Sample records for bright ns lmxbs

  1. A Hard Look at NS LMXBs with NuSTAR (United States)

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


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

  2. 50 ns Backup Solution

    CERN Document Server

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


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

  3. NS simulator for beginners

    CERN Document Server

    Altman, Eitan


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

  4. BrightFocus Foundation (United States)

    ... sooner. More science news Help us find a cure. Give to BrightFocus BrightFocus Updates BrightFocus Foundation Lauds Bill Gates Alzheimer’s Initiative “BrightFocus Foundation lauds today’s historic announcement by ...

  5. NS Ibar and NS Ulog: New winter feed barley varieties

    Directory of Open Access Journals (Sweden)

    Pržulj Novo


    Full Text Available At Institute of Field and Vegetable crops for decades, new varieties of winter six-row feed barley having high yield, good adaptability, stability and quality are produced. As a result of long process of breeding, two new varieties of winter six-row barley - NS Ibar and NS Ulog have been selected. The primary aim during creation of these varieties was selection for yield, and maintaining quality and other agronomic traits at least to the standard variety level. The two-year multilocation trial of Commission for the registration of varieties, showed that the NS Ibar and NS Ulog are distinct, uniform and stable varieties, and that on the base of average for all the test sites and years they achieved a significantly higher yield than the standard variety. New varieties of winter six-row feed barley are characterized by high genetic potential for yield, which is more than 10 t ha-1. NS Ibar i NS Ulog had a shorter plant, while the resistance to lodging was at the level of the standard variety.

  6. Burkina Faso - BRIGHT II (United States)

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


    Directory of Open Access Journals (Sweden)

    Juliana Wijaya


    Full Text Available In this study, I investigate cross-linguistic differences and similarities in the speech associated gesture in the NS (Native Speaker - NS and NNS (Nonnative Speaker - NS dyads when they are telling a narrative. The gesture production between Indonesian native speakers when communicating in Indonesian (L1 and in English (L2 was coded and assessed based on Mc.Neill's model of overall gesture units. The Indonesian speakers' gesture modification when interacting in English was measured by the size of the gestures. The results indicate that Indonesian native speakers gesture more when they communicate in English and modify their gestures by making them bigger and therefore more noticeable to their interlocutors. They use gestures as a communication strategy to help interlocutors comprehend their idea.

  8. NS&T Management Observations

    Energy Technology Data Exchange (ETDEWEB)

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


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

  9. Introduction to Network Simulator NS2

    CERN Document Server

    Issariyakul, Teerawat


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

  10. High Brightness OLED Lighting

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

  11. The brightness of colour.

    Directory of Open Access Journals (Sweden)

    David Corney

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

  12. Latest NS varieties of soybean

    Directory of Open Access Journals (Sweden)

    Vidić Miloš


    Full Text Available Results obtained from a network of large-plot trials conducted in 2009 and several previous years have shown that there are a number of newly released NS cultivars of soybean that can be recommended for large-scale commercial growing. We have placed on the market a broad range of new cultivars differing in their growth period duration (maturity groups 000, 00, 0, I, II and other agronomic traits (growing requirements, chemical grain composition, etc.. For the next planting season, we have secured sufficient quantities of top quality seed of both our well-established cultivars and our new releases, including the new early varieties Alisa, Galina and Bečejka, the medium-maturing new cultivars Sava and Diva, and the late-maturing new cultivars Rubin and Idila. We will also have limited quantities of our latest releases available, the varieties Iskra (I, Victoria (I and Trijumf (II. We have recently registered four very early cultivars, Gracija (000, Julija (00, Mercur (00 and Prima (00, all of which are particularly suitable for growing soybean as the second crop. Our recommendation is that the new cultivars be introduced gradually to large-scale production and we are hoping they will become popular with the growers. .

  13. HI Surface brightness mapping (United States)

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


    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.

  14. Lightness, brightness, and anchoring. (United States)

    Anderson, Barton L; Whitbread, Michael; de Silva, Chamila


    The majority of work in lightness perception has evaluated the perception of lightness using flat, matte, two-dimensional surfaces. In such contexts, the amount of light reaching the eye contains a conflated mixture of the illuminant and surface lightness. A fundamental puzzle of lightness perception is understanding how it is possible to experience achromatic surfaces as specific achromatic shades in the face of this ambiguity. It has been argued that the perception of lightness in such contexts implies that the visual system imposes an "anchoring rule" whereby a specific relative luminance (the highest) serves as a fixed point in the mapping of image luminance onto the lightness scale ("white"). We conducted a series of experiments to explicitly test this assertion in contexts where this mapping seemed most unlikely-namely, low-contrast images viewed in dim illumination. Our results provide evidence that the computational ambiguity in mapping luminance onto lightness is reflected in perceptual experience. The perception of the highest luminance in a two-dimensional Mondrian display varied monotonically with its brightness, ranging from midgray to white. Similar scaling occurred for the lowest luminance and, by implication, all other luminance values. We conclude that the conflation between brightness and lightness in two-dimensional Mondrian displays is reflected in perception and find no support for the claim that any specific relative luminance value acts as a fixed anchor point in this mapping function. © 2014 ARVO.

  15. Introduction to Network Simulator NS2

    CERN Document Server

    Issariyakul, Teerawat


    A beginners' guide for network simulator NS2, an open-source discrete event simulator designed mainly for networking research. It presents two fundamental NS2 concepts: how objects are assembled to create a network and how a packet flows from one object to another

  16. Optical and X-ray rebrightening in NS X-ray Nova Aql X-1 (United States)

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


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

  17. NS-Raubgut in hessischen Bibliotheken


    Kasperowski, Ira; Martin-Konle, Claudia


    Der Band dokumentiert die Werkstatt- und Erfahrungsberichte hessischer Bibliotheken und anderer Institutionen zum unrechtmäßigen Buchzugang während der NS-Zeit. Die Wege der systematischen Suche nach NS-Raubgut bei teilweise rudimentärer Quellenlage, ihre Ergebnisse sowie Beispiele restituierter Bestände waren im Januar 2013 Gegenstand des Gießener Fachsymposiums NS-Raubgut in hessischen Bibliotheken. Dabei wurden verschiedene Formen des unrechtmäßigen Erwerbs rekonstruiert, die beteiligten E...

  18. NS Pudarka: A new winter wheat cultivar

    Directory of Open Access Journals (Sweden)

    Hristov Nikola


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

  19. mScarlet : a bright monomeric red fluorescent protein for cellular imaging

    NARCIS (Netherlands)

    Bindels, D.S.; Haarbosch, L.; van Weeren, L.; Postma, M.; Wiese, K.E.; Mastop, M.; Aumonier, S.; Gotthard, G.; Royant, A.; Hink, M.A.; Gadella Jr, T.W.J.


    We report the engineering of mScarlet, a truly monomeric red fluorescent protein with record brightness, quantum yield (70%) and fluorescence lifetime (3.9 ns). We developed mScarlet starting with a consensus synthetic template and using improved spectroscopic screening techniques; mScarlet's

  20. NS/EP Implications of Electronic Commerce (United States)


    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

  1. Boron tolerance in NS wheat lines

    Directory of Open Access Journals (Sweden)

    Brdar Milka


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

  2. Characterisation of interaction between NS3 and NS5B protein of classical swine fever virus by deletion of terminal sequences of NS5B. (United States)

    Wang, Yujing; Zhu, Zailing; Wang, Ping; Yu, Jialin; Wan, Lingzhu; Chen, Jun; Xiao, Ming


    The NS3-NS5B interaction of classical swine fever virus (CSFV) is important for viral replication. For characterisation of the interaction between the NS3 and NS5B, a series of NS5B mutants with deletion of N-, C-terminal amino acids and quadruple alanine substitution mutations were produced. GST pull-down assays and immunoprecipitation analyses showed that NS5B and some NS5B mutants have NS3 binding activity. Further experimental data indicated that CSFV NS5B might contain two NS3 binding sites, one covering amino acids 63-99 located at the N-terminal end, another covering amino acids 611-642 at the C-terminal end. Assays for RNA-dependent RNA polymerase (RdRp) activity revealed that CSFV NS3 is able to enhance the RdRp activity of NS5B and some NS5B mutants in vitro. The enhancement might be obtained by NS3 binding to the two terminal sequences of NS5B, which could be attractive targets for drug development against CSFV. Copyright © 2011. Published by Elsevier B.V.

  3. New confectionary sunflower hybrids in NS palette

    Directory of Open Access Journals (Sweden)

    Hladni Nada


    Full Text Available Sunflower breeding is directed towards the increase of the genetic potential for yield, stability of the yield, health care, and the quality of nutrition along with the increase of the production economy. In accordance with the Serbian market demands there have been efforts in breeding highly productive hybrids for special uses of the confectionary type at the Institute of Field and Vegetable Crops in Novi Sad. In this program, special attention has been given to the increase of the protein content and quality while decreasing the seed oil content, to the increase of 1000 seed weight and the decrease of the hull ratio. New NS confectionary hybrids NS-H-6316, NS-H-6318 and NS-H-6320 are adequate for nutrition, dehulling and core production. They belong to the group of mid-early hybrids while their genetic potential for seed yield is above 4.5 t ha-1 and seed oil content is less than 40%. Protein content in the core is 23-27%, mass of 1000 seeds is above 95 g, and the hull ratio is low. With the creation of the new palette of NS sunflower hybrids for various production purposes and conditions, we have gained higher quality material for the needs of the oil, food and baking industry.

  4. Teradiode's high brightness semiconductor lasers (United States)

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


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

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

    African Journals Online (AJOL)

    In many researches, several models of peptides inhibitor were generated in complexes with the NS2B-NS3 DENV2 protease by performing molecular docking. The goal of this research was to study the interaction of ligands as inhibitors for protein (enzyme) in solvent explicit condition by performing molecular dynamics ...

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

    African Journals Online (AJOL)



    Jul 10, 2013 ... many researches, several models of peptides inhibitor were generated in complexes with the NS2B-NS3. DENV2 protease by performing molecular docking. The goal of this research was to study the interaction of ligands as inhibitors for protein (enzyme) in solvent explicit condition by performing molecular ...

  7. Lightness, brightness, and brightness contrast: 2. Reflectance variation. (United States)

    Arend, L E; Spehar, B


    Changes of annulus luminance in traditional disk-and-annulus patterns can be perceived to be either reflectance or illuminance changes. In the present experiments, we examined the effect of varying annulus reflectance. In Experiment 1, we placed test and standard patch-and-surround patterns in identical Mondrian patchworks. Only the luminance of the test surround changed from trial to trial, appearing as reflectance variation under constant illumination. Lightness matches were identical to brightness matches, as expected. In Experiment 2, we used only the patch and surround (no Mondrian). Instructions said that the illumination would change from trial to trial. Lightness and brightness-contrast data were identical; illumination gradients were indistinguishable from reflectance gradients. In Experiment 3, the patterns were the same, but the instructions said that the shade of gray of the test surround would change from trial to trial. Lightness matches were identical to brightness matches, again confirming the ambiguity of disk-and-annulus patterns.

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

    NARCIS (Netherlands)

    Feenstra, Femke; Drolet, B.S.; Boonstra, Jan; Rijn, Van P.A.


    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.

  9. Non-structural protein NS3/NS3a is required for propagation of bluetongue virus in Culicoides sonorensis (United States)

    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...

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

    CERN Document Server

    Wenninger, J


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

  11. Bright Light Treatment in Psychiatry

    Directory of Open Access Journals (Sweden)

    Pinar Guzel Ozdemir


    Full Text Available Bright light treatment is a treatment modality that leads elevation of mood due to attenuation in depressive symptoms, regulation in circadian rhythm activity, increase the effect of antidepressants and amelioration in sleep quality. Bright light treatment is considered among the first-line treatments for seasonal affective disorder because of high response rates. Additionally, bright light treatment being extended to other conditions, including non-seasonal mood disorders, Alzheimer's disease, circadian rhythm sleep disorders, eating disorders, attention deficit hyperactivity disorder and other behavioral syndromes is likely to have a far reached use. Side effects are often temporary and can generally be overcome by reducing exposure time. The central focus on this paper is to review the action mechanisms, efficacy, usage areas, the ways of administration and side effects of the light treatment. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2017; 9(2.000: 177-188

  12. Network based sky Brightness Monitor (United States)

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


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

  13. Investigation of high-temperature bright plasma X-ray sources produced in 5-MA X-pinch experiments. (United States)

    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


    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.

  14. Orientifold dual for stuck NS5 branes

    CERN Document Server

    Feng, B; Karch, A; Uranga, Angel M; Feng, Bo; He, Yang-Hui; Karch, Andreas; Uranga, Angel


    We establish T-duality between NS5 branes stuck on an orientifold 8-plane in type I' and an orientifold construction in type IIB with D7 branes intersecting at angles. Two applications are discussed. For one we obtain new brane constructions, realizing field theories with gauge group a product of symplectic factors, giving rise to a large new class of conformal N=1 theories embedded in string theory. Second, by studying a D2 brane probe in the type I' background, we get some information on the still elusive (0,4) linear sigma model describing a perturbative heterotic string on an ADE singularity.

  15. Helmholtz bright and boundary solitons

    Energy Technology Data Exchange (ETDEWEB)

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


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

  16. NS-417, a novel compound with neurotrophic-like effects

    DEFF Research Database (Denmark)

    Dagø, Lone; Peters, Dan; Meyer, Morten


    NS-417 (5-(4-Chlorophenyl)-8-methyl-6-7-8-9-tetrahydro-1-H-pyrrolo[3.2-h]isoquinoline-2,3-dione-3-oxim hydrochloric acid salt) belongs to a new chemical series of compounds. NS-417 rescued differentiated PC12 cells from death induced by withdrawal of serum and nerve growth factor. Furthermore, NS...

  17. Iapetus Bright and Dark Terrains (United States)


    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

  19. LSST Site: Sky Brightness Data (United States)

    Burke, Jamison; Claver, Charles


    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).

  20. Mutagenesis of the yellow fever virus NS2B protein: effects on proteolytic processing, NS2B-NS3 complex formation, and viral replication. (United States)

    Chambers, T J; Nestorowicz, A; Amberg, S M; Rice, C M


    To study the role of specific regions of the yellow fever virus NS2B protein in proteolytic processing and association with the NS3 proteinase domain, a series of mutations were created in the hydrophobic regions and in a central conserved hydrophilic region proposed as a domain important for NS2B function. The effects of these mutations on cis cleavage at the 2B/3 cleavage site and on processing at other consensus cleavage sites for the NS3 proteinase in the nonstructural region were then characterized by cell-free translation and transient expression in BHK cells. Association between NS2B and the NS3 proteinase domain and the effects of mutations on complex formation were investigated by nondenaturing immunoprecipitation of these proteins expressed in infected cells, by cell-free translation, or by recombinant vaccinia viruses. Mutations within the hydrophobic regions had subtle effects on proteolytic processing, whereas mutations within the conserved domain dramatically reduced cleavage efficiency or abolished all cleavages. The conserved domain of NS2B is also implicated in formation of an NS2B-NS3 complex on the basis of the ability of mutations in this region to eliminate both association of these two proteins and trans-cleavage activity. In addition, mutations which either eliminated proteolytic processing or had no apparent effect on processing were found to abolish recovery of infectious virus following RNA transfection. These results suggest that the conserved region of NS2B is a domain essential for the function of the NS3 proteinase. Hydrophobic regions of NS2B whose structural integrity may not be essential for proteolytic processing may have additional functions during viral replication.

  1. Achievements in NS rapeseed hybrids breeding

    Directory of Open Access Journals (Sweden)

    Marjanović-Jeromela Ana


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

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

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


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

  3. Implications of PSR J0737-3039B for the Galactic NS-NS binary merger rate (United States)

    Kim, Chunglee; Perera, Benetge Bhakthi Pranama; McLaughlin, Maura A.


    The Double Pulsar (PSR J0737-3039) is the only neutron star-neutron star (NS-NS) binary in which both NSs have been detectable as radio pulsars. The Double Pulsar has been assumed to dominate the Galactic NS-NS binary merger rate R_g among all known systems, solely based on the properties of the first-born, recycled pulsar (PSR J0737-3039A, or A) with an assumption for the beaming correction factor of 6. In this work, we carefully correct observational biases for the second-born, non-recycled pulsar (PSR J0737-0737B, or B) and estimate the contribution from the Double Pulsar on R_g using constraints available from both A and B. Observational constraints from the B pulsar favour a small beaming correction factor for A (˜2), which is consistent with a bipolar model. Considering known NS-NS binaries with the best observational constraints, including both A and B, we obtain R_g=21_{-14}^{+28} Myr-1 at 95 per cent confidence from our reference model. We expect the detection rate of gravitational waves from NS-NS inspirals for the advanced ground-based gravitational-wave detectors is to be 8^{+10}_{-5} yr-1 at 95 per cent confidence. Within several years, gravitational-wave detections relevant to NS-NS inspirals will provide us useful information to improve pulsar population models.

  4. Solution conformations of Zika NS2B-NS3pro and its inhibition by natural products from edible plants. (United States)

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


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

  5. How Bright Can Supernovae Get? (United States)

    Kohler, Susanna


    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

  6. Computer Aided Screening of Phytochemicals from Garcinia against the Dengue NS2B/NS3 Protease. (United States)

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


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

  7. GESPA: classifying nsSNPs to predict disease association. (United States)

    Khurana, Jay K; Reeder, Jay E; Shrimpton, Antony E; Thakar, Juilee


    Non-synonymous single nucleotide polymorphisms (nsSNPs) are the most common DNA sequence variation associated with disease in humans. Thus determining the clinical significance of each nsSNP is of great importance. Potential detrimental nsSNPs may be identified by genetic association studies or by functional analysis in the laboratory, both of which are expensive and time consuming. Existing computational methods lack accuracy and features to facilitate nsSNP classification for clinical use. We developed the GESPA (GEnomic Single nucleotide Polymorphism Analyzer) program to predict the pathogenicity and disease phenotype of nsSNPs. GESPA is a user-friendly software package for classifying disease association of nsSNPs. It allows flexibility in acceptable input formats and predicts the pathogenicity of a given nsSNP by assessing the conservation of amino acids in orthologs and paralogs and supplementing this information with data from medical literature. The development and testing of GESPA was performed using the humsavar, ClinVar and humvar datasets. Additionally, GESPA also predicts the disease phenotype associated with a nsSNP with high accuracy, a feature unavailable in existing software. GESPA's overall accuracy exceeds existing computational methods for predicting nsSNP pathogenicity. The usability of GESPA is enhanced by fast SQL-based cloud storage and retrieval of data. GESPA is a novel bioinformatics tool to determine the pathogenicity and phenotypes of nsSNPs. We anticipate that GESPA will become a useful clinical framework for predicting the disease association of nsSNPs. The program, executable jar file, source code, GPL 3.0 license, user guide, and test data with instructions are available at

  8. Brightness and darkness as perceptual dimensions

    NARCIS (Netherlands)

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


    A common-sense assumption concerning visual perception states that brightness and darkness cannot coexist at a given spatial location. One corollary of this assumption is that achromatic colors, or perceived grey shades, are contained in a one-dimensional (1-D) space varying from bright to dark. The


    NARCIS (Netherlands)



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

  10. Brightness Alteration with Interweaving Contours

    Directory of Open Access Journals (Sweden)

    Sergio Roncato


    Full Text Available 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

  12. Interaction study between HCV NS5A-D2 and NS5B using19F NMR. (United States)

    Dujardin, Marie; Cantrelle, François-Xavier; Lippens, Guy; Hanoulle, Xavier


    The non structural protein 5A (NS5A) regulates the replication of the hepatitis C viral RNA through a direct molecular interaction of its domain 2 (NS5A-D2) with the RNA dependent RNA polymerase NS5B. Because of conflicting data in the literature, we study here this molecular interaction using fluorinated versions of the NS5A-D2 protein derived from the JFH1 Hepatitis C Virus strain. Two methods to prepare fluorine-labelled NS5A-D2 involving the biosynthetic incorporation of a 19 F-tryptophan using 5-fluoroindole and the posttranslational introduction of fluorine by chemical conjugation of 2-iodo-N-(trifluoromethyl)acetamide with the NS5A-D2 cysteine side chains are presented. The dissociation constants (K D ) between NS5A-D2 and NS5B obtained with these two methods are in good agreement, and yield values comparable to those derived previously from a surface plasmon resonance study. We compare benefits and limitations of both labeling methods to study the interaction between an intrinsically disordered protein and a large molecular target by 19 F NMR.

  13. Agronomic and production characteristics of sunflower hybrids: NS Oskar and NS Fantazija

    Directory of Open Access Journals (Sweden)

    Cvejić Sandra


    Full Text Available The results of seed and oil yield obtained from the trials and production plots, single out sunflower hybrids NS Oskar and NS Fantazija as very promising and potentially leading in Serbia. They were created by breeding process at the Institute of Field and Vegetable Crops, Novi Sad. Hybrids are medium early ie. late maturity sunflower hybrids, have high yielding potential and high oil content. They are adjusted to different agro ecological conditions because they have wide adaptability to the different conditions of production. They also possess a high degree of tolerance and resistance to major parasites in the region, such as downy mildew, Phomopsis, white rot, broomrape etc. Hybrid seed is of excellent quality and germination. This paper presents the results of seed yield in trials from Department for variety testing of Ministry of Agriculture and environmental protection of the Republic of Serbia, as well as the results achieved in small-plot trials of the Institute of Field and Vegetable Crops and results from farm producers.

  14. Bluetongue virus without NS3/NS3a expression is not virulent and protects against virulent bluetongue virus challenge. (United States)

    Feenstra, Femke; van Gennip, René G P; Maris-Veldhuis, Mieke; Verheij, Eline; van Rijn, Piet A


    Bluetongue is a disease in ruminants caused by the bluetongue virus (BTV), and is spread by Culicoides biting midges. Bluetongue outbreaks cause huge economic losses and death in sheep in several parts of the world. The most effective measure to control BTV is vaccination. However, both commercially available vaccines and recently developed vaccine candidates have several shortcomings. Therefore, we generated and tested next-generation vaccines for bluetongue based on the backbone of a laboratory-adapted strain of BTV-1, avirulent BTV-6 or virulent BTV-8. All vaccine candidates were serotyped with VP2 of BTV-8 and did not express NS3/NS3a non-structural proteins, due to induced deletions in the NS3/NS3a ORF. Sheep were vaccinated once with one of these vaccine candidates and were challenged with virulent BTV-8 3 weeks after vaccination. The NS3/NS3a knockout mutation caused complete avirulence for all three BTV backbones, including for virulent BTV-8, indicating that safety is associated with the NS3/NS3a knockout phenotype. Viraemia of vaccine virus was not detected using sensitive PCR diagnostics. Apparently, the vaccine viruses replicated only locally, which will minimize spread by the insect vector. In particular, the vaccine based on the BTV-6 backbone protected against disease and prevented viraemia of challenge virus, showing the efficacy of this vaccine candidate. The lack of NS3/NS3a expression potentially enables the differentiation of infected from vaccinated animals, which is important for monitoring virus spread in vaccinated livestock. The disabled infectious single-animal vaccine for bluetongue presented here is very promising and will be the subject of future studies. © 2014 The Authors.

  15. Influenza NS1 directly modulates Hedgehog signaling during infection.

    Directory of Open Access Journals (Sweden)

    Margery G Smelkinson


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

  16. Bright Sparks of Our Future! (United States)

    Riordan, Naoimh


    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

  18. Space Brightness Evaluation for a Daylit Room

    Directory of Open Access Journals (Sweden)

    Takashi Maruyama


    Full Text Available One of the most important problems for lighting design is how to reduce an electric energy. One way to solve this problem is use of daylight, but little is known how to perceive a brightness of a room illuminated by daylight come in through a window and artificial light. Although the horizontal illuminance increases because of daylight, we would not perceive the room as bright as brightness estimated by the illuminance. The purpose of this study is to measure the space brightness for daylit room and to propose a evaluation method. The experiment was conducted with a couple of miniature office rooms, standard room and test room. Test room has several types of windows and standard room has no window. Subject was asked to evaluate the brightness of the test room relative to the standard room with method of magnitude estimation. It was found that brightness of daylit room did not increase simply with horizontal illuminance. Subject perceived a daylit room darker than a room illuminated only by the artificial light even if horizontal illuminance of these room was same. The effect of daylight on space brightness would vary with the window size and intensity of daylight or artificial light.

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

    Directory of Open Access Journals (Sweden)

    Amrita Roy

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

  20. Improvement of Java-based NS-2 Visualizer


    Cai, Junbo


    NS-2 (Network Simulator version 2) is the most popular open-source network simulation program. NS-2 kernel is made in C++ but simulation scenario design is done in TCL (Tool Command Language). TCL is not a popular language for most networking researchers and engineers; therefore a user-graphic interface program is highly appreciated. We are aimed to design this software and denote it as NSSV (NS-2 Scenario Setup Visualizer). In this project, my work is to continue the leading work done by ...

  1. Efficient, High Brightness Sources of Polarized Neutrons and Photons and Their Uses

    Energy Technology Data Exchange (ETDEWEB)

    Spencer, James E.


    There are many applications that could benefit from an easily accessible source of monochromatic, high brightness, polarized gammas and neutrons. A compact and comparatively inexpensive system is discussed based on a low-energy, electron storage ring with undulators that is expected to provide 10{sup 11} epithermal n/s and 10{sup 15} {gamma}/s. This method could provide a more efficient, cleaner way to produce epithermal neutrons than conventional means. Technical innovations that make it feasible are described together with some fundamental and practical applications that also take advantage of developments in the field of high power lasers.

  2. mScarlet: a bright monomeric red fluorescent protein for cellular imaging. (United States)

    Bindels, Daphne S; Haarbosch, Lindsay; van Weeren, Laura; Postma, Marten; Wiese, Katrin E; Mastop, Marieke; Aumonier, Sylvain; Gotthard, Guillaume; Royant, Antoine; Hink, Mark A; Gadella, Theodorus W J


    We report the engineering of mScarlet, a truly monomeric red fluorescent protein with record brightness, quantum yield (70%) and fluorescence lifetime (3.9 ns). We developed mScarlet starting with a consensus synthetic template and using improved spectroscopic screening techniques; mScarlet's crystal structure reveals a planar and rigidified chromophore. mScarlet outperforms existing red fluorescent proteins as a fusion tag, and it is especially useful as a Förster resonance energy transfer (FRET) acceptor in ratiometric imaging.

  3. Bright boys the making of information technology

    CERN Document Server

    Green, Tom


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

  4. BOREAS NS001 TMS Level-0 Images in BIL Format (United States)

    National Aeronautics and Space Administration — 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....

  5. A spectroscopic atlas of bright stars

    CERN Document Server

    Martin, Jack


    Suitable for amateur astronomers interested in practical spectroscopy or spectrography, this reference book identifies more than 70 (northern hemisphere) bright stars that are suitable observational targets. It provides finder charts for locating these sometimes-familiar stars.

  6. Nimbus-5 ESMR Polar Gridded Brightness Temperatures (United States)

    National Aeronautics and Space Administration — The Nimbus-5 Electrically Scanning Microwave Radiometer (ESMR) data set consists of gridded brightness temperature arrays for the Arctic and Antarctic, spanning 11...

  7. Magnetic topological analysis of coronal bright points (United States)

    Galsgaard, K.; Madjarska, M. S.; Moreno-Insertis, F.; Huang, Z.; Wiegelmann, T.


    Context. We report on the first of a series of studies on coronal bright points which investigate the physical mechanism that generates these phenomena. Aims: The aim of this paper is to understand the magnetic-field structure that hosts the bright points. Methods: We use longitudinal magnetograms taken by the Solar Optical Telescope with the Narrowband Filter Imager. For a single case, magnetograms from the Helioseismic and Magnetic Imager were added to the analysis. The longitudinal magnetic field component is used to derive the potential magnetic fields of the large regions around the bright points. A magneto-static field extrapolation method is tested to verify the accuracy of the potential field modelling. The three dimensional magnetic fields are investigated for the presence of magnetic null points and their influence on the local magnetic domain. Results: In nine out of ten cases the bright point resides in areas where the coronal magnetic field contains an opposite polarity intrusion defining a magnetic null point above it. We find that X-ray bright points reside, in these nine cases, in a limited part of the projected fan-dome area, either fully inside the dome or expanding over a limited area below which typically a dominant flux concentration resides. The tenth bright point is located in a bipolar loop system without an overlying null point. Conclusions: All bright points in coronal holes and two out of three bright points in quiet Sun regions are seen to reside in regions containing a magnetic null point. An as yet unidentified process(es) generates the brigh points in specific regions of the fan-dome structure. The movies are available at

  8. Biplot analysis of diallel crosses of NS maize inbred lines

    Directory of Open Access Journals (Sweden)

    Boćanski Jan


    Full Text Available Genetic markers, from morphological to molecular, in function with early Heterosis is a prerequisite for the successful commercial maize production. It does not appear in any cross of two inbred lines, and therefore, the determination of combining abilities of parental lines is essential. The most commonly used method for determining combining abilities is diallel analysis. Besides conventional methods for diallel analysis, a new biplot approach has been sugested. In this paper, we studied the combining ability for grain yield in a set of genotypes obtained by diallel crossing system of six inbred lines. Both, the Griffing’s conventional method and the biplot approach have been used for diallel analysis. Comparing the GCA values from biplot analysis and Griffing’s method, similar results can be observed, with the exception of NS L 1051 and NS L 1000 whose ranks are interchanged. Biplot analysis enables the SCA estimation of parent inbred, and the highest SCA has inbred B73D. Biplot analysis also allows the estimation of the best crosses. Inbred B73D shows the best results when crossed with testers Mo17Ht, NS L 1051 and N152, inbred N152 combines best with testers NS L 1001 and NS L 1000, whereas the cross of inbred NS L 1051 with tester B73D results with the highest grain yield per plant in comparison with other testers.

  9. Effect of Interior Chromaticness on Space Brightness

    Directory of Open Access Journals (Sweden)

    Hidenari Takada


    Full Text Available To design a lighting environment, horizontal illuminance is generally used as the brightness of a room. But it is reported that a subjective brightness does not always match the horizontal illuminance. For example, the room furnished with high saturated colored objects is perceived brighter than the room furnished with achromatic objects, even though the horizontal illuminance is the same. To investigate a effect of interior chromaticness on space brightness, we conducted the experiment in four miniature rooms that were different in terms of chromaticness of interior decorating surfaces, but kept lightness of surfaces constant. Subjects were asked to set the illuminance of reference room, that is furnished with achromatic objects, to equate the brightness of the test room, that is with chromatic objects. Four of seven subjects needed less illuminance to get the equality of space brightness if the test room had a saturated objects. The illuminance ratio of test to reference room was about 1.4. Other three subjects set the illuminance of reference room almost equal to test room. Thus, there are differences between individuals so further work would be needed to estimate the quantitative effect of interior chromaticness on space brightness.

  10. Energy-exchange collisions of dark-bright-bright vector solitons. (United States)

    Radhakrishnan, R; Manikandan, N; Aravinthan, K


    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.

  11. Nodding syndrome (NS) and Onchocerca Volvulus (OV) in Northern Uganda. (United States)

    Lagoro, David Kitara; Arony, Denis Anywar


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

  12. Structure of the H-NS-DNA nucleoprotein complex. (United States)

    van der Maarel, Johan R C; Guttula, Durgarao; Arluison, Véronique; Egelhaaf, Stefan U; Grillo, Isabelle; Forsyth, V Trevor


    Nucleoid associated proteins (NAPs) play a key role in the compaction and expression of the prokaryotic genome. Here we report the organisation of a major NAP, the protein H-NS on a double stranded DNA fragment. For this purpose we have carried out a small angle neutron scattering study in conjunction with contrast variation to obtain the contributions to the scattering (structure factors) from DNA and H-NS. The H-NS structure factor agrees with a heterogeneous, two-state binding model with sections of the DNA duplex surrounded by protein and other sections having protein bound to the major groove. In the presence of magnesium chloride, we observed a structural rearrangement through a decrease in cross-sectional diameter of the nucleoprotein complex and an increase in fraction of major groove bound H-NS. The two observed binding modes and their modulation by magnesium ions provide a structural basis for H-NS-mediated genome organisation and expression regulation.

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

    NARCIS (Netherlands)

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


    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

  14. In silico evaluation of inhibitory potential of triterpenoids from Azadirachta indica against therapeutic target of dengue virus, NS2B-NS3 protease. (United States)

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


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

  15. A selective deficit in the appreciation and recognition of brightness: brightness agnosia? (United States)

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


    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'.

  16. Some considerations about NS5 and LST Hawking radiation

    Energy Technology Data Exchange (ETDEWEB)

    Lorente-Espin, Oscar, E-mail: [Departament de Fisica i Enginyeria Nuclear, Universitat Politecnica de Catalunya, Comte Urgell 187, E-08036 Barcelona (Spain)


    We have studied the Hawking radiation corresponding to the NS5 and Little String Theory (LST) black hole models using two semi-classical methods: the complex path method and a gravitational anomaly. After summarizing some known concepts about the thermodynamics of these theories, we have computed the emission rates for the two black hole models. The temperature calculated from, e.g. the well-known surface gravity expression, is shown to be identical to that obtained from both the computation of the gravitational anomaly and the complex path method. Moreover, the two semi-classical methods show that NS5 exhibits non-thermal behavior that contrasts with the thermal behavior of LST. We remark that energy conservation is the key factor leading to a non-thermal profile for NS5. In contrast, LST keeps a thermal profile even when energy conservation is considered because temperature in this model does not depend on energy.

  17. High brightness semiconductor lasers with reduced filamentation

    DEFF Research Database (Denmark)

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


    High brightness semiconductor lasers have applications in spectroscopy, fiber lasers, manufacturing and materials processing, medicine and free space communication or energy transfer. The main difficulty associated with high brightness is that, because of COD, high power requires a large aperture....... Large apertures result in high order transverse modes, filamentation and spatio-temporal instabilities, all of which degrade spatial coherence and therefore brightness. We shall describe a combined assault on three fronts: (1) minimise aperture size required for a given power by maximising the facet...... damage threshold, (2) for a given aperture, minimise self-focusing and filamentation by minimising the effective nonlinear coefficient (the alpha parameter), and (3) for a given aperture and nonlinear coefficient, develop optical cavities and propagation structures to suppress filamentation and high...

  18. On the Brightness of Supernova Ia

    CERN Document Server

    Zheng, Yijia


    Before 1998 the universe expansion was thought to be slowing down. After 1998 the universe expansion is thought to be accelerating up. The key evidence came from the observed brightness of high redshift supernovae Ia in 1998. Astronomers found that the observed brightness of high redshift supernovae Ia is fainter than expected. Astronomers believe this means that the universe expansion is accelerating up. In this paper it is argued that if the ionized gas in the universe space is taken into account, then the brightness of the high redshift supernova Ia should be fainter than expected. The universe expansion does not need to be accelerating up. The exotic form of energy (dark energy) does not need to be introduce

  19. Increasing the brightness of light sources

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Ling


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

  20. Discovery of potent macrocyclic HCV NS5A inhibitors. (United States)

    Yu, Wensheng; Vibulbhan, Bancha; Rosenblum, Stuart B; Martin, Gregory S; Vellekoop, A Samuel; Holst, Christian L; Coburn, Craig A; Wong, Michael; Selyutin, Oleg; Ji, Tao; Zhong, Bin; Hu, Bin; Chen, Lei; Dwyer, Michael P; Jiang, Yueheng; Nair, Anilkumar G; Tong, Ling; Zeng, Qingbei; Agrawal, Sony; Carr, Donna; Rokosz, Laura; Liu, Rong; Curry, Stephanie; McMonagle, Patricia; Ingravallo, Paul; Lahser, Fred; Asante-Appiah, Ernest; Fells, James; Kozlowski, Joseph A


    HCV NS5A inhibitors have demonstrated impressive in vitro virologic profiles in HCV replicon assays and robust HCV RNA titer reduction in the clinic making them attractive components for inclusion in an all oral fixed-dose combination (FDC) regimen for the treatment of HCV infection. Merck's effort in this area identified MK-4882 and MK-8325 as early development leads. Herein, we describe the discovery of potent macrocyclic NS5A inhibitors bearing the MK-8325 or MK-4882 core structure. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Hepatitis C virus expressing reporter tagged NS5A protein

    DEFF Research Database (Denmark)


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

  2. D-Branes in the Background of NS Fivebranes

    CERN Document Server

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


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

  3. Further theoretical insight into the reaction mechanism of the hepatitis C NS3/NS4A serine protease (United States)

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


    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.

  4. Microwave brightness temperature imaging and dielectric properties ...

    Indian Academy of Sciences (India)

    material collected by former Soviet Union robots and Apollo astronauts. With the completion of the first round of lunar exploration by human beings, the study of lunar microwave brightness tempe- rature was completely forgotten. Accompanied by a new upcoming era of lunar exploration and the development of science and ...

  5. Dark matter in low surface brightness galaxies

    NARCIS (Netherlands)

    de Blok, WJG; McGaugh, SS; Persic, M; Salucci, P


    Low Surface Brightness (LSB) galaxies form a large population of disc galaxies that extend the Hubble sequence towards extreme late-types. They are only slowly evolving, and still in an early evolutionary state. The Tully-Fisher relation and rotation curves of LSB galaxies both show that LSB

  6. Robust fitting of diurnal brightness temperature cycle

    CSIR Research Space (South Africa)

    Udahemuka, G


    Full Text Available for a pixel concerned. Robust fitting of observed Diurnal Temperature Cycle (DTC) taken over a day of a given pixel without cloud cover and other abnormally conditions such as fire can give a data based brightness temperature model for a given pixel...

  7. Simultaneous brightness contrast of foraging Papilio butterflies (United States)

    Kinoshita, Michiyo; Takahashi, Yuki; Arikawa, Kentaro


    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

  8. Microwave brightness temperature imaging and dielectric properties ...

    Indian Academy of Sciences (India)

    In this paper,we give a rough analysis of the microwave brightness temperature images of the lunar disc observed using the NRAO 12 meter Telescope and Siberian Solar Radio Telescope.We also ... Center for Space Science and Applied Research, Chinese Academy of Sciences, P.O. Box 8701, Beijing 100 080, China.

  9. Dark Matter in Low Surface Brightness Galaxies

    NARCIS (Netherlands)

    Blok, W. J. G. de; McGaugh, S. S.


    Abstract: Low Surface Brightness (LSB) galaxies form a large population of disc galaxies that extend the Hubble sequence towards extreme late-types. They are only slowly evolving, and still in an early evolutionary state. The Tully-Fisher relation and rotation curves of LSB galaxies both show that

  10. NS Zitos: New two-row winter barley variety

    Directory of Open Access Journals (Sweden)

    Pržulj Novo


    Full Text Available At Institute of Field and Vegetable crops, plant breeders for a decade's are constantly developing new barley cultivars, which have better yield, quality and other agronomical traits then older barley varieties. At 2012 new winter malting barley cultivar NS Zitos was registered. The primary aim during creation of this variety was selection for barley quality, and to maintain yield and other agronomic traits at least at standard (control variety level. Commission for the registration of varieties of Ministry of Agriculture, Forestry and Water Management, conducted trial at multiple locations in two year, and it was found that the variety NS Zitos was distinct, uniform and stable cultivar, and had yield at all locations and in all year at standard (control variety level, and better technological quality. In both trial years NS Zitos, had grain yield over 11000 kg per hectare at location Novi Sad, which indicates that this variety has a high genetic yield potential. NS Zitos is medium early winter barley cultivar, which is characterized by good resistance to lodging, large seeds size and greater thousand kernel weight.

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

    CSIR Research Space (South Africa)

    Abu-Mahfouz, Adnan M


    Full Text Available where the nodes will be distributed, which allows evaluating the localisation algorithm considering different nodes distribution. If you comparing different localisation algorithms the same value(s) of SEED should be used (except the value of 0..."; /*========================================================================= =================================================*/ /*========~ns/common/mobilenode.h========================================== =================================================*/ Add the following: inline Topography* get_topography() { return T_;} // log the location information void log_loc(double...

  12. Biplot analysis of diallel crosses of NS maize inbred lines

    NARCIS (Netherlands)

    Bocanski, J.; Nastasic, A.; Stanisavljevic, D.; Sreckov, Z.; Mitrovic, B.; Treskic, S.; Vukosavljev, M.


    Bocanski J., A. Nastasic, D. Stanisavljevic, Z. Sreckov, B. Mitrovic, S. Treskic and M. Vukosavljev (2011): Biplot analysis of diallel crosses of NS maize inbred lines- Genetika, Vol 43, No. 2, 277 - 284. Genetic markers, from morphological to molecular, in function with early Heterosis is a

  13. The nature of solar brightness variations (United States)

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


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

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

    Directory of Open Access Journals (Sweden)

    Xun-Cheng Su

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

  15. Intermittent Episodes of Bright Light Suppress Myopia in the Chicken More than Continuous Bright Light (United States)

    Lan, Weizhong; Feldkaemper, Marita; Schaeffel, Frank


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

  16. Serotype-specific interactions among functional domains of dengue virus 2 nonstructural proteins (NS) 5 and NS3 are crucial for viral RNA replication. (United States)

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


    Four serotypes of mosquito-borne dengue virus (DENV), evolved from a common ancestor, are human pathogens of global significance for which 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), all of which are important for 5'-capping and RNA replication. The crystal structure of NS5 shows it as a dimer, but the functional evidence for NS5 dimer is lacking. Our studies showed that the substitution of DENV2 NS5 MTase or POL for DENV4 NS5 within DENV2 RNA resulted in a severe attenuation of replication in the transfected BHK-21 cells. A replication-competent species was evolved with the acquired mutations in the DENV2 and DENV4 NS5 MTase or POL domain or in the 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 the recovery of replication fitness in the chimera RNA. Our results, taken together, provide genetic evidence for a serotype-specific interaction between NS3 and NS5 as well as specific interdomain 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. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Circadian Phase-Shifting Effects of Bright Light, Exercise, and Bright Light + Exercise. (United States)

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


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

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

    DEFF Research Database (Denmark)

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


    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 ......Hepatitis C virus (HCV) is an important human pathogen infecting hepatocytes. With the advent of infectious cell culture systems, the HCV particle assembly and release processes are finally being uncovered. The HCV core and NS5A proteins co-localize on cytoplasmic lipid droplets (c...... 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...

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

    Directory of Open Access Journals (Sweden)

    Thi Thanh Hanh Nguyen


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

  20. Human CD56bright NK Cells

    DEFF Research Database (Denmark)

    Michel, Tatiana; Poli, Aurélie; Cuapio, Angelica


    Human NK cells can be subdivided into various subsets based on the relative expression of CD16 and CD56. In particular, CD56(bright)CD16(-/dim) NK cells are the focus of interest. They are considered efficient cytokine producers endowed with immunoregulatory properties, but they can also become...... cytotoxic upon appropriate activation. These cells were shown to play a role in different disease states, such as cancer, autoimmunity, neuroinflammation, and infection. Although their phenotype and functional properties are well known and have been extensively studied, their lineage relationship with other...... NK cell subsets is not fully defined, nor is their precise hematopoietic origin. In this article, we summarize recent studies about CD56(bright) NK cells in health and disease and briefly discuss the current controversies surrounding them....

  1. Companions of Bright Barred Shapley Ames Galaxies


    Garcia-Barreto, J. Antonio; Carrillo, Rene; Vera-Villamizar, Nelson


    Companion galaxy environment for a subset of 78 bright and nearby barred galaxies from the Shapley Ames Catalog is presented. Among spiral barred galaxies there are Seyfert galaxies, galaxies with circumnuclear structures, galaxies not associated with any large scale galaxy cloud structure, galaxies with peculiar disk morphology (crooked arms) and galaxies with normal disk morphology; the list includes all Hubble types. The companion galaxy list includes number of companion galaxies within 20...

  2. Modular Zero Energy. BrightBuilt Home

    Energy Technology Data Exchange (ETDEWEB)

    Aldrich, Robb [Steven Winter Associates, Inc., Norwalk, CT (United States); Butterfield, Karla [Steven Winter Associates, Inc., Norwalk, CT (United States)


    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.

  3. Data center network performance evaluation in ns3

    DEFF Research Database (Denmark)

    Andrus, Bogdan-Mihai; Vegas Olmos, Juan José


    In the following paper we present the analysis of highly interconnected topologies like hypercube and torus and how they can be implemented in data centers in order to cope with the rapid increase and demands for performance of the internal traffic. By replicating the topologies in NS3 and subjec......In the following paper we present the analysis of highly interconnected topologies like hypercube and torus and how they can be implemented in data centers in order to cope with the rapid increase and demands for performance of the internal traffic. By replicating the topologies in NS3...... we scale the network from 16 to 512 switches. The performance measurements are supported by abstract metrics that that also give a cost and complexity indication in choosing the right topology for the required application....

  4. NS&T Management Observations: Quarterly Performance Analysis

    Energy Technology Data Exchange (ETDEWEB)

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


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

  5. NS&T Management Observations - 3rd Quarter

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

  6. Process Performances of 2 ns Pulsed Discharge Plasma (United States)

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


    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.

  7. SAT: a late NS protein of porcine parvovirus. (United States)

    Zádori, Zoltán; Szelei, József; Tijssen, Peter


    The genomes of all members of the Parvovirus genus were found to contain a small open reading frame (ORF), designated SAT, with a start codon four or seven nucleotides downstream of the VP2 initiation codon. Green fluorescent protein or FLAG fusion constructs of SAT demonstrated that these ORFs were expressed. Although the SAT proteins of the different parvoviruses are not particularly conserved, they were all predicted to contain a membrane-spanning helix, and mutations in this hydrophobic stretch affected the localization of the SAT protein. SAT colocalized with calreticulin in the membranes of the endoplasmic reticulum and the nucleus. A knockout mutant (SAT(-)), with an unmodified VP sequence, showed a "slow-spreading" phenotype. These knockout mutants could be complemented with VP2(-) SAT(+) mutant. The SAT protein is a late nonstructural (NS) protein, in contrast to previously identified NS proteins, since it is expressed from the same mRNA as VP2.

  8. NS&T Managment Observations - 1st Quarter

    Energy Technology Data Exchange (ETDEWEB)

    David Gianotto


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

  9. NS maize hybrids in production regions of Serbia

    Directory of Open Access Journals (Sweden)

    Stojaković Milisav


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


    National Aeronautics and Space Administration — The TC4 AMPR Brightness Temperature (TB) dataset consists of brightness temperature data from July 19, 2007 through August 8, 2007. The Tropical Composition, Cloud...

  11. Brightness illusion in the guppy (Poecilia reticulata). (United States)

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


    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. (c) 2016 APA, all rights reserved).

  12. Discovery of an irreversible HCV NS5B polymerase inhibitor. (United States)

    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


    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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Biplot analysis of diallel crosses of NS maize inbred lines


    Boćanski Jan; Nastasić Aleksandra; Stanisavljević Dušan; Srećkov Zorana; Mitrović Bojan; Treskić Sanja; Vukosavljev Mirjana


    Bocanski J., A. Nastasic, D. Stanisavljevic, Z. Sreckov, B. Mitrovic, S. Treskic and M. Vukosavljev (2011): Biplot analysis of diallel crosses of NS maize inbred lines- Genetika, Vol 43, No. 2, 277 - 284. Genetic markers, from morphological to molecular, in function with early Heterosis is a prerequisite for the successful commercial maize production. It does not appear in any cross of two inbred lines, and therefore, the determination of combining abilities of parental lines is essential. Th...

  14. Structure of a murine norovirus NS6 protease-product complex revealed by adventitious crystallisation.

    Directory of Open Access Journals (Sweden)

    Eoin N Leen

    Full Text Available Murine noroviruses have emerged as a valuable tool for investigating the molecular basis of infection and pathogenesis of the closely related human noroviruses, which are the major cause of non-bacterial gastroenteritis. The replication of noroviruses relies on the proteolytic processing of a large polyprotein precursor into six non-structural proteins (NS1-2, NS3, NS4, NS5, NS6(pro, NS7(pol by the virally-encoded NS6 protease. We report here the crystal structure of MNV NS6(pro, which has been determined to a resolution of 1.6 Å. Adventitiously, the crystal contacts are mediated in part by the binding of the C-terminus of NS6(pro within the peptide-binding cleft of a neighbouring molecule. This insertion occurs for both molecules in the asymmetric unit of the crystal in a manner that is consistent with physiologically-relevant binding, thereby providing two independent views of a protease-peptide complex. Since the NS6(pro C-terminus is formed in vivo by NS6(pro processing, these crystal contacts replicate the protease-product complex that is formed immediately following cleavage of the peptide bond at the NS6-NS7 junction. The observed mode of binding of the C-terminal product peptide yields new insights into the structural basis of NS6(pro specificity.

