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Sample records for broad neutralizing activities

  1. Broadly Neutralizing Activity of Zika Virus-Immune Sera Identifies a Single Viral Serotype.

    Science.gov (United States)

    Dowd, Kimberly A; DeMaso, Christina R; Pelc, Rebecca S; Speer, Scott D; Smith, Alexander R Y; Goo, Leslie; Platt, Derek J; Mascola, John R; Graham, Barney S; Mulligan, Mark J; Diamond, Michael S; Ledgerwood, Julie E; Pierson, Theodore C

    2016-08-01

    Recent epidemics of Zika virus (ZIKV) have been associated with congenital malformation during pregnancy and Guillain-Barré syndrome. There are two ZIKV lineages (African and Asian) that share >95% amino acid identity. Little is known regarding the ability of neutralizing antibodies elicited against one lineage to protect against the other. We investigated the breadth of the neutralizing antibody response following ZIKV infection by measuring the sensitivity of six ZIKV strains to neutralization by ZIKV-confirmed convalescent human serum or plasma samples. Contemporary Asian and early African ZIKV strains were similarly sensitive to neutralization regardless of the cellular source of virus. Furthermore, mouse immune serum generated after infection with African or Asian ZIKV strains was capable of neutralizing homologous and heterologous ZIKV strains equivalently. Because our study only defines a single ZIKV serotype, vaccine candidates eliciting robust neutralizing antibody responses should inhibit infection of both ZIKV lineages, including strains circulating in the Americas. PMID:27481466

  2. Broadly Neutralizing Activity of Zika Virus-Immune Sera Identifies a Single Viral Serotype

    Directory of Open Access Journals (Sweden)

    Kimberly A. Dowd

    2016-08-01

    Full Text Available Recent epidemics of Zika virus (ZIKV have been associated with congenital malformation during pregnancy and Guillain-Barré syndrome. There are two ZIKV lineages (African and Asian that share >95% amino acid identity. Little is known regarding the ability of neutralizing antibodies elicited against one lineage to protect against the other. We investigated the breadth of the neutralizing antibody response following ZIKV infection by measuring the sensitivity of six ZIKV strains to neutralization by ZIKV-confirmed convalescent human serum or plasma samples. Contemporary Asian and early African ZIKV strains were similarly sensitive to neutralization regardless of the cellular source of virus. Furthermore, mouse immune serum generated after infection with African or Asian ZIKV strains was capable of neutralizing homologous and heterologous ZIKV strains equivalently. Because our study only defines a single ZIKV serotype, vaccine candidates eliciting robust neutralizing antibody responses should inhibit infection of both ZIKV lineages, including strains circulating in the Americas.

  3. Specifically modified Env immunogens activate B-cell precursors of broadly neutralizing HIV-1 antibodies in transgenic mice.

    Science.gov (United States)

    McGuire, Andrew T; Gray, Matthew D; Dosenovic, Pia; Gitlin, Alexander D; Freund, Natalia T; Petersen, John; Correnti, Colin; Johnsen, William; Kegel, Robert; Stuart, Andrew B; Glenn, Jolene; Seaman, Michael S; Schief, William R; Strong, Roland K; Nussenzweig, Michel C; Stamatatos, Leonidas

    2016-01-01

    VRC01-class broadly neutralizing HIV-1 antibodies protect animals from experimental infection and could contribute to an effective vaccine response. Their predicted germline forms (gl) bind Env inefficiently, which may explain why they are not elicited by HIV-1 Env-immunization. Here we show that an optimized Env immunogen can engage multiple glVRC01-class antibodies. Furthermore, this immunogen activates naive B cells expressing the human germline heavy chain of 3BNC60, paired with endogenous mouse light chains in vivo. To address whether it activates B cells expressing the fully humanized gl3BNC60 B-cell receptor (BCR), we immunized mice carrying both the heavy and light chains of gl3BNC60. B cells expressing this BCR display an autoreactive phenotype and fail to respond efficiently to soluble forms of the optimized immunogen, unless it is highly multimerized. Thus, specifically designed Env immunogens can activate naive B cells expressing human BCRs corresponding to precursors of broadly neutralizing HIV-1 antibodies even when the B cells display an autoreactive phenotype. PMID:26907590

  4. Neutralization of low energy broad ion beam

    International Nuclear Information System (INIS)

    The paper is devoted to experimental and theoretical investigation of a low energy broad ion beam space charge and current compensation and ion-beam plasma (IBP), which would be created in transport space of the beam. The beam had cylindrical symmetry. The continuous uniform and hole tube like ion beams are used in the experiments. Different channels of electron appearing have been investigated for cases of neutralization due to secondary γ-electrons from the target and by electrons from glow cathode-neutralizer with metal or dielectric target. Results of neutralizing electrons energy distributions function measurements are presented as well as dependences of electron temperature and self-consisted plasma potential vs. beam parameters, ambient gas pressure, neutralizer parameters. Role of the thermoelectrons and dependence of IBP parameters on neutralizer area, location and potential are discussed. Significant role in neutralization of spatial collisional processes has been revealed even in neutralization by thermocathode. On the base of the experimental results self-consistent theoretical model have been developed, which describes the behavior of intense ion beam passing through the neutral gas at low pressure within conductive walls. The collisionless approach is used which means absence of collisional relaxation of the beam. This theory is used to derive the plasma potential and electron temperature within the beam

  5. 9G4 autoreactivity is increased in HIV-infected patients and correlates with HIV broadly neutralizing serum activity.

    Directory of Open Access Journals (Sweden)

    James J Kobie

    Full Text Available The induction of a broadly neutralizing antibody (BNAb response against HIV-1 would be a desirable feature of a protective vaccine. Vaccine strategies thus far have failed to elicit broadly neutralizing antibody responses; however a minority of HIV-infected patients do develop circulating BNAbs, from which several potent broadly neutralizing monoclonal antibodies (mAbs have been isolated. The findings that several BNmAbs exhibit autoreactivity and that autoreactive serum antibodies are observed in some HIV patients have advanced the possibility that enforcement of self-tolerance may contribute to the rarity of BNAbs. To examine the possible breakdown of tolerance in HIV patients, we utilized the 9G4 anti-idiotype antibody system, enabling resolution of both autoreactive VH4-34 gene-expressing B cells and serum antibodies. Compared with healthy controls, HIV patients had significantly elevated 9G4+ serum IgG antibody concentrations and frequencies of 9G4+ B cells, a finding characteristic of systemic lupus erythematosus (SLE patients, both of which positively correlated with HIV viral load. Compared to the global 9G4-IgD--memory B cell population, the 9G4+IgD--memory fraction in HIV patients was dominated by isotype switched IgG+ B cells, but had a more prominent bias toward "IgM only" memory. HIV envelope reactivity was observed both in the 9G4+ serum antibody and 9G4+ B cell population. 9G4+ IgG serum antibody levels positively correlated (r = 0.403, p = 0.0019 with the serum HIV BNAbs. Interestingly, other serum autoantibodies commonly found in SLE (anti-dsDNA, ANA, anti-CL did not correlate with serum HIV BNAbs. 9G4-associated autoreactivity is preferentially expanded in chronic HIV infection as compared to other SLE autoreactivities. Therefore, the 9G4 system provides an effective tool to examine autoreactivity in HIV patients. Our results suggest that the development of HIV BNAbs is not merely a consequence of a general breakdown in

  6. Engineering broadly neutralizing antibodies for HIV prevention and therapy.

    Science.gov (United States)

    Hua, Casey K; Ackerman, Margaret E

    2016-08-01

    A combination of advances spanning from isolation to delivery of potent HIV-specific antibodies has begun to revolutionize understandings of antibody-mediated antiviral activity. As a result, the set of broadly neutralizing and highly protective antibodies has grown in number, diversity, potency, and breadth of viral recognition and neutralization. These antibodies are now being further enhanced by rational engineering of their anti-HIV activities and coupled to cutting edge gene delivery and strategies to optimize their pharmacokinetics and biodistribution. As a result, the prospects for clinical use of HIV-specific antibodies to treat, clear, and prevent HIV infection are gaining momentum. Here we discuss the diverse methods whereby antibodies are being optimized for neutralization potency and breadth, biodistribution, pharmacokinetics, and effector function with the aim of revolutionizing HIV treatment and prevention options. PMID:26827912

  7. Structural basis of hepatitis C virus neutralization by broadly neutralizing antibody HCV1

    Energy Technology Data Exchange (ETDEWEB)

    Kong, Leopold; Giang, Erick; Robbins, Justin B.; Stanfield, Robyn L.; Burton, Dennis R.; Wilson, Ian A.; Law, Mansun (Scripps)

    2012-10-29

    Hepatitis C virus (HCV) infects more than 2% of the global population and is a leading cause of liver cirrhosis, hepatocellular carcinoma, and end-stage liver diseases. Circulating HCV is genetically diverse, and therefore a broadly effective vaccine must target conserved T- and B-cell epitopes of the virus. Human mAb HCV1 has broad neutralizing activity against HCV isolates from at least four major genotypes and protects in the chimpanzee model from primary HCV challenge. The antibody targets a conserved antigenic site (residues 412-423) on the virus E2 envelope glycoprotein. Two crystal structures of HCV1 Fab in complex with an epitope peptide at 1.8-{angstrom} resolution reveal that the epitope is a {beta}-hairpin displaying a hydrophilic face and a hydrophobic face on opposing sides of the hairpin. The antibody predominantly interacts with E2 residues Leu{sup 413} and Trp{sup 420} on the hydrophobic face of the epitope, thus providing an explanation for how HCV isolates bearing mutations at Asn{sup 415} on the same binding face escape neutralization by this antibody. The results provide structural information for a neutralizing epitope on the HCV E2 glycoprotein and should help guide rational design of HCV immunogens to elicit similar broadly neutralizing antibodies through vaccination.

  8. Broadly Neutralizing Antibody Responses in a Large Longitudinal Sub-Saharan HIV Primary Infection Cohort.

    Directory of Open Access Journals (Sweden)

    Elise Landais

    2016-01-01

    Full Text Available Broadly neutralizing antibodies (bnAbs are thought to be a critical component of a protective HIV vaccine. However, designing vaccines immunogens able to elicit bnAbs has proven unsuccessful to date. Understanding the correlates and immunological mechanisms leading to the development of bnAb responses during natural HIV infection is thus critical to the design of a protective vaccine. The IAVI Protocol C program investigates a large longitudinal cohort of primary HIV-1 infection in Eastern and South Africa. Development of neutralization was evaluated in 439 donors using a 6 cross-clade pseudo-virus panel predictive of neutralization breadth on larger panels. About 15% of individuals developed bnAb responses, essentially between year 2 and year 4 of infection. Statistical analyses revealed no influence of gender, age or geographical origin on the development of neutralization breadth. However, cross-clade neutralization strongly correlated with high viral load as well as with low CD4 T cell counts, subtype-C infection and HLA-A*03(- genotype. A correlation with high overall plasma IgG levels and anti-Env IgG binding titers was also found. The latter appeared not associated with higher affinity, suggesting a greater diversity of the anti-Env responses in broad neutralizers. Broadly neutralizing activity targeting glycan-dependent epitopes, largely the N332-glycan epitope region, was detected in nearly half of the broad neutralizers while CD4bs and gp41-MPER bnAb responses were only detected in very few individuals. Together the findings suggest that both viral and host factors are critical for the development of bnAbs and that the HIV Env N332-glycan supersite may be a favorable target for vaccine design.

  9. "Unconventional" Neutralizing Activity of Antibodies Against HIV

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Neutralizing antibodies are recognized to be one of the essential elements of the adaptive immune response that must be induced by an effective vaccine against HIV. However, only a limited number of antibodies have been identified to neutralize a broad range of primary isolates of HIV-1 and attempts to induce such antibodies by immunization were unsuccessful. The difficulties to generate such antibodies are mainly due to intrinsic properties of HIV-1 envelope spikes, such as high sequence diversity, heavy glycosylation, and inducible and transient nature of certain epitopes. In vitro neutralizing antibodies are identified using "conventional" neutralization assay which uses phytohemagglutinin (PHA)-stimulated human PBMCs as target cells. Thus, in essence the assay evaluates HIV-1 replication in CD4+ T cells. Recently, several laboratories including us demonstrated that some monoclonal antibodies and HIV-1-specific polyclonal IgG purified from patient sera, although they do not have neutralizing activity when tested by the "conventional" neutralization assay, do exhibit potent and broad neutralizing activity in "unconventional" ways. The neutralizing activity of these antibodies and IgG fractions is acquired through post-translational modifications, through opsonization of virus particles into macrophages and immature dendritic cells (iDCs), or through expression of antibodies on the surface of HIV-1-susceptible cells. This review will focus on recent findings of this area and point out their potential applications in the development of preventive strategies against HIV.

  10. Broadly Neutralizing Alphavirus Antibodies Bind an Epitope on E2 and Inhibit Entry and Egress.

    Science.gov (United States)

    Fox, Julie M; Long, Feng; Edeling, Melissa A; Lin, Hueylie; van Duijl-Richter, Mareike K S; Fong, Rachel H; Kahle, Kristen M; Smit, Jolanda M; Jin, Jing; Simmons, Graham; Doranz, Benjamin J; Crowe, James E; Fremont, Daved H; Rossmann, Michael G; Diamond, Michael S

    2015-11-19

    We screened a panel of mouse and human monoclonal antibodies (MAbs) against chikungunya virus and identified several with inhibitory activity against multiple alphaviruses. Passive transfer of broadly neutralizing MAbs protected mice against infection by chikungunya, Mayaro, and O'nyong'nyong alphaviruses. Using alanine-scanning mutagenesis, loss-of-function recombinant proteins and viruses, and multiple functional assays, we determined that broadly neutralizing MAbs block multiple steps in the viral lifecycle, including entry and egress, and bind to a conserved epitope on the B domain of the E2 glycoprotein. A 16 Å resolution cryo-electron microscopy structure of a Fab fragment bound to CHIKV E2 B domain provided an explanation for its neutralizing activity. Binding to the B domain was associated with repositioning of the A domain of E2 that enabled cross-linking of neighboring spikes. Our results suggest that B domain antigenic determinants could be targeted for vaccine or antibody therapeutic development against multiple alphaviruses of global concern. PMID:26553503

  11. The Effects of Somatic Hypermutation on Neutralization and Binding in the PGT121 Family of Broadly Neutralizing HIV Antibodies

    Science.gov (United States)

    Vigneault, Francois; Julien, Jean-Philippe; Briney, Bryan; Ramos, Alejandra; Saye, Karen F.; Le, Khoa; Mahan, Alison; Wang, Shenshen; Kardar, Mehran; Yaari, Gur; Walker, Laura M.; Simen, Birgitte B.; St. John, Elizabeth P.; Chan-Hui, Po-Ying; Swiderek, Kristine; Kleinstein, Stephen H.; Alter, Galit; Seaman, Michael S.; Chakraborty, Arup K.; Koller, Daphne; Wilson, Ian A.; Church, George M.; Burton, Dennis R.; Poignard, Pascal

    2013-01-01

    Broadly neutralizing HIV antibodies (bnAbs) are typically highly somatically mutated, raising doubts as to whether they can be elicited by vaccination. We used 454 sequencing and designed a novel phylogenetic method to model lineage evolution of the bnAbs PGT121–134 and found a positive correlation between the level of somatic hypermutation (SHM) and the development of neutralization breadth and potency. Strikingly, putative intermediates were characterized that show approximately half the mutation level of PGT121–134 but were still capable of neutralizing roughly 40–80% of PGT121–134 sensitive viruses in a 74-virus panel at median titers between 15- and 3-fold higher than PGT121–134. Such antibodies with lower levels of SHM may be more amenable to elicitation through vaccination while still providing noteworthy coverage. Binding characterization indicated a preference of inferred intermediates for native Env binding over monomeric gp120, suggesting that the PGT121–134 lineage may have been selected for binding to native Env at some point during maturation. Analysis of glycan-dependent neutralization for inferred intermediates identified additional adjacent glycans that comprise the epitope and suggests changes in glycan dependency or recognition over the course of affinity maturation for this lineage. Finally, patterns of neutralization of inferred bnAb intermediates suggest hypotheses as to how SHM may lead to potent and broad HIV neutralization and provide important clues for immunogen design. PMID:24278016

  12. Broadly Neutralizing Anti-Influenza Virus Antibodies: Enhancement of Neutralizing Potency in Polyclonal Mixtures and IgA Backbones

    OpenAIRE

    He, Wenqian; Mullarkey, Caitlin E; Duty, J. Andrew; Moran, Thomas M.; Palese, Peter; Miller, Matthew S.

    2015-01-01

    Current influenza virus vaccines rely upon the accurate prediction of circulating virus strains months in advance of the actual influenza season in order to allow time for vaccine manufacture. Unfortunately, mismatches occur frequently, and even when perfect matches are achieved, suboptimal vaccine efficacy leaves several high-risk populations vulnerable to infection. However, the recent discovery of broadly neutralizing antibodies that target the hemagglutinin (HA) stalk domain has renewed h...

  13. Two Escape Mechanisms of Influenza A Virus to a Broadly Neutralizing Stalk-Binding Antibody

    Science.gov (United States)

    Chai, Ning; Swem, Lee R.; Reichelt, Mike; Chen-Harris, Haiyin; Luis, Elizabeth; Park, Summer; Fouts, Ashley; Lupardus, Patrick; Wu, Thomas D.; Li, Olga; McBride, Jacqueline; Lawrence, Michael; Xu, Min; Tan, Man-Wah

    2016-01-01

    Broadly neutralizing antibodies targeting the stalk region of influenza A virus (IAV) hemagglutinin (HA) are effective in blocking virus infection both in vitro and in vivo. The highly conserved epitopes recognized by these antibodies are critical for the membrane fusion function of HA and therefore less likely to be permissive for virus mutational escape. Here we report three resistant viruses of the A/Perth/16/2009 strain that were selected in the presence of a broadly neutralizing stalk-binding antibody. The three resistant viruses harbor three different mutations in the HA stalk: (1) Gln387Lys; (2) Asp391Tyr; (3) Asp391Gly. The Gln387Lys mutation completely abolishes binding of the antibody to the HA stalk epitope. The other two mutations, Asp391Tyr and Asp391Gly, do not affect antibody binding at neutral pH and only slightly reduce binding at low pH. Interestingly, they enhance the fusion ability of the HA, representing a novel mechanism that allows productive membrane fusion even in the presence of antibody and hence virus escape from antibody neutralization. Therefore, these mutations illustrate two different resistance mechanisms used by IAV to escape broadly neutralizing stalk-binding antibodies. Compared to the wild type virus, the resistant viruses release fewer progeny viral particles during replication and are more sensitive to Tamiflu, suggesting reduced viral fitness. PMID:27351973

  14. A Potent and Broad Neutralizing Antibody Recognizes and Penetrates the HIV Glycan Shield

    NARCIS (Netherlands)

    R. Pejchal; K.J. Doores; L.M. Walker; R. Khayat; P.S. Huang; S.K. Wang; R.L. Stanfield; J.P. Julien; A. Ramos; M. Crispin; R. Depetris; U. Katpally; A. Marozsan; A. Cupo; S. Maloveste; Y. Liu; R. McBride; Y. Ito; R.W. Sanders; C. Ogohara; J.C. Paulson; T. Feizi; C.N. Scanlan; C.H. Wong; J.P. Moore; W.C. Olson; A.B. Ward; P. Poignard; W.R. Schief; D.R. Burton; I.A. Wilson

    2011-01-01

    The HIV envelope (Env) protein gp120 is protected from antibody recognition by a dense glycan shield. However, several of the recently identified PGT broadly neutralizing antibodies appear to interact directly with the HIV glycan coat. Crystal structures of antigen-binding fragments (Fabs) PGT 127 a

  15. A Potent and Broad Neutralizing Antibody Recognizes and Penetrates the HIV Glycan Shield

    Energy Technology Data Exchange (ETDEWEB)

    Pejchal, Robert; Doores, Katie J.; Walker, Laura M.; Khayat, Reza; Huang, Po-Ssu; Wang, Sheng-Kai; Stanfield, Robyn L.; Julien, Jean-Philippe; Ramos, Alejandra; Crispin, Max; Depetris, Rafael; Katpally, Umesh; Marozsan, Andre; Cupo, Albert; Maloveste, Sebastien; Liu, Yan; McBride, Ryan; Ito, Yukishige; Sanders, Rogier W.; Ogohara, Cassandra; Paulson, James C.; Feizi, Ten; Scanlan, Christopher N.; Wong, Chi-Huey; Moore, John P.; Olson, William C.; Ward, Andrew B.; Poignard, Pascal; Schief, William R.; Burton, Dennis R.; Wilson, Ian A. (UWASH); (Progenics); (ICL); (Weill-Med); (NIH); (JSTA); (Scripps); (Oxford)

    2015-10-15

    The HIV envelope (Env) protein gp120 is protected from antibody recognition by a dense glycan shield. However, several of the recently identified PGT broadly neutralizing antibodies appear to interact directly with the HIV glycan coat. Crystal structures of antigen-binding fragments (Fabs) PGT 127 and 128 with Man{sub 9} at 1.65 and 1.29 angstrom resolution, respectively, and glycan binding data delineate a specific high mannose-binding site. Fab PGT 128 complexed with a fully glycosylated gp120 outer domain at 3.25 angstroms reveals that the antibody penetrates the glycan shield and recognizes two conserved glycans as well as a short {beta}-strand segment of the gp120 V3 loop, accounting for its high binding affinity and broad specificify. Furthermore, our data suggest that the high neutralization potency of PGT 127 and 128 immunoglobulin Gs may be mediated by cross-linking Env trimers on the viral surface.

  16. Enhanced clearance of HIV-1-infected cells by broadly neutralizing antibodies against HIV-1 in vivo.

    Science.gov (United States)

    Lu, Ching-Lan; Murakowski, Dariusz K; Bournazos, Stylianos; Schoofs, Till; Sarkar, Debolina; Halper-Stromberg, Ariel; Horwitz, Joshua A; Nogueira, Lilian; Golijanin, Jovana; Gazumyan, Anna; Ravetch, Jeffrey V; Caskey, Marina; Chakraborty, Arup K; Nussenzweig, Michel C

    2016-05-20

    Antiretroviral drugs and antibodies limit HIV-1 infection by interfering with the viral life cycle. In addition, antibodies also have the potential to guide host immune effector cells to kill HIV-1-infected cells. Examination of the kinetics of HIV-1 suppression in infected individuals by passively administered 3BNC117, a broadly neutralizing antibody, suggested that the effects of the antibody are not limited to free viral clearance and blocking new infection but also include acceleration of infected cell clearance. Consistent with these observations, we find that broadly neutralizing antibodies can target CD4(+) T cells infected with patient viruses and can decrease their in vivo half-lives by a mechanism that requires Fcγ receptor engagement in a humanized mouse model. The results indicate that passive immunotherapy can accelerate elimination of HIV-1-infected cells. PMID:27199430

  17. Elicitation of broadly neutralizing influenza antibodies in animals with previous influenza exposure.

    Science.gov (United States)

    Wei, Chih-Jen; Yassine, Hadi M; McTamney, Patrick M; Gall, Jason G D; Whittle, James R R; Boyington, Jeffrey C; Nabel, Gary J

    2012-08-15

    The immune system responds to influenza infection by producing neutralizing antibodies to the viral surface protein, hemagglutinin (HA), which regularly changes its antigenic structure. Antibodies that target the highly conserved stem region of HA neutralize diverse influenza viruses and can be elicited through vaccination in animals and humans. Efforts to develop universal influenza vaccines have focused on strategies to elicit such antibodies; however, the concern has been raised that previous influenza immunity may abrogate the induction of such broadly protective antibodies. We show here that prime-boost immunization can induce broadly neutralizing antibody responses in influenza-immune mice and ferrets that were previously infected or vaccinated. HA stem-directed antibodies were elicited in mice primed with a DNA vaccine and boosted with inactivated vaccine from H1N1 A/New Caledonia/20/1999 (1999 NC) HA regardless of preexposure. Similarly, gene-based vaccination with replication-defective adenovirus 28 (rAd28) and 5 (rAd5) vectors encoding 1999 NC HA elicited stem-directed neutralizing antibodies and conferred protection against unmatched 1934 and 2007 H1N1 virus challenge in influenza-immune ferrets. Indeed, previous exposure to certain strains could enhance immunogenicity: The strongest HA stem-directed immune response was observed in ferrets previously infected with a divergent 1934 H1N1 virus. These findings suggest that broadly neutralizing antibodies against the conserved stem region of HA can be elicited through vaccination despite previous influenza exposure, which supports the feasibility of developing stem-directed universal influenza vaccines for humans. PMID:22896678

  18. Broad iron lines in Active Galactic Nuclei

    CERN Document Server

    Fabian, A C; Reynolds, C S; Young, A J

    2000-01-01

    An intrinsically narrow line emitted by an accretion disk around a black hole appears broadened and skewed as a result of the Doppler effect and gravitational redshift. The fluorescent iron line in the X-ray band at 6.4-6.9keV is the strongest such line and is seen in the X-ray spectrum of many active galactic nuclei and, in particular, Seyfert galaxies. It is an important diagnostic with which to study the geometry and other properties of the accretion flow very close to the central black hole. The broad iron line indicates the presence of a standard thin accretion disk in those objects, often seen at low inclination. The broad iron line has opened up strong gravitational effects around black holes to observational study with wide-reaching consequences for both astrophysics and physics.

  19. Induction of broadly neutralizing H1N1 influenza antibodies by vaccination.

    Science.gov (United States)

    Wei, Chih-Jen; Boyington, Jeffrey C; McTamney, Patrick M; Kong, Wing-Pui; Pearce, Melissa B; Xu, Ling; Andersen, Hanne; Rao, Srinivas; Tumpey, Terrence M; Yang, Zhi-Yong; Nabel, Gary J

    2010-08-27

    The rapid dissemination of the 2009 pandemic influenza virus underscores the need for universal influenza vaccines that elicit protective immunity to diverse viral strains. Here, we show that vaccination with plasmid DNA encoding H1N1 influenza hemagglutinin (HA) and boosting with seasonal vaccine or replication-defective adenovirus 5 vector encoding HA stimulated the production of broadly neutralizing influenza antibodies. This prime/boost combination increased the neutralization of diverse H1N1 strains dating from 1934 to 2007 as compared to either component alone and conferred protection against divergent H1N1 viruses in mice and ferrets. These antibodies were directed to the conserved stem region of HA and were also elicited in nonhuman primates. Cross-neutralization of H1N1 subtypes elicited by this approach provides a basis for the development of a universal influenza vaccine for humans. PMID:20647428

  20. Structural Basis for Recognition of Human Enterovirus 71 by a Bivalent Broadly Neutralizing Monoclonal Antibody.

    Science.gov (United States)

    Ye, Xiaohua; Fan, Chen; Ku, Zhiqiang; Zuo, Teng; Kong, Liangliang; Zhang, Chao; Shi, Jinping; Liu, Qingwei; Chen, Tan; Zhang, Yingyi; Jiang, Wen; Zhang, Linqi; Huang, Zhong; Cong, Yao

    2016-03-01

    Enterovirus 71 (EV71) is the main pathogen responsible for hand, foot and mouth disease with severe neurological complications and even death in young children. We have recently identified a highly potent anti-EV71 neutralizing monoclonal antibody, termed D5. Here we investigated the structural basis for recognition of EV71 by the antibody D5. Four three-dimensional structures of EV71 particles in complex with IgG or Fab of D5 were reconstructed by cryo-electron microscopy (cryo-EM) single particle analysis all at subnanometer resolutions. The most critical EV71 mature virion-Fab structure was resolved to a resolution of 4.8 Å, which is rare in cryo-EM studies of virus-antibody complex so far. The structures reveal a bivalent binding pattern of D5 antibody across the icosahedral 2-fold axis on mature virion, suggesting that D5 binding may rigidify virions to prevent their conformational changes required for subsequent RNA release. Moreover, we also identified that the complementary determining region 3 (CDR3) of D5 heavy chain directly interacts with the extremely conserved VP1 GH-loop of EV71, which was validated by biochemical and virological assays. We further showed that D5 is indeed able to neutralize a variety of EV71 genotypes and strains. Moreover, D5 could potently confer protection in a mouse model of EV71 infection. Since the conserved VP1 GH-loop is involved in EV71 binding with its uncoating receptor, the scavenger receptor class B, member 2 (SCARB2), the broadly neutralizing ability of D5 might attribute to its inhibition of EV71 from binding SCARB2. Altogether, our results elucidate the structural basis for the binding and neutralization of EV71 by the broadly neutralizing antibody D5, thereby enhancing our understanding of antibody-based protection against EV71 infection. PMID:26938634

  1. Structural Basis for Recognition of Human Enterovirus 71 by a Bivalent Broadly Neutralizing Monoclonal Antibody.

    Directory of Open Access Journals (Sweden)

    Xiaohua Ye

    2016-03-01

    Full Text Available Enterovirus 71 (EV71 is the main pathogen responsible for hand, foot and mouth disease with severe neurological complications and even death in young children. We have recently identified a highly potent anti-EV71 neutralizing monoclonal antibody, termed D5. Here we investigated the structural basis for recognition of EV71 by the antibody D5. Four three-dimensional structures of EV71 particles in complex with IgG or Fab of D5 were reconstructed by cryo-electron microscopy (cryo-EM single particle analysis all at subnanometer resolutions. The most critical EV71 mature virion-Fab structure was resolved to a resolution of 4.8 Å, which is rare in cryo-EM studies of virus-antibody complex so far. The structures reveal a bivalent binding pattern of D5 antibody across the icosahedral 2-fold axis on mature virion, suggesting that D5 binding may rigidify virions to prevent their conformational changes required for subsequent RNA release. Moreover, we also identified that the complementary determining region 3 (CDR3 of D5 heavy chain directly interacts with the extremely conserved VP1 GH-loop of EV71, which was validated by biochemical and virological assays. We further showed that D5 is indeed able to neutralize a variety of EV71 genotypes and strains. Moreover, D5 could potently confer protection in a mouse model of EV71 infection. Since the conserved VP1 GH-loop is involved in EV71 binding with its uncoating receptor, the scavenger receptor class B, member 2 (SCARB2, the broadly neutralizing ability of D5 might attribute to its inhibition of EV71 from binding SCARB2. Altogether, our results elucidate the structural basis for the binding and neutralization of EV71 by the broadly neutralizing antibody D5, thereby enhancing our understanding of antibody-based protection against EV71 infection.

  2. Broad neutralizing human monoclonal antibodies against influenza virus from vaccinated healthy donors

    Energy Technology Data Exchange (ETDEWEB)

    Kubota-Koketsu, Ritsuko; Mizuta, Hiroyuki [Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871 (Japan); Oshita, Masatoshi; Ideno, Shoji [Osaka Research Laboratory, Benesis Corporation, Yodogawa-ku, Osaka 532-6505 (Japan); Yunoki, Mikihiro [Osaka Research Laboratory, Benesis Corporation, Yodogawa-ku, Osaka 532-6505 (Japan); Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871 (Japan); Kuhara, Motoki [Ina Laboratory, Medical and Biological Laboratories Corporation, Ltd., Ina, Nagano 396-0002 (Japan); Yamamoto, Naomasa [Department of Biochemistry, School of Pharmaceutical Sciences, Ohu University, Koriyama, Fukushima 963-8611 (Japan); Okuno, Yoshinobu [Kanonji Institute, The Research Foundation for Microbial Diseases of Osaka University, Kanonji, Kagawa 768-0061 (Japan); Ikuta, Kazuyoshi, E-mail: ikuta@biken.osaka-u.ac.jp [Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871 (Japan)

    2009-09-11

    Human monoclonal antibodies (HuMAbs) prepared from patients with viral infections could provide information on human epitopes important for the development of vaccines as well as potential therapeutic applications. Through the fusion of peripheral blood mononuclear cells from a total of five influenza-vaccinated volunteers, with newly developed murine-human chimera fusion partner cells, named SPYMEG, we obtained 10 hybridoma clones stably producing anti-influenza virus antibodies: one for influenza A H1N1, four for influenza A H3N2 and five for influenza B. Surprisingly, most of the HuMAbs showed broad reactivity within subtype and four (two for H3N2 and two for B) showed broad neutralizing ability. Importantly, epitope mapping revealed that the two broad neutralizing antibodies to H3N2 derived from different donors recognized the same epitope located underneath the receptor-binding site of the hemagglutinin globular region that is highly conserved among H3N2 strains.

  3. Broad neutralizing human monoclonal antibodies against influenza virus from vaccinated healthy donors

    International Nuclear Information System (INIS)

    Human monoclonal antibodies (HuMAbs) prepared from patients with viral infections could provide information on human epitopes important for the development of vaccines as well as potential therapeutic applications. Through the fusion of peripheral blood mononuclear cells from a total of five influenza-vaccinated volunteers, with newly developed murine-human chimera fusion partner cells, named SPYMEG, we obtained 10 hybridoma clones stably producing anti-influenza virus antibodies: one for influenza A H1N1, four for influenza A H3N2 and five for influenza B. Surprisingly, most of the HuMAbs showed broad reactivity within subtype and four (two for H3N2 and two for B) showed broad neutralizing ability. Importantly, epitope mapping revealed that the two broad neutralizing antibodies to H3N2 derived from different donors recognized the same epitope located underneath the receptor-binding site of the hemagglutinin globular region that is highly conserved among H3N2 strains.

  4. AAV Natural Infection Induces Broad Cross-Neutralizing Antibody Responses to Multiple AAV Serotypes in Chimpanzees.

    Science.gov (United States)

    Calcedo, Roberto; Wilson, James M

    2016-06-01

    Cross-sectional studies of primates have revealed that natural neutralizing antibody (NAb) responses to adeno-associated viruses (AAV) span multiple serotypes. This differs from the phenotype of the NAb response to an AAV vector delivered to seronegative nonhuman primates that is typically restricted to the administered AAV serotype. To better understand the mechanism by which natural AAV infections result in broad NAb responses, we conducted a longitudinal study spanning 10 years in which we evaluated serum-circulating AAV NAb levels in captive-housed chimpanzees. In a cohort of 25 chimpanzees we identified 3 distinct groups of animals: those that never seroconverted to AAV (naïve), those that were persistently seropositive (chronic), and those that seroconverted during the 10-year period (acute). For the chronic group we found a broad seroresponse characterized by NAbs reacting to multiple AAV serotypes. A similar cross-neutralization pattern of NAbs was observed in the acute group. These data support our hypothesis that a single natural infection with AAV induces a broadly cross-reactive NAb response to multiple AAV serotypes. PMID:27314914

  5. Targeting N-Glycan Cryptic Sugar Moieties for Broad-Spectrum Virus Neutralization: Progress in Identifying Conserved Molecular Targets in Viruses of Distinct Phylogenetic Origins

    Directory of Open Access Journals (Sweden)

    Denong Wang

    2015-03-01

    Full Text Available Identifying molecular targets for eliciting broadly virus-neutralizing antibodies is one of the key steps toward development of vaccines against emerging viral pathogens. Owing to genomic and somatic diversities among viral species, identifying protein targets for broad-spectrum virus neutralization is highly challenging even for the same virus, such as HIV-1. However, viruses rely on host glycosylation machineries to synthesize and express glycans and, thereby, may display common carbohydrate moieties. Thus, exploring glycan-binding profiles of broad-spectrum virus-neutralizing agents may provide key information to uncover the carbohydrate-based virus-neutralizing epitopes. In this study, we characterized two broadly HIV-neutralizing agents, human monoclonal antibody 2G12 and Galanthus nivalis lectin (GNA, for their viral targeting activities. Although these agents were known to be specific for oligomannosyl antigens, they differ strikingly in virus-binding activities. The former is HIV-1 specific; the latter is broadly reactive and is able to neutralize viruses of distinct phylogenetic origins, such as HIV-1, severe acute respiratory syndrome coronavirus (SARS-CoV, and human cytomegalovirus (HCMV. In carbohydrate microarray analyses, we explored the molecular basis underlying the striking differences in the spectrum of anti-virus activities of the two probes. Unlike 2G12, which is strictly specific for the high-density Man9GlcNAc2Asn (Man9-clusters, GNA recognizes a number of N-glycan cryptic sugar moieties. These include not only the known oligomannosyl antigens but also previously unrecognized tri-antennary or multi-valent GlcNAc-terminating N-glycan epitopes (Tri/m-Gn. These findings highlight the potential of N-glycan cryptic sugar moieties as conserved targets for broad-spectrum virus neutralization and suggest the GNA-model of glycan-binding warrants focused investigation.

  6. A broadly flavivirus cross-neutralizing monoclonal antibody that recognizes a novel epitope within the fusion loop of E protein.

    Directory of Open Access Journals (Sweden)

    Yong-Qiang Deng

    Full Text Available Flaviviruses are a group of human pathogenic, enveloped RNA viruses that includes dengue (DENV, yellow fever (YFV, West Nile (WNV, and Japanese encephalitis (JEV viruses. Cross-reactive antibodies against Flavivirus have been described, but most of them are generally weakly neutralizing. In this study, a novel monoclonal antibody, designated mAb 2A10G6, was determined to have broad cross-reactivity with DENV 1-4, YFV, WNV, JEV, and TBEV. Phage-display biopanning and structure modeling mapped 2A10G6 to a new epitope within the highly conserved flavivirus fusion loop peptide, the (98DRXW(101 motif. Moreover, in vitro and in vivo experiments demonstrated that 2A10G6 potently neutralizes DENV 1-4, YFV, and WNV and confers protection from lethal challenge with DENV 1-4 and WNV in murine model. Furthermore, functional studies revealed that 2A10G6 blocks infection at a step after viral attachment. These results define a novel broadly flavivirus cross-reactive mAb with highly neutralizing activity that can be further developed as a therapeutic agent against severe flavivirus infections in humans.

  7. Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza virus hemagglutinin

    Energy Technology Data Exchange (ETDEWEB)

    Whittle, James R.R.; Zhang, Ruijun; Khurana, Surender; King, Lisa R.; Manischewitz, Jody; Golding, Hana; Dormitzer, Philip R.; Haynes, Barton F.; Walter, Emmanuel B.; Moody, M. Anthony; Kepler, Thomas B.; Liao, Hua-Xin; Harrison, Stephen C. (Harvard-Med); (Novartis); (US-FDA); (Duke)

    2011-09-20

    Seasonal antigenic drift of circulating influenza virus leads to a requirement for frequent changes in vaccine composition, because exposure or vaccination elicits human antibodies with limited cross-neutralization of drifted strains. We describe a human monoclonal antibody, CH65, obtained by isolating rearranged heavy- and light-chain genes from sorted single plasma cells, coming from a subject immunized with the 2007 trivalent influenza vaccine. The crystal structure of a complex of the hemagglutinin (HA) from H1N1 strain A/Solomon Islands/3/2006 with the Fab of CH65 shows that the tip of the CH65 heavy-chain complementarity determining region 3 (CDR3) inserts into the receptor binding pocket on HA1, mimicking in many respects the interaction of the physiological receptor, sialic acid. CH65 neutralizes infectivity of 30 out of 36 H1N1 strains tested. The resistant strains have a single-residue insertion near the rim of the sialic-acid pocket. We conclude that broad neutralization of influenza virus can be achieved by antibodies with contacts that mimic those of the receptor.

  8. Minimally Mutated HIV-1 Broadly Neutralizing Antibodies to Guide Reductionist Vaccine Design.

    Science.gov (United States)

    Jardine, Joseph G; Sok, Devin; Julien, Jean-Philippe; Briney, Bryan; Sarkar, Anita; Liang, Chi-Hui; Scherer, Erin A; Henry Dunand, Carole J; Adachi, Yumiko; Diwanji, Devan; Hsueh, Jessica; Jones, Meaghan; Kalyuzhniy, Oleksandr; Kubitz, Michael; Spencer, Skye; Pauthner, Matthias; Saye-Francisco, Karen L; Sesterhenn, Fabian; Wilson, Patrick C; Galloway, Denise M; Stanfield, Robyn L; Wilson, Ian A; Burton, Dennis R; Schief, William R

    2016-08-01

    An optimal HIV vaccine should induce broadly neutralizing antibodies (bnAbs) that neutralize diverse viral strains and subtypes. However, potent bnAbs develop in only a small fraction of HIV-infected individuals, all contain rare features such as extensive mutation, insertions, deletions, and/or long complementarity-determining regions, and some are polyreactive, casting doubt on whether bnAbs to HIV can be reliably induced by vaccination. We engineered two potent VRC01-class bnAbs that minimized rare features. According to a quantitative features frequency analysis, the set of features for one of these minimally mutated bnAbs compared favorably with all 68 HIV bnAbs analyzed and was similar to antibodies elicited by common vaccines. This same minimally mutated bnAb lacked polyreactivity in four different assays. We then divided the minimal mutations into spatial clusters and dissected the epitope components interacting with those clusters, by mutational and crystallographic analyses coupled with neutralization assays. Finally, by synthesizing available data, we developed a working-concept boosting strategy to select the mutation clusters in a logical order following a germline-targeting prime. We have thus developed potent HIV bnAbs that may be more tractable vaccine goals compared to existing bnAbs, and we have proposed a strategy to elicit them. This reductionist approach to vaccine design, guided by antibody and antigen structure, could be applied to design candidate vaccines for other HIV bnAbs or protective Abs against other pathogens. PMID:27560183

  9. Neutralization of Japanese Encephalitis Virus by heme-induced broadly reactive human monoclonal antibody

    OpenAIRE

    Nimesh Gupta; Mélissanne de Wispelaere; Maxime Lecerf; Manjula Kalia; Tobias Scheel; Sudhanshu Vrati; Claudia Berek; Kaveri, Srinivas V.; Philippe Desprès; Sébastien Lacroix-Desmazes; Dimitrov, Jordan D.

