Science.gov

Sample records for bright ns lmxbs

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

    NASA Astrophysics Data System (ADS)

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

    2010-07-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2009-05-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

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

  5. Monitoring LMXBs with the Faulkes Telescope

    NASA Astrophysics Data System (ADS)

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

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

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

    NASA Technical Reports Server (NTRS)

    Paciesas, William S.

    2002-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

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

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

    NASA Astrophysics Data System (ADS)

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

    2017-04-01

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

  9. Helium-Rich Bursters Reveal the NS Interiors

    NASA Astrophysics Data System (ADS)

    Misanovic, Zdenka

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

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

    NASA Astrophysics Data System (ADS)

    Voss, R.; Gilfanov, M.

    2007-06-01

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

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

    NASA Astrophysics Data System (ADS)

    Bailyn, Charles

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

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

    NASA Technical Reports Server (NTRS)

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

    2004-01-01

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

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

    SciTech Connect

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

    2015-07-20

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

  14. Characterization of Dengue Virus NS4A and NS4B Protein Interaction

    PubMed Central

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

    2015-01-01

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

  15. [Bright light therapy].

    PubMed

    Poirrier, R; Cambron, L

    2007-01-01

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

  16. NS&T Management Observations

    SciTech Connect

    Gianotto, David

    2014-09-01

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

  17. High Brightness OLED Lighting

    SciTech Connect

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

    2016-05-25

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

  18. Brightness predictions for comets

    NASA Astrophysics Data System (ADS)

    Green, Daniel W. E.; Marsden, Brian G.; Morris, Charles S.

    2001-02-01

    Daniel W E Green, Brian G Marsden and Charles S Morris write with the aim of illuminating the issue of cometary light curves and brightness predictions, following the publication in this journal last October of the letter by John McFarland (2000).

  19. A Bright Shining Lesson

    ERIC Educational Resources Information Center

    Hurowitz, Amanda

    2010-01-01

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

  20. Bright Fireball Over Georgia

    NASA Video Gallery

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

  1. Bright Streak on Amalthea

    NASA Technical Reports Server (NTRS)

    2000-01-01

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

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

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

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

    PubMed Central

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

    2015-01-01

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

  3. Bright field illumination system

    NASA Technical Reports Server (NTRS)

    Huber, Edward D. (Inventor)

    1998-01-01

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

  4. Kiloamp high-brightness beams

    SciTech Connect

    Caporaso, G.J.

    1987-01-01

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

  5. HI Surface brightness mapping

    NASA Astrophysics Data System (ADS)

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

    2008-04-01

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

  6. Low surface brightness galaxies

    NASA Technical Reports Server (NTRS)

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

    1993-01-01

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

  7. High brightness electron sources

    SciTech Connect

    Sheffield, R.L.

    1995-07-01

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

  8. High brightness electron accelerator

    DOEpatents

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

    1994-01-01

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

  9. Tunable High Brightness Semiconductor Sources

    DTIC Science & Technology

    2015-05-01

    AFRL-RY-WP-TR-2015-0066 TUNABLE HIGH BRIGHTNESS SEMICONDUCTOR SOURCES Robert Bedford, Saima Husaini, Charles Reyner, and Tuoc Dang...3. DATES COVERED (From - To) May 2015 Final 5 November 2010 – 1 February 2015 4. TITLE AND SUBTITLE TUNABLE HIGH BRIGHTNESS SEMICONDUCTOR SOURCES 5a...included within the Tunable High Brightness Semiconductor Sources work unit includes several technology advancements. First, theoretical advances in mid

  10. NS/EP Implications of Electronic Commerce

    DTIC Science & Technology

    1999-06-01

    THE PRESIDENT’S NATIONAL SECURITY TELECOMMUNICATIONS ADVISORY COMMITTEE NS/EP IMPLICATIONS OF ELECTRONIC COMMERCE JUNE 1999 Form SF298 Citation Data... Electronic Commerce Procedures Contract or Grant Number Program Element Number Authors Project Number Task Number Work Unit Number Performing Organization...99 3. REPORT TYPE AND DATES COVERED Report 4. TITLE AND SUBTITLE NS/EP Implications of Electronic Commerce 5. FUNDING NUMBERS 6. AUTHOR(S) President’s

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

    PubMed

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

    2017-03-21

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

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Marcotrigiano, Joseph

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    SciTech Connect

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

    2014-08-18

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

  16. High brightness picosecond electron gun

    SciTech Connect

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

    2005-08-15

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

  17. In Situ Mosaic Brightness Correction

    NASA Technical Reports Server (NTRS)

    Deen, Robert G.; Lorre, Jean J.

    2012-01-01

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

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

    PubMed Central

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

    1996-01-01

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

  19. Bright Beginnings. WWC Intervention Report

    ERIC Educational Resources Information Center

    What Works Clearinghouse, 2009

    2009-01-01

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

  20. Network based sky Brightness Monitor

    NASA Astrophysics Data System (ADS)

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

    2009-01-01

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

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

    PubMed

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

    2012-10-12

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

  2. Binary NS simulations using SpEC

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

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

  3. Brightness-equalized quantum dots

    PubMed Central

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

    2015-01-01

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

  4. Low-brightness quantum radar

    NASA Astrophysics Data System (ADS)

    Lanzagorta, Marco

    2015-05-01

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

  5. Brightness-equalized quantum dots.

    PubMed

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

    2015-10-05

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

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

    SciTech Connect

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

    2006-02-01

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

  7. Iapetus Bright and Dark Terrains

    NASA Technical Reports Server (NTRS)

    1990-01-01

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

  8. Bright tunable ultraviolet squeezed light.

    PubMed

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

    1997-04-15

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

  9. LSST Site: Sky Brightness Data

    NASA Astrophysics Data System (ADS)

    Burke, Jamison; Claver, Charles

    2015-01-01

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

  10. High-brightness rf linear accelerators

    SciTech Connect

    Jameson, R.A.

    1986-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  12. Determinants of Dengue Virus NS4A Protein Oligomerization

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

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

    2013-10-20

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

  14. Binary NS simulations using SpEC

    NASA Astrophysics Data System (ADS)

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

    2012-03-01

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

  15. Binary NS simulations using SpEC

    NASA Astrophysics Data System (ADS)

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

    2013-04-01

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

  16. Exceptionally bright, compact starburst nucleus

    SciTech Connect

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

    1988-11-01

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

  17. High brightness beams and applications

    SciTech Connect

    Sheffield, R.L.

    1995-09-01

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

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

    PubMed Central

    Paredes, Anne M.; Blight, Keril J.

    2008-01-01

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

  19. A Closer Look at the NS1 of Influenza Virus

    PubMed Central

    Dundon, William G.; Capua, Ilaria

    2009-01-01

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

  20. How Bright Can Supernovae Get?

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-04-01

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

  1. Limb displacement and brightness seismology

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

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

  2. Bright diode laser light source.

    PubMed

    Lassila, Erkki; Hernberg, Rolf

    2006-05-20

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

  3. Night sky brightness measurement at PERMATApintar observatory

    NASA Astrophysics Data System (ADS)

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

    2016-11-01

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

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

    PubMed

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

    2016-03-01

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

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

    PubMed

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

    2016-03-01

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

  6. Synergistic Activity of Combined NS5A Inhibitors

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-15

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2011-12-19

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

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

    PubMed Central

    Akimitsu, Nobuyoshi

    2013-01-01

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

  11. Brightness alteration with interweaving contours.

    PubMed

    Roncato, Sergio

    2012-01-01

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

  12. Bright Star Astrometry with URAT

    NASA Astrophysics Data System (ADS)

    Zacharias, N.

    2015-10-01

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

  13. Spatial Brightness Perception of Trichromatic Stimuli

    SciTech Connect

    Royer, Michael P.; Houser, Kevin W.

    2012-11-16

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

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

    PubMed

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

    2017-03-01

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

  15. Novel Dengue Virus NS2B/NS3 Protease Inhibitors

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    2011-01-01

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

  17. Bright Sparks of Our Future!

    NASA Astrophysics Data System (ADS)

    Riordan, Naoimh

    2016-04-01

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

  18. Bright Streaks and Dark Fans

    NASA Technical Reports Server (NTRS)

    2007-01-01

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

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

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

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

  19. Brightness of the solar F-corona

    NASA Astrophysics Data System (ADS)

    Kimura, Hiroshi; Mann, Ingrid

    1998-06-01

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

  20. Galaxy Selection and the Surface Brightness Distribution

    NASA Astrophysics Data System (ADS)

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

    1995-08-01

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

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

    PubMed Central

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

    2000-01-01

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

  2. Differential Rotation via Tracking of Coronal Bright Points.

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

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

  3. Tetrahydrobenzothiophene inhibitors of hepatitis C virus NS5B polymerase.

    PubMed

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

    2006-01-01

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

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

    PubMed

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

    2006-07-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

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

  6. Just How Bright Is a Laser?

    ERIC Educational Resources Information Center

    Van Baak, David A.

    1995-01-01

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

  7. New Observations of Subarcsecond Photospheric Bright Points

    NASA Technical Reports Server (NTRS)

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

    1995-01-01

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

  8. New Observations of Subarcsecond Photospheric Bright Points

    NASA Technical Reports Server (NTRS)

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

    1995-01-01

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

  9. Apparent brightness distribution of GRB host galaxies

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

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

  10. Observations and diagnostics in high brightness beams

    NASA Astrophysics Data System (ADS)

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

    2016-09-01

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

  11. The analogy between stereo depth and brightness.

    PubMed

    Brookes, A; Stevens, K A

    1989-01-01

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

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Radhakrishnan, R; Manikandan, N; Aravinthan, K

    2015-12-01

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

  15. Microwave Brightness Temperatures of Tilted Convective Systems

    NASA Technical Reports Server (NTRS)

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

    1998-01-01

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

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

    PubMed

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

    2017-03-23

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

  17. Solar Cycle 23 in Coronal Bright Points

    NASA Astrophysics Data System (ADS)

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

    2010-04-01

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

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

    PubMed

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

    2011-03-28

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

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

    PubMed

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

    2009-01-01

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

  20. Brightness Discrimination in Budgerigars (Melopsittacus undulatus)

    PubMed Central

    Lind, Olle; Karlsson, Sandra; Kelber, Almut

    2013-01-01

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

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

    SciTech Connect

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

    2013-11-29

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

  2. Richard Bright and his neurological studies.

    PubMed

    Pearce, J M S

    2009-01-01

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

  3. Kinematics of Low Surface Brightness Galaxies

    NASA Astrophysics Data System (ADS)

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

    2008-10-01

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

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

    SciTech Connect

    Wang, Yimeng; Zhou, Jianhong; Du, Yuchun

    2014-01-20

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-01-01

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

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

    PubMed

    Boonyasuppayakorn, Siwaporn; Padmanabhan, Radhakrishnan

    2014-01-01

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

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

    PubMed

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

    2002-02-25

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

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

    PubMed

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

    2013-08-01

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

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

    SciTech Connect

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

    2008-04-25

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

  10. Simultaneous brightness contrast of foraging Papilio butterflies

    PubMed Central

    Kinoshita, Michiyo; Takahashi, Yuki; Arikawa, Kentaro

    2012-01-01

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

  11. Simultaneous brightness contrast of foraging Papilio butterflies.

    PubMed

    Kinoshita, Michiyo; Takahashi, Yuki; Arikawa, Kentaro

    2012-05-22

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

  12. Sky brightness during eclipses: a review.

    PubMed

    Silverman, S M; Mullen, E G

    1975-12-01

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

  13. AMSR-E/Aqua Gridded Brightness Temperatures

    NASA Astrophysics Data System (ADS)

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

    2006-12-01

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

  14. Bright Meteor Lights Up Atlanta Skies

    NASA Video Gallery

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

  15. Brightness versus roughness: a multiscale approach

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

  16. Brightness of synchrotron radiation from wigglers

    NASA Astrophysics Data System (ADS)

    Geloni, Gianluca; Kocharyan, Vitali; Saldin, Evgeni

    2016-01-01

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

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

    PubMed

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

    2008-01-01

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

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

    PubMed

    Arunajadai, Srikesh G

    2009-09-22

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

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

    PubMed

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

    2017-04-10

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

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

    NASA Technical Reports Server (NTRS)

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

    2003-01-01

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

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

    PubMed

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

    2017-03-22

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

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

    PubMed

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

    2017-02-07

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

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

    PubMed

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

    2012-02-01

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

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

    PubMed

    Wang, Yimeng; Zhou, Jianhong; Du, Yuchun

    2014-01-20

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

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

    PubMed

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

    2013-12-01

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

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

    PubMed

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

    2005-11-01

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

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

    PubMed Central

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

    2004-01-01

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

  8. Image mosaic with color and brightness correction

    NASA Astrophysics Data System (ADS)

    Zhao, Yili; Xu, Dan; Pan, Zhigeng

    2004-03-01

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

  9. Process Performances of 2 ns Pulsed Discharge Plasma

    NASA Astrophysics Data System (ADS)

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

    2011-08-01

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

  10. NS&T Management Observations - 3rd Quarter

    SciTech Connect

    Gianotto, David

    2014-07-01

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

  11. NS&T Management Observations: Quarterly Performance Analysis

    SciTech Connect

    Gianotto, David

    2014-09-01

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

  12. NS&T Managment Observations - 1st Quarter

    SciTech Connect

    David Gianotto

    2014-06-01

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

  13. Nonlinear Brightness Optimization in Compton Scattering

    SciTech Connect

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

    2013-07-26

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

  14. Extreme Ultraviolet Explorer Bright Source List

    NASA Technical Reports Server (NTRS)

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

    1994-01-01

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

  15. Australia 31-GHz brightness temperature exceedance statistics

    NASA Technical Reports Server (NTRS)

    Gary, B. L.

    1988-01-01

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

  16. UV-bright stars in globular clusters

    NASA Technical Reports Server (NTRS)

    Landsman, Wayne B.

    1994-01-01

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

  17. Spectral Characterization of Bright Materials on Vesta

    NASA Technical Reports Server (NTRS)

    Capaccioni, Fabrizio; DeSanctis, M. C.; Ammannito, E.; Li, Jian-Yang; Longobardo, A.; Mittlefehldt, David W.; Palomba, E.; Pieters, C. M.; Schroeder, S. E.; Tosi, F.; Hiesinger, H.; Blewett, D. T.; Russell, C. T.; Raymond, C. A.

    2012-01-01

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

  18. iPTF report of bright transients

    NASA Astrophysics Data System (ADS)

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

    2017-02-01

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

  19. Nonlinear Brightness Optimization in Compton Scattering

    NASA Astrophysics Data System (ADS)

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

    2013-07-01

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

  20. Modular Zero Energy. BrightBuilt Home

    SciTech Connect

    Aldrich, Robb; Butterfield, Karla

    2016-03-01

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

  1. Discovery of an irreversible HCV NS5B polymerase inhibitor.

    PubMed

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

    2013-12-15

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

  2. Bright and Dark Slopes on Ganymede

    NASA Technical Reports Server (NTRS)

    1997-01-01

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

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

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

  3. Brightness Changes in Sun-like Stars

    NASA Technical Reports Server (NTRS)

    Henry, Stephen M.; Henry, Gregory W.

    1998-01-01

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

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

    PubMed

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

    2016-02-01

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

  5. Search for bright stars with infrared excess

    SciTech Connect

    Raharto, Moedji

    2014-03-24

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

  6. Personal audio with a planar bright zone.

    PubMed

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

    2014-10-01

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

  7. Bright Ray Craters in Ganymede's Northern Hemisphere

    NASA Technical Reports Server (NTRS)

    1979-01-01

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

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

    PubMed

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

    2010-12-03

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

  9. Membrane Interacting Regions of Dengue Virus NS2A Protein

    PubMed Central

    2015-01-01

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

  10. Active Processes: Bright Streaks and Dark Fans

    NASA Technical Reports Server (NTRS)

    2007-01-01

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

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

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

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

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

  11. Discovery of Dengue Virus NS4B Inhibitors

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-08-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2011-08-01

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

  14. 7 CFR 51.2000 - Clean and bright.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

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

  15. 7 CFR 51.2000 - Clean and bright.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

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

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

    PubMed

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

    2016-12-02

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

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

    NASA Astrophysics Data System (ADS)

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

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

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

    PubMed

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

    2017-04-05

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

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

    PubMed

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

    2016-12-15

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

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

    PubMed Central

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

    2016-01-01

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

  1. Dark and Bright Ridges on Europa

    NASA Technical Reports Server (NTRS)

    1998-01-01

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

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

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

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

  2. Raman beam combining for laser brightness enhancement

    DOEpatents

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

    2015-10-27

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

  3. Two-color bright squeezed vacuum

    SciTech Connect

    Agafonov, Ivan N.; Chekhova, Maria V.

    2010-07-15

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

  4. Apparent brightness distribution of GRB host galaxies

    NASA Astrophysics Data System (ADS)

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

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

  5. Rotation and macroturbulence in bright giants

    SciTech Connect

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

    1986-11-01

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

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

    PubMed

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

    2015-04-22

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

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

    PubMed Central

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

    2015-01-01

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

  8. 16th International Conference on Nuclear Structure: NS2016

    SciTech Connect

    Galindo-Uribarri, Alfredo

    2016-10-28

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

  9. 16th International Conference on Nuclear Structure: NS2016

    DOE PAGES

    Galindo-Uribarri, Alfredo

    2016-10-28

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2013-10-01

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

  12. Sublimation in bright spots on (1) Ceres

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

  13. Coronal Bright Points Associated with Minifilament Eruptions

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

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

  14. Coronal bright points associated with minifilament eruptions

    SciTech Connect

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

    2014-12-01

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

  15. At Bright Band Inside Victoria Crater

    NASA Technical Reports Server (NTRS)

    2007-01-01

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

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

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

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

    PubMed

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

    2015-12-10

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

  17. A high brightness field emission display

    SciTech Connect

    Palevsky, A.

    1996-12-31

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

  18. Synchrotron brightness distribution of turbulent radio jets

    NASA Technical Reports Server (NTRS)

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

    1981-01-01

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

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

    PubMed Central

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

    1996-01-01

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

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

    PubMed

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

    1999-04-20

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

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

    NASA Astrophysics Data System (ADS)

    Plotch, Stephen J.; Krug, Robert M.

    1986-08-01

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

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

    NASA Astrophysics Data System (ADS)

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

    1987-05-01

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

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

    NASA Astrophysics Data System (ADS)

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

    1998-11-01

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

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

    PubMed Central

    Taylor, R. Travis; Best, Sonja M.

    2011-01-01

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

  5. Autonomous Magnetoexplosive Generator of Megavolt, 100 NS Pulses

    NASA Astrophysics Data System (ADS)

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

    2004-11-01

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

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

    PubMed

    Taylor, R Travis; Best, Sonja M

    2011-10-01

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

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

    NASA Astrophysics Data System (ADS)

    Singh, Ashish; Little, Jesse

    2016-11-01

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

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

    ERIC Educational Resources Information Center

    Bauer, Ben

    2009-01-01

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

  9. Solving the Brightness-from-Luminance Problem: A Neural Architecture for Invariant Brightness Perception

    DTIC Science & Technology

    1989-02-01

    lightness. Behavioral and Brain Sciences, 6, 625-692. Grossberg, S. (1987a). Cortical dynamics of three-dimensional form , color , and brightness...perception, I: Monocular theory. Perception and Psychophysics, 41, 87-116. Grossberg, S. (1987b). Cortical dynamics of three-dimensional form , color , and

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

    NASA Astrophysics Data System (ADS)

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

    2014-06-01

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

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

    SciTech Connect

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

    2014-06-10

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

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

    PubMed

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

    2014-03-21

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2007-12-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

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

  17. Infrared Sky Brightness Monitors for Antarctica

    NASA Astrophysics Data System (ADS)

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

    1999-06-01

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

  18. Extinction and Sky Brightness at Dome C

    NASA Astrophysics Data System (ADS)

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

    2012-06-01

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

  19. Dark Skies, Bright Kids Year 7

    NASA Astrophysics Data System (ADS)

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

    2016-01-01

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

  20. Dark Skies, Bright Kids Year 8

    NASA Astrophysics Data System (ADS)

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

    2017-01-01

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

  1. High brightness angled cavity quantum cascade lasers

    SciTech Connect

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

    2015-03-02

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

  2. Visualizing individual microtubules by bright field microscopy

    NASA Astrophysics Data System (ADS)

    Gutiérrez-Medina, Braulio; Block, Steven M.

    2010-11-01

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

  3. High brightness angled cavity quantum cascade lasers

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

  4. Bright Solitonic Matter-Wave Interferometer

    NASA Astrophysics Data System (ADS)

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

    2014-07-01

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

  5. Modelling Solar and Stellar Brightness Variabilities

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

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

  6. Statistical Properties of Solar Coronal Bright Points

    NASA Astrophysics Data System (ADS)

    Alipour, N.; Safari, H.

    2015-07-01

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

  7. The GPM Common Calibrated Brightness Temperature Product

    NASA Technical Reports Server (NTRS)

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

    2005-01-01

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

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

    PubMed

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

    1993-07-01

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

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

    SciTech Connect

    Ning, Zongjun; Guo, Yang

    2014-10-10

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

  10. Dengue NS1 antigen contributes to disease severity by inducing interleukin (IL)-10 by monocytes.

    PubMed

    Adikari, T N; Gomes, L; Wickramasinghe, N; Salimi, M; Wijesiriwardana, N; Kamaladasa, A; Shyamali, N L A; Ogg, G S; Malavige, G N

    2016-04-01

    Both dengue NS1 antigen and serum interleukin (IL)-10 levels have been shown to associate with severe clinical disease in acute dengue infection, and IL-10 has also been shown to suppress dengue-specific T cell responses. Therefore, we proceeded to investigate the mechanisms by which dengue NS1 contributes to disease pathogenesis and if it is associated with altered IL-10 production. Serum IL-10 and dengue NS1 antigen levels were assessed serially in 36 adult Sri Lankan individuals with acute dengue infection. We found that the serum IL-10 levels correlated positively with dengue NS1 antigen levels (Spearman's r = 0·47, P < 0·0001), and NS1 also correlated with annexin V expression by T cells in acute dengue (Spearman's r = 0·63, P = 0·001). However, NS1 levels did not associate with the functionality of T cell responses or with expression of co-stimulatory molecules. Therefore, we further assessed the effect of dengue NS1 on monocytes and T cells by co-culturing primary monocytes and peripheral blood mononuclear cells (PBMC), with varying concentrations of NS1 for up to 96 h. Monocytes co-cultured with NS1 produced high levels of IL-10, with the highest levels seen at 24 h, and then declined gradually. Therefore, our data show that dengue NS1 appears to contribute to pathogenesis of dengue infection by inducing IL-10 production by monocytes.

  11. High Brightness Neutron Source for Radiography

    SciTech Connect

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

    2008-12-08

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

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

    PubMed Central

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

    2015-01-01

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

  13. Discovery of a bright eclipsing cataclysmic variable

    NASA Astrophysics Data System (ADS)

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

    2007-11-01

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

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

    SciTech Connect

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

    2009-01-01

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

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

    PubMed

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

    2009-12-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2016-12-30

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

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

    PubMed Central

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

    2016-01-01

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

  19. The Bright Future of Gravitational Wave Astronomy

    NASA Astrophysics Data System (ADS)

    Gonzalez, Gabriela

    2008-04-01

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

  20. High output lamp with high brightness

    DOEpatents

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

    2002-01-01

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

  1. Dark Skies, Bright Kids Year 6

    NASA Astrophysics Data System (ADS)

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

    2015-01-01

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

  2. NuSTAR Observations of Bright AGNs

    NASA Astrophysics Data System (ADS)

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

    2013-01-01

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

  3. Intercomparisons of nine sky brightness detectors.

    PubMed

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

    2011-01-01

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

  4. Bright visible light emission from graphene

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

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

  5. Modular Zero Energy. BrightBuilt Home

    SciTech Connect

    Aldrich, Robb; Butterfield, Karla

    2016-03-01

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

  6. Broken Surface Brightness Profiles in Dwarf Galaxies

    NASA Astrophysics Data System (ADS)

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

    2011-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2017-03-21

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

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

    PubMed Central

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

    2014-01-01

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

  10. Challenging Exceptionally Bright Children in Early Childhood Classrooms

    ERIC Educational Resources Information Center

    Gadzikowski, Ann

    2013-01-01

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

  11. Spain 31-GHz observations of sky brightness temperatures

    NASA Technical Reports Server (NTRS)

    Gary, B. L.

    1988-01-01

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

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

    SciTech Connect

    Nangle, John; Simon, Joseph

    2015-06-17

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

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

    NASA Astrophysics Data System (ADS)

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

    2017-03-01

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

  14. 7 CFR 51.2000 - Clean and bright.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

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

  15. 7 CFR 51.2000 - Clean and bright.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

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

  16. 7 CFR 51.2000 - Clean and bright.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

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

  17. Expression of dengue virus NS3 protein in Drosophila alters its susceptibility to infection

    PubMed Central

    Querenet, Matthieu; Danjoy, Marie-Laure; Mollereau, Bertrand; Davoust, Nathalie

    2015-01-01

    We developed a Drosophila model in which the dengue virus NS3 protein is expressed in a tissue specific and inducible manner. Dengue virus NS3 is a multifunctional protein playing a major role during viral replication. Both protease and helicase domains of NS3 are interacting with human and insect host proteins including innate immune components of the host machinery. We characterized the NS3 transgenic flies showing that NS3 expression did not affect fly development. To further study the links between NS3 and the innate immune response, we challenge the flies with gram-positive and gram-negative bacteria. Interestingly, the Drosophila transgenic flies expressing NS3 were more susceptible to bacterial infections than control flies. However ubiquitous or immune-specific NS3 expression affected neither the life span nor the response to a non-infectious stress of the flies. In conclusion, we generated a new in vivo system to study the functional impact of DENV NS3 protein on the innate immune response. PMID:26267447

  18. Attenuation of equine influenza viruses through truncations of the NS1 protein.

    PubMed

    Quinlivan, Michelle; Zamarin, Dmitriy; García-Sastre, Adolfo; Cullinane, Ann; Chambers, Thomas; Palese, Peter

    2005-07-01

    Equine influenza is a common disease of the horse, causing significant morbidity worldwide. Here we describe the establishment of a plasmid-based reverse genetics system for equine influenza virus. Utilizing this system, we generated three mutant viruses encoding carboxy-terminally truncated NS1 proteins. We have previously shown that a recombinant human influenza virus lacking the NS1 gene (delNS1) could only replicate in interferon (IFN)-incompetent systems, suggesting that the NS1 protein is responsible for IFN antagonist activity. Contrary to previous findings with human influenza virus, we found that in the case of equine influenza virus, the length of the NS1 protein did not correlate with the level of attenuation of that virus. With equine influenza virus, the mutant virus with the shortest NS1 protein turned out to be the least attenuated. We speculate that the basis for attenuation of the equine NS1 mutant viruses generated is related to their level of NS1 protein expression. Our findings show that the recombinant mutant viruses are impaired in their ability to inhibit IFN production in vitro and they do not replicate as efficiently as the parental recombinant strain in embryonated hen eggs, in MDCK cells, or in vivo in a mouse model. Therefore, these attenuated mutant NS1 viruses may have potential as candidates for a live equine influenza vaccine.

  19. Nitrogen oxide removal dynamic process through 15 Ns DBD technique

    NASA Astrophysics Data System (ADS)

    Wang, Xiaojun; Zhang, Lianshui; Lai, Weidong; Liu, Fengliang

    2015-05-01

    Nitrogen oxides exhaust gas assumes the important responsibility on air pollution by forming acid rain. This paper discusses the NO removal mechanism in 15 ns pulse dielectric barrier discharge (DBD) plasma through experimental and simulating method. Emission spectra collected from plasma are evaluated as sourced from N+ and O(3P). The corresponding zero-dimensional model is established and verified through comparing the simulated concentration evolution and the experimental time-resolved spectra of N+. The electron impact ionization plays major role on NO removal and the produced NO+ are further decomposed into N+ and O(3P) through electron impact dissociative excitation rather than the usual reported dissociative recombination process. Simulation also indicates that the removal process can be accelerated by NO inputted at lower initial concentration or electrons streamed at higher concentration, due to the heightened electron impact probability on NO molecules. The repetitive pulse discharge is a benefit for improving the NO removal efficiency by effectively utilizing the radicals generated from the previous pulse under the condition that the pulse period should be shorter enough to ignore the spatial diffusion of radicals. Finally, slight attenuation on NO removal has been experimentally and simulatively observed after N2 mixed, due to the competitive consumption of electrons.

  20. Comments on D-brane dynamics near NS5-branes

    NASA Astrophysics Data System (ADS)

    Sahakyan, David A.

    2004-10-01

    We study the properties of a D-brane in the presence of k NS5 branes. The Dirac-Born-Infeld action describing the dynamics of this D-brane is very similar to that of a non-BPS D-brane in ten dimensions. As the D-brane approaches the fivebranes, its equation of state approaches that of a pressureless fluid. In non-BPS D-brane case this is considered as an evidence for the decay of the D-brane into ``tachyon matter''. We show that in our case similar behavior is the consequence of the motion of the D-brane. In particular in the rest frame of the moving D-brane the equation of state is that of a usual D-brane, for which the pressure is equal to the energy density. We also compute the total cross-section for the decay of the D-brane into closed string modes and show that the emitted energy has a power like divergence for D0, D1 and D2 branes, while converges for higher dimensional D-branes. We also speculate on the possibility that the infalling D-brane describes a decaying defect in six dimensional Little String Theory.

  1. The Putative Metal Coordination Motif in the Endonuclease Domain of Human Parvovirus B19 NS1 Is Critical for NS1 Induced S Phase Arrest and DNA Damage

    PubMed Central

    Kivovich, Violetta; Gilbert, Leona; Vuento, Matti; Naides, Stanley J.

    2012-01-01

    The non-structural proteins (NS) of the parvovirus family are highly conserved multi-functional molecules that have been extensively characterized and shown to be integral to viral replication. Along with NTP-dependent helicase activity, these proteins carry within their sequences domains that allow them to bind DNA and act as nucleases in order to resolve the concatameric intermediates developed during viral replication. The parvovirus B19 NS1 protein contains sequence domains highly similar to those previously implicated in the above-described functions of NS proteins from adeno-associated virus (AAV), minute virus of mice (MVM) and other non-human parvoviruses. Previous studies have shown that transient transfection of B19 NS1 into human liver carcinoma (HepG2) cells initiates the intrinsic apoptotic cascade, ultimately resulting in cell death. In an effort to elucidate the mechanism of mammalian cell demise in the presence of B19 NS1, we undertook a mutagenesis analysis of the protein's endonuclease domain. Our studies have shown that, unlike wild-type NS1, which induces an accumulation of DNA damage, S phase arrest and apoptosis in HepG2 cells, disruptions in the metal coordination motif of the B19 NS1 protein reduce its ability to induce DNA damage and to trigger S phase arrest and subsequent apoptosis. These studies support our hypothesis that, in the absence of replicating B19 genomes, NS1-induced host cell DNA damage is responsible for apoptotic cell death observed in parvoviral infection of non-permissive mammalian cells. PMID:22211107

  2. The putative metal coordination motif in the endonuclease domain of human Parvovirus B19 NS1 is critical for NS1 induced S phase arrest and DNA damage.

    PubMed

    Kivovich, Violetta; Gilbert, Leona; Vuento, Matti; Naides, Stanley J

    2012-01-01

    The non-structural proteins (NS) of the parvovirus family are highly conserved multi-functional molecules that have been extensively characterized and shown to be integral to viral replication. Along with NTP-dependent helicase activity, these proteins carry within their sequences domains that allow them to bind DNA and act as nucleases in order to resolve the concatameric intermediates developed during viral replication. The parvovirus B19 NS1 protein contains sequence domains highly similar to those previously implicated in the above-described functions of NS proteins from adeno-associated virus (AAV), minute virus of mice (MVM) and other non-human parvoviruses. Previous studies have shown that transient transfection of B19 NS1 into human liver carcinoma (HepG2) cells initiates the intrinsic apoptotic cascade, ultimately resulting in cell death. In an effort to elucidate the mechanism of mammalian cell demise in the presence of B19 NS1, we undertook a mutagenesis analysis of the protein's endonuclease domain. Our studies have shown that, unlike wild-type NS1, which induces an accumulation of DNA damage, S phase arrest and apoptosis in HepG2 cells, disruptions in the metal coordination motif of the B19 NS1 protein reduce its ability to induce DNA damage and to trigger S phase arrest and subsequent apoptosis. These studies support our hypothesis that, in the absence of replicating B19 genomes, NS1-induced host cell DNA damage is responsible for apoptotic cell death observed in parvoviral infection of non-permissive mammalian cells.

  3. Design, structure-based focusing and in silico screening of combinatorial library of peptidomimetic inhibitors of Dengue virus NS2B-NS3 protease

    NASA Astrophysics Data System (ADS)

    Frecer, Vladimir; Miertus, Stanislav

    2010-03-01

    Serine protease activity of the NS3 protein of Dengue virus is an important target of antiviral agents that interfere with the viral polyprotein precursor processing catalyzed by the NS3 protease (NS3pro), which is important for the viral replication and maturation. Recent studies showed that substrate-based peptidomimetics carrying an electrophilic warhead inhibit the NS2B-NS3pro cofactor-protease complex with inhibition constants in the low micromolar concentration range when basic amino acid residues occupy P1 and P2 positions of the inhibitor, and an aldehyde warhead is attached to the P1. We have used computer-assisted combinatorial techniques to design, focus using the NS2B-NS3pro receptor 3D structure, and in silico screen a virtual library of more than 9,200 peptidomimetic analogs targeted around the template inhibitor Bz-Nle-Lys-Arg-Arg- H (Bz—benzoyl) that are composed mainly of unusual amino acid residues in all positions P1-P4. The most promising virtual hits were analyzed in terms of computed enzyme-inhibitor interactions and Adsorption, Distribution, Metabolism and Excretion (ADME) related physico-chemical properties. Our study can direct the interest of medicinal chemists working on a next generation of antiviral chemotherapeutics against the Dengue Fever towards the explored subset of the chemical space that is predicted to contain peptide aldehydes with NS3pro inhibition potencies in nanomolar range which display ADME-related properties comparable to the training set inhibitors.

  4. Design, structure-based focusing and in silico screening of combinatorial library of peptidomimetic inhibitors of Dengue virus NS2B-NS3 protease.

    PubMed

    Frecer, Vladimir; Miertus, Stanislav

    2010-03-01

    Serine protease activity of the NS3 protein of Dengue virus is an important target of antiviral agents that interfere with the viral polyprotein precursor processing catalyzed by the NS3 protease (NS3pro), which is important for the viral replication and maturation. Recent studies showed that substrate-based peptidomimetics carrying an electrophilic warhead inhibit the NS2B-NS3pro cofactor-protease complex with inhibition constants in the low micromolar concentration range when basic amino acid residues occupy P(1) and P(2) positions of the inhibitor, and an aldehyde warhead is attached to the P(1). We have used computer-assisted combinatorial techniques to design, focus using the NS2B-NS3pro receptor 3D structure, and in silico screen a virtual library of more than 9,200 peptidomimetic analogs targeted around the template inhibitor Bz-Nle-Lys-Arg-Arg-H (Bz-benzoyl) that are composed mainly of unusual amino acid residues in all positions P(1)-P(4). The most promising virtual hits were analyzed in terms of computed enzyme-inhibitor interactions and Adsorption, Distribution, Metabolism and Excretion (ADME) related physico-chemical properties. Our study can direct the interest of medicinal chemists working on a next generation of antiviral chemotherapeutics against the Dengue Fever towards the explored subset of the chemical space that is predicted to contain peptide aldehydes with NS3pro inhibition potencies in nanomolar range which display ADME-related properties comparable to the training set inhibitors.

  5. Extended substrate specificity and first potent irreversible inhibitor/activity-based probe design for Zika virus NS2B-NS3 protease.

    PubMed

    Rut, Wioletta; Zhang, Linlin; Kasperkiewicz, Paulina; Poreba, Marcin; Hilgenfeld, Rolf; Drąg, Marcin

    2017-03-01

    Zika virus is spread by Aedes mosquitoes and is linked to acute neurological disorders, especially to microcephaly in newborn children and Guillan-Barré Syndrome. The NS2B-NS3 protease of this virus is responsible for polyprotein processing and therefore considered an attractive drug target. In this study, we have used the Hybrid Combinatorial Substrate Library (HyCoSuL) approach to determine the substrate specificity of ZIKV NS2B-NS3 protease in the P4-P1 positions using natural and a large spectrum of unnatural amino acids. Obtained data demonstrate a high level of specificity of the S3-S1 subsites, especially for basic amino acids. However, the S4 site exhibits a very broad preference toward natural and unnatural amino acids with selected D-amino acids being favored over L enantiomers. This information was used for the design of a very potent phosphonate inhibitor/activity-based probe of ZIKV NS2B-NS3 protease.

  6. Impact of snow on surface brightness

    NASA Astrophysics Data System (ADS)

    Kukla, George J.; Brown, Jeffrey A.

    The snow-covered land surface has different albedo than the snow-free surface, depending primarily on the type and density of the vegetation, the relief, and the continuity and age of the snow blanket. This is clearly demonstrated by the winter mosaic of east central Asia shown on the front cover. It is a section of a larger composite assembled from cloud-free satellite images to portray the land surface under continuous snow cover. The mosaic is a valuable tool for distinguishing (from remote positions) snow from clouds and for charting snow cover where illumination is poor. It also can be used to determine relative sensitivity of surface albedo to the occurrence of snow.Segments with a minimum of clouds along the orbital subtrack were selected from the transparencies of the Defense Meteorological Satellite Program (DMSP). Satellite sensors record in the spectral band 0.4-1.2 µm. The satellite is in polar orbit at a mean altitude of 830 km (450 nm) and crosses the equator at approximately local noon. The spatial resolution along the orbital subtrack is about 0.6 km [Dickinson et al., 1974]. The mosaic is assembled from imagery taken between mid-January and mid-February of 1979. The original hard-copy transparencies (on loan from the DMSP library) were reproduced as contact negatives to preserve detail.The snow cover marks the land surface with a characteristic signature that depends on the distribution, density, and type of vegetation; relief; presence of water bodies; distribution and type of land use, etc. This signature can be readily utilized, among others, to distinguish snow-covered land from clouds and from snow-free land [Barnes et al., 1974; Lillesand et al., 1982]. We have compared the brightness fields in the imagery with the vegetation density and land-use patterns charted in the World Forestry Atlas [Wiebecke, 1971].

  7. Dark Skies, Bright Kids! Year 5

    NASA Astrophysics Data System (ADS)

    Prager, Brian; Johnson, K. E.; Barcos-Munoz, L. D.; Beaton, R.; Bittle, L.; Borish, H.; Burkhardt, A.; Corby, J.; Damke, G.; Dean, J.; Dorsey, G.; Graninger, D.; Lauck, T.; Liss, S.; Oza, A.; Peacock, S.; Romero, C.; Sokal, K. R.; Stierwalt, S.; Walker, L.; Wenger, T.; Zucker, C.

