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

PubMed

Radhakrishnan, R; Manikandan, N; Aravinthan, K

2015-12-01

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

Implications of PSR J0737-3039B for the Galactic NS-NS binary merger rate

NASA Astrophysics Data System (ADS)

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

2015-03-01

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.

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

PubMed

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

2016-03-01

Contrasting flower color patterns that putatively attract or direct pollinators toward a reward are common among angiosperms. In the deceptive orchid Anacamptis morio, the lower petal, which makes up most of the floral display, has a light central patch with dark markings. Within populations, there is pronounced variation in petal brightness, patch size, amount of dark markings, and contrast between patch and petal margin. We tested whether pollinators mediate selection on these color traits and on morphology (plant height, number of flowers, corolla size, spur length), and whether selection is consistent with facilitated or negative frequency-dependent pollination. Pollinators mediated strong selection for increased petal brightness (Δβpoll = 0.42) and contrast (Δβpoll = 0.51). Pollinators also tended to mediate stabilizing selection on brightness (Δγpoll = -0.27, n.s.) favoring the most common phenotype in the population. Selection for reduced petal brightness among hand-pollinated plants indicated a fitness cost associated with brightness. The results demonstrate that flower color traits influence pollination success and seed production in A. morio, indicating that they affect attractiveness to pollinators, efficiency of pollen transfer, or both. The documented selection is consistent with facilitated pollination and selection for color convergence toward cooccurring rewarding species. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

A possible explanation of the parallel tracks in kilohertz quasi-periodic oscillations from low-mass-X-ray binaries

NASA Astrophysics Data System (ADS)

Shi, Chang-Sheng; Zhang, Shuang-Nan; Li, Xiang-Dong

2018-05-01

We recalculate the modes of the magnetohydrodynamics (MHD) waves in the MHD model (Shi, Zhang & Li 2014) of the kilohertz quasi-periodic oscillations (kHz QPOs) in neutron star low mass X-ray binaries (NS-LMXBs), in which the compressed magnetosphere is considered. A method on point-by-point scanning for every parameter of a normal LMXBs is proposed to determine the wave number in a NS-LMXB. Then dependence of the twin kHz QPO frequencies on accretion rates (\\dot{M}) is obtained with the wave number and magnetic field (B*) determined by our method. Based on the MHD model, a new explanation of the parallel tracks, i.e. the slowly varying effective magnetic field leads to the shift of parallel tracks in a source, is presented. In this study, we obtain a simple power-law relation between the kHz QPO frequencies and \\dot{M}/B_{\\ast }^2 in those sources. Finally, we study the dependence of kHz quasi-periodic oscillation frequencies on the spin, mass and radius of a neutron star. We find that the effective magnetic field, the spin, mass and radius of a neutron star lead to the parallel tracks in different sources.

Where are Low Mass X-ray Binaries Formed?

NASA Astrophysics Data System (ADS)

Kundu, A.; Maccarone, T. J.; Zepf, S. E.

2004-08-01

Chandra images of nearby galaxies reveal large numbers of low mass X-ray binaries (LMXBs). As in the Galaxy, a significant fraction of these are associated with globular clusters. We exploit the LMXB-globular cluster link in order to probe both the physical properties of globular clusters that promote the formation of LMXBs within clusters with specific characteristics, and to study whether the non-cluster field LMXB population was originally formed in clusters and then released into the field. The large population of globular clusters around nearby galaxies and the range of properties such as age, metallicity and host galaxy environment spanned by these objects enables us to identify and probe the link between these characteristics and the formation of LMXBs. We present the results of our study of a large sample of elliptical and S0 galaxies which reveals among other things that bright LMXBs definitively prefer metal-rich cluster hosts and that this relationship is unlikely to be driven by age effects. The ancestry of the non-cluster field LMXBs is a matter of some debate with suggestions that they they might have formed in the field, or created in globular clusters and then subsequently released into the field either by being ejected from clusters by dynamical processes or as remnants of dynamically destroyed clusters. Each of these scenarios has a specific spatial signature that can be tested by our combined optical and X-ray study. Furthermore, these scenarios predict additional statistical variations that may be driven by the specific host galaxy environment. We present a detailed analysis of our sample galaxies and comment on the probability that the field sources were actually formed in clusters.

Progress on New Hepatitis C Virus Targets: NS2 and NS5A

NASA Astrophysics Data System (ADS)

Marcotrigiano, Joseph

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

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

NASA Astrophysics Data System (ADS)

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

2018-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2016-03-01

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

Soft X-ray Absorption Edges in LMXBs

NASA Technical Reports Server (NTRS)

2004-01-01

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

Establishment of a robust dengue virus NS3-NS5 binding assay for identification of protein-protein interaction inhibitors.

PubMed

Takahashi, Hirotaka; Takahashi, Chikako; Moreland, Nicole J; Chang, Young-Tae; Sawasaki, Tatsuya; Ryo, Akihide; Vasudevan, Subhash G; Suzuki, Youichi; Yamamoto, Naoki

2012-12-01

Whereas the dengue virus (DENV) non-structural (NS) proteins NS3 and NS5 have been shown to interact in vitro and in vivo, the biological relevance of this interaction in viral replication has not been fully clarified. Here, we first applied a simple and robust in vitro assay based on AlphaScreen technology in combination with the wheat-germ cell-free protein production system to detect the DENV-2 NS3-NS5 interaction in a 384-well plate. The cell-free-synthesized NS3 and NS5 recombinant proteins were soluble and in possession of their respective enzymatic activities in vitro. In addition, AlphaScreen assays using the recombinant proteins detected a specific interaction between NS3 and NS5 with a robust Z' factor of 0.71. By employing the AlphaScreen assay, we found that both the N-terminal protease and C-terminal helicase domains of NS3 are required for its association with NS5. Furthermore, a competition assay revealed that the binding of full-length NS3 to NS5 was significantly inhibited by the addition of an excess of NS3 protease or helicase domains. Our results demonstrate that the AlphaScreen assay can be used to discover novel antiviral agents targeting the interactions between DENV NS proteins. Copyright © 2012 Elsevier B.V. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2018-05-01

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

Inhibitor Bound Dengue NS2B-NS3pro Reveals Multiple Dynamic Binding Modes.

PubMed

Gibbs, Alan C; Steele, Ruth; Liu, Gaohua; Tounge, Brett A; Montelione, Gaetano T

2018-03-13

Dengue virus poses a significant global health threat as the source of increasingly deleterious dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. As no specific antiviral treatment exists for dengue infection, considerable effort is being applied to discover therapies and drugs for maintenance and prevention of these afflictions. The virus is primarily transmitted by mosquitoes, and infection occurs following viral endocytosis by host cells. Upon entering the cell, viral RNA is translated into a large multisubunit polyprotein which is post-translationally cleaved into mature, structural and nonstructural (NS) proteins. The viral genome encodes the enzyme to carry out cleavage of the large polyprotein, specifically the NS2B-NS3pro cofactor-protease complex-a target of high interest for drug design. One class of recently discovered NS2B-NS3pro inhibitors is the substrate-based trifluoromethyl ketone containing peptides. These compounds interact covalently with the active site Ser135 via a hemiketal adduct. A detailed picture of the intermolecular protease/inhibitor interactions of the hemiketal adduct is crucial for rational drug design. We demonstrate, through the use of protein- and ligand-detected solution-state 19 F and 1 H NMR methods, an unanticipated multibinding mode behavior of a representative of this class of inhibitors to dengue NS2B-NS3pro. Our results illustrate the highly dynamic nature of both the covalently bound ligand and protease protein structure, and the need to consider these dynamics when designing future inhibitors in this class.

Discovery and SAR studies of methionine-proline anilides as dengue virus NS2B-NS3 protease inhibitors.

PubMed

Zhou, Guo-Chun; Weng, Zhibing; Shao, Xiaoxia; Liu, Fang; Nie, Xin; Liu, Jinsong; Wang, Decai; Wang, Chunguang; Guo, Kai

2013-12-15

A series of methionine-proline dipeptide derivatives and their analogues were designed, synthesized and assayed against the serotype 2 dengue virus NS2B-NS3 protease, and methionine-proline anilides 1 and 2 were found to be the most active DENV 2 NS2B-NS3 competitive inhibitors with Ki values of 4.9 and 10.5 μM. The structure and activity relationship and the molecular docking revealed that L-proline, L-methionine and p-nitroaniline in 1 and 2 are the important characters in blocking the active site of NS2B-NS3 protease. Our current results suggest that the title dipeptidic scaffold represents a promising structural core to discover a new class of active NS2B-NS3 competitive inhibitors. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

PubMed Central

2011-01-01

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

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

PubMed

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

2011-10-20

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

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

PubMed

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

2014-01-01

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

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

PubMed Central

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

2014-01-01

Dengue virus NS2/NS3 protease because of its ability to cleave viral proteins is considered as an attractive target to screen antiviral agents. Medicinal plants contain a variety of phytochemicals that can be used as drug against different diseases and infections. Therefore, this study was designed to uncover possible phytochemical of different classes (Aromatic, Carbohydrates, Lignin, Saponins, Steroids, Tannins, Terpenoids, Xanthones) that could be used as inhibitors against the NS2B/NS3 protease of DENV. With the help of molecular docking, Garcinia phytochemicals found to be bound deeply inside the active site of DENV NS2B/NS3 protease among all tested phytochemicals and had interactions with catalytic triad (His51, Asp75, Ser135). Thus, it can be concluded from the study that these Gracinia phytochemicals could serve as important inhibitors to inhibit the viral replication inside the host cell. Further in-vitro investigations require confirming their efficacy. PMID:24748749

Highly potent non-peptidic inhibitors of the HCV NS3/NS4A serine protease.

PubMed

Sperandio, David; Gangloff, Anthony R; Litvak, Joane; Goldsmith, Richard; Hataye, Jason M; Wang, Vivian R; Shelton, Emma J; Elrod, Kyle; Janc, James W; Clark, James M; Rice, Ken; Weinheimer, Steve; Yeung, Kap-Sun; Meanwell, Nicholas A; Hernandez, Dennis; Staab, Andrew J; Venables, Brian L; Spencer, Jeffrey R

2002-11-04

Screening of a diverse set of bisbenzimidazoles for inhibition of the hepatitis C virus (HCV) serine protease NS3/NS4A led to the identification of a potent Zn(2+)-dependent inhibitor (1). Optimization of this screening hit afforded a 10-fold more potent inhibitor (46) under Zn(2+) conditions (K(i)=27nM). This compound (46) binds also to NS3/NS4A in a Zn(2+) independent fashion (K(i)=1microM). The SAR of this class of compounds under Zn(2+) conditions is highly divergent compared to the SAR in the absence of Zn(2+), suggesting two distinct binding modes.

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

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

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

2007-11-10

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

Flavonoids as noncompetitive inhibitors of Dengue virus NS2B-NS3 protease: inhibition kinetics and docking studies.

PubMed

de Sousa, Lorena Ramos Freitas; Wu, Hongmei; Nebo, Liliane; Fernandes, João Batista; da Silva, Maria Fátima das Graças Fernandes; Kiefer, Werner; Kanitz, Manuel; Bodem, Jochen; Diederich, Wibke E; Schirmeister, Tanja; Vieira, Paulo Cezar

2015-02-01

NS2B-NS3 is a serine protease of the Dengue virus considered a key target in the search for new antiviral drugs. In this study flavonoids were found to be inhibitors of NS2B-NS3 proteases of the Dengue virus serotypes 2 and 3 with IC50 values ranging from 15 to 44 μM. Agathisflavone (1) and myricetin (4) turned out to be noncompetitive inhibitors of dengue virus serotype 2 NS2B-NS3 protease with Ki values of 11 and 4.7 μM, respectively. Docking studies propose a binding mode of the flavonoids in a specific allosteric binding site of the enzyme. Analysis of biomolecular interactions of quercetin (5) with NT647-NHS-labeled Dengue virus serotype 3 NS2B-NS3 protease by microscale thermophoresis experiments, yielded a dissociation constant KD of 20 μM. Our results help to understand the mechanism of inhibition of the Dengue virus serine protease by flavonoids, which is essential for the development of improved inhibitors. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

PubMed

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

2017-06-15

The NS2A protein of dengue virus (DENV) has eight predicted transmembrane segments (pTMS1 to -8) and participates in RNA replication, virion assembly, and host antiviral response. However, the roles of specific amino acid residues within the pTMS regions of NS2A during the viral life cycle are not clear. Here, we explore the function of DENV NS2A by introducing a series of alanine substitutions into the N-terminal half (pTMS1 to -4) of the protein in the context of a DENV infectious clone or subgenomic replicon. Six NS2A mutants (NM5, -7, -9, and -17 to -19) around pTMS1 and -2 displayed a novel phenotype showing a >1,000-fold reduction in virus yield, an absence of plaque formation despite wild-type-like replicon activity, and infectious-virus-like particle yields. HEK-293 cells infected with the six NS2A mutant viruses failed to cause a virus-induced cytopathic effect (CPE) by MitoCapture staining, cell proliferation, and lactate dehydrogenase release assays. Sequencing analyses of pseudorevertant viruses derived from lethal-mutant viruses revealed two consensus reversion mutations, leucine to phenylalanine at codon 181 (L181F) within pTMS7 of NS2A and isoleucine to threonine at codon 114 (I114T) within NS2B. The introduction of an NS2A-L181F mutation into the lethal (NM15, -16, -25, and -33) and CPE-defective (NM7, -9, and -19) mutants substantially rescued virus infectivity and virus-induced CPE, respectively, whereas the NS2B-L114T mutation rescued the NM16, -25, and -33 mutants. In conclusion, the results revealed the essential roles of the N-terminal half of NS2A in RNA replication and virus-induced CPE. Intramolecular interactions between pTMSs of NS2A and intermolecular interactions between the NS2A and NS2B proteins were also implicated. IMPORTANCE The characterization of the N-terminal (current study) and C-terminal halves of DENV NS2A is the most comprehensive mutagenesis study to date to investigate the function of NS2A during the flaviviral life cycle

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

PubMed

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

2011-03-28

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

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

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

Lee, Hyun; Ren, Jinhong; Nocadello, Salvatore

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 activitymore » (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.« less

Characterisation of divergent flavivirus NS3 and NS5 protein sequences detected in Rhipicephalus microplus ticks from Brazil

PubMed Central

Maruyama, Sandra Regina; Castro-Jorge, Luiza Antunes; Ribeiro, José Marcos Chaves; Gardinassi, Luiz Gustavo; Garcia, Gustavo Rocha; Brandão, Lucinda Giampietro; Rodrigues, Aline Rezende; Okada, Marcos Ituo; Abrão, Emiliana Pereira; Ferreira, Beatriz Rossetti; da Fonseca, Benedito Antonio Lopes; de Miranda-Santos, Isabel Kinney Ferreira

2013-01-01

Transcripts similar to those that encode the nonstructural (NS) proteins NS3 and NS5 from flaviviruses were found in a salivary gland (SG) complementary DNA (cDNA) library from the cattle tick Rhipicephalus microplus. Tick extracts were cultured with cells to enable the isolation of viruses capable of replicating in cultured invertebrate and vertebrate cells. Deep sequencing of the viral RNA isolated from culture supernatants provided the complete coding sequences for the NS3 and NS5 proteins and their molecular characterisation confirmed similarity with the NS3 and NS5 sequences from other flaviviruses. Despite this similarity, phylogenetic analyses revealed that this potentially novel virus may be a highly divergent member of the genus Flavivirus. Interestingly, we detected the divergent NS3 and NS5 sequences in ticks collected from several dairy farms widely distributed throughout three regions of Brazil. This is the first report of flavivirus-like transcripts in R. microplus ticks. This novel virus is a potential arbovirus because it replicated in arthropod and mammalian cells; furthermore, it was detected in a cDNA library from tick SGs and therefore may be present in tick saliva. It is important to determine whether and by what means this potential virus is transmissible and to monitor the virus as a potential emerging tick-borne zoonotic pathogen. PMID:24626302

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

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

Miyazaki, Masaya; Nishihara, Hiroshi, E-mail: hnishihara@med.hokudai.ac.jp; Hasegawa, Hideki

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

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

NASA Astrophysics Data System (ADS)

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

2018-04-01

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

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

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

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

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

Jet quenching in the neutron star low-mass X-ray binary 1RXS J180408.9-342058

NASA Astrophysics Data System (ADS)

Gusinskaia, N. V.; Deller, A. T.; Hessels, J. W. T.; Degenaar, N.; Miller-Jones, J. C. A.; Wijnands, R.; Parikh, A. S.; Russell, T. D.; Altamirano, D.

2017-09-01

We present quasi-simultaneous radio (VLA) and X-ray (Swift) observations of the neutron star low-mass X-ray binary (NS-LMXB) 1RXS J180408.9-342058 (J1804) during its 2015 outburst. We found that the radio jet of J1804 was bright (232 ± 4 μJy at 10 GHz) during the initial hard X-ray state, before being quenched by more than an order of magnitude during the soft X-ray state (19 ± 4 μJy). The source then was undetected in radio (<13 μJy) as it faded to quiescence. In NS-LMXBs, possible jet quenching has been observed in only three sources and the J1804 jet quenching we show here is the deepest and clearest example to date. Radio observations when the source was fading towards quiescence (LX = 1034-35 erg s-1) show that J1804 must follow a steep track in the radio/X-ray luminosity plane with β > 0.7 (where L_R ∝ L_X^{β }). Few other sources have been studied in this faint regime, but a steep track is inconsistent with the suggested behaviour for the recently identified class of transitional millisecond pulsars. J1804 also shows fainter radio emission at LX < 1035 erg s-1 than what is typically observed for accreting millisecond pulsars. This suggests that J1804 is likely not an accreting X-ray or transitional millisecond pulsar.

Spin Complicates Eccentric BH-NS Mergers

NASA Astrophysics Data System (ADS)

Kohler, Susanna

2015-08-01

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

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

PubMed Central

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

2014-01-01

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

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

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

D’Arcy, Allan, E-mail: allan.darcy@novartis.com; Chaillet, Maxime; Schiering, Nikolaus

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 maymore » 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.« less

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

PubMed

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

2013-12-29

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

Constraining the mass and radius of neutron star by future observations

NASA Astrophysics Data System (ADS)

Kwak, Kyujin; Lee, Chang-Hwan; Kim, Myungkuk; Kim, Young-Min

2018-04-01

The mass and radius of neutron star (NS) in the low mass X-ray binary (LMXB) can be measured simultaneously from the evolving spectra of the photospheric radius expansion (PRE) X-ray bursts (XRBs). Precise measurements require the distance to the target, information on the radiating surface, and the composition of accreted material. Future observations with large ground-based telescopes such as Giant Magellan Telescope (GMT) and Thirty Meter Telescope (TMT) may reduce the uncertainties in the estimation of the mass and radius of NS because they could provide information on the composition of accreted material by identifying the companion stars in LMXBs. We investigate these possibilities and present our results for selected targets.

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

PubMed

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

2016-02-26

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

Rationalizing meat consumption. The 4Ns.

PubMed

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

2015-08-01

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

GESPA: classifying nsSNPs to predict disease association.

PubMed

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

2015-07-25

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 http://sourceforge.net/projects/gespa.

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

NASA Technical Reports Server (NTRS)

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

2003-01-01

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

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

PubMed

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

2017-06-26

There are no feasible real-time and direct skin dosimeters for interventional radiology. One would be available if there were x-ray phosphors that had no brightness change caused by x-ray irradiation, but the emission of the Y 2 O 3 :Eu, (Y, Gd, Eu)BO 3 , and YVO 4 :Eu phosphors investigated in our previous study was reduced by x-ray irradiation. We found that the brightness of those phosphors recovered, and the purpose of this study is to investigate their recovery phenomena. It is expected that more kinds of phosphors could be used in x-ray dosimeters if the brightness changes caused by x-rays are elucidated and prevented. Three kinds of phosphors-Y 2 O 3 :Eu, (Y, Gd, Eu)BO 3 , and YVO 4 :Eu-were irradiated by x-rays (2 Gy) to reduce their brightness. After the irradiation, brightness changes occurring at room temperature and at 80 °C were investigated. The irradiation reduced the brightness of all the phosphors by 5%-10%, but the brightness of each recovered immediately both at room temperature and at 80 °C. The recovery at 80 °C was faster than that at room temperature, and at both temperatures the recovered brightness remained at 95%-98% of the brightness before the x-ray irradiation. The brightness recovery phenomena of Y 2 O 3 :Eu, (Y, Gd, Eu)BO 3 , and YVO 4 :Eu phosphors occurring after brightness deterioration due to x-ray irradiation were found to be more significant at 80 °C than at room temperature. More kinds of phosphors could be used in x-ray scintillation dosimeters if the reasons for the brightness changes caused by x-rays were elucidated.

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

PubMed

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

2011-12-19

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

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

PubMed Central

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

2016-01-01

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. PMID:27103935

Feeding a sub-ns-risetime rectangular pulse onto a rod-shaped resistive high-voltage divider in risetime <2 ns

NASA Astrophysics Data System (ADS)

Zeng, Zhengzhong; Ma, Lianying

2004-01-01

A simple and effective bridge-type feeding network consisting only of ordinary resistors and conductive wires is designed and tested which launches a 0.8 ns risetime, 40 ns width, and kV-level rectangular pulse from a coaxial cable onto a rod-shaped resistive high-voltage divider with risetime <2 ns with no significant distortion.

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

PubMed

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

2017-01-01

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

STD-NMR experiments identify a structural motif with novel second-site activity against West Nile virus NS2B-NS3 protease.

PubMed

Schöne, Tobias; Grimm, Lena Lisbeth; Sakai, Naoki; Zhang, Linlin; Hilgenfeld, Rolf; Peters, Thomas

2017-10-01

West Nile virus (WNV) belongs to the genus Flavivirus of the family Flaviviridae. This mosquito-borne virus that is highly pathogenic to humans has been evolving into a global threat during the past two decades. Despite many efforts, neither antiviral drugs nor vaccines are available. The viral protease NS2B-NS3 pro is essential for viral replication, and therefore it is considered a prime drug target. However, success in the development of specific NS2B-NS3 pro inhibitors had been moderate so far. In the search for new structural motifs with binding affinity for NS2B-NS3 pro , we have screened a fragment library, the Maybridge Ro5 library, employing saturation transfer difference (STD) NMR experiments as readout. About 30% of 429 fragments showed binding to NS2B-NS3 pro . Subsequent STD-NMR competition experiments using the known active site fragment A as reporter ligand yielded 14 competitively binding fragments, and 22 fragments not competing with A. In a fluorophore-based protease assay, all of these fragments showed inhibition in the micromolar range. Interestingly, 10 of these 22 fragments showed a notable increase of STD intensities in the presence of compound A suggesting cooperative binding. The most promising non-competitive inhibitors 1 and 2 (IC 50 ∼ 500 μM) share a structural motif that may guide the development of novel second-site (potentially allosteric) inhibitors of NS2B-NS3 pro . To identify the matching protein binding site, chemical shift perturbation studies employing 1 H, 15 N-TROSY-HSQC experiments with uniformly 2 H, 15 N-labeled protease were performed in the presence of 1, and in the concomitant absence or presence of A. The data suggest that 1 interacts with Met 52* of NS2B, identifying a secondary site adjacent to the binding site of A. Therefore, our study paves the way for the synthesis of novel bidentate NS2B-NS3 pro inhibitors. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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

2009-01-01

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

REX, a 5-MV pulsed-power source for driving high-brightness electron beam diodes

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

Carlson, R.L.; Kauppila, T.J.; Ridlon, R.N.

1991-01-01

The Relativistic Electron-beam Experiment, or REX accelerator, is a pulsed-power source capable of driving a 100-ohm load at 5 MV, 50 kA, 45 ns (FWHM) with less than a 10-ns rise and 15-ns fall time. This paper describes the pulsed-power modifications, modelling, and extensive measurements on REX to allow it to drive high impedance (100s of ohms) diode loads with a shaped voltage pulse. A major component of REX is the 1.83-m-diam {times} 25.4-cm-thick Lucite insulator with embedded grading rings that separates the output oil transmission line from the vacuum vessel that contains the re-entrant anode and cathode assemblies. Amore » radially tailored, liquid-based resistor provides a stiff voltage source that is insensitive to small variations of the diode current and, in addition, optimizes the electric field stress across the vacuum side of the insulator. The high-current operation of REX employs both multichannel peaking and point-plane diverter switches. This mode reduces the prepulse to less than 2 kV and the postpulse to less than 5% of the energy delivered to the load. Pulse shaping for the present diode load is done through two L-C transmission line filters and a tapered, glycol-based line adjacent to the water PFL and output switch. This has allowed REX to drive a diode producing a 4-MV, 4.5-kA, 55-ns flat-top electron beam with a normalized Lapostolle emittance of 0.96 mm-rad corresponding to a beam brightness in excess of 4.4 {times} 10{sup 8} A/m{sup 2} {minus}rad{sup 2}. 6 refs., 13 figs.« less

Substrate inhibition kinetic model for West Nile virus NS2B-NS3 protease.

PubMed

Tomlinson, Suzanne M; Watowich, Stanley J

2008-11-11

West Nile virus (WNV) has recently emerged in North America as a significant disease threat to humans and animals. Unfortunately, no approved antiviral drugs exist to combat WNV or other members of the genus Flavivirus in humans. The WNV NS2B-NS3 protease has been one of the primary targets for anti-WNV drug discovery and design since it is required for virus replication. As part of our efforts to develop effective WNV inhibitors, we reexamined the reaction kinetics of the NS2B-NS3 protease and the inhibition mechanisms of newly discovered inhibitors. The WNV protease showed substrate inhibition in assays utilizing fluorophore-linked peptide substrates GRR, GKR, and DFASGKR. Moreover, a substrate inhibition reaction step was required to accurately model kinetic data generated from protease assays with a peptide inhibitor. The substrate inhibition model suggested that peptide substrates could bind to two binding sites on the protease. Reaction product analogues also showed inhibition of the protease, demonstrating product inhibition in addition to and distinct from substrate inhibition. We propose that small peptide substrates and inhibitors may interact with protease residues that form either the P3-P1 binding surface (i.e., the S3-S1 sites) or the P1'-P3' interaction surface (i.e., the S1'-S3' sites). Optimization of substrate analogue inhibitors that target these two independent sites may lead to novel anti-WNV drugs.

Flavonoid from Carica papaya inhibits NS2B-NS3 protease and prevents Dengue 2 viral assembly.

PubMed

Senthilvel, Padmanaban; Lavanya, Pandian; Kumar, Kalavathi Murugan; Swetha, Rayapadi; Anitha, Parimelzaghan; Bag, Susmita; Sarveswari, Sundaramoorthy; Vijayakumar, Vijayaparthasarathi; Ramaiah, Sudha; Anbarasu, Anand

2013-01-01

Dengue virus belongs to the virus family Flaviviridae. Dengue hemorrhagic disease caused by dengue virus is a public health problem worldwide. The viral non structural 2B and 3 (NS2B-NS3) protease complex is crucial for virus replication and hence, it is considered to be a good anti-viral target. Leaf extracts from Carica papaya is generally prescribed for patients with dengue fever, but there are no scientific evidences for its anti-dengue activity; hence we intended to investigate the anti-viral activity of compounds present in the leaves of Carica papaya against dengue 2 virus (DENV-2). We analysed the anti-dengue activities of the extracts from Carica papaya by using bioinformatics tools. Interestingly, we find the flavonoid quercetin with highest binding energy against NS2B-NS3 protease which is evident by the formation of six hydrogen bonds with the amino acid residues at the binding site of the receptor. Our results suggest that the flavonoids from Carica papaya have significant anti-dengue activities. ADME - Absorption, distribution, metabolism and excretion, BBB - Blood brain barrier, CYP - Cytochrome P450, DENV - - Dengue virus, DHF - Dengue hemorrhagic fever, DSS - Dengue shock syndrome, GCMS - - Gas chromatography- Mass spectrometry, MOLCAD - Molecular Computer Aided Design, NS - Non structural, PDB - Protein data bank, PMF - Potential Mean Force.

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

PubMed

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

2017-03-01

Zika virus is spread by Aedes mosquitoes and is linked to acute neurological disorders, especially to microcephaly in newborn children and Guillan-Barré Syndrome. The NS2B-NS3 protease of this virus is responsible for polyprotein processing and therefore considered an attractive drug target. In this study, we have used the Hybrid Combinatorial Substrate Library (HyCoSuL) approach to determine the substrate specificity of ZIKV NS2B-NS3 protease in the P4-P1 positions using natural and a large spectrum of unnatural amino acids. Obtained data demonstrate a high level of specificity of the S3-S1 subsites, especially for basic amino acids. However, the S4 site exhibits a very broad preference toward natural and unnatural amino acids with selected D-amino acids being favored over L enantiomers. This information was used for the design of a very potent phosphonate inhibitor/activity-based probe of ZIKV NS2B-NS3 protease. Copyright © 2016 Elsevier B.V. All rights reserved.

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

NASA Astrophysics Data System (ADS)

Smith, N. S.; Tesch, P. P.; Martin, N. P.; Kinion, D. E.

2008-12-01

The two most prevalent ion source technologies in the field of surface analysis and surface machining are the Duoplasmatron and the liquid metal ion source (LMIS). There have been many efforts in this area of research to develop an alternative source [ S.K. Guharay, J. Orloff, M. Wada, IEEE Trans. Plasma Sci. 33 (6) (2005) 1911; N.S. Smith, W.P. Skoczylas, S.M. Kellogg, D.E. Kinion, P.P. Tesch, O. Sutherland, A. Aanesland, R.W. Boswell, J. Vac. Sci. Technol. B 24 (6) (2006) 2902-2906] with the brightness of a LMIS and yet the ability to produce secondary ion yield enhancing species such as oxygen. However, to date a viable alternative has not been realized. The high brightness and small virtual source size of the LMIS are advantageous for forming high resolution probes but a significant disadvantage when beam currents in excess of 100 nA are required, due to the effects of spherical aberration from the optical column. At these higher currents a source with a high angular intensity is optimal and in fact the relatively moderate brightness of today's plasma ion sources prevail in this operating regime. Both the LMIS and Duoplasmatron suffer from a large axial energy spread resulting in further limitations when forming focused beams at the chromatic limit where the figure-of-merit is inversely proportional to the square of the energy spread. Also, both of these ion sources operate with a very limited range of ion species. This article reviews some of the latest developments and some future potential in this area of instrument development. Here we present an approach to source development that could lead to oxygen ion beam SIMS imaging with 10 nm resolution, using a 'broad area' RF gas phase ion source.

Differential Rotation via Tracking of Coronal Bright Points.

NASA Astrophysics Data System (ADS)

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

2016-05-01

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

Anthracene-based Inhibitors of Dengue Virus NS2B-NS3 Protease†

PubMed Central

Tomlinson, Suzanne M.; Watowich, Stanley J.

2010-01-01

Summary Dengue virus (DENV) is a mosquito-borne flavivirus that has strained global healthcare systems throughout tropical and subtropical regions of the world. In addition to plaguing developing nations, it has re-emerged in several developed countries with recent outbreaks in the USA (CDC, 2010), Australia (Hanna et al., 2009), Taiwan (Kuan et al., 2010) and France (La Ruche et al., 2010). DENV infection can cause significant disease, including dengue fever, dengue hemorrhagic fever, dengue shock syndrome, and death. There are no approved vaccines or antiviral therapies to prevent or treat dengue-related illnesses. However, the viral NS2B-NS3 protease complex provides a strategic target for antiviral drug development since NS3 protease activity is required for virus replication. Recently, we reported two compounds with inhibitory activity against the DENV protease in vitro and antiviral activity against dengue 2 (DEN2V) in cell culture (Tomlinson et al., 2009a). Analogs of one of the lead compounds were purchased, tested in protease inhibition assays, and the data evaluated with detailed kinetic analyses. A structure activity relationship (SAR) identified key atomic determinants (i.e. functional groups) important for inhibitory activity. Four “second series” analogs were selected and tested to validate our SAR and structural models. Here, we report improvements to inhibitory activity ranging between ~2- and 60-fold, resulting in selective low micromolar dengue protease inhibitors. PMID:21185332

NMR study of complexes between low molecular mass inhibitors and the West Nile virus NS2B-NS3 protease.

PubMed

Su, Xun-Cheng; Ozawa, Kiyoshi; Yagi, Hiromasa; Lim, Siew P; Wen, Daying; Ekonomiuk, Dariusz; Huang, Danzhi; Keller, Thomas H; Sonntag, Sebastian; Caflisch, Amedeo; Vasudevan, Subhash G; Otting, Gottfried

2009-08-01

The two-component NS2B-NS3 protease of West Nile virus is essential for its replication and presents an attractive target for drug development. Here, we describe protocols for the high-yield expression of stable isotope-labelled samples in vivo and in vitro. We also describe the use of NMR spectroscopy to determine the binding mode of new low molecular mass inhibitors of the West Nile virus NS2B-NS3 protease which were discovered using high-throughput in vitro screening. Binding to the substrate-binding sites S1 and S3 is confirmed by intermolecular NOEs and comparison with the binding mode of a previously identified low molecular mass inhibitor. Our results show that all these inhibitors act by occupying the substrate-binding site of the protease rather than by an allosteric mechanism. In addition, the NS2B polypeptide chain was found to be positioned near the substrate-binding site, as observed previously in crystal structures of the protease in complex with peptide inhibitors or bovine pancreatic trypsin inhibitor. This indicates that the new low molecular mass compounds, although inhibiting the protease, also promote the proteolytically active conformation of NS2B, which is very different from the crystal structure of the protein without inhibitor.

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

PubMed Central

Lan, Weizhong; Feldkaemper, Marita; Schaeffel, Frank

2014-01-01

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

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

PubMed

Lan, Weizhong; Feldkaemper, Marita; Schaeffel, Frank

2014-01-01

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

PARP12 suppresses Zika virus infection through PARP-dependent degradation of NS1 and NS3 viral proteins.

PubMed

Li, Lili; Zhao, Hui; Liu, Ping; Li, Chunfeng; Quanquin, Natalie; Ji, Xue; Sun, Nina; Du, Peishuang; Qin, Cheng-Feng; Lu, Ning; Cheng, Genhong

2018-06-19

Zika virus infection stimulates a type I interferon (IFN) response in host cells, which suppresses viral replication. Type I IFNs exert antiviral effects by inducing the expression of hundreds of IFN-stimulated genes (ISGs). To screen for antiviral ISGs that restricted Zika virus replication, we individually knocked out 21 ISGs in A549 lung cancer cells and identified PARP12 as a strong inhibitor of Zika virus replication. Our findings suggest that PARP12 mediated the ADP-ribosylation of NS1 and NS3, nonstructural viral proteins that are involved in viral replication and modulating host defense responses. This modification of NS1 and NS3 triggered their proteasome-mediated degradation. These data increase our understanding of the antiviral activity of PARP12 and suggest a molecular basis for the potential development of therapeutics against Zika virus. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

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

NASA Astrophysics Data System (ADS)

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

2018-01-01

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

Exploring the Lead Compounds for Zika Virus NS2B-NS3 Protein: an e-Pharmacophore-Based Approach.

PubMed

Rohini, K; Agarwal, Pratika; Preethi, B; Shanthi, V; Ramanathan, K

2018-06-18

The rapid spread of the Zika virus and its association with the abnormal brain development constitute a global health emergency. With a continuing spread of the mosquito vector, the exposure is expected to accelerate in the coming years. Despite number of efforts, there is still no proper vaccine or medicine to combat this virus. Of note, the NS2B-NS3 protein is proven to be the potential target for the Zika virus therapeutics. Hence, e-pharmacophore-based drug design strategy was employed to identify potent inhibitors of NS2B-NS3 protein from ASINEX database consisting of 467,802 molecules. A 3D e-pharmacophore model was generated using PHASE module of Schrödinger Suite. The generated model consists of one hydrogen bond acceptor (A), two hydrogen bond donors (D), and two aromatic rings (R), ADDRR. The model was further evaluated for its ability to screen actives using enrichment analysis. Subsequently, high-throughput virtual screening protocol was employed, and the resultant hit molecules were also examined for its binding free energies and ADME properties using Prime MM-GBSA and Qikprop module of Schrodinger packages, respectively. Finally, the screened hit molecule was subjected to molecular dynamics simulation to examine its stability. Overall, the results from our analysis suggest that compound BAS 19192837 could be a potent inhibitor for the NS2B-NS3 protein of the Zika virus. It is also noteworthy to mention that our results are in good agreement with literature evidences. We hope that this result is of immense importance in designing potential drug molecules to combat the spread of Zika virus in the near future.

Identification and subcellular localization of porcine deltacoronavirus accessory protein NS6

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

Fang, Puxian; Fang, Liurong; Liu, Xiaorong

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

The Neutron Star Zoo

NASA Technical Reports Server (NTRS)

Harding, Alice K.