    2015-01-01

    International audience Geographical expansion and re-emerging new genotypes of the Japanese encephalitis virus (JEV) require the development of novel therapeutic approaches. Here, we studied a non-conventional approach for antibody therapy and show that, upon exposure to heme, a fraction of natural human immunoglobulins acquires high-affinity reactivity with the antigenic domain-III of JEV E glycoprotein. These JEV-reactive antibodies exhibited neutralizing activity against recently domina...

  10. Isolation and Characterization of Broad and Ultrapotent Human Monoclonal Antibodies with Therapeutic Activity against Chikungunya Virus.

    Science.gov (United States)

    Smith, Scott A; Silva, Laurie A; Fox, Julie M; Flyak, Andrew I; Kose, Nurgun; Sapparapu, Gopal; Khomandiak, Solomiia; Khomadiak, Solomiia; Ashbrook, Alison W; Kahle, Kristen M; Fong, Rachel H; Swayne, Sherri; Doranz, Benjamin J; McGee, Charles E; Heise, Mark T; Pal, Pankaj; Brien, James D; Austin, S Kyle; Diamond, Michael S; Dermody, Terence S; Crowe, James E

    2015-07-01

    Chikungunya virus (CHIKV) is a mosquito-transmitted RNA virus that causes acute febrile infection associated with polyarthralgia in humans. Mechanisms of protective immunity against CHIKV are poorly understood, and no effective therapeutics or vaccines are available. We isolated and characterized human monoclonal antibodies (mAbs) that neutralize CHIKV infectivity. Among the 30 mAbs isolated, 13 had broad and ultrapotent neutralizing activity (IC50 vaccine development. PMID:26159721

  11. Virologic effects of broadly neutralizing antibody VRC01 administration during chronic HIV-1 infection.

    Science.gov (United States)

    Lynch, Rebecca M; Boritz, Eli; Coates, Emily E; DeZure, Adam; Madden, Patrick; Costner, Pamela; Enama, Mary E; Plummer, Sarah; Holman, Lasonji; Hendel, Cynthia S; Gordon, Ingelise; Casazza, Joseph; Conan-Cibotti, Michelle; Migueles, Stephen A; Tressler, Randall; Bailer, Robert T; McDermott, Adrian; Narpala, Sandeep; O'Dell, Sijy; Wolf, Gideon; Lifson, Jeffrey D; Freemire, Brandie A; Gorelick, Robert J; Pandey, Janardan P; Mohan, Sarumathi; Chomont, Nicolas; Fromentin, Remi; Chun, Tae-Wook; Fauci, Anthony S; Schwartz, Richard M; Koup, Richard A; Douek, Daniel C; Hu, Zonghui; Capparelli, Edmund; Graham, Barney S; Mascola, John R; Ledgerwood, Julie E

    2015-12-23

    Passive immunization with HIV-1-neutralizing monoclonal antibodies (mAbs) is being considered for prevention and treatment of HIV-1 infection. As therapeutic agents, mAbs could be used to suppress active virus replication, maintain suppression induced by antiretroviral therapy (ART), and/or decrease the size of the persistent virus reservoir. We assessed the impact of VRC01, a potent human mAb targeting the HIV-1 CD4 binding site, on ART-treated and untreated HIV-1-infected subjects. Among six ART-treated individuals with undetectable plasma viremia, two infusions of VRC01 did not reduce the peripheral blood cell-associated virus reservoir measured 4 weeks after the second infusion. In contrast, six of eight ART-untreated, viremic subjects infused with a single dose of VRC01 experienced a 1.1 to 1.8 log10 reduction in plasma viremia. The two subjects with minimal responses to VRC01 were found to have predominantly VRC01-resistant virus before treatment. Notably, two subjects with plasma virus load <1000 copies/ml demonstrated virus suppression to undetectable levels for over 20 days until VRC01 levels declined. Among the remaining four subjects with baseline virus loads between 3000 and 30,000 copies, viremia was only partially suppressed by mAb infusion, and we observed strong selection pressure for the outgrowth of less neutralization-sensitive viruses. In summary, a single infusion of mAb VRC01 significantly decreased plasma viremia and preferentially suppressed neutralization-sensitive virus strains. These data demonstrate the virological effect of this neutralizing antibody and highlight the need for combination strategies to maintain virus suppression. PMID:26702094

  12. Ability to develop broadly neutralizing HIV-1 antibodies is not restricted by the germline immunoglobulin gene repertoire1

    Science.gov (United States)

    Scheepers, Cathrine; Shrestha, Ram K.; Lambson, Bronwen E.; Jackson, Katherine J. L.; Wright, Imogen A.; Naicker, Dshanta; Goosen, Mark; Berrie, Leigh; Ismail, Arshad; Garrett, Nigel; Karim, Quarraisha Abdool; Karim, Salim S. Abdool; Moore, Penny L.; Travers, Simon A.; Morris, Lynn

    2015-01-01

    The human immunoglobulin repertoire is vast, producing billions of unique antibodies from a limited number of germline immunoglobulin genes. The immunoglobulin heavy chain variable region (IGHV) is central to antigen binding and is comprised of 48 functional genes. Here we analyzed whether HIV-1 infected individuals who develop broadly neutralizing antibodies show a distinctive germline IGHV profile. Using both 454 and Illumina technologies we sequenced the IGHV repertoire of 28 HIV-infected South African women from the Center for the AIDS Programme of Research in South African (CAPRISA) 002 and 004 cohorts, 13 of whom developed broadly neutralizing antibodies. Of the 259 IGHV alleles identified in this study, approximately half were not found in the International Immunogenetics Database (IMGT). This included 85 entirely novel alleles and 38 alleles that matched rearranged sequences in non-IMGT databases. Analysis of the rearranged H chain V region genes of monoclonal antibodies isolated from 7 of the CAPRISA women and previously isolated broadly neutralizing antibodies from other donors provided evidence that at least 8 novel or non-IMGT alleles contributed to functional antibodies. Importantly, we found that despite a wide range in the number of IGHV alleles in each individual, including alleles used by known broadly neutralizing antibodies, there were no significant differences in germline IGHV repertoires between individuals who do and do not develop broadly neutralizing antibodies. This study reports novel IGHV repertoires and highlights the importance of a fully comprehensive immunoglobulin database for germline gene usage prediction. Furthermore, these data suggest a lack of genetic bias in broadly neutralizing antibody development in HIV-1 infection, with implications for HIV vaccine design. PMID:25825450

  13. Broadly neutralizing antibodies targeted to mucin-type carbohydrate epitopes of human immunodeficiency virus

    DEFF Research Database (Denmark)

    Hansen, J E; Nielsen, C; Arendrup, M;

    1991-01-01

    . This inhibition was found in infection of both lymphocytic cells and monocytoid cells. Viruses tested included six HIV-1 and five HIV-2 isolates propagated in different cells, as well as infectious plasma from AIDS patients. The antiviral effect of anti-Tn MAbs occurred by specific binding of the MAb...... to the virus; this binding was inhibitable by pure Tn antigen, and indications were found that this inhibition occurred at a pre-entry step. Boosting the naturally occurring low-titer anti-Tn activity may be of prophylactic value, as suggested by the in vitro neutralization found in this study....

  14. Low frequency of broadly neutralizing HIV antibodies during chronic infection even in quaternary epitope targeting antibodies containing large numbers of somatic mutations.

    Science.gov (United States)

    Hicar, Mark D; Chen, Xuemin; Kalams, Spyros A; Sojar, Hakimuddin; Landucci, Gary; Forthal, Donald N; Spearman, Paul; Crowe, James E

    2016-02-01

    Neutralizing antibodies (Abs) are thought to be a critical component of an appropriate HIV vaccine response. It has been proposed that Abs recognizing conformationally dependent quaternary epitopes on the HIV envelope (Env) trimer may be necessary to neutralize diverse HIV strains. A number of recently described broadly neutralizing monoclonal Abs (mAbs) recognize complex and quaternary epitopes. Generally, many such Abs exhibit extensive numbers of somatic mutations and unique structural characteristics. We sought to characterize the native antibody (Ab) response against circulating HIV focusing on such conformational responses, without a prior selection based on neutralization. Using a capture system based on VLPs incorporating cleaved envelope protein, we identified a selection of B cells that produce quaternary epitope targeting Abs (QtAbs). Similar to a number of broadly neutralizing Abs, the Ab genes encoding these QtAbs showed extensive numbers of somatic mutations. However, when expressed as recombinant molecules, these Abs failed to neutralize virus or mediate ADCVI activity. Molecular analysis showed unusually high numbers of mutations in the Ab heavy chain framework 3 region of the variable genes. The analysis suggests that large numbers of somatic mutations occur in Ab genes encoding HIV Abs in chronically infected individuals in a non-directed, stochastic, manner. PMID:26748387

  15. Broadly neutralizing human monoclonal JC polyomavirus VP1-specific antibodies as candidate therapeutics for progressive multifocal leukoencephalopathy.

    Science.gov (United States)

    Jelcic, Ivan; Combaluzier, Benoit; Jelcic, Ilijas; Faigle, Wolfgang; Senn, Luzia; Reinhart, Brenda J; Ströh, Luisa; Nitsch, Roger M; Stehle, Thilo; Sospedra, Mireia; Grimm, Jan; Martin, Roland

    2015-09-23

    In immunocompromised individuals, JC polyomavirus (JCPyV) may mutate and gain access to the central nervous system resulting in progressive multifocal leukoencephalopathy (PML), an often fatal opportunistic infection for which no treatments are currently available. Despite recent progress, the contribution of JCPyV-specific humoral immunity to controlling asymptomatic infection throughout life and to eliminating JCPyV from the brain is poorly understood. We examined antibody responses against JCPyV major capsid protein VP1 (viral protein 1) variants in the serum and cerebrospinal fluid (CSF) of healthy donors (HDs), JCPyV-positive multiple sclerosis patients treated with the anti-VLA-4 monoclonal antibody natalizumab (NAT), and patients with NAT-associated PML. Before and during PML, CSF antibody responses against JCPyV VP1 variants show "recognition holes"; however, upon immune reconstitution, CSF antibody titers rise, then recognize PML-associated JCPyV VP1 variants, and may be involved in elimination of the virus. We therefore reasoned that the memory B cell repertoire of individuals who recovered from PML could be a source for the molecular cloning of broadly neutralizing antibodies for passive immunization. We generated a series of memory B cell-derived JCPyV VP1-specific human monoclonal antibodies from HDs and a patient with NAT-associated PML-immune reconstitution inflammatory syndrome (IRIS). These antibodies exhibited diverse binding affinity, cross-reactivity with the closely related BK polyomavirus, recognition of PML-causing VP1 variants, and JCPyV neutralization. Almost all antibodies with exquisite specificity for JCPyV, neutralizing activity, recognition of all tested JCPyV PML variants, and high affinity were derived from one patient who had recovered from PML. These antibodies are promising drug candidates for the development of a treatment of PML. PMID:26400911

  16. Direct Administration in the Respiratory Tract Improves Efficacy of Broadly Neutralizing Anti-Influenza Virus Monoclonal Antibodies

    OpenAIRE

    Leyva-Grado, Victor H.; Tan, Gene S.; Leon, Paul E.; Yondola, Mark; Palese, Peter

    2015-01-01

    The emergence of influenza virus strains resistant to approved neuraminidase inhibitors and the time constrains after infection when these drugs can be effective constitute major drawbacks for this class of drugs. This highlights a critical need to discover new therapeutic agents that can be used for the treatment of influenza virus-infected patients. The use of broadly neutralizing anti-influenza monoclonal antibodies (MAbs) has been sought as an alternative immunotherapy against influenza i...

  17. HIV-1 clade C escapes broadly neutralizing autologous antibodies with N332 glycan specificity by distinct mechanisms.

    Science.gov (United States)

    Deshpande, Suprit; Patil, Shilpa; Kumar, Rajesh; Hermanus, Tandile; Murugavel, Kailapuri G; Srikrishnan, Aylur K; Solomon, Suniti; Morris, Lynn; Bhattacharya, Jayanta

    2016-01-01

    The glycan supersite centered on N332 in the V3 base of the HIV-1 envelope (Env) is a target for broadly neutralizing antibodies (bnAbs) such as PGT121 and PGT128. In this study, we examined the basis of resistance of HIV-1 clade C Envs obtained from broadly cross neutralizing (BCN) plasma of an Indian donor with N332 specificity. Pseudotyped viruses expressing autologous envs were found to be resistant to autologous BCN plasma as well as to PGT121 and PGT128 mAbs despite the majority of Envs containing an intact N332 residue. While resistance of one of the Envs to neutralization by autologous plasma antibodies with shorter V1 loop length was found to be correlated with a N332S mutation, resistance to neutralization of rest of the Envs was found to be associated with longer V1 loop length and acquisition of protective N-glycans. In summary, we show evidence of escape of circulating HIV-1 clade C in an individual from autologous BCN antibodies by three distinct mechanisms. PMID:27576440

  18. Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-120 interface

    Science.gov (United States)

    Huang, Jinghe; Kang, Byong H.; Pancera, Marie; Lee, Jeong Hyun; Tong, Tommy; Feng, Yu; Georgiev, Ivelin S.; Chuang, Gwo-Yu; Druz, Aliaksandr; Doria-Rose, Nicole A.; Laub, Leo; Sliepen, Kwinten; van Gils, Marit J.; de la Peña, Alba Torrents; Derking, Ronald; Klasse, Per-Johan; Migueles, Stephen A.; Bailer, Robert T.; Alam, Munir; Pugach, Pavel; Haynes, Barton F.; Wyatt, Richard T.; Sanders, Rogier W.; Binley, James M.; Ward, Andrew B.; Mascola, John R.; Kwong, Peter D.; Connors, Mark

    2014-01-01

    The isolation of human monoclonal antibodies (mAbs) is providing important insights regarding the specificities that underlie broad neutralization of HIV-1 (reviewed in1). Here we report a broad and extremely potent HIV-specific mAb, termed 35O22, which binds novel HIV-1 envelope glycoprotein (Env) epitope. 35O22 neutralized 62% of 181 pseudoviruses with an IC50<50 μg/ml. The median IC50 of neutralized viruses was 0.033 μg/ml, among the most potent thus far described. 35O22 did not bind monomeric forms of Env tested, but did bind the trimeric BG505 SOSIP.664. Mutagenesis and a reconstruction by negative-stain electron microscopy of the Fab in complex with trimer revealed it to bind a conserved epitope, which stretched across gp120 and gp41. The specificity of 35O22 represents a novel site of vulnerability on HIV Env, which serum analysis indicates to be commonly elicited by natural infection. Binding to this new site of vulnerability may thus be an important complement to current mAb-based approaches to immunotherapies, prophylaxis, and vaccine design. PMID:25186731

  19. Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-gp120 interface.

    Science.gov (United States)

    Huang, Jinghe; Kang, Byong H; Pancera, Marie; Lee, Jeong Hyun; Tong, Tommy; Feng, Yu; Imamichi, Hiromi; Georgiev, Ivelin S; Chuang, Gwo-Yu; Druz, Aliaksandr; Doria-Rose, Nicole A; Laub, Leo; Sliepen, Kwinten; van Gils, Marit J; de la Peña, Alba Torrents; Derking, Ronald; Klasse, Per-Johan; Migueles, Stephen A; Bailer, Robert T; Alam, Munir; Pugach, Pavel; Haynes, Barton F; Wyatt, Richard T; Sanders, Rogier W; Binley, James M; Ward, Andrew B; Mascola, John R; Kwong, Peter D; Connors, Mark

    2014-11-01

    The isolation of human monoclonal antibodies is providing important insights into the specificities that underlie broad neutralization of HIV-1 (reviewed in ref. 1). Here we report a broad and extremely potent HIV-specific monoclonal antibody, termed 35O22, which binds a novel HIV-1 envelope glycoprotein (Env) epitope. 35O22 neutralized 62% of 181 pseudoviruses with a half-maximum inhibitory concentration (IC50) <50 μg ml(-1). The median IC50 of neutralized viruses was 0.033 μg ml(-1), among the most potent thus far described. 35O22 did not bind monomeric forms of Env tested, but did bind the trimeric BG505 SOSIP.664. Mutagenesis and a reconstruction by negative-stain electron microscopy of the Fab in complex with trimer revealed that it bound to a conserved epitope, which stretched across gp120 and gp41. The specificity of 35O22 represents a novel site of vulnerability on HIV Env, which serum analysis indicates to be commonly elicited by natural infection. Binding to this new site of vulnerability may thus be an important complement to current monoclonal-antibody-based approaches to immunotherapies, prophylaxis and vaccine design. PMID:25186731

  20. Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-gp120 interface

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Jinghe; Kang, Byong H.; Pancera, Marie; Lee, Jeong Hyun; Tong, Tommy; Feng, Yu; Imamichi, Hiromi; Georgiev, Ivelin S.; Chuang, Gwo-Yu; Druz, Aliaksandr; Doria-Rose, Nicole A.; Laub, Leo; Sliepen, Kwinten; van Gils, Marit J.; de la Peña, Alba Torrents; Derking, Ronald; Klasse, Per-Johan; Migueles, Stephen A.; Bailer, Robert T.; Alam, Munir; Pugach, Pavel; Haynes, Barton F.; Wyatt, Richard T.; Sanders, Rogier W.; Binley, James M.; Ward, Andrew B.; Mascola, John R.; Kwong, Peter D.; Connors, Mark [NIH

    2015-10-15

    The isolation of human monoclonal antibodies is providing important insights into the specificities that underlie broad neutralization of HIV-1 (reviewed in ref. 1). Here we report a broad and extremely potent HIV-specific monoclonal antibody, termed 35O22, which binds a novel HIV-1 envelope glycoprotein (Env) epitope. 35O22 neutralized 62% of 181 pseudoviruses with a half-maximum inhibitory concentration (IC50) <50 μg ml-1. The median IC50 of neutralized viruses was 0.033 μg ml-1, among the most potent thus far described. 35O22 did not bind monomeric forms of Env tested, but did bind the trimeric BG505 SOSIP.664. Mutagenesis and a reconstruction by negative-stain electron microscopy of the Fab in complex with trimer revealed that it bound to a conserved epitope, which stretched across gp120 and gp41. The specificity of 35O22 represents a novel site of vulnerability on HIV Env, which serum analysis indicates to be commonly elicited by natural infection. Binding to this new site of vulnerability may thus be an important complement to current monoclonal-antibody-based approaches to immunotherapies, prophylaxis and vaccine design.

  1. Protection against SHIV Challenge by Subcutaneous Administration of the Plant-Derived PGT121 Broadly Neutralizing Antibody in Macaques

    Science.gov (United States)

    Rosenberg, Yvonne J.; Montefiori, David C.; LaBranche, Celia C.; Lewis, Mark G.; Sack, Markus; Lees, Jonathan P.; Jiang, Xiaoming

    2016-01-01

    Intravascular delivery of broadly neutralizing antibodies (bnAbs) has shown promise for prevention and treatment of HIV infection. However, multiple IV administrations in geographic locations with poor accessibility to medical care have practical limitations. We have assessed the efficacy of plant-derived PGT121 delivered subcutaneously (SC) against pre-and post-intravaginal challenge using a rigorous SHIV-SF162P3 macaque protection model. SC administered PGT121 exhibited a longer serum half-life than IV administration and was more consistent than intramuscular delivery. A dose of 3.5mg/kg PGT121 prevented infection at a minimum ID50 neutralization titer of 1:295 while 5mg/kg protected five of six macaques when delivered immediately post-challenge. These results suggest the utility of plant-derived bnAbs delivered SC for HIV prevention. PMID:27031108

  2. HIV-1 suppression and durable control by combining single broadly neutralizing antibodies and antiretroviral drugs in humanized mice.

    OpenAIRE

    Horwitz, Joshua A.; Halper-Stromberg, Ariel; Mouquet, Hugo; Gitlin, Alexander D.; Tretiakova, Anna; Eisenreich, Thomas R.; Malbec, Marine; Gravemann, Sophia; Billerbeck, Eva; Dorner, Marcus; Büning, Hildegard; Schwartz, Olivier; Knops, Elena; Kaiser, Rolf; Seaman, Michael S

    2013-01-01

    Effective control of HIV-1 infection in humans is achieved using combinations of antiretroviral therapy (ART) drugs. In humanized mice (hu-mice), control of viremia can be achieved using either ART or by immunotherapy using combinations of broadly neutralizing antibodies (bNAbs). Here we show that treatment of HIV-1–infected hu-mice with a combination of three highly potent bNAbs not only resulted in complete viremic control but also led to a reduction in cell-associated HIV-1 DNA. Moreover, ...

  3. Structures of HIV-1-Env V1V2 with broadly neutralizing antibodies reveal commonalities that enable vaccine design

    OpenAIRE

    Gorman, Jason; Soto, Cinque; Yang, Max M.; Davenport, Thaddeus M.; Guttman, Miklos; Robert T Bailer; Chambers, Michael; Chuang, Gwo-Yu; DeKosky, Brandon J.; Doria-Rose, Nicole A.; Druz, Aliaksandr; Ernandes, Michael J.; Georgiev, Ivelin S.; Jarosinski, Marissa C.; Joyce, M. Gordon

    2015-01-01

    Broadly neutralizing antibodies (bNAbs) against HIV-1-Env V1V2 arise in multiple donors. However, atomic-level interactions had only been determined with antibodies from a single donor, making commonalities in recognition uncertain. Here we report the co-crystal structure of V1V2 with antibody CH03 from a second donor and model Env interactions of antibody CAP256-VRC26 from a third. These V1V2-directed bNAbs utilized strand-strand interactions between a protruding antibody loop and a V1V2 str...

  4. Dusty origin of the Broad Line Region in active galaxies

    CERN Document Server

    Czerny, Bozena; Kaluzny, Janusz; Maity, Ishita

    2012-01-01

    The most characteristic property of active galaxies, including quasars, are prominent broad emission lines. I will discuss an interesting possibility that dust is responsible for this phenomenon. The dust is known to be present in quasars in the form of a dusty/molecular torus which results in complexity of the appearance of active galaxies. However, this dust is located further from the black hole than the Broad Line Region. We propose that the dust is present also closer in and it is actually responsible for formation of the broad emission lines. The argument is based on determination of the temperature of the disk atmosphere underlying the Broad Line Region: it is close to 1000 K, independently from the black hole mass and accretion rate of the object. The mechanism is simple and universal but leads to a considerable complexity of the active nucleus surrounding. The understanding the formation of BLR opens a way to use it reliably - in combination with reverberation measurement of its size - as standard ca...

  5. Crystallographic Identification of Lipid as an Integral Component of the Epitope of HIV Broadly Neutralizing Antibody 4E10.

    Science.gov (United States)

    Irimia, Adriana; Sarkar, Anita; Stanfield, Robyn L; Wilson, Ian A

    2016-01-19

    Numerous studies of the anti-HIV-1 envelope glycoprotein 41 (gp41) broadly neutralizing antibody 4E10 suggest that 4E10 also interacts with membrane lipids, but the antibody regions contacting lipids and its orientation with respect to the viral membrane are unknown. Vaccine immunogens capable of re-eliciting these membrane proximal external region (MPER)-like antibodies may require a lipid component to be successful. We performed a systematic crystallographic study of lipid binding to 4E10 to identify lipids bound by the antibody and the lipid-interacting regions. We identified phosphatidic acid, phosphatidylglycerol, and glycerol phosphate as specific ligands for 4E10 in the crystal structures. 4E10 used its CDRH1 loop to bind the lipid head groups, while its CDRH3 interacted with the hydrophobic lipid tails. Identification of the lipid binding sites on 4E10 may aid design of immunogens for vaccines that include a lipid component in addition to the MPER on gp41 for generation of broadly neutralizing antibodies. PMID:26777395

  6. sCD4-17b bifunctional protein: Extremely broad and potent neutralization of HIV-1 Env pseudotyped viruses from genetically diverse primary isolates

    Directory of Open Access Journals (Sweden)

    Dey Barna

    2010-02-01

    recombinant forms AE and AG. The neutralization breadth and potency were superior to what have been reported for the broadly neutralizing monoclonal antibodies IgG b12, 2G12, 2F5, and 4E10. The activity of sCD4-17b was found to be similar against isogenic virus particles from infectious molecular clones derived either directly from the transfected producer cell line or after a single passage through PBMCs; this contrasted with the monoclonal antibodies, which were less potent against the PMBC-passaged viruses. Conclusions The results highlight the extremely potent and broad neutralizing activity of sCD4-17b against genetically diverse HIV-1 primary isolates. The bifunctional protein has potential applications for antiviral approaches to combat HIV infection.

  7. Broad-line Balmer Decrements in Blue Active Galactic Nuclei

    CERN Document Server

    Dong, Xiaobo; Wang, Jianguo; Yuan, Weimin; Zhou, Hongyan; Dai, Haifeng; Zhang, Kai

    2007-01-01

    We have investigated the broad-line Balmer decrements (Halpha/Hbeta) for a large, homogeneous sample of Seyfert 1 galaxies and QSOs using spectroscopic data obtained in the Sloan Digital Sky Survey. The sample, drawn from the Fourth Data Release, comprises 446 low redshift (z < 0.35) active galactic nuclei (AGN) that have blue optical continua as indicated by the spectral slopes in order to minimize the effect of dust extinction. We find that (i) the distribution of the intrinsic broad-line Halpha/Hbeta ratio can be well described by log-Gaussian, with a peak at Halpha/Hbeta=3.06 and a standard deviation of about 0.03 dex only; (ii) the Balmer decrement does not correlate with AGN properties such as luminosity, accretion rate, and continuum slope, etc.; (iii) on average, the Balmer decrements are found to be only slightly larger in radio-loud sources (3.37) and sources having double-peaked emission-line profiles (3.27) compared to the rest of the sample. We therefore suggest that the broad-line Halpha/Hbet...

  8. Serum neutralizing activities from a Beijing homosexual male cohort infected with different subtypes of HIV-1 in China.

    Directory of Open Access Journals (Sweden)

    Mingshun Zhang

    Full Text Available Protective antibodies play a critical role in an effective HIV vaccine; however, eliciting antibodies to block infection by viruses from diverse genetic subtypes remains a major challenge. As the world's most populous country, China has been under the threat of at least three major subtypes of circulating HIV-1 viruses. Understanding the cross reactivity and specificities of serum antibody responses that mediate broad neutralization of the virus in HIV-1 infected Chinese patients will provide valuable information for the design of vaccines to prevent HIV-1 transmission in China. Sera from a cohort of homosexual men, who have been managed by a major HIV clinical center in Beijing, China, were analyzed for cross-sectional neutralizing activities against pseudotyped viruses expressing Env antigens of the major subtype viruses (AE, BC and B subtypes circulating in China. Neutralizing activities in infected patients' blood were most capable of neutralizing viruses in the homologous subtype; however, a subset of blood samples was able to achieve broad neutralizing activities across different subtypes. Such cross neutralizing activity took 1-2 years to develop and CD4 binding site antibodies were critical components in these blood samples. Our study confirmed the presence of broadly neutralizing sera in China's HIV-1 patient population. Understanding the specificity and breadth of these neutralizing activities can guide efforts for the development of HIV vaccines against major HIV-1 viruses in China.

  9. Structures of HIV-1-Env V1V2 with broadly neutralizing antibodies reveal commonalities that enable vaccine design

    Science.gov (United States)

    Gorman, Jason; Soto, Cinque; Yang, Max M.; Davenport, Thaddeus M.; Guttman, Miklos; Bailer, Robert T.; Chambers, Michael; Chuang, Gwo-Yu; DeKosky, Brandon J.; Doria-Rose, Nicole A.; Druz, Aliaksandr; Ernandes, Michael J.; Georgiev, Ivelin S.; Jarosinski, Marissa C.; Joyce, M. Gordon; Lemmin, Thomas M.; Leung, Sherman; Louder, Mark K.; McDaniel, Jonathan R.; Narpala, Sandeep; Pancera, Marie; Stuckey, Jonathan; Wu, Xueling; Yang, Yongping; Zhang, Baoshan; Zhou, Tongqing; Mullikin, James C.; Baxa, Ulrich; Georgiou, George; McDermott, Adrian B.; Bonsignori, Mattia; Haynes, Barton F.; Moore, Penny L.; Morris, Lynn; Lee, Kelly K.; Shapiro, Lawrence; Mascola, John R.; Kwong, Peter D.

    2016-01-01

    Broadly neutralizing antibodies (bNAbs) against HIV-1-Env V1V2 arise in multiple donors. However, atomic-level interactions had only been determined with antibodies from a single donor, making commonalities in recognition uncertain. Here we report the co-crystal structure of V1V2 with antibody CH03 from a second donor and model Env interactions of antibody CAP256-VRC26 from a third. These V1V2-directed bNAbs utilized strand-strand interactions between a protruding antibody loop and a V1V2 strand, but differed in their N-glycan recognition. Ontogeny analysis indicated protruding loops to develop early, with glycan interactions maturing over time. Altogether, the multidonor information suggested V1V2-directed bNAbs to form an ‘extended class’, for which we engineered ontogeny-specific antigens: Env trimers with chimeric V1V2s that interacted with inferred ancestor and intermediate antibodies. The ontogeny-based design of vaccine antigens described here may provide a general means for eliciting antibodies of a desired class. PMID:26689967

  10. Effects of Darwinian Selection and Mutability on Rate of Broadly Neutralizing Antibody Evolution during HIV-1 Infection.

    Science.gov (United States)

    Sheng, Zizhang; Schramm, Chaim A; Connors, Mark; Morris, Lynn; Mascola, John R; Kwong, Peter D; Shapiro, Lawrence

    2016-05-01

    Accumulation of somatic mutations in antibody variable regions is critical for antibody affinity maturation, with HIV-1 broadly neutralizing antibodies (bnAbs) generally requiring years to develop. We recently found that the rate at which mutations accumulate decreases over time, but the mechanism governing this slowing is unclear. In this study, we investigated whether natural selection and/or mutability of the antibody variable region contributed significantly to observed decrease in rate. We used longitudinally sampled sequences of immunoglobulin transcripts of single lineages from each of 3 donors, as determined by next generation sequencing. We estimated the evolutionary rates of the complementarity determining regions (CDRs), which are most significant for functional selection, and found they evolved about 1.5- to 2- fold faster than the framework regions. We also analyzed the presence of AID hotspots and coldspots at different points in lineage development and observed an average decrease in mutability of less than 10 percent over time. Altogether, the correlation between Darwinian selection strength and evolutionary rate trended toward significance, especially for CDRs, but cannot fully explain the observed changes in evolutionary rate. The mutability modulated by AID hotspots and coldspots changes correlated only weakly with evolutionary rates. The combined effects of Darwinian selection and mutability contribute substantially to, but do not fully explain, evolutionary rate change for HIV-1-targeting bnAb lineages. PMID:27191167

  11. Heating of dust in the broad-line regions of active galaxies and quasars

    International Nuclear Information System (INIS)

    In this paper we discuss the relevant energy sources which heat (and, in many cases, destroy) the dust grains in the emission-line clouds (ELCs) which give rise to the broad-line emission seen in active extragalactic objects. We compare the heating rates from the external radiation field, trapped line radiation, and the diffuse bound-free continua. We find that in hot clouds (T/sub e/ = 1.5 x 104 K) Lyα dominates the dust heating rate, while in cooler clouds (T/sub e/ = 1.0 x 104 K) the external radiation field dominates. In all cases, the dust residing in the broad-line clouds is quite hot (T>500 K). These results are discussed in light of the observed infrared properties of active galaxies and quasars, and the following conclusions are reached: (1) If the infrared emission of Seyfert 1 galaxies is primarily thermal in origin, then the redder near-IR colors distinguishing the Seyfert 1 galaxies from the Seyfert 2 galaxies may be understood in terms of the broad-line regions (BLR) concentrating hot dust within the inner parsec of the of the nucleus. (2) Substantial near-infrared dust emission may originate in the neutral regions of the ELCs with only minor accompanying reddening of the hydrogen Balmer lines, since dust confined to the neutral zone reddens only lines emitted from the back side of the cloud. (3) If the broad-line regions of the quasars are characterized by hotter temperatures than Seyfert 1 galaxies, dust may not be able to exist in this region, thereby explaining the apparent lack of thermal dust emission in quasars. (4) Because of the cooling times of the ELCs, near-IR variability due to changes in the dust temperature is dominated by light travel considerations. (5) The present calculations suggest that the dust-to-gas mass ratio in the BLRs of Seyfert 1 galaxies is substantially smaller than the value of 0.01 typically found in our Galaxy

  12. Glycan masking of hemagglutinin for adenovirus vector and recombinant protein immunizations elicits broadly neutralizing antibodies against H5N1 avian influenza viruses.

    Science.gov (United States)

    Lin, Shih-Chang; Liu, Wen-Chun; Jan, Jia-Tsrong; Wu, Suh-Chin

    2014-01-01

    The highly pathogenic avian influenza (HPAI) H5N1 virus, a known trigger of diseases in poultry and humans, is perceived as a serious threat to public health. There is a clear need for a broadly protective H5N1 vaccine or vaccines for inducing neutralizing antibodies against multiple clades/subclades. We constructed single, double, and triple mutants of glycan-masked hemagglutiinin (HA) antigens at residues 83, 127 and 138 (i.e., g83, g127, g138, g83+g127, g127+g138, g83+g138 and g83+g127+g138), and then obtained their corresponding HA-expressing adenovirus vectors and recombinant HA proteins using a prime-boost immunization strategy. Our results indicate that the glycan-masked g127+g138 double mutant induced more potent HA-inhibition, virus neutralization antibodies, cross-clade protection against heterologous H5N1 clades, correlated with the enhanced bindings to the receptor binding sites and the highly conserved stem region of HA. The immune refocusing stem-specific antibodies elicited by the glycan-masked H5HA g127+g138 and g83+g127+g138 mutants overlapped with broadly neutralizing epitopes of the CR6261 monoclonal antibody that neutralizes most group 1 subtypes. These findings may provide useful information in the development of a broadly protective H5N1 influenza vaccine. PMID:24671139

  13. A novel antibody discovery platform identifies anti-influenza A broadly neutralizing antibodies from human memory B cells.

    Science.gov (United States)

    Xiao, Xiaodong; Chen, Yan; Varkey, Reena; Kallewaard, Nicole; Koksal, Adem C; Zhu, Qing; Wu, Herren; Chowdhury, Partha S; Dall'Acqua, William F

    2016-07-01

    Monoclonal antibody isolation directly from circulating human B cells is a powerful tool to delineate humoral responses to pathological conditions and discover antibody therapeutics. We have developed a platform aimed at improving the efficiencies of B cell selection and V gene recovery. Here, memory B cells are activated and amplified using Epstein-Barr virus infection, co-cultured with CHO-muCD40L cells, and then assessed by functional screenings. An in vitro transcription and translation (IVTT) approach was used to analyze variable (V) genes recovered from each B cell sample and identify the relevant heavy/light chain pair(s). We achieved efficient amplification and activation of memory B cells, and eliminated the need to: 1) seed B cells at clonal level (≤1 cell/well) or perform limited dilution cloning; 2) immortalize B cells; or 3) assemble V genes into an IgG expression vector to confirm the relevant heavy/light chain pairing. Cross-reactive antibodies targeting a conserved epitope on influenza A hemagglutinin were successfully isolated from a healthy donor. In-depth analysis of the isolated antibodies suggested their potential uses as anti-influenza A antibody therapeutics and uncovered a distinct affinity maturation pathway. Importantly, our results showed that cognate heavy/light chain pairings contributed to both the expression level and binding abilities of our newly isolated VH1-69 family, influenza A neutralizing antibodies, contrasting with previous observations that light chains do not significantly contribute to the function of this group of antibodies. Our results further suggest the potential use of the IVTT as a powerful antibody developability assessment tool. PMID:27049174

  14. Broad neutralization of calcium-permeable amyloid pore channels with a chimeric Alzheimer/Parkinson peptide targeting brain gangliosides.

    Science.gov (United States)

    Di Scala, Coralie; Yahi, Nouara; Flores, Alessandra; Boutemeur, Sonia; Kourdougli, Nazim; Chahinian, Henri; Fantini, Jacques

    2016-02-01

    Growing evidence supports a role for brain gangliosides in the pathogenesis of neurodegenerative diseases including Alzheimer's and Parkinson's. Recently we deciphered the ganglioside-recognition code controlling specific ganglioside binding to Alzheimer's β-amyloid (Aβ1-42) peptide and Parkinson's disease-associated protein α-synuclein. Cracking this code allowed us to engineer a short chimeric Aβ/α-synuclein peptide that recognizes all brain gangliosides. Here we show that ganglioside-deprived neural cells do no longer sustain the formation of zinc-sensitive amyloid pore channels induced by either Aβ1-42 or α-synuclein, as assessed by single-cell Ca(2+) fluorescence microscopy. Thus, amyloid channel formation, now considered a key step in neurodegeneration, is a ganglioside-dependent process. Nanomolar concentrations of chimeric peptide competitively inhibited amyloid pore formation induced by Aβ1-42 or α-synuclein in cultured neural cells. Moreover, this peptide abrogated the intracellular calcium increases induced by Parkinson's-associated mutant forms of α-synuclein (A30P, E46K and A53T). The chimeric peptide also prevented the deleterious effects of Aβ1-42 on synaptic vesicle trafficking and decreased the Aβ1-42-induced impairment of spontaneous activity in rat hippocampal slices. Taken together, these data show that the chimeric peptide has broad anti-amyloid pore activity, suggesting that a common therapeutic strategy based on the prevention of amyloid-ganglioside interactions is a reachable goal for both Alzheimer's and Parkinson's diseases. PMID:26655601

  15. Potent and Broadly Reactive HIV-2 Neutralizing Antibodies Elicited by a Vaccinia Virus Vector Prime-C2V3C3 Polypeptide Boost Immunization Strategy▿ †

    Science.gov (United States)

    Marcelino, José Maria; Borrego, Pedro; Rocha, Cheila; Barroso, Helena; Quintas, Alexandre; Novo, Carlos; Taveira, Nuno

    2010-01-01

    Human immunodeficiency virus type 2 (HIV-2) infection affects about 1 to 2 million individuals, the majority living in West Africa, Europe, and India. As for HIV-1, new strategies for the prevention of HIV-2 infection are needed. Our aim was to produce new vaccine immunogens that elicit the production of broadly reactive HIV-2 neutralizing antibodies (NAbs). Native and truncated envelope proteins from the reference HIV-2ALI isolate were expressed in vaccinia virus or in bacteria. This source isolate was used due to its unique phenotype combining CD4 independence and CCR5 usage. NAbs were not elicited in BALB/c mice by single immunization with a truncated and fully glycosylated envelope gp125 (gp125t) or a recombinant polypeptide comprising the C2, V3, and C3 envelope regions (rpC2-C3). A strong and broad NAb response was, however, elicited in mice primed with gp125t expressed in vaccinia virus and boosted with rpC2-C3. Serum from these animals potently neutralized (median 50% neutralizing titer, 3,200) six of six highly divergent primary HIV-2 isolates. Coreceptor usage and the V3 sequence of NAb-sensitive isolates were similar to that of the vaccinating immunogen (HIV-2ALI). In contrast, NAbs were not reactive on three X4 isolates that displayed major changes in V3 loop sequence and structure. Collectively, our findings demonstrate that broadly reactive HIV-2 NAbs can be elicited by using a vaccinia virus vector-prime/rpC2-C3-boost immunization strategy and suggest a potential relationship between escape to neutralization and cell tropism. PMID:20844029

  16. Structure and function of broadly reactive antibody PG16 reveal an H3 subdomain that mediates potent neutralization of HIV-1

    Energy Technology Data Exchange (ETDEWEB)

    Pejchal, Robert; Walker, Laura M.; Stanfield, Robyn L.; Phogat, Sanjay K.; Koff, Wayne C.; Poignard, Pascal; Burton, Dennis R.; Wilson, Ian A. (Scripps); (IAVI)

    2010-11-15

    Development of an effective vaccine against HIV-1 will likely require elicitation of broad and potent neutralizing antibodies against the trimeric surface envelope glycoprotein (Env). Monoclonal antibodies (mAbs) PG9 and PG16 neutralize {approx}80% of HIV-1 isolates across all clades with extraordinary potency and target novel epitopes preferentially expressed on Env trimers. As these neutralization properties are ideal for a vaccine-elicited antibody response to HIV-1, their structural basis was investigated. The crystal structure of the antigen-binding fragment (Fab) of PG16 at 2.5 {angstrom} resolution revealed its unusually long, 28-residue, complementarity determining region (CDR) H3 forms a unique, stable subdomain that towers above the antibody surface. A 7-residue 'specificity loop' on the 'hammerhead' subdomain was identified that, when transplanted from PG16 to PG9 and vice versa, accounted for differences in the fine specificity and neutralization of these two mAbs. The PG16 electron density maps also revealed that a CDR H3 tyrosine was sulfated, which was confirmed for both PG9 (doubly) and PG16 (singly) by mass spectral analysis. We further showed that tyrosine sulfation plays a role in binding and neutralization. An N-linked glycan modification is observed in the variable light chain, but not required for antigen recognition. Further, the crystal structure of the PG9 light chain at 3.0 {angstrom} facilitated homology modeling to support the presence of these unusual features in PG9. Thus, PG9 and PG16 use unique structural features to mediate potent neutralization of HIV-1 that may be of utility in antibody engineering and for high-affinity recognition of a variety of therapeutic targets.