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

    DEFF Research Database (Denmark)

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


    ) from genotypes 1-6 and 2a(JFH1) NS5B-3' untranslated region, and tested the effects of NS3 protease and NS5A inhibitors on these recombinants. METHODS: The HCV 5-5A recombinants with previously identified mutations in the NS3-helicase (F1464L), NS4A (A1672S), and NS5B (D2979G) were adapted and improved......, by incorporating additional recovered mutations that increased their propagation in Huh7.5 cells. Concentration-response profiles were determined for each DAA agent in replicate infected Huh7.5 cells. RESULTS: Developed efficient 1a(H77), 1a(TN), 3a(S52), 4a(ED43), 5a(SA13), and 6a(HK6a) 5-5A recombinants did...... not require mutations after viral passage in the NS3 protease or NS5A domain-I regions targeted by the drugs. They were inhibited in a concentration-dependent manner by the NS3 protease inhibitors telaprevir, boceprevir, asunaprevir, simeprevir, vaniprevir, faldaprevir, and MK-5172 and by the NS5A inhibitor...

  16. VP2-serotyped live-attenuated bluetongue virus without NS3/NS3a expression provides serotype-specific protection and enables DIVA. (United States)

    Feenstra, Femke; Maris-Veldhuis, Mieke; Daus, Franz J; Tacken, Mirriam G J; Moormann, Rob J M; van Gennip, René G P; van Rijn, Piet A


    Bluetongue virus (BTV) causes Bluetongue in ruminants and is transmitted by Culicoides biting midges. Vaccination is the most effective measure to control vector borne diseases; however, there are 26 known BTV serotypes showing little cross protection. The BTV serotype is mainly determined by genome segment 2 encoding the VP2 protein. Currently, inactivated and live-attenuated Bluetongue vaccines are available for a limited number of serotypes, but each of these have their specific disadvantages, including the inability to differentiate infected from vaccinated animals (DIVA). BTV non-structural proteins NS3 and NS3a are not essential for virus replication in vitro, but are important for cytopathogenic effect in mammalian cells and for virus release from insect cells in vitro. Recently, we have shown that virulent BTV8 without NS3/NS3a is non-virulent and viremia in sheep is strongly reduced, whereas local in vivo replication leads to seroconversion. Live-attenuated BTV6 without NS3/NS3a expression protected sheep against BTV challenge. Altogether, NS3/NS3a knockout BTV6 is a promising vaccine candidate and has been named Disabled Infectious Single Animal (DISA) vaccine. Here, we show serotype-specific protection in sheep by DISA vaccine in which only genome segment 2 of serotype 8 was exchanged. Similarly, DISA vaccines against other serotypes could be developed, by exchange of only segment 2, and could therefore safely be combined in multi-serotype cocktail vaccines with respect to reassortment between vaccine viruses. Additionally, NS3 antibody responses are raised after natural BTV infection and NS3-based ELISAs are therefore appropriate tools for DIVA testing accompanying the DISA vaccine. To enable DIVA, we developed an experimental NS3 ELISA. Indeed, vaccinated sheep remained negative for NS3 antibodies, whereas seroconversion for NS3 antibodies was associated with viremia after heterologous BTV challenge. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Hepatitis C virus NS2 and NS3/4A proteins are potent inhibitors of host cell cytokine/chemokine gene expression

    Directory of Open Access Journals (Sweden)

    Hiscott John


    Full Text Available Abstract Background Hepatitis C virus (HCV encodes several proteins that interfere with the host cell antiviral response. Previously, the serine protease NS3/4A was shown to inhibit IFN-β gene expression by blocking dsRNA-activated retinoic acid-inducible gene I (RIG-I and Toll-like receptor 3 (TLR3-mediated signaling pathways. Results In the present work, we systematically studied the effect of all HCV proteins on IFN gene expression. NS2 and NS3/4A inhibited IFN gene activation. NS3/4A inhibited the Sendai virus-induced expression of multiple IFN (IFN-α, IFN-β and IFN-λ1/IL-29 and chemokine (CCL5, CXCL8 and CXCL10 gene promoters. NS2 and NS3/4A, but not its proteolytically inactive form NS3/4A-S139A, were found to inhibit promoter activity induced by RIG-I or its adaptor protein Cardif (or IPS-1/MAVS/VISA. Both endogenous and transfected Cardif were proteolytically cleaved by NS3/4A but not by NS2 indicating different mechanisms of inhibition of host cell cytokine production by these HCV encoded proteases. Cardif also strongly colocalized with NS3/4A at the mitochondrial membrane, implicating the mitochondrial membrane as the site for proteolytic cleavage. In many experimental systems, IFN priming dramatically enhances RNA virus-induced IFN gene expression; pretreatment of HEK293 cells with IFN-α strongly enhanced RIG-I expression, but failed to protect Cardif from NS3/4A-mediated cleavage and failed to restore Sendai virus-induced IFN-β gene expression. Conclusion HCV NS2 and NS3/4A proteins were identified as potent inhibitors of cytokine gene expression suggesting an important role for HCV proteases in counteracting host cell antiviral response.

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

    Directory of Open Access Journals (Sweden)

    Marijke van Rikxoort

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

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


    Hsing-Cheng Yu; Xie-Hong Tsai; An-Chun Luo; Ming Wu; Sei-Wang Chen


    When viewing three-dimensional (3D) images, whether in cinemas or on stereoscopic televisions, viewers experience the same problem of image brightness loss. This study aims to investigate image brightness loss in 3D displays, with the primary aim being to quantify the image brightness degradation in the 3D mode. A further aim is to determine the image brightness relationship to the corresponding two-dimensional (2D) images in order to adjust the 3D-image brightness values. In addition, the ph...

  20. Investigating the Bright End of LSST Photometry (United States)

    Ojala, Elle; Pepper, Joshua; LSST Collaboration


    The Large Synoptic Survey Telescope (LSST) will begin operations in 2022, conducting a wide-field, synoptic multiband survey of the southern sky. Some fraction of objects at the bright end of the magnitude regime observed by LSST will overlap with other wide-sky surveys, allowing for calibration and cross-checking between surveys. The LSST is optimized for observations of very faint objects, so much of this data overlap will be comprised of saturated images. This project provides the first in-depth analysis of saturation in LSST images. Using the PhoSim package to create simulated LSST images, we evaluate saturation properties of several types of stars to determine the brightness limitations of LSST. We also collect metadata from many wide-field photometric surveys to provide cross-survey accounting and comparison. Additionally, we evaluate the accuracy of the PhoSim modeling parameters to determine the reliability of the software. These efforts will allow us to determine the expected useable data overlap between bright-end LSST images and faint-end images in other wide-sky surveys. Our next steps are developing methods to extract photometry from saturated images.This material is based upon work supported in part by the National Science Foundation through Cooperative Agreement 1258333 managed by the Association of Universities for Research in Astronomy (AURA), and the Department of Energy under Contract No. DE-AC02-76SF00515 with the SLAC National Accelerator Laboratory. Additional LSST funding comes from private donations, grants to universities, and in-kind support from LSSTC Institutional Members.Thanks to NSF grant PHY-135195 and the 2017 LSSTC Grant Award #2017-UG06 for making this project possible.

  1. Dark and Bright Ridges on Europa (United States)


    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 galileo.

  2. An exceptionally bright, compact starburst nucleus (United States)

    Margon, Bruce; Anderson, Scott F.; Mateo, Mario; Fich, Michel; Massey, Philip


    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.

  3. Broadband bright twin beams and their upconversion (United States)

    Chekhova, Maria V.; Germanskiy, Semen; Horoshko, Dmitri B.; Kitaeva, Galiya Kh.; Kolobov, Mikhail I.; Leuchs, Gerd; Phillips, Chris R.; Prudkovskii, Pavel A.


    We report on the observation of broadband (40 THz) bright twin beams through high-gain parametric down-conversion in an aperiodically poled lithium niobate crystal. The output photon number is shown to scale exponentially with the pump power and not with the pump amplitude, as in homogeneous crystals. Photon-number correlations and the number of frequency/temporal modes are assessed by spectral covariance measurements. By using sum-frequency generation on the surface of a non-phasematched crystal, we measure a cross-correlation peak with the temporal width 90 fs.

  4. The NS3 and NS4A genes as the targets of RNA interference inhibit replication of Japanese encephalitis virus in vitro and in vivo. (United States)

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


    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. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Zika Virus NS4A and NS4B Proteins Deregulate Akt-mTOR Signaling in Human Fetal Neural Stem Cells to Inhibit Neurogenesis and Induce Autophagy

    DEFF Research Database (Denmark)

    Liang, Qiming; Luo, Zhifei; Zeng, Jianxiong


    The current widespread outbreak of Zika virus (ZIKV) infection has been linked to severe clinical birth defects, particularly microcephaly, warranting urgent study of the molecular mechanisms underlying ZIKV pathogenesis. Akt-mTOR signaling is one of the key cellular pathways essential for brain...... present in ZIKV, we found that two, NS4A and NS4B, cooperatively suppress the Akt-mTOR pathway and lead to cellular dysregulation. Corresponding proteins from the closely related dengue virus do not have the same effect on neurogenesis. Thus, our study highlights ZIKV NS4A and NS4B as candidate...

  6. Coronal bright points associated with minifilament eruptions

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Junchao; Jiang, Yunchun; Yang, Jiayan; Bi, Yi; Li, Haidong [Yunnan Observatories, Chinese Academy of Sciences, Kunming 650011 (China); Yang, Bo; Yang, Dan, E-mail: [Also at Graduate School of Chinese Academy of Sciences, Beijing, China. (China)


    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.

  7. Subpicosecond, high-brightness excimer laser systems

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, A.J.; Gosnell, T.R.; Roberts, J.P.; Lester, C.S.; Gibson, R.B.; Harper, S.E.; Tallman, C.R.


    Subpicosecond, high-brightness excimer laser systems are being used to explore the interaction of intense coherent ultraviolet radiation with matter. Applications of current systems include generation of picosecond x-ray pulses, investigation of possible x-ray laser pumping schemes, studies of multiphoton phenomena in atomic species, and time-resolved photochemistry. These systems, based on the amplification of subpicosecond pulses in small aperture (/approximately/1 cm/sup 2/) XeCl or KrF amplifiers, deliver focal spot intensities of /approximately/10/sup 17/ W/cm/sup 2/. Scaling to higher intensities, however, will require an additional large aperture amplifier which preserves near-diffraction-limited beam quality and subpicosecond pulse duration. We describe here both a small aperture KrF system which routinely provides intensities >10/sup 17/ W/cm/sup 2/ to several experiments, and a large aperture XeCl system designed to deliver /approximately/1 J subpicosecond pulses and yield intensities on target in excess of 10/sup 19/W/cm/sup 2/. We also discuss the effects of two-photon absorption on large-aperture, high-brightness excimer lasers. 4 refs., 2 figs.

  8. Optical Sky Brightness at Dome C, Antarctica (United States)

    Kenyon, S.; Storey, J. W. V.; Burton, M. G.


    Dome C, Antarctica is a prime site for astronomical observations in terms of climate, wind speeds and turbulence. The infrared and terahertz sky backgrounds are the lowest of any inhabited place on Earth. However, at present little is known about the optical sky brightness and atmospheric extinction. Using a variety of modelling techniques together with data from the South Pole, we estimate the brightness of the night sky including the contributions from scattered sunlight, moonlight, aurorae, airglow, zodiacal light and artificial sources. We compare our results to another prime astronomical site, Mauna Kea. We find moonlight has significantly less effect at Dome C than at Mauna Kea. Aurorae are expected to have a minor impact at both sites, and zodiacal light is expected to be less at Dome C than at Mauna Kea. Airglow emissions at Dome C are expected to be similar to those at temperate sites. With proper planning, artificial sources of light pollution should be non-existent. The overall atmospheric extinction, or opacity, is expected to be the minimum possible. We conclude that Dome C is a very promising site not only for infrared and terahertz astronomy, but for optical astronomy as well..

  9. Sublimation in bright spots on (1) Ceres (United States)

    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.


    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.

  10. Molecular Dynamics of the ZIKA Virus NS3 Helicase (United States)

    Raubenolt, Bryan; Rick, Steven; The Rick Group Team

    The recent outbreaks of the ZIKA virus (ZIKV) and its connection to microcephaly in newborns has raised its awareness as a global threat and many scientific research efforts are currently underway in attempt to create a vaccine. Molecular Dynamics is a powerful method of investigating the physical behavior of protein complexes. ZIKV is comprised of 3 structural and 7 nonstructural proteins. The NS3 helicase protein appears to play a significant role in the replication complex and its inhibition could be a crucial source of antiviral drug design. This research primarily focuses on studying the structural dynamics, over the course of few hundred nanoseconds, of NS3 helicase in the free state, as well as in complex form with human ssRNA, ATP, and an analogue of GTP. RMSD and RMSF plots of each simulation will provide details on the forces involved in the overall stability of the active and inactive states. Furthermore, free energy calculations on a per residue level will reveal the most interactive residues between states and ultimately the primary driving force behind these interactions. Together these analyses will provide highly relevant information on the binding surface chemistry and thus serve as the basis for potential drug design.

  11. Folding Proteins at 500 ns/hour with Work Queue. (United States)

    Abdul-Wahid, Badi'; Yu, Li; Rajan, Dinesh; Feng, Haoyun; Darve, Eric; Thain, Douglas; Izaguirre, Jesús A


    Molecular modeling is a field that traditionally has large computational costs. Until recently, most simulation techniques relied on long trajectories, which inherently have poor scalability. A new class of methods is proposed that requires only a large number of short calculations, and for which minimal communication between computer nodes is required. We considered one of the more accurate variants called Accelerated Weighted Ensemble Dynamics (AWE) and for which distributed computing can be made efficient. We implemented AWE using the Work Queue framework for task management and applied it to an all atom protein model (Fip35 WW domain). We can run with excellent scalability by simultaneously utilizing heterogeneous resources from multiple computing platforms such as clouds (Amazon EC2, Microsoft Azure), dedicated clusters, grids, on multiple architectures (CPU/GPU, 32/64bit), and in a dynamic environment in which processes are regularly added or removed from the pool. This has allowed us to achieve an aggregate sampling rate of over 500 ns/hour. As a comparison, a single process typically achieves 0.1 ns/hour.

  12. Bright Merger-nova Emission Powered by Magnetic Wind from a Newborn Black Hole (United States)

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


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

  13. New Distant Comet Headed for Bright Encounter (United States)


    How Impressive Will Comet Hale-Bopp Become in 1997 ? A very unusual comet was discovered last month, on its way from the outer reaches of the solar system towards the Sun. Although it is still situated beyond the orbit of Jupiter, it is so bright that it can be observed in even small telescopes. It has been named `Hale-Bopp' after the discoverers and is already of great interest to cometary astronomers. No less than seven telescopes have been used at the ESO La Silla observatory for the first observations of the new object. Together with data gathered at other sites, their aim is to elucidate the nature of this comet and also to determine whether there is reason to hope that it will become a bright and beautiful object in the sky from late 1996 and well into 1997. Further observations are now being planned at ESO and elsewhere to monitor closely the behaviour of this celestial visitor during the coming months. Discovery circumstances The comet was discovered on 23 July 1995, nearly simultaneously by two American amateur astronomers, Alan Hale of Cloudcroft (New Mexico) and Thomas Bopp of Glendale (Arizona). Although the chronology is slightly uncertain, it appears that Hale first saw it some 10 - 20 minutes before Bopp, at 06:10 - 06:15 UT on that day. In any case, he informed the IAU Central Bureau for Astronomical Telegrams (CBAT) in Cambridge (Massachussetts) about his discovery by email already at 06:50 UT, while Bopp's message was filed more than 2 hours later, after he had driven back to his home, 140 km from where he had been observing. Upon receipt of these messages, Brian Marsden at the CBAT assigned the designation `1995 O1' (indicating that it is the first comet found in the second half of July 1995). After further sightings had been made by other observers, and according to the venerable astronomical tradition, the new object was named after the discoverers. The magnitude, reported as 10.5 by Hale, is not unusual for a comet that is discovered within

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

    Directory of Open Access Journals (Sweden)

    Atkins John F


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

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

    Directory of Open Access Journals (Sweden)

    R. Balajee


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

  16. Bright sneezes and dark coughs, loud sunlight and soft moonlight. (United States)

    Marks, L E


    Synesthetic metaphors (such as "the dawn comes up like thunder") are expressions in which words or phrases describing experiences proper to one sense modality transfer their meanings to another modality. In a series of four experiments, subjects used scales of loudness, pitch, and brightness to evaluate the meanings of a variety of synesthetic (auditory-visual) metaphors. Loudness and pitch expressed themselves metaphorically as greater brightness; in turn, brightness expressed itself as greater loudness and as higher pitch. Although loudness thus shared with brightness a metaphorical connection, pitch and brightness showed a connection that was closer and that applied more generally to different kinds of visual brightness. The ways that people evaluate synesthetic metaphors emulate the characteristics of synesthetic perception, thereby suggesting that synesthesia in perception and synesthesia in language both may emenate from the same source-from a phenomenological similarity in the makeup of sensory experiences of different modalities.

  17. Bright photoluminescent hybrid mesostructured silica nanoparticles. (United States)

    Miletto, Ivana; Bottinelli, Emanuela; Caputo, Giuseppe; Coluccia, Salvatore; Gianotti, Enrica


    Bright photoluminescent mesostructured silica nanoparticles were synthesized by the incorporation of fluorescent cyanine dyes into the channels of MCM-41 mesoporous silica. Cyanine molecules were introduced into MCM-41 nanoparticles by physical adsorption and covalent grafting. Several photoluminescent nanoparticles with different organic loadings have been synthesized and characterized by X-ray powder diffraction, high resolution transmission electron microscopy and nitrogen physisorption porosimetry. A detailed photoluminescence study with the analysis of fluorescence lifetimes was carried out to elucidate the cyanine molecules distribution within the pores of MCM-41 nanoparticles and the influence of the encapsulation on the photoemission properties of the guests. The results show that highly stable photoluminescent hybrid materials with interesting potential applications as photoluminescent probes for diagnostics and imaging can be prepared by both methods.

  18. Bioinspired bright noniridescent photonic melanin supraballs. (United States)

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


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

  19. Kappa-effect and brightness oscillations of stars (United States)

    Zhugzhda, Y. D.; Roth, M.; Herzberg, W.


    In this paper the theory of visibility and darkening functions for the brightness oscillations of stars is outlined. For this the non-grey approximation is used and the effect of opacity disturbances on stellar brightness oscillations is explored for different types of stars. An explanation of the Procyon paradox is proposed. Special features of the brightness oscillations are discussed. The effect of opacity fluctuations on the damping of p-mode oscillations is considered. Furthermore, the photospheric kappa-mechanism is discussed.

  20. Cutaneous papilloma and squamous cell carcinoma therapy utilizing nanosecond pulsed electric fields (nsPEF.

    Directory of Open Access Journals (Sweden)

    Dong Yin

    Full Text Available Nanosecond pulsed electric fields (nsPEF induce apoptotic pathways in human cancer cells. The potential therapeutic effective of nsPEF has been reported in cell lines and in xenograft animal tumor model. The present study investigated the ability of nsPEF to cause cancer cell death in vivo using carcinogen-induced animal tumor model, and the pulse duration of nsPEF was only 7 and 14 nano second (ns. An nsPEF generator as a prototype medical device was used in our studies, which is capable of delivering 7-30 nanosecond pulses at various programmable amplitudes and frequencies. Seven cutaneous squamous cell carcinoma cell lines and five other types of cancer cell lines were used to detect the effect of nsPEF in vitro. Rate of cell death in these 12 different cancer cell lines was dependent on nsPEF voltage and pulse number. To examine the effect of nsPEF in vivo, carcinogen-induced cutaneous papillomas and squamous cell carcinomas in mice were exposed to nsPEF with three pulse numbers (50, 200, and 400 pulses, two nominal electric fields (40 KV/cm and 31 KV/cm, and two pulse durations (7 ns and 14 ns. Carcinogen-induced cutaneous papillomas and squamous carcinomas were eliminated efficiently using one treatment of nsPEF with 14 ns duration pulses (33/39 = 85%, and all remaining lesions were eliminated after a 2nd treatment (6/39 = 15%. 13.5% of carcinogen-induced tumors (5 of 37 were eliminated using 7 ns duration pulses after one treatment of nsPEF. Associated with tumor lysis, expression of the anti-apoptotic proteins Bcl-xl and Bcl-2 were markedly reduced and apoptosis increased (TUNEL assay after nsPEF treatment. nsPEF efficiently causes cell death in vitro and removes papillomas and squamous cell carcinoma in vivo from skin of mice. nsPEF has the therapeutic potential to remove human squamous carcinoma.

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

    Directory of Open Access Journals (Sweden)

    Hsing-Cheng Yu


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

  2. The night sky brightness at McDonald Observatory (United States)

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


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

  3. The capacitive sensing of NS1 Flavivirus biomarker. (United States)

    Cecchetto, Juliana; Fernandes, Flávio C B; Lopes, Rute; Bueno, Paulo R


    NS1 is a biomarker for different Flavivirus diseases such as dengue (DENV), zika (ZIKV) and chikungunya (CHIKV) and was herein selectively quantified by electrochemical capacitive sensing (an impedance-derived capacitance methodology wherein the redox probe is contained in the receptive layer) mainly aiming dengue diagnosis in phosphate buffer saline and blood serum environments (up to the neat level). The capacitive sensing was compared to traditional concurrent impedimetric approach (in which the redox probe is added in the biological solution) and other transient methods stated in the literature regarding figures of merit such as limit of detection, linear range, relative standard deviation and affinity constant. Capacitive and impedimetric assays showed equivalent results for linear range, repeatability, sensitivity and constant of affinity. Nonetheless capacitive assays presented better reproducibility with a relative standard deviation (RSD) of 3±1 and 7±4 (all in percentage) in PBS and serum, respectively, meanwhile for impedimetric assays the RSD values were 9±5 in PBS and 12±6 in serum. Thus, by using capacitive assays, an improvement on the analytical performance was observed with the limit of detection about sixty-fold lower in neat serum (∼0.5ngmL-1 for capacitive over ∼30ngmL-1 for impedimetric assays) compared to traditional electrochemistry methods in general hence demonstrating the superior detection sensitivity for NS1 protein. Accordingly, redox tagged capacitive assays are suitable for the development of multiplex point-of-care neglected diseases sensing applications. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Characterization of the Determinants of NS2-3-Independent Virion Morphogenesis of Pestiviruses. (United States)

    Klemens, O; Dubrau, D; Tautz, N


    A peculiarity of the Flaviviridae is the critical function of nonstructural (NS) proteins for virus particle formation. For pestiviruses, like bovine viral diarrhea virus (BVDV), uncleaved NS2-3 represents an essential factor for virion morphogenesis, while NS3 is an essential component of the viral replicase. Accordingly, in natural pestivirus isolates, processing at the NS2-3 cleavage site is not complete, to allow for virion morphogenesis. Virion morphogenesis of the related hepatitis C virus (HCV) shows a major deviation from that of pestiviruses: while RNA replication also requires free NS3, virion formation does not depend on uncleaved NS2-NS3. Recently, we described a BVDV-1 chimera based on strain NCP7 encompassing the NS2-4B*-coding region of strain Osloss (E. Lattwein, O. Klemens, S. Schwindt, P. Becher, and N. Tautz, J Virol 86:427-437, 2012, doi:10.1128/JVI.06133-11). This chimera allowed for the production of infectious virus particles in the absence of uncleaved NS2-3. The Osloss sequence deviates in the NS2-4B* part from NCP7 in 48 amino acids and also has a ubiquitin insertion between NS2 and NS3. The present study demonstrates that in the NCP7 backbone, only two amino acid exchanges in NS2 (E1576V) and NS3 (V1721A) are sufficient and necessary to allow for efficient NS2-3-independent virion morphogenesis. The adaptation of a bicistronic virus encompassing an internal ribosomal entry site element between the NS2 and NS3 coding sequences to efficient virion morphogenesis led to the identification of additional amino acids in E2, NS2, and NS5B that are critically involved in this process. The surprisingly small requirements for approximating the packaging schemes of pestiviruses and HCV with respect to the NS2-3 region is in favor of a common mechanism in an ancestral virus. For positive-strand RNA viruses, the processing products of the viral polyprotein serve in RNA replication as well as virion morphogenesis. For bovine viral diarrhea virus

  5. The possible existence of Pop III NS-BH binary and its detectability (United States)

    Kinugawa, Tomoya; Nakamura, Takashi; Nakano, Hiroyuki


    In the population synthesis simulations of Pop III stars, many BH (black hole)-BH binaries with merger time less than the age of the Universe (τH) are formed, while NS (neutron star)-BH binaries are not. The reason is that Pop III stars have no metal so that no mass loss is expected. Then, in the final supernova explosion to NS, much mass is lost so that the semimajor axis becomes too large for Pop III NS-BH binaries to merge within τH . However it is almost established that the kick velocity of the order of 200 ‑500  km s‑1 exists for NS from the observation of the proper motion of the pulsar. Therefore, the semimajor axis of the half of NS-BH binaries can be smaller than that of the previous argument for Pop III NS-BH binaries to decrease the merging time. We perform population synthesis Monte Carlo simulations of Pop III NS-BH binaries including the kick of NS and find that the event rate of Pop III NS-BH merger rate is 1  Gpc‑3 yr‑1 . This suggests that there is a good chance of detecting Pop III NS-BH mergers in O2 (Observation run 2) of Advanced LIGO and Advanced Virgo from this autumn.

  6. Characterising Non-Structural Protein NS4 of African Horse Sickness Virus.

    Directory of Open Access Journals (Sweden)

    Lizahn Zwart

    Full Text Available African horse sickness is a serious equid disease caused by the orbivirus African horse sickness virus (AHSV. The virus has ten double-stranded RNA genome segments encoding seven structural and three non-structural proteins. Recently, an additional protein was predicted to be encoded by genome segment 9 (Seg-9, which also encodes VP6, of most orbiviruses. This has since been confirmed in bluetongue virus and Great Island virus, and the non-structural protein was named NS4. In this study, in silico analysis of AHSV Seg-9 sequences revealed the existence of two main types of AHSV NS4, designated NS4-I and NS4-II, with different lengths and amino acid sequences. The AHSV NS4 coding sequences were in the +1 reading frame relative to that of VP6. Both types of AHSV NS4 were expressed in cultured mammalian cells, with sizes close to the predicted 17-20 kDa. Fluorescence microscopy of these cells revealed a dual cytoplasmic and nuclear, but not nucleolar, distribution that was very similar for NS4-I and NS4-II. Immunohistochemistry on heart, spleen, and lung tissues from AHSV-infected horses showed that NS4 occurs in microvascular endothelial cells and mononuclear phagocytes in all of these tissues, localising to the both the cytoplasm and the nucleus. Interestingly, NS4 was also detected in stellate-shaped dendritic macrophage-like cells with long cytoplasmic processes in the red pulp of the spleen. Finally, nucleic acid protection assays using bacterially expressed recombinant AHSV NS4 showed that both types of AHSV NS4 bind dsDNA, but not dsRNA. Further studies will be required to determine the exact function of AHSV NS4 during viral replication.

  7. Genetic analysis of nonstructural genes (NS1 and NS2) of H9N2 and H5N1 viruses recently isolated in Israel. (United States)

    Banet-Noach, Caroline; Panshin, Alexander; Golender, Natalia; Simanov, Lubov; Rozenblut, Ezra; Pokamunski, Shimon; Pirak, Michael; Tendler, Yevgenii; García, Maricarmen; Gelman, Boris; Pasternak, Ruslan; Perk, Shimon


    The avian influenza virus subtype H9N2 affects wild birds, domestic poultry, swine, and humans; it has circulated amongst domestic poultry in Israel during the last 6 years. The H5N1 virus was recorded in Israel for the first time in March 2006. Nonstructural (NS) genes and NS proteins are important in the life cycle of the avian influenza viruses. In the present study, NS genes of 21 examples of H9N2 and of two examples of H5N1 avian influenza viruses, isolated in Israel during 2000-2006, were completely sequenced and phylogenetically analyzed. All the H9N2 isolates fell into a single group that, in turn, was subdivided into three subgroups in accordance with the time of isolation; their NS1 and NS2 proteins possessed 230 and 121 amino acids, respectively. The NS1 protein of the H5N1 isolates had five amino acid deletions, which was typical of highly pathogenic H5N1 viruses isolated in various countries during 2005-2006. Comparative analysis showed that the NS proteins of the H9N2 Israeli isolates contained few amino acid sequences associated with high pathogenicity or human host specificity.

  8. A new perspective on the infrared brightness temperature ...

    Indian Academy of Sciences (India)

    And Johnson SB parameters are observed to be best in discriminating the Johnson SB distribution of infrared brightness temperatures of deep convective systems for each season. Due to these properties of Johnson SB function, it can be utilized in the modelling of the histogram of infrared brightness temperature of deep ...

  9. A new perspective on the infrared brightness temperature ...

    Indian Academy of Sciences (India)

    It is observed that Johnson SB function is the best continuous distribution function in explaining the histogram of infrared brightness temperatures of the convective clouds. The best fit is confirmed by Kolmogorov–Smirnov statistic. Johnson SB's distribution of histogram of infrared brightness temperatures clearly ...

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

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

  11. Edge integration and the perception of brightness and darkness

    NARCIS (Netherlands)

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


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

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

    DEFF Research Database (Denmark)

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


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

  13. Lamp spectrum and spatial brightness at photopic levels

    DEFF Research Database (Denmark)

    Fotios, Steve; Atli, Deniz; Cheal, Chris


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

  14. Brightness limitations of cold field emitters caused by Coulomb interactions

    NARCIS (Netherlands)

    Cook, B.J.; Verduin, T.; Hagen, C.W.; Kruit, P.


    Emission theory predicts that high brightness cold field emitters can enhance imaging in the electron microscope. This (neglecting chromatic aberration) is because of the large (coherent) probe current available from a high brightness source and is based on theoretically determined values of reduced

  15. Surface photometry of bulge dominated low surface brightness galaxies

    NARCIS (Netherlands)

    Beijersbergen, M; de Blok, WJG; van der Hulst, JM


    We present results of broad band BVRI observations of a sample of galaxies with a low surface brightness (LSB) disk and a bulge. These galaxies are well described as exponential disks and exponential bulges with no preferred value for either scale length or central surface brightness. The median B

  16. Spatial Model of Sky Brightness Magnitude in Langkawi Island, Malaysia (United States)

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


    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.

  17. An isolated, bright cusp aurora at Saturn (United States)

    Kinrade, J.; Badman, S. V.; Bunce, E. J.; Tao, C.; Provan, G.; Cowley, S. W. H.; Grocott, A.; Gray, R. L.; Grodent, D.; Kimura, T.; Nichols, J. D.; Arridge, C. S.; Radioti, A.; Clarke, J. T.; Crary, F. J.; Pryor, W. R.; Melin, H.; Baines, K. H.; Dougherty, M. K.


    Saturn's dayside aurora displays a number of morphological features poleward of the main emission region. We present an unusual morphology captured by the Hubble Space Telescope on 14 June 2014 (day 165), where for 2 h, Saturn's FUV aurora faded almost entirely, with the exception of a distinct emission spot at high latitude. The spot remained fixed in local time between 10 and 15 LT and moved poleward to a minimum colatitude of 4°. It was bright and persistent, displaying intensities of up to 49 kR over a lifetime of 2 h. Interestingly, the spot constituted the entirety of the northern auroral emission, with no emissions present at any other local time—including Saturn's characteristic dawn arc, the complete absence of which is rarely observed. Solar wind parameters from propagation models, together with a Cassini magnetopause crossing and solar wind encounter, indicate that Saturn's magnetosphere was likely to have been embedded in a rarefaction region, resulting in an expanded magnetosphere configuration during the interval. We infer that the spot was sustained by reconnection either poleward of the cusp or at low latitudes under a strong component of interplanetary magnetic field transverse to the solar wind flow. The subsequent poleward motion could then arise from either reconfiguration of successive open field lines across the polar cap or convection of newly opened field lines. We also consider the possible modulation of the feature by planetary period rotating current systems.

  18. Intercomparisons of Nine Sky Brightness Detectors

    Directory of Open Access Journals (Sweden)

    Henk Spoelstra


    Full Text Available 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/m2 on 12 April, and the largest value was 5.94 ± 0.03 mcd/m2 on 2 April. During both occurrences interfering circumstances like snow cover or moonlight were absent.

  19. The Los Alamos high-brightness photoinjector

    Energy Technology Data Exchange (ETDEWEB)

    O' Shea, P.G.


    For a number of years Los Alamos National Laboratory has been developing photocathode RF guns for high-brightness electron beam applications such as free-electron lasers (FELs). Previously thermionic high-voltage guns have been the source of choice for the electron accelerators used to drive FELs. The performance of such FELs is severely limited by the emittance growth produced by the subharmonic bunching process and also by the low peak current of the source. In a photoinjector, a laser driven photocathode is placed directly in a high-gradient RF accelerating cavity. A photocathode allows unsurpassed control over the current, and the spatial and temporal profile of the beam. In addition the electrodeless emission'' avoids many of the difficulties associated with multi-electrode guns, i.e. the electrons are accelerated very rapidly to relativistic energies, and there are no electrodes to distort the accelerating fields. For the past two years we have been integrating a photocathode into our existing FEL facility by replacing our thermionic gun and subharmonic bunchers with a high-gradient 1.3 GHz photoinjector. The photoinjector, which is approximately 0.6 m in length, produces 6 MeV, 300 A, 15 ps linac, and accelerated to a final energy of 40 MeV. We have recently begun lasing at wavelengths near 3 {mu}m. 16 refs., 2 figs., 5 tabs.

  20. Dark Skies, Bright Kids Year 6 (United States)

    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


    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.

  1. Dark Skies, Bright Kids Year 9 (United States)

    Burkhardt, Andrew Michael; Mathews, Allison M.; Johnson, Kelsey E.; Avilez, Ian; Beale, Luca; Bittle, Lauren E.; Bordenave, David; Finn, Molly; Firebaugh, Ariel; Hancock, Danielle; Hughes, Paul; Rochford Hayes, Christian; Lewis, Hannah; Linden, Sean; Liss, Sandra; Liu, Mengyao; McNair, Shunlante; Murphy, Edward; Prager, Brian; Pryal, Matthew; Richardson, Whitney; Song, Yiqing; Troup, Nicholas; Villadsen, Jackie; Wenger, Trey V.; Wilson, Robert Forrest


    We present updates from the ninth year of operation of Dark Skies, Bright Kids (DSBK) including new club content, continued assessments, and our seventh annual Star Party. 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 Virginia through fun, hands-on activities that introduce basic Astronomy concepts. DSBK’s most fundamental program is an 8-10 week long after-school Astronomy camp at surrounding local elementary schools, where each week introduces new concepts through interactive hands-on activities. Over the past two summers, we have traveled to four rural Virginia locations to bring week-long Astronomy camps to otherwise overlooked elementary school districts. These programs aim to inspire a curiosity for science and include inquiry based activities in topics ranging from the electromagnetic spectrum to the classification and evolution of galaxies. We strive to be self-reflective in our mission to inspire scientific curiosity in the minds of underserved demographics. In this effort, we continually assess the effectiveness of each activity through feedback in student-kept journal pages and observed excitement levels. This self-reflection has initiated the development of new curriculum. In addition, differing from our normal collaboration with local elementary schools, we have found great success partnering with local youth organizations, who may better represent DSBK's target demographics and have infrastructure to support incoming outreach groups.

  2. Bright visible light emission from graphene. (United States)

    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; Yoo, Yong Shim; 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


    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.

  3. Modular Zero Energy. BrightBuilt Home

    Energy Technology Data Exchange (ETDEWEB)

    Aldrich, Robb [Consortium for Advanced Residential Buildings (CARB), Norwalk, CT (United States). Steven Winters Associates, Inc.; Butterfield, Karla [Consortium for Advanced Residential Buildings (CARB), Norwalk, CT (United States). Steven Winters Associates, Inc.


    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.

  4. In Silico Approaches to the Design of NS5A Inhibitors. (United States)

    Ivanenkov, Yan A; Veselov, Mark S; Aladinskiy, Vladimir A; Shakhbazyan, Artem G; Yartseva, Sofya M; Majouga, Alexander G; Aladinskaya, Anastasia V; Vantskul, Anton S; Leonov, Sergey V; Ivachtchenko, Alexandre V; Koteliansky, Victor E


    In recent years, nonstructural protein 5A (NS5A) has rapidly emerged as a promising therapeutic target for Hepatitis C (HCV) virus therapy. It is involved in both viral RNA replication and virus assembly and NS5A plays a critical role in the regulation of HCV life cycle. NS5A replication complex inhibitors (NS5A RCIs) have demonstrated strong antiviral activity in vitro and in vivo. However, wild-type resistance mutations and a wide range of genotypes significantly reduce their clinical efficacy. The exact mechanism of NS5A action still remains elusive, therefore several in silico models have been constructed to gain insight into the drug binding and subsequent structural optimization to overcome resistance. This paper provides a comprehensive overview of the computational studies towards NS5A mechanism of action and the design of novel small-molecule inhibitors.

  5. Intracellular degradation and localization of NS1 of TBEV affects its protective properties. (United States)

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


    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.

  6. Intrinsic brightness temperatures of blazar jets at 15 GHz

    Directory of Open Access Journals (Sweden)

    Hovatta Talvikki


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

  7. Multifunctional adaptive NS1 mutations are selected upon human influenza virus evolution in the mouse.

    Directory of Open Access Journals (Sweden)

    Nicole E Forbes

    Full Text Available The role of the NS1 protein in modulating influenza A virulence and host range was assessed by adapting A/Hong Kong/1/1968 (H3N2 (HK-wt to increased virulence in the mouse. Sequencing the NS genome segment of mouse-adapted variants revealed 11 mutations in the NS1 gene and 4 in the overlapping NEP gene. Using the HK-wt virus and reverse genetics to incorporate mutant NS gene segments, we demonstrated that all NS1 mutations were adaptive and enhanced virus replication (up to 100 fold in mouse cells and/or lungs. All but one NS1 mutant was associated with increased virulence measured by survival and weight loss in the mouse. Ten of twelve NS1 mutants significantly enhanced IFN-β antagonism to reduce the level of IFN β production relative to HK-wt in infected mouse lungs at 1 day post infection, where 9 mutants induced viral yields in the lung that were equivalent to or significantly greater than HK-wt (up to 16 fold increase. Eight of 12 NS1 mutants had reduced or lost the ability to bind the 30 kDa cleavage and polyadenylation specificity factor (CPSF30 thus demonstrating a lack of correlation with reduced IFN β production. Mutant NS1 genes resulted in increased viral mRNA transcription (10 of 12 mutants, and protein production (6 of 12 mutants in mouse cells. Increased transcription activity was demonstrated in the influenza mini-genome assay for 7 of 11 NS1 mutants. Although we have shown gain-of-function properties for all mutant NS genes, the contribution of the NEP mutations to phenotypic changes remains to be assessed. This study demonstrates that NS1 is a multifunctional virulence factor subject to adaptive evolution.

  8. Daclatasvir inhibits hepatitis C virus NS5A motility and hyper-accumulation of phosphoinositides (United States)

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


    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

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

    Directory of Open Access Journals (Sweden)

    Koichi Higashi


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

  10. Latest advances in high brightness disk lasers (United States)

    Kuhn, Vincent; Gottwald, Tina; Stolzenburg, Christian; Schad, Sven-Silvius; Killi, Alexander; Ryba, Tracey


    In the last decade diode pumped solid state lasers have become an important tool for many industrial materials processing applications. They combine ease of operation with efficiency, robustness and low cost. This paper will give insight in latest progress in disk laser technology ranging from kW-class CW-Lasers over frequency converted lasers to ultra-short pulsed lasers. The disk laser enables high beam quality at high average power and at high peak power at the same time. The power from a single disk was scaled from 1 kW around the year 2000 up to more than 10 kW nowadays. Recently was demonstrated more than 4 kW of average power from a single disk close to fundamental mode beam quality (M²=1.38). Coupling of multiple disks in a common resonator results in even higher power. As an example we show 20 kW extracted from two disks of a common resonator. The disk also reduces optical nonlinearities making it ideally suited for short and ultrashort pulsed lasers. In a joint project between TRUMPF and IFSW Stuttgart more than 1.3 kW of average power at ps pulse duration and exceptionally good beam quality was recently demonstrated. The extremely low saturated gain makes the disk laser ideal for internal frequency conversion. We show >1 kW average power and >6 kW peak power in multi ms pulsed regime from an internally frequency doubled disk laser emitting at 515 nm (green). Also external frequency conversion can be done efficiently with ns pulses. >500 W of average UV power was demonstrated.

  11. H-NS mediates the silencing of laterally acquired genes in bacteria.

    Directory of Open Access Journals (Sweden)

    Sacha Lucchini


    Full Text Available Histone-like nucleoid structuring protein (H-NS is a modular protein that is associated with the bacterial nucleoid. We used chromatin immunoprecipitation to determine the binding sites of H-NS and RNA polymerase on the Salmonella enterica serovar Typhimurium chromosome. We found that H-NS does not bind to actively transcribed genes and does not co-localize with RNA polymerase. This shows that H-NS principally silences gene expression by restricting the access of RNA polymerase to the DNA. H-NS had previously been shown to preferentially bind to curved DNA in vitro. In fact, at the genomic level we discovered that the level of H-NS binding correlates better with the AT-content of DNA. This is likely to have evolutionary consequences because we show that H-NS binds to many Salmonella genes acquired by lateral gene transfer, and functions as a gene silencer. The removal of H-NS from the cell causes un-controlled expression of several Salmonella pathogenicity islands, and we demonstrate that this has deleterious consequences for bacterial fitness. Our discovery of this novel role for H-NS may have implications for the acquisition of foreign genes by enteric bacteria.

  12. Degradation of Dye Wastewater by ns-Pulse DBD Plasma (United States)

    Gao, Jin; Gu, Pingdao; Yuan, Li; Zhong, Fangchuan


    Two plasma reactors have been developed and used to degrade dye wastewater agents. The configuration of one plasma reactor is a comb-like extendable unit module consisting of 5 electrodes covered with a quartz tube and the other one is an array reactor which is extended from the unit module. The decomposition of wastewater by ns pulse dielectric barrier discharge (DBD) plasma have been carried out by atomizing the dyeing solutions into the reactors. During experiments, the indigo carmine has been treated as the waste agent. The measurements of UV-VIS absorption spectroscopy and the chemical oxygen demand (COD) are carried out to demonstrate the decomposition effect on the wastewater. It shows that the decoloration rate of 99% and the COD degradation rate of 65% are achieved with 15 min treatment in the unit reactor. The effect of electrical parameters on degradation has been studied in detail. Results from the array reactor indicate that it has a better degradation effect than the unit one. It can not only totally remove the chromogenic bond of the indigo carmine solution, but also effectively degrade unsaturated bonds. The decoloration rate reaches 99% after 10 min treatment, the decomposition rate of the unsaturated bond reaches 83% after 60 min treatment, and the COD degradation rate is nearly 74%.

  13. Time stamping of single optical photons with 10 ns resolution (United States)

    Chakaberia, Irakli; Cotlet, Mircea; Fisher-Levine, Merlin; Hodges, Diedra R.; Nguyen, Jayke; Nomerotski, Andrei


    High spatial and temporal resolution are key features for many modern applications, e.g. mass spectrometry, probing the structure of materials via neutron scattering, studying molecular structure, etc.1-5 Fast imaging also provides the capability of coincidence detection, and the further addition of sensitivity to single optical photons with the capability of timestamping them further broadens the field of potential applications. Photon counting is already widely used in X-ray imaging,6 where the high energy of the photons makes their detection easier. TimepixCam is a novel optical imager,7 which achieves high spatial resolution using an array of 256×256 55 μm × 55μm pixels which have individually controlled functionality. It is based on a thin-entrance-window silicon sensor, bump-bonded to a Timepix ASIC.8 TimepixCam provides high quantum efficiency in the optical wavelength range (400-1000 nm). We perform the timestamping of single photons with a time resolution of 20 ns, by coupling TimepixCam to a fast image-intensifier with a P47 phosphor screen. The fast emission time of the P479 allows us to preserve good time resolution while maintaining the capability to focus the optical output of the intensifier onto the 256×256 pixel Timepix sensor area. We demonstrate the capability of the (TimepixCam + image intensifier) setup to provide high-resolution single-photon timestamping, with an effective frame rate of 50 MHz.

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

    DEFF Research Database (Denmark)

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


    to modulate the channel. Here, we address this issue by synthesising a methylated analogue of the tool KCa1.1 channel activator NS11021. The compound (NS13558) is designed as a structurally closely related and biologically inactive analogue of NS11021. NS13558 did not elicit any significant opening of cloned...... derivate of NS11021, i.e., NS13558, did not confer any cardioprotection, demonstrated by an infarct size identical to control hearts. This suggests that NS11021 exerts its primary effect through KCa1.1 channels, which indicates an important role of these channels in protection against ischemia...

  15. Design, structure-based focusing and in silico screening of combinatorial library of peptidomimetic inhibitors of Dengue virus NS2B-NS3 protease (United States)

    Frecer, Vladimir; Miertus, Stanislav


    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.

  16. Dark Skies, Bright Kids: Year 2 (United States)

    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.


    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.

  17. Optical microvariability of bright type 2 quasars (United States)

    Polednikova, Jana; Ederoclite, Alessandro; Cepa, Jordi; de Diego Onsurbe, José Antonio; González-Serrano, José Ignacio


    We present results from a project focused on searching optical microvariabilty (also known as ``intra-night'' variability) in type 2 - obscured - quasars. Optical microvariability can be described as very small changes in the flux, typically in the order of hundredths of magnitude, which can be observed on timescales of hours. Such studies have been so far conducted for samples of blazars and type 1, unobscured, AGNs, where the optical microvariability was detected with success. We have focused on obscured targets which would pose a challenge to the AGN standard model. In the present work, however, we have observed a sample of three bright (g mag < 17) type 2 quasar, based on the catalog of type 2 quasars from SDSS of Reyes et al. (2008). The observations were carried out with the 1.5 meter telescope at San Pedro Martir observatory in Mexico. The sample was observed during an observation period of four days in Johnsons V filter, resulting in at least two continuous intervals of observations per target during the observational run. We have obtained differential light curves for our sources as well as for the comparison stars. They were analyzed using one-way analysis of variance statistical test (ANOVA), which has been repeatedly used in the past for studies of unobscured targets. Based on the results from the statistical analysis, we show that at least two out of three observed targets appear to be variable on time scales of hours. So far, this is the first study which confirmed existence of optical microvariability in type 2 quasars.

  18. Visual features underlying perceived brightness as revealed by classification images.

    Directory of Open Access Journals (Sweden)

    Ilmari Kurki

    Full Text Available Along with physical luminance, the perceived brightness is known to depend on the spatial structure of the stimulus. Often it is assumed that neural computation of the brightness is based on the analysis of luminance borders of the stimulus. However, this has not been tested directly. We introduce a new variant of the psychophysical reverse-correlation or classification image method to estimate and localize the physical features of the stimuli which correlate with the perceived brightness, using a brightness-matching task. We derive classification images for the illusory Craik-O'Brien-Cornsweet stimulus and a "real" uniform step stimulus. For both stimuli, classification images reveal a positive peak at the stimulus border, along with a negative peak at the background, but are flat at the center of the stimulus, suggesting that brightness is determined solely by the border information. Features in the perceptually completed area in the Craik-O'Brien-Cornsweet do not contribute to its brightness, nor could we see low-frequency boosting, which has been offered as an explanation for the illusion. Tuning of the classification image profiles changes remarkably little with stimulus size. This supports the idea that only certain spatial scales are used for computing the brightness of a surface.

