV dynamics, which we are developing in parallel but remain qualitative at this stage. Thus, our present study likely provides the first quantitative biophysical description of the movement of a viral component. Our spatio-temporal resolved ansatz paves new ways for understanding intricate spatial-defined processes central to specfic aspects of virus life cycles.

  7. Phase advancing human circadian rhythms with morning bright light, afternoon melatonin, and gradually shifted sleep: can we reduce morning bright-light duration?

    Science.gov (United States)

    Crowley, Stephanie J; Eastman, Charmane I

    2015-02-01

    Efficient treatments to phase-advance human circadian rhythms are needed to attenuate circadian misalignment and the associated negative health outcomes that accompany early-morning shift work, early school start times, jet lag, and delayed sleep phase disorder. This study compared three morning bright-light exposure patterns from a single light box (to mimic home treatment) in combination with afternoon melatonin. Fifty adults (27 males) aged 25.9 ± 5.1 years participated. Sleep/dark was advanced 1 h/day for three treatment days. Participants took 0.5 mg of melatonin 5 h before the baseline bedtime on treatment day 1, and an hour earlier each treatment day. They were exposed to one of three bright-light (~5000 lux) patterns upon waking each morning: four 30-min exposures separated by 30 min of room light (2-h group), four 15-min exposures separated by 45 min of room light (1-h group), and one 30-min exposure (0.5-h group). Dim-light melatonin onsets (DLMOs) before and after treatment determined the phase advance. Compared to the 2-h group (phase shift = 2.4 ± 0.8 h), smaller phase-advance shifts were seen in the 1-h (1.7 ± 0.7 h) and 0.5-h (1.8 ± 0.8 h) groups. The 2-h pattern produced the largest phase advance; however, the single 30-min bright-light exposure was as effective as 1 h of bright light spread over 3.25 h, and it produced 75% of the phase shift observed with 2 h of bright light. A 30-min morning bright-light exposure with afternoon melatonin is an efficient treatment to phase-advance human circadian rhythms. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Phase advancing human circadian rhythms with morning bright light, afternoon melatonin, and gradually shifted sleep: can we reduce morning bright light duration?

    Science.gov (United States)

    Crowley, Stephanie J.; Eastman, Charmane I.

    2015-01-01

    OBJECTIVE Efficient treatments to phase advance human circadian rhythms are needed to attenuate circadian misalignment and the associated negative health outcomes that accompany early morning shift work, early school start times, jet lag, and delayed sleep phase disorder. This study compared three morning bright light exposure patterns from a single light box (to mimic home treatment) in combination with afternoon melatonin. METHODS Fifty adults (27 males) aged 25.9±5.1 years participated. Sleep/dark was advanced 1 hour/day for 3 treatment days. Participants took 0.5 mg melatonin 5 hours before baseline bedtime on treatment day 1, and an hour earlier each treatment day. They were exposed to one of three bright light (~5000 lux) patterns upon waking each morning: four 30-minute exposures separated by 30 minutes of room light (2 h group); four 15-minute exposures separated by 45 minutes of room light (1 h group), and one 30-minute exposure (0.5 h group). Dim light melatonin onsets (DLMOs) before and after treatment determined the phase advance. RESULTS Compared to the 2 h group (phase shift=2.4±0.8 h), smaller phase advance shifts were seen in the 1 h (1.7±0.7 h) and 0.5 h (1.8±0.8 h) groups. The 2-hour pattern produced the largest phase advance; however, the single 30-minute bright light exposure was as effective as 1 hour of bright light spread over 3.25 h, and produced 75% of the phase shift observed with 2 hours of bright light. CONCLUSIONS A 30-minute morning bright light exposure with afternoon melatonin is an efficient treatment to phase advance human circadian rhythms. PMID:25620199

  9. Achievements in NS rapeseed hybrids breeding

    Directory of Open Access Journals (Sweden)

    Marjanović-Jeromela Ana

    2016-01-01

    Full Text Available The increased production of oilseed rape (Brassica napus L. is evident on a global scale, but also in Serbia in the last decade. Rapeseed is used primarily for vegetable oil and processing industry, but also as a source of protein for animal feed and green manure. Following the cultivation of varieties, breeding and cultivation of hybrid rapeseed started in the 1990's, to take advantage of heterosis in F1 generation, while protecting the breeder's rights during seed commercialization. The breeding of hybrid oilseed rape requires high quality starting material (lines with good combining abilities for introduction of male sterility. Ogura sterility system is primarily used at the Institute of Field and Vegetable Crops, Novi Sad, Serbia. To use this system, separate lines are modified with genes for cytoplasmic male sterility (cms female line - mother line and restoration of fertility (Rf male lines - father line. In order to maintain the sterility of the mother line it is necessary to produce a maintainer line of cytoplasmic male sterility. Creation of these lines and hybrids at the Institute of Field and Vegetable Crops was successfully monitored with intense use of cytogenetic laboratory methods. The structure and vitality of pollen, including different phases during meiosis were checked so that cms stability was confirmed during the introduction of these genes into different lines. Rapeseed breeding program in Serbia resulted in numerous varieties through collaboration of researchers engaged in breeding and genetics of this plant species. So far, in addition to 12 varieties of winter rapeseed and two varieties of spring rapeseed, a new hybrid of winter rapeseed NS Ras was registered in Serbia. NS Ras is an early-maturing hybrid characterized by high seed yield and oil content. Average yield of NS Ras for two seasons and three sites was 4256 kg ha-1 of seed and 1704 kg ha-1 of oil. Three promising winter rapeseed hybrids are in the process of

  10. Measuring and mapping the night sky brightness of Perth, Western Australia

    Science.gov (United States)

    Biggs, James D.; Fouché, Tiffany; Bilki, Frank; Zadnik, Marjan G.

    2012-04-01

    In order to study the light pollution produced in the city of Perth, Western Australia, we have used a hand-held sky brightness meter to measure the night sky brightness across the city. The data acquired facilitated the creation of a contour map of night sky brightness across the 2400 km2 area of the city - the first such map to be produced for a city. Importantly, this map was created using a methodology borrowed from the field of geophysics - the well proven and rigorous techniques of geostatistical analysis and modelling. A major finding of this study is the effect of land use on night sky brightness. By overlaying the night sky brightness map on to a suitably processed Landsat satellite image of Perth we found that locations near commercial and/or light industrial areas have a brighter night sky, whereas locations used for agriculture or having high vegetation coverage have a fainter night sky than surrounding areas. Urban areas have intermediate amounts of vegetation and are intermediate in brightness compared with the above-mentioned land uses. Regions with a higher density of major highways also appear to contribute to increased night sky brightness. When corrected for the effects of direct illumination from high buildings, we found that the night sky brightness in the central business district (CBD) is very close to that expected for a city of Perth's population from modelling work and observations obtained in earlier studies. Given that our night sky brightness measurements in Perth over 2009 and 2010 are commensurate with that measured in Canadian cities over 30 years earlier implies that the various lighting systems employed in Perth (and probably most other cities) have not been optimised to minimize light pollution over that time. We also found that night sky brightness diminished with distance with an exponent of approximately -0.25 ± 0.02 from 3.5 to 10 km from the Perth CBD, a region characterized by urban and commercial land use. For distances

  11. Variation reduction of brightness and pH of pulp sent to a paper mill

    Directory of Open Access Journals (Sweden)

    Napassavong Rojanarowan

    2015-03-01

    Full Text Available The variance of the brightness of pulp sent to the paper mill during the changing period of dry pulp grades affects the chemical control in the paper mill. This research aims to determine the mixing formula of pulp with different brightness from the EOP and D1 stages to handle this variation issue. This research uses response surface design with Central Composite Design type, regression technique and optimization technique to find the optimal setting of the mixing formula for each of the seven brightness levels to obtain the target brightness of 86% and the pH of 5.25. The mixing formulas are determined by the pulp mixing percentage and the sulfuric acid consumption. The experimental results reveal that when using higher EOP mixing ratio, the brightness decreases and the pH increases. Regarding the effect of the sulfuric acid, increasing the sulfuric acid makes the brightness and the pH decrease. After implementing the optimal formula in the production line, the mean of pulp brightness is closer to the target compared with the brightness before improvement and the brightness variation decreases without affecting the quality of other pulp grades, average of brightness decreased from 87.4% to 86.3% and standard deviation of brightness decreased from 1.09 to 0.46.

  12. Characterization of Pressure Transients Generated by Nanosecond Electrical Pulse (nsEP) Exposure

    OpenAIRE

    Caleb C. Roth; Ronald A. Barnes Jr.; Bennett L. Ibey; Hope T. Beier; L. Christopher Mimun; Saher M. Maswadi; Mehdi Shadaram; Randolph D. Glickman

    2015-01-01

    The mechanism(s) responsible for the breakdown (nanoporation) of cell plasma membranes after nanosecond pulse (nsEP) exposure remains poorly understood. Current theories focus exclusively on the electrical field, citing electrostriction, water dipole alignment and/or electrodeformation as the primary mechanisms for pore formation. However, the delivery of a high-voltage nsEP to cells by tungsten electrodes creates a multitude of biophysical phenomena, including electrohydraulic cavitation, el...

  13. Brightness of synchrotron radiation from wigglers

    International Nuclear Information System (INIS)

    Geloni, Gianluca; Kocharyan, Vitali; Saldin, Evgeni

    2014-12-01

    According to 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. In the geometrical optics limit computations can be performed analytically. Within this limit, we restrict ourselves to the case of the beam size-dominated regime, which is typical for synchrotron radiation facilities in the X-ray wavelength range. We give a direct demonstration of the fact that the apparent horizontal source size is broadened in proportion to the beamline opening angle and to the length of the wiggler. While this effect is well-understood, a direct proof appears not to have been given elsewhere. 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 literature.

  14. High brightness ion source

    International Nuclear Information System (INIS)

    Dreyfus, R.W.; Hodgson, R.T.

    1975-01-01

    A high brightness ion beam is obtainable by using lasers to excite atoms or molecules from the ground state to an ionized state in increments, rather than in one step. The spectroscopic resonances of the atom or molecule are used so that relatively long wavelength, low power lasers can be used to obtain such ion beam

  15. Molecular and biochemical characterization of the NS1 protein of non-cultured influenza B virus strains circulating in Singapore

    KAUST Repository

    Jumat, Muhammad; Sugrue, Richard J.; Tan, Boon Huan; Maurer-Stroh, Sebastian; Lee, Raphael Tze Chuen; Wong, Puisan

    2016-01-01

    In this study we compared the NS1 protein of Influenza B/Lee/40 and several non-cultured Influenza B virus clinical strains detected in Singapore. In B/Lee/40 virus-infected cells and in cells expressing the recombinant B/Lee/40 NS1 protein a full-length 35 kDa NS1 protein and a 23 kDa NS1 protein species (p23) were detected. Mutational analysis of the NS1 gene indicated that p23 was generated by a novel cleavage event within the linker domain between an aspartic acid and proline at amino acid residues at positions 92 and 93 respectively (DP92–93), and that p23 contained the first 92 amino acids of the NS1 protein. Sequence analysis of the Singapore strains indicated the presence of either DP92–93 or NP92–93 in the NS1 protein, but protein expression analysis showed that p23 was only detected in NS1 proteins with DP92–93.. An additional adjacent proline residue at position 94 (P94) was present in some strains and correlated with increased p23 levels, suggesting that P94 has a synergistic effect on the cleavage of the NS1 protein. The first 145 amino acids of the NS1 protein are required for inhibition of ISG15-mediated ubiquitination, and our analysis showed that Influenza B viruses circulating in Singapore with DP92–93 expressed truncated NS1 proteins and may differ in their capacity to inhibit ISG15 activity. Thus, DP92–93 in the NS1 protein may confer a disadvantage to Influenza B viruses circulating in the human population and interestingly the low frequency of DP92–93detection in the NS1 protein since 2004 is consistent with this suggestion.

  16. Molecular and biochemical characterization of the NS1 protein of non-cultured influenza B virus strains circulating in Singapore

    KAUST Repository

    Jumat, Muhammad Raihan

    2016-08-04

    In this study we compared the NS1 protein of Influenza B/Lee/40 and several non-cultured Influenza B virus clinical strains detected in Singapore. In B/Lee/40 virus-infected cells and in cells expressing the recombinant B/Lee/40 NS1 protein a full-length 35 kDa NS1 protein and a 23 kDa NS1 protein species (p23) were detected. Mutational analysis of the NS1 gene indicated that p23 was generated by a novel cleavage event within the linker domain between an aspartic acid and proline at amino acid residues at positions 92 and 93 respectively (DP92–93), and that p23 contained the first 92 amino acids of the NS1 protein. Sequence analysis of the Singapore strains indicated the presence of either DP92–93 or NP92–93 in the NS1 protein, but protein expression analysis showed that p23 was only detected in NS1 proteins with DP92–93.. An additional adjacent proline residue at position 94 (P94) was present in some strains and correlated with increased p23 levels, suggesting that P94 has a synergistic effect on the cleavage of the NS1 protein. The first 145 amino acids of the NS1 protein are required for inhibition of ISG15-mediated ubiquitination, and our analysis showed that Influenza B viruses circulating in Singapore with DP92–93 expressed truncated NS1 proteins and may differ in their capacity to inhibit ISG15 activity. Thus, DP92–93 in the NS1 protein may confer a disadvantage to Influenza B viruses circulating in the human population and interestingly the low frequency of DP92–93detection in the NS1 protein since 2004 is consistent with this suggestion.

  17. Design of New Competitive Dengue Ns2b/Ns3 Protease Inhibitors—A Computational Approach

    Directory of Open Access Journals (Sweden)

    Noorsaadah Abd. Rahman

    2011-02-01

    Full Text Available Dengue is a serious disease which has become a global health burden in the last decade. Currently, there are no approved vaccines or antiviral therapies to combat the disease. The increasing spread and severity of the dengue virus infection emphasizes the importance of drug discovery strategies that could efficiently and cost-effectively identify antiviral drug leads for development into potent drugs. To this effect, several computational approaches were applied in this work. Initially molecular docking studies of reference ligands to the DEN2 NS2B/NS3 serine protease were carried out. These reference ligands consist of reported competitive inhibitors extracted from Boesenbergia rotunda (i.e., 4-hydroxypanduratin A and panduratin A and three other synthesized panduratin A derivative compounds (i.e., 246DA, 2446DA and 20H46DA. The design of new lead inhibitors was carried out in two stages. In the first stage, the enzyme complexed to the reference ligands was minimized and their complexation energies (i.e., sum of interaction energy and binding energy were computed. New compounds as potential dengue inhibitors were then designed by putting various substituents successively on the benzyl ring A of the reference molecule. These substituted benzyl compounds were then computed for their enzyme-ligand complexation energies. New enzyme-ligand complexes, exhibiting the lowest complexation energies and closest to the computed energy for the reference compounds, were then chosen for the next stage manipulation and design, which involved substituting positions 4 and 5 of the benzyl ring A (positions 3 and 4 for 2446DA with various substituents.

  18. The role of the second zero-dispersion wavelength in generation of supercontinua and bright-bright soliton-pairs across the zero-dispersion wavelength: erratum

    DEFF Research Database (Denmark)

    Frosz, Michael Henoch; Falk, Peter Andreas; Bang, Ole

    2007-01-01

    An erratum is presented explaining that the observation in the original paper (Optics Express, volume 13, issue 16, page 6181-6192, 2005), of a bright-bright soliton with one color in the anomalous dispersion region and the other color in the normal dispersion region was mistaken; both parts...

  19. Multiplex Outputs ns Grade High-voltage Fast Pulse Generator Study

    International Nuclear Information System (INIS)

    Wang Xin; Chen Kenan

    2009-01-01

    Using a double-grid hydrogen thyratron, a fast pulse generator with four outputs, high-voltage, low jitter, was made to use at special occasion.In this paper, the basic structure of pulser, switching theory and double-grid driving of hydrogen thyratron was introduced, and also, the effects of grids driving pulses characteristics, the delay between too grids driving, the reservoir heater voltage and cathode heater voltage on the output are carefully examined in experiments. The pulse generator with four outputs was made to producing pulses with amplitude up to 4 kV, rise-time less than 15 ns and jitter less than 3 ns. (authors)

  20. Brightness-normalized Partial Least Squares Regression for hyperspectral data

    International Nuclear Information System (INIS)

    Feilhauer, Hannes; Asner, Gregory P.; Martin, Roberta E.; Schmidtlein, Sebastian

    2010-01-01

    Developed in the field of chemometrics, Partial Least Squares Regression (PLSR) has become an established technique in vegetation remote sensing. PLSR was primarily designed for laboratory analysis of prepared material samples. Under field conditions in vegetation remote sensing, the performance of the technique may be negatively affected by differences in brightness due to amount and orientation of plant tissues in canopies or the observing conditions. To minimize these effects, we introduced brightness normalization to the PLSR approach and tested whether this modification improves the performance under changing canopy and observing conditions. This test was carried out using high-fidelity spectral data (400-2510 nm) to model observed leaf chemistry. The spectral data was combined with a canopy radiative transfer model to simulate effects of varying canopy structure and viewing geometry. Brightness normalization enhanced the performance of PLSR by dampening the effects of canopy shade, thus providing a significant improvement in predictions of leaf chemistry (up to 3.6% additional explained variance in validation) compared to conventional PLSR. Little improvement was made on effects due to variable leaf area index, while minor improvement (mostly not significant) was observed for effects of variable viewing geometry. In general, brightness normalization increased the stability of model fits and regression coefficients for all canopy scenarios. Brightness-normalized PLSR is thus a promising approach for application on airborne and space-based imaging spectrometer data.

  1. A spectral k-means approach to bright-field cell image segmentation.

    Science.gov (United States)

    Bradbury, Laura; Wan, Justin W L

    2010-01-01

    Automatic segmentation of bright-field cell images is important to cell biologists, but difficult to complete due to the complex nature of the cells in bright-field images (poor contrast, broken halo, missing boundaries). Standard approaches such as level set segmentation and active contours work well for fluorescent images where cells appear as round shape, but become less effective when optical artifacts such as halo exist in bright-field images. In this paper, we present a robust segmentation method which combines the spectral and k-means clustering techniques to locate cells in bright-field images. This approach models an image as a matrix graph and segment different regions of the image by computing the appropriate eigenvectors of the matrix graph and using the k-means algorithm. We illustrate the effectiveness of the method by segmentation results of C2C12 (muscle) cells in bright-field images.

  2. T1 bright appendix sign to exclude acute appendicitis in pregnant women

    International Nuclear Information System (INIS)

    Shin, Ilah; An, Chansik; Lim, Joon Seok; Kim, Myeong-Jin; Chung, Yong Eun

    2017-01-01

    To evaluate the diagnostic value of the T1 bright appendix sign for the diagnosis of acute appendicitis in pregnant women. This retrospective study included 125 pregnant women with suspected appendicitis who underwent magnetic resonance (MR) imaging. The T1 bright appendix sign was defined as a high intensity signal filling more than half length of the appendix on T1-weighted imaging. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the T1 bright appendix sign for normal appendix identification were calculated in all patients and in those with borderline-sized appendices (6-7 mm). The T1 bright appendix sign was seen in 51% of patients with normal appendices, but only in 4.5% of patients with acute appendicitis. The overall sensitivity, specificity, PPV, and NPV of the T1 bright appendix sign for normal appendix diagnosis were 44.9%, 95.5%, 97.6%, and 30.0%, respectively. All four patients with borderline sized appendix with appendicitis showed negative T1 bright appendix sign. The T1 bright appendix sign is a specific finding for the diagnosis of a normal appendix in pregnant women with suspected acute appendicitis. (orig.)

  3. T1 bright appendix sign to exclude acute appendicitis in pregnant women

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Ilah; An, Chansik; Lim, Joon Seok; Kim, Myeong-Jin; Chung, Yong Eun [Yonsei University College of Medicine, Department of Radiology, Research Institute of Radiological Science, Severance Hospital, 50-1 Yonsei-ro, Seodaemun-gu, Seoul (Korea, Republic of)

    2017-08-15

    To evaluate the diagnostic value of the T1 bright appendix sign for the diagnosis of acute appendicitis in pregnant women. This retrospective study included 125 pregnant women with suspected appendicitis who underwent magnetic resonance (MR) imaging. The T1 bright appendix sign was defined as a high intensity signal filling more than half length of the appendix on T1-weighted imaging. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the T1 bright appendix sign for normal appendix identification were calculated in all patients and in those with borderline-sized appendices (6-7 mm). The T1 bright appendix sign was seen in 51% of patients with normal appendices, but only in 4.5% of patients with acute appendicitis. The overall sensitivity, specificity, PPV, and NPV of the T1 bright appendix sign for normal appendix diagnosis were 44.9%, 95.5%, 97.6%, and 30.0%, respectively. All four patients with borderline sized appendix with appendicitis showed negative T1 bright appendix sign. The T1 bright appendix sign is a specific finding for the diagnosis of a normal appendix in pregnant women with suspected acute appendicitis. (orig.)

  4. Quantitative measurement of brightness from living cells in the presence of photodepletion.

    Directory of Open Access Journals (Sweden)

    Kwang-Ho Hur

    Full Text Available The brightness of fluorescently labeled proteins provides an excellent marker for identifying protein interactions in living cells. Quantitative interpretation of brightness, however, hinges on a detailed understanding of the processes that affect the signal fluctuation of the fluorescent label. Here, we focus on the cumulative influence of photobleaching on brightness measurements in cells. Photobleaching within the finite volume of the cell leads to a depletion of the population of fluorescently labeled proteins with time. The process of photodepletion reduces the fluorescence signal which biases the analysis of brightness data. Our data show that even small reductions in the signal can introduce significant bias into the analysis of the data. We develop a model that quantifies the bias and introduce an analysis method that accurately determines brightness in the presence of photodepletion as verified by experiments with mammalian and yeast cells. In addition, photodepletion experiments with the fluorescent protein EGFP reveal the presence of a photoconversion process, which leads to a marked decrease in the brightness of the EGFP protein. We also identify conditions where the effect of EGFP's photoconversion on brightness experiments can be safely ignored.

  5. Dark and bright solitons in a quasi-one-dimensional Bose-Einstein condensate

    International Nuclear Information System (INIS)

    Wang, Shun-Jin; Jia, Cheng-Long; An, Jun-Hong; Zhao, Dun; Luo, Hong-Gang

    2003-01-01

    The analytical dark and bright soliton solutions of the one-dimensional Gross-Pitaevskii equation with a confining potential are obtained. For the bright soliton, the recent experimental finding is studied, and the particle number of the soliton and the window of the particle numbers for the bright soliton to occur are estimated analytically and in good agreement with the experimental data. The existence of dark soliton for the attractive interaction and bright soliton for the repulsive interaction is predicted under proper conditions

  6. Quadrature measurements of a bright squeezed state via sideband swapping

    DEFF Research Database (Denmark)

    Schneider, J.; Glockl, O.; Leuchs, G.

    2009-01-01

    The measurement of an arbitrary quadrature of a bright quantum state of light is a commonly requested action in many quantum information protocols, but it is experimentally challenging with previously proposed schemes. We suggest that the quadrature be measured at a specific sideband frequency...... of a bright quantum state by transferring the sideband modes under interrogation to a vacuum state and subsequently measuring the quadrature via homodyne detection. The scheme is implemented experimentally, and it is successfully tested with a bright squeezed state of light....

  7. Characterization of the expression and immunogenicity of the ns4b protein of human coronavirus 229E

    DEFF Research Database (Denmark)

    Chagnon, F; Lamarre, A; Lachance, C

    1998-01-01

    to demonstrate the expression of ns4b in HCV-229E-infected cells using flow cytometry. Given a previously reported contiguous five amino acid shared region between ns4b and myelin basic protein, a purified recombinant histidine-tagged ns4b protein and (or) human myelin basic protein were injected into mice......Sequencing of complementary DNAs prepared from various coronaviruses has revealed open reading frames encoding putative proteins that are yet to be characterized and are so far only described as nonstructural (ns). As a first step in the elucidation of its function, we characterized the expression...... and immunogenicity of the ns4b gene product from strain 229E of human coronavirus (HCV-229E), a respiratory virus with a neurotropic potential. The gene was cloned and expressed in bacteria. A fusion protein of ns4b with maltose-binding protein was injected into rabbits to generate specific antibodies that were used...

  8. Condensate bright solitons under transverse confinement

    International Nuclear Information System (INIS)

    Salasnich, L.; Reatto, L.; Parola, A.

    2002-01-01

    We investigate the dynamics of Bose-Einstein condensate bright solitons made of alkali-metal atoms with negative scattering length and under harmonic confinement in the transverse direction. Contrary to the one-dimensional (1D) case, the 3D bright soliton exists only below a critical attractive interaction that depends on the extent of confinement. Such a behavior is also found in multisoliton condensates with box boundary conditions. We obtain numerical and analytical estimates of the critical strength beyond which the solitons do not exist. By using an effective 1D nonpolynomial nonlinear Schroedinger equation, which accurately takes into account the transverse dynamics of cigarlike condensates, we numerically simulate the dynamics of the 'soliton train' reported in a recent experiment [Nature (London) 417, 150 (2002)]. Then, analyzing the macroscopic quantum tunneling of the bright soliton on a Gaussian barrier, we find that its interference in the tunneling region is strongly suppressed with respect to nonsolitonic case; moreover, the tunneling through a barrier breaks the shape invariance of the matter wave. Finally, we show that the collapse of the soliton is induced by the scattering on the barrier or by the collision with another matter wave when the density reaches a critical value, for which we derive an accurate analytical formula

  9. Possible Bright Starspots on TRAPPIST-1

    Science.gov (United States)

    Morris, Brett M.; Agol, Eric; Davenport, James R. A.; Hawley, Suzanne L.

    2018-04-01

    The M8V star TRAPPIST-1 hosts seven roughly Earth-sized planets and is a promising target for exoplanet characterization. Kepler/K2 Campaign 12 observations of TRAPPIST-1 in the optical show an apparent rotational modulation with a 3.3-day period, though that rotational signal is not readily detected in the Spitzer light curve at 4.5 μm. If the rotational modulation is due to starspots, persistent dark spots can be excluded from the lack of photometric variability in the Spitzer light curve. We construct a photometric model for rotational modulation due to photospheric bright spots on TRAPPIST-1 that is consistent with both the Kepler and Spitzer light curves. The maximum-likelihood model with three spots has typical spot sizes of R spot/R ⋆ ≈ 0.004 at temperature T spot ≳ 5300 ± 200 K. We also find that large flares are observed more often when the brightest spot is facing the observer, suggesting a correlation between the position of the bright spots and flare events. In addition, these flares may occur preferentially when the spots are increasing in brightness, which suggests that the 3.3-day periodicity may not be a rotational signal, but rather a characteristic timescale of active regions.

  10. Effects of the small molecule HERG activator NS1643 on Kv11.3 channels.

    Directory of Open Access Journals (Sweden)

    Arne Bilet

    Full Text Available NS1643 is one of the small molecule HERG (Kv11.1 channel activators and has also been found to increase erg2 (Kv11.2 currents. We now investigated whether NS1643 is also able to act as an activator of Kv11.3 (erg3 channels expressed in CHO cells. Activation of rat Kv11.3 current occurred in a dose-dependent manner and maximal current increasing effects were obtained with 10 µM NS1643. At this concentration, steady-state outward current increased by about 80% and the current increase was associated with a significant shift in the voltage dependence of activation to more negative potentials by about 15 mV. In addition, activation kinetics were accelerated, whereas deactivation was slowed. There was no significant effect on the kinetics of inactivation and recovery from inactivation. The strong current-activating agonistic effect of NS1643 did not result from a shift in the voltage dependence of Kv11.3 channel inactivation and was independent from external Na(+ or Ca(2+. At the higher concentration of 20 µM, NS1643 induced clearly less current increase. The left shift in the voltage dependence of activation reversed and the voltage sensitivity of activation dramatically decreased along with a slowing of Kv11.3 channel activation. These data show that, in comparison to other Kv11 family members, NS1643 exerts distinct effects on Kv11.3 channels with especially pronounced partial antagonistic effects at higher concentration.

  11. SKYMONITOR: A Global Network for Sky Brightness Measurements

    Science.gov (United States)

    Davis, Donald R.; Mckenna, D.; Pulvermacher, R.; Everett, M.

    2010-01-01

    We are implementing a global network to measure sky brightness at dark-sky critical sites with the goal of creating a multi-decade database. The heart of this project is the Night Sky Brightness Monitor (NSBM), an autonomous 2 channel photometer which measures night sky brightness in the visual wavelengths (Mckenna et al, AAS 2009). Sky brightness is measured every minute at two elevation angles typically zenith and 20 degrees to monitor brightness and transparency. The NSBM consists of two parts, a remote unit and a base station with an internet connection. Currently these devices use 2.4 Ghz transceivers with a range of 100 meters. The remote unit is battery powered with daytime recharging using a solar panel. Data received by the base unit is transmitted via email protocol to IDA offices in Tucson where it will be collected, archived and made available to the user community via a web interface. Two other versions of the NSBM are under development: one for radio sensitive areas using an optical fiber link and the second that reads data directly to a laptop for sites without internet access. NSBM units are currently undergoing field testing at two observatories. With support from the National Science Foundation, we will construct and install a total of 10 units at astronomical observatories. With additional funding, we will locate additional units at other sites such as National Parks, dark-sky preserves and other sites where dark sky preservation is crucial. We will present the current comparison with the National Park Service sky monitoring camera. We anticipate that the SKYMONITOR network will be functioning by the end of 2010.

  12. Influenza A virus NS1 gene mutations F103L and M106I increase replication and virulence

    Directory of Open Access Journals (Sweden)

    Ping Jihui

    2011-01-01

    Full Text Available Abstract Background To understand the evolutionary steps required for a virus to become virulent in a new host, a human influenza A virus (IAV, A/Hong Kong/1/68(H3N2 (HK-wt, was adapted to increased virulence in the mouse. Among eleven mutations selected in the NS1 gene, two mutations F103L and M106I had been previously detected in the highly virulent human H5N1 isolate, A/HK/156/97, suggesting a role for these mutations in virulence in mice and humans. Results To determine the selective advantage of these mutations, reverse genetics was used to rescue viruses containing each of the NS1 mouse adapted mutations into viruses possessing the HK-wt NS1 gene on the A/PR/8/34 genetic backbone. Both F103L and M106I NS1 mutations significantly enhanced growth in vitro (mouse and canine cells and in vivo (BALB/c mouse lungs as well as enhanced virulence in the mouse. Only the M106I NS1 mutation enhanced growth in human cells. Furthermore, these NS1 mutations enhanced early viral protein synthesis in MDCK cells and showed an increased ability to replicate in mouse interferon β (IFN-β pre-treated mouse cells relative to rPR8-HK-NS-wt NS1. The double mutant, rPR8-HK-NS-F103L + M106I, demonstrated growth attenuation late in infection due to increased IFN-β induction in mouse cells. We then generated a rPR8 virus possessing the A/HK/156/97 NS gene that possesses 103L + 106I, and then rescued the L103F + I106M mutant. The 103L + 106I mutations increased virulence by >10 fold in BALB/c mice. We also inserted the avian A/Ck/Beijing/1/95 NS1 gene (the source lineage of the A/HK/156/97 NS1 gene that possesses 103L + 106I, onto the A/WSN/33 backbone and then generated the L103F + I106M mutant. None of the H5N1 and H9N2 NS containing viruses resulted in increased IFN-β induction. The rWSN-A/Ck/Beijing/1/95-NS1 gene possessing 103L and 106I demonstrated 100 fold enhanced growth and >10 fold enhanced virulence that was associated with increased tropism for lung

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

    Directory of Open Access Journals (Sweden)

    Hugo de Almeida

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

  14. Amino Terminal Region of Dengue Virus NS4A Cytosolic Domain Binds to Highly Curved Liposomes

    Directory of Open Access Journals (Sweden)

    Yu-Fu Hung

    2015-07-01

    Full Text Available Dengue virus (DENV is an important human pathogen causing millions of disease cases and thousands of deaths worldwide. Non-structural protein 4A (NS4A is a vital component of the viral replication complex (RC and plays a major role in the formation of host cell membrane-derived structures that provide a scaffold for replication. The N-terminal cytoplasmic region of NS4A(1–48 is known to preferentially interact with highly curved membranes. Here, we provide experimental evidence for the stable binding of NS4A(1–48 to small liposomes using a liposome floatation assay and identify the lipid binding sequence by NMR spectroscopy. Mutations L6E;M10E were previously shown to inhibit DENV replication and to interfere with the binding of NS4A(1–48 to small liposomes. Our results provide new details on the interaction of the N-terminal region of NS4A with membranes and will prompt studies of the functional relevance of the curvature sensitive membrane anchor at the N-terminus of NS4A.

  15. A Review of Staphylococcal Cassette Chromosome mec (SCCmec) Types in Coagulase-Negative Staphylococci (CoNS) Species.

    Science.gov (United States)

    Saber, Huda; Jasni, Azmiza Syawani; Jamaluddin, Tengku Zetty Maztura Tengku; Ibrahim, Rosni

    2017-10-01

    Coagulase-negative staphylococci (CoNS) are considered low pathogenic organisms. However, they are progressively causing more serious infections with time because they have adapted well to various antibiotics owing to their ability to form biofilms. Few studies have been conducted on CoNS in both, hospital and community-acquired settings, especially in Malaysia. Thus, it is important to study their species and gene distributions. A mobile genetic element, staphylococcal cassette chromosome mec (SCC mec ), plays an important role in staphylococci pathogenesis. Among CoNS, SCC mec has been studied less frequently than Staphylococcus aureus (coagulase-positive staphylococci). A recent study (8) conducted in Malaysia successfully detected SCC mec type I to VIII as well as several new combination patterns in CoNS species, particularly Staphylococcus epidermidis . However, data are still limited, and further research is warranted. This paper provides a review on SCC mec types among CoNS species.

  16. A surface brightness analysis of eight RR Lyrae stars

    International Nuclear Information System (INIS)

    Hawley, S.L.; Barnes, T.G. III; Moffett, T.J.

    1987-01-01

    The authors have used a surface brightness, (V-R) relation to analyze new contemporaneous photometry and radial velocity data for 6 RR-ab type stars and to re-analyze previously published data for RR Lyrae and X Arietis. Systematic effects were found in the surface brightness at phases near minimum radius. Excluding these phases, they determine the slope of the surface brightness relation and the mean radius for each star. They also find a zero point which includes both a distance term and the zero point of the surface brightness relation. The sample includes stars with Preston's metallicity indicator ΔS = 0 to 9, with periods ranging from 0.397 days to 0.651 days. Their results indicate a log(R/R solar ) vs. log P relation in the sense that stars with longer periods have larger radii, in agreement with theoretical predictions. Their radii are consistent with bolometric magnitudes in the range 0.2 - 0.8 magnitude but accurate magnitudes must await a reliable T e - color calibration

  17. Solar brightness distribution at 8.6 mm from interferometer observations

    International Nuclear Information System (INIS)

    Kawabata, K.; Fujishita, M.; Kato, T.; Ogawa, H.; Omodaka, T.

    1980-01-01

    The radial brightness distribution of the quiet Sun at 8.6 mm is synthesized from observations using a sixteen element east-west interferometer in Nagoya. The observed brightness is flat from the disk center to 0.8 Rsub(sun). A slight darkening appeared between 0.8 Rsub(sun) and the limb. No evidence if the bright ring near the limb is found. The radio radius at 8.6 mm is 1.015 +- 0.005 Rsub(sun). In addition there exists a coronal component just outside the radio limb. (orig.)