2014-01-01

Neutron stars are a very diverse population, both in their observational and their physical properties. They prefer to radiate most of their energy at X-ray and gamma-ray wavelengths. But whether their emission is powered by rotation, accretion, heat, magnetic fields or nuclear reactions, they are all different species of the same animal whose magnetic field evolution and interior composition remain a mystery. This article will broadly review the properties of inhabitants of the neutron star zoo, with emphasis on their high-energy emission. XXX Neutron stars are found in a wide variety of sources, displaying an amazing array of behavior. They can be isolated or in binary systems, accreting, heating, cooling, spinning down, spinning up, pulsing, flaring and bursting. The one property that seems to determine their behavior most strongly is their magnetic field strength, structure and evolution. The hot polar caps, bursts and flares of magnetars are likely due to the rapid decay and twisting of their superstrong magnetic fields, whose very existence requires some kind of early dynamo activity. The intermediate-strength magnetic fields of RPPs determines their spin-down behavior and radiation properties. However, the overlap of the magnetar and RPP populations is not understood at present. Why don't high-field RPPs burst or flare? Why don't lower-field magnetars sometimes behave more like RPPs? INS may be old magnetars whose high fields have decayed, but they do not account for the existence of younger RPPs with magnetar-strength fields. Not only the strength of the magnetic field but also its configuration may be important in making a NS a magnetar or a RPP. Magnetic field decay is a critical link between other NS populations as well. "Decay" of the magnetic field is necessary for normal RPPs to evolve into MSPs through accretion and spin up in LMXBs. Some kind of accretion-driven field reduction is the most likely mechanism, but it is controversial since it is not

Coronal bright points in microwaves

NASA Technical Reports Server (NTRS)

Kundu, M. R.; Nitta, N.

1988-01-01

An excellent map of the quiet sun showing coronal bright points at 20-cm wavelength was produced using the VLA on February 13, 1987. The locations of bright points (BPs) were studied relative to features on the photospheric magnetogram and Ca K spectroheliogram. Most bright points appearing in the full 5-hour synthesized map are associated with small bipolar structures on the photospheric magnetogram; and the brightest part of a BP tends to lie on the boundary of a supergranulation network. The bright points exhibit rapid variations in intensity superposed on an apparently slow variation.

Faint Ring, Bright Arc

NASA Image and Video Library

2010-01-12

In this image taken by NASA Cassini spacecraft, the bright arc in Saturn faint G ring contains a little something special. Although it cant be seen here, the tiny moonlet Aegaeon orbits within the bright arc.

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

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

Fridriksson, Joel K.; Homan, Jeroen; Remillard, Ronald A., E-mail: J.K.Fridriksson@uva.nl

2015-08-10

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

A Statistical Study of the Mass Distribution of Neutron Stars

NASA Astrophysics Data System (ADS)

Cheng, Zheng; Zhang, Cheng-Min; Zhao, Yong-Heng; Wang, De-Hua; Pan, Yuan-Yue; Lei, Ya-Juan

2014-07-01

By reviewing the methods of mass measurements of neutron stars in four different kinds of systems, i.e., the high-mass X-ray binaries (HMXBs), low-mass X-ray binaries (LMXBs), double neutron star systems (DNSs) and neutron star-white dwarf (NS-WD) binary systems, we have collected the orbital parameters of 40 systems. By using the boot-strap method and the Monte-Carlo method, we have rebuilt the likelihood probability curves of the measured masses of 46 neutron stars. The statistical analysis of the simulation results shows that the masses of neutron stars in the X-ray neutron star systems and those in the radio pulsar systems exhibit different distributions. Besides, the Bayes statistics of these four different kind systems yields the most-probable probability density distributions of these four kind systems to be (1.340 ± 0.230)M8, (1, 505 ± 0.125)M8,(1.335 ± 0.055)M8 and (1.495 ± 0.225)M8, respectively. It is noteworthy that the masses of neutron stars in the HMXB and DNS systems are smaller than those in the other two kind systems by approximately 0.16M8. This result is consistent with the theoretical model of the pulsar to be accelerated to the millisecond order of magnitude via accretion of approximately 0.2M8. If the HMXBs and LMXBs are respectively taken to be the precursors of the BNS and NS-WD systems, then the influence of the accretion effect on the masses of neutron stars in the HMXB systems should be exceedingly small. Their mass distributions should be very close to the initial one during the formation of neutron stars. As for the LMXB and NS-WD systems, they should have already under- gone the process of suffcient accretion, hence there arises rather large deviation from the initial mass distribution.

Delayed and highly specific antibody response to nonstructural protein 1 (NS1) revealed during natural human ZIKV infection by NS1-based capture ELISA.

PubMed

Gao, Xiujie; Wen, Yingfen; Wang, Jian; Hong, Wenxin; Li, Chunlin; Zhao, Lingzhai; Yin, Chibiao; Jin, Xia; Zhang, Fuchun; Yu, Lei

2018-06-14

Zika virus (ZIKV) had spread rapidly in the past few years in southern hemisphere where dengue virus (DENV) had caused epidemic problems for over half a century. The high degree of cross-reactivity of Envelope (E) protein specific antibody responses between ZIKV and DENV made it challenging to perform differential diagnosis between the two infections using standard ELISA method for E protein. Using an IgG capture ELISA, we investigated the kinetics of nonstructural protein 1 (NS1) antibody response during natural ZIKV infection and the cross-reactivity to NS1 proteins using convalescent sera obtained from patients infected by either DENV or ZIKV. The analyses of the sequential serum samples from ZIKV infected individuals showed NS1 specific Abs appeared 2 weeks later than E specific Abs. Notably, human sera from ZIKV infected individuals did not contain cross-reactivity to NS1 proteins of any of the four DENV serotypes. Furthermore, four out of five NS1-specific monoclonal antibodies (mAbs) isolated from ZIKV infected individuals did not bind to DENV NS1 proteins. Only limited amount of cross-reactivity to ZIKV NS1 was displayed in 108 DENV1 immune sera at 1:100 dilution. The high degree of NS1-specific Abs in both ZIKV and DENV infection revealed here suggest that NS1-based diagnostics would significantly improve the differential diagnosis between DENV and ZIKV infections.

On the Evolution of Low-Mass X-Ray Binaries under the Influence of a Donor Stellar Wind Induced by X-Rays from the Accretor

NASA Astrophysics Data System (ADS)

Iben, Icko, Jr.; Tutukov, Alexander V.; Fedorova, Alexandra V.

1997-09-01

In a low-mass X-ray binary (LMXB), an intense stellar wind from the mass donor may be a consequence of the absorption of X-rays from the mass-accreting neutron star or black hole, and such a wind could change the evolution of these binaries dramatically compared with the evolution of cataclysmic variables (CVs), which are close binaries in which the accretor is a white dwarf. An analytical study and numerical models show that, in the closest and brightest LMXBs, a relativistic companion can capture up to ~10% of the mass lost in the induced stellar wind (ISW) from the main-sequence or subgiant donor, and this is enough to keep the X-ray luminosity of a typical LMXB on the level of LX ~ 5000 L⊙ and to accelerate the rotation of an old neutron star with a low magnetic field into the millisecond-period range. A self-sustained ISW may exist even if the donor does not fill its Roche lobe, but the system can be bright (LX > 100 L⊙) only if the radius of the donor is a substantial fraction (>~0.8) of the Roche lobe radius. A lower limit on the Roche lobe filling factor follows from the circumstance that both the rate Ėwind at which work must be done to lift wind matter off the donor and the rate Ėabs at which the donor absorbs X-ray energy are proportional to ṀISW (the ISW mass-loss rate) and from the requirement that Ėwind<Ėabs in order for energy to be conserved. The observed number (~100) of bright LMXBs in our Galaxy can be understood as the product of a relatively short lifetime (a few × 107 yr) and a small theoretical birthrate (~2 × 10-6-8 × 10-6 yr-1), which is comparable to semiempirical estimates of the birthrate of LMXBs and millisecond pulsars (~2 × 10-6 yr-1). The theoretical lifetime is ~10-60 times shorter than when the ISW is not taken into account, and the theoretical birthrate is ~3-6 times smaller, because of the fact that the ISW acts to expand the orbit and reduce the number of systems that can evolve through an X-ray bright stage under

Nonstructural proteins nsP3 and nsP4 of Ross River and O'Nyong-nyong viruses: sequence and comparison with those of other alphaviruses.

PubMed

Strauss, E G; Levinson, R; Rice, C M; Dalrymple, J; Strauss, J H

1988-05-01

We have sequenced the nsP3 and nsP4 region of two alphaviruses, Ross River virus and O'Nyong-nyong virus, in order to examine these viruses for the presence or absence of an opal termination codon present between nsP3 and nsP4 in many alphaviruses. We found that Ross River virus possesses an in-phase opal termination codon between nsP3 and nsP4, whereas in O'Nyong-nyong virus this termination codon is replaced by an arginine codon. Previous studies have shown that two other alphaviruses, Sindbis virus and Middelburg virus, possess an opal termination codon separating nsP3 and nsP4 [E.G. Strauss, C.M. Rice, and J.H. Strauss (1983), Proc. Natl. Acad. Sci. USA 80, 5271-5275], whereas Semliki Forest virus possesses an arginine codon in lieu of the opal codon [K. Takkinen (1986), Nucleic Acids Res. 14, 5667-5682]. Thus, of the five alphaviruses examined to date, three possess the opal codon and two do not. Production of nsP4 requires readthrough of the opal codon in those alphaviruses that possess this termination codon and the function of the termination codon may be to regulate the amount of nsP4 produced. It is an open question then as to whether alphaviruses with no termination codon use other mechanisms to regulate the activity of this gene. The nsP4s of these five alphaviruses are highly conserved, sharing 71-76% amino acid sequence similarity, and all five contain the Gly-Asp-Asp motif found in many RNA virus replicases. The nsP3s are somewhat less conserved, sharing 52-73% amino acid sequence similarity throughout most of the protein, but each possesses a nonconserved C-terminal domain of 134 to 246 amino acids of unknown function.

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

NASA Astrophysics Data System (ADS)

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

2015-01-01

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

Sindbis virus proteins nsP1 and nsP2 contain homology to nonstructural proteins from several RNA plant viruses.

PubMed Central

Ahlquist, P; Strauss, E G; Rice, C M; Strauss, J H; Haseloff, J; Zimmern, D

1985-01-01

Although the genetic organization of tobacco mosaic virus (TMV) differs considerably from that of the tripartite viruses (alfalfa mosaic virus [AlMV] and brome mosaic virus [BMV]), all of these RNA plant viruses share three domains of homology among their nonstructural proteins. One such domain, common to the AlMV and BMV 2a proteins and the readthrough portion of TMV p183, is also homologous to the readthrough protein nsP4 of Sindbis virus (Haseloff et al., Proc. Natl. Acad. Sci. U.S.A. 81:4358-4362, 1984). Two more domains are conserved among the AlMV and BMV 1a proteins and TMV p126. We show here that these domains have homology with portions of the Sindbis proteins nsP1 and nsP2, respectively. These results strengthen the view that the four viruses share mechanistic similarities in their replication strategies and may be evolutionarily related. These results also suggest that either the AlMV 1a, BMV 1a, and TMV p126 proteins are multifunctional or Sindbis proteins nsP1 and nsP2 function together as subunits in a single complex. PMID:3968720

Novel dengue virus NS2B/NS3 protease inhibitors.

PubMed

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

2015-02-01

Dengue fever is a severe, widespread, and neglected disease with more than 2 million diagnosed infections per year. The dengue virus NS2B/NS3 protease (PR) represents a prime target for rational drug design. At the moment, there are no clinical PR inhibitors (PIs) available. We have identified diaryl (thio)ethers as candidates for a novel class of PIs. Here, we report the selective and noncompetitive inhibition of the serotype 2 and 3 dengue virus PR in vitro and in cells by benzothiazole derivatives exhibiting 50% inhibitory concentrations (IC50s) in the low-micromolar range. Inhibition of replication of DENV serotypes 1 to 3 was specific, since all substances influenced neither hepatitis C virus (HCV) nor HIV-1 replication. Molecular docking suggests binding at a specific allosteric binding site. In addition to the in vitro assays, a cell-based PR assay was developed to test these substances in a replication-independent way. The new compounds inhibited the DENV PR with IC50s in the low-micromolar or submicromolar range in cells. Furthermore, these novel PIs inhibit viral replication at submicromolar concentrations. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Intrinsic Brightness Temperatures of AGN Jets

NASA Astrophysics Data System (ADS)

Homan, D. C.; Kovalev, Y. Y.; Lister, M. L.; Ros, E.; Kellermann, K. I.; Cohen, M. H.; Vermeulen, R. C.; Zensus, J. A.; Kadler, M.

2006-05-01

We present a new method for studying the intrinsic brightness temperatures of the parsec-scale jet cores of active galactic nuclei (AGNs). Our method uses observed superluminal motions and observed brightness temperatures for a large sample of AGNs to constrain the characteristic intrinsic brightness temperature of the sample as a whole. To study changes in intrinsic brightness temperature, we assume that the Doppler factors of individual jets are constant in time, as justified by their relatively small changes in observed flux density. We find that in their median-low brightness temperature state, the sources in our sample have a narrow range of intrinsic brightness temperatures centered on a characteristic temperature, Tint~=3×1010 K, which is close to the value expected for equipartition, when the energy in the radiating particles equals the energy stored in the magnetic fields. However, in their maximum brightness state, we find that sources in our sample have a characteristic intrinsic brightness temperature greater than 2×1011 K, which is well in excess of the equipartition temperature. In this state, we estimate that the energy in radiating particles exceeds the energy in the magnetic field by a factor of ~105. We suggest that the excess of particle energy when sources are in their maximum brightness state is due to injection or acceleration of particles at the base of the jet. Our results suggest that the common method of estimating jet Doppler factors by using a single measurement of observed brightness temperature, the assumption of equipartition, or both may lead to large scatter or systematic errors in the derived values.

Functional interplay among the flavivirus NS3 protease, helicase, and cofactors.

PubMed

Li, Kuohan; Phoo, Wint Wint; Luo, Dahai

2014-04-01

Flaviviruses are positive-sense RNA viruses, and many are important human pathogens. Nonstructural protein 2B and 3 of the flaviviruses (NS2BNS3) form an endoplasmic reticulum (ER) membrane-associated hetero-dimeric complex through the NS2B transmembrane region. The NS2BNS3 complex is multifunctional. The N-terminal region of NS3, and its cofactor NS2B fold into a protease that is responsible for viral polyprotein processing, and the C-terminal domain of NS3 possesses NTPase/RNA helicase activities and is involved in viral RNA replication and virus particle formation. In addition, NS2BNS3 complex has also been shown to modulate viral pathogenesis and the host immune response. Because of the essential functions that the NS2BNS3 complex plays in the flavivirus life cycle, it is an attractive target for antiviral development. This review focuses on the recent biochemical and structural advances of NS2BNS3 and provides a brief update on the current status of drug development targeting this viral protein complex.

Do Low Surface Brightness Galaxies Host Stellar Bars?

NASA Astrophysics Data System (ADS)

Cervantes Sodi, Bernardo; Sánchez García, Osbaldo

2017-09-01

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

Do Low Surface Brightness Galaxies Host Stellar Bars?

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

Cervantes Sodi, Bernardo; Sánchez García, Osbaldo, E-mail: b.cervantes@irya.unam.mx, E-mail: o.sanchez@irya.unam.mx

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

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

PubMed

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

2007-02-01

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

Map of Ceres' Bright Spots

NASA Image and Video Library

2017-12-12

This map from NASA's Dawn mission shows locations of bright material on dwarf planet Ceres. There are more than 300 bright areas, called "faculae," on Ceres. Scientists have divided them into four categories: bright areas on the floors of crater (red), on the rims or walls of craters (green), in the ejecta blankets of craters (blue), and on the flanks of the mountain Ahuna Mons (yellow). https://photojournal.jpl.nasa.gov/catalog/PIA21914

Synthesis and disulfide bond connectivity-activity studies of a kalata B1-inspired cyclopeptide against dengue NS2B-NS3 protease.

PubMed

Gao, Yaojun; Cui, Taian; Lam, Yulin

2010-02-01

Kalata B1 is a plant protein with remarkable thermal, chemical and enzymatic stability. Its potential applications could be centered on the possibility of using its cyclic structure and cystine knot motif as a scaffold for the design of stable pharmaceuticals. To discover potent dengue NS2B-NS3 protease inhibitors, we have prepared various kalata B1 analogues by varying the amino acid sequence. Mass spectrometric and biochemical investigations of these analogues revealed a cyclopeptide whose two fully oxidized forms are substrate-competitive inhibitors of the dengue viral NS2B-NS3 protease. Both oxidized forms showed potent inhibition with K(i) of 1.39+/-0.35 and 3.03+/-0.75 microM, respectively. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Little Bright Spot

NASA Image and Video Library

2015-01-12

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

Lunar and Venusian radar bright rings

NASA Technical Reports Server (NTRS)

Thompson, T. W.; Saunders, R. S.; Weissman, D. E.

1986-01-01

Twenty-one lunar craters have radar bright ring appearances which are analogous to eleven complete ring features in the earth-based 12.5 cm observations of Venus. Radar ring diameters and widths for the lunar and Venusian features overlap for sizes from 45 to 100 km. Radar bright areas for the lunar craters are associated with the slopes of the inner and outer rim walls, while level crater floors and level ejecta fields beyond the raised portion of the rim have average radar backscatter. It is proposed that the radar bright areas of the Venusian rings are also associated with the slopes on the rims of craters. The lunar craters have evolved to radar bright rings via mass wasting of crater rim walls and via post-impact flooding of crater floors. Aeolian deposits of fine-grained material on Venusian crater floors may produce radar scattering effects similar to lunar crater floor flooding. These Venusian aeolian deposits may preferentially cover blocky crater floors producing a radar bright ring appearance. It is proposed that the Venusian features with complete bright ring appearances and sizes less than 100 km are impact craters. They have the same sizes as lunar craters and could have evolved to radar bright rings via analogous surface processes.

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

PubMed

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

2017-05-15

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

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

PubMed

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

2015-10-01

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

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

PubMed Central

Liu, Binbin; Zhang, Jing; Koetzner, Cheri A.; Jones, Susan A.; Lin, Qishan

2017-01-01

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

The influenza virus NS1 protein as a therapeutic target.

PubMed

Engel, Daniel A

2013-09-01

Nonstructural protein 1 (NS1) of influenza A virus plays a central role in virus replication and blockade of the host innate immune response, and is therefore being considered as a potential therapeutic target. The primary function of NS1 is to dampen the host interferon (IFN) response through several distinct molecular mechanisms that are triggered by interactions with dsRNA or specific cellular proteins. Sequestration of dsRNA by NS1 results in inhibition of the 2'-5' oligoadenylate synthetase/RNase L antiviral pathway, and also inhibition of dsRNA-dependent signaling required for new IFN production. Binding of NS1 to the E3 ubiquitin ligase TRIM25 prevents activation of RIG-I signaling and subsequent IFN induction. Cellular RNA processing is also targeted by NS1, through recognition of cleavage and polyadenylation specificity factor 30 (CPSF30), leading to inhibition of IFN-β mRNA processing as well as that of other cellular mRNAs. In addition NS1 binds to and inhibits cellular protein kinase R (PKR), thus blocking an important arm of the IFN system. Many additional proteins have been reported to interact with NS1, either directly or indirectly, which may serve its anti-IFN and additional functions, including the regulation of viral and host gene expression, signaling pathways and viral pathogenesis. Many of these interactions are potential targets for small-molecule intervention. Structural, biochemical and functional studies have resulted in hypotheses for drug discovery approaches that are beginning to bear experimental fruit, such as targeting the dsRNA-NS1 interaction, which could lead to restoration of innate immune function and inhibition of virus replication. This review describes biochemical, cell-based and nucleic acid-based approaches to identifying NS1 antagonists. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

The influenza virus NS1 protein as a therapeutic target

PubMed Central

Engel, Daniel A.

2015-01-01

Nonstructural protein 1 (NS1) of influenza A virus plays a central role in virus replication and blockade of the host innate immune response, and is therefore being considered as a potential therapeutic target. The primary function of NS1 is to dampen the host interferon (IFN) response through several distinct molecular mechanisms that are triggered by interactions with dsRNA or specific cellular proteins. Sequestration of dsRNA by NS1 results in inhibition of the 2’-5’ oligoadenylate synthetase/RNase L antiviral pathway, and also inhibition of dsRNA-dependent signaling required for new IFN production. Binding of NS1 to the E3 ubiquitin ligase TRIM25 prevents activation of RIG-I signaling and subsequent IFN induction. Cellular RNA processing is also targeted by NS1, through recognition of cleavage and polyadenylation specificity factor 30 (CPSF30), leading to inhibition of IFN- mRNA processing as well as that of other cellular mRNAs. In addition NS1 binds to and inhibits cellular protein kinase R (PKR), thus blocking an important arm of the IFN system. Many additional proteins have been reported to interact with NS1, either directly or indirectly, which may serve its anti-IFN and additional functions, including the regulation of viral and host gene expression, signaling pathways and viral pathogenesis. Many of these interactions are potential targets for small-molecule intervention. Structural, biochemical and functional studies have resulted in hypotheses for drug discovery approaches that are beginning to bear experimental fruit, such as targeting the dsRNA-NS1 interaction, which could lead to restoration of innate immune function and inhibition of virus replication. This review describes biochemical, cell-based and nucleic acid-based approaches to identifying NS1 antagonists. PMID:23796981

[Bioinformatics analysis of mosquito densovirus nostructure protein NS1].

PubMed

Dong, Yun-qiao; Ma, Wen-li; Gu, Jin-bao; Zheng, Wen-ling

2009-12-01

To analyze and predict the structure and function of mosquito densovirus (MDV) nostructual protein1 (NS1). Using different bioinformatics software, the EXPASY pmtparam tool, ClustalX1.83, Bioedit, MEGA3.1, ScanProsite, and Motifscan, respectively to comparatively analyze and predict the physic-chemical parameters, homology, evolutionary relation, secondary structure and main functional motifs of NS1. MDV NS1 protein was a unstable hydrophilic protein and the amino acid sequence was highly conserved which had a relatively closer evolutionary distance with infectious hypodermal and hematopoietic necrosis virus (IHHNV). MDV NS1 has a specific domain of superfamily 3 helicase of small DNA viruses. This domain contains the NTP-binding region with a metal ion-dependent ATPase activity. A virus replication roller rolling-circle replication(RCR) initiation domain was found near the N terminal of this protein. This protien has the biological function of single stranded incision enzyme. The bioinformatics prediction results suggest that MDV NS1 protein plays a key role in viral replication, packaging, and the other stages of viral life.

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

PubMed

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

2017-06-01

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

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

PubMed Central

Firth, Andrew E; Atkins, John F

2009-01-01

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

BrightStat.com: free statistics online.

PubMed

Stricker, Daniel

2008-10-01

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

Characterization of NS5A and NS5B Resistance-Associated Substitutions from Genotype 1 Hepatitis C Virus Infected Patients in a Portuguese Cohort.

PubMed

Brandão, Ruben; Marcelino, Rute; Gonçalves, Fátima; Diogo, Isabel; Carvalho, Ana; Cabanas, Joaquim; Costa, Inês; Brogueira, Pedro; Ventura, Fernando; Miranda, Ana; Mansinho, Kamal; Gomes, Perpétua

2018-04-26

This study is focused on the prevalent NS5 coding region resistance-associated substitutions (RASs) in DAA-naive genotype (GT)1 HCV-infected patients and their potential impact on success rates. Plasma RNA from 81 GT1 HCV-infected patients was extracted prior to an in-house nested RT-PCR of the NS5 coding region, which is followed by Sanger population sequencing. NS5A RASs were present in 28.4% (23/81) of all GT1-infected patients with 9.9% (8/81) having the Y93C/H mutation. NS5B RASs showed a prevalence of 14.8% (12/81) and were only detected in GT1b. Overall 38.3% (31/81) of all GT1 HCV-infected patients presented baseline RASs. The obtained data supports the usefulness of resistance testing prior to treatment since a statistically significant association was found between treatment failure and the baseline presence of specific NS5 RASs known as Y93C/H ( p = 0.04).

Characterization of brightness and stoichiometry of bright particles by flow-fluorescence fluctuation spectroscopy.

PubMed

Johnson, Jolene; Chen, Yan; Mueller, Joachim D

2010-11-03

Characterization of bright particles at low concentrations by fluorescence fluctuation spectroscopy (FFS) is challenging, because the event rate of particle detection is low and fluorescence background contributes significantly to the measured signal. It is straightforward to increase the event rate by flow, but the high background continues to be problematic for fluorescence correlation spectroscopy. Here, we characterize the use of photon-counting histogram analysis in the presence of flow. We demonstrate that a photon-counting histogram efficiently separates the particle signal from the background and faithfully determines the brightness and concentration of particles independent of flow speed, as long as undersampling is avoided. Brightness provides a measure of the number of fluorescently labeled proteins within a complex and has been used to determine stoichiometry of protein complexes in vivo and in vitro. We apply flow-FFS to determine the stoichiometry of the group specific antigen protein within viral-like particles of the human immunodeficiency virus type-1 from the brightness. Our results demonstrate that flow-FFS is a sensitive method for the characterization of complex macromolecular particles at low concentrations. Copyright © 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Inverse Compton Scattered Merger-nova: Late X-Ray Counterpart of Gravitational-wave Signals from NS–NS/BH Mergers

NASA Astrophysics Data System (ADS)

Ai, Shunke; Gao, He

2018-01-01

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.

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-09-15

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

Bright Enceladus

NASA Image and Video Library

2011-02-14

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

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

NASA Astrophysics Data System (ADS)

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

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

The possible existence of Pop III NS-BH binary and its detectability

NASA Astrophysics Data System (ADS)

Kinugawa, Tomoya; Nakamura, Takashi; Nakano, Hiroyuki

2017-02-01

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.

Fast hepatitis C virus RNA elimination and NS5A redistribution by NS5A inhibitors studied by a multiplex assay approach.

PubMed

Liu, Dandan; Ji, Juan; Ndongwe, Tanya P; Michailidis, Eleftherios; Rice, Charles M; Ralston, Robert; Sarafianos, Stefan G

2015-01-01

While earlier therapeutic strategies for the treatment of hepatitis C virus (HCV) infection relied exclusively on interferon (IFN) and ribavirin (RBV), four direct-acting antiviral agents (DAAs) have now been approved, aiming for an interferon-free strategy with a short treatment duration and fewer side effects. To facilitate studies on the mechanism of action (MOA) and efficacy of DAAs, we established a multiplex assay approach, which employs flow cytometry, a Gaussia luciferase reporter system, Western blot analysis, reverse transcription-quantitative PCR (RT-qPCR), a limited dilution assay (50% tissue culture infectious dose [TCID50]), and an image profiling assay that follows the NS5A redistribution in response to drug treatment. We used this approach to compare the relative potency of various DAAs and the kinetics of their antiviral effects as a potential preclinical measure of their potential clinical utility. We evaluated the NS5A inhibitors ledipasvir (LDV) and daclatasvir (DCV), the NS3/4A inhibitor danoprevir (DNV), and the NS5B inhibitor sofosbuvir (SOF). In terms of kinetics, our data demonstrate that the NS5A inhibitor LDV, followed closely by DCV, has the fastest effect on suppression of viral proteins and RNA and on redistribution of NS5A. In terms of MOA, LDV has a more pronounced effect than DCV on the viral replication, assembly, and infectivity of released virus. Our approach can be used to facilitate the study of the biological processes involved in HCV replication and help identify optimal drug combinations. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Brightness and transparency in the early visual cortex.

PubMed

Salmela, Viljami R; Vanni, Simo

2013-06-24

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

Brightness and magnetic evolution of solar coronal bright points

NASA Astrophysics Data System (ADS)

Ugarte Urra, Ignacio

This thesis presents a study of the brightness and magnetic evolution of several Extreme ultraviolet (EUV) coronal bright points (hereafter BPs). The study was carried out using several instruments on board the Solar and Heliospheric Observatory, supported by the high resolution imaging from the Transition Region And Coronal Explorer. The results confirm that, down to 1" resolution, BPs are made of small loops with lengths of [approximate]6 Mm and cross-sections of ≈2 Mm. The loops are very dynamic, evolving in time scales as short as 1 - 2 minutes. This is reflected in a highly variable EUV response with fluctuations highly correlated in spectral lines at transition region temperatures, but not always at coronal temperatures. A wavelet analysis of the intensity variations reveals the existence of quasi-periodic oscillations with periods ranging 400--1000s, in the range of periods characteristic of the chromospheric network. The link between BPs and network bright points is discussed, as well as the interpretation of the oscillations in terms of global acoustic modes of closed magnetic structures. A comparison of the magnetic flux evolution of the magnetic polarities to the EUV flux changes is also presented. Throughout their lifetime, the intrinsic EUV emission of BPs is found to be dependent on the total magnetic flux of the polarities. In short time scales, co-spatial and co-temporal coronal images and magnetograms, reveal the signature of heating events that produce sudden EUV brightenings simultaneous to magnetic flux cancellations. This is interpreted in terms of magnetic reconnection events. Finally, a electron density study of six coronal bright points produces values of ≈1.6×10 9 cm -3 , closer to active region plasma than to quiet Sun. The analysis of a large coronal loop (half length of 72 Mm) introduces the discussion on the prospects of future plasma diagnostics of BPs with forthcoming solar missions.

Teradiode's high brightness semiconductor lasers

NASA Astrophysics Data System (ADS)

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

2016-03-01

TeraDiode is manufacturing multi-kW-class ultra-high brightness fiber-coupled direct diode lasers for industrial applications. A fiber-coupled direct diode laser with a power level of 4,680 W from a 100 μm core diameter, <0.08 numerical aperture (NA) output fiber at a single center wavelength was demonstrated. Our TeraBlade industrial platform achieves 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.

Interactome Analysis of NS1 Protein Encoded by Influenza A H7N9 Virus Reveals an Inhibitory Role of NS1 in Host mRNA Maturation.

PubMed

Kuo, Rei-Lin; Chen, Chi-Jene; Tam, Ee-Hong; Huang, Chung-Guei; Li, Li-Hsin; Li, Zong-Hua; Su, Pei-Chia; Liu, Hao-Ping; Wu, Chih-Ching

2018-04-06

Influenza A virus infections can result in severe respiratory diseases. The H7N9 subtype of avian influenza A virus has been transmitted to humans and caused severe disease and death. Nonstructural protein 1 (NS1) of influenza A virus is a virulence determinant during viral infection. To elucidate the functions of the NS1 encoded by influenza A H7N9 virus (H7N9 NS1), interaction partners of H7N9 NS1 in human cells were identified with immunoprecipitation followed by SDS-PAGE coupled with liquid chromatography-tandem mass spectrometry (GeLC-MS/MS). We identified 36 cellular proteins as the interacting partners of the H7N9 NS1, and they are involved in RNA processing, mRNA splicing via spliceosome, and the mRNA surveillance pathway. Two of the interacting partners, cleavage and polyadenylation specificity factor subunit 2 (CPSF2) and CPSF7, were confirmed to interact with H7N9 NS1 using coimmunoprecipitation and immunoblotting based on the previous finding that the two proteins are involved in pre-mRNA polyadenylation machinery. Furthermore, we illustrate that overexpression of H7N9 NS1, as well as infection by the influenza A H7N9 virus, interfered with pre-mRNA polyadenylation in host cells. This study comprehensively profiled the interactome of H7N9 NS1 in host cells, and the results demonstrate a novel endotype for H7N9 NS1 in inhibiting host mRNA maturation.

SPECTRAL PROPERTIES OF X-RAY BINARIES IN CENTAURUS A

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

Burke, Mark J.; Raychaudhury, Somak; Kraft, Ralph P.

2013-04-01

We present a spectral investigation of X-ray binaries (XBs) in NGC 5128 (Cen A), using six 100 ks Chandra observations taken over two months in 2007. We divide our sample into thermally and non-thermally dominated states based on the behavior of the fitted absorption column N{sub H}, and present the spectral parameters of sources with L{sub x} {approx}> 2 Multiplication-Sign 10{sup 37} erg s{sup -1}. The majority of sources are consistent with being neutron star low-mass X-ray binaries (NS LMXBs) and we identify three transient black hole (BH) LMXB candidates coincident with the dust lane, which is the remnant ofmore » a small late-type galaxy. Our results also provide tentative support for the apparent 'gap' in the mass distribution of compact objects between {approx}2-5 M{sub Sun }. We propose that BH LMXBs are preferentially found in the dust lane, and suggest this is because of the younger stellar population. The majority ({approx}70%-80%) of potential Roche lobe filling donors in the Cen A halo are {approx}> 12 Gyr old, while BH LMXBs require donors {approx}> 1 M{sub Sun} to produce the observed peak luminosities. This requirement for more massive donors may also explain recent results that claim a steepening of the X-ray luminosity function with age at L{sub x} {>=} 5 Multiplication-Sign 10{sup 38} erg s{sup -1} for the XB population of early-type galaxies; for older stellar populations, there are fewer stars {approx}> 1 M{sub Sun }, which are required to form the more luminous sources.« less

Brightness perception of unrelated self-luminous colors.

PubMed

Withouck, Martijn; Smet, Kevin A G; Ryckaert, Wouter R; Pointer, Michael R; Deconinck, Geert; Koenderink, Jan; Hanselaer, Peter

2013-06-01

The perception of brightness of unrelated self-luminous colored stimuli of the same luminance has been investigated. The Helmholtz-Kohlrausch (H-K) effect, i.e., an increase in brightness perception due to an increase in saturation, is clearly observed. This brightness perception is compared with the calculated brightness according to six existing vision models, color appearance models, and models based on the concept of equivalent luminance. Although these models included the H-K effect and half of them were developed to work with unrelated colors, none of the models seemed to be able to fully predict the perceived brightness. A tentative solution to increase the prediction accuracy of the color appearance model CAM97u, developed by Hunt, is presented.

Occator Bright Spots in 3-D

NASA Image and Video Library

2017-03-09

This 3-D image, or anaglyph, shows the center of Occator Crater, the brightest area on dwarf planet Ceres, using data from NASA's Dawn mission. The bright central area, including a dome that is 0.25 miles (400 meters) high, is called Cerealia Facula. The secondary, scattered bright areas are called Vinalia Faculae. A 2017 study suggests that the central bright area is significantly younger than Occator Crater. Estimates put Cerealia Facula at 4 million years old, while Occator Crater is approximately 34 million years old. The reflective material that appears so bright in this image is made of carbonate salts, according to Dawn researchers. The Vinalia Faculae seem to be composed of carbonates mixed with dark material. http://photojournal.jpl.nasa.gov/catalog/PIA21398

Time-resolved brightness measurements by streaking

NASA Astrophysics Data System (ADS)

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

2018-03-01

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

RNA Modulates the Interaction between Influenza A Virus NS1 and Human PABP1.

PubMed

Arias-Mireles, Bryan H; de Rozieres, Cyrus M; Ly, Kevin; Joseph, Simpson

2018-05-25

Nonstructural protein 1 (NS1) is a multifunctional protein involved in preventing host-interferon response in influenza A virus (IAV). Previous studies have indicated that NS1 also stimulates the translation of viral mRNA by binding to conserved sequences in the viral 5'-UTR. Additionally, NS1 binds to poly(A) binding protein 1 (PABP1) and eukaryotic initiation factor 4G (eIF4G). The interaction of NS1 with the viral 5'-UTR, PABP1, and eIF4G has been suggested to specifically enhance the translation of viral mRNAs. In contrast, we report that NS1 does not directly bind to sequences in the viral 5'-UTR, indicating that NS1 is not responsible for providing the specificity to stimulate viral mRNA translation. We also monitored the interaction of NS1 with PABP1 using a new, quantitative FRET assay. Our data show that NS1 binds to PABP1 with high affinity; however, the binding of double-stranded RNA (dsRNA) to NS1 weakens the binding of NS1 to PABP1. Correspondingly, the binding of PABP1 to NS1 weakens the binding of NS1 to double-stranded RNA (dsRNA). In contrast, the affinity of PABP1 for binding to poly(A) RNA is not significantly changed by NS1. We propose that the modulation of NS1·PABP1 interaction by dsRNA may be important for the viral cycle.

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

NASA Astrophysics Data System (ADS)

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

2017-12-01

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

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

NASA Astrophysics Data System (ADS)

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

2018-04-01

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

Unexpected Functional Divergence of Bat Influenza Virus NS1 Proteins.

PubMed

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

2018-03-01

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

Unexpected Functional Divergence of Bat Influenza Virus NS1 Proteins

PubMed Central

Turkington, Hannah L.; Juozapaitis, Mindaugas; Tsolakos, Nikos; Corrales-Aguilar, Eugenia; Schwemmle, Martin

2017-01-01

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

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

Lin, Dacheng; Irwin, Jimmy A.; Wong, Ka-Wah

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

Milky Way globular cluster metallicity and low-mass X-ray binaries: the red giant influence

NASA Astrophysics Data System (ADS)

Vulic, N.; Barmby, P.; Gallagher, S. C.