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

    Directory of Open Access Journals (Sweden)

    Kwang-Ho Hur

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

  20. High-speed CuBr brightness amplifier beam profile (United States)

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


    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.

  1. Identification and Analysis of Novel Inhibitors against NS3 Helicase and NS5B RNA-Dependent RNA Polymerase from Hepatitis C Virus 1b (Con1

    Directory of Open Access Journals (Sweden)

    Na Yang


    Full Text Available Hepatitis C virus (HCV leads to severe liver diseases, including liver fibrosis, cirrhosis and hepatocellular carcinoma. Non-structural protein 3 helicase (NS3h and non-structural protein 5B RNA-dependent RNA polymerase (NS5B are involved in the replication of HCV RNA genome, and have been proved to be excellent targets for discovery of direct-acting antivirals. In this study, two high-throughput screening systems, fluorescence polarization (FP-based ssDNA binding assay and fluorescence intensity (FI-based dsRNA formation assay, were constructed to identify candidate NS3h and NS5B inhibitors, respectively. A library of approximately 800 small molecules and crude extracts, derived from marine microorganisms or purchased from the National Compound Resource Center, China, were screened, with three hits selected for further study. Natural compound No.3A5, isolated from marine fungi, inhibited NS3h activity with an IC50 value of 2.8 μM. We further demonstrated that compound No.3A5 inhibited the abilities of NS3h to bind ssDNA in electrophoretic mobility shift assay and to hydrolyze ATP. The NS3h-inhibitory activity of compound No.3A5 was reversible in our dilution assay, which indicated there was no stable NS3h-No.3A5 complex formed. Additionally, compound No.3A5 exhibited no binding selectivity on NS3h or single strand binding protein of Escherichia coli. In NS5B assays, commercial compounds No.39 and No.94 previously reported as kinase inhibitors were found to disrupt dsRNA formation, and their IC50 values were 62.9 and 18.8 μM, respectively. These results highlight how identifying new uses for existing drugs is an effective method for discovering novel HCV inhibitors. To our knowledge, all inhibitors reported in this study were originally discovered with HCV anti-non-structural protein activities in vitro.

  2. Antiviral Activity and Resistance Analysis of NS3/4A Protease Inhibitor Grazoprevir and NS5A Inhibitor Elbasvir in Hepatitis C Virus GT4 Replicons. (United States)

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


    Although genotype 4 (GT4)-infected patients represent a minor overall percentage of the global hepatitis C virus (HCV)-infected population, the high prevalence of the genotype in specific geographic regions coupled with substantial sequence diversity makes it an important genotype to study for antiviral drug discovery and development. We evaluated two direct-acting antiviral agents-grazoprevir, an HCV NS3/4A protease inhibitor, and elbasvir, an HCV NS5A inhibitor-in GT4 replicons prior to clinical studies in this genotype. Following a bioinformatics analysis of available GT4 sequences, a set of replicons bearing representative GT4 clinical isolates was generated. For grazoprevir, the 50% effective concentration (EC50) against the replicon bearing the reference GT4a (ED43) NS3 protease and NS4A was 0.7 nM. The median EC50 for grazoprevir against chimeric replicons encoding NS3/4A sequences from GT4 clinical isolates was 0.2 nM (range, 0.11 to 0.33 nM; n = 5). The difficulty in establishing replicons bearing NS3/4A resistance-associated substitutions was substantially overcome with the identification of a G162R adaptive substitution in NS3. Single NS3 substitutions D168A/V identified from de novo resistance selection studies reduced grazoprevir antiviral activity by 137- and 47-fold, respectively, in the background of the G162R replicon. For elbasvir, the EC50 against the replicon bearing the reference full-length GT4a (ED43) NS5A gene was 0.0002 nM. The median EC50 for elbasvir against chimeric replicons bearing clinical isolates from GT4 was 0.0007 nM (range, 0.0002 to 34 nM; n = 14). De novo resistance selection studies in GT4 demonstrated a high propensity to suppress the emergence of amino acid substitutions that confer high-potency reductions to elbasvir. Phenotypic characterization of the NS5A amino acid substitutions identified (L30F, L30S, M31V, and Y93H) indicated that they conferred 15-, 4-, 2.5-, and 7.5-fold potency losses, respectively, to elbasvir. The

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

    DEFF Research Database (Denmark)

    Dagø, Lone; Bonde, Christian; Peters, Dan


    NS 1231 [5-(4-chlorophenyl)-6,7,8,9-tetrahydro-1H-pyrrolo-[3.2-h]naphthalene-2,3-dione-3-oxime] belongs to a chemical series of compounds, which exhibit neurotrophic-like activities. In vitro, NS 1231 rescued nerve growth factor (NGF)-differentiated PC12 cells from death induced by withdrawal...

  4. Differential regulation of horizontally acquired and core genome genes by the bacterial modulator H-NS.

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    Rosa C Baños


    Full Text Available Horizontal acquisition of DNA by bacteria dramatically increases genetic diversity and hence successful bacterial colonization of several niches, including the human host. A relevant issue is how this newly acquired DNA interacts and integrates in the regulatory networks of the bacterial cell. The global modulator H-NS targets both core genome and HGT genes and silences gene expression in response to external stimuli such as osmolarity and temperature. Here we provide evidence that H-NS discriminates and differentially modulates core and HGT DNA. As an example of this, plasmid R27-encoded H-NS protein has evolved to selectively silence HGT genes and does not interfere with core genome regulation. In turn, differential regulation of both gene lineages by resident chromosomal H-NS requires a helper protein: the Hha protein. Tight silencing of HGT DNA is accomplished by H-NS-Hha complexes. In contrast, core genes are modulated by H-NS homoligomers. Remarkably, the presence of Hha-like proteins is restricted to the Enterobacteriaceae. In addition, conjugative plasmids encoding H-NS variants have hitherto been isolated only from members of the family. Thus, the H-NS system in enteric bacteria presents unique evolutionary features. The capacity to selectively discriminate between core and HGT DNA may help to maintain horizontally transmitted DNA in silent form and may give these bacteria a competitive advantage in adapting to new environments, including host colonization.

  5. The mechanism underlying Ler-mediated alleviation of gene repression by H-NS. (United States)

    Shin, Minsang


    Secretion of effector proteins in Enteropathogeneic Escherichia coli (EPEC) and Enterohemorrhagic Escherichia coli (EHEC) is mediated by a specialized type III secretion system, components of which are encoded in the LEE operons 1 to 5. H-NS, a global repressor in E. coli, silences the expression of LEE operons. Ler, a master regulator in LEE operons, shares 24% amnio acid identity and 44% amino acid similarity to H-NS. Interestingly, rather than a gene silencer, its main role has been characterized as an antagonizing protein that relieves H-NS-mediated transcriptional silencing. In the previous study we reported molecular mechanism for the repression of LEE5 promoter in EPEC and EHEC by H-NS as a protein interaction between upstream DNA-bound H-NS and the αCTD of promoter-bound RNA polymerase. The mechanism underlying Ler-mediated alleviation of the genes repression by H-NS is largely unknown. We examined regulatory effect of these proteins on LEE5p activity using various in vitro tools. Our results revealed that binding affinity of Ler to the LEE5p DNA is about 40 folds greater than that of H-NS as determined by surface plasmon resonance. We verified that Ler binding removed H-NS bound to the same stretch of DNA on LEE5 promoter resulting in a derepression. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Experimental evidence and molecular modeling of the interaction between hRSV-NS1 and quercetin. (United States)

    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


    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. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Prevalence of natural polymorphisms at the HCV NS5A gene associated with resistance to daclatasvir, an NS5A inhibitor. (United States)

    Plaza, Zulema; Soriano, Vincent; Vispo, Eugenia; del Mar Gonzalez, Maria; Barreiro, Pablo; Seclén, Eduardo; Poveda, Eva


    Daclatasvir (BMS-790052) is an investigational molecule that inhibits the HCV NS5A protein and shows potent antiviral activity apparently across all HCV genotypes. Selection of drug resistance mutations has been reported only for HCV genotype 1, and no information exists for other HCV variants and/or in HIV-HCV-coinfected individuals. All interferon-α-naive, HIV-HCV-coinfected patients newly attended at Hospital Carlos III (Madrid, Spain) in 2011 were identified. Changes reported to be associated with daclatasvir resistance in the in vitro replication system for HCV genotype/subtypes 1a/1b (M28T, Q30H/R, L31F/M/V, P32L and Y93C/H/N) were examined. A total of 78 HIV-HCV-coinfected individuals as well as 635 NS5A sequences deposited at Los Alamos HCV database were analysed. None of the NS5A sequences from HCV-1a or HCV-3 showed changes associated with daclatasvir resistance. By contrast, all NS5A sequences from HCV-4 harboured L31M. The double mutant L31M+Y93H was found in 7% of HCV-1b and 13% of HCV-4. Finally, all NS5A sequences from HCV-1b and HCV-4 harboured changes at codon 28 (M28L) and 30 (L30R), which are of unknown significance. The rate of all these NS5A polymorphisms did not differ significantly when comparing HIV-HCV-coinfected patients and sequences from HCV-monoinfected subjects deposited at Los Alamos HCV database. Primary resistance mutations to daclatasvir, an investigational HCV NS5A inhibitor, are not seen in HCV-1a or in HCV-3 as natural polymorphisms. By contrast, they can be recognized in most HCV-1b and HCV-4 strains, regardless HIV coinfection.

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

    DEFF Research Database (Denmark)

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


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

  9. Identifying Bright X-Ray Beasts (United States)

    Kohler, Susanna


    Ultraluminous X-ray sources (ULXs) are astronomical sources of X-rays that, while dimmer than active galactic nuclei, are nonetheless brighter than any known stellar process. What are these beasts and why do they shine so brightly?Exceeding the LimitFirst discovered in the 1980s, ULXs are rare sources that have nonetheless been found in all types of galaxies. Though the bright X-ray radiation seems likely to be coming from compact objects accreting gas, theres a problem with this theory: ULXs outshine the Eddington luminosity for stellar-mass compact objects. This means that a stellar-mass object couldnt emit this much radiation isotropically without blowing itself apart.There are two alternative explanations commonly proposed for ULXs:Rather than being accreting stellar-mass compact objects, they are accreting intermediate-mass black holes. A hypothetical black hole of 100 solar masses or more would have a much higher Eddington luminosity than a stellar-mass black hole, making the luminosities that we observe from ULXs feasible.An example of one of the common routes the authors find for a binary system to become a ULX. In this case, the binary begins as two main sequence stars. As one star evolves off the main sequence, the binary undergoes a common envelope phase and a stage of mass transfer. The star ends its life as a supernova, and the resulting neutron star then accretes matter from the main sequence star as a ULX. [Wiktorowicz et al. 2017]They are ordinary X-ray binaries (a stellar-mass compact object accreting matter from a companion star), but they are undergoing a short phase of extreme accretion. During this time, their emission is beamed into jets, making them appear brighter than the Eddington luminosity.Clues from a New DiscoveryA few years ago, a new discovery shed some light on ULXs: M82 X-2, a pulsing ULX. Two more pulsing ULXs have been discovered since then, demonstrating that at least some ULXs contain pulsars i.e., neutron stars as the

  10. Millimeter-wave Imaging Radiometer Brightness Temperatures, Wakasa Bay, Japan (United States)

    National Aeronautics and Space Administration — This data set includes calibrated brightness temperatures measured over Wakasa Bay in the Sea of Japan in January and February 2003. The MIR was carried on a...

  11. Nimbus-5 ESMR Polar Gridded Brightness Temperatures, Version 2 (United States)

    National Aeronautics and Space Administration — The Nimbus-5 Electrically Scanning Microwave Radiometer (ESMR) data set consists of gridded brightness temperature arrays for the Arctic and Antarctic, spanning 11...

  12. SMEX03 SSM/I Brightness Temperature Data, Alabama (United States)

    National Aeronautics and Space Administration — This data set provides brightness temperature data acquired during the Soil Moisture Experiment 2003 (SMEX03) by the Special Sensor Microwave/Imager (SSM/I). The...

  13. Binocular Coordination in Reading When Changing Background Brightness

    Directory of Open Access Journals (Sweden)

    Köpsel Anne


    Full Text Available Contradicting results concerning binocular coordination in reading have been reported: Liversedge et al. (2006 reported a dominance of uncrossed fixations, whereas Nuthmann and Kliegl (2009 observed more crossed fixations in reading. Based on both earlier and continuing studies, we conducted a reading experiment involving varying brightness of background and font. Calibration was performed using Gabor patches presented on grey background. During the experimental session, text had to be read either on dark, bright, or grey background. The data corroborates former results that showed a predominance of uncrossed fixations when reading on dark background, as well as those showing a predominance of crossed fixations, when reading on bright background. Besides these systematic shifts, the new results show an increase in unsystematic variability when changing the overall brightness from calibration to test. The origins of the effects need to be clarified in future research.

  14. CLPX-Satellite: AVHRR/HRPT Brightness Temperatures and Reflectances (United States)

    National Aeronautics and Space Administration — This data set includes AVHRR/HRPT (Advanced Very High Resolution Radiometer/High Resolution Picture Transmission) brightness temperatures and reflectances over the...

  15. SMEX03 SSM/I Brightness Temperature Data, Brazil (United States)

    National Aeronautics and Space Administration — This data set provides brightness temperature data acquired during the Soil Moisture Experiment 2003 (SMEX03) by the Special Sensor Microwave/Imager (SSM/I). The...

  16. Ultra High Brightness/Low Cost Fiber Coupled Packaging Project (United States)

    National Aeronautics and Space Administration — The focus of the proposed effort is maximizing the brightness of fiber coupled laser diode pump sources at a minimum cost. The specific innovation proposed is to...

  17. DMSP SSM/I-SSMIS Daily Polar Gridded Brightness Temperatures (United States)

    National Aeronautics and Space Administration — NSIDC produces daily gridded brightness temperature data from orbital swath data generated by the Special Sensor Microwave/Imager (SSM/I) aboard the Defense...


    National Aeronautics and Space Administration — This volume contains the archive of Lunar brightness temperature data derived from images acquired by the Clementine Long Wavelength Infrared (LWIR) camera. The LWIR...

  19. SMEX02 SSM/I Brightness Temperature Data, Iowa (United States)

    National Aeronautics and Space Administration — The Special Sensor Microwave/Imager (SSM/I) is a seven-channel, four-frequency, linearly polarized passive microwave radiometric system. Data are brightness...

  20. CLASIC07 PALS Brightness Temperature Data V001 (United States)

    National Aeronautics and Space Administration — This data set contains brightness temperature data obtained by the Passive Active L-band System (PALS) microwave aircraft radiometer instrument as part of the Cloud...

  1. Operational Bright-Band Snow Level Detection Using Doppler Radar (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — A method to detect the bright-band snow level from radar reflectivity and Doppler vertical velocity data collection with an atmospheric profiling Doppler radar. The...

  2. Visible Color and Photometry of Bright Materials on Vesta (United States)

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


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

    Directory of Open Access Journals (Sweden)

    Spaan Willy JM


    Full Text Available Abstract Background Hepatitis C virus (HCV induces membrane rearrangements during replication. All HCV proteins are associated to membranes, pointing out the importance of membranes for HCV. Non structural protein 4B (NS4B has been reported to induce cellular membrane alterations like the membranous web. Four transmembrane segments in the middle of the protein anchor NS4B to membranes. An amphipatic helix at the amino-terminus attaches to membranes as well. The carboxy-terminal domain (CTD of NS4B is highly conserved in Hepaciviruses, though its function remains unknown. Results A cytosolic localization is predicted for the NS4B-CTD. However, using membrane floatation assays and immunofluorescence, we now show targeting of the NS4B-CTD to membranes. Furthermore, a profile-profile search, with an HCV NS4B-CTD multiple sequence alignment, indicates sequence similarity to the membrane binding domain of prokaryotic D-lactate dehydrogenase (d-LDH. The crystal structure of E. coli d-LDH suggests that the region similar to NS4B-CTD is located in the membrane binding domain (MBD of d-LDH, implying analogy in membrane association. Targeting of d-LDH to membranes occurs via electrostatic interactions of positive residues on the outside of the protein with negative head groups of lipids. To verify that anchorage of d-LDH MBD and NS4B-CTD is analogous, NS4B-CTD mutants were designed to disrupt these electrostatic interactions. Membrane association was confirmed by swopping the membrane contacting helix of d-LDH with the corresponding domain of the 4B-CTD. Furthermore, the functionality of these residues was tested in the HCV replicon system. Conclusion Together these data show that NS4B-CTD is associated to membranes, similar to the prokaryotic d-LDH MBD, and is important for replication.

  4. The Photometric Brightness Variation of Geostationary Orbit Satellite

    Directory of Open Access Journals (Sweden)

    Haingja Seo


    Full Text Available Photometric observation is one of the most effective techniques for determining the physical characteristics of unknown space objects and space debris. In this research, we examine the change in brightness of the Communication, Ocean, Meteorological Satellite-1 (COMS-1 Geostationary Orbit Satellite (GEO, and compare it to our estimate model. First, we calculate the maximum brightness time using our calculation method and then derive the light curve shape using our rendering model. The maximum brightness is then calculated using the induced equation from Pogson's formula. For a comparison with our estimation, we carried out photometric observation using an optical telescope. The variation in brightness and the shape of the light curve are similar to the calculations achieved using our model, but the maximum brightness shows a slightly different value from our calculation result depending on the input parameters. This paper examines the photometric phenomenon of the variation in brightness of a GEO satellite, and the implementation of our approach to understanding the characteristics of space objects.

  5. Global View of the Bright Material on Vesta (United States)

    Zambon, F.; DeSanctis, C.; Schroeder, S.; Tosi, F.; Li, J.-Y.; Longobardo, A.; Ammannito, E.; Blewett, D. T.; Palomba, E.; Capaccioni, F.; hide


    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.

  6. Synthesizing SMOS Zero-Baselines with Aquarius Brightness Temperature Simulator (United States)

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


    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.

  7. Virtual screening of commercial cyclic peptides as NS2B-NS3 protease inhibitor of dengue virus serotype 2 through molecular docking simulation (United States)

    Nasution, M. A. F.; Aini, R. N.; Tambunan, U. S. F.


    A disease caused by dengue virus infection has become one of the major health problems in the world, particularly in Asia, Africa, and South America. This disease has become endemic in more than 100 countries, and approximately 100 million cases occur each year with 2.5 billion people or 40% of the world population at risk of having this virus infection. Therefore, we need an antiviral drug that can inhibit the activity of the enzymes that involved in the virus replication in the body. Lately, the peptide-based drug design has been developed and proved to have interesting pharmacological properties. This study uses commercially cyclic peptides that have already marketed. The purpose of this study is to screen the commercial cyclic peptides that can be used as an inhibitor of the NS2B-NS3 protease of dengue virus serotype 2 (DENV-2) through molecular docking simulations. Inhibition of NS3 protease enzyme can lead to enzymatic inhibition activity so the formed polyprotein from the translation of RNA cannot be cut into pieces and remain in the long strand form. Consequently, proteins that are vital for the sustainability of dengue virus replication cannot be formed. This research resulted in [alpha]-ANF (1-28), rat, Brain Natriuretic Peptide, porcine, Atrial Natriuretic Factor (3-28) (human) and Atrial Natriuretic Peptide (126-150) (rat) as the best drug candidate for inhibiting the NS2B-NS3 protease of DENV-2.

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

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


    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 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.

  9. VP2, VP7, and NS1 proteins of bluetongue virus targeted in avian reovirus muNS-Mi microspheres elicit a protective immune response in IFNAR(-/-) mice. (United States)

    Marín-López, Alejandro; Otero-Romero, Iria; de la Poza, Francisco; Menaya-Vargas, Rebeca; Calvo-Pinilla, Eva; Benavente, Javier; Martínez-Costas, José M; Ortego, Javier


    Vaccination is critical for controlling the spread of bluetongue virus (BTV). The inactivated BTV vaccines that are now being used in Europe are effective in preventing outbreaks of BTV but secondary effects associated to repetitive inoculation of aluminum-containing adjuvants and the need to develop safer, cross-reactive, and more efficacious vaccines with differential diagnostic capability have re-stimulated the interest in developing improved vaccination strategies against BTV. We have engineered a subunit BTV vaccine candidate based on proteins VP2, VP7, and NS1 of BTV-4 incorporated into avian reovirus (ARV) muNS-Mi microspheres (MS-VP2/MS-VP7/MS-NS1). IFNAR(-/-) mice immunized with MS-VP2/MS-VP7/MS-NS1 without adjuvant generated significant levels of neutralizing antibodies specific to BTV-4. In addition, vaccination stimulated specific T cell responses, predominantly CD4+, against the virus. Immunized mice were fully protected against a homologous challenge with a lethal dose of BTV-4 and partially cross-protected against a heterologous challenge with a lethal dose of BTV-1. These results support MS-VP2/MS-VP7/MS-NS1 as a promising subunit vaccine candidate against multiple serotypes of BTV as well as the use of microspheres as an alternative delivery method with potent intrinsic adjuvant activity. Copyright © 2014 Elsevier B.V. All rights reserved.

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

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    Wang Nai-Jyuan


    Full Text Available Abstract Background Plant non-specific lipid transfer proteins (nsLTPs are small and basic proteins. Recently, nsLTPs have been reported involved in many physiological functions such as mediating phospholipid transfer, participating in plant defence activity against bacterial and fungal pathogens, and enhancing cell wall extension in tobacco. However, the lipid transfer mechanism of nsLTPs is still unclear, and comprehensive information of nsLTPs is difficult to obtain. Methods In this study, we identified 595 nsLTPs from 121 different species and constructed an nsLTPs database -- nsLTPDB -- which comprises the sequence information, structures, relevant literatures, and biological data of all plant nsLTPs Results Meanwhile, bioinformatics and statistics methods were implemented to develop a classification method for nsLTPs based on the patterns of the eight highly-conserved cysteine residues, and to suggest strict Prosite-styled patterns for Type I and Type II nsLTPs. The pattern of Type I is C X2 V X5-7 C [V, L, I] × Y [L, A, V] X8-13 CC × G X12 D × [Q, K, R] X2 CXC X16-21 P X2 C X13-15C, and that of Type II is C X4 L X2 C X9-11 P [S, T] X2 CC X5 Q X2-4 C[L, F]C X2 [A, L, I] × [D, N] P X10-12 [K, R] X4-5 C X3-4 P X0-2 C. Moreover, we referred the Prosite-styled patterns to the experimental mutagenesis data that previously established by our group, and found that the residues with higher conservation played an important role in the structural stability or lipid binding ability of nsLTPs. Conclusions Taken together, this research has suggested potential residues that might be essential to modulate the structural and functional properties of plant nsLTPs. Finally, we proposed some biologically important sites of the nsLTPs, which are described by using a new Prosite-styled pattern that we defined.

  11. Inverse Compton Scattered Merger-nova: Late X-Ray Counterpart of Gravitational-wave Signals from NS–NS/BH Mergers (United States)

    Ai, Shunke; Gao, He


    The recent observations of GW170817 and its electromagnetic (EM) counterparts show that double neutron star mergers could lead to rich and bright EM emissions. Recent numerical simulations suggest that neutron star and neutron star/black hole (NS–NS/BH) mergers would leave behind a central remnant surrounded by a mildly isotropic ejecta. The central remnant could launch a collimated jet and when the jet propagates through the ejecta, a mildly relativistic cocoon would be formed and the interaction between the cocoon and the ambient medium would accelerate electrons via external shock in a wide angle, so that the merger-nova photons (i.e., thermal emission from the ejecta) would be scattered into higher frequency via an inverse Compton (IC) process when they propagate through the cocoon shocked region. We find that the IC scattered component peaks at the X-ray band and it will reach its peak luminosity on the order of days (simultaneously with the merger-nova emission). With current X-ray detectors, such a late X-ray component could be detected out to 200 Mpc, depending on the merger remnant properties. It could serve as an important electromagnetic counterpart of gravitational-wave signals from NS–NS/BH mergers. Nevertheless, simultaneous detection of such a late X-ray signal and the merger-nova signal could shed light on the cocoon properties and the concrete structure of the jet.

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

    DEFF Research Database (Denmark)

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


    Hepatitis C virus (HCV) strains belong to seven genotypes with numerous subtypes that respond differently to antiviral therapies. Genotype 1, and primarily subtype 1b, is the most prevalent genotype worldwide. The development of recombinant HCV infectious cell culture systems for different variants...... cell culture adaptive substitutions A1226G, R1496L, and Q1773H. These viruses spread efficiently in Huh7.5 cells by acquiring additional adaptive substitutions, and final recombinants yielded peak supernatant infectivity titers of 4 to 5 log10 focus-forming units (FFU)/ml. We subsequently succeeded...... in adapting a JFH1- based 5=UTR-NS5A DH1 recombinant to efficient growth in cell culture. We evaluated the efficacy of clinically relevant NS3/4A protease and NS5A inhibitors against the novel genotype 1b viruses, as well as against previously developed 1a viruses. The inhibitors were efficient against all...

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

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    Atsushi Furuta


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

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

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    Leticia Barboza Rocha


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

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

    Gianulis, Elena C; Labib, Chantelle; Saulis, Gintautas; Novickij, Vitalij; Pakhomova, Olga N; Pakhomov, Andrei G


    Tumor ablation by nanosecond pulsed electric fields (nsPEF) is an emerging therapeutic modality. We compared nsPEF cytotoxicity for human cell lines of cancerous (IMR-32, Hep G2, HT-1080, and HPAF-II) and non-cancerous origin (BJ and MRC-5) under strictly controlled and identical conditions. Adherent cells were uniformly treated by 300-ns PEF (0-2000 pulses, 1.8 kV/cm, 50 Hz) on indium tin oxide-covered glass coverslips, using the same media and serum. Cell survival plotted against the number of pulses displayed three distinct regions (initial resistivity, logarithmic survival decline, and residual resistivity) for all tested cell types, but with differences in LD 50 spanning as much as nearly 80-fold. The non-cancerous cells were less sensitive than IMR-32 neuroblastoma cells but more vulnerable than the other cancers tested. The cytotoxic efficiency showed no apparent correlation with cell or nuclear size, cell morphology, metabolism level, or the extent of membrane disruption by nsPEF. Increasing pulse duration to 9 µs (0.75 kV/cm, 5 Hz) produced a different selectivity pattern, suggesting that manipulation of PEF parameters can, at least for certain cancers, overcome their resistance to nsPEF ablation. Identifying mechanisms and cell markers of differential nsPEF susceptibility will critically contribute to the proper choice and outcome of nsPEF ablation therapies.

  16. Prediction and experimental characterization of nsSNPs altering human PDZ-binding motifs.

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    David Gfeller

    Full Text Available Single nucleotide polymorphisms (SNPs are a major contributor to genetic and phenotypic variation within populations. Non-synonymous SNPs (nsSNPs modify the sequence of proteins and can affect their folding or binding properties. Experimental analysis of all nsSNPs is currently unfeasible and therefore computational predictions of the molecular effect of nsSNPs are helpful to guide experimental investigations. While some nsSNPs can be accurately characterized, for instance if they fall into strongly conserved or well annotated regions, the molecular consequences of many others are more challenging to predict. In particular, nsSNPs affecting less structured, and often less conserved regions, are difficult to characterize. Binding sites that mediate protein-protein or other protein interactions are an important class of functional sites on proteins and can be used to help interpret nsSNPs. Binding sites targeted by the PDZ modular peptide recognition domain have recently been characterized. Here we use this data to show that it is possible to computationally identify nsSNPs in PDZ binding motifs that modify or prevent binding to the proteins containing the motifs. We confirm these predictions by experimentally validating a selected subset with ELISA. Our work also highlights the importance of better characterizing linear motifs in proteins as many of these can be affected by genetic variations.

  17. Aptamer-Based ELISA Assay for Highly Specific and Sensitive Detection of Zika NS1 Protein. (United States)

    Lee, Kyung Hyun; Zeng, Huaqiang


    We report here a few Zika NS1-binding ssDNA aptamers selected using the conventional SELEX protocol, and their application in an ELISA assay for sensitive diagnosis of Zika NS1 protein. Among the aptamers identified, aptamers 2 and 10 could recognize different binding epitopes of Zika NS1 protein. This complementary in binding site, when coupled with an extraordinarily high binding affinity by 2 (41-nt, KD = 45 pM) and high specificity by 10, was used successfully to construct an ELISA-based assay where 2 and 10 serve as the capture and detection agents, respectively, giving rise to a highly specific detection of Zika NS1 with a detection limit of 100 ng/mL in buffer. Further testing of a few in-house anti-Zika NS1 antibodies show that 2 could also pair with an anti-Zika NS1 antibody. Such aptamer-antibody pairing not only lowers the detection sensitivity by 3 orders of magnitude to 0.1 ng/mL in buffer but also enable highly sensitive detection of as low as 1 and 10 ng/mL of Zika NS1 to be carried out in 10% and 100% human serum, respectively. These results suggest that the selected aptamers would be useful for medical diagnosis of Zika virus infection in various aptamer-based diagnostic devices including ELISA assay.

  18. Characterization of the Zika virus two-component NS2B-NS3 protease and structure-assisted identification of allosteric small-molecule antagonists. (United States)

    Shiryaev, Sergey A; Farhy, Chen; Pinto, Antonella; Huang, Chun-Teng; Simonetti, Nicole; Ngono, Annie Elong; Dewing, Antimone; Shresta, Sujan; Pinkerton, Anthony B; Cieplak, Piotr; Strongin, Alex Y; Terskikh, Alexey V


    The recent re-emergence of Zika virus (ZIKV)1, a member of the Flaviviridae family, has become a global emergency. Currently, there are no effective methods of preventing or treating ZIKV infection, which causes severe neuroimmunopathology and is particularly harmful to the developing fetuses of infected pregnant women. However, the pathology induced by ZIKV is unique among flaviviruses, and knowledge of the biology of other family members cannot easily be extrapolated to ZIKV. Thus, structure-function studies of ZIKV proteins are urgently needed to facilitate the development of effective preventative and therapeutic agents. Like other flaviviruses, ZIKV expresses an NS2B-NS3 protease, which consists of the NS2B cofactor and the NS3 protease domain and is essential for cleavage of the ZIKV polyprotein precursor and generation of fully functional viral proteins. Here, we report the enzymatic characterization of ZIKV protease, and we identify structural scaffolds for allosteric small-molecule inhibitors of this protease. Molecular modeling of the protease-inhibitor complexes suggests that these compounds bind to the druggable cavity in the NS2B-NS3 protease interface and affect productive interactions of the protease domain with its cofactor. The most potent compound demonstrated efficient inhibition of ZIKV propagation in vitro in human fetal neural progenitor cells and in vivo in SJL mice. The inhibitory scaffolds could be further developed into valuable research reagents and, ultimately, provide a roadmap for the selection of efficient inhibitors of ZIKV infection. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Resensitizing daclatasvir-resistant hepatitis C variants by allosteric modulation of NS5A. (United States)

    Sun, Jin-Hua; O'Boyle, Donald R; Fridell, Robert A; Langley, David R; Wang, Chunfu; Roberts, Susan B; Nower, Peter; Johnson, Benjamin M; Moulin, Frederic; Nophsker, Michelle J; Wang, Ying-Kai; Liu, Mengping; Rigat, Karen; Tu, Yong; Hewawasam, Piyasena; Kadow, John; Meanwell, Nicholas A; Cockett, Mark; Lemm, Julie A; Kramer, Melissa; Belema, Makonen; Gao, Min


    It is estimated that more than 170 million people are infected with hepatitis C virus (HCV) worldwide. Clinical trials have demonstrated that, for the first time in human history, the potential exists to eradicate a chronic viral disease using combination therapies that contain only direct-acting antiviral agents. HCV non-structural protein 5A (NS5A) is a multifunctional protein required for several stages of the virus replication cycle. NS5A replication complex inhibitors, exemplified by daclatasvir (DCV; also known as BMS-790052 and Daklinza), belong to the most potent class of direct-acting anti-HCV agents described so far, with in vitro activity in the picomolar (pM) to low nanomolar (nM) range. The potency observed in vitro has translated into clinical efficacy, with HCV RNA declining by ~3-4 log10 in infected patients after administration of single oral doses of DCV. Understanding the exceptional potency of DCV was a key objective of this study. Here we show that although DCV and an NS5A inhibitor analogue (Syn-395) are inactive against certain NS5A resistance variants, combinations of the pair enhance DCV potency by >1,000-fold, restoring activity to the pM range. This synergistic effect was validated in vivo using an HCV-infected chimaeric mouse model. The cooperative interaction of a pair of compounds suggests that NS5A protein molecules communicate with each other: one inhibitor binds to resistant NS5A, causing a conformational change that is transmitted to adjacent NS5As, resensitizing resistant NS5A so that the second inhibitor can act to restore inhibition. This unprecedented synergistic anti-HCV activity also enhances the resistance barrier of DCV, providing additional options for HCV combination therapy and new insight into the role of NS5A in the HCV replication cycle.

  20. Respiratory syncytial virus interferon antagonist NS1 protein suppresses and skews the human T lymphocyte response.

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    Shirin Munir


    Full Text Available We recently demonstrated that the respiratory syncytial virus (RSV NS1 protein, an antagonist of host type I interferon (IFN-I production and signaling, has a suppressive effect on the maturation of human dendritic cells (DC that was only partly dependent on released IFN-I. Here we investigated whether NS1 affects the ability of DC to activate CD8+ and CD4+ T cells. Human DC were infected with RSV deletion mutants lacking the NS1 and/or NS2 genes and assayed for the ability to activate autologous T cells in vitro, which were analyzed by multi-color flow cytometry. Deletion of the NS1, but not NS2, protein resulted in three major effects: (i an increased activation and proliferation of CD8+ T cells that express CD103, a tissue homing integrin that directs CD8+ T cells to mucosal epithelial cells of the respiratory tract and triggers cytolytic activity; (ii an increased activation and proliferation of Th17 cells, which have recently been shown to have anti-viral effects and also indirectly attract neutrophils; and (iii decreased activation of IL-4-producing CD4+ T cells--which are associated with enhanced RSV disease--and reduced proliferation of total CD4+ T cells. Except for total CD4+ T cell proliferation, none of the T cell effects appeared to be due to increased IFN-I signaling. In the infected DC, deletion of the NS1 and NS2 genes strongly up-regulated the expression of cytokines and other molecules involved in DC maturation. This was partly IFN-I-independent, and thus might account for the T cell effects. Taken together, these data demonstrate that the NS1 protein suppresses proliferation and activation of two of the protective cell populations (CD103+ CD8+ T cells and Th17 cells, and promotes proliferation and activation of Th2 cells that can enhance RSV disease.

  1. Comprehensive Mapping Antigenic Epitopes of NS1 Protein of Japanese Encephalitis Virus with Monoclonal Antibodies.

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    Rong-Hong Hua

    Full Text Available Japanese encephalitis virus (JEV non-structural protein 1 (NS1 contributes to virus replication and elicits protective immune responses during infection. JEV NS1-specific antibody responses could be a target in the differential diagnosis of different flavivirus infections. However, the epitopes on JEV NS1 are poorly characterized. The present study describes the full mapping of linear B-cell epitopes in JEV NS1. We generated eleven NS1-specific monoclonal antibodies from mice immunized with recombinant NS1. For epitope mapping of monoclonal antibodies, a set of 51 partially-overlapping peptides covering the entire NS1 protein were expressed with a GST-tag and then screened using monoclonal antibodies. Through enzyme-linked immunosorbent assay (ELISA, five linear epitope-containing peptides were identified. By sequentially removing amino acid residues from the carboxy and amino terminal of peptides, the minimal units of the five linear epitopes were identified and confirmed using monoclonal antibodies. Five linear epitopes are located in amino acids residues (5AIDITRK(11, (72RDELNVL(78, (251KSKHNRREGY(260, (269DENGIVLD(276, and (341DETTLVRS(348. Furthermore, it was found that the epitopes are highly conserved among JEV strains through sequence alignment. Notably, none of the homologous regions on NS1 proteins from other flaviviruses reacted with the MAbs when they were tested for cross-reactivity, and all five epitope peptides were not recognized by sera against West Nile virus or Dengue virus. These novel virus-specific linear B-cell epitopes of JEV NS1 would benefit the development of new vaccines and diagnostic assays.

  2. Induction of Cell Death Mechanisms and Apoptosis by Nanosecond Pulsed Electric Fields (nsPEFs

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    Nova M. Sain


    Full Text Available Pulse power technology using nanosecond pulsed electric fields (nsPEFs offers a new stimulus to modulate cell functions or induce cell death for cancer cell ablation. New data and a literature review demonstrate fundamental and basic cellular mechanisms when nsPEFs interact with cellular targets. NsPEFs supra-electroporate cells creating large numbers of nanopores in all cell membranes. While nsPEFs have multiple cellular targets, these studies show that nsPEF-induced dissipation of ΔΨm closely parallels deterioration in cell viability. Increases in intracellular Ca2+ alone were not sufficient for cell death; however, cell death depended of the presence of Ca2+. When both events occur, cell death ensues. Further, direct evidence supports the hypothesis that pulse rise-fall times or high frequency components of nsPEFs are important for decreasing ΔΨm and cell viability. Evidence indicates in Jurkat cells that cytochrome c release from mitochondria is caspase-independent indicating an absence of extrinsic apoptosis and that cell death can be caspase-dependent and –independent. The Ca2+ dependence of nsPEF-induced dissipation of ΔΨm suggests that nanoporation of inner mitochondria membranes is less likely and effects on a Ca2+-dependent protein(s or the membrane in which it is embedded are more likely a target for nsPEF-induced cell death. The mitochondria permeability transition pore (mPTP complex is a likely candidate. Data demonstrate that nsPEFs can bypass cancer mutations that evade apoptosis through mechanisms at either the DISC or the apoptosome.

  3. Approaches to hepatitis C treatment and cure using NS5A inhibitors

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    Kohler JJ


    Full Text Available James J Kohler,1,2 James H Nettles,1,2 Franck Amblard,1,2 Selwyn J Hurwitz,1,2 Leda Bassit,1,2 Richard A Stanton,1 Maryam Ehteshami,1 Raymond F Schinazi1,2 1Center for AIDS Research and Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA; 2Atlanta Veterans Affairs Medical Center, Decatur, GA, USA Abstract: Recent progress in the understanding of hepatitis C virus (HCV biology and the availability of in vitro models to study its replication have facilitated the development of direct-acting antiviral agents (DAAs that target specific steps in the viral replication cycle. Currently, there are three major classes of DAA in clinical development: NS3/4A protease inhibitors, NS5B polymerase inhibitors, and NS5A directed inhibitors. Several compounds thought to bind directly with NS5A are now in various clinical trial phases, including the most advanced, daclatasvir (BMS-790052, ledipasvir (GS-5885, and ABT-267. While many NS5A-targeted compounds demonstrate picomolar potency, the exact mechanism(s of their action is still unclear. In the clinic, NS5A HCV inhibitors show promise as important components in DAA regimens and have multifunctionality. In addition to inhibiting viral replication, they may synergize with other DAAs, possibly by modulating different viral proteins, to help suppress the emergence of resistant viruses. Structure-based models have identified target interaction domains and spatial interactions that explain drug resistance for mutations at specific positions (eg, residues 93 and 31 within NS5A and potential binding partners. This review provides, insights into the unique complexity of NS5A as a central platform for multiple viral/host protein interactions, and possible mechanism(s for the NS5A inhibitors currently undergoing clinical trials that target this nonstructural viral protein. Keywords: HCV replication complex, direct acting antivirals (DAAs, clinical trials

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

    Energy Technology Data Exchange (ETDEWEB)

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


    Bright, water-soluble CeF{sub 3} nanoparticles with small size and narrow size distribution have been synthesized using a simple co-precipitation method without any ligands. Size control of nanoparticles from 13 ± 2 to 9 ± 2 nm was achieved by varying the reaction time. Colloidal properties have been found to vary with pH and, independently, with dilution. The photoluminescence of the as-synthesized nanoparticles shows a highly photostable UV/Visible fluorescence band due to allowed 5d–4f transitions, also observed in the X-ray luminescence spectrum. This band is suitable for X-ray excitation of a range of photosensitizers. The photoluminescence quantum yield of nanoparticles was also determined to be 31 %. Using the measured fluorescence decay time of 25 ns, the radiative lifetime of Ce in CeF{sub 3} was found to be 80.6 ns. Both photoluminescence and cathodoluminescence emission are affected by the reaction time and measurement temperature. Electron-beam-induced defect annealing is also observed.

  5. Evaluación de un péptido quimérico NS4/NS5 para la detección de anticuerpos contra VHC


    lvonne Gómez; Milenen Hernández; Carlos Martínez; Marleby García; Antonio Melchor


    Para el diagnóstico del virus de la hepatitis C, se utilizan las pruebas de Elisa, debido a su sensibilidad y especificidad. Gran parte de estas pruebas se basa en el empleo de péptidos sintéticos y, en la actualidad, de péptidos quiméricos. En este estudio se sintetizó un péptido quimérico que comprende secuencias inmunodominantes de las regiones no estructurales NS4 y NS5 del virus de la hepatitis C. El péptido representativo de las dos secuencias está separado por un brazo espaciador de do...

  6. In vitro activity of daclatasvir on hepatitis C virus genotype 3 NS5A. (United States)

    Wang, Chunfu; Valera, Lourdes; Jia, Lingling; Kirk, Melissa J; Gao, Min; Fridell, Robert A


    The NS5A replication complex inhibitor daclatasvir (DCV; BMS-790052) inhibits hybrid replicons containing hepatitis C virus (HCV) genotype 3a (HCV3a) NS5A genes with 50% effective concentrations (EC(50)s) ranging from 120 to 870 pM. Selection studies with a hybrid HCV3a replicon identified NS5A residues 31 and 93 as sites for DCV-selected resistance. Our results support the potential use of DCV as a component in combination therapies for HCV3a chronic infection.

  7. Bioremediation of crude oil contaminated soil by bioaugmentation of Pseudomonas fluorescens NS1. (United States)

    Barathi, S; Vasudevan, N


    A feasibility study was conducted to evaluate the efficiency of Pseudomonas fluorescens NS1 bioaugmented to stimulate in situ bioremediation of crude oil-contaminated soil with different amendments in treatment units. Pure culture of P. fluorescens NS1 was isolated from a petroleum-contaminated soil. The rate of degradation of petroleum hydrocarbons by the indigenous soil microflora and in the presence of P. fluorescens NS1 was assessed with the addition of nutrients and bulking agents for a period of about 35 days. The study showed that addition of wheat bran as bulking agent rapidly enhanced bioremediation of crude oil-contaminated soil compared to amendments in other treatment units.

  8. Interactions between the Dengue Virus Polymerase NS5 and Stem-Loop A. (United States)

    Bujalowski, Paul J; Bujalowski, Wlodzimierz; Choi, Kyung H


    The process of RNA replication by dengue virus is still not completely understood despite the significant progress made in the last few years. Stem-loop A (SLA), a part of the viral 5' untranslated region (UTR), is critical for the initiation of dengue virus replication, but quantitative analysis of the interactions between the dengue virus polymerase NS5 and SLA in solution has not been performed. Here, we examine how solution conditions affect the size and shape of SLA and the formation of the NS5-SLA complex. We show that dengue virus NS5 binds SLA with a 1:1 stoichiometry and that the association reaction is primarily entropy driven. We also observe that the NS5-SLA interaction is influenced by the magnesium concentration in a complex manner. Binding is optimal with 1 mM MgCl 2 but decreases with both lower and higher magnesium concentrations. Additionally, data from a competition assay between SLA and single-stranded RNA (ssRNA) indicate that SLA competes with ssRNA for the same binding site on the NS5 polymerase. SLA 70 and SLA 80 , which contain the first 70 and 80 nucleotides (nt), respectively, bind NS5 with similar binding affinities. Dengue virus NS5 also binds SLAs from different serotypes, indicating that NS5 recognizes the overall shape of SLA as well as specific nucleotides. IMPORTANCE Dengue virus is an important human pathogen responsible for dengue hemorrhagic fever, whose global incidence has increased dramatically over the last several decades. Despite the clear medical importance of dengue virus infection, the mechanism of viral replication, a process commonly targeted by antiviral therapeutics, is not well understood. In particular, stem-loop A (SLA) and stem-loop B (SLB) located in the 5' untranslated region (UTR) are critical for binding the viral polymerase NS5 to initiate minus-strand RNA synthesis. However, little is known regarding the kinetic and thermodynamic parameters driving these interactions. Here, we quantitatively examine the

  9. Bluetongue Virus NS4 Protein Is an Interferon Antagonist and a Determinant of Virus Virulence. (United States)

    Ratinier, Maxime; Shaw, Andrew E; Barry, Gerald; Gu, Quan; Di Gialleonardo, Luigina; Janowicz, Anna; Varela, Mariana; Randall, Richard E; Caporale, Marco; Palmarini, Massimo


    Bluetongue virus (BTV) is the causative agent of bluetongue, a major infectious disease of ruminants with serious consequences to both animal health and the economy. The clinical outcome of BTV infection is highly variable and dependent on a variety of factors related to both the virus and the host. In this study, we show that the BTV nonstructural protein NS4 favors viral replication in sheep, the animal species most affected by bluetongue. In addition, NS4 confers a replication advantage on the virus in interferon (IFN)-competent primary sheep endothelial cells and immortalized cell lines. We determined that in cells infected with an NS4 deletion mutant (BTV8ΔNS4), there is increased synthesis of type I IFN compared to cells infected with wild-type BTV-8. In addition, using RNA sequencing (RNA-seq), we show that NS4 modulates the host IFN response and downregulates mRNA levels of type I IFN and interferon-stimulated genes. Moreover, using reporter assays and protein synthesis assays, we show that NS4 downregulates the activities of a variety of promoters, such as the cytomegalovirus immediate-early promoter, the IFN-β promoter, and a promoter containing interferon-stimulated response elements (ISRE). We also show that the NS4 inhibitory activity on gene expression is related to its nucleolar localization. Furthermore, NS4 does not affect mRNA splicing or cellular translation. The data obtained in this study strongly suggest that BTV NS4 is an IFN antagonist and a key determinant of viral virulence. Bluetongue is one of the main infectious diseases of ruminants and is caused by bluetongue virus (BTV), an arthropod-borne virus transmitted from infected to susceptible animals by Culicoides biting midges. Bluetongue has a variable clinical outcome that can be related to both virus and host factors. It is therefore critical to understand the interplay between BTV and the host immune responses. In this study, we show that a nonstructural protein of BTV (NS4) is

  10. PROFFIT: Analysis of X-ray surface-brightness profiles (United States)

    Eckert, Dominique


    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.

  11. A neurodynamical model of brightness induction in v1.

    Directory of Open Access Journals (Sweden)

    Olivier Penacchio

    Full Text Available Brightness induction is the modulation of the perceived intensity of an area by the luminance of surrounding areas. Recent neurophysiological evidence suggests that brightness information might be explicitly represented in V1, in contrast to the more common assumption that the striate cortex is an area mostly responsive to sensory information. Here we investigate possible neural mechanisms that offer a plausible explanation for such phenomenon. To this end, a neurodynamical model which is based on neurophysiological evidence and focuses on the part of V1 responsible for contextual influences is presented. The proposed computational model successfully accounts for well known psychophysical effects for static contexts and also for brightness induction in dynamic contexts defined by modulating the luminance of surrounding areas. This work suggests that intra-cortical interactions in V1 could, at least partially, explain brightness induction effects and reveals how a common general architecture may account for several different fundamental processes, such as visual saliency and brightness induction, which emerge early in the visual processing pathway.