  18. Cross-dimensional mapping of number, length and brightness by preschool children.

    Directory of Open Access Journals (Sweden)

    Maria Dolores de Hevia

    Full Text Available Human adults in diverse cultures, children, infants, and non-human primates relate number to space, but it is not clear whether this ability reflects a specific and privileged number-space mapping. To investigate this possibility, we tested preschool children in matching tasks where the dimensions of number and length were mapped both to one another and to a third dimension, brightness. Children detected variation on all three dimensions, and they reliably performed mappings between number and length, and partially between brightness and length, but not between number and brightness. Moreover, children showed reliably better mapping of number onto the dimension of length than onto the dimension of brightness. These findings suggest that number establishes a privileged mapping with the dimension of length, and that other dimensions, including brightness, can be mapped onto length, although less efficiently. Children's adeptness at number-length mappings suggests that these two dimensions are intuitively related by the end of the preschool years.

  19. Low surface brightness spiral galaxies

    International Nuclear Information System (INIS)

    Romanishin, W.

    1980-01-01

    This dissertation presents an observational overview of a sample of low surface brightness (LSB) spiral galaxies. The sample galaxies were chosen to have low surface brightness disks and indications of spiral structure visible on the Palomar Sky Survey. They are of sufficient angular size (diameter > 2.5 arcmin), to allow detailed surface photometry using Mayall 4-m prime focus plates. The major findings of this dissertation are: (1) The average disk central surface brightness of the LSB galaxies is 22.88 magnitude/arcsec 2 in the B passband. (2) From broadband color measurements of the old stellar population, we infer a low average stellar metallicity, on the order of 1/5 solar. (3) The spectra and optical colors of the HII regions in the LSB galaxies indicate a lack of hot ionizing stars compared to HII regions in other late-type galaxies. (4) The average surface mass density, measured within the radius containing half the total mass, is less than half that of a sample of normal late-type spirals. (5) The average LSB galaxy neutral hydrogen mass to blue luminosity ratio is about 0.6, significantly higher than in a sample of normal late-type galaxies. (6) We find no conclusive evidence of an abnormal mass-to-light ratio in the LSB galaxies. (7) Some of the LSB galaxies exhibit well-developed density wave patterns. (8) A very crude calculation shows the lower metallicity of the LSB galaxies compared with normal late-type spirals might be explained simply by the deficiency of massive stars in the LSB galaxies

  20. NS 1231, a novel compound with neurotrophic-like effects in vitro and in vivo

    DEFF Research Database (Denmark)

    Dagø, Lone; Bonde, Christian; Peters, Dan

    2002-01-01

    reduced NMDA-induced excitotoxicity in organotypic hippocampal slice cultures. In a gerbil model of transient global ischaemia, treatment with NS 1231 reduced the delayed loss of neurons in the hippocampal CA1 layer. Furthermore, NS 1231 treatment resulted in a 43% reduction in total infarct volume...

  1. T1 bright appendix sign to exclude acute appendicitis in pregnant women.

    Science.gov (United States)

    Shin, Ilah; An, Chansik; Lim, Joon Seok; Kim, Myeong-Jin; Chung, Yong Eun

    2017-08-01

    To evaluate the diagnostic value of the T1 bright appendix sign for the diagnosis of acute appendicitis in pregnant women. This retrospective study included 125 pregnant women with suspected appendicitis who underwent magnetic resonance (MR) imaging. The T1 bright appendix sign was defined as a high intensity signal filling more than half length of the appendix on T1-weighted imaging. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the T1 bright appendix sign for normal appendix identification were calculated in all patients and in those with borderline-sized appendices (6-7 mm). The T1 bright appendix sign was seen in 51% of patients with normal appendices, but only in 4.5% of patients with acute appendicitis. The overall sensitivity, specificity, PPV, and NPV of the T1 bright appendix sign for normal appendix diagnosis were 44.9%, 95.5%, 97.6%, and 30.0%, respectively. All four patients with borderline sized appendix with appendicitis showed negative T1 bright appendix sign. The T1 bright appendix sign is a specific finding for the diagnosis of a normal appendix in pregnant women with suspected acute appendicitis. • Magnetic resonance imaging is increasingly used in emergency settings. • Acute appendicitis is the most common cause of acute abdomen. • Magnetic resonance imaging is widely used in pregnant population. • T1 bright appendix sign can be a specific sign representing normal appendix.

  2. The Influenza NS1 Protein: What Do We Know in Equine Influenza Virus Pathogenesis?

    Directory of Open Access Journals (Sweden)

    Marta Barba

    2016-08-01

    Full Text Available Equine influenza virus remains a serious health and potential economic problem throughout most parts of the world, despite intensive vaccination programs in some horse populations. The influenza non-structural protein 1 (NS1 has multiple functions involved in the regulation of several cellular and viral processes during influenza infection. We review the strategies that NS1 uses to facilitate virus replication and inhibit antiviral responses in the host, including sequestering of double-stranded RNA, direct modulation of protein kinase R activity and inhibition of transcription and translation of host antiviral response genes such as type I interferon. Details are provided regarding what it is known about NS1 in equine influenza, especially concerning C-terminal truncation. Further research is needed to determine the role of NS1 in equine influenza infection, which will help to understand the pathophysiology of complicated cases related to cytokine imbalance and secondary bacterial infection, and to investigate new therapeutic and vaccination strategies.

  3. An NS5A single optimized method to determine genotype, subtype and resistance profiles of Hepatitis C strains.

    Directory of Open Access Journals (Sweden)

    Elisabeth Andre-Garnier

    Full Text Available The objective was to develop a method of HCV genome sequencing that allowed simultaneous genotyping and NS5A inhibitor resistance profiling. In order to validate the use of a unique RT-PCR for genotypes 1-5, 142 plasma samples from patients infected with HCV were analysed. The NS4B-NS5A partial region was successfully amplified and sequenced in all samples. In parallel, partial NS3 sequences were analyzed obtained for genotyping. Phylogenetic analysis showed concordance of genotypes and subtypes with a bootstrap >95% for each type cluster. NS5A resistance mutations were analyzed using the Geno2pheno [hcv] v0.92 tool and compared to the list of known Resistant Associated Substitutions recently published. In conclusion, this tool allows determination of HCV genotypes, subtypes and identification of NS5A resistance mutations. This single method can be used to detect pre-existing resistance mutations in NS5A before treatment and to check the emergence of resistant viruses while undergoing treatment in major HCV genotypes (G1-5 in the EU and the US.

  4. The NS1 Protein from Influenza Virus Stimulates Translation Initiation by Enhancing Ribosome Recruitment to mRNAs.

    Science.gov (United States)

    Panthu, Baptiste; Terrier, Olivier; Carron, Coralie; Traversier, Aurélien; Corbin, Antoine; Balvay, Laurent; Lina, Bruno; Rosa-Calatrava, Manuel; Ohlmann, Théophile

    2017-10-27

    The non-structural protein NS1 of influenza A viruses exerts pleiotropic functions during infection. Among these functions, NS1 was shown to be involved in the control of both viral and cellular translation; however, the mechanism by which this occurs remains to be determined. Thus, we have revisited the role of NS1 in translation by using a combination of influenza infection, mRNA reporter transfection, and in vitro functional and biochemical assays. Our data show that the NS1 protein is able to enhance the translation of virtually all tested mRNAs with the exception of constructs bearing the Dicistroviruses Internal ribosome entry segment (IRESes) (DCV and CrPV), suggesting a role at the level of translation initiation. The domain of NS1 required for translation stimulation was mapped to the RNA binding amino-terminal motif of the protein with residues R38 and K41 being critical for activity. Although we show that NS1 can bind directly to mRNAs, it does not correlate with its ability to stimulate translation. This activity rather relies on the property of NS1 to associate with ribosomes and to recruit them to target mRNAs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Fifty shades of white: how white feather brightness differs among species

    Science.gov (United States)

    Igic, Branislav; D'Alba, Liliana; Shawkey, Matthew D.

    2018-04-01

    White colouration is a common and important component of animal visual signalling and camouflage, but how and why it varies across species is poorly understood. White is produced by wavelength-independent and diffuse scattering of light by the internal structures of materials, where the degree of brightness is related to the amount of light scattered. Here, we investigated the morphological basis of brightness differences among unpigmented pennaceous regions of white body feathers across 61 bird species. Using phylogenetically controlled comparisons of reflectance and morphometric measurements, we show that brighter white feathers had larger and internally more complex barbs than duller white feathers. Higher brightness was also associated with more closely packed barbs and barbules, thicker and longer barbules, and rounder and less hollow barbs. Larger species tended to have brighter white feathers than smaller species because they had thicker and more complex barbs, but aquatic species were not significantly brighter than terrestrial species. As similar light scattering principals affect the brightness of chromatic signals, not just white colours, these findings help broaden our general understanding of the mechanisms that affect plumage brightness. Future studies should examine how feather layering on a bird's body contributes to differences between brightness of white plumage patches within and across species.

  6. Characterizing the Motion of Solar Magnetic Bright Points at High Resolution

    Science.gov (United States)

    Van Kooten, Samuel J.; Cranmer, Steven R.

    2017-11-01

    Magnetic bright points in the solar photosphere, visible in both continuum and G-band images, indicate footpoints of kilogauss magnetic flux tubes extending to the corona. The power spectrum of bright-point motion is thus also the power spectrum of Alfvén wave excitation, transporting energy up flux tubes into the corona. This spectrum is a key input in coronal and heliospheric models. We produce a power spectrum of bright-point motion using radiative magnetohydrodynamic simulations, exploiting spatial resolution higher than can be obtained in present-day observations, while using automated tracking to produce large data quantities. We find slightly higher amounts of power at all frequencies compared to observation-based spectra, while confirming the spectrum shape of recent observations. This also provides a prediction for observations of bright points with DKIST, which will achieve similar resolution and high sensitivity. We also find a granule size distribution in support of an observed two-population distribution, and we present results from tracking passive tracers, which show a similar power spectrum to that of bright points. Finally, we introduce a simplified, laminar model of granulation, with which we explore the roles of turbulence and of the properties of the granulation pattern in determining bright-point motion.

  7. Effects of nanosecond pulsed electric fields (nsPEFs) on the human fungal pathogen Candida albicans: an in vitro study

    Science.gov (United States)

    Guo, Jinsong; Dang, Jie; Wang, Kaile; Zhang, Jue; Fang, Jing

    2018-05-01

    Candida albicans is the leading human fungal pathogen that causes many life-threatening infections. Notably, the current clinical trial data indicate that Candida species shows the emerging resistance to anti-fungal drugs. The aim of this study was to evaluate the antifungal effects of nanosecond pulsed electric fields (nsPEFs) as a novel drug-free strategy in vitro. In this study, we investigated the inactivation and permeabilization effects of C. albicans under different nsPEFs exposure conditions (100 pulses, 100 ns in duration, intensities of 20, 40 kV cm‑1). Cell death was studied by annexin-V and propidium iodide staining. The changes of intracellular Ca2+ concentration after nsPEFs treatment were observed using Fluo-4 AM. Results show that C. albicans cells and biofilms were both obviously inhibited and destroyed after nsPEFs treatment. Furthermore, C. albicans cells were significantly permeabilized after nsPEFs treatment. Additionally, nsPEFs exposure led to a large amount of DNA and protein leakage. Importantly, nsPEFs induced a field strength-dependent apoptosis in C. albicans cells. Further experiments revealed that Ca2+ involved in nsPEFs induced C. albicans apoptosis. In conclusion, this proof-of-concept study provides a potential alternative drug-free strategy for killing pathogenic Candida species.

  8. Symposium on CIAE 600 kV ns pulse neutron generator

    International Nuclear Information System (INIS)

    Shen Guanren

    2001-01-01

    CIAE 600 kV ns Pulse Neutron Generator was built by China National Nuclear Corporation, which is an important facility mainly used for experimental researches of nuclear reactions induced by 14 MeV neutrons, experimental measurements of energy spectra of secondary neutrons and charged particles and macro-checking experiments of evaluated neutron database and dosimetry researches of neutrons and γ rays. It is the first home made one, but the fourth similar facility in the world. Six articles are included in this symposium. The articles details the general structure, radio frequency ion source, high current beam ns pulsed system, etc. The main technical problems resolved during development are discussed. And attentions and experiences in the generator adjustments are introduced

  9. Meissner effect in clean proximity-contact N-S double layer

    International Nuclear Information System (INIS)

    Higashitani, S.; Nagai, K.

    1994-01-01

    The Meissner effect in proximity-contact normal-superconducting (N-S) double layers is discussed in the clean limit. We obtain the quasi-classical Green's function linear in the vector potential such that satisfies the boundary conditions at the layer ends and also at the N-S interface with a finite reflection coefficient R. We find that, when there is no pairing interaction in the normal layer, the diamagnetic current in the normal layer is constant in space, consequently the magnetic field decreases linearly in the normal layer. To compare our theory with experiments, we calculate the screening length and find a good agreement in the temperature dependence with the experiments in the Au-Nb system. (orig.)

  10. Charged residues in the H-NS linker drive DNA binding and gene silencing in single cells.

    Science.gov (United States)

    Gao, Yunfeng; Foo, Yong Hwee; Winardhi, Ricksen S; Tang, Qingnan; Yan, Jie; Kenney, Linda J

    2017-11-21

    Nucleoid-associated proteins (NAPs) facilitate chromosome organization in bacteria, but the precise mechanism remains elusive. H-NS is a NAP that also plays a major role in silencing pathogen genes. We used genetics, single-particle tracking in live cells, superresolution microscopy, atomic force microscopy, and molecular dynamics simulations to examine H-NS/DNA interactions in single cells. We discovered a role for the unstructured linker region connecting the N-terminal oligomerization and C-terminal DNA binding domains. In the present work we demonstrate that linker amino acids promote engagement with DNA. In the absence of linker contacts, H-NS binding is significantly reduced, although no change in chromosome compaction is observed. H-NS is not localized to two distinct foci; rather, it is scattered all around the nucleoid. The linker makes DNA contacts that are required for gene silencing, while chromosome compaction does not appear to be an important H-NS function.

  11. Hepatitis C virus NS2 protein activates cellular cyclic AMP-dependent pathways

    International Nuclear Information System (INIS)

    Kim, Kyoung Mi; Kwon, Shi-Nae; Kang, Ju-Il; Lee, Song Hee; Jang, Sung Key; Ahn, Byung-Yoon; Kim, Yoon Ki

    2007-01-01

    Chronic infection of the hepatitis C virus (HCV) leads to liver cirrhosis and cancer. The mechanism leading to viral persistence and hepatocellular carcinoma, however, has not been fully understood. In this study, we show that the HCV infection activates cellular cAMP-dependent pathways. Expression of a luciferase reporter gene controlled by a basic promoter with the cAMP response element (CRE) was significantly elevated in human hepatoma Huh-7 cells infected with the HCV JFH1. Analysis with viral subgenomic replicons indicated that the HCV NS2 protein is responsible for the effect. Furthermore, the level of cellular transcripts whose stability is known to be regulated by cAMP was specifically reduced in cells harboring NS2-expressing replicons. These results allude to the HCV NS2 protein having a novel function of regulating cellular gene expression and proliferation through the cAMP-dependent pathway

  12. On the Relation Between Facular Bright Points and the Magnetic Field

    Science.gov (United States)

    Berger, Thomas; Shine, Richard; Tarbell, Theodore; Title, Alan; Scharmer, Goran

    1994-12-01

    Multi-spectral images of magnetic structures in the solar photosphere are presented. The images were obtained in the summers of 1993 and 1994 at the Swedish Solar Telescope on La Palma using the tunable birefringent Solar Optical Universal Polarimeter (SOUP filter), a 10 Angstroms wide interference filter tuned to 4304 Angstroms in the band head of the CH radical (the Fraunhofer G-band), and a 3 Angstroms wide interference filter centered on the Ca II--K absorption line. Three large format CCD cameras with shuttered exposures on the order of 10 msec and frame rates of up to 7 frames per second were used to create time series of both quiet and active region evolution. The full field--of--view is 60times 80 arcseconds (44times 58 Mm). With the best seeing, structures as small as 0.22 arcseconds (160 km) in diameter are clearly resolved. Post--processing of the images results in rigid coalignment of the image sets to an accuracy comparable to the spatial resolution. Facular bright points with mean diameters of 0.35 arcseconds (250 km) and elongated filaments with lengths on the order of arcseconds (10(3) km) are imaged with contrast values of up to 60 % by the G--band filter. Overlay of these images on contemporal Fe I 6302 Angstroms magnetograms and Ca II K images reveals that the bright points occur, without exception, on sites of magnetic flux through the photosphere. However, instances of concentrated and diffuse magnetic flux and Ca II K emission without associated bright points are common, leading to the conclusion that the presence of magnetic flux is a necessary but not sufficient condition for the occurence of resolvable facular bright points. Comparison of the G--band and continuum images shows a complex relation between structures in the two bandwidths: bright points exceeding 350 km in extent correspond to distinct bright structures in the continuum; smaller bright points show no clear relation to continuum structures. Size and contrast statistical cross

  13. ALMA Discovery of Solar Umbral Brightness Enhancement at λ = 3 mm

    Energy Technology Data Exchange (ETDEWEB)

    Iwai, Kazumasa [Institute for Space-Earth Environmental Research, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601 (Japan); Loukitcheva, Maria [Center for Solar-Terrestrial Research, New Jersey Institute of Technology, 323 Martin Luther King Boulevard, Newark, NJ 07102 (United States); Shimojo, Masumi [Chile Observatory, National Astronomical Observatory of Japan, Mitaka, Tokyo 181-8588 (Japan); Solanki, Sami K. [Max Planck Institute for Solar System Research, Justus-von-Liebig-Weg 3, D-37073 Göttingen (Germany); White, Stephen M., E-mail: k.iwai@isee.nagoya-u.ac.jp [Space Vehicles Directorate, Air Force Research Laboratory, Albuquerque, NM (United States)

    2017-06-01

    We report the discovery of a brightness enhancement in the center of a large sunspot umbra at a wavelength of 3 mm using the Atacama Large Millimeter/sub-millimeter Array (ALMA). Sunspots are among the most prominent features on the solar surface, but many of their aspects are surprisingly poorly understood. We analyzed a λ = 3 mm (100 GHz) mosaic image obtained by ALMA that includes a large sunspot within the active region AR12470, on 2015 December 16. The 3 mm map has a 300″ × 300″ field of view and 4.″9 × 2.″2 spatial resolution, which is the highest spatial resolution map of an entire sunspot in this frequency range. We find a gradient of 3 mm brightness from a high value in the outer penumbra to a low value in the inner penumbra/outer umbra. Within the inner umbra, there is a marked increase in 3 mm brightness temperature, which we call an umbral brightness enhancement. This enhanced emission corresponds to a temperature excess of 800 K relative to the surrounding inner penumbral region and coincides with excess brightness in the 1330 and 1400 Å slit-jaw images of the Interface Region Imaging Spectrograph ( IRIS ), adjacent to a partial lightbridge. This λ = 3 mm brightness enhancement may be an intrinsic feature of the sunspot umbra at chromospheric heights, such as a manifestation of umbral flashes, or it could be related to a coronal plume, since the brightness enhancement was coincident with the footpoint of a coronal loop observed at 171 Å.

  14. Hepatitis C Virus NS3/4A Protease Inhibitors: A Light at the End of the Tunnel

    Science.gov (United States)

    Chatel-Chaix, Laurent; Baril, Martin; Lamarre, Daniel

    2010-01-01

    Hepatitis C virus (HCV) infection is a serious and growing threat to human health. The current treatment provides limited efficacy and is poorly tolerated, highlighting the urgent medical need for novel therapeutics. The membrane-targeted NS3 protein in complex with the NS4A comprises a serine protease domain (NS3/4A protease) that is essential for viral polyprotein maturation and contributes to the evasion of the host innate antiviral immunity by HCV. Therefore, the NS3/4A protease represents an attractive target for drug discovery, which is tied in with the challenge to develop selective small-molecule inhibitors. A rational drug design approach, based on the discovery of N-terminus product inhibition, led to the identification of potent and orally bioavailable NS3 inhibitors that target the highly conserved protease active site. This review summarizes the NS3 protease inhibitors currently challenged in clinical trials as one of the most promising antiviral drug class, and possibly among the first anti-HCV agents to be approved for the treatment of HCV infection. PMID:21994705

  15. Hepatitis C Virus NS3/4A Protease Inhibitors: A Light at the End of the Tunnel

    Directory of Open Access Journals (Sweden)

    Laurent Chatel-Chaix

    2010-08-01

    Full Text Available Hepatitis C virus (HCV infection is a serious and growing threat to human health. The current treatment provides limited efficacy and is poorly tolerated, highlighting the urgent medical need for novel therapeutics. The membrane-targeted NS3 protein in complex with the NS4A comprises a serine protease domain (NS3/4A protease that is essential for viral polyprotein maturation and contributes to the evasion of the host innate antiviral immunity by HCV. Therefore, the NS3/4A protease represents an attractive target for drug discovery, which is tied in with the challenge to develop selective small-molecule inhibitors. A rational drug design approach, based on the discovery of N-terminus product inhibition, led to the identification of potent and orally bioavailable NS3 inhibitors that target the highly conserved protease active site. This review summarizes the NS3 protease inhibitors currently challenged in clinical trials as one of the most promising antiviral drug class, and possibly among the first anti-HCV agents to be approved for the treatment of HCV infection.

  16. Identification of human hnRNP C1/C2 as a dengue virus NS1-interacting protein

    International Nuclear Information System (INIS)

    Noisakran, Sansanee; Sengsai, Suchada; Thongboonkerd, Visith; Kanlaya, Rattiyaporn; Sinchaikul, Supachok; Chen, Shui-Tein; Puttikhunt, Chunya

    2008-01-01

    Dengue virus nonstructural protein 1 (NS1) is a key glycoprotein involved in the production of infectious virus and the pathogenesis of dengue diseases. Very little is known how NS1 interacts with host cellular proteins and functions in dengue virus-infected cells. This study aimed at identifying NS1-interacting host cellular proteins in dengue virus-infected cells by employing co-immunoprecipitation, two-dimensional gel electrophoresis, and mass spectrometry. Using lysates of dengue virus-infected human embryonic kidney cells (HEK 293T), immunoprecipitation with an anti-NS1 monoclonal antibody revealed eight isoforms of dengue virus NS1 and a 40-kDa protein, which was subsequently identified by quadrupole time-of-flight tandem mass spectrometry (Q-TOF MS/MS) as human heterogeneous nuclear ribonucleoprotein (hnRNP) C1/C2. Further investigation by co-immunoprecipitation and co-localization confirmed the association of hnRNP C1/C2 and dengue virus NS1 proteins in dengue virus-infected cells. Their interaction may have implications in virus replication and/or cellular responses favorable to survival of the virus in host cells

  17. Bright-Dark Mixed N-Soliton Solutions of the Multi-Component Mel'nikov System

    Science.gov (United States)

    Han, Zhong; Chen, Yong; Chen, Junchao

    2017-10-01

    By virtue of the Kadomtsev-Petviashvili (KP) hierarchy reduction technique, we construct the general bright-dark mixed N-soliton solution to the multi-component Mel'nikov system. This multi-component system comprised of multiple (say M) short-wave components and one long-wave component with all possible combinations of nonlinearities including all-positive, all-negative and mixed types. Firstly, the two-bright-one-dark (2-b-1-d) and one-bright-two-dark (1-b-2-d) mixed N-soliton solutions in short-wave components of the three-component Mel'nikov system are derived in detail. Then we extend our analysis to the M-component Mel'nikov system to obtain its general mixed N-soliton solution. The formula obtained unifies the all-bright, all-dark and bright-dark mixed N-soliton solutions. For the collision of two solitons, an asymptotic analysis shows that for an M-component Mel'nikov system with M ≥ 3, inelastic collision takes place, resulting in energy exchange among the short-wave components supporting bright solitons only if the bright solitons appear in at least two short-wave components. In contrast, the dark solitons in the short-wave components and the bright solitons in the long-wave component always undergo elastic collision which is only accompanied by a position shift.

  18. PBDE: Structure-Activity Studies for the Inhibition of Hepatitis C Virus NS3 Helicase

    Directory of Open Access Journals (Sweden)

    Kazi Abdus Salam

    2014-04-01

    Full Text Available The helicase portion of the hepatitis C virus nonstructural protein 3 (NS3 is considered one of the most validated targets for developing direct acting antiviral agents. We isolated polybrominated diphenyl ether (PBDE 1 from a marine sponge as an NS3 helicase inhibitor. In this study, we evaluated the inhibitory effects of PBDE (1 on the essential activities of NS3 protein such as RNA helicase, ATPase, and RNA binding activities. The structure-activity relationship analysis of PBDE (1 against the HCV ATPase revealed that the biphenyl ring, bromine, and phenolic hydroxyl group on the benzene backbone might be a basic scaffold for the inhibitory potency.

  19. HCV RNA traffic and association with NS5A in living cells

    Energy Technology Data Exchange (ETDEWEB)

    Fiches, Guillaume N.; Eyre, Nicholas S.; Aloia, Amanda L.; Van Der Hoek, Kylie [Department of Molecular and Cellular Biology, Research Centre for Infectious Diseases, University of Adelaide, Adelaide and Centre for Cancer Biology, SA Pathology, Adelaide, SA (Australia); Betz-Stablein, Brigit; Luciani, Fabio [Systems Immunology, School of Medical Sciences, University of New South Wales, Sydney, NSW (Australia); Chopra, Abha [Institute for Immunology and infectious diseases (IIID), Murdoch University, Perth, WA (Australia); Beard, Michael R., E-mail: michael.beard@adelaide.edu.au [Department of Molecular and Cellular Biology, Research Centre for Infectious Diseases, University of Adelaide, Adelaide and Centre for Cancer Biology, SA Pathology, Adelaide, SA (Australia)

    2016-06-15

    The spatiotemporal dynamics of Hepatitis C Virus (HCV) RNA localisation are poorly understood. To address this we engineered HCV genomes harbouring MS2 bacteriophage RNA stem-loops within the 3′-untranslated region to allow tracking of HCV RNA via specific interaction with a MS2-Coat-mCherry fusion protein. Despite the impact of these insertions on viral fitness, live imaging revealed that replication of tagged-HCV genomes induced specific redistribution of the mCherry-tagged-MS2-Coat protein to motile and static foci. Further analysis showed that HCV RNA was associated with NS5A in both static and motile structures while a subset of motile NS5A structures was devoid of HCV RNA. Further investigation of viral RNA traffic with respect to lipid droplets (LDs) revealed HCV RNA-positive structures in close association with LDs. These studies provide new insights into the dynamics of HCV RNA traffic with NS5A and LDs and provide a platform for future investigations of HCV replication and assembly. - Highlights: • HCV can tolerate can bacteriophage MS2 stem-loop insertions within the 3′ UTR. • MS2 stem-loop containing HCV genomes allow for real-time imaging of HCV RNA. • HCV RNA is both static and motile and associates with NS5A and lipid droplets.

  20. HCV RNA traffic and association with NS5A in living cells

    International Nuclear Information System (INIS)

    Fiches, Guillaume N.; Eyre, Nicholas S.; Aloia, Amanda L.; Van Der Hoek, Kylie; Betz-Stablein, Brigit; Luciani, Fabio; Chopra, Abha; Beard, Michael R.

    2016-01-01

    The spatiotemporal dynamics of Hepatitis C Virus (HCV) RNA localisation are poorly understood. To address this we engineered HCV genomes harbouring MS2 bacteriophage RNA stem-loops within the 3′-untranslated region to allow tracking of HCV RNA via specific interaction with a MS2-Coat-mCherry fusion protein. Despite the impact of these insertions on viral fitness, live imaging revealed that replication of tagged-HCV genomes induced specific redistribution of the mCherry-tagged-MS2-Coat protein to motile and static foci. Further analysis showed that HCV RNA was associated with NS5A in both static and motile structures while a subset of motile NS5A structures was devoid of HCV RNA. Further investigation of viral RNA traffic with respect to lipid droplets (LDs) revealed HCV RNA-positive structures in close association with LDs. These studies provide new insights into the dynamics of HCV RNA traffic with NS5A and LDs and provide a platform for future investigations of HCV replication and assembly. - Highlights: • HCV can tolerate can bacteriophage MS2 stem-loop insertions within the 3′ UTR. • MS2 stem-loop containing HCV genomes allow for real-time imaging of HCV RNA. • HCV RNA is both static and motile and associates with NS5A and lipid droplets.

  1. Comparative study and grouping of nonstructural (NS1)proteins of influenza A viruses by the method of oligopeptide mapping

    International Nuclear Information System (INIS)

    Sokolov, B.P.; Rudneva, I.A.; Zhdanov, V.M.

    1983-01-01

    Oligopeptide mapping of 35 S-methionine labeled non-stuctural (NS1) proteins of 23 influenza A virus strains showed the presence of both common and variable oligopeptides. Analysis of the oligopeptide maps revealed at least four groups of NS1 proteins. The first group includes NS1 proteins of several human H1N1 influenza viruses (that were designated as H0N1 according to the old classification). The second group is composed of NS1 proteins of H1N1 and H2N2 viruses. The third group includes NS1 proteins of H3N2 human influenza viruses. The fourth group is composed of NS1 proteins of five avian influenza viruses and an equine (H3N8) influenza virus. Two animal influenza viruses A/equi/Prague/56 (H7N7) and A/duck/England/56 (H11N6) contain NS1 proteins that belong to the second group. (Author)

  2. Bright galaxies in the Fornax cluster. Automated galaxy surface photometry: Pt. 7

    International Nuclear Information System (INIS)

    Disney, M.J.; Phillipps, S.; Davies, J.L.; Cawson, M.G.M.; Kibblewhite, E.J.

    1990-01-01

    We have determined surface-brightness profiles for all galaxies down to magnitude B = 16 in the central region of the Fornax cluster. Using existing redshift data, we have determined the distributions of surface brightness for both the whole sample and for cluster disc galaxies only. Although both distributions peak at extrapolated central surface brightness ∼ 21.7B mag/arcsec 2 (the canonical result), it is shown that they are, in fact, consistent with very broad distributions of disc central surface brightness once selection effects and the effects of bulge contamination of the profile are taken into account. (author)

  3. Identification of one B-cell epitope from NS1 protein of duck Tembusu virus with monoclonal antibodies.

    Directory of Open Access Journals (Sweden)

    Jinfeng Ti

    Full Text Available This study describes the identification of one linear B-cell epitope on TMUV NS1 protein with monoclonal antibody (mAb 3G2 by indirect enzyme-linked immunosorbent assay (ELISA. In this study, NS1 protein was expressed in prokaryotic expression system and purified. One mAb against NS1 protein was generated from Balb/c mice immunized with recombinant protein NS1. A set of 35 partially-overlapping polypeptides covering the entire NS1 protein was expressed with PGEX-6P-1 vector and screened with mAb 3G2. One polypeptide against the mAb was acquired and identified by indirect ELISA and western-blot. To map the epitope accurately, one or two amino acid residues were removed from the carboxy and amino terminal of polypeptide sequentially. A series of truncated oligopeptides were expressed and purified. The minimal determinant of the linear B cell epitope was recognized and identified with mAb 3G2. The accurate linear B-cell epitope was 269DEKEIV274 located in NS1 protein. Furthermore, sequence alignment showed that the epitope was highly conserved and specific among TMUV strains and other flavivirus respectively. The linear B-cell epitope of TMUV NS1 protein could benefit the development of new vaccines and diagnostic assays.

  4. Search for bright stars with infrared excess

    Energy Technology Data Exchange (ETDEWEB)

    Raharto, Moedji, E-mail: moedji@as.itb.ac.id [Astronomy Research Division, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Jl. Ganesha 10, Bandung 40132 (Indonesia)

    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.

  5. Diode lasers optimized in brightness for fiber laser pumping

    Science.gov (United States)

    Kelemen, M.; Gilly, J.; Friedmann, P.; Hilzensauer, S.; Ogrodowski, L.; Kissel, H.; Biesenbach, J.

    2018-02-01

    In diode laser applications for fiber laser pumping and fiber-coupled direct diode laser systems high brightness becomes essential in the last years. Fiber coupled modules benefit from continuous improvements of high-power diode lasers on chip level regarding output power, efficiency and beam characteristics resulting in record highbrightness values and increased pump power. To gain high brightness not only output power must be increased, but also near field widths and far field angles have to be below a certain value for higher power levels because brightness is proportional to output power divided by beam quality. While fast axis far fields typically show a current independent behaviour, for broadarea lasers far-fields in the slow axis suffer from a strong current and temperature dependence, limiting the brightness and therefore their use in fibre coupled modules. These limitations can be overcome by carefully optimizing chip temperature, thermal lensing and lateral mode structure by epitaxial and lateral resonator designs and processing. We present our latest results for InGaAs/AlGaAs broad-area single emitters with resonator lengths of 4mm emitting at 976nm and illustrate the improvements in beam quality over the last years. By optimizing the diode laser design a record value of the brightness for broad-area lasers with 4mm resonator length of 126 MW/cm2sr has been demonstrated with a maximum wall-plug efficiency of more than 70%. From these design also pump modules based on 9 mini-bars consisting of 5 emitters each have been realized with 360W pump power.

  6. Progress in extremely high brightness LED-based light sources

    Science.gov (United States)

    Hoelen, Christoph; Antonis, Piet; de Boer, Dick; Koole, Rolf; Kadijk, Simon; Li, Yun; Vanbroekhoven, Vincent; Van De Voorde, Patrick

    2017-09-01

    Although the maximum brightness of LEDs has been increasing continuously during the past decade, their luminance is still far from what is required for multiple applications that still rely on the high brightness of discharge lamps. In particular for high brightness applications with limited étendue, e.g. front projection, only very modest luminance values in the beam can be achieved with LEDs compared to systems based on discharge lamps or lasers. With dedicated architectures, phosphor-converted green LEDs for projection may achieve luminance values up to 200-300 Mnit. In this paper we report on the progress made in the development of light engines based on an elongated luminescent concentrator pumped by blue LEDs. This concept has recently been introduced to the market as ColorSpark High Lumen Density LED technology. These sources outperform the maximum brightness of LEDs by multiple factors. In LED front projection, green LEDs are the main limiting factor. With our green modules, we now have achieved peak luminance values of 2 Gnit, enabling LED-based projection systems with over 4000 ANSI lm. Extension of this concept to yellow and red light sources is presented. The light source efficiency has been increased considerably, reaching 45-60 lm/W for green under practical application conditions. The module architecture, beam shaping, and performance characteristics are reviewed, as well as system aspects. The performance increase, spectral range extensions, beam-shaping flexibility, and cost reductions realized with the new module architecture enable a breakthrough in LED-based projection systems and in a wide variety of other high brightness applications.