    2014-01-01

    Our public outreach group Dark Skies, Bright Kids! (DSBK) fosters science literacy in Virginia by bringing a hands-on approach to astronomy that engages children's natural excitement and curiosity. We are an entirely volunteer-run group based out of the Department of Astronomy at the University of Virginia and we enthusiastically utilize astronomy as a 'gateway science.' We create long-term relationships with students during an 8 to 10 week long, after-school astronomy club at under served elementary schools in neighboring counties, and we visited 3 different schools in 2013. Additionally, we organize and participate in science events throughout the community. The fifth year of DSBK was marked by surpassing 10,000 contact hours in Spring 2013 Semester and by ringing in the fall semester with our biggest, most successful star party to date. We hosted the Third Annual Central Virginia Star Party, free and open to the community to encourage families to enjoy astronomy together. Nearly four hundred people of all ages attended, double the number from previous years. Joining with local astronomical societies, we offered an enlightening and exciting night with resources rarely accessible to the public, such as an IR camera and a portable planetarium. With numerous telescopes pointed at the sky, and a beautifully clear night with views of the Milky Way, the International Space Station, and numerous meteors, the star party was a fantastic opportunity to introduce many of our guests to the natural wonders of our night sky and enjoy some of the darkest skies on the eastern seaboard.

  8. All Bright Cold Classical KBOs are Binary

    NASA Astrophysics Data System (ADS)

    Noll, Keith S.; Parker, Alex H.; Grundy, William M.

    2014-11-01

    When sorted by absolute magnitude as seen in ground based observations, an extremely high fraction of the brightest Cold Classical (CC) Kuiper Belt objects (KBO) are, in fact resolved as binaries when observed at higher angular resolution. Of the 22 CCs brighter than H=6.1 observed by HST, 16 have been found to be binary yielding a binary fraction of 73±10%. When low inclination interlopers from the hot population and close binaries are considered, this very high fraction is consistent with 100% of bright CCs being binary. At fainter absolute magnitudes, this fraction drops to ~20%. Such a situation is a natural outcome of a broken size distribution with a steep drop-off in the number of CCs with individual component diameters larger than 150 km (for an assumed albedo of 0.15). A sharp cutoff in the size distribution for CCs is consistent with formation models that suggest that most planetesimals form at a preferred modal size of order 100 km.The very high fraction of binaries among the largest CCs also serves to limit the separation distribution of KBO binaries. At most, 27% of the brightest CCs are possible unresolved binaries. The apparent power law distribution of binary separation must cut off near the current observational limits of HST ( 1800 km at 43 AU). It is worth noting, however, that this observation does not constrain how many components of resolved binaries may themselves be unresolved multiples like 47171 1999 TC36. Finally, it is important to point out that, when sorted by the size of the primary rather than absolute magnitude of the unresolved pair, the fraction of binaries is relatively constant with size (Nesvorny et al. 2011, AJ 141, 159) eliminating observational bias as cause of the pile up of binaries among the brightest Cold Classical Kuiper Belt objects.The very high fraction of binaries among the brightest CCs appears to be an effect of the underlying CC size distribution.

  9. Chromospheric evaporation in sympathetic coronal bright points

    NASA Astrophysics Data System (ADS)

    Zhang, Q. M.; Ji, H. S.

    2013-09-01

    Context. Chromospheric evaporation is a key process in solar flares that has been extensively investigated using spectroscopic observations. However, direct soft X-ray (SXR) imaging of the process is rare, especially in remote brightenings associated with the primary flares that have recently attracted a great deal of attention. Aims: We intend to find the evidence for chromospheric evaporation and figure out the cause of the process in sympathetic coronal bright points (CBPs), i.e., remote brightenings induced by the primary CBP. Methods: We utilised the high-cadence and high-resolution SXR observations of CBPs from the X-ray Telescope (XRT) aboard the Hinode spacecraft on 2009 August 23. Results: We discovered a thermal conduction front propagating from the primary CBP (hereafter BP1) to the first of the sympathetic CBPs (hereafter BP2) that is 60″ away from BP1. The apparent velocity of the thermal conduction is ~138 km s-1. Afterwards, hot plasma flowed upwards into the loop connecting BP1 and BP2 at a speed of ~76 km s-1, a clear signature of chromospheric evaporation. Similar upflow was also observed in the loop connecting BP1 and the other sympathetic CBP (hereafter BP3) that is 80″ away from BP1, though less significant than BP2. The apparent velocity of the upflow is ~47 km s-1. The thermal conduction front propagating from BP1 to BP3 was not well identified except for the jet-like motion also originating from BP1. Conclusions: We propose that the gentle chromospheric evaporation in the sympathetic CBPs were caused by thermal conduction originating from the primary CBP.

  10. Bright Times for an Ancient Star

    NASA Astrophysics Data System (ADS)

    Fuhrmann, K.; Chini, R.

    2017-01-01

    Field stars of Population II are among the oldest sources in the Galaxy. Most of their solar-type dwarfs are non-single and, given their extreme age, a significant fraction is accompanied by stellar remnants. Here we report the discovery of the bright F7V star 49 Lib as a massive and very metal-rich Population II field blue straggler, along with evidence for a white dwarf as its dark and unseen companion. 49 Lib is known as a relatively fast-rotating, single-lined spectroscopic binary in a 3 year orbit and with an apparent age of about τ ≃ 2.3 Gyr. Its chemistry and kinematics, however, both consistently imply that 49 Lib must be an ancient Population II star at τ ≃ 12 Gyr. With reference to the inclination from the astrometric orbit, leading to a {M}{WD}={0.50}-0.04+0.03 M⊙ low-mass white dwarf, and in view of the {M}{BS}={1.55}-0.13+0.07 M⊙ massive, evolved F-type blue straggler star, we demonstrate that 49 Lib must have been the subject of a mostly conservative mass transfer with a near-equal-mass M ≃ 1.06 + 1.00 M⊙ G-type binary at birth. For its future evolution, we point to the possibility as a progenitor system toward a type Ia supernova. Most importantly, however, we note that the remarkable metal enrichment of 49 Lib at [Mg/H] = +0.23 and [Fe/H] = ‑0.11 has principally very relevant implications for the early epoch when the Milky Way came into being.

  11. MAGNETIC FLUX SUPPLEMENT TO CORONAL BRIGHT POINTS

    SciTech Connect

    Mou, Chaozhou; Huang, Zhenghua; Xia, Lidong; Li, Bo; Fu, Hui; Jiao, Fangran; Hou, Zhenyong; Madjarska, Maria S.

    2016-02-10

    Coronal bright points (BPs) are associated with magnetic bipolar features (MBFs) and magnetic cancellation. Here we investigate how BP-associated MBFs form and how the consequent magnetic cancellation occurs. We analyze longitudinal magnetograms from the Helioseismic and Magnetic Imager to investigate the photospheric magnetic flux evolution of 70 BPs. From images taken in the 193 Å passband of the Atmospheric Imaging Assembly (AIA) we dermine that the BPs’ lifetimes vary from 2.7 to 58.8 hr. The formation of the BP MBFs is found to involve three processes, namely, emergence, convergence, and local coalescence of the magnetic fluxes. The formation of an MBF can involve more than one of these processes. Out of the 70 cases, flux emergence is the main process of an MBF buildup of 52 BPs, mainly convergence is seen in 28, and 14 cases are associated with local coalescence. For MBFs formed by bipolar emergence, the time difference between the flux emergence and the BP appearance in the AIA 193 Å passband varies from 0.1 to 3.2 hr with an average of 1.3 hr. While magnetic cancellation is found in all 70 BPs, it can occur in three different ways: (I) between an MBF and small weak magnetic features (in 33 BPs); (II) within an MBF with the two polarities moving toward each other from a large distance (34 BPs); (III) within an MBF whose two main polarities emerge in the same place simultaneously (3 BPs). While an MBF builds up the skeleton of a BP, we find that the magnetic activities responsible for the BP heating may involve small weak fields.

  12. Dark Skies, Bright Kids! Year 3

    NASA Astrophysics Data System (ADS)

    Whelan, David G.; Johnson, K. E.; Barcos-Munoz, L. D.; Beaton, R. L.; Borish, J.; Corby, J. F.; Dorsey, G.; Gugliucci, N. E.; Prager, B. J.; Ries, P. A.; Romero, C. E.; Sokal, K. R.; Tang, X.; Walker, L. M.; Yang, A. J.; Zasowski, G.

    2012-01-01

    Dark Skies, Bright Kids! (DSBK) is a program that brings astronomy education to elementary schools throughout central Virginia. In a relaxed, out-of-classroom atmosphere, we are able to foster the innate curiosity that young students have about science and the world around them. We target schools that are under-served due to their rural locale or special needs students, demonstrating that science is a fun and creative process to a segment of the population that might not otherwise be exposed to astronomy. Families are included in the learning experience during semi-annual `star parties'. Since last January, we have expanded the breadth and depth of our educational capabilities. We have developed new programs for use in our digital planetarium. We held the first Central Virginia Star Party, providing an atmosphere where local children from multiple schools were able to share their love for astronomy. Local government and University officials were also invited so that they could experience our focused science outreach. Most recently, we have become part of Ivy Creek School's Club Day activities, bringing our program to a new segment of the elementary school system in Albemarle County: those that have `low-incidence' disabilities, requiring special attention. We continue to develop a curriculum for after-school programs that functions as either a series of one-time activities or several months of focused outreach at one school. Many of these activities are provided on our website, http://www.astro.virginia.edu/dsbk/, for the wider astronomical community, including the new planetarium work. We have extended our book project to include two bilingual astronomy books called `Snapshots of the Universe,' one in Spanish and English, the other in French and English. These books introduce young people to some of the many wonders of the Universe through art and captions developed by DSBK volunteers.

  13. Dark Skies, Bright Kids! Year 4

    NASA Astrophysics Data System (ADS)

    Sokal, Kimberly R.; Johnson, K. E.; Barcos-Munoz, L. D.; Beaton, R.; Borish, J.; Crawford, S. B.; Corby, J.; Damke, G.; Dean, J.; Dorsey, G.; Jackson, L.; Liss, S.; Oza, A.; Peacock, S.; Prager, B.; Romero, C.; Sivakoff, G. R.; Walker, L.; Whelan, D. G.; Zucker, C.

    2013-01-01

    Aiming to engage young children's natural excitement and curiosity, the outreach group Dark Skies, Bright Kids (DSBK) brings a hands-on approach to astronomy to elementary schools in Virginia. We hope to enhance children's view and understanding of science while exploring the Universe using fun activities. DSBK focuses on rural and underserved schools in Albemarle County and offers a semester-long astronomy club for third through fifth grade students. We believe regular interactions foster personal relationships between students and volunteers that encourage a life-long interest in science. In our fourth year of hosting clubs, we returned to Ivy Creek Elementary School, where we saw wonderful responses from a special group of students with `low-incidence' disabilities. DSBK has grown to realize a broader reach beyond local astronomy clubs; we hope to ignite a spark of interest in astronomy and science more widely- in more children, their families, and their teachers. We also hosted the Second Annual Central Virginia Star Party with an open invitation to the community to encourage families to enjoy astronomy together. Throughout the year, DSBK now holds 'one-off' programs (akin to astronomy field days) for elementary schools and children's groups throughout Virginia. Furthermore, we are in the final stages of a project to create two bilingual astronomy books called "Snapshots of the Universe", in Spanish and French with English translations. This art book will be made available online and we are working to get a copy in every elementary school in the state. DSBK has begun to reach out to elementary school teachers in order to provide them with useful and engaging classroom material. We have adapted our volunteer-created activities into useful and ready-to-use lessons, available online. After improvements based on research through interactions and feedback from teachers, we have explicitly identified the learning goals in terms of Virginia's Standards of Learning

  14. Dark Skies, Bright Kids: Year 2

    NASA Astrophysics Data System (ADS)

    Carlberg, Joleen K.; Johnson, K.; Lynch, R.; Walker, L.; Beaton, R.; Corby, J.; de Messieres, G.; Drosback, M.; Gugliucci, N.; Jackson, L.; Kingery, A.; Layman, S.; Murphy, E.; Richardson, W.; Ries, P.; Romero, C.; Sivakoff, G.; Sokal, K.; Trammell, G.; Whelan, D.; Yang, A.; Zasowski, G.

    2011-01-01

    The Dark Skies, Bright Kids (DSBK) outreach program brings astronomy education into local elementary schools in central Virginia's Southern Albemarle County through an after-school club. Taking advantage of the unusually dark night skies in the rural countryside, DSBK targets economically disadvantaged schools that tend to be underserved due to their rural locale. The goals of DSBK are to foster children's natural curiosity, demonstrate that science is a fun and creative process, challenge students' conceptions of what a scientist is and does, and teach some basic astronomy. Furthermore, DSBK works to assimilate families into students' education by holding family observing nights at the school. Now in its third semester, DSBK has successfully run programs at two schools with very diverse student populations. Working with these students has helped us to revise our activities and to create new ones. A by-product of our work has been the development of lesson plans, complete with learning goals and detailed instructions, that we make publically available on our website. This year we are expanding our repertoire with our new planetarium, which allows us to visualize topics in novel ways and supplements family observing on cloudy nights. The DSBK volunteers have also created a bilingual astronomy artbook --- designed, written, and illustrated by UVa students --- that we will publish and distribute to elementary schools in Virginia. Our book debuted at the last AAS winter meeting, and since then it has been extensively revised and updated with input from many individuals, including parents, professional educators, and a children's book author. Because the club is currently limited to serving a few elementary schools, this book will be part of our efforts to broaden our impact by bringing astronomy to schools we cannot go to ourselves and reaching out to Spanish-speaking communities at the same time.

  15. Discovery of New Scaffolds for Rational Design of HCV NS5B Polymerase Inhibitors

    PubMed Central

    Golub, Andriy G.; Gurukumar, K. R.; Basu, Amartya; Bdzhola, Volodymyr G.; Bilokin, Yaroslav; Yarmoluk, Sergiy M.; Lee, Jin-Ching; Talele, Tanaji T.; Nichols, Daniel B.; Kaushik-Basu, Neerja

    2012-01-01

    Hepatitis C virus (HCV) NS5B polymerase is a key target for the development of anti-HCV drugs. Here we report on the identification of novel allosteric inhibitors of HCV NS5B through a combination of structure-based virtual screening and in vitro NS5B inhibition assays. One hundred and sixty thousand compounds from the Otava database were virtually screened against the thiazolone inhibitor binding site on NS5B (thumb pocket-2, TP-2), resulting in a sequential down-sizing of the library by 2.7 orders of magnitude to yield 59 NS5B non-nucleoside inhibitor (NNI) candidates. In vitro evaluation of the NS5B inhibitory activity of the 59 selected compounds resulted in a 14% hit rate, yielding 8 novel structural scaffolds. Of these, compound 1 bearing a 4-hydrazinoquinazoline scaffold was the most active (IC50 = 16.0 µM). The binding site of all 8 NNIs was mapped to TP-2 of NS5B as inferred by a decrease in their inhibition potency against the M423T NS5B mutant, employed as a screen for TP-2 site binders. At 100 µM concentration, none of the eight compounds exhibited any cytotoxicity, and all except compound 8 exhibited between 40–60% inhibition of intracellular NS5B polymerase activity in BHK-NS5B-FRLuc reporter cells. These inhibitor scaffolds will form the basis for future optimization and development of more potent NS5B inhibitors. PMID:23127989

  16. Novel ATP-Independent RNA Annealing Activity of the Dengue Virus NS3 Helicase

    PubMed Central

    Gebhard, Leopoldo G.; Kaufman, Sergio B.; Gamarnik, Andrea V.

    2012-01-01

    The flavivirus nonstructural protein 3 (NS3) bears multiple enzymatic activities and represents an attractive target for antiviral intervention. NS3 contains the viral serine protease at the N-terminus and ATPase, RTPase, and helicase activities at the C-terminus. These activities are essential for viral replication; however, the biological role of RNA remodeling by NS3 helicase during the viral life cycle is still unclear. Secondary and tertiary RNA structures present in the viral genome are crucial for viral replication. Here, we used the NS3 protein from dengue virus to investigate functions of NS3 associated to changes in RNA structures. Using different NS3 variants, we characterized a domain spanning residues 171 to 618 that displays ATPase and RNA unwinding activities similar to those observed for the full-length protein. Interestingly, we found that, besides the RNA unwinding activity, dengue virus NS3 greatly accelerates annealing of complementary RNA strands with viral or non-viral sequences. This new activity was found to be ATP-independent. It was determined that a mutated NS3 lacking ATPase activity retained full-RNA annealing activity. Using an ATP regeneration system and different ATP concentrations, we observed that NS3 establishes an ATP-dependent steady state between RNA unwinding and annealing, allowing modulation of the two opposing activities of this enzyme through ATP concentration. In addition, we observed that NS3 enhanced RNA-RNA interactions between molecules representing the ends of the viral genome that are known to be necessary for viral RNA synthesis. We propose that, according to the ATP availability, NS3 could function regulating the folding or unfolding of viral RNA structures. PMID:22558403

  17. Easy way to estimate meteor brightness on TV frames

    NASA Astrophysics Data System (ADS)

    Leonov, V. A.; Bagrov, A. V.

    2016-01-01

    The traditional method of the meteor brightness measurements claims that the meteor brightness is equal to the stellar magnitude of a star that looks like a meteor in the brightest point of its track. This rule was convenient for the comparison of meteor observations by different observers and for the analysis of the brightness distributions of meteors from observed showers. This traditional method suffers from systematic errors, particularly those that arise from using stellar brightness measured in specific spectral wave bands different from the observer's ones, but mainly due to neglecting the influence of the meteor angular velocity on the real meteor brightness. To get a proper estimate of the meteor brightness that is a measure of the ground meteor illumination in the non-systematic units, an observer must take into account that the effective exposition of a meteor image in any resolution element of its track is a few times shorter than the corresponding exposition of a star image in the same frame. We propose a very simple method for improved estimations of meteor brightness by applying a correction to the meteor stellar magnitude obtained within the traditional framework.

  18. Synergistic hemolysins of coagulase-negative staphylococci (CoNS).

    PubMed

    Różalska, Małgorzata; Derczyńska, Anna; Maszewska, Agnieszka

    2015-01-01

    A total of 104 coagulase negative staphylococci, belonging to S. capitis, S. hominis, S. haemolyticus and S. warneri, originating from the collection of the Department of Pharmaceutical Microbiology (ZMF), Medical University of Lodz, Poland, were tested for their synergistic hemolytic activity. 83% of strains produced δ-hemolysin, however, the percentage of positive strains of S. haemolyticus, S. warneri, S. capitis and S. hominis was different - 98%, 78%, 75% and 68%, respectively. Highly pure hemolysins were obtained from culture supernatants by protein precipitation with ammonium sulphate (0-70% of saturation) and extraction by using a mixture of organic solvents. The purity and molecular mass of hemolysins was determined by TRIS/Tricine PAGE. All CoNS hemolysins were small peptides with a molar mass of about 3.5 kDa; they possessed cytotoxic activity against the line of human foreskin fibroblasts ATCC Hs27 and lysed red cells from different mammalian species, however, the highest activity was observed when guinea pig, dog and human red blood cells were used. The cytotoxic effect on fibroblasts occurred within 30 minutes. The S. cohnii ssp. urealyticus strain was used as a control. The antimicrobial activity was examined using hemolysins of S. capitis, S. hominis, S. cohnii ssp. cohnii and S. cohnii ssp. urealyticus. Hemolysins of the two S. cohnii subspecies did not demonstrate antimicrobial activity. Cytolysins of S. capitis and S. hominis had a very narrow spectrum of action; out of 37 examined strains, the growth of only Micrococcus luteus, Corynebacterium diphtheriae and Pasteurella multocida was inhibited.

  19. Structure and Function of Flavivirus NS5 Methyltransferase

    SciTech Connect

    Zhou,Y.; Ray, D.; Zhao, Y.; Dong, H.; Ren, S.; Li, Z.; Guo, Y.; Bernard, K.; Shi, P.; Li, H.

    2007-01-01

    The plus-strand RNA genome of flavivirus contains a 5' terminal cap 1 structure (m{sup 7}GpppAmG). The flaviviruses encode one methyltransferase, located at the N-terminal portion of the NS5 protein, to catalyze both guanine N-7 and ribose 2'-OH methylations during viral cap formation. Representative flavivirus methyltransferases from dengue, yellow fever, and West Nile virus (WNV) sequentially generate GpppA {yields} m{sup 7}GpppA {yields} m{sup 7}GpppAm. The 2'-O methylation can be uncoupled from the N-7 methylation, since m{sup 7}GpppA-RNA can be readily methylated to m{sup 7}GpppAm-RNA. Despite exhibiting two distinct methylation activities, the crystal structure of WNV methyltransferase at 2.8 {angstrom} resolution showed a single binding site for S-adenosyl-L-methionine (SAM), the methyl donor. Therefore, substrate GpppA-RNA should be repositioned to accept the N-7 and 2'-O methyl groups from SAM during the sequential reactions. Electrostatic analysis of the WNV methyltransferase structure showed that, adjacent to the SAM-binding pocket, is a highly positively charged surface that could serve as an RNA binding site during cap methylations. Biochemical and mutagenesis analyses show that the N-7 and 2'-O cap methylations require distinct buffer conditions and different side chains within the K{sub 61}-D{sub 146}-K{sub 182}-E{sub 218} motif, suggesting that the two reactions use different mechanisms. In the context of complete virus, defects in both methylations are lethal to WNV; however, viruses defective solely in 2'-O methylation are attenuated and can protect mice from later wild-type WNV challenge. The results demonstrate that the N-7 methylation activity is essential for the WNV life cycle and, thus, methyltransferase represents a novel target for flavivirus therapy.

  20. Modulation of cell growth by the hepatitis C virus nonstructural protein NS5A.

    PubMed

    Arima, N; Kao, C Y; Licht, T; Padmanabhan, R; Sasaguri, Y; Padmanabhan, R

    2001-04-20

    Hepatitis C virus nonstructural protein, NS5A, is a phosphoprotein produced from the processing of the viral polyprotein precursor. NS5A associates with several cellular proteins in mammalian cells, and the biological consequences of this interaction are currently unknown. To this end, five stable NS5A-expressing murine and human cell lines were established. Tetracycline-regulated NIH3T3 cells and rat liver epithelial cells as well as the constitutive, NS5A-expressing, human Chang liver, HeLa, and NIH3T3 cells all exhibited cell growth retardation compared with the control cells. Cell cycle analysis by flow cytometry indicated that the NS5A-expressing human epitheloid tumor cells had a reduced S phase and an increase in the G(2)/M phase, which could be explained by a p53-dependent induction of p21(Waf1/Cip1) protein and mRNA levels. NS5A interacts with Cdk1 in vivo and in vitro, and a significant portion of the p21(Waf1/Cip1) was found to be in a complex with Cdk2 in the NS5A-expressing human hepatic cell line. Cdk1 and cyclin B1 proteins were also reduced in human Chang liver cells consistent with the increase in G(2)/M phase. Our results suggest that the NS5A protein causes growth inhibition and cell cycle perturbations by targeting the Cdk1/2-cyclin complexes.

  1. Identification of an NTPase motif in classical swine fever virus NS4B protein

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Classical swine fever (CSF) is a highly contagious and often fatal disease of swine caused by CSF virus (CSFV), a positive sense single-stranded RNA virus in the genus Pestivirus of the Flaviviridae family. Here, we have identified, within CSFV non-structural (NS) protein NS4B, conserved sequence el...

  2. Introduction to Cognitive and Affective Skills (NS 127): Competency-Based Course Syllabus.

    ERIC Educational Resources Information Center

    Brady, Marilyn H.; Wells, Tanya G.

    "Introduction to Cognitive and Affective Skills" (NS 127) is an associate degree nursing course offered at Chattanooga State Technical Community College to help students develop competencies in decision making, communication, teaching-learning, and management. The course syllabus for NS 127 begins with information on class, laboratory, and credit…

  3. Mutations in classical swine fever virus NS4B affect virulence in swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    NS4B is one of the non-structural proteins of Classical Swine Fever Virus (CSFV), a virus causing a severe disease in swine. Protein domain analysis of the predicted amino acid sequence of NS4B in highly pathogenic CSFV strain Brescia (BICv) identified a Toll/Interleukin-1 receptor like domain (TIR...

  4. Mutations in the classical swine fever virus NS4B protein affects virulence in swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    NS4B is one of the non-structural proteins of Classical Swine Fever Virus (CSFV), the etiological agent of a severe, highly lethal disease of swine. Protein domain analysis of the predicted amino acid sequence of the NS4B protein of highly pathogenic CSFV strain Brescia (BICv) identified a Toll/Inte...

  5. Canine parvovirus NS1 protein exhibits anti-tumor activity in a mouse mammary tumor model.

    PubMed

    Gupta, Shishir Kumar; Yadav, Pavan Kumar; Gandham, Ravi Kumar; Sahoo, A P; Harish, D R; Singh, Arvind Kumar; Tiwari, A K

    2016-02-02

    Many viral proteins have the ability to kill tumor cells specifically without harming the normal cells. These proteins, on ectopic expression, cause lysis or induction of apoptosis in the target tumor cells. Parvovirus NS1 is one of such proteins, which is known to kill high proliferating tumor cells. In the present study, we assessed the apoptosis inducing ability of canine parvovirus type 2 NS1 protein (CPV2.NS1) in vitro in 4T1 cells, and found it to cause significant cell death due to induction of apoptosis through intrinsic or mitochondrial pathway. Further, we also evaluated the oncolytic activity of CPV2.NS1 protein in a mouse mammary tumor model. The results suggested that CPV2.NS1 was able to inhibit the growth of 4T1 induced mouse mammary tumor as indicated by significantly reduced tumor volume, mitotic, AgNOR and PCNA indices. Further, inhibition of tumor growth was found to be because of induction of apoptosis in the tumor cells, which was evident by a significant increase in the number of TUNEL positive cells. Further, CPV2.NS1 was also able to stimulate the immune cells against the tumor antigens as indicated by the increased CD4+ and CD8+ counts in the blood of CVP2.NS1 treated mice. Further optimization of the delivery of NS1 protein and use of an adjuvant may further enhance its anti-tumor activity.

  6. Experimental evidence and molecular modeling of the interaction between hRSV-NS1 and quercetin.

    PubMed

    Gomes, Deriane Elias; Caruso, Ícaro Putinhon; de Araujo, Gabriela Campos; de Lourenço, Isabella Otenio; de Melo, Fernando Alves; Cornélio, Marinônio Lopes; Fossey, Marcelo Andrés; de Souza, Fátima Pereira

    2016-04-01

    Human Respiratory Syncytial Virus is one of the major causes of acute respiratory infections in children, causing bronchiolitis and pneumonia. Non-Structural Protein 1 (NS1) is involved in immune system evasion, a process that contributes to the success of hRSV replication. This protein can act by inhibiting or neutralizing several steps of interferon pathway, as well as by silencing the hRSV ribonucleoproteic complex. There is evidence that quercetin can reduce the infection and/or replication of several viruses, including RSV. The aims of this study include the expression and purification of the NS1 protein besides experimental and computational assays of the NS1-quercetin interaction. CD analysis showed that NS1 secondary structure composition is 30% alpha-helix, 21% beta-sheet, 23% turn and 26% random coils. The melting temperature obtained through DSC analysis was around 56°C. FRET analysis showed a distance of approximately 19Å between the NS1 and quercetin. Fluorescence titration results showed that the dissociation constant of the NS1-quercetin interaction was around 10(-6)M. In thermodynamic analysis, the enthalpy and entropy balanced forces indicated that the NS1-quercetin interaction presented both hydrophobic and electrostatic contributions. The computational results from the molecular modeling for NS1 structure and molecular docking regarding its interaction with quercetin corroborate the experimental data.

  7. Structural analysis and insight into Zika virus NS5 mediated interferon inhibition.

    PubMed

    Dar, Hamza Arshad; Zaheer, Tahreem; Paracha, Rehan Zafar; Ali, Amjad

    2017-03-30

    The Zika virus outbreak in 2015-2016 is the largest of its kind for which WHO declared a Public Health Emergency of International Concerns. No FDA approved drug is available for the treatment of the viral infection. The interaction of flavivirus NS5 protein with SIAH2 ubiquitin ligase has been previously known. NS5 of Zika virus has been implicated in the degradation of STAT2 protein, which activates interferon-stimulated antiviral activity. Based on our proposition that NS5 utilizes SIAH2-mediated proteasomal degradation of STAT2, an in-silico study was carried out to characterize the protein-protein interactions between NS5, SIAH2 and STAT2 proteins. The aim of our study was to identify the amino acid residues of NS5 involved in IFN antagonism as well as to find the association between NS5, SIAH2 and STAT2 to predict the interaction pattern of these proteins. Analysis proposed that NS5 recruits SIAH2 for the ubiquitination-dependent degradation of STAT2. NS5 residues involved in interaction with SIAH2 and/or STAT2 were found to be mostly conserved across related flaviviruses. These are novel findings regarding the Zika virus and require confirmation through experimental approaches.

  8. Identification and characterization of coumestans as novel HCV NS5B polymerase inhibitors

    PubMed Central

    Kaushik-Basu, Neerja; Bopda-Waffo, Alain; Talele, Tanaji T.; Basu, Amartya; Costa, Paulo R. R.; da Silva, Alcides J. M.; Sarafianos, Stefan G.; Noël, François

    2008-01-01

    The hepatitis C virus (HCV) NS5B is essential for viral RNA replication and is therefore a prime target for development of HCV replication inhibitors. Here, we report the identification of a new class of HCV NS5B inhibitors belonging to the coumestan family of phytoestrogens. Based on the in vitro NS5B RNA-dependent RNA polymerase (RdRp) inhibition in the low micromolar range by wedelolactone, a naturally occurring coumestan, we evaluated the anti-NS5B activity of four synthetic coumestan analogues bearing different patterns of substitutions in their A and D rings, and observed a good structure-activity correlation. Kinetic characterization of coumestans revealed a noncompetitive mode of inhibition with respect to nucleoside triphosphate (rNTP) substrate and a mixed mode of inhibition towards the nucleic acid template, with a major competitive component. The modified order of addition experiments with coumestans and nucleic acid substrates affected the potencies of the coumestan inhibitors. Coumestan interference at the step of NS5B–RNA binary complex formation was confirmed by cross-linking experiments. Molecular docking of coumestans within the allosteric site of NS5B yielded significant correlation between their calculated binding energies and IC50 values. Coumestans thus add to the diversifying pool of anti-NS5B agents and provide a novel scaffold for structural refinement and development of potent NS5B inhibitors. PMID:18203743

  9. NS1-mediated delay of type I interferon induction contributes to influenza A virulence in ferrets.

    PubMed

    Meunier, Isabelle; von Messling, Veronika

    2011-07-01

    Interference of the influenza A virus non-structural protein NS1 with type I interferon (IFN) signalling has been characterized extensively in vitro. To assess the contribution of NS1 to the virulence of a specific strain, we generated recombinant USSR/90/77 viruses bearing the NS1 proteins of the attenuated strain PR/8/34 or the highly pathogenic strain 1918 'Spanish flu', all belonging to the H1N1 subtype. In vitro, the extent of interference with type I IFN production exerted by the different NS1 proteins correlated with the reported virulence of the respective strain. Infection of ferrets with the recombinant viruses revealed that the presence of the 1918 NS1 resulted in a slightly more severe disease with generally higher clinical scores and increased lung pathology. Analysis of mRNA from nasal wash cells revealed that viruses carrying the 1918 and, to a lesser extent, USSR/90/77 NS1 proteins caused a delay in upregulation of type I IFNs compared with the NS1 PR/8/34-expressing virus, demonstrating the importance of NS1 for early host-response control and virulence.

  10. Structure and sequence based functional annotation of Zika virus NS2b protein: Computational insights.

    PubMed

    Aguilera-Pesantes, Daniel; Méndez, Miguel A

    2017-02-08

    While Zika virus (ZIKV) outbreaks are a growing concern for global health, a deep understanding about the virus is lacking. Here we report a contribution to the basic science on the virus- a detailed computational analysis of the non structural protein NS2b. This protein acts as a cofactor for the NS3 protease (NS3Pro) domain that is important on the viral life cycle, and is an interesting target for drug development. We found that ZIKV NS2b cofactor is highly similar to other virus within the Flavivirus genus, especially to West Nile Virus, suggesting that it is completely necessary for the protease complex activity. Furthermore, the ZIKV NS2b has an important role to the function and stability of the ZIKV NS3 protease domain even when presents a low conservation score. In addition, ZIKV NS2b is mostly rigid, which could imply a non dynamic nature in substrate recognition. Finally, by performing a computational alanine scanning mutagenesis, we found that residues Gly 52 and Asp 83 in the NS2b could be important in substrate recognition.

  11. Structural basis for substrate specificity of alphavirus nsP2 proteases.

    PubMed

    Russo, Andrew T; Malmstrom, Robert D; White, Mark A; Watowich, Stanley J

    2010-08-24

    The alphavirus nsP2 protease is essential for correct processing of the alphavirus nonstructural polyprotein (nsP1234) and replication of the viral genome. We have combined molecular dynamics simulations with our structural studies to reveal features of the nsP2 protease catalytic site and S1'-S4 subsites that regulate the specificity of the protease. The catalytic mechanism of the nsP2 protease appears similar to the papain-like cysteine proteases, with the conserved catalytic dyad forming a thiolate-imidazolium ion pair in the nsP2-activated state. Substrate binding likely stabilizes this ion pair. Analysis of bimolecular complexes of Venezuelan equine encephalitis virus (VEEV) nsP2 protease with each of the nsP1234 cleavage sites identified protease residues His(510), Ser(511), His(546) and Lys(706) as critical for cleavage site recognition. Homology modelling and molecular dynamics simulations of diverse alphaviruses and their cognate cleavage site sequences revealed general features of substrate recognition that operate across alphavirus strains as well as strain specific covariance between binding site and cleavage site residues. For instance, compensatory changes occurred in the P3 and S3 subsite residues to maintain energetically favourable complementary binding surfaces. These results help explain how alphavirus nsP2 proteases recognize different cleavage sites within the nonstructural polyprotein and discriminate between closely related cleavage targets.

  12. The 'Brightness Rules' alternative conception for light bulb circuits

    NASA Astrophysics Data System (ADS)

    Bryan, Joel A.; Stuessy, Carol

    2006-11-01

    An alternative conception for the observed differences in light bulb brightness was revealed during an unguided inquiry investigation in which prospective elementary teachers placed identical bulbs in series, parallel, and combination direct current circuits. Classroom observations, document analyses, and video and audio transcriptions led to the discovery of this alternative conception, appropriately christened 'Brightness Rules'. Assessments administered three weeks after the activity confirmed that several prospective teachers maintained the 'Brightness Rules' conception even after instructor-led intervention. Implications of the discovery of this alternative conception are discussed with respect to a previously administered assessment question that could not identify the presence of this alternative conception.

  13. High-speed CuBr brightness amplifier beam profile

    NASA Astrophysics Data System (ADS)

    Evtushenko, G. S.; Torgaev, S. N.; Trigub, M. V.; Shiyanov, D. V.; Evtushenko, T. G.; Kulagin, A. E.

    2017-01-01

    This paper addresses the experimental study of the beam profile of the CuBr brightness amplifier operating at a wide range of pulse repetition frequencies. The use of a medium-size gas discharge tube (2 cm) ensures the operation of the brightness amplifier both at typical PRFs (520 kHz) and at higher PRFs (up to 100 kHz), either with or without HBr additive. The effect of the active additive on the beam profile is demonstrated. The testing results on kinetic modeling of radial processes in the laser (brightness amplifier) plasma are also discussed.

  14. Cosmological models and the brightness profile of distant galaxies

    NASA Astrophysics Data System (ADS)

    Olivares-Salaverri, I.; Ribeiro, Marcelo B.

    2010-11-01

    This work aims to determine the feasibility of an assumed cosmological model by means of a detailed analysis of the brightness profiles of distant galaxies. Starting from the theory of Ellis & Perry (1979) connecting the angular diameter distance obtained from a relativistic cosmological model and the detailed photometry of galaxies, we assume the presently most accepted cosmology with Λ ¬ = 0 and seek to predict the brightness profile of a galaxy in a given redshift z. To do so, we have to make assumptions concerning the galactic brightness structure and evolution, assuming a scenario where the specific emitted surface brightness Be,νe can be characterized as, Be,νe (r,z) = B0(z)J(νe,z)f[r(z)/a(z)]. Here r is the intrinsic galactic radius, νe the emitted frequency, B0(z) the central surface brightness, J(νe,z) the spectral energy distribution (SED), f[r(z)/a(z)] characterizes the shape of the surface profile distribution and a(z) is the scaling radius. The dependence on z is due to the galactic evolution. As spacetime curvature affects the received surface brightness, the reciprocity theorem (Ellis 1971) allows us to predict the theoretical received surface brightness. So, we are able to compare the theoretical surface brightness with its equivalent observational data already available for high redshift galaxies in order to test the consistency of the assumed cosmological model. The function f[r(z)/a(z)] is represented in the literature by various different shapes, like the Hubble, Hubble-Oemler and Abell-Mihalas single parameter profiles, characterizing the galactic surface brightness quite well when the disk or bulge dependence is dominant. Sérsic and core-Sérsic profiles use two or more parameters and reproduce the galactic profile almost exactly (Trujillo et al. 2004). If we consider all wavelengths, the theory tells us that the total intensity is equal to the surface brightness, so the chosen bandwidth should include most of the SED. In order to

  15. HUBBLE FINDS MANY BRIGHT CLOUDS ON URANUS

    NASA Technical Reports Server (NTRS)

    2002-01-01

    A recent Hubble Space Telescope view reveals Uranus surrounded by its four major rings and by 10 of its 17 known satellites. This false-color image was generated by Erich Karkoschka using data taken on August 8, 1998, with Hubble's Near Infrared Camera and Multi-Object Spectrometer. Hubble recently found about 20 clouds - nearly as many clouds on Uranus as the previous total in the history of modern observations. The orange-colored clouds near the prominent bright band circle the planet at more than 300 mph (500 km/h), according to team member Heidi Hammel (MIT). One of the clouds on the right-hand side is brighter than any other cloud ever seen on Uranus. The colors in the image indicate altitude. Team member Mark Marley (New Mexico State University) reports that green and blue regions show where the atmosphere is clear and sunlight can penetrate deep into Uranus. In yellow and grey regions the sunlight reflects from a higher haze or cloud layer. Orange and red colors indicate very high clouds, such as cirrus clouds on Earth. The Hubble image is one of the first images revealing the precession of the brightest ring with respect to a previous image [LINK to PRC97-36a]. Precession makes the fainter part of the ring (currently on the upper right-hand side) slide around Uranus once every nine months. The fading is caused by ring particles crowding and hiding each other on one side of their eight-hour orbit around Uranus. The blue, green and red components of this false-color image correspond to exposures taken at near-infrared wavelengths of 0.9, 1.1, and 1.7 micrometers. Thus, regions on Uranus appearing blue, for example, reflect more sunlight at 0.9 micrometer than at the longer wavelengths. Apparent colors on Uranus are caused by absorption of methane gas in its atmosphere, an effect comparable to absorption in our atmosphere which can make distant clouds appear red. Credit: Erich Karkoschka (University of Arizona) and NASA

  16. BOREAS Level-2 NS001 TMS Imagery: Reflectance and Temperature in BSQ Format

    NASA Technical Reports Server (NTRS)

    Lobitz, Brad; Spanner, Michael; Hall, Forrest G. (Editor); Newcomer, Jeffrey A. (Editor); Strub, Richard

    2000-01-01

    For BOREAS, the NS001 TMS images, along with the other remotely sensed data, were collected to provide spatially extensive information over the primary study areas. This information includes detailed land cover and biophysical parameter maps such as fPAR and LAI. Collection of the NS001 images occurred over the study areas during the 1994 field campaigns. The level-2 NS001 data are atmospherically corrected versions of some of the best original NS001 imagery and cover the dates of 19-Apr-1994, 07-Jun-1994, 21-Jul-1994, 08-Aug-1994, and 16-Sep-1994. The data are not geographically/geometrically corrected; however, files of relative X and Y coordinates for each image pixel were derived by using the C130 INS data in an NS001 scan model. The data are provided in binary image format files.