  17. Fragments of the V1/V2 domain of HIV-1 glycoprotein 120 engineered for improved binding to the broadly neutralizing PG9 antibody.

    Science.gov (United States)

    Morales, Javier F; Yu, Bin; Perez, Gerardo; Mesa, Kathryn A; Alexander, David L; Berman, Phillip W

    2016-09-01

    The V1/V2 domain of the HIV-1 envelope protein gp120 possesses two important epitopes: a glycan-dependent epitope recognized by the prototypic broadly neutralizing monoclonal antibody (bN-mAb), PG9, as well as an epitope recognized by non-neutralizing antibodies that has been associated with protection from HIV infection in the RV144 HIV vaccine trial. Because both of these epitopes are poorly immunogenic in the context of full length envelope proteins, immunization with properly folded and glycosylated fragments (scaffolds) represents a potential way to enhance the immune response to these specific epitopes. Previous studies showed that V1/V2 domain scaffolds could be produced from a few selected isolates, but not from many of the isolates that would be advantageous in a multivalent vaccine. In this paper, we used a protein engineering approach to improve the conformational stability and antibody binding activity of V1/V2 domain scaffolds from multiple diverse isolates, including several that were initially unable to bind the prototypic PG9 bN-mAb. Significantly, this effort required replicating both the correct glycan structure as well as the β-sheet structure required for PG9 binding. Although scaffolds incorporating the glycans required for PG9 binding (e.g., mannose-5) can be produced using glycosylation inhibitors (e.g., swainsonine), or mutant cell lines (e.g. GnTI(-) 293 HEK), these are not practical for biopharmaceutical production of proteins intended for clinical trials. In this report, we describe engineered glycopeptide scaffolds from three different clades of HIV-1 that bind PG9 with high affinity when expressed in a wildtype cell line suitable for biopharmaceutical production. The mutations that improved PG9 binding to scaffolds produced in normal cells included amino acid positions outside of the antibody contact region designed to stabilize the β-sheet and turn structures. The scaffolds produced address three major problems in HIV vaccine

  18. LINE SHIFTS, BROAD-LINE REGION INFLOW, AND THE FEEDING OF ACTIVE GALACTIC NUCLEI

    International Nuclear Information System (INIS)

    Velocity-resolved reverberation mapping suggests that the broad-line regions (BLRs) of active galactic nuclei (AGNs) can have significant net inflow. We use the STOKES radiative transfer code to show that electron and Rayleigh scattering off the BLR and torus naturally explains the blueshifted profiles of high-ionization lines and the ionization dependence of the blueshifts. This result is insensitive to the geometry of the scattering region. If correct, then this model resolves the long-standing conflict between the absence of outflow implied by velocity-resolved reverberation mapping and the need for outflow if the blueshifting is the result of obscuration. The accretion rate implied by the inflow is sufficient to power the AGN. We suggest that the BLR is part of the outer accretion disk and that similar magnetohydrodynamic processes are operating. In the scattering model, the blueshifting is proportional to the accretion rate so high-accretion-rate AGNs will show greater high-ionization line blueshifts, as is observed. Scattering can lead to systematically too high black hole mass estimates from the C IV line. We note many similarities between narrow-line region (NLR) and BLR blueshiftings, and suggest that NLR blueshiftings have a similar explanation. Our model explains the higher blueshifts of broad absorption line QSOs if they are more highly inclined. Rayleigh scattering from the BLR and torus could be more important in the UV than electron scattering for predominantly neutral material around AGNs. The importance of Rayleigh scattering versus electron scattering can be assessed by comparing line profiles at different wavelengths arising from the same emission-line region.

  19. Broad-spectrum antimicrobial activity of human intestinal defensin 5.

    OpenAIRE

    Porter, E M; van Dam, E; Valore, E V; Ganz, T

    1997-01-01

    Defensins are antibiotic peptides expressed in human and animal myeloid and epithelial cells. Due to the limited availability of natural peptides, the properties of human epithelial defensins have not been studied. We assayed the microbicidal activity of recombinant human intestinal defensin 5 (rHD-5) in the presence of salt (O to 150 mM NaCl) with varied pH (pH 5.5 to pH 8.5) and trypsin (25 and 250 microg/ml). rHD-5 exhibits microbicidal activity against Listeria monocytogenes, Escherichia ...

  20. Topical gel formulation of broadly neutralizing anti-HIV-1 monoclonal antibody VRC01 confers protection against HIV-1 vaginal challenge in a humanized mouse model

    OpenAIRE

    Veselinovic, Milena; C Preston Neff; Mulder, Leila R.; Akkina, Ramesh

    2012-01-01

    The new generation broadly neutralizing antibody VRC01 against HIV-1 shows great potential as a topically administered microbicide to prevent sexual transmission. We evaluated its efficacy in a RAG-hu humanized mouse model of vaginal HIV-1 transmission. Mice were challenged vaginally with R5 tropic HIV-1 BaL an hour after intravaginal application of the VRC01 (1mg/ml concentration.) gel. A combination of four first generation bNAbs, namely b12, 2F5, 4E10 and 2G12, was used as a positive effic...

  1. Virilization of the Broad Line Region in Active Galactic Nuclei - connection between shifts and widths of broad emission lines

    CERN Document Server

    Jonic, Sanja; Ilic, Dragana; Popovic, Luka C

    2016-01-01

    We investigate the virilization of the emission lines Hbeta and Mg II in the sample of 287 Type 1 Active Galactic Nuclei taken from the Sloan Digital Sky Survey database. We explore the connections between the intrinsic line shifts and full widths at different levels of maximal intensity. We found that: (i) Hbeta seems to be a good virial estimator of black hole masses, and an intrinsic redshift of Hbeta is dominantly caused by the gravitational effect, (ii) there is an anti-correlation between the redshift and width of the wings of the Mg II line, (iii) the broad Mg II line can be used as virial estimator only at 50% of the maximal intensity, while the widths and intrinsic shifts of the line wings can not be used for this purpose.

  2. Identification of Ebsulfur Analogues with Broad-Spectrum Antifungal Activity.

    Science.gov (United States)

    Ngo, Huy X; Shrestha, Sanjib K; Garneau-Tsodikova, Sylvie

    2016-07-19

    Invasive fungal infections are on the rise due to an increased population of critically ill patients as a result of HIV infections, chemotherapies, and organ transplantations. Current antifungal drugs are helpful, but are insufficient in addressing the problem of drug-resistant fungal infections. Thus, there is a growing need for novel antimycotics that are safe and effective. The ebselen scaffold has been evaluated in clinical trials and has been shown to be safe in humans. This makes ebselen an attractive scaffold for facile translation from bench to bedside. We recently reported a library of ebselen-inspired ebsulfur analogues with antibacterial properties, but their antifungal activity has not been characterized. In this study, we repurposed ebselen, ebsulfur, and 32 additional ebsulfur analogues as antifungal agents by evaluating their antifungal activity against a panel of 13 clinically relevant fungal strains. The effect of induction of reactive oxygen species (ROS) by three of these compounds was evaluated. Their hemolytic and cytotoxicity activities were also determined using mouse erythrocytes and mammalian cells. The MIC values of these compounds were found to be in the range of 0.02-12.5 μg mL(-1) against the fungal strains tested. Notably, yeast cells treated with our compounds showed an accumulation of ROS, which may further contribute to the growth-inhibitory effect against fungi. This study provides new lead compounds for the development of antimycotic agents. PMID:27334363

  3. Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9

    Energy Technology Data Exchange (ETDEWEB)

    McLellan, Jason S.; Pancera, Marie; Carrico, Chris; Gorman, Jason; Julien, Jean-Philippe; Khayat, Reza; Louder, Robert; Pejchal, Robert; Sastry, Mallika; Dai, Kaifan; O’Dell, Sijy; Patel, Nikita; Shahzad-ul-Hussan, Syed; Yang, Yongping; Zhang, Baoshan; Zhou, Tongqing; Zhu, Jiang; Boyington, Jeffrey C.; Chuang, Gwo-Yu; Diwanji, Devan; Georgiev, Ivelin; Kwon, Young Do; Lee, Doyung; Louder, Mark K.; Moquin, Stephanie; Schmidt, Stephen D.; Yang, Zhi-Yong; Bonsignori, Mattia; Crump, John A.; Kapiga, Saidi H.; Sam, Noel E.; Haynes, Barton F.; Burton, Dennis R.; Koff, Wayne C.; Walker, Laura M.; Phogat, Sanjay; Wyatt, Richard; Orwenyo, Jared; Wang, Lai-Xi; Arthos, James; Bewley, Carole A.; Mascola, John R.; Nabel, Gary J.; Schief, William R.; Ward, Andrew B.; Wilson, Ian A.; Kwong, Peter D. (UWASH); (NIH); (Scripps); (Duke); (IAVI); (Maryland-MED)

    2012-12-13

    Variable regions 1 and 2 (V1/V2) of human immunodeficiency virus-1 (HIV-1) gp120 envelope glycoprotein are critical for viral evasion of antibody neutralization, and are themselves protected by extraordinary sequence diversity and N-linked glycosylation. Human antibodies such as PG9 nonetheless engage V1/V2 and neutralize 80% of HIV-1 isolates. Here we report the structure of V1/V2 in complex with PG9. V1/V2 forms a four-stranded {beta}-sheet domain, in which sequence diversity and glycosylation are largely segregated to strand-connecting loops. PG9 recognition involves electrostatic, sequence-independent and glycan interactions: the latter account for over half the interactive surface but are of sufficiently weak affinity to avoid autoreactivity. The structures of V1/V2-directed antibodies CH04 and PGT145 indicate that they share a common mode of glycan penetration by extended anionic loops. In addition to structurally defining V1/V2, the results thus identify a paradigm of antibody recognition for highly glycosylated antigens, which - with PG9 - involves a site of vulnerability comprising just two glycans and a strand.

  4. Early Antibody Lineage Diversification and Independent Limb Maturation Lead to Broad HIV-1 Neutralization Targeting the Env High-Mannose Patch.

    Science.gov (United States)

    MacLeod, Daniel T; Choi, Nancy M; Briney, Bryan; Garces, Fernando; Ver, Lorena S; Landais, Elise; Murrell, Ben; Wrin, Terri; Kilembe, William; Liang, Chi-Hui; Ramos, Alejandra; Bian, Chaoran B; Wickramasinghe, Lalinda; Kong, Leopold; Eren, Kemal; Wu, Chung-Yi; Wong, Chi-Huey; Kosakovsky Pond, Sergei L; Wilson, Ian A; Burton, Dennis R; Poignard, Pascal

    2016-05-17

    The high-mannose patch on HIV Env is a preferred target for broadly neutralizing antibodies (bnAbs), but to date, no vaccination regimen has elicited bnAbs against this region. Here, we present the development of a bnAb lineage targeting the high-mannose patch in an HIV-1 subtype-C-infected donor from sub-Saharan Africa. The Abs first acquired autologous neutralization, then gradually matured to achieve breadth. One Ab neutralized >47% of HIV-1 strains with only ∼11% somatic hypermutation and no insertions or deletions. By sequencing autologous env, we determined key residues that triggered the lineage and participated in Ab-Env coevolution. Next-generation sequencing of the Ab repertoire showed an early expansive diversification of the lineage followed by independent maturation of individual limbs, several of them developing notable breadth and potency. Overall, the findings are encouraging from a vaccine standpoint and suggest immunization strategies mimicking the evolution of the entire high-mannose patch and promoting maturation of multiple diverse Ab pathways. PMID:27192579

  5. Fully human broadly neutralizing monoclonal antibodies against influenza A viruses generated from the memory B cells of a 2009 pandemic H1N1 influenza vaccine recipient

    International Nuclear Information System (INIS)

    Whether the 2009 pandemic H1N1 influenza vaccine can induce heterosubtypic cross-protective anti-hemagglutinin (HA) neutralizing antibodies is an important issue. We obtained a panel of fully human monoclonal antibodies from the memory B cells of a 2009 pandemic H1N1 influenza vaccine recipient. Most of the monoclonal antibodies targeted the HA protein but not the HA1 fragment. Among the analyzed antibodies, seven mAbs exhibited neutralizing activity against several influenza A viruses of different subtypes. The conserved linear epitope targeted by the neutralizing mAbs (FIEGGWTGMVDGWYGYHH) is part of the fusion peptide on HA2. Our work suggests that a heterosubtypic neutralizing antibody response primarily targeting the HA stem region exists in recipients of the 2009 pandemic H1N1 influenza vaccine. The HA stem region contains various conserved neutralizing epitopes with the fusion peptide as an important one. This work may aid in the design of a universal influenza A virus vaccine.

  6. Fully human broadly neutralizing monoclonal antibodies against influenza A viruses generated from the memory B cells of a 2009 pandemic H1N1 influenza vaccine recipient

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Weibin [Molecular Virus Unit, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200025 (China); Chen, Aizhong [Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Miao, Yi [Shanghai Xuhui Central Hospital, Shanghai 200031 (China); Xia, Shengli [Center for Disease Control and Prevention of Henan Province, Zhengzhou 450016 (China); Ling, Zhiyang; Xu, Ke; Wang, Tongyan [Molecular Virus Unit, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200025 (China); Xu, Ying; Cui, Jun; Wu, Hongqiang; Hu, Guiyu; Tian, Lin; Wang, Lingling [Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Shu, Yuelong [Chinese Center for Disease Control and Prevention, Beijing 102206 (China); Ma, Xiaowei [Hualan Biological Bacterin Company, Xinxiang 453003 (China); Xu, Bianli; Zhang, Jin [Center for Disease Control and Prevention of Henan Province, Zhengzhou 450016 (China); Lin, Xiaojun, E-mail: linxiaojun@hualan.com [Hualan Biological Bacterin Company, Xinxiang 453003 (China); Bian, Chao, E-mail: cbian@sibs.ac.cn [Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Sun, Bing, E-mail: bsun@sibs.ac.cn [Molecular Virus Unit, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200025 (China); Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China)

    2013-01-20

    Whether the 2009 pandemic H1N1 influenza vaccine can induce heterosubtypic cross-protective anti-hemagglutinin (HA) neutralizing antibodies is an important issue. We obtained a panel of fully human monoclonal antibodies from the memory B cells of a 2009 pandemic H1N1 influenza vaccine recipient. Most of the monoclonal antibodies targeted the HA protein but not the HA1 fragment. Among the analyzed antibodies, seven mAbs exhibited neutralizing activity against several influenza A viruses of different subtypes. The conserved linear epitope targeted by the neutralizing mAbs (FIEGGWTGMVDGWYGYHH) is part of the fusion peptide on HA2. Our work suggests that a heterosubtypic neutralizing antibody response primarily targeting the HA stem region exists in recipients of the 2009 pandemic H1N1 influenza vaccine. The HA stem region contains various conserved neutralizing epitopes with the fusion peptide as an important one. This work may aid in the design of a universal influenza A virus vaccine.

  7. Modeling the LPS Neutralization Activity of Anti-Endotoxins

    Directory of Open Access Journals (Sweden)

    Virapong Prachayasittikul

    2009-05-01

    Full Text Available Bacterial lipopolysaccharides (LPS, also known as endotoxins, are major structural components of the outer membrane of Gram-negative bacteria that serve as a barrier and protective shield between them and their surrounding environment. LPS is considered to be a major virulence factor as it strongly stimulates the secretion of pro-inflammatory cytokines which mediate the host immune response and culminating in septic shock. Quantitative structure-activity relationship studies of the LPS neutralization activities of anti-endotoxins were performed using charge and quantum chemical descriptors. Artificial neural network implementing the back-propagation algorithm was selected for the multivariate analysis. The predicted activities from leave-one-out cross-validation were well correlated with the experimental values as observed from the correlation coefficient and root mean square error of 0.930 and 0.162, respectively. Similarly, the external testing set also yielded good predictivity with correlation coefficient and root mean square error of 0.983 and 0.130. The model holds great potential for the rational design of novel and robust compounds with enhanced neutralization activity.

  8. A human antibody recognizing a conserved epitope of H5 hemagglutinin broadly neutralizes highly pathogenic avian influenza H5N1 viruses.

    Science.gov (United States)

    Hu, Hongxing; Voss, Jarrod; Zhang, Guoliang; Buchy, Philippi; Zuo, Teng; Wang, Lulan; Wang, Feng; Zhou, Fan; Wang, Guiqing; Tsai, Cheguo; Calder, Lesley; Gamblin, Steve J; Zhang, Linqi; Deubel, Vincent; Zhou, Boping; Skehel, John J; Zhou, Paul

    2012-03-01

    Influenza A virus infection is a persistent threat to public health worldwide due to its ability to evade immune surveillance through rapid genetic drift and shift. Current vaccines against influenza A virus provide immunity to viral isolates that are similar to vaccine strains. High-affinity neutralizing antibodies against conserved epitopes could provide immunity to diverse influenza virus strains and protection against future pandemic viruses. In this study, by using a highly sensitive H5N1 pseudotype-based neutralization assay to screen human monoclonal antibodies produced by memory B cells from an H5N1-infected individual and molecular cloning techniques, we developed three fully human monoclonal antibodies. Among them, antibody 65C6 exhibited potent neutralization activity against all H5 clades and subclades except for subclade 7.2 and prophylactic and therapeutic efficacy against highly pathogenic avian influenza H5N1 viruses in mice. Studies on hemagglutinin (HA)-antibody complexes by electron microscopy and epitope mapping indicate that antibody 65C6 binds to a conformational epitope comprising amino acid residues at positions 118, 121, 161, 164, and 167 (according to mature H5 numbering) on the tip of the membrane-distal globular domain of HA. Thus, we conclude that antibody 65C6 recognizes a neutralization epitope in the globular head of HA that is conserved among almost all divergent H5N1 influenza stains. PMID:22238297

  9. Immunization of rabbits with highly purified, soluble, trimeric human immunodeficiency virus type 1 envelope glycoprotein induces a vigorous B cell response and broadly cross-reactive neutralization.

    Directory of Open Access Journals (Sweden)

    Gerald V Quinnan

    Full Text Available Previously we described induction of cross-reactive HIV-1 neutralizing antibody responses in rabbits using a soluble HIV-1 gp140 envelope glycoprotein (Env in an adjuvant containing monophosphoryl lipid A (MPL and QS21 (AS02A. Here, we compared different forms of the same HIV-1 strain R2 Env for antigenic and biophysical characteristics, and in rabbits characterized the extent of B cell induction for specific antibody expression and secretion and neutralizing responses. The forms of this Env that were produced in and purified from stably transformed 293T cells included a primarily dimeric gp140, a trimeric gp140 appended to a GCN4 trimerization domain (gp140-GCN4, gp140-GCN4 with a 15 amino acid flexible linker between the gp120 and gp41 ectodomain (gp140-GCN4-L, also trimeric, and a gp140 with the flexible linker purified from cell culture supernatants as either dimer (gp140-L(D or monomer (gp140-L(M. Multimeric states of the Env proteins were assessed by native gel electrophoresis and analytical ultracentrifugation. The different forms of gp140 bound broadly cross-reactive neutralizing (BCN human monoclonal antibodies (mAbs similarly in ELISA and immunoprecipitation assays. All Envs bound CD4i mAbs in the presence and absence of sCD4, as reported for the R2 Env. Weak neutralization of some strains of HIV-1 was seen after two additional doses in AS02A. Rabbits that were given a seventh dose of gp140-GCN4-L developed BCN responses that were weak to moderate, similar to our previous report. The specificity of these responses did not appear similar to that of any of the known BCN human mAbs. Induction of spleen B cell and plasma cells producing immunoglobulins that bound trimeric gp140-GCN4-L was vigorous, based on ELISpot and flow cytometry analyses. The results demonstrate that highly purified gp140-GCN4-L trimer in adjuvant elicits BCN responses in rabbits accompanied by vigorous B cell induction.

  10. A hepatitis C virus (HCV vaccine comprising envelope glycoproteins gpE1/gpE2 derived from a single isolate elicits broad cross-genotype neutralizing antibodies in humans.

    Directory of Open Access Journals (Sweden)

    John Lok Man Law

    Full Text Available Although a cure for HCV is on the near horizon, emerging drug cocktails will be expensive, associated with side-effects and resistance making a global vaccine an urgent priority given the estimated high incidence of infection around the world. Due to the highly heterogeneous nature of HCV, an effective HCV vaccine which could elicit broadly cross-neutralizing antibodies has represented a major challenge. In this study, we tested for the presence of cross-neutralizing antibodies in human volunteers who were immunized with recombinant glycoproteins gpE1/gpE2 derived from a single HCV strain (HCV1 of genotype 1a. Cross neutralization was tested in Huh-7.5 human hepatoma cell cultures using infectious recombinant HCV (HCVcc expressing structural proteins of heterologous HCV strains from all known major genotypes, 1-7. Vaccination induced significant neutralizing antibodies against heterologous HCV genotype 1a virus which represents the most common genotype in North America. Of the 16 vaccinees tested, 3 were selected on the basis of strong 1a virus neutralization for testing of broad cross-neutralizing responses. At least 1 vaccinee was shown to elicit broad cross-neutralization against all HCV genotypes. Although observed in only a minority of vaccinees, our results prove the key concept that a vaccine derived from a single strain of HCV can elicit broad cross-neutralizing antibodies against all known major genotypes of HCV and provide considerable encouragement for the further development of a human vaccine against this common, global pathogen.

  11. A hepatitis C virus (HCV) vaccine comprising envelope glycoproteins gpE1/gpE2 derived from a single isolate elicits broad cross-genotype neutralizing antibodies in humans

    OpenAIRE

    John Lok Man Law; Chao Chen; Jason Wong; Darren Hockman; Santer, Deanna M; Frey, Sharon E.; Belshe, Robert B.; Takaji Wakita; Jens Bukh; Jones, Christopher T.; Rice, Charles M.; Sergio Abrignani; Lorne Tyrrell, D; Michael Houghton

    2013-01-01

    Although a cure for HCV is on the near horizon, emerging drug cocktails will be expensive, associated with side-effects and resistance making a global vaccine an urgent priority given the estimated high incidence of infection around the world. Due to the highly heterogeneous nature of HCV, an effective HCV vaccine which could elicit broadly cross-neutralizing antibodies has represented a major challenge. In this study, we tested for the presence of cross-neutralizing antibodies in human volun...

  12. Observation of electro-activated localized structures in broad area VCSELs

    OpenAIRE

    Parravicini, J.; Brambilla, M; Columbo, L.; Prati, F.; C. Rizza; Tissoni, G.; Agranat, A. J.; DelRe, E.

    2014-01-01

    We demonstrate experimentally the electro-activation of a localized optical structure in a coherently driven broad-area vertical-cavity surface-emitting laser (VCSEL) operated below threshold. Control is achieved by electro-optically steering a writing beam through a pre-programmable switch based on a photorefractive funnel waveguide.

  13. Comprehensive mapping of functional epitopes on dengue virus glycoprotein E DIII for binding to broadly neutralizing antibodies 4E11 and 4E5A by phage display.

    Science.gov (United States)

    Frei, Julia C; Kielian, Margaret; Lai, Jonathan R

    2015-11-01

    Here we investigated the binding of Dengue virus envelope glycoprotein domain III (DIII) by two broadly neutralizing antibodies (bNAbs), 4E11 and 4E5A. There are four serotypes of Dengue virus (DENV-1 to -4), whose DIII sequences vary by up to 49%. We used combinatorial alanine scanning mutagenesis, a phage display approach, to map functional epitopes (those residues that contribute most significantly to the energetics of antibody-antigen interaction) on these four serotypes. Our results showed that 4E11, which binds strongly to DENV-1, -2, and -3, and moderately to DENV-4, recognized a common conserved core functional epitope involving DIII residues K310, L/I387, L389, and W391. There were also unique recognition features for each serotype, suggesting that 4E11 has flexible recognition requirements. Similar scanning studies for the related bNAb 4E5A, which binds more tightly to DENV-4, identified broader functional epitopes on DENV-1. These results provide useful information for immunogen and therapeutic antibody design. PMID:26339794

  14. Synthesis and Broad-Spectrum Antiviral Activity of Some Novel Benzo-Heterocyclic Amine Compounds

    Directory of Open Access Journals (Sweden)

    Da-Jun Zhang

    2014-01-01

    Full Text Available A series of novel unsaturated five-membered benzo-heterocyclic amine derivatives were synthesized and assayed to determine their in vitro broad-spectrum antiviral activities. The biological results showed that most of our synthesized compounds exhibited potent broad-spectrum antiviral activity. Notably, compounds 3f (IC50 = 3.21–5.06 μM and 3g (IC50 = 0.71–34.87 μM showed potent activity towards both RNA viruses (influenza A, HCV and Cox B3 virus and a DNA virus (HBV at low micromolar concentrations. An SAR study showed that electron-withdrawing substituents located on the aromatic or heteroaromatic ring favored antiviral activity towards RNA viruses.

  15. The Fundamental Plane of the Broad-line Region in Active Galactic Nuclei

    CERN Document Server

    Du, Pu; Hu, Chen; Ho, Luis C; Li, Yan-Rong; Bai, Jin-Ming

    2016-01-01

    Broad emission lines in active galactic nuclei (AGNs) mainly arise from gas photoionized by continuum radiation from an accretion disk around a central black hole. The shape of the broad-line profile, described by ${\\cal D}_{_{\\rm H\\beta}}={\\rm FWHM}/\\sigma_{_{\\rm H\\beta}}$, the ratio of full width at half maximum to the dispersion of broad H$\\beta$, reflects the dynamics of the broad-line region (BLR) and correlates with the dimensionless accretion rate ($\\dot{\\mathscr{M}}$) or Eddington ratio ($L_{\\rm bol}/L_{\\rm Edd}$). At the same time, $\\dot{\\mathscr{M}}$ and $L_{\\rm bol}/L_{\\rm Edd}$ correlate with ${\\cal R}_{\\rm Fe}$, the ratio of optical Fe II to H$\\beta$ line flux emission. Assembling all AGNs with reverberation mapping measurements of broad H$\\beta$, both from the literature and from new observations reported here, we find a strong bivariate correlation of the form $\\log(\\dot{\\mathscr{M}},L_{\\rm bol}/L_{\\rm Edd})=\\alpha+\\beta{\\cal D}_{_{\\rm H\\beta}}+\\gamma{\\cal R}_{\\rm Fe},$ where $\\alpha=(2.47,0.31...

  16. Constraints on the outer radius of the broad emission line region of active galactic nuclei

    CERN Document Server

    Landt, Hermine; Elvis, Martin; Karovska, Margarita

    2014-01-01

    Here we present observational evidence that the broad emission line region (BELR) of active galactic nuclei (AGN) generally has an outer boundary. This was already clear for sources with an obvious transition between the broad and narrow components of their emission lines. We show that the narrow component of the higher-order Paschen lines is absent in all sources, revealing a broad emission line profile with a broad, flat top. This indicates that the BELR is kinematically separate from the narrow emission line region. We use the virial theorem to estimate the BELR outer radius from the flat top width of the unblended profiles of the strongest Paschen lines, Pa alpha and Pa beta, and find that it scales with the ionising continuum luminosity roughly as expected from photoionisation theory. The value of the incident continuum photon flux resulting from this relationship corresponds to that required for dust sublimation. A flat-topped broad emission line profile is produced by both a spherical gas distribution ...

  17. First Membrane Proximal External Region-Specific Anti-HIV1 Broadly Neutralizing Monoclonal IgA1 Presenting Short CDRH3 and Low Somatic Mutations.

    Science.gov (United States)

    Benjelloun, Fahd; Oruc, Zeliha; Thielens, Nicole; Verrier, Bernard; Champier, Gael; Vincent, Nadine; Rochereau, Nicolas; Girard, Alexandre; Jospin, Fabienne; Chanut, Blandine; Genin, Christian; Cogné, Michel; Paul, Stephane

    2016-09-01

    Mucosal HIV-1-specific IgA have been described as being able to neutralize HIV-1 and to block viral transcytosis. In serum and saliva, the anti-HIV IgA response is predominantly raised against the envelope of HIV-1. In this work, we describe the in vivo generation of gp41-specific IgA1 in humanized α1KI mice to produce chimeric IgA1. Mice were immunized with a conformational immunogenic gp41-transfected cell line. Among 2300 clones screened by immunofluorescence microscopy, six different gp41-specific IgA with strong recognition of gp41 were identified. Two of them have strong neutralizing activity against primary HIV-1 tier 1, 2, and 3 strains and present a low rate of somatic mutations and autoreactivity, unlike what was described for classical gp41-specific IgG. Epitopes were identified and located in the hepted repeat 2/membrane proximal external region. These Abs could be of interest in prophylactic treatment to block HIV-1 penetration in mucosa or in chronically infected patients in combination with antiretroviral therapy to reduce viral load and reservoir. PMID:27481846

  18. Active steering system for the neutral beam injector for ITER

    International Nuclear Information System (INIS)

    ITER requires an additional power injection of 33 MW from neutral beams, which can be provided by two injectors, delivering 16.5 MW each, having an ion current of 40 A and an accelerating voltage of 1 MV. The requirement of on-axis and off-axis injection into ITER is presently accomplished by mechanical tilting of the injector source. To preserve the integrity of the beam line components, on the horizontal plane, very tight misalignment is tolerable (±3 mrad); such accuracy requires precise installation of the components. Breaking the vacuum and executing a long series of operations is required to provide proper beam alignment. It would be helpful if such alignments could be performed remotely. A study has been conducted on the possibility of steering the negative ions by suitable magnetic fields, generated by dedicated coils located at the exit of the accelerator. It results that the magnetic system can meet the requirements in terms of beam alignment. The steering system will heavily affect the trajectory of the electrons extracted from the accelerator and can be used to deflect the electrons onto suitable dump plates. The system can steer the ions and dump the electrons in a controlled way, even in case of modulation of the acceleration voltage; a flexible beam aiming system can be used to adapt the power deposition profile in ITER to the plasma characteristics; active steering can provide a suitable way to control the power deposition with respect to the possibility of exciting Alfven eigenmodes, which can reduce the performances of ITER plasmas. The present contribution reviews the preliminary design of the active steering system and provides an analysis of advantages and disadvantages. (author)

  19. Broad Hβ Emission-line Variability in a Sample of 102 Local Active Galaxies

    Science.gov (United States)

    Runco, Jordan N.; Cosens, Maren; Bennert, Vardha N.; Scott, Bryan; Komossa, S.; Malkan, Matthew A.; Lazarova, Mariana S.; Auger, Matthew W.; Treu, Tommaso; Park, Daeseong

    2016-04-01

    A sample of 102 local (0.02 ≤ z ≤ 0.1) Seyfert galaxies with black hole masses MBH > 107M⊙ was selected from the Sloan Digital Sky Survey (SDSS) and observed using the Keck 10 m telescope to study the scaling relations between MBH and host galaxy properties. We study profile changes of the broad Hβ emission line within the three to nine year time frame between the two sets of spectra. The variability of the broad Hβ emission line is of particular interest, not only because it is used to estimate MBH, but also because its strength and width are used to classify Seyfert galaxies into different types. At least some form of broad-line variability (in either width or flux) is observed in the majority (∼66%) of the objects, resulting in a Seyfert-type change for ∼38% of the objects, likely driven by variable accretion and/or obscuration. The broad Hβ line virtually disappears in 3/102 (∼3%) extreme cases. We discuss potential causes for these changing look active galactic nuclei. While similar dramatic transitions have previously been reported in the literature, either on a case-by-case basis or in larger samples focusing on quasars at higher redshifts, our study provides statistical information on the frequency of Hβ line variability in a sample of low-redshift Seyfert galaxies.

  20. [Activity of Ca(2+)-dependent neutral proteinases in rat organs under cobalt and mercury chloride injection].

    Science.gov (United States)

    Kaliman, P A; Samokhin, A A; Samokhina, L M

    2003-01-01

    The activity of Ca(2+)-dependent neutral proteinases in rats under cobalt and mercury chloride injection was investigated. The calpains activity increase in the lungs, heart, liver and kidneys was revealed after 2 h cobalt chloride action. The mercury chloride gives a reliable increase of calcium-dependent neutral proteinases only in the kidneys. PMID:14574747

  1. Nanostructure formation enhances the activity of LPS-neutralizing peptides.

    NARCIS (Netherlands)

    Mas-Moruno, C.; Cascales, L.; Cruz, L.J.; Mora, P.; Perez-Paya, E.; Albericio, F.

    2008-01-01

    Peptides that interact with lipopolysaccharide (LPS) can provide the basis for the development of new antisepsis agents. In this work, several LPS-neutralizing acyl peptides derived from LALF, BPI, and SAP were prepared, structurally characterized, and biologically evaluated. In all cases, peptides

  2. Evidence of the Link between Broad Emission Line Regions and Accretion Disks in Active Galactic Nuclei

    Institute of Scientific and Technical Information of China (English)

    Yun Xu; Xin-Wu Cao

    2007-01-01

    There is observational evidence that broad-line regions (BLRs) exist in most active galactic nuclei (AGNs), but their origin is still unclear. One scenario is that the BLRs originate from winds accelerated from the hot coronae of the disks, and the winds are suppressed when the black hole is accreting at low rates. This model predicts a relation between (m) ((m) = (M)/(M)Edd) and the FWHM of broad emission lines. We estimate the central black hole masses for a sample of bright AGNs by using their broad Hβ line-widths and optical luminosities. The dimensionless accretion rates (m) = (M)/(M)Edd are derived from the optical continuum luminosities by using two different models: using an empirical relation between the bolometric luminosity Lbol and the optical luminosity ((m) = Lbol/LEdd, a fixed radiative efficiency is adopted); and calculating the optical spectra of accretion disks as a function of (m). We find a significant correlation between the derived (m) and the observed line width of Hβ,FWHM∝ (m)-0.37, which almost overlaps the disk-corona model calculations, if the viscosity α≈ 0.1 - 0.2 is adopted. Our results provide strong evidence for the physical link between the BLRs and accretion disks in AGNs.

  3. Human monoclonal antibodies derived from a patient infected with 2009 pandemic influenza A virus broadly cross-neutralize group 1 influenza viruses

    International Nuclear Information System (INIS)

    Highlights: • Influenza infection can elicit heterosubtypic antibodies to group 1 influenza virus. • Three human monoclonal antibodies were generated from an H1N1-infected patient. • The antibodies predominantly recognized α-helical stem of viral hemagglutinin (HA). • The antibodies inhibited HA structural activation during the fusion process. • The antibodies are potential candidates for future antibody therapy to influenza. - Abstract: Influenza viruses are a continuous threat to human public health because of their ability to evolve rapidly through genetic drift and reassortment. Three human monoclonal antibodies (HuMAbs) were generated in this study, 1H11, 2H5 and 5G2, and they cross-neutralize a diverse range of group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H5N1 and H9N2. The three HuMAbs were prepared by fusing peripheral blood lymphocytes from an H1N1pdm-infected patient with a newly developed fusion partner cell line, SPYMEG. All the HuMAbs had little hemagglutination inhibition activity but had strong membrane-fusion inhibition activity against influenza viruses. A protease digestion assay showed the HuMAbs targeted commonly a short α-helix region in the stalk of the hemagglutinin. Furthermore, Ile45Phe and Glu47Gly double substitutions in the α-helix region made the HA unrecognizable by the HuMAbs. These two amino acid residues are highly conserved in the HAs of H1N1, H5N1 and H9N2 viruses. The HuMAbs reported here may be potential candidates for the development of therapeutic antibodies against group 1 influenza viruses

  4. Human monoclonal antibodies derived from a patient infected with 2009 pandemic influenza A virus broadly cross-neutralize group 1 influenza viruses

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Yang [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Sasaki, Tadahiro [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Kubota-Koketsu, Ritsuko [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Kanonji Institute, The Research Foundation for Microbial Diseases of Osaka University, Kanonji, Kagawa (Japan); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Inoue, Yuji [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Yasugi, Mayo [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka (Japan); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Yamashita, Akifumi; Ramadhany, Ririn; Arai, Yasuha [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Du, Anariwa [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Boonsathorn, Naphatsawan [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi (Thailand); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Ibrahim, Madiha S. [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Department of Microbiology and Immunology, Faculty of Veterinary Medicine, Damanhour University, Damanhour (Egypt); and others

    2014-07-18

    Highlights: • Influenza infection can elicit heterosubtypic antibodies to group 1 influenza virus. • Three human monoclonal antibodies were generated from an H1N1-infected patient. • The antibodies predominantly recognized α-helical stem of viral hemagglutinin (HA). • The antibodies inhibited HA structural activation during the fusion process. • The antibodies are potential candidates for future antibody therapy to influenza. - Abstract: Influenza viruses are a continuous threat to human public health because of their ability to evolve rapidly through genetic drift and reassortment. Three human monoclonal antibodies (HuMAbs) were generated in this study, 1H11, 2H5 and 5G2, and they cross-neutralize a diverse range of group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H5N1 and H9N2. The three HuMAbs were prepared by fusing peripheral blood lymphocytes from an H1N1pdm-infected patient with a newly developed fusion partner cell line, SPYMEG. All the HuMAbs had little hemagglutination inhibition activity but had strong membrane-fusion inhibition activity against influenza viruses. A protease digestion assay showed the HuMAbs targeted commonly a short α-helix region in the stalk of the hemagglutinin. Furthermore, Ile45Phe and Glu47Gly double substitutions in the α-helix region made the HA unrecognizable by the HuMAbs. These two amino acid residues are highly conserved in the HAs of H1N1, H5N1 and H9N2 viruses. The HuMAbs reported here may be potential candidates for the development of therapeutic antibodies against group 1 influenza viruses.

  5. Broad spectrum antiviral activity of favipiravir (T-705: protection from highly lethal inhalational Rift Valley Fever.

    Directory of Open Access Journals (Sweden)

    Amy L Caroline

    2014-04-01

    Full Text Available BACKGROUND: Development of antiviral drugs that have broad-spectrum activity against a number of viral infections would be of significant benefit. Due to the evolution of resistance to currently licensed antiviral drugs, development of novel anti-influenza drugs is in progress, including Favipiravir (T-705, which is currently in human clinical trials. T-705 displays broad-spectrum in vitro activity against a number of viruses, including Rift Valley Fever virus (RVFV. RVF is an important neglected tropical disease that causes human, agricultural, and economic losses in endemic regions. RVF has the capacity to emerge in new locations and also presents a potential bioterrorism threat. In the current study, the in vivo efficacy of T-705 was evaluated in Wistar-Furth rats infected with the virulent ZH501 strain of RVFV by the aerosol route. METHODOLOGY/PRINCIPAL FINDINGS: Wistar-Furth rats are highly susceptible to a rapidly lethal disease after parenteral or inhalational exposure to the pathogenic ZH501 strain of RVFV. In the current study, two experiments were performed: a dose-determination study and a delayed-treatment study. In both experiments, all untreated control rats succumbed to disease. Out of 72 total rats infected with RVFV and treated with T-705, only 6 succumbed to disease. The remaining 66 rats (92% survived lethal infection with no significant weight loss or fever. The 6 treated rats that succumbed survived significantly longer before succumbing to encephalitic disease. CONCLUSIONS/SIGNIFICANCE: Currently, there are no licensed antiviral drugs for treating RVF. Here, T-705 showed remarkable efficacy in a highly lethal rat model of Rift Valley Fever, even when given up to 48 hours post-infection. This is the first study to show protection of rats infected with the pathogenic ZH501 strain of RVFV. Our data suggest that T-705 has potential to be a broad-spectrum antiviral drug.