  12. Bright light therapy of subsyndromal seasonal affective disorder in the workplace: morning vs. afternoon exposure. (United States)

    Avery, D H; Kizer, D; Bolte, M A; Hellekson, C


    Bright light therapy in seasonal affective disorder (SAD) has been studied extensively. However, little attention has been given to subsyndromal seasonal affective disorder (SSAD) or the use of bright light in the workplace. Many patients using bright light boxes complain of the inconvenience of use. Much of this inconvenience involves the often-recommended early timing of the bright light therapy. Patients, who already have difficulty awakening, often have difficulty using the bright light therapy soon after awakening before going to work. If bright light could be used effectively in the workplace, the treatment would be more convenient; the improved convenience would probably improve compliance. In this study, we studied the effectiveness of bright light therapy in subjects with SSAD in the workplace, comparing morning bright light with afternoon bright light. Morning and afternoon bright light treatment (2500 lux) were compared in 30 subsyndromal seasonal affective disorder patients using the bright light therapy in the workplace. Hamilton Depression Ratings and subjective measures of mood, energy, alertness and productivity were assessed before and after 2 weeks of light therapy. Both morning and evening bright light significantly decreased the depression ratings and improved the subjective mood, energy, alertness and productivity scores. However, there were no significant differences between the two times of administration of the bright light treatment. Both bright light treatments were well tolerated. Bright light given in the workplace improves subjective ratings of mood, energy, alertness and productivity in SSAD subjects. Morning and afternoon bright lights resulted in similar levels of improvement.

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

    Directory of Open Access Journals (Sweden)

    Moheshwarnath Issur


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

  14. [11C]NS8880, a promising PET radiotracer targeting the norepinephrine transporter

    DEFF Research Database (Denmark)

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


    INTRODUCTION: Positron emission tomography (PET) imaging of the norepinephrine transporter (NET) is still hindered by the availability of useful PET imaging probes. The present study describes the radiosynthesis and pre-clinical evaluation of a new compound, exo-3-(6-methoxypyridin-2-yloxy)-8-H-8......]methanolate in a Boc-protected precursor. The isolated [11C]NS8880 was evaluated pre-clinically both in a pig model (PET scanning) and in a rat model (μPET scanning) and compared to (S,S)-[11C]-O-methylreboxetine ([11C]MeNER). RESULTS: The radiolabeling technique yielded [11C]NS8880 in low (... yields with high purity. The PET in vivo evaluation in pig and rat revealed a rapid brain uptake of [11C]NS8880 and fast obtaining of equilibrium. Highest binding was observed in thalamic and hypothalamic regions. Pretreatment with desipramine efficiently reduced binding of [11C]NS8880. CONCLUSION: Based...

  15. Technical noise supplement : TeNS : a technical supplement to the Traffic Noise Analysis Protocol. (United States)


    The purpose of this Technical Noise Supplement (TeNS) is to provide technical background : information on transportation-related noise in general and highway traffic noise in : particular. It is designed to elaborate on technical concepts and procedu...

  16. Aircraft Scanners = NASA Digital Aerial Scanners (TMS, TIMS, NS001): Pre 1996 (United States)

    U.S. Geological Survey, Department of the Interior — The Aircraft Scanners data set contains digital imagery acquired from several multispectral scanners including NS-001 Mutispectral scanner, Daedalus thematic mapper...

  17. Researchers develop CCD image sensor with 20ns per row parallel readout time

    CERN Multimedia

    Bush, S


    "Scientists at the Rutherford Appleton Laboratory (RAL) in Oxfordshire have developed what they claim is the fastest CCD (charge-coupled device) image sensor, with a readout time which is 20ns per row" (1/2 page)

  18. Bright and Not-So-Bright Prospects for Women in Physics in China-Beijing (United States)

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


    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.

  19. Influenza A virus attenuation by codon deoptimization of the NS gene for vaccine development. (United States)

    Nogales, Aitor; Baker, Steven F; Ortiz-Riaño, Emilio; Dewhurst, Stephen; Topham, David J; Martínez-Sobrido, Luis


    Influenza viral infection represents a serious public health problem that causes contagious respiratory disease, which is most effectively prevented through vaccination to reduce transmission and future infection. The nonstructural (NS) gene of influenza A virus encodes an mRNA transcript that is alternatively spliced to express two viral proteins, the nonstructural protein 1 (NS1) and the nuclear export protein (NEP). The importance of the NS gene of influenza A virus for viral replication and virulence has been well described and represents an attractive target to generate live attenuated influenza viruses with vaccine potential. Considering that most amino acids can be synthesized from several synonymous codons, this study employed the use of misrepresented mammalian codons (codon deoptimization) for the de novo synthesis of a viral NS RNA segment based on influenza A/Puerto Rico/8/1934 (H1N1) (PR8) virus. We generated three different recombinant influenza PR8 viruses containing codon-deoptimized synonymous mutations in coding regions comprising the entire NS gene or the mRNA corresponding to the individual viral protein NS1 or NEP, without modifying the respective splicing and packaging signals of the viral segment. The fitness of these synthetic viruses was attenuated in vivo, while they retained immunogenicity, conferring both homologous and heterologous protection against influenza A virus challenges. These results indicate that influenza viruses can be effectively attenuated by synonymous codon deoptimization of the NS gene and open the possibility of their use as a safe vaccine to prevent infections with these important human pathogens. Vaccination serves as the best therapeutic option to protect humans against influenza viral infections. However, the efficacy of current influenza vaccines is suboptimal, and novel approaches are necessary for the prevention of disease cause by this important human respiratory pathogen. The nonstructural (NS) gene of

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

    Directory of Open Access Journals (Sweden)

    Hugo de Almeida

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

  1. High-brightness ultra-cold metastable neon-beam

    CERN Document Server

    Shimizu, Fujio


    This paper presents detailed characteristics of an ultra-cold bright metastable neon atomic beam which we have been using for atom-interferometric applications. The basis of the device is an atomic beam released from a magneto-optical trap (MOT) which is operated with a high intensity trapping laser, high magnetic quadrupole field, and large laser detuining. Mainly due to the complex structure of three dimensional magnetic field and laser beams, a bright small spot of atoms is formed near the center of the quadrupole magnetic field under an appropriate operating condition. We obtained the minimum trap diameter of 50 micron meter, the atomic density nearly 10^{13}cm^{-3}, and the atomic temperature slightly less than the Doppler limited temperature of 200 micro-K. By releasing trapped atoms we obtained an bright cold atomic beam which is not far from the collision limited atomic density.

  2. A high brightness probe of polymer nanoparticles for biological imaging (United States)

    Zhou, Sirong; Zhu, Jiarong; Li, Yaping; Feng, Liheng


    Conjugated polymer nanoparticles (CPNs) with high brightness in long wavelength region were prepared by the nano-precipitation method. Based on fluorescence resonance energy transfer (FRET) mechanism, the high brightness property of the CPNs was realized by four different emission polymers. Dynamic light scattering (DLS) and scanning electron microscopy (SEM) displayed that the CPNs possessed a spherical structure and an average diameter of 75 nm. Analysis assays showed that the CPNs had excellent biocompatibility, good photostability and low cytotoxicity. The CPNs were bio-modified with a cell penetrating peptide (Tat, a targeted element) through covalent link. Based on the entire wave fluorescence emission, the functionalized CPNs1-4 can meet multichannel and high throughput assays in cell and organ imaging. The contribution of the work lies in not only providing a new way to obtain a high brightness imaging probe in long wavelength region, but also using targeted cell and organ imaging.

  3. Low dimensional neutron moderators for enhanced source brightness

    DEFF Research Database (Denmark)

    Mezei, Ferenc; Zanini, Luca; Takibayev, Alan


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

  4. On the relation between zenith sky brightness and horizontal illuminance (United States)

    Kocifaj, M.; Posch, Th.; Solano Lamphar, H. A.


    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.

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

    DEFF Research Database (Denmark)

    Chagnon, F; Lamarre, A; Lachance, C


    to demonstrate the expression of ns4b in HCV-229E-infected cells using flow cytometry. Given a previously reported contiguous five amino acid shared region between ns4b and myelin basic protein, a purified recombinant histidine-tagged ns4b protein and (or) human myelin basic protein were injected into mice...

  6. Effects of Bright Light Treatment on Psychomotor Speed in Athletes

    Directory of Open Access Journals (Sweden)

    Mikko Paavo Tulppo


    Full Text Available 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 8–12 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 x 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.

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

    Directory of Open Access Journals (Sweden)

    Saleha Shamim


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

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

    Directory of Open Access Journals (Sweden)

    Yue Gu


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

  9. Characterization of the magnetization reversal of perpendicular Nanomagnetic Logic clocked in the ns-range

    Directory of Open Access Journals (Sweden)

    Grazvydas Ziemys


    Full Text Available We have investigated the magnetization reversal of fabricated Co/Pt nanomagnets with perpendicular anisotropy within a wide range of magnetic field pulse widths. This experiment covers the pulse lengths from 700 ms to 20 ns. We observed that the commonly used Arrhenius model fits very well the experimental data with a single parameter set for pulse times above 100 ns (tp > 100 ns. However, below 100 ns (tp < 100 ns, a steep increase of the switching field amplitude is observed and the deviation from the Arrhenius model becomes unacceptable. For short pulse times the model can be adjusted by the reversal time term for the dynamic switching field which is only dependent on the pulse amplitude and not on temperature anymore. Precise modeling of the magnetization reversal in the sub-100 ns-range is crucially important to ensure reliable operation in the favored GHz-range as well as to explore and design new kinds of Nanomagnetic Logic circuits and architectures.

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

    KAUST Repository

    Knodel, Markus


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

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

    Directory of Open Access Journals (Sweden)

    Markus M. Knodel


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

  12. Nanometer-Scale Permeabilization and Osmotic Swelling Induced by 5-ns Pulsed Electric Fields. (United States)

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


    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.

  13. In-silico identification and evaluation of plant flavonoids as dengue NS2B/NS3 protease inhibitors using molecular docking and simulation approach. (United States)

    Qamar, Muhammad Tahirul; Ashfaq, Usman Ali; Tusleem, Kishver; Mumtaz, Arooj; Tariq, Quratulain; Goheer, Alina; Ahmed, Bilal


    Dengue infection is prevailing among the people not only from the developing countries but also from the developed countries due to its high morbidity rate around the globe. Hence, due to the unavailability of any suitable vaccine for rigorous dengue virus (DENV), the only mode of its treatment is prevention. The circumstances require an urgent development of efficient and practical treatment to deal with these serotypes. The severe effects and cost of synthetic vaccines simulated researchers to find anti-viral agents from medicinal plants. Flavonoids present in medicinal plants, holds anti-viral activity and can be used as vaccine against viruses. Therefore, present study was planned to find anti-viral potential of 2500 flavonoids inhibitors against the DENVNS2B/NS3 protease through computational screening which can hinder the viral replication within the host cell. By using molecular docking, it was revealed that flavonoids showed strong and stable bonding in the binding pocket of DENV NS2B/NS3 protease and had strong interactions with catalytic triad. Drug capability and anti-dengue potential of the flavonoids was also evaluated by using different bioinformatics tools. Some flavonoids effectively blocked the catalytic triad of DENV NS2B/NS3 protease and also passed through drug ability evaluation. It can be concluded from this study that these flavonoids could act as potential inhibitors to stop the replication of DENV and there is a need to study the action of these molecules in-vitro to confirm their action and other properties.

  14. Bright solitons in non-equilibrium coherent quantum matter. (United States)

    Pinsker, F; Flayac, H


    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.

  15. HSV Brightness Factor Matching for Gesture Recognition System


    Mokhtar M. Hasan; Pramod K. Mishra


    The main goal of gesture recognition research is to establish a system which can identify specific human gestures and use these identified gestures to be carried out by the machine, In this paper, we introduce a new method for gesture recognition that based on computing the local brightness for each block of the gesture image, the gesture image is divided into 25x25 blocks each of 5x5 block size, and we calculated the local brightness of each block, so, each gesture produces 25x25 features va...

  16. A basic cluster in the N terminus of yellow fever virus NS2A contributes to infectious particle production. (United States)

    Voßmann, Stephanie; Wieseler, Janett; Kerber, Romy; Kümmerer, Beate Mareike


    The flavivirus NS2A protein is involved in the assembly of infectious particles. To further understand its role in this process, a charged-to-alanine scanning analysis was performed on NS2A encoded by an infectious cDNA clone of yellow fever virus (YFV). Fifteen mutants containing single, double, or triple charged-to-alanine changes were tested. Five of them did not produce infectious particles, whereas efficient RNA replication was detectable for two of the five NS2A mutants (R22A-K23A-R24A and R99A-E100A-R101A mutants). Prolonged cultivation of transfected cells resulted in the recovery of pseudorevertants. Besides suppressor mutants in NS2A, a compensating second-site mutation in NS3 (D343G) arose for the NS2A R22A-K23A-R24A mutant. We found this NS3 mutation previously to be suppressive for the NS2Aα cleavage site Q189S mutant, also deficient in virion assembly. In this study, the subsequently suggested interaction between NS2A and NS3 was proven by coimmunoprecipitation analyses. Using selectively permeabilized cells, we could demonstrate that the regions encompassing R22A-K23A-R24A and Q189S in NS2A are localized to the cytoplasm, where NS3 is also known to reside. However, the defect in particle production observed for the NS2A R22A-K23A-R24A and Q189S mutants was not due to a defect in physical interaction between NS2A and NS3, as the NS2A mutations did not interrupt NS3 interaction. In fact, a region just upstream of R22-K23-R24 was mapped to be critical for NS2A-NS3 interaction. Taken together, these data support a complex interplay between YFV NS2A and NS3 in virion assembly and identify a basic cluster in the NS2A N terminus to be critical in this process. Despite an available vaccine, yellow fever remains endemic in tropical areas of South America and Africa. To control the disease, antiviral drugs are required, and an understanding of the determinants of virion assembly is central to their development. In this study, we identified a basic cluster of

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

    Directory of Open Access Journals (Sweden)

    Amol Hartalkar


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

  18. Evolution of broad-band SED during outburst rise in NS X-ray Nova Aql X-1 (United States)

    Meshcheryakov, Alexander V.; Tsygankov, Sergey S.; Khamitov, Irek M.; Shakura, Nikolay I.; Bikmaev, Ilfan F.; Eselevich, Maxim V.; Vlasyuk, Valeriy V.; Pavlinsky, Mikhail N.


    The observed evolution of the broad-band spectral energy distribution (SED) in NS X-ray Nova Aql X-1 during the rise phase of a bright Fast-Rise-Exponential-Decay-type outburst in 2013 can be understood in the framework of thermal emission from non-stationary accretion disc with radial temperature distribution transforming from a single-temperature blackbody emitting ring into the multicolour irradiated accretion disc. SED evolution during the hard to soft X-ray state transition looks unusual, as it cannot be reproduced by the standard disc irradiation model with a single irradiation parameter for NUV, Optical and NIR spectral bands. NIR (NUV) band is correlated with soft (hard) X-ray flux changes during the state transition interval, respectively. In our interpretation, at the moment of X-ray state transition UV-emitting parts of the accretion disc are screened from direct X-ray illumination from the central source and are heated primarily by hard X-rays (E > 10 keV), scattered in the hot corona or wind possibly formed above the optically thick outer accretion flow; the outer edge of multicolour disc, which emits in Optical-NIR, can be heated primarily by direct X-ray illumination. We point out that future simultaneous multiwavelength observations of X-ray Nova systems during the fast X-ray state transition interval are of great importance, as it can serve as 'X-ray tomograph' to study physical conditions in outer regions of accretion flow. This can provide an effective tool to directly test the energy-dependent X-ray heating efficiency, vertical structure and accretion flow geometry in transient low-mass X-ray binaries.

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

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Hyock Joo Kwon

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

  1. Direct binding of ledipasvir to HCV NS5A: mechanism of resistance to an HCV antiviral agent. (United States)

    Kwon, Hyock Joo; Xing, Weimei; Chan, Katie; Niedziela-Majka, Anita; Brendza, Katherine M; Kirschberg, Thorsten; Kato, Darryl; Link, John O; Cheng, Guofeng; Liu, Xiaohong; Sakowicz, Roman


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

  2. Matter-wave bright solitons in effective bichromatic lattice potentials

    Indian Academy of Sciences (India)

    Keywords. Bose–Einstein condensate; optical lattices; inhomogeneous nonlinearity. Abstract. Matter-wave bright solitons in bichromatic lattice potentials are considered and their dynamics for different lattice environments are studied. Bichromatic potentials are created from superpositions of (i) two linear optical lattices and ...

  3. Compact collimators for high brightness blue LEDs using dielectric multilayers

    NARCIS (Netherlands)

    Cornelissen, H.J.; Ma, H.; Ho, C.; Li, M.; Mu, C.


    A novel method is presented to inject the light of millimeter-sized high-brightness blue LEDs into light guides of submillimeter thickness. Use is made of an interference filter that is designed to pass only those modes that will propagate in the light guide by total internal reflection. Other modes

  4. Bright and dark soliton solutions of the (3+ 1)-dimensional ...

    Indian Academy of Sciences (India)

    In this paper, we obtain the 1-soliton solutions of the (3 + 1)-dimensional generalized Kadomtsev–Petviashvili (gKP) equation and the generalized Benjamin equation. By using two solitary wave ansatz in terms of sech p and tanh p functions, we obtain exact analytical bright and dark soliton solutions for the considered ...

  5. Brightness perception in low resolution images of 3d textures

    NARCIS (Netherlands)

    Spreeuwers, Lieuwe Jan; van der Heijden, Ferdinand; Siteur, J.


    A first step towards the analysis of the appearance of 3 dimensional textures is presented in this paper. It is assumed that the scale of the texture is small relative to the resolution of the camera. Therefore, the texture itself is not distinguishable.However, the perceived brightness of the

  6. Reducing Color/Brightness Interaction in Color Television (United States)

    Marchman, Robert H.


    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.

  7. The bright optical afterglow of the long GRB 001007

    DEFF Research Database (Denmark)

    Ceron, J.M.C.; Castro-Tirado, A.J.; Gorosabel, J.


    We present optical follow up observations of the long GRB 001007 between 6.14 hours and similar to468 days after the event. An unusually bright optical afterglow (OA) was seen to decline following a steep power law decay with index alpha = -2.03 +/- 0.11, possibly indicating a break in the light ...

  8. The star-bright hour : [luuletused] / Betti Alver

    Index Scriptorium Estoniae

    Alver, Betti, 1906-1989


    Sisu: The star-bright hour ; Not a dream ; The Piper ; Corals in an ancent river. Luuletused pärinevad kogumikust "Tuulelaeval valgusest on aerud = Windship with Oars of Light. (Tallinn : Huma, 2001). Orig.: Tähetund ; Mitte viirastus, meelepett ; Vilepuhuja ; Korallid Emajões

  9. Time series analysis of bright galactic X-ray sources

    DEFF Research Database (Denmark)

    Priedhorsky, W. C.; Brandt, Søren; Lund, Niels


    We analyze 70 to 110 day data sets from eight bright galactic X-ray binaries observed by WATCH/Eureca, in search of periodic variations. We obtain new epochs for the orbital variation of Cyg X-3 and 4U 1700-37, and confirmation of a dip in Cyg X-1 at superior conjunction of the X-ray star. No evi...

  10. Bright infrared LEDs based on colloidal quantum-dots

    KAUST Repository

    Sun, Liangfeng


    Record-brightness infrared LEDs based on colloidal quantum-dots have been achieved through control of the spacing between adjacent quantum-dots. By tuning the size of quantum-dots, the emission wavelengths can be tuned between 900nm and 1650nm. © 2013 Materials Research Society.

  11. Bright soliton trains of trapped Bose-Einstein condensates


    Al Khawaja, U.; Stoof, H.T C; Hulet, R. G.; Strecker, K. E.; Patridge, G.B.


    We variationally determine the dynamics of bright soliton trains composed of harmonically trapped Bose-Einstein condensates with attractive interatomic interactions. In particular, we obtain the interaction potential between two solitons. We also discuss the formation of soliton trains due to the quantum mechanical phase fluctuations of a one-dimensional condensate.




  13. Spectral Index Changes with Brightness for -Ray Loud Blazars

    Indian Academy of Sciences (India)

    Theoretic relation of spectral index changes depending on -ray brightness is obtained. The correlations between the ratio of -ray flux densities and the differences of the -ray spectral indices are discussed for the three subclasses of HBL, LBL and FSRQs. Results show that the ratio is related with the differences for the ...

  14. Bright soliton trains of trapped Bose-Einstein condensates

    NARCIS (Netherlands)

    Al Khawaja, U.; Stoof, H.T.C.; Hulet, R.G.; Strecker, K.E.; Patridge, G.B.


    We variationally determine the dynamics of bright soliton trains composed of harmonically trapped Bose-Einstein condensates with attractive interatomic interactions. In particular, we obtain the interaction potential between two solitons. We also discuss the formation of soliton trains due to the

  15. Henrietta Leavitt - A Bright Star of Astronomy; Resonance June 2001

    Indian Academy of Sciences (India)

    In fact, it was not known then that we live in a galaxy called the Milky Way, and that there were other galaxies in the universe like ours. This big handicap was elegantly removed by a momentous discovery by an American astronomer named Henrietta. Leavitt in 1912. She found a way to determine the actual brightness of a ...

  16. The star-bright hour : [poems] / Betti Alver

    Index Scriptorium Estoniae

    Alver, Betti, 1906-1989


    Autori lühitutvustus lk. 231. Sisu: The star-bright hour ; The debt ; Not a dream ; Fog-bound ; Corals in an Ancient river ; Frou-frou 1-3. Orig.: Tähetund ; Vilepuhuja ; Võlg ; "Mitte viirastus, meelepett..." ; Udus ; Korallid Emajões ; Froufrou 1-3

  17. Stability of bright solitons in some physical systems

    Energy Technology Data Exchange (ETDEWEB)

    Pelap, Francois B [Department of Physics, Faculty of Science, University of Dschang, P O Box 69, Dschang (Cameroon); Talla, Pierre K [Department of Physics, Faculty of Science, University of Dschang, P O Box 69, Dschang (Cameroon); Tchitnga, Robert [Department of Physics, Faculty of Science, University of Dschang, P O Box 69, Dschang (Cameroon); Faye, Mansour M [Departement de Physique, Faculte des Sciences et Techniques, Universite Cheikh Anta DIOP de Dakar, BP 5005, Dakar - Fann (Senegal)


    Dynamical systems described by the modified quintic complex Ginzburg Landau equation and its derivative forms are considered and the stability of their bright soliton solution is investigated numerically by means of the split-step Fourier method. Some discussions related to the way of ensuring the stability of this solution are presented.

  18. Does bright light have an anxiolytic effect? - an open trial

    Directory of Open Access Journals (Sweden)

    Kripke Daniel F


    Full Text Available Abstract Background The aim of this open trial was to examine the influence of acute bright light exposure on anxiety in older and young adults. Methods This study was ancillary to a complex 5-day laboratory experiment testing phase-responses to light at all times of the day. On 3 consecutive days, participants were exposed to bright light (3,000 lux for 3 hours. The Spielberger State-Trait Anxiety Inventory (Form Y1 was administered 5 minutes before and 20 minutes after each treatment. Mean state anxiety before and after treatment were analyzed by age, sex, and time ANOVA. To avoid floor effects, only participants with baseline STAI levels of ≥ 25 were included. Results A significant anxiolytic effect of bright light was found for the mean data, as well as for each of the three days. No significant main effect of age, sex, or interaction of these factors with STAI change were found. Conclusion The results show consistent and significant (albeit modest anxiolytic effects following acute bright light exposure in low anxiety adults. Further randomized, controlled trials in clinically anxious individuals are needed.

  19. Modeling laser brightness from cross porro prism resonators

    CSIR Research Space (South Africa)

    Forbes, A


    Full Text Available Laser brightness is a parameter often used to compare high power laser beam delivery from various sources, and incorporates both the power contained in the particular mode, as well as the propagation of that mode through the beam quality factor, M2...

  20. Giant Low Surface Brightness Galaxies: Evolution in Isolation M. Das

    Indian Academy of Sciences (India)

    Abstract. Giant Low Surface Brightness (GLSB) galaxies are amongst the most massive spiral galaxies that we know of in our Universe. Although they fall in the class of late type spiral galaxies, their properties are far more extreme. They have very faint stellar disks that are extremely rich in neutral hydrogen gas but low in ...

  1. Giant Low Surface Brightness Galaxies: Evolution in Isolation

    Indian Academy of Sciences (India)


    Jan 27, 2016 ... Giant Low Surface Brightness (GLSB) galaxies are amongst the most massive spiral galaxies that we know of in our Universe. Although they fall in the class of late type spiral galaxies, their properties are far more extreme. They have very faint stellar disks that are extremely rich in neutral hydrogen gas but ...

  2. Evaluation of brightness temperature from a forward model of ...

    Indian Academy of Sciences (India)

    Ground-based microwave radiometers are getting great attention in recent years due to their capability to profile the temperature and humidity at high temporal and vertical resolution in the lower troposphere. The process of retrieving these parameters from the measurements of radiometric brightness temperature () ...

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

    DEFF Research Database (Denmark)

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


    The measurement of an arbitrary quadrature of a bright quantum state of light is a commonly requested action in many quantum information protocols, but it is experimentally challenging with previously proposed schemes. We suggest that the quadrature be measured at a specific sideband frequency of...

  4. The "Brightness Rules" Alternative Conception for Light Bulb Circuits (United States)

    Bryan, Joel A.; Stuessy, Carol


    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…

  5. Protocol of networks using energy sharing collisions of bright solitons

    Indian Academy of Sciences (India)

    Soliton network; coupled nonlinear Schrödinger system; bright soliton; soliton collision. PACS Nos 42.65.Tg; 02.30. .... CNLS equations, we shall explore the dynamics of solitons in simple networks, i.e., PSG. In §4, the conclusion is ...... KS thank the Principal and management of Bishop Heber College for constant support.

  6. A transient homotypic interaction model for the influenza A virus NS1 protein effector domain.

    Directory of Open Access Journals (Sweden)

    Philip S Kerry

    Full Text Available Influenza A virus NS1 protein is a multifunctional virulence factor consisting of an RNA binding domain (RBD, a short linker, an effector domain (ED, and a C-terminal 'tail'. Although poorly understood, NS1 multimerization may autoregulate its actions. While RBD dimerization seems functionally conserved, two possible apo ED dimers have been proposed (helix-helix and strand-strand. Here, we analyze all available RBD, ED, and full-length NS1 structures, including four novel crystal structures obtained using EDs from divergent human and avian viruses, as well as two forms of a monomeric ED mutant. The data reveal the helix-helix interface as the only strictly conserved ED homodimeric contact. Furthermore, a mutant NS1 unable to form the helix-helix dimer is compromised in its ability to bind dsRNA efficiently, implying that ED multimerization influences RBD activity. Our bioinformatical work also suggests that the helix-helix interface is variable and transient, thereby allowing two ED monomers to twist relative to one another and possibly separate. In this regard, we found a mAb that recognizes NS1 via a residue completely buried within the ED helix-helix interface, and which may help highlight potential different conformational populations of NS1 (putatively termed 'helix-closed' and 'helix-open' in virus-infected cells. 'Helix-closed' conformations appear to enhance dsRNA binding, and 'helix-open' conformations allow otherwise inaccessible interactions with host factors. Our data support a new model of NS1 regulation in which the RBD remains dimeric throughout infection, while the ED switches between several quaternary states in order to expand its functional space. Such a concept may be applicable to other small multifunctional proteins.

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

    Directory of Open Access Journals (Sweden)

    Saqi Mansoor AS


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

  8. Computer aided screening of Accacia nilotica phytochemicals against HCV NS3/4a. (United States)

    Khan, Mahim; Qasim, Muhammad; Ashfaq, Usman Ali; Idrees, Sobia; Shah, Masoud


    HCV has become a leading cause of liver cirrhosis and hepatocellular carcinoma and is a major health concern worldwide. To date, there is no vaccine available in the market to tackle this disease, therefore there is a strong need to develop antiviral compounds that can target all genotypes of HCV with the same efficiency. Medicinal plants have low cost and are less toxic therefore, extracts of medicinal plants can serve as important antiviral agents against HCV. This study was designed to screen phytochemicals of Accacia nilotica to find a potent drug candidate that can inhibit HCV infection effectively. Docking of NS3/4A protease and Flavonoids of Accacia nilotica revealed that most of the flavonoids bound deeply with the active site of NS3/4A protease. Compound 01 showed a high ranking on docking score. All other compounds also showed reliable docking scores and had interactions with the binding cavity of NS3/4A protease, suggesting them as a potent drug candidate to block HCV replication. To recognize binding interactions of Accacia nilotica phytochemicals with NS3/4A protease, molecular docking was performed to find potential inhibitor against NS3/4A protease of HCV. After post docking analysis, important interactions were found between active compounds and active site of NS3/4A protease. It can be concluded from the study that phytochemicals of Accacia nilotica may serve as a potential drug candidate with relatively simple structural changes against HCV NS3/4A protease.

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

    Directory of Open Access Journals (Sweden)

    Subhamoy Pal

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

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

    DEFF Research Database (Denmark)

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


    The humoral antibody response against the nonstructural protein NS1 and the structural protein VP2 of porcine parvovirus (PPV) was evaluated by immuno-peroxidase test (IPT) and enzyme linked immune sorbent assay (ELISA) using recombinant PPV antigens. The coding sequence for NS1 and VP2 was inser......The humoral antibody response against the nonstructural protein NS1 and the structural protein VP2 of porcine parvovirus (PPV) was evaluated by immuno-peroxidase test (IPT) and enzyme linked immune sorbent assay (ELISA) using recombinant PPV antigens. The coding sequence for NS1 and VP2...... against rNS1 could only be detected in infected pigs and NS1 may in this way allow the specific detection of infected animals. Analysis of serum samples collected up to 18 days post infection (p.i.) from four pigs experimentally infected with PPV showed that antibodies against rNS1 and rVP2 could in all...

  11. SKYMONITOR: A Global Network for Sky Brightness Measurements (United States)

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


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

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

    Directory of Open Access Journals (Sweden)

    Nagasaka Kazunori


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

  13. Increased sensitivity of NS1 ELISA by heat dissociation in acute dengue 4 cases. (United States)

    Buonora, Sibelle Nogueira; Dos Santos, Flavia Barreto; Daumas, Regina Paiva; Passos, Sonia Regina Lambert; da Silva, Manoela Heringer; de Lima, Monique Rocha; Nogueira, Rita Maria Ribeiro


    Dengue is an acute febrile illness considered the major arboviral disease in terms of morbidity, mortality, economic impact and dissemination worldwide. Brazil accounts for the highest notification rate, with circulation of all four dengue serotypes. The NS1 antigen is a dengue highly conserved specific soluble glycoprotein essential for viral replication and viability that can be detected 0 to 18 days from the onset of fever (peak first 3 days). It induces a strong humoral response and is known as a complement-fixing antigen. Lower NS1 test sensitivity occurs in secondary dengue infections probably due to immune complex formation impairing antigen detection by ELISA. We compared the sensitivity of NS1 ELISA in heat dissociated and non-dissociated samples from 156 RT-PCR confirmed acute dengue-4 cases from 362 prospectively enrolled patients. Secondary infections accounted for 83.3% of cases. NS1 ELISA was positive in 42.5% and indeterminate in 10.2% of dengue-4 cases. After heat dissociation, 7 negative and 16 indeterminate samples turned positive, increasing the overall test sensitivity to 57.7%. Although it is time consuming and requires the use of specific laboratory equipment, NS1 ELISA combined with heat dissociation could be a slightly better alternative for triage in suspected dengue cases.

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

    Directory of Open Access Journals (Sweden)

    Sobia A. Halim


    Full Text Available Dengue fever is an emerging public health concern, with several million viral infections occur annually, for which no effective therapy currently exist. Non-structural protein 3 (NS-3 Helicase encoded by the dengue virus (DENV is considered as a potential drug target to design new and effective drugs against dengue. Helicase is involved in unwinding of dengue RNA. This study was conducted to design new NS-3 Helicase inhibitor by in silico ligand- and structure based approaches. Initially ligand-based pharmacophore model was generated that was used to screen a set of 1201474 compounds collected from ZINC Database. The compounds matched with the pharmacophore model were docked into the active site of NS-3 helicase. Based on docking scores and binding interactions, 25 compounds are suggested to be potential inhibitors of NS3 Helicase. The pharmacokinetic properties of these hits were predicted. The selected hits revealed acceptable ADMET properties. This study identified potential inhibitors of NS-3 Helicase in silico, and can be helpful in the treatment of Dengue.

  15. AGILE Observations of the Gravitational-wave Source GW170817: Constraining Gamma-Ray Emission from an NS-NS Coalescence (United States)

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


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

  16. A comparative analysis of the substrate permissiveness of HCV and GBV-B NS3/4A proteases reveals genetic evidence for an interaction with NS4B protein during genome replication. (United States)

    Benureau, Yann; Warter, Lucile; Malcolm, Bruce A; Martin, Annette


    The hepatitis C virus (HCV) serine protease (NS3/4A) processes the NS3-NS5B segment of the viral polyprotein and also cleaves host proteins involved in interferon signaling, making it an important target for antiviral drug discovery and suggesting a wide breadth of substrate specificity. We compared substrate specificities of the HCV protease with that of the GB virus B (GBV-B), a distantly related nonhuman primate hepacivirus, by exchanging amino acid sequences at the NS4B/5A and/or NS5A/5B cleavage junctions between these viruses within the backbone of subgenomic replicons. This mutagenesis study demonstrated that the GBV-B protease had a broader substrate tolerance, a feature corroborated by structural homology modeling. However, despite efficient polyprotein processing, GBV-B RNAs containing HCV sequences at the C-terminus of NS4B had a pseudo-lethal replication phenotype. Replication-competent revertants contained second-site substitutions within the NS3 protease or NS4B N-terminus, providing genetic evidence for an essential interaction between NS3 and NS4B during genome replication. Copyright © 2010 Elsevier Inc. All rights reserved.

  17. Antiviral phytochemicals identification from Azadirachta indica leaves against HCV NS3 protease: an in silico approach. (United States)

    Ashfaq, Usman Ali; Jalil, Asma; Ul Qamar, Muhammad Tahir


    Hepatitis C virus (HCV) is a major health problem across the world affecting the people of all age groups. It is the main cause of hepatitis and at chronic stage causes liver cirrhosis and hepatocellular carcinoma. Various therapeutics are made against HCV but still there is a need to find out potential therapeutics to combat the virus. The goal of this study is to identify the phytochemicals of Azadirachta indica leaves having antiviral activity against HCV NS3 protease through molecular docking and simulation approach. Results show that the compound 3-Deacetyl-3-cinnamoyl-azadirachtin possesses good binding properties with HCV NS3/4A protease. It can be concluded from this study that Deacetyl-3-cinnamoyl-azadirachtin may serve as a potential inhibitor against NS3/4A protease.

  18. 2D non-separable linear canonical transform (2D-NS-LCT) based cryptography (United States)

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


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

  19. Evaluation of seed and oil yield stability in NS rapeseed cultivars (Brassica napus L

    Directory of Open Access Journals (Sweden)

    Marjanović-Jeromela Ana


    Full Text Available Rapeseed trials performed in the period 2007-2010 were analyzed to evaluate seed and oil yield stability in NS rapeseed cultivars in changeable environmental conditions of northern Serbia. Seed yield, oil content and yield for 40 winter and 9 spring rapeseed cultivars were analyzed. It was found that the influence of year on seed and oil yield was most significant. Genotype (cultivars by environment (year interaction was further analyzed using AMMI (Additive Main Effects and Multiplicative Interaction model. In the environmental conditions present during the trial in Rimski Šančevi according to the analysis of regression coefficient (bi and ecovalence (Wi and AMMI model, winter cultivars Nena and NS-L-102 were the most stable and high seed yielding, and hybrid cultivar NS-H-R-3 was singled out for oil yield. These cultivars are recommended for implementation in future breeding programs and for growing in the conditions described in this paper.

  20. In silico mutation analysis of non-structural protein-5 (NS5) dengue virus (United States)

    Puspitasari, R. D.; Tambunan, U. S. F.


    Dengue fever is a world disease. It is endemic in more than 100 countries. Information about the effect of mutations in the virus is important in drug design and development. In this research, we studied the effect of mutation on NS5 dengue virus. NS5 is the large protein containing 67% amino acid similarity in DENV 1-4 and has multifunctional enzymatic activities. Dengue virus is an RNA virus that has very high mutation frequency with an average of 100 times higher than DNA mutations, and the accumulation of mutations will be possible to generate the new serotype. In this study, we report that mutation occurs in NS5 of DENV serotype 3, glutamine mutates into methionine at position 10 and threonine mutates into isoleucine at position 55. These residues are part of the domain named S-Adenosyl-L-Methionine-Dependent Methyltransferase (IPR029063).

  1. Hepatitis C virus NS2 protein activates cellular cyclic AMP-dependent pathways. (United States)

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


    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.

  2. Growth behavior of laser-induced damage on fused silica optics under UV, ns laser irradiation. (United States)

    Negres, Raluca A; Norton, Mary A; Cross, David A; Carr, Christopher W


    The growth behavior of laser-induced damage sites is affected by a large number of laser parameters as well as site morphology. Here we investigate the effects of pulse duration on the growth rate of damage sites located on the exit surface of fused silica optics. Results demonstrate a significant dependence of the growth parameters on laser pulse duration at 351 nm from 1 ns to 15 ns, including the observation of a dominant exponential versus linear, multiple-shot growth behavior for long and short pulses, respectively. These salient behaviors are tied to the damage morphology and suggest a shift in the fundamental growth mechanisms for pulses in the 1-5 ns range.

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

    Directory of Open Access Journals (Sweden)

    Wilhelm Kempf


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

  4. Alkyl substituted aminal derivatives of HCV NS5A inhibitor MK-8742. (United States)

    Yu, Wensheng; Coburn, Craig A; Nair, Anilkumar G; Wong, Michael; Tong, Ling; Dwyer, Michael P; Hu, Bin; Zhong, Bin; Hao, Jinglai; Yang, De-Yi; Selyutin, Oleg; Jiang, Yueheng; Rosenblum, Stuart B; Kim, Seong Heon; Lavey, Brian J; Zhou, Guowei; Rizvi, Razia; Shankar, Bandarpalle B; Zeng, Qingbei; Chen, Lei; Agrawal, Sony; Carr, Donna; Rokosz, Laura; Liu, Rong; Curry, Stephanie; McMonagle, Patricia; Ingravallo, Paul; Lahser, Fred; Asante-Appiah, Ernest; Nomeir, Amin; Kozlowski, Joseph A


    HCV NS5A inhibitors have demonstrated impressive in vitro potency profiles in HCV replicon assays and robust HCV RNA titer reduction in the clinic making them attractive components for inclusion in an all oral fixed dose combination regimen for the treatment of HCV infection. Herein we describe our continued research efforts around the alkyl "Z group" modification of the tetracyclic indole-based NS5A inhibitor MK-8742, which led to the discovery of a series of potent NS5A inhibitors. Compounds 10 and 19 are of particular interests since they are as potent as our previous leads and have much improved rat pharmacokinetic profiles. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Aryl or heteroaryl substituted aminal derivatives of HCV NS5A inhibitor MK-8742. (United States)

    Yu, Wensheng; Coburn, Craig A; Nair, Anilkumar G; Wong, Michael; Rosenblum, Stuart B; Zhou, Guowei; Dwyer, Michael P; Tong, Ling; Hu, Bin; Zhong, Bin; Hao, Jinglai; Ji, Tao; Zan, Shuai; Kim, Seong Heon; Zeng, Qingbei; Selyutin, Oleg; Chen, Lei; Masse, Frederic; Agrawal, Sony; Liu, Rong; Xia, Ellen; Zhai, Ying; Curry, Stephanie; McMonagle, Patricia; Ingravallo, Paul; Asante-Appiah, Ernest; Lin, Mingxiang; Kozlowski, Joseph A


    Herein we describe our research efforts around the aryl and heteroaryl substitutions at the aminal carbon of the tetracyclic indole-based HCV NS5A inhibitor MK-8742. A series of potent NS5A inhibitors are described, such as compounds 45-47, 54, 56, and 65, which showed improved potency against clinically relevant and resistance associated HCV variants. The improved potency profiles of these compounds demonstrated an SAR that can improve the potency against GT2b, GT1a Y93H, and GT1a L31V altogether, which was unprecedented in our previous efforts in NS5A inhibition. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Potent inhibitors of HCV-NS3 protease derived from boronic acids

    Energy Technology Data Exchange (ETDEWEB)

    Venkatraman, Srikanth; Wu, Wanli; Prongay, Andrew; Girijavallabhan, Viyyoor; Njoroge, F. George; (SPRI)


    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.

  7. Background gas collisional effects on expanding fs and ns laser ablation plumes (United States)

    Harilal, S. S.; Farid, N.; Freeman, J. R.; Diwakar, P. K.; LaHaye, N. L.; Hassanein, A.


    The collisional effects of a background gas on expanding ultrafast and short pulse laser ablation plumes were investigated by varying background pressure from vacuum to atmospheric pressure levels. For producing Cu ablation plumes, either 40 fs, 800 nm pulses from a Ti: Sapphire laser or 6 ns, 1,064 nm pulses from a Nd:YAG laser were used. The role of background pressure on plume hydrodynamics, spectral emission features, absolute line intensities, signal to background ratios and ablation craters was studied. Though the signal intensities were found to be maximum near to atmospheric pressure levels, the optimum signal to background ratios are observed ~20-50 Torr for both ns and fs laser ablation plumes. The differences in laser-target and laser-plasma couplings between ns and fs lasers were found to be more engraved in the crater morphologies and plasma hydrodynamic expansion features.

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

    Directory of Open Access Journals (Sweden)

    Liliana Morales


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

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

    KAUST Repository

    Jumat, Muhammad Raihan


    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.

  10. Generation of replication-proficient influenza virus NS1 point mutants with interferon-hyperinducer phenotype.

    Directory of Open Access Journals (Sweden)

    Maite Pérez-Cidoncha

    Full Text Available The NS1 protein of influenza A viruses is the dedicated viral interferon (IFN-antagonist. Viruses lacking NS1 protein expression cannot multiply in normal cells but are viable in cells deficient in their ability to produce or respond to IFN. Here we report an unbiased mutagenesis approach to identify positions in the influenza A NS1 protein that modulate the IFN response upon infection. A random library of virus ribonucleoproteins containing circa 40 000 point mutants in NS1 were transferred to infectious virus and amplified in MDCK cells unable to respond to interferon. Viruses that activated the interferon (IFN response were subsequently selected by their ability to induce expression of green-fluorescent protein (GFP following infection of A549 cells bearing an IFN promoter-dependent GFP gene. Using this approach we isolated individual mutant viruses that replicate to high titers in IFN-compromised cells but, compared to wild type viruses, induced higher levels of IFN in IFN-competent cells and had a reduced capacity to counteract exogenous IFN. Most of these viruses contained not previously reported NS1 mutations within either the RNA-binding domain, the effector domain or the linker region between them. These results indicate that subtle alterations in NS1 can reduce its effectiveness as an IFN antagonist without affecting the intrinsic capacity of the virus to multiply. The general approach reported here may facilitate the generation of replication-proficient, IFN-inducing virus mutants, that potentially could be developed as attenuated vaccines against a variety of viruses.

  11. Three Conformational Snapshots of the Hepatitis Virus NS3 Helicase Reveal a Ratchet Translocation Mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Gu, M.; Rice, C


    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.

  12. Productivity of NS sunflower hybrids in small-plot trials in Serbia in 2010

    Directory of Open Access Journals (Sweden)

    Miklič Vladimir


    Full Text Available The objective of this study was the evaluation of NS sunflower hybrids on the basis of the results of seed yield, seed oil content and oil yield obtained in a network of small-plot trials in Vojvodina and central Serbia in 2010, as well as recommendations for the sowing season 2011. Seed yield, seed oil content and oil yield were significantly different in small-plot trials in the investigated regions. In Vojvodina, the highest average seed yield was produced by Duško (3.08 t ha-1, Sremac (2.98 t ha-1, Orfej (2.97 t ha-1 Velja (2.93 t ha-1 and NS-H-111 (2.92 t ha-1. In the region of central Serbia, the highest seed yield was achieved by the hybrids NS-H-111 (2.97 t ha-1 and Duško (2.87 t ha-1. Hybrid Baća showed the highest average seed oil content both in the region of Vojvodina (48.54% and central Serbia (48.80%. The highest average oil yield (over 1.30 t ha-1 was produced by Duško, Bačvanin and NS-H-111 in the Vojvodina region, and in central Serbia oil yield (over 1.30 t ha-1 by NS-H-111, Oskar and Novosađanin. In the three-year trials in Vojvodina four hybrids (Duško, Sremac, Velja and NS-H-111 showed seed yield over general mean. The highest seed yield was reached by hybrid Duško (3.54 t ha-1.

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

    Directory of Open Access Journals (Sweden)

    Arne Bilet

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

  14. Electrochemical lateral flow immunosensor for detection and quantification of dengue NS1 protein. (United States)

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


    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. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Influenza virus non-structural protein 1 (NS1 disrupts interferon signaling.

    Directory of Open Access Journals (Sweden)

    Danlin Jia


    Full Text Available Type I interferons (IFNs function as the first line of defense against viral infections by modulating cell growth, establishing an antiviral state and influencing the activation of various immune cells. Viruses such as influenza have developed mechanisms to evade this defense mechanism and during infection with influenza A viruses, the non-structural protein 1 (NS1 encoded by the virus genome suppresses induction of IFNs-α/β. Here we show that expression of avian H5N1 NS1 in HeLa cells leads to a block in IFN signaling. H5N1 NS1 reduces IFN-inducible tyrosine phosphorylation of STAT1, STAT2 and STAT3 and inhibits the nuclear translocation of phospho-STAT2 and the formation of IFN-inducible STAT1:1-, STAT1:3- and STAT3:3- DNA complexes. Inhibition of IFN-inducible STAT signaling by NS1 in HeLa cells is, in part, a consequence of NS1-mediated inhibition of expression of the IFN receptor subunit, IFNAR1. In support of this NS1-mediated inhibition, we observed a reduction in expression of ifnar1 in ex vivo human non-tumor lung tissues infected with H5N1 and H1N1 viruses. Moreover, H1N1 and H5N1 virus infection of human monocyte-derived macrophages led to inhibition of both ifnar1 and ifnar2 expression. In addition, NS1 expression induces up-regulation of the JAK/STAT inhibitors, SOCS1 and SOCS3. By contrast, treatment of ex vivo human lung tissues with IFN-α results in the up-regulation of a number of IFN-stimulated genes and inhibits both H5N1 and H1N1 virus replication. The data suggest that NS1 can directly interfere with IFN signaling to enhance viral replication, but that treatment with IFN can nevertheless override these inhibitory effects to block H5N1 and H1N1 virus infections.

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

    DEFF Research Database (Denmark)

    Harmark, Troels; Obers, N. A.


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

  17. Discovery of fused tricyclic core containing HCV NS5A inhibitors with pan-genotype activity. (United States)

    Yu, Wensheng; Coburn, Craig A; Yang, De-Yi; Meinke, Peter T; Wong, Michael; Rosenblum, Stuart B; Chen, Kevin X; Njoroge, George F; Chen, Lei; Dwyer, Michael P; Jiang, Yueheng; Nair, Anilkumar G; Selyutin, Oleg; Tong, Ling; Zeng, Qingbei; Zhong, Bin; Ji, Tao; Hu, Bin; Agrawal, Sony; Xia, Ellen; Zhai, Ying; Liu, Rong; Kong, Rong; Ingravallo, Paul; Asante-Appiah, Ernest; Nomeir, Amin; Fells, James; Kozlowski, Joseph A


    HCV NS5A inhibitors have demonstrated impressive in vitro potency profiles in HCV replicon assays and robust HCV RNA titer reduction in the clinic making them attractive components for inclusion in an all oral fixed dose combination regimen for the treatment of HCV infection. Herein, we describe research efforts that led to the discovery of a series of fused tricyclic core containing HCV NS5A inhibitors such as 24, 39, 40, 43, and 44 which have pan-genotype activity and are orally bioavailable in the rat. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Analysis the parameters of seed quality in ns sunflower hybrid after processing in gravity separator

    Directory of Open Access Journals (Sweden)

    Jokić Goran


    Full Text Available This paper analyzed the processed seed of five sunflower hybrid seed developed at the Institute of Field and Vegetable Crops in Novi Sad before and after processing in gravity separator. The cultivars were Pegaz, Duško, NS Fantazija, Sumo 1 PR and NS Oskar. The analysis was conducted on seed lots processed in 2015 and involved the following parameters: seed purity percentage, 1.000-seed weight, germination energy, germination, seed moisture, number of sclerotinia per 1.000. The results showed that all the parameters of seed quality of sunflower hybrids were better after processing seeds in the gravity separator.