  17. H-NS, Its Family Members and Their Regulation of Virulence Genes in Shigella Species

    PubMed Central

    Picker, Michael A.; Wing, Helen J.

    2016-01-01

    The histone-like nucleoid structuring protein (H-NS) has played a key role in shaping the evolution of Shigella spp., and provides the backdrop to the regulatory cascade that controls virulence by silencing many genes found on the large virulence plasmid. H-NS and its paralogue StpA are present in all four Shigella spp., but a second H-NS paralogue, Sfh, is found in the Shigella flexneri type strain 2457T, which is routinely used in studies of Shigella pathogenesis. While StpA and Sfh have been proposed to serve as “molecular backups” for H-NS, the apparent redundancy of these proteins is questioned by in vitro studies and work done in Escherichia coli. In this review, we describe the current understanding of the regulatory activities of the H-NS family members, the challenges associated with studying these proteins and their role in the regulation of virulence genes in Shigella. PMID:27916940

  18. NsLTP1 and NsLTP2 isoforms in soft wheat (Triticum aestivum Cv. Centauro) and farro (Triticum dicoccon Schrank) bran.

    PubMed

    Capocchi, Antonella; Fontanini, Debora; Muccilli, Vera; Cunsolo, Vincenzo; Saviozzi, Franco; Saletti, Rosaria; Lorenzi, Roberto; Foti, Salvatore; Galleschi, Luciano

    2005-10-05

    Isoforms of nonspecific lipid-transfer protein 1 (nsLTP1) and nonspecific lipid-transfer protein 2 (nsLTP2) were investigated in bran tissues isolated from caryopses of two cereal crops quite relevant for the Italian market, the cultivar Centauro of soft wheat (Triticum aestivum) and Italian emmer or farro (Triticum dicoccon Schrank). By sequential separation of the bran extracts on cation-exchange and gel filtration chromatographies, fractions containing only proteins belonging to the nsLTP1 and nsLTP2 classes were obtained. The proteins were roughly identified by SDS-PAGE and by immunoreactions in Western blotting experiments. By MALDI-MS and RP-HPLC/ESI-MS analyses we were able to show the presence of several LTP1 and LTP2 isoforms in the investigated species. Bioinformatic searches based on the determined Mr indicated that (i) two nsLTP1s already identified in T. aestivum have Mr and number of Cys residues identical to that of a 9.6 kDa protein present both in soft wheat cv. Centauro and in farro; (ii) two isoforms of nsLTP2 detected in T. aestivum have the same Mr and number of Cys residues of two 7 kDa proteins found in Centauro; and (iii) a nsLTP1 detected in Ambrosia artemisiifolia has Mr and number of Cys residues coincident to that of a 9.9 kDa protein found both in soft wheat cv. Centauro and in farro.

  19. Raman spectroscopy based discrimination of NS1 positive and negative dengue virus infected serum

    NASA Astrophysics Data System (ADS)

    Bilal, M.; Saleem, M.; Bilal, Maria; Khurram, M.; Khan, Saranjam; Ullah, Rahat; Ali, Hina; Ahmed, M.

    2016-09-01

    This study is intended to develop a multivariate statistical model for the prediction of nonstructural protein 1 (NS1) in dengue virus (DENV) infected blood serum in humans. The model has been developed on the basis of partial least squares regression using the Raman spectra of NS1 positive and NS1 negative samples. Human blood sera of 218 subjects is included in this study, of which 95 were NS1 positive and 123 were NS1 negative, which was confirmed with the enzyme linked immunosorbent assay method. For model development, 80 NS1 positive and 98 NS1 negative samples were used, while 40 DENV suspected samples were used for double blind testing of the model. This selection of samples was performed by the code in an automatic manner to avoid biasing. A laser at 785 nm was used as the excitation source to acquire Raman spectra of samples with an integration time of 15 s. The multivariate model yields coefficients of regression at corresponding Raman shifts. These coefficients represent changes in the molecular structures associated with NS1 positive and negative samples. The analysis of the regression coefficients which differentiate NS1 positive and NS1 negative groups shows an increasing trend for phosphatidylinositol, ceramide, and amide-III, and a decreasing trend for thiocyanate in the DENV infected serum. The R-squared value of the model was found to be 0.91, which is clinically acceptable. The blind testing of 40 suspected samples yields an accuracy, sensitivity, and specificity of about 100% each.

  20. Dengue Virus NS1 Disrupts the Endothelial Glycocalyx, Leading to Hyperpermeability

    PubMed Central

    Puerta-Guardo, Henry; Glasner, Dustin R.; Harris, Eva

    2016-01-01

    Dengue is the most prevalent arboviral disease in humans and a major public health problem worldwide. Systemic plasma leakage, leading to hypovolemic shock and potentially fatal complications, is a critical determinant of dengue severity. Recently, we and others described a novel pathogenic effect of secreted dengue virus (DENV) non-structural protein 1 (NS1) in triggering hyperpermeability of human endothelial cells in vitro and systemic vascular leakage in vivo. NS1 was shown to activate toll-like receptor 4 signaling in primary human myeloid cells, leading to secretion of pro-inflammatory cytokines and vascular leakage. However, distinct endothelial cell-intrinsic mechanisms of NS1-induced hyperpermeability remained to be defined. The endothelial glycocalyx layer (EGL) is a network of membrane-bound proteoglycans and glycoproteins lining the vascular endothelium that plays a key role in regulating endothelial barrier function. Here, we demonstrate that DENV NS1 disrupts the EGL on human pulmonary microvascular endothelial cells, inducing degradation of sialic acid and shedding of heparan sulfate proteoglycans. This effect is mediated by NS1-induced expression of sialidases and heparanase, respectively. NS1 also activates cathepsin L, a lysosomal cysteine proteinase, in endothelial cells, which activates heparanase via enzymatic cleavage. Specific inhibitors of sialidases, heparanase, and cathepsin L prevent DENV NS1-induced EGL disruption and endothelial hyperpermeability. All of these effects are specific to NS1 from DENV1-4 and are not induced by NS1 from West Nile virus, a related flavivirus. Together, our data suggest an important role for EGL disruption in DENV NS1-mediated endothelial dysfunction during severe dengue disease. PMID:27416066

  1. NS5ATP13 Promotes Liver Fibrogenesis via Activation of Hepatic Stellate Cells.

    PubMed

    Li, Yaru; Liu, Shunai; Han, Ming; Lu, Hongping; Wang, Qi; Zhang, Yu; Tursun, Kelbinur; Li, Zhongshu; Feng, Shenghu; Cheng, Jun

    2017-01-29

    Liver fibrosis is a reversible wound-healing response to any etiology of chronic hepatic injuries. Activation of hepatic stellate cells (HSCs) is the key event in liver fibrogenesis. Generally, persistent activation and proliferation of HSCs results in liver fibrosis progression, while primary mechanisms of liver fibrosis resolution are apoptosis and reversion to a quiescent phenotype of activated HSCs. NS5ATP13 (HCV NS5A-transactivated protein 13) is involved in nucleologenesis and tumorigenesis, but its role in liver fibrosis and HSC activation remains unclear. This study found that NS5ATP13 was upregulated in both fibrotic liver tissues and activated human HSCs induced by TGF-β1. Moreover, NS5ATP13 enhanced extracellular matrix (ECM) production and HSC activation, with or without TGF-β1 treatment, likely involving the TGF-β1/Smad3 signaling pathway. Additionally, NS5ATP13 boosted HSC proliferation by inhibiting cell apoptosis. Furthermore, HCV NS5A promoted the profibrogenic effect of NS5ATP13 partly through TGF-β1 and NF-κB p65 (RelA) upregulation. Meanwhile, NS5ATP13 was required for the pro-fibrogenic effect of NF-κB. Moreover, NS5ATP13 and NF-κB phosphorylation as well as HSC activation were reduced by CX-4945, a CK2 specific inhibitor. These findings indicated that NS5ATP13 acts as a profibrogenic factor, providing a potential target for antifibrotic therapies. This article is protected by copyright. All rights reserved.

  2. Visible Color and Photometry of Bright Materials on Vesta

    NASA Technical Reports Server (NTRS)

    Schroder, S. E.; Li, J. Y.; Mittlefehldt, D. W.; Pieters, C. M.; De Sanctis, M. C.; Hiesinger, H.; Blewett, D. T.; Russell, C. T.; Raymond, C. A.; Keller, H. U.

    2012-01-01

    The Dawn Framing Camera (FC) collected images of the surface of Vesta at a pixel scale of 70 m in the High Altitude Mapping Orbit (HAMO) phase through its clear and seven color filters spanning from 430 nm to 980 nm. The surface of Vesta displays a large diversity in its brightness and colors, evidently related to the diverse geology [1] and mineralogy [2]. Here we report a detailed investigation of the visible colors and photometric properties of the apparently bright materials on Vesta in order to study their origin. The global distribution and the spectroscopy of bright materials are discussed in companion papers [3, 4], and the synthesis results about the origin of Vestan bright materials are reported in [5].

  3. Proposal for a High-Brightness Pulsed Electron Source

    SciTech Connect

    Zolotorev, Max; Commins, Eugene D.; Heifets, Sam; Sannibale,Fernando

    2006-03-15

    We propose a novel scheme for a high-brightness pulsedelectron source, which has the potential for many useful applications inelectron microscopy, inverse photo-emission, low energy electronscattering experiments, and electron holography. A description of theproposed scheme is presented.

  4. Female butterflies prefer males bearing bright iridescent ornamentation

    PubMed Central

    Kemp, Darrell J

    2007-01-01

    Butterflies are among nature's most colourful animals, and provide a living showcase for how extremely bright, chromatic and iridescent coloration can be generated by complex optical mechanisms. The gross characteristics of male butterfly colour patterns are understood to function for species and/or sex recognition, but it is not known whether female mate choice promotes visual exaggeration of this coloration. Here I show that females of the sexually dichromatic species Hypolimnas bolina prefer conspecific males that possess bright iridescent blue/ultraviolet dorsal ornamentation. In separate field and enclosure experiments, using both dramatic and graded wing colour manipulations, I demonstrate that a moderate qualitative reduction in signal brightness and chromaticity has the same consequences as removing the signal entirely. These findings validate a long-held hypothesis, and argue for the importance of intra- versus interspecific selection as the driving force behind the exaggeration of bright, iridescent butterfly colour patterns. PMID:17284412

  5. Perspective of Bright Angel stone vault, view south, with HAER ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Perspective of Bright Angel stone vault, view south, with HAER field team measuring (Michael Lee and Dominic Duran foreground, Christopher Marston rear). - Grand Canyon Village Utilities, Grand Canyon National Park, Grand Canyon Village, Coconino County, AZ

  6. South and west elevations of Bright Angel boiler house. Red ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    South and west elevations of Bright Angel boiler house. Red Horse log cabin visible in background. - Grand Canyon Village Utilities, Grand Canyon National Park, Grand Canyon Village, Coconino County, AZ

  7. Yellow steam and electrical pipes across from Bright Angel Lodge. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Yellow steam and electrical pipes across from Bright Angel Lodge. Note control valve to right of control box, view E. - Grand Canyon Village Utilities, Grand Canyon National Park, Grand Canyon Village, Coconino County, AZ

  8. Bright Angel stone vault, with HAER field team members Dominic ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Bright Angel stone vault, with HAER field team members Dominic Duran, Christopher Marston, and Michael Lee (l to r). - Grand Canyon Village Utilities, Grand Canyon National Park, Grand Canyon Village, Coconino County, AZ

  9. Significant increase in the optical brightness of V2492 Cyg

    NASA Astrophysics Data System (ADS)

    Ibryamov, Sunay; Semkov, Evgeni

    2017-03-01

    We observed a recent increase in the optical brightness of the young eruptive star V2492 Cyg using the 2-m and the 50/70-cm Schmidt telescopes administered by National Astronomical Observatory Rozhen in Bulgaria.

  10. Detail of Bright Angel stone vault, containing condenser, Hoffman condensation ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Detail of Bright Angel stone vault, containing condenser, Hoffman condensation pump, Jennings vacuum heating pump, and misc. pipes and valves. - Grand Canyon Village Utilities, Grand Canyon National Park, Grand Canyon Village, Coconino County, AZ

  11. Zernike analysis of all-sky night brightness maps.

    PubMed

    Bará, Salvador; Nievas, Miguel; Sánchez de Miguel, Alejandro; Zamorano, Jaime

    2014-04-20

    All-sky night brightness maps (calibrated images of the night sky with hemispherical field-of-view (FOV) taken at standard photometric bands) provide useful data to assess the light pollution levels at any ground site. We show that these maps can be efficiently described and analyzed using Zernike circle polynomials. The relevant image information can be compressed into a low-dimensional coefficients vector, giving an analytical expression for the sky brightness and alleviating the effects of noise. Moreover, the Zernike expansions allow us to quantify in a straightforward way the average and zenithal sky brightness and its variation across the FOV, providing a convenient framework to study the time course of these magnitudes. We apply this framework to analyze the results of a one-year campaign of night sky brightness measurements made at the UCM observatory in Madrid.

  12. Dominant recognition by human CD8+ cytotoxic T lymphocytes of dengue virus nonstructural proteins NS3 and NS1.2a.

    PubMed Central

    Mathew, A; Kurane, I; Rothman, A L; Zeng, L L; Brinton, M A; Ennis, F A

    1996-01-01

    A severe complication of dengue virus infection, dengue hemorrhagic fever (DHF), is hypothesized to be immunologically mediated and virus-specific cytotoxic T lymphocytes (CTLs) may trigger DHF. It is also likely that dengue virus-specific CTLs are important for recovery from dengue virus infections. There is little available information on the human CD8+ T cell responses to dengue viruses. Memory CD8+CTL responses were analyzed to determine the diversity of the T cell response to dengue virus and to identify immunodominant proteins using PBMC from eight healthy adult volunteers who had received monovalent, live-attenuated candidate vaccines of the four dengue serotypes. All the donors had specific T cell proliferation to dengue and to other flaviviruses that we tested. CTLs were generated from the stimulated PBMC of all donors, and in the seven donors tested, dengue virus-specific CD8+CTL activity was demonstrated. The nonstructural (NS3 and NS1.2a) and envelope (E) proteins were recognized by CD8+CTLs from six, five, and three donors, respectively. All donors recognized either NS3 or NS1.2a. In one donor who received a dengue 4 vaccine, CTL killing was seen in bulk culture against the premembrane protein (prM). This is the first demonstration of a CTL response against the prM protein. The CTL responses using the PBMC of two donors were serotype specific, whereas all other donors had serotype-cross-reactive responses. For one donor, CTLs specific for E, NS1.2a, and NS3 proteins were all HLA-B44 restricted. For three other donors tested, the potential restricting alleles for recognition of NS3 were B38, A24, and/or B62 and B35.These results indicate that the CD8+CTL responses of humans after immunization with one serotype of dengue virus are diverse and directed against a variety of proteins. The NS3 and NS1.2a proteins should be considered when designing subunit vaccines for dengue. PMID:8833919

  13. THE RELATION BETWEEN VISUAL ACUITY AND BRIGHTNESS DISCRIMINATION

    PubMed Central

    Hendley, Charles D.

    1948-01-01

    1. Visual acuity depends on the brightness contrast between test object and background; and conversely, brightness discrimination depends on the target size. Both functions vary with the brightness of the background. Measurements with rectangular targets of length-width ratio 2 were made over a range of sizes, contrasts, and brightnesses sufficient to determine the relations among these three variables. The rectangles were from 2' to 50' wide; the contrast fraction, ΔI/I, ranged from 0.01 to 40; the background brightness varied from 0.0001 to 2500 millilamberts. 2. When ΔI/I or visual acuity is plotted as a function of brightness the data do, in general, follow Hecht's equation. The departure from a simple photochemical theory which the larger targets show is probably due to changes in the functional retinal mosaic with changing brightness. 3. In general also, the relation between visual acuity and brightness, at selected contrasts, fits Hecht's derivation. At low contrasts, as the brightness is reduced a point is reached at which the test object becomes invisible at any size. 4. No simple relation emerges from the data relating visual acuity to contrast, at set levels of illumination. Over only a very short range are visual acuity and contrast directly related. At high contrasts, visual acuity reaches a maximum, whereas at low visual acuity, ΔI/I reaches a minimum which cannot be passed regardless of size. 5. The shape of the curves relating ΔI/I to brightness is not significantly altered by changing the exposure time. There is some evidence to show that a 3 second exposure of the target is equivalent to two looks of 0.2 second each. 6. In all these studies the thresholds were determined by a frequency of seeing method, and the data have been considered in terms of a quantum theory of threshold seeing. It was found that a threshold response involves between four and eight independent critical events, which are largely independent of size, brightness, and

  14. Antibiotic susceptibility of coagulase-negative staphylococci (CoNS): emergence of teicoplanin-non-susceptible CoNS strains with inducible resistance to vancomycin.

    PubMed

    Ma, Xiao Xue; Wang, En Hua; Liu, Yong; Luo, En Jie

    2011-11-01

    Coagulase-negative staphylococci (CoNS) have become increasingly recognized as important agents of nosocomial infection. One of the characteristics of CoNS is their resistance to multiple antimicrobial agents commonly used for the treatment of staphylococcal infections. CoNS strains (n = 745) isolated from a university teaching hospital in China between 2004 and 2009 were tested for antibiotic resistance. The antibiotics were placed into three categories based on resistance levels of the CoNS strains to these antibiotics: high resistance (resistance rate >70 %), including penicillin G, oxacillin and erythromycin; medium resistance (resistance rate between 30 and 70 %), including tetracycline, clindamycin, ciprofloxacin, trimethoprim/sulfamethoxazole and chloramphenicol; and low resistance (resistance rate <30 %), including rifampicin, ceftizoxime and gentamicin. We also found that the prevalence of strains non-susceptible to teicoplanin increased from 4.5 to 6.7 % between 2008 and 2009. A one-step vancomycin agar selection experiment and subsequent population analysis revealed potentially vancomycin-resistant subpopulations that have been selected from the teicoplanin-non-susceptible strains. Vigilant surveillance of nosocomial isolates of CoNS is needed to determine their resistance to glycopeptides.

  15. The NS4A Cofactor Dependent Enhancement of HCV NS3 Protease Activity Correlates with a 4D Geometrical Measure of the Catalytic Triad Region

    PubMed Central

    Hamad, Hamzah A.; Thurston, Jeremy; Teague, Thomas; Ackad, Edward; Yousef, Mohammad S.

    2016-01-01

    We are developing a 4D computational methodology, based on 3D structure modeling and molecular dynamics simulation, to analyze the active site of HCV NS3 proteases, in relation to their catalytic activity. In our previous work, the 4D analyses of the interactions between the catalytic triad residues (His57, Asp81, and Ser139) yielded divergent, gradual and genotype-dependent, 4D conformational instability measures, which strongly correlate with the known disparate catalytic activities among genotypes. Here, the correlation of our 4D geometrical measure is extended to intra-genotypic alterations in NS3 protease activity, due to sequence variations in the NS4A activating cofactor. The correlation between the 4D measure and the enzymatic activity is qualitatively evident, which further validates our methodology, leading to the development of an accurate quantitative metric to predict protease activity in silico. The results suggest plausible “communication” pathways for conformational propagation from the activation subunit (the NS4A cofactor binding site) to the catalytic subunit (the catalytic triad). The results also strongly suggest that the well-sampled (via convergence quantification) structural dynamics are more connected to the divergent catalytic activity observed in HCV NS3 proteases than to rigid structures. The method could also be applicable to predict patients’ responses to interferon therapy and better understand the innate interferon activation pathway. PMID:27936126

  16. Laser-heated X-ray flashlamp brightness measurements

    SciTech Connect

    Matthews, D.L.; Campbell, E.M.; Hagelstein, P.; Halsey, W.; Kauffman, R.L.; Koppel, L.; Phillion, D.; Price, R.; Toor, A.

    1983-12-01

    The authors present measurements of the X-ray emission characteristics of laser-irradiated flashlamp foils which are candidates to produce by resonant photoexcitation a population inversion in either a neon or fluorine lasant gas. Using the Shiva 1.06 ..mu.. laser, the authors heated Fe, Cr, and Ni foils to study the brightness and centroid energies of X-ray lines stemming from L-M transitions. Results indicate that appropriately bright and uniform sources can be produced.

  17. Catalogue of Galactic globular-cluster surface-brightness profiles

    NASA Technical Reports Server (NTRS)

    Trager, S. C.; King, Ivan R.; Djorgovski, S.

    1995-01-01

    We present a catalogue of surface-brightness profiles (SBPs) of 125 Galactic globular clusters, the largest such collection ever gathered. The SPBs are constructed from generally inhomogeneous data, but are based heavily on the Berkeley Global Cluster Survey of Djorgovski & King. All but four of the SBPs have photometric zero points. We derive central surface brightness, King-model concentrations, core radii, half-light, and other fraction-of-light radii where data permit, and we briefly discuss their use.

  18. Sky Brightness Analysis using a Million GEODSS Observations

    NASA Astrophysics Data System (ADS)

    Mandeville, W. Jody; McLaughlin, Tim; Six, Steve; Hollm, Rick

    2012-09-01

    Brightness of the sky background due to lunar phase and location can dramatically affect the limiting magnitude of astronomical detectors. Formerly, theoretical models have attained limited data sets with 10-20% differences between model and observation. This paper compares and contrasts previous investigations with over a million data points collected from various GEODSS sites located around the world and attempts to refine predictive modeling of sky brightness for use in scheduling as well as modeling and simulation tools.

  19. Detergent-Resistant Membrane Association of NS2 and E2 during Hepatitis C Virus Replication

    PubMed Central

    Shanmugam, Saravanabalaji; Saravanabalaji, Dhanaranjani

    2015-01-01

    ABSTRACT Previously, we demonstrated that the efficiency of hepatitis C virus (HCV) E2-p7 processing regulates p7-dependent NS2 localization to putative virus assembly sites near lipid droplets (LD). In this study, we have employed subcellular fractionations and membrane flotation assays to demonstrate that NS2 associates with detergent-resistant membranes (DRM) in a p7-dependent manner. However, p7 likely plays an indirect role in this process, since only the background level of p7 was detectable in the DRM fractions. Our data also suggest that the p7-NS2 precursor is not involved in NS2 recruitment to the DRM, despite its apparent targeting to this location. Deletion of NS2 specifically inhibited E2 localization to the DRM, indicating that NS2 regulates this process. Treatment of cells with methyl-β-cyclodextrin (MβCD) significantly reduced the DRM association of Core, NS2, and E2 and reduced infectious HCV production. Since disruption of the DRM localization of NS2 and E2, either due to p7 and NS2 defects, respectively, or by MβCD treatment, inhibited infectious HCV production, these proteins' associations with the DRM likely play an important role during HCV assembly. Interestingly, we detected the HCV replication-dependent accumulation of ApoE in the DRM fractions. Taking into consideration the facts that ApoE was shown to be a major determinant for infectious HCV particle production at the postenvelopment step and that the HCV Core protein strongly associates with the DRM, recruitment of E2 and ApoE to the DRM may allow the efficient coordination of Core particle envelopment and postenvelopment events at the DRM to generate infectious HCV production. IMPORTANCE The biochemical nature of HCV assembly sites is currently unknown. In this study, we investigated the correlation between NS2 and E2 localization to the detergent-resistant membranes (DRM) and HCV particle assembly. We determined that although NS2's DRM localization is dependent on p7, p7 was not

  20. Epitope mapping and functional analysis of sigma A and sigma NS proteins of avian reovirus

    SciTech Connect

    Huang, Pi H.; Li, Ying J.; Su, Yu P.; Lee, Long H.; Liu, Hung J. . E-mail: hjliu@mail.npust.edu.tw

    2005-02-20

    We have previously shown that avian reovirus (ARV) {sigma}A and {sigma}NS proteins possess dsRNA and ssRNA binding activity and suggested that there are two epitopes on {sigma}A (I and II) and three epitopes (A, B, and C) on {sigma}NS. To further define the location of epitopes on {sigma}A and {sigma}NS proteins and to further elucidate the biological functions of these epitopes by using monoclonal antibodies (MAbs) 62, 1F9, H1E1, and 4A123 against the ARV S1133 strain, the full-length and deletion fragments of S2 and S4 genes of ARV generated by polymerase chain reaction (PCR) were cloned into pET32 expression vectors and the fusion proteins were overexpressed in Escherichia coli BL21 strain. Epitope mapping using MAbs and E. coli-expressed deletion fragments of {sigma}A and {sigma}NS of the ARV S1133 strain, synthetic peptides, and the cross reactivity of MAbs to heterologous ARV strains demonstrated that epitope II on {sigma}A was located at amino acid residues {sup 340}QWVMAGLVSAA{sup 350} and epitope B on {sigma}NS at amino acid residues {sup 180}MLDMVDGRP{sup 188}. The MAbs (62, 1F9, and H1E1) directed against epitopes II and B did not require the native conformation of {sigma}A and {sigma}NS, suggesting that their binding activities were conformation-independent. On the other hand, MAb 4A123 only reacted with complete {sigma}NS but not with truncated {sigma}NS fusion proteins in Western blot, suggesting that the binding activity of MAb to epitope A on {sigma}NS was conformation-dependent. Amino acid sequence analysis and the binding assays of MAb 62 to heterologous ARV strains suggested that epitope II on {sigma}A was highly conserved among ARV strains and that this epitope is suitable as a serological marker for the detection of ARV antibodies following natural infection in chickens. On the contrary, an amino acid substitution at position 183 (M to V) in epitope B of ARV could hinder the reactivity of the {sigma}NS with MAb 1F9. The {sigma}NS of ARV with ss

  1. NMR and MD Studies Reveal That the Isolated Dengue NS3 Protease Is an Intrinsically Disordered Chymotrypsin Fold Which Absolutely Requests NS2B for Correct Folding and Functional Dynamics

    PubMed Central

    Gupta, Garvita; Lim, Liangzhong; Song, Jianxing

    2015-01-01

    Dengue genome encodes a two component protease complex (NS2B-NS3pro) essential for the viral maturation/infectivity, thus representing a key drug target. Previously, due to its “complete insolubility”, the isolated NS3pro could not be experimentally studied and it remains elusive what structure it adopts without NS2B and why NS2B is indispensable. Here as facilitated by our previous discovery, the isolated NS3pro has been surprisingly deciphered by NMR to be the first intrinsically-disordered chymotrypsin-like fold, which exists in a loosely-packed state with non-native long-range interactions as revealed by paramagnetic relaxation enhancement (PRE). The disordered NS3pro appears to be needed for binding a human host factor to trigger the membrane remodeling. Moreover, we have in vitro refolded the NS3pro in complex with either NS2B (48–100) or the full-length NS2B (1–130) anchored into the LMPC micelle, and the two complexes have similar activities but different dynamics. We also performed molecular dynamics (MD) simulations and the results revealed that NS2B shows the highest structural fluctuations in the complex, thus providing the dynamic basis for the observation on its conformational exchange between open and closed states. Remarkably, the NS2B cofactor plays a central role in maintaining the correlated motion network required for the catalysis as we previously decoded for the SARS 3CL protease. Indeed, a truncated NS2B (48–100;Δ77–84) with the flexible loop deleted is able to trap the NS2B-NS3pro complex in a highly dynamic and catalytically-impotent state. Taken together, our study implies potential strategies to perturb the NS2B-NS3pro interface for design of inhibitors for treating dengue infection. PMID:26258523

  2. Global View of the Bright Material on Vesta

    NASA Technical Reports Server (NTRS)

    Zambon, F.; DeSanctis, C.; Schroeder, S.; Tosi, F.; Li, J.-Y.; Longobardo, A.; Ammannito, E.; Blewett, D. T.; Palomba, E.; Capaccioni, F.; Frigeri, A.; Capria, M. T.; Fonte, S.; Mittlefehldt, D. W.; Nathues, A.; Pieters, C.; Russell, C. T.; Raymond, C. A.

    2014-01-01

    At 525 km in mean diameter, Vesta is the second-most massive and one of the brightest asteroids of the main-belt. Here we give a global view of the bright material (BM) units on Vesta. We classified the BMs according to the normal visual albedo. The global albedo map of Vesta allows to be divided the surface into three principal types of terrains: bright regions, dark regions and intermediate regions. The distribution of bright regions is not uniform. The mid-southern latitudes contain the most bright areas, while the northern hemisphere is poor in bright regions. The analysis of the spectral parameters and the normal visual albedo show a dependence between albedo and the strength (depth) of ferrous iron absorption bands, strong bands correspond with high albedo units. Vesta's average albedo is 0.38, but there are bright material whose albedo can exceed 0.50. Only the E-Type asteroids have albedos comparable to those of the BMs on Vesta. The Dawn mission observed a large fraction of Vesta's surface at high spatial resolution, allowing a detailed study of the morphology and mineralogy of it. In particular, reflectance spectra provided by the Visible and InfraRed spectrometer (VIR), confirmed that Vesta's mineralogy is dominated by pyroxenes. All Vesta spectra show two strong absorption bands at approx 0.9 and 1.9 micron, typical of the pyroxenes and associated with the howardite, eucrite and diogenite (HED) meteorites.

  3. The Influence of Microphysical Cloud Parameterization on Microwave Brightness Temperatures

    NASA Technical Reports Server (NTRS)

    Skofronick-Jackson, Gail M.; Gasiewski, Albin J.; Wang, James R.; Zukor, Dorothy J. (Technical Monitor)

    2000-01-01

    The microphysical parameterization of clouds and rain-cells plays a central role in atmospheric forward radiative transfer models used in calculating passive microwave brightness temperatures. The absorption and scattering properties of a hydrometeor-laden atmosphere are governed by particle phase, size distribution, aggregate density., shape, and dielectric constant. This study identifies the sensitivity of brightness temperatures with respect to the microphysical cloud parameterization. Cloud parameterizations for wideband (6-410 GHz observations of baseline brightness temperatures were studied for four evolutionary stages of an oceanic convective storm using a five-phase hydrometeor model in a planar-stratified scattering-based radiative transfer model. Five other microphysical cloud parameterizations were compared to the baseline calculations to evaluate brightness temperature sensitivity to gross changes in the hydrometeor size distributions and the ice-air-water ratios in the frozen or partly frozen phase. The comparison shows that, enlarging the rain drop size or adding water to the partly Frozen hydrometeor mix warms brightness temperatures by up to .55 K at 6 GHz. The cooling signature caused by ice scattering intensifies with increasing ice concentrations and at higher frequencies. An additional comparison to measured Convection and Moisture LA Experiment (CAMEX 3) brightness temperatures shows that in general all but, two parameterizations produce calculated T(sub B)'s that fall within the observed clear-air minima and maxima. The exceptions are for parameterizations that, enhance the scattering characteristics of frozen hydrometeors.

  4. Synthesizing SMOS Zero-Baselines with Aquarius Brightness Temperature Simulator

    NASA Technical Reports Server (NTRS)

    Colliander, A.; Dinnat, E.; Le Vine, D.; Kainulainen, J.

    2012-01-01

    SMOS [1] and Aquarius [2] are ESA and NASA missions, respectively, to make L-band measurements from the Low Earth Orbit. SMOS makes passive measurements whereas Aquarius measures both passive and active. SMOS was launched in November 2009 and Aquarius in June 2011.The scientific objectives of the missions are overlapping: both missions aim at mapping the global Sea Surface Salinity (SSS). Additionally, SMOS mission produces soil moisture product (however, Aquarius data will eventually be used for retrieving soil moisture too). The consistency of the brightness temperature observations made by the two instruments is essential for long-term studies of SSS and soil moisture. For resolving the consistency, the calibration of the instruments is the key. The basis of the SMOS brightness temperature level is the measurements performed with the so-called zero-baselines [3]; SMOS employs an interferometric measurement technique which forms a brightness temperature image from several baselines constructed by combination of multiple receivers in an array; zero-length baseline defines the overall brightness temperature level. The basis of the Aquarius brightness temperature level is resolved from the brightness temperature simulator combined with ancillary data such as antenna patterns and environmental models [4]. Consistency between the SMOS zero-baseline measurements and the simulator output would provide a robust basis for establishing the overall comparability of the missions.

  5. An observational correlation between stellar brightness variations and surface gravity.

    PubMed

    Bastien, Fabienne A; Stassun, Keivan G; Basri, Gibor; Pepper, Joshua

    2013-08-22

    Surface gravity is a basic stellar property, but it is difficult to measure accurately, with typical uncertainties of 25 to 50 per cent if measured spectroscopically and 90 to 150 per cent if measured photometrically. Asteroseismology measures gravity with an uncertainty of about 2 per cent but is restricted to relatively small samples of bright stars, most of which are giants. The availability of high-precision measurements of brightness variations for more than 150,000 stars provides an opportunity to investigate whether the variations can be used to determine surface gravities. The Fourier power of granulation on a star's surface correlates physically with surface gravity: if brightness variations on timescales of hours arise from granulation, then such variations should correlate with surface gravity. Here we report an analysis of archival data that reveals an observational correlation between surface gravity and root mean squared brightness variations on timescales of less than eight hours for stars with temperatures of 4,500 to 6,750 kelvin, log surface gravities of 2.5 to 4.5 (cgs units) and overall brightness variations of less than three parts per thousand. A straightforward observation of optical brightness variations therefore allows a determination of the surface gravity with a precision of better than 25 per cent for inactive Sun-like stars at main-sequence to giant stages of evolution.

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

    NASA Astrophysics Data System (ADS)

    Guo, Jinsong; Ma, Ruonan; Su, Bo; Li, Yinglong; Zhang, Jue; Fang, Jing

    2016-05-01

    Avermectins, a group of anthelmintic and insecticidal agents produced from Streptomyces avermitilis, are widely used in agricultural, veterinary, and medical fields. This study presents the first report on the potential of using nanosecond pulsed electric fields (nsPEFs) to improve avermectin production in S. avermitilis. The results of colony forming units showed that 20 pulses of nsPEFs at 10 kV/cm and 20 kV/cm had a significant effect on proliferation, while 100 pulses of nsPEFs at 30 kV/cm exhibited an obvious effect on inhibition of agents. Ultraviolet spectrophotometry assay revealed that 20 pulses of nsPEFs at 15 kV/cm increased avermectin production by 42% and reduced the time for reaching a plateau in fermentation process from 7 days to 5 days. In addition, the decreased oxidation reduction potential (ORP) and increased temperature of nsPEFs-treated liquid were evidenced to be closely associated with the improved cell growth and fermentation efficiency of avermectins in S. avermitilis. More importantly, the real-time RT-PCR analysis showed that nsPEFs could remarkably enhance the expression of aveR and malE in S. avermitilis during fermentation, which are positive regulator for avermectin biosynthesis. Therefore, the nsPEFs technology presents an alternative strategy to be developed to increase avermectin output in fermentation industry.

  7. Current Drug Discovery for Anti-hepatitis C Virus Targeting NS4B.

    PubMed

    Wang, Zhenya; Chen, Xinli; Wu, Chunli; Xu, Haiwei; Liu, Hongmin

    2016-01-01

    Hepatitis C virus (HCV) infection is a major worldwide epidemic disease. It is estimated that more than 170 million individuals are infected with HCV and with three to four million new cases each year. Many new direct-acting antiviral (DAA) agents that specifically target HCV NS3 protease or NS5B polymerase inhibitors are therefore in development, with a significant effect for the patient and for the market recently. The non-structural 4B (NS4B) protein, is among the least characterized of the HCV proteins. A variety of functions have been recognized for NS4B, such as the ability to induce the membranous web replication platform, RNA binding and NTPase activity. In order to maximize antiviral efficacy and prevent the emergence of resistance, novel NS4B inhibitors have been subjected to pharmacological studies. In this review, we discussed current understanding of the structure and function of NS4B, and novel drug discoveries targeting NS4B as anti-hepatitis C virus such as sulfonamide, piperidine, carboxamide, piperazinone and quinoline derivatives within the last three years.

  8. Purification and characterization of the major nonstructural protein (NS-1) of Aleutian mink disease parvovirus.

    PubMed Central

    Christensen, J; Pedersen, M; Aasted, B; Alexandersen, S

    1995-01-01

    We have previously described the expression of the major nonstructural protein (NS-1) of Aleutian mink disease parvovirus (ADV) in insect cells by using a baculovirus vector (J. Christensen, T. Storgaard, B. Bloch, S. Alexandersen, and B. Aasted, J. Virol. 67:229-238, 1993). To study its biochemical properties, ADV NS-1 was expressed in Sf9 insect cells and purified to apparent homogeneity with a combination of nuclear extraction, Zn2+ ion chromatography, and immunoaffinity chromatography on monoclonal antibodies. The purified protein showed ATP binding and ATPase- and ATP- or dATP-dependent helicase activity requiring either Mg2+ or Mn2+ as a cofactor. The ATPase activity of NS-1 was efficiently stimulated by single-stranded DNA and, to a lesser extent, double-stranded DNA. We also describe the expression, purification, and characterization of a mutant NS-1 protein, in which a lysine in the putative nucleotide binding consensus sequence of the molecule was replaced with serine. The mutated NS-1 was expressed at 10-fold higher levels than wild-type NS-1, but it exhibited no ATP binding. ATPase, or helicase activity. The availability of large amounts of purified functional NS-1 protein will facilitate studies of the biochemistry of ADV replication and gene regulation leading to disease in mink. PMID:7853520

  9. Efficacy of NS-718, a novel lipid nanosphere-encapsulated amphotericin B, against Cryptococcus neoformans.

    PubMed

    Hossain, M A; Maesaki, S; Kakeya, H; Noda, T; Yanagihara, K; Sasaki, E; Hirakata, Y; Tomono, K; Tashiro, T; Kohno, S

    1998-07-01

    In vitro and in vivo efficacies of NS-718, a lipid nanosphere-encapsulated amphotericin B (AMPH-B), have been studied. Of the tested AMPH-B formulations, NS-718 had the lowest MIC for Cryptococcus neoformans. In a murine model, low-dose therapy (0.8 mg/kg of body weight) with NS-718 showed higher efficacy than that with AmBisome. High-dose therapy (2.0 mg/kg) with NS-718 was much more effective than those with Fungizone and AmBisome. In mice treated with a high dose of NS-718, only a few yeast cells had grown in lung by 7 days after inoculation. A pharmacokinetic study showed higher concentrations of AMPH-B in lung following administration of NS-718 than after administration of AmBisome. Our results indicated that NS-718, a new AMPH-B formulation, is a promising antifungal agent for treatment of pulmonary cryptococcosis and could be the most effective antifungal agent against C. neoformans infections.