  6. Stability of Cloud Orbits in the Broad Line Region of Active Galactic Nuclei

    CERN Document Server

    schartmann, Martin Krause Andreas Burkert Marc

    2010-01-01

    We investigate the global dynamic stability of spherical clouds in the Broad Line Region (BLR) of Active Galactic Nuclei (AGN), exposed to radial radiation pressure, gravity of the central black hole (BH), and centrifugal forces assuming the clouds adapt their size according to the local pressure. We consider both, isotropic and anisotropic light sources. In both cases, stable orbits exist also for very sub-Keplerian rotation for which the radiation pressure contributes substantially to the force budget. We demonstrate that highly excentric, very sub-Keplerian stable orbits may be found that also agree with the recent finding by spectropolarimetry that the BLR is disk-like. This gives further support for the model of Marconi et al. 2008, which is designed to improve the agreement between black hole masses derived in certain active galaxies based on BLR dynamics, and black hole masses derived by other means in other galaxies by inclusion of a luminosity dependent term. For anisotropic illumination, the foresho...

  7. Comparative toxicity and efficacy of engineered anthrax lethal toxin variants with broad anti-tumor activities

    International Nuclear Information System (INIS)

    We have previously designed and characterized versions of anthrax lethal toxin that are selectively cytotoxic in the tumor microenvironment and which display broad and potent anti-tumor activities in vivo. Here, we have performed the first direct comparison of the safety and efficacy of three engineered anthrax lethal toxin variants requiring activation by either matrix-metalloproteinases (MMPs), urokinase plasminogen activator (uPA) or co-localized MMP/uPA activities. C57BL/6J mice were challenged with six doses of engineered toxins via intraperitoneal (I.P.) or intravenous (I.V.) dose routes to determine the maximum tolerated dose for six administrations (MTD6) and dose-limiting toxicities. Efficacy was evaluated using the B16-BL6 syngraft model of melanoma; mice bearing established tumors were treated with six I.P. doses of toxin and tumor measurements and immunohistochemistry, paired with terminal blood work, were used to elaborate upon the anti-tumor mechanism and relative efficacy of each variant. We found that MMP-, uPA- and dual MMP/uPA-activated anthrax lethal toxins exhibited the same dose-limiting toxicity; dose-dependent GI toxicity. In terms of efficacy, all three toxins significantly reduced primary B16-BL6 tumor burden, ranging from 32% to 87% reduction, and they also delayed disease progression as evidenced by dose-dependent normalization of blood work values. While target organ toxicity and effective doses were similar amongst the variants, the dual MMP/uPA-activated anthrax lethal toxin exhibited the highest I.P. MTD6 and was 1.5–3-fold better tolerated than the single MMP- and uPA-activated toxins. Overall, we demonstrate that this dual MMP/uPA-activated anthrax lethal toxin can be administered safely and is highly effective in a preclinical model of melanoma. This modified bacterial cytotoxin is thus a promising candidate for further clinical development and evaluation for use in treating human cancers. - Highlights: • Toxicity and anti

  8. Comparative toxicity and efficacy of engineered anthrax lethal toxin variants with broad anti-tumor activities

    Energy Technology Data Exchange (ETDEWEB)

    Peters, Diane E. [Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Program of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA (United States); Hoover, Benjamin [Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (United States); Cloud, Loretta Grey [Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Liu, Shihui [Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (United States); Molinolo, Alfredo A. [Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Leppla, Stephen H. [Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (United States); Bugge, Thomas H., E-mail: thomas.bugge@nih.go [Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States)

    2014-09-01

    We have previously designed and characterized versions of anthrax lethal toxin that are selectively cytotoxic in the tumor microenvironment and which display broad and potent anti-tumor activities in vivo. Here, we have performed the first direct comparison of the safety and efficacy of three engineered anthrax lethal toxin variants requiring activation by either matrix-metalloproteinases (MMPs), urokinase plasminogen activator (uPA) or co-localized MMP/uPA activities. C57BL/6J mice were challenged with six doses of engineered toxins via intraperitoneal (I.P.) or intravenous (I.V.) dose routes to determine the maximum tolerated dose for six administrations (MTD6) and dose-limiting toxicities. Efficacy was evaluated using the B16-BL6 syngraft model of melanoma; mice bearing established tumors were treated with six I.P. doses of toxin and tumor measurements and immunohistochemistry, paired with terminal blood work, were used to elaborate upon the anti-tumor mechanism and relative efficacy of each variant. We found that MMP-, uPA- and dual MMP/uPA-activated anthrax lethal toxins exhibited the same dose-limiting toxicity; dose-dependent GI toxicity. In terms of efficacy, all three toxins significantly reduced primary B16-BL6 tumor burden, ranging from 32% to 87% reduction, and they also delayed disease progression as evidenced by dose-dependent normalization of blood work values. While target organ toxicity and effective doses were similar amongst the variants, the dual MMP/uPA-activated anthrax lethal toxin exhibited the highest I.P. MTD6 and was 1.5–3-fold better tolerated than the single MMP- and uPA-activated toxins. Overall, we demonstrate that this dual MMP/uPA-activated anthrax lethal toxin can be administered safely and is highly effective in a preclinical model of melanoma. This modified bacterial cytotoxin is thus a promising candidate for further clinical development and evaluation for use in treating human cancers. - Highlights: • Toxicity and anti

  9. Draft Genome Sequence of Paenibacillus sp. Strain MSt1 with Broad Antimicrobial Activity, Isolated from Malaysian Tropical Peat Swamp Soil

    OpenAIRE

    Aw, Yoong Kit; Ong, Kuan Shion; Catherine M Yule; Gan, Han Ming; Lee, Sui Mae

    2014-01-01

    We report the draft genome sequence of Paenibacillus sp. strain MSt1, which has broad-range antimicrobial activity, isolated from tropical peat swamp soil. Genes involved in antimicrobial biosynthesis are found to be present in this genome.

  10. ß-defensin-2 in breast milk displays a broad antimicrobial activity against pathogenic bacteria

    Directory of Open Access Journals (Sweden)

    Joanna Baricelli

    2015-02-01

    Full Text Available OBJECTIVE: To describe the antimicrobial activity of ß-defensin-2 produced in the mammary gland and secreted in human breast milk. METHODS: The peptide production was performed by DNA cloning. ß-defensin-2 levels were quantified in 61 colostrum samples and 39 mature milk samples from healthy donors, by an indirect enzyme-linked immunosorbent assay (ELISA. Using halo inhibition assay, this study assessed activity against seven clinical isolates from diarrheal feces of children between 0 and 2 years of age. The activity of ß-defensin-2 against three opportunistic pathogens that can cause nosocomial infections was determined by microdilution test. RESULTS: The peptide levels were higher in colostrum (n = 61 than in mature milk samples (n = 39, as follows: median and range, 8.52 (2.6-16.3 µg/ml versus 0.97 (0.22-3.78, p < 0.0001; Mann-Whitney test. The recombinant peptide obtained showed high antimicrobial activity against a broad range of pathogenic bacteria. Its antibacterial activity was demonstrated in a disk containing between 1-4 µg, which produced inhibition zones ranging from 18 to 30 mm against three isolates of Salmonella spp. and four of E. coli. ß-defensin-2 showed minimum inhibitory concentrations (MICs of 0.25 µg/mL and 0.5 µg/mL for S. marcescen and P. aeruginosa, respectively, while a higher MIC (4 µg/mL was obtained against an isolated of multidrug-resistant strain of A. baumannii. CONCLUSIONS: To the authors' knowledge, this study is the first to report ß-defensin-2 levels in Latin American women. The production and the activity of ß-defensin-2 in breast milk prove its importance as a defense molecule for intestinal health in pediatric patients.

  11. Report for neutral buoyancy simulations of transfer orbit stage contingency extravehicular activities

    Science.gov (United States)

    Sexton, J. D.

    1992-06-01

    The transfer orbit stage (TOS) will propel the advanced communications technology satellite (ACTS) from the Space Shuttle to an Earth geosynchronous transfer orbit. Two neutral buoyancy test series were conducted at MSFC to validate the extravehicular activities (EVA) contingency operations for the ACTS/TOS/mission. The results of the neutral buoyancy tests are delineated and a brief history of the TOS EVA program is given.

  12. Black cobra (Naja naja karachiensis) lysates exhibit broad-spectrum antimicrobial activities

    Science.gov (United States)

    Sagheer, Mehwish; Siddiqui, Ruqaiyyah; Iqbal, Junaid; Khan, Naveed Ahmed

    2014-01-01

    It is hypothesized that animals living in polluted environments possess antimicrobials to counter pathogenic microbes. The fact that snakes feed on germ-infested rodents suggests that they encounter pathogenic microbes and likely possess antimicrobials. The venom is used only to paralyze the rodent, but the ability of snakes to counter potential infections in the gut due to disease-ridden rodents requires robust action of the immune system against a broad range of pathogens. To test this hypothesis, crude lysates of different organs of Naja naja karachiensis (black cobra) were tested for antimicrobial properties. The antimicrobial activities of extracts were tested against selected bacterial pathogens (neuropathogenic Escherichia coli K1, methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Streptococcus pneumonia), protist (Acanthamoeba castellanii), and filamentous fungus (Fusarium solani). The findings revealed that plasma and various organ extracts of N. n. karachiensis exhibited antimicrobial activity against E. coli K1, MRSA, P. aeruginosa, S. pneumoniae, A. castellanii, and F. solani in a concentration-dependent manner. The results of this study are promising for the development of new antimicrobials. PMID:24625321

  13. Antibodies against Marinobacter algicola and Salmonella typhimurium flagellins do not cross-neutralize TLR5 activation.

    Directory of Open Access Journals (Sweden)

    Raul Terron-Exposito

    Full Text Available Flagellins evoke strong innate and adaptive immune responses. These proteins may play a key role as radioprotectors, exert antitumoral activity in certain types of tumor and reduce graft-versus-host disease in allogeneic hematopoietic stem cell transplant recipients. Notwithstanding, flagellins are highly immunogenic, and repeated use leads to their neutralization by systemic antibodies. This neutralization is not prevented by using functional deleted flagellins. These observations led us to explore the possibility of preventing initial neutralization by means of another functional flagellin that does not belong to common pathogenic bacteria but that has the capacity to activate TLR5. Here we characterized the functional capacity of the two-phase Marinobacter algicola (MA-derived flagellins (F and FR as systemic and mucosal adjuvants and compared their performance with that of Salmonella typhimurium (STF flagellins (FljB and FliC. We also report for the first time on the in vitro and in vivo capacity of various flagellins to trigger TLR5 activation in the presence of species-specific anti-flagellin antibodies, the cross-neutralization mediated by these antibodies, and the sequential use of these flagellins for TLR5 activation. Our results showed that MA flagellins behave in a similar way to STF ones, inducing pro-inflammatory cytokines (IL8, CCL20, CCL2 and evoking a strong in vivo antibody response against a model epitope. More importantly, MA flagellins were fully functional, in vitro or in vivo, in the presence of a high concentration of neutralizing anti-flagellin STF antibodies, and STF flagellin was not inhibited by neutralizing anti-flagellin MA antibodies. The use of active flagellins from distinct bacteria could be a useful approach to prevent systemic neutralization of this group of adjuvants and to facilitate the rational design of flagellin-based vaccines and/or other therapeutic treatments (against ischemia, acute renal failure

  14. Broad Escovopsis-inhibition activity of Pseudonocardia associated with Trachymyrmex ants.

    Science.gov (United States)

    Meirelles, Lucas A; Mendes, Thaís D; Solomon, Scott E; Bueno, Odair C; Pagnocca, Fernando C; Rodrigues, Andre

    2014-08-01

    Attine ants maintain an association with antibiotic-producing Actinobacteria found on their integuments. Evidence supports these bacteria as auxiliary symbionts that help ants to defend the fungus gardens against pathogens. Using Pseudonocardia strains isolated from Trachymyrmex ants, we tested whether the inhibitory capabilities of such strains are restricted to Escovopsis parasites that infect gardens of this ant genus. Twelve Pseudonocardia strains were tested in in vitro bioassays against Escovopsis strains derived from fungus gardens of Trachymyrmex (n = 1) and leaf-cutting ants (n = 3). Overall, significant differences were observed in the mycelial growth among each Escovopsis strain in the presence of Pseudonocardia. Particularly, Escovopsis from Acromyrmex and Trachymyrmex were the most inhibited strains in comparison to Escovopsis isolated from Atta. This result suggests that Pseudonocardia isolated from Trachymyrmex possibly secrete antimicrobial compounds effective against diverse Escovopsis strains. The fact that Trachymyrmex ants harbour Pseudonocardia strains with broad spectrum of activity and its defensive role on attine gardens are discussed. PMID:24992532

  15. Off-axis irradiation and the polarization of broad emission lines in active galactic nuclei

    CERN Document Server

    Goosmann, Rene W; Marin, Frederic

    2013-01-01

    The STOKES Monte Carlo radiative transfer code has been extended to model the velocity dependence of the polarization of emission lines. We use STOKES to present improved modelling of the velocity-dependent polarization of broad emission lines in active galactic nuclei. We confirm that off-axis continuum emission can produce observed velocity dependencies of both the degree and position angle of polarization. The characteristic features are a dip in the percentage polarization and an S-shaped swing in the position angle of the polarization across the line profile. Some differences between our STOKES results and previous modelling of polarization due to off-axis emission are noted. In particular we find that the presence of an offset between the maximum in line flux and the dip in the percentage of polarization or the central velocity of the swing in position angle does not necessarily imply that the scattering material is moving radially. Our model is an alternative scenario to the equatorial scattering disk ...

  16. Expression of Aspergillus nidulans phy Gene in Nicotiana benthamiana Produces Active Phytase with Broad Specificities

    Directory of Open Access Journals (Sweden)

    Tae-Kyun Oh

    2014-09-01

    Full Text Available A full-length phytase gene (phy of Aspergillus nidulans was amplified from the cDNA library by polymerase chain reaction (PCR, and it was introduced into a bacterial expression vector, pET-28a. The recombinant protein (rPhy-E, 56 kDa was overexpressed in the insoluble fraction of Escherichia coli culture, purified by Ni-NTA resin under denaturing conditions and injected into rats as an immunogen. To express A. nidulans phytase in a plant, the full-length of phy was cloned into a plant expression binary vector, pPZP212. The resultant construct was tested for its transient expression by Agrobacterium-infiltration into Nicotiana benthamiana leaves. Compared with a control, the agro-infiltrated leaf tissues showed the presence of phy mRNA and its high expression level in N. benthamiana. The recombinant phytase (rPhy-P, 62 kDa was strongly reacted with the polyclonal antibody against the nonglycosylated rPhy-E. The rPhy-P showed glycosylation, two pH optima (pH 4.5 and pH 5.5, an optimum temperature at 45~55 °C, thermostability and broad substrate specificities. After deglycosylation by peptide-N-glycosidase F (PNGase-F, the rPhy-P significantly lost the phytase activity and retained 1/9 of the original activity after 10 min of incubation at 45 °C. Therefore, the deglycosylation caused a significant reduction in enzyme thermostability. In animal experiments, oral administration of the rPhy-P at 1500 U/kg body weight/day for seven days caused a significant reduction of phosphorus excretion by 16% in rat feces. Besides, the rPhy-P did not result in any toxicological changes and clinical signs.

  17. Performance study of the TFTR diagnostic neutral beam for active charge exchange measurements

    International Nuclear Information System (INIS)

    A neutral beam source will be incorporated in the Tokamak Fusion Test Reactor (TFTR) charge exchange diagnostic to provide a time modulated, spatially localized enhancement of the charge exchange efflux. Two autonomous Charge Exchange Neutral Analyzer (CENA) systems are being designed for the TFTR. One system measures the plasma ion temperature along twelve vertical line-of-sight chords spaced approximately equidistantly across the torus minor diameter. The other system is dedicated primarily to measurement of ion phenomena associated with neutral beam injection heating and has a fan-like field of view along eight sight-lines in the equitorial plane. The neutral beam is steerable in order to access the viewing field of both CENA systems, though in general not simultaneously. The performance of the diagnostic neutral beam is evaluated to determine the optimal beam specifications for active charge exchange measurements. Using the optimal beam design parameters, the efficacy of the neutral doping is examined for both CENA systems over the envisioned range of the TFTR plasma density and temperature

  18. Heterologous prime-boost immunization regimens using adenovirus vector and virus-like particles induce broadly neutralizing antibodies against H5N1 avian influenza viruses.

    Science.gov (United States)

    Lin, Shih-Chang; Liu, Wen-Chun; Lin, Yu-Fen; Huang, Yu-Hsuan; Liu, Jin-Hwang; Wu, Suh-Chin

    2013-11-01

    Highly pathogenic avian influenza (HPAI) H5N1 viruses continue to trigger severe diseases in poultry and humans, prompting efforts to develop an effective vaccine. Toward that goal, we constructed a recombinant adenovirus vector encoding influenza hemagglutin (rAd-HA) and a flagellin-containing virus-like particle (FliC-VLP). Using a murine model, we investigated a heterologous prime-boost vaccination regimen combining these two vectors. Our results indicate that priming with the rAd-HA vector followed by a FliC-VLP booster induced the highest HA-specific total IgG, IgG1and IgG2a. Maximum neutralizing antibody titers against homologous and heterologous clades of H5N1 virus strains and hemagglutination inhibition resulted from the heterologous vaccination strategy. Our results are likely to contribute to the development of more effective H5N1 vaccines. PMID:23813782

  19. Advances in near-neutral salts activation of blast furnace slags

    OpenAIRE

    Bernal Lopez, S.

    2016-01-01

    The utilisation of near-neutral salts as activators to produce alkali-activated slag cements offers several technical advantages, including reduced alkalinity of the binders, minimising the risk associated with handling of highly alkaline materials, and better workability of the fresh paste compared to that of sodium silicate-activated slag cements. Despite these evident advantages, the delayed setting and slow early-age mechanical strength development of these cements have limited their adop...

  20. A CENSUS OF BROAD-LINE ACTIVE GALACTIC NUCLEI IN NEARBY GALAXIES: COEVAL STAR FORMATION AND RAPID BLACK HOLE GROWTH

    International Nuclear Information System (INIS)

    We present the first quantified, statistical map of broad-line active galactic nucleus (AGN) frequency with host galaxy color and stellar mass in nearby (0.01 < z < 0.11) galaxies. Aperture photometry and z-band concentration measurements from the Sloan Digital Sky Survey are used to disentangle AGN and galaxy emission, resulting in estimates of uncontaminated galaxy rest-frame color, luminosity, and stellar mass. Broad-line AGNs are distributed throughout the blue cloud and green valley at a given stellar mass, and are much rarer in quiescent (red sequence) galaxies. This is in contrast to the published host galaxy properties of weaker narrow-line AGNs, indicating that broad-line AGNs occur during a different phase in galaxy evolution. More luminous broad-line AGNs have bluer host galaxies, even at fixed mass, suggesting that the same processes that fuel nuclear activity also efficiently form stars. The data favor processes that simultaneously fuel both star formation activity and rapid supermassive black hole accretion. If AGNs cause feedback on their host galaxies in the nearby universe, the evidence of galaxy-wide quenching must be delayed until after the broad-line AGN phase.

  1. Neutral-Line Magnetic Shear and Enhanced Coronal Heating in Solar Active Regions

    Science.gov (United States)

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

    1997-01-01

    By examining the magnetic structure at sites in the bright coronal interiors of active regions that are not flaring but exhibit persistent strong coronal heating, we establish some new characteristics of the magnetic origins of this heating. We have examined the magnetic structure of these sites in five active regions, each of which was well observed by both the Yohkoh SXT and the Marshall Space Flight Center Vector Magnetograph and showed strong shear in its magnetic field along part of at least one neutral line (polarity inversion). Thus, we can assess whether this form of nonpotential field structure in active regions is a characteristic of the enhanced coronal heating and vice versa. From 27 orbits' worth of Yohkoh SXT images of the five active regions, we have obtained a sample of 94 persistently bright coronal features (bright in all images from a given orbit), 40 long (greater than or approximately equals 20,000 km) neutral-line segments having strong magnetic shear throughout (shear angle greater than 45 deg), and 39 long neutral-line segments having weak magnetic shear throughout (shear angle less than 45 deg). From this sample, we find that: (1) all of our persistently bright coronal features are rooted in magnetic fields that are stronger than 150 G; (2) nearly all (95%) of these enhanced coronal features are rooted near neutral lines (closer than 10,000 km); (3) a great majority (80%) of the bright features are rooted near strong-shear portions of neutral lines; (4) a great majority (85%) of long strong-shear segments of neutral lines have persistently bright coronal features rooted near them; (5) a large minority (40%) of long weak-shear segments of neutral lines have persistently bright coronal features rooted near them; and (6) the brightness of a persistently bright Coronal feature often changes greatly over a few hours. From these results, we conclude that most persistent enhanced heating of coronal loops in active regions: (1) requires the

  2. Discovery of New Imidazole Derivatives Containing the 2,4-Dienone Motif with Broad-Spectrum Antifungal and Antibacterial Activity

    OpenAIRE

    Chunli Liu; Ce Shi; Fei Mao; Yong Xu; Jinyan Liu; Bing Wei; Jin Zhu; Mingjie Xiang; Jian Li

    2014-01-01

    A compound containing an imidazole moiety and a 2,4-dienone motif with significant activity toward several fungi was discovered in a screen for new antifungal compounds. Then, a total of 26 derivatives of this compound were designed, synthesized and evaluated through in vitro and in vivo antifungal activity assays. Several compounds exhibited improved antifungal activities compared to the lead compound. Of the derivatives, compounds 31 and 42 exhibited strong, broad-spectrum inhibitory effect...

  3. Potent Intratype Neutralizing Activity Distinguishes Human Immunodeficiency Virus Type 2 (HIV-2) from HIV-1

    OpenAIRE

    Özkaya Şahin, Gülşen; Holmgren, Birgitta; da Silva, Zacarias; Nielsen, Jens; Nowroozalizadeh, Salma; Esbjörnsson, Joakim; Månsson, Fredrik; Andersson, Sören; Norrgren, Hans; Aaby, Peter; Jansson, Marianne; Fenyö, Eva Maria

    2012-01-01

    HIV-2 has a lower pathogenicity and transmission rate than HIV-1. Neutralizing antibodies could be contributing to these observations. Here we explored side by side the potency and breadth of intratype and intertype neutralizing activity (NAc) in plasma of 20 HIV-1-, 20 HIV-2-, and 11 dually HIV-1/2 (HIV-D)-seropositive individuals from Guinea-Bissau, West Africa. Panels of primary isolates, five HIV-1 and five HIV-2 isolates, were tested in a plaque reduction assay using U87.CD4-CCR5 cells a...

  4. Broad Hbeta Emission-Line Variability in a Sample of 102 Local Active Galaxies

    CERN Document Server

    Runco, Jordan N; Bennert, Vardha N; Scott, Bryan; Komossa, S; Malkan, Matthew A; Lazarova, Mariana S; Auger, Matthew W; Treu, Tommaso; Park, Daeseong

    2016-01-01

    A sample of 102 local (0.02 10^7 M_sun was selected from the Sloan Digital Sky Survey (SDSS) and observed using the Keck 10-m telescope to study the scaling relations between MBH and host galaxy properties. We study profile changes of the broad Hbeta emission line within the ~3-9 year time-frame between the two sets of spectra. The variability of the broad Hbeta emission line is of particular interest, not only since it is used to estimate MBH, but also since its strength and width is used to classify Seyfert galaxies into different types. At least some form of broad-line variability (in either width or flux) is observed in the majority (~66%) of the objects, resulting in a Seyfert-type change for ~38% of the objects, likely driven by variable accretion and/or obscuration. The broad Hbeta line virtually disappears in 3/102 (~3%) extreme cases. We discuss potential causes for these changing-look AGNs. While similar dramatic transitions have previously been reported in the literature, either on a case-by-case ...

  5. Chemical acceleration of a neutral granulated blast-furnace slag activated by sodium carbonate

    International Nuclear Information System (INIS)

    This paper presents results of a study on chemical acceleration of a neutral granulated blast-furnace slag activated using sodium carbonate. As strength development of alkali-activated slag cements containing neutral GBFS and sodium carbonate as activator at room temperature is known to be slow, three accelerators were investigated: sodium hydroxide, ordinary Portland cement and a combination of silica fume and slaked lime. In all cements, the main hydration product is C–(A)–S–H, but its structure varies between tobermorite and riversideite depending on the accelerator used. Calcite and gaylussite are present in all systems and they were formed due to either cation exchange reaction between the slag and the activator, or carbonation. With accelerators, compressive strength up to 15 MPa can be achieved within 24 h in comparison to 2.5 MPa after 48 h for a mix without an accelerator

  6. Chemical acceleration of a neutral granulated blast-furnace slag activated by sodium carbonate

    Energy Technology Data Exchange (ETDEWEB)

    Kovtun, Maxim, E-mail: max.kovtun@up.ac.za; Kearsley, Elsabe P., E-mail: elsabe.kearsley@up.ac.za; Shekhovtsova, Julia, E-mail: j.shekhovtsova@gmail.com

    2015-06-15

    This paper presents results of a study on chemical acceleration of a neutral granulated blast-furnace slag activated using sodium carbonate. As strength development of alkali-activated slag cements containing neutral GBFS and sodium carbonate as activator at room temperature is known to be slow, three accelerators were investigated: sodium hydroxide, ordinary Portland cement and a combination of silica fume and slaked lime. In all cements, the main hydration product is C–(A)–S–H, but its structure varies between tobermorite and riversideite depending on the accelerator used. Calcite and gaylussite are present in all systems and they were formed due to either cation exchange reaction between the slag and the activator, or carbonation. With accelerators, compressive strength up to 15 MPa can be achieved within 24 h in comparison to 2.5 MPa after 48 h for a mix without an accelerator.

  7. A Census of Broad-Line Active Galactic Nuclei in Nearby Galaxies: Coeval Star Formation and Rapid Black Hole Growth

    CERN Document Server

    Trump, Jonathan R; Fang, Jerome J; Faber, S M; Koo, David C; Kocevski, Dale D

    2012-01-01

    We present the first quantified, statistical map of broad-line active galactic nucleus (AGN) frequency with host galaxy color and stellar mass in nearby (0.01 < z < 0.11) galaxies. Aperture photometry and z-band concentration measurements from the Sloan Digital Sky Survey (SDSS) are used to dis- entangle AGN and galaxy emission, resulting in estimates of uncontaminated galaxy rest-frame color, luminosity, and stellar mass. Broad-line AGNs are distributed throughout the blue cloud and green valley at a given stellar mass, and are much rarer in quiescent (red sequence) galaxies. This is in contrast to the published host galaxy properties of weaker narrow-line AGNs, indicating that broad-line AGNs occur during a different phase in galaxy evolution. More luminous broad-line AGNs have bluer host galaxies, even at fixed mass, suggesting that the same processes that fuel nuclear activity also efficiently form stars. The data favor processes that simultaneously fuel both star formation activity and rapid superm...

  8. Structure and Kinematics of the Broad-Line Region and Torus of Active Galactic Nuclei

    OpenAIRE

    Gaskell, C. Martin; Goosmann, Rene W.; Klimek, Elizabeth S.

    2008-01-01

    Energetics considerations imply that the broad-line region (BLR) has a high covering factor. The absence of absorption from the BLR means that the BLR has to have a flattened distribution and be seen through a polar hole. The BLR is the inward extension of the torus and they have similar geometries and covering factors. Reconciling velocity-resolved reverberation mapping, spectropolarimetry, and the increasing blueshifting of BLR lines with decreasing distance from the centre, implies that th...

  9. Black cobra (Naja naja karachiensis) lysates exhibit broad-spectrum antimicrobial activities

    OpenAIRE

    Sagheer, Mehwish; Siddiqui, Ruqaiyyah; Iqbal, Junaid; Khan, Naveed Ahmed

    2014-01-01

    It is hypothesized that animals living in polluted environments possess antimicrobials to counter pathogenic microbes. The fact that snakes feed on germ-infested rodents suggests that they encounter pathogenic microbes and likely possess antimicrobials. The venom is used only to paralyze the rodent, but the ability of snakes to counter potential infections in the gut due to disease-ridden rodents requires robust action of the immune system against a broad range of pathogens. To test this hypo...

  10. Complete epitopes for vaccine design derived from a crystal structure of the broadly neutralizing antibodies PGT128 and 8ANC195 in complex with an HIV-1 Env trimer.

    Science.gov (United States)

    Kong, Leopold; Torrents de la Peña, Alba; Deller, Marc C; Garces, Fernando; Sliepen, Kwinten; Hua, Yuanzi; Stanfield, Robyn L; Sanders, Rogier W; Wilson, Ian A

    2015-10-01

    The HIV-1 envelope gp160 glycoprotein (Env) is a trimer of gp120 and gp41 heterodimers that mediates cell entry and is the primary target of the humoral immune response. Broadly neutralizing antibodies (bNAbs) to HIV-1 have revealed multiple epitopes or sites of vulnerability, but mapping of most of these sites is incomplete owing to a paucity of structural information on the full epitope in the context of the Env trimer. Here, a crystal structure of the soluble BG505 SOSIP gp140 trimer at 4.6 Å resolution with the bNAbs 8ANC195 and PGT128 reveals additional interactions in comparison to previous antibody-gp120 structures. For 8ANC195, in addition to previously documented interactions with gp120, a substantial interface with gp41 is now elucidated that includes extensive interactions with the N637 glycan. Surprisingly, removal of the N637 glycan did not impact 8ANC195 affinity, suggesting that the antibody has evolved to accommodate this glycan without loss of binding energy. PGT128 indirectly affects the N262 glycan by a domino effect, in which PGT128 binds to the N301 glycan, which in turn interacts with and repositions the N262 glycan, thereby illustrating the important role of neighboring glycans on epitope conformation and stability. Comparisons with other Env trimer and gp120 structures support an induced conformation for glycan N262, suggesting that the glycan shield is allosterically modified upon PGT128 binding. These complete epitopes of two broadly neutralizing antibodies on the Env trimer can now be exploited for HIV-1 vaccine design. PMID:26457433

  11. High Power 940 nm Al-free Active Region Laser Diodes and Bars with a Broad Waveguide

    Institute of Scientific and Technical Information of China (English)

    FANG Gaozhan; XIAO Jianwei; MA Xiaoyu; XU Zuntu; ZHANG Jinming; TAN Manqing; LIU Zongshun; LIU Suping; FENG Xiaoming

    2002-01-01

    The 940 nm Al-free active region laser diodes and bars with a broad waveguide were designed and fabricated. The stuctures were grown by metal organic chemical vapour deposition. The devices show excellent performances. The maximum output power of 6.7 W in the 100 μm broad-area laser diodes has been measured, and is 2.5 times higher than that in the Al-containing active region laser diodes with a narrow waveguide and 1.7 times higher than that in Al-free active region laser diodes with a narrow waveguide. The 19% fill-factor laser diode bars emit 33 W, and they can operate at 15W with low degradation rates.

  12. Novel Clostridium difficile Anti-Toxin (TcdA and TcdB) Humanized Monoclonal Antibodies Demonstrate In Vitro Neutralization across a Broad Spectrum of Clinical Strains and In Vivo Potency in a Hamster Spore Challenge Model

    Science.gov (United States)

    Qiu, Hongyu; Cassan, Robyn; Johnstone, Darrell; Han, Xiaobing; Joyee, Antony George; McQuoid, Monica; Masi, Andrea; Merluza, John; Hrehorak, Bryce; Reid, Ross; Kennedy, Kieron; Tighe, Bonnie; Rak, Carla; Leonhardt, Melanie; Dupas, Brian; Saward, Laura; Berry, Jody D.; Nykiforuk, Cory L.

    2016-01-01

    Clostridium difficile (C. difficile) infection (CDI) is the main cause of nosocomial antibiotic-associated colitis and increased incidence of community-associated diarrhea in industrialized countries. At present, the primary treatment of CDI is antibiotic administration, which is effective but often associated with recurrence, especially in the elderly. Pathogenic strains produce enterotoxin, toxin A (TcdA), and cytotoxin, toxin B (TcdB), which are necessary for C. difficile induced diarrhea and gut pathological changes. Administration of anti-toxin antibodies provides an alternative approach to treat CDI, and has shown promising results in preclinical and clinical studies. In the current study, several humanized anti-TcdA and anti-TcdB monoclonal antibodies were generated and their protective potency was characterized in a hamster infection model. The humanized anti-TcdA (CANmAbA4) and anti-TcdB (CANmAbB4 and CANmAbB1) antibodies showed broad spectrum in vitro neutralization of toxins from clinical strains and neutralization in a mouse toxin challenge model. Moreover, co-administration of humanized antibodies (CANmAbA4 and CANmAbB4 cocktail) provided a high level of protection in a dose dependent manner (85% versus 57% survival at day 22 for 50 mg/kg and 20 mg/kg doses, respectively) in a hamster gastrointestinal infection (GI) model. This study describes the protective effects conferred by novel neutralizing anti-toxin monoclonal antibodies against C. difficile toxins and their potential as therapeutic agents in treating CDI. PMID:27336843

  13. Novel Clostridium difficile Anti-Toxin (TcdA and TcdB Humanized Monoclonal Antibodies Demonstrate In Vitro Neutralization across a Broad Spectrum of Clinical Strains and In Vivo Potency in a Hamster Spore Challenge Model.

    Directory of Open Access Journals (Sweden)

    Hongyu Qiu

    Full Text Available Clostridium difficile (C. difficile infection (CDI is the main cause of nosocomial antibiotic-associated colitis and increased incidence of community-associated diarrhea in industrialized countries. At present, the primary treatment of CDI is antibiotic administration, which is effective but often associated with recurrence, especially in the elderly. Pathogenic strains produce enterotoxin, toxin A (TcdA, and cytotoxin, toxin B (TcdB, which are necessary for C. difficile induced diarrhea and gut pathological changes. Administration of anti-toxin antibodies provides an alternative approach to treat CDI, and has shown promising results in preclinical and clinical studies. In the current study, several humanized anti-TcdA and anti-TcdB monoclonal antibodies were generated and their protective potency was characterized in a hamster infection model. The humanized anti-TcdA (CANmAbA4 and anti-TcdB (CANmAbB4 and CANmAbB1 antibodies showed broad spectrum in vitro neutralization of toxins from clinical strains and neutralization in a mouse toxin challenge model. Moreover, co-administration of humanized antibodies (CANmAbA4 and CANmAbB4 cocktail provided a high level of protection in a dose dependent manner (85% versus 57% survival at day 22 for 50 mg/kg and 20 mg/kg doses, respectively in a hamster gastrointestinal infection (GI model. This study describes the protective effects conferred by novel neutralizing anti-toxin monoclonal antibodies against C. difficile toxins and their potential as therapeutic agents in treating CDI.

  14. Broad emission lines in the duelling wind model of active galaxies

    International Nuclear Information System (INIS)

    The broad-line emission from clouds formed by the interaction of a nuclear mass outflow and a disc wind is investigated in the context of a quasar model. The line ratios and profiles are shown to be in general agreement with observation. Particular results include (i) a density range compatible with suggested solutions to the Lyα/Hβ problem which nevertheless yields the correct C III λ 1909 flux; (ii) broader lines from the inner higher density region despite an accelerated outflow; (iii) compatibility between BLR sizes from variability arguments and ionization parameters; (iv) blueshifted line-peaks apparently uncorrelated with line asymmetry. (author)

  15. Inhibitors of cellular kinases with broad-spectrum antiviral activity for hemorrhagic fever viruses.

    Science.gov (United States)

    Mohr, Emma L; McMullan, Laura K; Lo, Michael K; Spengler, Jessica R; Bergeron, Éric; Albariño, César G; Shrivastava-Ranjan, Punya; Chiang, Cheng-Feng; Nichol, Stuart T; Spiropoulou, Christina F; Flint, Mike

    2015-08-01

    Host cell kinases are important for the replication of a number of hemorrhagic fever viruses. We tested a panel of kinase inhibitors for their ability to block the replication of multiple hemorrhagic fever viruses. OSU-03012 inhibited the replication of Lassa, Ebola, Marburg and Nipah viruses, whereas BIBX 1382 dihydrochloride inhibited Lassa, Ebola and Marburg viruses. BIBX 1382 blocked both Lassa and Ebola virus glycoprotein-dependent cell entry. These compounds may be used as tools to understand conserved virus-host interactions, and implicate host cell kinases that may be targets for broad spectrum therapeutic intervention. PMID:25986249

  16. Highly selective palladium–benzothiazole carbene-catalyzed allylation of active methylene compounds under neutral conditions

    OpenAIRE

    Antonio Monopoli; Pietro Cotugno; Zambonin, Carlo G.; Francesco Ciminale; Angelo Nacci

    2015-01-01

    The Pd–benzothiazol-2-ylidene complex I was found to be a chemoselective catalyst for the Tsuji–Trost allylation of active methylene compounds carried out under neutral conditions and using carbonates as allylating agents. The proposed protocol consists in a simplified procedure adopting an in situ prepared catalyst from Pd2dba3 and 3-methylbenzothiazolium salt V as precursors. A comparison of the performance of benzothiazole carbene with phosphanes and an analogous imidazolium carbene ligand...

  17. Activity Coefficient Derivatives of Ternary Systems Based on Scatchard's Neutral Electrolyte description

    Energy Technology Data Exchange (ETDEWEB)

    Miller, D G

    2007-05-16

    Activity coefficient derivatives with respect to molality are presented for the Scatchard Neutral Electrolyte description of a ternary common-ion electrolyte system. These quantities are needed for the calculation of 'diffusion Onsager coefficients' and in turn for tests of the Onsager Reciprocal Relations in diffusion. The usually-omitted b{sub 23} term is included. The direct SNE binary approximations and a further approximation are discussed. Binary evaluation strategies other than constant ionic strength are considered.

  18. In vitro studies on the antibacterial activities of YM-13115, a new broad-spectrum cephalosporin.

    OpenAIRE

    Toda, M; Arao, N; Nohara, C; Susaki, K; Tachibana, A

    1985-01-01

    The in vitro antibacterial activities of YM-13115, a new parenteral cephalosporin, were compared with those of ceftazidime, cefoperazone, and cefsulodin. The compound was highly active against the common members of the Enterobacteriaceae and 2 to 256 times more active than cefoperazone. YM-13115 was as active as ceftazidime against Citrobacter freundii, Proteus vulgaris, and Morganella morganii and two to four times more active than ceftazidime against Escherichia coli, Klebsiella pneumoniae,...

  19. Structure and Kinematics of the Broad-Line Region and Torus of Active Galactic Nuclei

    CERN Document Server

    Gaskell, C Martin; Klimek, Elizabeth S

    2008-01-01

    Energetics considerations imply that the broad-line region (BLR) has a high covering factor. The absence of absorption from the BLR means that the BLR has to have a flattened distribution and be seen through a polar hole. The BLR is the inward extension of the torus and they have similar geometries and covering factors. Reconciling velocity-resolved reverberation mapping, spectropolarimetry, and the increasing blueshifting of BLR lines with decreasing distance from the centre, implies that the BLR has a significant inflow component. This inflow provides the mass inflow rate needed to power the AGN. We suggest that the mechanism producing the outward transport of angular momentum necessary for the net inflow of the BLR is the magneto-rotational instability, and that the BLR and outer accretion disc are one and the same.

  20. Structure and kinematics of the broad-line regions in active galaxies from IUE variability data

    International Nuclear Information System (INIS)

    IUE archival data are used here to investigate the structure and kinematics of the broad-line regions (BLRs) in nine AGN. It is found that the centroid of the line-continuum cross-correlation functions (CCFs) can be determined with reasonable reliability. The errors in BLR size estimates from CCFs for irregularly sampled light curves are fairly well understood. BLRs are found to have small luminosity-weighted radii, and lines of high ionization tend to be emitted closer to the central source than lines of low ionization, especially for low-luminosity objects. The motion of the gas is gravity-dominated with both pure inflow and pure outflow of high-velocity gas being excluded at a high confidence level for certain geometries. 66 refs

  1. Mechanical Activation-Assisted Reductive Leaching of Cadmium from Zinc Neutral Leaching Residue Using Sulfur Dioxide

    Science.gov (United States)

    Zhang, Chun; Min, Xiaobo; Chai, Liyuan; Zhang, Jianqiang; Wang, Mi

    2015-12-01

    In this work, zinc neutral leaching residue was mechanically activated by ball-milling. The subsequent leaching behavior and kinetics of cadmium extraction in a mixed SO2-H2SO4 system were studied. Changes in the crystalline phase, lattice distortion, particle size and morphology, which were induced by mechanical activation, were also investigated. The activated samples showed different physicochemical characteristics, and cadmium extraction was found to be easier than for the un-activated samples. Under the same conditions, mechanical activation contributed to higher cadmium leaching. The cadmium extraction kinetics at 75-95°C was found to fit the shrinking core model. The raw neutral leaching residue, and the samples activated for 60 min and 120 min had a calculated activation energy of 65.02 kJ/mol, 59.45 kJ/mol and 53.46 kJ/mol, respectively. The leaching residue was characterized by ICP, XRD and SEM analysis. According to XRD analysis, the main phases in the residue were lead sulfate (PbSO4), zinc sulfide (ZnS) and cadmium sulfide (CdS).