  19. Optical and EPR spectra of the thionitrosyl complex [Cr(OH2)5(NS)]2+

    DEFF Research Database (Denmark)

    Døssing, Anders Rørbæk; Dethlefsen, Johannes Wied


    . The optical data indicate that the NS ligand is a weaker p-acceptor than the NO ligand. The EPR parameters of [Cr(OH2)5(NS)]2+ were determined: giso, g¦ and g-: 1.96515, 1.92686(5) and 1.986860(8); Aiso(53Cr), A¦(53Cr) and A-(53Cr): 25.3´10-4, 38´10-4 and 18.5´10-4cm-1; Aiso(14N), A¦(14N) and A-(14N): 6...

  20. Extremely High Current, High-Brightness Energy Recovery Linac

    CERN Document Server

    Ben-Zvi, Ilan; Beavis, Dana; Blaskiewicz, Michael; Bluem, Hans; Brennan, Joseph M; Burger, Al; Burrill, Andrew; Calaga, Rama; Cameron, Peter; Chang, Xiangyun; Cole, Michael; Connolly, Roger; Delayen, Jean R; Favale, Anthony; Gassner, David M; Grimes, Jacob T; Hahn, Harald; Hershcovitch, Ady; Holmes, Douglas; Hseuh Hsiao Chaun; Johnson, Peter; Kayran, Dmitry; Kewisch, Jorg; Kneisel, Peter; Lambiase, Robert; Litvinenko, Vladimir N; McIntyre, Gary; Meng, Wuzheng; Nehring, Thomas; Nicoletti, Tony; Oerter, Brian; Pate, David; Phillips, Larry; Preble, Joseph P; Rank, Jim; Rao, Triveni; Rathke, John; Roser, Thomas; Russo, Thomas; Scaduto, Joseph; Schultheiss, Tom; Segalov, Zvi; Smith, Kevin T; Todd, Alan M M; Warren-Funk, L; Williams, Neville; Wu, Kuo-Chen; Yakimenko, Vitaly; Yip, Kin; Zaltsman, Alex; Zhao, Yongxiang


    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.

  1. Bright breathers in nonlinear left-handed metamaterial lattices (United States)

    Koukouloyannis, V.; Kevrekidis, P. G.; Veldes, G. P.; Frantzeskakis, D. J.; DiMarzio, D.; Lan, X.; Radisic, V.


    In the present work, we examine a prototypical model for the formation of bright breathers in nonlinear left-handed metamaterial lattices. Utilizing the paradigm of nonlinear transmission lines, we build a relevant lattice and develop a quasi-continuum multiscale approximation that enables us to appreciate both the underlying linear dispersion relation and the potential for bifurcation of nonlinear states. We focus here, more specifically, on bright discrete breathers which bifurcate from the lower edge of the linear dispersion relation at wavenumber k=π . Guided by the multiscale analysis, we calculate numerically both the stable inter-site centered and the unstable site-centered members of the relevant family. We quantify the associated stability via Floquet analysis and the Peierls-Nabarro barrier of the energy difference between these branches. Finally, we explore the dynamical implications of these findings towards the potential mobility or lack thereof (pinning) of such breather solutions.

  2. Improvement in brightness of multicusp-plasma ion source

    Energy Technology Data Exchange (ETDEWEB)

    Ji, Q.; Jiang, X.; King, T-J.; Leung, K-N.; Standiford, K.; Wilde, S.B.


    The beam brightness of a multicusp-plasma ion source has been substantially improved by optimizing the source configuration and extractor geometry. The current density of a 2 keV He{sup +} beam extracted from a 7.5-cm-diameter source operating at 2.5 kW RF power is {approx}100 mA/cm{sup 2}, which is {approx}10 times larger than that of a beam extracted from a 5-cm-diameter source operating at 1 kW RF power. A smaller focused beam spot size is achieved with a counter-bored extractor instead of a conventional (''through-hole'') extractor, resulting another order of magnitude improvement in beam current density. Measured brightness can be as high as 440 A/cm{sup 2}Sr, which represents a 30 times improvement over prior work.

  3. The ASAS-SN bright supernova catalogue - III. 2016 (United States)

    Holoien, T. W.-S.; Brown, J. S.; Stanek, K. Z.; Kochanek, C. S.; Shappee, B. J.; Prieto, J. L.; Dong, Subo; Brimacombe, J.; Bishop, D. W.; Bose, S.; Beacom, J. F.; Bersier, D.; Chen, Ping; Chomiuk, L.; Falco, E.; Godoy-Rivera, D.; Morrell, N.; Pojmanski, G.; Shields, J. V.; Strader, J.; Stritzinger, M. D.; Thompson, Todd A.; Woźniak, P. R.; Bock, G.; Cacella, P.; Conseil, E.; Cruz, I.; Fernandez, J. M.; Kiyota, S.; Koff, R. A.; Krannich, G.; Marples, P.; Masi, G.; Monard, L. A. G.; Nicholls, B.; Nicolas, J.; Post, R. S.; Stone, G.; Wiethoff, W. S.


    This catalogue summarizes information for all supernovae discovered by the All-Sky Automated Survey for SuperNovae (ASAS-SN) and all other bright (mpeak ≤ 17), spectroscopically confirmed supernovae discovered in 2016. We then gather the near-infrared through ultraviolet magnitudes of all host galaxies and the offsets of the supernovae from the centres of their hosts from public data bases. We illustrate the results using a sample that now totals 668 supernovae discovered since 2014 May 1, including the supernovae from our previous catalogues, with type distributions closely matching those of the ideal magnitude limited sample from Li et al. This is the third of a series of yearly papers on bright supernovae and their hosts from the ASAS-SN team.

  4. Changes in the brightness of Jupiter's hemispheres again become periodic (United States)

    Vidmachenko, A. P.


    Our analysis of data on relative brightness distribution along the central meridian of Jupiter showed that the ratio of brightness of northern and southern tropical zones Aj=BNTrZ/BSTrZ is a good index of activity of processes in Jovian atmosphere. In the years when the influence of solar activity is synchronized with the seasonal changes of irradiation of the northern and southern hemisphere, we note an increasing of the correlation of the activity index Aj with the periodic curve for change of distance to Sun at moving of planet on orbit. Analysis of Jupiter's images obtained in 2014-2017 showed, that if in 1998-2013 synchronization of change the Aj with the curve of change distance to the Sun when the planet moved on orbit, was somewhat disrupted; but in 2015-2017 such a correlation began to recover.

  5. Structure determination of Murine Norovirus NS6 proteases with C-terminal extensions designed to probe protease–substrate interactions

    Directory of Open Access Journals (Sweden)

    Humberto Fernandes


    Full Text Available Noroviruses are positive-sense single-stranded RNA viruses. They encode an NS6 protease that cleaves a viral polyprotein at specific sites to produce mature viral proteins. In an earlier study we obtained crystals of murine norovirus (MNV NS6 protease in which crystal contacts were mediated by specific insertion of the C-terminus of one protein (which contains residues P5-P1 of the NS6-7 cleavage junction into the peptide binding site of an adjacent molecule, forming an adventitious protease-product complex. We sought to reproduce this crystal form to investigate protease–substrate complexes by extending the C-terminus of NS6 construct to include residues on the C-terminal (P′ side of the cleavage junction. We report the crystallization and crystal structure determination of inactive mutants of murine norovirus NS6 protease with C-terminal extensions of one, two and four residues from the N-terminus of the adjacent NS7 protein (NS6 1′, NS6 2′, NS6 4′. We also determined the structure of a chimeric extended NS6 protease in which the P4-P4′ sequence of the NS6-7 cleavage site was replaced with the corresponding sequence from the NS2-3 cleavage junction (NS6 4′ 2|3.The constructs NS6 1′ and NS6 2′ yielded crystals that diffracted anisotropically. We found that, although the uncorrected data could be phased by molecular replacement, refinement of the structures stalled unless the data were ellipsoidally truncated and corrected with anisotropic B-factors. These corrections significantly improved phasing by molecular replacement and subsequent refinement.The refined structures of all four extended NS6 proteases are very similar in structure to the mature MNV NS6—and in one case reveal additional details of a surface loop. Although the packing arrangement observed showed some similarities to those observed in the adventitious protease-product crystals reported previously, in no case were specific protease–substrate interactions

  6. Origin of low surface brightness galaxies: a dynamical study (United States)

    Garg, Prerak; Banerjee, Arunima


    Low Surface Brightness Galaxies (LSBs), inspite of being gas rich, have low star formation rates and are therefore low surface brightness in nature. We calculate QRW, the 2-component disc stability parameter as proposed by Romeo & Wiegert, as a function of galactocentric radius R for a sample of five LSBs, for which mass models, as obtained from HI 21cm radio-synthesis observations and R-band photometry, were available in the literature. We find that the median value of Q_{RW}^{min}, the minimum of QRW over R, lies between 2.6 and 3.1 for our sample LSBs, which is higher than the median value of 1.8 ± 0.3 for Q_{RW}^{min} for a sample of high surface brightness galaxies (HSBs) as obtained in earlier studies. This clearly shows that LSBs have more stable discs than HSBs, which could explain their low star formation rates and, possibly, their low surface brightness nature. Interestingly, the calculated values of QRW decrease only slightly (median Q_{RW}^{min} ˜ 2.3-3) if the discs were taken to respond to the gravitational potential of the dark matter halo only, but reduce by ˜ a factor of 2-3 (median Q_{RW}^{min} ˜ 0.7-1.5) if they respond to their self-gravity alone. This implies that the dark matter halo is crucial in regulating disc stability in LSBs, which may have important implications for models of galaxy formation and evolution.

  7. Snap-shot survey of compact, radio-bright SNRs (United States)

    Garmire, Gordon


    We propose to observe a set of radio-bright remnants (SNRs) previously unobserved in X-rays. The SNRs have flat, non-thermal spectra suggesting efficient particle acceleration at the shock front. We also expect to find new pulsars or neutron stars within these remnants. These makes the selected SNRs good candidates for future TeV and GeV detections. The selected SNRs are also compact enough to be imaged within the ACIS-I field of view.

  8. Facilitating the Transition from Bright to Dim Environments (United States)


    librarian or other person designated to request documents from DTIC. Change of Address Organizations receiving reports from the U.S. Army...USAARL Report No. 2016-17 Facilitating the Transition from Bright to Dim Environments By David Walsh1, Morris R. Lattimore1, David L. Still1... ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR’S

  9. Human Adolescent Phase Response Curves to Bright White Light. (United States)

    Crowley, Stephanie J; Eastman, Charmane I


    Older adolescents are particularly vulnerable to circadian misalignment and sleep restriction, primarily due to early school start times. Light can shift the circadian system and could help attenuate circadian misalignment; however, a phase response curve (PRC) to determine the optimal time for receiving light and avoiding light is not available for adolescents. We constructed light PRCs for late pubertal to postpubertal adolescents aged 14 to 17 years. Participants completed 2 counterbalanced 5-day laboratory sessions after 8 or 9 days of scheduled sleep at home. Each session included phase assessments to measure the dim light melatonin onset (DLMO) before and after 3 days of free-running through an ultradian light-dark (wake-sleep) cycle (2 h dim [~20 lux] light, 2 h dark). In one session, intermittent bright white light (~5000 lux; four 20-min exposures) was alternated with 10 min of dim room light once per day for 3 consecutive days. The time of light varied among participants to cover the 24-h day. For each individual, the phase shift to bright light was corrected for the free-run derived from the other laboratory session with no bright light. One PRC showed phase shifts in response to light start time relative to the DLMO and another relative to home sleep. Phase delay shifts occurred around the hours corresponding to home bedtime. Phase advances occurred during the hours surrounding wake time and later in the afternoon. The transition from delays to advances occurred at the midpoint of home sleep. The adolescent PRCs presented here provide a valuable tool to time bright light in adolescents.

  10. Near-Real-Time DMSP SSM/I-SSMIS Daily Polar Gridded Brightness Temperatures (United States)

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

  11. Cell structure imaging with bright and homogeneous nanometric light source. (United States)

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


    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. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Death of Darkness: Artificial Sky Brightness in the Anthropocene (United States)

    Zender, C. S.


    Many species (including ours) need darkness to survive and thrive yet light pollution in the anthropocene has received scant attention in Earth System Models (ESMs). Anthropogenic aerosols can brighten background sky brightness and reduce the contrast between skylight and starlight. These are both aesthetic and health-related issues due to their accompanying disruption of circadian rhythms. We quantify aerosol contributions to light pollution using a single-column night sky model, NiteLite, suitable for implementation in ESMs. NiteLite accounts for physiologcal (photopic and scotopic vision, retinal diameter/age), anthropogenic (light and aerosol pollution properties), and natural (surface albedo, trace gases) effects on background brightness and threshold visibility. We find that stratospheric aerosol injection contemplated as a stop-gap measure to counter global warming would increase night-sky brightness by about 25%, and thus eliminate last pristine dark sky areas on Earth. Our results suggest that ESMs incorporate light pollution so that associated societal impacts can be better quantified and included in policy deliberations.

  13. Bright Soil Churned by Spirit's Sol 1861 Drive (United States)


    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.

  14. Achromatic form perception is based on luminance, not brightness. (United States)

    Shioiri, S; Cavanagh, P


    Two figures were examined, one a subjective disk and the other a cup whose shape was revealed by shadows. The figures were presented in a single color on a background of a different color, and the observers adjusted the radiance of one color until, in the first case, the vividness of the subjective contour reached a minimum (minimum subjective contour) or, in the second case, the impression of depth that is due to shadows disappeared (shadow disappearance). The results for these two tasks followed the data for minimum flicker matches (made with the same stimuli) much more closely than those for direct brightness matching. We therefore claim that achromatic form perception in general and subjective contour and shadow perception in particular are based on the intensity dimension measured by flicker photometry, not on that measured by brightness matching. Finally, in agreement with these findings, bleaching of short-wavelength sensitive cones did not affect settings for subjective contours, shadows, or flicker photometry but did affect brightness matching.

  15. SMOS brightness temperature assimilation into the Community Land Model

    Directory of Open Access Journals (Sweden)

    D. Rains


    Full Text Available SMOS (Soil Moisture and Ocean Salinity mission brightness temperatures at a single incident angle are assimilated into the Community Land Model (CLM across Australia to improve soil moisture simulations. Therefore, the data assimilation system DasPy is coupled to the local ensemble transform Kalman filter (LETKF as well as to the Community Microwave Emission Model (CMEM. Brightness temperature climatologies are precomputed to enable the assimilation of brightness temperature anomalies, making use of 6 years of SMOS data (2010–2015. Mean correlation R with in situ measurements increases moderately from 0.61 to 0.68 (11 % for upper soil layers if the root zone is included in the updates. A reduced improvement of 5 % is achieved if the assimilation is restricted to the upper soil layers. Root-zone simulations improve by 7 % when updating both the top layers and root zone, and by 4 % when only updating the top layers. Mean increments and increment standard deviations are compared for the experiments. The long-term assimilation impact is analysed by looking at a set of quantiles computed for soil moisture at each grid cell. Within hydrological monitoring systems, extreme dry or wet conditions are often defined via their relative occurrence, adding great importance to assimilation-induced quantile changes. Although still being limited now, longer L-band radiometer time series will become available and make model output improved by assimilating such data that are more usable for extreme event statistics.

  16. NS2 Proteins of GB Virus B and Hepatitis C Virus Share Common Protease Activities and Membrane Topologies (United States)

    Boukadida, Célia; Marnata, Caroline; Montserret, Roland; Cohen, Lisette; Blumen, Brigitte; Gouttenoire, Jérôme; Moradpour, Darius; Penin, François


    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

  17. Intracellular degradation and localization of NS1 of tick-borne encephalitis virus affect its protective properties. (United States)

    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


    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.

  18. Comparison of two dengue NS1 rapid tests for sensitivity, specificity and relationship to viraemia and antibody responses

    Directory of Open Access Journals (Sweden)

    Farrar Jeremy


    Full Text Available Abstract Background Dengue is a major public health problem in tropical and subtropical countries. Rapid and easy diagnosis of dengue can assist patient triage and care-management. The detection of DENV NS1 on rapid lateral flow tests offers a fast route to a presumptive dengue diagnosis but careful evaluations are urgently needed as more and more people use them. Methods The sensitivity and specificity of the Bio-Rad NS1 Ag Strip and SD Dengue Duo (NS1/IgM/IgG lateral flow rapid tests were evaluated in a panel of plasma samples from 245 Vietnamese patients with RT-PCR confirmed dengue and 47 with other febrile illnesses. Results The NS1 rapid tests had similar diagnostic sensitivities (respectively 61.6% and 62.4% in confirmed dengue cases but were 100% specific. When IgM/IgG results from the SD Dengue Duo were included in the test interpretation, the sensitivity improved significantly from 62.4% with NS1 alone to 75.5% when NS1 and/or IgM was positive and 83.7% when NS1 and/or IgM and/or IgG was positive. Both NS1 assays were significantly more sensitive for primary than secondary dengue. NS1 positivity was associated with the underlying viraemia as NS1-positive samples had a significantly higher viraemia than NS1-negative samples. Conclusions These data suggest that the NS1 test component of these assays are highly specific and have similar levels of sensitivity. The IgM parameter in the SD Duo test improved overall test sensitivity without compromising specificity. The SD Dengue Duo lateral flow rapid test deserves further prospective evaluation in dengue endemic settings.

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

    Directory of Open Access Journals (Sweden)

    Seiichi Mawatari

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

  20. Broadband Fan Noise Prediction System for Turbofan Engines. Volume 2; BFaNS User's Manual and Developer's Guide (United States)

    Morin, Bruce L.


    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.

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

    Morin, Bruce L.


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

  2. Development of a kilojoule channel for Nd-glass laser systems with a 70-ns pulse SBS compressor (United States)

    Sirazetdinov, Vladmir S.; Alekseev, V. N.; Charukhchev, A. V.; Kotilev, V. N.; Liber, V. I.; Serebryakov, Victor A.


    An optical scheme for a kJ channel of a neodymium glass laser system with SBS-compressor for a 70 ns pulse has been described. The use of a pump pulse of long duration - 70 ns - makes it possible to operate a near-steady SBS mode in compressed gasses. An experimental study of the SBS oscillator-compressor stage with pump focusing and a two- pass pattern has been carried out and a 70 ns, 8 J pump pulse has been compressed down to 1 ns.

  3. Functional dissection of hematopoietic stem cell populations with a stemness-monitoring system based on NS-GFP transgene expression. (United States)

    Ali, Mohamed A E; Fuse, Kyoko; Tadokoro, Yuko; Hoshii, Takayuki; Ueno, Masaya; Kobayashi, Masahiko; Nomura, Naho; Vu, Ha Thi; Peng, Hui; Hegazy, Ahmed M; Masuko, Masayoshi; Sone, Hirohito; Arai, Fumio; Tajima, Atsushi; Hirao, Atsushi


    Hematopoietic stem cells (HSCs) in a steady state can be efficiently purified by selecting for a combination of several cell surface markers; however, such markers do not consistently reflect HSC activity. In this study, we successfully enriched HSCs with a unique stemness-monitoring system using a transgenic mouse in which green florescence protein (GFP) is driven by the promoter/enhancer region of the nucleostemin (NS) gene. We found that the phenotypically defined long-term (LT)-HSC population exhibited the highest level of NS-GFP intensity, whereas NS-GFP intensity was strongly downregulated during differentiation in vitro and in vivo. Within the LT-HSC population, NS-GFPhigh cells exhibited significantly higher repopulating capacity than NS-GFPlow cells. Gene expression analysis revealed that nine genes, including Vwf and Cdkn1c (p57), are highly expressed in NS-GFPhigh cells and may represent a signature of HSCs, i.e., a stemness signature. When LT-HSCs suffered from remarkable stress, such as transplantation or irradiation, NS-GFP intensity was downregulated. Finally, we found that high levels of NS-GFP identified HSC-like cells even among CD34+ cells, which have been considered progenitor cells without long-term reconstitution ability. Thus, high NS-GFP expression represents stem cell characteristics in hematopoietic cells, making this system useful for identifying previously uncharacterized HSCs.

  4. Immunogenicity of Multi-Epitope DNA and Peptide Vaccine Candidates Based on Core, E2, NS3 and NS5B HCV Epitopes in BALB/c Mice. (United States)

    Pishraft Sabet, Leila; Taheri, Tahereh; Memarnejadian, Arash; Mokhtari Azad, Talat; Asgari, Fatemeh; Rahimnia, Ramin; Alavian, Seyed Moayed; Rafati, Sima; Samimi Rad, Katayoun


    Hypervariability of HCV proteins is an important obstacle to design an efficient vaccine for HCV infection. Multi-epitope vaccines containing conserved epitopes of the virus could be a promising approach for protection against HCV. Cellular and humoral immune responses against multi-epitope DNA and peptide vaccines were evaluated in BALB/c mice. In this experimental study, multi-epitope DNA- and peptide-based vaccines for HCV infection harboring immunodominant CD8+ T cell epitopes (HLA-A2 and H2-Dd) from Core (132-142), NS3 (1073-1081) and NS5B (2727-2735), a Th CD4+ epitope from NS3 (1248-1262) and a B-cell epitope from E2 (412-426) were designed. Multi-epitope DNA and peptide vaccines were tested in two regimens as heterologous DNA/peptide (group 1) and homologous peptide/peptide (group 2) prime/boost vaccine in BALB/c mice model. Electroporation was used for delivery of the DNA vaccine. Peptide vaccine was formulated with Montanide ISA 720 (M720) as adjuvant. Cytokine assay and antibody detection were performed to analyze the immune responses. Mice immunized with multi-epitope peptide formulated with M720 developed higher HCV-specific levels of total IgG, IgG1 and IgG2a than those immunized with multi-epitope DNA vaccine. IFN-γ levels in group 2 were significantly higher than group 1 (i.e. 3 weeks after the last immunization; 37.61 ± 2.39 vs. 14.43 ± 0.43, P epitope DNA and peptide-vaccines confirmed their specific immunogenicity in BALB/c mice. However, lower Th1 immune responses in mice immunized with DNA vaccine suggests further investigations to improve the immunogenicity of the multi-epitope DNA vaccine through immune enhancers.

  5. X-ray spots emitted in a hollow cathode ns-discharge (United States)

    Skowronek, M.; Ikhlef, A.; Louvet, G.; Roméas, P.; Mittal, K. C.


    A hollow cathode discharge using a tungsten pointed anode is fed by a low power Marx generator (1 J, 70 kV, 50 ns). The x-ray emission duration varies from 20 to 10 ns in the pressure range 0963-0252/5/1/009/img8 mbar, in air. The spatial distribution of the emitting sites has been determined, using a sensitive imaging device with a 5 ns exposure time, in the same range of pressures. This emission is strongly influenced by the occurrence of the `pseudo-spark' regime. X-rays are emitted by different mechanisms: (a) electron bremsstrahlung and by Auger cascade associated with particle emission from the Teflon insulator and also tungsten (0963-0252/5/1/009/img9 and 0963-0252/5/1/009/img10) characteristic lines; (b) pinching and collapse of the hot plasma surrounding the anode and the insulator. X-ray spots are observed. Their number is about 200 per shot, their radius is less than 40 0963-0252/5/1/009/img11m and their emission intensity is compatible with that of a dense plasma: 0963-0252/5/1/009/img12 with a temperature in the range 100 eV to 1 keV. Some of them are seen to follow linear trajectories, suggesting a 1 ns period wave propagation at 300 km 0963-0252/5/1/009/img13 which triggers the collapse.

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

    DEFF Research Database (Denmark)

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


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

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

  8. Phage Encoded H-NS: A Potential Achilles Heel in the Bacterial Defence System (United States)

    Skennerton, Connor T.; Angly, Florent E.; Breitbart, Mya; Bragg, Lauren; He, Shaomei; McMahon, Katherine D.; Hugenholtz, Philip; Tyson, Gene W.


    The relationship between phage and their microbial hosts is difficult to elucidate in complex natural ecosystems. Engineered systems performing enhanced biological phosphorus removal (EBPR), offer stable, lower complexity communities for studying phage-host interactions. Here, metagenomic data from an EBPR reactor dominated by Candidatus Accumulibacter phosphatis (CAP), led to the recovery of three complete and six partial phage genomes. Heat-stable nucleoid structuring (H-NS) protein, a global transcriptional repressor in bacteria, was identified in one of the complete phage genomes (EPV1), and was most similar to a homolog in CAP. We infer that EPV1 is a CAP-specific phage and has the potential to repress up to 6% of host genes based on the presence of putative H-NS binding sites in the CAP genome. These genes include CRISPR associated proteins and a Type III restriction-modification system, which are key host defense mechanisms against phage infection. Further, EPV1 was the only member of the phage community found in an EBPR microbial metagenome collected seven months prior. We propose that EPV1 laterally acquired H-NS from CAP providing it with a means to reduce bacterial defenses, a selective advantage over other phage in the EBPR system. Phage encoded H-NS could constitute a previously unrecognized weapon in the phage-host arms race. PMID:21625595

  9. Phage encoded H-NS: a potential achilles heel in the bacterial defence system.

    Directory of Open Access Journals (Sweden)

    Connor T Skennerton

    Full Text Available The relationship between phage and their microbial hosts is difficult to elucidate in complex natural ecosystems. Engineered systems performing enhanced biological phosphorus removal (EBPR, offer stable, lower complexity communities for studying phage-host interactions. Here, metagenomic data from an EBPR reactor dominated by Candidatus Accumulibacter phosphatis (CAP, led to the recovery of three complete and six partial phage genomes. Heat-stable nucleoid structuring (H-NS protein, a global transcriptional repressor in bacteria, was identified in one of the complete phage genomes (EPV1, and was most similar to a homolog in CAP. We infer that EPV1 is a CAP-specific phage and has the potential to repress up to 6% of host genes based on the presence of putative H-NS binding sites in the CAP genome. These genes include CRISPR associated proteins and a Type III restriction-modification system, which are key host defense mechanisms against phage infection. Further, EPV1 was the only member of the phage community found in an EBPR microbial metagenome collected seven months prior. We propose that EPV1 laterally acquired H-NS from CAP providing it with a means to reduce bacterial defenses, a selective advantage over other phage in the EBPR system. Phage encoded H-NS could constitute a previously unrecognized weapon in the phage-host arms race.

  10. Association of MTHFR polymorphisms with nsCL/P in Chinese Uyghur population

    Directory of Open Access Journals (Sweden)

    Xianrong Xu


    Conclusion: This study indicated that rs1801131 polymorphism in MTHFR was associated with nsCL/P in Chinese Uyghur population. Given the unique genetic and environmental characters of the Uyghur population, these findings may be helpful for exploring the pathogenesis of this complex disease.

  11. Sodium current inhibition by nanosecond pulsed electric field (nsPEF)--fact or artifact?

    NARCIS (Netherlands)

    Verkerk, Arie O.; van Ginneken, Antoni C. G.; Wilders, Ronald


    In two recent publications in Bioelectromagnetics it has been demonstrated that the voltage-gated sodium current (I(Na)) is inhibited in response to a nanosecond pulsed electric field (nsPEF). At the same time, there was an increase in a non-inactivating "leak" current (I(leak)), which was

  12. Sub-nanosecond resolution electric field measurements during ns pulse breakdown in ambient air (United States)

    Simeni Simeni, Marien; Goldberg, Ben; Gulko, Ilya; Frederickson, Kraig; Adamovich, Igor V.


    Electric field during ns pulse discharge breakdown in ambient air has been measured by ps four-wave mixing, with temporal resolution of 0.2 ns. The measurements have been performed in a diffuse plasma generated in a dielectric barrier discharge, in plane-to-plane geometry. Absolute calibration of the electric field in the plasma is provided by the Laplacian field measured before breakdown. Sub-nanosecond time resolution is obtained by using a 150 ps duration laser pulse, as well as by monitoring the timing of individual laser shots relative to the voltage pulse, and post-processing four-wave mixing signal waveforms saved for each laser shot, placing them in the appropriate ‘time bins’. The experimental data are compared with the analytic solution for time-resolved electric field in the plasma during pulse breakdown, showing good agreement on ns time scale. Qualitative interpretation of the data illustrates the effects of charge separation, charge accumulation/neutralization on the dielectric surfaces, electron attachment, and secondary breakdown. Comparison of the present data with more advanced kinetic modeling is expected to provide additional quantitative insight into air plasma kinetics on ~ 0.1–100 ns scales.

  13. Quantification of NS1 dengue biomarker in serum via optomagnetic nanocluster detection

    DEFF Research Database (Denmark)

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


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

  14. Large aperture fast neutron imaging detector with 10-ns time resolution (United States)

    Arikawa, Y.; Matsubara, S.; Abe, Y.; Kato, Y.; Kishimoto, H.; Yogo, A.; Nishimura, H.; Nakai, M.; Shiraga, H.; Fujioka, S.; Azechi, H.; Otake, Y.; Mima, K.; Honda, Y.


    Fast neutrons, which are neutrons with energies greater than 1 MeV, are expected to be a source of nondestructive inspection for a large-size infrastructure such as a bridge girder because of their mean free path exceeding the meter. A neutron-imaging device with 10-ns time resolution can discriminate pulsed neutrons from X-rays via time of flight. For this purpose, we require a fast-response neutron imager with large aperture and high image resolution. A neutron-imaging device with time resolution of 10 ns and aperture size of 40 cm × 60 cm was developed. It was filled with fast response liquid scintillator [1] in an aluminum honeycomb plate, which converts neutrons to optical light images. The scintillation light images were relayed using an optical lens and detected using a fast response image intensified CCD. The detector was tested at an electron linear accelerator (LINAC) facility in Osaka University. A short X-ray pulse (30 ps pulse duration) was generated using LINAC, and X-ray radiograph images were obtained with a 10- ns exposure time duration. The radiograph images were well attenuated within 10-ns from the X-ray injection. A high energy X-ray image and a neutron radiograph image of a 30-cm thick concrete block with iron blocks located behind it were successfully observed. This promising technique could facilitate nondestructive inspection of large concrete constructions.

  15. Association of MTHFR polymorphisms with nsCL/P in Chinese ...

    African Journals Online (AJOL)

    Xianrong Xu


    Apr 26, 2016 ... Abstract Background: nsCL/P (nonsyndromic cleft lip with or without cleft palate) is a complex disorder with a multifactorial .... ations apply to other ethnic populations and regions in China. More study is needed to confirm ... People's Hospital of Xinxiang Uyghur autonomous region, the Yili People's Hospital, ...

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

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

  17. A model of H-NS mediated compaction of bacterial DNA

    CERN Document Server

    Joyeux, Marc; 10.1016/j.bpj.2013.02.043


    The Histone-like Nucleoid Structuring protein (H-NS) is a nucleoid-associated protein, which is involved in both gene regulation and DNA compaction. H-NS can bind to DNA in two different ways: in trans, by binding to two separate DNA duplexes, or in cis, by binding to different sites on the same duplex. Based on scanning force microscopy imaging and optical trap-driven unzipping assays, it has recently been suggested that DNA compaction may result from the antagonistic effects of H-NS binding to DNA in trans and cis configurations. In order to get more insight into the compaction mechanism, we constructed a coarse-grained model description of the compaction of bacterial DNA by H-NS. These simulations highlight the fact that DNA compaction indeed results from the subtle equilibrium between several competing factors, which include the deformation dynamics of the plasmid and the several binding modes of protein dimers to DNA, i.e. dangling configurations, cis- and trans-binding. In particular, the degree of comp...

  18. Matched and mixed cap derivatives in the tetracyclic indole class of HCV NS5A inhibitors. (United States)

    Dwyer, Michael P; Keertikar, Kerry M; Chen, Lei; Tong, Ling; Selyutin, Oleg; Nair, Anilkumar G; Yu, Wensheng; Zhou, Guowei; Lavey, Brian J; Yang, De-Yi; Wong, Michael; Kim, Seong Heon; Coburn, Craig A; Rosenblum, Stuart B; Zeng, Qingbei; Jiang, Yueheng; Shankar, Bandarpalle B; Rizvi, Razia; Nomeir, Amin A; Liu, Rong; Agrawal, Sony; Xia, Ellen; Kong, Rong; Zhai, Ying; Ingravallo, Paul; Asante-Appiah, Ernest; Kozlowski, Joseph A


    A matched and mixed capping SAR study was conducted on the tetracyclic indole class of HCV NS5A inhibitors to examine the influence of modifications of this region on the overall HCV virologic resistance profiles. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. Alternative core development around the tetracyclic indole class of HCV NS5A inhibitors. (United States)

    Tong, Ling; Yu, Wensheng; Coburn, Craig A; Meinke, Peter T; Nair, Anilkumar G; Dwyer, Michael P; Chen, Lei; Selyutin, Oleg; Rosenblum, Stuart B; Jiang, Yueheng; Fells, James; Hu, Bin; Zhong, Bin; Soll, Richard M; Liu, Rong; Agrawal, Sony; Xia, Ellen; Zhai, Ying; Kong, Rong; Ingravallo, Paul; Nomeir, Amin; Asante-Appiah, Ernest; Kozlowski, Joseph A


    Herein, we describe our research efforts to develop unique cores in molecules which function as HCV nonstructural protein 5A (NS5A) inhibitors. In particular, various fused tetracyclic cores were identified which showed genotype and mutant activities comparable to the indole-based tetracyclic core. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Predicting the effect of ions on the conformation of the H-NS dimerization domain

    NARCIS (Netherlands)

    Vreede, J.; Dame, R.T.


    The histone-like nucleoid structuring protein (H-NS) is a DNA-organizing protein in bacteria. It contains a DNA-binding domain and a dimerization domain, connected by a flexible linker region. Dimerization occurs through the formation of a helical bundle, including a coiled-coil interaction motif.

  1. The NS3 protein of rice hoja blanca virus suppresses RNA silencing in mammalian cells

    NARCIS (Netherlands)

    Schnettler, E.; Hemmes, J.C.; Goldbach, R.W.; Prins, M.W.


    The NS3 protein of the tenuivirus rice hoja blanca virus (RHBV) has previously been shown to represent the viral RNA interference (RNAi) suppressor and is active in both plant and insect cells by binding short interfering RNAs (siRNAs) in vitro. Using a firefly luciferase-based silencing assay it is

  2. Interplay between the bacterial nucleoid protein H-NS and macromolecular crowding in compacting DNA

    NARCIS (Netherlands)

    Wintraecken, C.H.J.M.


      In this dissertation we discuss H-NS and its connection to nucleoid compaction and organization. Nucleoid formation involves a dramatic reduction in coil volume of the genomic DNA. Four factors are thought to influence coil volume: supercoiling, DNA charge neutralization, macromolecular

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

    CERN Document Server

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


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

  4. Numerical Simulations of NS-DBD Plasma Actuators For Flow Control

    NARCIS (Netherlands)

    Popov, I.


    Nanosecond dielectric barrier discharge (NS-DBD) plasma actuators is relatively
    new means of flow control. It has several advantages compared to more conventional
    means of flow control, such as small size, low weight, fast response time
    and controllability. It has been demonstrated to be

  5. Canine hepacivirus NS3 serine protease can cleave the human adaptor proteins MAVS and TRIF.

    Directory of Open Access Journals (Sweden)

    Mariona Parera

    Full Text Available Canine hepacivirus (CHV was recently identified in domestic dogs and horses. The finding that CHV is genetically the virus most closely related to hepatitis C virus (HCV has raised the question of whether HCV might have evolved as the result of close contact between dogs and/or horses and humans. The aim of this study was to investigate whether the NS3/4A serine protease of CHV specifically cleaves human mitochondrial antiviral signaling protein (MAVS and Toll-IL-1 receptor domain-containing adaptor inducing interferon-beta (TRIF. The proteolytic activity of CHV NS3/4A was evaluated using a bacteriophage lambda genetic screen. Human MAVS- and TRIF-specific cleavage sites were engineered into the lambda cI repressor. Upon infection of Escherichia coli cells coexpressing these repressors and a CHV NS3/4A construct, lambda phage replicated up to 2000-fold more efficiently than in cells expressing a CHV protease variant carrying the inactivating substitution S139A. Comparable results were obtained when several HCV NS3/4A constructs of genotype 1b were assayed. This indicates that CHV can disrupt the human innate antiviral defense signaling pathway and suggests a possible evolutionary relationship between CHV and HCV.

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

    Directory of Open Access Journals (Sweden)

    Mello Isabel MVGC


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

  7. Genetically engineered, biarsenically labeled influenza virus allows visualization of viral NS1 protein in living cells. (United States)

    Li, Yang; Lu, Xinya; Li, Junwei; Bérubé, Nathalie; Giest, Kerri-Lane; Liu, Qiang; Anderson, Deborah H; Zhou, Yan


    Real-time fluorescence imaging of viral proteins in living cells provides a valuable means to study virus-host interactions. The challenge of generating replication-competent fluorescent influenza A virus is that the segmented genome does not allow fusion of a fluorescent protein gene to any viral gene. Here, we introduced the tetracysteine (TC) biarsenical labeling system into influenza virus in order to fluorescently label viral protein in the virus life cycle. We generated infectious influenza A viruses bearing a small TC tag (CCPGCC) in the loop/linker regions of the NS1 proteins. In the background of A/Puerto Rico/8/34 (H1N1) (PR8) virus, the TC tag can be inserted into NS1 after amino acid 52 (AA52) (PR8-410), AA79 (PR8-412), or AA102 (PR8-413) or the TC tag can be inserted and replace amino acids 79 to 84 (AA79-84) (PR8-411). Although PR8-410, PR8-411, and PR8-412 viruses are attenuated than the wild-type (WT) virus to some extent in multiple-cycle infection, their growth potential is similar to that of the WT virus during a single cycle of infection, and their NS1 subcellular localization and viral protein synthesis rate are quite similar to those of the WT virus. Furthermore, labeling with membrane-permeable biarsenical dye resulted in fluorescent NS1 protein in the context of virus infection. We could exploit this strategy on NS1 protein of A/Texas/36/91 (H1N1) (Tx91) by successfully rescuing a TC-tagged virus, Tx91-445, which carries the TC tag replacement of AA79-84. The infectivity of Tx91-445 virus was similar to that of WT Tx91 during multiple cycles of replication and a single cycle of replication. The NS1 protein derived from Tx91-445 can be fluorescently labeled in living cells. Finally, with biarsenical labeling, the engineered replication-competent virus allowed us to visualize NS1 protein nuclear import in virus-infected cells in real time.

  8. The Physics and Applications of High Brightness Beams: Working Group A Summary on High Brightness Beam Production

    Energy Technology Data Exchange (ETDEWEB)

    Schmerge, John


    Working group A was devoted to high brightness beam production and characterization. The presentations and discussions could be categorized as cathode physics, new photoinjector designs, computational modeling of high brightness beams, and new experimental methods and results. Several novel injector and cathode designs were presented. However, a standard 1.5 cell rf photoinjector is still the most common source for high brightness beams. New experimental results and techniques were presented and thoroughly discussed. The brightest beam produced in a rf photoinjector published at the time of the workshop is approximately 2 10{sup 14} A/(m-rad){sup 2} at Sumitomo Heavy Industries in Japan with 1 nC of charge, a 9 ps FWHM long laser pulse and a normalized transverse emittance of 1.2 pm. The emittance was achieved by utilizing a temporally flat laser pulse which decreased the emittance by an estimated factor of 2 from the beam produced with a Gaussian pulse shape with an identical pulse length.

  9. Binding by the hepatitis C virus NS3 helicase partially melts duplex DNA. (United States)

    Raney, Veronica M; Reynolds, Kimberly A; Harrison, Melody K; Harrison, David K; Cameron, Craig E; Raney, Kevin D


    Binding of NS3 helicase to DNA was investigated by footprinting with KMnO(4), which reacts preferentially with thymidine residues in single-stranded DNA (ssDNA) compared to those in double-stranded DNA (dsDNA). A distinct pattern of reactivity was observed on ssDNA, which repeated every 8 nucleotides (nt) and is consistent with the known binding site size of NS3. Binding to a DNA substrate containing a partial duplex was also investigated. The DNA contained a 15 nt overhang made entirely of thymidine residues adjacent to a 22 bp duplex that contained thymidine at every other position. Surprisingly, the KMnO(4) reactivity pattern extended from the ssDNA into the dsDNA region of the substrate. Lengthening the partial duplex to 30 bp revealed a similar pattern extending from the ssDNA into the dsDNA, indicating that NS3 binds within the duplex region. Increasing the length of the ssDNA portion of the partial duplex by 4 nt resulted in a shift in the footprinting pattern for the ssDNA by 4 nt, which is consistent with binding to the 3'-end of the ssDNA. However, the footprinting pattern in the dsDNA region was shifted by only 1-2 bp, indicating that binding to the ssDNA-dsDNA region was preferred. Footprinting performed as a function of time indicated that NS3 binds to the ssDNA rapidly, followed by slower binding to the duplex. Hence, multiple molecules of NS3 can bind along a ssDNA-dsDNA partial duplex by interacting with the ssDNA as well as the duplex DNA.

  10. Limitations of the Oriented Difference of Gaussian Filter in Special Cases of Brightness Perception Illusions. (United States)

    Bakshi, Ashish; Roy, Sourya; Mallick, Arijit; Ghosh, Kuntal


    The Oriented Difference of Gaussian (ODOG) filter of Blakeslee and McCourt has been successfully employed to explain several brightness perception illusions which include illusions of both brightness-contrast type, for example, Simultaneous Brightness Contrast and Grating Induction and the brightness-assimilation type, for example, the White effect and the shifted White effect. Here, we demonstrate some limitations of the ODOG filter in predicting perceived brightness by comparing the ODOG responses to various stimuli (generated by varying two parameters, namely, test patch length and spatial frequency) with experimental observations of the same. © The Author(s) 2015.

  11. A high-speed two-frame, 1-2 ns gated X-ray CMOS imager used as a hohlraum diagnostic on the National Ignition Facility (invited) (United States)

    Chen, Hui; Palmer, N.; Dayton, M.; Carpenter, A.; Schneider, M. B.; Bell, P. M.; Bradley, D. K.; Claus, L. D.; Fang, L.; Hilsabeck, T.; Hohenberger, M.; Jones, O. S.; Kilkenny, J. D.; Kimmel, M. W.; Robertson, G.; Rochau, G.; Sanchez, M. O.; Stahoviak, J. W.; Trotter, D. C.; Porter, J. L.


    A novel x-ray imager, which takes time-resolved gated images along a single line-of-sight, has been successfully implemented at the National Ignition Facility (NIF). This Gated Laser Entrance Hole diagnostic, G-LEH, incorporates a high-speed multi-frame CMOS x-ray imager developed by Sandia National Laboratories to upgrade the existing Static X-ray Imager diagnostic at NIF. The new diagnostic is capable of capturing two laser-entrance-hole images per shot on its 1024 × 448 pixels photo-detector array, with integration times as short as 1.6 ns per frame. Since its implementation on NIF, the G-LEH diagnostic has successfully acquired images from various experimental campaigns, providing critical new information for understanding the hohlraum performance in inertial confinement fusion (ICF) experiments, such as the size of the laser entrance hole vs. time, the growth of the laser-heated gold plasma bubble, the change in brightness of inner beam spots due to time-varying cross beam energy transfer, and plasma instability growth near the hohlraum wall.

  12. Swift J0243.6+6124: Swift discovery of an accreting NS transient (United States)

    Kennea, J. A.; Lien, A. Y.; Krimm, H. A.; Cenko, S. B.; Siegel, M. H.


    At 02:37UT on October 3, 2017, Swift/BAT triggered on a source which was identified as a possible GRB or Galactic transient (Cenko et al., GCN #21960). Continued Swift observations showed that the source was at a constant X-ray brightness over 6 orbits, ruling out the GRB nature (Kennea et al., GCN #21963).

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

    DEFF Research Database (Denmark)

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


    To facilitate studies of hepatitis C virus (HCV) NS4A, we aimed at developing J6/JFH1-based recombinants with genotype 1- to 7-specific NS4A proteins. We developed efficient culture systems expressing NS4A proteins of genotypes (isolates) 1a (H77 and TN), 1b (J4), 2a (J6), 4a (ED43), 5a (SA13), 6a......), boceprevir (Sch503034), simeprevir (TMC435350), danoprevir (ITMN-191), and vaniprevir (MK-7009), to alpha interferon 2b, and to the putative NS4A inhibitor ACH-806. The efficacy of ACH-806 was lower than that of protease inhibitors and was not influenced by changes at amino acids 1042 and 1065 (in the NS3...

  14. Ultra-high resolution and high-brightness AMOLED (United States)

    Wacyk, Ihor; Ghosh, Amal; Prache, Olivier; Draper, Russ; Fellowes, Dave


    As part of its continuing effort to improve both the resolution and optical performance of AMOLED microdisplays, eMagin has recently developed an SXGA (1280×3×1024) microdisplay under a US Army RDECOM CERDEC NVESD contract that combines the world's smallest OLED pixel pitch with an ultra-high brightness green OLED emitter. This development is aimed at next-generation HMD systems with "see-through" and daylight imaging requirements. The OLED pixel array is built on a 0.18-micron CMOS backplane and contains over 4 million individually addressable pixels with a pixel pitch of 2.7 × 8.1 microns, resulting in an active area of 0.52 inches diagonal. Using both spatial and temporal enhancement, the display can provide over 10-bits of gray-level control for high dynamic range applications. The new pixel design also enables the future implementation of a full-color QSXGA (2560 × RGB × 2048) microdisplay in an active area of only 1.05 inch diagonal. A low-power serialized low-voltage-differential-signaling (LVDS) interface is integrated into the display for use as a remote video link for tethered systems. The new SXGA backplane has been combined with the high-brightness green OLED device developed by eMagin under an NVESD contract. This OLED device has produced an output brightness of more than 8000fL with all pixels on; lifetime measurements are currently underway and will presented at the meeting. This paper will describe the operational features and first optical and electrical test results of the new SXGA demonstrator microdisplay.

  15. Flux and brightness calculations for various synchrotron radiation sources

    Energy Technology Data Exchange (ETDEWEB)

    Weber, J.M.; Hulbert, S.L.


    Synchrotron radiation (SR) storage rings are powerful scientific and technological tools. The first generation of storage rings in the US., e.g., SURF (Washington, D.C.), Tantalus (Wisconsin), SSRL (Stanford), and CHESS (Cornell), revolutionized VUV, soft X-ray, and hard X-ray science. The second (present) generation of storage rings, e.g. the NSLS VUV and XRAY rings and Aladdin (Wisconsin), have sustained the revolution by providing higher stored currents and up to a factor of ten smaller electron beam sizes than the first generation sources. This has made possible a large number of experiments that could not performed using first generation sources. In addition, the NSLS XRAY ring design optimizes the performance of wigglers (high field periodic magnetic insertion devices). The third generation storage rings, e.g. ALS (Berkeley) and APS (Argonne), are being designed to optimize the performance of undulators (low field periodic magnetic insertion devices). These extremely high brightness sources will further revolutionize x-ray science by providing diffraction-limited x-ray beams. The output of undulators and wigglers is distinct from that of bending magnets in magnitude, spectral shape, and in spatial and angular size. Using published equations, we have developed computer programs to calculate the flux, central intensity, and brightness output bending magnets and selected wigglers and undulators of the NSLS VUV and XRAY rings, the Advanced Light Source (ALS), and the Advanced Photon Source (APS). Following is a summary of the equations used, the graphs and data produced, and the computer codes written. These codes, written in the C programming language, can be used to calculate the flux, central intensity, and brightness curves for bending magnets and insertion devices on any storage ring.