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

    PubMed Central

    Guo, Jinsong; Ma, Ruonan; Su, Bo; Li, Yinglong; Zhang, Jue; Fang, Jing

    2016-01-01

    Avermectins, a group of anthelmintic and insecticidal agents produced from Streptomyces avermitilis, are widely used in agricultural, veterinary, and medical fields. This study presents the first report on the potential of using nanosecond pulsed electric fields (nsPEFs) to improve avermectin production in S. avermitilis. The results of colony forming units showed that 20 pulses of nsPEFs at 10 kV/cm and 20 kV/cm had a significant effect on proliferation, while 100 pulses of nsPEFs at 30 kV/cm exhibited an obvious effect on inhibition of agents. Ultraviolet spectrophotometry assay revealed that 20 pulses of nsPEFs at 15 kV/cm increased avermectin production by 42% and reduced the time for reaching a plateau in fermentation process from 7 days to 5 days. In addition, the decreased oxidation reduction potential (ORP) and increased temperature of nsPEFs-treated liquid were evidenced to be closely associated with the improved cell growth and fermentation efficiency of avermectins in S. avermitilis. More importantly, the real-time RT-PCR analysis showed that nsPEFs could remarkably enhance the expression of aveR and malE in S. avermitilis during fermentation, which are positive regulator for avermectin biosynthesis. Therefore, the nsPEFs technology presents an alternative strategy to be developed to increase avermectin output in fermentation industry. PMID:27181521

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

    PubMed Central

    Furuta, Atsushi; Tsubuki, Masayoshi; Endoh, Miduki; Miyamoto, Tatsuki; Tanaka, Junichi; Abdus Salam, Kazi; Akimitsu, Nobuyoshi; Tani, Hidenori; Yamashita, Atsuya; Moriishi, Kohji; Nakakoshi, Masamichi; Sekiguchi, Yuji; Tsuneda, Satoshi; Noda, Naohiro

    2015-01-01

    Hepatitis C virus (HCV) is an important etiological agent of severe liver diseases, including cirrhosis and hepatocellular carcinoma. The HCV genome encodes nonstructural protein 3 (NS3) helicase, which is a potential anti-HCV drug target because its enzymatic activity is essential for viral replication. Some anthracyclines are known to be NS3 helicase inhibitors and have a hydroxyanthraquinone moiety in their structures; mitoxantrone, a hydroxyanthraquinone analogue, is also known to inhibit NS3 helicase. Therefore, we hypothesized that the hydroxyanthraquinone moiety alone could also inhibit NS3 helicase. Here, we performed a structure–activity relationship study on a series of hydroxyanthraquinones by using a fluorescence-based helicase assay. Hydroxyanthraquinones inhibited NS3 helicase with IC50 values in the micromolar range. The inhibitory activity varied depending on the number and position of the phenolic hydroxyl groups, and among different hydroxyanthraquinones examined, 1,4,5,8-tetrahydroxyanthraquinone strongly inhibited NS3 helicase with an IC50 value of 6 µM. Furthermore, hypericin and sennidin A, which both have two hydroxyanthraquinone-like moieties, were found to exert even stronger inhibition with IC50 values of 3 and 0.8 µM, respectively. These results indicate that the hydroxyanthraquinone moiety can inhibit NS3 helicase and suggest that several key chemical structures are important for the inhibition. PMID:26262613

  12. Structure of the catalytic domain of the hepatitis C virus NS2-3 protease

    SciTech Connect

    Lorenz,I.; Marcotrigiano, J.; Dentzer, T.; Rice, C.

    2006-01-01

    Hepatitis C virus is a major global health problem affecting an estimated 170 million people worldwide. Chronic infection is common and can lead to cirrhosis and liver cancer. There is no vaccine available and current therapies have met with limited success. The viral RNA genome encodes a polyprotein that includes two proteases essential for virus replication. The NS2-3 protease mediates a single cleavage at the NS2/NS3 junction, whereas the NS3-4A protease cleaves at four downstream sites in the polyprotein. NS3-4A is characterized as a serine protease with a chymotrypsin-like fold, but the enzymatic mechanism of the NS2-3 protease remains unresolved. Here we report the crystal structure of the catalytic domain of the NS2-3 protease at 2.3 Angstroms resolution. The structure reveals a dimeric cysteine protease with two composite active sites. For each active site, the catalytic histidine and glutamate residues are contributed by one monomer, and the nucleophilic cysteine by the other. The carboxy-terminal residues remain coordinated in the two active sites, predicting an inactive post-cleavage form. Proteolysis through formation of a composite active site occurs in the context of the viral polyprotein expressed in mammalian cells. These features offer unexpected insights into polyprotein processing by hepatitis C virus and new opportunities for antiviral drug design.

  13. The Dengue Virus NS5 Protein Intrudes in the Cellular Spliceosome and Modulates Splicing

    PubMed Central

    Shah, Priya; Pozzi, Berta; Gebhard, Leopoldo G.; Mammi, Pablo; Yanovsky, Marcelo J.; Andino, Raul; Krogan, Nevan; Srebrow, Anabella; Gamarnik, Andrea V.

    2016-01-01

    Dengue virus NS5 protein plays multiple functions in the cytoplasm of infected cells, enabling viral RNA replication and counteracting host antiviral responses. Here, we demonstrate a novel function of NS5 in the nucleus where it interferes with cellular splicing. Using global proteomic analysis of infected cells together with functional studies, we found that NS5 binds spliceosome complexes and modulates endogenous splicing as well as minigene-derived alternative splicing patterns. In particular, we show that NS5 alone, or in the context of viral infection, interacts with core components of the U5 snRNP particle, CD2BP2 and DDX23, alters the inclusion/exclusion ratio of alternative splicing events, and changes mRNA isoform abundance of known antiviral factors. Interestingly, a genome wide transcriptome analysis, using recently developed bioinformatics tools, revealed an increase of intron retention upon dengue virus infection, and viral replication was improved by silencing specific U5 components. Different mechanistic studies indicate that binding of NS5 to the spliceosome reduces the efficiency of pre-mRNA processing, independently of NS5 enzymatic activities. We propose that NS5 binding to U5 snRNP proteins hijacks the splicing machinery resulting in a less restrictive environment for viral replication. PMID:27575636

  14. Molecular Modeling and Docking Study to Elucidate Novel Chikungunya Virus nsP2 Protease Inhibitors.

    PubMed

    Agarwal, T; Asthana, Somya; Bissoyi, A

    2015-01-01

    Chikungunya is one of the tropical viral infections that severely affect the Asian and African countries. Absence of any suitable drugs or vaccines against Chikungunya virus till date makes it essential to identify and develop novel leads for the same. Recently, nsP2 cysteine protease has been classified as a crucial drug target to combat infections caused by Alphaviruses including Chikungunya virus due to its involvement viral replication. Here in, we investigated the structural aspects of the nsP2 protease through homology modeling based on nsP2 protease from Venezuelan equine encephalitis virus. Further, the ligands were virtually screened based on various pharmacological, ADME/Tox filters and subjected to docking with the modeled Chikungunya nsP2 protease using AutoDock4.2. The interaction profiling of ligand with the protein was carried out using LigPlot(+). The results demonstrated that the ligand with PubChem Id (CID_5808891) possessed highest binding affinity towards Chikungunya nsP2 protease with a good interaction profile with the active site residues. We hereby propose that these compounds could inhibit the nsP2 protease by binding to its active site. Moreover, they may provide structural scaffold for the design of novel leads with better efficacy and specificity for the nsP2 protease.

  15. Molecular Modeling and Docking Study to Elucidate Novel Chikungunya Virus nsP2 Protease Inhibitors

    PubMed Central

    Agarwal, T.; Asthana, Somya; Bissoyi, A.

    2015-01-01

    Chikungunya is one of the tropical viral infections that severely affect the Asian and African countries. Absence of any suitable drugs or vaccines against Chikungunya virus till date makes it essential to identify and develop novel leads for the same. Recently, nsP2 cysteine protease has been classified as a crucial drug target to combat infections caused by Alphaviruses including Chikungunya virus due to its involvement viral replication. Here in, we investigated the structural aspects of the nsP2 protease through homology modeling based on nsP2 protease from Venezuelan equine encephalitis virus. Further, the ligands were virtually screened based on various pharmacological, ADME/Tox filters and subjected to docking with the modeled Chikungunya nsP2 protease using AutoDock4.2. The interaction profiling of ligand with the protein was carried out using LigPlot+. The results demonstrated that the ligand with PubChem Id (CID_5808891) possessed highest binding affinity towards Chikungunya nsP2 protease with a good interaction profile with the active site residues. We hereby propose that these compounds could inhibit the nsP2 protease by binding to its active site. Moreover, they may provide structural scaffold for the design of novel leads with better efficacy and specificity for the nsP2 protease. PMID:26664062

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

    PubMed

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

    2017-03-01

    The rapid spread of the recent Zika virus (ZIKV) epidemic across various countries in the American continent poses a major health hazard for the unborn fetuses of pregnant women. To date, there is no effective medical intervention. The nonstructural protein 5 of Zika virus (ZIKV-NS5) is critical for ZIKV replication through the 5'-RNA capping and RNA polymerase activities present in its N-terminal methyltransferase (MTase) and C-terminal RNA-dependent RNA polymerase (RdRp) domains, respectively. The crystal structure of the full-length ZIKV-NS5 protein has been determined at 3.05 Å resolution from a crystal belonging to space group P21212 and containing two protein molecules in the asymmetric unit. The structure is similar to that reported for the NS5 protein from Japanese encephalitis virus and suggests opportunities for structure-based drug design targeting either its MTase or RdRp domain.

  17. Results of Satellite Brightness Modeling Using Kringing Optimized Interpolation

    NASA Astrophysics Data System (ADS)

    Weeden, C.; Hejduk, M.

    At the 2005 AMOS conference, Kriging Optimized Interpolation (KOI) was presented as a tool to model satellite brightness as a function of phase angle and solar declination angle (J.M Okada and M.D. Hejduk). Since November 2005, this method has been used to support the tasking algorithm for all optical sensors in the Space Surveillance Network (SSN). The satellite brightness maps generated by the KOI program are compared to each sensor's ability to detect an object as a function of the brightness of the background sky and angular rate of the object. This will determine if the sensor can technically detect an object based on an explicit calculation of the object's probability of detection. In addition, recent upgrades at Ground-Based Electro Optical Deep Space Surveillance Sites (GEODSS) sites have increased the amount and quality of brightness data collected and therefore available for analysis. This in turn has provided enough data to study the modeling process in more detail in order to obtain the most accurate brightness prediction of satellites. Analysis of two years of brightness data gathered from optical sensors and modeled via KOI solutions are outlined in this paper. By comparison, geo-stationary objects (GEO) were tracked less than non-GEO objects but had higher density tracking in phase angle due to artifices of scheduling. A statistically-significant fit to a deterministic model was possible less than half the time in both GEO and non-GEO tracks, showing that a stochastic model must often be used alone to produce brightness results, but such results are nonetheless serviceable. Within the Kriging solution, the exponential variogram model was the most frequently employed in both GEO and non-GEO tracks, indicating that monotonic brightness variation with both phase and solar declination angle is common and testifying to the suitability to the application of regionalized variable theory to this particular problem. Finally, the average nugget value, or

  18. Evidence for the existence of an Ns-type regulatory protein in Trypanosoma cruzi membranes.

    PubMed Central

    Eisenschlos, C D; Paladini, A A; Molina y Vedia, L; Torres, H N; Flawiá, M M

    1986-01-01

    The existence of a GTP-binding protein of the Ns type in Trypanosoma cruzi was explored. Epimastigote membranes were labelled by cholera toxin in the presence of [adenine-14C]NAD+. After SDS/polyacrylamide-gel electrophoresis of extracted membrane proteins, a single labelled polypeptide band of apparent Mr approx. 45,000 was detected. Epimastigote cells were treated with N-ethylmaleimide and electrofused to lymphoma S49 cells lacking the Ns protein. Evidence indicates that in such electrofusion-generated cell hybrids a heterologous adenylate cyclase system was reconstituted with the Ns protein provided by T. cruzi epimastigotes. Images Fig. 2. PMID:3099761

  19. Flexibility of NS5 Methyltransferase-Polymerase Linker Region Is Essential for Dengue Virus Replication

    PubMed Central

    Zhao, Yongqian; Soh, Tingjin Sherryl; Chan, Kitti Wing Ki; Fung, Sarah Suet Yin; Swaminathan, Kunchithapadam; Lim, Siew Pheng; Shi, Pei-Yong; Huber, Thomas; Lescar, Julien

    2015-01-01

    We examined the function of the conserved Val/Ile residue within the dengue virus NS5 interdomain linker (residues 263 to 272) by site-directed mutagenesis. Gly substitution or Gly/Pro insertion after the conserved residue increased the linker flexibility and created slightly attenuated viruses. In contrast, Pro substitution abolished virus replication by imposing rigidity in the linker and restricting NS5's conformational plasticity. Our biochemical and reverse genetics experiments demonstrate that NS5 utilizes conformational regulation to achieve optimum viral replication. PMID:26269182

  20. Revisiting the interplay between ablation, collisional, and radiative processes during ns-laser ablation

    NASA Astrophysics Data System (ADS)

    Autrique, D.; Gornushkin, I.; Alexiades, V.; Chen, Z.; Bogaerts, A.; Rethfeld, B.

    2013-10-01

    A study of ns-laser ablation is presented, which focuses on the transient behavior of the physical processes that act in and above a copper sample. A dimensionless multiphase collisional radiative model describes the interplay between the ablation, collisional, and radiative mechanisms. Calculations are done for a 6 ns-Nd:YAG laser pulse operating at 532 nm and fluences up to 15 J/cm2. Temporal intensity profiles as well as transmissivities are in good agreement with experimental results. It is found that volumetric ablation mechanisms and photo-processes both play an essential role in the onset of ns-laser induced breakdown.

  1. [Preparation of reactive bright blue praseodymium dyestuff and its spectral properties].

    PubMed

    Liu, Xiao-Zhen; Yuan, Ya-Qin; Cai, Yu; Zhu, Xian; Wang, Yan-Hong

    2004-08-01

    Reactive bright blue praseodymium dyestuff was prepared by using reactive bright blue and praseodymium oxide. The spectra of reactive bright blue praseodymium and dyed silk cloth by reactive bright blue praseodymium dyestuff were studied by UV-Vis and IR spectra respectively. In the range of 200-800 nm, reactive bright blue has four absorption peaks, and lambda(max) is 259 nm; reactive bright blue praseodymium has three absorption peaks, while lambda(max), is 264.00 nm. In the range of 420-760 nm, reactive bright blue has two absorption peaks at 661.50 and 625.50 nm, respectively, and lambda(max) is 661.50 nm; reactive bright blue praseodymium has only one absorption peak at 618.00 nm. Coordinate bond links reactive bright blue to praseodymium ion. Reactive bright blue praseodymium increases linking radicals as compared with reactive bright blue.

  2. Hepatitis C virus NS5A protein modulates IRF-7-mediated interferon-α signaling.

    PubMed

    Chowdhury, Joydip Bhanja; Kim, Hangeun; Ray, Ranjit; Ray, Ratna B

    2014-01-01

    Hepatitis C virus (HCV) establishes chronic infection in a large number of infected individuals. We have previously shown that HCV infection in hepatocytes blocks poly (I-C) or interferon (IFN)-α-mediated IRF-7 nuclear translocation (Raychoudhuri and others 2010). However, the mechanism of IRF-7 regulation by HCV remained unknown. In this study, we have observed that HCV NS5A physically associates with IRF-7. A subsequent study suggested that the HCV NS5A protein blocks IRF-7-mediated IFN-α14 promoter activation. Further analyses demonstrated that site-specific mutagenesis of the 2 basic arginine residues (amino acids Arg(216) and Arg(217)) in the NS5A is critical for IRF-7-mediated IFN-α14 promoter regulation. Together, our results suggested that the HCV NS5A protein limits the IFN-α-signaling pathway in association with IRF-7, and may, in part, be responsible for the establishment of chronic infection.

  3. Identification of cleavage of NS5A of C-strain classical swine fever virus.

    PubMed

    Xie, Jinxin; Guo, Huancheng; Gong, Wenjie; Jiang, Daliang; Zhang, Li; Jia, Junjie; Tu, Changchun

    2017-02-01

    NS5A is a multifunctional non-structural protein of classical swine fever virus (CSFV) that plays an important role in viral replication, but how it exerts its functions is unknown. Here, we report the cleavage of NS5A of the vaccine C-strain, resulting in two truncated forms (b and c). Further experiments using calpain- and caspase-family-specific inhibitors, followed by a caspase-6-specific shRNAs and inhibitor, showed that the cleavage of C-strain NS5A to produce truncated form c is mediated by caspase-6, mapping to (272)DTTD(275), while the cleavage producing truncated form b is probably mediated by another unknown protease. shRNA-mediated downregulation of caspase-6 and blocking of enzyme activity in ST cells significantly impaired genome replication and virus production, indicating that NS5A cleavage is required for CSFV replication.

  4. Detection of dengue NS1 antigen using long-range surface plasmon waveguides.

    PubMed

    Wong, Wei Ru; Sekaran, Shamala Devi; Adikan, Faisal Rafiq Mahamd; Berini, Pierre

    2016-04-15

    The non-structural 1 (NS1) protein of the dengue virus circulates in infected patients' blood samples and can be used for early diagnosis of dengue infection. In this paper, we present the detection of naturally-occurring dengue NS1 antigen in infected patient blood plasma using straight long-range surface plasmon waveguides. Three commercially-available anti-NS1 monoclonal antibodies were used for recognition and their performance was compared and discussed. A similar figure of merit to the one used in conventional dengue NS1 capture using an enzyme-linked immunosorbent assay (ELISA) was applied to our results. In general, the positive patient samples can be clearly differentiated from the negative ones and the results agree with those obtained using ELISA. The largest signal-to-noise ratio observed during the experiments was 356 and the best detection limit observed is estimated as 5.73 pg/mm(2).

  5. The crystal structure of Zika virus NS5 reveals conserved drug targets.

    PubMed

    Duan, Wenqian; Song, Hao; Wang, Haiyuan; Chai, Yan; Su, Chao; Qi, Jianxun; Shi, Yi; Gao, George F

    2017-04-03

    Zika virus (ZIKV) has emerged as major health concern, as ZIKV infection has been shown to be associated with microcephaly, severe neurological disease and possibly male sterility. As the largest protein component within the ZIKV replication complex, NS5 plays key roles in the life cycle and survival of the virus through its N-terminal methyltransferase (MTase) and C-terminal RNA-dependent RNA polymerase (RdRp) domains. Here, we present the crystal structures of ZIKV NS5 MTase in complex with an RNA cap analogue ((m7)GpppA) and the free NS5 RdRp. We have identified the conserved features of ZIKV NS5 MTase and RdRp structures that could lead to development of current antiviral inhibitors being used against flaviviruses, including dengue virus and West Nile virus, to treat ZIKV infection. These results should inform and accelerate the structure-based design of antiviral compounds against ZIKV.

  6. Structure and function of the Zika virus full-length NS5 protein.

    PubMed

    Zhao, Baoyu; Yi, Guanghui; Du, Fenglei; Chuang, Yin-Chih; Vaughan, Robert C; Sankaran, Banumathi; Kao, C Cheng; Li, Pingwei

    2017-03-27

    The recent outbreak of Zika virus (ZIKV) has infected over 1 million people in over 30 countries. ZIKV replicates its RNA genome using virally encoded replication proteins. Nonstructural protein 5 (NS5) contains a methyltransferase for RNA capping and a polymerase for viral RNA synthesis. Here we report the crystal structures of full-length NS5 and its polymerase domain at 3.0 Å resolution. The NS5 structure has striking similarities to the NS5 protein of the related Japanese encephalitis virus. The methyltransferase contains in-line pockets for substrate binding and the active site. Key residues in the polymerase are located in similar positions to those of the initiation complex for the hepatitis C virus polymerase. The polymerase conformation is affected by the methyltransferase, which enables a more efficiently elongation of RNA synthesis in vitro. Overall, our results will contribute to future studies on ZIKV infection and the development of inhibitors of ZIKV replication.

  7. Structure and function of the Zika virus full-length NS5 protein

    PubMed Central

    Zhao, Baoyu; Yi, Guanghui; Du, Fenglei; Chuang, Yin-Chih; Vaughan, Robert C.; Sankaran, Banumathi; Kao, C. Cheng; Li, Pingwei

    2017-01-01

    The recent outbreak of Zika virus (ZIKV) has infected over 1 million people in over 30 countries. ZIKV replicates its RNA genome using virally encoded replication proteins. Nonstructural protein 5 (NS5) contains a methyltransferase for RNA capping and a polymerase for viral RNA synthesis. Here we report the crystal structures of full-length NS5 and its polymerase domain at 3.0 Å resolution. The NS5 structure has striking similarities to the NS5 protein of the related Japanese encephalitis virus. The methyltransferase contains in-line pockets for substrate binding and the active site. Key residues in the polymerase are located in similar positions to those of the initiation complex for the hepatitis C virus polymerase. The polymerase conformation is affected by the methyltransferase, which enables a more efficiently elongation of RNA synthesis in vitro. Overall, our results will contribute to future studies on ZIKV infection and the development of inhibitors of ZIKV replication. PMID:28345656

  8. The structure of Zika virus NS5 reveals a conserved domain conformation

    PubMed Central

    Wang, Boxiao; Tan, Xiao-Feng; Thurmond, Stephanie; Zhang, Zhi-Min; Lin, Asher; Hai, Rong; Song, Jikui

    2017-01-01

    The recent outbreak of Zika virus (ZIKV) has imposed a serious threat to public health. Here we report the crystal structure of the ZIKV NS5 protein in complex with S-adenosyl-L-homocysteine, in which the tandem methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRp) domains stack into one of the two alternative conformations of flavivirus NS5 proteins. The activity of this NS5 protein is verified through a de novo RdRp assay on a subgenomic ZIKV RNA template. Importantly, our structural analysis leads to the identification of a potential drug-binding site of ZIKV NS5, which might facilitate the development of novel antivirals for ZIKV. PMID:28345600

  9. The structure of Zika virus NS5 reveals a conserved domain conformation.

    PubMed

    Wang, Boxiao; Tan, Xiao-Feng; Thurmond, Stephanie; Zhang, Zhi-Min; Lin, Asher; Hai, Rong; Song, Jikui

    2017-03-27

    The recent outbreak of Zika virus (ZIKV) has imposed a serious threat to public health. Here we report the crystal structure of the ZIKV NS5 protein in complex with S-adenosyl-L-homocysteine, in which the tandem methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRp) domains stack into one of the two alternative conformations of flavivirus NS5 proteins. The activity of this NS5 protein is verified through a de novo RdRp assay on a subgenomic ZIKV RNA template. Importantly, our structural analysis leads to the identification of a potential drug-binding site of ZIKV NS5, which might facilitate the development of novel antivirals for ZIKV.

  10. Compaction of isolated Escherichia coli nucleoids: Polymer and H-NS protein synergetics.

    PubMed

    Wegner, Anna S; Wintraecken, Kathelijne; Spurio, Roberto; Woldringh, Conrad L; de Vries, Renko; Odijk, Theo

    2016-04-01

    Escherichia coli nucleoids were compacted by the inert polymer polyethylene glycol (PEG) in the presence of the H-NS protein. The protein by itself appears to have little impact on the size of the nucleoids as determined by fluorescent microscopy. However, it has a significant impact on the nucleoidal collapse by PEG. This is quantitatively explained by assuming the H-NS protein enhances the effective diameter of the DNA helix leading to an increase in the depletion forces induced by the PEG. Ultimately, however, the free energy of the nucleoid itself turns out to be independent of the H-NS concentration. This is because the enhancement of the supercoil excluded volume is negligible. The experiments on the nucleoids are corroborated by dynamic light scattering and EMSA analyses performed on DNA plasmids in the presence of PEG and H-NS.

  11. Oxygen abundances in low surface-brightness galaxies

    NASA Technical Reports Server (NTRS)

    Roennback, Jari

    1993-01-01

    Recent theories predict that some protogalaxies, in low-density environments of the field, are contracting and interacting so slowly that global star formation can be delayed until today. These systems should be gas rich and have low surface-brightness. Blue compact galaxies (BCG's) and other compact HII region galaxies currently experiencing a burst of star formation are good candidates of truly young galaxies (in the sense that global star formation recently has been initiated). If they really are young, they ought to have a recent phase when their brightness was much lower than in the bursting phase. No claims of observations of such proto-BCG's exist. Observations of galaxies in their juvenile phases would undoubtedly be of great interest, e.g. the determination of the primordial helium abundance would improve. A proper place to search for young nearby galaxies could be among blue low surface-brightness galaxies (BLSBG's) in the local field. The study of low surface-brightness galaxies (LSBG's) as a group began relatively recently. They are galaxies with extraordinary properties both as individuals and as a group. A few years ago we started an optical study of a sample of BLSBG's selected from the ESO/Uppsala catalogue. Results of spectroscopic observations obtained on a subsample - 8 galaxies - of our selection are reported. The HII region oxygen chemical abundances and its relation to the blue absolute magnitude and surface-brightness is investigated.

  12. Dark-bright soliton interactions beyond the integrable limit

    NASA Astrophysics Data System (ADS)

    Katsimiga, G. C.; Stockhofe, J.; Kevrekidis, P. G.; Schmelcher, P.

    2017-01-01

    In this work we present a systematic theoretical analysis regarding dark-bright solitons and their interactions, motivated by recent advances in atomic two-component repulsively interacting Bose-Einstein condensates. In particular, we study analytically via a two-soliton ansatz adopted within a variational formulation the interaction between two dark-bright solitons in a homogeneous environment beyond the integrable regime, by considering general inter- and intra-atomic interaction coefficients. We retrieve the possibility of a fixed point in the case where the bright solitons are out of phase. As the intercomponent interaction is increased, we also identify an exponential instability of the two-soliton state, associated with a subcritical pitchfork bifurcation. The latter gives rise to an asymmetric partition of the bright soliton mass and dynamically leads to spontaneous splitting of the bound pair. In the case of the in-phase bright solitons, we explain via parsing the analytical approximations and monitoring the direct dynamics why no such pair is identified, despite its prediction by the variational analysis.

  13. Night Sky Brightness at San Pedro Martir Observatory

    NASA Astrophysics Data System (ADS)

    Plauchu-Frayn, I.; Richer, M. G.; Colorado, E.; Herrera, J.; Córdova, A.; Ceseña, U.; Ávila, F.

    2017-03-01

    We present optical UBVRI zenith night sky brightness measurements collected on 18 nights during 2013 to 2016 and SQM measurements obtained daily over 20 months during 2014 to 2016 at the Observatorio Astronómico Nacional on the Sierra San Pedro Mártir (OAN-SPM) in México. The UBVRI data is based upon CCD images obtained with the 0.84 m and 2.12 m telescopes, while the SQM data is obtained with a high-sensitivity, low-cost photometer. The typical moonless night sky brightness at zenith averaged over the whole period is U = 22.68, B = 23.10, V = 21.84, R = 21.04, I = 19.36, and SQM = 21.88 {mag} {{arcsec}}-2, once corrected for zodiacal light. We find no seasonal variation of the night sky brightness measured with the SQM. The typical night sky brightness values found at OAN-SPM are similar to those reported for other astronomical dark sites at a similar phase of the solar cycle. We find a trend of decreasing night sky brightness with decreasing solar activity during period of the observations. This trend implies that the sky has become darker by Δ U = 0.7, Δ B = 0.5, Δ V = 0.3, Δ R=0.5 mag arcsec‑2 since early 2014 due to the present solar cycle.

  14. PROFFIT: Analysis of X-ray surface-brightness profiles

    NASA Astrophysics Data System (ADS)

    Eckert, Dominique

    2016-08-01

    PROFFIT analyzes X-ray surface-brightness profiles for data from any X-ray instrument. It can extract surface-brightness profiles in circular or elliptical annuli, using constant or logarithmic bin size, from the image centroid, the surface-brightness peak, or any user-given center, and provides surface-brightness profiles in any circular or elliptical sectors. It offers background map support to extract background profiles, can excise areas using SAO DS9-compatible (ascl:0003.002) region files to exclude point sources, provides fitting with a number of built-in models, including the popular beta model, double beta, cusp beta, power law, and projected broken power law, uses chi-squared or C statistic, and can fit on the surface-brightness or counts data. It has a command-line interface similar to HEASOFT’s XSPEC (ascl:9910.005) package, provides interactive help with a description of all the commands, and results can be saved in FITS, ROOT or TXT format.

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

    NASA Astrophysics Data System (ADS)

    Herdiwijaya, Dhani

    2016-11-01

    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.

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

    PubMed

    de Almeida, Hugo; Bastos, Izabela M D; Ribeiro, Bergmann M; Maigret, Bernard; Santana, Jaime M

    2013-01-01

    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.

  17. Zika virus NS1 structure reveals diversity of electrostatic surfaces among flaviviruses.

    PubMed

    Song, Hao; Qi, Jianxun; Haywood, Joel; Shi, Yi; Gao, George F

    2016-05-01

    The association of Zika virus (ZIKV) infections with microcephaly has resulted in an ongoing public-health emergency. Here we report the crystal structure of a C-terminal fragment of ZIKV nonstructural protein 1 (NS1), a major host-interaction molecule that functions in flaviviral replication, pathogenesis and immune evasion. Comparison with West Nile and dengue virus NS1 structures reveals conserved features but diverse electrostatic characteristics at host-interaction interfaces, thus possibly implying different modes of flavivirus pathogenesis.

  18. Differentiation of infected and vaccinated animals (DIVA) using the NS1 protein of avian influenza virus.

    PubMed

    Avellaneda, Gloria; Mundt, Egbert; Lee, Chang-Won; Jadhao, Samadhan; Suarez, David L

    2010-03-01

    Vaccination against avian influenza (AI) virus, a powerful tool for control of the disease, may result in issues related to surveillance programs and international trade of poultry and poultry products. The use of AI vaccination in poultry would have greater worldwide acceptance if a reliable test were available that clearly discriminated between naturally infected and vaccinated-only animals (DIVA). Because the nonstructural protein (NS1) is expressed in influenza virus-infected cells, and it is not packaged in the virion, it is an attractive candidate for a DIVA differential diagnostic test. The aim of this work was to determine the onset of the antibody response to the NS1 protein in chickens infected with low pathogenic avian influenza (LPAI) virus, and to evaluate the diagnostic potential of a baculovirus-expressed purified NS1 protein in an indirect ELISA-based DIVA strategy. An antibody response against NS1 was first detected 3 wk after infection, but the antibody levels were decreasing rapidly by 5 wk after infection. However, most chickens did not have detectable antibodies in spite of high hemagglutination inhibition (HI) antibody titers in one group. In birds vaccinated with inactivated oil-emulsion vaccines, antibodies against NS1 were not detected before virulent challenge, and only a small percentage of birds seroconverted after homologous LPAI virus challenge. Vaccinated birds challenged with highly pathogenic AI showed a higher NS1 antibody response, but at most only 40% of birds seroconverted against NS1 protein by 3 wk after challenge. Because of the variability of seroconversion and the duration of the antibody response in chickens, the NS1 protein DIVA strategy did not perform as well as expected, and if this strategy were to be used, it would require sampling a higher number of birds to compensate for the lower seroconversion rate.

  19. NTPase and 5'-RNA triphosphatase activities of Chikungunya virus nsP2 protein.

    PubMed

    Karpe, Yogesh A; Aher, Pankaj P; Lole, Kavita S

    2011-01-01

    Chikungunya virus (CHIKV) is an insect borne virus (genus: Alphavirus) which causes acute febrile illness in humans followed by a prolonged arthralgic disease that affects the joints of the extremities. Re-emergence of the virus in the form of outbreaks in last 6-7 years has posed a serious public health problem. CHIKV has a positive sense single stranded RNA genome of about 12,000 nt. Open reading frame 1 of the viral genome encodes a polyprotein precursor, nsP1234, which is processed further into different non structural proteins (nsP1, nsP2, nsP3 and nsP4). Sequence based analyses have shown helicase domain at the N-terminus and protease domain at C-terminus of nsP2. A detailed biochemical analysis of NTPase/RNA helicase and 5'-RNA phosphatase activities of recombinant CHIKV-nsP2T protein (containing conserved NTPase/helicase motifs in the N-terminus and partial papain like protease domain at the C-terminus) was carried out. The protein could hydrolyze all NTPs except dTTP and showed better efficiency for ATP, dATP, GTP and dGTP hydrolysis. ATP was the most preferred substrate by the enzyme. CHIKV-nsP2T also showed 5'-triphosphatase (RTPase) activity that specifically removes the γ-phosphate from the 5' end of RNA. Both NTPase and RTPase activities of the protein were completely dependent on Mg(2+) ions. RTPase activity was inhibited by ATP showing sharing of the binding motif by NTP and RNA. Both enzymatic activities were drastically reduced by mutations in the NTP binding motif (GKT) and co-factor, Mg(2+) ion binding motif (DEXX) suggesting that they have a common catalytic site.

  20. Hepatitis C virus NS3-NS4A protease inhibitors from the endophytic Penicillium chrysogenum isolated from the red alga Liagora viscida.

    PubMed

    Hawas, Usama W; El-Halawany, Ali M; Ahmed, Eman F

    2013-01-01

    Hepatitis C virus (HCV) NS3-NS4A protease is an attractive target for anti-HCV agents because of its important role in replication. In this work, we demonstrated that the ethyl acetate extract of the endophytic fungus Penicillium chrysogenum exhibited a potent activity against HCV NS3-NS4A protease with an IC50 value of 20 microg/ml. The fungus was isolated from the red alga Liagora viscida and identified by its morphology and 18S rDNA. Large-scale fermentation of the fungus in Czapek's peptone liquid medium followed by chromatographic purification of the active extract from the liquid medium allowed the isolation of twelve known metabolites. The biological properties of the isolated compounds were explored for anti-HCV protease as well as antimicrobial and anticancer activities. A computational docking study of the active isolated compounds against HCV protease was used to formulate a hypothetical mechanism for the inhibitory activity of the active compounds on the tested enzymes.

  1. Bright and Not-So-Bright Prospects for Women in Physics in China-Beijing

    NASA Astrophysics Data System (ADS)

    Wu, Ling-An; Yang, Zhongqin; Ma, Wanyun

    2009-04-01

    Science in China-Beijing is enjoying a healthy increase in funding year by year, so the prospects for physicists are also bright. However, employment discrimination against women, formerly unthinkable, is becoming more and more explicit as the country evolves toward a market economy. Some recruitment notices bluntly state that only men will be considered, or impose restrictions upon potential female candidates. Female associate professors in many institutions are forced to retire at age 55, compared with 60 for men. This double-pinching discrimination against both younger and older women threatens to lead to a "pincer" effect, more serious than the "scissors" effect. Indeed, the ratio of senior-level women physicists in general has dropped significantly in recent years in China. Ironically, the number of female students applying for graduate studies is on the rise, as it is becoming increasingly difficult for them to compete with men in the job market with just an undergraduate degree. The Chinese Physical Society has made certain efforts to promote the image of women physicists, but it will take time and effort to reverse the trend.

  2. An NS-segment exonic splicing enhancer regulates influenza A virus replication in mammalian cells

    PubMed Central

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

    2017-01-01

    Influenza virus utilizes host splicing machinery to process viral mRNAs expressed from both M and NS segments. Through genetic analysis and functional characterization, we here show that the NS segment of H7N9 virus contains a unique G540A substitution, located within a previously undefined exonic splicing enhancer (ESE) motif present in the NEP mRNA of influenza A viruses. G540A supports virus replication in mammalian cells while retaining replication ability in avian cells. Host splicing regulator, SF2, interacts with this ESE to regulate splicing of NEP/NS1 mRNA and G540A substitution affects SF2–ESE interaction. The NS1 protein directly interacts with SF2 in the nucleus and modulates splicing of NS mRNAs during virus replication. We demonstrate that splicing of NEP/NS1 mRNA is regulated through a cis NEP-ESE motif and suggest a unique NEP-ESE may contribute to provide H7N9 virus with the ability to both circulate efficiently in avian hosts and replicate in mammalian cells. PMID:28323816

  3. NS5ATP9 Promotes Beclin 1-Dependent Starvation-Induced Autophagy of Hepatoblastoma Cells.

    PubMed

    Quan, Min; Liu, Shunai; Wang, Qi; Li, Guoli; Zhang, Yu; Feng, Shenghu; Liang, Jinqiu; Cheng, Jun

    2015-08-01

    NS5ATP9, a gene up-regulated by NS5A, plays a crucial oncogenic role in several types of human tumours. However, the underlying mechanisms remain unclear. Autophagy, an evolutionarily conserved catabolic process, maintains cellular homeostasis under stress conditions, such as starvation, and plays a crucial role in tumour initiation and progression. Here, we report that NS5ATP9 mRNA and protein expression was up-regulated in starved HepG2 cells and that the up-regulated NS5ATP9 played a functional role in starvation-induced autophagy. Overexpression or silencing of this gene showed contrasting effects on Beclin 1 and on starvation-induced autophagy. Furthermore, NS5ATP9-mediated autophagy is required for promotion of tumour cell growth, and this effect could be inhibited with 3-methyladenine, chloroquine or by Beclin 1-silencing. Thus, the mechanism for NS5ATP9-promoted autophagy is Beclin 1-dependent in the condition of starvation, and for hepatoblastoma cell growth is also Beclin 1-dependent.