  2. Broad-band linear polarization in late-type active dwarfs

    Science.gov (United States)

    Patel, Manoj K.; Pandey, Jeewan C.; Karmakar, Subhajeet; Srivastava, D. C.; Savanov, Igor S.

    2016-04-01

    We present recent polarimetric results of magnetically active late-type dwarfs. The polarization in these stars is found to be wavelength dependent, decreasing towards the longer wavelength. The average values of degree of polarization in these active dwarfs are found to be 0.16 ± 0.01, 0.080 ± 0.006, 0.056 ± 0.004 and 0.042 ± 0.003 per cent in B, V, R, and I bands, respectively. Present results indicate that polarization in the majority of active dwarfs are primarily due to sum of the polarization by magnetic intensification and scattering. However, supplementary sources of the polarization are also found to be present in some active stars. The correlations between the degree of polarization and various activity parameters like Rossby number, chromospheric activity indicator and coronal activity indicator are found to be stronger in B band and weaker in I band.

  3. Broad-band linear polarization in late-type active dwarfs

    CERN Document Server

    Patel, Manoj K; Karmakar, Subhajeet; Srivastava, D C; Savanov, Igor S

    2016-01-01

    We present recent polarimetric results of magnetically active late-type dwarfs. The polarization in these stars is found to be wavelength dependent, decreasing towards the longer wavelength. The average values of degree of polarization in these active dwarfs are found to be 0.16+/-0.01, 0.080+/-0.006, 0.056+/-0.004 and 0.042+/-0.003 per cent in B, V, R, and I bands, respectively. Present results indicate that polarization in the majority of active dwarfs are primarily due to sum of the polarization by magnetic intensification and scattering. However, supplementary sources of the polarization are also found to be present in some active stars. The correlations between the degree of polarization and various activity parameters like Rossby number, chromospheric activity indicator and coronal activity indicator are found to be stronger in B band and weaker in I band.

  4. Comparative study on active soil organic matter in Chinese fir plantation and native broad-leaved forest in subtropical China

    Institute of Scientific and Technical Information of China (English)

    WANG Qing-kui; WANG Si-long; DENG Shi-jian

    2005-01-01

    Active soil organic matter (ASOM) has a main effect on biochemical cycles of soil nutrient elements such as N, P and S, and the quality and quantity of ASOM reflect soil primary productivity. The changes of ASOM fractions and soil nutrients in the first rotation site and the second rotation site of Chinese fir plantation and the native broad-leaved forest were investigated and analyzed by soil sampling at the Huitong Experimental Station of Forestry Ecology (at latitude 26°48′N and longitude 109°30′E under a subtropical climate conditions), Chinese Academy of Sciences in March, 2004. The results showed that values of ASOM fractions for the Chinese fir plantations were lower than those for the broad-leaved forest. The contents of easily oxidisable carbon (EOC), microbial biomass carbon (MBC), water soluble carbohydrate (WSC) and water-soluble organic carbon (WSOC) for the first rotation of Chinese fir plantation were 35.9%, 13.7%, 87.8% and 50.9% higher than those for the second rotation of Chinese fir plantation, and were 15.8%, 47.3%, 38.1% and 30.2% separately lower than those for the broad-leaved forest. For the three investigated forest sites, the contents of MBC and WSOC had a larger decrease, followed by WSC, and the change of EOC was least. Moreover, soil physico-chemistry properties such as soil nutrients in Chinese fir plantation were lower than those in broad-leaved forest. It suggested that soil fertility declined after Chinese fir plantation replaced native broad-leaved forest through continuous artificial plantation.

  5. Highly active cobalt phosphate and borate based oxygen evolving catalysts operating in neutral and natural waters

    Energy Technology Data Exchange (ETDEWEB)

    Esswein, AJ; Surendranath, Y; Reece, SY; Nocera, DG

    2011-02-01

    A high surface area electrode is functionalized with cobalt-based oxygen evolving catalysts (Co-OEC = electrodeposited from pH 7 phosphate, Pi, pH 8.5 methylphosphonate, MePi, and pH 9.2 borate electrolyte, Bi). Co-OEC prepared from MePi and operated in Pi and Bi achieves a current density of 100 mA cm(-2) for water oxidation at 442 and 363 mV overpotential, respectively. The catalyst retains activity in near-neutral pH buffered electrolyte in natural waters such as those from the Charles River (Cambridge, MA) and seawater (Woods Hole, MA). The efficacy and ease of operation of anodes functionalized with Co-OEC at appreciable current density together with its ability to operate in near neutral pH buffered natural water sources bodes well for the translation of this catalyst to a viable renewable energy storage technology.

  6. Improving the neutral phytase activity from Bacillus amyloliquefaciens DSM 1061 by site-directed mutagenesis.

    Science.gov (United States)

    Xu, Wei; Shao, Rong; Wang, Zupeng; Yan, Xiuhua

    2015-03-01

    Neutral phytase is used as a feed additive for degradation of anti-nutritional phytate in aquatic feed industry. Site-directed mutagenesis of Bacillus amyloliquefaciens DSM 1061 phytase was performed with an aim to increase its activity. Mutation residues were chosen based on multiple sequence alignments and structure analysis of neutral phytsaes from different microorganisms. The mutation sites on surface (D148E, S197E and N156E) and around the active site (D52E) of phytase were selected. Analysis of the phytase variants showed that the specific activities of mutants D148E and S197E remarkably increased by about 35 and 13% over a temperature range of 40-75 °C at pH 7.0, respectively. The k cat of mutants D148E and S197E were 1.50 and 1.25 times than that of the wild-type phytase, respectively. Both D148E and S197E showed much higher thermostability than that of the wild-type phytase. However, mutants N156E and D52E led to significant loss of specific activity of the enzyme. Structural analysis revealed that these mutations may affect conformation of the active site of phytase. The present mutant phytases D148E and S197E with increased activities and thermostabilities have application potential as additives in aquaculture feed. PMID:25613522

  7. The cross-neutralizing activity of enterovirus 71 subgenotype c4 vaccines in healthy chinese infants and children.

    Directory of Open Access Journals (Sweden)

    Qunying Mao

    Full Text Available BACKGROUND: EV71 is one of major etiologic causes of hand-foot-mouth disease (HFMD and leads to severe neurological complications in young children and infants. Recently inactivated EV71 vaccines have been developed by five manufactures and clinically show good safety and immunogenicity. However, the cross-neutralizing activity of these vaccines remains unclear, and is of particular interest because RNA recombination is seen more frequently in EV71 epidemics. METHODOLOGY/PRINCIPAL FINDINGS: In this post-hoc study, sera from a subset of 119 infants and children in two clinical trials of EV71 subgenotype C4 vaccines (ClinicalTrials.gov Identifier: NCT01313715 and NCT01273246, were detected for neutralizing antibody (NTAb titres with sera from infected patients as controls. Cytopathogenic effect method was employed to test NTAb against EV71 subgenotype B4, B5, C2, C4 and C5, which were prominent epidemic strains worldwide over the past decade. To validate the accuracy of the results, ELISpot assay was employed in parallel to detect NTAb in all the post-vaccine sera. After two-dose vaccination, 49 out of 53 participants in initially seronegative group and 52 out of 53 participants in initially seropositive group showed less than 4-fold differences in NTAb titers against five EV71 strains, whereas corresponding values among sera from pediatric patients recovering from EV71-induced HFMD and subclinically infected participants were 8/8 and 41/43, respectively. The geometric mean titers of participants against five subgenotypes EV71 all grew significantly after vaccinations, irrespective of the baseline NTAb titer. The relative fold increase in antibody titers (NTAb-FI against B4, B5, C2, and C5 displayed a positive correlation to the NTAb-FI against C4. CONCLUSIONS/SIGNIFICANCE: The results demonstrated broad cross-neutralizing activity induced by two C4 EV71 vaccines in healthy Chinese infants and children. However, the degree of induced cross

  8. Kinematics and Structure of Clumps in Broad-line Regions in Active Galactic Nuclei

    CERN Document Server

    Ghayuri, Mohammad

    2016-01-01

    We use the Jeans equations for an ensemble of collisionless particles to describe the distribution of broad-line region (BLR) cloud in three classes: (A) non disc (B) disc-wind (c) pure disc structure. We propose that clumpy structures in the brightest quasars belong to class A, fainter quasars and brighter Seyferts belong to class B, and dimmer Seyfert galaxies and all low-luminosity AGNs (LLAGNs) belong to class C. We derive the virial factor, $f$, for disc-like structures and find a negative correlation between the inclination angle, $\\theta_{0}$, and $f$. We find similar behaviour for $f$ as a function of the FWHM and $\\sigma_{z}$, the $z$ component of velocity dispersion. For different values of $\\theta_{0}$ we find that $ 1.0 \\lesssim f \\lesssim 9.0 $ in type1 AGNs and $ 0.5 \\lesssim f \\lesssim 1.0 $ in type2 AGNs. Moreover we have $ 0.5 \\lesssim f \\lesssim 6.5 $ for different values of FWHM and $ 1.4 \\lesssim f \\lesssim 1.8 $ for different values of $ \\sigma_{z} $. We also find that $ f $ is relatively...

  9. Restarting radio activity and dust emission in radio-loud broad absorption line quasars

    CERN Document Server

    Bruni, G; Montenegro-Montes, F M; Brienza, M; González-Serrano, J I

    2015-01-01

    Broad absorption line quasars (BAL QSOs) are objects showing absorption from relativistic outflows, with velocities up to 0.2c. These manifest, in about 15% of quasars, as absorption troughs on the blue side of UV emission lines, such as C iv and Mg ii. In this work, we complement the information collected in the cm band for our previously presented sample of radio loud BAL QSOs with new observations at m and mm bands. Our aim is to verify the presence of old, extended radio components in the MHz range, and probe the emission of dust (linked to star formation) in the mm domain. We observed 5 sources from our sample, already presenting hints of low-frequency emission, with the GMRT at 235 and 610 MHz. Other 17 sources (more than half the sample) were observed with bolometer cameras at IRAM-30m and APEX. All sources observed with the GMRT present extended emission at a scale of tens of kpc. In some cases these measurements allow us to identify a second component in the SED, at frequencies below 1.4 GHz, beyond ...

  10. Myxozoan infections of caecilians demonstrate broad host specificity and indicate a link with human activity.

    Science.gov (United States)

    Hartigan, Ashlie; Wilkinson, Mark; Gower, David J; Streicher, Jeffrey W; Holzer, Astrid S; Okamura, Beth

    2016-05-01

    Myxozoans are parasitic cnidarians that infect a wide variety of hosts. Vertebrates typically serve as intermediate hosts whereas definitive hosts are invertebrates, including annelids and bryozoans. Myxozoans are known to exploit species in two of the three extant amphibian orders (Anura: frogs and toads; Caudata: newts and salamanders). Here we use museum collections to determine, to our knowledge for the first time, whether myxozoans also exploit the third amphibian order (Gymnophiona: caecilians). Caecilians are a poorly known group of limbless amphibians, the ecologies of which range from aquatic to fully terrestrial. We examined 12 caecilian species in seven families (148 individuals total) characterised by a diversity of ecologies and life histories. Using morphological and molecular surveys, we discovered the presence of the myxozoan Cystodiscus axonis in two South American species (one of seven examined families) of aquatic caecilians - Typhlonectes natans and Typhlonectes compressicauda. All infected caecilians had been maintained in captivity in the United Kingdom prior to their preservation. Cystodiscus axonis is known from several Australian frog species and its presence in caecilians indicates a capacity for infecting highly divergent amphibian hosts. This first known report of myxozoan infections in caecilians provides evidence of a broad geographic and host range. However, the source of these infections remains unknown and could be related to exposure in South America, the U.K. or to conditions in captivity. PMID:26945641

  11. Broadly Tunable SOA-Based Active Mode-Locked Fibre Ring Laser by Forward Injection Optical Pulse

    International Nuclear Information System (INIS)

    We present a broadly tunable active mode-locked fibre ring laser based on a semiconductor optical amplifier (SOA), with forward injection optical pulses. The laser can generate pulse sequence with pulsewidth about 12ps and high output power up to 8.56dBm at 2.5 GHz stably. Incorporated with a wavelength-tunable optical bandpass filter, the pulse laser can operate with a broad wavelength tunable span up to 37nm with almost constant pulsewidth. A detailed experimental analysis is also carried out to investigate the relationship between the power of the internal cavity and the pulsewidth of the output pulse sequence. The experimental configuration of the pulse laser is very simple and easy to setup with no polarization-sensitive components. (fundamental areas of phenomenology (including applications))

  12. Structural and Enzymatic Characterization of ABgp46, a Novel Phage Endolysin with Broad Anti-Gram-Negative Bacterial Activity

    Science.gov (United States)

    Oliveira, Hugo; Vilas Boas, Diana; Mesnage, Stéphane; Kluskens, Leon D.; Lavigne, Rob; Sillankorva, Sanna; Secundo, Francesco; Azeredo, Joana

    2016-01-01

    The present study demonstrates the antibacterial potential of a phage endolysin against Gram-negative pathogens, particularly against multidrug resistant strains of Acinetobacter baumannii. We have cloned, heterologously expressed and characterized a novel endolysin (ABgp46) from Acinetobacter phage vb_AbaP_CEB1 and tested its antibacterial activity against several multidrug-resistant A. baumannii strains. LC-MS revealed that ABgp46 is an N-acetylmuramidase, that is also active over a broad pH range (4.0–10.0) and temperatures up to 50°C. Interestingly, ABgp46 has intrinsic and specific anti-A. baumannii activity, reducing multidrug resistant strains by up to 2 logs within 2 h. By combining ABgp46 with several organic acids that act as outer membrane permeabilizing agents, it is possible to increase and broaden antibacterial activity to include other Gram-negative bacterial pathogens. In the presence of citric and malic acid, ABgp46 reduces A. baumannii below the detection limit (>5 log) and more than 4 logs Pseudomonas aeruginosa and Salmonella typhimurium strains. Overall, this globular endolysin exhibits a broad and high activity against Gram-negative pathogens, that can be enhanced in presence of citric and malic acid, and be used in human and veterinary medicine. PMID:26955368

  13. Activity and stability trends of perovskite oxides for oxygen evolution catalysis at neutral pH.

    Science.gov (United States)

    Han, Binghong; Risch, Marcel; Lee, Yueh-Lin; Ling, Chen; Jia, Hongfei; Shao-Horn, Yang

    2015-09-21

    Perovskite oxides (ABO3) have been studied extensively to promote the kinetics of the oxygen evolution reaction (OER) in alkaline electrolytes. However, developing highly active catalysts for OER at near-neutral pH is desirable for many photoelectrochemical/electrochemical devices. In this paper, we systematically studied the activity and stability of well-known perovskite oxides for OER at pH 7. Previous activity descriptors established for perovskite oxides at pH 13, such as having an eg occupancy close to unity or having an O p-band center close to Fermi level, were shown to scale with OER activity at pH 7. Stability was a greater challenge at pH 7 than at pH 13, where two different modes of instability were identified from combined transmission electron microscopy and density functional theory analyses. Perovskites with O p-band close to Fermi level showed leaching of A-site atoms and surface amorphization under all overpotentials examined at pH 7, while those with O p-band far from Fermi level were stable under low OER current/potential but became unstable at high current/potential accompanied by leaching of B-site atoms. Therefore, efforts are needed to enhance the activity and stability of perovskites against A-site or B-site loss if used at neutral pH. PMID:26271910

  14. Non-neutralized Electric Current Patterns in Solar Active Regions: Origin of the Shear-Generating Lorentz Force

    CERN Document Server

    Georgoulis, Manolis K; Mikic, Zoran

    2012-01-01

    Using solar vector magnetograms of the highest available spatial resolution and signal-to-noise ratio we perform a detailed study of electric current patterns in two solar active regions: a flaring/eruptive, and a flare-quiet one. We aim to determine whether active regions inject non-neutralized (net) electric currents in the solar atmosphere, responding to a debate initiated nearly two decades ago that remains inconclusive. We find that well-formed, intense magnetic polarity inversion lines (PILs) within active regions are the only photospheric magnetic structures that support significant net current. More intense PILs seem to imply stronger non-neutralized current patterns per polarity. This finding revises previous works that claim frequent injections of intense non-neutralized currents by most active regions appearing in the solar disk but also works that altogether rule out injection of non-neutralized currents. In agreement with previous studies, we also find that magnetically isolated active regions re...

  15. Novel engineered cationic antimicrobial peptides display broad-spectrum activity against Francisella tularensis, Yersinia pestis and Burkholderia pseudomallei.

    Science.gov (United States)

    Abdelbaqi, Suha; Deslouches, Berthony; Steckbeck, Jonathan; Montelaro, Ronald; Reed, Douglas S

    2016-02-01

    Broad-spectrum antimicrobials are needed to effectively treat patients infected in the event of a pandemic or intentional release of a pathogen prior to confirmation of the pathogen's identity. Engineered cationic antimicrobial peptides (eCAPs) display activity against a number of bacterial pathogens including multi-drug-resistant strains. Two lead eCAPs, WLBU2 and WR12, were compared with human cathelicidin (LL-37) against three highly pathogenic bacteria: Francisella tularensis, Yersinia pestis and Burkholderia pseudomallei. Both WLBU2 and WR12 demonstrated bactericidal activity greater than that of LL-37, particularly against F. tularensis and Y. pestis. Only WLBU2 had bactericidal activity against B. pseudomallei. WLBU2, WR12 and LL-37 were all able to inhibit the growth of the three bacteria in vitro. Because these bacteria can be facultative intracellular pathogens, preferentially infecting macrophages and dendritic cells, we evaluated the activity of WLBU2 against F. tularensis in an ex vivo infection model with J774 cells, a mouse macrophage cell line. In that model WLBU2 was able to achieve greater than 50 % killing of F. tularensis at a concentration of 12.5 μM. These data show the therapeutic potential of eCAPs, particularly WLBU2, as a broad-spectrum antimicrobial for treating highly pathogenic bacterial infections. PMID:26673248

  16. Rational design of berberine-based FtsZ inhibitors with broad-spectrum antibacterial activity.

    Directory of Open Access Journals (Sweden)

    Ning Sun

    Full Text Available Inhibition of the functional activity of Filamenting temperature-sensitive mutant Z (FtsZ protein, an essential and highly conserved bacterial cytokinesis protein, is a promising approach for the development of a new class of antibacterial agents. Berberine, a benzylisoquinoline alkaloid widely used in traditional Chinese and native American medicines for its antimicrobial properties, has been recently reported to inhibit FtsZ. Using a combination of in silico structure-based design and in vitro biological assays, 9-phenoxyalkyl berberine derivatives were identified as potent FtsZ inhibitors. Compared to the parent compound berberine, the derivatives showed a significant enhancement of antibacterial activity against clinically relevant bacteria, and an improved potency against the GTPase activity and polymerization of FtsZ. The most potent compound 2 strongly inhibited the proliferation of Gram-positive bacteria, including methicillin-resistant S. aureus and vancomycin-resistant E. faecium, with MIC values between 2 and 4 µg/mL, and was active against the Gram-negative E. coli and K. pneumoniae, with MIC values of 32 and 64 µg/mL respectively. The compound perturbed the formation of cytokinetic Z-ring in E. coli. Also, the compound interfered with in vitro polymerization of S. aureus FtsZ. Taken together, the chemical modification of berberine with 9-phenoxyalkyl substituent groups greatly improved the antibacterial activity via targeting FtsZ.

  17. Broad Spectrum Activity of a Lectin-Like Bacterial Serine Protease Family on Human Leukocytes

    Science.gov (United States)

    Ayala-Lujan, Jorge Luis; Vijayakumar, Vidhya; Gong, Mei; Smith, Rachel; Santiago, Araceli E.; Ruiz-Perez, Fernando

    2014-01-01

    The serine protease autotransporter from Enterobacteriaceae (SPATE) family, which number more than 25 proteases with apparent diverse functions, have been phylogenetically divided into two distinct classes, designated 1 and 2. We recently demonstrated that Pic and Tsh, two members of the class-2 SPATE family produced by intestinal and extraintestinal pathogenic E. coli, were able to cleave a number of O-glycosylated proteins on neutrophils and lymphocytes resulting in impaired leukocyte functions. Here we show that most members of the class-2 SPATE family have lectin-like properties and exhibit differential protease activity reliant on glycoprotein type and cell lineage. Protease activity was seen in virtually all tested O-glycosylated proteins including CD34, CD55, CD164, TIM1, TIM3, TIM4 and C1-INH. We also show that although SPATE proteins bound and cleaved glycoproteins more efficiently on granulocytes and monocytes, they also targeted glycoproteins on B, T and natural killer lymphocytes. Finally, we found that the characteristic domain-2 of class-2 SPATEs is not required for glycoprotease activity, but single amino acid mutations in Pic domain-1 to those residues naturally occurring in domain-1 of SepA, were sufficient to hamper Pic glycoprotease activity. This study shows that most class-2 SPATEs have redundant activities and suggest that they may function as immunomodulators at several levels of the immune system. PMID:25251283

  18. Broad spectrum activity of a lectin-like bacterial serine protease family on human leukocytes.

    Directory of Open Access Journals (Sweden)

    Jorge Luis Ayala-Lujan

    Full Text Available The serine protease autotransporter from Enterobacteriaceae (SPATE family, which number more than 25 proteases with apparent diverse functions, have been phylogenetically divided into two distinct classes, designated 1 and 2. We recently demonstrated that Pic and Tsh, two members of the class-2 SPATE family produced by intestinal and extraintestinal pathogenic E. coli, were able to cleave a number of O-glycosylated proteins on neutrophils and lymphocytes resulting in impaired leukocyte functions. Here we show that most members of the class-2 SPATE family have lectin-like properties and exhibit differential protease activity reliant on glycoprotein type and cell lineage. Protease activity was seen in virtually all tested O-glycosylated proteins including CD34, CD55, CD164, TIM1, TIM3, TIM4 and C1-INH. We also show that although SPATE proteins bound and cleaved glycoproteins more efficiently on granulocytes and monocytes, they also targeted glycoproteins on B, T and natural killer lymphocytes. Finally, we found that the characteristic domain-2 of class-2 SPATEs is not required for glycoprotease activity, but single amino acid mutations in Pic domain-1 to those residues naturally occurring in domain-1 of SepA, were sufficient to hamper Pic glycoprotease activity. This study shows that most class-2 SPATEs have redundant activities and suggest that they may function as immunomodulators at several levels of the immune system.

  19. Cystatin SN neutralizes the inhibitory effect of cystatin C on cathepsin B activity.

    Science.gov (United States)

    Kim, J-T; Lee, S-J; Kang, M A; Park, J E; Kim, B-Y; Yoon, D-Y; Yang, Y; Lee, C-H; Yeom, Y I; Choe, Y-K; Lee, H G

    2013-01-01

    Cystatin SN (CST1) is one of the several salivary cystatins that form tight equimolar complexes with cysteine proteases, such as the cathepsins. High expression of CST1 is correlated with advanced pTNM stage in gastric cancer. However, the functional role of CST1 in tumorigenesis has not been elucidated. In this study, we showed that CST1 was highly expressed in colon tumor tissues, compared with nontumor regions. Increased cell proliferation and invasiveness were observed in HCT116 cell lines stably transfected with CST1 cDNA (HCT116-CST1) but not in CST3-transfected cells. We also demonstrated that CST1-overexpressing cell lines exhibited increased tumor growth as well as metastasis in a xenograft nude mouse model. Interestingly, CST1 interacted with cystatin C (CST3), a potent cathepsin B (CTSB) inhibitor, with a higher affinity than the interaction between CST3 and CTSB in the extracellular space of HCT116 cells. CTSB-mediated cellular invasiveness and proteolytic activities were strongly inhibited by CST3, but in the presence of CST1 CTSB activities recovered significantly. Furthermore, domain mapping of CST1 showed that the disulfide-bonded conformation, or conserved folding, of CST1 is important for its secretion and for the neutralization of CST3 activity. These results suggest that CST1 upregulation might be involved in colorectal tumorigenesis and acts by neutralizing the inhibition of CTSB proteolytic activity by CST3. PMID:24357805

  20. Physiological characterization of the ARO10-dependent, broad-substrate-specificity 2-oxo acid decarboxylase activity of Saccharomyces cerevisiae.

    Science.gov (United States)

    Vuralhan, Zeynep; Luttik, Marijke A H; Tai, Siew Leng; Boer, Viktor M; Morais, Marcos A; Schipper, Dick; Almering, Marinka J H; Kötter, Peter; Dickinson, J Richard; Daran, Jean-Marc; Pronk, Jack T

    2005-06-01

    Aerobic, glucose-limited chemostat cultures of Saccharomyces cerevisiae CEN.PK113-7D were grown with different nitrogen sources. Cultures grown with phenylalanine, leucine, or methionine as a nitrogen source contained high levels of the corresponding fusel alcohols and organic acids, indicating activity of the Ehrlich pathway. Also, fusel alcohols derived from the other two amino acids were detected in the supernatant, suggesting the involvement of a common enzyme activity. Transcript level analysis revealed that among the five thiamine-pyrophospate-dependent decarboxylases (PDC1, PDC5, PDC6, ARO10, and THI3), only ARO10 was transcriptionally up-regulated when phenylalanine, leucine, or methionine was used as a nitrogen source compared to growth on ammonia, proline, and asparagine. Moreover, 2-oxo acid decarboxylase activity measured in cell extract from CEN.PK113-7D grown with phenylalanine, methionine, or leucine displayed similar broad-substrate 2-oxo acid decarboxylase activity. Constitutive expression of ARO10 in ethanol-limited chemostat cultures in a strain lacking the five thiamine-pyrophosphate-dependent decarboxylases, grown with ammonia as a nitrogen source, led to a measurable decarboxylase activity with phenylalanine-, leucine-, and methionine-derived 2-oxo acids. Moreover, even with ammonia as the nitrogen source, these cultures produced significant amounts of the corresponding fusel alcohols. Nonetheless, the constitutive expression of ARO10 in an isogenic wild-type strain grown in a glucose-limited chemostat with ammonia did not lead to any 2-oxo acid decarboxylase activity. Furthermore, even when ARO10 was constitutively expressed, growth with phenylalanine as the nitrogen source led to increased decarboxylase activities in cell extracts. The results reported here indicate the involvement of posttranscriptional regulation and/or a second protein in the ARO10-dependent, broad-substrate-specificity decarboxylase activity. PMID:15933030

  1. Constraints on the broad line region from regularized linear inversion: Velocity-delay maps for five nearby active galactic nuclei

    CERN Document Server

    Skielboe, Andreas; Treu, Tommaso; Park, Daeseong; Barth, Aaron J; Bentz, Misty C

    2015-01-01

    Reverberation mapping probes the structure of the broad emission-line region (BLR) in active galactic nuclei (AGN). The radius of the BLR along with the virial velocity of the BLR gas can be used to measure the mass of the supermassive black hole. The main systematic uncertainty affecting reverberation mapping is the unknown structure of the BLR. We develop a new method for analysing reverberation mapping data based on regularized linear inversion (RLI) that includes statistical modelling of the AGN continuum light curves. This method enables fast, flexible, and robust calculation of velocity-resolved response maps to probe BLR structure. Contrary to other methods, RLI allows for negative response in the BLR, such as when some areas of the BLR respond in inverse proportion to a change in ionizing continuum luminosity. We present time delays, integrated response functions, and velocity-delay maps for the H{\\beta} broad emission line in five nearby AGN, as well as H{\\alpha} and H{\\gamma} broad emission lines in...

  2. Highly selective palladium–benzothiazole carbene-catalyzed allylation of active methylene compounds under neutral conditions

    Directory of Open Access Journals (Sweden)

    Antonio Monopoli

    2015-06-01

    Full Text Available The Pd–benzothiazol-2-ylidene complex I was found to be a chemoselective catalyst for the Tsuji–Trost allylation of active methylene compounds carried out under neutral conditions and using carbonates as allylating agents. The proposed protocol consists in a simplified procedure adopting an in situ prepared catalyst from Pd2dba3 and 3-methylbenzothiazolium salt V as precursors. A comparison of the performance of benzothiazole carbene with phosphanes and an analogous imidazolium carbene ligand is also proposed.

  3. Killed but Metabolically Active Bacillus anthracis Vaccines Induce Broad and Protective Immunity against Anthrax▿

    OpenAIRE

    Skoble, Justin; Beaber, John W.; Gao, Yi; Lovchik, Julie A.; Sower, Laurie E.; Liu, Weiqun; Luckett, William; Johnny W. Peterson; Calendar, Richard; Daniel A Portnoy; Lyons, C. Rick; Dubensky, Thomas W

    2009-01-01

    Bacillus anthracis is the causative agent of anthrax. We have developed a novel whole-bacterial-cell anthrax vaccine utilizing B. anthracis that is killed but metabolically active (KBMA). Vaccine strains that are asporogenic and nucleotide excision repair deficient were engineered by deleting the spoIIE and uvrAB genes, rendering B. anthracis extremely sensitive to photochemical inactivation with S-59 psoralen and UV light. We also introduced point mutations into the lef and cya genes, which ...

  4. Reduced influenza viral neutralizing activity of natural human trimers of surfactant protein D

    DEFF Research Database (Denmark)

    Hartshorn, Kevan L; White, Mitchell R; Tecle, Tesfaldet;

    2007-01-01

    neutralize the virus. We then purified natural human trimeric and multimeric forms of SP-D from amniotic fluid and tested ability of these preparations to bind to IAV, to inhibit infectivity and hemagglutination activity of IAV in vitro. RESULTS: In initial experiments mAbs directed against different areas....../Thr 11 form of SP-D is associated with low serum levels and assembles predominantly as trimers as opposed to the more common multimeric forms of SP-D. METHODS: Preliminary experiments were done to establish the effects of different monoclonal antibodies against SP-D on ability of SP-D to bind to or...... on the CRD of SP-D were found to have differing effects on antiviral activity. Using an mAb that did not interfere with antiviral activity of SP-D, we confirm that natural SP-D trimers had reduced ability to bind to IAV. In addition, the trimers had reduced ability to neutralize IAV as compared to...

  5. Production in yeast of pseudotype virus-like particles harboring functionally active antibody fragments neutralizing the cytolytic activity of vaginolysin

    Directory of Open Access Journals (Sweden)

    Pleckaityte Milda

    2011-12-01

    Full Text Available Abstract Background Recombinant antibodies can be produced in different formats and different expression systems. Single chain variable fragments (scFvs represent an attractive alternative to full-length antibodies and they can be easily produced in bacteria or yeast. However, the scFvs exhibit monovalent antigen-binding properties and short serum half-lives. The stability and avidity of the scFvs can be improved by their multimerization or fusion with IgG Fc domain. The aim of the current study was to investigate the possibilities to produce in yeast high-affinity scFv-Fc proteins neutralizing the cytolytic activity of vaginolysin (VLY, the main virulence factor of Gardnerella vaginalis. Results The scFv protein derived from hybridoma cell line producing high-affinity neutralizing antibodies against VLY was fused with human IgG1 Fc domain. Four different variants of anti-VLY scFv-Fc fusion proteins were constructed and produced in yeast Saccharomyces cerevisiae. The non-tagged scFv-Fc and hexahistidine-tagged scFv-Fc proteins were found predominantly as insoluble aggregates and therefore were not suitable for further purification and activity testing. The addition of yeast α-factor signal sequence did not support secretion of anti-VLY scFv-Fc but increased the amount of its intracellular soluble form. However, the purified protein showed a weak VLY-neutralizing capability. In contrast, the fusion of anti-VLY scFv-Fc molecules with hamster polyomavirus-derived VP2 protein and its co-expression with VP1 protein resulted in an effective production of pseudotype virus-like particles (VLPs that exhibited strong VLY-binding activity. Recombinant scFv-Fc molecules displayed on the surface of VLPs neutralized VLY-mediated lysis of human erythrocytes and HeLa cells with high potency comparable to that of full-length antibody. Conclusions Recombinant scFv-Fc proteins were expressed in yeast with low efficiency. New approach to display the sc

  6. Similar Neutralizing Activity in the HIV-1 Infected Long Term Non-progressors(LTNPs) and Typical Progressors(TPs)

    Institute of Scientific and Technical Information of China (English)

    Zheng Wang; Si-yang Liu; Lin Li; Tian-yi Li; Jing-yun Li; Li-li Chen; Yong-jian Liu; Han-ping Li; Zuo-yi Bao; Xiao-lin Wang; Dao-min Zhuang

    2012-01-01

    Neutralizing antibodies are considered to be an important protective parameter used in HIV-l vaccine evaluation.However,the exact role that neutralizing antibodies plays in controlling the disease progression of HIV-1 infected peoples is still undetermined.In this paper,we compared the protective function of the neutralizing antibody response in the plasma from LTNP and TP against clade B and clade C pseudoviruses.No difference in the neutralizing activities between the plasma from LTNP and TP was found,which was consistent with the most recent reports.In addition,no correlations between the titer or breadth and CD4+ or viral load in HIV-1 infected individuals were found.The protective roles played by neutralizing antibodies in controlling disease progression of HIV-1 infected people need to be considered in a new viewpoint.

  7. Dengue Virus Infection-Enhancing Activity in Serum Samples with Neutralizing Activity as Determined by Using FcγR-Expressing Cells

    OpenAIRE

    Meng Ling Moi; Chang-Kweng Lim; Kaw Bing Chua; Tomohiko Takasaki; Ichiro Kurane

    2012-01-01

    BACKGROUND: Progress in dengue vaccine development has been hampered by limited understanding of protective immunity against dengue virus infection. Conventional neutralizing antibody titration assays that use FcγR-negative cells do not consider possible infection-enhancement activity. We reasoned that as FcγR-expressing cells are the major target cells of dengue virus, neutralizing antibody titration assays using FcγR-expressing cells that determine the sum of neutralizing and infection-enha...

  8. Dengue Virus Infection-Enhancing Activity in Serum Samples with Neutralizing Activity as Determined by Using FcγR-Expressing Cells

    OpenAIRE

    Moi, Meng Ling; Lim, Chang-Kweng; Chua, Kaw Bing; Takasaki, Tomohiko; Kurane, Ichiro

    2012-01-01

    Background Progress in dengue vaccine development has been hampered by limited understanding of protective immunity against dengue virus infection. Conventional neutralizing antibody titration assays that use FcγR-negative cells do not consider possible infection-enhancement activity. We reasoned that as FcγR-expressing cells are the major target cells of dengue virus, neutralizing antibody titration assays using FcγR-expressing cells that determine the sum of neutralizing and infection-enhan...

  9. The antioxidant activities effect of neutral and acidic polysaccharides from Epimedium acuminatum Franch. on Caenorhabditis elegans.

    Science.gov (United States)

    Xu, Zhou; Feng, Shiling; Shen, Shian; Wang, Handong; Yuan, Ming; Liu, Jing; Huang, Yan; Ding, Chunbang

    2016-06-25

    A neutral polysaccharide (EAP-1N) and an acidic polysaccharide (EAP-2A) were purified from Epimedium acuminatum by DEAE-52 cellulose anion-exchange chromatography and gel-filtration chromatography. Their structures were characterized by chemical composition analysis, high-performance size exclusion chromatography (HPSEC), Fourier transform infrared spectrometry (FT-IR), and gas chromatography-mass spectrometry (GC-MS). Further, their antioxidant activities were investigated both in vitro and in vivo. Results showed that EAP-2A had higher uronic acid content and larger average molecular weight than EAP-1N. Compared with EAP-1N, EAP-2A exhibited significantly scavenging activities against free radical in vitro, as well as strongly stimulating effect on antioxidant enzyme activities (including superoxide dismutases (SOD), catalases (CAT), and glutathione peroxidases (GSH-PX)) and preferably inhibitory effect on lipid peroxidation and protein carboxyl in the mode of Caenorhabditis elegans. PMID:27083801

  10. Broad-spectrum therapeutic suppression of metastatic melanoma through nuclear hormone receptor activation.

    Science.gov (United States)

    Pencheva, Nora; Buss, Colin G; Posada, Jessica; Merghoub, Taha; Tavazoie, Sohail F

    2014-02-27

    Melanoma metastasis is a devastating outcome lacking an effective preventative therapeutic. We provide pharmacologic, molecular, and genetic evidence establishing the liver-X nuclear hormone receptor (LXR) as a therapeutic target in melanoma. Oral administration of multiple LXR agonists suppressed melanoma invasion, angiogenesis, tumor progression, and metastasis. Molecular and genetic experiments revealed these effects to be mediated by LXRβ, which elicits these outcomes through transcriptional induction of tumoral and stromal apolipoprotein-E (ApoE). LXRβ agonism robustly suppressed tumor growth and metastasis across a diverse mutational spectrum of melanoma lines. LXRβ targeting significantly prolonged animal survival, suppressed the progression of established metastases, and inhibited brain metastatic colonization. Importantly, LXRβ activation displayed melanoma-suppressive cooperativity with the frontline regimens dacarbazine, B-Raf inhibition, and the anti-CTLA-4 antibody and robustly inhibited melanomas that had acquired resistance to B-Raf inhibition or dacarbazine. We present a promising therapeutic approach that uniquely acts by transcriptionally activating a metastasis suppressor gene. PMID:24581497

  11. Identification and characterization of the host protein DNAJC14 as a broadly active flavivirus replication modulator.

    Directory of Open Access Journals (Sweden)

    Zhigang Yi

    Full Text Available Viruses in the Flavivirus genus of the Flaviviridae family are arthropod-transmitted and contribute to staggering numbers of human infections and significant deaths annually across the globe. To identify cellular factors with antiviral activity against flaviviruses, we screened a cDNA library using an iterative approach. We identified a mammalian Hsp40 chaperone protein (DNAJC14 that when overexpressed was able to mediate protection from yellow fever virus (YFV-induced cell death. Further studies revealed that DNAJC14 inhibits YFV at the step of viral RNA replication. Since replication of bovine viral diarrhea virus (BVDV, a member of the related Pestivirus genus, is also known to be modulated by DNAJC14, we tested the effect of this host factor on diverse Flaviviridae family members. Flaviviruses, including the pathogenic Asibi strain of YFV, Kunjin, and tick-borne Langat virus, as well as a Hepacivirus, hepatitis C virus (HCV, all were inhibited by overexpression of DNAJC14. Mutagenesis showed that both the J-domain and the C-terminal domain, which mediates self-interaction, are required for anti-YFV activity. We found that DNAJC14 does not block YFV nor HCV NS2-3 cleavage, and using non-inhibitory mutants demonstrate that DNAJC14 is recruited to YFV replication complexes. Immunofluorescence analysis demonstrated that endogenous DNAJC14 rearranges during infection and is found in replication complexes identified by dsRNA staining. Interestingly, silencing of endogenous DNAJC14 results in impaired YFV replication suggesting a requirement for DNAJC14 in YFV replication complex assembly. Finally, the antiviral activity of overexpressed DNAJC14 occurs in a time- and dose-dependent manner. DNAJC14 overexpression may disrupt the proper stoichiometry resulting in inhibition, which can be overcome upon restoration of the optimal ratios due to the accumulation of viral nonstructural proteins. Our findings, together with previously published work

  12. Monetary Neutrality

    OpenAIRE

    Apostolos Serletis; Zisimos Koustas

    2015-01-01

    We test the long-run neutrality of money proposition for the United States using the King and Watson (1997) methodology paying attention to the integration and cointegration properties of the variables. We use quarterly data (over the period from 1967:1 to 2014:1) and the new Center for Financial Stability Divisia monetary aggregates, documented in detail in Barnett et al. (2013). We make a comparison among the narrower monetary aggregates, M1 M2M, M2M, M2, and ALL, and the broad monetary agg...