2018-02-01

Galactic and extragalactic studies have shown that metal-rich globular clusters (GCs) are approximately three times more likely to host bright low-mass X-ray binaries (LMXBs) than metal-poor GCs. There is no satisfactory explanation for this metallicity effect. We tested the hypothesis that the number density of red giant branch (RGB) stars is larger in metal-rich GCs, and thus potentially the cause of the metallicity effect. Using Hubble Space Telescope photometry for 109 unique Milky Way GCs, we investigated whether RGB star density was correlated with GC metallicity. Isochrone fitting was used to calculate the number of RGB stars, which were normalized by the GC mass and fraction of observed GC luminosity, and determined density using the volume at the half-light radius (rh). The RGB star number density was weakly correlated with metallicity [Fe/H], giving Spearman and Kendall Rank test p-values of 0.000 16 and 0.000 21 and coefficients rs = 0.35 and τ = 0.24, respectively. This correlation may be biased by a possible dependence of rh on [Fe/H], although studies have shown that rh is correlated with Galactocentric distance and independent of [Fe/H]. The dynamical origin of the rh-metallicity correlation (tidal stripping) suggests that metal-rich GCs may have had more active dynamical histories, which would promote LMXB formation. No correlation between the RGB star number density and metallicity was found when using only the GCs that hosted quiescent LMXBs. A complete census of quiescent LMXBs in our Galaxy is needed to further probe the metallicity effect, which will be possible with the upcoming launch of eROSITA.

New Observations of Subarcsecond Photospheric Bright Points

NASA Technical Reports Server (NTRS)

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

1995-01-01

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

New Observations of Subarcsecond Photospheric Bright Points

NASA Technical Reports Server (NTRS)

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

1995-01-01

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

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

PubMed

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

2018-01-23

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

Pharmacophoric characteristics of dengue virus NS2B/NS3pro inhibitors: a systematic review of the most promising compounds.

PubMed

Leonel, Camyla Alves; Lima, William Gustavo; Dos Santos, Michelli; Ferraz, Ariane Coelho; Taranto, Alex Gutterres; de Magalhães, José Carlos; Dos Santos, Luciana Lara; Ferreira, Jaqueline Maria Siqueira

2018-03-01

Dengue virus (DENV) infection can lead to a wide range of clinical manifestations, including fatal hemorrhagic complications. There is a need to find effective pharmacotherapies to treat this disease due to the lack of specific immunotherapies and antiviral drugs. That said, the DENV NS2B/NS3pro protease complex is essential in both the viral multiplication cycle and in disease pathogenesis, and is considered a promising target for new antiviral therapies. Here, we performed a systematic review to evaluate the pharmacophoric characteristics of promising compounds against NS2B/NS3pro reported in the past 10 years. Online searches in the PUBMED/MEDLINE and SCOPUS databases resulted in 165 articles. Eight studies, which evaluated 3,384,268 molecules exhibiting protease inhibition activity, were included in this review. These studies evaluated anti-dengue activity in vitro and the IC 50 and EC 50 values were provided. Most compounds exhibited non-competitive inhibition. Cytotoxicity was evaluated in BHK-21, Vero, and LLC-MK2 cells, and the CC 50 values obtained ranged from < 1.0 to 780.5 µM. Several groups were associated with biological activity against dengue, including nitro, catechol, halogen and ammonium quaternaries. Thus, these groups seem to be potential pharmacophores that can be further investigated to treat dengue infections.

Magnetic topological analysis of coronal bright points

NASA Astrophysics Data System (ADS)

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

2017-10-01

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 http://www.aanda.org

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

PubMed

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

2017-09-01

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

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

NASA Astrophysics Data System (ADS)

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

2018-06-01

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

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

PubMed

Boonyasuppayakorn, Siwaporn; Padmanabhan, Radhakrishnan

2014-01-01

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

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

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

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

2014-06-10

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

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

PubMed

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

2017-07-01

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

Network based sky Brightness Monitor

NASA Astrophysics Data System (ADS)

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

2009-01-01

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

Bright light induces choroidal thickening in chickens.

PubMed

Lan, Weizhong; Feldkaemper, Marita; Schaeffel, Frank

2013-11-01

Bright light is a potent inhibitor of myopia development in animal models. Because development of refractive errors has been linked to changes in choroidal thickness, we have studied in chickens whether bright light may exert its effects on myopia also through changes in choroidal thickness. Three-day-old chickens were exposed to "bright light" (15,000 lux; n = 14) from 10 AM to 4 PM but kept under "normal light" (500 lux) during the remaining time of the light phase for 5 days (total duration of light phase 8 AM to 6 PM). A control group (n = 14) was kept under normal light during the entire light phase. Choroidal thickness was measured in alert, hand-held animals with optical coherence tomography at 10 AM, 4 PM, and 8 PM every day. Complete data sets were available for 12 chicks in bright light group and nine in normal light group. The striking inter-individual variability in choroidal thickness (coefficient of variance: 23%) made it necessary to normalize changes to the individual baseline thickness of the choroid. During the 6 hours of exposure to bright light, choroidal thickness decreased by -5.2 ± 4.0% (mean ± SEM). By contrast, in the group kept under normal light, choroidal thickness increased by +15.4 ± 4.7% (difference between both groups p = 0.003). After an additional 4 hours, choroidal thickness increased also in the "bright light group" by +17.8 ± 3.5%, while there was little further change (+0.6 ± 4.0%) in the "normal light group" (difference p = 0.004). Finally, the choroid was thicker in the "bright light group" (+7.6 ± 26.0%) than in the "normal light group" (day 5: -18.6 ± 26.9%; difference p = 0.036). Bright light stimulates choroidal thickening in chickens, although the response is smaller than with experimentally imposed myopic defocus, and it occurs with some time delay. It nevertheless suggests that choroidal thickening is also involved in myopia inhibition by bright light.

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

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

Upadhyay, Anup K.; Cyr, Matthew; Longenecker, Kenton

The rapid spread of the recentZika virus(ZIKV) epidemic across various countries in the American continent poses a major health hazard for the unborn fetuses of pregnant women. To date, there is no effective medical intervention. The nonstructural protein 5 ofZika virus(ZIKV-NS5) is critical for ZIKV replication through the 5'-RNA capping and RNA polymerase activities present in its N-terminal methyltransferase (MTase) and C-terminal RNA-dependent RNA polymerase (RdRp) domains, respectively. The crystal structure of the full-length ZIKV-NS5 protein has been determined at 3.05 Å resolution from a crystal belonging to space groupP2 12 12 and containing two protein molecules in the asymmetricmore » unit. The structure is similar to that reported for the NS5 protein fromJapanese encephalitis virusand suggests opportunities for structure-based drug design targeting either its MTase or RdRp domain.« less

Galaxy Selection and the Surface Brightness Distribution

NASA Astrophysics Data System (ADS)

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

1995-08-01

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

Spatiotemporal analysis of brightness induction

PubMed Central

McCourt, Mark E.

2011-01-01

Brightness induction refers to a class of visual illusions in which the perceived intensity of a region of space is influenced by the luminance of surrounding regions. These illusions are significant because they provide insight into the neural organization of the visual system. A novel quadrature-phase motion cancelation technique was developed to measure the magnitude of the grating induction brightness illusion across a wide range of spatial frequencies, temporal frequencies and test field heights. Canceling contrast is greatest at low frequencies and declines with increasing frequency in both dimensions, and with increasing test field height. Canceling contrast scales as the product of inducing grating spatial frequency and test field height (the number of inducing grating cycles per test field height). When plotted using a spatial axis which indexes this product, the spatiotemporal induction surfaces for four test field heights can be described as four partially overlapping sections of a single larger surface. These properties of brightness induction are explained in the context of multiscale spatial filtering. The present study is the first to measure the magnitude of grating induction as a function of temporal frequency. Taken in conjunction with several other studies (Blakeslee & McCourt, 2008; Robinson & de Sa, 2008; Magnussen & Glad, 1975) the results of this study illustrate that at least one form of brightness induction is very much faster than that reported by DeValois et al. (1986) and Rossi and Paradiso (1996), and are inconsistent with the proposition that brightness induction results from a slow “filling in” process. PMID:21763339

A brightness exceeding simulated Langmuir limit

NASA Astrophysics Data System (ADS)

Nakasuji, Mamoru

2013-08-01

When an excitation of the first lens determines a beam is parallel beam, a brightness that is 100 times higher than Langmuir limit is measured experimentally, where Langmuir limits are estimated using a simulated axial cathode current density which is simulated based on a measured emission current. The measured brightness is comparable to Langmuir limit, when the lens excitation is such that an image position is slightly shorter than a lens position. Previously measured values of brightness for cathode apical radii of curvature 20, 60, 120, 240, and 480 μm were 8.7, 5.3, 3.3, 2.4, and 3.9 times higher than their corresponding Langmuir limits, respectively, in this experiment, the lens excitation was such that the lens and the image positions were 180 mm and 400 mm, respectively. From these measured brightness for three different lens excitation conditions, it is concluded that the brightness depends on the first lens excitation. For the electron gun operated in a space charge limited condition, some of the electrons emitted from the cathode are returned to the cathode without having crossed a virtual cathode. Therefore, method that assumes a Langmuir limit defining method using a Maxwellian distribution of electron velocities may need to be revised. For the condition in which the values of the exceeding the Langmuir limit are measured, the simulated trajectories of electrons that are emitted from the cathode do not cross the optical axis at the crossover, thus the law of sines may not be valid for high brightness electron beam systems.

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

PubMed Central

URATA, Maho; WATANABE, Rie; IWATA, Hiroyuki

2015-01-01

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

Brightness masking is modulated by disparity structure.

PubMed

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

2015-05-01

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

Virtual screening of commercial cyclic peptides as NS2B-NS3 protease inhibitor of dengue virus serotype 2 through molecular docking simulation

NASA Astrophysics Data System (ADS)

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

2017-04-01

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

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

PubMed

Hirota, Naoko; Sone, Yoshiaki; Tokura, Hiromi

2010-01-01

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

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

PubMed Central

Zheng, Fengwei; Lu, Guoliang; Li, Ling

2017-01-01

ABSTRACT The nonstructural protein NS3 from the Flaviviridae family is a multifunctional protein that contains an N-terminal protease and a C-terminal helicase, playing essential roles in viral polyprotein processing and genome replication. Here we report a full-length crystal structure of the classical swine fever virus (CSFV) NS3 in complex with its NS4A protease cofactor segment (PCS) at a 2.35-Å resolution. The structure reveals a previously unidentified ∼2,200-Å2 intramolecular protease-helicase interface comprising three clusters of interactions, representing a “closed” global conformation related to the NS3-NS4A cis-cleavage event. Although this conformation is incompatible with protease trans-cleavage, it appears to be functionally important and beneficial to the helicase activity, as the mutations designed to perturb this conformation impaired both the helicase activities in vitro and virus production in vivo. Our work reveals important features of protease-helicase coordination in pestivirus NS3 and provides a key basis for how different conformational states may explicitly contribute to certain functions of this natural protease-helicase fusion protein. IMPORTANCE Many RNA viruses encode helicases to aid their RNA genome replication and transcription by unwinding structured RNA. Being naturally fused to a protease participating in viral polyprotein processing, the NS3 helicases encoded by the Flaviviridae family viruses are unique. Therefore, how these two enzyme modules coordinate in a single polypeptide is of particular interest. Here we report a previously unidentified conformation of pestivirus NS3 in complex with its NS4A protease cofactor segment (PCS). This conformational state is related to the protease cis-cleavage event and is optimal for the function of helicase. This work provides an important basis to understand how different enzymatic activities of NS3 may be achieved by the coordination between the protease and helicase through

Microwave Brightness Temperatures of Tilted Convective Systems

NASA Technical Reports Server (NTRS)

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

1998-01-01

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

Brightness and magnetic evolution of solar coronal bright points

NASA Astrophysics Data System (ADS)

Ugarte-Urra, I.

2004-12-01

This thesis presents a study of the brightness and magnetic evolution of several Extreme ultraviolet (EUV) coronal bright points (hereafter BPs). BPs are loop-like features of enhanced emission in the coronal EUV and X-ray images of the Sun, that are associated to the interaction of opposite photospheric magnetic polarities with magnetic fluxes of ≈1018 - 1019 Mx. The study was carried out using several instruments on board the Solar and Heliospheric Observatory (SOHO): the Extreme Ultraviolet Imager (EIT), the Coronal Diagnostic Spectrometer (CDS) and the Michelson Doppler Imager (MDI), supported by the high resolution imaging from the Transition Region And Coronal Explorer (TRACE). The results confirm that, down to 1'' (i.e. ~715 km) resolution, BPs are made of small loops with lengths of ~6 Mm and cross-sections of ~2 Mm. The loops are very dynamic, evolving in time scales as short as 1 - 2 minutes. This is reflected in a highly variable EUV response with fluctuations highly correlated in spectral lines at transition region temperatures (in the range 3.2x10^4 - 3.5x10^5 K), but not always at coronal temperatures. A wavelet analysis of the intensity variations reveals, for the first time, the existence of quasi-periodic oscillations with periods ranging 400 -- 1000 s, in the range of periods characteristic of the chromospheric network. The link between BPs and network bright points is discussed, as well as the interpretation of the oscillations in terms of global acoustic modes of closed magnetic structures. A comparison of the magnetic flux evolution of the magnetic polarities to the EUV flux changes is also presented. Throughout their lifetime, the intrinsic EUV emission of BPs is found to be dependent on the total magnetic flux of the polarities. In short time scales, co-spatial and co-temporal TRACE and MDI images, reveal the signature of heating events that produce sudden EUV brightenings simultaneous to magnetic flux cancellations. This is interpreted in

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

PubMed

Yates, Christopher M; Sternberg, Michael J E

2013-11-01

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

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

PubMed

Lagoro, David Kitara; Arony, Denis Anywar

2017-01-01

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

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

PubMed Central

Lagoro, David Kitara; Arony, Denis Anywar

2017-01-01

Nodding Syndrome (NS) is a childhood neurological disorder characterized by atonic seizures, cognitive decline, school dropout, muscle weakness, thermal dysfunction, wasting and stunted growth. There are recent published information suggesting associations between Nodding Syndrome (NS) with cerebrospinal fluid (CSF) VGKC antibodies and serum leiomidin-1 antibody cross reacting with Onchocerca Volvulus (OV). These findings suggest a neuro-inflammatory cause of NS and they are important findings in the search for the cause of Nodding Syndrome. These observations perhaps provide further, the unique explanation for the association between Nodding Syndrome and Onchocerca Volvulus. Many clinical and epidemiological studies had shown a significant correlation between NS and infestation with a nematode, Onchocerca volvulus which causes a disease, Onchocerciasis, some of which when left untreated can develop visual defect ("River Blindness"). While these studies conducted in Northern Uganda and Southern Sudan indicate a statistically significant association with (OV infection (using positive skin snips), we observe that (OV is generally endemic in many parts of Sub Saharan Africa and Latin America and that to date, no NS cases have been recorded in those regions. This letter to the Editor is to provide additional information on the current view about the relationship between Nodding Syndrome and Onchocerca Volvulus as seen in Northern Uganda. PMID:29138647

The Brightness of Colour

PubMed Central

Corney, David; Haynes, John-Dylan; Rees, Geraint; Lotto, R. Beau

2009-01-01

Background 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. Results 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. Conclusions The data suggest that perceptions of brightness

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2017-01-01

Dengue is a febrile disease caused by infection of dengue virus (DENV). Early diagnosis of dengue infection is important for better management of the disease. The DENV Non-Structural Protein 1 (NS1) antigen has been routinely used for the early dengue detection. In dengue epidemic countries such as Indonesia, clinicians are increasingly relying on the NS1 detection for confirmation of dengue infection. Various NS1 diagnostic tests are commercially available, however different sensitivities and specificities were observed in various settings. This study was aimed to generate dengue NS1 recombinant protein for the development of dengue diagnostic tests. Four Indonesian DENV isolates were used as the source of the NS1 gene cloning, expression, and purification in bacterial expression system. Recombinant NS1 proteins were successfully purified and their antigenicities were assessed. Immunization of mice with recombinant proteins observed the immunogenicity of the NS1 protein. The generated recombinant proteins can be potentially used in the development of NS1 diagnostic test. With minimal modifications, this method can be used for producing NS1 recombinant proteins from isolates obtained from other geographical regions. Copyright © 2016 Elsevier Inc. All rights reserved.

[System of ns time-resolved spectroscopy diagnosis and radioprotection].

PubMed

Yao, Wei-Bo; Guo, Jian-Ming; Zhang, Yong-min; Tang, Jun-Ping; Cheng, Liang; Xu, Qi-fuo

2014-06-01

Cathode plasma of high current electron beam diode is an important research on high power microwave and strong pulsed radio accelerator. It is a reliable method to study cathode plasma by diagnosing the cathode plasma parameters with non-contact spectroscopy measurement system. The present paper introduced the work principle, system composition and performance of the nanosecond (ns) time-resolved spectroscopy diagnosis system. Furthermore, it introduced the implementing method and the temporal relation of lower jitter synchronous trigger system. Simultaneously, the authors designed electromagnetic and radio shield room to protect the diagnosis system due to the high electromagnetic and high X-ray and γ-ray radiation, which seriously interferes with the system. Time-resolved spectroscopy experiment on brass (H62) cathode shows that, the element and matter composition of cathode plasma is clearly increase with the increase in the diode pulsed voltage and current magnitude. The spectroscopy diagnosis system could be of up to 10 ns time resolve capability. It's least is 2 ns. Synchronous trigger system's jitter is less than 4 ns. The spectroscopy diagnosis system will open a new way to study the cathode emission mechanism in depth.

A single residue mutation in Hha preserving structure and binding to H-NS results in loss of H-NS mediated gene repression properties.

PubMed

Cordeiro, Tiago N; Garcia, Jesús; Pons, José-Ignacio; Aznar, Sonia; Juárez, Antonio; Pons, Miquel

2008-09-03

In this study, we report that a single mutation of cysteine 18 to isoleucine (C18I) in Escherichia coli Hha abolishes the repression of the hemolysin operon observed in the wild-type protein. The phenotype also includes a significant decrease in the growth rate of E. coli cells at low ionic strength. Other substitutions at this position (C18A, C18S) have no observable effects in E. coli growth or hemolysin repression. All mutants are stable and well folded and bind H-NS in vitro with similar affinities suggesting that Cys 18 is not directly involved in H-NS binding but this position is essential for the activity of the H-NS/Hha heterocomplexes in the regulation of gene expression.

FORMATION AND EVOLUTION OF GALACTIC INTERMEDIATE/LOW-MASS X-RAY BINARIES

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

Shao, Yong; Li, Xiang-Dong, E-mail: lixd@nju.edu.cn

2015-08-10

We investigate the formation and evolutionary sequences of Galactic intermediate- and low-mass X-ray binaries (I/LMXBs) by combining binary population synthesis (BPS) and detailed stellar evolutionary calculations. Using an updated BPS code we compute the evolution of massive binaries that leads to the formation of incipient I/LMXBs and present their distribution in the initial donor mass versus initial orbital period diagram. We then follow the evolution of the I/LMXBs until the formation of binary millisecond pulsars (BMSPs). We find that the birthrate of the I/LMXB population is in the range of 9 × 10{sup −6}–3.4 × 10{sup −5} yr{sup −1}, compatiblemore » with that of BMSPs that are thought to descend from I/LMXBs. We show that during the evolution of I/LMXBs they are likely to be observed as relatively compact binaries with orbital periods ≲1 day and donor masses ≲0.3M{sub ⊙}. The resultant BMSPs have orbital periods ranging from less than 1 day to a few hundred days. These features are consistent with observations of LMXBs and BMSPs. We also confirm the discrepancies between theoretical predictions and observations mentioned in the literature, that is, the theoretical average mass transfer rates (∼10{sup −10} M{sub ⊙} yr{sup −1}) of LMXBs are considerably lower than observed, and the number of BMSPs with orbital periods ∼0.1–10 days is severely underestimated. These discrepancies imply that something is missing in the modeling of LMXBs, which is likely to be related to the mechanisms of the orbital angular momentum loss.« less

Exposure to bright light biases effort-based decisions.

PubMed

Bijleveld, Erik; Knufinke, Melanie

2018-06-01

Secreted in the evening and the night, melatonin suppresses activity of the mesolimbic dopamine pathway, a brain pathway involved in reward processing. However, exposure to bright light diminishes-or even prevents-melatonin secretion. Thus, we hypothesized that reward processing, in the evening, is more pronounced in bright light (vs. dim light). Healthy human participants carried out three tasks that tapped into various aspects of reward processing (effort expenditure for rewards task [EEfRT]; two-armed bandit task [2ABT]; balloon analogue risk task [BART). Brightness was manipulated within-subjects (bright vs. dim light), in separate evening sessions. During the EEfRT, participants used reward-value information more strongly when they were exposed to bright light (vs. dim light). This finding supported our hypothesis. However, exposure to bright light did not significantly affect task behavior on the 2ABT and the BART. While future research is necessary (e.g., to zoom in on working mechanisms), these findings have potential implications for the design of physical work environments. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Coronal bright points at 6cm wavelength

NASA Technical Reports Server (NTRS)

Fu, Qijun; Kundu, M. R.; Schmahl, E. J.

1988-01-01

Results are presented from observations of bright points at a wavelength of 6-cm using the VLA with a spatial resolution of 1.2 arcsec. During two hours of observations, 44 sources were detected with brightness temperatures between 2000 and 30,000 K. Of these sources, 27 are associated with weak dark He 10830 A features at distances less than 40 arcsecs. Consideration is given to variations in the source parameters and the relationship between ephemeral regions and bright points.

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

PubMed

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

2017-11-01

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.

The ZTF Bright Transient Survey

NASA Astrophysics Data System (ADS)

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

2018-06-01

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

The night sky brightness at McDonald Observatory

NASA Technical Reports Server (NTRS)

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

1975-01-01

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

Gelatin nanoparticles enhance delivery of hepatitis C virus recombinant NS2 gene

PubMed Central

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

2017-01-01

Background Development of an effective non-viral vaccine against hepatitis C virus infection is of a great importance. Gelatin nanoparticles (Gel.NPs) have an attention and promising approach as a viable carrier for delivery of vaccine, gene, drug and other biomolecules in the body. Aim of work The present study aimed to develop stable Gel.NPs conjugated with nonstructural protein 2 (NS2) gene of Hepatitis C Virus genotype 4a (HCV4a) as a safe and an efficient vaccine delivery system. Methods and results Gel.NPs were synthesized and characterized (size: 150±2 nm and zeta potential +17.6 mv). NS2 gene was successfully cloned and expressed into E. coli M15 using pQE-30 vector. Antigenicity of the recombinant NS2 protein was confirmed by Western blotting to verify the efficiency of NS2 as a possible vaccine. Then NS2 gene was conjugated to gelatin nanoparticles and a successful conjugation was confirmed by labeling and imaging using Confocal Laser Scanning Microscope (CLSM). Interestingly, the transformation of the conjugated NS2/Gel.NPs complex into E. coli DH5-α was 50% more efficient than transformation with the gene alone. In addition, conjugated NS2/Gel.NPs with ratio 1:100 (w/w) showed higher transformation efficiency into E. coli DH5-α than the other ratios (1:50 and 2:50). Conclusion Gel.NPs effectively enhanced the gene delivery in bacterial cells without affecting the structure of NS2 gene and could be used as a safe, easy, rapid, cost-effective and non-viral vaccine delivery system for HCV. PMID:28746382

Dengue virus NS1 cytokine-independent vascular leak is dependent on endothelial glycocalyx components

PubMed Central

Beatty, P. Robert

2017-01-01

Dengue virus (DENV) is the most prevalent, medically important mosquito-borne virus. Disease ranges from uncomplicated dengue to life-threatening disease, characterized by endothelial dysfunction and vascular leakage. Previously, we demonstrated that DENV nonstructural protein 1 (NS1) induces endothelial hyperpermeability in a systemic mouse model and human pulmonary endothelial cells, where NS1 disrupts the endothelial glycocalyx-like layer. NS1 also triggers release of inflammatory cytokines from PBMCs via TLR4. Here, we examined the relative contributions of inflammatory mediators and endothelial cell-intrinsic pathways. In vivo, we demonstrated that DENV NS1 but not the closely-related West Nile virus NS1 triggers localized vascular leak in the dorsal dermis of wild-type C57BL/6 mice. In vitro, we showed that human dermal endothelial cells exposed to DENV NS1 do not produce inflammatory cytokines (TNF-α, IL-6, IL-8) and that blocking these cytokines does not affect DENV NS1-induced endothelial hyperpermeability. Further, we demonstrated that DENV NS1 induces vascular leak in TLR4- or TNF-α receptor-deficient mice at similar levels to wild-type animals. Finally, we blocked DENV NS1-induced vascular leak in vivo using inhibitors targeting molecules involved in glycocalyx disruption. Taken together, these data indicate that DENV NS1-induced endothelial cell-intrinsic vascular leak is independent of inflammatory cytokines but dependent on endothelial glycocalyx components. PMID:29121099

Bright Solar Flare

NASA Image and Video Library

2017-12-08

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

Conclusions and future directions for the REiNS International Collaboration

PubMed Central

Blakeley, Jaishri O.; Dombi, Eva; Fisher, Michael J.; Hanemann, Clemens O.; Walsh, Karin S.; Wolters, Pamela L.; Plotkin, Scott R.

2013-01-01

The Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration was established with the goal to develop consensus recommendations for the use of endpoints in neurofibromatosis (NF) clinical trials. This supplement includes the first series of REiNS recommendations for the use of patient-reported, functional, and visual outcomes, and for the evaluation of imaging response in NF clinical trials. Recommendations for neurocognitive outcome measures, the use of whole-body MRI in NF, the evaluation of potential biomarkers of disease, and the comprehensive evaluation of functional and patient-reported outcomes in NF are in development. The REiNS recommendations are made based on current knowledge. Experience with the use of the recommended endpoints in clinical trials, development of new tools and technologies, new knowledge of the natural history of NF, and advances in the methods used to analyze endpoints will likely lead to modifications of the currently proposed guidelines, which will be shared with the NF research community through the REiNS Web site www.reinscollaboration.org. Due to the clinical complexity of NF, there is a need to seek expertise from multiple medical disciplines, regulatory agencies, and industry to develop trial endpoints and designs, which will lead to the identification and approval of effective treatments for NF tumor and nontumor manifestations. The REiNS Collaboration welcomes anyone interested in providing his or her expertise toward this effort. PMID:24249805

Dark-Bright Soliton Dynamics Beyond the Mean-Field Approximation

NASA Astrophysics Data System (ADS)

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

2017-04-01

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

Dark-bright soliton pairs: Bifurcations and collisions

NASA Astrophysics Data System (ADS)

Katsimiga, G. C.; Kevrekidis, P. G.; Prinari, B.; Biondini, G.; Schmelcher, P.

2018-04-01

The statics, stability, and dynamical properties of dark-bright soliton pairs are investigated here, motivated by applications in a homogeneous two-component repulsively interacting Bose-Einstein condensate. One of the intraspecies interaction coefficients is used as the relevant parameter controlling the deviation from the integrable Manakov limit. Two different families of stationary states are identified consisting of dark-bright solitons that are either antisymmetric (out-of-phase) or asymmetric (mass imbalanced) with respect to their bright soliton. Both of the above dark-bright configurations coexist at the integrable limit of equal intra and interspecies repulsions and are degenerate in that limit. However, they are found to bifurcate from it in a transcritical bifurcation. This bifurcation interchanges the stability properties of the bound dark-bright pairs rendering the antisymmetric states unstable and the asymmetric ones stable past the associated critical point (and vice versa before it). Finally, on the dynamical side, it is found that large kinetic energies and thus rapid soliton collisions are essentially unaffected by the intraspecies variation, while cases involving near equilibrium states or breathing dynamics are significantly modified under such a variation.

Moon night sky brightness simulation for the Xinglong station

NASA Astrophysics Data System (ADS)

Yao, Song; Zhang, Hao-Tong; Yuan, Hai-Long; Zhao, Yong-Heng; Dong, Yi-Qiao; Bai, Zhong-Rui; Deng, Li-Cai; Lei, Ya-Juan

2013-10-01

Using a sky brightness monitor at the Xinglong station of National Astronomical Observatories, Chinese Academy of Sciences, we collected data from 22 dark clear nights and 90 moon nights. We first measured the sky brightness variation with time for dark nights and found a clear correlation between sky brightness and human activity. Then with a modified sky brightness model of moon nights and data from these nights, we derived the typical value for several important parameters in the model. With these results, we calculated the sky brightness distribution under a given moon condition for the Xinglong station. Furthermore, we simulated the sky brightness distribution of a moon night for a telescope with a 5° field of view (such as LAMOST). These simulations will be helpful for determining the limiting magnitude and exposure time, as well as planning the survey for LAMOST during moon nights.

Color constancy using bright-neutral pixels

NASA Astrophysics Data System (ADS)

Wang, Yanfang; Luo, Yupin

2014-03-01

An effective illuminant-estimation approach for color constancy is proposed. Bright and near-neutral pixels are selected to jointly represent the illuminant color and utilized for illuminant estimation. To assess the representing capability of pixels, bright-neutral strength (BNS) is proposed by combining pixel chroma and brightness. Accordingly, a certain percentage of pixels with the largest BNS is selected to be the representative set. For every input image, a proper percentage value is determined via an iterative strategy by seeking the optimal color-corrected image. To compare various color-corrected images of an input image, image color-cast degree (ICCD) is devised using means and standard deviations of RGB channels. Experimental evaluation on standard real-world datasets validates the effectiveness of the proposed approach.

The structure of Zika virus NS5 reveals a conserved domain conformation

DOE PAGES

Wang, Boxiao; Tan, Xiao -Feng; Thurmond, Stephanie; ...

2017-03-27

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

Identification of potential hit compounds for Dengue virus NS2B/NS3 protease inhibitors by combining virtual screening and binding free energy calculations.

PubMed

Wichapong, K; Nueangaudom, A; Pianwanit, S; Sippl, W; Kokpol, S

2013-09-01

Dengue virus (DV) infections are a serious public health problem and there is currently no vaccine or drug treatment. NS2B/NS3 protease, an essential enzyme for viral replication, is one of the promising targets in the search for drugs against DV. In this research work, virtual screening (VS) was carried out on four multi-conformational databases using several criteria. Firstly, molecular dynamics simulations of the NS2B/NS3 protease and four known inhibitors, which reveal an importance of both electrostatic and van der Waals interactions in stabilizing the ligand-enzyme interaction, were used to generate three different pharmacophore models (a structure-based, a static and a dynamic). Subsequently, these three models were employed for pharmacophore search in the VS. Secondly, compounds passing the first criterion were further reduced using the Lipinski's rule of five to keep only compounds with drug-like properties. Thirdly, molecular docking calculations were performed to remove compounds with unsuitable ligand-enzyme interactions. Finally, binding free energy of each compound was calculated. Compounds having better energy than the known inhibitors were selected and thus 20 potential hits were obtained.

The Spectral Signatures Of BH Versus NS Sources

NASA Astrophysics Data System (ADS)

Seifina, E.; Titarchuk, L.

2011-09-01

We present a comparative analysis of spectral properties of Black Hole (BH) and Neutron Star (NS) X-ray binaries during transition events observed with BeppoSAX and RXTE satellites. In particular, we investigated the behavior of Comptonized component of X-ray spectra when object evolves from the low to high spectral states. The basic models to fit X-ray spectra of these objects are upscattering models (so called BMC and COMPTB models) which are the first principal models. These models taking into account both dynamical and thermal Comptonization and allow to study separate contributions of thermal component and Comptonization component (bulk and thermal effect of Comptonization processes). Specifically, we tested quite a few observations of BHs (GRS 1915+105 and SS 433) and NSs (4U 1728-34 and GX 3+1) applying BMC and COMPTB models. In this way it was found a crucial difference in behavior of photon index vs mass accretion rate (mdot) for BHs and NSs. Namely, we revealed the stability of the photon index around typical value of Gamma=2 versus mdot (or electron temperature) during spectral evolution of NS sources. This stability effect was previously suggested for a number of other neutron binaries (see Farinelli and Titarchuk, 2011). This intrinsic property of NS is fundamentally different from that in BH binary sources for which the index demonstrates monotonic growth with mass accretion rate followed by its saturation at high values of mdot. These index-mass accretion rate behavior during X-ray spectral transition events can be considered as signatures, which allow to differ NS from BH.

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.

PubMed

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

2017-07-01

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

Dynamic resetting of the human circadian pacemaker by intermittent bright light

NASA Technical Reports Server (NTRS)

Rimmer, D. W.; Boivin, D. B.; Shanahan, T. L.; Kronauer, R. E.; Duffy, J. F.; Czeisler, C. A.

2000-01-01

In humans, experimental studies of circadian resetting typically have been limited to lengthy episodes of exposure to continuous bright light. To evaluate the time course of the human endogenous circadian pacemaker's resetting response to brief episodes of intermittent bright light, we studied 16 subjects assigned to one of two intermittent lighting conditions in which the subjects were presented with intermittent episodes of bright-light exposure at 25- or 90-min intervals. The effective duration of bright-light exposure was 31% or 63% compared with a continuous 5-h bright-light stimulus. Exposure to intermittent bright light elicited almost as great a resetting response compared with 5 h of continuous bright light. We conclude that exposure to intermittent bright light produces robust phase shifts of the endogenous circadian pacemaker. Furthermore, these results demonstrate that humans, like other species, exhibit an enhanced sensitivity to the initial minutes of bright-light exposure.

Dark-bright soliton pairs in nonlocal nonlinear media.

PubMed

Lin, Yuan Yao; Lee, Ray-Kuang

2007-07-09

We study the formation of dark-bright vector soliton pairs in nonlocal Kerr-type nonlinear medium. We show, by analytical analysis and direct numerical calculation, that in addition to stabilize of vector soliton pairs nonlocal nonlinearity also helps to reduce the threshold power for forming a guided bright soliton. With help of the nonlocality, it is expected that the observation of dark-bright vector soliton pairs in experiments becomes more workable.

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-01-01

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

Structural Insights into the Regulation of Foreign Genes in Salmonella by the Hha/H-NS Complex*

PubMed Central

Ali, Sabrina S.; Whitney, John C.; Stevenson, James; Robinson, Howard; Howell, P. Lynne; Navarre, William Wiley

2013-01-01

The bacterial nucleoid-associated proteins Hha and H-NS jointly repress horizontally acquired genes in Salmonella, including essential virulence loci encoded within Salmonella pathogenicity islands. Hha is known to interact with the N-terminal dimerization domain of H-NS; however, the manner in which this interaction enhances transcriptional silencing is not understood. To further understand this process, we solved the x-ray crystal structure of Hha in complex with the N-terminal dimerization domain of H-NS (H-NS(1–46)) to 3.2 Å resolution. Two monomers of Hha bind to symmetrical sites on either side of the H-NS(1–46) dimer. Disruption of the Hha/H-NS interaction by the H-NS site-specific mutation I11A results in increased expression of the Hha/H-NS co-regulated gene hilA without affecting the expression levels of proV, a target gene repressed by H-NS in an Hha-independent fashion. Examination of the structure revealed a cluster of conserved basic amino acids that protrude from the surface of Hha on the opposite side of the Hha/H-NS(1–46) interface. Hha mutants with a diminished positively charged surface maintain the ability to interact with H-NS but can no longer regulate hilA. Increased expression of the hilA locus did not correspond to significant depletion of H-NS at the promoter region in chromatin immunoprecipitation assays. However, in vitro, we find Hha improves H-NS binding to target DNA fragments. Taken together, our results show for the first time how Hha and H-NS interact to direct transcriptional repression and reveal that a positively charged surface of Hha enhances the silencing activity of H-NS nucleoprotein filaments. PMID:23515315

Molecular mechanism of influenza A NS1-mediated TRIM25 recognition and inhibition.

PubMed

Koliopoulos, Marios G; Lethier, Mathilde; van der Veen, Annemarthe G; Haubrich, Kevin; Hennig, Janosch; Kowalinski, Eva; Stevens, Rebecca V; Martin, Stephen R; Reis E Sousa, Caetano; Cusack, Stephen; Rittinger, Katrin

2018-05-08

RIG-I is a viral RNA sensor that induces the production of type I interferon (IFN) in response to infection with a variety of viruses. Modification of RIG-I with K63-linked poly-ubiquitin chains, synthesised by TRIM25, is crucial for activation of the RIG-I/MAVS signalling pathway. TRIM25 activity is targeted by influenza A virus non-structural protein 1 (NS1) to suppress IFN production and prevent an efficient host immune response. Here we present structures of the human TRIM25 coiled-coil-PRYSPRY module and of complexes between the TRIM25 coiled-coil domain and NS1. These structures show that binding of NS1 interferes with the correct positioning of the PRYSPRY domain of TRIM25 required for substrate ubiquitination and provide a mechanistic explanation for how NS1 suppresses RIG-I ubiquitination and hence downstream signalling. In contrast, the formation of unanchored K63-linked poly-ubiquitin chains is unchanged by NS1 binding, indicating that RING dimerisation of TRIM25 is not affected by NS1.

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

NASA Technical Reports Server (NTRS)

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

2000-01-01

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

Bright ZTF transients

NASA Astrophysics Data System (ADS)

Fremling, C.; Kulkarni, S. R.; Taggart, K.; Perley, D.

2018-05-01

As a part of ongoing commissioning of the Zwicky Transient Facility (ZTF; ATel #11266) Alert Infrastructure, here we report bright probable supernovae identified in the raw alert stream resulting from the public ZTF Northern Sky Survey ("Celestial Cinematagrophy"; see Bellm & Kulkarni, Nature Astronomy 1, 71, 2017).