  4. A Mutation Identified in Neonatal Microcephaly Destabilizes Zika Virus NS1 Assembly in Vitro.

    PubMed

    Wang, Deping; Chen, Cheng; Liu, Shengnan; Zhou, Han; Yang, Kailin; Zhao, Qi; Ji, Xiaoyun; Chen, Chen; Xie, Wei; Wang, Zefang; Mi, Li-Zhi; Yang, Haitao

    2017-02-15

    An unprecedented epidemic of Zika virus (ZIKV) infection had spread to South and Central America. ZIKV infection was recently confirmed by CDC (the Centers for Disease Control and Prevention) to cause neonatal microcephaly, which posed a significant public health emergency of international concern. No specific vaccines or drugs are currently available to fight ZIKV infection. ZIKV nonstructural protein 1 (NS1) plays an essential role in viral replication and immune evasion. We determined the crystal structure of ZIKV NS1172-352, which forms a head-to-head, symmetric dimer with a unique 14-stranded β-ladder conserved among flaviviruses. The assembly of the β-ladder dimer is concentration dependent. Strikingly, one pathogenic mutation T233A (NCBI accession no. KU527068), found in the brain tissue of infected fetus with neonatal microcephaly, is located at the dimer interface. Thr233, a unique residue found in ZIKV but not in other flaviviruses, organizes a central hydrogen bonding network at NS1 dimer interface. Mutation of Thr233 to Ala disrupts this elaborated interaction network, and destabilizes the NS1 dimeric assembly in vitro. In addition, our structural comparison of epitopes for protective antibody 22NS1, targeting West Nile Virus NS1, could potentially be valuable in understanding its anti-virus specificities and in the development of antibodies against ZIKV.

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

    PubMed

    Hung, Yu-Fu; Schwarten, Melanie; Hoffmann, Silke; Willbold, Dieter; Sklan, Ella H; Koenig, BerndW

    2015-07-21

    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.

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

    PubMed

    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.

  7. Nanometer-Scale Permeabilization and Osmotic Swelling Induced by 5-ns Pulsed Electric Fields.

    PubMed

    Sözer, Esin B; Wu, Yu-Hsuan; Romeo, Stefania; Vernier, P Thomas

    2017-02-01

    High-intensity nanosecond pulsed electric fields (nsPEFs) permeabilize cell membranes. Although progress has been made toward an understanding of the mechanism of nsPEF-induced membrane poration, the dependence of pore size and distribution on pulse duration, strength, number, and repetition rate remains poorly defined experimentally. In this paper, we characterize the size of nsPEF-induced pores in living cell membranes by isosmotically replacing the solutes in pulsing media with polyethylene glycols and sugars before exposing Jurkat T lymphoblasts to 5 ns, 10 MV/m electric pulses. Pore size was evaluated by analyzing cell volume changes resulting from the permeation of osmolytes through the plasma membrane. We find that pores created by 5 ns pulses have a diameter between 0.7 and 0.9 nm at pulse counts up to 100 with a repetition rate of 1 kHz. For larger number of pulses, either the pore diameter or the number of pores created, or both, increase with increasing pulse counts. But the prevention of cell swelling by PEG 1000 even after 2000 pulses suggests that 5 ns, 10 MV/m pulses cannot produce pores with a diameter larger than 1.9 nm.

  8. NS3 Protease from Hepatitis C Virus: Biophysical Studies on an Intrinsically Disordered Protein Domain

    PubMed Central

    Vega, Sonia; Neira, Jose L.; Marcuello, Carlos; Lostao, Anabel; Abian, Olga; Velazquez-Campoy, Adrian

    2013-01-01

    The nonstructural protein 3 (NS3) from the hepatitis C virus (HCV) is responsible for processing the non-structural region of the viral precursor polyprotein in infected hepatic cells. NS3 protease activity, located at the N-terminal domain, is a zinc-dependent serine protease. A zinc ion, required for the hydrolytic activity, has been considered as a structural metal ion essential for the structural integrity of the protein. In addition, NS3 interacts with another cofactor, NS4A, an accessory viral protein that induces a conformational change enhancing the hydrolytic activity. Biophysical studies on the isolated protease domain, whose behavior is similar to that of the full-length protein (e.g., catalytic activity, allosteric mechanism and susceptibility to inhibitors), suggest that a considerable global conformational change in the protein is coupled to zinc binding. Zinc binding to NS3 protease can be considered as a folding event, an extreme case of induced-fit binding. Therefore, NS3 protease is an intrinsically (partially) disordered protein with a complex conformational landscape due to its inherent plasticity and to the interaction with its different effectors. Here we summarize the results from a detailed biophysical characterization of this enzyme and present new experimental data. PMID:23803659

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

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

    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.

  10. Electrochemical lateral flow immunosensor for detection and quantification of dengue NS1 protein.

    PubMed

    Sinawang, Prima Dewi; Rai, Varun; Ionescu, Rodica E; Marks, Robert S

    2016-03-15

    An Electrochemical Lateral Flow Immunosensor (ELFI) is developed combining screen-printed gold electrodes (SPGE) enabling quantification together with the convenience of a lateral flow test strip. A cellulose glassy fiber paper conjugate pad retains the marker immunoelectroactive nanobeads which will bind to the target analyte of interest. The specific immunorecognition event continues to occur along the lateral flow bed until reaching the SPGE-capture antibodies at the end of the cellulosic lateral flow strip. The rationale of the immunoassay consists in the analyte antigen NS1 protein being captured selectively and specifically by the dengue NS1 antibody conjugated onto the immunonanobeads thus forming an immunocomplex. With the aid of a running buffer, the immunocomplexes flow and reach the immuno-conjugated electrode surface and form specific sandwich-type detection due to specific, molecular recognition, while unbound beads move along past the electrodes. The successful sandwich immunocomplex formation is then recorded electrochemically. Specific detection of NS1 is translated into an electrochemical signal contributed by a redox label present on the bead-immobilized detection dengue NS1 antibody while a proportional increase of faradic current is observed with increase in analyte NS1 protein concentration. The first generation ELFI prototype is simply assembled in a cassette and successfully demonstrates wide linear range over a concentration range of 1-25 ng/mL with an ultrasensitive detection limit of 0.5 ng/mL for the qualitative and quantitative detection of analyte dengue NS1 protein.

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

    PubMed Central

    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

  12. Nuclear Translocation of Crk Adaptor Proteins by the Influenza A Virus NS1 Protein

    PubMed Central

    Ylösmäki, Leena; Fagerlund, Riku; Kuisma, Inka; Julkunen, Ilkka; Saksela, Kalle

    2016-01-01

    The non-structural protein-1 (NS1) of many influenza A strains, especially those of avian origin, contains an SH3 ligand motif, which binds tightly to the cellular adaptor proteins Crk (Chicken tumor virus number 10 (CT10) regulator of kinase) and Crk-like adapter protein (CrkL). This interaction has been shown to potentiate NS1-induced activation of the phosphatidylinositol 3-kinase (PI3K), but additional effects on the host cell physiology may exist. Here we show that NS1 can induce an efficient translocation of Crk proteins from the cytoplasm into the nucleus, which results in an altered pattern of nuclear protein tyrosine phosphorylation. This was not observed using NS1 proteins deficient in SH3 binding or engineered to be exclusively cytoplasmic, indicating a physical role for NS1 as a carrier in the nuclear translocation of Crk. These data further emphasize the role of Crk proteins as host cell interaction partners of NS1, and highlight the potential for host cell manipulation gained by a viral protein simply via acquiring a short SH3 binding motif. PMID:27092521

  13. A Mutation Identified in Neonatal Microcephaly Destabilizes Zika Virus NS1 Assembly in Vitro

    PubMed Central

    Wang, Deping; Chen, Cheng; Liu, Shengnan; Zhou, Han; Yang, Kailin; Zhao, Qi; Ji, Xiaoyun; Chen, Chen; Xie, Wei; Wang, Zefang; Mi, Li-Zhi; Yang, Haitao

    2017-01-01

    An unprecedented epidemic of Zika virus (ZIKV) infection had spread to South and Central America. ZIKV infection was recently confirmed by CDC (the Centers for Disease Control and Prevention) to cause neonatal microcephaly, which posed a significant public health emergency of international concern. No specific vaccines or drugs are currently available to fight ZIKV infection. ZIKV nonstructural protein 1 (NS1) plays an essential role in viral replication and immune evasion. We determined the crystal structure of ZIKV NS1172–352, which forms a head-to-head, symmetric dimer with a unique 14-stranded β-ladder conserved among flaviviruses. The assembly of the β-ladder dimer is concentration dependent. Strikingly, one pathogenic mutation T233A (NCBI accession no. KU527068), found in the brain tissue of infected fetus with neonatal microcephaly, is located at the dimer interface. Thr233, a unique residue found in ZIKV but not in other flaviviruses, organizes a central hydrogen bonding network at NS1 dimer interface. Mutation of Thr233 to Ala disrupts this elaborated interaction network, and destabilizes the NS1 dimeric assembly in vitro. In addition, our structural comparison of epitopes for protective antibody 22NS1, targeting West Nile Virus NS1, could potentially be valuable in understanding its anti-virus specificities and in the development of antibodies against ZIKV. PMID:28198446

  14. Cell structure imaging with bright and homogeneous nanometric light source.

    PubMed

    Fukuta, Masahiro; Ono, Atsushi; Nawa, Yasunori; Inami, Wataru; Shen, Lin; Kawata, Yoshimasa; Terekawa, Susumu

    2017-04-01

    Label-free optical nano-imaging of dendritic structures and intracellular granules in biological cells is demonstrated using a bright and homogeneous nanometric light source. The optical nanometric light source is excited using a focused electron beam. A zinc oxide (ZnO) luminescent thin film was fabricated by atomic layer deposition (ALD) to produce the nanoscale light source. The ZnO film formed by ALD emitted the bright, homogeneous light, unlike that deposited by another method. The dendritic structures of label-free macrophage receptor with collagenous structure-expressing CHO cells were clearly visualized below the diffraction limit. The inner fiber structure was observed with 120 nm spatial resolution. Because the bright homogeneous emission from the ZnO film suppresses the background noise, the signal-to-noise ratio (SNR) for the imaging results was greater than 10. The ALD method helps achieve an electron beam excitation assisted microscope with high spatial resolution and high SNR.

  15. Brightness of the Sky during a Solar Eclipse

    NASA Astrophysics Data System (ADS)

    Milisavljevic, D.; Nedeljkovic, S.; Miovic, V.

    2000-01-01

    Observations of the relative brightness of the sky were carried out in Horgos, Yugoslavia, and in Kamen Bryag, Bulgaria, during the total solar eclipse on August 11, 1999. The results were compared with observations of the partial solar eclipse of October 24, 1995, in Calcutta, India, and with some simple eclipse models based on the approximations for the limb darkening of the solar disc. The differences between the relative brightness of the sky during partial and during total solar eclipses are noticed, The measured brightness curve of the total eclipse rapidly declines immediately before, and it starts to grow rapidly immediately after the eclipse totality, while the curve of the partial eclipse has neither rapid declining nor growing.

  16. Shiftwork in space - Bright light as a chronobiologic countermeasure

    NASA Technical Reports Server (NTRS)

    Gander, Philippa H.; Samel, Alexander

    1991-01-01

    The potential of timed exposures to bright light as a countermeasure to the changes in the work/rest schedules during space missions was investigated. In the experiments, four human subjects were exposed to two sessions of eleven days of simulated weightlessness (6-deg head-down-tilt bedrest) with 6-hr extensions of the scheduled wake time on days 3 and 4 (a 12-hr phase delay). In a blind crossover design, subjects were exposed to bright light (greater than 3500 lux) for 5 hrs on each of the two shift days and on the following day, at times expected to accelerate adaptation to the phase delay (experimental group), or have no phase shifting effect (control group). Results indicate that bright light may accelerate the rate of adaptation to work/rest schedule delays under simulated weightlessness conditions. However, such effect was found to be largely independent of the timing of the light exposure.

  17. Intensity oscillations in chromospheric bright points and network elements

    NASA Astrophysics Data System (ADS)

    Kariyappa, R.

    1994-09-01

    From a 35-min time series of photographic spectra in the Ca II H-line obtained at the Vacuum Tower Telescope (VTT) of the Sacramento Peak Observatory under high spatial, spectral, and temporal resolution, we have derived a large number of H-line profiles at the sites of the bright points in the interior of the supergranulation cells, and at the network elements, on a quiet region at the center of the solar disc. It is shown that the bright points are associated with 3-min periodicity in their intensity oscillations whereas the network elements exhibit approximately 7-min periodicity. It is surmised that the large difference in periods of the intensity oscillations, the strength of the magnetic fields, and the intensity enhancements at the sites of the bright points and the network elements themselves may probably be taken as evidence to argue that the mechanisms of heating in the two cases are dissimilar, irrespective of the sizes of these structures.

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

    NASA Technical Reports Server (NTRS)

    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

  19. The ASAS-SN Bright Supernova Catalog - II. 2015

    NASA Astrophysics Data System (ADS)

    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.; Basu, U.; Beacom, J. F.; Bersier, D.; Chen, Ping; Danilet, A. B.; Falco, E.; Godoy-Rivera, D.; Goss, N.; Pojmanski, G.; Simonian, G. V.; Skowron, D. M.; Thompson, Todd A.; Woźniak, P. R.; Ávila, C. G.; Bock, G.; Carballo, J.-L. G.; Conseil, E.; Contreras, C.; Cruz, I.; Andújar, J. M. F.; Guo, Zhen; Hsiao, E. Y.; Kiyota, S.; Koff, R. A.; Krannich, G.; Madore, B. F.; Marples, P.; Masi, G.; Morrell, N.; Monard, L. A. G.; Munoz-Mateos, J. C.; Nicholls, B.; Nicolas, J.; Wagner, R. M.; Wiethoff, W. S.

    2017-01-01

    This manuscript presents information for all supernovae discovered by the All-Sky Automated Survey for SuperNovae (ASAS-SN) during 2015, its second full year of operations. The same information is presented for bright (mV ≤ 17), spectroscopically confirmed supernovae discovered by other sources in 2015. As with the first ASAS-SN bright supernova catalog, we also present redshifts and near-UV through IR magnitudes for all supernova host galaxies in both samples. Combined with our previous catalog, this work comprises a complete catalog of 455 supernovae from multiple professional and amateur sources, allowing for population studies that were previously impossible. This is the second of a series of yearly papers on bright supernovae and their hosts from the ASAS-SN team.

  20. On the relation between zenith sky brightness and horizontal illuminance

    NASA Astrophysics Data System (ADS)

    Kocifaj, M.; Posch, Th.; Solano Lamphar, H. A.

    2015-01-01

    The effects of artificial light at night are an emergent research topic for astronomers, physicists, engineers and biologists around the world. This leads to a need for measurements of the night sky brightness (= diffuse luminance of the night sky) and nocturnal illuminance. Currently, the most sensitive light meters measure the zenith sky brightness in magV/arcsec2 or - less frequently - in cd m-2. However, the horizontal illuminance resulting only from the night sky is an important source of information that is difficult to obtain with common instruments. Here we present a set of approximations to convert the zenith luminance into horizontal illuminance. Three different approximations are presented for three idealized atmospheric conditions: homogeneous sky brightness, an isotropically scattering atmosphere and a turbid atmosphere. We also apply the resulting conversion formulae to experimental data on night sky luminance, obtained during the past three years.

  1. Life-threatening motor vehicle crashes in bright sunlight.

    PubMed

    Redelmeier, Donald A; Raza, Sheharyar

    2017-01-01

    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 estimated by evaluating the prevailing weather at the time and place of the crash compared with the weather at the same hour and location on control days a week earlier and a week later.The majority of patients (n = 6962) were injured during daylight hours and bright sunlight was the most common weather condition at the time and place of the crash. The risk of a life-threatening crash was 16% higher during bright sunlight than normal weather (95% confidence interval: 9-24, P < 0.001). The increased risk was accentuated in the early afternoon, disappeared at night, extended to patients with different characteristics, involved crashes with diverse features, not apparent with cloudy weather, and contributed to about 5000 additional patient-days in hospital. The increased risk extended to patients with high crash severity as indicated by ambulance involvement, surgical procedures, length of hospital stay, intensive care unit admission, and patient mortality. The increased risk was not easily attributed to differences in alcohol consumption, driving distances, or anomalies of adverse weather.Bright sunlight is associated with an increased risk of a life-threatening motor vehicle crash. An awareness of this risk might inform driver education, trauma staffing, and safety warnings to prevent a life-threatening motor vehicle crash.

  2. The possible origin of facular brightness in the solar atmosphere

    NASA Astrophysics Data System (ADS)

    Kostik, R.; Khomenko, E.

    2016-05-01

    This paper studies the dependence of the Ca ii H line core brightness on the strength and inclination of the photospheric magnetic field, and on the parameters of convective and wave motions in a facular region at the center of the solar disc. We use three simultaneous data sets that were obtained at the German Vacuum Tower Telescope (Observatorio del Teide, Tenerife): (1) spectra of Ba ii 4554 Å line, registered with the instrument TESOS to measure the variations of intensity and velocity through the photosphere up to the temperature minimum; (2) spectropolarimetric data in Fe i 1.56 μm lines (registered with the instrument TIP II) to measure photospheric magnetic fields; (3) filtergrams in Ca ii H that give information about brightness fluctuations in the chromosphere. The results show that the Ca ii H brightness in the facula strongly depends on the power of waves with periods in the 5-min range, which propagate upwards, and also on the phase shift between velocity oscillations at the bottom photosphere and around the temperature minimum height that is measured from Ba ii line. The Ca ii H brightness is maximum at locations where the phase shift between temperature and velocity oscillations lies within 0°-100°. There is an indirect influence of convective motions on the Ca ii H brightness. The higher the amplitude of convective velocities is and the greater the height is where they change their direction of motion, the brighter the facula. In summary, our results lead to conclusions that facular regions appear bright not only because of the Wilson depression in magnetic structures, but also owing to real heating.

  3. Brightness discrimination in the South African fur seal (Arctocephalus pusillus).

    PubMed

    Scholtyssek, C; Dehnhardt, G

    2013-05-24

    Underwater, the contrast between object and background is much larger reduced with increasing distance between object and observer than in air. For marine predators, such as pinnipeds, it would therefore be advantageous to possess a high sensitivity for brightness differences, since this would increase the distance at which prey can be detected visually. Few studies have examined the brightness discrimination thresholds of pinnipeds. Two studies with phocid seals have confirmed low brightness discrimination thresholds in pinnipeds whereas the threshold obtained for the South African fur seal seems to be twice as high as that of the phocids. However, the experiments with the South African fur seal have been conducted under inadequate conditions which likely resulted in an underestimation of the brightness discrimination ability of this species. The study at hand reinvestigated the brightness discrimination threshold of the South African fur seal under well controlled conditions. In a two alternative forced choice task, one fur seal was trained to indicate the position of the brighter of two gray discs presented on a black background on a monitor. The thresholds were determined for 11 standard intensities each tested against 8 lower comparison intensities. It was found that the fur seal was able to perceive brightness differences of 8-10%, which is better than the phocid species tested so far. For low standard intensities, however, the threshold increased which could to be due to a relative slow dark adaptation rate of the fur seal. The results are discussed in terms of the relevance of visual information for pinnipeds during foraging dives and are directly compared to the results obtained for the harbor seal which has been tested under the same conditions as the fur seal in a previous study.

  4. Life-threatening motor vehicle crashes in bright sunlight

    PubMed Central

    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 estimated by evaluating the prevailing weather at the time and place of the crash compared with the weather at the same hour and location on control days a week earlier and a week later. The majority of patients (n = 6962) were injured during daylight hours and bright sunlight was the most common weather condition at the time and place of the crash. The risk of a life-threatening crash was 16% higher during bright sunlight than normal weather (95% confidence interval: 9–24, P < 0.001). The increased risk was accentuated in the early afternoon, disappeared at night, extended to patients with different characteristics, involved crashes with diverse features, not apparent with cloudy weather, and contributed to about 5000 additional patient-days in hospital. The increased risk extended to patients with high crash severity as indicated by ambulance involvement, surgical procedures, length of hospital stay, intensive care unit admission, and patient mortality. The increased risk was not easily attributed to differences in alcohol consumption, driving distances, or anomalies of adverse weather. Bright sunlight is associated with an increased risk of a life-threatening motor vehicle crash. An awareness of this risk might inform driver education, trauma staffing, and safety warnings to prevent a life-threatening motor vehicle crash. Level of evidence: Epidemiologic Study, level III. PMID:28072708

  5. Effects of bright light treatment on psychomotor speed in athletes

    PubMed Central

    Tulppo, Mikko P.; Jurvelin, Heidi; Roivainen, Eka; Nissilä, Juuso; Hautala, Arto J.; Kiviniemi, Antti M.; Kiviniemi, Vesa J.; Takala, Timo

    2014-01-01

    Purpose: A recent study suggests that transcranial brain targeted light treatment via ear canals may have physiological effects on brain function studied by functional magnetic resonance imaging (fMRI) techniques in humans. We tested the hypothesis that bright light treatment could improve psychomotor speed in professional ice hockey players. Methods: Psychomotor speed tests with audio and visual warning signals were administered to a Finnish National Ice Hockey League team before and after 24 days of transcranial bright light or sham treatment. The treatments were given during seasonal darkness in the Oulu region (latitude 65 degrees north) when the strain on the players was also very high (10 matches during 24 days). A daily 12-min dose of bright light or sham (n = 11 for both) treatment was given every morning between 8 and 12 am at home with a transcranial bright light device. Mean reaction time and motor time were analyzed separately for both psychomotor tests. Analysis of variance for repeated measures adjusted for age was performed. Results: Time × group interaction for motor time with a visual warning signal was p = 0.024 after adjustment for age. In Bonferroni post-hoc analysis, motor time with a visual warning signal decreased in the bright light treatment group from 127 ± 43 to 94 ± 26 ms (p = 0.024) but did not change significantly in the sham group 121 ± 23 vs. 110 ± 32 ms (p = 0.308). Reaction time with a visual signal did not change in either group. Reaction or motor time with an audio warning signal did not change in either the treatment or sham group. Conclusion: Psychomotor speed, particularly motor time with a visual warning signal, improves after transcranial bright light treatment in professional ice-hockey players during the competition season in the dark time of the year. PMID:24860513

  6. Bright and dark excitons in semiconductor carbon nanotubes

    SciTech Connect

    Tretiak, Sergei

    2008-01-01

    We report electronic structure calculations of finite-length semiconducting carbon nanotubes using the time dependent density functional theory (TD-DFT) and the time dependent Hartree Fock (TD-HF) approach coupled with semiempirical AM1 and ZINDO Hamiltonians. We specifically focus on the energy splitting, relative ordering, and localization properties of the optically active (bright) and optically forbidden (dark) states from the lowest excitonic band of the nanotubes. These excitonic states are very important in competing radiative and non-radiative processes in these systems. Our analysis of excitonic transition density matrices demonstrates that pure DFT functionals overdelocalize excitons making an electron-hole pair unbound; consequently, excitonic features are not presented in this method. In contrast, the pure HF and A111 calculations overbind excitons inaccurately predicting the lowest energy state as a bright exciton. Changing AM1 with ZINDO Hamiltonian in TD-HF calculations, predicts the bright exciton as the second state after the dark one. However, in contrast to AM1 calculations, the diameter dependence of the excitation energies obtained by ZINDO does not follow the experimental trends. Finally, the TD-DFT approach incorporating hybrid functions with a moderate portion of the long-range HF exchange, such as B3LYP, has the most generality and predictive capacity providing a sufficiently accurate description of excitonic structure in finite-size nanotubes. These methods characterize four important lower exciton bands. The lowest state is dark, the upper band is bright, and the two other dark and nearly degenerate excitons lie in-between. Although the calculated energy splittings between the lowest dark and the bright excitons are relatively large ({approx}0.1 eV), the dense excitonic manifold below the bright exciton allows for fast non-radiative relaxation leasing to the fast population of the lowest dark exciton. This rationalizes the low

  7. RXS J16437+3402: A New Bright Cataclysmic Variable

    NASA Astrophysics Data System (ADS)

    Mickaelian, A. M.; Balayan, S. K.; Ilovaisky, S.; Chevalier, C.; Veron-Cetty, M. P.; Veron, P.

    The Second part of the FBS was devoted to search and study of blue stellar objects. Optical identifications have been made for a number of ROSAT sources to find new QSO and Sy candidates. One of the objects, RXS J16437+3402, appeared to be a bright (m = 15.2) and very interesting cataclysmic variable: the Byurakan 2.6 m and OHP 1.93 m observations in 2000 show rapid variations of brightness, colour, and spectral lines. The object is possibly a low-inclination SW Sextantis star.

  8. Laser ion source for high brightness heavy ion beam

    SciTech Connect

    Okamura, M.

    2016-09-01

    A laser ion source is known as a high current high charge state heavy ion source. But, we place great emphasis on the capability to realize a high brightness ion source. A laser ion source has a pinpoint small volume where materials are ionized and can achieve quite uniform low temperature ion beam. Those features may enable us to realize very small emittance beams. Furthermore, a low charge state high brightness laser ion source was successfully commissioned in Brookhaven National Laboratory in 2014. Now most of all the solid based heavy ions are being provided from the laser ion source for regular operation.

  9. Laser ion source for high brightness heavy ion beam

    DOE PAGES

    Okamura, M.

    2016-09-01

    A laser ion source is known as a high current high charge state heavy ion source. But, we place great emphasis on the capability to realize a high brightness ion source. A laser ion source has a pinpoint small volume where materials are ionized and can achieve quite uniform low temperature ion beam. Those features may enable us to realize very small emittance beams. Furthermore, a low charge state high brightness laser ion source was successfully commissioned in Brookhaven National Laboratory in 2014. Now most of all the solid based heavy ions are being provided from the laser ion sourcemore » for regular operation.« less

  10. A bright PPKTP waveguide source of polarization entangled photons

    SciTech Connect

    Fanto, Michael; Tison, Christoper C.; Holwand, Gregory A; Preble, Dr. Stefan F; Alsing, Paul; Smith IV, Amos M

    2015-01-01

    The need for bright efficient sources of entangled photons has been a subject of tremendous research over the last decade. Researchers have been working to increase the brightness and purity to help overcome the spontaneous nature of the sources. Periodic poling has been implemented to allow for the use of crystals that would not normally satisfy the phase matching conditions. Utilizing periodic poling and single mode waveguide confinement of the pump field has yielded extremely large effective nonlinearities in sources easily producing millions of photon pairs. Here we will demonstrate these large nonlinearity effects in a periodically poled potassium titanyl phosphate (PPKTP) waveguide as well as characterizing the source purity.

  11. Bright solitons in non-equilibrium coherent quantum matter

    PubMed Central

    Pinsker, F.; Flayac, H.

    2016-01-01

    We theoretically demonstrate a mechanism for bright soliton generation in spinor non-equilibrium Bose–Einstein condensates made of atoms or quasi-particles such as polaritons in semiconductor microcavities. We give analytical expressions for bright (half) solitons as minimizing functions of a generalized non-conservative Lagrangian elucidating the unique features of inter and intra-competition in non-equilibrium systems. The analytical results are supported by a detailed numerical analysis that further shows the rich soliton dynamics inferred by their instability and mutual cross-interactions. PMID:26997892

  12. Histogram Equalization with Variable Enhancement Degree for Preserving Mean Brightness

    NASA Astrophysics Data System (ADS)

    Kawakami, Takashi; Murahira, Kota; Taguchi, Akira

    The histogram equalization (HE) is one of the common methods used for improving contrast in digital images. However, this technique causes a fluctuation of mean brightness. The fluctuation leads to the flicker for video signal. In order to preserve the mean brightness, the dynamic histogram equalization (DHE) is proposed. In this letter, we propose a novel DHE which is called the DHE with variable enhancement degree (DHEwVED). This method can change from DHE to HE by turning one parameter. We also show the effectiveness of the proposed method.

  13. A Complete Sample of Long Bright Swift GRBs

    NASA Astrophysics Data System (ADS)

    Tagliaferri, G.; Salvaterra, R.; Campana, S.; Covino, S.; D'Avanzo, P.; Fugazza, D.; Ghirlanda, G.; Ghisellini, G.; Melandri, A.; Sbarufatti, B.; Vergani, S.; Nava, L.

    2013-07-01

    Starting from the Swift sample we defined a complete sub-sample of 58 bright long Gamma Ray Bursts (GRB), 52 of them (90%) with a redshift determination, in order to characterize their properties. This complete sample of bright long- GRBs allowed us to investigate their evolution with cosmic time and properties. We focused in particular on the GRB luminosity function, on the spectral-energy correlations of their prompt emission, on the nature of dark bursts and on possible correlations between the prompt and the X-ray afterglow properties.

  14. Erratum - the Lowest Surface Brightness Disc Galaxy Known

    NASA Astrophysics Data System (ADS)

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

    1988-11-01

    The paper "The lowest surface brightness disc galaxy known' by J.I. Davies, S. Phillipps and M.J. Disney was published in Mon. Not. R. astr. Soc. (1988), 231, 69p. The declination of the object given in section 2 of the paper is incorrect and should be changed to +19^deg^48'23". Thus the object cannot be identified with GP 1444 as in the original paper. To minimize confusion we propose to refer to the low surface brightness galaxy as GP 1444A.

  15. Laser ion source for high brightness heavy ion beam

    NASA Astrophysics Data System (ADS)

    Okamura, M.

    2016-09-01

    A laser ion source is known as a high current high charge state heavy ion source. However we place great emphasis on the capability to realize a high brightness ion source. A laser ion source has a pinpoint small volume where materials are ionized and can achieve quite uniform low temperature ion beam. Those features may enable us to realize very small emittance beams. In 2014, a low charge state high brightness laser ion source was successfully commissioned in Brookhaven National Laboratory. Now most of all the solid based heavy ions are being provided from the laser ion source for regular operation.

  16. Extremely Low Passive Microwave Brightness Temperatures Due to Thunderstorms

    NASA Technical Reports Server (NTRS)

    Cecil, Daniel J.

    2015-01-01

    Extreme events by their nature fall outside the bounds of routine experience. With imperfect or ambiguous measuring systems, it is appropriate to question whether an unusual measurement represents an extreme event or is the result of instrument errors or other sources of noise. About three weeks after the Tropical Rainfall Measuring Mission (TRMM) satellite began collecting data in Dec 1997, a thunderstorm was observed over northern Argentina with 85 GHz brightness temperatures below 50 K and 37 GHz brightness temperatures below 70 K (Zipser et al. 2006). These values are well below what had previously been observed from satellite sensors with lower resolution. The 37 GHz brightness temperatures are also well below those measured by TRMM for any other storm in the subsequent 16 years. Without corroborating evidence, it would be natural to suspect a problem with the instrument, or perhaps an irregularity with the platform during the first weeks of the satellite mission. Automated quality control flags or other procedures in retrieval algorithms could treat these measurements as errors, because they fall outside the expected bounds. But the TRMM satellite also carries a radar and a lightning sensor, both confirming the presence of an intense thunderstorm. The radar recorded 40+ dBZ reflectivity up to about 19 km altitude. More than 200 lightning flashes per minute were recorded. That same storm's 19 GHz brightness temperatures below 150 K would normally be interpreted as the result of a low-emissivity water surface (e.g., a lake, or flood waters) if not for the simultaneous measurements of such intense convection. This paper will examine records from TRMM and related satellite sensors including SSMI, AMSR-E, and the new GMI to find the strongest signatures resulting from thunderstorms, and distinguishing those from sources of noise. The lowest brightness temperatures resulting from thunderstorms as seen by TRMM have been in Argentina in November and December. For

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

    SciTech Connect

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

    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.

  18. Evaluation of Dengue NS1 Antigen Rapid Tests and ELISA Kits Using Clinical Samples

    PubMed Central

    Pal, Subhamoy; Dauner, Allison L.; Mitra, Indrani; Forshey, Brett M.; Garcia, Paquita; Morrison, Amy C.; Halsey, Eric S.; Kochel, Tadeusz J.; Wu, Shuenn-Jue L.

    2014-01-01

    Background 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. Methodology/Principal Findings 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%. Conclusions 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. PMID:25412170

  19. Effect of Lactobacillus acidophilus NS1 on plasma cholesterol levels in diet-induced obese mice.

    PubMed

    Song, M; Park, S; Lee, H; Min, B; Jung, S; Park, S; Kim, E; Oh, S

    2015-03-01

    We investigated the probiotic properties of Lactobacillus acidophilus NS1, such as acid resistance, bile tolerance, adherence to HT-29 cells, and cholesterol assimilation activity. In an animal study, 7-wk-old male C57BL/6 mice were fed a normal diet, a high-fat diet (HFD), or an HFD with L. acidophilus NS1 (ca. 1.0×10(8) cfu/mL) for 10 wk. Total cholesterol and low-density lipoprotein (LDL) cholesterol levels were significantly lower in mice fed an HFD with L. acidophilus NS1 than in those fed an HFD only, whereas high-density lipoprotein cholesterol levels were similar between these 2 groups. To understand the mechanism of the cholesterol-lowering effect of L. acidophilus NS1 on the HFD-mediated increase in plasma cholesterol levels, we determined mRNA levels of genes involved in cholesterol homeostasis in the liver. Expression of sterol regulatory element-binding protein 2 (Srebp2) and LDL receptor (Ldlr) in the liver was dramatically reduced in mice fed a HFD compared with those fed a normal diet. When L. acidophilus NS1 was administered orally to HFD-fed mice, an HFD-induced suppression of Srebp2 and Ldlr expression in the liver was abolished. These results suggest that the oral administration of L. acidophilus NS1 to mice fed an HFD increased the expression of Srebp2 and Ldlr in the liver, which was inhibited by high fat intake, thus leading to a decrease in plasma cholesterol levels. Lactobacillus acidophilus NS1 could be a useful probiotic microorganism for cholesterol-lowering dairy products and the improvement of hyperlipidemia and hepatic lipid metabolism.

  20. Macrocyclic Hepatitis C Virus NS3/4A Protease Inhibitors: An Overview of Medicinal Chemistry.

    PubMed

    Pillaiyar, Thanigaimalai; Namasivayam, Vigneshwaran; Manickam, Manoj

    2016-01-01

    Hepatitis C virus (HCV) is a causative agent of hepatitis C infectious disease that primarily affects the liver, ranging in severity from a mild illness lasting a few weeks to a lifelong illness. The 9.6 kb RNA genome of HCV encodes approximately 3000 amino acid polyprotein that must be processed by host and viral proteases into both structural (S) and non-structural (NS) proteins, respectively. Targeting the serine protease NS3 with an activating factor NS4A, i.e., NS3/4A has been considered as one of the most attractive targets for the development of anti-HCV therapy. Although there is no vaccine available, antiviral medicines cure approximately 90% of the persons with hepatitis C infection. On the other hand, efficacy of these medications can be hampered due to the rapid drug and cross resistances. To date, all developed HCV NS3/4A inhibitors are mainly peptide-based compounds derived from the cleavage products of substrate. Specifically macrocyclic peptidomimetics have rapidly emerged as a classical NS3/4A protease inhibitors for treating the HCV infection. This review highlights the development of macrocyclic anti-HCV NS3/4A protease, as well as clinically important inhibitors developed from linear peptides, discovered during the last 12 years (2003-2015) from all sources, including laboratory synthetic methods, virtual screening and structure-based molecular docking studies. We emphasize the rationale behind the design, study of structure-activity relationships, and mechanism of inhibitions and cellular effect of the macrocyclic inhibitors.

  1. Caveolin-1 in Lipid Rafts Interacts with Dengue Virus NS3 during Polyprotein Processing and Replication in HMEC-1 Cells

    PubMed Central

    García Cordero, Julio; León Juárez, Moisés; González-Y-Merchand, Jorge A.; Cedillo Barrón, Leticia; Gutiérrez Castañeda, Benito

    2014-01-01

    Lipid rafts are ordered microdomains within cellular membranes that are rich in cholesterol and sphingolipids. Caveolin (Cav-1) and flotillin (Flt-1) are markers of lipid rafts, which serve as an organizing center for biological phenomena and cellular signaling. Lipid rafts involvement in dengue virus (DENV) processing, replication, and assembly remains poorly characterized. Here, we investigated the role of lipid rafts after DENV endocytosis in human microvascular endothelial cells (HMEC-1). The non-structural viral proteins NS3 and NS2B, but not NS5, were associated with detergent-resistant membranes. In sucrose gradients, both NS3 and NS2B proteins appeared in Cav-1 and Flt-1 rich fractions. Additionally, double immunofluorescence staining of DENV-infected HMEC-1 cells showed that NS3 and NS2B, but not NS5, colocalized with Cav-1 and Flt-1. Furthermore, in HMEC-1cells transfected with NS3 protease, shown a strong overlap between NS3 and Cav-1, similar to that in DENV-infected cells. In contrast, double-stranded viral RNA (dsRNA) overlapped weakly with Cav-1 and Flt-1. Given these results, we investigated whether Cav-1 directly interacted with NS3. Cav-1 and NS3 co-immunoprecipitated, indicating that they resided within the same complex. Furthermore, when cellular cholesterol was depleted by methyl-beta cyclodextrin treatment after DENV entrance, lipid rafts were disrupted, NS3 protein level was reduced, besides Cav-1 and NS3 were displaced to fractions 9 and 10 in sucrose gradient analysis, and we observed a dramatically reduction of DENV particles release. These data demonstrate the essential role of caveolar cholesterol-rich lipid raft microdomains in DENV polyprotein processing and replication during the late stages of the DENV life cycle. PMID:24643062

  2. Replicative Functions of Minute Virus of Mice NS1 Protein Are Regulated In Vitro by Phosphorylation through Protein Kinase C

    PubMed Central

    Nüesch, Jürg P. F.; Dettwiler, Sabine; Corbau, Romuald; Rommelaere, Jean

    1998-01-01

    NS1, the major nonstructural protein of the parvovirus minute virus of mice, is a multifunctional phosphoprotein which is involved in cytotoxicity, transcriptional regulation, and initiation of viral DNA replication. For coordination of these various functions during virus propagation, NS1 has been proposed to be regulated by posttranslational modifications, in particular phosphorylation. Recent in vitro studies (J. P. F. Nüesch, R. Corbau, P. Tattersall, and J. Rommelaere, J. Virol. 72:8002–8012, 1998) provided evidence that distinct NS1 activities, notably the intrinsic helicase function, are modulated by the phosphorylation state of the protein. In order to study the dependence of the initiation of viral DNA replication on NS1 phosphorylation and to identify the protein kinases involved, we established an in vitro replication system that is devoid of endogenous protein kinases and is based on plasmid substrates containing the minimal left-end origins of replication. Cellular components necessary to drive NS1-dependent rolling-circle replication (RCR) were freed from endogenous serine/threonine protein kinases by affinity chromatography, and the eukaryotic DNA polymerases were replaced by the bacteriophage T4 DNA polymerase. While native NS1 (NS1P) supported RCR under these conditions, dephosphorylated NS1 (NS1O) was impaired. Using fractionated HeLa cell extracts, we identified two essential protein components which are able to phosphorylate NS1O, are enriched in protein kinase C (PKC), and, when present together, reactivate NS1O for replication. One of these components, containing atypical PKC, was sufficient to restore NS1O helicase activity. The requirement of NS1O reactivation for characteristic PKC cofactors such as Ca2+/phosphatidylserine or phorbol esters strongly suggests the involvement of this protein kinase family in regulation of NS1 replicative functions in vitro. PMID:9811734

  3. Development and characterization of a replicon-based phenotypic assay for assessing HCV NS4B from clinical isolates.

    PubMed

    Rajyaguru, Sonal; Yang, Huiling; Martin, Ross; Miller, Michael D; Mo, Hongmei

    2013-11-01

    The hepatitis C virus (HCV) NS4B inhibitors have shown potent inhibition of HCV replication in vitro. To assess the effect of viral diversity on the susceptibility to NS4B inhibitors, genotype (GT)-specific GT1a and GT1b replicon shuttle vectors were designed and created for cloning HCV NS4B genes from clinical isolates. For the GT1b NS4B shuttle vector, the S2204I adaptive mutation was introduced in NS5A to improve replication due to the replacement of the K1846T adaptive mutation in NS4B with NS4B from the clinical isolates. In addition to the adaptive mutations, a newly identified Huh-7 cell line, Huh-7-1C, which is highly permissive for both GT1a and GT1b replication, was used to further enhance the replication levels. HCV NS4B gene from clinical isolates was amplified and inserted into the corresponding GT1a and GT1b modified lab strain chimeric replicons. GT1a and GT1b chimeric replicons expressing diverse NS4B genes from corresponding subtypes of clinical isolates replicated at highly efficient levels for phenotypic analysis. Due to natural variation in their amino acid residues in NS4B, these isolates displayed varying drug susceptibilities to an NS4B inhibitor. In mixed populations with wild-type, the sensitivity of resistance detection of NS4B resistant mutants H94R and V105M was between 20% and 80%. The chimeric shuttle vectors can be used to characterize the activity of antiviral drugs targeting NS4B from diverse natural clinical isolates and aid in the development of novel compounds against HCV NS4B.