  16. Confidence intervals for concentration and brightness from fluorescence fluctuation measurements. (United States)

    Pryse, Kenneth M; Rong, Xi; Whisler, Jordan A; McConnaughey, William B; Jiang, Yan-Fei; Melnykov, Artem V; Elson, Elliot L; Genin, Guy M


    The theory of photon count histogram (PCH) analysis describes the distribution of fluorescence fluctuation amplitudes due to populations of fluorophores diffusing through a focused laser beam and provides a rigorous framework through which the brightnesses and concentrations of the fluorophores can be determined. In practice, however, the brightnesses and concentrations of only a few components can be identified. Brightnesses and concentrations are determined by a nonlinear least-squares fit of a theoretical model to the experimental PCH derived from a record of fluorescence intensity fluctuations. The χ(2) hypersurface in the neighborhood of the optimum parameter set can have varying degrees of curvature, due to the intrinsic curvature of the model, the specific parameter values of the system under study, and the relative noise in the data. Because of this varying curvature, parameters estimated from the least-squares analysis have varying degrees of uncertainty associated with them. There are several methods for assigning confidence intervals to the parameters, but these methods have different efficacies for PCH data. Here, we evaluate several approaches to confidence interval estimation for PCH data, including asymptotic standard error, likelihood joint-confidence region, likelihood confidence intervals, skew-corrected and accelerated bootstrap (BCa), and Monte Carlo residual resampling methods. We study these with a model two-dimensional membrane system for simplicity, but the principles are applicable as well to fluorophores diffusing in three-dimensional solution. Using simulated fluorescence fluctuation data, we find the BCa method to be particularly well-suited for estimating confidence intervals in PCH analysis, and several other methods to be less so. Using the BCa method and additional simulated fluctuation data, we find that confidence intervals can be reduced dramatically for a specific non-Gaussian beam profile. Copyright © 2012 Biophysical Society

  17. Beyond pragmatism: defending the 'bright line' of birth. (United States)

    Burin, Achas K


    It is usually accepted by ethicists that birth does not alter moral status. Rather, it is thought that the rule according full legal rights at birth is pragmatic. Pragmatic reasoning is vulnerable to competing practical concerns and stronger moral principles. This 'bright line' has therefore been criticised both by those who believe personhood begins before birth and those who believe it begins afterward. In particular, a recent article by Giubilini and Minerva puts forward both pragmatic and moral arguments in favour of permitting infanticide, and the New South Wales Court of Criminal Appeal has suggested there is a strong case for abandoning the bright line (R v Iby (2005) 63 NSWLR 278). If we desire to defend current legal doctrine against such criticism, a medical and philosophical basis for the law should be articulated. This article suggests such a medical and philosophical basis. It argues that both the multiplicity of biological changes occurring in the neonate at birth and the extrauterine context (the world) provide a justification for the distinction drawn at law between abortion and infanticide. With reference to Robert Nozick's 'experience machine' thought-experiment and elements of phenomenological philosophy, it advances two propositions to explain the status-changing nature of the neonate's emergence out of the womb. First, that expressing sentience in the world is essential for the attainment of personhood. Second, that having become a person, the harm in killing is disruption of this engagement with the world and the reduction from personhood to non-existence. This is the distinction between a neonate's death and the termination of a foetus, underscoring the qualitative difference between the two sides of the bright line drawn in law. © The Author [2014]. Published by Oxford University Press; all rights reserved. For Permissions, please email:

  18. The new World Atlas of Artificial Sky Brightness (United States)

    Falchi, Fabio; Cinzano, Pierantonio; Kyba, Christopher C. M.; Portnov, Boris A.


    I present the main steps toward the completion of the new World Atlas of Artificial Sky Brightness (WA II) and some results. The computational technique has been updated, in comparison to the first World Atlas, to take into account both sources and sites elevation. The elevation data are from USGS GTOPO30 global digital elevation model, with the same pixel size as the WA II maps. The upward emission function used to compute the Atlas is a three parameters function. The parameters can be constrained to the database of Earth based night sky brightness measurements. In this way we can use the better fitting upward function for the final map’s calibration. We maintained constant atmosphere parameters over the entire Earth, identical to those used for the first Atlas (Garstang atmospheric clarity coefficient k=1, equivalent to a vertical extinction at sea level of 0.33 magnitude in the V band). This was done in order to avoid introducing a local bias due to different conditions that may confound the light pollution propagation effects. The radiance data used are those from Visible Infrared Imaging Radiometer Suite (VIIRS) Day-Night Band (DNB) on board the Suomi NPP satellite. The use of this newly available radiance data allows for an increased real resolution, even while maintaining the same 30"x30" lat-lon pixel size. Anyway, a higher resolution is really appreciable only in the immediate proximity of sources of light pollution (e.g. inside a big city). The VIIRS DNB data used for the input data were chosen from the months ranging from May to September in order to avoid introducing bias from the variable snow coverage in mid to high northern latitudes. In the southern hemisphere this problem is far less pronounced. The WA II takes advantage of the now enormous database of Earth based sky brightness measurements obtained mainly with Sky Quality Meters, but also with CCD measurements.

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

    Directory of Open Access Journals (Sweden)

    Napassavong Rojanarowan


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

  20. Technological Challenges for High-Brightness Photo-Injectors

    CERN Multimedia

    Suberlucq, Guy


    Many applications, from linear colliders to free-electron lasers, passing through light sources and many other electron sources, require high brightness electron beams, usually produced by photo-injectors. Because certain parameters of these applications differ by several orders of magnitude, various solutions were implemented for the design and construction of the three main parts of the photo-injectors: lasers, photocathodes and guns. This paper summarizes the different requirements, how they lead to technological challenges and how R&D programs try to overcome these challenges. Some examples of state-of-the-art parts are presented.

  1. Aqueous origins of bright salt deposits on Ceres (United States)

    Zolotov, Mikhail Yu.


    Bright materials have been reported in association with impact craters on Ceres. The abundant Na2CO3 and some ammonium salts, NH4HCO3 and/or NH4Cl, were detected in bright deposits within Occator crater with Dawn near infrared spectroscopy. The composition and appearance of the salts suggest their aqueous mobilization and emplacement after formation of the crater. Here we consider origins of the bright deposits through calculation of speciation in the H-C-N-O-Na-Cl water-salt type system constrained by the mass balance of observed salts. Calculations of chemical equilibria show that initial solutions had the pH of ∼10. The temperature and salinity of solutions could have not exceeded ∼273 K and ∼100 g per kg H2O, respectively. Freezing models reveal an early precipitation of Na2CO3·10H2O followed by minor NaHCO3. Ammonium salts precipitate near eutectic from brines enriched in NH4+, Cl- and Na+. A late-stage precipitation of NaCl·2H2O is modeled for solution compositions with added NaCl. Calculated eutectics are above 247 K. The apparently unabundant ammonium and chloride salts in Occator's deposits imply a rapid emplacement without a compositional evolution of solution. Salty ice grains could have deposited from post-impact ballistic plumes formed through low-pressure boiling of subsurface solutions. Hydrated and ammonium salts are unstable at maximum temperatures of Ceres' surface and could decompose through space weathering. Occator's ice-free salt deposits formed through a post-depositional sublimation of ice followed by dehydration of Na2CO3·10H2O and NaHCO3 to Na2CO3. In other regions, excavated and exposed bright materials could be salts initially deposited from plumes and accumulated at depth via post-impact boiling. The lack of detection of sulfates and an elevated carbonate/chloride ratio in Ceres' materials suggest an involvement of compounds abundant in the outer solar system.

  2. Bright X-ray transient in the LMC (United States)

    Saxton, R.; Read, A. M.; Li, D. Y.


    We report a bright X-ray transient in the LMC from an XMM-Newton slew made on 5th January 2018. The source, XMMSL2 J053629.4-675940, had a soft X-ray (0.2-2 keV) count rate in the EPIC-pn detector, medium filter of 1.82+/-0.56 c/s, equivalent to a flux Fx=2.3+/-0.7E-12 ergs/s/cm2 for a nominal spectrum of a power-law of slope 2 absorbed by a column NH=3E20 cm^-2.

  3. Thin Sea-ice Thickness Retrievals from SMAP Brightness Temperatures (United States)

    Bayler, E. J.; Smith, R.


    The retrieval of thin sea-ice thicknesses has been developed for data from the European Space Agency's Soil Moisture - Ocean Salinity (SMOS) mission, employing the transition of observed surface emissivity from open water to thick sea ice. This technique is now applied to brightness temperature data from NASA's Soil Moisture Active-Passive (SMAP) mission, addressing the instrument differences between the SMOS Microwave Imaging Radiometer using Aperture Synthesis (MIRAS) and the SMAP scanning radiometer. This study demonstrates the utility of SMAP data for addressing a critical data gap for numerical prediction in polar regions, particularly as operational modeling advances toward coupled ocean-atmosphere-cryosphere modeling.

  4. Discovery, identification and comparative analysis of non-specific lipid transfer protein (nsLtp) family in Solanaceae. (United States)

    Liu, Wanfei; Huang, Dawei; Liu, Kan; Hu, Songnian; Yu, Jun; Gao, Gang; Song, Shuhui


    Plant non-specific lipid transfer proteins (nsLtps) have been reported to be involved in plant defense activity against bacterial and fungal pathogens. In this study, we identified 135 (122 putative and 13 previously identified) Solanaceae nsLtps, which are clustered into 8 different groups. By comparing with Boutrot's nsLtp classification, we classified these eight groups into five types (I, II, IV, IX and X). We compared Solanaceae nsLtps with Arabi-dopsis and Gramineae nsLtps and found that (1) Types I, II and IV are shared by Solanaceae, Gramineae and Arabidopsis; (2) Types III, V, VI and VIII are shared by Gramineae and Arabidopsis but not detected in Solanaceae so far; (3) Type VII is only found in Gramineae whereas type IX is present only in Arabidopsis and Solanaceae; (4) Type X is a new type that accounts for 52.59% Solanaceae nsLtps in our data, and has not been reported in any other plant so far. We further built and compared the three-dimensional structures of the eight groups, and found that the major functional diversification within the nsLtp family could be predated to the monocot/dicot divergence, and many gene duplications and sequence variations had happened in the nsLtp family after the monocot/dicot divergence, especially in Solanaceae. Copyright © 2010 Beijing Genomics Institute. Published by Elsevier Ltd. All rights reserved.

  5. Structure-activity relationships of proline modifications around the tetracyclic-indole class of NS5A inhibitors. (United States)

    Tong, Ling; Yu, Wensheng; Coburn, Craig A; Chen, Lei; Selyutin, Oleg; Zeng, Qingbei; Dwyer, Michael P; Nair, Anilkumar G; Shankar, Bandarpalle B; Kim, Seong Heon; Yang, De-Yi; Rosenblum, Stuart B; Ruck, Rebecca T; Davies, Ian W; Hu, Bin; Zhong, Bin; Hao, Jinglai; Ji, Tao; Zan, Shuai; Liu, Rong; Agrawal, Sony; Carr, Donna; Curry, Stephanie; McMonagle, Patricia; Bystol, Karin; Lahser, Frederick; Ingravallo, Paul; Chen, Shiying; Asante-Appiah, Ernest; Kozlowski, Joseph A


    We describe the impact of proline modifications, in our tetracyclic-indole based series of nonstructural protein 5A (NS5A) inhibitors, to their replicon profiles. This work identified NS5A inhibitors with an improved and flattened resistance profiles. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. The Herschel Planetary Nebula Survey (HerPlaNS). I. Data overview and analysis demonstration with NGC 6781

    NARCIS (Netherlands)

    Ueta, T.; Ladjal, D.; Exter, K.M.; Otsuka, M.; Szczerba, R.; Siódmiak, N.; Guerra, Aleman I.R.; van, Hoof P. A. M.; Kastner, J.H.; Montez, R.; McDonald, I.; Wittkowski, M.; Sandin, C.; Ramstedt, S.; De, Marco O.; Villaver, E.; Chu, Y.-H.; Vlemmings, W.; Izumiura, H.; Sahai, R.; Lopez, J.A.; Balick, B.; Zijlstra, A.; Tielens, A.G.G.M.; Rattray, R. E.; Behar, E.; Blackman, E. G.; Hebden, K.; Hora, J. L.; Murakawa, K.; Nordhaus, J.; Nordon, R.; Yamamura, I.


    Context. This is the first of a series of investigations into far-IR characteristics of 11 planetary nebulae (PNe) under the Herschel Space Observatory open time 1 program, Herschel Planetary Nebula Survey (HerPlaNS).Aims: Using the HerPlaNS data set, we look into the PN energetics and variations of

  7. Localization of mammalian orthoreovirus proteins to cytoplasmic factory-like structures via nonoverlapping regions of microNS. (United States)

    Miller, Cathy L; Arnold, Michelle M; Broering, Teresa J; Hastings, Craig E; Nibert, Max L


    Virally induced structures called viral factories form throughout the cytoplasm of cells infected with mammalian orthoreoviruses (MRV). When expressed alone in cells, MRV nonstructural protein microNS forms factory-like structures very similar in appearance to viral factories, suggesting that it is involved in forming the structural matrix of these structures. microNS also associates with MRV core particles; the core proteins mu2, lambda1, lambda2, lambda3, and sigma2; and the RNA-binding nonstructural protein sigmaNS. These multiple associations result in the recruitment or retention of these viral proteins or particles at factory-like structures. In this study, we identified the regions of microNS necessary and sufficient for these associations and additionally examined the localization of viral RNA synthesis in infected cells. We found that short regions within the amino-terminal 220 residues of microNS are necessary for associations with core particles and necessary and sufficient for associations with the proteins mu2, lambda1, lambda2, sigma2, and sigmaNS. We also found that only the lambda3 protein associates with the carboxyl-terminal one-third of microNS and that viral RNA is synthesized within viral factories. These results suggest that microNS may act as a cytoplasmic scaffolding protein involved in localizing and coordinating viral replication or assembly intermediates for the efficient production of progeny core particles during MRV infection.

  8. GPS2 is required for the association of NS5A with VAP-A and hepatitis C virus replication.

    Directory of Open Access Journals (Sweden)

    Guodong Xu

    Full Text Available Hepatitis C virus (HCV nonstructural protein 5A (NS5A is a component of the replication complex associated with various cellular proteins. It has been reported that G protein pathway suppressor 2 (GPS2 is a potential NS5A-binding factor, as identified in a yeast two-hybrid screens of human cDNA library using viral proteins as baits [1]. In this study, we demonstrated the interaction between GPS2 and NS5A in mammalian cells by coimmunoprecipitation analysis and found that both exogenously and endogenously expressed GPS2 interacted with NS5A of genotype 1b and 2a. Mutagenesis study demonstrated that Domain I of NS5A and coiled-coil domain of GPS2 are responsible for the interaction. Knockdown of GPS2 in hepatoma cell lines suppressed the replication of HCV RNA, which can be rescued by the expression of an RNAi-resistant GPS2. Furthermore, overexpression of GPS2 enhanced the association of NS5A with a proviral cellular factor, human vesicle-associated membrane protein-associated protein A (VAP-A, while knockdown of GPS2 disrupted interaction between VAP-A and NS5A. Taken together, our results suggest that GPS2 acts as a bridge between NS5A and VAP-A and is required for efficient HCV replication.

  9. Inhibition of the Membrane Attack Complex by Dengue Virus NS1 through Interaction with Vitronectin and Terminal Complement Proteins. (United States)

    Conde, Jonas Nascimento; da Silva, Emiliana Mandarano; Allonso, Diego; Coelho, Diego Rodrigues; Andrade, Iamara da Silva; de Medeiros, Luciano Neves; Menezes, Joice Lima; Barbosa, Angela Silva; Mohana-Borges, Ronaldo


    Dengue virus (DENV) infects millions of people worldwide and is a major public health problem. DENV nonstructural protein 1 (NS1) is a conserved glycoprotein that associates with membranes and is also secreted into the plasma in DENV-infected patients. The present study describes a novel mechanism by which NS1 inhibits the terminal complement pathway. We first identified the terminal complement regulator vitronectin (VN) as a novel DENV2 NS1 binding partner by using a yeast two-hybrid system. This interaction was further assessed by enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) assay. The NS1-VN complex was also detected in plasmas from DENV-infected patients, suggesting that this interaction occurs during DENV infection. We also demonstrated that the DENV2 NS1 protein, either by itself or by interacting with VN, hinders the formation of the membrane attack complex (MAC) and C9 polymerization. Finally, we showed that DENV2, West Nile virus (WNV), and Zika virus (ZIKV) NS1 proteins produced in mammalian cells inhibited C9 polymerization. Taken together, our results points to a role for NS1 as a terminal pathway inhibitor of the complement system. Dengue is the most important arthropod-borne viral disease nowadays and is caused by dengue virus (DENV). The flavivirus NS1 glycoprotein has been characterized functionally as a complement evasion protein that can attenuate the activation of the classical, lectin, and alternative pathways. The present study describes a novel mechanism by which DENV NS1 inhibits the terminal complement pathway. We identified the terminal complement regulator vitronectin (VN) as a novel DENV NS1 binding partner, and the NS1-VN complex was detected in plasmas from DENV-infected patients, suggesting that this interaction occurs during DENV infection. We also demonstrated that the NS1-VN complex inhibited membrane attack complex (MAC) formation, thus interfering with the complement terminal pathway. Interestingly

  10. Two-Dimensional Metal-Organic Layers as a Bright and Processable Phosphor for Fast White-Light Communication. (United States)

    Hu, Xuefu; Wang, Zi; Lin, Bangjiang; Zhang, Cankun; Cao, Lingyun; Wang, Tingting; Zhang, Jingzheng; Wang, Cheng; Lin, Wenbin


    A metal-organic layer (MOL) is a new type of 2D material that is derived from metal-organic frameworks (MOFs) by reducing one dimension to a single layer or a few layers. Tetraphenylethylene-based tetracarboxylate ligands (TCBPE), with aggregation-induced emission properties, were assembled into the first luminescent MOL by linking with Zr6 O4 (OH)6 (H2 O)2 (HCO2 )6 clusters. The emissive MOL can replace the lanthanide phosphors in white light emitting diodes (WLEDs) with remarkable processability, color rendering, and brightness. Importantly, the MOL-WLED exhibited a physical switching speed three times that of commercial WLEDs, which is crucial for visible-light communication (VLC), an alternative wireless communication technology to Wi-Fi and Bluetooth, by using room lighting to carry transmitted signals. The short fluorescence lifetime (2.6 ns) together with high quantum yield (50 %) of the MOL affords fast switching of the assembled WLEDs for efficient information encoding and transmission. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Therapeutic Effects of Monoclonal Antibody against Dengue Virus NS1 in a STAT1 Knockout Mouse Model of Dengue Infection. (United States)

    Wan, Shu-Wen; Chen, Pei-Wei; Chen, Chin-Yu; Lai, Yen-Chung; Chu, Ya-Ting; Hung, Chia-Yi; Lee, Han; Wu, Hsuan Franziska; Chuang, Yung-Chun; Lin, Jessica; Chang, Chih-Peng; Wang, Shuying; Liu, Ching-Chuan; Ho, Tzong-Shiann; Lin, Chiou-Feng; Lee, Chien-Kuo; Wu-Hsieh, Betty A; Anderson, Robert; Yeh, Trai-Ming; Lin, Yee-Shin


    Dengue virus (DENV) is the causative agent of dengue fever, dengue hemorrhagic fever, and dengue shock syndrome and is endemic to tropical and subtropical regions of the world. Our previous studies showed the existence of epitopes in the C-terminal region of DENV nonstructural protein 1 (NS1) which are cross-reactive with host Ags and trigger anti-DENV NS1 Ab-mediated endothelial cell damage and platelet dysfunction. To circumvent these potentially harmful events, we replaced the C-terminal region of DENV NS1 with the corresponding region from Japanese encephalitis virus NS1 to create chimeric DJ NS1 protein. Passive immunization of DENV-infected mice with polyclonal anti-DJ NS1 Abs reduced viral Ag expression at skin inoculation sites and shortened DENV-induced prolonged bleeding time. We also investigated the therapeutic effects of anti-NS1 mAb. One mAb designated 2E8 does not recognize the C-terminal region of DENV NS1 in which host-cross-reactive epitopes reside. Moreover, mAb 2E8 recognizes NS1 of all four DENV serotypes. We also found that mAb 2E8 caused complement-mediated lysis in DENV-infected cells. In mouse model studies, treatment with mAb 2E8 shortened DENV-induced prolonged bleeding time and reduced viral Ag expression in the skin. Importantly, mAb 2E8 provided therapeutic effects against all four serotypes of DENV. We further found that mAb administration to mice as late as 1 d prior to severe bleeding still reduced prolonged bleeding time and hemorrhage. Therefore, administration with a single dose of mAb 2E8 can protect mice against DENV infection and pathological effects, suggesting that NS1-specific mAb may be a therapeutic option against dengue disease. Copyright © 2017 by The American Association of Immunologists, Inc.

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

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


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

  13. Unveiling the Low Surface Brightness Stellar Peripheries of Galaxies (United States)

    Ferguson, Annette M. N.


    The low surface brightness peripheral regions of galaxies contain a gold mine of information about how minor mergers and accretions have influenced their evolution over cosmic time. Enormous stellar envelopes and copious amounts of faint tidal debris are natural outcomes of the hierarchical assembly process and the search for and study of these features, albeit highly challenging, offers the potential for unrivalled insight into the mechanisms of galaxy growth. Over the last two decades, there has been burgeoning interest in probing galaxy outskirts using resolved stellar populations. Wide-field surveys have uncovered vast tidal debris features and new populations of very remote globular clusters, while deep Hubble Space Telescope photometry has provided exquisite star formation histories back to the earliest epochs. I will highlight some recent results from studies within and beyond the Local Group and conclude by briefly discussing the great potential of future facilities, such as JWST, Euclid, LSST and WFIRST, for major breakthroughs in low surface brightness galaxy periphery science.

  14. Observations of Bright Massive Stars Using Small Size Telescopes (United States)

    Beradze, Sopia; Kochiashvili, Nino


    The size of a telescope determines goals and objects of observations. During the latest decades it becomes more and more difficult to get photometric data of bright stars because most of telescopes of small sizes do not operate already. But there are rather interesting questions connected to the properties and evolution ties between different types of massive stars. Multi-wavelength photometric data are needed for solution of some of them. We are presenting our observational plans of bright Massive X-ray binaries, WR and LBV stars using a small size telescope. All these stars, which are presented in the poster are observational targets of Sopia Beradze's future PhD thesis. We already have got very interesting results on the reddening and possible future eruption of the massive hypergiant star P Cygni. Therefore, we decided to choose some additional interesting massive stars of different type for future observations. All Massive stars play an important role in the chemical evolution of galaxies because of they have very high mass loss - up to 10-4M⊙/a year. Our targets are on different evolutionary stages and three of them are the members of massive binaries. We plan to do UBVRI photometric observations of these stars using the 48 cm Cassegrain telescope of the Abastumani Astrophisical Observatory.

  15. Lightness and brightness judgments of coplanar retinally noncontiguous surfaces. (United States)

    Schirillo, J A; Shevell, S K


    Several experiments reveal that judgments of lightness and brightness of an achromatic surface depend, in part, on the luminances of other surfaces perceived to share the same depth plane, even if the surfaces are well separated on the retina. Two Mondrians, simulated on a CRT, were viewed through a haploscope. The more highly illuminated Mondrian contained a comparison patch and appeared nearer than the more dimly illuminated Mondrian, which contained the test patch. By independently varying the disparity of the test patch, observers could make the test patch appear to be in the depth plane of either the dimly or the highly illuminated Mondrian. Observers set the luminance of the test patch to match that of the comparison patch. The test was set as high as 15% more luminous when it was perceived in the depth plane of the highly illuminated rather than the dimly illuminated Mondrian. Both brightness and lightness judgments were affected by the perceived depth of the test, although the lightness judgments of inexperienced observers sometimes were dominated by local-contrast matching.

  16. Bright Solitons in a PT-Symmetric Chain of Dimers

    Directory of Open Access Journals (Sweden)

    Omar B. Kirikchi


    Full Text Available We study the existence and stability of fundamental bright discrete solitons in a parity-time- (PT- symmetric coupler composed by a chain of dimers that is modelled by linearly coupled discrete nonlinear Schrödinger equations with gain and loss terms. We use a perturbation theory for small coupling between the lattices to perform the analysis, which is then confirmed by numerical calculations. Such analysis is based on the concept of the so-called anticontinuum limit approach. We consider the fundamental onsite and intersite bright solitons. Each solution has symmetric and antisymmetric configurations between the arms. The stability of the solutions is then determined by solving the corresponding eigenvalue problem. We obtain that both symmetric and antisymmetric onsite mode can be stable for small coupling, in contrast to the reported continuum limit where the antisymmetric solutions are always unstable. The instability is either due to the internal modes crossing the origin or the appearance of a quartet of complex eigenvalues. In general, the gain-loss term can be considered parasitic as it reduces the stability region of the onsite solitons. Additionally, we analyse the dynamic behaviour of the onsite and intersite solitons when unstable, where typically it is either in the form of travelling solitons or soliton blow-ups.

  17. Bright PanSTARRS Nuclear Transients – what are they?

    Directory of Open Access Journals (Sweden)

    Smartt S.


    Full Text Available We present an initial analysis of 49 bright transients occurring in the nuclei of galaxies with no previous known Active Galactic Nucleus (AGN. They have been discovered as part of the PanSTARRs 3π survey, and followed up with the Liverpool Telescope. Based on colours, light curve shape, and a small number with optical spectra, these transients seem to fall into three groups. Red/fast transients are nuclear supernovae of various types. Some bright nuclear transients are blue and decay on a timescale of a few months; these may be candidates for tidal disruption events. However most of the events we have found are blue and are either still rising or decaying slowly, on a timescale of years; the few spectra we have show AGN at z ∼ 1. We argue that these transients are background AGN microlensed by stars in foreground galaxies by a factor 10–100. Monitoring such events gives us very promising prospects for measuring the structure of AGN and so testing current theories.

  18. MD421: Electron cloud studies on 25 ns beam variants (BCMS, 8b+4e)

    CERN Document Server

    Iadarola, Giovanni; Belli, Eleonora; Carver, Lee Robert; Dijkstal, Philipp; Li, Kevin Shing Bruce; Mether, Lotta; Romano, Annalisa; Rumolo, Giovanni; CERN. Geneva. ATS Department


    This note describes a Machine Development session performed with the main goal of studying the e-cloud mitigation that can be obtained by injecting mixed trains of 8b+4e beam type and trains having the standard 25 ns structure. Additionally, in the course of the MD, the pure 8b+4e beam was also checked to be stable when injected with low chromaticity and octupole current settings. Subsequently, the operational BCMS 25 ns beam was also injected with the 8b+4e settings and found to be unstable. The operational settings for injection were re-found by gradually increasing the chromaticity and octupole knobs until all the bunches of the injected beam could remain stable after injection.

  19. Symposium on CIAE 600 kV ns pulse neutron generator

    CERN Document Server

    Shen Guan Ren


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

  20. Performance analysis of aodv, dsdv and aomdv using wimax in NS - 2

    Directory of Open Access Journals (Sweden)

    Madhusrhee B


    Full Text Available WiMAX (IEEE 802.16 technology empowers ubiquitous delivery of wireless broadband facility for fixed and mobile users. WiMAX standard describes numerous physical and MAC layer characteristics. Here, an attempt is made to implement some of these physical and MAC layer structures including the mobility extension 802.16e. NS2 (Network Simulator - 2 is chosen as the simulator to implement these features as NS2 provides suitable library to simulate network scenario. The performance of the simulated module is analyzed by running AODV, DSDV and AOMDV routing protocols on a wired - cum - wireless WiMAX scenario. The throughput for each routing protocol is calculated for varying number of mobile nodes or subs criber stations.

  1. The Nature of Emission from Optical Breakdown Induced by Pulses of fs and ns Duration

    Energy Technology Data Exchange (ETDEWEB)

    Carr, C W; Feit, M D; Rubenchik, A M; Demange, P; Kucheyev, S; Shirk, M D; Radousky, H B; Demos, S G


    Spectral emission from optical breakdown in the bulk of a transparent dielectric contains information about the nature of the breakdown medium. We have made time resolved measurements of the breakdown induced emission caused by nanosecond and femtosecond infrared laser pulses. We previously demonstrated that the emission due to ns pulses is blackbody in nature allowing determination of the fireball temperature and pressure during and after the damage event. The emission due to femtosecond pulse breakdown is not blackbody in nature; two different spectral distributions being noted. In one case, the peak spectral distribution occurs at the second harmonic of the incident radiation, in the other the distribution is broader and flatter and presumably due to continuum generation. The differences between ns and fs breakdown emission can be explained by the differing breakdown region geometries for the two pulse durations. The possibility to use spectral emission as a diagnostic of the emission region morphology will be discussed.

  2. Naringenin and quercetin--potential anti-HCV agents for NS2 protease targets. (United States)

    Lulu, S Sajitha; Thabitha, A; Vino, S; Priya, A Mohana; Rout, Madhusmita


    Nonstructural proteins of hepatitis C virus had drawn much attention for the scientific fraternity in drug discovery due to its important role in the disease. 3D structure of the protein was predicted using molecular modelling protocol. Docking studies of 10 medicinal plant compounds and three drugs available in the market (control) with NS2 protease were employed by using rigid docking approach of AutoDock 4.2. Among the molecules tested for docking study, naringenin and quercetin revealed minimum binding energy of - 7.97 and - 7.95 kcal/mol with NS2 protease. All the ligands were docked deeply within the binding pocket region of the protein. The docking study results showed that these compounds are potential inhibitors of the target; and also all these docked compounds have good inhibition constant, vdW+Hbond+desolv energy with best RMSD value.

  3. Holographic approach to deformations of NS5-brane distributions and exact CFTs

    CERN Document Server

    Fotopoulos, Angelos; Prezas, Nikolaos; Sfetsos, Konstadinos


    We consider general planar deformations of a circular distribution of NS5-branes. The near-horizon region of the latter admits, after a T-duality transformation, an exact conformal-field-theory description in terms of the coset model SU(2)/U(1) X SL(2,R)/U(1). We derive the exactly marginal operators corresponding to an infinitesimal planar deformation using the conjectured holography between the coset model and the little string theory that resides on the worldvolume of the NS5-branes. Subsequently, we perform a complementary analysis of the same deformations using the associated N=1 supersymmetric sigma model and verify the holographic correspondence. We explicitly demonstrate a precise match between the two approaches which rests upon a delicate interplay between exact conformal-field-theory operators and their semiclassical realizations in terms of target-space variables.

  4. 25 ns studies in the LHC – MD held on 14/10/2011

    CERN Document Server

    Arduini, G; Biancacci, N; Buffat, X; Dominguez, O; Iadarola, G; Métral, E; Rumolo, G; Salvant, B; Zannini, C; Roncarolo, F; Esteban Muller, JF; Höfle, W; Shaposhnikova, E; Valuch, D; Cettour-Cave, S; Kain, V; Redaelli, S; Barnes, M; Bartmann, W; Bracco, C; Goddard, B; Claudet, S; Tavian, L; Baglin, V; Bregliozzi, G; Kersevan, R; Lanza, G


    The machine development session (12 hours) was devoted to the injection of several trains of 72 bunches with nominal bunch population and 25 ns bunch spacing with the aim of injecting up to 1000 bunches/beam. This was the third of a series MD periods (in total 72 hours were requested at the beginning of the year) dedicated to electron cloud and scrubbing studies with 25 ns beams. The first one (8 hours on 26/08/2011) was lost due to a cryogenics problem. The second (12 hours) took place on 6/10/2011 and was mostly dedicated to the setting-up of the injection and of the transverse damper.

  5. Screening and Production of Antibacterial from Lactobacillus plantarum NS(9 Isolated from Nile Tilapia Bekasam

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    Desniar Desniar


    Full Text Available Lactic acid bacteria has been used as biopreservatif becouse produce a number of antibacterialsubstances are safety and has inhibitory activity against enteropatogenic bacteria. The aims of this studywere to screen of antibacterial compounds produced by Lactobacillus plantarum NS (9 and to producetheir antibacterial compounds. The research was devided into two stages. In the first stage was L. plantarumNS (9 inoculated at 37°C, for 24 hours in semi-anaerobic conditions. The cell-free supertnatant was giventhree treatment, ie not neutralized (A, neutralized (pH 7 (N, and precipitated with ammonium sulfate50% (P. This three supernatant was assayed their antibacterial activity against E. coli, S. typhimuriumATCC 14028, S. aureus, B. cereus and L. monocytogenes using the agar well diffusion method. In the secondstage, production of antibacterial compound was L. plantarum NS (9 inoculated at 37°C, for 24 hoursin semi-anaerobic conditions. The Dencity Optical, value pH, acid total and antibacterial activity weremeasured every three hours during growth of bacteria. The results of the antibacterial screening showedthat L. plantarum NS (9 produced inhibitory zone againts the five indicator bacteria from a supernatant,whereas N and P supernatant were not produced inhibitory zone. This result indicated that inhibition.produced at 6 hours of incubation and were increased to simultaneously with increasing of bacteria growth.The highest antibacterial activity against E. coli, B. cereus and L.monocytogenes were produced at the endof the exponential growth phase (12 -15 hours incubation while against S. aureus and S. typhimuriumATCC 14028 at 21 and 24 hour of incubation, respectively. The antibacterial activity also was increased tosimultaniously with increasing of acid total (1.350 to 4.050% and decreasing of pH value (6-4 duringgrowth of bacteria.

  6. NS-187 (INNO-406, a Bcr-Abl/Lyn Dual Tyrosine Kinase Inhibitor

    Directory of Open Access Journals (Sweden)

    Tomoko Niwa


    Full Text Available Protein kinases catalyze the transfer of the γ-phosphoryl group of adenosine triphosphate (ATP to the hydroxyl groups of protein side chains, and they play critical roles in regulating cellular signal transduction and other biochemical processes. They are attractive targets for today’s drug discovery and development, and many pharmaceutical companies are intensively developing various kinds of protein kinase inhibitors. A good example is the recent success with the Bcr-Abl tyrosine kinase inhibitor imatinib mesylate (GleevecTM in the treatment of chronic myeloid leukemia. Though imatinib has dramatically improved the treatment of Bcr-Abl-positive chronic myeloid leukemia, resistance is often found in patients with advanced-stage disease. Several mechanisms have been proposed to explain this resistance, including point mutations within the Abl kinase domain, amplification of the bcr-abl gene, overexpression of the corresponding mRNA, increased drug efflux mediated by P-glycoprotein, and activation of the Src-family kinase (SFK Lyn. We set out to develop a novel drug whose affinity for Abl is higher than that of imatinib and whose specifi city in inhibiting Lyn is higher than that of SFK/Abl inhibitors such as dasatinib (SprycelTM or bosutinib (SKI-606. Our work has led to the development of NS-187 (INNO-406, a novel Abl/Lyn dual tyrosine kinase inhibitor with clinical prospects. To provide an overview of how a selective kinase inhibitor has been developed, this review presents chemical-modification studies carried out with the guidance of molecular modeling, the structural basis for the high potency and selectivity of NS-187 based on the X-ray structure of the NS-187/Abl complex, and the biological profi ling of NS-187, including site-directed mutagenesis experiments.

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


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


    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 investiga...


    Directory of Open Access Journals (Sweden)

    Fathima Cader


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

  9. Diffraction-assisted micropatterning of silicon surfaces by ns-laser irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Haro-Poniatowski, E., E-mail:; Acosta-Zepeda, C.; Mecalco, G.; Hernández-Pozos, J. L. [Departamento de Física, Universidad Autónoma Metropolitana Iztapalapa, Av. San Rafael Atlixco No. 186, Col. Vicentina, C.P. 09340 México D. F. (Mexico); Batina, N.; Morales-Reyes, I. [Departamento de Química, Universidad Autónoma Metropolitana Iztapalapa, Av. San Rafael Atlixco No. 186, Col. Vicentina, C.P. 09340 México D. F. (Mexico); Bonse, J. [BAM Bundesanstalt für Materialforschung und-prüfung, Unter den Eichen 87, D-12205 Berlin (Germany)


    Single-pulse (532 nm, 8 ns) micropatterning of silicon with nanometric surface modulation is demonstrated by irradiating through a diffracting pinhole. The irradiation results obtained at fluences above the melting threshold are characterized by scanning electron and scanning force microscopy and reveal a good agreement with Fresnel diffraction theory. The physical mechanism is identified and discussed on basis of both thermocapillary and chemicapillary induced material transport during the molten state of the surface.

  10. The R35 residue of the influenza A virus NS1 protein has minimal effects on nuclear localization but alters virus replication through disrupting protein dimerization

    Energy Technology Data Exchange (ETDEWEB)

    Lalime, Erin N.; Pekosz, Andrew, E-mail:


    The influenza A virus NS1 protein has a nuclear localization sequence (NLS) in the amino terminal region. This NLS overlaps sequences that are important for RNA binding as well as protein dimerization. To assess the significance of the NS1 NLS on influenza virus replication, the NLS amino acids were individually mutated to alanines and recombinant viruses encoding these mutations were rescued. Viruses containing NS1 proteins with mutations at R37, R38 and K41 displayed minimal changes in replication or NS1 protein nuclear localization. Recombinant viruses encoding NS1 R35A were not recovered but viruses containing second site mutations at position D39 in addition to the R35A mutation were isolated. The mutations at position 39 were shown to partially restore NS1 protein dimerization but had minimal effects on nuclear localization. These data indicate that the amino acids in the NS1 NLS region play a more important role in protein dimerization compared to nuclear localization. - Highlights: • Mutations were introduced into influenza NS1 NLS1. • NS1 R37A, R38A, K41A viruses had minimal changes in replication and NS1 localization. • Viruses from NS1 R35A rescue all contained additional mutations at D39. • NS1 R35A D39X mutations recover dimerization lost in NS1 R35A mutations. • These results reaffirm the importance of dimerization for NS1 protein function.

  11. Screen Printed Carbon Electrode Based Electrochemical Immunosensor for the Detection of Dengue NS1 Antigen

    Directory of Open Access Journals (Sweden)

    Om Parkash


    Full Text Available An electrochemical immunosensor modified with the streptavidin/biotin system on screen printed carbon electrodes (SPCEs for the detection of the dengue NS1 antigen was developed in this study. Monoclonal anti-NS1 capture antibody was immobilized on streptavidin-modified SPCEs to increase the sensitivity of the assay. Subsequently, a direct sandwich enzyme linked immunosorbent assay (ELISA format was developed and optimized. An anti-NS1 detection antibody conjugated with horseradish peroxidase enzyme (HRP and 3,3,5,5'-tetramethybezidine dihydrochloride (TMB/H2O2 was used as an enzyme mediator. Electrochemical detection was conducted using the chronoamperometric technique, and electrochemical responses were generated at −200 mV reduction potential. The calibration curve of the immunosensor showed a linear response between 0.5 µg/mL and 2 µg/mL and a detection limit of 0.03 µg/mL. Incorporation of a streptavidin/biotin system resulted in a well-oriented antibody immobilization of the capture antibody and consequently enhanced the sensitivity of the assay. In conclusion, this immunosensor is a promising technology for the rapid and convenient detection of acute dengue infection in real serum samples.

  12. ToxR Antagonizes H-NS Regulation of Horizontally Acquired Genes to Drive Host Colonization.

    Directory of Open Access Journals (Sweden)

    Misha I Kazi


    Full Text Available The virulence regulator ToxR initiates and coordinates gene expression needed by Vibrio cholerae to colonize the small intestine and cause disease. Despite its prominence in V. cholerae virulence, our understanding of the direct ToxR regulon is limited to four genes: toxT, ompT, ompU and ctxA. Here, we determine ToxR's genome-wide DNA-binding profile and demonstrate that ToxR is a global regulator of both progenitor genome-encoded genes and horizontally acquired islands that encode V. cholerae's major virulence factors and define pandemic lineages. We show that ToxR shares more than a third of its regulon with the histone-like nucleoid structuring protein H-NS, and antagonizes H-NS binding at shared binding locations. Importantly, we demonstrate that this regulatory interaction is the critical function of ToxR in V. cholerae colonization and biofilm formation. In the absence of H-NS, ToxR is no longer required for V. cholerae to colonize the infant mouse intestine or for robust biofilm formation. We further illustrate a dramatic difference in regulatory scope between ToxR and other prominent virulence regulators, despite similar predicted requirements for DNA binding. Our results suggest that factors in addition to primary DNA structure influence the ability of ToxR to recognize its target promoters.

  13. Analysis of the electron cloud observations with 25 ns bunch spacing at LHC

    CERN Document Server

    Iadarola, G; Rumolo, G; Arduini, G; Baglin, V; Banfi, D; Claudet, S; Dominguez, O; Esteban Müller, J; Pieloni, T; Shaposhnikova, E; Tavian, L; Zannini, C; Zimmermann, F


    Electron Cloud (EC) effects have been identified as a major performance limitation for the Large Hadron Collider (LHC) when operating with the nominal bunch spacing of 25 ns. During the LHC Run 1 (2010 - 2013) the luminosity production mainly used beams with 50 ns spacing, while 25 ns beams were only employed for short periods in 2011 and 2012 for test purposes. On these occasions, observables such as pressure rise, heat load in the cold sections as well as clear signatures on bunch-by-bunch emittance blow up, particle loss and energy loss indicated the presence of an EC in a large portion of the LHC. The analysis of the recorded data, together with EC build up simulations, has led to a significant improvement of our understanding of the EC effect in the different components of the LHC. Studies were carried out both at injection energy (450 GeV) and at top energy (4 TeV) aiming at determining the energy dependence of the EC formation and its impact on the quality of the proton beam.

  14. Viperin restricts Zika virus and tick-borne encephalitis virus replication by targeting NS3 for proteasomal degradation. (United States)

    Panayiotou, Christakis; Lindqvist, Richard; Kurhade, Chaitanya; Vonderstein, Kirstin; Pasto, Jenny; Edlund, Karin; Upadhyay, Arunkumar S; Överby, Anna K


    Flaviviruses are arthropod-borne viruses that constitute a major global health problem, with millions of human infections annually. Their pathogenesis ranges from mild illness to severe manifestations such as hemorrhagic fever and fatal encephalitis. Type I interferons (IFNs) are induced in response to viral infection, and stimulate the expression of interferon-stimulated genes (ISGs), including that encoding viperin (virus-inhibitory protein, endoplasmic reticulum-associated, IFN-inducible), which shows antiviral activity against a broad spectrum of viruses including several flaviviruses. Here we describe a novel antiviral mechanism exerted by viperin against two prominent flaviviruses, tick-borne encephalitis virus (TBEV) and Zika virus (ZIKV). Viperin was found to interact and co-localize with the structural proteins pre-membrane (prM) and envelope (E) of TBEV, as well as the non-structural (NS) proteins NS2A, NS2B, and NS3. Interestingly, viperin expression reduced the NS3 protein level, and the stability of the other interacting viral proteins, but only in the presence of NS3. We also found that although viperin interacted with NS3 of mosquito-borne flaviviruses (ZIKV, Japanese encephalitis virus, and yellow fever virus), only ZIKV was sensitive to the antiviral effect of viperin. This sensitivity correlated with viperin's ability to induce proteasome-dependent degradation of NS3. ZIKV and TBEV replication was rescued completely when NS3 was overexpressed, suggesting that the viral NS3 is the specific target of viperin. In summary, we present here a novel antiviral mechanism of viperin that is selective for specific viruses in the genus Flavivirus, affording the possibility of new drug targets that can be used for therapeutic intervention.ImportanceFlaviviruses are a group of enveloped RNA viruses that cause severe diseases in humans and animals worldwide, but no antiviral treatment is yet available. Viperin, a host protein produced in response to infection

  15. Searching for Jet Emission in LMXBs: A Polarimetric View

    Directory of Open Access Journals (Sweden)

    Maria Cristina Baglio


    Full Text Available We present results taken from a study aiming at detecting the emission from relativistic particles jets in neutron star-low mass X-ray binaries using optical polarimetric observations. First, we focus on a polarimetric study performed on the persistent LMXB 4U 0614+091. Once corrected for interstellar effects, we measured an intrinsic linear polarization in the r-band of ~3% at a 3σ confidence level. This is in-line with the observation of an infrared excess in the spectral energy distribution (SED of the source, reported in a previous work, which the authors linked to the optically thin synchrotron emission of a jet. We then present a study performed on the transitional millisecond pulsar PSR J1023+0038 during quiescence. We measured a linear polarization of 1.09 ± 0.27% and 0.90 ± 0.17% in the V and R bands, respectively. The phase-resolved polarimetric curve of the source in the R-band reveals a hint of a sinusoidal modulation at the source orbital period. The NIR -optical SED of the system did not suggest the presence of a jet. We conclude that the optical linear polarization observed for PSR J1023+0038 is possibly due to Thomson scattering with electrons in the disc, as also suggested by the hint of the modulation of the R-band linear polarization at the system orbital period.

  16. Long-lived bright red emitting azaoxa-triangulenium fluorophores.

    Directory of Open Access Journals (Sweden)

    Badri P Maliwal

    Full Text Available The fluorescence lifetimes of most red emitting organic probes are under 4 nanoseconds, which is a limiting factor in studying interactions and conformational dynamics of macromolecules. In addition, the nanosecond background autofluorescence is a significant interference during fluorescence measurements in cellular environment. Therefore, red fluorophores with longer lifetimes will be immensely helpful. Azaoxa-triangulenium fluorophores ADOTA and DAOTA are red emitting small organic molecules with high quantum yield, long fluorescence lifetime and high limiting anisotropy. In aqueous environment, ADOTA and DAOTA absorption and emission maxima are respectively 540 nm and 556 nm, and 556 nm and 589 nm. Their emission extends beyond 700 nm. Both probes have the limiting anisotropy between 0.36-0.38 at their absorption peak. In both protic and aprotic solvents, their lifetimes are around 20 ns, making them among the longest-lived red emitting organic fluorophores. Upon labeling of avidin, streptavidin and immunoglobulin their absorption and fluorescence are red-shifted. Unlike in free form, the protein-conjugated probes have heterogeneous fluorescence decays, with the presence of both significantly quenched and unquenched populations. Despite the presence of significant local motions due to a flexible trimethylene linker, we successfully measured both intermediate nanosecond intra-protein motions and slower rotational correlation times approaching 100 ns. Their long lifetimes are unaffected by the cell membrane (hexadecyl-ADOTA and the intra-cellular (DAOTA-Arginine localization. Their long lifetimes also enabled successful time-gating of the cellular autofluorescence resulting in background-free fluorescence lifetime based images. ADOTA and DAOTA retain a long fluorescence lifetime when free, as protein conjugate, in membranes and inside the cell. Our successful measurements of intermediate nanosecond internal motions and long correlations times

  17. ns2 type luminescence in Pb-bearing carbonates using cathodoluminescence (United States)

    Nomi, S.; Kusano, N.