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

DTIC Science & Technology

2017-12-01

real systems with less work compared to ns-2. In order to meet the design goals of ns-3, the entire code structure changed to a modular design . As a...NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS COMPARATIVE ANALYSIS OF DISRUPTION TOLERANT NETWORK ROUTING SIMULATIONS IN THE ONE AND NS-3...Thesis 03-23-2016 to 12-15-2017 4. TITLE AND SUBTITLE COMPARATIVE ANALYSIS OF DISRUPTION TOLERANT NETWORK ROUTING SIMULATIONS IN THE ONE AND NS-3 5

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

PubMed

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

2006-02-01

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.

Protective immunity to Japanese encephalitis virus associated with anti-NS1 antibodies in a mouse model.

PubMed

Li, Yize; Counor, Dorian; Lu, Peng; Duong, Veasna; Yu, Yongxin; Deubel, Vincent

2012-07-24

Japanese encephalitis virus (JEV) is a major mosquito-borne pathogen that causes viral encephalitis throughout Asia. Vaccination with an inactive JEV particle or attenuated virus is an efficient preventative measure for controlling infection. Flavivirus NS1 protein is a glycoprotein secreted during viral replication that plays multiple roles in the viral life cycle and pathogenesis. Utilizing JEV NS1 as an antigen in viral vectors induces a limited protective immune response against infection. Previous studies using E. coli-expressed JEV NS1 to immunize mice induced protection against lethal challenge; however, the protection mechanism through cellular and humoral immune responses was not described. JEV NS1 was expressed in and purified from Drosophila S2 cells in a native glycosylated multimeric form, which induced T-cell and antibody responses in immunized C3H/HeN mice. Mice vaccinated with 1 μg NS1 with or without water-in-oil adjuvant were partially protected against viral challenge and higher protection was observed in mice with higher antibody titers. IgG1 was preferentially elicited by an adjuvanted NS1 protein, whereas a larger load of IFN-γ was produced in splenocytes from mice immunized with aqueous NS1. Mice that passively received anti-NS1 mouse polyclonal immune sera were protected, and this phenomenon was dose-dependent, whereas protection was low or delayed after the passive transfer of anti-NS1 MAbs. The purified NS1 subunit induced protective immunity in relation with anti-NS1 IgG1 antibodies. NS1 protein efficiently stimulated Th1-cell proliferation and IFN-γ production. Protection against lethal challenge was elicited by passive transfer of anti-NS1 antisera, suggesting that anti-NS1 antibodies play a substantial role in anti-viral immunity.

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2015-10-09

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

Discovery of Dengue Virus NS4B Inhibitors

PubMed Central

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

2015-01-01

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

Molecular Mechanism by Which a Potent Hepatitis C Virus NS3-NS4A Protease Inhibitor Overcomes Emergence of Resistance

PubMed Central

O'Meara, Jeff A.; Lemke, Christopher T.; Godbout, Cédrickx; Kukolj, George; Lagacé, Lisette; Moreau, Benoît; Thibeault, Diane; White, Peter W.; Llinàs-Brunet, Montse

2013-01-01

Although optimizing the resistance profile of an inhibitor can be challenging, it is potentially important for improving the long term effectiveness of antiviral therapy. This work describes our rational approach toward the identification of a macrocyclic acylsulfonamide that is a potent inhibitor of the NS3-NS4A proteases of all hepatitis C virus genotypes and of a panel of genotype 1-resistant variants. The enhanced potency of this compound versus variants D168V and R155K facilitated x-ray determination of the inhibitor-variant complexes. In turn, these structural studies revealed a complex molecular basis of resistance and rationalized how such compounds are able to circumvent these mechanisms. PMID:23271737

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

ERIC Educational Resources Information Center

Bauer, Ben

2009-01-01

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

The nature of solar brightness variations

NASA Astrophysics Data System (ADS)

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

2017-09-01

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

Rough Interface Effects on N-S Proximity-Contact Systems

NASA Astrophysics Data System (ADS)

Nagato, Yasushi; Nagai, Katsuhiko

2003-03-01

We discuss the influence of atomic scale roughness of the interface on the properties of the N-S contact systems. To treat the interface roughness effects we extend our previous quasi-classical theory of the rough surface effect and construct a formal solution for the quasi-classical Green's function. We apply the formulation to N-S systems with two-dimensional anisotropic dx2-y2 superconductor and calculate the self-consistent pair potential and the density of states at the interface.

Induction of apoptosis of liver cancer cells by nanosecond pulsed electric fields (nsPEFs).

PubMed

He, Ling; Xiao, Deyou; Feng, Jianguo; Yao, Chenguo; Tang, Liling

2017-02-01

The application of nanosecond pulsed electric fields (nsPEFs) is a novel method to induce the death of cancer cells. NsPEFs could directly function on the cell membrane and activate the apoptosis pathways, then induce apoptosis in various cell lines. However, the nsPEFs-inducing-apoptosis action sites and the exact pathways are not clear now. In this study, nsPEFs were applied to the human liver cancer cells HepG2 with different parameters. By apoptosis assay, morphological observation, detecting the mitochondrial membrane potential (ΔΨ m ), intracellular calcium ion concentration ([Ca 2+ ]i) and the expressions of key apoptosis factors, we demonstrated that nsPEFs could induce the morphology of cell apoptosis, the change in ΔΨ m , [Ca 2+ ]i and the upregulation of some key apoptosis factors, which revealed the responses of liver cancer cells and indicated that cells may undergo apoptosis through the mitochondria-dependent pathway after nsPEFs were applied.

Are solar brightness variations faculae- or spot-dominated?

NASA Astrophysics Data System (ADS)

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

2016-05-01

Context. Regular spaceborne measurements have revealed that solar brightness varies on multiple timescales, variations on timescales greater than a day being attributed to a surface magnetic field. Independently, ground-based and spaceborne measurements suggest that Sun-like stars show a similar, but significantly broader pattern of photometric variability. Aims: To understand whether the broader pattern of stellar variations is consistent with the solar paradigm, we assess relative contributions of faculae and spots to solar magnetically-driven brightness variability. We investigate how the solar brightness variability and its facular and spot contributions depend on the wavelength, timescale of variability, and position of the observer relative to the ecliptic plane. Methods: We performed calculations with the SATIRE model, which returns solar brightness with daily cadence from solar disc area coverages of various magnetic features. We took coverages as seen by an Earth-based observer from full-disc SoHO/MDI and SDO/HMI data and projected them to mimic out-of-ecliptic viewing by an appropriate transformation. Results: Moving the observer away from the ecliptic plane increases the amplitude of 11-year variability as it would be seen in Strömgren (b + y)/2 photometry, but decreases the amplitude of the rotational brightness variations as it would appear in Kepler and CoRoT passbands. The spot and facular contributions to the 11-year solar variability in the Strömgren (b + y)/2 photometry almost fully compensate each other so that the Sun appears anomalously quiet with respect to its stellar cohort. Such a compensation does not occur on the rotational timescale. Conclusions: The rotational solar brightness variability as it would appear in the Kepler and CoRoT passbands from the ecliptic plane is spot-dominated, but the relative contribution of faculae increases for out-of-ecliptic viewing so that the apparent brightness variations are faculae-dominated for

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

PubMed

Aguilera-Pesantes, Daniel; Méndez, Miguel A

2017-10-28

While Zika virus (ZIKV) outbreaks are a growing concern for global health, a deep understanding about the virus is lacking. Here we report a contribution to the basic science on the virus- a detailed computational analysis of the non structural protein NS2b. This protein acts as a cofactor for the NS3 protease (NS3Pro) domain that is important on the viral life cycle, and is an interesting target for drug development. We found that ZIKV NS2b cofactor is highly similar to other virus within the Flavivirus genus, especially to West Nile Virus, suggesting that it is completely necessary for the protease complex activity. Furthermore, the ZIKV NS2b has an important role to the function and stability of the ZIKV NS3 protease domain even when presents a low conservation score. In addition, ZIKV NS2b is mostly rigid, which could imply a non dynamic nature in substrate recognition. Finally, by performing a computational alanine scanning mutagenesis, we found that residues Gly 52 and Asp 83 in the NS2b could be important in substrate recognition. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed

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

2015-11-14

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

The Discovery of a Second Luminous Low Mass X-ray Binary in the Globular Cluster M15

NASA Technical Reports Server (NTRS)

White, Nicholas E.; Angelini, Lorella

2001-01-01

We report an observation by the Chandra X-ray Observatory of 4U2127+119, the X-ray source identified with the globular cluster M15. The Chandra observation reveals that 4U2127+119 is in fact two bright sources, separated by 2.7". One source is associated with AC21 1, the previously identified optical counterpart to 4U2127+119, a low mass X-ray binary (LMXB). The second source, M15-X2, is coincident with a 19th U magnitude blue star that is 3.3" from the cluster core. The Chandra count rate of M15-X2 is 2.5 times higher than that of AC211. Prior to the 0.5" imaging capability of Chandra the presence of two so closely separated bright sources would not have been resolved, The optical counterpart, X-ray luminosity and spectrum of M15-X2 are consistent with it also being an LMXB system. This is the first time that two LMXBS have been seen to be simultaneously active in a globular cluster. The discovery of a second active LMXB in M15 solves a long standing puzzle where the properties of AC211 appear consistent with it being dominated by an extended accretion disk corona, and yet 4U2127+119 also shows luminous X-ray bursts requiring that the neutron star be directly visible. The resolution of 4U2127+119 into two sources suggests that the X-ray bursts did not come from AC211, but rather from M15X2. We discuss the implications of this discovery for understanding the origin and evolution of LMXBs in GCs as well as X-ray observations of globular clusters in nearby galaxies.

The Discovery of a Second Luminous Low-Mass X-Ray Binary in the Globular Cluster M15

NASA Technical Reports Server (NTRS)

White, Nicholas E.; Angelini, Lorella

2001-01-01

We report an observation by the Chandra X-Ray Observatory of 4U 2127+119, the X-ray source identified with the globular cluster M15. The Chandra observation reveals that 4U 2127+119 is in fact two bright sources, separated by 2.7 arcsec. One source is associated with AC 211, the previously identified optical counterpart to 4U 2127+119, a low-mass X-ray binary (LMXB). The second source, M15 X-2, is coincident with a 19th U magnitude blue star that is 3.3 arcsec from the cluster core. The Chandra count rate of M15 X-2 is 2.5 times higher than that of AC 211. Prior to the 0.5 arcsec imaging capability of Chandra, the presence of two so closely separated bright sources would not have been resolved. The optical counterpart, X-ray luminosity, and spectrum of M15 X-2 are consistent with it also being an LMXB system. This is the first time that two LMXBs have been seen to be simultaneously active in a globular cluster. The discovery of a second active LMXB in M15 solves a long-standing puzzle where the properties of AC 211 appear consistent with it being dominated by an extended accretion disk corona, and yet 4U 2127+119 also shows luminous X-ray bursts requiring that the neutron star be directly visible. The resolution of 4U 2127+119 into two sources suggests that the X-ray bursts did not come from AC 211 but rather from M15 X-2. We discuss the implications of this discovery for understanding the origin and evolution of LMXBs in globular clusters as well as X-ray observations of globular clusters in nearby galaxies.

Controlling biofilm formation, prophage excision and cell death by rewiring global regulator H‐NS of Escherichia coli

PubMed Central

Hong, Seok Hoon; Wang, Xiaoxue; Wood, Thomas K.

2010-01-01

Summary The global regulator H‐NS of Escherichia coli controls genes related to stress response, biofilm formation and virulence by recognizing curved DNA and by silencing acquired genes. Here, we rewired H‐NS to control biofilm formation using protein engineering; H‐NS variant K57N was obtained that reduces biofilm formation 10‐fold compared with wild‐type H‐NS (wild‐type H‐NS increases biofilm formation whereas H‐NS K57N reduces it). Whole‐transcriptome analysis revealed that H‐NS K57N represses biofilm formation through its interaction with the nucleoid‐associated proteins Cnu and StpA and in the absence of these proteins, H‐NS K57N was unable to reduce biofilm formation. Significantly, H‐NS K57N enhanced the excision of defective prophage Rac while wild‐type H‐NS represses excision, and H‐NS controlled only Rac excision among the nine resident E. coli K‐12 prophages. Rac prophage excision not only led to the change in biofilm formation but also resulted in cell lysis through the expression of toxin HokD. Hence, the H‐NS regulatory system may be evolved through a single‐amino‐acid change in its N‐terminal oligomerization domain to control biofilm formation, prophage excision and apoptosis. PMID:21255333

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

PubMed Central

2013-01-01

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

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

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

Haggard, Daryl; Heinke, Craig; Hooper, Dan

2017-05-01

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

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

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

Haggard, Daryl; Heinke, Craig; Hooper, Dan

2017-05-01

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

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

PubMed Central

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

2016-01-01

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

Discovery of the Ubiquitous Cation NS+ in Space Confirmed by Laboratory Spectroscopy

NASA Astrophysics Data System (ADS)

Cernicharo, J.; Lefloch, B.; Agúndez, M.; Bailleux, S.; Margulès, L.; Roueff, E.; Bachiller, R.; Marcelino, N.; Tercero, B.; Vastel, C.; Caux, E.

2018-02-01

We report the detection in space of a new molecular species that has been characterized spectroscopically and fully identified from astrophysical data. The observations were carried out with the IRAM 30 m telescope. The molecule is ubiquitous as its J=2\\to 1 transition has been found in cold molecular clouds, prestellar cores, and shocks. However, it is not found in the hot cores of Orion-KL and in the carbon-rich evolved star IRC+10216. Three rotational transitions in perfect harmonic relation J\\prime =2/3/5 have been identified in the prestellar core B1b. The molecule has a 1Σ electronic ground state and its J=2\\to 1 transition presents the hyperfine structure characteristic of a molecule containing a nucleus with spin 1. A careful analysis of possible carriers shows that the best candidate is NS+. The derived rotational constant agrees within 0.3%–0.7% with ab initio calculations. NS+ was also produced in the laboratory to unambiguously validate the astrophysical assignment. The observed rotational frequencies and determined molecular constants confirm the discovery of the nitrogen sulfide cation in space. The chemistry of NS+ and related nitrogen-bearing species has been analyzed by means of a time-dependent gas-phase model. The model reproduces well the observed NS/NS+ abundance ratio, in the range 30–50, and indicates that NS+ is formed by reactions of the neutral atoms N and S with the cations SH+ and NH+, respectively.

Bright Lights, Green City

NASA Image and Video Library

2010-07-28

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

Hepatitis C virus NS3 helicase forms oligomeric structures that exhibit optimal DNA unwinding activity in vitro.

PubMed

Sikora, Bartek; Chen, Yingfeng; Lichti, Cheryl F; Harrison, Melody K; Jennings, Thomas A; Tang, Yong; Tackett, Alan J; Jordan, John B; Sakon, Joshua; Cameron, Craig E; Raney, Kevin D

2008-04-25

HCV NS3 helicase exhibits activity toward DNA and RNA substrates. The DNA helicase activity of NS3 has been proposed to be optimal when multiple NS3 molecules are bound to the same substrate molecule. NS3 catalyzes little or no measurable DNA unwinding under single cycle conditions in which the concentration of substrate exceeds the concentration of enzyme by 5-fold. However, when NS3 (100 nm) is equimolar with the substrate, a small burst amplitude of approximately 8 nm is observed. The burst amplitude increases as the enzyme concentration increases, consistent with the idea that multiple molecules are needed for optimal unwinding. Protein-protein interactions may facilitate optimal activity, so the oligomeric properties of the enzyme were investigated. Chemical cross-linking indicates that full-length NS3 forms higher order oligomers much more readily than the NS3 helicase domain. Dynamic light scattering indicates that full-length NS3 exists as an oligomer, whereas NS3 helicase domain exists in a monomeric form in solution. Size exclusion chromatography also indicates that full-length NS3 behaves as an oligomer in solution, whereas the NS3 helicase domain behaves as a monomer. When NS3 was passed through a small pore filter capable of removing protein aggregates, greater than 95% of the protein and the DNA unwinding activity was removed from solution. In contrast, only approximately 10% of NS3 helicase domain and approximately 20% of the associated DNA unwinding activity was removed from solution after passage through the small pore filter. The results indicate that the optimally active form of full-length NS3 is part of an oligomeric species in vitro.

Structure-based design of NS2 mutants for attenuated influenza A virus vaccines.

PubMed

Akarsu, Hatice; Iwatsuki-Horimoto, Kiyoko; Noda, Takeshi; Kawakami, Eiryo; Katsura, Hiroaki; Baudin, Florence; Horimoto, Taisuke; Kawaoka, Yoshihiro

2011-01-01

We previously characterised the matrix 1 (M1)-binding domain of the influenza A virus NS2/nuclear export protein (NEP), reporting a critical role for the tryptophan (W78) residue that is surrounded by a cluster of glutamate residues in the C-terminal region that interacts with the M1 protein (Akarsu et al., 2003). To gain further insight into the functional role of this interaction, here we used reverse genetics to generate a series of A/WSN/33 (H1N1)-based NS2/NEP mutants for W78 or the C-terminal glutamate residues and assessed their effect on virus growth. We found that simultaneous mutations at three positions (E67S/E74S/E75S) of NS2/NEP were important for inhibition of influenza viral polymerase activity, although the W78S mutant and other glutamate mutants with single substitutions were not. In addition, double and triple substitutions in the NS2/NEP glutamine residues, which resulted in the addition of seven amino acids to the C-terminus of NS1 due to gene overlapping, resulted in virus attenuation in mice. Animal studies with this mutant suggest a potential benefit to incorporating these NS mutations into live vaccines. Copyright © 2010 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2015-12-01

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

Investigation of the moving structures in a coronal bright point

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

Ning, Zongjun; Guo, Yang, E-mail: ningzongjun@pmo.ac.cn

2014-10-10

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

Zernike analysis of all-sky night brightness maps.

PubMed

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

2014-04-20

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

Self-deflection of a bright soliton in a separate bright-dark spatial soliton pair based on a higher-order space charge field

NASA Astrophysics Data System (ADS)

Liu, Jin-Song; Hao, Zhong-Hua

2003-10-01

The self-deflection of a bright solitary beam can be controlled by a dark solitary beam via a parametric coupling effect between the bright and dark solitary beams in a separate bright-dark spatial soliton pair supported by an unbiased series photorefractive crystal circuit. The spatial shift of the bright solitary beam centre as a function of the input intensity of the dark solitary beam (hat rho) is investigated by taking into account the higher-order space charge field in the dynamics of the bright solitary beam via both numerical and perturbation methods under steady-state conditions. The deflection amount (Deltas0), defined as the value of the spatial shift at the output surface of the crystal, is a monotonic and nonlinear function of hat rho. When hat rho is weak or strong enough, Deltas0 is, in fact, unchanged with hat rho, whereas Deltas0 increases or decreases monotonically with hat rho in a middle range of hat rho. The corresponding variation range (deltas) depends strongly on the value of the input intensity of the bright solitary beam (r). There are some peak and valley values in the curve of deltas versus r under some conditions. When hat rho increases, the bright solitary beam can scan toward both the direction same as and opposite to the crystal's c-axis. Whether the direction is the same as or opposite to the c-axis depends on the parameter values and configuration of the crystal circuit, as well as the value of r. Some potential applications are discussed.

The Enigmatic Alphavirus Non-Structural Protein 3 (nsP3) Revealing Its Secrets at Last

PubMed Central

Götte, Benjamin; Liu, Lifeng

2018-01-01

Alphaviruses encode 4 non-structural proteins (nsPs), most of which have well-understood functions in capping and membrane association (nsP1), polyprotein processing and RNA helicase activity (nsP2) and as RNA-dependent RNA polymerase (nsP4). The function of nsP3 has been more difficult to pin down and it has long been referred to as the more enigmatic of the nsPs. The protein comprises three domains, an N-terminal macro domain, a central zinc-binding domain and a C-terminal hypervariable domain (HVD). In this article, we review old and new literature about the functions of the three domains. Much progress in recent years has contributed to a picture of nsP3, particularly through its HVD as a hub for interactions with host cell molecules, with multiple effects on the biology of the host cell at early points in infection. These and many future discoveries will provide targets for anti-viral therapies as well as strategies for modification of vectors for vaccine and oncolytic interventions. PMID:29495654

Spatial Model of Sky Brightness Magnitude in Langkawi Island, Malaysia

NASA Astrophysics Data System (ADS)

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

2017-03-01

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

Apparent Brightness and Topography Images of Vibidia Crater

NASA Image and Video Library

2012-03-09

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

Giant Low Surface Brightness Galaxies

NASA Astrophysics Data System (ADS)

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

2018-04-01

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

Reovirus Nonstructural Protein σNS Acts as an RNA-Stability Factor Promoting Viral Genome Replication.

PubMed

Zamora, Paula F; Hu, Liya; Knowlton, Jonathan J; Lahr, Roni M; Moreno, Rodolfo A; Berman, Andrea J; Prasad, B V Venkataram; Dermody, Terence S

2018-05-16

Viral nonstructural proteins, which are not packaged into virions, are essential for replication of most viruses. Reovirus, a nonenveloped, double-stranded RNA (dsRNA) virus, encodes three nonstructural proteins that are required for viral replication and dissemination in the host. Reovirus nonstructural protein σNS is a single-stranded RNA (ssRNA)-binding protein that must be expressed in infected cells for production of viral progeny. However, activities of σNS during individual steps of the reovirus replication cycle are poorly understood. We explored the function of σNS by disrupting its expression during infection using cells expressing a small interfering RNA (siRNA) targeting the σNS-encoding S3 gene and found that σNS is required for viral genome replication. Using complementary biochemical assays, we determined that σNS forms complexes with viral and nonviral RNAs. We also discovered that σNS increases RNA half-life using in vitro and cell-based RNA degradation experiments. Cryo-electron microscopy revealed that σNS and ssRNAs organize into long, filamentous structures. Collectively, our findings indicate that σNS functions as an RNA-binding protein that increases viral RNA half-life. These results suggest that σNS forms RNA-protein complexes in preparation for genome replication. IMPORTANCE Following infection, viruses synthesize nonstructural proteins that mediate viral replication and promote dissemination. Viruses from the Reoviridae family encode nonstructural proteins that are required for the formation of progeny viruses. Although nonstructural proteins of different Reoviridae family viruses are diverged in primary sequence, these proteins are functionally homologous and appear to facilitate conserved mechanisms of dsRNA virus replication. Using in vitro and cell-culture approaches, we found that the mammalian reovirus nonstructural protein σNS binds and stabilizes viral RNA and is required for genome synthesis. This work contributes new

A single-chip 32-channel analog beamformer with 4-ns delay resolution and 768-ns maximum delay range for ultrasound medical imaging with a linear array transducer.

PubMed

Um, Ji-Yong; Kim, Yoon-Jee; Cho, Seong-Eun; Chae, Min-Kyun; Kim, Byungsub; Sim, Jae-Yoon; Park, Hong-June

2015-02-01

A single-chip 32-channel analog beamformer is proposed. It achieves a delay resolution of 4 ns and a maximum delay range of 768 ns. It has a focal-point based architecture, which consists of 7 sub-analog beamformers (sub-ABF). Each sub-ABF performs a RX focusing operation for a single focal point. Seven sub-ABFs perform a time-interleaving operation to achieve the maximum delay range of 768 ns. Phase interpolators are used in sub-ABFs to generate sampling clocks with the delay resolution of 4 ns from a low frequency system clock of 5 MHz. Each sub-ABF samples 32 echo signals at different times into sampling capacitors, which work as analog memory cells. The sampled 32 echo signals of each sub-ABF are originated from one target focal point at one instance. They are summed at one instance in a sub-ABF to perform the RX focusing for the target focal point. The proposed ABF chip has been fabricated in a 0.13- μ m CMOS process with an active area of 16 mm (2). The total power consumption is 287 mW. In measurement, the digital echo signals from a commercial ultrasound medical imaging machine were applied to the fabricated chip through commercial DAC chips. Due to the speed limitation of the DAC chips, the delay resolution was relaxed to 10 ns for the real-time measurement. A linear array transducer with no steering operation is used in this work.

Virulence, Speciation and Antibiotic Susceptibility of Ocular Coagualase Negative Staphylococci (CoNS)

PubMed Central

Priya, Ravindran; Mythili, Arumugam; Singh, Yendremban Randhir Babu; Sreekumar, Haridas; Manikandan, Palanisamy; Panneerselvam, Kanesan

2014-01-01

Background: Coagulase negative Staphylococci (CoNS) are common inhabitants of human skin and mucous membranes. With the emergence of these organisms as prominent pathogens in patients with ocular infections, investigation has intensified in an effort to identify important virulence factors and to inform new approaches to treatment and prevention. Aim: To isolate CoNS from ocular specimens; to study the possible virulence factors; speciation of coagulase negative staphylococci (CoNS) which were isolated from ocular complications; antibiotic susceptibility testing of ocular CoNS. Materials and Methods: The specimens were collected from the target patients who attended the Microbiology Laboratory of a tertiary care eye hospital in Coimbatore, Tamilnadu state, India. The isolates were subjected to tube and slide coagulase tests for the identification of CoNS. All the isolates were subjected to screening for lipase and protease activities. Screening for other virulence factors viz., slime production on Congo red agar medium and haemagglutination assay with use of 96-well microtitre plates. These isolates were identified upto species level by performing biochemical tests such as phosphatase test, arginine test, maltose and trehalose fermentation tests and novobiocin sensitivity test. The isolates were subjected to antibiotic susceptibility studies, based on the revised standards of Clinical and Laboratory Standards Institutes (CLSI). Results: During the one year of study, among the total 260 individuals who were screened, 100 isolates of CoNS were obtained. Lipolytic activity was seen in all the isolates, whereas 38 isolates showed a positive result for protease. A total of 63 isolates showed slime production. Of 100 isolates, 30 isolates were analyzed for haemagglutination, where 4 isolates showed the capacity to agglutinate the erythrocytes. The results of the biochemical analysis revealed that of the 100 isolates of CoNS, 43% were Staphylococcus epidermidis. The other

A first-principles based study of ns2 containing ternary iodides and their possibility of scintillation

NASA Astrophysics Data System (ADS)

Kang, Byungkyun; Fang, C. M.; Biswas, Koushik

2016-10-01

A recently investigated scintillator material CsBa2I5 showed promising properties when activated with ns2 ions In+, Tl+ or the lanthanide Eu2+. This sparked our interest in an analogous group of materials, e.g. InBa2I5 or TlBa2I5 where the ns2 ion is part of the crystal framework, replacing the alkali ion. Many of these compounds of the type AB2X5 (X  =  halogen) have been previously synthesized and have interesting stereochemical activity. Using density functional calculations we have studied the stable monoclinic phase of the aforementioned ns2 containing iodides. One objective is to explore them as scintillators where the ns2 ions, now appearing as part of the crystal, play a central role. Compared to CsBa2I5, their reduced fundamental band gap and possibility of higher light yield may be attributed to an induced degree of covalency in the ns2-I bonds. The valence and conduction band edges have discernible contributions from the ns2 ions’ s and p orbitals which is crucial in carrier localization. The antibonding Ga or In s sates near valence edge may be a favored site for a hole trap, as against a {{V}k} center. Additional differences among the ns2 compounds lead to qualitatively different self-trapped excitons that may fundamentally affect luminescence. The possibility of fast electron capture at the ns2 sites and the prospect of self-activated scintillation via ns2-p  →  {{V}k} or ns2-p  →  ns2-s transitions may draw interest in related applications.

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

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

Campos-Gomez, Javier; Ahmad, Fahim; Rodriguez, Efrain

2016-09-15

The encephalitic alphaviruses encode nsP2 protease (nsP2pro), which because of its vital role in virus replication, represents an attractive target for therapeutic intervention. To facilitate the discovery of nsP2 inhibitors we have developed a novel assay for quantitative measurement of nsP2pro activity in a cell-based format. The assay is based on a substrate fusion protein consisting of eGFP and Gaussia luciferase (Gluc) linked together by a small peptide containing a VEEV nsp2pro cleavage sequence. The expression of the substrate protein in cells along with recombinant nsP2pro results in cleavage of the substrate protein resulting in extracellular release of free Gluc.more » 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.« less

Stunningly bright optical emission

NASA Astrophysics Data System (ADS)

Heinke, Craig O.

2017-12-01

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

Changes of ns-soot mixing states and shapes in an urban area during CalNex

NASA Astrophysics Data System (ADS)

Adachi, Kouji; Buseck, Peter R.

2013-05-01

Aerosol particles from megacities influence the regional and global climate as well as the health of their occupants. We used transmission electron microscopes (TEMs) to study aerosol particles collected from the Los Angeles area during the 2010 CalNex campaign. We detected major amounts of ns-soot, defined as consisting of carbon nanospheres, sulfate, sea salt, and organic aerosol (OA) and lesser amounts of brochosome particles from leaf hoppers. Ns-soot-particle shapes, mixing states, and abundances varied significantly with sampling times and days. Within plumes having high CO2 concentrations, much ns-soot was compacted and contained a relatively large number of carbon nanospheres. Ns-soot particles from both CalNex samples and Mexico City, the latter collected in 2006, had a wide range of shapes when mixed with other aerosol particles, but neither sets showed spherical ns-soot nor the core-shell configuration that is commonly used in optical calculations. Our TEM observations and light-absorption calculations of modeled particles indicate that, in contrast to ns-soot particles that are embedded within other materials or have the hypothesized core-shell configurations, those attached to other aerosol particles hardly enhance their light absorption. We conclude that the ways in which ns-soot mixes with other particles explain the observations of smaller light amplification by ns-soot coatings than model calculations during the CalNex campaign and presumably in other areas.

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

NASA Technical Reports Server (NTRS)

Morin, Bruce L.

2010-01-01

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

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

PubMed

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

2017-04-03

Zika virus (ZIKV) has emerged as major health concern, as ZIKV infection has been shown to be associated with microcephaly, severe neurological disease and possibly male sterility. As the largest protein component within the ZIKV replication complex, NS5 plays key roles in the life cycle and survival of the virus through its N-terminal methyltransferase (MTase) and C-terminal RNA-dependent RNA polymerase (RdRp) domains. Here, we present the crystal structures of ZIKV NS5 MTase in complex with an RNA cap analogue ( m7 GpppA) and the free NS5 RdRp. We have identified the conserved features of ZIKV NS5 MTase and RdRp structures that could lead to development of current antiviral inhibitors being used against flaviviruses, including dengue virus and West Nile virus, to treat ZIKV infection. These results should inform and accelerate the structure-based design of antiviral compounds against ZIKV. © 2017 The Authors.

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

DOE PAGES

Zhao, Baoyu; Yi, Guanghui; Du, Fenglei; ...

2017-03-27

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

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

PubMed

Wilms, Lisa; Oberfeld, Daniel

2017-06-13

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

A Systematic Review of Bright Light Therapy for Eating Disorders.

PubMed

Beauchamp, Marshall T; Lundgren, Jennifer D

2016-10-27

Bright light therapy is a noninvasive biological intervention for disorders with nonnormative circadian features. Eating disorders, particularly those with binge-eating and night-eating features, have documented nonnormative circadian eating and mood patterns, suggesting that bright light therapy may be an efficacious stand-alone or adjunctive intervention. The purpose of this systematic literature review, using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, was (1) to evaluate the state of the empirical treatment outcome literature on bright light therapy for eating disorders and (2) to explore the timing of eating behavior, mood, and sleep-related symptom change so as to understand potential mechanisms of bright light therapy action in the context of eating disorder treatment. A comprehensive literature search using PsycInfo and PubMed/MEDLINE was conducted in April 2016 with no date restrictions to identify studies published using bright light therapy as a treatment for eating disorders. Keywords included combinations of terms describing disordered eating (eating disorder, anorexia nervosa, bulimia nervosa, binge eating, binge, eating behavior, eating, and night eating) and the use of bright light therapy (bright light therapy, light therapy, phototherapy). After excluding duplicates, 34 articles were reviewed for inclusion. 14 published studies of bright light therapy for eating disorders met inclusion criteria (included participants with an eating disorder/disordered-eating behaviors; presented as a case study, case series, open-label clinical trial, or randomized/nonrandomized controlled trial; written in English; and published and available by the time of manuscript review). Results suggest that bright light therapy is potentially effective at improving both disordered-eating behavior and mood acutely, although the timing of symptom response and the duration of treatment effects remain unknown. Future research should

Bright light and thermoregulatory responses to exercise.

PubMed

Atkinson, G; Barr, D; Chester, N; Drust, B; Gregson, W; Reilly, T; Waterhouse, J

2008-03-01

The thermoregulatory responses to morning exercise after exposure to different schedules of bright light were examined. At 07:00 h, six males ran on two occasions in an environmental chamber (temperature = 31.4 +/- 1.0 degrees C, humidity = 66 +/- 6 %) for 40 min at 60 % of maximal oxygen uptake. Participants were exposed to bright light (10,000 lux) either between 22:00 - 23:00 h (BT (low)) or 06:00 - 07:00 h (BT (high)). Otherwise, participants remained in dim light (< 50 lux). It was hypothesized that BT (low) attenuates core temperature during morning exercise via the phase-delaying properties of evening bright light and by avoiding bright light in the morning. Evening bright light in BT (low) suppressed (p = 0.037) the increase in melatonin compared to dim light (1.1 +/- 11.4 vs. 15.2 +/- 19.7 pg x ml (-1)) and delayed (p = 0.034) the core temperature minimum by 1.46 +/- 1.24 h. Core temperature was 0.20 +/- 0.17 degrees C lower in BT (low) compared to BT (high) during the hour before exercise (p = 0.036), with evidence (p = 0.075) that this difference was maintained during exercise. Conversely, mean skin temperature was 1.0 +/- 1.7 degrees C higher during the first 10 min of exercise in BT (low) than in BT (high) (p = 0.030). There was evidence that the increase in perceived exertion was attenuated in BT (low) (p = 0.056). A chronobiologically-based light schedule can lower core temperature before and during morning exercise in hot conditions.

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

NASA Astrophysics Data System (ADS)

Tayloe, R.

2018-04-01

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

Iapetus Bright and Dark Terrains

NASA Technical Reports Server (NTRS)

1990-01-01

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

Two distinct sets of NS2A molecules are responsible for dengue virus RNA synthesis and virion assembly.

PubMed

Xie, Xuping; Zou, Jing; Puttikhunt, Chunya; Yuan, Zhiming; Shi, Pei-Yong

2015-01-15

Flavivirus nonstructural protein 2A (NS2A) plays important roles in both viral RNA synthesis and virion assembly. The molecular details of how the NS2A protein modulates the two distinct events have not been defined. To address this question, we have performed a systematic mutagenesis of NS2A using dengue virus (DENV) serotype 2 (DENV-2) as a model. We identified two sets of NS2A mutations with distinct defects during a viral infection cycle. One set of NS2A mutations (D125A and G200A) selectively abolished viral RNA synthesis. Mechanistically, the D125A mutation abolished viral RNA synthesis through blocking the N-terminal cleavage of the NS2A protein, leading to an unprocessed NS1-NS2A protein; this result suggests that amino acid D125 (far downstream of the N terminus of NS2A) may contribute to the recognition of host protease at the NS1-NS2A junction. The other set of NS2A mutations (G11A, E20A, E100A, Q187A, and K188A) specifically impaired virion assembly without significantly affecting viral RNA synthesis. Remarkably, mutants defective in virion assembly could be rescued by supplying in trans wild-type NS2A molecules expressed from a replicative replicon, by wild-type NS2A protein expressed alone, by a mutant NS2A (G200A) that is lethal for viral RNA synthesis, or by a different mutant NS2A that is defective in virion assembly. In contrast, none of the mutants defective in viral RNA synthesis could be rescued by trans-complementation. Collectively, the results indicate that two distinct sets of NS2A molecules are responsible for DENV RNA synthesis and virion assembly. Dengue virus (DENV) represents the most prevalent mosquito-borne human pathogen. Understanding the replication of DENV is essential for development of vaccines and therapeutics. Here we characterized the function of DENV-2 NS2A using a systematic mutagenesis approach. The mutagenesis results revealed two distinct sets of NS2A mutations: one set of mutations that result in defects in viral RNA

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

PubMed

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

2014-01-01

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

Automatic brightness control of laser spot vision inspection system

NASA Astrophysics Data System (ADS)

Han, Yang; Zhang, Zhaoxia; Chen, Xiaodong; Yu, Daoyin

2009-10-01

The laser spot detection system aims to locate the center of the laser spot after long-distance transmission. The accuracy of positioning laser spot center depends very much on the system's ability to control brightness. In this paper, an automatic brightness control system with high-performance is designed using the device of FPGA. The brightness is controlled by combination of auto aperture (video driver) and adaptive exposure algorithm, and clear images with proper exposure are obtained under different conditions of illumination. Automatic brightness control system creates favorable conditions for positioning of the laser spot center later, and experiment results illuminate the measurement accuracy of the system has been effectively guaranteed. The average error of the spot center is within 0.5mm.

Visible Color and Photometry of Bright Materials on Vesta

NASA Technical Reports Server (NTRS)

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

2012-01-01

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

A basic cluster in the N terminus of yellow fever virus NS2A contributes to infectious particle production.