  4. Brightness Rural Electrification Program: Renewable Energy in China

    SciTech Connect

    Not Available

    2004-04-01

    Fact sheet describes China's New Brightness Rural Electrification Program to provide electricity for 23 million people in remote areas of China using renewable energy such as wind energy and solar power (photovoltaics). Targets, results, and progress are described. Regions targeted are Inner Mongolia, Tibet, and Gansu.

  5. RESPONSES OF BRIGHT, NORMAL, AND RETARDED CHILDREN TO LEARNING TASKS.

    ERIC Educational Resources Information Center

    CARRIER, NEIL A.; AND OTHERS

    THE RELATIONSHIPS AMONG THE VARIABLES OF INTELLIGENCE, LEARNING TASK PERFORMANCE, EMOTIONAL TENSION, AND TASK MOTIVATION WERE STUDIED. ABOUT 120 BRIGHT, NORMAL, AND RETARDED CHILDREN PERFORMED SIX TRIALS OF NUMBER LEARNING, CONCEPT FORMATION, PROBLEM SOLVING, PERCEPTUAL-MOTOR COORDINATION, AND VERBAL LEARNING TASKS. DURING THE LEARNING SESSIONS,…

  6. Proposal for a High-Brightness Pulsed Electron Source

    SciTech Connect

    Zolotorev, M.; Commins, E.D.; Heifets, S.; Sannibale, F.; /LBL, Berkeley /UC, Berkeley /SLAC

    2006-10-16

    We propose a novel scheme for a high-brightness pulsed electron source, which has the potential for many useful applications in electron microscopy, inverse photo-emission, low energy electron scattering experiments, and electron holography. A description of the proposed scheme is presented.

  7. Bright Sneezes and Dark Coughs, Loud Sunlight and Soft Moonlight.

    ERIC Educational Resources Information Center

    Marks, Lawrence E.

    1982-01-01

    In a series of four experiments, subjects used scales of loudness, pitch, and brightness to evaluate the meanings of a variety of synesthetic metaphors--expressions in which words or phrases describing experiences proper to one sense modality transfer their meaning to another modality. (Author/PN)

  8. Dynamical behaviour of photospheric bright points during merging

    NASA Astrophysics Data System (ADS)

    Criscuoli, S.; Stangalini, M.; Ermolli, I.; Zuccarello, F.; Cristaldi, A.; Falco, M.; Guglielmino, S.; Giorgi, F.

    2014-12-01

    We investigate the merging of bright points observed at high spatial and temporal resolution with CRISP/SST in a quiet region region. We analyze the MHD perturbations excited during the merging, their role in the energy budget of the magnetic structure and the potential role that they can play in heating the upper layers of the Sun's atmosphere.

  9. The "Brightness Rules" Alternative Conception for Light Bulb Circuits

    ERIC Educational Resources Information Center

    Bryan, Joel A.; Stuessy, Carol

    2006-01-01

    An alternative conception for the observed differences in light bulb brightness was revealed during an unguided inquiry investigation in which prospective elementary teachers placed identical bulbs in series, parallel, and combination direct current circuits. Classroom observations, document analyses, and video and audio transcriptions led to the…

  10. Apparatus Would Position Bright Spot On Projection Screen

    NASA Technical Reports Server (NTRS)

    Rayman, Marc D.

    1996-01-01

    Proposed apparatus aims beam of visible light at wavelength lambda(2) to create bright spot at desired position in image on projection screen. Intended to replace handheld laser and flashlight pointers lecturers sometimes use to indicate features in projected images. Beam of light cannot be inadvertently aimed toward audience.

  11. Scattering models for the solar infrared F-corona brightness

    NASA Astrophysics Data System (ADS)

    Davidson, W. C.; MacQueen, R. M.; Mann, I.

    1995-02-01

    Model calculations are made of the infrared brightness in the solar F-corona motivated by recent infrared solar eclipse observations. Two different approaches are employed to describe the scattering properties of interplanetary dust : Mie scattering theory and diffraction theory, with and without an isotropic scattering term. In addition. two different particle size distributions are used in the calculations and the resultant line of sight brightness is compared with observational data of the solar F-corona between 3 and 8 solar radii ( R) in the ecliptic plane. It is found that the use of diffraction theory without an isotropic scattering contribution gives a very poor match with the observations, for both assumed particle size distributions. However, both the diffraction theory including isotropic scattering and the Mie scattering theory agree reasonably with the observed brightness, and especially its radial slope within the corona. for the model size distribution which is dominated by large particles. Only Mie theory may be employed in describing the second model size distribution because diffraction theory poorly describes the scattering due to the small particles which dominate this size distribution. It is concluded that the derivation of particle size distributions from the F-coronal brightness is still ambiguous and a further analysis needs either improved observations, or the application of further reasonable physical assumptions.

  12. Variations in the Fe mineralogy of bright Martian soil

    NASA Technical Reports Server (NTRS)

    Murchie, Scott; Mustard, John; Erard, Stephane; Geissler, Paul; Singer, Robert

    1993-01-01

    Bright regions on Mars are interpreted as 'soil' derived by chemical alteration of crustal rocks, whose main pigmentary component is ferric oxide or oxyhydroxide. The mineralogy and mineralogic variability of ferric iron are important evidence for the evolution of Martian soil: mineralogy of ferric phases is sensitive to chemical conditions in their genetic environments, and the spatial distributions of different ferric phases would record a history of both chemical environments and physical mixing. Reflectance spectroscopic studies provide several types of evidence that discriminate possible pigmentary phases, including the position of a crystal field absorption near 0.9 microns and position and strengths of absorptions in the UV-visible wavelength region. Recent telescopic spectra and laboratory measurements of Mars soil analogs suggest that spectral features of bright soil can be explained based on a single pigmentary phase, hematite (alpha-Fe2O3), occurring in both 'nanophase' and more crystalline forms. Here we report on a systematic investigation of Martian bright regions using ISM imaging spectrometer data, in which we examined spatial variations in the position and shape of the approximately 0.9 microns absorption. We found both local and regional heterogeneities that indicate differences in Fe mineralogy. These results demonstrate that bright soils do not represent a single lithology that has been homogenized by eolian mixing, and suggest that weathering of soils in different geologic settings has followed different physical and chemical pathways.

  13. High Precision Photometry of Bright Transiting Exoplanet Hosts

    NASA Astrophysics Data System (ADS)

    Wilson, Maurice; Eastman, Jason; Johnson, John A.

    2016-01-01

    Within the past two decades, the successful search for exoplanets and the characterization of their physical properties have shown the immense progress that has been made towards finding planets with characteristics similar to Earth. For most exoplanets with a radius about the size of Earth, evaluating their physical properties, such as the mass, radius and equilibrium temperature, cannot be determined with satisfactory precision. The MINiature Exoplanet Radial Velocity Array (MINERVA) was recently built to obtain spectroscopic and photometric measurements to find, confirm, and characterize Earth-like exoplanets. MINERVA's spectroscopic survey targets the brightest, nearby stars which are well-suited to the array's capabilities, while its primary photometric goal is to search for transits around these bright targets. Typically, it is difficult to find satisfactory comparison stars within a telescope's field of view when the primary target is very bright. This issue is resolved by using one of MINERVA's telescopes to observe the primary bright star while the other telescopes observe a distinct field of view that contains satisfactory bright comparison stars. We describe the code used to identify nearby comparison stars, schedule the four telescopes, produce differential photometry from multiple telescopes, and show the first results from this effort.This work has been funded by the Ronald E. McNair Post-Baccalaureate Achievement Program, the ERAU Honors Program, the ERAU Undergraduate Research Spark Fund, and the Banneker Institute at the Harvard-Smithsonian Center for Astrophysics.

  14. iPTF discovery and identification of bright transients

    NASA Astrophysics Data System (ADS)

    Kupfer, Thomas; Ho, Anna; Karamehmetoglu, Emir; Petrushevska, Tanja; Adams, Scott; Neill, James D.; Walters, Richard; Cannella, Chris; Blagorodnova, Nadejda; Yan, Lin; Kulkarni, Shri

    2017-02-01

    The intermediate Palomar Transient Factory (ATel #4807) reports the discovery of the following bright transients. We report as ATel alerts all objects brighter than 19 mag. Our discoveries are reported in two filters: sdss-g and Mould-I, denoted as g, and I. Both are in the AB magnitude system.

  15. SKYMONITOR: A Global Network for Night Sky Brightness Measurements

    NASA Astrophysics Data System (ADS)

    McKenna, Dan; Davis, Donald; Boley, Paul

    2015-03-01

    We have deployed a network of autonomous photometers that continuously measures the night sky brightness in the visual region at two sky positions simultaneously, typically near the zenith and the second at an elevation angle of 20 degrees. The Photometers are calibrated as a network to better than 5.

  16. Aviation -- Where Career Opportunities are Bright, Counselor's Guide.

    ERIC Educational Resources Information Center

    Zaharevitz, Walter; Marshall, Jane N.

    This aviation occupations guide is designed for use as a unit as well as in conjunction with an aviation careers package of material that contains a film strip and recording. Chapter One contains the script of the film strip, Aviation--Where Career Opportunities are Bright, and includes all photographs used in the film strip plus numerous…

  17. iPTF discovery and classification of bright transients

    NASA Astrophysics Data System (ADS)

    Blagorodnova, Nadejda; Ho, Anna; Karamehmetoglu, Emir; Petrushevska, Tanja; Kupfer, Thomas; Adams, Scott; Cannella, Chris; Yan, Lin; Kasliwal, Mansi; Kulkarni, Shri; Neill, James D.; Walters, Richard

    2017-01-01

    The intermediate Palomar Transient Factory (ATel #4807) reports the discovery of the following bright transients. We report as ATel alerts all objects brighter than 19 mag. Our discoveries are reported in three filters: sdss-r, Mould-R and Mould-I, denoted as g, r and i. All three are in the AB magnitude system.

  18. Soil Moisture Active/Passive (SMAP) Forward Brightness Temperature Simulator

    NASA Technical Reports Server (NTRS)

    Peng, Jinzheng; Peipmeier, Jeffrey; Kim, Edward

    2012-01-01

    The SMAP is one of four first-tier missions recommended by the US National Research Council's Committee on Earth Science and Applications from Space (Earth Science and Applications from Space: National Imperatives for the Next Decade and Beyond, Space Studies Board, National Academies Press, 2007) [1]. It is to measure the global soil moisture and freeze/thaw from space. One of the spaceborne instruments is an L-band radiometer with a shared single feedhorn and parabolic mesh reflector. While the radiometer measures the emission over a footprint of interest, unwanted emissions are also received by the antenna through the antenna sidelobes from the cosmic background and other error sources such as the Sun, the Moon and the galaxy. Their effects need to be considered accurately, and the analysis of the overall performance of the radiometer requires end-to-end performance simulation from Earth emission to antenna brightness temperature, such as the global simulation of L-band brightness temperature simulation over land and sea [2]. To assist with the SMAP radiometer level 1B algorithm development, the SMAP forward brightness temperature simulator is developed by adapting the Aquarius simulator [2] with necessary modifications. This poster presents the current status of the SMAP forward brightness simulator s development including incorporating the land microwave emission model and its input datasets, and a simplified atmospheric radiative transfer model. The latest simulation results are also presented to demonstrate the ability of supporting the SMAP L1B algorithm development.

  19. Preparing Young Adolescents for a Bright Future--Right Now!

    ERIC Educational Resources Information Center

    Deering, Paul D.; Martin, Kathryn L.; Buelow, Stephanie M.; Hoffman, Jennifer T.; Cameli, Sandy; Martin, Matt; Walker, Robert E.; O'Neill, Tara B.

    2016-01-01

    We must prepare young adolescents for a bright future by examining all of our educational practices in terms of their current and future relevance. The education we provide our students must prepare them to address enormously complex issues involving demographics and international relations, environmental and human health, and the development and…

  20. Apollo experiment S-211 low brightness, astronomical photography

    NASA Technical Reports Server (NTRS)

    Mercer, R. D.

    1974-01-01

    The low brightness image analysis for the Apollo flights is reported. The objectives of Experiment S-21 are discussed along with the photographic equipment, and the data processing and analysis flow are presented. Photographic data for Apollo 14, 15, 16, and 17 are included.

  1. High brightness laser systems incorporating advanced laser bars

    NASA Astrophysics Data System (ADS)

    Strohmaier, Stephan; Vethake, Thilo; Gottdiener, Mark; Wunderlin, Jens; Negoita, Viorel; Li, Yufeng; Barnowski, Tobias; Gong, Tim; An, Haiyan; Treusch, Georg

    2013-02-01

    The performance of high power and high brightness systems has been developing and is developing fast. In the multi kW regime both very high spatial and spectral brightness systems are emerging. Also diode laser pumped and direct diode lasers are becoming the standard laser sources for many applications. The pump sources for thin Disk Laser systems at TRUMPF Photonics enabled by high power and efficiency laser bars are becoming a well established standard in the industry with over two thousand 8 kW Disk Laser pumps installed in TruDisk systems at the customer site. These systems have proven to be a robust and reliable industrial tool. A further increase in power and efficiency of the bar can be easily used to scale the TruDisk output power without major changes in the pump source design. This publication will highlight advanced laser systems in the multi kW range for both direct application and solid state laser pumping using specifically tailored diode laser bars for high spatial and/or high spectral brightness. Results using wavelength stabilization techniques suitable for high power CW laser system applications will be presented. These high power and high brightness diode laser systems, fiber coupled or in free space configuration, depending on application or customer need, typically operate in the range of 900 to 1070 nm wavelength.

  2. The 1997 Reference of Diffuse Night Sky Brightness

    NASA Technical Reports Server (NTRS)

    Leinert, C.; Bowyer, S.; Haikala, L. K.; Hanner, M. S.; Hauser, M. G.; Levasseur-Regourd, A. C.; Mann, I.; Mattila, K.; Reach, W. T.; Schlosser, W.; Staude, J. J.; Toller, G. N.; Weiland, J. L.; Weinberg, J. L.; Witt, A. N.

    1997-01-01

    In the following we present material in tabular and graphical form, with the aim to allow the non specialist to obtain a realistic estimate of the diffuse night sky brightness over a wide range of wavelengths from the far UV longward of Ly to the far-infrared.

  3. Finding Bright-Spot Coordinates in Television Images

    NASA Technical Reports Server (NTRS)

    Richardson, T. E.; Tietz, J. C.

    1985-01-01

    Circuit provides data for computer to calculate coordinates of bright spot of light in video image. Calculation performed while image being scanned, and results available immediately at end of video frame. Video-processing circuit has variety of potential uses in commerce and industry. For example, locates tagged-parts on factory assembly line or track airplane landing lights.

  4. Reducing Color/Brightness Interaction in Color Television

    NASA Technical Reports Server (NTRS)

    Marchman, Robert H.

    1987-01-01

    Proposed digitally sampled scan-conversion scheme for color television reduces unwanted interactions between chrominance and luminance signals. New scheme reduces luminance and chrominance bandwidth to increase frequency separation between signals. To avoid proportionally reducing horizontal brightness resolution and horizontal color resolution, horizontal interlace of luminance signal and two color-difference signals used.

  5. Structure-guided Discovery of a Novel Non-peptide Inhibitor of Dengue Virus NS2B-NS3 Protease.

    PubMed

    Li, Linfeng; Basavannacharya, Chandrakala; Chan, Kitti Wing Ki; Shang, Luqing; Vasudevan, Subhash G; Yin, Zheng

    2015-09-01

    Dengue fever is a fast emerging epidemic-prone viral disease caused by dengue virus serotypes 1-4. NS2B-NS3 protease of dengue virus is a validated target to develop antiviral agents. A major limitation in developing dengue virus protease inhibitors has been the lack of or poor cellular activity. In this work, we extracted and refined a pharmacophore model based on X-ray crystal structure and predicted binding patterns, followed by a three-dimensional flexible database filtration. These output molecules were screened according to a docking-based protocol, leading to the discovery of a compound with novel scaffold and good cell-based bioactivity that has potential to be further optimized. The discovery of this novel scaffold by combination of in silico methods suggests that structure-guided drug discovery can lead to the development of potent dengue virus protease inhibitors.

  6. SKYMONITOR: A Global Network for Sky Brightness Measurements

    NASA Astrophysics Data System (ADS)

    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.

  7. Quantification of NS1 dengue biomarker in serum via optomagnetic nanocluster detection

    NASA Astrophysics Data System (ADS)

    Antunes, Paula; Watterson, Daniel; Parmvi, Mattias; Burger, Robert; Boisen, Anja; Young, Paul; Cooper, Matthew A.; Hansen, Mikkel F.; Ranzoni, Andrea; Donolato, Marco

    2015-11-01

    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 architecture. The presence of the target antigen NS1 triggers MNP agglutination and the formation of nanoclusters with rapid kinetics enhanced by external magnetic actuation. The amount and size of the nanoclusters correlate with the target concentration and can be quantified using an optomagnetic readout 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 is implemented on a low-cost microfluidic disc the platform is suited for further expansion to multiplexed detection of a wide panel of biomarkers.

  8. Flavivirus NS1 protein in infected host sera enhances viral acquisition by mosquitoes

    PubMed Central

    Liu, Jianying; Liu, Yang; Nie, Kaixiao; Du, Senyan; Qiu, Jingjun; Pang, Xiaojing; Wang, Penghua; Cheng, Gong

    2016-01-01

    Summary The arbovirus life cycle involves viral transfer between a vertebrate host and an arthropod vector, and acquisition of virus from an infected mammalian host by a vector is an essential step in this process. Here, we report that flavivirus nonstructural protein-1 (NS1), which is abundantly secreted into the serum of an infected host, plays a critical role in flavivirus acquisition by mosquitoes. The presence of dengue virus (DENV) and Japanese encephalitis virus (JEV) NS1s in the blood of infected interferon alpha and gamma receptor-deficient mice (AG6) facilitated virus acquisition by their native mosquito vectors because the protein enabled the virus to overcome the immune barrier of the mosquito midgut. Active immunization of AG6 mice with a modified DENV NS1 reduced DENV acquisition by mosquitoes and protected mice against a lethal DENV challenge, suggesting that immunization with NS1 could reduce the number of virus-carrying mosquitoes as well as the incidence of flaviviral diseases. Our study demonstrates that flaviviruses utilize NS1 proteins produced during their vertebrate phases to enhance their acquisition by vectors, which might be a result of flavivirus evolution to adapt to multiple host environments. PMID:27562253

  9. The Many Faces of the Flavivirus NS5 Protein in Antagonism of Type I Interferon Signaling.

    PubMed

    Best, Sonja M

    2017-02-01

    The vector-borne flaviviruses cause severe disease in humans on every inhabited continent on earth. Their transmission by arthropods, particularly mosquitoes, facilitates large emergence events such as witnessed with Zika virus (ZIKV) or West Nile virus in the Americas. Every vector-borne flavivirus examined thus far that causes disease in humans, from dengue virus to ZIKV, antagonizes the host type I interferon (IFN-I) response by preventing JAK-STAT signaling, suggesting that suppression of this pathway is an important determinant of infection. The most direct and potent viral inhibitor of this pathway is the nonstructural protein NS5. However, the mechanisms utilized by NS5 from different flaviviruses are often quite different, sometimes despite close evolutionary relationships between viruses. The varied mechanisms of NS5 as an IFN-I antagonist are also surprising given that the evolution of NS5 is restrained by the requirement to maintain function of two enzymatic activities critical for virus replication, the methyltransferase and RNA-dependent RNA polymerase. This review discusses the different strategies used by flavivirus NS5 to evade the antiviral effects of IFN-I and how this information can be used to better model disease and develop antiviral countermeasures.

  10. Conclusions and future directions for the REiNS International Collaboration.

    PubMed

    Widemann, Brigitte C; Blakeley, Jaishri O; Dombi, Eva; Fisher, Michael J; Hanemann, Clemens O; Walsh, Karin S; Wolters, Pamela L; Plotkin, Scott R

    2013-11-19

    The Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration was established with the goal to develop consensus recommendations for the use of endpoints in neurofibromatosis (NF) clinical trials. This supplement includes the first series of REiNS recommendations for the use of patient-reported, functional, and visual outcomes, and for the evaluation of imaging response in NF clinical trials. Recommendations for neurocognitive outcome measures, the use of whole-body MRI in NF, the evaluation of potential biomarkers of disease, and the comprehensive evaluation of functional and patient-reported outcomes in NF are in development. The REiNS recommendations are made based on current knowledge. Experience with the use of the recommended endpoints in clinical trials, development of new tools and technologies, new knowledge of the natural history of NF, and advances in the methods used to analyze endpoints will likely lead to modifications of the currently proposed guidelines, which will be shared with the NF research community through the REiNS Web site www.reinscollaboration.org. Due to the clinical complexity of NF, there is a need to seek expertise from multiple medical disciplines, regulatory agencies, and industry to develop trial endpoints and designs, which will lead to the identification and approval of effective treatments for NF tumor and nontumor manifestations. The REiNS Collaboration welcomes anyone interested in providing his or her expertise toward this effort.

  11. Radiative Properties of High Wire Number Tungsten Arrays with Implosion Times up to 250 ns

    SciTech Connect

    Beg, F.N.; Coverdale, C.A.; Deeney, C.; Douglas, M.R.; Haines, M.G.; Peterson, D.L.; Roderick, N.F.; Ruiz-Camacho, J.; Spielman, R.B.; Struve, K.W.; Stygar, W.A.

    1999-02-02

    High wire number, 25-mm diameter tungsten wire arrays have been imploded on the 8-MA Saturn generator, operating in a long-pulse mode. By varying the mass load from 710 to 6140 ps/cm, implosion times of 130 to 250 ns have been obtained with implosion velocities of 50 to 25 cn-dys, respectively. These z-pinch implosions produced plasmas with millimeter diameters that radiated 600 to 800 kJ of x-rays, with powers of 20 to 49 TW; the corresponding pulse widths were 19 to 7.5 ns, with risetimes ranging from 6.5 to 4.0 ns. These powers and pulse widths are similar to those achieved with 50 ns implosion times on Saturn. Two-dimensional, radiation- magnetohydrodynamic calculations indicate that the imploding shells in these long implosion time experiments are comparable in width to those in the short pulse cases. This can only be due to lower initial perturbations. A heuristic wire array model suggests that the reduced perturbations, in the long pulse cases, may be due to the individual wire merger occurring well before the acceleration of the shell. The experiments and modeling suggest that 150 to 200 ns implosion time z-pinches could be employed for high-power, x-ray source applications.

  12. Glycosylation-related genes in NS0 cells are insensitive to moderately elevated ammonium concentrations.

    PubMed

    Brodsky, Arthur Nathan; Caldwell, Mary; Bae, Sooneon; Harcum, Sarah W

    2014-10-10

    NS0 and Chinese hamster ovary (CHO) cell lines are used to produce recombinant proteins for human therapeutics; however, ammonium accumulation can negatively impact cell growth, recombinant protein production, and protein glycosylation. To improve product quality and decrease costs, the relationship between ammonium and protein glycosylation needs to be elucidated. While ammonium has been shown to adversely affect glycosylation-related gene expression in CHO cells, NS0 studies have not been performed. Therefore, this study sought to determine if glycosylation in NS0 cells were ammonium-sensitive at the gene expression level. Using a DNA microarray that contained mouse glycosylation-related and housekeeping genes, these genes were analyzed in response to various culture conditions - elevated ammonium, elevated salt, and elevated ammonium with proline. Surprisingly, no significant differences in gene expression levels were observed between the control and these conditions. Further, the elevated ammonium cultures were analyzed using real-time quantitative reverse transcriptase PCR (qRT-PCR) for key glycosylation genes, and the qRT-PCR results corroborated the DNA microarray results, demonstrating that NS0 cells are ammonium-insensitive at the gene expression level. Since NS0 are known to have elevated nucleotide sugar pools under ammonium stress, and none of the genes directly responsible for these metabolic pools were changed, consequently cellular control at the translational or substrate-level must be responsible for the universally observed decreased glycosylation quality under elevated ammonium.

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

    PubMed Central

    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

  14. Modeling feedback loops in the H-NS-mediated regulation of the Escherichia coli bgl operon.

    PubMed

    Radde, Nicole; Gebert, Jutta; Faigle, Ulrich; Schrader, Rainer; Schnetz, Karin

    2008-01-21

    The histone-like nucleoid-associated protein H-NS is a global transcriptional repressor that controls approximately 5% of all genes in Escherichia coli and other enterobacteria. H-NS binds to DNA with low specificity. Nonetheless, repression of some loci is exceptionally specific. Experimental data for the E. coli bgl operon suggest that highly specific repression is caused by regulatory feedback loops. To analyze whether such feedback loops can account for the observed specificity of repression, here a model was built based on expression data. The model includes several regulatory interactions, which are synergy of repression by binding of H-NS to two regulatory elements, an inverse correlation of the rate of repression by H-NS and transcription, and a threshold for positive regulation by anti-terminator BglG, which is encoded within the operon. The latter two regulatory interactions represent feedback loops in the model. The resulting system of equations was solved for the expression level of the operon and analyzed with respect to different promoter activities. This analysis demonstrates that a small (3-fold) increase of the bgl promoter activity results in a strong (80-fold) enhancement of bgl operon expression. Thus, the parameters included into the model are sufficient to simulate specific repression by H-NS.

  15. Quantification of NS1 dengue biomarker in serum via optomagnetic nanocluster detection

    PubMed Central

    Antunes, Paula; Watterson, Daniel; Parmvi, Mattias; Burger, Robert; Boisen, Anja; Young, Paul; Cooper, Matthew A.; Hansen, Mikkel F.; Ranzoni, Andrea; Donolato, Marco

    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 architecture. The presence of the target antigen NS1 triggers MNP agglutination and the formation of nanoclusters with rapid kinetics enhanced by external magnetic actuation. The amount and size of the nanoclusters correlate with the target concentration and can be quantified using an optomagnetic readout 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 is implemented on a low-cost microfluidic disc the platform is suited for further expansion to multiplexed detection of a wide panel of biomarkers. PMID:26536916

  16. Interferon resistance promotes oncolysis by influenza virus NS1-deletion mutants.

    PubMed

    Muster, Thomas; Rajtarova, Julia; Sachet, Monika; Unger, Hermann; Fleischhacker, Reinhard; Romirer, Ingrid; Grassauer, Andreas; Url, Angelika; García-Sastre, Adolfo; Wolff, Klaus; Pehamberger, Hubert; Bergmann, Michael

    2004-05-20

    NS1 protein of influenza virus is a virulence factor that counteracts Type I interferon (IFN)-mediated antiviral response by the host. A recombinant influenza A virus that lacks the NS1 protein only replicates efficiently in systems that contain defective IFN pathways. We demonstrate that the conditional replication properties of NS1-modified influenza A virus mutants can be exploited for the virus-mediated oncolysis of IFN-resistant tumor cells. IFN resistance in analyzed tumor cell lines correlated with a reduced expression of STAT1. Addition of exogenous IFNalpha or supernatant of virus-infected endothelial cells inhibited viral oncolysis in IFN-sensitive but not in IFN-resistant cell lines. The oncolytic potential of NS1-modified influenza A virus mutants could be exploited in vivo in a SCID mouse model of a subcutaneously-implanted human IFN-resistant melanoma. The data indicate that IFN-resistant tumors are a suitable target for oncolysis induced by NS1-modified influenza virus mutants. STAT1 might serve as a marker to identify these IFN-resistant tumors.

  17. Discrepancy between Hepatitis C Virus Genotypes and NS4-Based Serotypes: Association with Their Subgenomic Sequences

    PubMed Central

    Win, Nan Nwe; Nakamoto, Shingo; Kanda, Tatsuo; Takahashi, Hiroki; Takahashi-Nakaguchi, Azusa; Yasui, Shin; Nakamura, Masato; Wu, Shuang; Imazeki, Fumio; Mikami, Shigeru; Yokosuka, Osamu; Gonoi, Tohru; Shirasawa, Hiroshi

    2017-01-01

    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. PMID:28106726

  18. HCV NS5A co-operates with PKR in modulating HCV IRES-dependent translation.

    PubMed

    Karamichali, Eirini; Foka, Pelagia; Tsitoura, Eliza; Kalliampakou, Katerina; Kazazi, Dorothea; Karayiannis, Peter; Georgopoulou, Urania; Mavromara, Penelope

    2014-08-01

    Translation initiation of the Hepatitis C virus (HCV) genome is driven by an internal ribosome entry site (IRES), located within the 5' non-coding region. Several studies have suggested that different cellular non canonical proteins or viral proteins can regulate the HCV IRES activity. However, the role of the viral proteins on HCV translation remains controversial. In this report, we confirmed previous studies showing that NS5A down-regulates IRES activity in HepG2 but not in Huh7 cells suggesting that the NS5A effect on HCV IRES is cell-type dependent. Additionally, we provide strong evidence that activated PKR up-regulates the IRES activity while silencing of endogenous PKR had the opposite effect. Furthermore, we present data indicating that the NS5A-mediated inhibitory effect on IRES-dependent translation could be linked with the PKR inactivation. Finally, we show that NS5A from GBV-C but not from GBV-B down-regulates HCV IRES activity in the absence or the presence of PKR over expression. Notably, HCV and GBV-C but not GBV-B NS5A contains a previously identified PKR interacting protein domain.

  19. Structural characterization of the H-NS protein from Xylella fastidiosa and its interaction with DNA.

    PubMed

    Rosselli-Murai, Luciana K; Sforça, Maurício L; Sassonia, Rogério C; Azzoni, Adriano R; Murai, Marcelo J; de Souza, Anete P; Zeri, Ana C

    2012-10-01

    The nucleoid-associated protein H-NS is a major component of the bacterial nucleoid involved in DNA compaction and transcription regulation. The NMR solution structure of the Xylella fastidiosa H-NS C-terminal domain (residues 56-134) is presented here and consists of two beta-strands and two alpha helices, with one loop connecting the two beta-strands and a second loop connecting the second beta strand and the first helix. The amide (1)H and (15)N chemical shift signals for a sample of XfH-NS(56-134) were monitored in the course of a titration series with a 14-bp DNA duplex. Most of the residues involved in contacts to DNA are located around the first and second loops and in the first helix at a positively charged side of the protein surface. The overall structure of the Xylella H-NS C-terminal domain differ significantly from Escherichia coli and Salmonella enterica H-NS proteins, even though the DNA binding motif in loop 2 adopt similar conformation, as well as β-strand 2 and loop 1. Interestingly, we have also found that the DNA binding site is expanded to include helix 1, which is not seen in the other structures.

  20. Characterization of methicillin-resistant coagulase-negative staphylococci (MRCoNS) in retail meat.

    PubMed

    Bhargava, Kanika; Zhang, Yifan

    2014-09-01

    This study was to understand the extent of methicillin-resistant coagulase-negative staphylococci (MRCoNS) serving as a mecA reservoir in retail meat. MRCoNS were isolated from retail meat (beef, chicken, and turkey) in Detroit and characterized by sodA gene sequencing for species identification, staphylococcal cassette chromosome mec (SCCmec) typing, and pulsed-field gel electrophoresis (PFGE). Unique MRCoNS isolates recovered from 25 meat samples were comprised of Staphylococcus sciuri (n = 13), Staphylococcus fleuretti (n = 4), Staphylococcus lentus (n = 3), Staphylococcus epidermidis (n = 2), Staphylococcus vitulinus (n = 1), Staphylococcus saprophyticus (n = 1) and Staphylococcus pasteuri (n = 1). Heterogeneous and composite SCCmec types, including I, III, IV, V, I + V and III + V were identified in 16 isolates. Same SCCmec types were recovered in different staphylococcal species and meat sources. Indistinguishable PFGE patterns were also observed in S. sciuri isolated from beef, chicken, and turkey, and with different SCCmec types. In conclusion, multiple CoNS species can serve as reservoirs for mecA. In addition to the clonal transmission of MRCoNS in meat, horizontal occurrence of SCCmec is observed in staphylococcal species.

  1. Structure-function relationship of Chikungunya nsP2 protease: A comparative study with papain.

    PubMed

    Ramakrishnan, Chandrasekaran; Kutumbarao, Nidamarthi H V; Suhitha, Sivasubramanian; Velmurugan, Devadasan

    2016-11-07

    Chikungunya virus is a growing human pathogen transmitted by mosquito bite. It causes fever, chills, nausea, vomiting, joint pain, headache, and swelling in the joints. Its replication and propagation depend on the protease activity of the Chikungunya virus-nsP2 protein, which cleaves the nsP1234 polyprotein replication complex into individual functional units. The N-terminal segment of papain is structurally identical with the Chikungunya virus-nsP2 protease. Hence, molecular dynamics simulations were performed to compare molecular mechanism of these proteases. The Chikungunya virus-snP2 protease shows more conformational changes and adopts an alternate conformation. However, N-terminal segment of these two proteases has identical active site scaffold with the conserved catalytic diad. Hence, some of the non-peptide inhibitors of papain were used for induced fit docking at the active site of the nsP2 to assess the binding mode. In addition, the peptides that connect different domains/protein in Chikungunya virus poly-protein were also subjected for docking. The overall results suggest that the active site scaffold is the same in both the proteases and a possibility exists to experimentally assess the efficacy of some of the papain inhibitors to inhibit the Chikungunya virus-nsP2.

  2. Dynamic resetting of the human circadian pacemaker by intermittent bright light

    NASA Technical Reports Server (NTRS)

    Rimmer, D. W.; Boivin, D. B.; Shanahan, T. L.; Kronauer, R. E.; Duffy, J. F.; Czeisler, C. A.

    2000-01-01

    In humans, experimental studies of circadian resetting typically have been limited to lengthy episodes of exposure to continuous bright light. To evaluate the time course of the human endogenous circadian pacemaker's resetting response to brief episodes of intermittent bright light, we studied 16 subjects assigned to one of two intermittent lighting conditions in which the subjects were presented with intermittent episodes of bright-light exposure at 25- or 90-min intervals. The effective duration of bright-light exposure was 31% or 63% compared with a continuous 5-h bright-light stimulus. Exposure to intermittent bright light elicited almost as great a resetting response compared with 5 h of continuous bright light. We conclude that exposure to intermittent bright light produces robust phase shifts of the endogenous circadian pacemaker. Furthermore, these results demonstrate that humans, like other species, exhibit an enhanced sensitivity to the initial minutes of bright-light exposure.

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

    PubMed Central

    Upadhyay, Anup K.; Longenecker, Kenton; Tripathi, Rakesh; Sun, Chaohong; Kempf, Dale J.

    2017-01-01

    The rapid spread of the recent Zika virus (ZIKV) epidemic across various countries in the American continent poses a major health hazard for the unborn fetuses of pregnant women. To date, there is no effective medical intervention. The nonstructural protein 5 of Zika virus (ZIKV-NS5) is critical for ZIKV replication through the 5′-RNA capping and RNA polymerase activities present in its N-terminal methyltransferase (MTase) and C-terminal RNA-dependent RNA polymerase (RdRp) domains, respectively. The crystal structure of the full-length ZIKV-NS5 protein has been determined at 3.05 Å resolution from a crystal belonging to space group P21212 and containing two protein molecules in the asymmetric unit. The structure is similar to that reported for the NS5 protein from Japanese encephalitis virus and suggests opportunities for structure-based drug design targeting either its MTase or RdRp domain. PMID:28291746

  4. Comparison of HCV NS3 protease and NS5B polymerase inhibitor activity in 1a, 1b and 2a replicons and 2a infectious virus.

    PubMed

    Paulson, Matthew S; Yang, Huiling; Shih, I-hung; Feng, Joy Y; Mabery, Eric M; Robinson, Margaret F; Zhong, Weidong; Delaney, William E

    2009-08-01

    The hepatitis C virus infection system represents an important new tool for drug discovery. In this study, we compared the in vitro antiviral efficacy of several NS3 and NS5B inhibitors in genotype 1a, 1b, and 2a replicons and in the 2a infectious virus system. The nucleoside inhibitor 2'-C-methyl adenosine showed similar efficacy in each system tested. Three non-nucleoside inhibitors had small differences in potency between genotype 1a and 1b. In contrast, there was a dramatic loss of potency for these non-nucleoside inhibitors in the genotype 2a replicon, 2a infectious virus, and 2a NS5B biochemical assays. The protease inhibitor BILN-2061 had similar efficacy against 1a and 1b replicons but was 61-109-fold less potent against the 2a replicon and virus, respectively. VX-950, a covalent protease inhibitor, had similar efficacy (<3-fold changes in EC(50)) regardless of genotype or subtype. Importantly, we observed a significant correlation (p<0.0001) in antiviral potency between the 2a replicon and 2a infectious virus for all classes of compounds tested.

  5. High Speed Optical Photometry of LMXBs and CVs

    NASA Astrophysics Data System (ADS)

    Mason, Paul A.; Robinson, Edward L.; Gomez, Sebastian; Gonzalez, Emmanuel; Lopez, Isaac D.; Monroy, Lorena; Price, Alex

    2013-02-01

    High speed photometry of several accreting binaries was obtained using the McDonald Observatory 2.1m telescope and ARGOS CCD photometer. A broad-band filter (BVR) was used in order to maximize flux and maintain a short (1-10s) integration time on faint targets. Such observations obtained over several years allow for variability study over time scales covering many orders of magnitude. Observations and analysis for several binaries are summarized.