    We conducted to clarify an emission mechanism of ns2 type activation in Pb-bearing carbonates crystal structure with calcite and aragonite structures by cathodoluminescence (CL) analysis. Single crystals of tarnowitzite (Namibia and Morocco) and plumbocalcite (Namibia) were employed for CL measurements. Their color CL image were obtained with a cold-cathodo microscopy of the Luminoscope. CL spectra were measured by using a SEM-CL comprised of SEM combined with a grating monochromator at accelerating voltage of 15 kV and beam current of 0.1 nA in the wavelength-range of 300-800 nm. The sample temperature was controlled in the range from -192 to 25 °C with a cryo-stage. Color CL imaging shows a blue emission in tarnowitzite and a red emission in plumbocalcite. CL spectra of tarnowitzite have an intense broad band emission at around 390 nm in a blue region, whereas plumbocalcite exhibits two broad band emissions at around 320 nm in a UV region and at 620 nm in a red region. A blue CL is derived from Pb2+ activator as ns2 emission center from s2-sp transition in tarnowitzite. Its intensity depends on Pb content, which suggests a concentration quenching of CL above PbO 10 wt%. Tarnowitzite with aragonite structure shows the ns2 emission caused by Pb2+, whereas plumbocalcite gives no emission related to ns2 type. Pb ions in plumbocalcite behave as a sensitizer to transfer the energy to Mn activator for a red emission. Blue CL intensities at various temperatures of tarnowizite shows almost unchanged between 25 to -70 °C, and subsequent sudden reduction below -90 °C, and gradual sensitizing above -150 °C. The change in CL intensity below -90 °C might be due to the Jahn-Teller effect, which alters the symmetry of the electron configuration responsible for stability of a crystal field at low temperature. Conclusively, blue Pb activation in tarnowitzite should be characteristic in ns2 type emission, which of process might be related to electron transfer among two or more

  18. Pharmacophore anchor models of flaviviral NS3 proteases lead to drug repurposing for DENV infection. (United States)

    Pathak, Nikhil; Lai, Mei-Ling; Chen, Wen-Yu; Hsieh, Betty-Wu; Yu, Guann-Yi; Yang, Jinn-Moon


    Viruses of the flaviviridae family are responsible for some of the major infectious viral diseases around the world and there is an urgent need for drug development for these diseases. Most of the virtual screening methods in flaviviral drug discovery suffer from a low hit rate, strain-specific efficacy differences, and susceptibility to resistance. It is because they often fail to capture the key pharmacological features of the target active site critical for protein function inhibition. So in our current work, for the flaviviral NS3 protease, we summarized the pharmacophore features at the protease active site as anchors (subsite-moiety interactions). For each of the four flaviviral NS3 proteases (i.e., HCV, DENV, WNV, and JEV), the anchors were obtained and summarized into 'Pharmacophore anchor (PA) models'. To capture the conserved pharmacophore anchors across these proteases, were merged the four PA models. We identified five consensus core anchors (CEH1, CH3, CH7, CV1, CV3) in all PA models, represented as the "Core pharmacophore anchor (CPA) model" and also identified specific anchors unique to the PA models. Our PA/CPA models complied with 89 known NS3 protease inhibitors. Furthermore, we proposed an integrated anchor-based screening method using the anchors from our models for discovering inhibitors. This method was applied on the DENV NS3 protease to screen FDA drugs discovering boceprevir, telaprevir and asunaprevir as promising anti-DENV candidates. Experimental testing against DV2-NGC virus by in-vitro plaque assays showed that asunaprevir and telaprevir inhibited viral replication with EC50 values of 10.4 μM & 24.5 μM respectively. The structure-anchor-activity relationships (SAAR) showed that our PA/CPA model anchors explained the observed in-vitro activities of the candidates. Also, we observed that the CEH1 anchor engagement was critical for the activities of telaprevir and asunaprevir while the extent of inhibitor anchor occupation guided

  19. A Novel Benzodiazepine Compound Inhibits Yellow Fever Virus Infection by Specifically Targeting NS4B Protein. (United States)

    Guo, Fang; Wu, Shuo; Julander, Justin; Ma, Julia; Zhang, Xuexiang; Kulp, John; Cuconati, Andrea; Block, Timothy M; Du, Yanming; Guo, Ju-Tao; Chang, Jinhong


    Although a highly effective vaccine is available, the number of yellow fever cases has increased over the past two decades, which highlights the pressing need for antiviral therapeutics. In a high throughput screening campaign, we identified an acetic acid benzodiazepine (BDAA) compound, which potently inhibits yellow fever virus (YFV). Interestingly, while treatment of YFV infected cultures with 2 μM of BDAA reduced the virion production by greater than 2 logs, the compound is not active against 21 other viruses from 14 different viral families. Selection and genetic analysis of drug resistant viruses revealed that substitution of proline at amino acid 219 (P219) of the nonstructural protein 4B (NS4B) with serine, threonine or alanine confers YFV resistance to BDAA without apparent loss of replication fitness in cultured mammalian cells. However, substitution of P219 with glycine confers BDAA resistance with significant loss of replication ability. Bioinformatics analysis predicts that the P219 localizes at the endoplasmic reticulum lumen side of the fifth putative trans-membrane domain of NS4B and the mutation may render the viral protein incapable of interacting with BDAA. Our studies thus revealed important role and structural basis for NS4B protein in supporting YFV replication. Moreover, in YFV-infected hamsters, oral administration of BDAA protected 90% of the animals from death, significantly reduced viral load by greater than 2 logs and attenuated viral infection-induced liver injury and body weight loss. The encouraging preclinical results thus warrant further development of BDAA or its derivatives as antiviral agents to treat yellow fever. Yellow fever is an acute viral hemorrhagic disease which threatens approximately one billion people living in tropical areas of Africa and Latin America. Although a highly effective yellow fever vaccine has been available for more than seven decades, the low vaccination rate fails to prevent outbreaks in at

  20. Adapted J6/JFH1-Based Hepatitis C Virus Recombinants with Genotype-Specific NS4A Show Similar Efficacies against Lead Protease Inhibitors, Alpha Interferon, and a Putative NS4A Inhibitor (United States)

    Gottwein, Judith M.; Jensen, Sanne B.; Serre, Stéphanie B. N.; Ghanem, Lubna; Scheel, Troels K. H.; Jensen, Tanja B.; Krarup, Henrik; Uzcategui, Nathalie; Mikkelsen, Lotte S.


    To facilitate studies of hepatitis C virus (HCV) NS4A, we aimed at developing J6/JFH1-based recombinants with genotype 1- to 7-specific NS4A proteins. We developed efficient culture systems expressing NS4A proteins of genotypes (isolates) 1a (H77 and TN), 1b (J4), 2a (J6), 4a (ED43), 5a (SA13), 6a (HK6a), and 7a (QC69), with peak infectivity titers of ∼3.5 to 4.5 log10 focus-forming units per ml. Except for genotype 2a (J6), growth depended on adaptive mutations identified in long-term culture. Genotype 1a, 1b, and 4a recombinants were adapted by amino acid substitutions F772S (p7) and V1663A (NS4A), while 5a, 6a, and 7a recombinants required additional substitutions in the NS3 protease and/or NS4A. We demonstrated applicability of the developed recombinants for study of antivirals. Genotype 1 to 7 NS4A recombinants showed similar responses to the protease inhibitors telaprevir (VX-950), boceprevir (Sch503034), simeprevir (TMC435350), danoprevir (ITMN-191), and vaniprevir (MK-7009), to alpha interferon 2b, and to the putative NS4A inhibitor ACH-806. The efficacy of ACH-806 was lower than that of protease inhibitors and was not influenced by changes at amino acids 1042 and 1065 (in the NS3 protease), which have been suggested to mediate resistance to ACH-806 in replicons. Genotype 1a, 1b, and 2a recombinants showed viral spread under long-term treatment with ACH-806, without acquisition of resistance mutations in the NS3-NS4A region. Relatively high concentrations of ACH-806 inhibited viral assembly, but not replication, in a single-cycle production assay. The developed HCV culture systems will facilitate studies benefitting from expression of genotype-specific NS4A in a constant backbone in the context of the complete viral replication cycle, including functional studies and evaluations of the efficacy of antivirals. PMID:24060868

  1. Human fetal striatum-derived neural stem (NS) cells differentiate to mature neurons in vitro and in vivo. (United States)

    Monni, Emanuela; Cusulin, Carlo; Cavallaro, Maurizio; Lindvall, Olle; Kokaia, Zaal


    Clonogenic neural stem (NS) cell lines grown in adherent cultures have previously been established from embryonic stem cells and fetal and adult CNS in rodents and from human fetal brain and spinal cord. Here we describe the isolation of a new cell line from human fetal striatum (hNS cells). These cells showed properties of NS cells in vitro such as monolayer growth, high proliferation rate and expression of radial glia markers. The hNS cells expressed an early neuronal marker while being in the proliferative state. Under appropriate conditions, the hNS cells were efficiently differentiated to neurons, and after 4 weeks about 50% of the cells were βIII tubulin positive. They also expressed the mature neuronal marker NeuN and markers of neuronal subtypes, GABA, calbindin, and DARPP32. After intrastriatal implantation into newborn rats, the hNS cells survived and many of them migrated outside the transplant core into the surrounding tissue. A high percentage of cells in the grafts expressed the neuroblast marker DCX, indicating their neurogenic potential, and some of the cells differentiated to NeuN+ mature neurons. The human fetal striatum-derived NS cell line described here should be a useful tool for studies on cell replacement strategies in models of the striatal neuronal loss occurring in Huntington's disease and stroke.

  2. Phosphorylation of NS5A Serine-235 is essential to hepatitis C virus RNA replication and normal replication compartment formation

    Energy Technology Data Exchange (ETDEWEB)

    Eyre, Nicholas S., E-mail: [School of Biological Sciences and Research Centre for Infectious Diseases, University of Adelaide, Adelaide (Australia); Centre for Cancer Biology, SA Pathology, Adelaide (Australia); Hampton-Smith, Rachel J.; Aloia, Amanda L. [School of Biological Sciences and Research Centre for Infectious Diseases, University of Adelaide, Adelaide (Australia); Centre for Cancer Biology, SA Pathology, Adelaide (Australia); Eddes, James S. [Adelaide Proteomics Centre, School of Biological Sciences, University of Adelaide, Adelaide (Australia); Simpson, Kaylene J. [Victorian Centre for Functional Genomics, Peter MacCallum Cancer Centre, East Melbourne (Australia); The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville (Australia); Hoffmann, Peter [Adelaide Proteomics Centre, School of Biological Sciences, University of Adelaide, Adelaide (Australia); Institute for Photonics and Advanced Sensing (IPAS), University of Adelaide, Adelaide (Australia); Beard, Michael R. [School of Biological Sciences and Research Centre for Infectious Diseases, University of Adelaide, Adelaide (Australia); Centre for Cancer Biology, SA Pathology, Adelaide (Australia)


    Hepatitis C virus (HCV) NS5A protein is essential for HCV RNA replication and virus assembly. Here we report the identification of NS5A phosphorylation sites Ser-222, Ser-235 and Thr-348 during an infectious HCV replication cycle and demonstrate that Ser-235 phosphorylation is essential for HCV RNA replication. Confocal microscopy revealed that both phosphoablatant (S235A) and phosphomimetic (S235D) mutants redistribute NS5A to large juxta-nuclear foci that display altered colocalization with known replication complex components. Using electron microscopy (EM) we found that S235D alters virus-induced membrane rearrangements while EM using ‘APEX2’-tagged viruses demonstrated S235D-mediated enrichment of NS5A in irregular membranous foci. Finally, using a customized siRNA screen of candidate NS5A kinases and subsequent analysis using a phospho-specific antibody, we show that phosphatidylinositol-4 kinase III alpha (PI4KIIIα) is important for Ser-235 phosphorylation. We conclude that Ser-235 phosphorylation of NS5A is essential for HCV RNA replication and normal replication complex formation and is regulated by PI4KIIIα. - Highlights: • NS5A residues Ser-222, Ser-235 and Thr-348 are phosphorylated during HCV infection. • Phosphorylation of Ser-235 is essential to HCV RNA replication. • Mutation of Ser-235 alters replication compartment localization and morphology. • Phosphatidylinositol-4 kinase III alpha is important for Ser-235 phosphorylation.

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

    Directory of Open Access Journals (Sweden)

    Jinfeng Ti

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

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

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


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

  5. The non-structural protein μNS of piscine orthoreovirus (PRV) forms viral factory-like structures. (United States)

    Haatveit, Hanne Merethe; Nyman, Ingvild B; Markussen, Turhan; Wessel, Øystein; Dahle, Maria Krudtaa; Rimstad, Espen


    Piscine orthoreovirus (PRV) is associated with heart- and skeletal muscle inflammation in farmed Atlantic salmon. The virus is ubiquitous and found in both farmed and wild salmonid fish. It belongs to the family Reoviridae, closely related to the genus Orthoreovirus. The PRV genome comprises ten double-stranded RNA segments encoding at least eight structural and two non-structural proteins. Erythrocytes are the major target cells for PRV. Infected erythrocytes contain globular inclusions resembling viral factories; the putative site of viral replication. For the mammalian reovirus (MRV), the non-structural protein μNS is the primary organizer in factory formation. The analogous PRV protein was the focus of the present study. The subcellular location of PRV μNS and its co-localization with the PRV σNS, µ2 and λ1 proteins was investigated. We demonstrated that PRV μNS forms dense globular cytoplasmic inclusions in transfected fish cells, resembling the viral factories of MRV. In co-transfection experiments with μNS, the σNS, μ2 and λ1 proteins were recruited to the globular structures. The ability of μNS to recruit other PRV proteins into globular inclusions indicates that it is the main viral protein involved in viral factory formation and pivotal in early steps of viral assembly.

  6. Single-molecule imaging reveals the translocation and DNA looping dynamics of hepatitis C virus NS3 helicase. (United States)

    Lin, Chang-Ting; Tritschler, Felix; Lee, Kyung Suk; Gu, Meigang; Rice, Charles M; Ha, Taekjip


    Non-structural protein 3 (NS3) is an essential enzyme and a therapeutic target of hepatitis C virus (HCV). Compared to NS3-catalyzed nucleic acids unwinding, its translation on single stranded nucleic acids have received relatively little attention. To investigate the NS3h translocation with single-stranded nucleic acids substrates directly, we have applied a hybrid platform of single-molecule fluorescence detection combined with optical trapping. With the aid of mechanical manipulation and fluorescence localization, we probed the translocase activity of NS3h on laterally stretched, kilobase-size single-stranded DNA and RNA. We observed that the translocation rate of NS3h on ssDNA at a rate of 24.4 nucleotides per second, and NS3h translocates about three time faster on ssRNA, 74 nucleotides per second. The translocation speed was minimally affected by the applied force. A subpopulation of NS3h underwent a novel translocation mode on ssDNA where the stretched DNA shortened gradually and then recovers its original length abruptly before repeating the cycle repetitively. The speed of this mode of translocation was reduced with increasing force. With corroborating data from single-molecule fluorescence resonance energy transfer (smFRET) experiments, we proposed that NS3h can cause repetitive looping of DNA. The smFRET dwell time analysis showed similar translocation time between sole translocation mode versus repetitive looping mode, suggesting that the motor domain exhibits indistinguishable enzymatic activities between the two translocation modes. We propose a potential secondary nucleic acids binding site at NS3h which might function as an anchor point for translocation-coupled looping. © 2017 The Protein Society.

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

    Directory of Open Access Journals (Sweden)

    Gaya Prasad


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

  8. The HCV non-nucleoside inhibitor Tegobuvir utilizes a novel mechanism of action to inhibit NS5B polymerase function. (United States)

    Hebner, Christy M; Han, Bin; Brendza, Katherine M; Nash, Michelle; Sulfab, Maisoun; Tian, Yang; Hung, Magdeleine; Fung, Wanchi; Vivian, Randall W; Trenkle, James; Taylor, James; Bjornson, Kyla; Bondy, Steven; Liu, Xiaohong; Link, John; Neyts, Johan; Sakowicz, Roman; Zhong, Weidong; Tang, Hengli; Schmitz, Uli


    Tegobuvir (TGV) is a novel non-nucleoside inhibitor (NNI) of HCV RNA replication with demonstrated antiviral activity in patients with genotype 1 chronic HCV infection. The mechanism of action of TGV has not been clearly defined despite the identification of resistance mutations mapping to the NS5B polymerase region. TGV does not inhibit NS5B enzymatic activity in biochemical assays in vitro, suggesting a more complex antiviral mechanism with cellular components. Here, we demonstrate that TGV exerts anti-HCV activity utilizing a unique chemical activation and subsequent direct interaction with the NS5B protein. Treatment of HCV subgenomic replicon cells with TGV results in a modified form of NS5B with a distinctly altered mobility on a SDS-PAGE gel. Further analysis reveals that the aberrantly migrating NS5B species contains the inhibitor molecule. Formation of this complex does not require the presence of any other HCV proteins. The intensity of the aberrantly migrating NS5B species is strongly dependent on cellular glutathione levels as well as CYP 1A activity. Furthermore analysis of NS5B protein purified from a heterologous expression system treated with TGV by mass spectrometry suggests that TGV undergoes a CYP- mediated intracellular activation step and the resulting metabolite, after forming a glutathione conjugate, directly and specifically interacts with NS5B. Taken together, these data demonstrate that upon metabolic activation TGV is a specific, covalent inhibitor of the HCV NS5B polymerase and is mechanistically distinct from other classes of the non-nucleoside inhibitors (NNI) of the viral polymerase.

  9. The HCV non-nucleoside inhibitor Tegobuvir utilizes a novel mechanism of action to inhibit NS5B polymerase function.

    Directory of Open Access Journals (Sweden)

    Christy M Hebner

    Full Text Available Tegobuvir (TGV is a novel non-nucleoside inhibitor (NNI of HCV RNA replication with demonstrated antiviral activity in patients with genotype 1 chronic HCV infection. The mechanism of action of TGV has not been clearly defined despite the identification of resistance mutations mapping to the NS5B polymerase region. TGV does not inhibit NS5B enzymatic activity in biochemical assays in vitro, suggesting a more complex antiviral mechanism with cellular components. Here, we demonstrate that TGV exerts anti-HCV activity utilizing a unique chemical activation and subsequent direct interaction with the NS5B protein. Treatment of HCV subgenomic replicon cells with TGV results in a modified form of NS5B with a distinctly altered mobility on a SDS-PAGE gel. Further analysis reveals that the aberrantly migrating NS5B species contains the inhibitor molecule. Formation of this complex does not require the presence of any other HCV proteins. The intensity of the aberrantly migrating NS5B species is strongly dependent on cellular glutathione levels as well as CYP 1A activity. Furthermore analysis of NS5B protein purified from a heterologous expression system treated with TGV by mass spectrometry suggests that TGV undergoes a CYP- mediated intracellular activation step and the resulting metabolite, after forming a glutathione conjugate, directly and specifically interacts with NS5B. Taken together, these data demonstrate that upon metabolic activation TGV is a specific, covalent inhibitor of the HCV NS5B polymerase and is mechanistically distinct from other classes of the non-nucleoside inhibitors (NNI of the viral polymerase.

  10. Herschel SPIRE fourier transform spectrometer: calibration of its bright-source mode (United States)

    Lu, Nanyao; Polehampton, Edward T.; Swinyard, Bruce M.; Benielli, Dominique; Fulton, Trevor; Hopwood, Rosalind; Imhof, Peter; Lim, Tanya; Marchili, Nicola; Naylor, David A.; Schulz, Bernhard; Sidher, Sunil; Valtchanov, Ivan


    The Fourier Transform Spectrometer (FTS) of the Spectral and Photometric Imaging REceiver (SPIRE) on board the ESA Herschel Space Observatory has two detector setting modes: (a) a nominal mode, which is optimized for observing moderately bright to faint astronomical targets, and (b) a bright-source mode recommended for sources significantly brighter than 500 Jy, within the SPIRE FTS bandwidth of 446.7-1544 GHz (or 194-671 microns in wavelength), which employs a reduced detector responsivity and out-of-phase analog signal amplifier/demodulator. We address in detail the calibration issues unique to the bright-source mode, describe the integration of the bright-mode data processing into the existing pipeline for the nominal mode, and show that the flux calibration accuracy of the bright-source mode is generally within 2 % of that of the nominal mode, and that the bright-source mode is 3 to 4 times less sensitive than the nominal mode.

  11. Three Millisecond Pulsars in Fermi LAT Unassociated Bright Sources (United States)

    Ransom, S. M.; Ray, P. S.; Camilo, F.; Roberts, M. S. E.; Celik, O.; Wolff, M. T.; Cheung, C. C.; Kerr, M.; Pennucci, T.; DeCesar, M. E.; hide


    We searched for radio pulsars in 25 of the non-variable, unassociated sources in the Fermi LAT Bright Source List with the Green Bank Telescope at 820 MHz. We report the discovery of three radio and gamma-ray millisecond pulsar (MSPs) from a high Galactic latitude subset of these sources. All of the pulsars are in binary systems, which would have made them virtually impossible to detect in blind gamma-ray pulsation searches. They seem to be relatively normal, nearby (pulsars are power law in nature with exponential cutoffs at a few Ge V, as has been found with most other pulsars. The MSPs have all been detected as X-ray point sources. Their soft X-ray luminosities of approx 10(exp 30) - 10(exp 31) erg/s are typical of the rare radio MSPs seen in X-rays.

  12. Bright Spots in X-pinch Plasmas at 6 MA (United States)

    Sinars, D. B.; Ampleford, D. J.; Yu, E. P.; Jennings, C. A.; Cuneo, M. E.; Wenger, D. F.; Pikuz, S. A.; Shelkovenko, T. A.; Bland, S. N.; Chittenden, J. P.


    Bright, ˜1 μm, 10-100 ps x-ray sources with extreme plasma parameters are routinely created using X-pinch plasmas driven by 0.2 MA. Modeling suggests that even more extreme plasma parameters might be possible at higher current. We present data from the first 6 MA X-pinch experiments on the SATURN facility at Sandia National Laboratories. The mass required to pinch near peak current was surprisingly low (˜14 mg/cm vs. ˜3 mg/cm at 1 MA) and the smallest x-ray source measured was ˜60 μm in size. Following up on recent work by Pikuz et al. at 1 MA, experiments in September will use nested-array X-pinch implosions to improve the symmetry.

  13. Types and Distribution of Bright Materials in 4 Vesta (United States)

    Mittlefehldt, D. W.; Li, Jian-Yang; Pieters, C. M.; De Sanctis, M. C.; Schroder, S. E.; Hiesinger, H.; Blewett, D. T.; Russell, C. T.; Raymond, C. A.; Yingst, R. A.


    A strong case can be made that Vesta is the parent asteroid of the howardite, eucrite and diogenite (HED) meteorites [1]. As such, we have over a century of detailed sample analysis experience to call upon when formulating hypotheses regarding plausible lithologic diversity on Vesta. It thus came as a surprise when Dawn s Framing Camera (FC) first revealed distinctly localized materials of exceptionally low and high albedos, often closely associated. To understand the nature and origin of these materials, and how they inform us of the geological evolution of Vesta, task forces began their study. An initial step of the scientific endeavor is to develop a descriptive, non-genetic classification of objects to use as a basis for developing hypotheses and observational campaigns. Here we present a catalog of the types of light-toned deposits and their distribution across Vesta. A companion abstract [2] discusses possible origins of bright materials and the constraints they suggest for vestan geology.

  14. CCD Photometry of bright stars using objective wire mesh

    Energy Technology Data Exchange (ETDEWEB)

    Kamiński, Krzysztof; Zgórz, Marika [Astronomical Observatory Institute, Faculty of Physics, A. Mickiewicz University, Słoneczna 36, 60-286 Poznań (Poland); Schwarzenberg-Czerny, Aleksander, E-mail: [Copernicus Astronomical Centre, ul. Bartycka 18, PL 00-716 Warsaw (Poland)


    Obtaining accurate photometry of bright stars from the ground remains problematic due to the danger of overexposing the target and/or the lack of suitable nearby comparison stars. The century-old method of using objective wire mesh to produce multiple stellar images seems promising for the precise CCD photometry of such stars. Furthermore, our tests on β Cep and its comparison star, differing by 5 mag, are very encouraging. Using a CCD camera and a 20 cm telescope with the objective covered by a plastic wire mesh, in poor weather conditions, we obtained differential photometry with a precision of 4.5 mmag per two minute exposure. Our technique is flexible and may be tuned to cover a range as big as 6-8 mag. We discuss the possibility of installing a wire mesh directly in the filter wheel.

  15. Broad band spectral energy distribution studies of Fermi bright blazars

    Energy Technology Data Exchange (ETDEWEB)

    Monte, C., E-mail: claudia.monte@ba.infn.i [Istituto Nazionale di Fisica Nucleare, Sezione di Bari, I-70126 Bari (Italy); Dipartimento di Fisica ' M. Merlin' dell' Universita e del Politecnico, I-70126 Bari (Italy); Giommi, P.; Cavazzuti, E.; Gasparrini, D. [Agenzia Spaziale Italiana (ASI) Science Data Center I-00044 Frascati (Roma) (Italy); Raino, S. [Istituto Nazionale di Fisica Nucleare, Sezione di Bari, I-70126 Bari (Italy); Dipartimento di Fisica ' M. Merlin' dell' Universita e del Politecnico, I-70126 Bari (Italy); Fuhrmann, L.; Angelakis, E. [Max-Planck-Institut fuer Radioastronomie, Auf dem Huegel 69, D-53121 Bonn (Germany); Villata, M.; Raiteri, C.M. [INAF, Osservatorio Astronomico di Torino, I-10025 Pino Torinese (Italy); Perri, M. [Agenzia Spaziale Italiana (ASI) Science Data Center I-00044 Frascati (Roma) (Italy); Richards, J. [California Institute of Technology, Pasadena, CA (United States)


    The Fermi Gamma-ray Space Telescope was successfully launched on June 11, 2008 and has already opened a new era for gamma-ray astronomy. The Large Area Telescope (LAT), the main instrument on board Fermi, presents a significant improvement in sensitivity over its predecessor EGRET, due to its large field of view and effective area, combined with its excellent timing capabilities. The preliminary results of the Spectral Energy Distribution Analysis performed on a sample of bright blazars are presented. For this study, the data from the first three months of data collection of Fermi have been used. The analysis is extended down to radio, mm, near-IR, optical, UV and X-ray bands and up to TeV energies based on unprecedented sample of simultaneous multi-wavelength observations by GASP-WEBT.

  16. Broad band spectral energy distribution studies of Fermi bright blazars (United States)

    Monte, C.; Giommi, P.; Cavazzuti, E.; Gasparrini, D.; Rainò, S.; Fuhrmann, L.; Angelakis, E.; Villata, M.; Raiteri, C. M.; Perri, M.; Richards, J.


    The Fermi Gamma-ray Space Telescope was successfully launched on June 11, 2008 and has already opened a new era for gamma-ray astronomy. The Large Area Telescope (LAT), the main instrument on board Fermi, presents a significant improvement in sensitivity over its predecessor EGRET, due to its large field of view and effective area, combined with its excellent timing capabilities. The preliminary results of the Spectral Energy Distribution Analysis performed on a sample of bright blazars are presented. For this study, the data from the first three months of data collection of Fermi have been used. The analysis is extended down to radio, mm, near-IR, optical, UV and X-ray bands and up to TeV energies based on unprecedented sample of simultaneous multi-wavelength observations by GASP-WEBT.

  17. A complete sample of long bright Swift gamma ray bursts. (United States)

    Tagliaferri, Gianpiero; Salvaterra, Ruben; Campana, Sergio; Covino, Stefano; D'Avanzo, Paolo; Fugazza, Dino; Ghirlanda, Giancarlo; Ghisellini, Gabriele; Melandri, Andrea; Nava, Lara; Sbarufatti, Boris; Vergani, Susanna


    Complete samples are the basis of any population study. To this end, we selected a complete subsample of Swift long bright gamma ray bursts (GRBs). The sample, made up of 58 bursts, was selected by considering bursts with favourable observing conditions for ground-based follow-up observations and with the 15-150 keV 1 s peak flux above a flux threshold of 2.6 photons cm(-2) s(-1). This sample has a redshift completeness level higher than 90 per cent. Using this complete sample, we investigate the properties of long GRBs and their evolution with cosmic time, focusing in particular on the GRB luminosity function, the prompt emission spectral-energy correlations and the nature of dark bursts.

  18. Investigation of fundamental limits to beam brightness available from photoinjectors

    Energy Technology Data Exchange (ETDEWEB)

    Bazarov, Ivan [Cornell Univ., Ithaca, NY (United States)


    The goal of this project was investigation of fundamental limits to beam brightness available from photoinjectors. This basic research in accelerator physics spanned over 5 years aiming to extend the fundamental understanding of high average current, low emittance sources of relativistic electrons based on photoemission guns, a necessary prerequisite for a new generation of coherent X-ray synchrotron radiation facilities based on continuous duty superconducting linacs. The program focused on two areas critical to making advances in the electron source performance: 1) the physics of photocathodes for the production of low emittance electrons and 2) control of space charge forces in the immediate vicinity to the cathode via 3D laser pulse shaping.

  19. Relationships between brightness of nighttime lights and population density (United States)

    Naizhuo, Z.


    Brightness of nighttime lights has been proven to be a good proxy for socioeconomic and demographic statistics. Moreover, the satellite nighttime lights data have been used to spatially disaggregate amounts of gross domestic product (GDP), fossil fuel carbon dioxide emission, and electric power consumption (Ghosh et al., 2010; Oda and Maksyutov, 2011; Zhao et al., 2012). Spatial disaggregations were performed in these previous studies based on assumed linear relationships between digital number (DN) value of pixels in the nighttime light images and socioeconomic data. However, reliability of the linear relationships was never tested due to lack of relative high-spatial-resolution (equal to or finer than 1 km × 1 km) statistical data. With the similar assumption that brightness linearly correlates to population, Bharti et al. (2011) used nighttime light data as a proxy for population density and then developed a model about seasonal fluctuations of measles in West Africa. The Oak Ridge National Laboratory used sub-national census population data and high spatial resolution remotely-sensed-images to produce LandScan population raster datasets. The LandScan population datasets have 1 km × 1 km spatial resolution which is consistent with the spatial resolution of the nighttime light images. Therefore, in this study I selected 2008 LandScan population data as baseline reference data and the contiguous United State as study area. Relationships between DN value of pixels in the 2008 Defense Meteorological Satellite Program's Operational Linescan System (DMSP-OLS) stable light image and population density were established. Results showed that an exponential function can more accurately reflect the relationship between luminosity and population density than a linear function. Additionally, a certain number of saturated pixels with DN value of 63 exist in urban core areas. If directly using the exponential function to estimate the population density for the whole brightly

  20. Novel Bat Influenza Virus NS1 Proteins Bind Double-Stranded RNA and Antagonize Host Innate Immunity. (United States)

    Turkington, Hannah L; Juozapaitis, Mindaugas; Kerry, Philip S; Aydillo, Teresa; Ayllon, Juan; García-Sastre, Adolfo; Schwemmle, Martin; Hale, Benjamin G


    We demonstrate that novel bat HL17NL10 and HL18NL11 influenza virus NS1 proteins are effective interferon antagonists but do not block general host gene expression. Solving the RNA-binding domain structures revealed the canonical NS1 symmetrical homodimer, and RNA binding required conserved basic residues in this domain. Interferon antagonism was strictly dependent on RNA binding, and chimeric bat influenza viruses expressing NS1s defective in this activity were highly attenuated in interferon-competent cells but not in cells unable to establish antiviral immunity. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

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


    Bhattacharya, Joydeep; Lindsen, Job P.


    A prevalent conceptual metaphor is the association of the concepts of good and evil with brightness and darkness, respectively. Music cognition, like metaphor, is possibly embodied, yet no study has addressed the question whether musical emotion can modulate brightness judgment in a metaphor consistent fashion. In three separate experiments, participants judged the brightness of a grey square that was presented after a short excerpt of emotional music. The results of Experiment 1 showed that ...

  2. Suomi NPP ATMS Level 1B Brightness Temperature V1 (SNPPATMSL1B) at GES DISC (United States)

    National Aeronautics and Space Administration — The Advanced Technology Microwave Sounder (ATMS) Level 1B data files contain brightness temperature measurements along with ancillary spacecraft, instrument, and...

  3. Enhanced-Resolution SSM/I and AMSR-E Daily Polar Brightness Temperatures (United States)

    National Aeronautics and Space Administration — This data set contains enhanced-resolution brightness temperatures produced using the Scatterometer Image Reconstruction (SIR) algorithm developed by the Microwave...

  4. CLPX-Satellite: AMSR-E Brightness Temperature Grids, Version 1 (United States)

    National Aeronautics and Space Administration — This data set includes Aqua Advanced Microwave Scanning Radiometer - Earth Observing System (AMSR-E) passive microwave brightness temperatures gridded to the...

  5. CD56bright NK cells exhibit potent antitumor responses following IL-15 priming. (United States)

    Wagner, Julia A; Rosario, Maximillian; Romee, Rizwan; Berrien-Elliott, Melissa M; Schneider, Stephanie E; Leong, Jeffrey W; Sullivan, Ryan P; Jewell, Brea A; Becker-Hapak, Michelle; Schappe, Timothy; Abdel-Latif, Sara; Ireland, Aaron R; Jaishankar, Devika; King, Justin A; Vij, Ravi; Clement, Dennis; Goodridge, Jodie; Malmberg, Karl-Johan; Wong, Hing C; Fehniger, Todd A


    NK cells, lymphocytes of the innate immune system, are important for defense against infectious pathogens and cancer. Classically, the CD56dim NK cell subset is thought to mediate antitumor responses, whereas the CD56bright subset is involved in immunomodulation. Here, we challenge this paradigm by demonstrating that brief priming with IL-15 markedly enhanced the antitumor response of CD56bright NK cells. Priming improved multiple CD56bright cell functions: degranulation, cytotoxicity, and cytokine production. Primed CD56bright cells from leukemia patients demonstrated enhanced responses to autologous blasts in vitro, and primed CD56bright cells controlled leukemia cells in vivo in a murine xenograft model. Primed CD56bright cells from multiple myeloma (MM) patients displayed superior responses to autologous myeloma targets, and furthermore, CD56bright NK cells from MM patients primed with the IL-15 receptor agonist ALT-803 in vivo displayed enhanced ex vivo functional responses to MM targets. Effector mechanisms contributing to IL-15-based priming included improved cytotoxic protein expression, target cell conjugation, and LFA-1-, CD2-, and NKG2D-dependent activation of NK cells. Finally, IL-15 robustly stimulated the PI3K/Akt/mTOR and MEK/ERK pathways in CD56bright compared with CD56dim NK cells, and blockade of these pathways attenuated antitumor responses. These findings identify CD56bright NK cells as potent antitumor effectors that warrant further investigation as a cancer immunotherapy.

  6. Enhanced-Resolution SSM/I and AMSR-E Daily Polar Brightness Temperatures, Version 1 (United States)

    National Aeronautics and Space Administration — This data set contains enhanced-resolution brightness temperatures produced using the Scatterometer Image Reconstruction (SIR) algorithm developed by the Microwave...

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

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


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

  8. A Novel Adeno-Associated Virus-Based Genetic Vaccine Encoding the Hepatitis C Virus NS3/4 Protein Exhibits Immunogenic Properties in Mice Superior to Those of an NS3-Protein-Based Vaccine.

    Directory of Open Access Journals (Sweden)

    Fengqin Zhu

    Full Text Available More than 170 million individuals worldwide are infected with hepatitis C virus (HCV, and up to an estimated 30% of chronically infected individuals will go on to develop progressive liver disease. Despite the recent advances in antiviral treatment of HCV infection, it remains a major public health problem. Thus, development of an effective vaccine is urgently required. In this study, we constructed novel adeno-associated virus (AAV vectors expressing the full-length NS3 or NS3/4 protein of HCV genotype 1b. The expression of the NS3 or NS3/4 protein in HepG2 cells was confirmed by western blotting. C57BL/6 mice were intramuscularly immunised with a single injection of AAV vectors, and the resultant immune response was investigated. The AAV2/rh32.33.NS3/4 vaccine induced stronger humoral and cellular responses than did the AAV2/rh32.33.NS3 vaccine. Our results demonstrate that AAV-based vaccines exhibit considerable potential for the development of an effective anti-HCV vaccine.

  9. NS-Kaća: High-protein, very early soybean cultivar

    Directory of Open Access Journals (Sweden)

    Vidić Miloš


    Full Text Available NS-Kaća, a new, very early soybean cultivar, has been created at the Institute of Field and Vegetable Crops Novi Sad by crossing domestic and foreign genotypes. The main traits of the cultivar are its early maturity, which placed it into the 000 maturity group, and excellent technological quality of grain. Due to the short vegetation period, it is primarily sown as the second crop in our country, or as the first crop in northern countries (Russia, Ukraine, Austria, Slovenia and hilly regions. It provides economically justifiable yield gain during the second crop harvest if sowing is conducted by the end of early July, so each day of sowing delay significantly reduces yield. It achieved significantly higher yields in the multiannual macro- and micro-trials compared to standard cultivars from the same maturity group. Producers are advised to sow 600,000 germinated seeds per hectare. The cultivar is also suitable for narrow-row planting (with inter-row spacing of 12.5 cm or 25 cm, whereby the planting rate can be increased by 15-20%. Seed of the cultivar NS-Kaća can also be used as raw material in the production of products intended for human consumption, thanks to the high protein content which is usually between 44% and 47% (in absolutely dry grain. It is suitable for the production of soy milk and soy milk products, due to its large grain, coated with light-yellow seed coat without mottled appearance, and weak expression of hilum colour same as the seed coat, which provides a natural, milkywhite colour of the final products. Development and dissemination of the newly released cultivar NS-Kaća is a major step forward in soybean breeding, as the cultivar exhibited a significantly higher protein content while maintaining its high-yielding potential, despite the strong negative correlation of these traits.

  10. The influence of medium conductivity on cells exposed to nsPEF (United States)

    Moen, Erick K.; Ibey, Bennett L.; Roth, Caleb C.; Barnes, Ronald A.; Beier, Hope T.; Armani, Andrea M.


    Nanosecond pulsed electric fields (nsPEF) have proven useful for transporting cargo across cell membranes and selectively activating cellular pathways. The chemistry and biophysics governing this cellular response, however, are complex and not well understood. Recent studies have shown that the conductivity of the solution cells are exposed in could play a significant role in plasma membrane permeabilization and, thus, the overall cellular response. Unfortunately, the means of detecting this membrane perturbation has traditionally been limited to analyzing one possible consequence of the exposure - diffusion of molecules across the membrane. This method has led to contradictory results with respect to the relationship between permeabilization and conductivity. Diffusion experiments also suffer from "saturation conditions" making multi-pulse experiments difficult. As a result, this method has been identified as a key stumbling block to understanding the effects of nsPEF exposure. To overcome these limitations, we recently developed a nonlinear optical imaging technique based on second harmonic generation (SHG) that allows us to identify nanoporation in live cells during the pulse in a wide array of conditions. As a result, we are able to explore and fully test whether lower conductivity extracellular solutions could induce more efficient nanoporation. This hypothesis is based on membrane charging and the relative difference between the extracellular solution and the cytoplasm. The experiments also allow us to test the noise floor of our methodology against the effects of ion leakage. The results emphasize that the electric field, not ionic phenomenon, are the driving force behind nsPEF-induced membrane nanoporation.

  11. Toward the laboratory identification of the not-so-simple NS2 neutral and anion isomers (United States)

    Fortenberry, Ryan C.; Thackston, Russell; Francisco, Joseph S.; Lee, Timothy J.


    The NS2 radical is a simple arrangement of atoms with a complex electronic structure. This molecule was first reported by Hassanzadeh and Andrew's group [J. Am. Chem. Soc. 114, 83 (1992)] through Ar matrix isolation experiments. In the quarter century since this seminal work was published, almost nothing has been reported about nitrogen disulfide even though NS2 is isovalent with the common NO2. The present study aims to shed new insight into possible challenges with the characterization of this radical. No less than three potential energy surfaces all intersect in the C2v region of the SNS radical isomer. A type-C Renner-Teller molecule is present for the linear 2Πu state where the potential energy surface is fully contained within the 2.05 kcal/mol lower energy X ˜ 2A1 state. A C2v, 1 2B1 state is present in this same region, but a double excitation is required to access this state from the X ˜ 2A1 state of SNS. Additionally, a 1 2A' NSS isomer is also present but with notable differences in the geometry from the global minimum. Consequently, the rovibronic spectrum of these NS2 isomers is quite complicated. While the present theory and previous Ar matrix experiments agree well on isotopic shifts, they differ notably for the absolute fundamental vibrational frequency transitions. These differences are likely a combination of matrix shifts and issues associated with the neglect of non-adiabatic coupling in the computations. In either case, it is clear that high-resolution gas phase experimental observations will be complicated to sort. The present computations should aid in their analysis.

  12. Genetic variability of Myzus persicae nicotianae densovirus based on partial NS and VP gene sequences. (United States)

    Song, X R; Tang, S H; Tang, Z Q; Yang, X M; Wang, X W; Wang, X F; Xu, P J; Ren, G W


    We previously described a novel densovirus [Myzus persicae nicotianae densovirus (MpnDV)] infecting M. persicae nicotianae (Hemiptera: Aphididae) with 34% prevalence. This single-stranded DNA virus has a 5480-nucleotide ambisense genome and belongs to the Densovirinae subfamily within the family Parvoviridae. In the present study, we estimated the genetic diversity of MpnDV using partial nonstructural protein (NS) and capsid protein (VP) gene sequences from 10 locations in China. First, we identified MpnDV-positive samples by amplifying a 445-bp fragment with primers MpDVF/MpDVR. Subsequently, we amplified and sequenced COI genes with primers MpCOIF/ MpCOIR, and partial NS and VP sequences with primers MpnDVF1/MpnDVR1. The respective 655-, 1461-, and 423-bp COI, NS, and VP fragments were used to analyze the genetic diversity of MpnDV using MEGA 6.0 and DnaSP 5.0. The high level of identity shared by all COI sequences (>99%) suggested that the aphids sampled were of the same species, and indicated population homogeneity across the 10 locations investigated. The nucleotide diversity of MpnDV sequences (0.0020 ± 0.0025) was significantly higher than that of the COI genes (0.0002 ± 0.0005). The pairwise fixation index for MpnDV was 0.832, and the total gene flow was 0.05. Phylogenetic analysis revealed that the MpnDV haplotypes clustered according to geographical location, except for those from the Liaoning and Shanxi provinces. In conclusion, MpnDV demonstrated a low level of gene flow and high genetic diversity, suggesting that it is vertically transmitted, and implying that endosymbiotic viruses could be used as markers in studies of insect population genetics.

  13. H-NS suppresses pilE intragenic transcription and antigenic variation in Neisseria gonorrhoeae. (United States)

    Masters, Thao L; Wachter, Shaun; Wachter, Jenny; Hill, Stuart A


    Initially, pilE transcription in Neisseria gonorrhoeae appeared to be complicated, yet it was eventually simplified into a model where integration host factor activates a single -35/ -10 promoter. However, with the advent of high-throughput RNA sequencing, numerous small pil-specific RNAs (sense as well as antisense) have been identified at the pilE locus as well as at various pilS loci. Using a combination of in vitro transcription, site-directed mutagenesis, Northern analysis and quantitative reverse transcriptase PCR (qRT-PCR) analysis, we have identified three additional non-canonical promoter elements within the pilE gene; two are located within the midgene region (one sense and one antisense), with the third, an antisense promoter, located immediately downstream of the pilE ORF. Using strand-specific qRT-PCR analysis, an inverse correlation exists between the level of antisense expression and the amount of sense message. By their nature, promoter sequences tend to be AT-rich. In Escherichia coli, the small DNA-binding protein H-NS binds to AT-rich sequences and inhibits intragenic transcription. In N. gonorrhoeae hns mutants, pilE antisense transcription was increased twofold, with a concomitant decrease in sense transcript levels. However, most noticeably in these mutants, the absence of H-NS protein caused pilE/pilS recombination to increase dramatically when compared with WT values. Consequently, H-NS protein suppresses pilE intragenic transcription as well as antigenic variation through the pilE/pilS recombination system.

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

    Directory of Open Access Journals (Sweden)

    Ping Jihui


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

  15. Depopulation of lowly excited ns-states of Rb colliding with the He atom

    Energy Technology Data Exchange (ETDEWEB)

    Verma, S.K. [Jagdam College, Chapra (India). Dept. of Physics; Khan, A.A. [ZAI College, Siwan (India). Dept. of Physics; Kumar, V. [Rajendra College, Chapra (India). Dept. of Physics; Kumar, A. [JP University, Chapra (India). Dept. of Physics


    A semiclassical impact-parameter method has been used to study the total depopulation of lowly excited ns-states of the Rb atom colliding with ground-state He in the thermal energy region. A fairly large basis set of STO has been used to generate MO states and then a 14-state calculation has been carried out to evaluate the total as well as individual cross sections for quenching. A comparative study with the previously investigated Li-He and Na-He pairs is also presented. (Author).

  16. Evaluation of NS sunflower hybrids in small-plot trials via hybrid × location interaction

    Directory of Open Access Journals (Sweden)

    Balalić Igor


    Full Text Available The aim of this study was to evaluate NS sunflower hybrids on the basis of the results of seed yield, seed oil content and oil yield obtained in a network of small-plot trials in Serbia in 2011. The trial included 9 hybrids and 14 locations. Seed yield, seed oil content and oil yield were significantly different in small-plot trials in the investigated regions of Serbia. The highest average seed yield was produced by Sremac (3.67 t ha-1, Velja (3.62 t ha-1, Duško (3.56 t ha-1 and Novosađanin (3.55 t ha-1. On the location Rimski šančevi the seed yield (4.48 t ha-1 was significantly highest. Average oil content for hybrids grown in 14 locations was 47.25%. Hybrids Baća (50.26%, NS-H-111 (48.91%, Bačvanin (48.70% and Novosađanin (47.83% showed the highest average seed oil content. The highest average oil yield was produced by Baća (1.71 t ha-1, Novosađanin (1.70, Velja (1.67 t ha-1, Sremac (1.63 t ha-1 and NS-H-111 (1.63 t ha-1. Locations with the highest oil yield were Rimski šančevi (2.03 t ha-1 and Sombor (1.96 t ha-1. In the four-year trials in Vojvodina, the average seed yield of 9 hybrids was 3.35 t ha-1. Seed yield over general mean was reached by three hybrids (Duško, Sremac and Velja. The highest seed yield was reached by hybrid Duško (3.56 t ha-1. AMMI1 biplot showed that most stable and with high seed and oil yield were the hybrids Duško, Sremac and Baća, and for oil content Baća, Bačvanin and NS-H-111.

  17. Rotating NS5-brane solution and its exact string theoretical description


    Sfetsos, K.


    We construct the most general solution in type-II string theory that represents N coincident non-extremal rotating NS5-branes and determine the relevant thermodynamic quantities. We show that in the field theory limit, it has an exact description. In particular, it can be obtained by an O(3,3) duality transformation on the exact string background for the coset model SL(2,R)_{-N}/U(1) \\times SU(2)_N. In the extreme supersymmetric limit we recover the multicenter solution, with a ring singulari...

  18. Geheime Fotos. Die Kooperation von Associated Press und NS-Regime (1942–1945

    Directory of Open Access Journals (Sweden)

    Norman Domeier


    Full Text Available This article is based on a new archival find from the papers of foreign correspondent Louis P. Lochner. It proves the existence of a secret German-American cooperation between Associated Press (AP and the ›Bureau Laux‹, an agency of the SS and the German Foreign Office, during the war years 1942–1945. With the permission of the Roosevelt administration, AP and the Bureau Laux exchanged photos via diplomatic pouch on a daily basis until spring 1945, first via Lisbon and from 1944 via Stockholm as well. Approximately 40,000 photos were swapped in this way between the war enemies while the battles of the Second World War were fought and the Holocaust was taking place. In Berlin, the AP photos were presented daily to the highest Nazi leadership. They were then also used for anti-American and anti-Semitic propaganda in the German press. Conversely, thousands of Nazi photos received by AP New York via Lisbon and Stockholm were printed in the American and international press. This article sheds new light on both AP as a news and picture agency and on foreign reporting during the Nazi era and the Second World War. * * * Der im vorliegenden Aufsatz präsentierte Quellenfund aus dem Nachlass des Auslandskorrespondenten Louis P. Lochner belegt eine geheime deutsch-amerikanische Kooperation zwischen Associated Press (AP und dem »Büro Laux«, einer Agentur von SS und Auswärtigem Amt, während der Kriegsjahre 1942–1945. Mit Genehmigung der Roosevelt-Administration tauschten AP und Büro Laux bis zum Frühjahr 1945 täglich per Diplomatenpost Fotomaterial aus – zunächst via Lissabon, ab 1944 auch via Stockholm. Schätzungsweise 40.000 Fotos wurden so zwischen den Feinden übermittelt, während die Schlachten des Zweiten Weltkrieges geschlagen wurden und der Holocaust stattfand. In Berlin war das AP-Fotomaterial für die oberste Führung des NS-Regimes bestimmt; zudem wurde es für antiamerikanische und antisemitische Propaganda in der NS

  19. Water data: bad TPC pads, 3.6 µs and 100 ns problems

    CERN Document Server

    Dydak, F; Nefedov, Y; Wotschack, J; Zhemchugov, A


    Out of the 3972 pads of the HARP TPC, about 9% are 'bad' and not useful for the correct reconstruction of clusters. Bad pads comprise dead pads, noisy pads, and pads with low or undefined amplification. Pads may be bad at one time, but not at another. This memo discusses the sources of information which were used to declare a pad 'bad', and gives the list of bad pads for the water data (runs 19146 to 19301). Also, the 3.6 µs and 100 ns problems of the TPC readout are discussed, including the corrective measures which have been taken.