  7. Afternoon nap and bright light exposure improve cognitive flexibility post lunch.

    Directory of Open Access Journals (Sweden)

    Hichem Slama

    Full Text Available Beneficial effects of napping or bright light exposure on cognitive performance have been reported in participants exposed to sleep loss. Nonetheless, few studies investigated the effect of these potential countermeasures against the temporary drop in performance observed in mid-afternoon, and even less so on cognitive flexibility, a crucial component of executive functions. This study investigated the impact of either an afternoon nap or bright light exposure on post-prandial alterations in task switching performance in well-rested participants. Twenty-five healthy adults participated in two randomized experimental conditions, either wake versus nap (n=15, or bright light versus placebo (n=10. Participants were tested on a switching task three times (morning, post-lunch and late afternoon sessions. The interventions occurred prior to the post-lunch session. In the nap/wake condition, participants either stayed awake watching a 30-minute documentary or had the opportunity to take a nap for 30 minutes. In the bright light/placebo condition, participants watched a documentary under either bright blue light or dim orange light (placebo for 30 minutes. The switch cost estimates cognitive flexibility and measures task-switching efficiency. Increased switch cost scores indicate higher difficulties to switch between tasks. In both control conditions (wake or placebo, accuracy switch-cost score increased post lunch. Both interventions (nap or bright light elicited a decrease in accuracy switch-cost score post lunch, which was associated with diminished fatigue and decreased variability in vigilance. Additionally, there was a trend for a post-lunch benefit of bright light with a decreased latency switch-cost score. In the nap group, improvements in accuracy switch-cost score were associated with more NREM sleep stage N1. Thus, exposure to bright light during the post-lunch dip, a countermeasure easily applicable in daily life, results in similar

  8. Structural Basis for dsRNA Recognition by NS1 Protein of Influenza A Virus

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, A.; Wong, S; Yuan, Y

    2009-01-01

    Influenza A viruses are important human pathogens causing periodic pandemic threats. Nonstructural protein 1 (NS1) protein of influenza A virus (NS1A) shields the virus against host defense. Here, we report the crystal structure of NS1A RNA-binding domain (RBD) bound to a double-stranded RNA (dsRNA) at 1.7A. NS1A RBD forms a homodimer to recognize the major groove of A-form dsRNA in a length-independent mode by its conserved concave surface formed by dimeric anti-parallel alpha-helices. dsRNA is anchored by a pair of invariable arginines (Arg38) from both monomers by extensive hydrogen bonds. In accordance with the structural observation, isothermal titration calorimetry assay shows that the unique Arg38-Arg38 pair and two Arg35-Arg46 pairs are crucial for dsRNA binding, and that Ser42 and Thr49 are also important for dsRNA binding. Agrobacterium co-infiltration assay further supports that the unique Arg38 pair plays important roles in dsRNA binding in vivo.

  9. A search for RNA insertions and NS3 gene duplication in the genome of cytopathic isolates of bovine viral diarrhea virus

    Directory of Open Access Journals (Sweden)

    V.L. Quadros

    2006-07-01

    Full Text Available Calves born persistently infected with non-cytopathic bovine viral diarrhea virus (ncpBVDV frequently develop a fatal gastroenteric illness called mucosal disease. Both the original virus (ncpBVDV and an antigenically identical but cytopathic virus (cpBVDV can be isolated from animals affected by mucosal disease. Cytopathic BVDVs originate from their ncp counterparts by diverse genetic mechanisms, all leading to the expression of the non-structural polypeptide NS3 as a discrete protein. In contrast, ncpBVDVs express only the large precursor polypeptide, NS2-3, which contains the NS3 sequence within its carboxy-terminal half. We report here the investigation of the mechanism leading to NS3 expression in 41 cpBVDV isolates. An RT-PCR strategy was employed to detect RNA insertions within the NS2-3 gene and/or duplication of the NS3 gene, two common mechanisms of NS3 expression. RT-PCR amplification revealed insertions in the NS2-3 gene of three cp isolates, with the inserts being similar in size to that present in the cpBVDV NADL strain. Sequencing of one such insert revealed a 296-nucleotide sequence with a central core of 270 nucleotides coding for an amino acid sequence highly homologous (98% to the NADL insert, a sequence corresponding to part of the cellular J-Domain gene. One cpBVDV isolate contained a duplication of the NS3 gene downstream from the original locus. In contrast, no detectable NS2-3 insertions or NS3 gene duplications were observed in the genome of 37 cp isolates. These results demonstrate that processing of NS2-3 without bulk mRNA insertions or NS3 gene duplications seems to be a frequent mechanism leading to NS3 expression and BVDV cytopathology.

  10. Positioning system in wireless sensor networks using NS-2

    CSIR Research Space (South Africa)

    Abu-Mahfouz, Adnan M

    2012-10-01

    Full Text Available The practical difficulties of setting up a wireless sensor network (WSN) and analysing its performance have made simulation essential for the study of WSNs. The ns-2 network simulator is one of the most widely used tools by researchers...

  11. NS5A Sequence Heterogeneity and Mechanisms of Daclatasvir Resistance in Hepatitis C Virus Genotype 4 Infection.

    Science.gov (United States)

    Zhou, Nannan; Hernandez, Dennis; Ueland, Joseph; Yang, Xiaoyan; Yu, Fei; Sims, Karen; Yin, Philip D; McPhee, Fiona

    2016-01-15

    Daclatasvir is an NS5A inhibitor approved for treatment of infection due to hepatitis C virus (HCV) genotypes (GTs) 1-4. To support daclatasvir use in HCV genotype 4 infection, we examined a diverse genotype 4-infected population for HCV genotype 4 subtype prevalence, NS5A polymorphisms at residues associated with daclatasvir resistance (positions 28, 30, 31, or 93), and their effects on daclatasvir activity in vitro and clinically. We performed phylogenetic analysis of genotype 4 NS5A sequences from 186 clinical trial patients and 43 sequences from the European HCV database, and susceptibility analyses of NS5A polymorphisms and patient-derived NS5A sequences by using genotype 4 NS5A hybrid genotype 2a replicons. The clinical trial patients represented 14 genotype 4 subtypes; most prevalent were genotype 4a (55%) and genotype 4d (27%). Daclatasvir 50% effective concentrations for 10 patient-derived NS5A sequences representing diverse phylogenetic clusters were ≤0.080 nM. Most baseline sequences had ≥1 NS5A polymorphism at residues associated with daclatasvir resistance; however, only 3 patients (1.6%) had polymorphisms conferring ≥1000-fold daclatasvir resistance in vitro. Among 46 patients enrolled in daclatasvir trials, all 20 with baseline resistance polymorphisms achieved a sustained virologic response. Circulating genotype 4 subtypes are genetically diverse. Polymorphisms conferring high-level daclatasvir resistance in vitro are uncommon before therapy, and clinical data suggest that genotype 4 subtype and baseline polymorphisms have minimal impact on responses to daclatasvir-containing regimens. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.

  12. NS309 decreases rat detrusor smooth muscle membrane potential and phasic contractions by activating SK3 channels

    Science.gov (United States)

    Parajuli, Shankar P; Hristov, Kiril L; Soder, Rupal P; Kellett, Whitney F; Petkov, Georgi V

    2013-01-01

    Background and Purpose Overactive bladder (OAB) is often associated with abnormally increased detrusor smooth muscle (DSM) contractions. We used NS309, a selective and potent opener of the small or intermediate conductance Ca2+-activated K+ (SK or IK, respectively) channels, to evaluate how SK/IK channel activation modulates DSM function. Experimental Approach We employed single-cell RT-PCR, immunocytochemistry, whole cell patch-clamp in freshly isolated rat DSM cells and isometric tension recordings of isolated DSM strips to explore how the pharmacological activation of SK/IK channels with NS309 modulates DSM function. Key Results We detected SK3 but not SK1, SK2 or IK channels expression at both mRNA and protein levels by RT-PCR and immunocytochemistry in DSM single cells. NS309 (10 μM) significantly increased the whole cell SK currents and hyperpolarized DSM cell resting membrane potential. The NS309 hyperpolarizing effect was blocked by apamin, a selective SK channel inhibitor. NS309 inhibited the spontaneous phasic contraction amplitude, force, frequency, duration and tone of isolated DSM strips in a concentration-dependent manner. The inhibitory effect of NS309 on spontaneous phasic contractions was blocked by apamin but not by TRAM-34, indicating no functional role of the IK channels in rat DSM. NS309 also significantly inhibited the pharmacologically and electrical field stimulation-induced DSM contractions. Conclusions and Implications Our data reveal that SK3 channel is the main SK/IK subtype in rat DSM. Pharmacological activation of SK3 channels with NS309 decreases rat DSM cell excitability and contractility, suggesting that SK3 channels might be potential therapeutic targets to control OAB associated with detrusor overactivity. PMID:23145946

  13. Anticuerpos policlonales contra la proteína recombinante NS3 del virus del dengue

    Directory of Open Access Journals (Sweden)

    Liliana Morales

    2017-01-01

    Resultados. Los anticuerpos producidos fueron útiles en ensayos de Western blot e inmunofluorescencia y se reportó por primera vez un anticuerpo policlonal anti-NS3 que permitió la inmunoprecipitación de la proteína viral y la detecta con Western blot sin necesidad de inducir sobreexpresión de NS3 o de usar extractos de células marcados metabólicamente con radioisótopos. Conclusión. Las proteínas recombinantes expresadas y los anticuerpos producidos constituyen herramientas valiosas para estudiar procesos infecciosos del DENV que involucren a la proteína NS3 y evaluar pruebas dirigidas a interferir las funciones de esta proteína.

  14. Targeting Dengue Virus NS-3 Helicase by Ligand based Pharmacophore Modeling and Structure based Virtual Screening

    Science.gov (United States)

    Halim, Sobia A.; Khan, Shanza; Khan, Ajmal; Wadood, Abdul; Mabood, Fazal; Hussain, Javid; Al-Harrasi, Ahmed

    2017-10-01

    Dengue fever is an emerging public health concern, with several million viral infections occur annually, for which no effective therapy currently exist. Non-structural protein 3 (NS-3) Helicase encoded by the dengue virus (DENV) is considered as a potential drug target to design new and effective drugs against dengue. Helicase is involved in unwinding of dengue RNA. This study was conducted to design new NS-3 Helicase inhibitor by in silico ligand- and structure based approaches. Initially ligand-based pharmacophore model was generated that was used to screen a set of 1201474 compounds collected from ZINC Database. The compounds matched with the pharmacophore model were docked into the active site of NS-3 helicase. Based on docking scores and binding interactions, twenty five compounds are suggested to be potential inhibitors of NS3 Helicase. The pharmacokinetic properties of these hits were predicted. The selected hits revealed acceptable ADMET properties. This study identified potential inhibitors of NS-3 Helicase in silico, and can be helpful in the treatment of Dengue.

  15. Sensitive detection of novel Indian isolate of BTV 21 using ns1 gene based real-time PCR assay

    Directory of Open Access Journals (Sweden)

    Gaya Prasad

    2013-06-01

    Full Text Available Aim: The study was conducted to develop ns1 gene based sensitive real-time RT-PCR assay for diagnosis of India isolates of bluetongue virus (BTV. Materials and Methods: The BTV serotype 21 isolate (KMNO7 was isolated from Andhra Pradesh and propagated in BHK-21 cell line in our laboratory. The Nucleic acid (dsRNA of virus was extracted using Trizol method and cDNA was prepared using a standard protocol. The cDNA was allowed to ns1 gene based group specific PCR to confirm the isolate as BTV. The viral RNA was diluted 10 folds and the detection limit of ns1 gene based RT-PCR was determined. Finally the tenfold diluted viral RNA was subjected to real-time RT-PCR using ns1 gene primer and Taq man probe to standardized the reaction and determine the detection limit. Results: The ns1 gene based group specific PCR showed a single 366bp amplicon in agarose gel electrophoresis confirmed the sample as BTV. The ns1 gene RT-PCR using tenfold diluted viral RNA showed the detection limit of 70.0 fg in 1%agarose gel electrophoresis. The ns1 gene based real time RT-PCR was successfully standardized and the detection limit was found to be 7.0 fg. Conclusion: The ns1 gene based real-time RT-PCR was successfully standardized and it was found to be 10 times more sensitive than conventional RT-PCR. Key words: bluetongue, BTV21, RT-PCR, Real time RT-PCR, ns1 gene [Vet World 2013; 6(8.000: 554-557

  16. Hepatitis C Virus Particle Assembly Involves Phosphorylation of NS5A by the c-Abl Tyrosine Kinase.

    Science.gov (United States)

    Yamauchi, Shota; Takeuchi, Kenji; Chihara, Kazuyasu; Sun, Xuedong; Honjoh, Chisato; Yoshiki, Hatsumi; Hotta, Hak; Sada, Kiyonao

    2015-09-04

    Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is thought to regulate the replication of viral RNA and the assembly of virus particles in a serine/threonine phosphorylation-dependent manner. However, the host kinases that phosphorylate NS5A have not been fully identified. Here, we show that HCV particle assembly involves the phosphorylation of NS5A by the c-Abl tyrosine kinase. Pharmacological inhibition or knockdown of c-Abl reduces the production of infectious HCV (J6/JFH1) particles in Huh-7.5 cells without markedly affecting viral RNA translation and replication. NS5A is tyrosine-phosphorylated in HCV-infected cells, and this phosphorylation is also reduced by the knockdown of c-Abl. Mutational analysis reveals that NS5A tyrosine phosphorylation is dependent, at least in part, on Tyr(330) (Tyr(2306) in polyprotein numbering). Mutation of this residue to phenylalanine reduces the production of infectious HCV particles but does not affect the replication of the JFH1 subgenomic replicon. These findings suggest that c-Abl promotes HCV particle assembly by phosphorylating NS5A at Tyr(330). © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Detection of antibodies against porcine parvovirus nonstructural protein NS1 may distinguish between vaccinated and infected pigs

    DEFF Research Database (Denmark)

    Madsen, Eva Smedegaard; Madsen, Knud Gert; Nielsen, Jens

    1997-01-01

    The humoral antibody response against the nonstructural protein NS1 and the structural protein VP2 of porcine parvovirus (PPV) was evaluated by immuno-peroxidase test (IPT) and enzyme linked immune sorbent assay (ELISA) using recombinant PPV antigens. The coding sequence for NS1 and VP2...... was inserted into the baculovirus Autographa californica nuclear polyhedrosis virus (AcNPV) genome resulting in two recombinant baculoviruses AcNPV-NS1 and AcNPV-VP2, respectively. Sf9 cells (Spodoptora frugidiperda) inoculated with AcNPV-NS1 producing recombinant nonstructural protein (rNS1) and AcNPV-VP2...... producing recombinant virion protein (rVP2) were used in IPT and ELISA to analyse serum antibodies. Pigs vaccinated with an inactivated whole virus vaccine and experimentally infected pigs were studied. Significant titers against rVP2 were obtained in both vaccinated and infected pigs. Specific antibodies...

  18. A Proline-Rich N-Terminal Region of the Dengue Virus NS3 Is Crucial for Infectious Particle Production.

    Science.gov (United States)

    Gebhard, Leopoldo G; Iglesias, Néstor G; Byk, Laura A; Filomatori, Claudia V; De Maio, Federico A; Gamarnik, Andrea V

    2016-06-01

    Dengue virus is currently the most important insect-borne viral human pathogen. Viral nonstructural protein 3 (NS3) is a key component of the viral replication machinery that performs multiple functions during viral replication and participates in antiviral evasion. Using dengue virus infectious clones and reporter systems to dissect each step of the viral life cycle, we examined the requirements of different domains of NS3 on viral particle assembly. A thorough site-directed mutagenesis study based on solvent-accessible surface areas of NS3 revealed that, in addition to being essential for RNA replication, different domains of dengue virus NS3 are critically required for production of infectious viral particles. Unexpectedly, point mutations in the protease, interdomain linker, or helicase domain were sufficient to abolish infectious particle formation without affecting translation, polyprotein processing, or RNA replication. In particular, we identified a novel proline-rich N-terminal unstructured region of NS3 that contains several amino acid residues involved in infectious particle formation. We also showed a new role for the interdomain linker of NS3 in virion assembly. In conclusion, we present a comprehensive genetic map of novel NS3 determinants for viral particle assembly. Importantly, our results provide evidence of a central role of NS3 in the coordination of both dengue virus RNA replication and particle formation. Dengue virus is an important human pathogen, and its prominence is expanding globally; however, basic aspects of its biology are still unclear, hindering the development of effective therapeutic and prophylactic treatments. Little is known about the initial steps of dengue and other flavivirus particle assembly. This process involves a complex interplay between viral and cellular components, making it an attractive antiviral target. Unpredictably, we identified spatially separated regions of the large NS3 viral protein as determinants for

  19. Comprehensive Screening for Naturally Occurring Hepatitis C Virus Resistance to Direct-Acting Antivirals in the NS3, NS5A, and NS5B Genes in Worldwide Isolates of Viral Genotypes 1 to 6.

    Science.gov (United States)

    Patiño-Galindo, Juan Ángel; Salvatierra, Karina; González-Candelas, Fernando; López-Labrador, F Xavier

    2016-04-01

    There is no comprehensive study available on the natural hepatitis C virus (HCV) polymorphism in sites associated with resistance including all viral genotypes which may present variable susceptibilities to particular direct-acting antivirals (DAAs). This study aimed to analyze the frequencies, genetic barriers, and evolutionary histories of naturally occurring resistance-associated variants (RAVs) in the six main HCV genotypes. A comprehensive analysis of up to 103 RAVs was performed in 2,901, 2,216, and 1,344 HCV isolates for the NS3, NS5A, and NS5B genes, respectively. We report significant intergenotypic differences in the frequencies of natural RAVs for these three HCV genes. In addition, we found a low genetic barrier for the generation of new RAVs, irrespective of the viral genotype. Furthermore, in 1,126 HCV genomes, including sequences spanning the three genes, haplotype analysis revealed a remarkably high frequency of viruses carrying more than one natural RAV to DAAs (53% of HCV-1a, 28.5% of HCV-1b, 67.1% of HCV-6, and 100% of genotype 2, 3, 4, and 5 haplotypes). With the exception of HCV-1a, the most prevalent haplotypes showed RAVs in at least two different viral genes. Finally, evolutionary analyses revealed that, while most natural RAVs appeared recently, others have been efficiently transmitted over time and cluster in well-supported clades. In summary, and despite the observed high efficacy of DAA-based regimens, we show that naturally occurring RAVs are common in all HCV genotypes and that there is an overall low genetic barrier for the selection of resistance mutations. There is a need for natural DAA resistance profiling specific for each HCV genotype. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

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

    Directory of Open Access Journals (Sweden)

    R. Balajee

    2016-01-01

    Full Text Available 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Nangle, John [National Renewable Energy Lab. (NREL), Golden, CO (United States); Simon, Joseph [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    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.

  2. Differential responses of rabbit ventricular and atrial transient outward current (Ito) to the Ito modulator NS5806.

    Science.gov (United States)

    Cheng, Hongwei; Cannell, Mark B; Hancox, Jules C

    2017-03-01

    Transient outward potassium current (I to ) in the heart underlies phase 1 repolarization of cardiac action potentials and thereby affects excitation-contraction coupling. Small molecule activators of I to may therefore offer novel treatments for cardiac dysfunction, including heart failure and atrial fibrillation. NS5806 has been identified as a prototypic activator of canine I to This study investigated, for the first time, actions of NS5806 on rabbit atrial and ventricular I to Whole cell patch-clamp recordings of I to and action potentials were made at physiological temperature from rabbit ventricular and atrial myocytes. 10  μ mol/L NS5806 increased ventricular I to with a leftward shift in I to activation and accelerated restitution. At higher concentrations, stimulation of I to was followed by inhibition. The EC 50 for stimulation was 1.6  μ mol/L and inhibition had an IC 50 of 40.7  μ mol/L. NS5806 only inhibited atrial I to (IC 50 of 18  μ mol/L) and produced a modest leftward shifts in I to activation and inactivation, without an effect on restitution. 10  μ mol/L NS5806 shortened ventricular action potential duration (APD) at APD 20 -APD 90 but prolonged atrial APD NS5806 also reduced atrial AP upstroke and amplitude, consistent with an additional atrio-selective effect on Na + channels. In contrast to NS5806, flecainide, which discriminates between Kv1.4 and 4.x channels, produced similar levels of inhibition of ventricular and atrial I to NS5806 discriminates between rabbit ventricular and atrial I to, with mixed activator and inhibitor actions on the former and inhibitor actions against the later. NS5806 may be of significant value for pharmacological interrogation of regional differences in native cardiac I to . © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  3. Sensitive luminescent reporter viruses reveal appreciable release of hepatitis C virus NS5A protein into the extracellular environment.

    Science.gov (United States)

    Eyre, Nicholas S; Aloia, Amanda L; Joyce, Michael A; Chulanetra, Monrat; Tyrrell, D Lorne; Beard, Michael R

    2017-07-01

    The HCV NS5A protein is essential for viral RNA replication and virus particle assembly. To study the viral replication cycle and NS5A biology we generated an infectious HCV construct with a NanoLuciferase (NLuc) insertion within NS5A. Surprisingly, beyond its utility as a sensitive reporter of cytoplasmic viral RNA replication, we also observed strong luminescence in cell culture fluids. Further analysis using assembly-defective viruses and subgenomic replicons revealed that infectious virus production was not required for extracellular NS5A-NLuc activity but was associated with enrichment of extracellular NS5A-NLuc in intermediate-density fractions similar to those of exosomes and virus particles. Additionally, BRET analysis indicated that intracellular and extracellular forms of NS5A may adopt differing conformations. Importantly, infection studies using a human liver chimeric mouse model confirmed robust infection in vivo and ready detection of NLuc activity in serum. We hypothesise that the presence of NS5A in extracellular fluids contributes to HCV pathogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Synthesis and characterisation of NS13558: a new important tool for addressing KCa1.1 channel function ex vivo

    DEFF Research Database (Denmark)

    Bentzen, Bo Hjorth; Andersen, Rune Wederkinck; Olesen, Søren-Peter

    2009-01-01

    Pharmacological activation of the large-conductance Ca(2+)-activated K(+) channel (KCa1.1) in the cardiac inner mitochondrial membrane has been found to protect the heart against ischemia reperfusion injuries. However, there are concerns about the selectivity of the pharmacological tools used...... to modulate the channel. Here, we address this issue by synthesising a methylated analogue of the tool KCa1.1 channel activator NS11021. The compound (NS13558) is designed as a structurally closely related and biologically inactive analogue of NS11021. NS13558 did not elicit any significant opening of cloned...... human KCa1.1 channels, but maintained comparable biological activity towards other cardiac ion channels as compared to NS11021. In isolated perfused rat hearts subjected to ischemia-reperfusion, infarct size was reduced from 29% in control to 7% in NS11021 treated hearts. In comparison, the inactive...

  5. Ebselen inhibits hepatitis C virus NS3 helicase binding to nucleic acid and prevents viral replication.

    Science.gov (United States)

    Mukherjee, Sourav; Weiner, Warren S; Schroeder, Chad E; Simpson, Denise S; Hanson, Alicia M; Sweeney, Noreena L; Marvin, Rachel K; Ndjomou, Jean; Kolli, Rajesh; Isailovic, Dragan; Schoenen, Frank J; Frick, David N

    2014-10-17

    The hepatitis C virus (HCV) nonstructural protein 3 (NS3) is both a protease, which cleaves viral and host proteins, and a helicase that separates nucleic acid strands, using ATP hydrolysis to fuel the reaction. Many antiviral drugs, and compounds in clinical trials, target the NS3 protease, but few helicase inhibitors that function as antivirals have been reported. This study focuses on the analysis of the mechanism by which ebselen (2-phenyl-1,2-benzisoselenazol-3-one), a compound previously shown to be a HCV antiviral agent, inhibits the NS3 helicase. Ebselen inhibited the abilities of NS3 to unwind nucleic acids, to bind nucleic acids, and to hydrolyze ATP, and about 1 μM ebselen was sufficient to inhibit each of these activities by 50%. However, ebselen had no effect on the activity of the NS3 protease, even at 100 times higher ebselen concentrations. At concentrations below 10 μM, the ability of ebselen to inhibit HCV helicase was reversible, but prolonged incubation of HCV helicase with higher ebselen concentrations led to irreversible inhibition and the formation of covalent adducts between ebselen and all 14 cysteines present in HCV helicase. Ebselen analogues with sulfur replacing the selenium were just as potent HCV helicase inhibitors as ebselen, but the length of the linker between the phenyl and benzisoselenazol rings was critical. Modifications of the phenyl ring also affected compound potency over 30-fold, and ebselen was a far more potent helicase inhibitor than other, structurally unrelated, thiol-modifying agents. Ebselen analogues were also more effective antiviral agents, and they were less toxic to hepatocytes than ebselen. Although the above structure-activity relationship studies suggest that ebselen targets a specific site on NS3, we were unable to confirm binding to either the NS3 ATP binding site or nucleic acid binding cleft by examining the effects of ebselen on NS3 proteins lacking key cysteines.

  6. 2D non-separable linear canonical transform (2D-NS-LCT) based cryptography

    Science.gov (United States)

    Zhao, Liang; Muniraj, Inbarasan; Healy, John J.; Malallah, Ra'ed; Cui, Xiao-Guang; Ryle, James P.; Sheridan, John T.

    2017-05-01

    The 2D non-separable linear canonical transform (2D-NS-LCT) can describe a variety of paraxial optical systems. Digital algorithms to numerically evaluate the 2D-NS-LCTs are not only important in modeling the light field propagations but also of interest in various signal processing based applications, for instance optical encryption. Therefore, in this paper, for the first time, a 2D-NS-LCT based optical Double-random- Phase-Encryption (DRPE) system is proposed which offers encrypting information in multiple degrees of freedom. Compared with the traditional systems, i.e. (i) Fourier transform (FT); (ii) Fresnel transform (FST); (iii) Fractional Fourier transform (FRT); and (iv) Linear Canonical transform (LCT), based DRPE systems, the proposed system is more secure and robust as it encrypts the data with more degrees of freedom with an augmented key-space.

  7. Production of a Recombinant Dengue Virus 2 NS5 Protein and Potential Use as a Vaccine Antigen.

    Science.gov (United States)

    Alves, Rúbens Prince Dos Santos; Pereira, Lennon Ramos; Fabris, Denicar Lina Nascimento; Salvador, Felipe Scassi; Santos, Robert Andreata; Zanotto, Paolo Marinho de Andrade; Romano, Camila Malta; Amorim, Jaime Henrique; Ferreira, Luís Carlos de Souza

    2016-06-01

    Dengue fever is caused by any of the four known dengue virus serotypes (DENV1 to DENV4) that affect millions of people worldwide, causing a significant number of deaths. There are vaccines based on chimeric viruses, but they still are not in clinical use. Anti-DENV vaccine strategies based on nonstructural proteins are promising alternatives to those based on whole virus or structural proteins. The DENV nonstructural protein 5 (NS5) is the main target of anti-DENV T cell-based immune responses in humans. In this study, we purified a soluble recombinant form of DENV2 NS5 expressed in Escherichia coli at large amounts and high purity after optimization of expression conditions and purification steps. The purified DENV2 NS5 was recognized by serum from DENV1-, DENV2-, DENV3-, or DENV4-infected patients in an epitope-conformation-dependent manner. In addition, immunization of BALB/c mice with NS5 induced high levels of NS5-specific antibodies and expansion of gamma interferon- and tumor necrosis factor alpha-producing T cells. Moreover, mice immunized with purified NS5 were partially protected from lethal challenges with the DENV2 NGC strain and with a clinical isolate (JHA1). These results indicate that the recombinant NS5 protein preserves immunological determinants of the native protein and is a promising vaccine antigen capable of inducing protective immune responses. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  8. Structural insight and flexible features of NS5 proteins from all four serotypes of Dengue virus in solution

    Energy Technology Data Exchange (ETDEWEB)

    Saw, Wuan Geok; Tria, Giancarlo; Grüber, Ardina; Subramanian Manimekalai, Malathy Sony; Zhao, Yongqian; Chandramohan, Arun; Srinivasan Anand, Ganesh; Matsui, Tsutomu; Weiss, Thomas M.; Vasudevan, Subhash G.; Grüber, Gerhard

    2015-10-31

    Infection by the four serotypes ofDengue virus(DENV-1 to DENV-4) causes an important arthropod-borne viral disease in humans. The multifunctional DENV nonstructural protein 5 (NS5) is essential for capping and replication of the viral RNA and harbours a methyltransferase (MTase) domain and an RNA-dependent RNA polymerase (RdRp) domain. In this study, insights into the overall structure and flexibility of the entire NS5 of all fourDengue virusserotypes in solution are presented for the first time. The solution models derived revealed an arrangement of the full-length NS5 (NS5FL) proteins with the MTase domain positioned at the top of the RdRP domain. The DENV-1 to DENV-4 NS5 forms are elongated and flexible in solution, with DENV-4 NS5 being more compact relative to NS5 from DENV-1, DENV-2 and DENV-3. Solution studies of the individual MTase and RdRp domains show the compactness of the RdRp domain as well as the contribution of the MTase domain and the ten-residue linker region to the flexibility of the entire NS5. Swapping the ten-residue linker between DENV-4 NS5FL and DENV-3 NS5FL demonstrated its importance in MTase–RdRp communication and in concerted interaction with viral and host proteins, as probed by amide hydrogen/deuterium mass spectrometry. Conformational alterations owing to RNA binding are presented.

  9. Dark and bright vortex solitons in electromagnetically induced transparent media

    International Nuclear Information System (INIS)

    Wu Xuan; Xie Xiaotao; Yang Xiaoxue

    2006-01-01

    We show that dark and bright vortex solitons can exist in three-state electromagnetically induced transparent media under some appropriate conditions. We also analyse the stability of the dark and bright vortex solitons. This work may provide other research opportunities in nonlinear optical experiments and may result in a substantial impact on technology

  10. SPS Injection and Beam Quality for LHC Heavy Ions With 150 ns Kicker Rise Time

    CERN Document Server

    Goddard, Brennan; Ducimetière, Laurent; Kotzian, Gerd; Uythoven, Jan; Velotti, Francesco

    2016-01-01

    As part of the LHC Injectors Upgrade project for LHC heavy ions, the SPS injection kicker system rise time needs reduction below its present 225 ns. One technically challenging option under consideration is the addition of fast Pulse Forming Lines in parallel to the existing Pulse Forming Networks for the 12 kicker magnets MKP-S, targeting a system field rise time of 100 ns. An alternative option is to optimise the system to approach the existing individual magnet field rise time (2-98%) of 150 ns. This would still significantly increase the number of colliding bunches in LHC while minimising the cost and effort of the system upgrade. The observed characteristics of the present system are described, compared to the expected system rise time, together with results of simulations and measurements with 175 and 150 ns injection batch spacing. The expected beam quality at injection into LHC is quantified, with the emittance growth and simulated tail population taking into account expected jitter and synchronisatio...

  11. Robust brightness enhancement across a luminance range of the glare illusion.

    Science.gov (United States)

    Tamura, Hideki; Nakauchi, Shigeki; Koida, Kowa

    2016-01-01

    The glare illusion refers to brightness enhancement and the perception of a self-luminous appearance that occurs when a central region is surrounded by a luminance gradient. The center region appears to be a light source, with its light dispersing into the surrounding region. If the luminous edge is critical for generating the illusion, modulating the perceived luminance of the image, and switching its appearance from luminous to nonluminous, would have a strong impact on lightness and brightness estimation. Here, we quantified the illusion in two ways, by assessing brightness enhancement and examining whether the center region appeared luminous. Thus, we could determine whether the two effects occurred jointly or independently. We examined a wide luminance range of center regions, from 0 to 200% relative to background. Brightness enhancement in the illusion was observed for a wide range of luminances (20% to 200% relative to background), while a luminous-white appearance was observed when the center region luminance was 145% of the background. These results exclude the possibility that brightness enhancement occurs because the stimuli appear self-luminous. We suggest that restoring the original image intensity precedes the perceptual process of lightness estimation.

  12. SKY BRIGHTNESS AND TRANSPARENCY IN THE i-BAND AT DOME A, ANTARCTICA

    International Nuclear Information System (INIS)

    Zou Hu; Zhou Xu; Jiang Zhaoji; Hu Jingyao; Ma Jun; Ashley, M. C. B.; Luong-Van, D. M.; Storey, J. W. V.; Cui Xiangqun; Feng Longlong; Gong Xuefei; Kulesa, C. A.; Lawrence, J. S.; Liu Genrong; Moore, A. M.; Pennypacker, C. R.; Travouillon, T.; Qin Weijia; Sun Bo; Shang Zhaohui

    2010-01-01

    The i-band observing conditions at Dome A on the Antarctic plateau have been investigated using data acquired during 2008 with the Chinese Small Telescope Array. The sky brightness, variations in atmospheric transparency, cloud cover, and the presence of aurorae are obtained from these images. The median sky brightness of moonless clear nights is 20.5 mag arcsec -2 in the SDSS i band at the south celestial pole (which includes a contribution of about 0.06 mag from diffuse Galactic light). The median over all Moon phases in the Antarctic winter is about 19.8 mag arcsec -2 . There were no thick clouds in 2008. We model contributions of the Sun and the Moon to the sky background to obtain the relationship between the sky brightness and transparency. Aurorae are identified by comparing the observed sky brightness to the sky brightness expected from this model. About 2% of the images are affected by relatively strong aurorae.

  13. Leonids 2017 from Norway – A bright surprise!

    Science.gov (United States)

    Gaarder, K.

    2018-01-01

    I am very pleased to have been able to observe near maximum activity of the Leonids, and clearly witnessed the unequal mass distribution during these hours. A lot of bright Leonids were seen, followed by a short period of high activity of fainter meteors, before a sharp drop in activity. The Leonids is undoubtedly a shower to watch closely, with its many variations in activity level and magnitude distribution. I already look forward to observing the next years’ display, hopefully under a dark and clear sky, filled with bright meteors!

  14. A Global Interactome Map of the Dengue Virus NS1 Identifies Virus Restriction and Dependency Host Factors

    Directory of Open Access Journals (Sweden)

    Mohamed Lamine Hafirassou

    2017-12-01

    Full Text Available Dengue virus (DENV infections cause the most prevalent mosquito-borne viral disease worldwide, for which no therapies are available. DENV encodes seven non-structural (NS proteins that co-assemble and recruit poorly characterized host factors to form the DENV replication complex essential for viral infection. Here, we provide a global proteomic analysis of the human host factors that interact with the DENV NS1 protein. Combined with a functional RNAi screen, this study reveals a comprehensive network of host cellular processes involved in DENV infection and identifies DENV host restriction and dependency factors. We highlight an important role of RACK1 and the chaperonin TRiC (CCT and oligosaccharyltransferase (OST complexes during DENV replication. We further show that the OST complex mediates NS1 and NS4B glycosylation, and pharmacological inhibition of its N-glycosylation function strongly impairs DENV infection. In conclusion, our study provides a global interactome of the DENV NS1 and identifies host factors targetable for antiviral therapies.

  15. Dynamic Nucleolar Targeting of Dengue Virus Polymerase NS5 in Response to Extracellular pH

    Science.gov (United States)

    Fraser, Johanna E.; Rawlinson, Stephen M.; Heaton, Steven M.

    2016-01-01

    ABSTRACT The nucleolar subcompartment of the nucleus is increasingly recognized as an important target of RNA viruses. Here we document for the first time the ability of dengue virus (DENV) polymerase, nonstructural protein 5 (NS5), to accumulate within the nucleolus of infected cells and to target green fluorescent protein (GFP) to the nucleolus of live transfected cells. Intriguingly, NS5 exchange between the nucleus and nucleolus is dynamically modulated by extracellular pH, responding rapidly and reversibly to pH change, in contrast to GFP alone or other nucleolar and non-nucleolar targeted protein controls. The minimal pH-sensitive nucleolar targeting region (pHNTR), sufficient to target GFP to the nucleolus in a pH-sensitive fashion, was mapped to NS5 residues 1 to 244, with mutation of key hydrophobic residues, Leu-165, Leu-167, and Val-168, abolishing pHNTR function in NS5-transfected cells, and severely attenuating DENV growth in infected cells. This is the first report of a viral protein whose nucleolar targeting ability is rapidly modulated by extracellular stimuli, suggesting that DENV has the ability to detect and respond dynamically to the extracellular environment. IMPORTANCE Infections by dengue virus (DENV) threaten 40% of the world's population yet there is no approved vaccine or antiviral therapeutic to treat infections. Understanding the molecular details that govern effective viral replication is key for the development of novel antiviral strategies. Here, we describe for the first time dynamic trafficking of DENV nonstructural protein 5 (NS5) to the subnuclear compartment, the nucleolus. We demonstrate that NS5's targeting to the nucleolus occurs in response to acidic pH, identify the key amino acid residues within NS5 that are responsible, and demonstrate that their mutation severely impairs production of infectious DENV. Overall, this study identifies a unique subcellular trafficking event and suggests that DENV is able to detect and respond

  16. Low-Surface-Brightness Galaxies: Hidden Galaxies Revealed

    Science.gov (United States)

    Bothun, G.; Impey, C.; McGaugh, S.