  6. CHD3 facilitates vRNP nuclear export by interacting with NES1 of influenza A virus NS2.

    PubMed

    Hu, Yong; Liu, Xiaokun; Zhang, Anding; Zhou, Hongbo; Liu, Ziduo; Chen, Huanchun; Jin, Meilin

    2015-03-01

    NS2 from influenza A virus mediates Crm1-dependent vRNP nuclear export through interaction with Crm1. However, even though the nuclear export signal 1 (NES1) of NS2 does not play a requisite role in NS2-Crm1 interaction, there is no doubt that NES1 is crucial for vRNP nuclear export. While the mechanism of the NES1 is still unclear, it is speculated that certain host partners might mediate the NES1 function through their interaction with NES1. In the present study, chromodomain-helicase-DNA-binding protein 3 (CHD3) was identified as a novel host nuclear protein for locating NS2 and Crm1 on dense chromatin for NS2 and Crm1-dependent vRNP nuclear export. CHD3 was confirmed to interact with NES1 in NS2, and a disruption to this interaction by mutation in NES1 significantly delayed viral vRNPs export and viral propagation. Further, the knockdown of CHD3 would affect the propagation of the wild-type virus but not the mutant with the weakened NS2-CHD3 interaction. Therefore, this study demonstrates that NES1 is required for maximal binding of NS2 to CHD3, and that the NS2-CHD3 interaction on the dense chromatin contributed to the NS2-mediated vRNP nuclear export.

  7. Assessing positivity and circulating levels of NS1 in samples from a 2012 dengue outbreak in Rio de Janeiro, Brazil.

    PubMed

    Allonso, Diego; Meneses, Marcelo D F; Fernandes, Carlos A; Ferreira, Davis F; Mohana-Borges, Ronaldo

    2014-01-01

    Dengue virus (DENV) represents a major threat to public health worldwide. Early DENV diagnosis should not only detect the infection but also identify patients with a higher likelihood to develop severe cases. Previous studies have suggested the potential for NS1 to serve as a viral marker for dengue severity. However, further studies using different sera panels are required to confirm this hypothesis. In this context, we developed a lab-based ELISA to detect and quantitate NS1 protein from the four DENV serotypes and from primary and secondary cases. This approach was used to calculate the circulating NS1 concentration in positive samples. We also tested the NS1 positivity of DENV-positive samples according to the Platelia Dengue NS1 Ag assay. A total of 128 samples were positive for DENV infection and were classified according to the WHO guidelines. The overall NS1 positivity was 68% according to the Platelia assay, whereas all samples were NS1-positive when analyzed with our lab-based ELISA. Fifty-four samples were positive by PCR, revealing a co-circulation of DENV1 and DENV4, and the NS1 positivity for DENV4 samples was lower than that for DENV1. The circulating NS1 concentration ranged from 7 to 284 ng/mL. Our results support previous data indicating the low efficiency of the Platelia assay to detect DENV4 infection. Moreover, this work is the first to analyze NS1 antigenemia using retrospective samples from a Brazilian outbreak.

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

    PubMed Central

    Jumat, Muhammad Raihan; Wong, Puisan; Lee, Raphael Tze Chuen; Maurer-Stroh, Sebastian; Tan, Boon Huan

    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. PMID:28348873

  9. Adaptation of NS cells growth and differentiation to high-throughput screening-compatible plates

    PubMed Central

    2010-01-01

    Background There is an urgent need of neuronal cell models to be applied to high-throughput screening settings while recapitulating physiological and/or pathological events occurring in the Central Nervous System (CNS). Stem cells offer a great opportunity in this direction since their self renewal capacity allows for large scale expansion. Protocols for directed differentiation also promise to generate populations of biochemically homogenous neuronal progenies. NS (Neural Stem) cells are a novel population of stem cells that undergo symmetric cell division in monolayer and chemically defined media, while remaining highly neurogenic. Results We report the full adaptation of the NS cell systems for their growth and neuronal differentiation to 96- and 384-well microplates. This optimized system has also been exploited in homogeneous and high-content assays. Conclusions Our results show that these mouse NS cells may be suitable for a series of applications in high-throughput format. PMID:20085655

  10. Producing human ceramide-NS by metabolic engineering using yeast Saccharomyces cerevisiae

    PubMed Central

    Murakami, Suguru; Shimamoto, Toshi; Nagano, Hideaki; Tsuruno, Masahiro; Okuhara, Hiroaki; Hatanaka, Haruyo; Tojo, Hiromasa; Kodama, Yukiko; Funato, Kouichi

    2015-01-01

    Ceramide is one of the most important intercellular components responsible for the barrier and moisture retention functions of the skin. Because of the risks involved with using products of animal origin and the low productivity of plants, the availability of ceramides is currently limited. In this study, we successfully developed a system that produces sphingosine-containing human ceramide-NS in the yeast Saccharomyces cerevisiae by eliminating the genes for yeast sphingolipid hydroxylases (encoded by SUR2 and SCS7) and introducing the gene for a human sphingolipid desaturase (encoded by DES1). The inactivation of the ceramidase gene YDC1, overexpression of the inositol phosphosphingolipid phospholipase C gene ISC1, and endoplasmic reticulum localization of the DES1 gene product resulted in enhanced production of ceramide-NS. The engineered yeast strains can serve as hosts not only for providing a sustainable source of ceramide-NS but also for developing further systems to produce sphingosine-containing sphingolipids. PMID:26573460

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

    SciTech Connect

    Kim, Kyoung Mi; Kwon, Shi-Nae; Kang, Ju-Il; Lee, Song Hee; Jang, Sung Key; Ahn, Byung-Yoon; Kim, Yoon Ki . E-mail: yk-kim@korea.ac.kr

    2007-05-18

    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. Potent inhibitors of HCV-NS3 protease derived from boronic acids

    SciTech Connect

    Venkatraman, Srikanth; Wu, Wanli; Prongay, Andrew; Girijavallabhan, Viyyoor; Njoroge, F. George

    2009-07-23

    Chronic hepatitis C infection is the leading causes for cirrhosis of the liver and hepatocellular carcinoma, leading to liver failure and liver transplantation. The etiological agent, HCV virus produces a single positive strand of RNA that is processed with the help of serine protease NS3 to produce mature virus. Inhibition of NS3 protease can be potentially used to develop effective drugs for HCV infections. Numerous efforts are now underway to develop potent inhibitors of HCV protease that contain ketoamides as serine traps. Herein we report the synthesis of a series of potent inhibitors that contain a boronic acid as a serine trap. The activity of these compounds were optimized to 200 pM. X-ray structure of compound 17 bound to NS3 protease is also discussed.

  13. H-NS: an overarching regulator of the Vibrio cholerae life cycle.

    PubMed

    Ayala, Julio C; Silva, Anisia J; Benitez, Jorge A

    2017-01-01

    Vibrio cholerae has become a model organism for studies connecting virulence, pathogen evolution and infectious disease ecology. The coordinate expression of motility, virulence and biofilm enhances its pathogenicity, environmental fitness and fecal-oral transmission. The histone-like nucleoid structuring protein negatively regulates gene expression at multiple phases of the V. cholerae life cycle. Here we discuss: (i) the regulatory and structural implications of H-NS chromatin-binding in the two-chromosome cholera bacterium; (ii) the factors that counteract H-NS repression; and (iii) a model for the regulation of the V. cholerae life cycle that integrates H-NS repression, cyclic diguanylic acid signaling and the general stress response.

  14. Producing human ceramide-NS by metabolic engineering using yeast Saccharomyces cerevisiae.

    PubMed

    Murakami, Suguru; Shimamoto, Toshi; Nagano, Hideaki; Tsuruno, Masahiro; Okuhara, Hiroaki; Hatanaka, Haruyo; Tojo, Hiromasa; Kodama, Yukiko; Funato, Kouichi

    2015-11-17

    Ceramide is one of the most important intercellular components responsible for the barrier and moisture retention functions of the skin. Because of the risks involved with using products of animal origin and the low productivity of plants, the availability of ceramides is currently limited. In this study, we successfully developed a system that produces sphingosine-containing human ceramide-NS in the yeast Saccharomyces cerevisiae by eliminating the genes for yeast sphingolipid hydroxylases (encoded by SUR2 and SCS7) and introducing the gene for a human sphingolipid desaturase (encoded by DES1). The inactivation of the ceramidase gene YDC1, overexpression of the inositol phosphosphingolipid phospholipase C gene ISC1, and endoplasmic reticulum localization of the DES1 gene product resulted in enhanced production of ceramide-NS. The engineered yeast strains can serve as hosts not only for providing a sustainable source of ceramide-NS but also for developing further systems to produce sphingosine-containing sphingolipids.

  15. Direct interaction between alpha-actinin and hepatitis C virus NS5B.

    PubMed

    Lan, Shuiyun; Wang, Hua; Jiang, Hong; Mao, Hongxia; Liu, Xiaoying; Zhang, Xiaonan; Hu, Yunwen; Xiang, Li; Yuan, Zhenghong

    2003-11-20

    It has been suggested that cellular proteins are involved in hepatitis C virus (HCV) RNA replication. By using the yeast two-hybrid system, we isolated seven cDNA clones encoding proteins interacting with HCV RNA polymerase (NS5B) from a human liver cDNA library. For one of these, alpha-actinin, we confirmed the interaction by coimmunoprecipitation, immunofluorescent staining and confocal microscopic analysis. Experiments with deletion mutants showed that domains NS5B(84-95), NS5B(466-478), and alpha-actinin(621-733) are responsible for the interaction. Studies of the HCV subgenomic replicon system with small interference RNA indicate that alpha-actinin is essential for HCV RNA replication. Our results suggest alpha-actinin may be a component of the HCV replication complex.

  16. Preclinical Profile and Characterization of the Hepatitis C Virus NS3 Protease Inhibitor Asunaprevir (BMS-650032)

    PubMed Central

    Sheaffer, Amy K.; Friborg, Jacques; Hernandez, Dennis; Falk, Paul; Zhai, Guangzhi; Levine, Steven; Chaniewski, Susan; Yu, Fei; Barry, Diana; Chen, Chaoqun; Lee, Min S.; Mosure, Kathy; Sun, Li-Qiang; Sinz, Michael; Meanwell, Nicholas A.; Colonno, Richard J.; Knipe, Jay; Scola, Paul

    2012-01-01

    Asunaprevir (ASV; BMS-650032) is a hepatitis C virus (HCV) NS3 protease inhibitor that has demonstrated efficacy in patients chronically infected with HCV genotype 1 when combined with alfa interferon and/or the NS5A replication complex inhibitor daclatasvir. ASV competitively binds to the NS3/4A protease complex, with Ki values of 0.4 and 0.24 nM against recombinant enzymes representing genotypes 1a (H77) and 1b (J4L6S), respectively. Selectivity was demonstrated by the absence of any significant activity against the closely related GB virus-B NS3 protease and a panel of human serine or cysteine proteases. In cell culture, ASV inhibited replication of HCV replicons representing genotypes 1 and 4, with 50% effective concentrations (EC50s) ranging from 1 to 4 nM, and had weaker activity against genotypes 2 and 3 (EC50, 67 to 1,162 nM). Selectivity was again demonstrated by the absence of activity (EC50, >12 μM) against a panel of other RNA viruses. ASV exhibited additive or synergistic activity in combination studies with alfa interferon, ribavirin, and/or inhibitors specifically targeting NS5A or NS5B. Plasma and tissue exposures in vivo in several animal species indicated that ASV displayed a hepatotropic disposition (liver-to-plasma ratios ranging from 40- to 359-fold across species). Twenty-four hours postdose, liver exposures across all species tested were ≥110-fold above the inhibitor EC50s observed with HCV genotype-1 replicons. Based on these virologic and exposure properties, ASV holds promise for future utility in a combination with other anti-HCV agents in the treatment of HCV-infected patients. PMID:22869577

  17. Preclinical Characterization of BMS-791325, an Allosteric Inhibitor of Hepatitis C Virus NS5B Polymerase

    PubMed Central

    Liu, Mengping; Gentles, Robert G.; Ding, Min; Voss, Stacey; Pelosi, Lenore A.; Wang, Ying-Kai; Rigat, Karen L.; Mosure, Kathleen W.; Bender, John A.; Knipe, Jay O.; Colonno, Richard; Meanwell, Nicholas A.; Kadow, John F.; Santone, Kenneth S.; Roberts, Susan B.; Gao, Min

    2014-01-01

    BMS-791325 is an allosteric inhibitor that binds to thumb site 1 of the hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase. BMS-791325 inhibits recombinant NS5B proteins from HCV genotypes 1, 3, 4, and 5 at 50% inhibitory concentrations (IC50) below 28 nM. In cell culture, BMS-791325 inhibited replication of HCV subgenomic replicons representing genotypes 1a and 1b at 50% effective concentrations (EC50s) of 3 nM and 6 nM, respectively, with similar (3 to 18 nM) values for genotypes 3a, 4a, and 5a. Potency against genotype 6a showed more variability (9 to 125 nM), and activity was weaker against genotype 2 (EC50, 87 to 925 nM). Specificity was demonstrated by the absence of activity (EC50s of >4 μM) against a panel of mammalian viruses, and cytotoxic concentrations (50%) were >3,000-fold above the HCV EC50. Resistance substitutions selected by BMS-791325 in genotype 1 replicons mostly mapped to a single site, NS5B amino acid 495 (P495A/S/L/T). Additive or synergistic activity was observed in combination studies using BMS-791325 with alfa interferon plus ribavirin, inhibitors of NS3 protease or NS5A, and other classes of NS5B inhibitor (palm site 2-binding or nucleoside analogs). Plasma and liver exposures in vivo in several animal species indicated that BMS-791325 has a hepatotropic disposition (liver-to-plasma ratios ranging from 1.6- to 60-fold across species). Twenty-four hours postdose, liver exposures across all species tested were ≥10-fold above the inhibitor EC50s observed with HCV genotype 1 replicons. These findings support the evaluation of BMS-791325 in combination regimens for the treatment of HCV. Phase 3 studies are ongoing. PMID:24733465

  18. Three Conformational Snapshots of the Hepatitis Virus NS3 Helicase Reveal a Ratchet Translocation Mechanism

    SciTech Connect

    Gu, M.; Rice, C

    2010-01-01

    A virally encoded superfamily-2 (SF2) helicase (NS3h) is essential for the replication of hepatitis C virus, a leading cause of liver disease worldwide. Efforts to elucidate the function of NS3h and to develop inhibitors against it, however, have been hampered by limited understanding of its molecular mechanism. Here we show x-ray crystal structures for a set of NS3h complexes, including ground-state and transition-state ternary complexes captured with ATP mimics (ADP {center_dot} BeF{sub 3} and ADP {center_dot} AlF{sub 4}{sup -}). These structures provide, for the first time, three conformational snapshots demonstrating the molecular basis of action for a SF2 helicase. Upon nucleotide binding, overall domain rotation along with structural transitions in motif V and the bound DNA leads to the release of one base from the substrate base-stacking row and the loss of several interactions between NS3h and the 3{prime} DNA segment. As nucleotide hydrolysis proceeds into the transition state, stretching of a 'spring' helix and another overall conformational change couples rearrangement of the (d)NTPase active site to additional hydrogen-bonding between NS3h and DNA. Together with biochemistry, these results demonstrate a 'ratchet' mechanism involved in the unidirectional translocation and define the step size of NS3h as one base per nucleotide hydrolysis cycle. These findings suggest feasible strategies for developing specific inhibitors to block the action of this attractive, yet largely unexplored drug target.

  19. High dengue NS1 antigenemia in febrile patients in Ibadan, Nigeria.

    PubMed

    Oyero, Olufunmilayo G; Ayukekbong, James A

    2014-10-13

    We conducted a dengue seroprevalence survey among febrile patients positive or negative for malaria in Ibadan, Nigeria. Dengue IgG and NS1 seroprevalence of 73% and 35%, respectively, was observed, and 43% of those with malaria had acute dengue infection (NS1 determination). On the other hand, all participants with malaria were IgG dengue seropositive consistent with the endemicity of both arthropod-borne infections in the region. These data indicate that dengue is emerging as a major and neglected cause of fever in Nigeria.

  20. Hepatitis C Virus NS4B Can Suppress STING Accumulation To Evade Innate Immune Responses

    PubMed Central

    Wen, Yahong; Shu, Chang; Han, Qingxia; Konan, Kouacou V.; Li, Pingwei; Kao, C. Cheng

    2015-01-01

    ABSTRACT The cyclic dinucleotide 2′,3′-cGAMP can bind the adaptor protein STING (stimulator of interferon [IFN] genes) to activate the production of type I IFNs and proinflammatory cytokines. We found that cGAMP added to the culture medium could suppress the replication of the hepatitis C virus (HCV) genotype 1b strain Con1 subgenomic replicon in human hepatoma cells. Knockdown of STING expression diminished the inhibitory effect on replicon replication, while overexpression of STING enhanced the inhibitory effects of cGAMP. The addition of cGAMP into 1b/Con1 replicon cells significantly increased the expression of type I IFNs and antiviral interferon-stimulated genes. Unexpectedly, replication of the genotype 2a JFH1 replicon and infectious JFH1 virus was less sensitive to the inhibitory effect of cGAMP than was that of 1b/Con1 replicon. Using chimeric replicons, 2a NS4B was identified to confer resistance to cGAMP. Transient expression of 2a NS4B resulted in a pronounced inhibitory effect on STING-mediated beta IFN (IFN-β) reporter activation compared to that of 1b NS4B. 2a NS4B was found to suppress STING accumulation in a dose-dependent manner. The predicted transmembrane domain of 2a NS4B was required to inhibit STING accumulation. These results demonstrate a novel genotype-specific inhibition of the STING-mediated host antiviral immune response. IMPORTANCE The cyclic dinucleotide cGAMP was found to potently inhibit the replication of HCV genotype 1b Con1 replicon but was less effective for the 2a/JFH1 replicon and infectious JFH1 virus. The predicted transmembrane domain in 2a NS4B was shown to be responsible for the decreased sensitivity to cGAMP. The N terminus of NS4B has been reported to suppress STING-mediated signaling by disrupting the interaction of STING and TBK1 and/or MAVS. We show that 2a/JFH1 NS4B has an additional mechanism to evade STING signaling through suppressing STING accumulation. PMID:26468527

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

    PubMed

    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.

  2. Fragment-based discovery of hepatitis C virus NS5b RNA polymerase inhibitors

    SciTech Connect

    Antonysamy, Stephen S.; Aubol, Brandon; Blaney, Jeff; Browner, Michelle F.; Giannetti, Anthony M.; Harris, Seth F.; Hébert, Normand; Hendle, Jörg; Hopkins, Stephanie; Jefferson, Elizabeth; Kissinger, Charles; Leveque, Vincent; Marciano, David; McGee, Ethel; Nájera, Isabel; Nolan, Brian; Tomimoto, Masaki; Torres, Eduardo; Wright, Tobi

    2009-07-22

    Non-nucleoside inhibitors of HCV NS5b RNA polymerase were discovered by a fragment-based lead discovery approach, beginning with crystallographic fragment screening. The NS5b binding affinity and biochemical activity of fragment hits and inhibitors was determined by surface plasmon resonance (Biacore) and an enzyme inhibition assay, respectively. Crystallographic fragment screening hits with {approx}1-10 mM binding affinity (K{sub D}) were iteratively optimized to give leads with {approx}200 nM biochemical activity and low {micro}M cellular activity in a Replicon assay.

  3. A 0.2 ns beam pulse for the 6 MV Van de Graaff accelerator

    NASA Astrophysics Data System (ADS)

    McMurray, W. R.; Kritzinger, J. J.; Wikner, V. C.; Swart, T.; Schmitt, H.

    1984-01-01

    The 1.5 ns pulsed beam of the SUNI Van de Graaff accelerator has been used for neutron time-of-flight studies. To provide sufficient resolution for neutron scattering measurements at 22 MeV, a post-acceleration bunching system has been installed. Bunching of 2-6 MeV p, d and 3He beams is achieved in a simple quarter-wave coaxial resonator chamber designed for high Q and low power. The bunched pulse has a fwhm of less than 0.2 ns. The design and testing of the bunching system are outlined. Optimum power requirements are tabulated together with the induced beam energy spreads.

  4. Development and characterization of mouse monoclonal antibodies against monomeric dengue virus non-structural glycoprotein 1 (NS1).

    PubMed

    Gelanew, Tesfaye; Poole-Smith, B Katherine; Hunsperger, Elizabeth

    2015-09-15

    Dengue virus (DENV) nonstructural-1 (NS1) glycoprotein is useful for diagnosis of DENV infections in the first 8 days of illness with any of the four serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). However, NS1 diagnostics are less sensitive for secondary DENV infections so the utility of NS1 diagnostics in dengue endemic countries where there is predominantly secondary infections is being questioned. Heat-mediated immunecomplex dissociation (ICD) prior to testing serum samples can significantly improve NS1 test sensitivity in secondary infections but requires monoclonal antibodies (MAbs) reactive to heat-denatured NS1. In order to incorporate a simple heat-mediated ICD step, a crucial step was to develop new MAbs with high affinity and specificity to heat-denatured DENV NS1 protein. In the present study, six new MAbs were isolated from BALB/c mice immunized with recombinant monomeric NS1 of DENV-1 and DENV-2. Characterization using three different methods: indirect ELISA, fixed cell ELISA and western blot revealed that all six MAbs are serotype-cross-reactive and capable of recognizing dimeric and hexameric isoforms as well as heat-denatured NS1 from all four DENV serotypes. No cross-reactivity to NS1 of West Nile virus and Yellow fever virus was observed on western blot and indirect ELISA. Five of the six MAbs mapped to the DENV NS1 region of 105-119 amino acids. The remaining MAb mapped to DENV NS1 region of 25-39 amino acids. These two NS1 regions were found to be highly conserved among all four DENV serotypes by sequences analysis and database comparison. These MAbs were used to develop an NS1 capture ELISA and tested using a small panel of clinical specimens. The results from the NS1 capture ELISA indicated at least a three-fold increase in NS1 antigen detection in heat-denatured samples compared to untreated specimens. Furthermore, artificial immunecomplexed results also demonstrated the binding efficiency of these MAbs to heat denatured NS1. Taken together

  5. NS2 Proteins of GB Virus B and Hepatitis C Virus Share Common Protease Activities and Membrane Topologies

    PubMed Central

    Boukadida, Célia; Marnata, Caroline; Montserret, Roland; Cohen, Lisette; Blumen, Brigitte; Gouttenoire, Jérôme; Moradpour, Darius; Penin, François

    2014-01-01

    ABSTRACT GB virus B (GBV-B), which is hepatotropic in experimentally infected small New World primates, is a member of the Hepacivirus genus but phylogenetically relatively distant from hepatitis C virus (HCV). To gain insights into the role and specificity of hepaciviral nonstructural protein 2 (NS2), which is required for HCV polyprotein processing and particle morphogenesis, we investigated whether NS2 structural and functional features are conserved between HCV and GBV-B. We found that GBV-B NS2, like HCV NS2, has cysteine protease activity responsible for cleavage at the NS2/NS3 junction, and we experimentally confirmed the location of this junction within the viral polyprotein. A model for GBV-B NS2 membrane topology was experimentally established by determining the membrane association properties of NS2 segments fused to green fluorescent protein (GFP) and their nuclear magnetic resonance structures using synthetic peptides as well as by applying an N-glycosylation scanning approach. Similar glycosylation studies confirmed the HCV NS2 organization. Together, our data show that despite limited amino acid sequence similarity, GBV-B and HCV NS2 proteins share a membrane topology with 3 N-terminal transmembrane segments, which is also predicted to apply to other recently discovered hepaciviruses. Based on these data and using trans-complementation systems, we found that intragenotypic hybrid NS2 proteins with heterologous N-terminal membrane segments were able to efficiently trans-complement an assembly-deficient HCV mutant with a point mutation in the NS2 C-terminal domain, while GBV-B/HCV or intergenotypic NS2 chimeras were not. These studies indicate that virus- and genotype-specific intramolecular interactions between N- and C-terminal domains of NS2 are critically involved in HCV morphogenesis. IMPORTANCE Nonstructural protein 2 (NS2) of hepatitis C virus (HCV) is a multifunctional protein critically involved in polyprotein processing and virion

  6. Gene 5. 5 protein of bacteriophaze T7 inhibits the nucleoid protein H-NS of Escherichia coli

    SciTech Connect

    Liu, Q.; Richardson, C.C. )

    1993-03-01

    Gene 5.5 of coliphage T7 is one of the most highly expressed genes during T7 infection. Gene 5.5 protein, purified from cells overexpressing the cloned gene, purifies with the nucleoid protein H-NS of Escherichia coli during three chromatographic steps. A fusion protein of gene 5.5 protein and maltose binding protein also purifies with H-NS. The fusion protein binds to the DNA-H-NS complex and abolishes H-NS-mediated inhibition of transcription by Escherichia coli and T7 RNA polymerases in vitro. Expression of gene 5.5 also relieves the repression of the Escherichia coli proU promoter by H-NS in vivo. The change of leucine to proline at residue 30 of gene 5.5 protein abolishes the interaction between gene 5.5 protein and H-NS. 30 refs., 4 figs., 1 tab.

  7. Intracellular degradation and localization of NS1 of tick-borne encephalitis virus affect its protective properties.

    PubMed

    Kuzmenko, Yulia V; Starodubova, Elizaveta S; Shevtsova, Anastasia S; Chernokhaeva, Liubov L; Latanova, Anastasia A; Preobrazhenskaia, Olga V; Timofeev, Andrey V; Karganova, Galina G; Karpov, Vadim L

    2017-01-01

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

  8. Bright-White Beetle Scales Optimise Multiple Scattering of Light

    NASA Astrophysics Data System (ADS)

    Burresi, Matteo; Cortese, Lorenzo; Pattelli, Lorenzo; Kolle, Mathias; Vukusic, Peter; Wiersma, Diederik S.; Steiner, Ullrich; Vignolini, Silvia

    2014-08-01

    Whiteness arises from diffuse and broadband reflection of light typically achieved through optical scattering in randomly structured media. In contrast to structural colour due to coherent scattering, white appearance generally requires a relatively thick system comprising randomly positioned high refractive-index scattering centres. Here, we show that the exceptionally bright white appearance of Cyphochilus and Lepidiota stigma beetles arises from a remarkably optimised anisotropy of intra-scale chitin networks, which act as a dense scattering media. Using time-resolved measurements, we show that light propagating in the scales of the beetles undergoes pronounced multiple scattering that is associated with the lowest transport mean free path reported to date for low-refractive-index systems. Our light transport investigation unveil high level of optimisation that achieves high-brightness white in a thin low-mass-per-unit-area anisotropic disordered nanostructure.

  9. Integration, test and operation of the BRIght Target Explorer payload

    NASA Astrophysics Data System (ADS)

    Chaumont, Monica J. M.

    The BRIght Target Explorer mission consists of six nanosatellites, each equipped with an instrument capable of capturing defocused images of stars suitable for milli-magnitude accuracy differential photometry. BRITE is expected to provide information about the dynamics and life cycles of bright stars. The satellites are funded in pairs by Austria, Poland and Canada and designed at the University of Toronto Institute for Aerospace Studies, Space Flight Laboratory. The present thesis document summarizes the contribution of the author to this project. This includes unit level integration, calibration, functional testing and science acceptance testing of the two BRITE Canada payloads; high level assembly and spacecraft level testing of the BRITE Canada spacecraft; sun stare testing and ground based observations of stars with engineering model instruments; launch campaign functional testing and preparations of UniBRITE, the first BRITE satellite funded by Austria; and on-orbit operations of UniBRITE.

  10. Extremely High Current, High-Brightness Energy Recovery Linac

    SciTech Connect

    I. Ben-Zvi; D.S. Barton; D.B. Beavis; M. Blaskiewicz; J.M. Brennan; A. Burrill; R. Calaga; P. Cameron; X.Y. Chang; R. Connolly; D.M. Gassner; J.G. Grimes; H. Hahn; A. Hershcovitch; H.-C. Hseuh; P.D.J. Johnson; D. Kayran; J. Kewisch; R.F. Lambiase; V. Litvinenko; G.T. McIntyre; W. Meng; T.C.N. Nehring; T. Nicoletti; B. Oerter; D. Pate; J. Rank; T. Rao; T. Roser; T. Russo; J. Scaduto; Z. Segalov; K. Smith; N.W.W. Williams; K.-C. Wu; V. Yakimenko; K. Yip; A. Zaltsman; Y. Zhao; H. Bluem; A. Burger; M.D. Cole; A.J. Favale; D. Holmes; J. Rathke; T. Schultheiss; A.M.M. Todd; J.R. Delayen; L. W. Funk; P. Kneisel; H.L. Phillips; J.P. Preble

    2005-05-16

    Next generation ERL light-sources, high-energy electron coolers, high-power Free-Electron Lasers, powerful Compton X-ray sources and many other accelerators were made possible by the emerging technology of high-power, high-brightness electron beams. In order to get the anticipated performance level of ampere-class currents, many technological barriers are yet to be broken. BNL's Collider-Accelerator Department is pursuing some of these technologies for its electron cooling of RHIC application, as well as a possible future electron-hadron collider. We will describe work on CW, high-current and high-brightness electron beams. This will include a description of a superconducting, laser-photocathode RF gun and an accelerator cavity capable of producing low emittance (about 1 micron rms normalized) one nano-Coulomb bunches at currents of the order of one ampere average.

  11. EXTREMELY HIGH CURRECT, HIGH-BRIGHTNESS ENERGY RECOVERY LINAC.

    SciTech Connect

    BEN-ZVI, I.; BARTON, D.; BEAVIS, D. BLASKIEWICZ, M.; ET AL.

    2005-05-16

    Next generation ERL light-sources, high-energy electron coolers, high-power Free-Electron Lasers, powerful Compton X-ray sources and many other accelerators were made possible by the emerging technology of high-power, high-brightness electron beams. In order to get the anticipated performance level of ampere-class currents, many technological barriers are yet to be broken. BNL's Collider-Accelerator Department is pursuing some of these technologies for its electron cooling of RHIC application, as well as a possible future electron-hadron collider. We will describe work on CW, high-current and high-brightness electron beams. This will include a description of a superconducting, laser-photocathode RF gun and an accelerator cavity capable of producing low emittance (about 1 micron rms normalized) one nano-Coulomb bunches at currents of the order of one ampere average.

  12. Temperature and brightness distribution in the components of binary systems

    NASA Astrophysics Data System (ADS)

    Barman, S. K.

    1993-03-01

    From the theoretical model of a binary system for gravity darkening (Barman 1991), the temperature and brightness distributions along the surface of the components have been calculated using the third and fourth orders of the ratio (r/R) in the tidal potentials created by the secondary components, where r is radial distance and R the distance between the centers of gravities of the binary stars. Results of both distributions have been presented in seven figures. On analyzing the results, it has been suggested that if the expansion technique be used to calculate the combined potentials and related matters e.g. the temperature and brightness distributions of a binary system, one should at least consider the fourth order of the ratio (r/R).

  13. Ultra-bright pulsed electron beam with low longitudinal emittance

    DOEpatents

    Zolotorev, Max

    2010-07-13

    A high-brightness pulsed electron source, which has the potential for many useful applications in electron microscopy, inverse photo-emission, low energy electron scattering experiments, and electron holography has been described. The source makes use of Cs atoms in an atomic beam. The source is cycled beginning with a laser pulse that excites a single Cs atom on average to a band of high-lying Rydberg nP states. The resulting valence electron Rydberg wave packet evolves in a nearly classical Kepler orbit. When the electron reaches apogee, an electric field pulse is applied that ionizes the atom and accelerates the electron away from its parent ion. The collection of electron wave packets thus generated in a series of cycles can occupy a phase volume near the quantum limit and it can possess very high brightness. Each wave packet can exhibit a considerable degree of coherence.

  14. Countermeasure against tailored bright illumination attack for DPS-QKD.

    PubMed

    Honjo, Toshimori; Fujiwara, Mikio; Shimizu, Kaoru; Tamaki, Kiyoshi; Miki, Shigehito; Yamashita, Taro; Terai, Hirotaka; Wang, Zhen; Sasaki, Masahide

    2013-02-11

    We propose a countermeasure against the so-called tailored bright illumination attack for differential-phase-shift QKD (DPS-QKD). By monitoring a rate of coincidence detection at a pair of superconducting nanowire single-photon detectors (SSPDs) which is connected at each of the output ports of Bob's Mach-Zehnder interferometer, Alice and Bob can detect and defeat this kind of attack. We also experimentally confirmed the feasibility of this countermeasure using our 1 GHz-clocked DPS-QKD system. In the emulation of the attack, we achieved much lower power of the bright illumination light compared with the original demonstration by using a pulse stream instead of broad pulses.

  15. Bright-White Beetle Scales Optimise Multiple Scattering of Light

    PubMed Central

    Burresi, Matteo; Cortese, Lorenzo; Pattelli, Lorenzo; Kolle, Mathias; Vukusic, Peter; Wiersma, Diederik S.; Steiner, Ullrich; Vignolini, Silvia

    2014-01-01

    Whiteness arises from diffuse and broadband reflection of light typically achieved through optical scattering in randomly structured media. In contrast to structural colour due to coherent scattering, white appearance generally requires a relatively thick system comprising randomly positioned high refractive-index scattering centres. Here, we show that the exceptionally bright white appearance of Cyphochilus and Lepidiota stigma beetles arises from a remarkably optimised anisotropy of intra-scale chitin networks, which act as a dense scattering media. Using time-resolved measurements, we show that light propagating in the scales of the beetles undergoes pronounced multiple scattering that is associated with the lowest transport mean free path reported to date for low-refractive-index systems. Our light transport investigation unveil high level of optimisation that achieves high-brightness white in a thin low-mass-per-unit-area anisotropic disordered nanostructure. PMID:25123449

  16. Fast microtomography using bright monochromatic x-rays

    SciTech Connect

    Jung, J. W.; Lee, J. S.; Park, S. J.; Chang, S.; Pyo, J.; Kwon, N.; Kim, J.; Kohmura, Y.; Nishino, Y.; Yamamoto, M.; Ishikawa, T.

    2012-09-15

    A fast microtomography system for high-resolution high-speed imaging has been developed using bright monochromatic x-rays at the BL29XU beamline of SPring-8. The shortest scan time for microtomography we attained was 0.25 s in 1.25 {mu}m effective pixel size by combining the bright monochromatic x-rays, a fast rotating sample stage, and a high performance x-ray imaging detector. The feasibility of the tomography system was successfully demonstrated by visualization of rising bubbles in a viscous liquid, an interesting issue in multiphase flow physics. This system also provides a high spatial (a measurable feature size of 300 nm) or a very high temporal (9.8 {mu}s) resolution in radiographs.

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

    NASA Technical Reports Server (NTRS)

    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.

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

    NASA Technical Reports Server (NTRS)

    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.

  19. GRB 990712 optical decay: indication of bright host galaxy.

    NASA Astrophysics Data System (ADS)

    Hjorth, J.; Courbin, F.; Cuadra, J.; Minniti, D.

    We have obtained a 5-min R-band exposure of the optical afterglow of GRB 990712 (Frontera, GCN #385; Bakos et al., GCN #387) with the ESO 3.5-m NTT on 16.403 July 1999 UT. We detect an unresolved (seeing FWHM = 1.8") object at RA (2000) = 22 31 53.03, Dec (2000) = -73 24 28.3 (with a positional uncertainty of +- 0.6" relative to the USNO-A2.0 system), consistent with the position of the bright decaying source discovered by Bakos et al. (IAUC 7225). We have tied our photometry to the PLANET photometric zeropoint (K. Sahu, personal communication) and find that the object has continued to fade to R = 21.48 +- 0.02 (systematic) +- 0.05 (random). The combined SAAO data (Bakos et al., IAUC 7225) and NTT data indicate that the light curve is leveling off relative to a power law decline. Assuming that the light curve can be modeled as the combined effects of a power law decline of the OT and a constant contribution from the host galaxy we find an OT decay slope of -0.81 (i.e. a rather slow decay) and a bright host galaxy with R = 22.0. Such a bright host galaxy would be consistent with its fairly low redshift (z = 0.43) and would possibly even account for the prominent emission lines seen in the VLT spectrum (Galama et al., GCN #388). We caution however that the hypothesis of a bright host galaxy is based on just a few data points. To test this hypothesis continued monitoring of the system is therefore urged. The NTT image and the R-band light curve are posted at http://www.astro.ku.dk/~jens/grb990712/ .

  20. High Brightness and high polarization electron source using transmission photocathode

    SciTech Connect

    Yamamoto, Naoto; Jin Xiuguang; Ujihara, Toru; Takeda, Yoshikazu; Mano, Atsushi; Nakagawa, Yasuhide; Nakanishi, Tsutomu; Okumi, Shoji; Yamamoto, Masahiro; Konomi, Taro; Ohshima, Takashi; Saka, Takashi; Kato, Toshihiro; Horinaka, Hiromichi; Yasue, Tsuneo; Koshikawa, Takanori

    2009-08-04

    A transmission photocathode was fabricated based on GaAs-GaAsP strained superlattice layers on a GaP substrate and a 20 kV-gun was built to generate the polarized electron beams with the diameter of a few micro-meter. As the results, the reduced brightness of 1.3x10{sup 7} A/cm{sup 2}/sr and the polarization of 90% were achieved.

  1. Hybrid bright-field and hologram imaging of cell dynamics

    PubMed Central

    Byeon, Hyeokjun; Lee, Jaehyun; Doh, Junsang; Lee, Sang Joon

    2016-01-01

    Volumetric observation is essential for understanding the details of complex biological phenomena. In this study, a bright-field microscope, which provides information on a specific 2D plane, and a holographic microscope, which provides information spread over 3D volumes, are integrated to acquire two complementary images simultaneously. The developed system was successfully applied to capture distinct T-cell adhesion dynamics on inflamed endothelial layers, including capture, rolling, crawling, transendothelial migration, and subendothelial migration. PMID:27640337

  2. Manakins can produce iridescent and bright feather colours without melanosomes.

    PubMed

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

    2016-06-15

    Males of many species often use colourful and conspicuous ornaments to attract females. Among these, male manakins (family: Pipridae) provide classic examples of sexual selection favouring the evolution of bright and colourful plumage coloration. The highly iridescent feather colours of birds are most commonly produced by the periodic arrangement of melanin-containing organelles (melanosomes) within barbules. Melanin increases the saturation of iridescent colours seen from optimal viewing angles by absorbing back-scattered light; however, this may reduce the wide-angle brightness of these signals, contributing to a dark background appearance. We examined the nanostructure of four manakin species (Lepidothrix isidorei, L. iris, L. nattereri and L. coeruleocapilla) to identify how they produce their bright plumage colours. Feather barbs of all four species were characterized by dense and fibrous internal spongy matrices that likely increase scattering of light within the barb. The iridescent, yet pale or whitish colours of L. iris and L. nattereri feathers were produced not by periodically arranged melanosomes within barbules, but by periodic matrices of air and β-keratin within barbs. Lepidothrix iris crown feathers were able to produce a dazzling display of colours with small shifts in viewing geometry, likely because of a periodic nanostructure, a flattened barb morphology and disorder at a microstructural level. We hypothesize that iridescent plumage ornaments of male L. iris and L. nattereri are under selection to increase brightness or luminance across wide viewing angles, which may potentially increase their detectability by females during dynamic and fast-paced courtship displays in dim light environments.