  13. Novel Peptides from Skins of Amphibians Showed Broad-Spectrum Antimicrobial Activities.

    Science.gov (United States)

    Wang, Ying; Zhang, Yue; Lee, Wen-Hui; Yang, Xinwang; Zhang, Yun

    2016-03-01

    Peptide agents are often considered as potential biomaterials for developing new drugs that can overcome the rising resistance of pathogenic micro-organisms to classic antibiotic treatments. One key source of peptide agents is amphibian skin, as they provide a great deal of naturally occurring antimicrobial peptide (AMP) templates awaiting further exploitation and utilization. In this study, 12 novel AMPs from the skins of 3 ranid frogs, Rana limnocharis, R. exilispinosa, and Amolops afghanus, were identified using a 5' PCR primer. A total of 11 AMPs exhibited similarities with currently known AMP families, including brevinin-1, brevinin-2, esculentin-1, and nigrocin, besides, one AMP, named as Limnochariin, represented a novel AMP family. All 12 AMPs contain a C-terminus cyclic motif and most of them show obvious antimicrobial activities against 18 standard and clinically isolated strains of bacteria, including 4 Gram-positive bacteria, 11 Gram-negative bacteria, and 3 fungus. These findings provide helpful insight that will be useful in the design of anti-infective peptide agents. PMID:26452973

  14. Broadly continuously tunable slot waveguide quantum cascade lasers based on a continuum-to-continuum active region design

    Science.gov (United States)

    Meng, Bo; Zeng, Yong Quan; Liang, Guozhen; Tao, Jin; Hu, Xiao Nan; Rodriguez, Etienne; Wang, Qi Jie

    2015-09-01

    We report our progress in the development of broadly tunable single-mode slot waveguide quantum cascade lasers based on a continuum-to-continuum active region design. The electroluminescence spectrum of the continuum-to-continuum active region design has a full width at half maximum of 440 cm-1 at center wavelength ˜10 μm at room temperature (300 K). Devices using the optimized slot waveguide structure and the continuum-to-continuum design can be tuned continuously with a lasing emission over 42 cm-1, from 9.74 to 10.16 μm, at room temperature by using only current tuning scheme, together with a side mode suppression ratio of above 15 dB within the whole tuning range.

  15. Broadly continuously tunable slot waveguide quantum cascade lasers based on a continuum-to-continuum active region design

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Bo; Zeng, Yong Quan; Liang, Guozhen; Hu, Xiao Nan; Rodriguez, Etienne [OPTIMUS, Centre for OptoElectronics and Biophotonics, School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore, Singapore 639798 (Singapore); CINTRA CNRS/NTU/THALES, UMI 3288, Research Techno Plaza, 50 Nanyang Drive, Border X Block, Level 6, Singapore 637553 (Singapore); Tao, Jin [OPTIMUS, Centre for OptoElectronics and Biophotonics, School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore, Singapore 639798 (Singapore); CINTRA CNRS/NTU/THALES, UMI 3288, Research Techno Plaza, 50 Nanyang Drive, Border X Block, Level 6, Singapore 637553 (Singapore); CDPT, Centre for Disruptive Photonic Technologies, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore, Singapore 637371 (Singapore); Wang, Qi Jie, E-mail: qjwang@ntu.edu.sg [OPTIMUS, Centre for OptoElectronics and Biophotonics, School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore, Singapore 639798 (Singapore); CDPT, Centre for Disruptive Photonic Technologies, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore, Singapore 637371 (Singapore)

    2015-09-14

    We report our progress in the development of broadly tunable single-mode slot waveguide quantum cascade lasers based on a continuum-to-continuum active region design. The electroluminescence spectrum of the continuum-to-continuum active region design has a full width at half maximum of 440 cm{sup −1} at center wavelength ∼10 μm at room temperature (300 K). Devices using the optimized slot waveguide structure and the continuum-to-continuum design can be tuned continuously with a lasing emission over 42 cm{sup −1}, from 9.74 to 10.16 μm, at room temperature by using only current tuning scheme, together with a side mode suppression ratio of above 15 dB within the whole tuning range.

  16. Broadly continuously tunable slot waveguide quantum cascade lasers based on a continuum-to-continuum active region design

    International Nuclear Information System (INIS)

    We report our progress in the development of broadly tunable single-mode slot waveguide quantum cascade lasers based on a continuum-to-continuum active region design. The electroluminescence spectrum of the continuum-to-continuum active region design has a full width at half maximum of 440 cm−1 at center wavelength ∼10 μm at room temperature (300 K). Devices using the optimized slot waveguide structure and the continuum-to-continuum design can be tuned continuously with a lasing emission over 42 cm−1, from 9.74 to 10.16 μm, at room temperature by using only current tuning scheme, together with a side mode suppression ratio of above 15 dB within the whole tuning range

  17. Urinary neutral endopeptidase 24.11 activity: modulation by chronic salt loading.

    Science.gov (United States)

    Aviv, R; Gurbanov, K; Hoffman, A; Blumberg, S; Winaver, J

    1995-03-01

    Neutral endopeptidase (NEP) 24.11 is a zinc-metallopeptidase involved in the metabolism of several biologically active peptides including enkephalin, atrial natriuretic peptide, bradykinin, and endothelin. The enzyme is found in abundant amounts in the brush border of renal proximal epithelial cells. A soluble form of NEP was previously identified in human urine with characteristics similar to the renal enzyme. The present study further characterized the excreted form of NEP activity in urine of normal rats using a sensitive two-stage enzymatic assay. The response of urinary NEP to known inhibitors such as phosphoramidon and thiorphan, and its dependence on pH and salt concentration was studied. In addition, we evaluated the effects of acute and chronic changes in salt balance, induced by i.v. saline infusion and drinking of saline solution, on urinary NEP and on the activity of the enzyme in isolated proximal tubules. Our findings demonstrated that abundant NEP activity was detected in the urine of normal rats. Furthermore, chronic salt loading, but not acute salt infusion, was associated with increased activity of NEP in urine and in isolated proximal tubules, suggesting that the enzyme may be regulated by salt balance. Finally, the data suggest that urinary NEP may be used as an index of enzyme activity in the kidney. PMID:7752584

  18. Active galactic nuclei at z~1.5: II. Black Hole Mass estimation by means of broad emission lines

    CERN Document Server

    Mejía-Restrepo, Julián E; Lira, Paulina; Netzer, Hagai; Capellupo, Daniel M

    2016-01-01

    This is the second in a series of papers aiming to test how the mass ($M_{\\rm BH}$), accretion rate ($\\dot{M}$) and spin ($a_{*}$) of super massive black holes (SMBHs) determine the observed properties of type-I active galactic nuclei (AGN). Our project utilizes a sample of 39 unobscured AGN at $z\\simeq1.55$ observed by VLT/X-shooter, selected to map a large range in $M_{\\rm BH}$ and $L/L_{\\rm edd}$ and covers the most prominent UV-optical (broad) emission lines, including H$\\alpha$, H$\\beta$, MgII, and CIV. This paper focuses on single-epoch, "virial" $M_{\\rm BH}$ determinations from broad emission lines and examines the implications of different continuum modeling approaches in line width measurements. We find that using a "local" power-law continuum instead of a physically-motivated thin disk continuum leads to only slight underestimation of the FWHM of the lines and the associated $M_{\\rm BH}\\left({\\rm FWHM}\\right)$. However, the line dispersion $\\sigma_{\\rm line}$ and associated $M_{\\rm BH}\\left(\\sigma_{...

  19. On the difference of torus geometry between hidden and non-hidden broad line active galactic nuclei

    CERN Document Server

    Ichikawa, Kohei; Almeida, Cristina Ramos; Ramos, Andres Asensio; Alonso-Herrero, Almudena; Gonzalez-Martin, Omaira; Lopez-Rodriguez, Enrique; Ueda, Yoshihiro; Diaz-Santos, Tanio; Elitzur, Moshe; Hoenig, Sebastian F; Imanishi, Masatoshi; Levenson, Nancy A; Mason, Rachel E; Perlman, Eric S; Alsip, Crystal D

    2015-01-01

    We present results from the fitting of infrared (IR) spectral energy distributions of 21 active galactic nuclei (AGN) with clumpy torus models. We compiled high spatial resolution ($\\sim 0.3$--$0.7$ arcsec) mid-IR $N$-band spectroscopy, $Q$-band imaging and nuclear near- and mid-IR photometry from the literature. Combining these nuclear near- and mid-IR observations, far-IR photometry and clumpy torus models, enables us to put constraints on the torus properties and geometry. We divide the sample into three types according to the broad line region (BLR) properties; type-1s, type-2s with scattered or hidden broad line region (HBLR) previously observed, and type-2s without any published HBLR signature (NHBLR). Comparing the torus model parameters gives us the first quantitative torus geometrical view for each subgroup. We find that NHBLR AGN have smaller torus opening angles and larger covering factors than those of HBLR AGN. This suggests that the chance to observe scattered (polarized) flux from the BLR in NH...

  20. The Black Hole-Bulge Relationship in Luminous Broad-Line Active Galactic Nuclei and Host Galaxies

    CERN Document Server

    Shen, J; Schneider, D P; Hall, P B

    2007-01-01

    We have measured the stellar velocity dispersions (\\sigma_*) and estimated the central black hole (BH) masses for over 900 broad-line active galactic nuclei (AGNs) observed with the Sloan Digital Sky Survey. The sample includes objects which have redshifts up to z=0.452, high quality spectra, and host galaxy spectra dominated by an early-type (bulge) component. The AGN and host galaxy spectral components were decomposed using an eigenspectrum technique. The BH masses (M_BH) were estimated from the AGN broad-line widths, and the velocity dispersions were measured from the stellar absorption spectra of the host galaxies. The range of black hole masses covered by the sample is approximately 10^6 < M_BH < 10^9 M_Sun. The host galaxy luminosity-velocity dispersion relationship follows the well-known Faber-Jackson relation for early-type galaxies, with a power-law slope 4.33+-0.21. The estimated BH masses are correlated with both the host luminosities (L_{H}) and the stellar velocity dispersions (\\sigma_*), s...

  1. The investigation of copper-based impregnated activated carbons prepared from water-soluble materials for broad spectrum respirator applications

    International Nuclear Information System (INIS)

    The preparation of impregnated activated carbons (IACs) from aqueous, copper-containing solutions for broad spectrum gas filtration applications is studied here. Several samples were studied to determine the effect that impregnant loading, impregnant distribution and impregnant recipe had on the overall performance. Dynamic flow testing was used to determine the gas filtration capacity of the IAC samples versus a variety of challenge gases. X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX) were used to characterize the impregnant distribution on the carbon as a function of impregnant loading. Oven tests were performed to determine the thermal stability of the IAC samples exposed to elevated temperatures. The role impregnant distribution plays in gas filtration capacity and the overall performance of the IAC samples is discussed. The IAC samples prepared in this work were found to have gas filtration capacities as good as or better than broad spectrum respirator carbon samples prepared from the patent literature. IACs impregnated with an aqueous 2.4 M Cu(NO3)2/0.04 M H3PO4.12MoO3/4 M HNO3 solution that were heated to 200 deg. C under argon were found to have the best overall performance of the samples studied in this work.

  2. The investigation of copper-based impregnated activated carbons prepared from water-soluble materials for broad spectrum respirator applications

    Energy Technology Data Exchange (ETDEWEB)

    Smith, J.W.H.; Westreich, P.; Abdellatif, H.; Filbee-Dexter, P.; Smith, A.J. [Department of Physics and Atmospheric Science, Dalhousie University, Halifax, Nova Scotia, B3H 3J5 (Canada); Wood, T.E. [3M Company, St. Paul, MN, 55144 (United States); Croll, L.M.; Reynolds, J.H. [3M Canada Company, Brockville, Ontario, K6V 5V8 (Canada); Dahn, J.R., E-mail: jeff.dahn@dal.ca [Department of Physics and Atmospheric Science, Dalhousie University, Halifax, Nova Scotia, B3H 3J5 (Canada); Department of Chemistry, Dalhousie University, Halifax, Nova Scotia, B3H 4J3 (Canada)

    2010-08-15

    The preparation of impregnated activated carbons (IACs) from aqueous, copper-containing solutions for broad spectrum gas filtration applications is studied here. Several samples were studied to determine the effect that impregnant loading, impregnant distribution and impregnant recipe had on the overall performance. Dynamic flow testing was used to determine the gas filtration capacity of the IAC samples versus a variety of challenge gases. X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX) were used to characterize the impregnant distribution on the carbon as a function of impregnant loading. Oven tests were performed to determine the thermal stability of the IAC samples exposed to elevated temperatures. The role impregnant distribution plays in gas filtration capacity and the overall performance of the IAC samples is discussed. The IAC samples prepared in this work were found to have gas filtration capacities as good as or better than broad spectrum respirator carbon samples prepared from the patent literature. IACs impregnated with an aqueous 2.4 M Cu(NO{sub 3}){sub 2}/0.04 M H{sub 3}PO{sub 4}.12MoO{sub 3}/4 M HNO{sub 3} solution that were heated to 200 deg. C under argon were found to have the best overall performance of the samples studied in this work.

  3. Characterisation of neutral hydrogen beam by means of active balmer-a-spectroscopy

    International Nuclear Information System (INIS)

    Neutral particle beams are used in thermal nuclear experiments for plasma heating and current drive, and as a diagnostic tool for active spectroscopy. Within the frame of this thesis eight viewing lines for Hα-spectroscopy have been installed at the end of the injector to observe the fully established neutral beam. The viewing lines are all parallel to the horizontal plane and include small angles with the beam axis, in order to make use of the Doppler effect which separates the signals from the three energy components from each other and from the Hα-emission of the thermal particles. A multi-Gaussian fit code has been applied to give the amplitudes, positions and widths of the Gauss shaped signals. From this data, the beam composition and, including the physics processes in the acceleration and neutralisation sections, the ion species fractions in the source have been calculated. Furthermore, the vertical density profile and an estimation of the absolute particle density distribution based on an absolute calibration resulted. From the line positions the exact acceleration voltage has been obtained. The line widths allow an estimate of the horizontal divergence. During this work, two ion sources, the 'Pagoda' and the 'Sourcette', have been investigated to obtain the ion species ratio and beam profile. The comparison of the spectroscopic with the calorimetric results gives a useful insight into the beam steering geometry. (author)

  4. Characterisation of neutral hydrogen beam by means of active balmer-a-spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Wachter, C

    1999-01-01

    Neutral particle beams are used in thermal nuclear experiments for plasma heating and current drive, and as a diagnostic tool for active spectroscopy. Within the frame of this thesis eight viewing lines for H{sub {alpha}}-spectroscopy have been installed at the end of the injector to observe the fully established neutral beam. The viewing lines are all parallel to the horizontal plane and include small angles with the beam axis, in order to make use of the Doppler effect which separates the signals from the three energy components from each other and from the H{sub {alpha}}-emission of the thermal particles. A multi-Gaussian fit code has been applied to give the amplitudes, positions and widths of the Gauss shaped signals. From this data, the beam composition and, including the physics processes in the acceleration and neutralisation sections, the ion species fractions in the source have been calculated. Furthermore, the vertical density profile and an estimation of the absolute particle density distribution based on an absolute calibration resulted. From the line positions the exact acceleration voltage has been obtained. The line widths allow an estimate of the horizontal divergence. During this work, two ion sources, the 'Pagoda' and the 'Sourcette', have been investigated to obtain the ion species ratio and beam profile. The comparison of the spectroscopic with the calorimetric results gives a useful insight into the beam steering geometry. (author)

  5. Synthesis, structural characterisation and antibacterial activity of Ag+-doped fluorapatite nanomaterials prepared by neutralization method

    International Nuclear Information System (INIS)

    Graphical abstract: - Highlights: • The neutralization method has been used for synthesis of silver-doped fluorapatite powders. • Particles of silver-doped fluorapatite samples are of nano size and homogenous in composition. • The Ag+-doped fluorapatite samples showed antibacterial effect against Kllebsiela pneumoniae, Staphylococcus aureus and Micrococcus luteus. • AFM studies showed that silver-doped sample causes considerable morphological changes of tested bacterial cells. - Abstract: Silver doped fluorapatite nanopowders were synthesised by neutralization method, which consists of dissolving Ag2O in solution of HF and H3PO4 and addition to suspension of Ca(OH)2. The powder XRD, SEM and FTIR studies indicated the formation of a fluorapatite nanomaterials with average length of the particles is about 80 nm and a width of about 15 nm. The FTIR studies show that carbonate content in samples is very small and carbonte ions substitute both phosphate and hydroxyl groups in the crystal structure of samples, forming AB-type fluorapatite. Antibacterial studies have demonstrated that all Ag+-doped fluorapatite samples exhibit bactericidal effect against pathogens: Staphylococcus aureus, Micrococcus luteus and Kllebsiela pneumoniae. Antibacterial activity increased with the increase of Ag+ in the samples. The atomic force microscopy studies revealed extensive damage to the bacterial cell envelops in the presence of Ag+-doped fluorapatite particles which may lead to their death. The synthesized Ag+-doped fluorapatite nanomaterials are promising as antibacterial biomaterials in orthopedics and dentistry

  6. Self-shadowing Effects of Slim Accretion Disks in Active Galactic Nuclei: Diverse Appearance of the Broad-line Region

    CERN Document Server

    Wang, J -M; Du, P; Ho, L C

    2014-01-01

    Supermassive black holes in active galactic nuclei (AGNs) undergo a wide range of accretion rates, which lead to diversity of appearance. We consider the effects of anisotropic radiation from accretion disks on the broad-line region (BLR), from the Shakura-Sunyaev regime to slim disks with super-Eddington accretion rates. The geometrically thick funnel of the inner region of slim disks produces strong self-shadowing effects that lead to very strong anisotropy of the radiation field. We demonstrate that the degree of anisotropy of the radiation fields grows with increasing accretion rate. As a result of this anisotropy, BLR clouds receive different spectral energy distributions depending on their location relative to the disk, resulting in diverse observational appearance of the BLR. We show that the self-shadowing of the inner parts of the disk naturally produces two dynamically distinct regions of the BLR, depending on accretion rate. These two regions manifest themselves as kinematically distinct components...

  7. Formation of Turbulent Cones in Accretion Disk Outflows and Application to Broad Line Regions of Active Galactic Nuclei

    CERN Document Server

    Poludnenko, A Y; Frank, A

    2002-01-01

    We consider the stability of an accretion disk wind to cloud formation when subject to a central radiation force. For a vertical launch velocity profile that is Keplerian or flatter and the presence of a significant radiation pressure, the wind flow streamlines cross in a conical layer. We argue that such regions are highly unstable, and are natural sites for supersonic turbulence and, consequently, density compressions. We suggest that combined with thermal instability these will all conspire to produce clouds. Such clouds can exist in dynamical equilibrium, constantly dissipating and reforming. As long as there is an inner truncation radius to the wind, our model emerges with a biconical structure similar to that inferred by Elvis (2000) for the broad line region (BLR) of active galactic nuclei (AGN). Our results may also apply to other disk-wind systems.

  8. Line-emitting clouds in broad-line regions of active galaxy nuclei their geometry and phase functions

    International Nuclear Information System (INIS)

    For a spherical cosmic cloud photoionized by a distant point source, a phase function, which describes anisotropy on the cloud radiation in a given line, is derived. The assumptions made are as follows: (1) the cloud is completely opaque to the line photons, and the line photons are generated at small optical depths; (2) the surface of the cloud emits in the line orthotropically; (3) the dependence of the line luminosity of a surface element on the value of the incident ionizing flux is described by a power law. The derived formulae may be useful n investigations of the structure of broad-line regions of active galactic nuclei. The effect of cloud geometry on phase function is discussed

  9. Recombinant broad-range phospholipase C from Listeria monocytogenes exhibits optimal activity at acidic pH.

    Science.gov (United States)

    Huang, Qiongying; Gershenson, Anne; Roberts, Mary F

    2016-06-01

    The broad-range phospholipase C (PLC) from Listeria monocytogenes has been expressed using an intein expression system and characterized. This zinc metalloenzyme, similar to the homologous enzyme from Bacillus cereus, targets a wide range of lipid substrates. With monomeric substrates, the length of the hydrophobic acyl chain has significant impact on enzyme efficiency by affecting substrate affinity (Km). Based on a homology model of the enzyme to the B. cereus protein, several active site residue mutations were generated. While this PLC shares many of the mechanistic characteristics of the B. cereus PLC, a major difference is that the L. monocytogenes enzyme displays an acidic pH optimum regardless of substrate status (monomer, micelle, or vesicle). This unusual behavior might be advantageous for its role in the pathogenicity of L. monocytogenes. PMID:26976751

  10. A Broadly-Based Training Program in Volcano Hazards Monitoring at the Center for the Study of Active Volcanoes

    Science.gov (United States)

    Thomas, D. M.; Bevens, D.

    2015-12-01

    The Center for the Study of Active Volcanoes, in cooperation with the USGS Volcano Hazards Program at HVO and CVO, offers a broadly based volcano hazards training program targeted toward scientists and technicians from developing nations. The program has been offered for 25 years and provides a hands-on introduction to a broad suite of volcano monitoring techniques, rather than detailed training with just one. The course content has evolved over the life of the program as the needs of the trainees have changed: initially emphasizing very basic monitoring techniques (e.g. precise leveling, interpretation of seismic drum records, etc.) but, as the level of sophistication of the trainees has increased, training in more advanced technologies has been added. Currently, topics of primary emphasis have included volcano seismology and seismic networks; acquisition and modeling of geodetic data; methods of analysis and monitoring of gas geochemistry; interpretation of volcanic deposits and landforms; training in LAHARZ, GIS mapping of lahar risks; and response to and management of volcanic crises. The course also provides training on public outreach, based on CSAV's Hawaii-specific hazards outreach programs, and volcano preparedness and interactions with the media during volcanic crises. It is an intensive eight week course with instruction and field activities underway 6 days per week; it is now offered in two locations, Hawaii Island, for six weeks, and the Cascades volcanoes of the Pacific Northwest, for two weeks, to enable trainees to experience field conditions in both basaltic and continental volcanic environments. The survival of the program for more than two decades demonstrates that a need for such training exists and there has been interaction and contribution to the program by the research community, however broader engagement with the latter continues to present challenges. Some of the reasons for this will be discussed.

  11. A novel alkaloid from marine-derived actinomycete Streptomyces xinghaiensis with broad-spectrum antibacterial and cytotoxic activities.

    Directory of Open Access Journals (Sweden)

    Wence Jiao

    Full Text Available Due to the increasing emergence of drug-resistant bacteria and tumor cell lines, novel antibiotics with antibacterial and cytotoxic activities are urgently needed. Marine actinobacteria are rich sources of novel antibiotics, and here we report the discovery of a novel alkaloid, xinghaiamine A, from a marine-derived actinomycete Streptomyces xinghaiensis NRRL B24674(T. Xinghaiamine A was purified from the fermentation broth, and its structure was elucidated based on extensive spectroscopic analysis, including 1D and 2D NMR spectrum as well as mass spectrometry. Xinghaiamine A was identified to be a novel alkaloid with highly symmetric structure on the basis of sulfoxide functional group, and sulfoxide containing compound has so far never been reported in microorganisms. Biological assays revealed that xinghaiamine A exhibited broad-spectrum antibacterial activities to both Gram-negative persistent hospital pathogens (e.g. Acinetobacter baumannii, Pseudomonas aeruginosa and Escherichia coli and Gram-positive ones, which include Staphylococcus aureus and Bacillus subtilis. In addition, xinghaiamine A also exhibited potent cytotoxic activity to human cancer cell lines of MCF-7 and U-937 with the IC50 of 0.6 and 0.5 µM, respectively.

  12. A regulatory hydrophobic area in the flexible joint region of plasminogen activator inhibitor-1, defined with fluorescent activity-neutralizing ligands. Ligand-induced serpin polymerization

    DEFF Research Database (Denmark)

    Egelund, R; Einholm, A P; Pedersen, K E; Nielsen, R W; Christensen, A; Deinum, J; Andreasen, Peter A

    2001-01-01

    all tested nonfluorescent neutralizers, indicating that all neutralizers bind to a common hydrophobic area preferentially accessible in active PAI-1. Activity neutralization proceeded through two consecutive steps as follows: first step is conversion to forms displaying substrate behavior toward u...... having overlapping, but not identical, binding sites in the region around alpha-helices D and E and beta-strand 1A, known to act as a flexible joint when beta-sheet A opens and the reactive center loop inserts as beta-strand 4A during reaction with target proteinases. The defined binding area may be a...

  13. Dengue virus infection-enhancing activity in serum samples with neutralizing activity as determined by using FcγR-expressing cells.

    Directory of Open Access Journals (Sweden)

    Meng Ling Moi

    Full Text Available BACKGROUND: Progress in dengue vaccine development has been hampered by limited understanding of protective immunity against dengue virus infection. Conventional neutralizing antibody titration assays that use FcγR-negative cells do not consider possible infection-enhancement activity. We reasoned that as FcγR-expressing cells are the major target cells of dengue virus, neutralizing antibody titration assays using FcγR-expressing cells that determine the sum of neutralizing and infection-enhancing activity, may better reflect the biological properties of antibodies in vivo. METHODS AND FINDINGS: We evaluated serum samples from 80 residents of a dengue endemic country, Malaysia, for neutralizing activity, and infection-enhancing activity at 1∶10 serum dilution by using FcγR-negative BHK cells and FcγR-expressing BHK cells. The serum samples consisted of a panel of patients with acute DENV infection (31%, 25/80 and a panel of donors without acute DENV infection (69%, 55/80. A high proportion of the tested serum samples (75%, 60/80 demonstrated DENV neutralizing activity (PRNT(50≥10 and infection-enhancing activity. Eleven of 18 serum samples from patients with acute secondary DENV infection demonstrated neutralizing activity to the infecting serotype determined by using FcγR-negative BHK cells (PRNT(50≥10, but not when determined by using FcγR-expressing cells. CONCLUSION: Human serum samples with low neutralizing activity determined by using FcγR-negative cells showed DENV infection-enhancing activity using FcγR-expressing cells, whereas those with high neutralizing activity determined by using FcγR-negative cells demonstrate low or no infection-enhancing activity using FcγR-expressing cells. The results suggest an inverse relationship between neutralizing antibody titer and infection-enhancing activity, and that neutralizing activity determined by using FcγR-expressing cells, and not the activity determined by using Fc

  14. Active galactic nuclei at z ˜ 1.5 - II. Black hole mass estimation by means of broad emission lines

    Science.gov (United States)

    Mejía-Restrepo, J. E.; Trakhtenbrot, B.; Lira, P.; Netzer, H.; Capellupo, D. M.

    2016-07-01

    This is the second in a series of papers aiming to test how the mass (MBH), accretion rate (Ṁ) and spin (a*) of supermassive black holes (SMBHs) determine the observed properties of type I active galactic nuclei (AGN). Our project utilizes a sample of 39 unobscured AGN at z ≃ 1.55 observed by Very Large Telescope/X-Shooter, selected to map a large range in MBH and L/LEdd and covers the most prominent UV-optical (broad) emission lines, including Hα, Hβ, Mg II λ2798 and C IV λ1549. This paper focuses on single-epoch, `virial' MBH determinations from broad emission lines and examines the implications of different continuum modelling approaches in line width measurements. We find that using a local power-law continuum instead of a physically motivated thin disc continuum leads to only slight underestimation of the full width at half-maximum (FWHM) of the lines and the associated MBH(FWHM). However, the line dispersion σline and associated MBH(σline) are strongly affected by the continuum placement and provides less reliable mass estimates than FWHM-based methods. Our analysis shows that Hα, Hβ and Mg II can be safely used for virial MBH estimation. The C IV line, on the other hand, is not reliable in the majority of the cases; this may indicate that the gas emitting this line is not virialized. While Hα and Hβ show very similar line widths, the mean FWHM(Mg II) is about 30 per cent narrower than FWHM(Hβ). We confirm several recent suggestions to improve the accuracy in C IV-based mass estimates, relying on other UV emission lines. Such improvements do not reduce the scatter between C IV-based and Balmer-line-based mass estimates.

  15. Active galactic nuclei at z ˜ 1.5: II. Black Hole Mass estimation by means of broad emission lines

    Science.gov (United States)

    Mejia-Restrepo, J. E.; Trakhtenbrot, B.; Lira, P.; Netzer, H.; Capellupo, D. M.

    2016-03-01

    This is the second in a series of papers aiming to test how the mass (MBH), accretion rate (dot{M}) and spin (a★) of super massive black holes (SMBHs) determine the observed properties of type-I active galactic nuclei (AGN). Our project utilizes a sample of 39 unobscured AGN at z ≃ 1.55 observed by VLT/X-shooter, selected to map a large range in MBH and L/LEddand covers the most prominent UV-optical (broad) emission lines, including Hα, Hβ, Mg II λ2798, and C IV λ1549. This paper focuses on single-epoch, "virial" MBH determinations from broad emission lines and examine the implications of different continuum modeling approaches in line width measurements. We find that using a local power-law continuum instead of a physically-motivated thin disk continuum leads to only slight underestimation of the FWHM of the lines and the associated MBH(FWHM). However, the line dispersion σline and associated MBH(σline) are strongly affected by the continuum placement and provides less reliable mass estimates than FWHM-based methods. Our analysis shows that Hα, Hβ and Mg II can be safely used for virial MBH estimation. The C IV line, on the other hand, is not reliable in the majority of the cases, this may indicate that the gas emitting this line is not virialized. While Hα and Hβ show very similar line widths, the mean FWHM(Mg II) is about 30% narrower than FWHM(Hβ). We confirm several recent suggestions to improve the accuracy in C IV-based mass estimates, relying on other UV emission lines. Such improvements do not reduce the scatter between C IV-based and Balmer-line-based mass estimates.

  16. Fibrillar amyloid-β-activated human astroglia kill primary human neurons via neutral sphingomyelinase: Implications for Alzheimer’s disease

    OpenAIRE

    Jana, Arundhati; Pahan, Kalipada

    2010-01-01

    Glial activation plays an important role in the pathogenesis of various neurodegenerative disorders including Alzheimer’s disease (AD). However, molecular mechanisms by which activated glia could kill neurons are poorly understood. The present study underlines the importance of neutral sphingomyelinase (N-SMase) in mediating the damaging effect of fibrillar amyloid-β 1-42 (Aβ1-42) peptide-activated astroglia on neurons. In trans-well experiments, soluble products released from activated prima...

  17. Steady state performance test analysis of actively cooled extractor grids for SST-1 neutral beam injector

    International Nuclear Information System (INIS)

    Neutral beam injection (NBI) system is a workhorse to heat magnetically confined tokamak fusion plasma. The heart of any NBI system is an ion extractor system. Steady State Superconducting Tokamak-1 (SST-1) needs 0.5 MW of hydrogen beam power at 30 kV to raise the plasma ion temperature to ∼1 keV and 1.7 MW of hydrogen beam power at 55 kV for future upgradation. To meet this requirement, an ion extractor system consisting of three actively cooled grids has been designed, fabricated, and its performance test has been done at MARION test stand, IPP, Julich, Germany. During long pulse (14 s) operation, hydrogen ion beam of energy 31 MJ has been extracted at 41 kV. In this paper, we have presented detailed analysis of calorimetric data of actively cooled extractor grids and showed that by monitoring outlet water temperature, grid material temperature can be monitored for safe steady state operation of a NBI system. Steady state operation of NBI is the present day interest of fusion research. In the present experimental case, performance test analysis indicates that the actively cooled grids attain steady state heat removal condition and the grid material temperature rise is ∼18 deg. C and saturates after 10 s of beam pulse.

  18. Broad spectrum antibacterial and antifungal polymeric paint materials: synthesis, structure-activity relationship, and membrane-active mode of action.

    Science.gov (United States)

    Hoque, Jiaul; Akkapeddi, Padma; Yadav, Vikas; Manjunath, Goutham B; Uppu, Divakara S S M; Konai, Mohini M; Yarlagadda, Venkateswarlu; Sanyal, Kaustuv; Haldar, Jayanta

    2015-01-28

    Microbial attachment and subsequent colonization onto surfaces lead to the spread of deadly community-acquired and hospital-acquired (nosocomial) infections. Noncovalent immobilization of water insoluble and organo-soluble cationic polymers onto a surface is a facile approach to prevent microbial contamination. In the present study, we described the synthesis of water insoluble and organo-soluble polymeric materials and demonstrated their structure-activity relationship against various human pathogenic bacteria including drug-resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and beta lactam-resistant Klebsiella pneumoniae as well as pathogenic fungi such as Candida spp. and Cryptococcus spp. The polymer coated surfaces completely inactivated both bacteria and fungi upon contact (5 log reduction with respect to control). Linear polymers were more active and found to have a higher killing rate than the branched polymers. The polymer coated surfaces also exhibited significant activity in various complex mammalian fluids such as serum, plasma, and blood and showed negligible hemolysis at an amount much higher than minimum inhibitory amounts (MIAs). These polymers were found to have excellent compatibility with other medically relevant polymers (polylactic acid, PLA) and commercial paint. The cationic hydrophobic polymer coatings disrupted the lipid membrane of both bacteria and fungi and thus showed a membrane-active mode of action. Further, bacteria did not develop resistance against these membrane-active polymers in sharp contrast to conventional antibiotics and lipopeptides, thus the polymers hold great promise to be used as coating materials for developing permanent antimicrobial paint. PMID:25541751

  19. Multifrequency VLBI Observations of the Broad Absorption Line Quasar J1020+4320: Recently Restarted Jet Activity?

    Science.gov (United States)

    Doi, Akihiro; Murata, Yasuhiro; Mochizuki, Nanako; Takeuchi, Hiroshi; Asada, Keiichi; Hayashi, Takayuki J.; Nagai, Hiroshi; Shibata, Katsunori M.; Oyama, Tomoaki; Jike, Takaaki; Fujisawa, Kenta; Sugiyama, Koichiro; Ogawa, Hideo; Kimura, Kimihiro; Honma, Mareki; Kobayashi, Hideyuki; Koyama, Shoko

    2013-06-01

    This paper reports on very-long-baseline interferometry observations of the radio-loud broad absorption line (BAL) quasar J1020+4320 at 1.7, 2.3, 6.7, and 8.4 GHz using the Japanese VLBI network (JVN) and European VLBI network (EVN). The radio morphology is compact with a size of ˜10 pc. The convex radio spectrum has been stable over the last decade; an observed peak frequency of 3.2 GHz is equivalent to 9.5 GHz in the rest frame, suggesting an age on the order of ˜100 years as a radio source, according to an observed correlation between the linear size and the peak frequency of compact steep spectrum (CSS) and giga-hertz peaked spectrum (GPS) radio sources. A low-frequency radio excess suggests a relic of past jet activity. J1020+4320 may be one of the quasars with recurrent and short-lived jet activity during a BAL-outflowing phase.

  20. Multifrequency VLBI Observations of the Broad Absorption Line Quasar J1020+4320: Recently Restarted Jet Activity?

    CERN Document Server

    Doi, Akihiro; Mochizuki, Nanako; Takeuchi, Hiroshi; Asada, Keiichi; Hayashi, Takayuki J; Nagai, Hiroshi; Shibata, Katsunori M; Oyama, Tomoaki; Jike, Takaaki; Fujisawa, Kenta; Sugiyama, Koichiro; Ogawa, Hideo; Kimura, Kimihiro; Honma, Mareki; Kobayashi, Hideyuki; Koyama, Shoko

    2013-01-01

    This paper reports very-long-baseline interferometry observations of the radio-loud broad absorption line (BAL) quasar J1020+4320 at 1.7, 2.3, 6.7, and 8.4 GHz using the Japanese VLBI network (JVN) and European VLBI network (EVN). The radio morphology is compact with a size of ~10 pc. The convex radio spectrum is stable over the last decade; an observed peak frequency of 3.2 GHz is equivalent to 9.5 GHz in the rest frame, suggesting an age of the order of ~100 years as a radio source, according to an observed correlation between linear size and peak frequency of compact steep spectrum (CSS) and giga-hertz peaked spectrum (GPS) radio sources. A low-frequency radio excess suggests relic of past jet activity. J1020+4320 may be one of the quasars with recurrent and short-lived jet activity during a BAL-outflowing phase.

  1. Generation of recombinant single-chain antibodies neutralizing the cytolytic activity of vaginolysin, the main virulence factor of Gardnerella vaginalis

    Directory of Open Access Journals (Sweden)

    Pleckaityte Milda

    2011-11-01

    Full Text Available Abstract Background Gardnerella vaginalis is identified as the predominant colonist of the vaginal tract in women with bacterial vaginosis. Vaginolysin (VLY is a protein toxin released by G. vaginalis. VLY possesses cytolytic activity and is considered as a main virulence factor of G. vaginalis. Inhibition of VLY-mediated cell lysis by antibodies may have important physiological relevance. Results Single-chain variable fragments of immunoglobulins (scFvs were cloned from two hybridoma cell lines producing neutralizing antibodies against VLY and expressed as active proteins in E. coli. For each hybridoma, two variants of anti-VLY scFv consisting of either VL-VH or VH-VL linked with a 20 aa-long linker sequence (G4S4 were constructed. Recovery of scFvs from inclusion bodies with subsequent purification by metal-chelate chromatography resulted in VLY-binding proteins that were predominantly monomeric. The antigen-binding activity of purified scFvs was verified by an indirect ELISA. The neutralizing activity was investigated by in vitro hemolytic assay and cytolytic assay using HeLa cell line. Calculated apparent Kd values and neutralizing potency of scFvs were in agreement with those of parental full-length antibodies. VH-VL and VL-VH variants of scFvs showed similar affinity and neutralizing potency. The anti-VLY scFvs derived from hybridoma clone 9B4 exhibited high VLY-neutralizing activity both on human erythrocytes and cervical epithelial HeLa cells. Conclusions Hybridoma-derived scFvs with VLY-binding activity were expressed in E. coli. Recombinant anti-VLY scFvs inhibited VLY-mediated cell lysis. The monovalent scFvs showed reduced affinity and neutralizing potency as compared to the respective full-length antibodies. The loss of avidity could be restored by generating scFv constructs with multivalent binding properties. Generated scFvs is the first example of recombinant single-chain antibodies with VLY-neutralizing activity produced in

  2. Performance of thermally activated dolomite for the treatment of Ni and Zn in contaminated neutral drainage.

    Science.gov (United States)

    Calugaru, Iuliana Laura; Neculita, Carmen Mihaela; Genty, Thomas; Bussière, Bruno; Potvin, Robin

    2016-06-01

    Intensive research is ongoing for developing low-cost and highly efficient materials in metal removal from contaminated effluents. The present study evaluated dolomite [CaMg(CO3)2], both raw and modified by thermal activation (charring), for Ni and Zn treatment in contaminated neutral drainage (CND). Batch adsorption testing (equilibrium and kinetics) were conducted at pH 6, to evaluate the performance of initial vs. modified dolomite, and to assess potential mechanisms of metal removal. Charring of dolomite led to a rigid and porous material, mainly consisting of CaCO3 and MgO, which showed a sorption capacity increased sevenfold for Zn and doubled for Ni, relative to the raw material. In addition, Freundlich model best described the sorption of the both metals by dolomite, whereas the Langmuir model best described their sorption on charred dolomite. Plausible mechanisms of metal removal include cation exchange, surface precipitation and sorption processes, with carbonate ions and magnesium oxides acting as active centers. Based on these results, charred dolomite seems a promising option for the efficient treatment of Ni and Zn in CND. PMID:26897574

  3. Hydrolytic and autolytic behavior of two forms of calcium-activated neutral protease (CANP).

    Science.gov (United States)

    Inomata, M; Hayashi, M; Nakamura, M; Imahori, K; Kawashima, S

    1985-08-01

    Some endogenous substrates were incubated with two forms of calcium-activated neutral protease (CANP) with high (muCANP) and low (mCANP) sensitivities to calcium ions. In addition to analyses of the processes of their degradation, changes in the molecular properties of these CANPs were also examined. Among the tested substrate proteins, the myosin heavy chain of rabbit skeletal muscle myofibrils and spectrin or band 3 protein of human erythrocyte membranes were degraded relatively rapidly. So far as these proteins were concerned, a higher degradation velocity was observed for muCANP than for mCANP. Vimentin from ascites tumor cells was degraded most rapidly and no difference was observed in degradation velocity between muCANP and mCANP. In all cases, muCANP and mCANP produced different proteolytic peptide fragments, suggesting the different substrate-specificities of these CANPs. The degradation of substrates always accompanied the autodigestion of CANPs, and the small subunits of both CANPs were degraded in the early stage of the autodigestion. The large subunit of muCANP (79K) was converted to a 76K polypeptide via a 77K polypeptide as an intermediate. The autodigested muCANP with 76K polypeptide retained sufficient protease activity and, moreover, its calcium-sensitivity was higher than that of intact muCANP. The possibility is thus proposed that restricted autodigestion is a necessary activation step for the appearance of activity of muCANP. No such transition was observed for mCANP. PMID:2999095

  4. Constraining UV Continuum Slopes of Active Galactic Nuclei With CLOUDY Models of Broad Line Region EUV Emission Lines

    CERN Document Server

    Moloney, Joshua

    2014-01-01

    Understanding the composition and structure of the broad-line region (BLR) of active galactic nuclei (AGN) is important for answering many outstanding questions in supermassive black hole evolution, galaxy evolution, and ionization of the intergalactic medium. We used single-epoch UV spectra from the Cosmic Origins Spectrograph (COS) on the Hubble Space Telescope to measure EUV emission-line fluxes from four individual AGN with $0.49 \\le z \\le 0.64$, two AGN with $0.32 \\le z \\le 0.40$, and a composite of 159 AGN. With the Cloudy photoionization code, we calculated emission-line fluxes from BLR clouds with a range of density, hydrogen ionizing flux and incident continuum spectral indices. The photoionization grids were fit to the observations using single-component and locally optimally emitting cloud (LOC) models. The LOC models provide good fits to the measured fluxes, while the single-component models do not. The UV spectral indices preferred by our LOC models are consistent with those measured from COS spe...