PubMed

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

2015-05-01

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

A Basic Cluster in the N Terminus of Yellow Fever Virus NS2A Contributes to Infectious Particle Production

PubMed Central

Voßmann, Stephanie; Wieseler, Janett; Kerber, Romy

2015-01-01

ABSTRACT 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. IMPORTANCE 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

Ultrashort high-brightness pulses from storage rings

NASA Astrophysics Data System (ADS)

Khan, Shaukat

2017-09-01

The brightness of short-wavelength radiation from accelerator-based sources can be increased by coherent emission in which the radiation intensity scales with the number of contributing electrons squared. This requires a microbunched longitudinal electron distribution, which is the case in free-electron lasers. The brightness of light sources based on electron storage rings was steadily improved, but could profit further from coherent emission. The modulation of the electron energy by a continuous-wave laser field may provide steady-state microbunching in the infrared regime. For shorter wavelengths, the energy modulation can be converted into a temporary density modulation by a dispersive chicane. One particular goal is coherent emission from a very short "slice" within an electron bunch in order to produce ultrashort radiation pulses with high brightness.

Differential roles for the C-terminal hexapeptide domains of NS2 splice variants during MVM infection of murine cells.

PubMed

Ruiz, Zandra; D'Abramo, Anthony; Tattersall, Peter

2006-06-05

The MVM NS2 proteins are required for viral replication in cells of its normal murine host, but are dispensable in transformed human 324K cells. Alternate splicing at the minor intron controls synthesis of three forms of this protein, which differ in their C-terminal hexapeptides and in their relative abundance, with NS2P and NS2Y, the predominant isoforms, being expressed at a 5:1 ratio. Mutant genomes were constructed with premature termination codons in the C-terminal exons of either NS2P or NS2Y, which resulted in their failure to accumulate in vivo. To modulate their expression levels, we also introduced a mutation at the putative splice branch point of the large intron, dubbed NS2(lo), that reduced total NS2 expression in murine A9 cells such that NS2P accumulated to approximately half the level normally seen for NS2Y. All mutants replicated productively in human 324K cells. In A9 cells, NS2Y(-) mutants replicated like wildtype, and the NS2(lo) mutants expressed NS1 and replicated duplex viral DNA like wildtype, although their progeny single-strand DNA synthesis was reduced. However, while NS2P(-) and NS2-null viruses initiated infection efficiently in A9 cells, they gave diminished NS1 levels, and viral macromolecular synthesis appeared to become paralyzed shortly after the onset of viral duplex DNA amplification, such that no progeny single-strand DNA could be detected. Thus, the NS2P isoform, even when expressed at a level lower than that of NS2Y, performs a critical role in infection of A9 cells that cannot be accomplished by the NS2Y isoform alone.

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

PubMed

Shanmugam, Saravanabalaji; Saravanabalaji, Dhanaranjani; Yi, MinKyung

2015-04-01

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

Bright Spokes, Dark Shadow

NASA Image and Video Library

2010-04-06

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

Black holes in short period X-ray binaries and the transition to radiatively inefficient accretion

NASA Astrophysics Data System (ADS)

Knevitt, G.; Wynn, G. A.; Vaughan, S.; Watson, M. G.

2014-02-01

By comparing the orbital period distributions of black hole and neutron star low-mass X-ray binaries (LMXBs) in the Ritter-Kolb catalogue we show that there is statistical evidence for a dearth of black hole systems at short orbital periods (Porb < 4 h). This could either be due to a true divergence in orbital period distributions of these two types of system, or to black hole LMXBs being preferentially hidden from view at short orbital periods. We explore the latter possibility, by investigating whether black hole LMXBs could be concealed by a switch to radiatively inefficient accretion at low luminosities. The peak luminosity and the duration of X-ray binary outbursts are related to the disc radius and, hence, the orbital period. At short periods, where the peak outburst luminosity drops close to the threshold for radiatively inefficient accretion, black hole LMXBs have lower outburst luminosities, shorter outburst durations and lower X-ray duty cycles than comparable neutron star systems. These factors can combine to severely reduce the detection probability of short period black hole LMXBs relative to those containing neutron stars. We estimate the outburst properties and orbital period distribution of black hole LMXBs using two models of the transition to radiatively inefficient accretion: an instantaneous drop in accretion efficiency (η) to zero, at a fraction (f) of the Eddington luminosity (LEdd) and a power-law efficiency decrease, η ∝ dot{M}^n, for L < f LEdd. We show that a population of black hole LMXBs at short orbital periods can only be hidden by a sharp drop in efficiency, either instantaneous or for n ≳ 3. This could be achieved by a genuine drop in luminosity or through abrupt spectral changes that shift the accretion power out of a given X-ray band.

Extremely Low Passive Microwave Brightness Temperatures Due to Thunderstorms

NASA Technical Reports Server (NTRS)

Cecil, Daniel J.

2015-01-01

Extreme events by their nature fall outside the bounds of routine experience. With imperfect or ambiguous measuring systems, it is appropriate to question whether an unusual measurement represents an extreme event or is the result of instrument errors or other sources of noise. About three weeks after the Tropical Rainfall Measuring Mission (TRMM) satellite began collecting data in Dec 1997, a thunderstorm was observed over northern Argentina with 85 GHz brightness temperatures below 50 K and 37 GHz brightness temperatures below 70 K (Zipser et al. 2006). These values are well below what had previously been observed from satellite sensors with lower resolution. The 37 GHz brightness temperatures are also well below those measured by TRMM for any other storm in the subsequent 16 years. Without corroborating evidence, it would be natural to suspect a problem with the instrument, or perhaps an irregularity with the platform during the first weeks of the satellite mission. Automated quality control flags or other procedures in retrieval algorithms could treat these measurements as errors, because they fall outside the expected bounds. But the TRMM satellite also carries a radar and a lightning sensor, both confirming the presence of an intense thunderstorm. The radar recorded 40+ dBZ reflectivity up to about 19 km altitude. More than 200 lightning flashes per minute were recorded. That same storm's 19 GHz brightness temperatures below 150 K would normally be interpreted as the result of a low-emissivity water surface (e.g., a lake, or flood waters) if not for the simultaneous measurements of such intense convection. This paper will examine records from TRMM and related satellite sensors including SSMI, AMSR-E, and the new GMI to find the strongest signatures resulting from thunderstorms, and distinguishing those from sources of noise. The lowest brightness temperatures resulting from thunderstorms as seen by TRMM have been in Argentina in November and December. For

Synthesizing SMOS Zero-Baselines with Aquarius Brightness Temperature Simulator

NASA Technical Reports Server (NTRS)

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

2012-01-01

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

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

PubMed

Bhattacharya, Joydeep; Lindsen, Job P

2016-01-01

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

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

PubMed Central

2018-01-01

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

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

PubMed

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

2018-01-01

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

RSV-encoded NS2 promotes epithelial cell shedding and distal airway obstruction

PubMed Central

Liesman, Rachael M.; Buchholz, Ursula J.; Luongo, Cindy L.; Yang, Lijuan; Proia, Alan D.; DeVincenzo, John P.; Collins, Peter L.; Pickles, Raymond J.

2014-01-01

Respiratory syncytial virus (RSV) infection is the major cause of bronchiolitis in young children. The factors that contribute to the increased propensity of RSV-induced distal airway disease compared with other commonly encountered respiratory viruses remain unclear. Here, we identified the RSV-encoded nonstructural 2 (NS2) protein as a viral genetic determinant for initiating RSV-induced distal airway obstruction. Infection of human cartilaginous airway epithelium (HAE) and a hamster model of disease with recombinant respiratory viruses revealed that NS2 promotes shedding of infected epithelial cells, resulting in two consequences of virus infection. First, epithelial cell shedding accelerated the reduction of virus titers, presumably by clearing virus-infected cells from airway mucosa. Second, epithelial cells shedding into the narrow-diameter bronchiolar airway lumens resulted in rapid accumulation of detached, pleomorphic epithelial cells, leading to acute distal airway obstruction. Together, these data indicate that RSV infection of the airway epithelium, via the action of NS2, promotes epithelial cell shedding, which not only accelerates viral clearance but also contributes to acute obstruction of the distal airways. Our results identify RSV NS2 as a contributing factor for the enhanced propensity of RSV to cause severe airway disease in young children and suggest NS2 as a potential therapeutic target for reducing the severity of distal airway disease. PMID:24713657

Quantification of NS1 dengue biomarker in serum via optomagnetic nanocluster detection

NASA Astrophysics Data System (ADS)

Antunes, Paula; Watterson, Daniel; Parmvi, Mattias; Burger, Robert; Boisen, Anja; Young, Paul; Cooper, Matthew A.; Hansen, Mikkel F.; Ranzoni, Andrea; Donolato, Marco

2015-11-01

Dengue is a tropical vector-borne disease without cure or vaccine that progressively spreads into regions with temperate climates. Diagnostic tools amenable to resource-limited settings would be highly valuable for epidemiologic control and containment during outbreaks. Here, we present a novel low-cost automated biosensing platform for detection of dengue fever biomarker NS1 and demonstrate it on NS1 spiked in human serum. Magnetic nanoparticles (MNPs) are coated with high-affinity monoclonal antibodies against NS1 via bio-orthogonal Cu-free ‘click’ chemistry on an anti-fouling surface molecular architecture. The presence of the target antigen NS1 triggers MNP agglutination and the formation of nanoclusters with rapid kinetics enhanced by external magnetic actuation. The amount and size of the nanoclusters correlate with the target concentration and can be quantified using an optomagnetic readout method. The resulting automated dengue fever assay takes just 8 minutes, requires 6 μL of serum sample and shows a limit of detection of 25 ng/mL with an upper detection range of 20000 ng/mL. The technology holds a great potential to be applied to NS1 detection in patient samples. As the assay is implemented on a low-cost microfluidic disc the platform is suited for further expansion to multiplexed detection of a wide panel of biomarkers.

The non-structural (NS) gene segment of H9N2 influenza virus isolated from backyard poultry in Pakistan reveals strong genetic and functional similarities to the NS gene of highly pathogenic H5N1

PubMed Central

Munir, Muhammad; Zohari, Siamak; Iqbal, Munir; Abbas, Muhammad; Perez, Daniel Roberto; Berg, Mikael

2013-01-01

Apart from natural reassortment, co-circulation of different avian influenza virus strains in poultry populations can lead to generation of novel variants and reassortant viruses. In this report, we studied the genetics and functions of a reassorted non-structural gene (NS) of H9N2 influenza virus collected from back yard poultry (BYP) flock. Phylogenetic reconstruction based on hemagglutinin and neuraminidase genes indicates that an isolate from BYP belongs to H9N2. However, the NS gene-segment of this isolate cluster into genotype Z, clade 2.2 of the highly pathogenic H5N1. The NS gene plays essential roles in the host-adaptation, cell-tropism, and virulence of influenza viruses. However, such interpretations have not been investigated in naturally recombinant H9N2 viruses. Therefore, we compared the NS1 protein of H9N2 (H9N2/NS1) and highly pathogenic H5N1 (H5N1/NS1) in parallel for their abilities to regulate different signaling pathways, and investigated the molecular mechanisms of IFN-β production in human, avian, and mink lung cells. We found that H9N2/NS1 and H5N1/NS1 are comparably similar in inhibiting TNF-α induced nuclear factor κB and double stranded RNA induced activator protein 1 and interferon regulatory factor 3 transcription factors. Thus, the production of IFN-β was inhibited equally by both NS1s as demonstrated by IFN stimulatory response element and IFN-β promoter activation. Moreover, both NS1s predominantly localized in the nucleus when transfected to human A549 cells. This study therefore suggests the possible increased virulence of natural reassortant viruses for their efficient invasion of host immune responses, and proposes that these should not be overlooked for their epizootic and zoonotic potential. PMID:23959028

Flavivirus NS1 protein in infected host sera enhances viral acquisition by mosquitoes.

PubMed

Liu, Jianying; Liu, Yang; Nie, Kaixiao; Du, Senyan; Qiu, Jingjun; Pang, Xiaojing; Wang, Penghua; Cheng, Gong

2016-06-20

The arbovirus life cycle involves viral transfer between a vertebrate host and an arthropod vector, and acquisition of virus from an infected mammalian host by a vector is an essential step in this process. Here, we report that flavivirus nonstructural protein-1 (NS1), which is abundantly secreted into the serum of an infected host, plays a critical role in flavivirus acquisition by mosquitoes. The presence of dengue virus (DENV) and Japanese encephalitis virus NS1s in the blood of infected interferon-α and γ receptor-deficient mice (AG6) facilitated virus acquisition by their native mosquito vectors because the protein enabled the virus to overcome the immune barrier of the mosquito midgut. Active immunization of AG6 mice with a modified DENV NS1 reduced DENV acquisition by mosquitoes and protected mice against a lethal DENV challenge, suggesting that immunization with NS1 could reduce the number of virus-carrying mosquitoes as well as the incidence of flaviviral diseases. Our study demonstrates that flaviviruses utilize NS1 proteins produced during their vertebrate phases to enhance their acquisition by vectors, which might be a result of flavivirus evolution to adapt to multiple host environments.

Flavivirus NS1 protein in infected host sera enhances viral acquisition by mosquitoes

PubMed Central

Liu, Jianying; Liu, Yang; Nie, Kaixiao; Du, Senyan; Qiu, Jingjun; Pang, Xiaojing; Wang, Penghua; Cheng, Gong

2016-01-01

Summary The arbovirus life cycle involves viral transfer between a vertebrate host and an arthropod vector, and acquisition of virus from an infected mammalian host by a vector is an essential step in this process. Here, we report that flavivirus nonstructural protein-1 (NS1), which is abundantly secreted into the serum of an infected host, plays a critical role in flavivirus acquisition by mosquitoes. The presence of dengue virus (DENV) and Japanese encephalitis virus (JEV) NS1s in the blood of infected interferon alpha and gamma receptor-deficient mice (AG6) facilitated virus acquisition by their native mosquito vectors because the protein enabled the virus to overcome the immune barrier of the mosquito midgut. Active immunization of AG6 mice with a modified DENV NS1 reduced DENV acquisition by mosquitoes and protected mice against a lethal DENV challenge, suggesting that immunization with NS1 could reduce the number of virus-carrying mosquitoes as well as the incidence of flaviviral diseases. Our study demonstrates that flaviviruses utilize NS1 proteins produced during their vertebrate phases to enhance their acquisition by vectors, which might be a result of flavivirus evolution to adapt to multiple host environments. PMID:27562253

Excitation Spectra and Brightness Optimization of Two-Photon Excited Probes

PubMed Central

Mütze, Jörg; Iyer, Vijay; Macklin, John J.; Colonell, Jennifer; Karsh, Bill; Petrášek, Zdeněk; Schwille, Petra; Looger, Loren L.; Lavis, Luke D.; Harris, Timothy D.

2012-01-01

Two-photon probe excitation data are commonly presented as absorption cross section or molecular brightness (the detected fluorescence rate per molecule). We report two-photon molecular brightness spectra for a diverse set of organic and genetically encoded probes with an automated spectroscopic system based on fluorescence correlation spectroscopy. The two-photon action cross section can be extracted from molecular brightness measurements at low excitation intensities, while peak molecular brightness (the maximum molecular brightness with increasing excitation intensity) is measured at higher intensities at which probe photophysical effects become significant. The spectral shape of these two parameters was similar across all dye families tested. Peak molecular brightness spectra, which can be obtained rapidly and with reduced experimental complexity, can thus serve as a first-order approximation to cross-section spectra in determining optimal wavelengths for two-photon excitation, while providing additional information pertaining to probe photostability. The data shown should assist in probe choice and experimental design for multiphoton microscopy studies. Further, we show that, by the addition of a passive pulse splitter, nonlinear bleaching can be reduced—resulting in an enhancement of the fluorescence signal in fluorescence correlation spectroscopy by a factor of two. This increase in fluorescence signal, together with the observed resemblance of action cross section and peak brightness spectra, suggests higher-order photobleaching pathways for two-photon excitation. PMID:22385865

Asymmetric 511 keV Positron Annihilation Line Emission from the Inner Galactic Disk

NASA Technical Reports Server (NTRS)

Skinner, Gerry; Weidenspointner, Georg; Jean, Pierre; Knodlseder, Jurgen; Ballmoos, Perer von; Bignami, Giovanni; Diehl, Roland; Strong, Andrew; Cordier, Bertrand; Schanne, Stephane;

Transmembrane Domains of NS2B Contribute to both Viral RNA Replication and Particle Formation in Japanese Encephalitis Virus.

PubMed

Li, Xiao-Dan; Deng, Cheng-Lin; Ye, Han-Qing; Zhang, Hong-Lei; Zhang, Qiu-Yan; Chen, Dong-Dong; Zhang, Pan-Tao; Shi, Pei-Yong; Yuan, Zhi-Ming; Zhang, Bo

2016-06-15

Flavivirus nonstructural protein 2B (NS2B) is a transmembrane protein that functions as a cofactor for viral NS3 protease. The cytoplasmic region (amino acids 51 to 95) alone of NS2B is sufficient for NS3 protease activity, whereas the role of transmembrane domains (TMDs) remains obscure. Here, we demonstrate for the first time that flavivirus NS2B plays a critical role in virion assembly. Using Japanese encephalitis virus (JEV) as a model, we performed a systematic mutagenesis at the flavivirus conserved residues within the TMDs of NS2B. As expected, some mutations severely attenuated (L38A and R101A) or completely destroyed (G12L) viral RNA synthesis. Interestingly, two mutations (G37L and P112A) reduced viral RNA synthesis and blocked virion assembly. None of the mutations affected NS2B-NS3 protease activity. Because mutations G37L and P112A affected virion assembly, we selected revertant viruses for these two mutants. For mutant G37L, replacement with G37F, G37H, G37T, or G37S restored virion assembly. For mutant P112A, insertion of K at position K127 (leading to K127KK) of NS2B rescued virion assembly. A biomolecular fluorescent complementation (BiFC) analysis demonstrated that (i) mutation P112A selectively weakened NS2B-NS2A interaction and (ii) the adaptive mutation K127KK restored NS2B-NS2A interaction. Collectively, our results demonstrate that, in addition to being a cofactor for NS3 protease, flavivirus NS2B also functions in viral RNA replication, as well as virion assembly. Many flaviviruses are important human pathogens. Understanding the molecular mechanisms of the viral infection cycle is essential for vaccine and antiviral development. In this study, we demonstrate that the TMDs of JEV NS2B participate in both viral RNA replication and virion assembly. A viral genetic study and a BiFC assay demonstrated that interaction between NS2B and NS2A may participate in modulating viral assembly in the flavivirus life cycle. Compensatory-mutation analysis

Identification of high-specificity H-NS binding site in LEE5 promoter of enteropathogenic Esherichia coli (EPEC).

PubMed

Bhat, Abhay Prasad; Shin, Minsang; Choy, Hyon E

2014-07-01

Histone-like nucleoid structuring protein (H-NS) is a small but abundant protein present in enteric bacteria and is involved in compaction of the DNA and regulation of the transcription. Recent reports have suggested that H-NS binds to a specific AT rich DNA sequence than to intrinsically curved DNA in sequence independent manner. We detected two high-specificity H-NS binding sites in LEE5 promoter of EPEC centered at -110 and -138, which were close to the proposed consensus H-NS binding motif. To identify H-NS binding sequence in LEE5 promoter, we took a random mutagenesis approach and found the mutations at around -138 were specifically defective in the regulation by H-NS. It was concluded that H-NS exerts maximum repression via the specific sequence at around -138 and subsequently contacts a subunit of RNAP through oligomerization.

Night Sky Brightness at San Pedro Martir Observatory

NASA Astrophysics Data System (ADS)

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

2017-03-01

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

Simultaneous brightness contrast of foraging Papilio butterflies

PubMed Central

Kinoshita, Michiyo; Takahashi, Yuki; Arikawa, Kentaro

2012-01-01

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

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

PubMed

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

2018-06-20

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

The Changing Face of Hepatitis C: Recent Advances on HCV Inhibitors Targeting NS5A

PubMed

Rai, Diwakar; Wang, Liu; Jiang, Xuemei; Zhan, Peng; Jia, Haiyong; De Clercq, Erik; Liu, Xinyong

2015-05-05

Current treatment for HCV infections consists of approved direct acting antivirals (DAAs), viz. the protease inhibitors (boceprevir, telaprevir, and simeprevir), NS5B polymerase inhibitors (sofosbuvir) and NS5A inhibitor (ledipasvir) in combination with pegylated interferon α and ribavirin). These treatments have made a great improvement in the treatment of chronic HCV infections in recent years, but their adverse side effects, emergence of resistant mutants, high cost, and increased pill burden have limited their clinical use. Recently, with the increasing knowledge in understanding the HCV life cycle, more targets have been recognized. NS5A protein plays a critical role in assembly of infectious HCV particles and offering potential for HCV therapies. Therefore, discovery and development of novel DAAs targeting NS5A with novel mechanisms of action, is of great necessity to improve the quality of existing HCV treatments. In the present review, we discuss recent advances with NS5A inhibitors with potent anti-HCV activity, and the potential for the development of HCV NS5A inhibitors to combat HCV infections.

Interaction between the bacterial nucleoid associated proteins Hha and H-NS involves a conformational change of Hha.

PubMed

García, Jesús; Cordeiro, Tiago N; Nieto, José M; Pons, Ignacio; Juárez, Antonio; Pons, Miquel

2005-06-15

The H-NS family of proteins has been shown to participate in the regulation of a large number of genes in Gram-negative bacteria in response to environmental factors. In recent years, it has become apparent that proteins of the Hha family are essential elements for H-NS-regulated gene expression. Hha has been shown to bind H-NS, although the details for this interaction are still unknown. In the present paper, we report fluorescence anisotropy and NMR studies of the interaction between Hha and H-NS64, a truncated form of H-NS containing only its N-terminal dimerization domain. We demonstrate the initial formation of a complex between one Hha and two H-NS64 monomers in 150 mM NaCl. This complex seems to act as a nucleation unit for higher-molecular-mass complexes. NMR studies suggest that Hha is in equilibrium between two different conformations, one of which is stabilized by binding to H-NS64. A similar exchange is also observed for Hha in the absence of H-NS when temperature is increased to 37 degrees C, suggesting a key role for intrinsic conformational changes of Hha in modulating its interaction with H-NS.

Interaction between the bacterial nucleoid associated proteins Hha and H-NS involves a conformational change of Hha

PubMed Central

2005-01-01

The H-NS family of proteins has been shown to participate in the regulation of a large number of genes in Gram-negative bacteria in response to environmental factors. In recent years, it has become apparent that proteins of the Hha family are essential elements for H-NS-regulated gene expression. Hha has been shown to bind H-NS, although the details for this interaction are still unknown. In the present paper, we report fluorescence anisotropy and NMR studies of the interaction between Hha and H-NS64, a truncated form of H-NS containing only its N-terminal dimerization domain. We demonstrate the initial formation of a complex between one Hha and two H-NS64 monomers in 150 mM NaCl. This complex seems to act as a nucleation unit for higher-molecular-mass complexes. NMR studies suggest that Hha is in equilibrium between two different conformations, one of which is stabilized by binding to H-NS64. A similar exchange is also observed for Hha in the absence of H-NS when temperature is increased to 37 °C, suggesting a key role for intrinsic conformational changes of Hha in modulating its interaction with H-NS. PMID:15720293

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

PubMed

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

2016-02-02

Many viral proteins have the ability to kill tumor cells specifically without harming the normal cells. These proteins, on ectopic expression, cause lysis or induction of apoptosis in the target tumor cells. Parvovirus NS1 is one of such proteins, which is known to kill high proliferating tumor cells. In the present study, we assessed the apoptosis inducing ability of canine parvovirus type 2 NS1 protein (CPV2.NS1) in vitro in 4T1 cells, and found it to cause significant cell death due to induction of apoptosis through intrinsic or mitochondrial pathway. Further, we also evaluated the oncolytic activity of CPV2.NS1 protein in a mouse mammary tumor model. The results suggested that CPV2.NS1 was able to inhibit the growth of 4T1 induced mouse mammary tumor as indicated by significantly reduced tumor volume, mitotic, AgNOR and PCNA indices. Further, inhibition of tumor growth was found to be because of induction of apoptosis in the tumor cells, which was evident by a significant increase in the number of TUNEL positive cells. Further, CPV2.NS1 was also able to stimulate the immune cells against the tumor antigens as indicated by the increased CD4+ and CD8+ counts in the blood of CVP2.NS1 treated mice. Further optimization of the delivery of NS1 protein and use of an adjuvant may further enhance its anti-tumor activity. Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed

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

2015-11-01

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

A study of coronal bright points at 20 cm wavelength

NASA Technical Reports Server (NTRS)

Nitta, N.; Kundu, M. R.

1988-01-01

The paper presents the results of a study of coronal bright points observed at 20 cm with the VLA on a day when the sun was exceptionally quiet. Microwave maps of bright points were obtained using data for the entire observing period of 5 hours, as well as for shorter periods of a few minutes. Most bright points, especially those appearing in the full-period maps, appear to be associated with small bipolar structures on the photospheric magnetogram. Overlays of bright point (BP) maps on the Ca(+) K picture, show that the brightest part of BP tends to lie on the boundary of a supergranulation network.

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

NASA Technical Reports Server (NTRS)

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

1997-01-01

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

Life-threatening motor vehicle crashes in bright sunlight

PubMed Central

Redelmeier, Donald A.; Raza, Sheharyar

2017-01-01

Abstract Bright sunlight may create visual illusions that lead to driver error, including fallible distance judgment from aerial perspective. We tested whether the risk of a life-threatening motor vehicle crash was increased when driving in bright sunlight. This longitudinal, case-only, paired-comparison analysis evaluated patients hospitalized because of a motor vehicle crash between January 1, 1995 and December 31, 2014. The relative risk of a crash associated with bright sunlight was estimated by evaluating the prevailing weather at the time and place of the crash compared with the weather at the same hour and location on control days a week earlier and a week later. The majority of patients (n = 6962) were injured during daylight hours and bright sunlight was the most common weather condition at the time and place of the crash. The risk of a life-threatening crash was 16% higher during bright sunlight than normal weather (95% confidence interval: 9–24, P < 0.001). The increased risk was accentuated in the early afternoon, disappeared at night, extended to patients with different characteristics, involved crashes with diverse features, not apparent with cloudy weather, and contributed to about 5000 additional patient-days in hospital. The increased risk extended to patients with high crash severity as indicated by ambulance involvement, surgical procedures, length of hospital stay, intensive care unit admission, and patient mortality. The increased risk was not easily attributed to differences in alcohol consumption, driving distances, or anomalies of adverse weather. Bright sunlight is associated with an increased risk of a life-threatening motor vehicle crash. An awareness of this risk might inform driver education, trauma staffing, and safety warnings to prevent a life-threatening motor vehicle crash. Level of evidence: Epidemiologic Study, level III. PMID:28072708

Life-threatening motor vehicle crashes in bright sunlight.

PubMed

Redelmeier, Donald A; Raza, Sheharyar

2017-01-01

Bright sunlight may create visual illusions that lead to driver error, including fallible distance judgment from aerial perspective. We tested whether the risk of a life-threatening motor vehicle crash was increased when driving in bright sunlight.This longitudinal, case-only, paired-comparison analysis evaluated patients hospitalized because of a motor vehicle crash between January 1, 1995 and December 31, 2014. The relative risk of a crash associated with bright sunlight was estimated by evaluating the prevailing weather at the time and place of the crash compared with the weather at the same hour and location on control days a week earlier and a week later.The majority of patients (n = 6962) were injured during daylight hours and bright sunlight was the most common weather condition at the time and place of the crash. The risk of a life-threatening crash was 16% higher during bright sunlight than normal weather (95% confidence interval: 9-24, P < 0.001). The increased risk was accentuated in the early afternoon, disappeared at night, extended to patients with different characteristics, involved crashes with diverse features, not apparent with cloudy weather, and contributed to about 5000 additional patient-days in hospital. The increased risk extended to patients with high crash severity as indicated by ambulance involvement, surgical procedures, length of hospital stay, intensive care unit admission, and patient mortality. The increased risk was not easily attributed to differences in alcohol consumption, driving distances, or anomalies of adverse weather.Bright sunlight is associated with an increased risk of a life-threatening motor vehicle crash. An awareness of this risk might inform driver education, trauma staffing, and safety warnings to prevent a life-threatening motor vehicle crash. Epidemiologic Study, level III.

Two-Dimensional Metal-Organic Layers as a Bright and Processable Phosphor for Fast White-Light Communication.

PubMed

Hu, Xuefu; Wang, Zi; Lin, Bangjiang; Zhang, Cankun; Cao, Lingyun; Wang, Tingting; Zhang, Jingzheng; Wang, Cheng; Lin, Wenbin

2017-06-22

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 Zr 6 O 4 (OH) 6 (H 2 O) 2 (HCO 2 ) 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.

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

PubMed Central

2016-01-01

A prevalent conceptual metaphor is the association of the concepts of good and evil with brightness and darkness, respectively. Music cognition, like metaphor, is possibly embodied, yet no study has addressed the question whether musical emotion can modulate brightness judgment in a metaphor consistent fashion. In three separate experiments, participants judged the brightness of a grey square that was presented after a short excerpt of emotional music. The results of Experiment 1 showed that short musical excerpts are effective emotional primes that cross-modally influence brightness judgment of visual stimuli. Grey squares were consistently judged as brighter after listening to music with a positive valence, as compared to music with a negative valence. The results of Experiment 2 revealed that the bias in brightness judgment does not require an active evaluation of the emotional content of the music. By applying a different experimental procedure in Experiment 3, we showed that this brightness judgment bias is indeed a robust effect. Altogether, our findings demonstrate a powerful role of musical emotion in biasing brightness judgment and that this bias is aligned with the metaphor viewpoint. PMID:26863420

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

PubMed

da Silveira, Nelson J F; Arcuri, Helen A; Bonalumi, Carlos E; de Souza, Fátima P; Mello, Isabel M V G C; Rahal, Paula; Pinho, João R R; de Azevedo, Walter F

2005-01-21

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. 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. 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-based drug design of a new generation of NS3 protease variants

Noncytopathogenic Pestivirus Strains Generated by Nonhomologous RNA Recombination: Alterations in the NS4A/NS4B Coding Region

PubMed Central

Gallei, Andreas; Orlich, Michaela; Thiel, Heinz-Juergen; Becher, Paul

2005-01-01

Several studies have demonstrated that cytopathogenic (cp) pestivirus strains evolve from noncytopathogenic (noncp) viruses by nonhomologous RNA recombination. In addition, two recent reports showed the rapid emergence of noncp Bovine viral diarrhea virus (BVDV) after a few cell culture passages of cp BVDV strains by homologous recombination between identical duplicated viral sequences. To allow the identification of recombination sites from noncp BVDV strains that evolve from cp viruses, we constructed the cp BVDV strains CP442 and CP552. Both harbor duplicated viral sequences of different origin flanking the cellular insertion Nedd8*; the latter is a prerequisite for their cytopathogenicity. In contrast to the previous studies, isolation of noncp strains was possible only after extensive cell culture passages of CP442 and CP552. Sequence analysis of 15 isolated noncp BVDVs confirmed that all recombinant strains lack at least most of Nedd8*. Interestingly, only one strain resulted from homologous recombination while the other 14 strains were generated by nonhomologous recombination. Accordingly, our data suggest that the extent of sequence identity between participating sequences influences both frequency and mode (homologous versus nonhomologous) of RNA recombination in pestiviruses. Further analyses of the noncp recombinant strains revealed that a duplication of 14 codons in the BVDV nonstructural protein 4B (NS4B) gene does not interfere with efficient viral replication. Moreover, an insertion of viral sequences between the NS4A and NS4B genes was well tolerated. These findings thus led to the identification of two genomic loci which appear to be suited for the insertion of heterologous sequences into the genomes of pestiviruses and related viruses. PMID:16254361

Two bright fireballs over Great Britain

NASA Astrophysics Data System (ADS)

Koukal, Jakub; Káčerek, Richard

2018-02-01

On November 24, 2017 shortly before midnight and on November 25, 2017 shortly before sunrise, two very bright fireballs lit up the sky over the United Kingdom. The UKMON (United Kingdom Meteor Observation Network) cameras and onboard cameras in the automobiles recorded their flight. The fireballs paths in the Earth's atmosphere were calculated, as well as the orbits of bodies in the Solar System. The flight of both bodies, the absolute magnitude of which approached the brightness of the full Moon, was also observed by numerous random observers from the public in Great Britain, Ireland and France.

Sky brightness and twilight measurements at Jogyakarta city, Indonesia

NASA Astrophysics Data System (ADS)

Herdiwijaya, Dhani

2016-11-01

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

Extended Surface for Membrane Association in Zika Virus NS1 Structure

PubMed Central

Brown, W. Clay; Akey, David L.; Konwerski, Jamie; Tarrasch, Jeffrey T.; Skiniotis, Georgios; Kuhn, Richard J.; Smith, Janet L.

2018-01-01

The Zika virus, which is implicated in an increase in neonatal microcephaly and Guillain-Barré syndrome, has spread rapidly through tropical regions of the world. The virulence protein NS1 functions in genome replication and host immune system modulation. Here we report the crystal structure of full-length Zika virus NS1, revealing an elongated hydrophobic surface for membrane association and a polar surface that varies substantially among flaviviruses. PMID:27455458

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

NASA Astrophysics Data System (ADS)

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

2016-05-01

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

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

NASA Technical Reports Server (NTRS)

Morin, Bruce L.

2010-01-01

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

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

PubMed

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

2016-03-15

An Electrochemical Lateral Flow Immunosensor (ELFI) is developed combining screen-printed gold electrodes (SPGE) enabling quantification together with the convenience of a lateral flow test strip. A cellulose glassy fiber paper conjugate pad retains the marker immunoelectroactive nanobeads which will bind to the target analyte of interest. The specific immunorecognition event continues to occur along the lateral flow bed until reaching the SPGE-capture antibodies at the end of the cellulosic lateral flow strip. The rationale of the immunoassay consists in the analyte antigen NS1 protein being captured selectively and specifically by the dengue NS1 antibody conjugated onto the immunonanobeads thus forming an immunocomplex. With the aid of a running buffer, the immunocomplexes flow and reach the immuno-conjugated electrode surface and form specific sandwich-type detection due to specific, molecular recognition, while unbound beads move along past the electrodes. The successful sandwich immunocomplex formation is then recorded electrochemically. Specific detection of NS1 is translated into an electrochemical signal contributed by a redox label present on the bead-immobilized detection dengue NS1 antibody while a proportional increase of faradic current is observed with increase in analyte NS1 protein concentration. The first generation ELFI prototype is simply assembled in a cassette and successfully demonstrates wide linear range over a concentration range of 1-25 ng/mL with an ultrasensitive detection limit of 0.5 ng/mL for the qualitative and quantitative detection of analyte dengue NS1 protein. Copyright © 2015 Elsevier B.V. All rights reserved.

Molecular Docking Based Screening of Plant Flavonoids as Dengue NS1 Inhibitors

PubMed Central

Qamar, Muhammad Tahir ul; Mumtaz, Arooj; Naseem, Rabbia; Ali, Amna; Fatima, Tabeer; Jabbar, Tehreem; Ahmad, Zubair; Ashfaq, Usman Ali

2014-01-01

Dengue infection has turned into a serious health concern globally due to its high morbidity rate and a high possibility of increase in its mortality rate on the account of unavailability of any proper treatment for severe dengue infection. The situation demands an urgent development of efficient and practicable treatment to deal with Dengue virus (DENV). Flavonoids, a class of phytochemicals present in medicinal plants, possess anti-viral activity and can be strong drug candidates against viruses. NS1 glycoprotein of Dengue virus is involved in its RNA replication and can be a strong target for screening of drugs against this virus. Current study focuses on the identification of flavonoids which can block Asn-130 glycosylation site of Dengue virus NS1 to inhibit viral replication as glycosylation of NS1 is required for its biological functioning. Molecular docking approach was used in this study and the results revealed that flavonoids have strong potential interactions with active site of NS1. Six flavonoids (Deoxycalyxin A; 3,5,7,3',4'-pentahydroxyflavonol-3-O-beta-D-galactopyranoside; (3R)-3',8-Dihydroxyvestitol; Sanggenon O; Epigallocatechin gallate; Chamaejasmin) blocked the Asn-130 glycosylation site of NS1 and could be able to inhibit the viral replication. It can be concluded from this study that these flavonoids could serve as antiviral drugs for dengue infections. Further in-vitro analyses are required to confirm their efficacy and to evaluate their drug potency. PMID:25187688

Evaluation of an enzyme immunoassay for detection of dengue virus NS1 antigen in human serum.