    1997-07-01

    In twenty years, low surface brightness (LSB) galaxies have evolved from being an idiosyncratic notion to being one of the major baryonic repositories in the Universe. The story of their discovery and the characterization of their properties is told here. Their recovery from the noise of the night sky background is a strong testament to the severity of surface brightness selection effects. LSB galaxies have a number of remarkable properties which distinguish them from the more familiar Hubble Sequence of spirals. The two most important are 1) they evolve at a significantly slower rate and may well experience star formation outside of the molecular cloud environment, 2) they are embedded in dark matter halos which are of lower density and more extended than the halos around high surface brightness (HSB) disk galaxies. Compared to HSB disks, LSB disks are strongly dark matter dominated at all radii and show a systematic increase in $M/L$ with decreasing central surface brightness. In addition, the recognition that large numbers of LSB galaxies actually exist has changed the form of the galaxy luminosity function and has clearly increased the space density of galaxies at z =0. Recent CCD surveys have uncovered a population of red LSB disks that may be related to the excess of faint blue galaxies detected at moderate redshifts. LSB galaxies offer us a new window into galaxy evolution and formation which is every bit as important as those processes which have produced easy to detect galaxies. Indeed, the apparent youth of some LSB galaxies suggest that galaxy formation is a greatly extended process. While the discovery of LSB galaxies have lead to new insights, it remains unwise to presume that we now have a representative sample which encompasses all galaxy types and forms. (SECTION: Invited Review Paper)

  17. Evaluation of the Genetic Response of U937 and Jurkat Cells to 10-Nanosecond Electrical Pulses (nsEP.

    Directory of Open Access Journals (Sweden)

    Caleb C Roth

    Full Text Available Nanosecond electrical pulse (nsEP exposure activates signaling pathways, produces oxidative stress, stimulates hormone secretion, causes cell swelling and induces apoptotic and necrotic death. The underlying biophysical connection(s between these diverse cellular reactions and nsEP has yet to be elucidated. Using global genetic analysis, we evaluated how two commonly studied cell types, U937 and Jurkat, respond to nsEP exposure. We hypothesized that by studying the genetic response of the cells following exposure, we would gain direct insight into the stresses experienced by the cell and in turn better understand the biophysical interaction taking place during the exposure. Using Ingenuity Systems software, we found genes associated with cell growth, movement and development to be significantly up-regulated in both cell types 4 h post exposure to nsEP. In agreement with our hypothesis, we also found that both cell lines exhibit significant biological changes consistent with mechanical stress induction. These results advance nsEP research by providing strong evidence that the interaction of nsEPs with cells involves mechanical stress.

  18. The Bright Universe Cosmology

    International Nuclear Information System (INIS)

    Surdin, M.

    1980-01-01

    It is shown that viewed from the 'outside', our universe is a black hole. Hence the 'inside' cosmology considered is termed as the Bright Universe Cosmology. The model proposed avoids the singularities of cosmologies of the Big Bang variety, it gives a good account of the redshifts, the cosmic background radiation, the number counts; it also gives a satisfactory explanation of the 'large numbers coincidence' and of the variation in time of fundamental constants. (Auth.)

  19. Amino acids 16-275 of minute virus of mice NS1 include a domain that specifically binds (ACCA)2-3-containing DNA.

    Science.gov (United States)

    Mouw, M; Pintel, D J

    1998-11-10

    GST-NS1 purified from Escherichia coli and insect cells binds double-strand DNA in an (ACCA)2-3-dependent fashion under similar ionic conditions, independent of the presence of anti-NS1 antisera or exogenously supplied ATP and interacts with single-strand DNA and RNA in a sequence-independent manner. An amino-terminal domain (amino acids 1-275) of NS1 [GST-NS1(1-275)], representing 41% of the full-length NS1 molecule, includes a domain that binds double-strand DNA in a sequence-specific manner at levels comparable to full-length GST-NS1, as well as single-strand DNA and RNA in a sequence-independent manner. The deletion of 15 additional amino-terminal amino acids yielded a molecule [GST-NS1(1-275)] that maintained (ACCA)2-3-specific double-strand DNA binding; however, this molecule was more sensitive to increasing ionic conditions than full-length GST-NS1 and GST-NS1(1-275) and could not be demonstrated to bind single-strand nucleic acids. A quantitative filter binding assay showed that E. coli- and baculovirus-expressed GST-NS1 and E. coli GST-NS1(1-275) specifically bound double-strand DNA with similar equilibrium kinetics [as measured by their apparent equilibrium DNA binding constants (KD)], whereas GST-NS1(16-275) bound 4- to 8-fold less well. Copyright 1998 Academic Press.

  20. Bright intracranial lesions on diffusion-weighted images: a pictorial review

    International Nuclear Information System (INIS)

    Choi, Dae Seob

    2006-01-01

    Diffusion-weighted imaging (DWI) is a MR sequence that is used to evaluate the rate of microscopic water diffusion within the tissues. The ability to measure the rate of water diffusion is important because this is frequently altered in various disease processes. Generally, the lesions with restricted water diffusion show bright intensity on DWI, but the lesions without restricted water diffusion can also show bright intensity on DWI, which is called the 'T2 shine through effect'. With DWI, we can sensitively detect hyperacute infarction (within 6 hours after symptom onset), and this is difficult to detect with using CT and the conventional MR sequenced. The acute and subacute lesions of hypoxic-ischemic encephalopathy and carbon monoxide intoxication also show bright intensity on the DWI. The other diseases that can show bright intensity on the DWI include acute and subacute diffuse axonal injury lesion, hyperacute and late subacute hematomas, cerebral abscess, subdural empyema, acute herpes encephalitis, various tumors and such degenerative and demyelinating diseases as multiple sclerosis, posterior reversible encephalopathy syndrome, Wilson's disease and Wernicke's encephalopathy

  1. Bright intracranial lesions on diffusion-weighted images: a pictorial review

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Dae Seob [Gyeongsang National University College of Medicine, Jinju (Korea, Republic of)

    2006-06-15

    Diffusion-weighted imaging (DWI) is a MR sequence that is used to evaluate the rate of microscopic water diffusion within the tissues. The ability to measure the rate of water diffusion is important because this is frequently altered in various disease processes. Generally, the lesions with restricted water diffusion show bright intensity on DWI, but the lesions without restricted water diffusion can also show bright intensity on DWI, which is called the 'T2 shine through effect'. With DWI, we can sensitively detect hyperacute infarction (within 6 hours after symptom onset), and this is difficult to detect with using CT and the conventional MR sequenced. The acute and subacute lesions of hypoxic-ischemic encephalopathy and carbon monoxide intoxication also show bright intensity on the DWI. The other diseases that can show bright intensity on the DWI include acute and subacute diffuse axonal injury lesion, hyperacute and late subacute hematomas, cerebral abscess, subdural empyema, acute herpes encephalitis, various tumors and such degenerative and demyelinating diseases as multiple sclerosis, posterior reversible encephalopathy syndrome, Wilson's disease and Wernicke's encephalopathy.

  2. HCV Core Residues Critical for Infectivity Are Also Involved in Core-NS5A Complex Formation

    Science.gov (United States)

    Gawlik, Katarzyna; Baugh, James; Chatterji, Udayan; Lim, Precious J.; Bobardt, Michael D.; Gallay, Philippe A.

    2014-01-01

    Hepatitis C virus (HCV) infection is a major cause of liver disease. The molecular machinery of HCV assembly and particle release remains obscure. A better understanding of the assembly events might reveal new potential antiviral strategies. It was suggested that the nonstructural protein 5A (NS5A), an attractive recent drug target, participates in the production of infectious particles as a result of its interaction with the HCV core protein. However, prior to the present study, the NS5A-binding site in the viral core remained unknown. We found that the D1 domain of core contains the NS5A-binding site with the strongest interacting capacity in the basic P38-K74 cluster. We also demonstrated that the N-terminal basic residues of core at positions 50, 51, 59 and 62 were required for NS5A binding. Analysis of all substitution combinations of R50A, K51A, R59A, and R62A, in the context of the HCVcc system, showed that single, double, triple, and quadruple mutants were fully competent for viral RNA replication, but deficient in secretion of viral particles. Furthermore, we found that the extracellular and intracellular infectivity of all the mutants was abolished, suggesting a defect in the formation of infectious particles. Importantly, we showed that the interaction between the single and quadruple core mutants and NS5A was impaired in cells expressing full-length HCV genome. Interestingly, mutations of the four basic residues of core did not alter the association of core or NS5A with lipid droplets. This study showed for the first time that basic residues in the D1 domain of core that are critical for the formation of infectious extracellular and intracellular particles also play a role in core-NS5A interactions. PMID:24533158

  3. Human Parvovirus B19 NS1 Protein Aggravates Liver Injury in NZB/W F1 Mice

    Science.gov (United States)

    Tsai, Chun-Chou; Chiu, Chun-Ching; Hsu, Jeng-Dong; Hsu, Huai-Sheng; Tzang, Bor-Show; Hsu, Tsai-Ching

    2013-01-01

    Human parvovirus B19 (B19) has been associated with a variety of diseases. However, the influence of B19 viral proteins on hepatic injury in SLE is still obscure. To elucidate the effects of B19 viral proteins on livers in SLE, recombinant B19 NS1, VP1u or VP2 proteins were injected subcutaneously into NZB/W F1 mice, respectively. Significant expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were detected in NZB/W F1 mice receiving B19 NS1 as compared to those mice receiving PBS. Markedly hepatocyte disarray and lymphocyte infiltration were observed in livers from NZB/WF 1 mice receiving B19 NS1 as compared to those mice receiving PBS. Additionally, significant increases of Tumor Necrosis Factor –α (TNF-α), TNF-α receptor, IκB kinase –α (IKK-α), nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (IκB) and nuclear factor-kappa B (NF-κB) were detected in livers from NZB/W F1 mice receiving B19 NS1 as compared to those mice receiving PBS. Accordingly, significant increases of matrix metalloproteinase-9 (MMP9) and U-plasminogen activator (uPA) were also detected in livers from NZB/W F1 mice receiving B19 NS1 as compared to those mice receiving PBS. Contrarily, no significant variation on livers from NZB/W F1 mice receiving B19 VP1u or VP2 was observed as compared to those mice receiving PBS. These findings firstly demonstrated the aggravated effects of B19 NS1 but not VP1u or VP2 protein on hepatic injury and provide a clue in understanding the role of B19 NS1 on hepatic injury in SLE. PMID:23555760

  4. Guía del investigador americanista: La Universidad de Tulane en Nueva Orleáns

    OpenAIRE

    Betancourt, Margarita Vargas

    2009-01-01

    Introducción La Universidad de Tulane se encuentra en una de las ciudades más interesantes de Estados Unidos, y probablemente, una de las ciudades norteamericanas que más se parece a las ciudades de Latino América: Nueva Orleáns. Copyright © (fotografías de Daniela Castillo y James Huck) Ejemplo de ello es que Nueva Orleáns tiene un centro histórico (el barrio francés) y una plaza o zócalo (Jackson Square). Antes de que Napoleón vendiera Luisiana a Thomas Jefferson en 1803, Nueva Orleáns fue...

  5. Processing quality of NS soybean varieties

    Directory of Open Access Journals (Sweden)

    Đorđević Vuk

    2012-01-01

    Full Text Available Current NS soybean varieties are of satisfactory technological quality, and also significant technological diversity. Varieties Triumf and Venera possess higher oil content. Variety Sava has a balanced oil and protein content, and can be used for obtaining different soy products. Variety Rubin has the highest protein content and is suitable for new high protein products. Estimated processing value is a good parameter to describe the processing quality of soybeans. Based on several years and spatial analysis, it is possible to separate the geographic regions with prevailing favourable conditions for obtaining higher protein or oil content.

  6. A thiophene-modified screen printed electrode for detection of dengue virus NS1 protein.

    Science.gov (United States)

    Silva, M M S; Dias, A C M S; Cordeiro, M T; Marques, E; Goulart, M O F; Dutra, R F

    2014-10-01

    A thiophene-modified screen printed electrode (SPE) for detection of the Dengue virus non-structural protein 1 (NS1), an important marker for acute phase diagnosis, is described. A sulfur-containing heterocyclic compound, the thiophene was incorporated to a carbon ink to prepare reproducible screen printed electrodes. After cured, the thiophene SPE was coated by gold nanoparticles conjugated to Protein A to form a nanostrutured surface. The Anti-NS1 antibodies immobilized via their Fc portions via Protein A, leaving their antigen specific sites free circumventing the problem of a random antibodies immobilization. Amperometric responses to the NS1 protein of dengue virus were obtained by cyclic voltammetries performed in presence of ferrocyanide/ferricyanide as redox probe. The calibration curve of immunosensor showed a linear response from 0.04 µg mL(-1) to 0.6 µg mL(-1) of NS1 with a good linear correlation (r=0.991, pink enhanced the electroanalytical properties of the SPEs, increasing their reproducibility and sensitivity. This point-of-care testing represents a great potential for use in epidemic situations, facilitating the early diagnosis in acute phase of dengue virus. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. SH3 domain-mediated recruitment of host cell amphiphysins by alphavirus nsP3 promotes viral RNA replication.

    Directory of Open Access Journals (Sweden)

    Maarit Neuvonen

    2011-11-01

    Full Text Available Among the four non-structural proteins of alphaviruses the function of nsP3 is the least well understood. NsP3 is a component of the viral replication complex, and composed of a conserved aminoterminal macro domain implicated in viral RNA synthesis, and a poorly conserved carboxyterminal region. Despite the lack of overall homology we noted a carboxyterminal proline-rich sequence motif shared by many alphaviral nsP3 proteins, and found it to serve as a preferred target site for the Src-homology 3 (SH3 domains of amphiphysin-1 and -2. Nsp3 proteins of Semliki Forest (SFV, Sindbis (SINV, and Chikungunya viruses all showed avid and SH3-dependent binding to amphiphysins. Upon alphavirus infection the intracellular distribution of amphiphysin was dramatically altered and colocalized with nsP3. Mutations in nsP3 disrupting the amphiphysin SH3 binding motif as well as RNAi-mediated silencing of amphiphysin-2 expression resulted in impaired viral RNA replication in HeLa cells infected with SINV or SFV. Infection of Balb/c mice with SFV carrying an SH3 binding-defective nsP3 was associated with significantly decreased mortality. These data establish SH3 domain-mediated binding of nsP3 with amphiphysin as an important host cell interaction promoting alphavirus replication.

  8. Differential sensitivity of 5'UTR-NS5A recombinants of hepatitis C virus genotypes 1-6 to protease and NS5A inhibitors

    DEFF Research Database (Denmark)

    Li, Yi-Ping; Ramirez, Santseharay; Humes, Daryl

    2014-01-01

    BACKGROUND & AIMS: Hepatitis C virus (HCV) therapy will benefit from the preclinical evaluation of direct-acting antiviral (DAA) agents in infectious culture systems that test the effects on different virus genotypes. We developed HCV recombinants comprising the 5' untranslated region-NS5A (5-5A...... daclatasvir. The 1a(TN) 5-5A and JFH1-independent full-length viruses had similar levels of sensitivity to the DAA agents, validating the 5-5A recombinants as surrogates for full-length viruses in DAA testing. Compared with the 1a(TN) full-length virus, the 3a(S52) 5-5A recombinant was highly resistant to all...... protease inhibitors, and the 4a(ED43) recombinant was highly resistant to telaprevir and boceprevir, but most sensitive to other protease inhibitors. Compared with other protease inhibitors, MK-5172 had exceptional potency against all HCV genotypes. The NS5A inhibitor daclatasvir had the highest potency...

  9. The Great Wall: Urca Cooling Layers in the Accreted NS Crust

    Directory of Open Access Journals (Sweden)

    Meisel Zach

    2018-01-01

    Full Text Available Accreting neutron stars host a number of astronomical observables which can be used to infer the properties of the underlying dense matter. These observables are sensitive to the heating and cooling processes taking place in the accreted neutron star (NS crust. Within the past few years it has become apparent that electron-capture/beta-decay (urca cycles can operate within the NS crust at high temperatures. Layers of nuclei undergoing urca cycling can create a thermal barrier, or Great Wall, between heating occurring deep in the crust and the regions above the urca layers. This paper briefly reviews the urca process and the implications for observables from accreting neutron stars.

  10. Multiple Sensing Application on Wireless Sensor Network Simulation using NS3

    Science.gov (United States)

    Kurniawan, I. F.; Bisma, R.

    2018-01-01

    Hardware enhancement provides opportunity to install various sensor device on single monitoring node which then enables users to acquire multiple data simultaneously. Constructing multiple sensing application in NS3 is a challenging task since numbers of aspects such as wireless communication, packet transmission pattern, and energy model must be taken into account. Despite of numerous types of monitoring data available, this study only considers two types such as periodic, and event-based data. Periodical data will generate monitoring data follows configured interval, while event-based transmit data when certain determined condition is met. Therefore, this study attempts to cover mentioned aspects in NS3. Several simulations are performed with different number of nodes on arbitrary communication scheme.

  11. Structure-Based Mutational Analysis of the Hepatitis C Virus NS3 Helicase

    Science.gov (United States)

    Tai, Chun-Ling; Pan, Wen-Ching; Liaw, Shwu-Huey; Yang, Ueng-Cheng; Hwang, Lih-Hwa; Chen, Ding-Shinn

    2001-01-01

    The carboxyl terminus of the hepatitis C virus (HCV) nonstructural protein 3 (NS3) possesses ATP-dependent RNA helicase activity. Based on the conserved sequence motifs and the crystal structures of the helicase domain, 17 mutants of the HCV NS3 helicase were generated. The ATP hydrolysis, RNA binding, and RNA unwinding activities of the mutant proteins were examined in vitro to determine the functional role of the mutated residues. The data revealed that Lys-210 in the Walker A motif and Asp-290, Glu-291, and His-293 in the Walker B motif were crucial to ATPase activity and that Thr-322 and Thr-324 in motif III and Arg-461 in motif VI significantly influenced ATPase activity. When the pairing between His-293 and Gln-460, referred to as gatekeepers, was replaced with the Asp-293/His-460 pair, which makes the NS3 helicase more like the DEAD helicase subgroup, ATPase activity was not restored. It thus indicated that the whole microenvironment surrounding the gatekeepers, rather than the residues per se, was important to the enzymatic activities. Arg-461 and Trp-501 are important residues for RNA binding, while Val-432 may only play a coadjutant role. The data demonstrated that RNA helicase activity was possibly abolished by the loss of ATPase activity or by reduced RNA binding activity. Nevertheless, a low threshold level of ATPase activity was found sufficient for helicase activity. Results in this study provide a valuable reference for efforts under way to develop anti-HCV therapeutic drugs targeting NS3. PMID:11483774

  12. MADE YOU LOOK: NIQABS, THE MUSLIM CANADIAN CONGRESS, AND R V NS

    Directory of Open Access Journals (Sweden)

    Fathima Cader

    2013-02-01

    Full Text Available R v NS was the first Canadian case to involve a niqab-wearing sexual assault complainant. At the Supreme Court of Canada, the Muslim Canadian Congress [MCC] was especially vocal in arguing it would be un-Canadian to allow NS to testify while wearing a niqab. This paper sets out to investigate the MCC’s depictions of Muslim women, Muslim men, and the mainstream public, with specific attention paid to the details of the MCC’s “clash of civilisations” framing, its impact on the Court’s reasons, and its implications for women combatting sexual violence.   R c NS a été la première cause canadienne où une plaignante, victime d’une agression sexuelle, portait le niqab. Dans ses interventions devant la Cour suprême du Canada, le Congrès musulman canadien [CMC] a souligné avec beaucoup d’insistance qu’il serait anti-canadien de permettre à NS de témoigner en portant son niqab. Le présent article vise à briser les stéréotypes que le CMC a véhiculé dans ses arguments concernant les femmes musulmanes, les hommes musulmans et le grand public, et porte une attention spéciale aux particularités de la conception par le CMC du « choc des civilisations », leur impact sur les motifs de la Cour et leurs conséquences pour les femmes qui luttent contre la violence sexuelle.

  13. Analysis of functional differences between hepatitis C virus NS5A of genotypes 1-7 in infectious cell culture systems

    DEFF Research Database (Denmark)

    Scheel, Troels K H; Prentoe, Jannick; Carlsen, Thomas H R

    2012-01-01

    , but ED43(4a) and SA13(5a) also displayed impaired particle assembly. Compared to the original H77C(1a) NS5A recombinant, the changes in LCSII and domain III reduced the amounts of NS5A present. For H77C(1a) and TN(1a) NS5A recombinants, we observed a genetic linkage between NS5A and p7, since introduced...

  14. Near-Real-Time DMSP SSM/I-SSMIS Daily Polar Gridded Brightness Temperatures

    Data.gov (United States)

    National Aeronautics and Space Administration — The Near-Real-Time DMSP SSM/I-SSMIS Daily Polar Gridded Brightness Temperature product provides near-real-time brightness temperatures for both the Northern and...

  15. Lipid droplet-binding protein TIP47 regulates hepatitis C Virus RNA replication through interaction with the viral NS5A protein.

    Directory of Open Access Journals (Sweden)

    Dorothee A Vogt

    Full Text Available The nonstructural protein NS5A has emerged as a new drug target in antiviral therapies for Hepatitis C Virus (HCV infection. NS5A is critically involved in viral RNA replication that takes place at newly formed membranes within the endoplasmic reticulum (membranous web and assists viral assembly in the close vicinity of lipid droplets (LDs. To identify host proteins that interact with NS5A, we performed a yeast two-hybrid screen with the N-terminus of NS5A (amino acids 1-31, a well-studied α-helical domain important for the membrane tethering of NS5A. Our studies identified the LD-associated host protein, Tail-Interacting Protein 47 (TIP47 as a novel NS5A interaction partner. Coimmunoprecipitation experiments in Huh7 hepatoma cells confirmed the interaction of TIP47 with full-length NS5A. shRNA-mediated knockdown of TIP47 caused a more than 10-fold decrease in the propagation of full-length infectious HCV in Huh7.5 hepatoma cells. A similar reduction was observed when TIP47 was knocked down in cells harboring an autonomously replicating HCV RNA (subgenomic replicon, indicating that TIP47 is required for efficient HCV RNA replication. A single point mutation (W9A in NS5A that disrupts the interaction with TIP47 but preserves proper subcellular localization severely decreased HCV RNA replication. In biochemical membrane flotation assays, TIP47 cofractionated with HCV NS3, NS5A, NS5B proteins, and viral RNA, and together with nonstructural viral proteins was uniquely distributed to lower-density LD-rich membrane fractions in cells actively replicating HCV RNA. Collectively, our data support a model where TIP47--via its interaction with NS5A--serves as a novel cofactor for HCV infection possibly by integrating LD membranes into the membranous web.

  16. Bright solitons in Bose-Fermi mixtures

    International Nuclear Information System (INIS)

    Karpiuk, Tomasz; Brewczyk, Miroslaw; RzaPewski, Kazimierz

    2006-01-01

    We consider the formation of bright solitons in a mixture of Bose and Fermi degenerate gases confined in a three-dimensional elongated harmonic trap. The Bose and Fermi atoms are assumed to effectively attract each other whereas bosonic atoms repel each other. Strong enough attraction between bosonic and fermionic components can change the character of the interaction within the bosonic cloud from repulsive to attractive making thus possible the generation of bright solitons in the mixture. On the other hand, such structures might be in danger due to the collapse phenomenon existing in attractive gases. We show, however, that under some conditions (defined by the strength of the Bose-Fermi components attraction) the structures which neither spread nor collapse can be generated. For elongated enough traps the formation of solitons is possible even at the 'natural' value of the mutual Bose-Fermi ( 87 Rb- 40 K in our case) scattering length

  17. Distribution of surface brightness in Seyfert galaxies. III. Analysis of data

    International Nuclear Information System (INIS)

    Afanas'ev, V.L.; Doroshenko, V.T.; Terebizh, V.Yu.

    1987-01-01

    The observational data on the distribution of the surface brightness μ(r) in normal and Seyfert galaxies given in the first two parts of the study [1,2] are considered. The general form of μ(r) for r ≤ approximately equals 2 kpc is the same for the two groups of galaxies. The values of the parameters that characterize the central part of the spherical component are found, namely, the surface brightness μ 1 /sup (0)/, the brightness, the brightness gradient n 1 , and the color indices (U-B) 1 /sup (0)/ and (B-V) 1 /sup (0)/ at distance 1 kpc from the center. The range of variation of the basic parameters and the correlations of the parameters with each other and with the absolute magnitudes M/sub B//sup (0)/ of the galaxies find a natural explanation in the framework of the standard models of the spherical subsystems of galaxies. The relationships have approximately the same form for normal and Seyfert galaxies. The photometric characteristics of the central regions of Sy 1 and Sy 2 type galaxies are similar. The obtained results do not contradict the idea that all sufficiently bright spiral galaxies can pass through a Seyfert stage with a characteristic time of ∼10 8 yr

  18. Low surface brightness galaxies in the cluster A1367

    International Nuclear Information System (INIS)

    Davies, J.I.; Phillipps, S.; Disney, M.J.

    1989-01-01

    We have obtained deep CCD frames of apparently blank regions of sky in the hope of detecting very low surface brightness (LSB) objects in the cluster A1367. We discuss our data reduction, and image detection and selection techniques. If the galaxies detected are actually cluster members then they are dwarfs and the conclusions of a previous paper on the Fornax cluster are essentially confirmed. One area of variance is that the lowest surface brightness galaxies do not appear to be preferentially concentrated towards the cluster centre. This can be explained by there being a much larger density of dwarf galaxies over this bright galaxy-rich region of the universe. We find over our small area approximately four times as many LSB galaxies as would be expected from our Fornax data. We speculate on the possible origin and likely intensity of intergalactic light within clusters. (author)

  19. Hagedorn Behavior of Little String Theories from string corrections to NS5-branes

    DEFF Research Database (Denmark)

    Harmark, Troels; Obers, N. A.

    2000-01-01

    We examine the Hagedorn behavior of little string theory using its conjectured duality with near-horizon NS5-branes. In particular, by studying the string-corrected NS5-brane supergravity solution, it is shown that tree-level corrections to the temperature vanish, while the leading one-loop string...... correction generates the correct temperature dependence of the entropy near the Hagedorn temperature. Finally, the Hagedorn behavior of ODp-brane theories, which are deformed versions of little string theory, is considered via their supergravity duals....

  20. Tolerance of brightness and contrast adjustments on chronic apical abscess and apical granuloma interpretation

    Science.gov (United States)

    Purnamasari, L.; Iskandar, H. H. B.; Makes, B. N.

    2017-08-01

    In digitized radiography techniques, adjusting the image enhancement can improve the subjective image quality by optimizing the brightness and contrast for diagnostic needs. To determine the value range of image enhancement (brightness and contrast) on chronic apical abscess and apical granuloma interpretation. 30 periapical radiographs that diagnosed chronic apical abscess and 30 that diagnosed apical granuloma were adjusted by changing brightness and contrast values. The value range of brightness and contrast adjustment that can be tolerated in radiographic interpretations of chronic apical abscess and apical granuloma spans from -10 to +10. Brightness and contrast adjustments on digital radiographs do not affect the radiographic interpretation of chronic apical abscess and apical granuloma if conducted within the value range.

  1. Bright Stuff on Ceres = Sulfates and Carbonates on CI Chondrites

    Science.gov (United States)

    Zolensky, Michael; Chan, Queenie H. S.; Gounelle, Matthieu; Fries, Marc

    2016-01-01

    Recent reports of the DAWN spacecraft's observations of the surface of Ceres indicate that there are bright areas, which can be explained by large amounts of the Mg sulfate hexahydrate (MgSO4•6(H2O)), although the identification appears tenuous. There are preliminary indications that water is being evolved from these bright areas, and some have inferred that these might be sites of contemporary hydro-volcanism. A heat source for such modern activity is not obvious, given the small size of Ceres, lack of any tidal forces from nearby giant planets, probable age and presumed bulk composition. We contend that observations of chondritic materials in the lab shed light on the nature of the bright spots on Ceres

  2. Role of N-S strike-slip faulting in structuring of north-eastern Tunisia; geodynamic implications

    Science.gov (United States)

    Arfaoui, Aymen; Soumaya, Abdelkader; Ben Ayed, Noureddine; Delvaux, Damien; Ghanmi, Mohamed; Kadri, Ali; Zargouni, Fouad

    2017-05-01

    Three major compressional events characterized by folding, thrusting and strike-slip faulting occurred in the Eocene, Late Miocene and Quaternary along the NE Tunisian domain between Bou Kornine-Ressas-Msella and Cap Bon Peninsula. During the Plio-Quaternary, the Grombalia and Mornag grabens show a maximum of collapse in parallelism with the NNW-SSE SHmax direction and developed as 3rd order distensives zones within a global compressional regime. Using existing tectonic and geophysical data supplemented by new fault-kinematic observations, we show that Cenozoic deformation of the Mesozoic sedimentary sequences is dominated by first order N-S faults reactivation, this sinistral wrench system is responsible for the formation of strike-slip duplexes, thrusts, folds and grabens. Following our new structural interpretation, the major faults of N-S Axis, Bou Kornine-Ressas-Messella (MRB) and Hammamet-Korbous (HK) form an N-S first order compressive relay within a left lateral strike-slip duplex. The N-S master MRB fault is dominated by contractional imbricate fans, while the parallel HK fault is characterized by a trailing of extensional imbricate fans. The Eocene and Miocene compression phases in the study area caused sinistral strike-slip reactivation of pre-existing N-S faults, reverse reactivation of NE-SW trending faults and normal-oblique reactivation of NW-SE faults, creating a NE-SW to N-S trending system of east-verging folds and overlaps. Existing seismic tomography images suggest a key role for the lithospheric subvertical tear or STEP fault (Slab Transfer Edge Propagator) evidenced below this region on the development of the MRB and the HK relay zone. The presence of extensive syntectonic Pliocene on top of this crustal scale fault may be the result of a recent lithospheric vertical kinematic of this STEP fault, due to the rollback and lateral migration of the Calabrian slab eastward.

  3. The 150 ns detector project: Prototype preamplifier results

    Science.gov (United States)

    Warburton, W. K.; Russell, S. R.; Kleinfelder, Stuart A.

    1994-08-01

    The long-term goal of the 150 ns detector project is to develop a pixel area detector capable of 6 MHz frame rates (150 ns/frame). Our milestones toward this goal are: a single pixel, 1×256 1D and 8×8 2D detectors, 256×256 2D detectors and, finally, 1024 × 1024 2D detectors. The design strategy is to supply a complete electronics chain (resetting preamp, selectable gain amplifier, analog-to-digital converter (ADC), and memory) for each pixel. In the final detectors these will all be custom integrated circuits. The front-end preamplifiers are integrated first, since their design and performance are the most unusual and also critical to the project's success. Similarly, our early work is concentrated on devising and perfecting detector structures. In this paper we demonstrate the performance of prototypes of our integrated preamplifiers. While the final design will have 64 preamps to a chip, including a switchable gain stage, the prototypes were integrated 8 channels to a "Tiny Chip" and tested in 4 configurations (feedback capacitor Cf equal 2.5 or 4.0 pF, output directly or through a source follower). These devices have been tested thoroughly for reset settling times, gain, linearity, and electronic noise. They generally work as designed, being fast enough to easily integrate detector charge, settle, and reset in 150 ns. Gain and linearity appear to be acceptable. Current values of electronic noise, in double-sampling mode, are about twice the design goal of {2}/{3} of a single photon at 6 keV. We expect this figure to improve with the addition of the onboard amplifier stage and improved packaging. Our next test chip will include these improvements and allow testing with our first detector samples, which will be 1×256 (50 μm wide pixels) and 8×8 (1 mm 2 pixels) element detector on 1 mm thick silicon.

  4. Structure-based drug design of novel peptidomimetic cellulose derivatives as HCV-NS3 protease inhibitors.

    Science.gov (United States)

    Saleh, Noha A; Elshemey, Wael M

    2017-10-15

    Hepatitis C Virus (HCV) represents a global health threat not only due to the large number of reported worldwide HCV infections, but also due to the absence of a reliable vaccine for its prevention. HCV NS3 protease is one of the most important targets for drug design aiming at the deactivation of HCV. In the present work, molecular docking simulations are carried out for suggested novel NS3 protease inhibitors applied to the Egyptian genotype 4. These inhibitors are modifications of dimer cellulose by adding a hexa-peptide to the cellulose at one of the positions 2, 3, 6, 2', 3' or 6'. Results show that the inhibitor compound with the hexa-peptide at position 6 shows significantly higher simulation docking score with HCV NS3 protease active site. This is supported by low total energy value of docking system, formation of two H-bonds with HCV NS3 protease active site residues, high binding affinity and increased stability in the interaction system. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Response of noctilucent cloud brightness to daily solar variations

    Science.gov (United States)

    Dalin, P.; Pertsev, N.; Perminov, V.; Dubietis, A.; Zadorozhny, A.; Zalcik, M.; McEachran, I.; McEwan, T.; Černis, K.; Grønne, J.; Taustrup, T.; Hansen, O.; Andersen, H.; Melnikov, D.; Manevich, A.; Romejko, V.; Lifatova, D.

    2018-04-01

    For the first time, long-term data sets of ground-based observations of noctilucent clouds (NLC) around the globe have been analyzed in order to investigate a response of NLC to solar UV irradiance variability on a day-to-day scale. NLC brightness has been considered versus variations of solar Lyman-alpha flux. We have found that day-to-day solar variability, whose effect is generally masked in the natural NLC variability, has a statistically significant effect when considering large statistics for more than ten years. Average increase in day-to-day solar Lyman-α flux results in average decrease in day-to-day NLC brightness that can be explained by robust physical mechanisms taking place in the summer mesosphere. Average time lags between variations of Lyman-α flux and NLC brightness are short (0-3 days), suggesting a dominant role of direct solar heating and of the dynamical mechanism compared to photodissociation of water vapor by solar Lyman-α flux. All found regularities are consistent between various ground-based NLC data sets collected at different locations around the globe and for various time intervals. Signatures of a 27-day periodicity seem to be present in the NLC brightness for individual summertime intervals; however, this oscillation cannot be unambiguously retrieved due to inevitable periods of tropospheric cloudiness.