  5. Silver Nanoparticles: Biosynthesis Using an ATCC Reference Strain of Pseudomonas aeruginosa and Activity as Broad Spectrum Clinical Antibacterial Agents

    Science.gov (United States)

    Quinteros, Melisa A.; Aiassa Martínez, Ivana M.; Dalmasso, Pablo R.; Páez, Paulina L.

    2016-01-01

    Currently, the biosynthesis of silver-based nanomaterials attracts enormous attention owing to the documented antimicrobial properties of these ones. This study reports the extracellular biosynthesis of silver nanoparticles (Ag-NPs) using a Pseudomonas aeruginosa strain from a reference culture collection. A greenish culture supernatant of P. aeruginosa incubated at 37°C with a silver nitrate solution for 24 h changed to a yellowish brown color, indicating the formation of Ag-NPs, which was confirmed by UV-vis spectroscopy, transmission electron microscopy, and X-ray diffraction. TEM analysis showed spherical and pseudospherical nanoparticles with a distributed size mainly between 25 and 45 nm, and the XRD pattern revealed the crystalline nature of Ag-NPs. Also it provides an evaluation of the antimicrobial activity of the biosynthesized Ag-NPs against human pathogenic and opportunistic microorganisms, namely, Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Proteus mirabilis, Acinetobacter baumannii, Escherichia coli, P. aeruginosa, and Klebsiella pneumonia. Ag-NPs were found to be bioactive at picomolar concentration levels showing bactericidal effects against both Gram-positive and Gram-negative bacterial strains. This work demonstrates the first helpful use of biosynthesized Ag-NPs as broad spectrum bactericidal agents for clinical strains of pathogenic multidrug-resistant bacteria such as methicillin-resistant S. aureus, A. baumannii, and E. coli. In addition, these Ag-NPs showed negligible cytotoxic effect in human neutrophils suggesting low toxicity to the host. PMID:27340405

  6. Characterization of a type-I crustin with broad-spectrum antimicrobial activity from red swamp crayfish Procambarus clarkii.

    Science.gov (United States)

    Liu, Ning; Zhang, Ran-Ran; Fan, Zhen-Xu; Zhao, Xiao-Fan; Wang, Xian-Wei; Wang, Jin-Xing

    2016-08-01

    Crustins are a family of antimicrobial peptides mainly identified in crustaceans and characterized by a whey acidic protein (WAP) domain and an additional glycine-, cysteine-, or proline-rich region. In this study, we identified and characterized PcCru, a new crustin isolated from red swamp crayfish Procambarus clarkii. The open reading frame of PcCru was 333 base pairs long and encoded a 110-residue polypeptide, which contained a signal peptide, a cysteine-rich region, and a WAP domain. The architecture and phylogenetic analysis suggested that PcCru was a new member of the type-I crustin family. PcCru was highly expressed in hemocytes and was significantly induced by viral and bacterial stimulations at both the translational and transcriptional levels. The titer of PcCru in circulating plasma was also increased considerably by bacterial challenge. Recombinant PcCru from both prokaryotic and eukaryotic expression systems were generated, and the proteins exhibited broad-spectrum antimicrobial activity. Furthermore, PcCru protected crayfish from infection by pathogenic bacteria Aeromonas hydrophila in vivo. This study provided new information emphasizing the important role of the crustin family in the crustacean antibacterial immune response. PMID:27021077

  7. Variability of the X-ray Broad Iron Spectral Features in Active Galactic Nuclei and Black-hole Binaries

    CERN Document Server

    Mizumoto, Misaki; Tsujimoto, Masahiro; Inoue, Hajime

    2015-01-01

    The "broad iron spectral features" are often seen in X-ray spectra of Active Galactic Nuclei (AGN) and black-hole binaries (BHB). These features may be explained either by the "relativistic disc reflection" scenario or the "partial covering" scenario: It is hardly possible to determine which model is valid from time-averaged spectral analysis. Thus, X-ray spectral variability has been investigated to constrain spectral models. To that end, it is crucial to study iron structure of BHBs in detail at short time-scales, which is, for the first time, made possible with the Parallel-sum clocking (P-sum) mode of XIS detectors on board Suzaku. This observational mode has a time-resolution of 7.8~ms as well as a CCD energy-resolution. We have carried out systematic calibration of the P-sum mode, and investigated spectral variability of the BHB GRS 1915+105. Consequently, we found that the spectral variability of GRS 1915+105 does not show iron features at sub-seconds. This is totally different from variability of AGN ...

  8. X-ray heating and ionization of broad-emission-line regions in QSO's and active galaxies

    Energy Technology Data Exchange (ETDEWEB)

    Weisheit, J.C.; Shields, G.A.; Tarter, C.B.

    1980-07-01

    Absorption of x-rays deep within the broad-line emitting clouds in QSO's and the nuclei of active galaxies creates extensive zones of warm (T approx. 10/sup 4/K), partially ionized N/sub e//N approx. 0.1) gas. Because Lyman alpha photons are trapped in these regions, the x-ray energy is efficiently channeled into Balmer lines collisionally excited from the n = 2 level. The HI regions plus the HII regions created by ultraviolet photons illuminating the surfaces of the clouds give rise to integrated L..cap alpha../H..cap alpha.. line emission ratios between 1 and 2. Enhanced MgII line emission from the HI regions gives rise to integrated MgII/H..cap alpha.. ratios near 0.5. The OI line lambda 8446 is efficiently pumped by trapped H..cap alpha.. photons and in the x-ray heated zone an intensity ratio I (lambda 8446)/I(H..cap alpha..) approx. < 0.1 is calculated. All of these computed ratios now are in agreement with observations.

  9. The Seismic Broad Band Western Mediterranean (wm) Network and the Obs Fomar Pool: Current state and Obs activities.

    Science.gov (United States)

    Pazos, Antonio; Davila, Jose Martin; Buforn, Elisa; Bezzeghoud, Mourad; Harnafi, Mimoun; Mattesini, Mauricio; Caldeira, Bento; Hanka, Winfried; El Moudnib, Lahcen; Strollo, Angelo; Roca, Antoni; Lopez de Mesa, Mireya; Dahm, Torsten; Cabieces, Roberto

    2016-04-01

    The Western Mediterranean (WM) seismic network started in 1996 as an initiative of the Royal Spanish Navy Observatory (ROA) and the Universidad Complutense de Madrid (UCM), with the collaboration of the GeoForschungsZentrum (GFZ) of Potsdam. A first broad band seismic station (SFUC) was installed close to Cádiz (South Spain). Since then, additional stations have been installed in the Ibero-Moghrebian region. In 2005, the "WM" code was assigned by the FDSN and new partners were jointed: Evora University (UEVO, Portugal), the Scientifique Institute of Rabat (ISRABAT, Morocco), and GFZ. Now days, the WM network is composed by 15 BB stations, all of them with Streckaisen STS-2 or STS-2.5 sensors, Quanterra or Earthdata digitizers and SeiscomP. Most them have co-installed a permanent geodetic GPS stations, and some them also have an accelerometer. There are 10 stations deployed in Spanish territory (5 in the Iberian peninsula, 1 in Balearic islands and 4 in North Africa Spanish places) with VSAT or Internet communications, 2 in Portugal (one of them without real time), and 3 in Morocco (2 VSAT and 1 ADSL). Additionally, 2 more stations (one in South Spain and one in Morocco) will be installed along this year. Additionally ROA has deployed a permanent real time VBB (CMG-3T: 360s) station at the Alboran Island. Due to the fact that part of the seismic activity is located at marine areas, and also because of the poor geographic azimuthal coverage at some zones provided by the land stations (specially in the SW of the San Vicente Cape area), ROA and UCM have acquired six broad band "LOBSTERN" OBS, manufactured by KUM (Kiel, Germany), conforming the OBS FOMAR pool. Three of them with CMG-40T sensor and the other with Trillium 120. These OBS were deployed along the Gibraltar strait since January to November 2014 to study the microseismicity in the Gibraltar strait area. In September 2015 FOMAR network has been deployed in SW of the San Vicente Cape for 8 months as a part of

  10. Comparison of ACE inhibitory activity in skimmed goat and cow milk hydrolyzed by alcalase, flavourzyme, neutral protease and proteinase K

    Directory of Open Access Journals (Sweden)

    Bao Chunju

    2016-06-01

    Full Text Available Angiotensin I converting enzyme (ACE inhibitory peptides derived from milk proteins have obvious effect of lowering blood pressure, safe and non-toxic side effects. This study compared four commercial proteases, namely alcalase, flavourzyme, neutral protease and proteinase K for their ACE inhibitory activity in skimmed goat and cow milk and identified the best one with higher ACE inhibitory activity. The degree of hydrolysis (DH of alcalase and proteinase K were much higher than flavourzyme, neutral protease for both skimmed goat and cow milk. Alcalase was the best enzyme to produce ACE inhibitory peptides from goat milk, with the ACE inhibitory activity 95.31%, while proteinase K was the optimal protease for hydrolyzing cow milk, with 81.28% ACE inhibitory activity. Furthermore, no correlation was obtained between the ACE inhibitory activity and DH for both goat and cow milk.

  11. Sialorphin, a natural inhibitor of rat membrane-bound neutral endopeptidase that displays analgesic activity

    Science.gov (United States)

    Rougeot, Catherine; Messaoudi, Michaël; Hermitte, Véronique; Rigault, Anne Gaëlle; Blisnick, Thierry; Dugave, Christophe; Desor, Didier; Rougeon, François

    2003-01-01

    Sialorphin is an exocrine and endocrine signaling mediator, which has been identified by a genomic approach. It is synthesized predominantly in the submandibular gland and prostate of adult rats in response to androgen steroids and is released locally and systemically in response to stress. We now demonstrate that the cell surface molecule to which sialorphin binds in vivo in the rat kidney is the membrane-anchored neutral endopeptidase (neprilysin; NEP, EC 3.4.24.11). NEP plays an important role in nervous and peripheral tissues, as it turns off several peptide-signaling events at the cell surface. We show that sialorphin prevents spinal and renal NEP from breaking down its two physiologically relevant substrates, substance P and Met-enkephalin in vitro. Sialorphin inhibited the breakdown of substance P with an IC50 of 0.4–1 μM and behaved as a competitive inhibitor. In vivo, i.v. sialorphin elicited potent antinociceptive responses in two behavioral rat models of injury-induced acute and tonic pain, the pin-pain test and formalin test. The analgesia induced by 100–200 μg/kg doses of sialorphin required the activation of μ- and δ-opioid receptors, consistent with the involvement of endogenous opioid receptors in enkephalinergic transmission. We conclude that sialorphin protects endogenous enkephalins released after nociceptive stimuli by inhibiting NEP in vivo. Sialorphin is a natural systemically active regulator of NEP activity. Furthermore, our study provides evidence that it is a physiological modulator of pain perception after injury and might be the progenitor of a new class of therapeutic molecules. PMID:12835417

  12. Pre-existing immunity with high neutralizing activity to 2009 pandemic H1N1 influenza virus in Shanghai population.

    Directory of Open Access Journals (Sweden)

    Xiaoqing Liu

    Full Text Available Pre-existing immunity is an important factor countering the pandemic potential of an emerging influenza virus strain. Thus, studying of pre-existing immunity to the 2009 pandemic H1N1 virus (2009 H1N1 will advance our understanding of the pathogenesis and epidemiology of this emerging pathogen. In the present study, sera were collected from 486 individuals in a hospital in Shanghai, China, before the 2009 H1N1 influenza pandemic. The serum anti-hemagglutinins (HA antibody, hemagglutination inhibition (HI antibody and neutralizing antibody against the 2009 H1N1 were assayed. Among this population, 84.2%, 14.61% and 26.5% subjects possessed anti-HA antibody, HI antibody and neutralizing antibody, respectively. Although neutralizing antibody only existed in those sera with detectable anti-HA antibody, there was no obvious correlation between the titers of anti-HA and neutralizing antibody. However, the titers of anti-HA and neutralizing antibody against seasonal H1N1 virus were highly correlated. In the same population, there was no correlation between titers of neutralizing antibody against 2009 H1N1 and seasonal H1N1. DNA immunization performed on mice demonstrated that antibodies to the HA of 2009 pandemic and seasonal H1N1 influenza viruses were strain-specific and had no cross-neutralizing activity. In addition, the predicted conserved epitope in the HA of 2009 H1N1 and recently circulating seasonal H1N1 virus, GLFGAIAGFIE, was not an immunologically valid B-cell epitope. The data in this report are valuable for advancing our understanding of 2009 H1N1 influenza virus infection.

  13. Active neutral particle diagnostics on LHD by locally enhanced charge exchange on an impurity pellet ablation cloud

    International Nuclear Information System (INIS)

    Production, confinement and thermalization of high-energy particles are the fundamental issues in fusion plasma ion kinetics. The ion distribution function and its evolution under the ion cyclotron heating and neutral beam injection are studied by energy resolved charge exchange neutral flux measurements. For helical systems, such as LHD, local diagnostics are required due to the complex 3D magnetic field. In passive methods one needs to analyze the integral relation between the plasma ion distribution function and the observed neutral flux, which is a superposition along the diagnostic sightline, taking into account the charge exchange target density profile. In active measurements either a diagnostic neutral beam or a solid pellet injection are used to enhance the charge exchange locally. An impurity pellet ablation cloud rcloud plasma provides a localized charge exchange target scanning the plasma radially. Pellet-induced neutral fluxes were previously measured on LHD with a natural diamond detector. However, obtaining the energy spectra from these data in the main energy range of interest (101-102 keV in the present experiments) is complicated due to the high operating speed, i.e. the spatial resolution requirement. A new diagnostic based on a compact neutral particle analyser (CNPA) has been installed on LHD for measurements in the H0 energy range 1 - 170 keV. CNPA employs a thin 50 A diamond-like carbon stripping film instead of a traditional gas stripping cell, a high-field-strength permanent analysing magnet and an array of 40 channel electron multipliers (CEMs) for particle detection. CEMs can be used in both counting and current modes to be able to process high neutral particle fluxes from the charge exchange on the dense pellet cloud. Thus, the system is suitable for both passive measurements and the active probing with a diagnostic pellet. Pneumatically accelerated polystyrene (-C8H8-)n balls are injected transversally; typical Dpel = 500-900 μm, vpel

  14. Generating Active "L-Pd(0)" via Neutral or Cationic π-Allylpalladium Complexes Featuring Biaryl/Bipyrazolylphosphines: Synthetic, Mechanistic, and Structure-Activity Studies in Challenging Cross-Coupling Reactions.

    Science.gov (United States)

    DeAngelis, A J; Gildner, Peter G; Chow, Ruishan; Colacot, Thomas J

    2015-07-01

    Two new classes of highly active yet air- and moisture-stable π-R-allylpalladium complexes containing bulky biaryl- and bipyrazolylphosphines with extremely broad ligand scope have been developed. Neutral π-allylpalladium complexes incorporated a range of biaryl/bipyrazolylphosphine ligands, while extremely bulky ligands were accommodated by a cationic scaffold. These complexes are easily activated under mild conditions and are efficient for a wide array of challenging C-C and C-X (X = heteroatom) cross-coupling reactions. Their high activity is correlated to their facile activation to a 12-electron-based "L-Pd(0)" catalyst under commonly employed conditions for cross-coupling reactions, noninhibitory byproduct release upon activation, and suppression of the off-cycle pathway to form dinuclear (μ-allyl)(μ-Cl)Pd2(L)2 species, supported by structural (single crystal X-ray) and kinetic studies. A broad scope of C-C and C-X coupling reactions with low catalyst loadings and short reaction times highlight the versatility and practicality of these catalysts in organic synthesis. PMID:26035637

  15. Neutralization of lymphokine-mediated antirickettsial activity of fibroblasts and macrophages with monoclonal antibody specific for murine interferon gamma.

    OpenAIRE

    Jerrells, T R; Turco, J; Winkler, H H; Spitalny, G L

    1986-01-01

    Lymphokine-mediated inhibition of Rickettsia prowazekii multiplication in L929 fibroblasts was eliminated by treatment of the lymphokine with a monoclonal antibody specific for interferon-gamma. Soluble monoclonal antibody and antibody conjugated to Sepharose beads were equally effective. Macrophage activation to limit the multiplication of Rickettsia conorii was eliminated with antibody-conjugated beads; however, neutralization of the ability to activate macrophages with soluble antibody was...

  16. Preclinical evaluation of three polyspecific antivenoms against the venom of Echis ocellatus: Neutralization of toxic activities and antivenomics.

    Science.gov (United States)

    Calvete, Juan J; Arias, Ana Silvia; Rodríguez, Yania; Quesada-Bernat, Sarai; Sánchez, Laura V; Chippaux, Jean Philippe; Pla, Davinia; Gutiérrez, José María

    2016-09-01

    Snakebite envenoming has a heavy burden in the public health in sub-Saharan Africa. The viperid species Echis ocellatus (carpet viper or saw-scaled viper) is the medically most important snake in the savannahs of western sub-Saharan Africa. Several antivenoms are being distributed and used in this region for the treatment of envenomings by E. ocellatus, but the preclinical efficacy of some of these antivenoms has not been assessed. The present study evaluated the preclinical efficacy against E. ocellatus venom of three polyspecific antivenoms: (a) Snake Venom Antiserum (Pan Africa), manufactured by Premium Serums and Vaccines (India); (b) Snake Venom Antiserum (Africa), manufactured by VINS Bioproducts (India); and (c) Antivipmyn(®) Africa, manufactured by Instituto Bioclon (Mexico). Antivenomics analysis revealed the ability of the three antivenoms to immunocapture the majority of components of the venoms of E. ocellatus from Cameroon, Nigeria and Mali, although their maximal immunocapturing capability varied. Bioclon and Premium Serums antivenoms were effective in the neutralization of lethal, hemorrhagic and in vitro coagulant activities of the venom of E. ocellatus from Cameroon, albeit with different potencies. VINS antivenom neutralized hemorrhagic activity of this venom, but failed to neutralize lethality at the highest antivenom dose tested, and had a low neutralizing efficacy against in vitro coagulant effect. PMID:27377229

  17. To test dual supermassive black hole model for broad line active galactic nucleus with double-peaked narrow [O III] lines

    Science.gov (United States)

    Zhang, Xue-Guang; Feng, Long-Long

    2016-04-01

    In this paper, we proposed an interesting method to test the dual supermassive black hole model for active galactic nucleus (AGN) with double-peaked narrow [O III] lines (double-peaked narrow emitters) through their broad optical Balmer line properties. Under the dual supermassive black hole model for double-peaked narrow emitters, we could expect statistically smaller virial black hole masses estimated by observed broad Balmer line properties than true black hole masses (total masses of central two black holes). Then, we compare the virial black hole masses between a sample of 37 double-peaked narrow emitters with broad Balmer lines and samples of Sloan Digital Sky Survey selected normal broad line AGN with single-peaked [O III] lines. However, we can find clearly statistically larger calculated virial black hole masses for the 37 broad line AGN with double-peaked [O III] lines than for samples of normal broad line AGN. Therefore, we give our conclusion that the dual supermassive black hole model is probably not statistically preferred to the double-peaked narrow emitters, and more efforts should be necessary to carefully find candidates for dual supermassive black holes by observed double-peaked narrow emission lines.

  18. Essential Oils and Non-volatile Compounds Derived from Chamaecyparis obtusa: Broad Spectrum Antimicrobial Activity against Infectious Bacteria and MDR(multidrug resistant) Strains.

    Science.gov (United States)

    Bae, Min-Suk; Park, Dae-Hun; Choi, Chul-Yung; Kim, Gye-Yeop; Yoo, Jin-Cheol; Cho, Seung-Sik

    2016-05-01

    The aim of this study was to evaluate the antibacterial activity of essential oil from Chamaecyparis obtusa against general infectious microbes and drug resistant strains of clinical origin. The results indicate that both essential oil and non-volatile residue have broad inhibitory activity against test strains. Essential oil and non-volatile residues showed antimicrobial activity not only against general infectious bacteria, but also against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) strains. PMID:27319153

  19. Unusual non-fluorescent broad spectrum siderophore activity (SID EGYII) by Pseudomonas aeruginosa strain EGYII DSM 101801 and a new insight towards simple siderophore bioassay.

    Science.gov (United States)

    Embaby, Amira M; Heshmat, Yasmin; Hussein, Ahmed

    2016-03-01

    Present study highlights an unusual non-fluorescent hydroxamate broad spectrum siderophore (SID EGYII) activity from Pseudomonas aeruginosa strain EGYII DSM 101801, a soil bacterial isolate, along with simple low cost effective siderophore bioassay. Detection of SID EGYII activity qualitatively was proved by masking this activity against Erwinia amylovora strain EGY1 DSM 101800, an indicator strain, in well-cut diffusion assay containing 100 µM FeCl3. SID EGYII activity was expressed quantitatively as arbitrary units [Siderophore arbitrary units (SAU)] 380 SAU/mL against E. amylovora strain EGY1 DSM 101800. Maximal SID EGYII activity was achieved upon growing P. aeruginosa strain EGYII DSM 101801 in PYB broth at 180 rpm for 24 h. SID EGYII displayed a broad spectrum antimicrobial activity against some human pathogens (i.e., Gram-positive bacteria, Gram-negative bacteria and yeasts) and a fireblight plant pathogen. Interestingly, transformants of Escherichia coli JM109 (DE3)pSID/EGYII harboring P. aeruginosa strain EGYII DSM 101801 plasmid demonstrated a perceivable antimicrobial activity against E. amylovora strain EGY1 DSM 101800. The broad spectrum antimicrobial activity of the unusual non-fluorescent SID EGYII would underpin its high potential in targeting bacterial pathogens posing probable threats to human health and agricultural economy. The present simple low cost effective bioassay is a new insight towards an alternative to the expensive cumbersome siderophore Chrome Azurol S assay. PMID:27015845

  20. Limited Neutrality

    DEFF Research Database (Denmark)

    Nielsen, Morten Ebbe Juul

    2006-01-01

    Article Concerning the prospect of a kind of limited neutrality in place of the standard liberal egalitarian "neutrality of justification."......Article Concerning the prospect of a kind of limited neutrality in place of the standard liberal egalitarian "neutrality of justification."...

  1. De Novo Whole-Genome Sequence of Micromonospora carbonacea JXNU-1 with Broad-Spectrum Antimicrobial Activity, Isolated from Soil Samples

    OpenAIRE

    Jiang, Yun; Huang, Yun-hong; Long, Zhong-er

    2015-01-01

    Micromonospora carbonacea JXNU-1 is an actinomycete with broad-spectrum antimicrobial activity, isolated from soil samples from the farmland in the area of Yaohu Lake in Nanchang, China. Here, we report the whole-genome sequence of M. carbonacea JXNU-1.

  2. NON-NEUTRALIZED ELECTRIC CURRENT PATTERNS IN SOLAR ACTIVE REGIONS: ORIGIN OF THE SHEAR-GENERATING LORENTZ FORCE

    Energy Technology Data Exchange (ETDEWEB)

    Georgoulis, Manolis K. [Research Center for Astronomy and Applied Mathematics of the Academy of Athens, 4 Soranou Efesiou Street, Athens GR-11527 (Greece); Titov, Viacheslav S.; Mikic, Zoran [Predictive Science, Inc., 9990 Mesa Rim Road, San Diego, CA 92121 (United States)

    2012-12-10

    Using solar vector magnetograms of the highest available spatial resolution and signal-to-noise ratio, we perform a detailed study of electric current patterns in two solar active regions (ARs): a flaring/eruptive and a flare-quiet one. We aim to determine whether ARs inject non-neutralized (net) electric currents in the solar atmosphere, responding to a debate initiated nearly two decades ago that remains inconclusive. We find that well-formed, intense magnetic polarity inversion lines (PILs) within ARs are the only photospheric magnetic structures that support significant net current. More intense PILs seem to imply stronger non-neutralized current patterns per polarity. This finding revises previous works that claim frequent injections of intense non-neutralized currents by most ARs appearing in the solar disk but also works that altogether rule out injection of non-neutralized currents. In agreement with previous studies, we also find that magnetically isolated ARs remain globally current-balanced. In addition, we confirm and quantify the preference of a given magnetic polarity to follow a given sense of electric currents, indicating a dominant sense of twist in ARs. This coherence effect is more pronounced in more compact ARs with stronger PILs and must be of sub-photospheric origin. Our results yield a natural explanation of the Lorentz force, invariably generating velocity and magnetic shear along strong PILs, thus setting a physical context for the observed pre-eruption evolution in solar ARs.

  3. Neutralizing Activity of Vaccine-Induced Antibodies to Two Bacillus anthracis Toxin Components, Lethal Factor and Edema Factor▿

    OpenAIRE

    Taft, Sarah C.; Weiss, Alison A.

    2007-01-01

    Anthrax vaccine adsorbed (AVA; BioThrax), the current FDA-licensed human anthrax vaccine, contains various amounts of the three anthrax toxin components, protective antigen (PA), lethal factor (LF), and edema factor (EF). While antibody to PA is sufficient to mediate protection against anthrax in animal models, it is not known if antibodies to LF or EF contribute to protection in humans. Toxin-neutralizing activity was evaluated in sera from AVA-vaccinated volunteers, all of whom had antibody...

  4. New LMI-Based Conditions on Neural Networks of Neutral Type with Discrete Interval Delays and General Activation Functions

    OpenAIRE

    Guoquan Liu; Shumin Zhou; He Huang

    2012-01-01

    The stability analysis of global asymptotic stability of neural networks of neutral type with both discrete interval delays and general activation functions is discussed. New delay-dependent conditions are obtained by using more general Lyapunov-Krasovskii functionals. Meanwhile, these conditions are expressed in terms of a linear matrix inequality (LMI) and can be verified using the MATLAB LMI toolbox. Numerical examples are used to illustrate the effectiveness of the proposed approach.

  5. New LMI-Based Conditions on Neural Networks of Neutral Type with Discrete Interval Delays and General Activation Functions

    Directory of Open Access Journals (Sweden)

    Guoquan Liu

    2012-01-01

    Full Text Available The stability analysis of global asymptotic stability of neural networks of neutral type with both discrete interval delays and general activation functions is discussed. New delay-dependent conditions are obtained by using more general Lyapunov-Krasovskii functionals. Meanwhile, these conditions are expressed in terms of a linear matrix inequality (LMI and can be verified using the MATLAB LMI toolbox. Numerical examples are used to illustrate the effectiveness of the proposed approach.

  6. The Cross-Neutralizing Activity of Enterovirus 71 Subgenotype C4 Vaccines in Healthy Chinese Infants and Children

    OpenAIRE

    Mao, Qunying; Cheng, Tong; Zhu, Fengcai; Li, Jingxin; Wang, Yiping; Li, Yanping; Gao, Fan; Yang, Lisheng; Xin YAO; Shao, Jie; Xia, Ningshao; Liang, Zhenglun; Wang, Junzhi

    2013-01-01

    Background EV71 is one of major etiologic causes of hand-foot-mouth disease (HFMD) and leads to severe neurological complications in young children and infants. Recently inactivated EV71 vaccines have been developed by five manufactures and clinically show good safety and immunogenicity. However, the cross-neutralizing activity of these vaccines remains unclear, and is of particular interest because RNA recombination is seen more frequently in EV71 epidemics. Methodology/Principal Findings In...

  7. Influence of Partial Neutralization on Catalytic Activity of Ion Exchange Resin

    Czech Academy of Sciences Publication Activity Database

    Holub, Ladislav; Jeřábek, Karel

    2005-01-01

    Roč. 231, 1-2 (2005), s. 21-26. ISSN 1381-1169 R&D Projects: GA ČR(CZ) GA104/02/1104 Institutional research plan: CEZ:AV0Z40720504 Keywords : catalysis * partial neutralization * polymer supports Subject RIV: CI - Industrial Chemistry, Chemical Engineering Impact factor: 2.348, year: 2005

  8. Localized activation of the distant tail neutral line just prior to substorm onsets

    Science.gov (United States)

    Watanabe, Masakazu; Pinnock, Michael; Rodger, Alan S.; Sato, Natsuo; Yamagishi, Hisao; Sessai Yukimatu, A.; Greenwald, Raymond A.; Villain, Jean-Paul; Hairston, Marc R.

    1998-08-01

    We have found flow burst features in the nightside ionosphere that are thought to be the ionospheric signature of distant tail reconnection. These are observed to form just prior to substorm onsets. Simultaneous observations by the Goose Bay-Stokkseyri dual HF radars and DMSP satellites provide the data. Our conclusions are based on equatorward flow bursts on the nightside during two isolated substorms that followed a long period of magnetospheric inactivity associated with a northward interplanetary magnetic field. Both flow bursts start ~60 min after the growth phase onset and last ~10-20 min until the expansion phase onset, migrating equatorward with time. Simultaneous DMSP observations of precipitating particles show that the flow burst occurs at the polar cap boundary, suggesting that the equatorward migration corresponds to the expansion of the polar cap during the growth phase. For one event, the reconnection electric field at 400 km altitude was 14 mV/m and its longitudinal scale was 290 km, which is equivalent to a reconnection voltage of 4.1 kV. For the other event, these values were 11 mV/m (reconnection electric field), 380 km (longitudinal scale), and 4.0 kV (reconnection voltage). In addition to the reconnection signatures, we discuss implications for substorm dynamics during the final stage of the substorm growth phase. The morphology indicates that the distant tail neutral line is activated ~1 hour after the growth phase onset and at the same time the nightside separatrix starts to move equatorward much faster than during the preceding early and middle growth phases. The 1-hour time lag would correspond to the timescale on which slow rarefaction waves from both northern and southern tail lobes converge in the equatorial magnetotail. The fast-moving separatrix on the nightside implies a rapid change of magnetotail configuration resulting from nonlinear enhancement and/or earthward movement of the cross-tail current for the last 10-20 min prior to the

  9. Towards energy neutrality by optimising the activated sludge process of the WWTP Bochum-Ölbachtal.

    Science.gov (United States)

    Marner, S T; Schröter, D; Jardin, N

    2016-01-01

    As a result of Ruhrverband's regularly performed energy audits the wastewater treatment plant (WWTP) Bochum-Ölbachtal shows substantial deficits concerning energy efficiency. Due to the energy consumption of internal recirculation, mixers and return activated sludge (RAS) pumping the existing pre-denitrification process configuration offers a specific energy consumption for biological treatment of 23 kWh (PE · a)(-1). In order to optimise the energy situation and to improve the treatment efficiency, the process layout was changed completely to a three-stage step-feed process. By optimising the hydraulic conditions, it was possible to reconstruct the plant with a free flow throughout the whole biological treatment system without any additional pumping. The total investment costs for this process scheme were 3.9 million €. These costs could be partly offset against the wastewater charge paid (2.9 million €). Compared to the overall energy consumption before the process modification, today the energy consumption for biological treatment amounts to 12.4 kWh (PE · a)(-1). The highest saving potential has been achieved by optimising mixing and reducing the energy demand for internal recirculation and RAS pumping. In the case of the WWTP Bochum-Ölbachtal, the modification of the treatment process not only results in an improved energy situation but also increased the treatment efficiency in such a way that the nitrogen concentration in the effluent could be constantly kept below 5 mg L(-1) N(tot), which provides the basis for being exempted from the wastewater discharge for nitrogen. As a result of all these measures, the rate of self-sufficiency by using biogas from the digester in combined heat and power units has been increased substantially from 60% before process modifications to 97%. With the upcoming optimisation measures, a further increase of self-sufficiency is expected to finally achieve energy neutrality based on yearly averages. The example of the

  10. Structure-Based Design of a Small Molecule CD4-Antagonist with Broad Spectrum Anti-HIV-1 Activity.

    Science.gov (United States)

    Curreli, Francesca; Kwon, Young Do; Zhang, Hongtao; Scacalossi, Daniel; Belov, Dmitry S; Tikhonov, Artur A; Andreev, Ivan A; Altieri, Andrea; Kurkin, Alexander V; Kwong, Peter D; Debnath, Asim K

    2015-09-10

    Earlier we reported the discovery and design of NBD-556 and their analogs which demonstrated their potential as HIV-1 entry inhibitors. However, progress in developing these inhibitors has been stymied by their CD4-agonist properties, an unfavorable trait for use as drug. Here, we demonstrate the successful conversion of a full CD4-agonist (NBD-556) through a partial CD4-agonist (NBD-09027), to a full CD4-antagonist (NBD-11021) by structure-based modification of the critical oxalamide midregion, previously thought to be intolerant of modification. NBD-11021 showed unprecedented neutralization breath for this class of inhibitors, with pan-neutralization against a panel of 56 Env-pseudotyped HIV-1 representing diverse subtypes of clinical isolates (IC50 as low as 270 nM). The cocrystal structure of NBD-11021 complexed to a monomeric HIV-1 gp120 core revealed its detail binding characteristics. The study is expected to provide a framework for further development of NBD series as HIV-1 entry inhibitors for clinical application against AIDS. PMID:26301736

  11. Structures and anti-HSV-2 activities of neutral polysaccharides from an edible plant, Basella rubra L.

    Science.gov (United States)

    Dong, Cai-Xia; Hayashi, Kyoko; Mizukoshi, Yusuke; Lee, Jung-Bum; Hayashi, Toshimitsu

    2012-01-01

    Four neutral polysaccharides (BRN-1, BRN-2, BRN-3 and BRN-4) were isolated from the hot water extract of the aerial part of Basella rubra L. They were found to consist of a large amount of D-galactose (81.0-92.4%) and small amounts of L-arabinose (5.4-7.8%), D-glucose (2.2-11.0%) and mannose (~2.9%). Linkage analysis revealed that all these neutral polysaccharides might be arabinogalactan type I polysaccharides in different molecular weight and chain length. Among them, only BRN-3 showed antiviral activity against herpes simplex virus type 2 (HSV-2) with 50% inhibitory concentration of 55 μg/mL without showing the cytotoxicity up to 2300 μg/mL. Furthermore, the main antiviral target of BRN-3 was shown to be the inhibition of virus adsorption to host cells. This is the first report on the neutral polysaccharide with anti-HSV-2 activity obtained from B. rubra L. PMID:22085753

  12. The potential for using slags activated with near neutral salts as immobilisation matrices for nuclear wastes containing reactive metals

    Energy Technology Data Exchange (ETDEWEB)

    Bai, Y. [Immobilisation Science Laboratory, Department of Engineering Materials, Sir Robert Hadfield Building, University of Sheffield, Mappin Street, Sheffield S1 3JD (United Kingdom); Collier, N.C., E-mail: nick.collier@nnl.co.uk [Immobilisation Science Laboratory, Department of Engineering Materials, Sir Robert Hadfield Building, University of Sheffield, Mappin Street, Sheffield S1 3JD (United Kingdom); Milestone, N.B. [Immobilisation Science Laboratory, Department of Engineering Materials, Sir Robert Hadfield Building, University of Sheffield, Mappin Street, Sheffield S1 3JD (United Kingdom); Yang, C.H. [Department of Building Materials and Engineering, College of Materials and Engineering, Chongqing University, Chongqing 400045 (China)

    2011-06-30

    The UK currently uses composite blends of Portland cement and other inorganic cementitious material such as blastfurnace slag and pulverised fuel ash to encapsulate or immobilise intermediate and low level radioactive wastes. Typically levels up 9:1 blast furnace slag:Portland cement or 4:1 pulverised fuel ash:Portland cement are used. Whilst these systems offer many advantages, their high pH causes corrosion of various metallic intermediate level radioactive wastes. To address this issue, lower pH/weakly alkaline cementitious systems have to be explored. While the blast furnace slag:Portland cement system is referred to as a composite cement system, the underlying reaction is actually an indirect activation of the slag hydration by the calcium hydroxide generated by the cement hydration, and by the alkali ions and gypsum present in the cement. However, the slag also can be activated directly with activators, creating a system known as alkali-activated slag. Whilst these activators used are usually strongly alkaline, weakly alkaline and near neutral salts can also be used. In this paper, the potential for using weakly alkaline and near neutral salts to activate slag in this manner is reviewed and discussed, with particular emphasis placed on the immobilisation of reactive metallic nuclear wastes.

  13. Sialorphin, a natural inhibitor of rat membrane-bound neutral endopeptidase that displays analgesic activity

    OpenAIRE

    Rougeot, Catherine; Messaoudi, Michaël; Hermitte, Véronique; Rigault, Anne Gaëlle; Blisnick, Thierry; Dugave, Christophe; Desor, Didier; Rougeon, François

    2003-01-01

    Sialorphin is an exocrine and endocrine signaling mediator, which has been identified by a genomic approach. It is synthesized predominantly in the submandibular gland and prostate of adult rats in response to androgen steroids and is released locally and systemically in response to stress. We now demonstrate that the cell surface molecule to which sialorphin binds in vivo in the rat kidney is the membrane-anchored neutral endopeptidase (neprilysin; NEP, EC 3.4.24.11)....

  14. Protective antiviral antibodies that lack neutralizing activity: precedents and evolution of concepts.

    Science.gov (United States)

    Schmaljohn, Alan L

    2013-07-01

    Antibody-mediated resistance to viral disease is often attributed solely to neutralizing antibodies (NAbs) despite a body of evidence -- more than 30 years in the making -- to show that other populations of antibodies (protective non-neutralizing antibodies, PnNAbs) can also contribute and are sometimes pivotal in host resistance to viruses. Recently, interest in varieties of PnNAbs has been restored and elevated by an HIV vaccine trial in which virus-specific nNAbs have been highlighted as a positive correlate of immunity. Here, I briefly review some of the historical precedents with many viruses other than HIV, along with the emergence of data over the course of some four decades, pointing emphatically to the importance of subsets of antiviral antibodies that operate by mechanisms other than classical virus neutralization. Foremost among suspected mechanisms of protection by PnNAbs is antibody-dependent cellular cytotoxicty (ADCC), but additional mechanisms have sometimes been incriminated or not experimentally excluded. Examples are given for the diversity of proteins and cognate epitopes bound by PnNAbs. Some such epitopes are restricted to virus-infected cell surfaces or found on secreted proteins; others may be associated with virions but unavailable to antibodies during much of the viral cycle; these are epitopes variously described as cryptic, transitional, dynamic, or reversibly masked. PMID:24191933

  15. The neuromuscular activity of Micrurus pyrrhocryptus venom and its neutralization by commercial and specific coral snake antivenoms.

    Science.gov (United States)

    Camargo, Thiago Magalhães; de Roodt, Adolfo Rafael; da Cruz-Höfling, Maria Alice; Rodrigues-Simioni, Léa

    2011-01-01

    The neuromuscular activity ofMicrurus pyrrochryptus venom was studied in chick biventer cervicis (BC) and mouse phrenic nerve-diaphragm (PND) preparations. The venom (0.5-50μg/ml) caused irreversible, time- and concentration-dependent blockade, with BC being more sensitive than PND (50% blockade with 10μg/ml in 22±;3min and 62±4min, respectively; mean±SEM, n=6; pPLA(2) activity. Neurotoxicity was effectively neutralized by commercial Micrurus antivenom and specific antivenom. These findings indicate that M. pyrrhocryptus venom acts postsynaptically on nicotinic receptors, with no significant myotoxicity. PMID:21858249

  16. The korF region of broad-host-range plasmid RK2 encodes two polypeptides with transcriptional repressor activity.

    OpenAIRE

    Jagura-Burdzy, G; Ibbotson, J P; Thomas, C M

    1991-01-01

    Broad-host-range IncP plasmid RK2 possesses a series of operons involved in plasmid maintenance, whose expression is coordinated by a number of regulators, most of which are encoded in the central regulatory korA-korB operon. The nucleotide sequence of two new cistrons in this operon, comprising what we have previously designated the korF locus located between coordinates 57.0 and 56.0 kb on the genome of the IncP alpha plasmid RK2, is presented. The cistrons encode polypeptides of 173 and 17...

  17. [Neutralization of toxic and enzyme activities of 4 venoms from snakes of Guatemala and Honduras by the polyvalent antivenin produced in Costa Rica].