PubMed

Dussart, Philippe; Labeau, Bhety; Lagathu, Gisèle; Louis, Philippe; Nunes, Marcio R T; Rodrigues, Sueli G; Storck-Herrmann, Cécile; Cesaire, Raymond; Morvan, Jacques; Flamand, Marie; Baril, Laurence

2006-11-01

We evaluated a one-step sandwich-format microplate enzyme immunoassay for detecting dengue virus NS1 antigen (Ag) in human serum by use of Platelia Dengue NS1 Ag kits (Bio-Rad Laboratories, Marnes La Coquette, France). We collected 299 serum samples from patients with dengue disease and 50 serum samples from patients not infected with dengue virus. For the 239 serum samples from patients with acute infections testing positive by reverse transcription-PCR and/or virus isolation for one of the four dengue virus serotypes, the sensitivity of the Platelia Dengue NS1 Ag kit was 88.7% (95% confidence interval, 84.0% to 92.4%). None of the serum samples from patients not infected with dengue virus tested positive with the Platelia Dengue NS1 Ag kit. A diagnostic strategy combining the Platelia Dengue NS1 Ag test for acute-phase sera and immunoglobulin M capture enzyme-linked immunosorbent assay for early-convalescent-phase sera increased sensitivity only from 88.7% to 91.9%. Thus, NS1 antigen detection with the Platelia Dengue NS1 Ag kit could be used for first-line testing for acute dengue virus infection in clinical diagnostic laboratories.

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

PubMed

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

2018-01-01

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

Recombinant dengue 2 virus NS3 protein conserves structural antigenic and immunological properties relevant for dengue vaccine design.

PubMed

Ramírez, Rosa; Falcón, Rosabel; Izquierdo, Alienys; García, Angélica; Alvarez, Mayling; Pérez, Ana Beatriz; Soto, Yudira; Muné, Mayra; da Silva, Emiliana Mandarano; Ortega, Oney; Mohana-Borges, Ronaldo; Guzmán, María G

2014-10-01

The NS3 protein is a multifunctional non-structural protein of flaviviruses implicated in the polyprotein processing. The predominance of cytotoxic T cell lymphocytes epitopes on the NS3 protein suggests a protective role of this protein in limiting virus replication. In this work, we studied the antigenicity and immunogenicity of a recombinant NS3 protein of the Dengue virus 2. The full-length NS3 gene was cloned and expressed as a His-tagged fusion protein in Escherichia coli. The pNS3 protein was purified by two chromatography steps. The recombinant NS3 protein was recognized by anti-protease NS3 polyclonal antibody and anti-DENV2 HMAF by Western Blot. This purified protein was able to stimulate the secretion of high levels of gamma interferon and low levels of interleukin-10 and tumor necrosis factor-α in mice splenocytes, suggesting a predominantly Th-1-type T cell response. Immunized BALB/c mice with the purified NS3 protein showed a strong induction of anti-NS3 IgG antibodies, essentially IgG2b, as determined by ELISA. Immunized mice sera with recombinant NS3 protein showed specific recognition of native dengue protein by Western blotting and immunofluorescence techniques. The successfully purified recombinant protein was able to preserv the structural and antigenic determinants of the native dengue protein. The antigenicity shown by the recombinant NS3 protein suggests its possible inclusion into future DENV vaccine preparations.

Species-Specific Inhibition of RIG-I Ubiquitination and IFN Induction by the Influenza A Virus NS1 Protein

PubMed Central

Rajsbaum, Ricardo; Albrecht, Randy A.; Wang, May K.; Maharaj, Natalya P.; Versteeg, Gijs A.; Nistal-Villán, Estanislao; García-Sastre, Adolfo; Gack, Michaela U.

2012-01-01

Influenza A viruses can adapt to new host species, leading to the emergence of novel pathogenic strains. There is evidence that highly pathogenic viruses encode for non-structural 1 (NS1) proteins that are more efficient in suppressing the host immune response. The NS1 protein inhibits type-I interferon (IFN) production partly by blocking the TRIM25 ubiquitin E3 ligase-mediated Lys63-linked ubiquitination of the viral RNA sensor RIG-I, required for its optimal downstream signaling. In order to understand possible mechanisms of viral adaptation and host tropism, we examined the ability of NS1 encoded by human (Cal04), avian (HK156), swine (SwTx98) and mouse-adapted (PR8) influenza viruses to interact with TRIM25 orthologues from mammalian and avian species. Using co-immunoprecipitation assays we show that human TRIM25 binds to all tested NS1 proteins, whereas the chicken TRIM25 ortholog binds preferentially to the NS1 from the avian virus. Strikingly, none of the NS1 proteins were able to bind mouse TRIM25. Since NS1 can inhibit IFN production in mouse, we tested the impact of TRIM25 and NS1 on RIG-I ubiquitination in mouse cells. While NS1 efficiently suppressed human TRIM25-dependent ubiquitination of RIG-I 2CARD, NS1 inhibited the ubiquitination of full-length mouse RIG-I in a mouse TRIM25-independent manner. Therefore, we tested if the ubiquitin E3 ligase Riplet, which has also been shown to ubiquitinate RIG-I, interacts with NS1. We found that NS1 binds mouse Riplet and inhibits its activity to induce IFN-β in murine cells. Furthermore, NS1 proteins of human but not swine or avian viruses were able to interact with human Riplet, thereby suppressing RIG-I ubiquitination. In conclusion, our results indicate that influenza NS1 protein targets TRIM25 and Riplet ubiquitin E3 ligases in a species-specific manner for the inhibition of RIG-I ubiquitination and antiviral IFN production. PMID:23209422

Species-specific inhibition of RIG-I ubiquitination and IFN induction by the influenza A virus NS1 protein.

PubMed

Rajsbaum, Ricardo; Albrecht, Randy A; Wang, May K; Maharaj, Natalya P; Versteeg, Gijs A; Nistal-Villán, Estanislao; García-Sastre, Adolfo; Gack, Michaela U

2012-01-01

Influenza A viruses can adapt to new host species, leading to the emergence of novel pathogenic strains. There is evidence that highly pathogenic viruses encode for non-structural 1 (NS1) proteins that are more efficient in suppressing the host immune response. The NS1 protein inhibits type-I interferon (IFN) production partly by blocking the TRIM25 ubiquitin E3 ligase-mediated Lys63-linked ubiquitination of the viral RNA sensor RIG-I, required for its optimal downstream signaling. In order to understand possible mechanisms of viral adaptation and host tropism, we examined the ability of NS1 encoded by human (Cal04), avian (HK156), swine (SwTx98) and mouse-adapted (PR8) influenza viruses to interact with TRIM25 orthologues from mammalian and avian species. Using co-immunoprecipitation assays we show that human TRIM25 binds to all tested NS1 proteins, whereas the chicken TRIM25 ortholog binds preferentially to the NS1 from the avian virus. Strikingly, none of the NS1 proteins were able to bind mouse TRIM25. Since NS1 can inhibit IFN production in mouse, we tested the impact of TRIM25 and NS1 on RIG-I ubiquitination in mouse cells. While NS1 efficiently suppressed human TRIM25-dependent ubiquitination of RIG-I 2CARD, NS1 inhibited the ubiquitination of full-length mouse RIG-I in a mouse TRIM25-independent manner. Therefore, we tested if the ubiquitin E3 ligase Riplet, which has also been shown to ubiquitinate RIG-I, interacts with NS1. We found that NS1 binds mouse Riplet and inhibits its activity to induce IFN-β in murine cells. Furthermore, NS1 proteins of human but not swine or avian viruses were able to interact with human Riplet, thereby suppressing RIG-I ubiquitination. In conclusion, our results indicate that influenza NS1 protein targets TRIM25 and Riplet ubiquitin E3 ligases in a species-specific manner for the inhibition of RIG-I ubiquitination and antiviral IFN production.

Effects of nanosecond pulsed electrical fields (nsPEFs) on the cell cycle of CHO and Jurkat cells

NASA Astrophysics Data System (ADS)

Mahlke, Megan A.; Navara, Christopher; Ibey, Bennett L.

2014-03-01

Exposure to nano-second pulsed electrical fields (nsPEFs) can cause poration of external and internal cell membranes, DNA damage, and disassociation of cytoskeletal components, all of which are capable of disrupting a cell's ability to replicate. Variations between cell lines in membrane and cytoskeletal structure as well as in survival of nsPEF exposure should correspond to unique line-dependent cell cycle effects. Additionally, phase of cell cycle during exposure may be linked to differential sensitivities to nsPEFs across cell lines, as DNA structure, membrane elasticity, and cytoskeletal structure change dramatically during the cell cycle. Populations of Jurkat and Chinese Hamster Ovary (CHO) cells were examined post-exposure (10 ns pulse trains at 150kV/cm) by analysis of DNA content via propidium iodide staining and flow cytometric analysis at various time points (1, 6, and 12h post-exposure) to determine population distribution in cell cycle phases. Additionally, CHO and Jurkat cells were synchronized in G1/S and G2/M phases, pulsed, and analyzed to evaluate role of cell cycle phase in survival of nsPEFs. CHO populations recovered similarly to sham populations postnsPEF exposure and did not exhibit a phase-specific change in response. Jurkat cells exhibited considerable apoptosis/necrosis in response to nsPEF exposure and were unable to recover and proliferate in a manner similar to sham exposed cells. Additionally, Jurkat cells appear to be more sensitive to nsPEFs in G2/M phases than in G1/S phases. Recovery of CHO populations suggests that nsPEFs do not inhibit proliferation in CHO cells; however, inhibition of Jurkat cells post-nsPEF exposure coupled with preferential cell death in G2/M phases suggest that cell cycle phase during exposure may be an important factor in determining nsPEF toxicity in certain cell lines. Interestingly, CHO cells have a more robust and rigid cytoskeleton than Jurkat cells which is thought to contribute to their ability to

Structure and function of Zika virus NS5 protein: perspectives for drug design.

PubMed

Wang, Boxiao; Thurmond, Stephanie; Hai, Rong; Song, Jikui

2018-05-01

Zika virus (ZIKV) belongs to the positive-sense single-stranded RNA-containing Flaviviridae family. Its recent outbreak and association with human diseases (e.g. neurological disorders) have raised global health concerns, and an urgency to develop a therapeutic strategy against ZIKV infection. However, there is no currently approved antiviral against ZIKV. Here we present a comprehensive overview on recent progress in structure-function investigation of ZIKV NS5 protein, the largest non-structural protein of ZIKV, which is responsible for replication of the viral genome, RNA capping and suppression of host interferon responses. Structural comparison of the N-terminal methyltransferase domain and C-terminal RNA-dependent RNA polymerase domain of ZIKV NS5 with their counterparts from related viruses provides mechanistic insights into ZIKV NS5-mediated RNA replication, and identifies residues critical for its enzymatic activities. Finally, a collection of recently identified small molecule inhibitors against ZIKV NS5 or its closely related flavivirus homologues are also discussed.

Recombinant Dengue 2 Virus NS3 Helicase Protein Enhances Antibody and T-Cell Response of Purified Inactivated Vaccine

PubMed Central

Simmons, Monika; Sun, Peifang; Putnak, Robert

2016-01-01

Dengue virus purified inactivated vaccines (PIV) are highly immunogenic and protective over the short term, but may be poor at inducing cell-mediated immune responses and long-term protection. The dengue nonstructural protein 3 (NS3) is considered the main target for T-cell responses during viral infection. The amino (N)-terminal protease and the carboxy (C)-terminal helicase domains of DENV-2 NS3 were expressed in E. coli and analyzed for their immune-potentiating capacity. Mice were immunized with DENV-2 PIV with and without recombinant NS3 protease or NS3 helicase proteins, and NS3 proteins alone on days 0, 14 and 28. The NS3 helicase but not the NS3 protease was effective in inducing T-cell responses quantified by IFN-γ ELISPOT. In addition, markedly increased total IgG antibody titer against virus antigen was seen in mice immunized with the PIV/NS3 helicase combination in the ELISA, as well as increased neutralizing antibody titer measured by the plaque reduction neutralization test. These results indicate the potential immunogenic properties of the NS3 helicase protein and its use in a dengue vaccine formulation. PMID:27035715

Chaperone-Assisted Protein Folding Is Critical for Yellow Fever Virus NS3/4A Cleavage and Replication.

PubMed

Bozzacco, Leonia; Yi, Zhigang; Andreo, Ursula; Conklin, Claire R; Li, Melody M H; Rice, Charles M; MacDonald, Margaret R

2016-01-06

DNAJC14, a heat shock protein 40 (Hsp40) cochaperone, assists with Hsp70-mediated protein folding. Overexpressed DNAJC14 is targeted to sites of yellow fever virus (YFV) replication complex (RC) formation, where it interacts with viral nonstructural (NS) proteins and inhibits viral RNA replication. How RCs are assembled and the roles of chaperones in this coordinated process are largely unknown. We hypothesized that chaperones are diverted from their normal cellular protein quality control function to play similar roles during viral infection. Here, we show that DNAJC14 overexpression affects YFV polyprotein processing and alters RC assembly. We monitored YFV NS2A-5 polyprotein processing by the viral NS2B-3 protease in DNAJC14-overexpressing cells. Notably, DNAJC14 mutants that did not inhibit YFV replication had minimal effects on polyprotein processing, while overexpressed wild-type DNAJC14 affected the NS3/4A and NS4A/2K cleavage sites, resulting in altered NS3-to-NS3-4A ratios. This suggests that DNAJC14's folding activity normally modulates NS3/4A/2K cleavage events to liberate appropriate levels of NS3 and NS4A and promote RC formation. We introduced amino acid substitutions at the NS3/4A site to alter the levels of the NS3 and NS4A products and examined their effects on YFV replication. Residues with reduced cleavage efficiency did not support viral RNA replication, and only revertant viruses with a restored wild-type arginine or lysine residue at the NS3/4A site were obtained. We conclude that DNAJC14 inhibition of RC formation upon DNAJC14 overexpression is likely due to chaperone dysregulation and that YFV probably utilizes DNAJC14's cochaperone function to modulate processing at the NS3/4A site as a mechanism ensuring virus replication. Flaviviruses are single-stranded RNA viruses that cause a wide range of illnesses. Upon host cell entry, the viral genome is translated on endoplasmic reticulum (ER) membranes to produce a single polyprotein, which is

Chaperone-Assisted Protein Folding Is Critical for Yellow Fever Virus NS3/4A Cleavage and Replication

PubMed Central

Bozzacco, Leonia; Yi, Zhigang; Andreo, Ursula; Conklin, Claire R.; Li, Melody M. H.; Rice, Charles M.

2016-01-01

ABSTRACT DNAJC14, a heat shock protein 40 (Hsp40) cochaperone, assists with Hsp70-mediated protein folding. Overexpressed DNAJC14 is targeted to sites of yellow fever virus (YFV) replication complex (RC) formation, where it interacts with viral nonstructural (NS) proteins and inhibits viral RNA replication. How RCs are assembled and the roles of chaperones in this coordinated process are largely unknown. We hypothesized that chaperones are diverted from their normal cellular protein quality control function to play similar roles during viral infection. Here, we show that DNAJC14 overexpression affects YFV polyprotein processing and alters RC assembly. We monitored YFV NS2A-5 polyprotein processing by the viral NS2B-3 protease in DNAJC14-overexpressing cells. Notably, DNAJC14 mutants that did not inhibit YFV replication had minimal effects on polyprotein processing, while overexpressed wild-type DNAJC14 affected the NS3/4A and NS4A/2K cleavage sites, resulting in altered NS3-to-NS3-4A ratios. This suggests that DNAJC14's folding activity normally modulates NS3/4A/2K cleavage events to liberate appropriate levels of NS3 and NS4A and promote RC formation. We introduced amino acid substitutions at the NS3/4A site to alter the levels of the NS3 and NS4A products and examined their effects on YFV replication. Residues with reduced cleavage efficiency did not support viral RNA replication, and only revertant viruses with a restored wild-type arginine or lysine residue at the NS3/4A site were obtained. We conclude that DNAJC14 inhibition of RC formation upon DNAJC14 overexpression is likely due to chaperone dysregulation and that YFV probably utilizes DNAJC14's cochaperone function to modulate processing at the NS3/4A site as a mechanism ensuring virus replication. IMPORTANCE Flaviviruses are single-stranded RNA viruses that cause a wide range of illnesses. Upon host cell entry, the viral genome is translated on endoplasmic reticulum (ER) membranes to produce a single

A New Sky Brightness Monitor

NASA Astrophysics Data System (ADS)

Crawford, David L.; McKenna, D.

2006-12-01

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

Normal dimensions of the posterior pituitary bright spot on magnetic resonance imaging.

PubMed

Côté, Martin; Salzman, Karen L; Sorour, Mohammad; Couldwell, William T

2014-02-01

The normal pituitary bright spot seen on unenhanced T1-weighted MRI is thought to result from the T1-shortening effect of the vasopressin stored in the posterior pituitary. Individual variations in its size may be difficult to differentiate from pathological conditions resulting in either absence of the pituitary bright spot or in T1-hyperintense lesions of the sella. The objective of this paper was to define a range of normal dimensions of the pituitary bright spot and to illustrate some of the most commonly encountered pathologies that result in absence or enlargement of the pituitary bright spot. The authors selected normal pituitary MRI studies from 106 patients with no pituitary abnormality. The size of each pituitary bright spot was measured in the longest axis and in the dimension perpendicular to this axis to describe the typical dimensions. The authors also present cases of patients with pituitary abnormalities to highlight the differences and potential overlap between normal and pathological pituitary imaging. All of the studies evaluated were found to have pituitary bright spots, and the mean dimensions were 4.8 mm in the long axis and 2.4 mm in the short axis. The dimension of the pituitary bright spot in the long axis decreased with patient age. The distribution of dimensions of the pituitary bright spot was normal, indicating that 99.7% of patients should have a pituitary bright spot measuring between 1.2 and 8.5 mm in its long axis and between 0.4 and 4.4 mm in its short axis, an interval corresponding to 3 standard deviations below and above the mean. In cases where the dimension of the pituitary bright spot is outside this range, pathological conditions should be considered. The pituitary bright spot should always be demonstrated on T1-weighted MRI, and its dimensions should be within the identified normal range in most patients. Outside of this range, pathological conditions affecting the pituitary bright spot should be considered.

18F-labeled norepinephrine transporter tracer [18F]NS12137: radiosynthesis and preclinical evaluation.

PubMed

Kirjavainen, Anna K; Forsback, Sarita; López-Picón, Francisco R; Marjamäki, Päivi; Takkinen, Jatta; Haaparanta-Solin, Merja; Peters, Dan; Solin, Olof

2018-01-01

Several psychiatric and neurodegenerative diseases are associated with malfunction of brain norepinephrine transporter (NET). However, current clinical evaluations of NET function are limited by the lack of sufficiently sensitive methods of detection. To this end, we have synthesized exo-3-[(6-[ 18 F]fluoro-2-pyridyl)oxy]-8-azabicyclo[3.2.1]-octane ([ 18 F]NS12137) as a radiotracer for positron emission tomography (PET) and have demonstrated that it is highly specific for in vivo detection of NET-rich regions of rat brain tissue. We applied two methods of electrophilic, aromatic radiofluorination of the precursor molecule, exo-3-[(6-trimethylstannyl-2-pyridyl)oxy]-8-azabicyclo-[3.2.1]octane-8-carboxylate: (1) direct labeling with [ 18 F]F 2 , and (2) labeling with [ 18 F]Selectfluor, a derivative of [ 18 F]F 2 , using post-target produced [ 18 F]F 2 . The time-dependent distribution of [ 18 F]NS12137 in brain tissue of healthy, adult Sprague-Dawley rats was determined by ex vivo autoradiography. The specificity of [ 18 F]NS12137 binding was demonstrated on the basis of competitive binding by nisoxetine, a known NET antagonist of high specificity. [ 18 F]NS12137 was successfully synthesized with radiochemical yields of 3.9% ± 0.3% when labeled with [ 18 F]F 2 and 10.2% ± 2.7% when labeled with [ 18 F]Selectfluor. The molar activity of radiotracer was 8.8 ± 0.7 GBq/μmol with [ 18 F]F 2 labeling and 6.9 ± 0.4 GBq/μmol with [ 18 F]Selectfluor labeling at the end of synthesis of [ 18 F]NS12137. Uptake of [ 18 F]NS12137 in NET-rich areas in rat brain was demonstrated with the locus coeruleus (LCoe) having the highest regional uptake. Prior treatment of rats with nisoxetine showed no detectable [ 18 F]NS12137 in the LCoe. Analyses of whole brain samples for radiometabolites showed only the parent compound [ 18 F]NS12137. Uptake of 18 F-radioactivity in bone increased with time. The two electrophilic 18 F-labeling methods proved to be suitable for synthesis of [ 18 F]NS

CHD3 facilitates vRNP nuclear export by interacting with NES1 of influenza A virus NS2.

PubMed

Hu, Yong; Liu, Xiaokun; Zhang, Anding; Zhou, Hongbo; Liu, Ziduo; Chen, Huanchun; Jin, Meilin

2015-03-01

NS2 from influenza A virus mediates Crm1-dependent vRNP nuclear export through interaction with Crm1. However, even though the nuclear export signal 1 (NES1) of NS2 does not play a requisite role in NS2-Crm1 interaction, there is no doubt that NES1 is crucial for vRNP nuclear export. While the mechanism of the NES1 is still unclear, it is speculated that certain host partners might mediate the NES1 function through their interaction with NES1. In the present study, chromodomain-helicase-DNA-binding protein 3 (CHD3) was identified as a novel host nuclear protein for locating NS2 and Crm1 on dense chromatin for NS2 and Crm1-dependent vRNP nuclear export. CHD3 was confirmed to interact with NES1 in NS2, and a disruption to this interaction by mutation in NES1 significantly delayed viral vRNPs export and viral propagation. Further, the knockdown of CHD3 would affect the propagation of the wild-type virus but not the mutant with the weakened NS2-CHD3 interaction. Therefore, this study demonstrates that NES1 is required for maximal binding of NS2 to CHD3, and that the NS2-CHD3 interaction on the dense chromatin contributed to the NS2-mediated vRNP nuclear export.

Mutation of Putative N-Glycosylation Sites on Dengue Virus NS4B Decreases RNA Replication.

PubMed

Naik, Nenavath Gopal; Wu, Huey-Nan

2015-07-01

Dengue virus (DENV) nonstructural protein 4B (NS4B) is an endoplasmic reticulum (ER) membrane-associated protein, and mutagenesis studies have revealed its significance in viral genome replication. In this work, we demonstrated that NS4B is an N-glycosylated protein in virus-infected cells as well as in recombinant protein expression. NS4B is N glycosylated at residues 58 and 62 and exists in two forms, glycosylated and unglycosylated. We manipulated full-length infectious RNA clones and subgenomic replicons to generate N58Q, N62Q, and N58QN62Q mutants. Each of the single mutants had distinct effects, but the N58QN62Q mutation resulted in dramatic reduction of viral production efficiency without affecting secretion or infectivity of the virion in mammalian and mosquito C6/36 hosts. Real-time quantitative PCR (qPCR), subgenomic replicon, and trans-complementation assays indicated that the N58QN62Q mutation affected RNA replication possibly by the loss of glycans. In addition, four intragenic mutations (S59Y, S59F, T66A, and A137T) were obtained from mammalian and/or mosquito C6/36 cell culture systems. All of these second-site mutations compensated for the replication defect of the N58QN62Q mutant without creating novel glycosylation sites. In vivo protein stability analyses revealed that the N58QN62Q mutation alone or plus a compensatory mutation did not affect the stability of NS4B. Overall, our findings indicated that mutation of putative N-glycosylation sites affected the biological function of NS4B in the viral replication complex. This is the first report to identify and reveal the biological significance of dengue virus (DENV) nonstructural protein 4B (NS4B) posttranslation N-glycosylation to the virus life cycle. The study demonstrated that NS4B is N glycosylated in virus-infected cells and in recombinant protein expression. NS4B is modified by glycans at Asn-58 and Asn-62. Functional characterization implied that DENV NS4B utilizes the glycosylation

Brightness field distributions of microlens arrays using micro molding.

PubMed

Cheng, Hsin-Chung; Huang, Chiung-Fang; Lin, Yi; Shen, Yung-Kang

2010-12-20

This study describes the brightness field distributions of microlens arrays fabricated by micro injection molding (μIM) and micro injection-compression molding (μICM). The process for fabricating microlens arrays used room-temperature imprint lithography, photoresist reflow, electroforming, μIM, μICM, and optical properties measurement. Analytical results indicate that the brightness field distribution of the molded microlens arrays generated by μICM is better than those made using μIM. Our results further demonstrate that mold temperature is the most important processing parameter for brightness field distribution of molded microlens arrays made by μIM or μICM.

StarBright Learning Exchange

ERIC Educational Resources Information Center

Kalinowski, Michael

2007-01-01

This article features StarBright Learning Exchange, a program that provides a cross-cultural exchange between Australian and South African early childhood educators. The program was originated when its president, Carol Allen, and her colleague, Karen Williams, decided that they could no longer sit by and watch the unfolding social catastrophe that…

High Brightness OLED Lighting

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

Spindler, Jeffrey; Kondakova, Marina; Boroson, Michael

2016-05-25

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

3D-QSAR pharmacophore-based virtual screening, molecular docking and molecular dynamics simulation toward identifying lead compounds for NS2B-NS3 protease inhibitors.

PubMed

Luo, Pei H; Zhang, Xuan R; Huang, Lan; Yuan, Lun; Zhou, Xang Z; Gao, X; Li, Ling S

2017-10-01

NS2B-NS3 protease has been identified to serve as lead drug design target due to its significant role in West Nile viral (WNV) and dengue virus (DENV) reproduction and replication. There are currently no approved chemotherapeutic drugs and effective vaccines to inhibit DENV and WNV infections. In this work, 3D-QSAR pharmacophore model has been developed to discover potential inhibitory candidates. Validation through Fischer's model and decoy test indicate that the developed 3D pharmacophore model is highly predictive for DENV inhibitors, which was then employed to screen ZINC chemical library to obtain reasonable hits. Following ADMET filtering, 15 hits were subjected to further filter through molecular docking and CoMFA modeling. Finally, top three hits were identified as lead compounds or potential inhibitory candidates with IC 50 values of ∼0.4637 µM and fitness of ∼57.73. It is implied from CoMFA modeling that substituents at the side site of benzotriazole such as a p-nitro group (e.g. biphenyl head) and a carbonyl (e.g. carboxylate function) at the side site of furan or amino group may improve bioactivity of ZINC85645245, respectively. Molecular dynamics simulations (MDS) were performed to discover new interactions and reinforce the binding modes from docking for the hits also. The QSAR and MDS results obtained from this work should be useful in determining structural requirements for inhibitor development as well as in designing more potential inhibitors for NS2B-NS3 protease.

The universal and automatic association between brightness and positivity.

PubMed

Specker, Eva; Leder, Helmut; Rosenberg, Raphael; Hegelmaier, Lisa Mira; Brinkmann, Hanna; Mikuni, Jan; Kawabata, Hideaki

2018-05-01

The present study investigates the hypothesis that brightness of colors is associated with positivity, postulating that this is an automatic and universal effect. The Implicit Association Test (IAT; Greenwald, McGhee, & Schwartz, 1998) was used in all studies. Study 1 used color patches varying on brightness, Study 2 used achromatic stimuli to eliminate the potential confounding effects of hue and saturation. Study 3 replicated Study 2 in a different cultural context (Japan vs. Austria), both studies also included a measure of explicit association. All studies confirmed the hypothesis that brightness is associated with positivity, at a significance level of p < .001 and Cohen's D varying from 0.90 to 3.99. Study 1-3 provided support for the notion that this is an automatic effect. Additionally, Study 2 and Study 3 showed that people also have an explicit association of brightness with positivity. However, as expected, our results also show that the implicit association was stronger than the explicit association. Study 3 shows clear support for the universality of our effects. In sum, our results support the idea that brightness is associated with positivity and that these associations are automatic and universal. Copyright © 2018 Elsevier B.V. All rights reserved.

Alternate SlyA and H-NS nucleoprotein complexes control hlyE expression in Escherichia coli K-12

PubMed Central

Lithgow, James K; Haider, Fouzia; Roberts, Ian S; Green, Jeffrey

2007-01-01

Haemolysin E is a cytolytic pore-forming toxin found in several Escherichia coli and Salmonella enterica strains. Expression of hlyE is repressed by the global regulator H-NS (histone-like nucleoid structuring protein), but can be activated by the regulator SlyA. Expression of a chromosomal hlyE–lacZ fusion in an E. coli slyA mutant was reduced to 60% of the wild-type level confirming a positive role for SlyA. DNase I footprint analysis revealed the presence of two separate SlyA binding sites, one located upstream, the other downstream of the hlyE transcriptional start site. These sites overlap AT-rich H-NS binding sites. Footprint and gel shift data showed that whereas H-NS prevented binding of RNA polymerase (RNAP) at the hlyE promoter (PhlyE), SlyA allowed binding of RNAP, but inhibited binding of H-NS. Accordingly, in vitro transcription analyses showed that addition of SlyA protein relieved H-NS-mediated repression of hlyE. Based on these observations a model for SlyA/H-NS regulation of hlyE expression is proposed in which the relative concentrations of SlyA and H-NS govern the nature of the nucleoprotein complexes formed at PhlyE. When H-NS is dominant RNAP binding is inhibited and hlyE expression is silenced; when SlyA is dominant H-NS binding is inhibited allowing RNAP access to the promoter facilitating hlyE transcription. PMID:17892462

Hippocampal A-type current and Kv4.2 channel modulation by the sulfonylurea compound NS5806.

PubMed

Witzel, Katrin; Fischer, Paul; Bähring, Robert

2012-12-01

We examined the effects of the sulfonylurea compound NS5806 on neuronal A-type channel function. Using whole-cell patch-clamp we studied the effects of NS5806 on the somatodendritic A-type current (I(SA)) in cultured hippocampal neurons and the currents mediated by Kv4.2 channels coexpressed with different auxiliary β-subunits, including both Kv channel interacting proteins (KChIPs) and dipeptidyl aminopeptidase-related proteins (DPPs), in HEK 293 cells. The amplitude of the I(SA) component in hippocampal neurons was reduced in the presence of 20 μM NS5806. I(SA) decay kinetics were slowed and the recovery kinetics accelerated, but the voltage dependence of steady-state inactivation was shifted to more negative potentials by NS5806. The peak amplitudes of currents mediated by ternary Kv4.2 channel complexes, associated with DPP6-S (short splice-variant) and either KChIP2, KChIP3 or KChIP4, were potentiated and their macroscopic inactivation slowed by NS5806, whereas the currents mediated by binary Kv4.2 channels, associated only with DPP6-S, were suppressed, and the NS5806-mediated slowing of macroscopic inactivation was less pronounced. Neither potentiation nor suppression and no effect on current decay kinetics in the presence of NS5806 were observed for Kv4.2 channels associated with KChIP3 and the N-type inactivation-conferring DPP6a splice-variant. For all recombinant channel complexes, NS5806 slowed the recovery from inactivation and shifted the voltage dependence of steady-state inactivation to more negative potentials. Our results demonstrate the activity of NS5806 on native I(SA) and possible molecular correlates in the form of recombinant Kv4.2 channels complexed with different KChIPs and DPPs, and they shed some light on the mechanism of NS5806 action. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

PubMed

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

2014-10-01

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

Process Performances of 2 ns Pulsed Discharge Plasma

NASA Astrophysics Data System (ADS)

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

2011-08-01

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

Plasma Membrane Permeabilization by 60- and 600-ns Electric Pulses Is Determined by the Absorbed Dose

PubMed Central

Ibey, Bennett L.; Xiao, Shu; Schoenbach, Karl H.; Murphy, Michael R.; Pakhomov, Andrei G.

2008-01-01

We explored how the effect of plasma membrane permeabilization by nanosecond-duration electric pulses (nsEP) depends on the physical characteristics of exposure. The resting membrane resistance (Rm) and membrane potential (MP) were measured in cultured GH3 and CHO cells by conventional whole-cell patch-clamp technique. Intact cells were exposed to a single nsEP (60 or 600 ns duration, 0-22 kV/cm), followed by patch-clamp measurements after a 2-3 min delay. Consistent with earlier findings, nsEP caused long-lasting Rm decrease, accompanied by the loss of MP. The threshold for these effects was about 6 kV/cm for 60 ns pulses, and about 1 kV/cm for 600 ns pulses. Further analysis established that it was neither pulse duration nor the E-field amplitude per se, but the absorbed dose that determined the magnitude of the biological effect. In other words, exposure to nsEP at either pulse duration caused equal effects if the absorbed doses were equal. The threshold absorbed dose to produce plasma membrane effects in either GH3 or CHO cells at either pulse duration was found to be at or below 10 mJ/g. Despite being determined by the dose, the nsEP effect clearly is not thermal, as the maximum heating at the threshold dose is less than 0.01 °C. The use of the absorbed dose as a universal exposure metric may help to compare and quantify nsEP sensitivity of different cell types and of cells in different physiological conditions. The absorbed dose may also prove to be a more useful metric than the incident E-field in determining safety limits for high peak, lowaverage power EMF emissions. PMID:18839412

X-ray structure of NS1 from a highly pathogenic H5N1 influenza virus

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

Bornholdt, Zachary A.; Prasad, B.V. Venkataram

2009-04-08

The recent emergence of highly pathogenic avian (H5N1) influenza viruses, their epizootic and panzootic nature, and their association with lethal human infections have raised significant global health concerns. Several studies have underlined the importance of non-structural protein NS1 in the increased pathogenicity and virulence of these strains. NS1, which consists of two domains - a double-stranded RNA (dsRNA) binding domain and the effector domain, separated through a linker - is an antagonist of antiviral type-I interferon response in the host. Here we report the X-ray structure of the full-length NS1 from an H5N1 strain (A/Vietnam/1203/2004) that was associated with 60%more » of human deaths in an outbreak in Vietnam. Compared to the individually determined structures of the RNA binding domain and the effector domain from non-H5N1 strains, the RNA binding domain within H5N1 NS1 exhibits modest structural changes, while the H5N1 effector domain shows significant alteration, particularly in the dimeric interface. Although both domains in the full-length NS1 individually participate in dimeric interactions, an unexpected finding is that these interactions result in the formation of a chain of NS1 molecules instead of distinct dimeric units. Three such chains in the crystal interact with one another extensively to form a tubular organization of similar dimensions to that observed in the cryo-electron microscopy images of NS1 in the presence of dsRNA. The tubular oligomeric organization of NS1, in which residues implicated in dsRNA binding face a 20-{angstrom}-wide central tunnel, provides a plausible mechanism for how NS1 sequesters varying lengths of dsRNA, to counter cellular antiviral dsRNA response pathways, while simultaneously interacting with other cellular ligands during an infection.« less

Lactobacillus fermentum NS9 restores the antibiotic induced physiological and psychological abnormalities in rats.

PubMed

Wang, T; Hu, X; Liang, S; Li, W; Wu, X; Wang, L; Jin, F

2015-01-01

Gut microbiota play a vital role in maintaining the health of the host. Many factors affect gut microbiota; application of broad range antibiotics disturb microbiota, while probiotic application protects the microbiota. To investigate how probiotics alter the physiological and psychological changes induced by antibiotics, we tested the performance of ampicillin-treated rats in the presence or absence of Lactobacillus fermentum strain NS9, in elevated plus maze and Morris water maze. The results showed that NS9 normalised the composition of gut microbiota and alleviated the ampicillin-induced inflammation in the colon. The levels of the mineralocorticoid and N-methyl-D-aspartate receptors were also elevated in the hippocampus of the ampillicin+NS9 treated group. NS9 administration also reduced the anxiety-like behaviour and alleviated the ampicillin-induced impairment in memory retention. These findings suggest that NS9 is beneficial to the host, because it restores the physiological and psychological abnormalities induced by ampicillin. Our results highlight how gut contents regulate the brain, and shed light on the clinical applications of probiotics to treat the side effect of antibiotics and mental disorders.

Quantum noise in bright soliton matterwave interferometry

NASA Astrophysics Data System (ADS)

Haine, Simon A.

2018-03-01

There has been considerable recent interest in matterwave interferometry with bright solitons in quantum gases with attractive interactions, for applications such as rotation sensing. We model the quantum dynamics of these systems and find that the attractive interactions required for the presence of bright solitons causes quantum phase-diffusion, which severely impairs the sensitivity. We propose a scheme that partially restores the sensitivity, but find that in the case of rotation sensing, it is still better to work in a regime with minimal interactions if possible.

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

NASA Astrophysics Data System (ADS)

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

2018-03-01

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

Producing human ceramide-NS by metabolic engineering using yeast Saccharomyces cerevisiae.

PubMed

Murakami, Suguru; Shimamoto, Toshi; Nagano, Hideaki; Tsuruno, Masahiro; Okuhara, Hiroaki; Hatanaka, Haruyo; Tojo, Hiromasa; Kodama, Yukiko; Funato, Kouichi

2015-11-17

Ceramide is one of the most important intercellular components responsible for the barrier and moisture retention functions of the skin. Because of the risks involved with using products of animal origin and the low productivity of plants, the availability of ceramides is currently limited. In this study, we successfully developed a system that produces sphingosine-containing human ceramide-NS in the yeast Saccharomyces cerevisiae by eliminating the genes for yeast sphingolipid hydroxylases (encoded by SUR2 and SCS7) and introducing the gene for a human sphingolipid desaturase (encoded by DES1). The inactivation of the ceramidase gene YDC1, overexpression of the inositol phosphosphingolipid phospholipase C gene ISC1, and endoplasmic reticulum localization of the DES1 gene product resulted in enhanced production of ceramide-NS. The engineered yeast strains can serve as hosts not only for providing a sustainable source of ceramide-NS but also for developing further systems to produce sphingosine-containing sphingolipids.