  3. Brightness/darkness induction and the genesis of a contour

    PubMed Central

    Roncato, Sergio

    2014-01-01

    Visual contours often result from the integration or interpolation of fragmented edges. The strength of the completion increases when the edges share the same contrast polarity (CP). Here we demonstrate that the appearance in the perceptual field of this integrated unit, or contour of invariant CP, is concomitant with a vivid brightness alteration of the surfaces at its opposite sides. To observe this effect requires some stratagems because the formation in the visual field of a contour of invariant CP normally engenders the formation of a second contour and then the rise of two streams of induction signals that interfere in different ways. Particular configurations have been introduced that allow us to observe the induction effects of one contour taken in isolation. I documented these effects by phenomenological observations and psychophysical measurement of the brightness alteration in relation to luminance contrast. When the edges of the same CP complete to form a contour, the background of homogeneous luminance appears to dim at one side and to brighten at the opposite side (in accord with the CP). The strength of the phenomenon is proportional to the local luminance contrast. This effect weakens or nulls when the contour of the invariant CP separates surfaces filled with different gray shades. These conflicting results stimulate a deeper exploration of the induction phenomena and their role in the computation of brightness contrast. An alternative perspective is offered to account for some brightness illusions and their relation to the phenomenal transparency. The main assumption asserts that, when in the same region induction signals of opposite CP overlap, the filling-in is blocked unless the image is stratified into different layers, one for each signal of the same polarity. Phenomenological observations document this “solution” by the visual system. PMID:25368570

  4. Brightness/darkness induction and the genesis of a contour.

    PubMed

    Roncato, Sergio

    2014-01-01

    Visual contours often result from the integration or interpolation of fragmented edges. The strength of the completion increases when the edges share the same contrast polarity (CP). Here we demonstrate that the appearance in the perceptual field of this integrated unit, or contour of invariant CP, is concomitant with a vivid brightness alteration of the surfaces at its opposite sides. To observe this effect requires some stratagems because the formation in the visual field of a contour of invariant CP normally engenders the formation of a second contour and then the rise of two streams of induction signals that interfere in different ways. Particular configurations have been introduced that allow us to observe the induction effects of one contour taken in isolation. I documented these effects by phenomenological observations and psychophysical measurement of the brightness alteration in relation to luminance contrast. When the edges of the same CP complete to form a contour, the background of homogeneous luminance appears to dim at one side and to brighten at the opposite side (in accord with the CP). The strength of the phenomenon is proportional to the local luminance contrast. This effect weakens or nulls when the contour of the invariant CP separates surfaces filled with different gray shades. These conflicting results stimulate a deeper exploration of the induction phenomena and their role in the computation of brightness contrast. An alternative perspective is offered to account for some brightness illusions and their relation to the phenomenal transparency. The main assumption asserts that, when in the same region induction signals of opposite CP overlap, the filling-in is blocked unless the image is stratified into different layers, one for each signal of the same polarity. Phenomenological observations document this "solution" by the visual system.

  5. Hybrid bright-field and hologram imaging of cell dynamics

    NASA Astrophysics Data System (ADS)

    Byeon, Hyeokjun; Lee, Jaehyun; Doh, Junsang; Lee, Sang Joon

    2016-09-01

    Volumetric observation is essential for understanding the details of complex biological phenomena. In this study, a bright-field microscope, which provides information on a specific 2D plane, and a holographic microscope, which provides information spread over 3D volumes, are integrated to acquire two complementary images simultaneously. The developed system was successfully applied to capture distinct T-cell adhesion dynamics on inflamed endothelial layers, including capture, rolling, crawling, transendothelial migration, and subendothelial migration.

  6. Bright spots among the world’s coral reefs

    NASA Astrophysics Data System (ADS)

    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

  7. Background Sky Brightness Measurements for Application to Space Surveillance Systems

    DTIC Science & Technology

    1981-05-29

    Schuerman (1979, henceforth Paper I) and Buitrago (1979, henceforth Paper II) independently derived expressions for the general’, mathematical inversion...dimensional inversion of the zodiacal light brightness integral was first formulated (Schuerman, 1977). In Paper II, Buitrago used a different set of...Instituto de Astrofisica de Canarias) and Dr. J. Buitrago for helpful communications. This work was supported by the U.S. Air Force Office of

  8. A Study of Magnetic Fields on Bright-Rimmed Clouds

    NASA Astrophysics Data System (ADS)

    Kusune, Takayoshi; Sugitani, Koji

    2015-08-01

    Bright-rimmed clouds (BRCs), which are located at periphery of HII regions, are considered to be potential sites for induced star formation by UV radiation from nearby massive stars. Many theorists have developed 2D/3D hydrodynamical models to understand dynamical evolution of such molecular clouds. Most simulations, however, did not always include the magnetic field effect, which is of importance in the astrophysics. This is because that there are few observation results examining the magnetic field configuration of BRCs in detail. In order to obtain information on magnetic field in and around BRCs, we have made near-infrared (JHKs) imaging polarimetry toward 24 BRCs showing strong interaction with HII region (Urquhart et al. 2009). We used the imaging polarimeter SIRPOL/SIRIUS (FOV ~7.7’ x 7.7’) mounted on IRSF 1.4 m telescope at the South African Astronomical Observatory.We found that polarization vectors, i.e., magnetic fields inside the clouds, follow the curved bright rim just behind the bright rim for almost all of the observed BRCs. Our investigation into the relation between the ambient magnetic field direction and the UV radiation direction suggests a following tendency. In the case that the ambient magnetic field is perpendicular to the direction of incident UV radiation, the clouds are likely to have bright rims with small curvatures. On the other hand, in the case that the ambient field is parallel to the UV radiation, they would have those with larger curvatures. In this presentation, we will present the physical quantities for these BRCs (i.e., magnetic field strength, the post shock pressure by the ionization front, etc.) as well as these morphological results.

  9. Winter sky brightness & cloud cover over Dome A

    NASA Astrophysics Data System (ADS)

    Yang, Yi; Moore, A. M.; Fu, J.; Ashley, M.; Cui, X.; Feng, L.; Gong, X.; Hu, Z.; Laurence, J.; LuongVan, D.; Riddle, R. L.; Shang, Z.; Sims, G.; Storey, J.; Tothill, N.; Travouillon, T.; Wang, L.; Yang, H.; Yang, J.; Zhou, X.; Zhu, Z.; Burton, M. G.

    2014-01-01

    At the summit of the Antarctic plateau, Dome A offers an intriguing location for future large scale optical astronomical Observatories. The Gattini DomeA project was created to measure the optical sky brightness and large area cloud cover of the winter-time sky above this high altitude Antarctic site. The wide field camera and multi-filter system was installed on the PLATO instrument module as part of the Chinese-led traverse to Dome A in January 2008. This automated wide field camera consists of an Apogee U4000 interline CCD coupled to a Nikon fish-eye lens enclosed in a heated container with glass window. The system contains a filter mechanism providing a suite of standard astronomical photometric filters (Bessell B, V, R), however, the absence of tracking systems, together with the ultra large field of view 85 degrees) and strong distortion have driven us to seek a unique way to build our data reduction pipeline. We present here the first measurements of sky brightness in the photometric B, V, and R band, cloud cover statistics measured during the 2009 winter season and an estimate of the transparency. In addition, we present example light curves for bright targets to emphasize the unprecedented observational window function available from this ground-based location. A ~0.2 magnitude agreement of our simultaneous test at Palomar Observatory with NSBM(National Sky Brightness Monitor), as well as an 0.04 magnitude photometric accuracy for typical 6th magnitude stars limited by the instrument design, indicating we obtained reasonable results based on our ~7mm effective aperture fish-eye lens.

  10. Dark and bright blocker soliton interaction in defocusing waveguide arrays.

    PubMed

    Smirnov, Eugene; Rüter, Christian E; Stepić, Milutin; Shandarov, Vladimir; Kip, Detlef

    2006-11-13

    We experimentally demonstrate the interaction of an optical probe beam with both bright and dark blocker solitons formed with low optical light power in a saturable defocusing waveguide array in photorefractive lithium niobate. A phase insensitive interaction of the beams is achieved by means of counterpropagating light waves. Partial and full reflection (blocking) of the probe beam on the positive or negative light-induced defect is obtained, respectively, in good agreement with numerical simulations.

  11. Characterization of influenza virus variants with different sizes of the non-structural (NS) genes and their potential as live influenza vaccine in poultry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The influenza virus isolate A/turkey/Oregon/71-delNS1 (H7N3) has a 10 nucleotide deletion in the coding region of the NS1 gene and as a result produces a truncated NS1 protein. From a stock of this virus, we found that several variants with different sizes of the NS genes exist. The number of varian...

  12. Optical Variability of X-Ray Bright Southern Symbiotic Stars

    NASA Astrophysics Data System (ADS)

    Hedrick, C.; Sokoloski, J.

    2004-12-01

    We performed weekly B- and V-band observations of four X-ray bright southern symbiotic binary stars -- CD-43 14304, Hen 3-1591, LMC S63, and SMC LN 358 -- using the 1.3-m telescope at Cerro Tololo Inter-American Observatory (CTIO). We began optical monitoring in August 2003 for two of the objects (LMC S63 and SMC LN 358) and in January 2004 for the other two objects (CD-43 14304 and Hen 3-1591). None of the four survey objects experienced a major outburst during the monitoring period. We did, however, detect small-amplitude ( 0.1 mag) optical variability on a time scale of tens of days, for the first time, in each of the four systems. Both the structure and amplitude of the variations are roughly the same in the B band and V band in all of the symbiotics in our sample except one (LMC S63), and is most consistent with the idea that the week-time-scale variability originates with the hot component (most likely an accreting white dwarf) rather than the red giant. We compare the variability properties of our small sample of X-ray-bright symbiotic stars to those of samples of both X-ray-bright and X-ray-dim symbiotic stars from the database of the American Association of Variable Star Observers (AAVSO).

  13. Cell-free measurements of brightness of fluorescently labeled antibodies

    NASA Astrophysics Data System (ADS)

    Zhou, Haiying; Tourkakis, George; Shi, Dennis; Kim, David M.; Zhang, Hairong; Du, Tommy; Eades, William C.; Berezin, Mikhail Y.

    2017-02-01

    Validation of imaging contrast agents, such as fluorescently labeled imaging antibodies, has been recognized as a critical challenge in clinical and preclinical studies. As the number of applications for imaging antibodies grows, these materials are increasingly being subjected to careful scrutiny. Antibody fluorescent brightness is one of the key parameters that is of critical importance. Direct measurements of the brightness with common spectroscopy methods are challenging, because the fluorescent properties of the imaging antibodies are highly sensitive to the methods of conjugation, degree of labeling, and contamination with free dyes. Traditional methods rely on cell-based assays that lack reproducibility and accuracy. In this manuscript, we present a novel and general approach for measuring the brightness using antibody-avid polystyrene beads and flow cytometry. As compared to a cell-based method, the described technique is rapid, quantitative, and highly reproducible. The proposed method requires less than ten microgram of sample and is applicable for optimizing synthetic conjugation procedures, testing commercial imaging antibodies, and performing high-throughput validation of conjugation procedures.

  14. High brightness formamidinium lead bromide perovskite nanocrystal light emitting devices.

    PubMed

    Perumal, Ajay; Shendre, Sushant; Li, Mingjie; Tay, Yong Kang Eugene; Sharma, Vijay Kumar; Chen, Shi; Wei, Zhanhua; Liu, Qing; Gao, Yuan; Buenconsejo, Pio John S; Tan, Swee Tiam; Gan, Chee Lip; Xiong, Qihua; Sum, Tze Chien; Demir, Hilmi Volkan

    2016-11-09

    Formamidinium lead halide (FAPbX3) has attracted greater attention and is more prominent recently in photovoltaic devices due to its broad absorption and higher thermal stability in comparison to more popular methylammonium lead halide MAPbX3. Herein, a simple and highly reproducible room temperature synthesis of device grade high quality formamidinium lead bromide CH(NH2)2PbBr3 (FAPbBr3) colloidal nanocrystals (NC) having high photoluminescence quantum efficiency (PLQE) of 55-65% is reported. In addition, we demonstrate high brightness perovskite light emitting device (Pe-LED) with these FAPbBr3 perovskite NC thin film using 2,2',2″-(1,3,5-Benzinetriyl)-tris(1-phenyl-1-H-benzimidazole) commonly known as TPBi and 4,6-Bis(3,5-di(pyridin-3-yl)phenyl)-2-methylpyrimidine (B3PYMPM) as electron transport layers (ETL). The Pe-LED device with B3PYMPM as ETL has bright electroluminescence of up to 2714 cd/m(2), while the Pe-LED device with TPBi as ETL has higher peak luminous efficiency of 6.4 cd/A and peak luminous power efficiency of 5.7 lm/W. To our knowledge this is the first report on high brightness light emitting device based on CH(NH2)2PbBr3 widely known as FAPbBr3 nanocrystals in literature.

  15. A General Purpose Stacking Technique to Analyze Low Brightness Signal

    NASA Astrophysics Data System (ADS)

    Wavle, Daniel; Leroy, Adam K.; Donovan Meyer, Jennifer

    2015-01-01

    We present an implementation of a general purpose stacking technique in which the detections of bright emission lines are used as priors to analyze low-brightness signal. We demonstrate the use of the technique on ALMA observations of the nuclear region of the nearby galaxy NGC 253 but emphasize its general applicability to a wide class of problems. The conceptual basis for the technique is to use closely associated brighter lines as priors to establish the local velocity (and potentially velocity profile) of a faint line. With this prior, the faint line can be coherently averaged by assuming that it shares a mean velocity with the bright prior. The coherent spectral averaging allows one to more clearly distinguish real astronomical signals from systematic effects, unstable baselines, or imaging artifacts. In our example application, we apply the technique to measure the intensity of faint isotopologues of dense gas tracers in NGC 253, lines that are otherwise hard to distinguish from the noise. The implementation of the code is intended for release as a general purpose cube analysis tool compatible with other astronomical python packages.

  16. Cell-free measurements of brightness of fluorescently labeled antibodies

    PubMed Central

    Zhou, Haiying; Tourkakis, George; Shi, Dennis; Kim, David M.; Zhang, Hairong; Du, Tommy; Eades, William C.; Berezin, Mikhail Y.

    2017-01-01

    Validation of imaging contrast agents, such as fluorescently labeled imaging antibodies, has been recognized as a critical challenge in clinical and preclinical studies. As the number of applications for imaging antibodies grows, these materials are increasingly being subjected to careful scrutiny. Antibody fluorescent brightness is one of the key parameters that is of critical importance. Direct measurements of the brightness with common spectroscopy methods are challenging, because the fluorescent properties of the imaging antibodies are highly sensitive to the methods of conjugation, degree of labeling, and contamination with free dyes. Traditional methods rely on cell-based assays that lack reproducibility and accuracy. In this manuscript, we present a novel and general approach for measuring the brightness using antibody-avid polystyrene beads and flow cytometry. As compared to a cell-based method, the described technique is rapid, quantitative, and highly reproducible. The proposed method requires less than ten microgram of sample and is applicable for optimizing synthetic conjugation procedures, testing commercial imaging antibodies, and performing high-throughput validation of conjugation procedures. PMID:28150730

  17. Melanopsin-based brightness discrimination in mice and humans.

    PubMed

    Brown, Timothy M; Tsujimura, Sei-Ichi; Allen, Annette E; Wynne, Jonathan; Bedford, Robert; Vickery, Graham; Vugler, Anthony; Lucas, Robert J

    2012-06-19

    Photoreception in the mammalian retina is not restricted to rods and cones but extends to a small number of intrinsically photoreceptive retinal ganglion cells (ipRGCs), expressing the photopigment melanopsin. ipRGCs are known to support various accessory visual functions including circadian photoentrainment and pupillary reflexes. However, despite anatomical and physiological evidence that they contribute to the thalamocortical visual projection, no aspect of visual discrimination has been shown to rely upon ipRGCs. Based on their currently known roles, we hypothesized that ipRGCs may contribute to distinguishing brightness. This percept is related to an object's luminance-a photometric measure of light intensity relevant for cone photoreceptors. However, the perceived brightness of different sources is not always predicted by their respective luminance. Here, we used parallel behavioral and electrophysiological experiments to first show that melanopsin contributes to brightness discrimination in both retinally degenerate and fully sighted mice. We continued to use comparable paradigms in psychophysical experiments to provide evidence for a similar role in healthy human subjects. These data represent the first direct evidence that an aspect of visual discrimination in normally sighted subjects can be supported by inner retinal photoreceptors.

  18. HI--line Observations of Low Surface Brightness Dwarf Galaxies

    NASA Astrophysics Data System (ADS)

    Thomas, D. L.; Taylor, C. L.; Brinks, E.; Skillman, E. D.

    1995-12-01

    We present HI--line observations of low--surface brightness (LSB) dwarf galaxies to survey their nearby environment (r <= 100 kpc) for HI bright companions. It is possible that star formation histories in dwarf galaxies can be strongly affected by interactions with nearby companions. If massive star formation can be triggered by galaxy--galaxy interactions, then the absence of such interactions likely explains the lack of star formation in LSB dwarf galaxies relative to their high surface brightness counterparts (HII galaxies). Taylor et al. (1995, ApJS, 99, 427) surveyed a sample of HII galaxies and found that 60% of the sample had nearby HI companions. In our sample of 18 LSB galaxies, we found that only 22% had companions detectable in HI. Furthermore, we find that the peak column densities for the LSB sample are all below {10(21) } HI atoms cm(-2) . This is below the empirically established level needed for star formation to occur in dwarf galaxies as discussed by Skillman (1987, in Star Formation in Galaxies, ed. C.J. Lonsdale Persson (NASA Conf. Pub. CP--2466), p.263), Kennicutt (1989, ApJ, 344, 685), van der Hulst et al. (1993, AJ, 106, 548), and Taylor et al. (1994, AJ, 107, 971).

  19. The KELT Survey for Transiting Planets around Bright Stars

    NASA Astrophysics Data System (ADS)

    Pepper, Joshua; Siverd, R. J.; Kuhn, R.; Beatty, T.; Gaudi, S.; Stassun, K.; Eastman, J.

    2012-01-01

    The KELT project is a transit survey using two robotic, wide-field, small aperture telescopes, with the primary goal of discovering transiting exoplanets of bright (8 < V < 11) stars. Transiting planets around bright stars are accessible to intensive followup observations at extremely high signal-to-noise, and are the best individual laboratories for studying planet atmospheres and compositions. Discoveries of new bright-star transits are hence of great scientific value. In Arizona, KELT-North has been running for 5 years, and in South Africa KELT-South has been running for 1.5 years. The KELT pipeline implements a modified version of the ISIS difference imaging software package and achieves the required (< 1% RMS) precision to detect Jupiter-sized transiting planets for the typical host stars in our sample. The data are also being used to create catalogs of variable stars, identify EBs for testing stellar astrophysics, and to acquire lightcurves of inner solar system comets. The KELT team is currently following up transit candidates and the KELT data set has potential value for future exoplanet surveys. The KELT project has received funding from the Vanderbilt Initiative in Data-intensive Astrophysics (VIDA), NSF PAARE grant AST-0849736, NASA Grant No. NNG04G070G, and from NSF CAREER Grant AST-1056524.

  20. Night-sky brightness and extinction at Mt Shatdzhatmaz

    NASA Astrophysics Data System (ADS)

    Kornilov, V.; Kornilov, M.; Voziakova, O.; Shatsky, N.; Safonov, B.; Gorbunov, I.; Potanin, S.; Cheryasov, D.; Senik, V.

    2016-11-01

    The photometric sky quality of Mt Shatdzhatmaz, the site of the Sternberg Astronomical Institute Caucasian Observatory 2.5-m telescope, is characterized here by the statistics of the night-time sky brightness and extinction. The data were obtained as a by-product of atmospheric optical turbulence measurements with the MASS (Multi-Aperture Scintillation Sensor) device conducted in 2007-2013. The factors biasing night-sky brightness measurements are considered and a technique to reduce their impact on the statistics is proposed. The single-band photometric estimations provided by MASS are easy to transform to the standard photometric bands. The median moonless night-sky brightness is 22.1, 21.1, 20.3 and 19.0 mag arcsec-2 for the B, V, R and I spectral bands, respectively. The median extinction coefficients for the same photometric bands are 0.28, 0.17, 0.13 and 0.09 mag. The best atmospheric transparency is observed in winter.

  1. High brightness formamidinium lead bromide perovskite nanocrystal light emitting devices

    PubMed Central

    Perumal, Ajay; Shendre, Sushant; Li, Mingjie; Tay, Yong Kang Eugene; Sharma, Vijay Kumar; Chen, Shi; Wei, Zhanhua; Liu, Qing; Gao, Yuan; Buenconsejo, Pio John S.; Tan, Swee Tiam; Gan, Chee Lip; Xiong, Qihua; Sum, Tze Chien; Demir, Hilmi Volkan

    2016-01-01

    Formamidinium lead halide (FAPbX3) has attracted greater attention and is more prominent recently in photovoltaic devices due to its broad absorption and higher thermal stability in comparison to more popular methylammonium lead halide MAPbX3. Herein, a simple and highly reproducible room temperature synthesis of device grade high quality formamidinium lead bromide CH(NH2)2PbBr3 (FAPbBr3) colloidal nanocrystals (NC) having high photoluminescence quantum efficiency (PLQE) of 55–65% is reported. In addition, we demonstrate high brightness perovskite light emitting device (Pe-LED) with these FAPbBr3 perovskite NC thin film using 2,2′,2″-(1,3,5-Benzinetriyl)-tris(1-phenyl-1-H-benzimidazole) commonly known as TPBi and 4,6-Bis(3,5-di(pyridin-3-yl)phenyl)-2-methylpyrimidine (B3PYMPM) as electron transport layers (ETL). The Pe-LED device with B3PYMPM as ETL has bright electroluminescence of up to 2714 cd/m2, while the Pe-LED device with TPBi as ETL has higher peak luminous efficiency of 6.4 cd/A and peak luminous power efficiency of 5.7 lm/W. To our knowledge this is the first report on high brightness light emitting device based on CH(NH2)2PbBr3 widely known as FAPbBr3 nanocrystals in literature. PMID:27827424

  2. High brightness formamidinium lead bromide perovskite nanocrystal light emitting devices

    NASA Astrophysics Data System (ADS)

    Perumal, Ajay; Shendre, Sushant; Li, Mingjie; Tay, Yong Kang Eugene; Sharma, Vijay Kumar; Chen, Shi; Wei, Zhanhua; Liu, Qing; Gao, Yuan; Buenconsejo, Pio John S.; Tan, Swee Tiam; Gan, Chee Lip; Xiong, Qihua; Sum, Tze Chien; Demir, Hilmi Volkan

    2016-11-01

    Formamidinium lead halide (FAPbX3) has attracted greater attention and is more prominent recently in photovoltaic devices due to its broad absorption and higher thermal stability in comparison to more popular methylammonium lead halide MAPbX3. Herein, a simple and highly reproducible room temperature synthesis of device grade high quality formamidinium lead bromide CH(NH2)2PbBr3 (FAPbBr3) colloidal nanocrystals (NC) having high photoluminescence quantum efficiency (PLQE) of 55–65% is reported. In addition, we demonstrate high brightness perovskite light emitting device (Pe-LED) with these FAPbBr3 perovskite NC thin film using 2,2‧,2″-(1,3,5-Benzinetriyl)-tris(1-phenyl-1-H-benzimidazole) commonly known as TPBi and 4,6-Bis(3,5-di(pyridin-3-yl)phenyl)-2-methylpyrimidine (B3PYMPM) as electron transport layers (ETL). The Pe-LED device with B3PYMPM as ETL has bright electroluminescence of up to 2714 cd/m2, while the Pe-LED device with TPBi as ETL has higher peak luminous efficiency of 6.4 cd/A and peak luminous power efficiency of 5.7 lm/W. To our knowledge this is the first report on high brightness light emitting device based on CH(NH2)2PbBr3 widely known as FAPbBr3 nanocrystals in literature.

  3. The first World Atlas of the artificial night sky brightness

    NASA Astrophysics Data System (ADS)

    Cinzano, P.; Falchi, F.; Elvidge, C. D.

    2001-12-01

    We present the first World Atlas of the zenith artificial night sky brightness at sea level. Based on radiance-calibrated high-resolution DMSP satellite data and on accurate modelling of light propagation in the atmosphere, it provides a nearly global picture of how mankind is proceeding to envelop itself in a luminous fog. Comparing the Atlas with the United States Department of Energy (DOE) population density data base, we determined the fraction of population who are living under a sky of given brightness. About two-thirds of the World population and 99 per cent of the population in the United States (excluding Alaska and Hawaii) and European Union live in areas where the night sky is above the threshold set for polluted status. Assuming average eye functionality, about one-fifth of the World population, more than two-thirds of the United States population and more than one half of the European Union population have already lost naked eye visibility of the Milky Way. Finally, about one-tenth of the World population, more than 40 per cent of the United States population and one sixth of the European Union population no longer view the heavens with the eye adapted to night vision, because of the sky brightness.

  4. Bright Soil Churned by Spirit's Sol 1861 Drive

    NASA Technical Reports Server (NTRS)

    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.

  5. A nucleostemin family GTPase, NS3, acts in serotonergic neurons to regulate insulin signaling and control body size

    PubMed Central

    Kaplan, Daniel D.; Zimmermann, Gregor; Suyama, Kaye; Meyer, Tobias; Scott, Matthew P.

    2008-01-01

    Growth and body size are regulated by the CNS, integrating the genetic developmental program with assessments of an animal’s current energy state and environmental conditions. CNS decisions are transmitted to all cells of the animal by insulin/insulin-like signals. The molecular biology of the CNS growth control system has remained, for the most part, elusive. Here we identify NS3, a Drosophila nucleostemin family GTPase, as a powerful regulator of body size. ns3 mutants reach <60% of normal size and have fewer and smaller cells, but exhibit normal body proportions. NS3 does not act cell-autonomously, but instead acts at a distance to control growth. Rescue experiments were performed by expressing wild-type ns3 in many different cells of ns3 mutants. Restoring NS3 to only 106 serotonergic neurons rescued global growth defects. These neurons are closely apposed with those of insulin-producing neurons, suggesting possible communication between the two neuronal systems. In the brains of ns3 mutants, excess serotonin and insulin accumulate, while peripheral insulin pathway activation is low. Peripheral insulin pathway activation rescues the growth defects of ns3 mutants. The findings suggest that NS3 acts in serotonergic neurons to regulate insulin signaling and thus exert global growth control. PMID:18628395

  6. Visual estimates of brightness and analysis of observations of variable stars

    NASA Technical Reports Server (NTRS)

    Tsesevich, V. P.

    1973-01-01

    Methods of visual estimation of the brightness of variable stars include the Argelander method, Pickering method, and Neyland-Blazhko method. Systematic errors are discussed together with methods of plotting brightness curves.

  7. Determination of periods of change in brightness for variable stars by the aid of digital computers

    NASA Technical Reports Server (NTRS)

    Kolopov, P. N.

    1973-01-01

    Computer techniques used for determination of periods of brightness change in variable stars are discussed, with emphasis on the Lafler-Kinman method and a presentation of Kholopov's own method based on brightness extremes.

  8. Bright optical outburst with rapid optical variability of the blazar 3C 279

    NASA Astrophysics Data System (ADS)

    Jankowsky, F.; Glawion, D.; Schwemmer, S.; Wagner, S.

    2017-03-01

    Optical observations of the gamma-ray bright, flat-spectrum radio quasar 3C 279 (z=0.536) with the Automatic Telescope for Optical Monitoring (ATOM) confirm a very bright optical state and rapid flares.

  9. Cooperative translocation enhances the unwinding of duplex DNA by SARS coronavirus helicase nsP13.

    PubMed

    Lee, Na-Ra; Kwon, Hyun-Mi; Park, Kkothanahreum; Oh, Sangtaek; Jeong, Yong-Joo; Kim, Dong-Eun

    2010-11-01

    SARS coronavirus encodes non-structural protein 13 (nsP13), a nucleic acid helicase/NTPase belonging to superfamily 1 helicase, which efficiently unwinds both partial-duplex RNA and DNA. In this study, unwinding of DNA substrates that had different duplex lengths and 5'-overhangs was examined under single-turnover reaction conditions in the presence of excess enzyme. The amount of DNA unwound decreased significantly as the length of the duplex increased, indicating a poor in vitro processivity. However, the quantity of duplex DNA unwound increased as the length of the single-stranded 5'-tail increased for the 50-bp duplex. This enhanced processivity was also observed for duplex DNA that had a longer single-stranded gap in between. These results demonstrate that nsP13 requires the presence of a long 5'-overhang to unwind longer DNA duplexes. In addition, enhanced DNA unwinding was observed for gapped DNA substrates that had a 5'-overhang, indicating that the translocated nsP13 molecules pile up and the preceding helicase facilitate DNA unwinding. Together with the propensity of oligomer formation of nsP13 molecules, we propose that the cooperative translocation by the functionally interacting oligomers of the helicase molecules loaded onto the 5'-overhang account for the observed enhanced processivity of DNA unwinding.

  10. Thermodynamics of superstring on near-extremal NS5 and effective Hagedorn behavior

    NASA Astrophysics Data System (ADS)

    Sugawara, Yuji

    2012-10-01

    We study the thermodynamical torus partition function of superstring on the near-extremal black NS5-brane background. The exact partition function has been computed with the helps of our previous works: [arXiv:1012.5721 [hep-th

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

    SciTech Connect

    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.

  12. Synthesis and SAR optimization of diketo acid pharmacophore for HCV NS5B polymerase inhibition

    PubMed Central

    Bhatt, Aaditya; Gurukumar, K. R.; Basu, Amartya; Patel, Maulik R.; Kaushik-Basu, Neerja; Talele, Tanaji T.

    2011-01-01

    Hepatitis C virus (HCV) NS5B polymerase is a key target for anti-HCV therapeutics development. Here we report the synthesis and biological evaluation of a new series of α,γ-diketo acids (DKAs) as NS5B polymerase inhibitors. We initiated structure-activity relationship (SAR) optimization around the furan moiety of compound 1a [IC50 = 21.8 μM] to achieve more active NS5B inhibitors. This yielded compound 3a [IC50 = 8.2 μM] bearing the 5-bromobenzofuran-2-yl moiety, the first promising lead compound of the series. Varying the furan moiety with thiophene, thiazole and indazole moieties resulted in compound 11a [IC50 = 7.5 μM] bearing 3-methylthiophen-2-yl moiety. Finally replacement of the thiophene ring with a bioisosteric phenyl ring further improved the inhibitory activity as seen in compounds 21a [IC50 = 5.2 μM] and 24a [IC50 = 2.4 μM]. Binding mode of compound 24a using glide docking within the active site of NS5B polymerase will form the basis for future SAR optimization. PMID:21893371

  13. The influenza virus NEP (NS2 protein) mediates the nuclear export of viral ribonucleoproteins.

    PubMed Central

    O'Neill, R E; Talon, J; Palese, P

    1998-01-01

    Nuclear import and export of viral nucleic acids is crucial for the replication cycle of many viruses, and elucidation of the mechanism of these steps may provide a paradigm for understanding general biological processes. Influenza virus replicates its RNA genome in the nucleus of infected cells. The influenza virus NS2 protein, which had no previously assigned function, was shown to mediate the nuclear export of virion RNAs by acting as an adaptor between viral ribonucleoprotein complexes and the nuclear export machinery of the cell. A functional domain on the NS2 with characteristics of a nuclear export signal was mapped: it interacts with cellular nucleoporins, can functionally replace the effector domain of the human immunodeficiency virus type 1 (HIV-1) Rev protein and mediates rapid nuclear export when cross-linked to a reporter protein. Microinjection of anti-NS2 antibodies into infected cells inhibited nuclear export of viral ribonucleoproteins, suggesting that the Rev-like NS2 mediates this process. Therefore, we have renamed this Rev-like factor the influenza virus nuclear export protein or NEP. We propose a model by which NEP acts as a protein adaptor molecule bridging viral ribonucleoproteins and the nuclear pore complex. PMID:9427762

  14. Overcoming NS1-Mediated Immune Antagonism Involves Both Interferon-Dependent and Independent Mechanisms

    PubMed Central

    Thakar, Juilee; Schmid, Sonja; Duke, Jamie L.; García-Sastre, Adolfo

    2013-01-01

    To ensure survival, our immune system must overcome the action of pathogen-encoded immune antagonists, such as influenza A nonstructural protein-1 (NS1). NS1 subverts the host interferon (IFN) response at multiple levels and blocks the induction of IFN-β, a critical antiviral cytokine. This immune antagonism can be overcome in some cases. It has been shown that IFN-β is upregulated by 48 h in the lungs of wild-type C57BL/6 mice infected with influenza A. In contrast, it is shown here that IFNB1 continues to be repressed in IFNAR1−/− IL28Rα−/− mice, which are deficient in Type-I and III IFN signaling, implying induction of IFNB1 depends on effective IFN signaling. Despite the complete lack of IFN signaling in this system, some IFN stimulated genes (ISGs) were induced following infection with a Flu strain lacking NS1. While the expression of these viral stress-inducible genes (VSIGs) was initially repressed following infection with wild-type Flu, many of these genes became upregulated by 48 h postinfection. These results demonstrate the existence of IFN-independent mechanisms that can overcome NS1-mediated immune antagonism of VSIGs. PMID:23772952

  15. BOREAS Level-0 NS001 TMS Imagery: Digital Counts in BIL Format

    NASA Technical Reports Server (NTRS)

    Hall, Forrest G. (Editor); Newcomer, Jeffrey A.; Dominguez, Roseanne

    2000-01-01

    For BOREAS, the NS001 TMS imagery, along with the other remotely sensed images, was collected in order to provide spatially extensive information over the primary study areas. This information includes detailed land cover and biophysical parameter maps such as fPAR and LAI. Data collections occurred over the study areas during the 1994 field campaigns.

  16. Introduction to Psychomotor Skills (NS 117): Competency-Based Course Syllabus.

    ERIC Educational Resources Information Center

    Brady, Marilyn H.; Wells, Tanya G.

    "Introduction to Psychomotor Skills" (NS 117) is the first of seven core courses in the associate degree nursing program at Chattanooga State Technical Community College. The course was designed to help students develop competencies in psychomotor skills necessary to assume the role of provider of direct patient care. The course syllabus for NS…

  17. Phylogenetic analysis of the NS5 gene of dengue viruses isolated in Ecuador.

    PubMed

    Regato, Mary; Recarey, Ricardo; Moratorio, Gonzalo; de Mora, Domenica; Garcia-Aguirre, Laura; Gónzalez, Manuel; Mosquera, Carlos; Alava, Aracely; Fajardo, Alvaro; Alvarez, Macarena; D' Andrea, Lucia; Dubra, Ana; Martínez, Mariela; Khan, Baldip; Cristina, Juan

    2008-03-01

    Dengue virus (DENV) is a member of the genus Flavivirus of the family Flaviviridae. DENV causes a wide range of diseases in humans, from the acute febrile illness dengue fever (DF) to life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). There is not knowledge of the genetic relations among DENV circulating in Ecuador. Given the emerging behaviour of DENV, a single tube RT-PCR assay using a pair of consensus primers to target the NS5 coding region has been recently validated for rapid detection of flaviviruses. In order to gain insight into the degree of genetic variation of DENV strains isolated in Ecuador, DENV NS5 sequences from 23 patients were obtained by direct sequencing of PCR fragments using the mentioned one step RT-PCR assay. Phylogenetic analysis carried out using the 23 Ecuadorian DENV NS5 sequences, as well as 56 comparable sequences from DENV strains isolated elsewhere, revealed a close genetic relation among Ecuadorian strains and DENV isolates of Caribbean origin. The use of partial NS5 gene sequences may represent a useful alternative for a rapid phylogenetic analysis of DENV outbreaks.

  18. NS21: Re-defined and Modified Supplement B27 for Neuronal Cultures

    PubMed Central

    Chen, Yucui; Stevens, Beth; Chang, Jufang; Milbrandt, Jeffrey; Barres, Ben A.; Hell, Johannes W.

    2009-01-01

    In vitro culturing of primary neurons is a mainstay of neurobiological research. Many of these culture paradigms have taken advantage of defined culture media rather than serum additives that contain undefined survival factors to facilitate experimental manipulations and interpretation of the results. To culture neurons in the absence of serum, defined supplements such as B27 are now widely used. However, commercially available supplements exhibit large variability in their capabilities to support neurons in culture. We re-optimized and modified earlier published formulations of B27 using 21 different ingredients (NS21). NS21 supports neuronal cultures of high quality as manifested by their morphological characteristics, formation of synapses, and postsynaptic responses. Much of the variability in the quality of B27/NS21 was due to variability in the quality of different sources of bovine serum albumin. Furthermore, we found that holo-transferrin used in NS21 is preferable over apo-transferrin used in B27 for the quality of neuronal cultures. PMID:18471889

  19. Peptide inhibitors of Dengue virus NS3 protease. Part 1: Warhead.

    PubMed

    Yin, Zheng; Patel, Sejal J; Wang, Wei-Ling; Wang, Gang; Chan, Wai-Ling; Rao, K R Ranga; Alam, Jenefer; Jeyaraj, Duraiswamy A; Ngew, Xinyi; Patel, Viral; Beer, David; Lim, Siew Pheng; Vasudevan, Subhash G; Keller, Thomas H

    2006-01-01

    Substrate-based tetrapeptide inhibitors with various warheads were designed, synthesized, and evaluated against the Dengue virus NS3 protease. Effective inhibition was achieved by peptide inhibitors with electrophilic warheads such as aldehyde, trifluoromethyl ketone, and boronic acid. A boronic acid has the highest affinity, exhibiting a K(i) of 43 nM.

  20. Inhibitors of hepatitis C virus NS3.4A protease 2. Warhead SAR and optimization.

    PubMed

    Perni, Robert B; Pitlik, Janos; Britt, Shawn D; Court, John J; Courtney, Lawrence F; Deininger, David D; Farmer, Luc J; Gates, Cynthia A; Harbeson, Scott L; Levin, Rhonda B; Lin, Chao; Lin, Kai; Moon, Young-Choon; Luong, Yu-Ping; O'Malley, Ethan T; Rao, B Govinda; Thomson, John A; Tung, Roger D; Van Drie, John H; Wei, Yunyi

    2004-03-22

    The alpha-ketoamide warhead (e.g., 15) was found to be a practical replacement for aliphatic aldehydes in a series of HCV NS3.4A protease inhibitors. Structure-activity relationships and prime side optimization are discussed.