  6. Assessment of {alpha}7 nicotinic acetylcholine receptor availability in juvenile pig brain with [{sup 18}F]NS10743

    Energy Technology Data Exchange (ETDEWEB)

    Deuther-Conrad, Winnie; Fischer, Steffen; Hiller, Achim; Funke, Uta; Brust, Peter [Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmacy, Leipzig (Germany); Becker, Georg; Sabri, Osama [Univ. of Leipzig, Dept. of Nuclear Medicine, Leipzig (Germany); Cumming, Paul; Xiong, Guoming [Univ. of Munich, Dept. of Nuclear Medicine, Munich (Germany); Peters, Dan [NeuroSearch A/S, Ballerup (Denmark)

    2011-08-15

    To conduct a quantitative PET assessment of the specific binding sites in the brain of juvenile pigs for [{sup 18}F]NS10743, a novel diazabicyclononane derivative targeting {alpha}7 nicotinic acetylcholine receptors ({alpha}7 nAChRs). Dynamic PET recordings were made in isoflurane-anaesthetized juvenile pigs during 120 min after administration of [{sup 18}F]NS10743 under baseline conditions (n = 3) and after blocking of the {alpha}7 nAChR with NS6740 (3 mg.kg{sup -1} bolus + 1 mg.kg{sup -1}.h{sup -1} continuous infusion; n = 3). Arterial plasma samples were collected for determining the input function of the unmetabolized tracer. Kinetic analysis of regional brain time-radioactivity curves was performed, and parametric maps were calculated relative to arterial input. Plasma [{sup 18}F]NS10743 passed readily into the brain, with peak uptake occurring in {alpha}7 nAChR-expressing brain regions such as the colliculi, thalamus, temporal lobe and hippocampus. The highest SUV{sub max} was approximately 2.3, whereas the lowest uptake was in the olfactory bulb (SUV{sub max} 1.53 {+-} 0.32). Administration of NS6740 significantly decreased [{sup 18}F]NS10743 binding late in the emission recording throughout the brain, except in the olfactory bulb, which was therefore chosen as reference region for calculation of BP{sub ND}. The baseline BP{sub ND} ranged from 0.39 {+-} 0.08 in the cerebellum to 0.76 {+-} 0.07 in the temporal lobe. Pretreatment and constant infusion with NS6740 significantly reduced the BP{sub ND} in regions with high [{sup 18}F]NS10743 binding (temporal lobe -29%, p = 0.01; midbrain: -35%, p = 0.02), without significantly altering the BP{sub ND} in low binding regions (cerebellum: -16%, p = 0.2). This study confirms the potential of [{sup 18}F]NS10743 as a target-specific radiotracer for the molecular imaging of central {alpha}7 nAChRs by PET. (orig.)

  7. Growth behavior of laser-induced damage on fused silica optics under UV, ns laser irradiation.

    Science.gov (United States)

    Negres, Raluca A; Norton, Mary A; Cross, David A; Carr, Christopher W

    2010-09-13

    The growth behavior of laser-induced damage sites is affected by a large number of laser parameters as well as site morphology. Here we investigate the effects of pulse duration on the growth rate of damage sites located on the exit surface of fused silica optics. Results demonstrate a significant dependence of the growth parameters on laser pulse duration at 351 nm from 1 ns to 15 ns, including the observation of a dominant exponential versus linear, multiple-shot growth behavior for long and short pulses, respectively. These salient behaviors are tied to the damage morphology and suggest a shift in the fundamental growth mechanisms for pulses in the 1-5 ns range.

  8. Synthesis and evaluation of racemic [11C]NS2456 and its enantiomers as selective serotonin reuptake radiotracers for PET

    International Nuclear Information System (INIS)

    Smith, D.F.; Bender, D.; Marthi, K.; Cumming, P.; Hansen, S.B.; Peters, D.; Oestergaard Nielsen, E.; Scheel-Krueger, J.; Gjedde, A.

    2001-01-01

    Positron emission tomography (PET) radiotracers are needed for quantifying serotonin uptake sites in the living brain. Therefore, we evaluated a new selective serotonin reuptake inhibitor, NS2456, to determine whether it is suited for use in PET. Racemic NS2456 [(1RS,5SR)-8-methyl-3-[4-trifluoromethoxyphenyl]-8-azabicyclo [3.2.1]oct-2-ene] and its N-demethylated analog, racemic NS2463, selectively inhibited serotonin uptake in rat brain synaptosomes; their IC 50 values were 3000-fold lower for [ 3 H]serotonin than for either [ 3 H]dopamine or [ 3 H]noradrenaline. The enantiomers of NS2463 were also potent inhibitors of serotonin uptake in vitro, but they failed to show stereoselectivity. Racemic NS2463 as well as its enantiomers were radiolabelled by N-methylation with C-11, yielding [ 11 C]NS2456 for use in PET of the living porcine brain. The compounds crossed the blood-brain barrier rapidly and accumulated preferentially in regions rich in serotonin uptake sites (e.g., brainstem, subthalamus and thalamus). However, their binding potentials were relatively low and no stereoselectivity was found. Thus, neither racemic [ 11 C]NS2456 nor its [ 11 C]-labelled enantiomers are ideal for PET neuroimaging of neuronal serotonin uptake sites

  9. Robust translocation along a molecular monorail: the NS3 helicase from hepatitis C virus traverses unusually large disruptions in its track.

    Science.gov (United States)

    Beran, Rudolf K F; Bruno, Michael M; Bowers, Heath A; Jankowsky, Eckhard; Pyle, Anna Marie

    2006-05-12

    The NS3 helicase is essential for replication of the hepatitis C virus. This multifunctional Superfamily 2 helicase protein unwinds nucleic acid duplexes in a stepwise, ATP-dependent manner. Although kinetic features of its mechanism are beginning to emerge, little is known about the physical determinants for NS3 translocation along a strand of nucleic acid. For example, it is not known whether NS3 can traverse covalent or physical discontinuities on the tracking strand. Here we provide evidence that NS3 translocates with a mechanism that is different from its well-studied relative, the Vaccinia helicase NPH-II. Like NPH-II, NS3 translocates along the loading strand (the strand bearing the 3'-overhang) and it fails to unwind substrates that contain nicks, or covalent discontinuities in the loading strand. However, unlike NPH-II, NS3 readily unwinds RNA duplexes that contain long stretches of polyglycol, which are moieties that bear no resemblance to nucleic acid. Whether located on the tracking strand, the top strand, or both, long polyglycol regions fail to disrupt the function of NS3. This suggests that NS3 does not require the continuous formation of specific contacts with the ribose-phosphate backbone as it translocates along an RNA duplex, which is an observation consistent with the large NS3 kinetic step size (18 base-pairs). Rather, once NS3 loads onto a substrate, the helicase can translocate along the loading strand of an RNA duplex like a monorail train following a track. Bumps in the track do not significantly disturb NS3 unwinding, but a break in the track de-rails the helicase.

  10. Bright to dim oscillatory response of the Neurospora circadian oscillator.

    Science.gov (United States)

    Gooch, Van D; Johnson, Alicia E; Larrondo, Luis F; Loros, Jennifer J; Dunlap, Jay C

    2014-02-01

    The fungus Neurospora crassa constitutes an important model system extensively used in chronobiology. Several studies have addressed how environmental cues, such as light, can reset or synchronize a circadian system. By means of an optimized firefly luciferase reporter gene and a controllable lighting system, we show that Neurospora can display molecular circadian rhythms in dim light when cultures receive bright light prior to entering dim light conditions. We refer to this behavior as the "bright to dim oscillatory response" (BDOR). The bright light treatment can be applied up to 76 h prior to dim exposure, and it can be as short as 15 min in duration. We have characterized this response in respect to the duration of the light pulse, the time of the light pulse before dim, the intensity of dim light, and the oscillation dynamics in dim light. Although the molecular mechanism that drives the BDOR remains obscure, these findings suggest that a long-term memory of bright light exists as part of the circadian molecular components. It is important to consider the ecological significance of such dim light responses in respect to how organisms naturally maintain their timing mechanism in moonlight.

  11. Conservation of a crystallographic interface suggests a role for β-sheet augmentation in influenza virus NS1 multifunctionality

    International Nuclear Information System (INIS)

    Kerry, Philip S.; Long, Elizabeth; Taylor, Margaret A.; Russell, Rupert J. M.

    2011-01-01

    The structure of a monomeric effector domain from influenza A virus NS1 is presented from diffraction data extending to 1.8 Å resolution. Comparison of this and other NS1 effector-domain structures shows conformational changes at a strand–strand packing interface, hinting at a role for β-strand augmentation in NS1 function. The effector domain (ED) of the influenza virus virulence factor NS1 is capable of interaction with a variety of cellular and viral targets, although regulation of these events is poorly understood. Introduction of a W187A mutation into the ED abolishes dimer formation; however, strand–strand interactions between mutant NS1 ED monomers have been observed in two previous crystal forms. A new condition for crystallization of this protein [0.1 M Bis-Tris pH 6.0, 0.2 M NaCl, 22%(w/v) PEG 3350, 20 mM xylitol] was discovered using the hanging-drop vapour-diffusion method. Diffraction data extending to 1.8 Å resolution were collected from a crystal grown in the presence of 40 mM thieno[2,3-b]pyridin-2-ylmethanol. It was observed that there is conservation of the strand–strand interface in crystals of this monomeric NS1 ED in three different space groups. This observation, coupled with conformational changes in the interface region, suggests a potential role for β-sheet augmentation in NS1 function

  12. Detecting gradual visual changes in colour and brightness agnosia: a double dissociation.

    Science.gov (United States)

    Nijboer, Tanja C W; te Pas, Susan F; van der Smagt, Maarten J

    2011-03-09

    Two patients, one with colour agnosia and one with brightness agnosia, performed a task that required the detection of gradual temporal changes in colour and brightness. The results for these patients, who showed anaverage or an above-average performance on several tasks designed to test low-level colour and luminance (contrast) perception in the spatial domain, yielded a double dissociation; the brightness agnosic patient was within the normal range for the coloured stimuli, but much slower to detect brightness differences, whereas the colour agnosic patient was within the normal range for the achromatic stimuli, but much slower for the coloured stimuli. These results suggest that a modality-specific impairment in the detection of gradual temporal changes might be related to, if not underlie, the phenomenon of visual agnosia.

  13. The bright-star masks for the HSC-SSP survey

    Science.gov (United States)

    Coupon, Jean; Czakon, Nicole; Bosch, James; Komiyama, Yutaka; Medezinski, Elinor; Miyazaki, Satoshi; Oguri, Masamune

    2018-01-01

    We present the procedure to build and validate the bright-star masks for the Hyper-Suprime-Cam Strategic Subaru Proposal (HSC-SSP) survey. To identify and mask the saturated stars in the full HSC-SSP footprint, we rely on the Gaia and Tycho-2 star catalogues. We first assemble a pure star catalogue down to GGaia SSP, finding that our star catalogue is 99.2% pure down to GGaia SSP observations at "ftp://obsftp.unige.ch/pub/coupon/brightStarMasks/HSC-SSP/".

  14. Low-mass X-ray binaries from black hole retaining globular clusters

    Science.gov (United States)

    Giesler, Matthew; Clausen, Drew; Ott, Christian D.

    2018-06-01

    Recent studies suggest that globular clusters (GCs) may retain a substantial population of stellar-mass black holes (BHs), in contrast to the long-held belief of a few to zero BHs. We model the population of BH low-mass X-ray binaries (BH-LMXBs), an ideal observable proxy for elusive single BHs, produced from a representative group of Milky Way GCs with variable BH populations. We simulate the formation of BH binaries in GCs through exchange interactions between binary and single stars in the company of tens to hundreds of BHs. Additionally, we consider the impact of the BH population on the rate of compact binaries undergoing gravitational wave driven mergers. The characteristics of the BH-LMXB population and binary properties are sensitive to the GCs structural parameters as well as its unobservable BH population. We find that GCs retaining ˜1000 BHs produce a galactic population of ˜150 ejected BH-LMXBs, whereas GCs retaining only ˜20 BHs produce zero ejected BH-LMXBs. Moreover, we explore the possibility that some of the presently known BH-LMXBs might have originated in GCs and identify five candidate systems.

  15. Low-mass X-ray binaries from black-hole retaining globular clusters

    Science.gov (United States)

    Giesler, Matthew; Clausen, Drew; Ott, Christian D.

    2018-03-01

    Recent studies suggest that globular clusters (GCs) may retain a substantial population of stellar-mass black holes (BHs), in contrast to the long-held belief of a few to zero BHs. We model the population of BH low-mass X-ray binaries (BH-LMXBs), an ideal observable proxy for elusive single BHs, produced from a representative group of Milky Way GCs with variable BH populations. We simulate the formation of BH-binaries in GCs through exchange interactions between binary and single stars in the company of tens to hundreds of BHs. Additionally, we consider the impact of the BH population on the rate of compact binaries undergoing gravitational wave driven mergers. The characteristics of the BH-LMXB population and binary properties are sensitive to the GCs structural parameters as well as its unobservable BH population. We find that GCs retaining ˜1000 BHs produce a galactic population of ˜150 ejected BH-LMXBs whereas GCs retaining only ˜20 BHs produce zero ejected BH-LMXBs. Moreover, we explore the possibility that some of the presently known BH-LMXBs might have originated in GCs and identify five candidate systems.

  16. High-brightness beamline for x-ray spectroscopy at the ALS

    Energy Technology Data Exchange (ETDEWEB)

    Perera, R.C.C.; Jones, G. [Ernest Orlando Lawrence Berkeley National Lab., CA (United States); Lindle, D.W. [Univ. of Nevada, Las Vegas, NV (United States)

    1997-04-01

    Beamline 9.3.1 at the Advanced Light Source (ALS) is a windowless beamline, covering the 1-6 keV photon-energy range, designed to achieve the goals of high energy resolution, high flux, and high brightness at the sample. When completed later this year, it will be the first ALS monochromatic hard x-ray beamline, and its brightness will be an order of magnitude higher than presently available in this energy range. In addition, it will provide flux and resolution comparable to any other beamline now in operation. To achieve these goals, two technical improvements, relative to existing x-ray beamlines, were incorporated. First, a somewhat novel optical design for x-rays, in which matched toroidal mirrors are positioned before and after the double-crystal monochromator, was adopted. This configuration allows for high resolution by passing a collimated beam through the monochromator, and for high brightness by focusing the ALS source on the sample with unit magnification. Second, a new {open_quotes}Cowan type{close_quotes} double-crystal monochromator based on the design used at NSLS beamline X-24A was developed. The measured mechanical precision of this new monochromator shows significant improvement over existing designs, without using positional feedback available with piezoelectric devices. Such precision is essential because of the high brightness of the radiation and the long distance (12 m) from the source (sample) to the collimating (focusing) mirror. This combination of features will provide a bright, high resolution, and stable x-ray beam for use in the x-ray spectroscopy program at the ALS.

  17. Brightness measurement of an electron impact gas ion source for proton beam writing applications

    Energy Technology Data Exchange (ETDEWEB)

    Liu, N.; Santhana Raman, P. [Centre for Ion Beam Applications, Department of Physics, National University of Singapore, Singapore 117542 (Singapore); Department of Electrical and Computer Engineering, National University of Singapore, Singapore 117583 (Singapore); Xu, X.; Pang, R.; Kan, J. A. van, E-mail: phyjavk@nus.edu.sg [Centre for Ion Beam Applications, Department of Physics, National University of Singapore, Singapore 117542 (Singapore); Khursheed, A. [Department of Electrical and Computer Engineering, National University of Singapore, Singapore 117583 (Singapore)

    2016-02-15

    We are developing a high brightness nano-aperture electron impact gas ion source, which can create ion beams from a miniature ionization chamber with relatively small virtual source sizes, typically around 100 nm. A prototype source of this kind was designed and successively micro-fabricated using integrated circuit technology. Experiments to measure source brightness were performed inside a field emission scanning electron microscope. The total output current was measured to be between 200 and 300 pA. The highest estimated reduced brightness was found to be comparable to the injecting focused electron beam reduced brightness. This translates into an ion reduced brightness that is significantly better than that of conventional radio frequency ion sources, currently used in single-ended MeV accelerators.

  18. Rift Valley fever virus NS{sub S} gene expression correlates with a defect in nuclear mRNA export

    Energy Technology Data Exchange (ETDEWEB)

    Copeland, Anna Maria; Van Deusen, Nicole M.; Schmaljohn, Connie S., E-mail: Connie.s.schmaljohn.civ@mail.mil

    2015-12-15

    We investigated the localization of host mRNA during Rift Valley fever virus (RVFV) infection. Fluorescence in situ hybridization revealed that infection with RVFV altered the localization of host mRNA. mRNA accumulated in the nuclei of RVFV-infected but not mock-infected cells. Further, overexpression of the NS{sub S} gene, but not the N, G{sub N} or NS{sub M} genes correlated with mRNA nuclear accumulation. Nuclear accumulation of host mRNA was not observed in cells infected with a strain of RVFV lacking the gene encoding NS{sub S}, confirming that expression of NS{sub S} is likely responsible for this phenomenon. - Highlights: • Rift Valley fever virus (RVFV) infection alters the localization of host mRNA. • mRNA accumulates in the nuclei of RVFV-infected but not mock-infected cells. • NS{sub S} is likely responsible for mRNA relocalization to the nucleus.

  19. Decommissioning of NS OTTO HAHN

    International Nuclear Information System (INIS)

    Lettnin, H.K.J.; Viecenz, H.J.

    1982-01-01

    With NS OTTO HAHN for the first time a nuclear propelled merchant vessel has been regularly decommissioned after more than 10 years of successful operation. Based on the concept of the total decontamination about 1100 ts of contaminated and decontaminated components have been dismantled and removed from board ship. 260 ts of contaminated components packed in 10 ft containers and 400-liter drums and the 480 ts RPV unit are stored at the GKSS site for post investigations. A total mass of about 370 ts has been decontaminated by mechanical and chemical procedures below the required radiological limits. The nuclear status of OTTO HAHN has been removed by the competent licensing authority in June 1982 so that the vessel is now offered for sale for conventionel operations. 8 references, 11 figures

  20. Therapeutic Effects of Monoclonal Antibody against Dengue Virus NS1 in a STAT1 Knockout Mouse Model of Dengue Infection.

    Science.gov (United States)

    Wan, Shu-Wen; Chen, Pei-Wei; Chen, Chin-Yu; Lai, Yen-Chung; Chu, Ya-Ting; Hung, Chia-Yi; Lee, Han; Wu, Hsuan Franziska; Chuang, Yung-Chun; Lin, Jessica; Chang, Chih-Peng; Wang, Shuying; Liu, Ching-Chuan; Ho, Tzong-Shiann; Lin, Chiou-Feng; Lee, Chien-Kuo; Wu-Hsieh, Betty A; Anderson, Robert; Yeh, Trai-Ming; Lin, Yee-Shin

    2017-10-15

    Dengue virus (DENV) is the causative agent of dengue fever, dengue hemorrhagic fever, and dengue shock syndrome and is endemic to tropical and subtropical regions of the world. Our previous studies showed the existence of epitopes in the C-terminal region of DENV nonstructural protein 1 (NS1) which are cross-reactive with host Ags and trigger anti-DENV NS1 Ab-mediated endothelial cell damage and platelet dysfunction. To circumvent these potentially harmful events, we replaced the C-terminal region of DENV NS1 with the corresponding region from Japanese encephalitis virus NS1 to create chimeric DJ NS1 protein. Passive immunization of DENV-infected mice with polyclonal anti-DJ NS1 Abs reduced viral Ag expression at skin inoculation sites and shortened DENV-induced prolonged bleeding time. We also investigated the therapeutic effects of anti-NS1 mAb. One mAb designated 2E8 does not recognize the C-terminal region of DENV NS1 in which host-cross-reactive epitopes reside. Moreover, mAb 2E8 recognizes NS1 of all four DENV serotypes. We also found that mAb 2E8 caused complement-mediated lysis in DENV-infected cells. In mouse model studies, treatment with mAb 2E8 shortened DENV-induced prolonged bleeding time and reduced viral Ag expression in the skin. Importantly, mAb 2E8 provided therapeutic effects against all four serotypes of DENV. We further found that mAb administration to mice as late as 1 d prior to severe bleeding still reduced prolonged bleeding time and hemorrhage. Therefore, administration with a single dose of mAb 2E8 can protect mice against DENV infection and pathological effects, suggesting that NS1-specific mAb may be a therapeutic option against dengue disease. Copyright © 2017 by The American Association of Immunologists, Inc.

  1. Ns-scaled time-gated fluorescence lifetime imaging for forensic document examination

    Science.gov (United States)

    Zhong, Xin; Wang, Xinwei; Zhou, Yan

    2018-01-01

    A method of ns-scaled time-gated fluorescence lifetime imaging (TFLI) is proposed to distinguish different fluorescent substances in forensic document examination. Compared with Video Spectral Comparator (VSC) which can examine fluorescence intensity images only, TFLI can detect questioned documents like falsification or alteration. TFLI system can enhance weak signal by accumulation method. The two fluorescence intensity images of the interval delay time tg are acquired by ICCD and fitted into fluorescence lifetime image. The lifetimes of fluorescence substances are represented by different colors, which make it easy to detect the fluorescent substances and the sequence of handwritings. It proves that TFLI is a powerful tool for forensic document examination. Furthermore, the advantages of TFLI system are ns-scaled precision preservation and powerful capture capability.

  2. Thin film removal mechanisms in ns-laser processing of photovoltaic materials

    International Nuclear Information System (INIS)

    Bovatsek, J.; Tamhankar, A.; Patel, R.S.; Bulgakova, N.M.; Bonse, J.

    2010-01-01

    The removal of thin films widely used in photovoltaics (amorphous silicon, tin oxide, zinc oxide, aluminum, and molybdenum) is studied experimentally using multi-kHz Q-switched solid-state lasers at 532 nm and 1064 nm wavelengths. The processing ('scribing') is performed through the film-supporting glass plate at scribing speeds of the order of m/s. The dependence of the film removal threshold on the laser pulse duration (8 ns to 40 ns) is investigated and the results are complemented by a multi-layer thermal model used for numerical simulations of the laser-induced spatio-temporal temperature field within the samples. Possible film removal mechanisms are discussed upon consideration of optical, geometrical, thermal and mechanical properties of the layers.

  3. Bright triplet excitons in caesium lead halide perovskites

    Science.gov (United States)

    Becker, Michael A.; Vaxenburg, Roman; Nedelcu, Georgian; Sercel, Peter C.; Shabaev, Andrew; Mehl, Michael J.; Michopoulos, John G.; Lambrakos, Samuel G.; Bernstein, Noam; Lyons, John L.; Stöferle, Thilo; Mahrt, Rainer F.; Kovalenko, Maksym V.; Norris, David J.; Rainò, Gabriele; Efros, Alexander L.

    2018-01-01

    Nanostructured semiconductors emit light from electronic states known as excitons. For organic materials, Hund’s rules state that the lowest-energy exciton is a poorly emitting triplet state. For inorganic semiconductors, similar rules predict an analogue of this triplet state known as the ‘dark exciton’. Because dark excitons release photons slowly, hindering emission from inorganic nanostructures, materials that disobey these rules have been sought. However, despite considerable experimental and theoretical efforts, no inorganic semiconductors have been identified in which the lowest exciton is bright. Here we show that the lowest exciton in caesium lead halide perovskites (CsPbX3, with X = Cl, Br or I) involves a highly emissive triplet state. We first use an effective-mass model and group theory to demonstrate the possibility of such a state existing, which can occur when the strong spin-orbit coupling in the conduction band of a perovskite is combined with the Rashba effect. We then apply our model to CsPbX3 nanocrystals, and measure size- and composition-dependent fluorescence at the single-nanocrystal level. The bright triplet character of the lowest exciton explains the anomalous photon-emission rates of these materials, which emit about 20 and 1,000 times faster than any other semiconductor nanocrystal at room and cryogenic temperatures, respectively. The existence of this bright triplet exciton is further confirmed by analysis of the fine structure in low-temperature fluorescence spectra. For semiconductor nanocrystals, which are already used in lighting, lasers and displays, these excitons could lead to materials with brighter emission. More generally, our results provide criteria for identifying other semiconductors that exhibit bright excitons, with potential implications for optoelectronic devices.

  4. Secreted NS1 of dengue virus attaches to the surface of cells via interactions with heparan sulfate and chondroitin sulfate E.

    Directory of Open Access Journals (Sweden)

    Panisadee Avirutnan

    2007-11-01

    Full Text Available Dengue virus (DENV nonstructural protein-1 (NS1 is a secreted glycoprotein that is absent from viral particles but accumulates in the supernatant and on the plasma membrane of cells during infection. Immune recognition of cell surface NS1 on endothelial cells has been hypothesized as a mechanism for the vascular leakage that occurs during severe DENV infection. However, it has remained unclear how NS1 becomes associated with the plasma membrane, as it contains no membrane-spanning sequence motif. Using flow cytometric and ELISA-based binding assays and mutant cell lines lacking selective glycosaminoglycans, we show that soluble NS1 binds back to the surface of uninfected cells primarily via interactions with heparan sulfate and chondroitin sulfate E. DENV NS1 binds directly to the surface of many types of epithelial and mesenchymal cells yet attaches poorly to most peripheral blood cells. Moreover, DENV NS1 preferentially binds to cultured human microvascular compared to aortic or umbilical cord vein endothelial cells. This binding specificity was confirmed in situ as DENV NS1 bound to lung and liver but not intestine or brain endothelium of mouse tissues. Differential binding of soluble NS1 by tissue endothelium and subsequent recognition by anti-NS1 antibodies could contribute to the selective vascular leakage syndrome that occurs during severe secondary DENV infection.

  5. The relationship between brightness temperature and soil moisture. Selection of frequency range for microwave remote sensing

    International Nuclear Information System (INIS)

    Rao, K.S.; Chandra, G.; Rao, P.V.N.

    1987-01-01

    The analysis of brightness temperature data acquired from field and aircraft experiments demonstrates a linear relationship between soil moisture and brightness temperature. However, the analysis of brightness temperature data acquired by the Skylab radiometer demonstrates a non-linear relationship between soil moisture and brightness temperature. In view of the above and also because of recent theoretical developments for the calculation of the dielectric constant and brightness temperature under varying soil moisture profile conditions, an attempt is made to study the theoretical relationship between brightness temperature and soil moisture as a function of frequency. Through the above analysis, the appropriate microwave frequency range for soil moisture studies is recommended

  6. Artificial light alters natural regimes of night-time sky brightness

    Science.gov (United States)

    Davies, Thomas W.; Bennie, Jonathan; Inger, Richard; Gaston, Kevin J.

    2013-01-01

    Artificial light is globally one of the most widely distributed forms of anthropogenic pollution. However, while both the nature and ecological effects of direct artificial lighting are increasingly well documented, those of artificial sky glow have received little attention. We investigated how city lights alter natural regimes of lunar sky brightness using a novel ten month time series of measurements recorded across a gradient of increasing light pollution. In the city, artificial lights increased sky brightness to levels six times above those recorded in rural locations, nine and twenty kilometers away. Artificial lighting masked natural monthly and seasonal regimes of lunar sky brightness in the city, and increased the number and annual regime of full moon equivalent hours available to organisms during the night. The changes have potentially profound ecological consequences.

  7. ns-ms excitation of alkali atoms in the Glauber approximation

    International Nuclear Information System (INIS)

    Barros, H.G. de P.L. de

    1980-05-01

    An expression for the scattering amplitude in the Glauber approximation for ns-ms electronic excitation of alkali atoms is obtained. The interaction potential between the incident electron, the core electrons and N-1 protons is approximated by an appropriate spherical potential. (Author) [pt

  8. Folding Proteins at 500 ns/hour with Work Queue.

    Science.gov (United States)

    Abdul-Wahid, Badi'; Yu, Li; Rajan, Dinesh; Feng, Haoyun; Darve, Eric; Thain, Douglas; Izaguirre, Jesús A

    2012-10-01

    Molecular modeling is a field that traditionally has large computational costs. Until recently, most simulation techniques relied on long trajectories, which inherently have poor scalability. A new class of methods is proposed that requires only a large number of short calculations, and for which minimal communication between computer nodes is required. We considered one of the more accurate variants called Accelerated Weighted Ensemble Dynamics (AWE) and for which distributed computing can be made efficient. We implemented AWE using the Work Queue framework for task management and applied it to an all atom protein model (Fip35 WW domain). We can run with excellent scalability by simultaneously utilizing heterogeneous resources from multiple computing platforms such as clouds (Amazon EC2, Microsoft Azure), dedicated clusters, grids, on multiple architectures (CPU/GPU, 32/64bit), and in a dynamic environment in which processes are regularly added or removed from the pool. This has allowed us to achieve an aggregate sampling rate of over 500 ns/hour. As a comparison, a single process typically achieves 0.1 ns/hour.

  9. High-brightness H/sup -/ accelerators

    International Nuclear Information System (INIS)

    Jameson, R.A.

    1987-01-01

    Neutral particle beam (NPB) devices based on high-brightness H/sup -/ accelerators are an important component of proposed strategic defense systems. The basic rational and R and D program are outlined and examples given of the underlying technology thrusts toward advanced systems. Much of the research accomplished in the past year is applicable to accelerator systems in general; some of these activities are discussed

  10. The surface brightness of 1550 galaxies in Fornax: automated galaxy surface photometry: Pt. 2

    International Nuclear Information System (INIS)

    Phillipps, S.; Disney, M.J.; Kibblewhite, E.J.; Cawson, M.G.M.

    1987-01-01

    A survey of a complete sample of galaxies in the region of the Fornax cluster is presented. Measurements with the Automatic Plate Measuring machine are used to derive the observed distribution of galaxy surface brightness for 1550 objects. Corrections for surface brightness dependent selection effects are then made in order to estimate the true distribution. It is found that the sample (with 16.6 ≤ Msub(APM) ≤ 19.1) is divided into two distinct populations. The 'normal' galaxies with extrapolated central surface brightness Ssub(x) ≤ 22.5 Bμ form a uniformly distributed background of field galaxies. Low surface brightness galaxies (Ssub(x) ≥ 22.5 Bμ), on the other hand, are strongly clumped about the cluster centre. There appear to be few low surface brightness field galaxies. (author)

  11. High-brightness electron injectors

    International Nuclear Information System (INIS)

    Sheffield, R.L.

    1987-01-01

    Free-electron laser (FEL) oscillators and synchrotron light sources require pulse trains of high peak brightness and, in some applications, high-average power. Recent developments in the technology of photoemissive and thermionic electron sources in rf cavities for electron-linac injector applications offer promising advances over conventional electron injectors. Reduced emittance growth in high peak-current electron injectors may be achieved by using high field strengths and by linearizing the radial component of the cavity electric field at the expense of lower shunt impedance

  12. Evaluation of the Tone Fan Noise Design/Prediction System (TFaNS) at the NASA Glenn Research Center

    Science.gov (United States)

    Koch, L. Danielle

    1999-01-01

    Version 1.4 of TFaNS, the Tone Fan Noise Design/Prediction System. has recently been evaluated at the NASA Glenn Research Center. Data from tests of the Allison Ultra High Bypass Fan (UHBF) were used to compare to predicted farfield directivities for the radial stator configuration. There was good agreement between measured and predicted directivities at low fan speeds when rotor effects were neglected in the TFaNS calculations. At higher fan speeds, TFaNS is shown to be useful in predicting overall trends rather than absolute sound pressure levels.

  13. Coordination chemistry and bioactivity of Ni2+, Cu2+, and Zn2+ complexes containing a bidentate NS ligand, β-N-phenyldithiocarbazic acid, and the crystal structure of β-hydroxy-β-phenylmethylene α-phenylimine

    International Nuclear Information System (INIS)

    Tarafder, M.T.H.; Ahmed Faizal Shamsuddin; Grouse, Karen A.; Yamin, B.M.; Ali, A.M.; Fun, H.-K.

    2003-07-01

    A bidentate ligand (PhDTCH) with NS donor sequence was prepared from the reaction between carbon disulfide and phenylhydrazine in ethanol. Complexes of this ligand with Ni(II), Cu(II) and Zn(II) were synthesized and characterized by elemental analyses, and various physicochemical techniques. The metal complexes were all four coordinated. In an attempt to resolve the crystal structure of PhDTCH, an ethanolic solution, after leaving for a few days gave bright crystals of PhD6, β-hydroxy-β-phenylmethylene α-phenylimine, the crystal structure of which has been resolved. The crystal packing indicated that it is monoclinic with a space group of P21/n. All of the compounds were tested against different bacteria and fungi, and also against leukemic cell lines. All of the compounds showed weak biological properties compared to standard drugs. (author)

  14. The NS1 polypeptide of the murine parvovirus minute virus of mice binds to DNA sequences containing the motif [ACCA]2-3.

    Science.gov (United States)

    Cotmore, S F; Christensen, J; Nüesch, J P; Tattersall, P

    1995-03-01

    A DNA fragment containing the minute virus of mice 3' replication origin was specifically coprecipitated in immune complexes containing the virally coded NS1, but not the NS2, polypeptide. Antibodies directed against the amino- or carboxy-terminal regions of NS1 precipitated the NS1-origin complexes, but antibodies directed against NS1 amino acids 284 to 459 blocked complex formation. Using affinity-purified histidine-tagged NS1 preparations, we have shown that the specific protein-DNA interaction is of moderate affinity, being stable in 0.1 M salt but rapidly lost at higher salt concentrations. In contrast, generalized (or nonspecific) DNA binding by NS1 could be demonstrated only in low salt. Addition of ATP or gamma S-ATP enhanced specific DNA binding by wild-type NS1 severalfold, but binding was lost under conditions which favored ATP hydrolysis. NS1 molecules with mutations in a critical lysine residue (amino acid 405) in the consensus ATP-binding site bound to the origin, but this binding could not be enhanced by ATP addition. DNase I protection assays carried out with wild-type NS1 in the presence of gamma S-ATP gave footprints which extended over 43 nucleotides on both DNA strands, from the middle of the origin bubble sequence to a position some 14 bp beyond the nick site. The DNA-binding site for NS1 was mapped to a 22-bp fragment from the middle of the 3' replication origin which contains the sequence ACCAACCA. This conforms to a reiterated motif (ACCA)2-3, which occurs, in more or less degenerate form, at many sites throughout the minute virus of mice genome (J. W. Bodner, Virus Genes 2:167-182, 1989). Insertion of a single copy of the sequence (ACCA)3 was shown to be sufficient to confer NS1 binding on an otherwise unrecognized plasmid fragment. The functions of NS1 in the viral life cycle are reevaluated in the light of this result.

  15. Discrepancy between Hepatitis C Virus Genotypes and NS4-Based Serotypes: Association with Their Subgenomic Sequences

    Directory of Open Access Journals (Sweden)

    Nan Nwe Win

    2017-01-01

    Full Text Available Determination of hepatitis C virus (HCV genotypes plays an important role in the direct-acting agent era. Discrepancies between HCV genotyping and serotyping assays are occasionally observed. Eighteen samples with discrepant results between genotyping and serotyping methods were analyzed. HCV serotyping and genotyping were based on the HCV nonstructural 4 (NS4 region and 5′-untranslated region (5′-UTR, respectively. HCV core and NS4 regions were chosen to be sequenced and were compared with the genotyping and serotyping results. Deep sequencing was also performed for the corresponding HCV NS4 regions. Seventeen out of 18 discrepant samples could be sequenced by the Sanger method. Both HCV core and NS4 sequences were concordant with that of genotyping in the 5′-UTR in all 17 samples. In cloning analysis of the HCV NS4 region, there were several amino acid variations, but each sequence was much closer to the peptide with the same genotype. Deep sequencing revealed that minor clones with different subgenotypes existed in two of the 17 samples. Genotyping by genome amplification showed high consistency, while several false reactions were detected by serotyping. The deep sequencing method also provides accurate genotyping results and may be useful for analyzing discrepant cases. HCV genotyping should be correctly determined before antiviral treatment.