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

PubMed

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

2018-01-08

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

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

PubMed Central

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

2018-01-01

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

The impact of bottom brightness on spectral reflectance of suspended sediments

USGS Publications Warehouse

Tolk, Brian L.; Han, L.; Rundquist, D. C.

2000-01-01

Two experiments were conducted outdoors to investigate how bottom brightness impacts the spectral response of a water column under varied suspended sediment concentrations. A white aluminum panel placed at the bottom of the tank was used as the bright bottom, and a flat-black tank liner served as the dark bottom. Sixteen levels of suspended sediment from 25 to 400 mg litre -1 were used in each experiment. Spectral data were collected using a Spectron SE-590 spectroradiometer. The major findings include the following: the bright bottom had the greatest impact at visible wavelengths; when suspended sediment concentrations exceeded 100 mg litre -1, the bright bottom response was found to be negligible; and, substrate brightness has minimal impact between 740 and 900 nm, suggesting that these wavelengths are best for measuring suspended sediment concentrations by means of remote sensing.

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

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

Saw, Wuan Geok; Tria, Giancarlo; Grüber, Ardina

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

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

PubMed Central

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

2015-01-01

Infection by the four serotypes of Dengue virus (DENV-1 to DENV-4) causes an important arthropod-borne viral disease in humans. The multifunctional DENV nonstructural protein 5 (NS5) is essential for capping and replication of the viral RNA and harbours a methyltransferase (MTase) domain and an RNA-dependent RNA polymerase (RdRp) domain. In this study, insights into the overall structure and flexibility of the entire NS5 of all four Dengue virus serotypes in solution are presented for the first time. The solution models derived revealed an arrangement of the full-length NS5 (NS5FL) proteins with the MTase domain positioned at the top of the RdRP domain. The DENV-1 to DENV-4 NS5 forms are elongated and flexible in solution, with DENV-4 NS5 being more compact relative to NS5 from DENV-1, DENV-2 and DENV-3. Solution studies of the individual MTase and RdRp domains show the compactness of the RdRp domain as well as the contribution of the MTase domain and the ten-residue linker region to the flexibility of the entire NS5. Swapping the ten-residue linker between DENV-4 NS5FL and DENV-3 NS5FL demonstrated its importance in MTase–RdRp communication and in concerted interaction with viral and host proteins, as probed by amide hydrogen/deuterium mass spectrometry. Conformational alterations owing to RNA binding are presented. PMID:26527147

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

PubMed

Crowley, Stephanie J; Eastman, Charmane I

2015-02-01

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

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

PubMed Central

Crowley, Stephanie J.; Eastman, Charmane I.

2015-01-01

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

Characterization and evaluation of apoptotic potential of double gene construct pVIVO.VP3.NS1.

PubMed

Saxena, Shikha; Desai, G S; Kumar, G Ravi; Sahoo, A P; Santra, Lakshman; Singh, Lakshya Veer

2015-05-01

Viral gene oncotherapy, targeted killing of cancer cells by viral genes, is an emerging non-infectious therapeutic cancer treatment modality. Chemo and radiotherapy in cancer treatment is limited due to their genotoxic side effects on healthy cells and need of functional p53, which is mutated in most of the cancers. VP3 (apoptin) of chicken infectious anaemia (CIA) and NS1 (Non structural protein 1) of Canine Parvovirus-2 (CPV-2) have been proven to have oncolytic potential in our laboratory. To evaluate oncolytic potential of VP3 and NS1 together these genes needed to be cloned in a bicistronic vector. In this study, both these genes were cloned and characterized for expression of their gene products and its apoptotic potential. The expression of VP3 and NS1 was studied by confocal microscopy and flowcytometry. Expression of VP3 and NS1 in pVIVO.VP3.NS1 transfected HeLa cells in comparison to mock transfected cells indicated that the double gene construct expresses both the products. This was further confirmed by flowcytometry where there was increase in cells expressing VP3 and NS1 in pVIVO.VP3.NS1 transfected group in comparison with the mock control group. The apoptotic inducing potential of this characterized pVIVO.VP3.NS1 was evaluated in human cervical cancer cell line (HeLa) by DNA fragmentation assay, TUNEL assay and Hoechst staning. This double construct was observed to induce apoptosis in HeLa cells.

A Deep Pulse Search in 11 Low Mass X-Ray Binaries

NASA Astrophysics Data System (ADS)

Patruno, A.; Wette, K.; Messenger, C.

2018-06-01

We present a systematic coherent X-ray pulsation search in 11 low mass X-ray binaries (LMXBs). We select a relatively broad variety of LMXBs, including persistent and transient sources, spanning orbital periods between 0.3 and 17 hr. We use about 3.6 Ms of data collected by the Rossi X-Ray Timing Explorer and XMM-Newton and apply a semi-coherent search strategy to look for weak and persistent pulses in a wide spin frequency range. We find no evidence for X-ray pulsations in these systems and consequently set upper limits on the pulsed sinusoidal semi-amplitude below 1.6% for ten outbursting/persistent LMXBs and 6% for a quiescent system; the upper limits are further refined, by searching a narrower parameter space around the outliers, down to 0.14%–0.78% and 2.9%, respectively. These results suggest that weak pulsations might not form in (most) non pulsating LMXBs.

Cellular RNA binding proteins NS1-BP and hnRNP K regulate influenza A virus RNA splicing.

PubMed

Tsai, Pei-Ling; Chiou, Ni-Ting; Kuss, Sharon; García-Sastre, Adolfo; Lynch, Kristen W; Fontoura, Beatriz M A

2013-01-01

Influenza A virus is a major human pathogen with a genome comprised of eight single-strand, negative-sense, RNA segments. Two viral RNA segments, NS1 and M, undergo alternative splicing and yield several proteins including NS1, NS2, M1 and M2 proteins. However, the mechanisms or players involved in splicing of these viral RNA segments have not been fully studied. Here, by investigating the interacting partners and function of the cellular protein NS1-binding protein (NS1-BP), we revealed novel players in the splicing of the M1 segment. Using a proteomics approach, we identified a complex of RNA binding proteins containing NS1-BP and heterogeneous nuclear ribonucleoproteins (hnRNPs), among which are hnRNPs involved in host pre-mRNA splicing. We found that low levels of NS1-BP specifically impaired proper alternative splicing of the viral M1 mRNA segment to yield the M2 mRNA without affecting splicing of mRNA3, M4, or the NS mRNA segments. Further biochemical analysis by formaldehyde and UV cross-linking demonstrated that NS1-BP did not interact directly with viral M1 mRNA but its interacting partners, hnRNPs A1, K, L, and M, directly bound M1 mRNA. Among these hnRNPs, we identified hnRNP K as a major mediator of M1 mRNA splicing. The M1 mRNA segment generates the matrix protein M1 and the M2 ion channel, which are essential proteins involved in viral trafficking, release into the cytoplasm, and budding. Thus, reduction of NS1-BP and/or hnRNP K levels altered M2/M1 mRNA and protein ratios, decreasing M2 levels and inhibiting virus replication. Thus, NS1-BP-hnRNPK complex is a key mediator of influenza A virus gene expression.

FerriBRIGHT: a rationally designed fluorescent probe for redox active metals.

PubMed

Kennedy, Daniel P; Kormos, Chad M; Burdette, Shawn C

2009-06-24

The novel catechol-BODIPY dyad, 8-(3,4-dihydroxyphenyl)-2,6-bis(ethoxycarbonyl)-1,3,5,7-tetramethyl-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (FerriBRIGHT) was rationally designed with the aid of computational methods. FerriBRIGHT could be prepared by standard one-pot synthesis of BODIPY fluorophores from 3,4-bis(benzyloxy)benzaldehyde (1) and 3,5-dimethyl-4-(ethoxycarbonyl)pyrrole (3); however, isolating the dipyrrin intermediate 8-[3,4-bis(benzyloxy)phenyl]-2,6-bis(ethoxycarbonyl)-1,3,5,7-tetramethyl-4,4-diaza-s-indacene (7) prior to reaction with excess BF(3).OEt(2) led to marked improvements in the isolated overall yield of the desired compound. In addition to these improvements in fluorophore synthesis, microwave-assisted palladium-catalyzed hydrogenolysis of benzyl ethers was used to reduce reaction times and catalyst loading in preparation of the desired compound. When FerriBRIGHT is exposed to excess FeCl(3), CuCl(2), [Co(NH(3))(5)Cl]Cl(2), 2,3-dichloro-5,6-dicyanobenzoquinone, or ceric ammonium nitrate in methanol, a significant enhancement of fluorescence is observed. FerriBRIGHT-Q, the product resulting from the oxidation of the pendant catechol to the corresponding quinone, was found to be the emissive species. FerriBRIGHT-Q was synthesized independently, isolated, and fully characterized to allow for direct comparison with the spectroscopic data acquired in solution. Biologically relevant reactive oxygen species, such as H(2)O(2), (*)OH, (1)O(2), O(2)(*-), and bleach (NaOCl), failed to cause any changes in the emission intensity of FerriBRIGHT. In accordance with the quantum mechanical calculations, the quantum yield of fluorescence for FerriBRIGHT (Phi(fl) approximately 0) and FerriBRIGHT-Q (Phi(fl) = 0.026, lambda(ex)/lambda(em) = 490 nm/510 nm) suggests that photoinduced electron transfer between the catechol and the BODIPY dye is attenuated upon oxidation, which results in fluorescence enhancement. Binding studies of FerriBRIGHT with Ga(NO(3

A split face study to document the safety and efficacy of clearance of melasma with a 5 ns q switched Nd YAG laser versus a 50 ns q switched Nd YAG laser.

PubMed

Alsaad, Salman M S; Ross, E Victor; Mishra, Vineet; Miller, Lee

2014-12-01

To determine the safety and efficacy of a 50 ns Q switched Nd YAG laser vs. a 5 ns Q switched Nd YAG laser for clearance of melasma. To compare subject satisfaction, efficacy, and comfort level between the two lasers. This is a prospective, randomized split face clinical study. The study was approved by the Scripps IRB. Ten healthy female subjects with moderate to severe melasma were enrolled. Each subject had three laser treatments one month apart. Patients were followed up approximately 1 month, 3 months, and 6 months after the final laser treatment. A treatment session consisted of a microdermabrasion, 1064 nm QS laser, and topicals. Subjects were asked to rate treatment pain based on a numerical scale range 0-10 (0 = no pain and 10 = worst pain). A melasma area and severity index (MASI) grading system was applied. Also, melanin measurements were acquired by a reflectance spectrophotometer. Side effects were documented during the study including post treatment erythema. Eight patients completed the study. Subjects showed improvement on both sides of the face. From baseline to 1 month post the final laser treatment, the average MASI scores showed a 16% reduction for the 50 ns QS 1064 nm laser vs. a 27% reduction for the 5 ns QS 1064 nm laser (both significant versus baseline pigment, P < 0.05). This difference in MASI scores between the two lasers was not statistically significant (P = 0.87930). Laser treatments displayed mild erythema that resolved after one day. The melanin meter measurements showed a reduction in pigment readings on both sides. Three months after the final treatment there was some relapse in the melasma, as the mean pigment reduction fell to 12% for the 50 ns laser and 11% for the 5 ns laser. By 3 months pigment reduction was not statistically significant for either laser, and no significant differences in pigment reduction were noted between the two pulse durations. There was a statistically significant difference (P < 0.05) in pain scores

Use of bright light therapy among psychiatrists in massachusetts: an e-mail survey.

PubMed

Oldham, Mark A; Ciraulo, Domenic A

2014-01-01

Evidence on the use of bright light therapy for conditions beyond seasonal affective disorder continues to accrue; however, data on the prevalent use of bright light therapy in the community or in hospitals remain limited, particularly in the United States. We conducted a 5-minute e-mail survey of practicing psychiatrists in Massachusetts using the membership roster through the Massachusetts Psychiatric Society to evaluate prevalent use of bright light therapy as well as to solicit attitudes toward the treatment. Three e-mails were sent out over a 2-week period, and responses were obtained from March 2-24, 2013. An iPad raffle was used to incentivize survey completion. Of the 1,366 delivered e-mails, 197 responses were obtained. Of respondents, 72% indicated that they used bright light therapy in their practice, and, among these, all but 1 used bright light therapy for seasonal affective disorder. Only 55% of responding psychiatrists who use bright light therapy consider it to treat nonseasonal depression, and 11% of respondents who recommend bright light therapy would consider its use in inpatient settings. Lack of insurance coverage for light-delivery devices was identified as the largest barrier to using bright light therapy, being cited by 55% of respondents. Survey results suggest that limitations in practitioner knowledge of bright light therapy and the absence of bright light therapy in treatment algorithms are the 2 leading modifiable factors to encourage broader implementation. The principal limitation of our survey was the low response rate. As such, we consider these data preliminary. Response bias very likely led to an overestimation in prevalent use of bright light therapy; however, this bias notwithstanding, it appears that bright light therapy is used significantly less often for nonseasonal depression than for seasonal affective disorder. Further, its use in inpatient settings is significantly less than in outpatient settings. We expect that efforts

F Ring Bright Core Clumps

NASA Image and Video Library

2010-07-20

Bright clumps of ring material and a fan-like structure appear near the core of Saturn tenuous F ring in this mosaic of images from NASA Cassini spacecraft. Such features suggest the existence of additional objects in the F ring.

Landcover Based Optimal Deconvolution of PALS L-band Microwave Brightness Temperature

NASA Technical Reports Server (NTRS)

Limaye, Ashutosh S.; Crosson, William L.; Laymon, Charles A.; Njoku, Eni G.

2004-01-01

An optimal de-convolution (ODC) technique has been developed to estimate microwave brightness temperatures of agricultural fields using microwave radiometer observations. The technique is applied to airborne measurements taken by the Passive and Active L and S band (PALS) sensor in Iowa during Soil Moisture Experiments in 2002 (SMEX02). Agricultural fields in the study area were predominantly soybeans and corn. The brightness temperatures of corn and soybeans were observed to be significantly different because of large differences in vegetation biomass. PALS observations have significant over-sampling; observations were made about 100 m apart and the sensor footprint extends to about 400 m. Conventionally, observations of this type are averaged to produce smooth spatial data fields of brightness temperatures. However, the conventional approach is in contrast to reality in which the brightness temperatures are in fact strongly dependent on landcover, which is characterized by sharp boundaries. In this study, we mathematically de-convolve the observations into brightness temperature at the field scale (500-800m) using the sensor antenna response function. The result is more accurate spatial representation of field-scale brightness temperatures, which may in turn lead to more accurate soil moisture retrieval.

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

PubMed

Bradbury, Laura; Wan, Justin W L

2010-01-01

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

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

PubMed

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

2017-09-12

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-GFP high cells exhibited significantly higher repopulating capacity than NS-GFP low cells. Gene expression analysis revealed that nine genes, including Vwf and Cdkn1c (p57), are highly expressed in NS-GFP high 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.

Tolerance limit value of brightness and contrast adjustment on digitized radiographs

NASA Astrophysics Data System (ADS)

Utami, S. N.; Kiswanjaya, B.; Syahraini, S. I.; Ustriyana, P.

2017-08-01

The aim of this study was to measure the tolerance limit value of brightness and contrast adjustment on digitized radiograph with apical periodontitis and early apical abscess. Brightness and contrast adjustment on 60 periapical radiograph with apical periodontitis and early apical abscess made by 2 observers. Reliabilities tested by Cohen’s Kappa Coefficient and significance tested by wilcoxon test. Tolerance limit value of brightness and contrast adjustment for apical periodontitis is -5 and +5, early apical abscess is -10 and +10, and both is -5 and +5. Brightness and contrast adjustment which not appropriate can alter the evaluation and differential diagnosis of periapical lesion.

Possible Bright Starspots on TRAPPIST-1

NASA Astrophysics Data System (ADS)

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

2018-04-01

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

Radiometric properties of the NS001 Thematic Mapper Simulator aircraft multispectral scanner

NASA Technical Reports Server (NTRS)

Markham, Brian L.; Ahmad, Suraiya P.

1990-01-01

Laboratory tests of the NS001 TM are described emphasizing absolute calibration to determine the radiometry of the simulator's reflective channels. In-flight calibration of the data is accomplished with the NS001 internal integrating-sphere source because instabilities in the source can limit the absolute calibration. The data from 1987-89 indicate uncertainties of up to 25 percent with an apparent average uncertainty of about 15 percent. Also identified are dark current drift and sensitivity changes along the scan line, random noise, and nonlinearity which contribute errors of 1-2 percent. Uncertainties similar to hysteresis are also noted especially in the 2.08-2.35-micron range which can reduce sensitivity and cause errors. The NS001 TM Simulator demonstrates a polarization sensitivity that can generate errors of up to about 10 percent depending on the wavelength.

SKYMONITOR: A Global Network for Sky Brightness Measurements

NASA Astrophysics Data System (ADS)

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

2010-01-01

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

[Monitoring of brightness temperature fluctuation of water in SHF range].

PubMed

Ivanov, Yu D; Kozlov, A F; Galiullin, R A; Tatu, V Yu; Vesnin, S G; Ziborov, V S; Ivanova, N D; Pleshakova, T O

2017-01-01

The purpose of the research consisted in detection of fluctuation of brightness temperature (TSHF) of water in the area of the temperature Т = 42°С (that is critical for human) during its evaporation by SHF radiometry. Methods: Monitoring of the changes in brightness temperature of water in superhigh frequency (SHF) range (3.8-4.2 GHz) near the phase transition temperature of water Т = 42°С during its evaporation in the cone dielectric cell. The brightness temperature measurements were carried out using radiometer. Results: Fluctuation with maximum of brightness temperature was detected in 3.8-4.2 GHz frequency range near at the temperature of water Т = 42°С. It was characteristic for these TSHF fluctuations that brightness temperature rise time in this range of frequencies in ~4°С temperature range with 0.05-15°С/min gradient and a sharp decrease during 10 s connected with measuring vapor conditions. Then nonintensive fluctuation series was observed. At that, the environment temperature remained constant. Conclusion: The significant increasing in brightness temperature of water during its evaporation in SHF range near the temperature of Т ~42°С were detected. It was shown that for water, ТSHF pull with the amplitude DТSHF ~4°C are observed. At the same time, thermodynamic temperature virtually does not change. The observed effects can be used in the development of the systems for diadnostics of pathologies in human and analytical system.

The Influence of Microphysical Cloud Parameterization on Microwave Brightness Temperatures

NASA Technical Reports Server (NTRS)

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

2000-01-01

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

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

PubMed

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

2017-10-01

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

Isolation and Characterization of Wheat Derived Nonspecific Lipid Transfer Protein 2 (nsLTP2).

PubMed

Bosi, Sara; Fiori, Jessica; Dinelli, Giovanni; Rigby, Neil; Leoncini, Emanuela; Prata, Cecilia; Bregola, Valeria; Marotti, Ilaria; Gotti, Roberto; Naldi, Marina; Massaccesi, Luca; Malaguti, Marco; Kroon, Paul; Hrelia, Silvana

2018-05-22

Numerous studies support the protective role of bioactive peptides against cardiovascular diseases. Cereals represent the primary source of carbohydrates, but they also contain substantial amounts of proteins, therefore representing a potential dietary source of bioactive peptides with nutraceutical activities. The analysis of wheat extracts purified by chromatographic techniques by means of HPLC-UV/nanoLC-nanoESI-QTOF allowed the identification of a signal of about 7 kDa which, following data base searches, was ascribed to a nonspecific lipid-transfer protein (nsLTP) type 2 from Triticum aestivum (sequence coverage of 92%). For the first time nsLTP2 biological activities have been investigated. In particular, in experiments with human umbilical vein endothelial cells (HUVEC), nsLTP2 displayed antioxidant and cytoprotective activities, being able to significantly decrease reactive oxygen species (ROS) levels and to reduce lactate dehydrogenase (LDH) release, generated following oxidative (hydrogen peroxide) and inflammatory (tumor necrosis factor α, interleukin-1β, and lipopolysaccharide) stimulation. The obtained promising results suggest potential protective role of nsLTP2 in vascular diseases prevention. PRACTICAL APPLICATION: nsLTP 2 peptide is resistant to proteases throughout the gastrointestinal tract and exerts antioxidant and cytoprotective activities. These characteristics could be exploited in vascular diseases prevention. © 2018 Institute of Food Technologists®.

Viperin Restricts Zika Virus and Tick-Borne Encephalitis Virus Replication by Targeting NS3 for Proteasomal Degradation.

PubMed

Panayiotou, Christakis; Lindqvist, Richard; Kurhade, Chaitanya; Vonderstein, Kirstin; Pasto, Jenny; Edlund, Karin; Upadhyay, Arunkumar S; Överby, Anna K

2018-04-01

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 employed by viperin against two prominent flaviviruses, tick-borne encephalitis virus (TBEV) and Zika virus (ZIKV). Viperin was found to interact and colocalize with the structural proteins premembrane (prM) and envelope (E) of TBEV, as well as with nonstructural (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 possible availability of new drug targets that can be used for therapeutic intervention. IMPORTANCE Flaviviruses 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

The modulation of delta responses in the interaction of brightness and emotion.

PubMed

Kurt, Pınar; Eroğlu, Kübra; Bayram Kuzgun, Tubanur; Güntekin, Bahar

2017-02-01

The modulation of delta oscillations (0.5-3.5Hz) by emotional stimuli is reported. Physical attributes such as color, brightness and spatial frequency of emotional visual stimuli have crucial effect on the perception of complex scene. Brightness is intimately related with emotional valence. Here we explored the effect of brightness on delta oscillatory responses upon presentation of pleasant, unpleasant and neutral pictures. We found that bright unpleasant pictures elicited lower amplitude of delta response than original unpleasant pictures. The electrophysiological finding of the study was in accordance with behavioral data. These results denoted the importance of delta responses on the examination of the association between perceptual and conceptual processes while in the question of brightness and emotion. Copyright © 2016 Elsevier B.V. All rights reserved.

Large Bright Ripples

NASA Technical Reports Server (NTRS)

2004-01-01

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

Identification of small molecule inhibitors of the Chikungunya virus nsP1 RNA capping enzyme.

PubMed

Feibelman, Kristen M; Fuller, Benjamin P; Li, Linfeng; LaBarbera, Daniel V; Geiss, Brian J

2018-06-01

Chikungunya virus (CHIKV) is an arthropod-borne alphavirus. Alphaviruses are positive strand RNA viruses that require a 5' cap structure to direct translation of the viral polyprotein and prevent degradation of the viral RNA genome by host cell nucleases. Formation of the 5' RNA cap is orchestrated by the viral protein nsP1, which binds GTP and provides the N-7 methyltransferase and guanylyltransferase activities that are necessary for cap formation. Viruses with aberrant nsP1 activity are unable to replicate effectively suggesting that nsP1 is a promising target for antiviral drug discovery. Given the absence of commercially available antiviral therapies for CHIKV, it is imperative to identify compounds that could be developed as potential therapeutics. This study details a high-throughput screen of 3051 compounds from libraries containing FDA-approved drugs, natural products, and known bioactives against CHIKV nsP1 using a fluorescence polarization-based GTP competition assay. Several small molecule hits from this screen were able to compete with GTP for the CHIKV nsP1 GTP binding site at low molar concentrations. Compounds were also evaluated with an orthogonal assay that measured the ability of nsP1 to perform the guanylation step of the capping reaction in the presence of inhibitor. In addition, live virus assays with CHIKV and closely related alphavirus, Sindbis virus, were used in conjunction with cell toxicity assays to determine the antiviral activity of compounds in cell culture. The naturally derived compound lobaric acid was found to inhibit CHIKV nsP1 GTP binding and guanylation as well as attenuate viral growth in vitro at both 24 hpi and 48 hpi in hamster BHK21 and human Huh 7 cell lines. These data indicate that development of lobaric acid and further exploration of CHIKV nsP1 as a drug target may aid in the progress of anti-alphaviral drug development strategies. Copyright © 2018. Published by Elsevier B.V.

Single bright light exposure decreases sweet taste threshold in healthy volunteers.

PubMed

Srivastava, Shrikant; Donaldson, Lucy F; Rai, Dheeraj; Melichar, Jan K; Potokar, John

2013-10-01

Bright light exposure can alter circulating serotonin levels, and alteration of available serotonin by acute selective serotonin reuptake inhibition significantly lowers sweet but not salt taste recognition thresholds. We tested the hypothesis that bright light exposure would increase sweet but not salt taste sensitivity in healthy adults. Fourteen healthy volunteers were exposed to bright (10,000 lux) and dim (<20 lux) light for 30 min each, in counterbalanced order. Measures of taste perception (salt and sweet) and mood were determined at baseline, and before and after each light exposure period. Recognition thresholds for sucrose were significantly lower after bright but not dim light exposure. Thresholds for salt were unaffected by either condition. There were no significant changes in taste acuity, intensity or pleasantness for both the taste modalities and on visual analogue scales (VASs) for mood, anxiety, sleepiness and alertness, under either light condition. Brief bright light exposure reduces sweet but not salt taste recognition thresholds in healthy humans.

A Bright Shining Lesson

ERIC Educational Resources Information Center

Hurowitz, Amanda

2010-01-01

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

Replicative Functions of Minute Virus of Mice NS1 Protein Are Regulated In Vitro by Phosphorylation through Protein Kinase C

PubMed Central

Nüesch, Jürg P. F.; Dettwiler, Sabine; Corbau, Romuald; Rommelaere, Jean

1998-01-01

NS1, the major nonstructural protein of the parvovirus minute virus of mice, is a multifunctional phosphoprotein which is involved in cytotoxicity, transcriptional regulation, and initiation of viral DNA replication. For coordination of these various functions during virus propagation, NS1 has been proposed to be regulated by posttranslational modifications, in particular phosphorylation. Recent in vitro studies (J. P. F. Nüesch, R. Corbau, P. Tattersall, and J. Rommelaere, J. Virol. 72:8002–8012, 1998) provided evidence that distinct NS1 activities, notably the intrinsic helicase function, are modulated by the phosphorylation state of the protein. In order to study the dependence of the initiation of viral DNA replication on NS1 phosphorylation and to identify the protein kinases involved, we established an in vitro replication system that is devoid of endogenous protein kinases and is based on plasmid substrates containing the minimal left-end origins of replication. Cellular components necessary to drive NS1-dependent rolling-circle replication (RCR) were freed from endogenous serine/threonine protein kinases by affinity chromatography, and the eukaryotic DNA polymerases were replaced by the bacteriophage T4 DNA polymerase. While native NS1 (NS1P) supported RCR under these conditions, dephosphorylated NS1 (NS1O) was impaired. Using fractionated HeLa cell extracts, we identified two essential protein components which are able to phosphorylate NS1O, are enriched in protein kinase C (PKC), and, when present together, reactivate NS1O for replication. One of these components, containing atypical PKC, was sufficient to restore NS1O helicase activity. The requirement of NS1O reactivation for characteristic PKC cofactors such as Ca2+/phosphatidylserine or phorbol esters strongly suggests the involvement of this protein kinase family in regulation of NS1 replicative functions in vitro. PMID:9811734

Auroral bright spot in Jupiter’s active region in corresponding to solar wind dynamic

NASA Astrophysics Data System (ADS)

Haewsantati, K.; Wannawichian, S.; Clarke, J. T.; Nichols, J. D.

2017-09-01

Jupiter’s polar emission has brightness whose behavior appears to be unstable. This work focuses on the bright spot in active region which is a section of Jupiter’s polar emission. Images of the aurora were taken by Advanced Camera for Surveys (ACS) onboard the Hubble Space Telescope (HST). Previously, two bright spots, which were found on 13 th May 2007, were suggested to be fixed on locations described by system III longitude. The bright spot’s origin in equatorial plane was proposed to be at distance 80-90 Jovian radii and probably associated with the solar wind properties. This study analyzes additional data on May 2007 to study long-term variation of brightness and locations of bright spots. The newly modified magnetosphere-ionosphere mapping based on VIP4 and VIPAL model is used to locate the origin of bright spot in magnetosphere. Furthermore, the Michigan Solar Wind Model or mSWiM is also used to study the variation of solar wind dynamic pressure during the time of bright spot’s observation. We found that the bright spots appear in similar locations which correspond to similar origins in magnetosphere. In addition, the solar wind dynamic pressure should probably affect the bright spot’s variation.

Entrainment of oviposition in the fowl using bright and dim light cycles.

PubMed

Morris, T R; Bhatti, B M

1978-05-01

1. Nine short trial, involving 96 different treatments, were used to investigate the critical intensities and duration of bright and dim periods of lighting needed to entrain oviposition in cycles ranging from 21 to 30 h. 2. Entrainment was shown to depend upon the contrast between bright and dim lighting, and to be independent of the absolute light intensity. 3. A bright: dim ratio of 13:1 fully entrained oviposition in cycles of 25 h and 27 h. For 23-h and 28-h cycles a 30:1 ratio was required. Twenty-one-hour cycles required a ratio of 300:1 and with 30-h cycles a ratio of 1000:1 was needed to achieve full entrainment of oviposition. 4. In 24-h cycles, 1 h of bright lighting at 02.00 h was sufficient to override other environmental signals and cause eggs to be laid in the late evening, but a minimum bright period of 6 h was needed to cause full phase setting with 21-h cycles. 5. Circadian periodicity can easily be imposed on hens by providing a short exposure to bright light with a background of continuous dim light; but the signal must be increased (by providing a greater contrast between bright and dim lights and/or a longer period of bright lighting) to entrain oviposition when the cycle deviates markedly from the natural period of 24 h.

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

PubMed

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

2017-08-01

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

The 5.5 protein of phage T7 inhibits H-NS through interactions with the central oligomerization domain.

PubMed

Ali, Sabrina S; Beckett, Emily; Bae, Sandy Jeehoon; Navarre, William Wiley

2011-09-01

The 5.5 protein (T7p32) of coliphage T7 (5.5(T7)) was shown to bind and inhibit gene silencing by the nucleoid-associated protein H-NS, but the mechanism by which it acts was not understood. The 5.5(T7) protein is insoluble when expressed in Escherichia coli, but we find that 5.5(T7) can be isolated in a soluble form when coexpressed with a truncated version of H-NS followed by subsequent disruption of the complex during anion-exchange chromatography. Association studies reveal that 5.5(T7) binds a region of H-NS (residues 60 to 80) recently found to contain a distinct domain necessary for higher-order H-NS oligomerization. Accordingly, we find that purified 5.5(T7) can disrupt higher-order H-NS-DNA complexes in vitro but does not abolish DNA binding by H-NS per se. Homologues of the 5.5(T7) protein are found exclusively among members of the Autographivirinae that infect enteric bacteria, and despite fairly low sequence conservation, the H-NS binding properties of these proteins are largely conserved. Unexpectedly, we find that the 5.5(T7) protein copurifies with heterogeneous low-molecular-weight RNA, likely tRNA, through several chromatography steps and that this interaction does not require the DNA binding domain of H-NS. The 5.5 proteins utilize a previously undescribed mechanism of H-NS antagonism that further highlights the critical importance that higher-order oligomerization plays in H-NS-mediated gene repression. Copyright © 2011, American Society for Microbiology. All Rights Reserved.

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

PubMed

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

2017-10-27

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

pH-Dependent Conformational Changes in the HCV NS3 Protein Modulate Its ATPase and Helicase Activities

PubMed Central

Ventura, Gustavo Tavares; da Costa, Emmerson Corrêa Brasil; Capaccia, Anne Miranda; Mohana-Borges, Ronaldo

2014-01-01

The hepatitis C virus (HCV) infects 170 to 200 million people worldwide and is, therefore, a major health problem. The lack of efficient treatments that specifically target the viral proteins or RNA and its high chronicity rate make hepatitis C the cause of many deaths and hepatic transplants annually. The NS3 protein is considered an important target for the development of anti-HCV drugs because it is composed of two domains (a serine protease in the N-terminal portion and an RNA helicase/NTPase in the C-terminal portion), which are essential for viral replication and proliferation. We expressed and purified both the NS3 helicase domain (NS3hel) and the full-length NS3 protein (NS3FL) and characterized pH-dependent structural changes associated with the increase in their ATPase and helicase activities at acidic pH. Using intrinsic fluorescence experiments, we have observed that NS3hel was less stable at pH 6.4 than at pH 7.2. Moreover, binding curves using an extrinsic fluorescent probe (bis-ANS) and ATPase assays performed under different pH conditions demonstrated that the hydrophobic clefts of NS3 are significantly more exposed to the aqueous medium at acidic pH. Using fluorescence spectroscopy and anisotropy assays, we have also observed more protein interaction with DNA upon pH acidification, which suggests that the hydrophobic clefts exposure on NS3 might be related to a loss of stability that could lead it to adopt a more open conformation. This conformational change at acidic pH would stimulate both its ATPase and helicase activities, as well as its ability to bind DNA. Taken together, our results indicate that the NS3 protein adopts a more open conformation due to acidification from pH 7.2 to 6.4, resulting in a more active form at a pH that is found near Golgi-derived membranes. This increased activity could better allow NS3 to carry out its functions during HCV replication. PMID:25551442

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

NASA Astrophysics Data System (ADS)

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

2018-04-01

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

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

NASA Astrophysics Data System (ADS)

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

2018-05-01

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

Inhibition of the Membrane Attack Complex by Dengue Virus NS1 through Interaction with Vitronectin and Terminal Complement Proteins

PubMed Central

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

2016-01-01

ABSTRACT 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. IMPORTANCE 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

Inhibition of the Membrane Attack Complex by Dengue Virus NS1 through Interaction with Vitronectin and Terminal Complement Proteins.

PubMed

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

2016-11-01

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

Phosphorylation of influenza A virus NS1 protein at threonine 49 suppresses its interferon antagonistic activity.

PubMed

Kathum, Omer Abid; Schräder, Tobias; Anhlan, Darisuren; Nordhoff, Carolin; Liedmann, Swantje; Pande, Amit; Mellmann, Alexander; Ehrhardt, Christina; Wixler, Viktor; Ludwig, Stephan

2016-06-01

Phosphorylation and dephosphorylation acts as a fundamental molecular switch that alters protein function and thereby regulates many cellular processes. The non-structural protein 1 (NS1) of influenza A virus is an important factor regulating virulence by counteracting cellular immune responses against viral infection. NS1 was shown to be phosphorylated at several sites; however, so far, no function has been conclusively assigned to these post-translational events yet. Here, we show that the newly identified phospho-site threonine 49 of NS1 is differentially phosphorylated in the viral replication cycle. Phosphorylation impairs binding of NS1 to double-stranded RNA and TRIM25 as well as complex formation with RIG-I, thereby switching off its interferon antagonistic activity. Because phosphorylation was shown to occur at later stages of infection, we hypothesize that at this stage other functions of the multifunctional NS1 beyond its interferon-antagonistic activity are needed. © 2016 The Authors Cellular Microbiology published by John Wiley & Sons Ltd.

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

PubMed

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

2017-11-21

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

On the Relation Between Facular Bright Points and the Magnetic Field

NASA Astrophysics Data System (ADS)

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

1994-12-01

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

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

NASA Astrophysics Data System (ADS)

Iwai, K.; Loukitcheva, M.; Shimojo, M.; Solanki, S. K.; White, S. M.

2017-12-01

We report the discovery of a brightness enhancement in the center of a large sunspot umbra at a wavelength of 3 mm using the Atacama Large Millimeter/sub-millimeter Array (ALMA). Sunspots are among the most prominent features on the solar surface, but many of their aspects are surprisingly poorly understood. We analyzed a λ = 3 mm (100 GHz) mosaic image obtained by ALMA that includes a large sunspot within the active region AR12470, on 2015 December 16. The 3 mm map has a 300''×300'' field of view and 4.9''×2.2'' spatial resolution, which is the highest spatial resolution map of an entire sunspot in this frequency range. We find a gradient of 3 mm brightness from a high value in the outer penumbra to a low value in the inner penumbra/outer umbra. Within the inner umbra, there is a marked increase in 3 mm brightness temperature, which we call an umbral brightness enhancement. This enhanced emission corresponds to a temperature excess of 800 K relative to the surrounding inner penumbral region and coincides with excess brightness in the 1330 and 1400 Å slit-jaw images of the Interface Region Imaging Spectrograph (IRIS), adjacent to a partial lightbridge. This λ = 3 mm brightness enhancement may be an intrinsic feature of the sunspot umbra at chromospheric heights, such as a manifestation of umbral flashes, or it could be related to a coronal plume, since the brightness enhancement was coincident with the footpoint of a coronal loop observed at 171 Å.

Sub-nanosecond resolution electric field measurements during ns pulse breakdown in ambient air

NASA Astrophysics Data System (ADS)

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

2018-01-01

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.

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

PubMed Central

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

2010-01-01

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

Crystal structure of a novel conformational state of the flavivirus NS3 protein: implications for polyprotein processing and viral replication.