  20. Copper bromide vapour laser with an output pulse duration of up to 320 ns

    Energy Technology Data Exchange (ETDEWEB)

    Gubarev, F A; Fedorov, K V; Evtushenko, G S [National Research Tomsk Polytechnic University, Tomsk (Russian Federation); Fedorov, V F; Shiyanov, D V [V.E. Zuev Institute of Atmospheric Optics, Siberian Branch, Russian Academy of Sciences, Tomsk (Russian Federation)


    We report the development of a copper bromide vapour laser with an output pulse duration of up to 320 ns. To lengthen the pulse, the discharge current was limited using a compound switch comprising a pulsed hydrogen thyratron and a tacitron. This technique permits limiting the excitation of the working levels at the initial stage of the discharge development to lengthen the inversion lifetime. The longest duration of a laser pulse was reached in tubes 25 and 50 mm in diameter for a pulse repetition rate of 2 – 4 kHz. (lasers and laser beams)

  1. Simulación de redes móviles ad hoc mediante ns-3


    Yuste Delgado, Antonio


    Introducción a la herramienta de simulación de redes network simulator 3 (ns-3). Este simulador es una de los programas más utilizados en la actualidad para la simulación de redes de diversos tipos, desde las redes ad hoc a redes móviles. El profesor Antonio Yuste especialista en protocolos de enrutamiento en redes móviles ad hoc utiliza este software en sus simulaciones. El objetivo de la charla es una dar una visión general del simulador y explicarnos cómo simular redes ad hoc móviles. U...

  2. The Norovirus NS3 Protein Is a Dynamic Lipid- and Microtubule-Associated Protein Involved in Viral RNA Replication. (United States)

    Cotton, Ben T; Hyde, Jennifer L; Sarvestani, Soroush T; Sosnovtsev, Stanislav V; Green, Kim Y; White, Peter A; Mackenzie, Jason M


    Norovirus (NoV) infections are a significant health burden to society, yet the lack of reliable tissue culture systems has hampered the development of appropriate antiviral therapies. Here we show that the NoV NS3 protein, derived from murine NoV (MNV), is intimately associated with the MNV replication complex and the viral replication intermediate double-stranded RNA (dsRNA). We observed that when expressed individually, MNV NS3 and NS3 encoded by human Norwalk virus (NV) induced the formation of distinct vesicle-like structures that did not colocalize with any particular protein markers to cellular organelles but localized to cellular membranes, in particular those with a high cholesterol content. Both proteins also showed some degree of colocalization with the cytoskeleton marker β-tubulin. Although the distribution of MNV and NV NS3s were similar, NV NS3 displayed a higher level of colocalization with the Golgi apparatus and the endoplasmic reticulum (ER). However, we observed that although both proteins colocalized in membranes counterstained with filipin, an indicator of cholesterol content, MNV NS3 displayed a greater association with flotillin and stomatin, proteins known to associate with sphingolipid- and cholesterol-rich microdomains. Utilizing time-lapse epifluorescence microscopy, we observed that the membrane-derived vesicular structures induced by MNV NS3 were highly motile and dynamic in nature, and their movement was dependent on intact microtubules. These results begin to interrogate the functions of NoV proteins during virus replication and highlight the conserved properties of the NoV NS3 proteins among the seven Norovirus genogroups. Many mechanisms involved in the replication of norovirus still remain unclear, including the role for the NS3 protein, one of seven nonstructural viral proteins, which remains to be elucidated. This study reveals that murine norovirus (MNV) NS3 is intimately associated with the viral replication complex and ds

  3. NS5A Sequence Heterogeneity and Mechanisms of Daclatasvir Resistance in Hepatitis C Virus Genotype 4 Infection. (United States)

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


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

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


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


    Background. ?Daclatasvir is an NS5A inhibitor approved for treatment of infection due to hepatitis C virus (HCV) genotypes (GTs) 1?4. To support daclatasvir use in HCV genotype 4 infection, we examined a diverse genotype 4?infected population for HCV genotype 4 subtype prevalence, NS5A polymorphisms at residues associated with daclatasvir resistance (positions 28, 30, 31, or 93), and their effects on daclatasvir activity in vitro and clinically. Methods. ?We performed phylogenetic analysis of...

  5. Roles of the phosphorylation of specific serines and threonines in the NS1 protein of human influenza A viruses. (United States)

    Hsiang, Tien-Ying; Zhou, Ligang; Krug, Robert M


    We demonstrate that phosphorylation of the NS1 protein of a human influenza A virus occurs not only at the threonine (T) at position 215 but also at serines (Ss), specifically at positions 42 and 48. By generating recombinant influenza A/Udorn/72 (Ud) viruses that encode mutant NS1 proteins, we determined the roles of these phosphorylations in virus replication. At position 215 only a T-to-A substitution attenuated replication, whereas other substitutions (T to E to mimic constitutive phosphorylation, T to N, and T to P, the amino acid in avian influenza A virus NS1 proteins) had no effect. We conclude that attenuation resulting from the T-to-A substitution at position 215 is attributable to a deleterious structural change in the NS1 protein that is not caused by other amino acid substitutions and that phosphorylation of T215 does not affect virus replication. At position 48 neither an S-to-A substitution nor an S-to-D substitution that mimics constitutive phosphorylation affected virus replication. In contrast, at position 42, an S-to-D, but not an S-to-A, substitution caused attenuation. The S-to-D substitution eliminates detectable double-stranded RNA binding by the NS1 protein, accounting for attenuation of virus replication. We show that protein kinase C α (PKCα) catalyzes S42 phosphorylation. Consequently, the only phosphorylation of the NS1 protein of this human influenza A virus that regulates its replication is S42 phosphorylation catalyzed by PKCα. In contrast, phosphorylation of Ts or Ss in the NS1 protein of the 2009 H1N1 pandemic virus was not detected, indicating that NS1 phosphorylation probably does not play any role in the replication of this virus.

  6. Four Aromatic Sulfates with an Inhibitory Effect against HCV NS3 Helicase from the Crinoid Alloeocomatella polycladia (United States)

    Hermawan, Idam; Furuta, Atsushi; Higashi, Masahiro; Fujita, Yoshihisa; Akimitsu, Nobuyoshi; Yamashita, Atsuya; Moriishi, Kohji; Tsuneda, Satoshi; Tani, Hidenori; Nakakoshi, Masamichi; Tsubuki, Masayoshi; Sekiguchi, Yuji; Noda, Naohiro; Tanaka, Junichi


    Bioassay-guided separation of a lipophilic extract of the crinoid Alloeocomatella polycladia, inhibiting the activity of HCV NS3 helicase, yielded two groups of molecules: cholesterol sulfate and four new aromatic sulfates 1–4. The structures of the aromatics were elucidated by spectroscopic analysis in addition to theoretical studies. The aromatic sulfates 1–4 showed moderate inhibition against NS3 helicase with IC50 values of 71, 95, 7, and 5 μM, respectively. PMID:28398249

  7. NS309 decreases rat detrusor smooth muscle membrane potential and phasic contractions by activating SK3 channels (United States)

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


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

  8. Kinetic analyses reveal potent and early blockade of hepatitis C virus assembly by NS5A inhibitors. (United States)

    McGivern, David R; Masaki, Takahiro; Williford, Sara; Ingravallo, Paul; Feng, Zongdi; Lahser, Frederick; Asante-Appiah, Ernest; Neddermann, Petra; De Francesco, Raffaele; Howe, Anita Y; Lemon, Stanley M


    All-oral regimens combining different classes of direct-acting antivirals (DAA) are highly effective for treatment of patients with chronic hepatitis C. NS5A inhibitors will likely form a component of future interferon-sparing treatment regimens. However, despite their potential, the detailed mechanism of action of NS5A inhibitors is unclear. To study their mechanisms, we compared their kinetics of antiviral suppression with those of other classes of DAA, using the hepatitis C virus genotype 1a cell culture-infectious virus H77S.3. We performed detailed kinetic analyses of specific steps in the hepatitis C virus life cycle using cell cultures incubated with protease inhibitors, polymerase inhibitors, or NS5A inhibitors. Assays were designed to measure active viral RNA synthesis and steady-state RNA abundance, polyprotein synthesis, virion assembly, and infectious virus production. Despite their high potency, NS5A inhibitors were slow to inhibit viral RNA synthesis compared with protease or polymerase inhibitors. By 24 hours after addition of an NS5A inhibitor, polyprotein synthesis was reduced <50%, even at micromolar concentrations. In contrast, inhibition of virus release by NS5A inhibitors was potent and rapid, with onset of inhibition as early as 2 hours. Cells incubated with NS5A inhibitors were rapidly depleted of intracellular infectious virus and RNA-containing hepatitis C virus particles, indicating a block in virus assembly. DAAs that target NS5A rapidly inhibit intracellular assembly of genotype 1a virions. They also inhibit formation of functional replicase complexes, but have no activity against preformed replicase, thereby resulting in slow shut-off of viral RNA synthesis. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  9. Discovery of silyl proline containing HCV NS5A inhibitors with pan-genotype activity: SAR development. (United States)

    Nair, Anilkumar G; Zeng, Qingbei; Selyutin, Oleg; Rosenblum, Stuart B; Jiang, Yueheng; Yang, De-Yi; Keertikar, Kerry; Zhou, Guowei; Dwyer, Michael P; Kim, Seong Heon; Shankar, Bandarpalle; Yu, Wensheng; Tong, Ling; Chen, Lei; Mazzola, Robert; Caldwell, John; Tang, Haiqun; Allard, Melissa L; Buckle, Ronald N; Gauuan, Polivina Jolicia F; Holst, Christian L; Martin, Gregory S; Naicker, Kannan P; Vellekoop, Samuel; Agrawal, Sony; Liu, Rong; Kong, Rong; Ingravallo, Paul; Xia, Ellen; Zhai, Ying; Nomeir, Amin; Kozlowski, Joseph A


    HCV NS5A inhibitors have shown impressive in vitro potency profiles in HCV replicon assays thus making them attractive components for inclusion in an all oral fixed dose combination treatment regimen. Herein we describe the research efforts that led to the discovery of silyl proline containing HCV NS5A inhibitors such as 7e and 8a with pan-genotype activity profile and acceptable pharmacokinetic properties. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Probing the relation between protein–protein interactions and DNA binding for a linker mutant of the bacterial nucleoid protein H-NS

    NARCIS (Netherlands)

    Giangrossi, M.; Wintraecken, K.; Spurio, R.; Vries, de R.J.


    We have investigated the relationship between oligomerization in solution and DNA binding for the bacterial nucleoid protein H-NS. This was done by comparing oligomerization and DNA binding of H-NS with that of a H-NS D68V-D71V linker mutant. The double linker mutation D68V-D71V, that makes the

  11. Controlling excitons. Concepts for phosphorescent organic LEDs at high brightness

    Energy Technology Data Exchange (ETDEWEB)

    Reineke, Sebastian


    This work focusses on the high brightness performance of phosphorescent organic light-emitting diodes (OLEDs). The use of phosphorescent emitter molecules in OLEDs is essential to realize internal electron-photon conversion efficiencies of 100 %. However, due to their molecular nature, the excited triplet states have orders of magnitude longer time constants compared to their fluorescent counterparts which, in turn, strongly increases the probability of bimolecular annihilation. As a consequence, the efficiencies of phosphorescent OLEDs decline at high brightness - an effect known as efficiency roll-off, for which it has been shown to be dominated by triplet-triplet annihilation (TTA). In this work, TTA of the archetype phosphorescent emitter Ir(ppy){sub 3} is investigated in time-resolved photoluminescence experiments. For the widely used mixed system CBP:Ir(ppy){sub 3}, host-guest TTA - an additional unwanted TTA channel - is experimentally observed at high excitation levels. By using matrix materials with higher triplet energies, this effect is efficiently suppressed, however further studies show that the efficiency roll-off of Ir(ppy)3 is much more pronounced than predicted by a model based on Foerster-type energy transfer, which marks the intrinsic limit for TTA. These results suggest that the emitter molecules show a strong tendency to form aggregates in the mixed film as the origin for enhanced TTA. Transmission electron microscopy images of Ir(ppy){sub 3} doped mixed films give direct proof of emitter aggregates. Based on these results, two concepts are developed that improve the high brightness performance of OLEDs. In a first approach, thin intrinsic matrix interlayers are incorporated in the emission layer leading to a one-dimensional exciton confinement that suppresses exciton migration and, consequently, TTA. The second concept reduces the efficiency roll-off by using an emitter molecule with slightly different chemical structure, i.e. Ir(ppy){sub 2

  12. The Spectral Energy Distribution of Fermi Bright Blazars (United States)

    Abdo, A. A.; Ackermann, M.; Agudo, I.; Ajello, M.; Aller, H. D.; Aller, M. F.; Angelakis, E.; Arkharov, A. A.; Axelsson, M.; Bach, U.; Baldini, L.; Ballet, J.; Barbiellini, G.; Bastieri, D.; Baughman, B. M.; Bechtol, K.; Bellazzini, R.; Benitez, E.; Berdyugin, A.; Berenji, B.; Blandford, R. D.; Bloom, E. D.; Boettcher, M.; Bonamente, E.; Borgland, A. W.; Bregeon, J.; Brez, A.; Brigida, M.; Bruel, P.; Burnett, T. H.; Burrows, D.; Buson, S.; Caliandro, G. A.; Calzoletti, L.; Cameron, R. A.; Capalbi, M.; Caraveo, P. A.; Carosati, D.; Casandjian, J. M.; Cavazzuti, E.; Cecchi, C.; Çelik, Ö.; Charles, E.; Chaty, S.; Chekhtman, A.; Chen, W. P.; Chiang, J.; Chincarini, G.; Ciprini, S.; Claus, R.; Cohen-Tanugi, J.; Colafrancesco, S.; Cominsky, L. R.; Conrad, J.; Costamante, L.; Cutini, S.; D'ammando, F.; Deitrick, R.; D'Elia, V.; Dermer, C. D.; de Angelis, A.; de Palma, F.; Digel, S. W.; Donnarumma, I.; Silva, E. do Couto e.; Drell, P. S.; Dubois, R.; Dultzin, D.; Dumora, D.; Falcone, A.; Farnier, C.; Favuzzi, C.; Fegan, S. J.; Focke, W. B.; Forné, E.; Fortin, P.; Frailis, M.; Fuhrmann, L.; Fukazawa, Y.; Funk, S.; Fusco, P.; Gómez, J. L.; Gargano, F.; Gasparrini, D.; Gehrels, N.; Germani, S.; Giebels, B.; Giglietto, N.; Giommi, P.; Giordano, F.; Giuliani, A.; Glanzman, T.; Godfrey, G.; Grenier, I. A.; Gronwall, C.; Grove, J. E.; Guillemot, L.; Guiriec, S.; Gurwell, M. A.; Hadasch, D.; Hanabata, Y.; Harding, A. K.; Hayashida, M.; Hays, E.; Healey, S. E.; Heidt, J.; Hiriart, D.; Horan, D.; Hoversten, E. A.; Hughes, R. E.; Itoh, R.; Jackson, M. S.; Jóhannesson, G.; Johnson, A. S.; Johnson, W. N.; Jorstad, S. G.; Kadler, M.; Kamae, T.; Katagiri, H.; Kataoka, J.; Kawai, N.; Kennea, J.; Kerr, M.; Kimeridze, G.; Knödlseder, J.; Kocian, M. L.; Kopatskaya, E. N.; Koptelova, E.; Konstantinova, T. S.; Kovalev, Y. Y.; Kovalev, Yu. A.; Kurtanidze, O. M.; Kuss, M.; Lande, J.; Larionov, V. M.; Latronico, L.; Leto, P.; Lindfors, E.; Longo, F.; Loparco, F.; Lott, B.; Lovellette, M. N.; Lubrano, P.; Madejski, G. M.; Makeev, A.; Marchegiani, P.; Marscher, A. P.; Marshall, F.; Max-Moerbeck, W.; Mazziotta, M. N.; McConville, W.; McEnery, J. E.; Meurer, C.; Michelson, P. F.; Mitthumsiri, W.; Mizuno, T.; Moiseev, A. A.; Monte, C.; Monzani, M. E.; Morselli, A.; Moskalenko, I. V.; Murgia, S.; Nestoras, I.; Nilsson, K.; Nizhelsky, N. A.; Nolan, P. L.; Norris, J. P.; Nuss, E.; Ohsugi, T.; Ojha, R.; Omodei, N.; Orlando, E.; Ormes, J. F.; Osborne, J.; Ozaki, M.; Pacciani, L.; Padovani, P.; Pagani, C.; Page, K.; Paneque, D.; Panetta, J. H.; Parent, D.; Pasanen, M.; Pavlidou, V.; Pelassa, V.; Pepe, M.; Perri, M.; Pesce-Rollins, M.; Piranomonte, S.; Piron, F.; Pittori, C.; Porter, T. A.; Puccetti, S.; Rahoui, F.; Rainò, S.; Raiteri, C.; Rando, R.; Razzano, M.; Reimer, A.; Reimer, O.; Reposeur, T.; Richards, J. L.; Ritz, S.; Rochester, L. S.; Rodriguez, A. Y.; Romani, R. W.; Ros, J. A.; Roth, M.; Roustazadeh, P.; Ryde, F.; Sadrozinski, H. F.-W.; Sadun, A.; Sanchez, D.; Sander, A.; Saz Parkinson, P. M.; Scargle, J. D.; Sellerholm, A.; Sgrò, C.; Shaw, M. S.; Sigua, L. A.; Siskind, E. J.; Smith, D. A.; Smith, P. D.; Spandre, G.; Spinelli, P.; Starck, J.-L.; Stevenson, M.; Stratta, G.; Strickman, M. S.; Suson, D. J.; Tajima, H.; Takahashi, H.; Takahashi, T.; Takalo, L. O.; Tanaka, T.; Thayer, J. B.; Thayer, J. G.; Thompson, D. J.; Tibaldo, L.; Torres, D. F.; Tosti, G.; Tramacere, A.; Uchiyama, Y.; Usher, T. L.; Vasileiou, V.; Verrecchia, F.; Vilchez, N.; Villata, M.; Vitale, V.; Waite, A. P.; Wang, P.; Winer, B. L.; Wood, K. S.; Ylinen, T.; Zensus, J. A.; Zhekanis, G. V.; Ziegler, M.


    We have conducted a detailed investigation of the broadband spectral properties of the γ-ray selected blazars of the Fermi LAT Bright AGN Sample (LBAS). By combining our accurately estimated Fermi γ-ray spectra with Swift, radio, infra-red, optical, and other hard X-ray/γ-ray data, collected within 3 months of the LBAS data taking period, we were able to assemble high-quality and quasi-simultaneous spectral energy distributions (SED) for 48 LBAS blazars. The SED of these γ-ray sources is similar to that of blazars discovered at other wavelengths, clearly showing, in the usual log ν-log ν F ν representation, the typical broadband spectral signatures normally attributed to a combination of low-energy synchrotron radiation followed by inverse Compton emission of one or more components. We have used these SED to characterize the peak intensity of both the low- and the high-energy components. The results have been used to derive empirical relationships that estimate the position of the two peaks from the broadband colors (i.e., the radio to optical, αro, and optical to X-ray, αox, spectral slopes) and from the γ-ray spectral index. Our data show that the synchrotron peak frequency (ν S peak) is positioned between 1012.5 and 1014.5 Hz in broad-lined flat spectrum radio quasars (FSRQs) and between 1013 and 1017 Hz in featureless BL Lacertae objects. We find that the γ-ray spectral slope is strongly correlated with the synchrotron peak energy and with the X-ray spectral index, as expected at first order in synchrotron-inverse Compton scenarios. However, simple homogeneous, one-zone, synchrotron self-Compton (SSC) models cannot explain most of our SED, especially in the case of FSRQs and low energy peaked (LBL) BL Lacs. More complex models involving external Compton radiation or multiple SSC components are required to reproduce the overall SED and the observed spectral variability. While more than 50% of known radio bright high energy peaked (HBL) BL Lacs are

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

    Directory of Open Access Journals (Sweden)

    Laurent Chatel-Chaix


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

  14. West Nile Virus Temperature Sensitivity and Avian Virulence Are Modulated by NS1-2B Polymorphisms. (United States)

    Dietrich, Elizabeth A; Langevin, Stanley A; Huang, Claire Y-H; Maharaj, Payal D; Delorey, Mark J; Bowen, Richard A; Kinney, Richard M; Brault, Aaron C


    West Nile virus (WNV) replicates in a wide variety of avian species, which serve as reservoir and amplification hosts. WNV strains isolated in North America, such as the prototype strain NY99, elicit a highly pathogenic response in certain avian species, notably American crows (AMCRs; Corvus brachyrhynchos). In contrast, a closely related strain, KN3829, isolated in Kenya, exhibits a low viremic response with limited mortality in AMCRs. Previous work has associated the difference in pathogenicity primarily with a single amino acid mutation at position 249 in the helicase domain of the NS3 protein. The NY99 strain encodes a proline residue at this position, while KN3829 encodes a threonine. Introduction of an NS3-T249P mutation in the KN3829 genetic background significantly increased virulence and mortality; however, peak viremia and mortality were lower than those of NY99. In order to elucidate the viral genetic basis for phenotype variations exclusive of the NS3-249 polymorphism, chimeric NY99/KN3829 viruses were created. We show herein that differences in the NS1-2B region contribute to avian pathogenicity in a manner that is independent of and additive with the NS3-249 mutation. Additionally, NS1-2B residues were found to alter temperature sensitivity when grown in avian cells.

  15. Host competence and helicase activity differences exhibited by West Nile viral variants expressing NS3-249 amino acid polymorphisms.

    Directory of Open Access Journals (Sweden)

    Stanley A Langevin

    Full Text Available A single helicase amino acid substitution, NS3-T249P, has been shown to increase viremia magnitude/mortality in American crows (AMCRs following West Nile virus (WNV infection. Lineage/intra-lineage geographic variants exhibit consistent amino acid polymorphisms at this locus; however, the majority of WNV isolates associated with recent outbreaks reported worldwide have a proline at the NS3-249 residue. In order to evaluate the impact of NS3-249 variants on avian and mammalian virulence, multiple amino acid substitutions were engineered into a WNV infectious cDNA (NY99; NS3-249P and the resulting viruses inoculated into AMCRs, house sparrows (HOSPs and mice. Differential viremia profiles were observed between mutant viruses in the two bird species; however, the NS3-249P virus produced the highest mean peak viral loads in both avian models. In contrast, this avian modulating virulence determinant had no effect on LD50 or the neurovirulence phenotype in the murine model. Recombinant helicase proteins demonstrated variable helicase and ATPase activities; however, differences did not correlate with avian or murine viremia phenotypes. These in vitro and in vivo data indicate that avian-specific phenotypes are modulated by critical viral-host protein interactions involving the NS3-249 residue that directly influence transmission efficiency and therefore the magnitude of WNV epizootics in nature.

  16. Bright and ultra-fast scintillation from a semiconductor?

    Energy Technology Data Exchange (ETDEWEB)

    Derenzo, Stephen E., E-mail:; Bourret-Courshesne, Edith; Bizarri, Gregory; Canning, Andrew


    Semiconductor scintillators are worth studying because they include both the highest luminosities and shortest decay times of all known scintillators. Moreover, many semiconductors have the heaviest stable elements (Tl, Hg, Pb, and Bi) as a major constituent and a high ion pair yield that is proportional to the energy deposited. We review the scintillation properties of semiconductors activated by native defects, isoelectronic impurities, donors and acceptors with special emphasis on those that have exceptionally high luminosities (e.g. ZnO:Zn; ZnS:Ag, Cl; CdS:Ag, Cl) and those that have ultra-fast decay times (e.g. ZnO:Ga; CdS:In). We discuss underlying mechanisms that are consistent with these properties and the possibilities for achieving (1) 200,000 photons/MeV and 1% fwhm energy resolution for 662 keV gamma rays, (2) ultra-fast (ns) decay times and coincident resolving times of 30 ps fwhm for time-of-flight positron emission tomography, and (3) both a high luminosity and an ultra-fast decay time from the same scintillator at cryogenic temperatures.

  17. Bright and ultra-fast scintillation from a semiconductor? (United States)

    Derenzo, Stephen E; Bourret-Courshesne, Edith; Bizarri, Gregory; Canning, Andrew


    Semiconductor scintillators are worth studying because they include both the highest luminosities and shortest decay times of all known scintillators. Moreover, many semiconductors have the heaviest stable elements (Tl, Hg, Pb, Bi) as a major constituent and a high ion pair yield that is proportional to the energy deposited. We review the scintillation properties of semiconductors activated by native defects, isoelectronic impurities, donors and acceptors with special emphasis on those that have exceptionally high luminosities (e.g. ZnO:Zn, ZnS:Ag,Cl, CdS:Ag,Cl) and those that have ultra-fast decay times (e.g. ZnO:Ga; CdS:In). We discuss underlying mechanisms that are consistent with these properties and the possibilities for achieving (1) 200,000 photons/MeV and 1% fwhm energy resolution for 662 keV gamma rays, (2) ultra-fast (ns) decay times and coincident resolving times of 30 ps fwhm for time-of-flight positron emission tomography, and (3) both a high luminosity and an ultra-fast decay time from the same scintillator at cryogenic temperatures.

  18. Hi-C Observations of Penumbral Bright Dots (United States)

    Alpert, S. E.; Tiwari, S. K.; Moore, R. L.; Savage, S. L.; Winebarger, A. R.


    We use high-quality data obtained by the High Resolution Coronal Imager (Hi-C) to examine bright dots (BDs) in a sunspot's penumbra. The sizes of these BDs are on the order of 1 arcsecond (1") and are therefore hard to identify using the Atmospheric Imaging Assembly's (AIA) 0.6" pixel(exp -1) resolution. These BD become readily apparent with Hi-C's 0.1" pixel(exp -1) resolution. Tian et al. (2014) found penumbral BDs in the transition region (TR) by using the Interface Region Imaging Spectrograph (IRIS). However, only a few of their dots could be associated with any enhanced brightness in AIA channels. In this work, we examine the characteristics of the penumbral BDs observed by Hi-C in a sunspot penumbra, including their sizes, lifetimes, speeds, and intensity. We also attempt to find any association of these BDs to the IRIS BDs. There are fewer Hi-C BDs in the penumbra than seen by IRIS, though different sunspots were studied. We use 193 Angstroms Hi-C data from July 11, 2012 which observed from approximately 18:52:00 UT- 18:56:00 UT and supplement it with data from AIA's 193 Angstrom passband to see the complete lifetime of the dots that were born before and/or lasted longer than Hi- C's 5-minute observation period. We use additional AIA passbands and compare the light curves of the BDs at different temperatures to test whether the Hi-C BDs are TR BDs. We find that most Hi-C BDs show clear movement, and of those that do, they move in a radial direction, toward or away from the sunspot umbra. Single BDs interact with other BDs, combining to fade away or brighten. The BDs that do not interact with other BDs tend to move less. Many of the properties of our BDs are similar to the extreme values of the IRIS BDs, e.g., they move slower on average and their sizes and lifetimes are on the higher end of the IRIS BDs. We infer that our penumbral BDs are the large-scale end of the distribution of BDs observed by IRIS.

  19. Electrochemical corrosion behaviors of the X90 linepipe steel in NS4 solution

    Directory of Open Access Journals (Sweden)

    Jinheng Luo


    Full Text Available Oil and gas line pipes are laid underground and run through different areas in the laying process, so they will be subjected to different degrees of corrosion and even crack, leading to enormous casualties and economic losses. In order to guarantee the safe operation of line pipes, therefore, it is significant to investigate the electrochemical corrosion behaviors of pipe steel in a simulated soil environment. In this paper, the electrochemical corrosion behaviors of the base metals and welding materials of API 5L X90 steel longitudinally submerged arc welding pipes in near-neutral simulated soil solution (NS4 were studied by means of the electrochemical impedance spectroscopy (EIS and the potentiodynamic polarization testing technology. It is shown that the typical characteristic of anodic dissolution is presented but with no passivation phenomenon when X90 linepipe steel is put in NS4 solution. The base material is thermodynamically more stable than the seam weld material. The base material and seam weld samples were polarized under −850 mV polarization potential for different durations. It is demonstrated that with the proceeding of polarization, the polarization resistance and the corrosion resistance increase while the corrosion current density decreases. And the corrosion resistance of base material is better than that of seam weld material.

  20. Identification of natural rubber degradation gene in Rhizobacter gummiphilus NS21. (United States)

    Kasai, Daisuke; Imai, Shunsuke; Asano, Shota; Tabata, Michiro; Iijima, So; Kamimura, Naofumi; Masai, Eiji; Fukuda, Masao


    A Gram-negative rubber-degrading bacterium, Rhizobacter gummiphilus NS21 grew and produced aldehyde metabolites on a deproteinized natural rubber (DPNR)-overlay agar medium forming a clearing zone. A transposon-insertion mutant, which had lost the ability to degrade DPNR, was isolated to identify the rubber degradation genes. Sequencing analysis indicated that the transposon was inserted into a putative oxygenase gene, latA. The deduced amino acid sequence of latA has 36% identity with that of roxA, which encodes a rubber oxygenase of Xanthomonas sp. strain 35Y. Phylogenetic analysis revealed that LatA constitutes a distinct group from RoxA. Heterologous expression in a Methylibium host and deletion analysis of latA indicated that the latA product is responsible for the depolymerization of DPNR. The quantitative reverse transcription-PCR analysis indicated that the transcription of latA is induced during the growth on DPNR. These results strongly suggest that latA is directly involved in the degradation of rubber in NS21.

  1. Computational Identification of Antibody Epitopes on the Dengue Virus NS1 Protein. (United States)

    Jones, Martina L; Legge, Fiona S; Lebani, Kebaneilwe; Mahler, Stephen M; Young, Paul R; Watterson, Daniel; Treutlein, Herbert R; Zeng, Jun


    We have previously described a method to predict antigenic epitopes on proteins recognized by specific antibodies. Here we have applied this method to identify epitopes on the NS1 proteins of the four Dengue virus serotypes (DENV1-4) that are bound by a small panel of monoclonal antibodies 1H7.4, 1G5.3 and Gus2. Several epitope regions were predicted for these antibodies and these were found to reflect the experimentally observed reactivities. The known binding epitopes on DENV2 for the antibodies 1H7.4 and 1G5.3 were identified, revealing the reasons for the serotype specificity of 1H7.4 and 1G5.3, and the non-selectivity of Gus2. As DENV NS1 is critical for virus replication and a key vaccine candidate, epitope prediction will be valuable in designing appropriate vaccine control strategies. The ability to predict potential epitopes by computational methods significantly reduces the amount of experimental work required to screen peptide libraries for epitope mapping.

  2. Classification of HCV NS5B Polymerase Inhibitors Using Support Vector Machine

    Directory of Open Access Journals (Sweden)

    Changyuan Yu


    Full Text Available Using a support vector machine (SVM, three classification models were built to predict whether a compound is an active or weakly active inhibitor based on a dataset of 386 hepatitis C virus (HCV NS5B polymerase NNIs (non-nucleoside analogue inhibitors fitting into the pocket of the NNI III binding site. For each molecule, global descriptors, 2D and 3D property autocorrelation descriptors were calculated from the program ADRIANA.Code. Three models were developed with the combination of different types of descriptors. Model 2 based on 16 global and 2D autocorrelation descriptors gave the highest prediction accuracy of 88.24% and MCC (Matthews correlation coefficient of 0.789 on test set. Model 1 based on 13 global descriptors showed the highest prediction accuracy of 86.25% and MCC of 0.732 on external test set (including 80 compounds. Some molecular properties such as molecular shape descriptors (InertiaZ, InertiaX and Span, number of rotatable bonds (NRotBond, water solubility (LogS, and hydrogen bonding related descriptors performed important roles in the interactions between the ligand and NS5B polymerase.

  3. Classification of HCV NS5B Polymerase Inhibitors Using Support Vector Machine (United States)

    Wang, Maolin; Wang, Kai; Yan, Aixia; Yu, Changyuan


    Using a support vector machine (SVM), three classification models were built to predict whether a compound is an active or weakly active inhibitor based on a dataset of 386 hepatitis C virus (HCV) NS5B polymerase NNIs (non-nucleoside analogue inhibitors) fitting into the pocket of the NNI III binding site. For each molecule, global descriptors, 2D and 3D property autocorrelation descriptors were calculated from the program ADRIANA.Code. Three models were developed with the combination of different types of descriptors. Model 2 based on 16 global and 2D autocorrelation descriptors gave the highest prediction accuracy of 88.24% and MCC (Matthews correlation coefficient) of 0.789 on test set. Model 1 based on 13 global descriptors showed the highest prediction accuracy of 86.25% and MCC of 0.732 on external test set (including 80 compounds). Some molecular properties such as molecular shape descriptors (InertiaZ, InertiaX and Span), number of rotatable bonds (NRotBond), water solubility (LogS), and hydrogen bonding related descriptors performed important roles in the interactions between the ligand and NS5B polymerase. PMID:22605964

  4. Miracle: The Multi-Interface Cross-Layer Extension of ns2

    Directory of Open Access Journals (Sweden)

    Nicola Baldo


    Full Text Available We present Miracle, a novel framework which extends ns2 to facilitate the simulation and the design of beyond 4G networks. Miracle enhances ns2 by providing an efficient and embedded engine for handling cross-layer messages and, at the same time, enabling the coexistence of multiple modules within each layer of the protocol stack. We also present a novel framework developed as an extension of Miracle called Miracle PHY and MAC. This framework facilitates the development of more realistic Channel, PHY and MAC modules, considering features currently lacking in most state-of-the-art simulators, while at the same time giving a strong emphasis on code modularity, interoperability and reusability. Finally, we provide an overview of the wireless technologies implemented in Miracle, discussing in particular the models for the IEEE 802.11, UMTS and WiMAX standards and for Underwater Acoustic Networks. We observe that, thanks to Miracle and its extensions, it is possible to carefully simulate complex network architectures at all the OSI layers, from the physical reception model to standard applications and system management schemes. This allows to have a comprehensive view of all the interactions among network components, which play an important role in many research areas, such as cognitive networking and cross-layer design.

  5. NS1 gene based molecular characteristics of Aleutian mink disease virus circulating in Poland

    Directory of Open Access Journals (Sweden)

    Reichert Michał


    Full Text Available The aim of this study was to characterise the genetic variability of the Aleutian mink disease virus (AMDV circulating among mink farmed in Poland and to compare Polish isolates with AMDV variants available in the GenBank database. For this purpose PCR amplification and analysis of the 429 bp DNA fragment of the AMDV NS1 gene from 13 randomly selected AMDV infected mink was performed. A comparison showed that all tested amplicons were closely related to the sequence of the NS1 gene of AMDV and showed high (94%-97% homology to virus variants from American mink (Neovison vison isolated in Canada in 2007-2008. Eleven samples showing a high percentage (95%-97% of sequence similarity together with three similar isolates originating from Canada formed one clade (monophyletic group. Two variants showing a lower percentage (about 94%- 95% of sequence similarity to isolates from Canada formed a separate clade. Polish viruses can be subdivided into two main groups with a putative ancestor common to both Polish and three Canadian isolates. This result confirms the literature data indicating the occurrence of American mink in Eastern Europe (including Poland from the 1950s when the animals were imported for breeding purposes. In conclusion, we provide for the first time a report on the genetic characteristics of the AMDV variants circulating in the Polish population of farmed mink and their relationship with previously known AMDV variants isolated and described abroad.

  6. Lipase NS81006 immobilized on Fe3O4 magnetic nanoparticles for biodiesel production

    Directory of Open Access Journals (Sweden)

    Thangaraj Baskar


    Full Text Available Lipase-catalyzed biodiesel production is being the object of extensive research due to the demerits of chemical based catalytic system. Lipase immobilized on Fe3O4 magnetic nanoparticles has the integrated advantages of traditional immobilized lipase and free lipase for its rather fast reaction rate and easy separation. It has been demonstrated that free lipase NS81006 has potential in catalyzing the alcoholysis of renewable oils for biodiesel preparation. In this study, Fe3O4 magnetic nanoparticles functionalized with organosilane compounds like (3-aminopropyltriethyloxysilane (APTES and (3-mercaptopropyltrimethoxysilane MPTMS were used as carriers for lipase immobilization. Lipase NS81006 was covalently bound to the organosilane-functionalized magnetic nanoparticles by using glutaraldehyde cross-linking reagent. A biodiesel yield of 89% and 81% could be achieved by lipase immobilized on APTES-Fe3O4 and MPTMS-Fe3O4 magnetic nanoparticles respectively under optimized conditions of oil to methanol molar ratio 1:3 with three step addition of methanol, reaction temperature 45°C and reaction time duration 12 h. The lipases immobilized on magnetic nanoparticles could be recovered easily by external magnetic field for further use.

  7. Structure and functionality in flavivirus NS-proteins: perspectives for drug design. (United States)

    Bollati, Michela; Alvarez, Karin; Assenberg, René; Baronti, Cécile; Canard, Bruno; Cook, Shelley; Coutard, Bruno; Decroly, Etienne; de Lamballerie, Xavier; Gould, Ernest A; Grard, Gilda; Grimes, Jonathan M; Hilgenfeld, Rolf; Jansson, Anna M; Malet, Hélène; Mancini, Erika J; Mastrangelo, Eloise; Mattevi, Andrea; Milani, Mario; Moureau, Grégory; Neyts, Johan; Owens, Raymond J; Ren, Jingshan; Selisko, Barbara; Speroni, Silvia; Steuber, Holger; Stuart, David I; Unge, Torsten; Bolognesi, Martino


    Flaviviridae are small enveloped viruses hosting a positive-sense single-stranded RNA genome. Besides yellow fever virus, a landmark case in the history of virology, members of the Flavivirus genus, such as West Nile virus and dengue virus, are increasingly gaining attention due to their re-emergence and incidence in different areas of the world. Additional environmental and demographic considerations suggest that novel or known flaviviruses will continue to emerge in the future. Nevertheless, up to few years ago flaviviruses were considered low interest candidates for drug design. At the start of the European Union VIZIER Project, in 2004, just two crystal structures of protein domains from the flaviviral replication machinery were known. Such pioneering studies, however, indicated the flaviviral replication complex as a promising target for the development of antiviral compounds. Here we review structural and functional aspects emerging from the characterization of two main components (NS3 and NS5 proteins) of the flavivirus replication complex. Most of the reviewed results were achieved within the European Union VIZIER Project, and cover topics that span from viral genomics to structural biology and inhibition mechanisms. The ultimate aim of the reported approaches is to shed light on the design and development of antiviral drug leads. Copyright 2009 Elsevier B.V. All rights reserved.

  8. Testing the dark matter hypothesis with low surface brightness galaxies and other evidence

    NARCIS (Netherlands)

    McGaugh, SS; de Blok, WJG


    The severity of the mass discrepancy in spiral galaxies is strongly correlated with the central surface brightness of their disks. Progressively lower surface brightness galaxies have ever larger mass discrepancies. No other parameter (luminosity, size, velocity, morphology) is so well correlated

  9. T1 bright appendix sign to exclude acute appendicitis in pregnant women. (United States)

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


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

  10. The dark and visible matter content of low surface brightness disc galaxies

    NARCIS (Netherlands)

    deBlok, WJG; McGaugh, SS


    We present mass models of a sample of 19 low surface brightness (LSB) galaxies and compare the properties of their constituent mass components with those of a sample of high surface brightness (HSB) galaxies. We find that LSB galaxies are dark matter dominated, Their halo parameters are only

  11. HI observations of low surface brightness galaxies : Probing low-density galaxies

    NARCIS (Netherlands)

    deBlok, WJG; McGaugh, SS; vanderHulst, JM


    We present Very Large Array (VLA) and Westerbork Synthesis Radio Telescope (WSRT) 21-cm HI observations of 19 late-type low surface brightness (LSB) galaxies. Our main findings are that these galaxies, as well as having low surface brightnesses, have low HI surface densities, about a factor of

  12. Functional magnetic resonance imaging of brightness induction in the human visual cortex

    NARCIS (Netherlands)

    Boucard, CC; van Es, JJ; Maguire, RP; Cornelissen, FW


    A grey surface on a bright background appears to be darker than the same surface on a dark background. We used functional magnetic resonance imaging to study this phenomenon called brightness induction. While being scanned, participants viewed centre-surround displays in which either centre or

  13. Bright morning light advances the human circadian system without affecting NREM sleep homeostasis

    NARCIS (Netherlands)

    Dijk, Derk Jan; Beersma, Domien G.M.; Daan, Serge; Lewy, Alfred J.

    Eight male subjects were exposed to either bright light or dim light between 0600 and 0900 h for 3 consecutive days each. Relative to the dim light condition, the bright light treatment advanced the evening rise in plasma melatonin and the time of sleep termination (sleep onset was held constant)

  14. Reduction of human sleep duration after bright light exposure in the morning

    NARCIS (Netherlands)

    Dijk, D.J.; Visscher, C.A.; Bloem, G.M.; Beersma, D.G.M.; Daan, S.


    In 8 subjects the spontaneous termination of sleep was determined after repetitive exposure to either bright or dim light, between 6:00 and 9:00 h, on 3 days preceding sleep assessment. Sleep duration was significantly shorter following bright light than following dim light. During sleep the time

  15. Inter-comparison of SMAP, SMOS and Aquarius L-band brightness temperature observations (United States)

    Verifying the calibration of the SMAP radiometer over land observations is an important mission requirement. Inter-comparison of L-band brightness temperature observations from different satellites (SMAP, SMOS and Aquarius) is a useful tool for radiometer calibration. Brightness temperatures observa...

  16. Mutagenesis of the yellow fever virus NS2A/2B cleavage site: effects on proteolytic processing, viral replication, and evidence for alternative processing of the NS2A protein. (United States)

    Nestorowicz, A; Chambers, T J; Rice, C M


    The yellow fever virus NS2B-3 proteinase mediates cleavages within the nonstructural region at a consensus sequence defined by G/ARR decreases S/G and also at an alternative site within the NS4A region. To determine the importance of specific residues within the consensus sequence for cleavage at the 2A/2B site, amino acid substitutions were introduced at each of the P4, P3, P2, P1, and P1' positions and the effects on proteolytic processing of a sig2A-5(356) polyprotein were examined using a vaccinia virus-T7 transient expression system. At the P1 and P1' positions, only the conservative substitutions P1:R-->K and P1':S-->G allowed efficient cleavage, suggesting that basic and small aliphatic amino acids are preferred at the P1 and P1' positions, respectively. At the P2 position, a preference for a basic amino acid was observed. In contrast, the P3 and P4 positions tolerated nonconservative substitutions and at P4 both enhancement and reduction in cleavage efficiency was observed. Evidence for cleavage at an alternative site within NS2A, defined by the sequence QK decreases T (NS2A residues 189-191) was obtained. Cleavage at this site, designated at NS2A alpha, is dependent upon an active NS2B-3 proteinase. To examine the effects of reduced cleavage efficiency at the 2A/2B and NS2A alpha cleavage sites on viral replication, mutations at each or both of these sites were incorporated into a full-length YF-17D cDNA template. RNA transcripts containing mutations which abolish cleavage were noninfectious whereas virus was recovered from several clones with mutations allowing partial cleavage at 2A/2B. However, some of these mutants exhibited a small plaque phenotype as well as reductions in RNA-specific infectivity and virus yield.

  17. High Brightness HDR Projection Using Dynamic Freeform Lensing

    KAUST Repository

    Damberg, Gerwin


    Cinema projectors need to compete with home theater displays in terms of image quality. High frame rate and spatial resolution as well as stereoscopic 3D are common features today, but even the most advanced cinema projectors lack in-scene contrast and, more important, high peak luminance, both of which are essential perceptual attributes of images appearing realistic. At the same time, HDR image statistics suggest that the average image intensity in a controlled ambient viewing environment such as the cinema can be as low as 1% for cinematic HDR content and not often higher than 18%, middle gray in photography. Traditional projection systems form images and colors by blocking the source light from a lamp, therefore attenuating between 99% and 82% of light, on average. This inefficient use of light poses significant challenges for achieving higher peak brightness levels. In this work, we propose a new projector architecture built around commercially available components, in which light can be steered to form images. The gain in system efficiency significantly reduces the total cost of ownership of a projector (fewer components and lower operating cost), and at the same time increases peak luminance and improves black level beyond what is practically achievable with incumbent projector technologies. At the heart of this computational display technology is a new projector hardware design using phase modulation in combination with a new optimization algorithm that is capable of on-the-fly computation of freeform lens surfaces. © 2016 ACM.

  18. Low Cost Lithography Tool for High Brightness LED Manufacturing

    Energy Technology Data Exchange (ETDEWEB)

    Andrew Hawryluk; Emily True


    The objective of this activity was to address the need for improved manufacturing tools for LEDs. Improvements include lower cost (both capital equipment cost reductions and cost-ofownership reductions), better automation and better yields. To meet the DOE objective of $1- 2/kilolumen, it will be necessary to develop these highly automated manufacturing tools. Lithography is used extensively in the fabrication of high-brightness LEDs, but the tools used to date are not scalable to high-volume manufacturing. This activity addressed the LED lithography process. During R&D and low volume manufacturing, most LED companies use contact-printers. However, several industries have shown that these printers are incompatible with high volume manufacturing and the LED industry needs to evolve to projection steppers. The need for projection lithography tools for LED manufacturing is identified in the Solid State Lighting Manufacturing Roadmap Draft, June 2009. The Roadmap states that Projection tools are needed by 2011. This work will modify a stepper, originally designed for semiconductor manufacturing, for use in LED manufacturing. This work addresses improvements to yield, material handling, automation and throughput for LED manufacturing while reducing the capital equipment cost.

  19. Resistance to immunotherapy: clouds in a bright sky. (United States)

    Milano, Gérard


    Two major challenges persist for an optimal management of immunotherapy: i) identifying those patients who will benefit from this type of therapy, and ii) determining the biological, cellular and molecular mechanisms that trigger disease progression while on therapy. There is a consensual view in favor of standardizing practices currently used to measure programmed death ligand 1 (PD-L1) expression that relates to innate resistance. The tumor mutation landscape has been widely explored as a potential predictor of treatment efficacy. In contrast, our knowledge is rather limited as concerns the mechanisms sustaining acquired resistance to checkpoint blockade immunotherapy in patients under treatment. Upregulation of T cell immunoglobulin mucin domain 3 (TIM-3) in CD8+ T-cells has been reported in patients developing acquired resistance to anti-PD-1 treatment. Resistance mechanisms are even more complex for combinatorial strategies linking immunotherapeutic agents and conventional therapies, an area that is expanding rapidly. However, with the arrival of advanced analytical methods such as mass cytometry, there is reason for optimism. These methods can identify cellular mechanisms governing response to therapy and resistance. The clinical use of inhibitors of tumor-microenvironment-modulated pathways, such as those targeting indoleamine 2, 3-dioxygenase (IDO), hold promise for resistance management. Graphical abstract Clouds in a bright sky - Joseph Mallord William Turner.

  20. The bright and the dark sides of motor simulation. (United States)

    Panasiti, Maria Serena; Porciello, Giuseppina; Aglioti, Salvatore Maria


    While the acquisition of knowledge about the sensory, emotional, and motor states of others has long been thought to derive from abstract inferential operations, recent theories based on neuroscientific and psychological models emphasize that motor simulation is essential to a variety of complex functions ranging from the monitoring of one's own performance to the understanding of others' actions, and matching self and others' states to optimize social interactions. In this review, we discuss evidence that simulating the actions of others has both bright and dark sides. On the one hand, we show that simulation can aid the anticipation and prediction of errors in the actions of others (e.g., in the case of competitive sports), as well as the establishment of social bonds (e.g., in the case of mimicry). On the other hand, based on findings from our and other research groups, we describe specific circumstances in which simulating the actions of others is detrimental to performance (e.g., when we automatically follow the gaze of a person who is actually trying to deceive us). Finally, we show how the presence of a shared goal between agents (such as in joint actions) maximizes the cost benefit of motor simulation, suggesting that the top-down modulation of this process is vital for adapting in a social environment. Copyright © 2017 Elsevier Ltd. All rights reserved.