  16. Sky Brightness During Eclipses: A Compendium from the Literature

    Science.gov (United States)

    1974-08-05

    Star Sightings 1880A 11 Jan 1880 Santa- Lucia Jupiter -3 Mars .3 No stars 1882A 17 May 1882 Sohag, Egypt Stars shone brightly 1883A 6 M.»y 1883...1870 E 1880 A 1886 BA 1887 F 1889 A2 1900 EB 1914 A 1927 B Location London Venice Bue Island Gottenbui g Vumpurthy Seville Santa- Lucia ...manner, and at the peak of day the stars ap- peared brightly. (Tatti Annali sacri della citta di Como.) 5 MAY 840 840 DB Ginzel p. 668 Italy In

  17. Development and characterization of serotype-specific monoclonal antibodies against the dengue virus-4 (DENV-4) non-structural protein (NS1).

    Science.gov (United States)

    Gelanew, Tesfaye; Hunsperger, Elizabeth

    2018-02-06

    Dengue, caused by one of the four serologically distinct dengue viruses (DENV-1 to - 4), is a mosquito-borne disease of serious global health significance. Reliable and cost-effective diagnostic tests, along with effective vaccines and vector-control strategies, are highly required to reduce dengue morbidity and mortality. Evaluation studies revealed that many commercially available NS1 antigen (Ag) tests have limited sensitivity to DENV-4 serotype compared to the other three serotypes. These studies indicated the need for development of new NS1 Ag detection test with improved sensitivity to DENV-4. An NS1 capture enzyme linked immunoassay (ELISA) specific to DENV-4 may improve the detection of DENV-4 cases worldwide. In addition, a serotype-specific NS1 Ag test identifies both DENV and the infecting serotype. In this study, we used a small-ubiquitin-like modifier (SUMO*) cloning vector to express a SUMO*-DENV-4 rNS1 fusion protein to develop NS1 DENV-4 specific monoclonal antibodies (MAbs). These newly developed MAbs were then optimized for use in an anti-NS1 DENV-4 capture ELISA. The serotype specificity and sensitivity of this ELISA was evaluated using (i) supernatants from DENV (1-4)-infected Vero cell cultures, (ii) rNS1s from all the four DENV (1-4) and, (iii) rNS1s of related flaviviruses (yellow fever virus; YFV and West Nile virus; WNV). From the evaluation studies of the newly developed MAbs, we identified three DENV-4 specific anti-NS1 MAbs: 3H7A9, 8A6F2 and 6D4B10. Two of these MAbs were optimal for use in a DENV-4 serotype-specific NS1 capture ELISA: MAb 8A6F2 as the capture antibody and 6D4B10 as a detection antibody. This ELISA was sensitive and specific to DENV-4 with no cross-reactivity to other three DENV (1-3) serotypes and other heterologous flaviviruses. Taken together these data indicated that our MAbs are useful reagents for the development of DENV-4 immunodiagnostic tests.

  18. Mutation of CD2AP and SH3KBP1 Binding Motif in Alphavirus nsP3 Hypervariable Domain Results in Attenuated Virus.

    Science.gov (United States)

    Mutso, Margit; Morro, Ainhoa Moliner; Smedberg, Cecilia; Kasvandik, Sergo; Aquilimeba, Muriel; Teppor, Mona; Tarve, Liisi; Lulla, Aleksei; Lulla, Valeria; Saul, Sirle; Thaa, Bastian; McInerney, Gerald M; Merits, Andres; Varjak, Margus

    2018-04-27

    Infection by Chikungunya virus (CHIKV) of the Old World alphaviruses (family Togaviridae) in humans can cause arthritis and arthralgia. The virus encodes four non-structural proteins (nsP) (nsP1, nsp2, nsP3 and nsP4) that act as subunits of the virus replicase. These proteins also interact with numerous host proteins and some crucial interactions are mediated by the unstructured C-terminal hypervariable domain (HVD) of nsP3. In this study, a human cell line expressing EGFP tagged with CHIKV nsP3 HVD was established. Using quantitative proteomics, it was found that CHIKV nsP3 HVD can bind cytoskeletal proteins, including CD2AP, SH3KBP1, CAPZA1, CAPZA2 and CAPZB. The interaction with CD2AP was found to be most evident; its binding site was mapped to the second SH3 ligand-like element in nsP3 HVD. Further assessment indicated that CD2AP can bind to nsP3 HVDs of many different New and Old World alphaviruses. Mutation of the short binding element hampered the ability of the virus to establish infection. The mutation also abolished ability of CD2AP to co-localise with nsP3 and replication complexes of CHIKV; the same was observed for Semliki Forest virus (SFV) harbouring a similar mutation. Similar to CD2AP, its homolog SH3KBP1 also bound the identified motif in CHIKV and SFV nsP3.

  19. In Vitro Antiviral Activity and Resistance Profile of the Next-Generation Hepatitis C Virus NS5A Inhibitor Pibrentasvir.

    Science.gov (United States)

    Ng, Teresa I; Krishnan, Preethi; Pilot-Matias, Tami; Kati, Warren; Schnell, Gretja; Beyer, Jill; Reisch, Thomas; Lu, Liangjun; Dekhtyar, Tatyana; Irvin, Michelle; Tripathi, Rakesh; Maring, Clarence; Randolph, John T; Wagner, Rolf; Collins, Christine

    2017-05-01

    Pibrentasvir (ABT-530) is a novel and pan-genotypic hepatitis C virus (HCV) NS5A inhibitor with 50% effective concentration (EC 50 ) values ranging from 1.4 to 5.0 pM against HCV replicons containing NS5A from genotypes 1 to 6. Pibrentasvir demonstrated similar activity against a panel of chimeric replicons containing HCV NS5A of genotypes 1 to 6 from clinical samples. Resistance selection studies were conducted using HCV replicon cells with NS5A from genotype 1a, 1b, 2a, 2b, 3a, 4a, 5a, or 6a at a concentration of pibrentasvir that was 10- or 100-fold over its EC 50 for the respective replicon. With pibrentasvir at 10-fold over the respective EC 50 , only a small number of colonies (0.00015 to 0.0065% of input cells) with resistance-associated amino acid substitutions were selected in replicons containing genotype 1a, 2a, or 3a NS5A, and no viable colonies were selected in replicons containing NS5A from other genotypes. With pibrentasvir at 100-fold over the respective EC 50 , very few colonies (0.0002% of input cells) were selected by pibrentasvir in genotype 1a replicon cells while no colonies were selected in other replicons. Pibrentasvir is active against common resistance-conferring substitutions in HCV genotypes 1 to 6 that were identified for other NS5A inhibitors, including those at key amino acid positions 28, 30, 31, or 93. The combination of pibrentasvir with HCV inhibitors of other classes produced synergistic inhibition of HCV replication. In summary, pibrentasvir is a next-generation HCV NS5A inhibitor with potent and pan-genotypic activity, and it maintains activity against common amino acid substitutions of HCV genotypes 1 to 6 that are known to confer resistance to currently approved NS5A inhibitors. Copyright © 2017 Ng et al.

  20. Investigating a population of infrared-bright gamma-ray burst host galaxies

    Science.gov (United States)

    Chrimes, Ashley A.; Stanway, Elizabeth R.; Levan, Andrew J.; Davies, Luke J. M.; Angus, Charlotte R.; Greis, Stephanie M. L.

    2018-04-01

    We identify and explore the properties of an infrared-bright gamma-ray burst (GRB) host population. Candidate hosts are selected by coincidence with sources in WISE, with matching to random coordinates and a false alarm probability analysis showing that the contamination fraction is ˜ 0.5. This methodology has already identified the host galaxy of GRB 080517. We combine survey photometry from Pan-STARRS, SDSS, APASS, 2MASS, GALEX and WISE with our own WHT/ACAM and VLT/X-shooter observations to classify the candidates and identify interlopers. Galaxy SED fitting is performed using MAGPHYS, in addition to stellar template fitting, yielding 13 possible IR-bright hosts. A further 7 candidates are identified from previously published work. We report a candidate host for GRB 061002, previously unidentified as such. The remainder of the galaxies have already been noted as potential hosts. Comparing the IR-bright population properties including redshift z, stellar mass M⋆, star formation rate SFR and V-band attenuation AV to GRB host catalogues in the literature, we find that the infrared-bright population is biased toward low z, high M⋆ and high AV. This naturally arises from their initial selection - local and dusty galaxies are more likely to have the required IR flux to be detected in WISE. We conclude that while IR-bright GRB hosts are not a physically distinct class, they are useful for constraining existing GRB host populations, particularly for long GRBs.

  1. The Eindhoven High-Brightness Electron Programme

    NARCIS (Netherlands)

    Brussaard, G.J.H.; Wiel, van der M.J.

    2004-01-01

    The Eindhoven High-Brightness programme is aimed at producing ultra-short intense electron bunches from compact accelerators. The RF electron gun is capable of producing 100 fs electron bunches at 7.5 MeV and 10 pC bunch charge. The DC/RF hybrid gun under development will produce bunches <75 fs at

  2. Engineered toxins "zymoxins" are activated by the HCV NS3 protease by removal of an inhibitory protein domain.

    Directory of Open Access Journals (Sweden)

    Assaf Shapira

    Full Text Available The synthesis of inactive enzyme precursors, also known as "zymogens," serves as a mechanism for regulating the execution of selected catalytic activities in a desirable time and/or site. Zymogens are usually activated by proteolytic cleavage. Many viruses encode proteases that execute key proteolytic steps of the viral life cycle. Here, we describe a proof of concept for a therapeutic approach to fighting viral infections through eradication of virally infected cells exclusively, thus limiting virus production and spread. Using the hepatitis C virus (HCV as a model, we designed two HCV NS3 protease-activated "zymogenized" chimeric toxins (which we denote "zymoxins". In these recombinant constructs, the bacterial and plant toxins diphtheria toxin A (DTA and Ricin A chain (RTA, respectively, were fused to rationally designed inhibitor peptides/domains via an HCV NS3 protease-cleavable linker. The above toxins were then fused to the binding and translocation domains of Pseudomonas exotoxin A in order to enable translocation into the mammalian cells cytoplasm. We show that these toxins exhibit NS3 cleavage dependent increase in enzymatic activity upon NS3 protease cleavage in vitro. Moreover, a higher level of cytotoxicity was observed when zymoxins were applied to NS3 expressing cells or to HCV infected cells, demonstrating a potential therapeutic window. The increase in toxin activity correlated with NS3 protease activity in the treated cells, thus the therapeutic window was larger in cells expressing recombinant NS3 than in HCV infected cells. This suggests that the "zymoxin" approach may be most appropriate for application to life-threatening acute infections where much higher levels of the activating protease would be expected.

  3. On the relation of Hsub(α) plage brightness variations in solar active regions

    International Nuclear Information System (INIS)

    Ogir', M.B.

    1980-01-01

    The variations of hydrogen plage brightnesses in seven spot groups belonging to five active regions are discussed. The observations were made on the Crimean observatory coronograph in 1974 and 1977. The correlation in brightness variations of plages situated in the regions of growing magnetic field was obtained. This was observed in the plages on one spot group as well as in the different groups removing on about 27x10 4 km. In developed groups correlations are mainly seen within a spot group and they are expressed better during flares. The correlations of brightnesses are changing during the active region evolution. Three days observations showed good brightness correlations of all plages in the growing magnetic field region and their decrease that can be explained by the field weakening during natural active region evolution or by the strong flare influence. The existence of the simultaneous variations of brightness in the regions with the growing magnetic field speaks in favour of the simultaneous carring-out of magnetic field or its disturbances into the chromosphere [ru

  4. Spots on electrodes and images of a gap during pulsed discharges in an inhomogeneous electric field at elevated pressures of air, nitrogen and argon

    International Nuclear Information System (INIS)

    Shao, Tao; Yang, Wenjin; Zhang, Cheng; Yan, Ping; Tarasenko, Victor F; Beloplotov, Dmitry V; Lomaev, Mikhail I; Sorokin, Dmitry A

    2014-01-01

    Pulsed discharge in a nonuniform electric field accompanied by the appearance of bright spots due to explosive electron emission on electrodes has been investigated. The experiments were carried out using three experimental setups, a voltage pulse duration at a matched load of 2 ns, 40 ns, and 130 ns, respectively. Data on the formation of electrode spots during diffuse discharges in tube-plate or needle-plate gap configurations filled with gases at elevated pressures (air, nitrogen and argon) were obtained. It was found that in the air and other gases, bright spots arise on the flat electrode, and on the negative polarity of the electrode with a small radius of curvature, during the direction change of the current through the gap and the increase of the voltage pulse duration. It was shown that at the positive polarity of the electrode with a small radius of curvature, bright spots on the flat electrode arise due to the participation of the dynamic displacement current in the gap conductance. (paper)

  5. Optical and EPR spectra of the thionitrosyl complex [Cr(OH2)5(NS)]2+

    DEFF Research Database (Denmark)

    Døssing, Anders Rørbæk; Dethlefsen, Johannes Wied

    2008-01-01

    . The optical data indicate that the NS ligand is a weaker p-acceptor than the NO ligand. The EPR parameters of [Cr(OH2)5(NS)]2+ were determined: giso, g¦ and g-: 1.96515, 1.92686(5) and 1.986860(8); Aiso(53Cr), A¦(53Cr) and A-(53Cr): 25.3´10-4, 38´10-4 and 18.5´10-4cm-1; Aiso(14N), A¦(14N) and A-(14N): 6...

  6. Electronic structures and valence band splittings of transition metals doped GaNs

    International Nuclear Information System (INIS)

    Lee, Seung-Cheol; Lee, Kwang-Ryeol; Lee, Kyu-Hwan

    2007-01-01

    For a practical viewpoint, presence of spin splitting of valence band in host semiconductors by the doping of transition metal (TM) ions is an essential property when designing a diluted magnetic semiconductors (DMS) material. The first principle calculations were performed on the electronic and magnetic structure of 3d transition metal doped GaN. V, Cr, and Mn doped GaNs could not be candidates for DMS materials since most of their magnetic moments is concentrated on the TM ions and the splittings of valence band were negligible. In the cases of Fe, Co, Ni, and Cu doped GaNs, on the contrary, long-ranged spin splitting of valence band was found, which could be candidates for DMS materials

  7. Computational study on the inhibitor binding mode and allosteric regulation mechanism in hepatitis C virus NS3/4A protein.

    Directory of Open Access Journals (Sweden)

    Weiwei Xue

    Full Text Available HCV NS3/4A protein is an attractive therapeutic target responsible for harboring serine protease and RNA helicase activities during the viral replication. Small molecules binding at the interface between the protease and helicase domains can stabilize the closed conformation of the protein and thus block the catalytic function of HCV NS3/4A protein via an allosteric regulation mechanism. But the detailed mechanism remains elusive. Here, we aimed to provide some insight into the inhibitor binding mode and allosteric regulation mechanism of HCV NS3/4A protein by using computational methods. Four simulation systems were investigated. They include: apo state of HCV NS3/4A protein, HCV NS3/4A protein in complex with an allosteric inhibitor and the truncated form of the above two systems. The molecular dynamics simulation results indicate HCV NS3/4A protein in complex with the allosteric inhibitor 4VA adopts a closed conformation (inactive state, while the truncated apo protein adopts an open conformation (active state. Further residue interaction network analysis suggests the communication of the domain-domain interface play an important role in the transition from closed to open conformation of HCV NS3/4A protein. However, the inhibitor stabilizes the closed conformation through interaction with several key residues from both the protease and helicase domains, including His57, Asp79, Asp81, Asp168, Met485, Cys525 and Asp527, which blocks the information communication between the functional domains interface. Finally, a dynamic model about the allosteric regulation and conformational changes of HCV NS3/4A protein was proposed and could provide fundamental insights into the allosteric mechanism of HCV NS3/4A protein function regulation and design of new potent inhibitors.

  8. The bidirectional congruency effect of brightness-valence metaphoric association in the Stroop-like and priming paradigms.

    Science.gov (United States)

    Huang, Yanli; Tse, Chi-Shing; Xie, Jiushu

    2017-11-04

    The conceptual metaphor theory (Lakoff & Johnson, 1980, 1999) postulates a unidirectional metaphoric association between abstract and concrete concepts: sensorimotor experience activated by concrete concepts facilitates the processing of abstract concepts, but not the other way around. However, this unidirectional view has been challenged by studies that reported a bidirectional metaphoric association. In three experiments, we tested the directionality of the brightness-valence metaphoric association, using Stroop-like paradigm, priming paradigm, and Stroop-like paradigm with a go/no-go manipulation. Both mean and vincentile analyses of reaction time data were performed. We showed that the directionality of brightness-valence metaphoric congruency effect could be modulated by the activation level of the brightness/valence information. Both brightness-to-valence and valence-to-brightness metaphoric congruency effects occurred in the priming paradigm, which could be attributed to the presentation of prime that pre-activated the brightness or valence information. However, in the Stroop-like paradigm the metaphoric congruency effect was only observed in the brightness-to-valence direction, but not in the valence-to-brightness direction. When the go/no-go manipulation was used to boost the activation of word meaning in the Stroop-like paradigm, the valence-to-brightness metaphoric congruency effect was observed. Vincentile analyses further revealed that valence-to-brightness metaphoric congruency effect approached significance in the Stroop-like paradigm when participants' reaction times were slower (at around 490ms). The implications of the current findings on the conceptual metaphor theory and embodied cognition are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Three Bright X-ray Sources in NGC 1313

    Science.gov (United States)

    Colbert, E.; Petre, R.; Schlegel, E.

    1992-12-01

    Three bright X-ray sources were detected in a recent (April/May 1991) ROSAT PSPC observation of the nearby (D ~ 4.5 Mpc) face--on barred spiral galaxy NGC 1313. Two of the sources were at positions coincident with X-ray sources detected by Fabbiano & Trinchieri (ApJ 315, 1987) in a previous (Jan 1980) Einstein IPC observation. The position of the brightest Einstein source is near the center of NGC 1313, and the second Einstein source is ~ 7' south of the ``nuclear'' source, in the outskirts of the spiral arms. A third bright X-ray source was detected in the ROSAT observation ~ 7' southwest of the ``nuclear'' source. We present X-ray spectra and X-ray images for the three bright sources found in the ROSAT observation of NGC 1313, and compare with previous Einstein results. Spectral analysis of these sources require them to have very large soft X-ray luminosities ( ~ 10(40) erg s(-1) ) when compared with typical X-ray sources in our Galaxy. Feasible explanations for the X-ray emission are presented. The third X-ray source is positively identified with the recently discovered (Ryder et. al., ApJ 1992) peculiar type-II supernova 1978K.

  10. NS5B RNA dependent RNA polymerase inhibitors: the promising approach to treat hepatitis C virus infections.

    Science.gov (United States)

    Deore, R R; Chern, J-W

    2010-01-01

    Hepatitis C virus (HCV), a causative agent for non-A and non-B hepatitis, has infected approximately 3% of world's population. The current treatment option of ribavirin in combination with pegylated interferon possesses lower sustained virological response rates, and has serious disadvantages. Unfortunately, no prophylactic vaccine has been approved yet. Therefore, there is an unmet clinical need for more effective and safe anti-HCV drugs. HCV NS5B RNA dependent RNA polymerase is currently pursued as the most popular target to develop safe anti-HCV agents, as it is not expressed in uninfected cells. More than 25 pharmaceutical companies and some research groups have developed ≈50 structurally diverse scaffolds to inhibit NS5B. Here we provide comprehensive account of the drug development process of these scaffolds. NS5B polymerase inhibitors have been broadly classified in nucleoside and non nucleoside inhibitors and are sub classified according to their mechanism of action and structural diversities. With some additional considerations about the inhibitor bound NS5B enzyme X-ray crystal structure information and pharmacological aspects of the inhibitors, this review summarizes the lead identification, structure activity relationship (SAR) studies leading to the most potent NS5B inhibitors with subgenomic replicon activity.

  11. Bright patches on chernozems - from space to surface and soil properties

    Science.gov (United States)

    Smetanova, Anna; Burian, Libor; Holec, Juraj; Minár, Jozef

    2016-04-01

    The bright patches on chernozems can be easily visually distinguished in the aerial images, due to their bright colour contrasting with the dark colour of the surrounding chernozems. They present a typical feature of the loess hilly lands in the Danube Lowland. They reffer predominantely to the areas where (i) the soil substrate - loess is tilled, (ii) the transitional AC horizon of chernozems is tilled, (iii) or one of them, or both are mixed into the plough layer during tillage. They are usually categorized as eroded chernozems or regosols. To the lower extent, the accumulation patches might occur, if the loess material redeposited from upper part of the slope in the colluvium is tilled. This study focuses on uncovering the soil properties of bright patches, identified on different scales - spatial and temporal, combining three methods - the remote sensing, morphometric analysis and soil mapping. In the area of 31 km² (located in the Trnavska pahorkatina Hilly Land, south of Trnava), the bright patches were identified using visual analysis of georeferenced aerial images from 1949 and 2004, representing two types of landscape structure characteristic for the 20th Century. In 1949 small, in one direction elongated fields, with mean size 0.008 km2 prevailed, while in 2004 the mean size of a field was 0.28 km2. The morphometric analysis was performed based on DEM derived from topographical maps (scale 1:10 000). Soil sampling in the first phase of the project was performed in a subset of the patches in small agriculture catchment (0.28 km2), situated in one single field (in 2004). The percussion drilling or hand augering (with undisturbed structure) were used in order to describe the depth of the soil horizons and the soil properties. Together 365 bright patches covering 3.2% of the study area (31 km²) were identified in 1949; while it was twice more in 2004 (776 patches), when they covered approximately 12% of the same area. The bright patches were predominantly

  12. Analytically derived conversion of spectral band radiance to brightness temperature

    Energy Technology Data Exchange (ETDEWEB)

    Berk, Alexander [Spectral Sciences, Inc., 44th Avenue, Burlington, MA 01803 (United States)], E-mail: lex@spectral.com

    2008-05-15

    Simple analytic expressions for brightness temperature have been derived in terms of band response function spectral moments. Accuracy measures are also derived. Application of these formulas to GOES-12 Sounder thermal infrared bands produces brightness temperature residuals between -5.0 and 2.5 mK for a 150-400 K temperature range. The magnitude of residuals for the five ASTER Radiometer thermal infrared bands over the same temperature range is less than 0.22 mK.

  13. Bright matter wave solitons and their collision in Bose-Einstein condensates

    International Nuclear Information System (INIS)

    Radha, R.; Ramesh Kumar, V.

    2007-01-01

    We obtain the bright matter wave solitons in Bose-Einstein condensates from a trivial input solution by solving the time dependent Gross-Pitaevskii (GP) equation with quadratic potential and exponentially varying scattering length. We observe that the matter wave density of bright soliton increases with time by virtue of the exponentially increasing scattering length. We also understand that the matter wave densities of bright soliton trains remain finite despite the exchange of atoms during interaction and they travel along different trajectories (diverge) after interaction. We also observe that their amplitudes continue to fluctuate with time. For exponentially decaying scattering lengths, instability sets in the condensates. However, the scattering length can be suitably manipulated without causing the explosion or the collapse of the condensates

  14. Energy and Emission Characteristics of a Short-Arc Xenon Flash Lamp Under "Saturated" Optical Brightness Conditions

    Science.gov (United States)

    Kamrukov, A. S.; Kireev, S. G.; Kozlov, N. P.; Shashkovskii, S. G.

    2017-09-01

    We present the results of a study of the electrical, energy, and spectral brightness characteristics of an experimental three-electrode high-pressure xenon flash lamp under conditions ensuring close to maximum possible spectral brightness for the xenon emission. We show that under saturated optical brightness conditions (brightness temperature in the visible region of the spectrum 30,000 K), emission of a pulsed discharge in xenon is quite different from the emission from an ideal blackbody: the maximum brightness temperatures are 24,000 K in the short-wavelength UV region and 19,000 K in the near IR range. The relative fraction of UV radiation in the emission spectrum of the lamp is >50%, which lets us consider such lamps as promising broadband sources of radiation with high spectral brightness for many important practical applications.

  15. A high brightness probe of polymer nanoparticles for biological imaging

    Science.gov (United States)

    Zhou, Sirong; Zhu, Jiarong; Li, Yaping; Feng, Liheng

    2018-03-01

    Conjugated polymer nanoparticles (CPNs) with high brightness in long wavelength region were prepared by the nano-precipitation method. Based on fluorescence resonance energy transfer (FRET) mechanism, the high brightness property of the CPNs was realized by four different emission polymers. Dynamic light scattering (DLS) and scanning electron microscopy (SEM) displayed that the CPNs possessed a spherical structure and an average diameter of 75 nm. Analysis assays showed that the CPNs had excellent biocompatibility, good photostability and low cytotoxicity. The CPNs were bio-modified with a cell penetrating peptide (Tat, a targeted element) through covalent link. Based on the entire wave fluorescence emission, the functionalized CPNs1-4 can meet multichannel and high throughput assays in cell and organ imaging. The contribution of the work lies in not only providing a new way to obtain a high brightness imaging probe in long wavelength region, but also using targeted cell and organ imaging.

  16. Orientation of coronal bright points and small-scale magnetic bipoles

    International Nuclear Information System (INIS)

    MINENKO, E.P.; SHERDANOV, CH.T.; SATTAROV, I.; KARACHIK, N.V.

    2014-01-01

    Using the observations from Extreme-Ultraviolet Imaging Telescope (EIT) on the SOHO board and longitudinal full-disk magnetograms (vector spectromagnetograph - VSM) from the Synoptic Optical Long-Term Investigations of the Sun (SOLIS), we explore the orientation and relationship between the coronal bright points at 195 A o (hereafter CBPs) and magnetic bipoles (only for the central zone of solar disk). The magnetic bipoles are identified as a pair of streams of positive and negative polarities with a shortest distance between them. This paper presents a study of the structure and orientation (angles) of magnetic bipoles to the solar equator and two types of CBPs: 'dim' CBPs in the quiet regions of the Sun and 'bright' CBPs associated with active regions. For these magnetic bipoles associated with 'bright' CBPs, we find that their orientation angles are distributed randomly along the equator. (authors)

  17. Three-dimensional analysis of free-electron laser performance using brightness scaled variables

    Directory of Open Access Journals (Sweden)

    M. Gullans

    2008-06-01

    Full Text Available A three-dimensional analysis of radiation generation in a free-electron laser (FEL is performed in the small signal regime. The analysis includes beam conditioning, harmonic generation, flat beams, and a new scaling of the FEL equations using the six-dimensional beam brightness. The six-dimensional beam brightness is an invariant under Liouvillian flow; therefore, any nondissipative manipulation of the phase space, performed, for example, in order to optimize FEL performance, must conserve this brightness. This scaling is more natural than the commonly used scaling with the one-dimensional growth rate. The brightness-scaled equations allow for the succinct characterization of the optimal FEL performance under various additional constraints. The analysis allows for the simple evaluation of gain enhancement schemes based on beam phase space manipulations such as emittance exchange and conditioning. An example comparing the gain in the first and third harmonics of round or flat and conditioned or unconditioned beams is presented.

  18. The SDSS view of the Palomar-Green bright quasar survey

    Energy Technology Data Exchange (ETDEWEB)

    Jester, Sebastian; Schneider, Donald P.; Richards, Gordon T.; Green, Richard F.; Schmidt, Maarten; Hall, Patrick B.; Strauss, Michael A.; Vanden Berk, Daniel E.; Stoughton, Chris; Gunn, James E.; Brinkmann, Jon; Kent, Stephen M.; Smith, J.Allyn; Tucker, Douglas, L.; Yanny, Brian; /Fermilab /Penn State U., Astron. Astrophys. /Princeton U.

    2005-02-01

    The author investigates the extent to which the Palomar-Green (PG) Bright Quasar Survey (BQS) is complete and representative of the general quasar population by comparing with imaging and spectroscopy from the Sloan Digital Sky Survey. A comparison of SDSS and PG photometry of both stars and quasars reveals the need to apply a color and magnitude recalibration to the PG data. Using the SDSS photometric catalog, they define the PG's parent sample of objects that are not main-sequence stars and simulate the selection of objects from this parent sample using the PG photometric criteria and errors. This simulation shows that the effective U-B cut in the PG survey is U-B < -0.71, implying a color-related incompleteness. As the color distribution of bright quasars peaks near U-B = -0.7 and the 2-{sigma} error in U-B is comparable to the full width of the color distribution of quasars, the color incompleteness of the BQS is approximately 50% and essentially random with respect to U-B color for z < 0.5. There is however, a bias against bright quasars at 0.5 < z < 1, which is induced by the color-redshift relation of quasars (although quasars at z > 0.5 are inherently rare in bright surveys in any case). They find no evidence for any other systematic incompleteness when comparing the distributions in color, redshift, and FIRST radio properties of the BQS and a BQS-like subsample of the SDSS quasar sample. However, the application of a bright magnitude limit biases the BQS toward the inclusion of objects which are blue in g-i, in particular compared to the full range of g-i colors found among the i-band limited SDSS quasars, and even at i-band magnitudes comparable to those of the BQS objects.

  19. Mutation of CD2AP and SH3KBP1 Binding Motif in Alphavirus nsP3 Hypervariable Domain Results in Attenuated Virus

    Directory of Open Access Journals (Sweden)

    Margit Mutso

    2018-04-01

    Full Text Available Infection by Chikungunya virus (CHIKV of the Old World alphaviruses (family Togaviridae in humans can cause arthritis and arthralgia. The virus encodes four non-structural proteins (nsP (nsP1, nsp2, nsP3 and nsP4 that act as subunits of the virus replicase. These proteins also interact with numerous host proteins and some crucial interactions are mediated by the unstructured C-terminal hypervariable domain (HVD of nsP3. In this study, a human cell line expressing EGFP tagged with CHIKV nsP3 HVD was established. Using quantitative proteomics, it was found that CHIKV nsP3 HVD can bind cytoskeletal proteins, including CD2AP, SH3KBP1, CAPZA1, CAPZA2 and CAPZB. The interaction with CD2AP was found to be most evident; its binding site was mapped to the second SH3 ligand-like element in nsP3 HVD. Further assessment indicated that CD2AP can bind to nsP3 HVDs of many different New and Old World alphaviruses. Mutation of the short binding element hampered the ability of the virus to establish infection. The mutation also abolished ability of CD2AP to co-localise with nsP3 and replication complexes of CHIKV; the same was observed for Semliki Forest virus (SFV harbouring a similar mutation. Similar to CD2AP, its homolog SH3KBP1 also bound the identified motif in CHIKV and SFV nsP3.

  20. Bright point study. [of solar corona

    Science.gov (United States)

    Tang, F.; Harvey, K.; Bruner, M.; Kent, B.; Antonucci, E.

    1982-01-01

    Transition region and coronal observations of bright points by instruments aboard the Solar Maximum Mission and high resolution photospheric magnetograph observations on September 11, 1980 are presented. A total of 31 bipolar ephemeral regions were found in the photosphere from birth in 9.3 hours of combined magnetograph observations from three observatories. Two of the three ephemeral regions present in the field of view of the Ultraviolet Spectrometer-Polarimeter were observed in the C IV 1548 line. The unobserved ephemeral region was determined to be the shortest-lived (2.5 hr) and lowest in magnetic flux density (13G) of the three regions. The Flat Crystal Spectrometer observed only low level signals in the O VIII 18.969 A line, which were not statistically significant to be positively identified with any of the 16 ephemeral regions detected in the photosphere. In addition, the data indicate that at any given time there lacked a one-to-one correspondence between observable bright points and photospheric ephemeral regions, while more ephemeral regions were observed than their counterparts in the transition region and the corona.

  1. Influences of diurnal bright or dim light exposure on urine volume in humans.

    Science.gov (United States)

    Hyun, Ki-Ja; Nishimura, Shinya; Tokura, Hiromi

    2006-03-01

    We investigated with eight healthy females if 8 hr diurnal (0700 to 1500 h) bright rather than dim light (5,000 vs. 80 lx) influenced urine volume. Environmental illuminance was made identical at all other times besides 07:00 to 15:00 h. The participants spent time at strictly regulated schedules in a bioclimatic chamber (26 degrees C, relative humidity 60%) for 57 h. Blood was drawn (2 ml) just before lunch in order to calculate Creatinine clearance (Ccr). Urine volume was significantly higher during wakefulness and the 8-h sleep period with bright rather than dim light. Ccr was significantly higher after bright light. The results were discussed in terms of suppression of the sympathetic nerve system under the influence of diurnal bright light exposure. We also discussed these in terms of physiological polymorphisms.

  2. Sn ion energy distributions of ns- and ps-laser produced plasmas

    Science.gov (United States)

    Bayerle, A.; Deuzeman, M. J.; van der Heijden, S.; Kurilovich, D.; de Faria Pinto, T.; Stodolna, A.; Witte, S.; Eikema, K. S. E.; Ubachs, W.; Hoekstra, R.; Versolato, O. O.

    2018-04-01

    Ion energy distributions arising from laser-produced plasmas of Sn are measured over a wide laser parameter space. Planar-solid and liquid-droplet targets are exposed to infrared laser pulses with energy densities between 1 J cm‑2 and 4 kJ cm‑2 and durations spanning 0.5 ps to 6 ns. The measured ion energy distributions are compared to two self-similar solutions of a hydrodynamic approach assuming isothermal expansion of the plasma plume into vacuum. For planar and droplet targets exposed to ps-long pulses, we find good agreement between the experimental results and the self-similar solution of a semi-infinite simple planar plasma configuration with an exponential density profile. The ion energy distributions resulting from solid Sn exposed to ns-pulses agrees with solutions of a limited-mass model that assumes a Gaussian-shaped initial density profile.

  3. ASAS-SN Discovery of a Bright Be Star Undergoing a Possible Outburst

    Science.gov (United States)

    Jayasinghe, T.; Stanek, K. Z.; Kochanek, C. S.; Thorstensen, J.; Rupert, J.; Prieto, J. L.; Shields, J. V.; Thompson, T. A.; Holoien, T. W.-S.; Shappee, B. J.; Dong, Subo

    2017-09-01

    As part of an ongoing effort by ASAS-SN project (Shappee et al. 2014; Kochanek et al. 2017) to characterize and catalog all bright variable stars (e.g., Jayasinghe et al. 2017, ATel #10634, #10677), we report the discovery of a bright Be star undergoing a possible outburst.

  4. Bright green light treatment of depression for older adults [ISRCTN69400161

    Directory of Open Access Journals (Sweden)

    Knickerbocker Nancy C

    2005-11-01

    Full Text Available Abstract Background Bright white light has been successfully used for the treatment of depression. There is interest in identifying which spectral colors of light are the most efficient in the treatment of depression. It is theorized that green light could decrease the intensity duration of exposure needed. Late Wake Treatment (LWT, sleep deprivation for the last half of one night, is associated with rapid mood improvement which has been sustained by light treatment. Because spectral responsiveness may differ by age, we examined whether green light would provide efficient antidepressant treatment in an elder age group. Methods We contrasted one hour of bright green light (1,200 Lux and one hour of dim red light placebo ( Results The protocol was completed by 33 subjects who were 59 to 80 years old. Mood improved on average 23% for all subjects, but there were no significant statistical differences between treatment and placebo groups. There were negligible adverse reactions to the bright green light, which was well tolerated. Conclusion Bright green light was not shown to have an antidepressant effect in the age group of this study, but a larger trial with brighter green light might be of value.