PubMed

Assenberg, René; Mastrangelo, Eloise; Walter, Thomas S; Verma, Anil; Milani, Mario; Owens, Raymond J; Stuart, David I; Grimes, Jonathan M; Mancini, Erika J

2009-12-01

The flavivirus genome comprises a single strand of positive-sense RNA, which is translated into a polyprotein and cleaved by a combination of viral and host proteases to yield functional proteins. One of these, nonstructural protein 3 (NS3), is an enzyme with both serine protease and NTPase/helicase activities. NS3 plays a central role in the flavivirus life cycle: the NS3 N-terminal serine protease together with its essential cofactor NS2B is involved in the processing of the polyprotein, whereas the NS3 C-terminal NTPase/helicase is responsible for ATP-dependent RNA strand separation during replication. An unresolved question remains regarding why NS3 appears to encode two apparently disconnected functionalities within one protein. Here we report the 2.75-A-resolution crystal structure of full-length Murray Valley encephalitis virus NS3 fused with the protease activation peptide of NS2B. The biochemical characterization of this construct suggests that the protease has little influence on the helicase activity and vice versa. This finding is in agreement with the structural data, revealing a single protein with two essentially segregated globular domains. Comparison of the structure with that of dengue virus type 4 NS2B-NS3 reveals a relative orientation of the two domains that is radically different between the two structures. Our analysis suggests that the relative domain-domain orientation in NS3 is highly variable and dictated by a flexible interdomain linker. The possible implications of this conformational flexibility for the function of NS3 are discussed.

CD56bright NK cells exhibit potent antitumor responses following IL-15 priming

PubMed Central

Wagner, Julia A.; Berrien-Elliott, Melissa M.; Schneider, Stephanie E.; Leong, Jeffrey W.; Sullivan, Ryan P.; Jewell, Brea A.; Becker-Hapak, Michelle; 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.

2017-01-01

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. PMID:28972539

Effect of Lactobacillus acidophilus NS1 on plasma cholesterol levels in diet-induced obese mice.

PubMed

Song, M; Park, S; Lee, H; Min, B; Jung, S; Park, S; Kim, E; Oh, S

2015-03-01

We investigated the probiotic properties of Lactobacillus acidophilus NS1, such as acid resistance, bile tolerance, adherence to HT-29 cells, and cholesterol assimilation activity. In an animal study, 7-wk-old male C57BL/6 mice were fed a normal diet, a high-fat diet (HFD), or an HFD with L. acidophilus NS1 (ca. 1.0×10(8) cfu/mL) for 10 wk. Total cholesterol and low-density lipoprotein (LDL) cholesterol levels were significantly lower in mice fed an HFD with L. acidophilus NS1 than in those fed an HFD only, whereas high-density lipoprotein cholesterol levels were similar between these 2 groups. To understand the mechanism of the cholesterol-lowering effect of L. acidophilus NS1 on the HFD-mediated increase in plasma cholesterol levels, we determined mRNA levels of genes involved in cholesterol homeostasis in the liver. Expression of sterol regulatory element-binding protein 2 (Srebp2) and LDL receptor (Ldlr) in the liver was dramatically reduced in mice fed a HFD compared with those fed a normal diet. When L. acidophilus NS1 was administered orally to HFD-fed mice, an HFD-induced suppression of Srebp2 and Ldlr expression in the liver was abolished. These results suggest that the oral administration of L. acidophilus NS1 to mice fed an HFD increased the expression of Srebp2 and Ldlr in the liver, which was inhibited by high fat intake, thus leading to a decrease in plasma cholesterol levels. Lactobacillus acidophilus NS1 could be a useful probiotic microorganism for cholesterol-lowering dairy products and the improvement of hyperlipidemia and hepatic lipid metabolism. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Introgression of Chromosome 3Ns from Psathyrostachys huashanica into Wheat Specifying Resistance to Stripe Rust

PubMed Central

Kang, Houyang; Wang, Yi; Fedak, George; Cao, Wenguang; Zhang, Haiqin; Fan, Xing; Sha, Lina; Xu, Lili; Zheng, Youliang; Zhou, Yonghong

2011-01-01

Wheat stripe rust is a destructive disease in the cool and humid wheat-growing areas of the world. Finding diverse sources of stripe rust resistance is critical for increasing genetic diversity of resistance for wheat breeding programs. Stripe rust resistance was identified in the alien species Psathyrostachys huashanica, and a wheat- P. huashanica amphiploid line (PHW-SA) with stripe rust resistance was reported previously. In this study, a P. huashanica 3Ns monosomic addition line (PW11) with superior resistance to stripe rust was developed, which was derived from the cross between PHW-SA and wheat J-11. We evaluated the alien introgressions PW11-2, PW11-5 and PW11-8 which were derived from line PW11 for reaction to new Pst race CYR32, and used molecular and cytogenetic tools to characterize these lines. The introgressions were remarkably resistant to CYR32, suggesting that the resistance to stripe rust of the introgressions thus was controlled by gene(s) located on P. huashanica chromosome 3Ns. All derived lines were cytologically stable in term of meiotic chromosome behavior. Two 3Ns chromosomes of P. huashanica were detected in the disomic addition line PW11-2. Chromosomes 1B of substitution line PW11-5 had been replaced by a pair of P. huashanica 3Ns chromosomes. In PW11-8, a small terminal segment from P. huashanica chromosome arm 3NsS was translocated to the terminal region of wheat chromosomes 3BL. Thus, this translocated chromosome is designated T3BL-3NsS. These conclusions were further confirmed by SSR analyses. Two 3Ns-specific markers Xgwm181 and Xgwm161 will be useful to rapidly identify and trace the translocated fragments. These introgressions, which had significant characteristics of resistance to stripe rust, could be utilized as novel germplasms for wheat breeding. PMID:21760909

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

USDA-ARS?s Scientific Manuscript database

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

HCV RNA traffic and association with NS5A in living cells

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

Fiches, Guillaume N.; Eyre, Nicholas S.; Aloia, Amanda L.

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.more » 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.« less

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

PubMed

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

2008-07-01

The long QT syndrome is characterized by a prolongation of the QT interval measured on the surface electrocardiogram. Prolonging the QT interval increases the risk of dangerous ventricular fibrillations, eventually leading to sudden cardiac death. Pharmacologically induced QT interval prolongations are most often caused by antagonizing effects on the repolarizing cardiac current called IKr. In humans IKr is mediated by the human ether-a-go-go related gene (hERG) potassium channel. We recently presented NS3623, a compound that selectively activates this channel. The present study was dedicated 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 hERG 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.

Dark and Bright Terrains of Pluto

NASA Image and Video Library

2015-07-10

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

Characterization of molecular interactions between Zika virus protease and peptides derived from the C-terminus of NS2B.

PubMed

Li, Yan; Loh, Ying Ru; Hung, Alvin W; Kang, CongBao

2018-06-21

Zika virus (ZIKV) protease is a two-component complex in which NS3 contains the catalytic triad and NS2B cofactor region is important for protease folding and activity. A protease construct-eZiPro without the transmembrane domains of NS2B was designed. Structural study on eZiPro reveals that the Thr-Gly-Lys-Arg (TGKR) sequence at the C-terminus of NS2B binds to the active site after cleavage. The bZiPro construct only contains NS2B cofactor region and the N-terminus of NS3 without any artificial linker or protease cleavage site, giving rise to an empty pocket accessible to substrate and inhibitor binding. Herein, we demonstrate that the TGKR sequence of NS2B in eZiPro is dynamic. Peptides from NS2B with various lengths exhibit different binding affinities to bZiPro. TGKR binding to the active site in eZiPro does not affect protease binding to small-molecule compounds. Our results suggest that eZiPro will also be useful for evaluating small-molecule protease inhibitors. Copyright © 2018 Elsevier Inc. All rights reserved.

Active Processes: Bright Streaks and Dark Fans

NASA Technical Reports Server (NTRS)

2007-01-01

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

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

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

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

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

Automated Adaptive Brightness in Wireless Capsule Endoscopy Using Image Segmentation and Sigmoid Function.

PubMed

Shrestha, Ravi; Mohammed, Shahed K; Hasan, Md Mehedi; Zhang, Xuechao; Wahid, Khan A

2016-08-01

Wireless capsule endoscopy (WCE) plays an important role in the diagnosis of gastrointestinal (GI) diseases by capturing images of human small intestine. Accurate diagnosis of endoscopic images depends heavily on the quality of captured images. Along with image and frame rate, brightness of the image is an important parameter that influences the image quality which leads to the design of an efficient illumination system. Such design involves the choice and placement of proper light source and its ability to illuminate GI surface with proper brightness. Light emitting diodes (LEDs) are normally used as sources where modulated pulses are used to control LED's brightness. In practice, instances like under- and over-illumination are very common in WCE, where the former provides dark images and the later provides bright images with high power consumption. In this paper, we propose a low-power and efficient illumination system that is based on an automated brightness algorithm. The scheme is adaptive in nature, i.e., the brightness level is controlled automatically in real-time while the images are being captured. The captured images are segmented into four equal regions and the brightness level of each region is calculated. Then an adaptive sigmoid function is used to find the optimized brightness level and accordingly a new value of duty cycle of the modulated pulse is generated to capture future images. The algorithm is fully implemented in a capsule prototype and tested with endoscopic images. Commercial capsules like Pillcam and Mirocam were also used in the experiment. The results show that the proposed algorithm works well in controlling the brightness level accordingly to the environmental condition, and as a result, good quality images are captured with an average of 40% brightness level that saves power consumption of the capsule.

Probing the structure, function, and interactions of the Escherichia coli H-NS and StpA proteins by using dominant negative derivatives.

PubMed

Williams, R M; Rimsky, S; Buc, H

1996-08-01

Twelve different dominant negative mutants of the Escherichia coli nucleoid-associated protein, H-NS, have been selected and characterized in vivo. The mutants are all severely defective in promoter repression activity in a strain lacking H-NS, and they all disrupt the repression normally exerted by H-NS at two of its target promoters. From the locations of the alterations in these mutants, which result in both large truncations and amino acid substitutions, we propose that H-NAS contains at least two distinct domains. The in vitro protein-protein cross-linking data presented in this report indicate that the proposed N-terminal domain of H-NS has a role in H-NS multimerization. StpA is a protein with known structural and functional homologies to H-NS. We have analyzed the extent of these homologies by constructing and studying StpA mutants predicted to be dominant negative. Our data indicate that the substitutions and deletions found in dominant negative H-NS have similar effects in the context of StpA. We conclude that the domain organizations and functions in StpA and H-NS are closely related. Furthermore, dominant negative H-NS can disrupt the activity of native StpA, and reciprocally, dominant negative StpA can disrupt the activity of native H-NS. We demonstrate that the N-terminal domain of H-NS can be chemically cross-linked to both full-length H-NS and StpA. We account for these observations by proposing that H-NS and StpA have the ability to form hybrid species.

Measuring night sky brightness: methods and challenges

NASA Astrophysics Data System (ADS)

Hänel, Andreas; Posch, Thomas; Ribas, Salvador J.; Aubé, Martin; Duriscoe, Dan; Jechow, Andreas; Kollath, Zoltán; Lolkema, Dorien E.; Moore, Chadwick; Schmidt, Norbert; Spoelstra, Henk; Wuchterl, Günther; Kyba, Christopher C. M.

2018-01-01

Measuring the brightness of the night sky has become an increasingly important topic in recent years, as artificial lights and their scattering by the Earth's atmosphere continue spreading around the globe. Several instruments and techniques have been developed for this task. We give an overview of these, and discuss their strengths and limitations. The different quantities that can and should be derived when measuring the night sky brightness are discussed, as well as the procedures that have been and still need to be defined in this context. We conclude that in many situations, calibrated consumer digital cameras with fisheye lenses provide the best relation between ease-of-use and wealth of obtainable information on the night sky. While they do not obtain full spectral information, they are able to sample the complete sky in a period of minutes, with colour information in three bands. This is important, as given the current global changes in lamp spectra, changes in sky radiance observed only with single band devices may lead to incorrect conclusions regarding long term changes in sky brightness. The acquisition of all-sky information is desirable, as zenith-only information does not provide an adequate characterization of a site. Nevertheless, zenith-only single-band one-channel devices such as the "Sky Quality Meter" continue to be a viable option for long-term studies of night sky brightness and for studies conducted from a moving platform. Accurate interpretation of such data requires some understanding of the colour composition of the sky light. We recommend supplementing long-term time series derived with such devices with periodic all-sky sampling by a calibrated camera system and calibrated luxmeters or luminance meters.

Dark Lakes on a Bright Landscape

NASA Image and Video Library

2013-10-23

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

SNPdbe: constructing an nsSNP functional impacts database.

PubMed

Schaefer, Christian; Meier, Alice; Rost, Burkhard; Bromberg, Yana

2012-02-15

Many existing databases annotate experimentally characterized single nucleotide polymorphisms (SNPs). Each non-synonymous SNP (nsSNP) changes one amino acid in the gene product (single amino acid substitution;SAAS). This change can either affect protein function or be neutral in that respect. Most polymorphisms lack experimental annotation of their functional impact. Here, we introduce SNPdbe-SNP database of effects, with predictions of computationally annotated functional impacts of SNPs. Database entries represent nsSNPs in dbSNP and 1000 Genomes collection, as well as variants from UniProt and PMD. SAASs come from >2600 organisms; 'human' being the most prevalent. The impact of each SAAS on protein function is predicted using the SNAP and SIFT algorithms and augmented with experimentally derived function/structure information and disease associations from PMD, OMIM and UniProt. SNPdbe is consistently updated and easily augmented with new sources of information. The database is available as an MySQL dump and via a web front end that allows searches with any combination of organism names, sequences and mutation IDs. http://www.rostlab.org/services/snpdbe.

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

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

Iwai, Kazumasa; Loukitcheva, Maria; Shimojo, Masumi

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

Diode lasers optimized in brightness for fiber laser pumping

NASA Astrophysics Data System (ADS)

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

2018-02-01

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

Progress in extremely high brightness LED-based light sources

NASA Astrophysics Data System (ADS)

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

2017-09-01

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

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

PubMed

Slama, Hichem; Deliens, Gaétane; Schmitz, Rémy; Peigneux, Philippe; Leproult, Rachel

2015-01-01

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

Afternoon Nap and Bright Light Exposure Improve Cognitive Flexibility Post Lunch

PubMed Central

Schmitz, Rémy; Peigneux, Philippe; Leproult, Rachel

2015-01-01

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

Comet brightness parameters: Definition, determination, and correlations

NASA Technical Reports Server (NTRS)

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

1976-01-01

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

Just How Bright Is a Laser?

ERIC Educational Resources Information Center

Van Baak, David A.

1995-01-01

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

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

PubMed Central

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

2013-01-01

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

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

PubMed

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

2016-01-15

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

Bright Beginnings. WWC Intervention Report

ERIC Educational Resources Information Center

What Works Clearinghouse, 2009

2009-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2017-10-01

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

High-energy 100-ns single-frequency all-fiber laser at 1064 nm

NASA Astrophysics Data System (ADS)

Fu, Shijie; Shi, Wei; Tang, Zhao; Shi, Chaodu; Bai, Xiaolei; Sheng, Quan; Chavez-Pirson, Arturo; Peyghambarian, N.; Yao, Jianquan

2018-02-01

A high-energy, single-frequency fiber laser with long pulse duration of 100 ns has been experimentally investigated in an all-fiber architecture. Only 34-cm long heavily Yb-doped phosphate fiber was employed in power scaling stage to efficiently suppress the Stimulated Brillouin effect (SBS). In the experiment, 0.47 mJ single pulse energy was achieved in power scaling stage at the pump power of 16 W. The pre-shaped pulse was gradually broadened from 103 to 140 ns during the amplification without shape distortion.

Colour cues proved to be more informative for dogs than brightness.

PubMed

Kasparson, Anna A; Badridze, Jason; Maximov, Vadim V

2013-09-07

The results of early studies on colour vision in dogs led to the conclusion that chromatic cues are unimportant for dogs during their normal activities. Nevertheless, the canine retina possesses two cone types which provide at least the potential for colour vision. Recently, experiments controlling for the brightness information in visual stimuli demonstrated that dogs have the ability to perform chromatic discrimination. Here, we show that for eight previously untrained dogs colour proved to be more informative than brightness when choosing between visual stimuli differing both in brightness and chromaticity. Although brightness could have been used by the dogs in our experiments (unlike previous studies), it was not. Our results demonstrate that under natural photopic lighting conditions colour information may be predominant even for animals that possess only two spectral types of cone photoreceptors.

Prolactin Regulatory Element Binding Protein Is Involved in Hepatitis C Virus Replication by Interaction with NS4B

PubMed Central

Kong, Lingbao; Fujimoto, Akira; Nakamura, Mariko; Aoyagi, Haruyo; Matsuda, Mami; Watashi, Koichi; Suzuki, Ryosuke; Arita, Minetaro; Yamagoe, Satoshi; Dohmae, Naoshi; Suzuki, Takehiro; Sakamaki, Yuriko; Ichinose, Shizuko; Suzuki, Tetsuro; Wakita, Takaji

2016-01-01

ABSTRACT It has been proposed that the hepatitis C virus (HCV) NS4B protein triggers the membranous HCV replication compartment, but the underlying molecular mechanism is not fully understood. Here, we screened for NS4B-associated membrane proteins by tandem affinity purification and proteome analysis and identified 202 host proteins. Subsequent screening of replicon cells with small interfering RNA identified prolactin regulatory element binding (PREB) to be a novel HCV host cofactor. The interaction between PREB and NS4B was confirmed by immunoprecipitation, immunofluorescence, and proximity ligation assays. PREB colocalized with double-stranded RNA and the newly synthesized HCV RNA labeled with bromouridine triphosphate in HCV replicon cells. Furthermore, PREB shifted to detergent-resistant membranes (DRMs), where HCV replication complexes reside, in the presence of NS4B expression in Huh7 cells. However, a PREB mutant lacking the NS4B-binding region (PREBd3) could not colocalize with double-stranded RNA and did not shift to the DRM in the presence of NS4B. These results indicate that PREB locates at the HCV replication complex by interacting with NS4B. PREB silencing inhibited the formation of the membranous HCV replication compartment and increased the protease and nuclease sensitivity of HCV replicase proteins and RNA in DRMs, respectively. Collectively, these data indicate that PREB promotes HCV RNA replication by participating in the formation of the membranous replication compartment and by maintaining its proper structure by interacting with NS4B. Furthermore, PREB was induced by HCV infection in vitro and in vivo. Our findings provide new insights into HCV host cofactors. IMPORTANCE The hepatitis C virus (HCV) protein NS4B can induce alteration of the endoplasmic reticulum and the formation of a membranous web structure, which provides a platform for the HCV replication complex. The molecular mechanism by which NS4B induces the membranous HCV replication

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

PubMed

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

2015-09-04

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

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

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

Noisakran, Sansanee; Medical Molecular Biology Unit, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Adulyadejvikrom Building; Sengsai, Suchada

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

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

Jia, Kun; Li, Xiang-Dong, E-mail: lixd@nju.edu.cn

Millisecond pulsars (MSPs) are thought to originate from low-mass X-ray binaries (LMXBs). The discovery of eclipsing radio MSPs, including redbacks and black widows, indicates that evaporation of the donor star by the MSP’s irradiation takes place during the LMXB evolution. In this work, we investigate the effect of donor evaporation on the secular evolution of LMXBs, considering different evaporation efficiencies and related angular momentum loss. We find that for widening LMXBs, the donor star leaves a less massive white dwarf than without evaporation; for contracting systems, evaporation can speed up the evolution, resulting in dynamically unstable mass transfer and possiblymore » the formation of isolated MSPs.« less

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

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

Gu, M.; Rice, C

2010-01-01

A virally encoded superfamily-2 (SF2) helicase (NS3h) is essential for the replication of hepatitis C virus, a leading cause of liver disease worldwide. Efforts to elucidate the function of NS3h and to develop inhibitors against it, however, have been hampered by limited understanding of its molecular mechanism. Here we show x-ray crystal structures for a set of NS3h complexes, including ground-state and transition-state ternary complexes captured with ATP mimics (ADP {center_dot} BeF{sub 3} and ADP {center_dot} AlF{sub 4}{sup -}). These structures provide, for the first time, three conformational snapshots demonstrating the molecular basis of action for a SF2 helicase. Uponmore » 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.« less

Erratum - the Lowest Surface Brightness Disc Galaxy Known

NASA Astrophysics Data System (ADS)

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

1988-11-01

The paper "The lowest surface brightness disc galaxy known' by J.I. Davies, S. Phillipps and M.J. Disney was published in Mon. Not. R. astr. Soc. (1988), 231, 69p. The declination of the object given in section 2 of the paper is incorrect and should be changed to +19^deg^48'23". Thus the object cannot be identified with GP 1444 as in the original paper. To minimize confusion we propose to refer to the low surface brightness galaxy as GP 1444A.

Bright solitons in non-equilibrium coherent quantum matter

PubMed Central

Pinsker, F.; Flayac, H.

2016-01-01

We theoretically demonstrate a mechanism for bright soliton generation in spinor non-equilibrium Bose–Einstein condensates made of atoms or quasi-particles such as polaritons in semiconductor microcavities. We give analytical expressions for bright (half) solitons as minimizing functions of a generalized non-conservative Lagrangian elucidating the unique features of inter and intra-competition in non-equilibrium systems. The analytical results are supported by a detailed numerical analysis that further shows the rich soliton dynamics inferred by their instability and mutual cross-interactions. PMID:26997892

The ASAS-SN Bright Supernova Catalog – II. 2015

DOE PAGES

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

2017-01-16

Here, this paper presents information for all supernovae discovered by the All-Sky Automated Survey for SuperNovae (ASAS-SN) during 2015, its second full year of operations. The same information is presented for bright (mV ≤ 17), spectroscopically confirmed supernovae discovered by other sources in 2015. As with the first ASAS-SN bright supernova catalogue, we also present redshifts and near-ultraviolet through infrared magnitudes for all supernova host galaxies in both samples. Combined with our previous catalogue, this work comprises a complete catalogue of 455 supernovae from multiple professional and amateur sources, allowing for population studies that were previously impossible. This is themore » second of a series of yearly papers on bright supernovae and their hosts from the ASAS-SN team.« less

The ASAS-SN Bright Supernova Catalog – II. 2015

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

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

Here, this paper presents information for all supernovae discovered by the All-Sky Automated Survey for SuperNovae (ASAS-SN) during 2015, its second full year of operations. The same information is presented for bright (mV ≤ 17), spectroscopically confirmed supernovae discovered by other sources in 2015. As with the first ASAS-SN bright supernova catalogue, we also present redshifts and near-ultraviolet through infrared magnitudes for all supernova host galaxies in both samples. Combined with our previous catalogue, this work comprises a complete catalogue of 455 supernovae from multiple professional and amateur sources, allowing for population studies that were previously impossible. This is themore » second of a series of yearly papers on bright supernovae and their hosts from the ASAS-SN team.« less

Hha has a defined regulatory role that is not dependent upon H-NS or StpA

PubMed Central

Solórzano, Carla; Srikumar, Shabarinath; Canals, Rocío; Juárez, Antonio; Paytubi, Sonia; Madrid, Cristina

2015-01-01

The Hha family of proteins is involved in the regulation of gene expression in enterobacteria by forming complexes with H-NS-like proteins. Whereas several amino acid residues of both proteins participate in the interaction, some of them play a key role. Residue D48 of Hha protein is essential for the interaction with H-NS, thus the D48N substitution in Hha protein abrogates H-NS/Hha interaction. Despite being a paralog of H-NS protein, StpA interacts with HhaD48N with higher affinity than with the wild type Hha protein. To analyze whether Hha is capable of acting independently of H-NS and StpA, we conducted transcriptomic analysis on the hha and stpA deletion strains and the hhaD48N substitution strain of Salmonella Typhimurium using a custom microarray. The results obtained allowed the identification of 120 genes regulated by Hha in an H-NS/StpA-independent manner, 38% of which are horizontally acquired genes. A significant number of the identified genes are involved in functions related to cell motility, iron uptake, and pathogenicity. Thus, motility assays, siderophore detection and intra-macrophage replication assays were performed to confirm the transcriptomic data. Our findings point out the importance of Hha protein as an independent regulator in S. Typhimurium, highlighting a regulatory role on virulence. PMID:26284052

West Nile Virus Temperature Sensitivity and Avian Virulence Are Modulated by NS1-2B Polymorphisms.

PubMed

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

2016-08-01

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.

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

PubMed

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

2016-06-01

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

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

PubMed

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

2016-04-01

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

NF-κB is required for dengue virus NS5-induced RANTES expression.

PubMed

Khunchai, Sasiprapa; Junking, Mutita; Suttitheptumrong, Aroonroong; Kooptiwut, Suwattanee; Haegeman, Guy; Limjindaporn, Thawornchai; Yenchitsomanus, Pa-Thai

2015-02-02

Dengue virus (DENV) infection associates with renal disorders. Patients with dengue hemorrhagic fever and acute kidney injury have a high mortality rate. Increased levels of cytokines may contribute to the pathogenesis of DENV-induced kidney injury. Currently, molecular mechanisms how DENV induces kidney cell injury has not been thoroughly investigated. Excessive cytokine production may be involved in this process. Using human cytokine RT(2) Profiler PCR array, 14 genes including IP-10, RANTES, IL-8, CXCL-9 and MIP-1β were up-regulated more than 2 folds in DENV-infected HEK 293 cells compared to that of mock-infected HEK 293 cells. In the present study, RANTES was suppressed by the NF-κB inhibitor, compound A (CpdA), in DENV-infected HEK 293 cells implying the role of NF-κB in RANTES expression. Chromatin immunoprecipitation (ChIP) assay showed that NF-κB binds more efficiently to its binding sites on the RANTES promoter in NS5-transfected HEK 293 cells than in HEK 293 cells expressing the vector lacking NS5 gene. To further examine whether the NS5-activated RANTES promoter is mediated through NF-κB, the two NF-κB binding sites on the RANTES promoter were mutated and this promoter was coupled to the luciferase cDNA. The result showed that when both binding sites of NF-κB in the RANTES promoter were mutated, the ability of NS5 to induce the luciferase activity was significantly decreased. Therefore, DENV NS5 activates RANTES production by increasing NF-κB binding to its binding sites on the RANTES promoter. Copyright © 2014 Elsevier B.V. All rights reserved.

Analysis of Bright Harvest Remote Analysis for Residential Solar Installations

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

Nangle, John; Simon, Joseph

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.

Development of a quantitative NS1-capture enzyme-linked immunosorbent assay for early detection of yellow fever virus infection.

PubMed

Ricciardi-Jorge, Taissa; Bordignon, Juliano; Koishi, Andrea; Zanluca, Camila; Mosimann, Ana Luiza; Duarte Dos Santos, Claudia Nunes

2017-11-24

Yellow fever is an arboviral disease that causes thousands of deaths every year in Africa and the Americas. However, few commercial diagnostic kits are available. Non-structural protein 1 (NS1) is an early marker of several flavivirus infections and is widely used to diagnose dengue virus (DENV) infection. Nonetheless, little is known about the dynamics of Yellow fever virus (YFV) NS1 expression and secretion, to encourage its use in diagnosis. To tackle this issue, we developed a quantitative NS1-capture ELISA specific for YFV using a monoclonal antibody and recombinant NS1 protein. This test was used to quantify NS1 in mosquito and human cell line cultures infected with vaccine and wild YFV strains. Our results showed that NS1 was detectable in the culture supernatants of both cell lines; however, a higher concentration was maintained as cell-associated rather than secreted into the extracellular milieu. A panel of 73 human samples was used to demonstrate the suitability of YFV NS1 as a diagnostic tool, resulting in 80% sensitivity, 100% specificity, a 100% positive predictive value and a 95.5% negative predictive value compared with RT-PCR. Overall, the developed NS1-capture ELISA showed potential as a promising assay for the detection of early YF infection.

Structural characterization of the H-NS protein from Xylella fastidiosa and its interaction with DNA.

PubMed

Rosselli-Murai, Luciana K; Sforça, Maurício L; Sassonia, Rogério C; Azzoni, Adriano R; Murai, Marcelo J; de Souza, Anete P; Zeri, Ana C

2012-10-01

The nucleoid-associated protein H-NS is a major component of the bacterial nucleoid involved in DNA compaction and transcription regulation. The NMR solution structure of the Xylella fastidiosa H-NS C-terminal domain (residues 56-134) is presented here and consists of two beta-strands and two alpha helices, with one loop connecting the two beta-strands and a second loop connecting the second beta strand and the first helix. The amide (1)H and (15)N chemical shift signals for a sample of XfH-NS(56-134) were monitored in the course of a titration series with a 14-bp DNA duplex. Most of the residues involved in contacts to DNA are located around the first and second loops and in the first helix at a positively charged side of the protein surface. The overall structure of the Xylella H-NS C-terminal domain differ significantly from Escherichia coli and Salmonella enterica H-NS proteins, even though the DNA binding motif in loop 2 adopt similar conformation, as well as β-strand 2 and loop 1. Interestingly, we have also found that the DNA binding site is expanded to include helix 1, which is not seen in the other structures. Copyright © 2012 Elsevier Inc. All rights reserved.

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

PubMed

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

2017-03-01

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

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

PubMed

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

2017-07-01

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

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

PubMed

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

2014-10-17

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

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

NASA Astrophysics Data System (ADS)

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

2017-05-01

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

Glycosylation-related genes in NS0 cells are insensitive to moderately elevated ammonium concentrations

PubMed Central

Brodsky, Arthur Nathan; Caldwell, Mary; Bae, Sooneon; Harcum, Sarah W.

2014-01-01

NS0 and Chinese hamster ovary (CHO) cell lines are used to produce recombinant proteins for human therapeutics; however, ammonium accumulation can negatively impact cell growth, recombinant protein production, and protein glycosylation. To improve product quality and decrease costs, the relationship between ammonium and protein glycosylation needs to be elucidated. While ammonium has been shown to adversely affect glycosylation-related gene expression in CHO cells, NS0 studies have not been performed. Therefore, this study sought to determine if glycosylation in NS0 cells were ammonium-sensitive at the gene expression level. Using a DNA microarray that contained mouse glycosylation-related and housekeeping genes, the of these genes was analysed in response to various culture conditions – elevated ammonium, elevated salt, and elevated ammonium with proline. Surprisingly, no significant differences in gene expression levels were observed between the control and these conditions. Further, the elevated ammonium cultures were analysed using real-time quantitative reverse transcriptase PCR (qRT-PCR) for key glycosylation genes, and the qRT-PCR results corroborated the DNA microarray results, demonstrating that NS0 cells are ammonium-insensitive at the gene expression level. Since NS0 are known to have elevated nucleotide sugar pools under ammonium stress, and none of the genes directly responsible for these metabolic pools were changed, consequently cellular control at the translational or substrate-level must be responsible for the universally observed decreased glycosylation quality under elevated ammonium. PMID:25062658

High Precision Photometry of Bright Transiting Exoplanet Hosts

NASA Astrophysics Data System (ADS)

Wilson, Maurice; Eastman, Jason; Johnson, John A.

2016-01-01

Within the past two decades, the successful search for exoplanets and the characterization of their physical properties have shown the immense progress that has been made towards finding planets with characteristics similar to Earth. For most exoplanets with a radius about the size of Earth, evaluating their physical properties, such as the mass, radius and equilibrium temperature, cannot be determined with satisfactory precision. The MINiature Exoplanet Radial Velocity Array (MINERVA) was recently built to obtain spectroscopic and photometric measurements to find, confirm, and characterize Earth-like exoplanets. MINERVA's spectroscopic survey targets the brightest, nearby stars which are well-suited to the array's capabilities, while its primary photometric goal is to search for transits around these bright targets. Typically, it is difficult to find satisfactory comparison stars within a telescope's field of view when the primary target is very bright. This issue is resolved by using one of MINERVA's telescopes to observe the primary bright star while the other telescopes observe a distinct field of view that contains satisfactory bright comparison stars. We describe the code used to identify nearby comparison stars, schedule the four telescopes, produce differential photometry from multiple telescopes, and show the first results from this effort.This work has been funded by the Ronald E. McNair Post-Baccalaureate Achievement Program, the ERAU Honors Program, the ERAU Undergraduate Research Spark Fund, and the Banneker Institute at the Harvard-Smithsonian Center for Astrophysics.

Two cases of false-positive dengue non-structural protein 1 (NS1) antigen in patients with hematological malignancies and a review of the literature on the use of NS1 for the detection of Dengue infection.

PubMed

Chung, Shimin J; Krishnan, Prabha U; Leo, Yee Sin

2015-02-01

Early diagnosis of dengue has been made easier in recent years owing to the advancement in diagnostic technologies. The rapid non-structural protein 1 (NS1) test strip is widely used in many developed and developing regions at risk of dengue. Despite the relatively high specificity of this test, we recently encountered two cases of false-positive dengue NS1 antigen in patients with underlying hematological malignancies. We reviewed the literature for causes of false-positive dengue NS1. © The American Society of Tropical Medicine and Hygiene.

Bright and Dark Slopes on Ganymede

NASA Technical Reports Server (NTRS)

1997-01-01

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

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

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

Brightness discrimination and contrast sensitivity in chronic glaucoma--a clinical study.

PubMed

Teoh, S L; Allan, D; Dutton, G N; Foulds, W S

1990-04-01

The visual acuity, the difference in sensitivity of the two eyes to light (brightness ratio), and contrast sensitivity were assessed in 28 patients with chronic open angle glaucoma and compared with those of 41 normal controls of similar ages and visual acuity. The results obtained were related to the results of Tübingen visual field analysis in patients with glaucoma. Twenty-four of the 28 glaucoma patients (86%) had a significant disparity in brightness ratio between the two eyes. This was found to match the frequency of visual field loss. Moreover, there was a significant relationship between the interocular differences in brightness sense and the difference in the degree of visual field loss between the two eyes. Of the glaucoma patients 39% had sum contrast sensitivities outside the normal range for age-matched normal controls. No significant correlation was found between the interocular difference in brightness sense and the visual acuity or the interocular difference in sum contrast sensitivity. It is concluded that, in the presence of a normal visual acuity, the brightness ratio test warrants evaluation as a potential screening test for chronic open angle glaucoma.

Brightness discrimination and contrast sensitivity in chronic glaucoma--a clinical study.

PubMed Central

Teoh, S L; Allan, D; Dutton, G N; Foulds, W S

1990-01-01

The visual acuity, the difference in sensitivity of the two eyes to light (brightness ratio), and contrast sensitivity were assessed in 28 patients with chronic open angle glaucoma and compared with those of 41 normal controls of similar ages and visual acuity. The results obtained were related to the results of Tübingen visual field analysis in patients with glaucoma. Twenty-four of the 28 glaucoma patients (86%) had a significant disparity in brightness ratio between the two eyes. This was found to match the frequency of visual field loss. Moreover, there was a significant relationship between the interocular differences in brightness sense and the difference in the degree of visual field loss between the two eyes. Of the glaucoma patients 39% had sum contrast sensitivities outside the normal range for age-matched normal controls. No significant correlation was found between the interocular difference in brightness sense and the visual acuity or the interocular difference in sum contrast sensitivity. It is concluded that, in the presence of a normal visual acuity, the brightness ratio test warrants evaluation as a potential screening test for chronic open angle glaucoma. PMID:2186795

Leonids 2017 from Norway – A bright surprise!

NASA Astrophysics Data System (ADS)

Gaarder, K.

2018-01-01

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

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

PubMed Central

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

2016-01-01

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

Twilight sky brightness measurements as a useful tool for stratospheric aerosol investigations

NASA Astrophysics Data System (ADS)

Mateshvili, Nina; Fussen, Didier; Vanhellemont, Filip; Bingen, Christine; KyröLä, Erkki; Mateshvili, Iuri; Mateshvili, Giuli

2005-05-01

In this paper we demonstrate how twilight sky brightness measurements can be used to obtain information about stratospheric aerosols. Beside this, the measurements of the distribution and the variability of the twilight sky brightness may help to understand how the stratospheric aerosols affect the radiation field, which is important for correct calculations of photodissociation rates. Multispectral measurements of twilight sky brightness were carried out in Abastumani Observatory (41.8°N, 42.8°E), Georgia, South Caucasus, during the period (1991-1993) when the level of stratospheric aerosols was substantially enhanced after the 1991 Mount Pinatubo eruption. The twilight sky brightness was measured at 9 wavelengths (422, 474, 496, 542, 610, 642, 678, 713, and 820 nm) for solar zenith angles from 89° to 107°. There are clear indications of a growth of the stratospheric aerosol layer after the eruption of Mount Pinatubo that manifests itself by "humps" in twilight sky brightness dependences versus solar zenith angle. Similar features were obtained using a radiative transfer code constrained by the SAGE II aerosol optical thicknesses. It is shown how an enhancement of stratospheric aerosol loading perturbs the twilight sky brightness due to light scattering and absorption in the aerosol layer. The influence of ozone variations and background stratospheric aerosols on twilight sky brightness has also been analyzed. The optical thicknesses of the stratospheric aerosol layer obtained from the twilight measurements of 1990-1993 show a good agreement with SAGE II results. The spectral variations of the stratospheric aerosol extinction for pre-Pinatubo and post-Pinatubo measurements reflect the aerosol growth after the eruption. Finally, the utilization of twilight sky brightness measurements for validation of satellite-based measurements of the stratospheric aerosol is proposed.

NS1643 Interacts around L529 of hERG to Alter Voltage Sensor Movement on the Path to Activation