  5. Fluorescence brightness and photostability of individual copper (I) oxide nanocubes.

    Science.gov (United States)

    Zohora, Nafisa; Kandjani, Ahmad Esmaielzadeh; Orth, Antony; Brown, Hannah M; Hutchinson, Mark R; Gibson, Brant C

    2017-12-04

    Conventional organic fluorophores lose their ability to fluoresce after repeated exposure to excitation light due to photobleaching. Therefore, research into emerging bright and photostable nanomaterials has become of great interest for a range of applications such as bio-imaging and tracking. Among these emerging fluorophores, metal oxide-based nanomaterials have attracted significant attention as a potential multifunctional material with photocatalytic and angeogenisis abilities in addition to fluorescnce applications. However, most of these applications are highly dependent on size, morphology, and chemo-physical properties of individual particles. In this manuscript, we present a method to study the intrinsic optical characteristics of individual copper (I) oxide (Cu 2 O) nanocubes. When excited at 520 nm using only 11 µW excitation power (1.7 W/cm2), individual nanocubes were observed to emit light with peak wavelengths ~760 nm which is conveniently within the near-infrared 1 (NIR1) biological window where tissue autofluorescence is minimal. Bright and photostable fluorescence was observed with intensities up to 487 K counts/s under constant illumination for at least 2 minutes with a brightness approximately four times higher than the autofluorescence from a fixed cumulus-oocyte complex. With near-IR emission, high fluorescence brightness, and outstanding photostability, Cu 2 O nanocubes are attractive candidates for long-term fluorescent bioimaging applications.

  6. Bright solitons in coupled defocusing NLS equation supported by coupling: Application to Bose-Einstein condensation

    International Nuclear Information System (INIS)

    Adhikari, Sadhan K.

    2005-01-01

    We demonstrate the formation of bright solitons in coupled self-defocusing nonlinear Schroedinger (NLS) equation supported by attractive coupling. As an application we use a time-dependent dynamical mean-field model to study the formation of stable bright solitons in two-component repulsive Bose-Einstein condensates (BECs) supported by interspecies attraction in a quasi one-dimensional geometry. When all interactions are repulsive, there cannot be bright solitons. However, bright solitons can be formed in two-component repulsive BECs for a sufficiently attractive interspecies interaction, which induces an attractive effective interaction among bosons of same type

  7. The star-bright hour : [luuletused] / Betti Alver

    Index Scriptorium Estoniae

    Alver, Betti, 1906-1989

    2006-01-01

    Sisu: The star-bright hour ; Not a dream ; The Piper ; Corals in an ancent river. Luuletused pärinevad kogumikust "Tuulelaeval valgusest on aerud = Windship with Oars of Light. (Tallinn : Huma, 2001). Orig.: Tähetund ; Mitte viirastus, meelepett ; Vilepuhuja ; Korallid Emajões

  8. The star-bright hour : [poems] / Betti Alver

    Index Scriptorium Estoniae

    Alver, Betti, 1906-1989

    2003-01-01

    Autori lühitutvustus lk. 231. Sisu: The star-bright hour ; The debt ; Not a dream ; Fog-bound ; Corals in an Ancient river ; Frou-frou 1-3. Orig.: Tähetund ; Vilepuhuja ; Võlg ; "Mitte viirastus, meelepett..." ; Udus ; Korallid Emajões ; Froufrou 1-3

  9. Nanosecond pulsed electric field (nsPEF) disrupts the structure and metabolism of human Echinococcus granulosus protoscolex in vitro with a dose effect.

    Science.gov (United States)

    Zhang, Ruiqing; Aji, Tuerganaili; Shao, Yingmei; Jiang, Tiemin; Yang, Lei; Lv, Weimin; Chen, Yonggang; Chen, Xinhua; Wen, Hao

    2017-04-01

    The number of interventional treatments for hepatic cystic echinococcosis is increasing, but the chemicals or high temperatures used in these methodologies cause biliary complications, thus limiting their clinical applications. This experimental study aimed to apply a novel, non-thermal, non-chemical ablation method termed nanosecond pulsed electric field (nsPEF) for the treatment of human hepatic cystic echinococcosis. The nsPEF treatment parameters against protoscolices from human hepatic cystic echinococcosis were optimized in vitro. The efficacy and mechanism of nsPEF treatment were also investigated. Fresh protoscolices were isolated from human hepatic cystic echinococcosis and were exposed to 300 ns of nsPEF with different field strengths (0, 7, 14, 21, and 29 kV/cm) and pulse numbers (50 and 100 pulses). Then, the viability of the nsPEF-treated protoscolices was evaluated in vitro. Morphological and ultra-structural changes were visualized with H&E staining and scanning electron microscopy. The membrane enzyme activity of alkaline phosphatase (AP) and gamma-glutamyl-transpeptidase (GGT) was measured. nsPEF caused dose-dependent protoscolex death. One-hundred pulses of nsPEF at 21 kV/cm or higher caused a significant increase in the death rate of protoscolices. nsPEF induced significant lethal damage with 50 pulses at 21 or 29 kV/cm and with 100 pulses at 14, 21, or 29 kV/cm, accompanied by morphological destruction and increased levels of AP and GGT membrane enzymes. Thus, nsPEF induced dose-dependent protoscolex mortality and caused destruction of protoscolices and increased membrane enzymes. The mechanism may involve direct damage to the membrane structures of the protoscolices, promoting enzyme exhaustion and disruption of metabolism.

  10. FIRST EXPERIMENTAL RESULTS FROM DEGAS, THE QUANTUM LIMITED BRIGHTNESS ELECTRON SOURCE

    International Nuclear Information System (INIS)

    Zolotorev, Max S.; Commins, Eugene D.; Oneill, James; Sannibale, Fernando; Tremsin, Anton; Wan, Weishi

    2008-01-01

    The construction of DEGAS (DEGenerate Advanced Source), a proof of principle for a quantum limited brightness electron source, has been completed at the Lawrence Berkeley National Laboratory. The commissioning and the characterization of this source, designed to generate coherent single electron 'bunches' with brightness approaching the quantum limit at a repetition rate of few MHz, has been started. In this paper the first experimental results are described

  11. The ASAS-SN bright supernova catalogue - III. 2016

    Science.gov (United States)

    Holoien, T. W.-S.; Brown, J. S.; Stanek, K. Z.; Kochanek, C. S.; Shappee, B. J.; Prieto, J. L.; Dong, Subo; Brimacombe, J.; Bishop, D. W.; Bose, S.; Beacom, J. F.; Bersier, D.; Chen, Ping; Chomiuk, L.; Falco, E.; Godoy-Rivera, D.; Morrell, N.; Pojmanski, G.; Shields, J. V.; Strader, J.; Stritzinger, M. D.; Thompson, Todd A.; Woźniak, P. R.; Bock, G.; Cacella, P.; Conseil, E.; Cruz, I.; Fernandez, J. M.; Kiyota, S.; Koff, R. A.; Krannich, G.; Marples, P.; Masi, G.; Monard, L. A. G.; Nicholls, B.; Nicolas, J.; Post, R. S.; Stone, G.; Wiethoff, W. S.

    2017-11-01

    This catalogue summarizes information for all supernovae discovered by the All-Sky Automated Survey for SuperNovae (ASAS-SN) and all other bright (mpeak ≤ 17), spectroscopically confirmed supernovae discovered in 2016. We then gather the near-infrared through ultraviolet magnitudes of all host galaxies and the offsets of the supernovae from the centres of their hosts from public data bases. We illustrate the results using a sample that now totals 668 supernovae discovered since 2014 May 1, including the supernovae from our previous catalogues, with type distributions closely matching those of the ideal magnitude limited sample from Li et al. This is the third of a series of yearly papers on bright supernovae and their hosts from the ASAS-SN team.

  12. Radiometric calibration of the reflective bands of NS001-Thematic Mapper Simulator (TMS) and modular multispectral radiometers (MMR)

    Science.gov (United States)

    Markham, Brian L.; Wood, Frank M., Jr.; Ahmad, Suraiya P.

    1988-01-01

    The NS001 Thematic Mapper Simulator scanner (TMS) and several modular multispectral radiometers (MMRs) are among the primary instruments used in the First ISLSCP (International Satellite Land Surface Climatology Project) Field Experiment (FIFE). The NS001 has a continuously variable gain setting. Calibration of the NS001 data is influenced by drift in the dark current level of up to six counts during a mirror scan at typical gain settings. The MMR instruments are being used in their 1 deg FOV configuration on the helicopter and 15 deg FOV on the ground.

  13. Arctic sea ice signatures: L-band brightness temperature sensitivity comparison using two radiation transfer models

    Science.gov (United States)

    Richter, Friedrich; Drusch, Matthias; Kaleschke, Lars; Maaß, Nina; Tian-Kunze, Xiangshan; Mecklenburg, Susanne

    2018-03-01

    Sea ice is a crucial component for short-, medium- and long-term numerical weather predictions. Most importantly, changes of sea ice coverage and areas covered by thin sea ice have a large impact on heat fluxes between the ocean and the atmosphere. L-band brightness temperatures from ESA's Earth Explorer SMOS (Soil Moisture and Ocean Salinity) have been proven to be a valuable tool to derive thin sea ice thickness. These retrieved estimates were already successfully assimilated in forecasting models to constrain the ice analysis, leading to more accurate initial conditions and subsequently more accurate forecasts. However, the brightness temperature measurements can potentially be assimilated directly in forecasting systems, reducing the data latency and providing a more consistent first guess. As a first step towards such a data assimilation system we studied the forward operator that translates geophysical parameters provided by a model into brightness temperatures. We use two different radiative transfer models to generate top of atmosphere brightness temperatures based on ORAP5 model output for the 2012/2013 winter season. The simulations are then compared against actual SMOS measurements. The results indicate that both models are able to capture the general variability of measured brightness temperatures over sea ice. The simulated brightness temperatures are dominated by sea ice coverage and thickness changes are most pronounced in the marginal ice zone where new sea ice is formed. There we observe the largest differences of more than 20 K over sea ice between simulated and observed brightness temperatures. We conclude that the assimilation of SMOS brightness temperatures yields high potential for forecasting models to correct for uncertainties in thin sea ice areas and suggest that information on sea ice fractional coverage from higher-frequency brightness temperatures should be used simultaneously.

  14. Arctic sea ice signatures: L-band brightness temperature sensitivity comparison using two radiation transfer models

    Directory of Open Access Journals (Sweden)

    F. Richter

    2018-03-01

    Full Text Available Sea ice is a crucial component for short-, medium- and long-term numerical weather predictions. Most importantly, changes of sea ice coverage and areas covered by thin sea ice have a large impact on heat fluxes between the ocean and the atmosphere. L-band brightness temperatures from ESA's Earth Explorer SMOS (Soil Moisture and Ocean Salinity have been proven to be a valuable tool to derive thin sea ice thickness. These retrieved estimates were already successfully assimilated in forecasting models to constrain the ice analysis, leading to more accurate initial conditions and subsequently more accurate forecasts. However, the brightness temperature measurements can potentially be assimilated directly in forecasting systems, reducing the data latency and providing a more consistent first guess. As a first step towards such a data assimilation system we studied the forward operator that translates geophysical parameters provided by a model into brightness temperatures. We use two different radiative transfer models to generate top of atmosphere brightness temperatures based on ORAP5 model output for the 2012/2013 winter season. The simulations are then compared against actual SMOS measurements. The results indicate that both models are able to capture the general variability of measured brightness temperatures over sea ice. The simulated brightness temperatures are dominated by sea ice coverage and thickness changes are most pronounced in the marginal ice zone where new sea ice is formed. There we observe the largest differences of more than 20 K over sea ice between simulated and observed brightness temperatures. We conclude that the assimilation of SMOS brightness temperatures yields high potential for forecasting models to correct for uncertainties in thin sea ice areas and suggest that information on sea ice fractional coverage from higher-frequency brightness temperatures should be used simultaneously.

  15. Baseline NS5A resistance associated substitutions may impair DAA response in real-world hepatitis C patients.

    Science.gov (United States)

    Carrasco, Itzíar; Arias, Ana; Benítez-Gutiérrez, Laura; Lledó, Gemma; Requena, Silvia; Cuesta, Miriam; Cuervas-Mons, Valentín; de Mendoza, Carmen

    2018-03-01

    Oral DAA have demonstrated high efficacy as treatment of hepatitis C. However, the presence of resistance-associated substitutions (RAS) at baseline has occasionally been associated with impaired treatment response. Herein, we examined the impact of baseline RAS at the HCV NS5A gene region on treatment response in a real-life setting. All hepatitis C patients treated with DAA including NS5A inhibitors at our institution were retrospectively examined. The virus NS5A gene was analyzed using population sequencing at baseline and after 24 weeks of completing therapy in all patients that failed. All changes recorded at positions 28, 29, 30, 31, 32, 58, 62, 92, and 93 were considered. A total of 166 patients were analyzed. HCV genotypes were as follows: G1a (31.9%), G1b (48.2%), G3 (10.2%), and G4 (9.6%). Overall, 69 (41.6%) patients were coinfected with HIV and 46.7% had advanced liver fibrosis (Metavir F3-F4). Sixty (36.1%) patients had at least one RAS at baseline, including M28A/G/T (5), Q30X (12), L31I/F/M/V (6), T58P/S (25), Q/E62D (1), A92 K (7), and Y93C/H (15). Overall, 4.8% had two or more RAS, being more frequent in G4 (12.5%) followed by G1b (6.3%) and G1a (1.9%). Of 10 (6%) patients that failed DAA therapy, five had baseline NS5A RAS. No association was found for specific baseline RAS, although changes at position 30 were more frequent in failures than cures (22.2% vs 6.4%, P = 0.074). Moreover, the presence of two or more RAS at baseline was more frequent in failures (HR: 7.2; P = 0.029). Upon failure, six patients showed emerging RAS, including Q30C/H/R (3), L31M (1), and Y93C/H (2). Baseline NS5A RAS are frequently seen in DAA-naïve HCV patients. Two or more baseline NS5A RAS were found in nearly 5% and were significantly associated to DAA failure. Therefore, baseline NS5A testing should be considered when HCV treatment is planned with NS5A inhibitors. © 2017 Wiley Periodicals, Inc.

  16. Exposure to bright light for several hours during the daytime lowers tympanic temperature

    Science.gov (United States)

    Aizawa, Seika; Tokura, H.

    The present study investigates the effect on thympanic temperature of exposure to different light intensities for several hours during the daytime. Nine healthy young adult volunteers (two male, seven female) were exposed to bright light of 4000 lx or dim light of 100 lx during the daytime from 0930 to 1800 hours; the light condition was then kept at 100 lx for a further hour. Tympanic temperature was measured continuously at a neutral condition (28° C, 60% relative humidity) from 1000 to 1800 hours. Urinary samples were collected from 1100 to 1900 hours every 2 h, and melatonin excretion rate was measured by enzyme immunoassay. Of nine subjects, six showed clearly lower tympanic temperatures in the bright compared with the dim condition from 1400 to 1800 hours. Average tympanic temperatures were significantly lower in the bright than in the dim condition from 1645 to 1800 hours. Melatonin excretion rate tended to be higher in the bright than in the dim condition. It was concluded that exposure to bright light of 4000 lx during the daytime for several hours could reduce tympanic temperature, compared with that measured in dim light of 100 lx.

  17. Exposure to bright light for several hours during the daytime lowers tympanic temperature.

    Science.gov (United States)

    Aizawa, S; Tokura, H

    1997-11-01

    The present study investigates the effect on thympanic temperature of exposure to different light intensities for several hours during the daytime. Nine healthy young adult volunteers (two male, seven female) were exposed to bright light of 4000 lx or dim light of 100 lx during the daytime from 0930 to 1800 hours; the light condition was then kept at 100 lx for a further hour. Tympanic temperature was measured continuously at a neutral condition (28 degrees C, 60% relative humidity) from 1000 to 1800 hours. Urinary samples were collected from 1100 to 1900 hours every 2 h, and melatonin excretion rate was measured by enzyme immunoassay. Of nine subjects, six showed clearly lower tympanic temperatures in the bright compared with the dim condition from 1400 to 1800 hours. Average tympanic temperatures were significantly lower in the bright than in the dim condition from 1645 to 1800 hours. Melatonin excretion rate tended to be higher in the bright than in the dim condition. It was concluded that exposure to bright light of 4000 lx during the daytime for several hours could reduce tympanic temperature, compared with that measured in dim light of 100 lx.

  18. Evaluating vacquinol-1 in rats carrying glioblastoma models RG2 and NS1.

    Science.gov (United States)

    Ahlstedt, Jonatan; Förnvik, Karolina; Zolfaghari, Shaian; Kwak, Dongoh; Hammarström, Lars G J; Ernfors, Patrik; Salford, Leif G; Redebrandt, Henrietta Nittby

    2018-02-02

    Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor, and available experimental and routine therapies result in limited survival benefits. A vulnerability of GBM cells to catastrophic vacuolization and cell death, a process termed methuosis, induced by Vacquinol-1 (VQ-1) has been described earlier. In the present study, we investigate the efficacy of VQ-1 treatment in two syngeneic rat GBM models, RG2 and NS1. VQ-1 treatment affected growth of both RG2 and NS1 cells in vitro . Intracranially, significant reduction in RG2 tumor size was observed, although no effect was seen on overall survival. No survival advantage or effect on tumor size was seen in animals carrying the NS1 models compared to untreated controls. Furthermore, immunological staining of FOXP3, CD4 and CD8 showed no marked difference in immune cell infiltrate in tumor environment following treatment. Taken together, a survival advantage of VQ-1 treatment alone could not be demonstrated here, even though some effect upon tumor size was seen. Staining for immune cell markers did not indicate that VQ-1 either reduced or increased host anti-tumor immune response.

  19. On correct evaluation techniques of brightness enhancement effect measurement data

    Science.gov (United States)

    Kukačka, Leoš; Dupuis, Pascal; Motomura, Hideki; Rozkovec, Jiří; Kolář, Milan; Zissis, Georges; Jinno, Masafumi

    2017-11-01

    This paper aims to establish confidence intervals of the quantification of brightness enhancement effects resulting from the use of pulsing bright light. It is found that the methods used so far may yield significant bias in the published results, overestimating or underestimating the enhancement effect. The authors propose to use a linear algebra method called the total least squares. Upon an example dataset, it is shown that this method does not yield biased results. The statistical significance of the results is also computed. It is concluded over an observation set that the currently used linear algebra methods present many patterns of noise sensitivity. Changing algorithm details leads to inconsistent results. It is thus recommended to use the method with the lowest noise sensitivity. Moreover, it is shown that this method also permits one to obtain an estimate of the confidence interval. This paper neither aims to publish results about a particular experiment nor to draw any particular conclusion about existence or nonexistence of the brightness enhancement effect.

  20. Outbreak tracking of Aleutian mink disease virus (AMDV) using partial NS1 gene sequencing

    DEFF Research Database (Denmark)

    Ryt-Hansen, Pia; Hjulsager, Charlotte Kristiane; Hagberg, E. E.

    2017-01-01

    . However, in 2015, several outbreaks of AMDV occurred at mink farms throughout Denmark, and the sources of these outbreaks were not known. Partial NS1 gene sequencing, phylogenetic analyses data were utilized along with epidemiological to determine the origin of the outbreaks. The phylogenetic analyses...... not be excluded. This study confirmed that partial NS1 sequencing can be used in outbreak tracking to determine major viral clusters of AMDV. Using this method, two new distinct AMDV clusters with low intra-cluster sequence diversity were identified, and epidemiological data helped to reveal possible ways...

  1. [Determination of drug resistance mutations of NS3 inhibitors in chronic hepatitis C patients infected with genotype 1].

    Science.gov (United States)

    Şanlıdağ, Tamer; Sayan, Murat; Akçalı, Sinem; Kasap, Elmas; Buran, Tahir; Arıkan, Ayşe

    2017-04-01

    Direct-acting antiviral agents (DAA) such as NS3 protease inhibitors is the first class of drugs used for chronic hepatitis C (CHC) treatment. NS3 inhibitors (PI) with low genetic barrier have been approved to be used in the CHC genotype 1 infections, and in the treatment of compensated liver disease including cirrhosis together with pegile interferon and ribavirin. Consequently, the development of drug resistance during DAA treatment of CHC is a major problem. NS3 resistant variants can be detected before treatment as they can occurnaturally. The aim of this study was to investigate new and old generation NS3 inhibitors resistance mutations before DAA treatment in hepatitis C virus (HCV) that were isolated from CHC. The present study was conducted in 2015 and included 97 naive DAA patients infected with HCV genotype 1, who were diagnosed in Manisa and Kocaeli cities of Turkey. Magnetic particle based HCV RNA extraction and than RNA detection and quantification were performed using commercial real-time PCR assay QIASypmhony + Rotorgene Q/ArtusHCV QS-RGQ and COBAS Ampliprep/COBAS TaqMan HCV Tests. HCV NS3 viral protease genome region was amplified with PCR and mutation analysis was performed by Sanger dideoxy sequencing technique of NS3 protease codons (codon 32-185). HCV NS3 protease inhibitors; asunaprevir, boceprevir, faldaprevir, grazoprevir, pariteprevir, simeprevir and telaprevir were analysed for resistant mutations by Geno2pheno-HCV resistance tool. HCV was genotyped in all patients and 88 patients (n= 88/97, 91%) had genotype 1. Eight (n= 8/97, 8.2%) and 80 (n= 80/97, 82.4%) HCC patients were subgenotyped as 1a and 1b, respectively. Many aminoacid substitutions and resistance mutations were determined in 39/88 (44%) patients in the study group. Q80L, S122C/N, S138W were defined as potential substitutions (6/88 patients; 7%); R109K, R117C, S122G, I132V, I170V, N174S were described as potential resistance (34/88 patients; 39%); V36L, T54S, V55A, Q80H were

  2. Robust fitting of diurnal brightness temperature cycle

    CSIR Research Space (South Africa)

    Udahemuka, G

    2007-11-01

    Full Text Available for a pixel concerned. Robust fitting of observed Diurnal Temperature Cycle (DTC) taken over a day of a given pixel without cloud cover and other abnormally conditions such as fire can give a data based brightness temperature model for a given pixel...

  3. Phosphorylation states of cell cycle and DNA repair proteins can be altered by the nsSNPs

    International Nuclear Information System (INIS)

    Savas, Sevtap; Ozcelik, Hilmi

    2005-01-01

    Phosphorylation is a reversible post-translational modification that affects the intrinsic properties of proteins, such as structure and function. Non-synonymous single nucleotide polymorphisms (nsSNPs) result in the substitution of the encoded amino acids and thus are likely to alter the phosphorylation motifs in the proteins. In this study, we used the web-based NetPhos tool to predict candidate nsSNPs that either introduce or remove putative phosphorylation sites in proteins that act in DNA repair and cell cycle pathways. Our results demonstrated that a total of 15 nsSNPs (16.9%) were likely to alter the putative phosphorylation patterns of 14 proteins. Three of these SNPs (CDKN1A-S31R, OGG1-S326C, and XRCC3-T241M) have already found to be associated with altered cancer risk. We believe that this set of nsSNPs constitutes an excellent resource for further molecular and genetic analyses. The novel systematic approach used in this study will accelerate the understanding of how naturally occurring human SNPs may alter protein function through the modification of phosphorylation mechanisms and contribute to disease susceptibility

  4. Green fluorescent protein (GFP color reporter gene visualizes parvovirus B19 non-structural segment 1 (NS1 transfected endothelial modification.

    Directory of Open Access Journals (Sweden)

    Thomas Wurster

    Full Text Available BACKGROUND: Human Parvovirus B19 (PVB19 has been associated with myocarditis putative due to endothelial infection. Whether PVB19 infects endothelial cells and causes a modification of endothelial function and inflammation and, thus, disturbance of microcirculation has not been elucidated and could not be visualized so far. METHODS AND FINDINGS: To examine the PVB19-induced endothelial modification, we used green fluorescent protein (GFP color reporter gene in the non-structural segment 1 (NS1 of PVB19. NS1-GFP-PVB19 or GFP plasmid as control were transfected in an endothelial-like cell line (ECV304. The endothelial surface expression of intercellular-adhesion molecule-1 (CD54/ICAM-1 and extracellular matrix metalloproteinase inducer (EMMPRIN/CD147 were evaluated by flow cytometry after NS-1-GFP or control-GFP transfection. To evaluate platelet adhesion on NS-1 transfected ECs, we performed a dynamic adhesion assay (flow chamber. NS-1 transfection causes endothelial activation and enhanced expression of ICAM-1 (CD54: mean ± standard deviation: NS1-GFP vs. control-GFP: 85.3 ± 11.2 vs. 61.6 ± 8.1; P<0.05 and induces endothelial expression of EMMPRIN/CD147 (CD147: mean ± SEM: NS1-GFP vs. control-GFP: 114 ± 15.3 vs. 80 ± 0.91; P<0.05 compared to control-GFP transfected cells. Dynamic adhesion assays showed that adhesion of platelets is significantly enhanced on NS1 transfected ECs when compared to control-GFP (P<0.05. The transfection of ECs was verified simultaneously through flow cytometry, immunofluorescence microscopy and polymerase chain reaction (PCR analysis. CONCLUSIONS: GFP color reporter gene shows transfection of ECs and may help to visualize NS1-PVB19 induced endothelial activation and platelet adhesion as well as an enhanced monocyte adhesion directly, providing in vitro evidence of possible microcirculatory dysfunction in PVB19-induced myocarditis and, thus, myocardial tissue damage.

  5. Molecular imaging of {alpha}7 nicotinic acetylcholine receptors: design and evaluation of the potent radioligand [{sup 18}F]NS10743

    Energy Technology Data Exchange (ETDEWEB)

    Deuther-Conrad, Winnie; Fischer, Steffen; Hiller, Achim; Brust, Peter [Institute of Interdisciplinary Isotope Research, Leipzig (Germany); Oestergaard Nielsen, Elsebet; Brunicardi Timmermann, Daniel; Peters, Dan [NeuroSearch A/S, Ballerup (Denmark); Steinbach, Joerg [Institute of Interdisciplinary Isotope Research, Leipzig (Germany); Forschungszentrum Dresden-Rossendorf, Institute of Radiopharmacy, Dresden (Germany); Sabri, Osama [Universitaet Leipzig, Department of Nuclear Medicine, Leipzig (Germany)

    2009-05-15

    The outstanding diversity of cellular properties mediated by neuronal and nonneuronal {alpha}7 nicotinic acetylcholine receptors ({alpha}7 nAChR) points to the diagnostic potential of quantitative nuclear molecular imaging of {alpha}7 nAChR in neurology and oncology. It was our goal to radiolabel the {alpha}7 nAChR agonist 4-[5-(4-fluoro-phenyl)-[1,3,4]oxadiazol-2-yl]-1,4-diaza-bicyclo[3.2.2]nonane (NS10743) and to assess the selectivity of [{sup 18}F]NS10743 binding site occupancy in animal experiments. [{sup 18}F]NS10743 was synthesized by nucleophilic substitution of the nitro precursor. In vitro receptor affinity and selectivity were assessed by radioligand competition and autoradiography. The radiotracer properties were evaluated in female CD-1 mice by brain autoradiography and organ distribution. Target specificity was validated after treatment with SSR180711 (10 mg/kg, intraperitoneal), and metabolic stability was investigated using radio-HPLC. The specific activity of [{sup 18}F]NS10743 exceeded 150 GBq/{mu}mol at a radiochemical purity >99%. In vitro, NS10743 and [{sup 18}F]NS10743 showed high affinity and specificity towards {alpha}7 nAChR. The brain permeation of [{sup 18}F]NS10743 was fast and sufficient with values of 4.83 and 1.60% injected dose per gram and brain to plasma ratios of 3.83 and 2.05 at 5 and 60 min after radiotracer administration. Brain autoradiography and organ distribution showed target-specific accumulation of [{sup 18}F]NS10743 in brain substructures and various {alpha}7 nAChR-expressing organs. The radiotracer showed a high metabolic stability in vivo with a single polar radiometabolite, which did not cross the blood-brain barrier. The good in vitro and in vivo features of [{sup 18}F]NS10743 make this radioligand a promising candidate for quantitative in vivo imaging of {alpha}7 nAChR expression and encourage further investigations. (orig.)

  6. Human Adolescent Phase Response Curves to Bright White Light.

    Science.gov (United States)

    Crowley, Stephanie J; Eastman, Charmane I

    2017-08-01

    Older adolescents are particularly vulnerable to circadian misalignment and sleep restriction, primarily due to early school start times. Light can shift the circadian system and could help attenuate circadian misalignment; however, a phase response curve (PRC) to determine the optimal time for receiving light and avoiding light is not available for adolescents. We constructed light PRCs for late pubertal to postpubertal adolescents aged 14 to 17 years. Participants completed 2 counterbalanced 5-day laboratory sessions after 8 or 9 days of scheduled sleep at home. Each session included phase assessments to measure the dim light melatonin onset (DLMO) before and after 3 days of free-running through an ultradian light-dark (wake-sleep) cycle (2 h dim [~20 lux] light, 2 h dark). In one session, intermittent bright white light (~5000 lux; four 20-min exposures) was alternated with 10 min of dim room light once per day for 3 consecutive days. The time of light varied among participants to cover the 24-h day. For each individual, the phase shift to bright light was corrected for the free-run derived from the other laboratory session with no bright light. One PRC showed phase shifts in response to light start time relative to the DLMO and another relative to home sleep. Phase delay shifts occurred around the hours corresponding to home bedtime. Phase advances occurred during the hours surrounding wake time and later in the afternoon. The transition from delays to advances occurred at the midpoint of home sleep. The adolescent PRCs presented here provide a valuable tool to time bright light in adolescents.

  7. Efficacy of NS5A Inhibitors Against Hepatitis C Virus Genotypes 1–7 and Escape Variants

    DEFF Research Database (Denmark)

    Gottwein, Judith M.; Pham, Long V.; Mikkelsen, Lotte S.

    2018-01-01

    , or that contained RAS previously reported from patients. Results: NS5A inhibitors had varying levels of efficacy against original and resistant viruses. Only velpatasvir and pibrentasvir had uniform high activity against all HCV genotypes tested. RAS hotspots in NS5A were found at amino acids 28, 30, 31, and 93...

  8. Bright Soil Churned by Spirit's Sol 1861 Drive

    Science.gov (United States)

    2009-01-01

    NASA's Mars Exploration Rover Spirit drove 22.7 meters (74 feet) toward the southwest on the 1,861st Martian day, or sol, of Spirit's mission on Mars (March 28, 2009). After the drive, the rover took this image with its front hazard-avoidance camera, looking back at the tracks from the drive. As usual since losing the use of its right-front wheel in 2006, Spirit drove backwards. The immobile right-front wheel churned up a long stripe of bright soil during this drive. Where Spirit has found such bright soil in the past, subsequent analysis of the composition found concentrations of sulfur or silica that testified to past action of water at the site. When members of the rover team saw the large quantity of bright soil exposed by the Sol 1861 drive, they quickly laid plans to investigate the composition with Spirit's alpha particle X-ray spectrometer. The Sol 1861 drive took the rover past the northwest corner of the low plateau called 'Home Plate,' making progress on a route around the western side of Home Plate. The edge of Home Plate forms the horizon on the right side of this image. Husband Hill is on the horizon on the left side. For scale, the parallel rover wheel tracks are about 1 meter (40 inches) apart. The rover's hazard-avoidance cameras take 'fisheye' wide-angle images.

  9. Phosphorylation of NS5A Serine-235 is essential to hepatitis C virus RNA replication and normal replication compartment formation

    Energy Technology Data Exchange (ETDEWEB)

    Eyre, Nicholas S., E-mail: nicholas.eyre@adelaide.edu.au [School of Biological Sciences and Research Centre for Infectious Diseases, University of Adelaide, Adelaide (Australia); Centre for Cancer Biology, SA Pathology, Adelaide (Australia); Hampton-Smith, Rachel J.; Aloia, Amanda L. [School of Biological Sciences and Research Centre for Infectious Diseases, University of Adelaide, Adelaide (Australia); Centre for Cancer Biology, SA Pathology, Adelaide (Australia); Eddes, James S. [Adelaide Proteomics Centre, School of Biological Sciences, University of Adelaide, Adelaide (Australia); Simpson, Kaylene J. [Victorian Centre for Functional Genomics, Peter MacCallum Cancer Centre, East Melbourne (Australia); The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville (Australia); Hoffmann, Peter [Adelaide Proteomics Centre, School of Biological Sciences, University of Adelaide, Adelaide (Australia); Institute for Photonics and Advanced Sensing (IPAS), University of Adelaide, Adelaide (Australia); Beard, Michael R. [School of Biological Sciences and Research Centre for Infectious Diseases, University of Adelaide, Adelaide (Australia); Centre for Cancer Biology, SA Pathology, Adelaide (Australia)

    2016-04-15

    Hepatitis C virus (HCV) NS5A protein is essential for HCV RNA replication and virus assembly. Here we report the identification of NS5A phosphorylation sites Ser-222, Ser-235 and Thr-348 during an infectious HCV replication cycle and demonstrate that Ser-235 phosphorylation is essential for HCV RNA replication. Confocal microscopy revealed that both phosphoablatant (S235A) and phosphomimetic (S235D) mutants redistribute NS5A to large juxta-nuclear foci that display altered colocalization with known replication complex components. Using electron microscopy (EM) we found that S235D alters virus-induced membrane rearrangements while EM using ‘APEX2’-tagged viruses demonstrated S235D-mediated enrichment of NS5A in irregular membranous foci. Finally, using a customized siRNA screen of candidate NS5A kinases and subsequent analysis using a phospho-specific antibody, we show that phosphatidylinositol-4 kinase III alpha (PI4KIIIα) is important for Ser-235 phosphorylation. We conclude that Ser-235 phosphorylation of NS5A is essential for HCV RNA replication and normal replication complex formation and is regulated by PI4KIIIα. - Highlights: • NS5A residues Ser-222, Ser-235 and Thr-348 are phosphorylated during HCV infection. • Phosphorylation of Ser-235 is essential to HCV RNA replication. • Mutation of Ser-235 alters replication compartment localization and morphology. • Phosphatidylinositol-4 kinase III alpha is important for Ser-235 phosphorylation.

  10. Dimerization site 2 of the bacterial DNA-binding protein H-NS is required for gene silencing and stiffened nucleoprotein filament formation.

    Science.gov (United States)

    Yamanaka, Yuki; Winardhi, Ricksen S; Yamauchi, Erika; Nishiyama, So-Ichiro; Sowa, Yoshiyuki; Yan, Jie; Kawagishi, Ikuro; Ishihama, Akira; Yamamoto, Kaneyoshi

    2018-06-15

    The bacterial nucleoid-associated protein H-NS is a DNA-binding protein, playing a major role in gene regulation. To regulate transcription, H-NS silences genes, including horizontally acquired foreign genes. Escherichia coli H-NS is 137 residues long and consists of two discrete and independent structural domains: an N-terminal oligomerization domain and a C-terminal DNA-binding domain, joined by a flexible linker. The N-terminal oligomerization domain is composed of two dimerization sites, dimerization sites 1 and 2, which are both required for H-NS oligomerization, but the exact role of dimerization site 2 in gene silencing is unclear. To this end, we constructed a whole set of single amino acid substitution variants spanning residues 2 to 137. Using a well-characterized H-NS target, the slp promoter of the glutamic acid-dependent acid resistance (GAD) cluster promoters, we screened for any variants defective in gene silencing. Focusing on the function of dimerization site 2, we analyzed four variants, I70C/I70A and L75C/L75A, which all could actively bind DNA but are defective in gene silencing. Atomic force microscopy analysis of DNA-H-NS complexes revealed that all of these four variants formed condensed complexes on DNA, whereas WT H-NS formed rigid and extended nucleoprotein filaments, a conformation required for gene silencing. Single-molecule stretching experiments confirmed that the four variants had lost the ability to form stiffened filaments. We conclude that dimerization site 2 of H-NS plays a key role in the formation of rigid H-NS nucleoprotein filament structures required for gene silencing. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. The R35 residue of the influenza A virus NS1 protein has minimal effects on nuclear localization but alters virus replication through disrupting protein dimerization

    Energy Technology Data Exchange (ETDEWEB)

    Lalime, Erin N.; Pekosz, Andrew, E-mail: apekosz@jhsph.edu

    2014-06-15

    The influenza A virus NS1 protein has a nuclear localization sequence (NLS) in the amino terminal region. This NLS overlaps sequences that are important for RNA binding as well as protein dimerization. To assess the significance of the NS1 NLS on influenza virus replication, the NLS amino acids were individually mutated to alanines and recombinant viruses encoding these mutations were rescued. Viruses containing NS1 proteins with mutations at R37, R38 and K41 displayed minimal changes in replication or NS1 protein nuclear localization. Recombinant viruses encoding NS1 R35A were not recovered but viruses containing second site mutations at position D39 in addition to the R35A mutation were isolated. The mutations at position 39 were shown to partially restore NS1 protein dimerization but had minimal effects on nuclear localization. These data indicate that the amino acids in the NS1 NLS region play a more important role in protein dimerization compared to nuclear localization. - Highlights: • Mutations were introduced into influenza NS1 NLS1. • NS1 R37A, R38A, K41A viruses had minimal changes in replication and NS1 localization. • Viruses from NS1 R35A rescue all contained additional mutations at D39. • NS1 R35A D39X mutations recover dimerization lost in NS1 R35A mutations. • These results reaffirm the importance of dimerization for NS1 protein function.

  12. The R35 residue of the influenza A virus NS1 protein has minimal effects on nuclear localization but alters virus replication through disrupting protein dimerization

    International Nuclear Information System (INIS)

    Lalime, Erin N.; Pekosz, Andrew

    2014-01-01

    The influenza A virus NS1 protein has a nuclear localization sequence (NLS) in the amino terminal region. This NLS overlaps sequences that are important for RNA binding as well as protein dimerization. To assess the significance of the NS1 NLS on influenza virus replication, the NLS amino acids were individually mutated to alanines and recombinant viruses encoding these mutations were rescued. Viruses containing NS1 proteins with mutations at R37, R38 and K41 displayed minimal changes in replication or NS1 protein nuclear localization. Recombinant viruses encoding NS1 R35A were not recovered but viruses containing second site mutations at position D39 in addition to the R35A mutation were isolated. The mutations at position 39 were shown to partially restore NS1 protein dimerization but had minimal effects on nuclear localization. These data indicate that the amino acids in the NS1 NLS region play a more important role in protein dimerization compared to nuclear localization. - Highlights: • Mutations were introduced into influenza NS1 NLS1. • NS1 R37A, R38A, K41A viruses had minimal changes in replication and NS1 localization. • Viruses from NS1 R35A rescue all contained additional mutations at D39. • NS1 R35A D39X mutations recover dimerization lost in NS1 R35A mutations. • These results reaffirm the importance of dimerization for NS1 protein function

  13. Engineered Toxins “Zymoxins” Are Activated by the HCV NS3 Protease by Removal of an Inhibitory Protein Domain

    Science.gov (United States)

    Shapira, Assaf; Gal-Tanamy, Meital; Nahary, Limor; Litvak-Greenfeld, Dana; Zemel, Romy; Tur-Kaspa, Ran; Benhar, Itai

    2011-01-01

    The synthesis of inactive enzyme precursors, also known as “zymogens,” serves as a mechanism for regulating the execution of selected catalytic activities in a desirable time and/or site. Zymogens are usually activated by proteolytic cleavage. Many viruses encode proteases that execute key proteolytic steps of the viral life cycle. Here, we describe a proof of concept for a therapeutic approach to fighting viral infections through eradication of virally infected cells exclusively, thus limiting virus production and spread. Using the hepatitis C virus (HCV) as a model, we designed two HCV NS3 protease-activated “zymogenized” chimeric toxins (which we denote “zymoxins”). In these recombinant constructs, the bacterial and plant toxins diphtheria toxin A (DTA) and Ricin A chain (RTA), respectively, were fused to rationally designed inhibitor peptides/domains via an HCV NS3 protease-cleavable linker. The above toxins were then fused to the binding and translocation domains of Pseudomonas exotoxin A in order to enable translocation into the mammalian cells cytoplasm. We show that these toxins exhibit NS3 cleavage dependent increase in enzymatic activity upon NS3 protease cleavage in vitro. Moreover, a higher level of cytotoxicity was observed when zymoxins were applied to NS3 expressing cells or to HCV infected cells, demonstrating a potential therapeutic window. The increase in toxin activity correlated with NS3 protease activity in the treated cells, thus the therapeutic window was larger in cells expressing recombinant NS3 than in HCV infected cells. This suggests that the “zymoxin” approach may be most appropriate for application to life-threatening acute infections where much higher levels of the activating protease would be expected. PMID:21264238

  14. Size dependence of upconversion photoluminescence in MPA capped CdTe quantum dots: Existence of upconversion bright point

    Energy Technology Data Exchange (ETDEWEB)

    Ananthakumar, S. [Crystal Growth Centre, Anna University, Chennai 600025 (India); Jayabalan, J., E-mail: jjaya@rrcat.gov.in [Laser Physics Applications Section, Raja Ramanna Centre for Advanced Technology, Indore 452013 (India); Singh, Asha; Khan, Salahuddin [Laser Physics Applications Section, Raja Ramanna Centre for Advanced Technology, Indore 452013 (India); Babu, S. Moorthy [Crystal Growth Centre, Anna University, Chennai 600025 (India); Chari, Rama [Laser Physics Applications Section, Raja Ramanna Centre for Advanced Technology, Indore 452013 (India)

    2016-01-15

    The photoluminescence (PL) from semiconductor quantum dots can show a “PL bright point”, that is the PL from as prepared quantum dots is maximum at a particular size. In this work we show that, for CdTe quantum dots, upconversion photoluminescence (UCPL) originating from nonlinear absorption shows a similar “UCPL bright point”. The PL and UCPL bright points occur at nearly the same size. The existence of a UCPL bright point has important implications for upconversion microscopy applications. - Highlights: • The size dependence of the upconversion photoluminescence (UCPL) spectrum of CdTe quantum dots has been reported. • We show that the UCPL from the CdTe quantum dots is highest at a particular size. • Thus the occurrence of a 'UCPL bright point' in CdTe quantum dots has been demonstrated. • It has been shown that the UCPL bright point occurs at nearly the same size as a normal bright point.

  15. Size dependence of upconversion photoluminescence in MPA capped CdTe quantum dots: Existence of upconversion bright point

    International Nuclear Information System (INIS)

    Ananthakumar, S.; Jayabalan, J.; Singh, Asha; Khan, Salahuddin; Babu, S. Moorthy; Chari, Rama

    2016-01-01

    The photoluminescence (PL) from semiconductor quantum dots can show a “PL bright point”, that is the PL from as prepared quantum dots is maximum at a particular size. In this work we show that, for CdTe quantum dots, upconversion photoluminescence (UCPL) originating from nonlinear absorption shows a similar “UCPL bright point”. The PL and UCPL bright points occur at nearly the same size. The existence of a UCPL bright point has important implications for upconversion microscopy applications. - Highlights: • The size dependence of the upconversion photoluminescence (UCPL) spectrum of CdTe quantum dots has been reported. • We show that the UCPL from the CdTe quantum dots is highest at a particular size. • Thus the occurrence of a "UCPL bright point" in CdTe quantum dots has been demonstrated. • It has been shown that the UCPL bright point occurs at nearly the same size as a normal bright point.

  16. A crystal structure of the Dengue virus NS5 protein reveals a novel inter-domain interface essential for protein flexibility and virus replication.

    Directory of Open Access Journals (Sweden)

    Yongqian Zhao

    2015-03-01

    Full Text Available Flavivirus RNA replication occurs within a replication complex (RC that assembles on ER membranes and comprises both non-structural (NS viral proteins and host cofactors. As the largest protein component within the flavivirus RC, NS5 plays key enzymatic roles through its N-terminal methyltransferase (MTase and C-terminal RNA-dependent-RNA polymerase (RdRp domains, and constitutes a major target for antivirals. We determined a crystal structure of the full-length NS5 protein from Dengue virus serotype 3 (DENV3 at a resolution of 2.3 Å in the presence of bound SAH and GTP. Although the overall molecular shape of NS5 from DENV3 resembles that of NS5 from Japanese Encephalitis Virus (JEV, the relative orientation between the MTase and RdRp domains differs between the two structures, providing direct evidence for the existence of a set of discrete stable molecular conformations that may be required for its function. While the inter-domain region is mostly disordered in NS5 from JEV, the NS5 structure from DENV3 reveals a well-ordered linker region comprising a short 310 helix that may act as a swivel. Solution Hydrogen/Deuterium Exchange Mass Spectrometry (HDX-MS analysis reveals an increased mobility of the thumb subdomain of RdRp in the context of the full length NS5 protein which correlates well with the analysis of the crystallographic temperature factors. Site-directed mutagenesis targeting the mostly polar interface between the MTase and RdRp domains identified several evolutionarily conserved residues that are important for viral replication, suggesting that inter-domain cross-talk in NS5 regulates virus replication. Collectively, a picture for the molecular origin of NS5 flexibility is emerging with profound implications for flavivirus replication and for the development of therapeutics targeting NS5.

  17. Very bright, near-infrared single photon emitters in diamond

    Directory of Open Access Journals (Sweden)

    D. W. M. Lau

    2013-09-01

    Full Text Available We demonstrate activation of bright diamond single photon emitters in the near infrared range by thermal annealing alone, i.e., without ion implantation. The activation is crucially dependent on the annealing ambient. The activation of the single photon emitters is only observed when the sample is annealed in forming gas (4% H2 in Ar above temperatures of 1000 °C. By contrast, no emitters are activated by annealing in vacuum, oxygen, argon or deuterium. The emitters activated by annealing in forming gas exhibit very bright emission in the 730-760 nm wavelength range and have linewidths of ∼1.5-2.5 nm at room temperature.

  18. Record high-average current from a high-brightness photoinjector

    Energy Technology Data Exchange (ETDEWEB)

    Dunham, Bruce; Barley, John; Bartnik, Adam; Bazarov, Ivan; Cultrera, Luca; Dobbins, John; Hoffstaetter, Georg; Johnson, Brent; Kaplan, Roger; Karkare, Siddharth; Kostroun, Vaclav; Li Yulin; Liepe, Matthias; Liu Xianghong; Loehl, Florian; Maxson, Jared; Quigley, Peter; Reilly, John; Rice, David; Sabol, Daniel [Cornell Laboratory for Accelerator-Based Sciences and Education, Cornell University, Ithaca, New York 14853 (United States); and others

    2013-01-21

    High-power, high-brightness electron beams are of interest for many applications, especially as drivers for free electron lasers and energy recovery linac light sources. For these particular applications, photoemission injectors are used in most cases, and the initial beam brightness from the injector sets a limit on the quality of the light generated at the end of the accelerator. At Cornell University, we have built such a high-power injector using a DC photoemission gun followed by a superconducting accelerating module. Recent results will be presented demonstrating record setting performance up to 65 mA average current with beam energies of 4-5 MeV.

  19. Discussion of high brightness rf linear accelerators

    International Nuclear Information System (INIS)

    Jameson, R.A.

    1987-01-01

    The fundamental aspects of high-brightness rf linacs are outlined, showing the breadth and complexity of the technology and indicating that synergism with advancements in other areas is important. Areas of technology reviewed include ion sources, injectors, rf accelerator structures, beam dynamics, rf power, and automatic control

  20. AXIAL RATIO OF EDGE-ON SPIRAL GALAXIES AS A TEST FOR BRIGHT RADIO HALOS

    International Nuclear Information System (INIS)

    Singal, J.; Jones, E.; Dunlap, H.; Kogut, A.

    2015-01-01

    We use surface brightness contour maps of nearby edge-on spiral galaxies to determine whether extended bright radio halos are common. In particular, we test a recent model of the spatial structure of the diffuse radio continuum by Subrahmanyan and Cowsik which posits that a substantial fraction of the observed high-latitude surface brightness originates from an extended Galactic halo of uniform emissivity. Measurements of the axial ratio of emission contours within a sample of normal spiral galaxies at 1500 MHz and below show no evidence for such a bright, extended radio halo. Either the Galaxy is atypical compared to nearby quiescent spirals or the bulk of the observed high-latitude emission does not originate from this type of extended halo. (letters)

  1. Bright spots among the world’s coral reefs

    Science.gov (United States)

    Cinner, Joshua E.; Huchery, Cindy; MacNeil, M. Aaron; Graham, Nicholas A. J.; McClanahan, Tim R.; Maina, Joseph; Maire, Eva; Kittinger, John N.; Hicks, Christina C.; Mora, Camilo; Allison, Edward H.; D'Agata, Stephanie; Hoey, Andrew; Feary, David A.; Crowder, Larry; Williams, Ivor D.; Kulbicki, Michel; Vigliola, Laurent; Wantiez, Laurent; Edgar, Graham; Stuart-Smith, Rick D.; Sandin, Stuart A.; Green, Alison L.; Hardt, Marah J.; Beger, Maria; Friedlander, Alan; Campbell, Stuart J.; Holmes, Katherine E.; Wilson, Shaun K.; Brokovich, Eran; Brooks, Andrew J.; Cruz-Motta, Juan J.; Booth, David J.; Chabanet, Pascale; Gough, Charlie; Tupper, Mark; Ferse, Sebastian C. A.; Sumaila, U. Rashid; Mouillot, David

    2016-07-01

    Ongoing declines in the structure and function of the world’s coral reefs require novel approaches to sustain these ecosystems and the millions of people who depend on them. A presently unexplored approach that draws on theory and practice in human health and rural development is to systematically identify and learn from the ‘outliers’—places where ecosystems are substantially better (‘bright spots’) or worse (‘dark spots’) than expected, given the environmental conditions and socioeconomic drivers they are exposed to. Here we compile data from more than 2,500 reefs worldwide and develop a Bayesian hierarchical model to generate expectations of how standing stocks of reef fish biomass are related to 18 socioeconomic drivers and environmental conditions. We identify 15 bright spots and 35 dark spots among our global survey of coral reefs, defined as sites that have biomass levels more than two standard deviations from expectations. Importantly, bright spots are not simply comprised of remote areas with low fishing pressure; they include localities where human populations and use of ecosystem resources is high, potentially providing insights into how communities have successfully confronted strong drivers of change. Conversely, dark spots are not necessarily the sites with the lowest absolute biomass and even include some remote, uninhabited locations often considered near pristine. We surveyed local experts about social, institutional, and environmental conditions at these sites to reveal that bright spots are characterized by strong sociocultural institutions such as customary taboos and marine tenure, high levels of local engagement in management, high dependence on marine resources, and beneficial environmental conditions such as deep-water refuges. Alternatively, dark spots are characterized by intensive capture and storage technology and a recent history of environmental shocks. Our results suggest that investments in strengthening fisheries

  2. A very bright SAR arc: implications for extreme magnetosphere-ionosphere coupling

    Directory of Open Access Journals (Sweden)

    J. Baumgardner

    2007-01-01

    Full Text Available In contrast to the polar aurora visible during geomagnetic storms, stable auroral red (SAR arcs offer a sub-visual manifestation of direct magnetosphere-ionosphere (M-I coupling at midlatitudes. The SAR arc emission at 6300 Å is driven by field-aligned magnetospheric energy transport from ring current/plasmapause locations into the ionosphere-thermosphere system. The first SAR arc was observed at the dawn of the space age (1956, and the typical brightness levels and occurrence patterns obtained from subsequent decades of observations appear to be consistent with the downward heat conduction theory, i.e., heated ambient F-layer electrons excite oxygen atoms to produce a spectrally pure emission. On very rare occasions, a SAR arc has been reported to be at brightness levels visible to the naked eye. Here we report on the first case of a very bright SAR arc (~13 kilo-Rayleighs observed by four diagnostic systems that sampled various aspects of the sub-auroral domain near Millstone Hill, MA, on the night of 29 October 1991: an imaging spectrograph, an all-sky camera, an incoherent scatter radar (ISR, and a DMSP satellite. Simulations of emission using the ISR and DMSP data with the MSIS neutral atmosphere succeed in reproducing the brightness levels observed. This provides a robust confirmation of M-I coupling theory in its most extreme aeronomic form within the innermost magnetosphere (L~2 during a rare superstorm event. The unusually high brightness value appears to be due to the rare occurrence of the heating of dense ionospheric plasma just equatorward of the trough/plasmapause location, in contrast to the more typical heating of the less dense F-layer within the trough.

  3. A system to measure isomeric state half-lives in the 10 ns to 10 μs range

    Energy Technology Data Exchange (ETDEWEB)

    Toufen, D. L., E-mail: dennis@if.usp.br [Institute of Physics, University of São Paulo, C.P. 66318, 05315-970 São Paulo, São Paulo (Brazil); Federal Institute of Education, Science and Technology of São Paulo - IFSP, 07115-000 Guarulhos, São Paulo (Brazil); Allegro, P. R. P.; Medina, N. H.; Oliveira, J. R. B.; Cybulska, E. W.; Seale, W. A.; Ribas, R. V. [Institute of Physics, University of São Paulo, C.P. 66318, 05315-970 São Paulo, São Paulo (Brazil); Linares, R. [Fluminense Federal University, 24220-900 Niterói, Rio de Janeiro (Brazil); Silveira, M. A. G. [Universitary Center of FEI, 09850-901 São Bernardo do Campo, São Paulo (Brazil)

    2014-07-15

    The Isomeric State Measurement System (SISMEI) was developed to search for isomeric nuclear states produced by fusion-evaporation reactions. The SISMEI consists of 10 plastic phoswich telescopes, two lead shields, one NaI(Tl) scintillation detector, two Compton suppressed HPGe γ-ray detectors, and a cone with a recoil product catcher. The new system was tested at the 8 UD Pelletron tandem accelerator of the University of São Paulo with the measurement of two known isomeric states: {sup 54}Fe, 10{sup +} state (E = 6527.1 (11) keV, T{sub 1/2} = 364(7) ns) and the 5/2{sup +} state of {sup 19}F (E = 197.143 (4) keV, T{sub 1/2} = 89.3 (10) ns). The results indicate that the system is capable of identifying delayed transitions, of measuring isomeric state lifetimes, and of identifying the feeding transitions of the isomeric state through the delayed γ-γ coincidence method. The measured half-life for the 10{sup +} state was T{sub 1/2} = 365(14) ns and for the 5/2{sup +} state, 100(36) ns.

  4. A system to measure isomeric state half-lives in the 10 ns to 10 μs range

    Science.gov (United States)

    Toufen, D. L.; Allegro, P. R. P.; Medina, N. H.; Oliveira, J. R. B.; Cybulska, E. W.; Seale, W. A.; Linares, R.; Silveira, M. A. G.; Ribas, R. V.

    2014-07-01

    The Isomeric State Measurement System (SISMEI) was developed to search for isomeric nuclear states produced by fusion-evaporation reactions. The SISMEI consists of 10 plastic phoswich telescopes, two lead shields, one NaI(Tl) scintillation detector, two Compton suppressed HPGe γ-ray detectors, and a cone with a recoil product catcher. The new system was tested at the 8 UD Pelletron tandem accelerator of the University of São Paulo with the measurement of two known isomeric states: 54Fe, 10+ state (E = 6527.1 (11) keV, T1/2 = 364(7) ns) and the 5/2+ state of 19F (E = 197.143 (4) keV, T1/2 = 89.3 (10) ns). The results indicate that the system is capable of identifying delayed transitions, of measuring isomeric state lifetimes, and of identifying the feeding transitions of the isomeric state through the delayed γ-γ coincidence method. The measured half-life for the 10+ state was T1/2 = 365(14) ns and for the 5/2+ state, 100(36) ns.

  5. 2′-O Methylation of Internal Adenosine by Flavivirus NS5 Methyltransferase

    Science.gov (United States)

    Dong, Hongping; Chang, David C.; Hua, Maggie Ho Chia; Lim, Siew Pheng; Chionh, Yok Hian; Hia, Fabian; Lee, Yie Hou; Kukkaro, Petra; Lok, Shee-Mei; Dedon, Peter C.; Shi, Pei-Yong

    2012-01-01

    RNA modification plays an important role in modulating host-pathogen interaction. Flavivirus NS5 protein encodes N-7 and 2′-O methyltransferase activities that are required for the formation of 5′ type I cap (m7GpppAm) of viral RNA genome. Here we reported, for the first time, that flavivirus NS5 has a novel internal RNA methylation activity. Recombinant NS5 proteins of West Nile virus and Dengue virus (serotype 4; DENV-4) specifically methylates polyA, but not polyG, polyC, or polyU, indicating that the methylation occurs at adenosine residue. RNAs with internal adenosines substituted with 2′-O-methyladenosines are not active substrates for internal methylation, whereas RNAs with adenosines substituted with N6-methyladenosines can be efficiently methylated, suggesting that the internal methylation occurs at the 2′-OH position of adenosine. Mass spectroscopic analysis further demonstrated that the internal methylation product is 2′-O-methyladenosine. Importantly, genomic RNA purified from DENV virion contains 2′-O-methyladenosine. The 2′-O methylation of internal adenosine does not require specific RNA sequence since recombinant methyltransferase of DENV-4 can efficiently methylate RNAs spanning different regions of viral genome, host ribosomal RNAs, and polyA. Structure-based mutagenesis results indicate that K61-D146-K181-E217 tetrad of DENV-4 methyltransferase forms the active site of internal methylation activity; in addition, distinct residues within the methyl donor (S-adenosyl-L-methionine) pocket, GTP pocket, and RNA-binding site are critical for the internal methylation activity. Functional analysis using flavivirus replicon and genome-length RNAs showed that internal methylation attenuated viral RNA translation and replication. Polymerase assay revealed that internal 2′-O-methyladenosine reduces the efficiency of RNA elongation. Collectively, our results demonstrate that flavivirus NS5 performs 2′-O methylation of internal adenosine of

  6. Properties of bright solitons in averaged and unaveraged models for SDG fibres

    Science.gov (United States)

    Kumar, Ajit; Kumar, Atul

    1996-04-01

    Using the slowly varying envelope approximation and averaging over the fibre cross-section the evolution equation for optical pulses in semiconductor-doped glass (SDG) fibres is derived from the nonlinear wave equation. Bright soliton solutions of this equation are obtained numerically and their properties are studied and compared with those of the bright solitons in the unaveraged model.

  7. Large-scale brightness inhomogeneities in the solar atmosphere

    International Nuclear Information System (INIS)

    Mitchell, W.E. Jr.

    1982-01-01

    The intensity residuals are analyzed from a series of solar limb-darkening measurements in the wavelength range 5656 to 2997 A. The lengths of residual strings of the same sign exceed expectation by several orders of magnitude. The power spectrum fo the residuals shows a weak excess around 6000 km. For further study the 34000 limb-darkening residuals are subdivided into 5100 bright and faint cells. The frequency distribution of cell sizes peaks around 4500 km and increases from center to limb, the faint cells showing the greater center-limb effect. The cells are also studied as to contrast. A synoptic view indicates that only 12% of the cells are identifiable after a half hour. Phenomena that may combine to produce the observed wide spectrum of brightness inhomogeneities are briefly discussed. (orig.)

  8. The effect of bright light on sleepiness among rapid-rotating 12-hour shift workers.

    Science.gov (United States)

    Sadeghniiat-Haghighi, Khosro; Yazdi, Zohreh; Jahanihashemi, Hassan; Aminian, Omid

    2011-01-01

    About 20% of workers in industrialized countries are shift workers and more than half of them work on night or rotating shifts. Most night workers complain of sleepiness due to lack of adjustment of the circadian rhythm. In simulated night-work experiments, scheduled exposure to bright light has been shown to reduce these complaints. Our study assessed the effects of bright light exposure on sleepiness during night work in an industrial setting. In a cross-over design, 94 workers at a ceramic factory were exposed to either bright (2500 lux) or normal light (300 lux) during breaks on night shifts. We initiated 20-minute breaks between 24.00 and 02.00 hours. Sleepiness ratings were determined using the Stanford Sleepiness Scale at 22.00, 24.00, 02.00 and 04.00 hours. Under normal light conditions, sleepiness peaked at 02:00 hours. A significant reduction (22% compared to normal light conditions) in sleepiness was observed after workers were exposed to bright light. Exposure to bright light may be effective in reducing sleepiness among night workers.

  9. Global Observations of the 630-nm Nightglow and Patterns of Brightness Measured by ISUAL

    Directory of Open Access Journals (Sweden)

    Chih-Yu Chiang

    2013-01-01

    Full Text Available This study investigates the distributions and occurrence mechanisms of the global local-midnight airglow brightness through FORMOSAT-2/ISUAL satellite imaging observations. We focus on the OI 630.0 nm nightglow emission at altitudes of ~250 km along equatorial space. The database used in this study included data from 2007 to 2008 under solar minimum conditions. The data were classified into four specified types in the statistical study. We found that the occurrence of equatorial brightness was often in the vicinity of the geographic equator and mostly at equinoxes with a tendency to move toward the summer hemisphere as the season changes. Conjugate brightness occurring simultaneously on both sides of the geomagnetic equator was observed predominantly in the northern winter. Furthermore, midnight brightness appeared to have lower luminosity from May to July. We suggest that the global midnight brightness associated with the locations and seasons was the result of several effects which include the influence of the thermospheric midnight temperature maximum (MTM, summer-to-winter neutral wind, and ionospheric anomalies.

  10. High brightness beams and applications

    International Nuclear Information System (INIS)

    Sheffield, R.L.

    1995-01-01

    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

  11. The Physics and Applications of High Brightness Electron Beams

    Science.gov (United States)

    Palumbo, Luigi; Rosenzweig, J.; Serafini, Luca

    2007-09-01

    Plenary sessions. RF deflector based sub-Ps beam diagnostics: application to FEL and advanced accelerators / D. Alesini. Production of fermtosecond pulses and micron beam spots for high brightness electron beam applications / S.G. Anderson ... [et al.]. Wakefields of sub-picosecond electron bunches / K.L.F. Bane. Diamond secondary emitter / I. Ben-Zvi ... [et al.]. Parametric optimization for an X-ray free electron laser with a laser wiggler / R. Bonifacio, N. Piovella and M.M. Cola. Needle cathodes for high-brightness beams / C.H. Boulware ... [et al.]. Non linear evolution of short pulses in FEL cascaded undulators and the FEL harmonic cascade / L. Giannessi and P. Musumeci. High brightness laser induced multi-meV electron/proton sources / D. Giulietti ... [et al.]. Emittance limitation of a conditioned beam in a strong focusing FEL undulator / Z. Huang, G. Stupakov and S. Reiche. Scaled models: space-charge dominated electron storage rings / R.A. Kishek ... [et al.]. High brightness beam applications: energy recovered linacs / G.A. Krafft. Maximizing brightness in photoinjectors / C. Limborg-Deprey and H. Tomizawa. Ultracold electron sources / O.J. Luiten ... [et al.]. Scaling laws of structure-based optical accelerators / A. Mizrahi, V. Karagodsky and L. Schächter. High brightness beams-applications to free-electron lasers / S. Reiche. Conception of photo-injectors for the CTF3 experiment / R. Roux. Superconducting RF photoinjectors: an overview / J. Sekutowicz. Status and perspectives of photo injector developments for high brightness beams / F. Stephan. Results from the UCLA/FNLP underdense plasma lens experiment / M.C. Thompson ... [et al.]. Medical application of multi-beam compton scattering monochromatic tunable hard X-ray source / M. Uesaka ... [et al.]. Design of a 2 kA, 30 fs RF-photoinjector for waterbag compression / S.B. Van Der Geer, O.J. Luiten and M.J. De Loos. Proposal for a high-brightness pulsed electron source / M. Zolotorev ... [et al

  12. Short Pulse High Brightness X-ray Production with the PLEIADES Thomson Scattering Source

    International Nuclear Information System (INIS)

    Anderson, S.G.; Barty, C.P.J.; Betts, S.M.; Brown, W.J.; Crane, J.K.; Cross, R.R.; Fittinghoff, D.N.; Gibson, D.J.; Hartemann, F.V.; Kuba, J.; LaSage, G.P.; Rosenzweig, J.B.; Slaughter, D.R.; Springer, P.T.; Tremaine, A.M.

    2003-01-01

    We describe PLEIADES, a compact, tunable, high-brightness, ultra-short pulse, Thomson x-ray source. The peak brightness of the source is expected to exceed 10 20 photons/s/0.1% bandwidth/mm 2 /mrad 2 . Initial results are reported and compared to theoretical calculations

  13. Polarization mechanism in a ns laser-induced plasma spectroscopy of Al alloy

    Science.gov (United States)

    Aghababaei Nejad, Mahboobeh; Soltanolkotabi, Mahmood; Eslami Majd, Abdollah

    2018-01-01

    Polarization emission from aluminum alloy by ns laser-induced breakdown spectroscopy (LIBS) is carefully investigated in air using a non-gated CCD camera at integration time of 100 ms. First, the analysis reveals that the small polarization degree is the same for both continuum and discrete line emission spectra which also increases slowly with wavelength growth; second, laser fluence in the range of 347.81-550.10 J/cm2 has no significant changes in plasma polarization; and third, larger polarization in comparison with polarization introduced by preferential reflection of emission from the target surface (Fresnel reflectivity) is observed. The residual fluctuations of the anisotropic recombining plasma and the dynamic polarization of an ion's core are suggested as the possible main sources for observed polarized radiation in ns-LIBS.

  14. Two- and 4-hour bright-light exposures differentially effect sleepiness and performance the subsequent night.

    Science.gov (United States)

    Thessing, V C; Anch, A M; Muehlbach, M J; Schweitzer, P K; Walsh, J K

    1994-03-01

    The effect of two durations of bright light upon sleepiness and performance during typical night shift hours was assessed. Thirty normal, healthy young adults participated in a 2-night protocol. On the 1st night subjects were exposed to bright or dim light beginning at 2400 hours, under one of the following three conditions: bright light for 4 hours, dim light for 2 hours followed by bright light for 2 hours or dim light for 4 hours. Following light exposure, subjects remained awake until 0800 hours in a dimly lit room and slept in the laboratory between 0800 and 1600 hours, during which time sleep was estimated with actigraphy. Throughout the 2nd night, the multiple sleep latency test (MSLT), simulated assembly line task (SALT) performance, and subjective sleepiness were recorded. The single, 4-hour exposure to bright light was found to significantly increase MSLT scores and improve SALT performance during the early morning hours on the night following bright-light exposure. No significant effects were noted with a 2-hour exposure. The most likely explanation for these findings is a phase delay in the circadian rhythm of sleepiness-alertness.

  15. A new perspective on the infrared brightness temperature ...

    Indian Academy of Sciences (India)

    CEAWMT), ... temperatures clearly discriminates the cloud pixels of deep convective and ... utilized in the modelling of the histogram of infrared brightness temperature of deep convective and ..... Henderson-Sellers A 1978 Surface type and its effect.

  16. Tolerance of image enhancement brightness and contrast in lateral cephalometric digital radiography for Steiner analysis

    Science.gov (United States)

    Rianti, R. A.; Priaminiarti, M.; Syahraini, S. I.

    2017-08-01

    Image enhancement brightness and contrast can be adjusted on lateral cephalometric digital radiographs to improve image quality and anatomic landmarks for measurement by Steiner analysis. To determine the limit value for adjustments of image enhancement brightness and contrast in lateral cephalometric digital radiography for Steiner analysis. Image enhancement brightness and contrast were adjusted on 100 lateral cephalometric radiography in 10-point increments (-30, -20, -10, 0, +10, +20, +30). Steiner analysis measurements were then performed by two observers. Reliabilities were tested by the Interclass Correlation Coefficient (ICC) and significance tested by ANOVA or the Kruskal Wallis test. No significant differences were detected in lateral cephalometric analysis measurements following adjustment of the image enhancement brightness and contrast. The limit value of adjustments of the image enhancement brightness and contrast associated with incremental 10-point changes (-30, -20, -10, 0, +10, +20, +30) does not affect the results of Steiner analysis.

  17. Brightness enhancement of plasma ion source by utilizing anode spot for nano applications

    International Nuclear Information System (INIS)

    Park, Yeong-Shin; Lee, Yuna; Chung, Kyoung-Jae; Hwang, Y. S.; Kim, Yoon-Jae; Park, Man-Jin; Moon, Dae Won

    2012-01-01

    Anode spots are known as additional discharges on positively biased electrode immersed in plasmas. The anode spot plasma ion source (ASPIS) has been investigated as a high brightness ion source for nano applications such as focused ion beam (FIB) and nano medium energy ion scattering (nano-MEIS). The generation of anode spot is found to enhance brightness of ion beam since the anode spot increases plasma density near the extraction aperture. Brightness of the ASPIS has been estimated from measurement of emittance for total ion beam extracted through sub-mm aperture. The ASPIS is installed to the FIB system. Currents and diameters of the focused beams with/without anode spot are measured and compared. As the anode spot is turned on, the enhancement of beam current is observed at fixed diameter of the focused ion beam. Consequently, the brightness of the focused ion beam is enhanced as well. For argon ion beam, the maximum normalized brightness of 12 300 A/m 2 SrV is acquired. The ASPIS is applied to nano-MEIS as well. The ASPIS is found to increase the beam current density and the power efficiency of the ion source for nano-MEIS. From the present study, it is shown that the ASPIS can enhance the performance of devices for nano applications.

  18. 150 southern compact and bright-nucleus galaxies

    International Nuclear Information System (INIS)

    Fairall, A.P.

    1977-01-01

    Galaxies having regions of exceptionally high surface brightness have been selected from the ESO Quick Blue Survey and investigated by 'grating photography' -direct photography plus low-dispersion slitless spectroscopy. Two new Seyfert galaxies and a peculiar multiple system have been discovered. Differences in red continua are also noted. (author)

  19. Near-infrared photometry of bright elliptical galaxies

    NARCIS (Netherlands)

    Peletier, R. F.; Valentijn, E. A.; Jameson, R. F.

    High-quality visual-infrared color profiles have been determined for elliptical galaxies for the first time. Surface photometry in J and K is presented for 12 bright elliptical galaxies, and the results have been combined with CCD data in visual passbands. It is shown that the galaxies become bluer

  20. Molecular Dynamics of the ZIKA Virus NS3 Helicase

    Science.gov (United States)

    Raubenolt, Bryan; Rick, Steven; The Rick Group Team

    The recent outbreaks of the ZIKA virus (ZIKV) and its connection to microcephaly in newborns has raised its awareness as a global threat and many scientific research efforts are currently underway in attempt to create a vaccine. Molecular Dynamics is a powerful method of investigating the physical behavior of protein complexes. ZIKV is comprised of 3 structural and 7 nonstructural proteins. The NS3 helicase protein appears to play a significant role in the replication complex and its inhibition could be a crucial source of antiviral drug design. This research primarily focuses on studying the structural dynamics, over the course of few hundred nanoseconds, of NS3 helicase in the free state, as well as in complex form with human ssRNA, ATP, and an analogue of GTP. RMSD and RMSF plots of each simulation will provide details on the forces involved in the overall stability of the active and inactive states. Furthermore, free energy calculations on a per residue level will reveal the most interactive residues between states and ultimately the primary driving force behind these interactions. Together these analyses will provide highly relevant information on the binding surface chemistry and thus serve as the basis for potential drug design.