    Science.gov (United States)

    Rojas, G; Gutiérrez, J M; Gené, J A; Gómez, M; Cerdas, L

    1987-06-01

    We studied the ability of the polyvalent antivenom produced in Costa Rica to neutralize lethal, hemorrhagic, edema-forming, proteolytic, hemolytic, hyaluronidase and fibrinolytic activities of the venoms of Bothrops asper and B. nummifer from Honduras, and of Agkistrodon bilineatus and Crotalus durissus durissus from Guatemala. Neutralizing ability of antivenom was expressed as ED50 (effective dose 50%), defined as the antivenom/venom ratio at which the activity of the venom is reduced 50%. Antivenom is highly effective in the neutralization of lethal, hemorrhagic, hemolytic, hyaluronidase, and caseinolytic activities of B. asper, B. nummifer, and C. d. durissus venoms. In the case of B. nummifer venom, neutralization of fibrinolytic effect was only partial, whereas this activity was adequately neutralized when studying the venoms of B. asper and C. d. durissus. The venom of A. bilineatus was adequately neutralized by the antivenom, with the only exception of hemolytic effect that was reduced only partially. However, in quantitative terms, a relatively large volume of antivenom was required to neutralize some effects induced by A. bilineatus venom. Regarding edema-forming activity, antivenom neutralized efficiently the venoms of B. asper and A. bilineatus, whereas that of B. nummifer was neutralized only partially; on the other hand, edema induced by the venom of C. d. durissus was not neutralized at all. Immunochemical results indicate a close immunological relationship between venoms of B. asper, B. nummifer and C. d. durissus collected in Honduras and Guatemala with those of the same species collected in Costa Rica. Interspecies comparison, however, showed variation between venoms obtained from different species.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3444924

  18. Broad line emission from iron K- and L-shell transitions in the active galaxy 1H 0707-495.

    Science.gov (United States)

    Fabian, A C; Zoghbi, A; Ross, R R; Uttley, P; Gallo, L C; Brandt, W N; Blustin, A J; Boller, T; Caballero-Garcia, M D; Larsson, J; Miller, J M; Miniutti, G; Ponti, G; Reis, R C; Reynolds, C S; Tanaka, Y; Young, A J

    2009-05-28

    Since the 1995 discovery of the broad iron K-line emission from the Seyfert galaxy MCG-6-30-15 (ref. 1), broad iron K lines have been found in emission from several other Seyfert galaxies, from accreting stellar-mass black holes and even from accreting neutron stars. The iron K line is prominent in the reflection spectrum created by the hard-X-ray continuum irradiating dense accreting matter. Relativistic distortion of the line makes it sensitive to the strong gravity and spin of the black hole. The accompanying iron L-line emission should be detectable when the iron abundance is high. Here we report the presence of both iron K and iron L emission in the spectrum of the narrow-line Seyfert 1 galaxy 1H 0707-495. The bright iron L emission has enabled us to detect a reverberation lag of about 30 s between the direct X-ray continuum and its reflection from matter falling into the black hole. The observed reverberation timescale is comparable to the light-crossing time of the innermost radii around a supermassive black hole. The combination of spectral and timing data on 1H 0707-495 provides strong evidence that we are witnessing emission from matter within a gravitational radius, or a fraction of a light minute, from the event horizon of a rapidly spinning, massive black hole. PMID:19478778

  19. Irreversible photolabeling of active site of neutral endopeptidase-24.11 enkephalinase by azidothiorphan and [14C]-azidothiorphan

    International Nuclear Information System (INIS)

    Azidothiorphan and its [14C]-labeled analogue have been developed as photoaffinity ligands for the active site of the neutral endopeptidase 24.11. In in vitro assays azidothiorphan inhibits the endopeptidase activity with a Ki of 0.75 nM. After ultraviolet irradiation the inhibitor binds irreversibly to the enzyme, and many factors suggest that the photolabeling occurs at the active site. The binding is accompanied by a loss of enzymatic activity, and the inclusion of the competitive inhibitor thiorphan protects the endopeptidase from this inactivation. In addition the binding of another competitive inhibitor [3H]N-[(R,S)-3-hydroxyaminocarbonyl-2-benzyl-1-oxopropyl]-glycine to the active site of endopeptidase-24.11 is inhibited after irradiation with azidothiorphan. Experiments with [14C]-azidothiorphan have shown that very little nonspecific binding of inhibitor to enzyme occurs and the the labeled probe remains bound under denaturing conditions. Azidothiorphan has also been found to produce a long-lasting naloxone-reversible analgesia after intracerebroventricular administration. The results show that azidothiorphan should prove useful both for structural studies and for investigations on the synthesis and turnover of the neutral endopeptidase-24.11

  20. Irreversible photolabeling of active site of neutral endopeptidase-24. 11 enkephalinase by azidothiorphan and (/sup 14/C)-azidothiorphan

    Energy Technology Data Exchange (ETDEWEB)

    Beaumont, A.; Hernandez, J.F.; Chaillet, P.; Crine, P.; Roques, B.P.

    1987-11-01

    Azidothiorphan and its (/sup 14/C)-labeled analogue have been developed as photoaffinity ligands for the active site of the neutral endopeptidase 24.11. In in vitro assays azidothiorphan inhibits the endopeptidase activity with a Ki of 0.75 nM. After ultraviolet irradiation the inhibitor binds irreversibly to the enzyme, and many factors suggest that the photolabeling occurs at the active site. The binding is accompanied by a loss of enzymatic activity, and the inclusion of the competitive inhibitor thiorphan protects the endopeptidase from this inactivation. In addition the binding of another competitive inhibitor (/sup 3/H)N-((R,S)-3-hydroxyaminocarbonyl-2-benzyl-1-oxopropyl)-glycine to the active site of endopeptidase-24.11 is inhibited after irradiation with azidothiorphan. Experiments with (/sup 14/C)-azidothiorphan have shown that very little nonspecific binding of inhibitor to enzyme occurs and the the labeled probe remains bound under denaturing conditions. Azidothiorphan has also been found to produce a long-lasting naloxone-reversible analgesia after intracerebroventricular administration. The results show that azidothiorphan should prove useful both for structural studies and for investigations on the synthesis and turnover of the neutral endopeptidase-24.11.

  1. A novel short anionic antibacterial peptide isolated from the skin of Xenopus laevis with broad antibacterial activity and inhibitory activity against breast cancer cell.

    Science.gov (United States)

    Li, Siming; Hao, Linlin; Bao, Wanguo; Zhang, Ping; Su, Dan; Cheng, Yunyun; Nie, Linyan; Wang, Gang; Hou, Feng; Yang, Yang

    2016-07-01

    A vastarray of bioactive peptides from amphibian skin secretions is attracting increasing attention due to the growing problem of bacteria resistant to conventional antibiotics. In this report, a small molecular antibacterial peptide, named Xenopus laevis antibacterial peptide-P1 (XLAsp-P1), was isolated from the skin of Xenopus laevis using reversed-phase high-performance liquid chromatography. The primary structure of XLAsp-P1, which has been proved to be a novel peptide by BLAST search in AMP database, was DEDDD with a molecular weight of 607.7 Da analysed by Edman degradation and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF-MS). The highlight of XLAsp-P1 is the strong in vitro potency against a variety of Gram-positive and Gram-negative bacteria with minimum inhibitory concentrations (MICs) starting at 10 μg/mL and potent inhibitory activity against breast cancer cell at tested concentrations from 5 to 50 μg/mL. In addition, only 6.2 % of red blood cells was haemolytic when incubated with 64 μg/mL (higher than MICs of all bacterial strain) of XLAsp-P1. The antimicrobial mechanism for this novel peptide was the destruction of the cell membrane investigated by transmission electron microscopy. All these showed that XLAsp-P1 is a novel short anionic antibacterial peptide with broad antibacterial activity and inhibitory activity against breast cancer cell. PMID:26952034

  2. Canine distemper virus neutralization activity is low in human serum and it is sensitive to an amino acid substitution in the hemagglutinin protein

    International Nuclear Information System (INIS)

    Serum was analyzed from 146 healthy adult volunteers in eastern Africa to evaluate measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb) prevalence and potency. MV plaque reduction neutralization test (PRNT) results indicated that all sera were positive for MV nAbs. Furthermore, the 50% neutralizing dose (ND50) for the majority of sera corresponded to antibody titers induced by MV vaccination. CDV nAbs titers were low and generally were detected in sera with high MV nAb titers. A mutant CDV was generated that was less sensitive to neutralization by human serum. The mutant virus genome had 10 nucleotide substitutions, which coded for single amino acid substitutions in the fusion (F) and hemagglutinin (H) glycoproteins and two substitutions in the large polymerase (L) protein. The H substitution occurred in a conserved region involved in receptor interactions among morbilliviruses, implying that this region is a target for cross-reactive neutralizing antibodies. - Highlights: • Screened 146 serum samples for measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb). • MV nAb is prevalent in the sera. • CDV neutralizing activity is generally low or absent and when detected it is present in sera with high MV nAb titers. • A neutralization-resistant CDV mutant was isolated using human serum selection. • A mutation was identified in the receptor-binding region of CDV hemagglutinin protein that confers the neutralization resistance

  3. Canine distemper virus neutralization activity is low in human serum and it is sensitive to an amino acid substitution in the hemagglutinin protein

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xinsheng, E-mail: xzhang@iavi.org [AIDS Vaccine Design and Development Laboratory, International AIDS Vaccine Initiative (IAVI), Brooklyn, NY (United States); Molecular and Cellular Biology Program, State University of New York, Brooklyn, NY (United States); Wallace, Olivia L.; Domi, Arban; Wright, Kevin J.; Driscoll, Jonathan [AIDS Vaccine Design and Development Laboratory, International AIDS Vaccine Initiative (IAVI), Brooklyn, NY (United States); Anzala, Omu [Kenya AIDS Vaccine Initiative (KAVI)-Institute of Clinical Research, Nairobi (Kenya); Sanders, Eduard J. [Centre for Geographic Medicine Research, Kenya Medical Research Institute (KEMRI), Kilifi, Kenya & Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Headington (United Kingdom); Kamali, Anatoli [MRC/UVRI Uganda Virus Research Unit on AIDS, Masaka and Entebbe (Uganda); Karita, Etienne [Projet San Francisco, Kigali (Rwanda); Allen, Susan [Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA (United States); Fast, Pat [Department of Medical Affairs, International AIDS Vaccine Initiative, NY, NY (United States); Gilmour, Jill [Human Immunology Laboratory, International AIDS Vaccine Initiative, London (United Kingdom); Price, Matt A. [Department of Medical Affairs, International AIDS Vaccine Initiative, NY, NY (United States); Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, CA (United States); Parks, Christopher L. [AIDS Vaccine Design and Development Laboratory, International AIDS Vaccine Initiative (IAVI), Brooklyn, NY (United States); Molecular and Cellular Biology Program, State University of New York, Brooklyn, NY (United States)

    2015-08-15

    Serum was analyzed from 146 healthy adult volunteers in eastern Africa to evaluate measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb) prevalence and potency. MV plaque reduction neutralization test (PRNT) results indicated that all sera were positive for MV nAbs. Furthermore, the 50% neutralizing dose (ND50) for the majority of sera corresponded to antibody titers induced by MV vaccination. CDV nAbs titers were low and generally were detected in sera with high MV nAb titers. A mutant CDV was generated that was less sensitive to neutralization by human serum. The mutant virus genome had 10 nucleotide substitutions, which coded for single amino acid substitutions in the fusion (F) and hemagglutinin (H) glycoproteins and two substitutions in the large polymerase (L) protein. The H substitution occurred in a conserved region involved in receptor interactions among morbilliviruses, implying that this region is a target for cross-reactive neutralizing antibodies. - Highlights: • Screened 146 serum samples for measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb). • MV nAb is prevalent in the sera. • CDV neutralizing activity is generally low or absent and when detected it is present in sera with high MV nAb titers. • A neutralization-resistant CDV mutant was isolated using human serum selection. • A mutation was identified in the receptor-binding region of CDV hemagglutinin protein that confers the neutralization resistance.

  4. High-Performance 1.55-µm Superluminescent Diode Based on Broad Gain InAs/InGaAlAs/InP Quantum Dash Active Region

    KAUST Repository

    Khan, Mohammed Zahed Mustafa

    2014-08-01

    We report on the high-performance characteristics from superluminescent diodes (SLDs) based on four-stack InAs/InGaAlAs chirped-barrier thickness quantum dash (Qdash) in a well structure. The active region exhibits a measured broad gain spectrum of 140 nm, with a peak modal gain of ~41 cm-1. The noncoated two-section gainabsorber broad-area and ridge-waveguide device configuration exhibits an output power of > 20 mW and > 12 mW, respectively. The corresponding -3-dB bandwidths span ~82 nm and ~72 nm, with a small spectral ripple of <; 0.2 dB, related largely to the contribution from dispersive height dash ensembles of the highly inhomogeneous active region. These C-L communication band devices will find applications in various cross-disciplinary fields of optical metrology, optical coherent tomography, etc.

  5. Stepwise design, synthesis, and in vitro antifungal screening of (Z)-substituted-propenoic acid derivatives with potent broad-spectrum antifungal activity

    OpenAIRE

    Khedr MA

    2015-01-01

    Mohammed A KhedrDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Cairo, EgyptAbstract: Fungal infections are a main reason for the high mortality rate worldwide. It is a challenge to design selective antifungal agents with broad-spectrum activity. Lanosterol 14α-demethylase is an attractive target in the design of antifungal agents. Seven compounds were selected from a number of designed compounds using a rational docking study. These compounds were sy...

  6. Observations of the interaction of a plasma stream with neutral gas: evidence of plasma loss through molecular-activated recombination

    International Nuclear Information System (INIS)

    We describe an experiment, the UMIST Linear System (ULS), in which a hydrogen plasma stream, guided by a longitudinal magnetic field, is injected through a diaphragm containing an orifice into a separately-pumped target chamber in which the neutral hydrogen pressure can be raised to a maximum of 8 mTorr. The stream is about 6 mm in diameter, has an electron temperature of up to 15 eV and an ion flux of 3 018s-1; it is supersonic with Mach number up to M approx.= 3. We have studied both the passage of the stream through the orifice and the interaction of the supersonic plasma with neutral hydrogen in the target chamber. We find that transmission is incomplete even when the orifice diameter is five times that of the plasma; we attribute this to the presence of ion trajectories which extend well outside the visible plasma and are intercepted by the diaphragm. In the target chamber, the stream does not broaden, but the ion flux decreases approximately exponentially with distance, with a scale length of the order of the mean free path for momentum transfer in ion-neutral collisions, and much less than that expected for other processes, such as charge exchange or electron-ion recombination. Elastic collisions alone cannot decrease the flux, but would lead to a large accumulation of slow ions in thermal equilibrium with the neutral gas, which must be limited by some other loss process: collisional diffusion and electron-ion recombination are too slow, leading to a density approaching 1020m-3. The observed density is of the order of 1018m-3, requiring a process with a rate of 10-100 times faster. Calculated rates for molecular-activated recombination (MAR) of the slow ions are of this order, and the predicted density agrees with our observations to order of magnitude. (author)

  7. Partial in vitro and in vivo red scorpion venom neutralization activity of Andrographis paniculata

    Directory of Open Access Journals (Sweden)

    Ranjana I Brahmane

    2011-01-01

    Full Text Available Objective: Red scorpion (Mesobuthus tamulus is the most lethal among all poisonous species of scorpions. Envenoming by Mesobuthus tamulus is quite common along the western coast of India, without any established therapy. Andrographis paniculata is one of the plants that has long been used in traditional herbal medicine for the treatment of poisoning by animal bites. Hence, the study was planned to evaluate the ethanolic extract of Andrographis paniculata for the treatment of Mesobuthus tamulus envenoming. Materials and Methods: Ethanolic extract of the plant Andrographis paniculata was obtained using a soxhelet apparatus. Lyophilized venom sample of Mesobuthus tamulus was used. Swiss albino mice weighing 20-30 g were used in the study. Calculation of LD 99 of Mesobuthus tamulus venom was performed using Turner′s method. Acute toxicity of Mesobuthus tamulus venom and its neutralization by the plant extract at a dose of 1 g/kg and 2 g/kg in vivo was seen. Neutralization of the lethal venom effect of Mesobuthus tamulus by plant extract at the dose of 1 g/kg and 2 g/kg by Alam and Gome′s method (in vitro was also seen. Results: The LD 99 of Mesobuthus tamulus venom from this study was determined to be 25.12 ΅g/g and the LD 50 was 15.85 ΅g/g. In the acute toxicity and in vivo neutralization study, plant extract at the dose of 1 g/kg and 2 g/kg resulted in a mean survival of 62.667 min and 39.333 min, respectively. Neutralization of the lethal venom effect of Mesobuthus tamulus by the plant extract at the dose of 1 g/kg and 2 g/kg by Alam and Gome′s method (in vitro showed a mean survival of 49.667 min and 42.5 min, respectively. Conclusion: The ethanolic extract of Adrographis paniculata has some protective effect against the red scorpion venom in mice but does not offer any survival benefit.

  8. Fishbone activity in experimental advanced superconducting tokamak neutral beam injection plasma

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Liqing; Zhang, Jizong; Chen, Kaiyun, E-mail: Kychen@ipp.cas.cn, E-mail: lqhu@ipp.cas.cn; Hu, Liqun, E-mail: Kychen@ipp.cas.cn, E-mail: lqhu@ipp.cas.cn; Li, Erzhong; Lin, Shiyao; Shi, Tonghui; Duan, Yanmin [Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); Zhu, Yubao [Department of Physics and Astronomy, University of California, Irvine, California 92697-4575 (United States)

    2015-12-15

    Repetitive fishbones near the trapped ion procession frequency were observed for the first time in the neutral beam injection high confinement plasmas in Experimental Advanced Superconducting Tokamak (EAST) tokamak, and diagnosed using a solid-state neutral particle analyzer based on a compact silicon photodiode together with an upgraded high spatial-temporal-resolution multi-arrays soft X-ray (SX) system. This 1/1 typical internal kink mode propagates in the ion-diamagnetism direction with a rotation speed faster than the bulk plasma in the plasma frame. From the SX measurements, this mode frequency is typical of chirping down and the energetic particle effect related to the twisting mode structure. This ion fishbone was found able to trigger a multiple core sawtooth crashes with edge-2/1 sideband modes, as well as to lead to a transition from fishbone to long lived saturated kink mode to fishbone. Furthermore, using SX tomography, a correlation between mode amplitude and mode frequency was found. Finally, a phenomenological prey–predator model was found to reproduce the fishbone nonlinear process well.

  9. Fishbone activity in experimental advanced superconducting tokamak neutral beam injection plasma

    International Nuclear Information System (INIS)

    Repetitive fishbones near the trapped ion procession frequency were observed for the first time in the neutral beam injection high confinement plasmas in Experimental Advanced Superconducting Tokamak (EAST) tokamak, and diagnosed using a solid-state neutral particle analyzer based on a compact silicon photodiode together with an upgraded high spatial-temporal-resolution multi-arrays soft X-ray (SX) system. This 1/1 typical internal kink mode propagates in the ion-diamagnetism direction with a rotation speed faster than the bulk plasma in the plasma frame. From the SX measurements, this mode frequency is typical of chirping down and the energetic particle effect related to the twisting mode structure. This ion fishbone was found able to trigger a multiple core sawtooth crashes with edge-2/1 sideband modes, as well as to lead to a transition from fishbone to long lived saturated kink mode to fishbone. Furthermore, using SX tomography, a correlation between mode amplitude and mode frequency was found. Finally, a phenomenological prey–predator model was found to reproduce the fishbone nonlinear process well

  10. Optimizing 50kV hydrogen diagnostic neutral beam performance for active spectroscopy in MST

    Science.gov (United States)

    Feng, X.; Boguski, J.; Craig, D.; den Hartog, D. J.; Munaretto, S.; Nornberg, M. D.; Olivia, S.

    2015-11-01

    The 50 kV hydrogen diagnostic neutral beam on MST provides local measurements of impurity ion emission through charge exchange recombination spectroscopy (CHERS) and of core-localized magnetic field through the motional Stark effect (MSE). The beam, which was designed to provide 5A of neutral current at 50 kV to meet these needs, is currently on a test stand to accommodate diagnosis, in order to increase the reliability of beam formation, sustain a steady current of 5 amps for 20ms, and optimize the primary energy fraction. The reliability of arc formation was increased from 40% to 80% success rate with increase of cathode gas pressure from 150kPa to 200kPa, and the stability of the arc current is improved with a decrease of the insulation magnetic field. A calorimeter with 5 thermocouples is installed to measure the horizontal and vertical beam profiles as well as beam divergence. Beam energy components are quantified through Doppler-shift spectroscopy. Preliminary simulation results of the beam using the ALCBEAM code as well as a description of how changes to the beam performance can affect CHERS and MSE measurements are presented. This work is supported by the U.S. DOE.

  11. N-terminal amino acids of bovine alpha interferons are relevant for the neutralization of their antiviral activity

    Directory of Open Access Journals (Sweden)

    Barreto Filho J.B.

    2001-01-01

    Full Text Available The structure-function relationship of interferons (IFNs has been studied by epitope mapping. Epitopes of bovine IFNs, however, are practically unknown, despite their importance in virus infections and in the maternal recognition of pregnancy. It has been shown that recombinant bovine (rBoIFN-alphaC and rBoIFN-alpha1 differ only in 12 amino acids and that the F12 monoclonal antibody (mAb binds to a linear sequence of residues 10 to 34. We show here that the antiviral activities of these two IFNs were neutralized by the F12 mAb to different extents using two tests. In residual activity tests the antiviral activity dropped by more than 99% with rBoIFN-alphaC and by 84% with rBoIFN-alpha1. In checkerboard antibody titrations, the F12 mAb titer was 12,000 with rBoIFN-alphaC and only 600 with rBoIFN-alpha1. Since these IFNs differ in their amino acid sequence at positions 11, 16 and 19 of the amino terminus, only these amino acids could account for the different neutralization titers, and they should participate in antibody binding. According to the three-dimensional structure described for human and murine IFNs, these amino acids are located in the alpha helix A; amino acids 16 and 19 of the bovine IFNs would be expected to be exposed and could bind to the antibody directly. The amino acid at position 11 forms a hydrogen bond in human IFNs-alpha and it is possible that, in bovine IFNs-alpha, the F12 mAb, binding near position 11, would disturb this hydrogen bond, resulting in the difference in the extent of neutralization observed.

  12. In vivo evaluation of the cross-genotype neutralizing activity of polyclonal antibodies against hepatitis C virus

    DEFF Research Database (Denmark)

    Meuleman, Philip; Bukh, Jens; Verhoye, Lieven;

    2011-01-01

    1977 (H77). In this study we investigated whether polyclonal antibodies isolated from Patient H in 2006 (H06), which display high cross-genotype neutralizing activity in both the HCV pseudoparticle (HCVpp) and HCV cell culture (HCVcc) systems, were also able to prevent HCV infection of different...... genotypes (gt) in vivo. Following passive immunization with H06-antibodies, chimeric mice were challenged with the consensus strains H77C (gt1a), ED43 (gt4a), or HK6a (gt6a). In accordance with previous results, H06-antibodies prevented infection of chimeric mice with the autologous virus. However, the...

  13. Structure, Aggregation, and Activity of a Covalent Insulin Dimer Formed During Storage of Neutral Formulation of Human Insulin

    DEFF Research Database (Denmark)

    Hjorth, Christian Fogt; Norrman, Mathias; Wahlund, Per-Olof; Benie, Andrew J.; Petersen, Bent O.; Jessen, Christian M; Pedersen, Thomas Å.; Vestergaard, Kirsten; Steensgaard, Dorte B; Pedersen, Jan Skov; Naver, Helle; Hubálek, František; Poulsen, Christian; Otzen, Daniel

    2016-01-01

    first detailed characterization of a specific type of human insulin HMWP formed during storage of a marketed pharmaceutical formulation. These results indicate that this specific type of HMWP is unlikely to antagonize the physical stability of the formulation, as HMWP retained a tertiary structure......A specific covalently linked dimeric species of insulin high molecular weight products (HMWPs), formed during prolonged incubation of a neutral pharmaceutical formulation of human insulin, were characterized in terms of tertiary structure, self-association, biological activity, and fibrillation...

  14. Czech ethanol-free propolis extract displays inhibitory activity against a broad spectrum of bacterial and fungal pathogens.

    Science.gov (United States)

    Netíková, Ladislava; Bogusch, Petr; Heneberg, Petr

    2013-09-01

    Propolis acts primarily as a biocide against invasive bacteria and fungi in the hive, suggesting its potential for industrial applications. In food application, propolis is considered as a chemical preservative in meat products, extending shelf life of frozen meat and other food. The mechanism of action is still unclear due to the synergy of multiple compounds contained in propolis and due to parallel targeting of multiple pathways within each affected organism. Here, we examined the antimicrobial properties of dimethylsulfoxide (DMSO) Czech propolis extract. Until recently, DMSO was only rarely used in the propolis studies, although the other solvents tested (mostly ethanol) may significantly affect the observed inhibitory effects, notwithstanding the antimicrobial effects of ethanol itself. Here, we provide results of zone inhibition tests against Aspergillus fumigatus, Microsporum gypseum, Microsporum canis, Candida albicans, Escherichia coli, Staphylococcus aureus, Listeria monocytogenes, and Enterococcus faecalis. Although we determined inhibitory effects against all the microorganisms tested, the dose-dependent response curves were not similar to each other. While inhibitory effects against C. albicans or S. aureus were strictly dose-dependent, responses of M. gypseum and E. faecalis displayed plateau across the broad range of concentrations tested. Interestingly, response of E. coli revealed the double-peak dose-dependent curve, and responses of M. canis and L. monocytogenes decreased at the highest concentrations tested. Suggested is evaluation of DMSO propolis extracts in experimental treatment of human and veterinary infections, preferably in multitherapy with antibiotics. PMID:23915150

  15. Epimedium koreanum Nakai displays broad spectrum of antiviral activity in vitro and in vivo by inducing cellular antiviral state.

    Science.gov (United States)

    Cho, Won-Kyung; Weeratunga, Prasanna; Lee, Byeong-Hoon; Park, Jun-Seol; Kim, Chul-Joong; Ma, Jin Yeul; Lee, Jong-Soo

    2015-01-01

    Epimedium koreanum Nakai has been extensively used in traditional Korean and Chinese medicine to treat a variety of diseases. Despite the plant's known immune modulatory potential and chemical make-up, scientific information on its antiviral properties and mode of action have not been completely investigated. In this study, the broad antiviral spectrum and mode of action of an aqueous extract from Epimedium koreanum Nakai was evaluated in vitro, and moreover, the protective effect against divergent influenza A subtypes was determined in BALB/c mice. An effective dose of Epimedium koreanum Nakai markedly reduced the replication of Influenza A Virus (PR8), Vesicular Stomatitis Virus (VSV), Herpes Simplex Virus (HSV) and Newcastle Disease Virus (NDV) in RAW264.7 and HEK293T cells. Mechanically, we found that an aqueous extract from Epimedium koreanum Nakai induced the secretion of type I IFN and pro-inflammatory cytokines and the subsequent stimulation of the antiviral state in cells. Among various components present in the extract, quercetin was confirmed to have striking antiviral properties. The oral administration of Epimedium koreanum Nakai exhibited preventive effects on BALB/c mice against lethal doses of highly pathogenic influenza A subtypes (H1N1, H5N2, H7N3 and H9N2). Therefore, an extract of Epimedium koreanum Nakai and its components play roles as immunomodulators in the innate immune response, and may be potential candidates for prophylactic or therapeutic treatments against diverse viruses in animal and humans. PMID:25609307

  16. Epimedium koreanum Nakai Displays Broad Spectrum of Antiviral Activity in Vitro and in Vivo by Inducing Cellular Antiviral State

    Directory of Open Access Journals (Sweden)

    Won-Kyung Cho

    2015-01-01

    Full Text Available Epimedium koreanum Nakai has been extensively used in traditional Korean and Chinese medicine to treat a variety of diseases. Despite the plant’s known immune modulatory potential and chemical make-up, scientific information on its antiviral properties and mode of action have not been completely investigated. In this study, the broad antiviral spectrum and mode of action of an aqueous extract from Epimedium koreanum Nakai was evaluated in vitro, and moreover, the protective effect against divergent influenza A subtypes was determined in BALB/c mice. An effective dose of Epimedium koreanum Nakai markedly reduced the replication of Influenza A Virus (PR8, Vesicular Stomatitis Virus (VSV, Herpes Simplex Virus (HSV and Newcastle Disease Virus (NDV in RAW264.7 and HEK293T cells. Mechanically, we found that an aqueous extract from Epimedium koreanum Nakai induced the secretion of type I IFN and pro-inflammatory cytokines and the subsequent stimulation of the antiviral state in cells. Among various components present in the extract, quercetin was confirmed to have striking antiviral properties. The oral administration of Epimedium koreanum Nakai exhibited preventive effects on BALB/c mice against lethal doses of highly pathogenic influenza A subtypes (H1N1, H5N2, H7N3 and H9N2. Therefore, an extract of Epimedium koreanum Nakai and its components play roles as immunomodulators in the innate immune response, and may be potential candidates for prophylactic or therapeutic treatments against diverse viruses in animal and humans.

  17. Epimedium koreanum Nakai Displays Broad Spectrum of Antiviral Activity in Vitro and in Vivo by Inducing Cellular Antiviral State

    Science.gov (United States)

    Cho, Won-Kyung; Weeratunga, Prasanna; Lee, Byeong-Hoon; Park, Jun-Seol; Kim, Chul-Joong; Ma, Jin Yeul; Lee, Jong-Soo

    2015-01-01

    Epimedium koreanum Nakai has been extensively used in traditional Korean and Chinese medicine to treat a variety of diseases. Despite the plant’s known immune modulatory potential and chemical make-up, scientific information on its antiviral properties and mode of action have not been completely investigated. In this study, the broad antiviral spectrum and mode of action of an aqueous extract from Epimedium koreanum Nakai was evaluated in vitro, and moreover, the protective effect against divergent influenza A subtypes was determined in BALB/c mice. An effective dose of Epimedium koreanum Nakaimarkedly reduced the replication of Influenza A Virus (PR8), Vesicular Stomatitis Virus (VSV), Herpes Simplex Virus (HSV) and Newcastle Disease Virus (NDV) in RAW264.7 and HEK293T cells. Mechanically, we found that an aqueous extract from Epimedium koreanum Nakai induced the secretion of type I IFN and pro-inflammatory cytokines and the subsequent stimulation of the antiviral state in cells. Among various components present in the extract, quercetin was confirmed to have striking antiviral properties. The oral administration of Epimedium koreanum Nakai exhibited preventive effects on BALB/c mice against lethal doses of highly pathogenic influenza A subtypes (H1N1, H5N2, H7N3 and H9N2). Therefore, an extract of Epimedium koreanum Nakai and its components play roles as immunomodulators in the innate immune response, and may be potential candidates for prophylactic or therapeutic treatments against diverse viruses in animal and humans. PMID:25609307

  18. Mercuric reductase activity and evidence of broad-spectrum mercury resistance among clinical isolates of rapidly growing mycobacteria

    International Nuclear Information System (INIS)

    Resistance to mercury was evaluated in 356 rapidly growing mycobacteria belonging to eight taxonomic groups. Resistance to inorganic Hg2+ ranged from 0% among the unnamed third biovariant complex of Mycobacterium fortuitum to 83% among M. chelonae-like organisms. With cell extracts and 203Hg(NO3)2 as the substrate, mercuric reductase (HgRe) activity was demonstrable in six of eight taxonomic groups. HgRe activity was inducible and required NADPH or NADH and a thiol donor for optimai activity. Species with HgRe activity were also resistant to organomercurial compounds, including phenylmercuric acetate. Attempts at intraspecies and intragenus transfer of HgRe activity by conjugation or transformation were unsuccessful. Mercury resistance is common in rapidly growing mycobacteria and appears to function via the same inducible enzyme systems already defined in other bacterial species. This system offers potential as a strain marker for epidemiologic investigations and for studying genetic systems in rapidly growing mycobacteria

  19. Rice RING protein OSBBI1 with E3 ligase activity confers broad-spectrum resistance against Magnaporthe oryzae by modifying the cell wall defence

    Institute of Scientific and Technical Information of China (English)

    Wei Li; Zuhua He; Sihui Zhong; Guojun Li; Qun Li; Bizeng Mao; Yiwen Deng; Huijuan Zhang; Longjun Zeng; Fengming Song

    2011-01-01

    Emerging evidence suggests that E3 ligases play critical roles in diverse biological processes, including innate immune responses in plants. However, the mechanism of the E3 ligase involvement in plant innate immunity is unclear.We report that a rice gene, OsBBI1, encoding a RING finger protein with E3 ligase activity, mediates broad-spectrum disease resistance. The expression of OSBBI1 was induced by rice blast fungus Magnaporthe oryzae, as well as chemical inducers, benzothiadiazole and salicylic acid. Biochemical analysis revealed that OsBBI1 protein possesses E3ubiquitin ligase activity in vitro. Genetic analysis revealed that the loss of OsBBI1 function in a Tos17-insertion line increased susceptibility, while the overexpression of OsBBI1 in transgenic plants conferred enhanced resistance to multiple races of M.oryzae. This indicates that OsBBI1 modulates broad-spectrum resistance against the blast fungus. The OsBBII-overexpressing plants showed higher levels of H,O, accumulation in cells and higher levels of phenolic compounds and cross-linking of proteins in cell walls at infection sites by M. Oryzae compared with wild-type(WT)plants. The cell walls were thicker in the OsBB11-overexpressing plants and thinner in the mutant plants than in the WT plants. Our results suggest that OsBBH modulates broad-spectrum resistance to blast fungus by modifying cell wall defence responses. The functional characterization of OsBBI1 provides insight into the E3 ligase-mediated innate immunity, and a practical tool for constructing broad-spectrum resistance against the most destructive disease in rice.

  20. Potent in vitro antibacterial activity of DS-8587, a novel broad-spectrum quinolone, against Acinetobacter baumannii.

    Science.gov (United States)

    Higuchi, Saito; Onodera, Yoshikuni; Chiba, Megumi; Hoshino, Kazuki; Gotoh, Naomasa

    2013-04-01

    We investigated the in vitro activity of DS-8587, a novel fluoroquinolone, against Acinetobacter baumannii. The MICs of DS-8587 against clinical isolates and its inhibitory activity against target enzymes were superior to those of ciprofloxacin and levofloxacin. Furthermore, the antibacterial activity of DS-8587 was less affected by adeA/adeB/adeC or abeM efflux pumps than was that of ciprofloxacin and the frequency of single-step mutations with DS-8587 was lower than that with ciprofloxacin. DS-8587 might be an effective agent against A. baumannii infection. PMID:23380726

  1. In vitro antimicrobial activity of piperacillin/tazobactam in comparison with other broad-spectrum beta-lactams.

    Science.gov (United States)

    Roland, R K; Mendes, R E; Silbert, S; Bolsoni, A P; Sader, H S

    2000-10-01

    Combining tazobactam, a beta-lactamase inhibitor, with the ureidopenicillin, piperacillin, successfully restores the activity of piperacillin against beta-lactamase producing bacteria. Thus, piperacillin/tazobactam is highly active against most clinically important species of Gram-negative and Gram-positive bacteria, including anaerobes. We evaluated the in vitro activity of piperacillin/tazobactam against clinical isolates from a tertiary university hospital located in Sao Paulo, Brazil. Its activity was compared to that of ticarcillin/clavulanic acid, ampicillin/sulbactam, ceftazidime, ceftriaxone, cefotaxime, cefoxitin, aztreonam, and imipenem against 820 isolates (608 Gram-negative and 212 Gram-positive) collected from hospitalized patients in 1999. The most frequent species tested were Pseudomonas aeruginosa (168/20%), Escherichia coli (139/17%), Acinetobacter spp. (131/16%), and Staphylococcus aureus (76/9%). Of the isolates studied, 30% were from the bloodstream, 16% from the lower respiratory tract, and 11% from surgical wounds or soft tissue. The isolates were susceptibility tested by the broth microdilution method according to NCCLS procedures. The isolates tested were highly resistant to most antimicrobial agents evaluated. Imipenem resistance was not verified among Enterobacteriaceae, and piperacillin/tazobactam was the second most active beta-lactams against this group of bacteria (80.0% susceptibility). Extended-spectrum beta-lactamase production was very high among E. coli (approximately 20%) and Klebsiella pneumoniae (approximately 40%). Imipenem was uniformly active against these species (100% susceptibility) and piperacillin/tazobactam was the second most active compound inhibiting 84.4% of isolates. Pseudomonas aeruginosa was highly resistant to all beta-lactams evaluated and piperacillin/tazobactam was the most active compound against this species. Our results demonstrate an extremely high level of antimicrobial resistance in the hospital

  2. "Women of broad vision": nature and gender in the environmental activism of Australia's 'Women in Agriculture' movement

    OpenAIRE

    Liepins, R

    1998-01-01

    The author examines the construction of nature and gendered subjectivities occurring in environmental activism. The paper follows recent thinking in rural geography in attending to the discourses and agency of activists. Such an approach enables a reading of Australian agricultural women's environmental activism. Initially it is shown how the 'women in agriculture' movement engages with the range of discourses that contextualise the agri-environmental arena. This is then followed by a critica...

  3. In Vitro Activity of LK-157, a Novel Tricyclic Carbapenem As Broad-Spectrum β-Lactamase Inhibitor▿

    OpenAIRE

    Paukner, Susanne; Hesse, Lars; Preželj, Andrej; Šolmajer, Tomaž; Urleb, Uroš

    2008-01-01

    LK-157 is a novel tricyclic carbapenem with potent activity against class A and class C β-lactamases. When tested against the purified TEM-1 and SHV-1 enzymes, LK-157 exhibited 50% inhibitory concentrations (IC50s) in the ranges of the clavulanic acid and tazobactam IC50s (55 nM and 151 nM, respectively). Moreover, LK-157 significantly inhibited AmpC β-lactamase (IC50, 62 nM), as LK-157 was >2,000-fold more potent than clavulanic acid and approximately 28-fold more active than tazobactam. The...

  4. A Fungal α-Galactosidase from Tricholoma matsutake with Broad Substrate Specificity and Good Hydrolytic Activity on Raffinose Family Oligosaccharides

    Directory of Open Access Journals (Sweden)

    Xueran Geng

    2015-07-01

    Full Text Available An acidic α-galactosidase designated as TMG was purified from the fruiting bodies The purification protocol entailed ion exchange chromatography on Q-Sepharose and of Tricholoma matsutake with 136-fold purification and a specific activity of 909 units/mg. Mono-Q and fast protein liquid chromatography on Superdex 75. TMG is a monomeric protein exhibiting a molecular mass of 47 kDa in SDS-PAGE and gel filtration. The purified enzyme was identified by LC-MS/MS and three inner amino acid sequences were obtained. The optimum pH and temperature for TMG with pNPGal as substrate were pH 4.5 and 55 °C, respectively. The α-galactosidase activity was strongly inhibited by K+, Ca2+, Cd2+, Hg2+, Ag+ and Zn2+ ions. The enzyme activity was inhibited by the chemical modification agent N-bromosuccinimide (NBS, indicating the importance of tryptophan residue(s at or near the active site. Besides hydrolyzing pNPGal, TMG also efficaciously catalyzed the degradation of natural substrates such as stachyose, raffinose, and melibiose. Thus TMG can be exploited commercially for improving the nutritional value of soy milk by degradation of indigestible oligosaccharides.

  5. Draft Genome Sequence of Brevibacillus brevis DZQ7, a Plant Growth-Promoting Rhizobacterium with Broad-Spectrum Antimicrobial Activity

    OpenAIRE

    Hou, Qihui; Wang, Chengqiang; Hou, Xiaoyang; Xia, Zhilin; Ye, Jiangping; Liu, Kai; Liu, Hu; Wang, Jun; Guo, Haimeng; Yu, Xiaoning; Yang, Yanan; Du, Binghai; Ding, Yanqin

    2015-01-01

    Brevibacillus brevis DZQ7 is a plant growth-promoting rhizobacterium (PGPR) isolated from tobacco rhizosphere. Here, we report the draft genome sequence of B. brevis DZQ7. Several functional genes related to antimicrobial activity were identified in the genome.

  6. Draft Genome Sequence of Brevibacillus brevis DZQ7, a Plant Growth-Promoting Rhizobacterium with Broad-Spectrum Antimicrobial Activity.

    Science.gov (United States)

    Hou, Qihui; Wang, Chengqiang; Hou, Xiaoyang; Xia, Zhilin; Ye, Jiangping; Liu, Kai; Liu, Hu; Wang, Jun; Guo, Haimeng; Yu, Xiaoning; Yang, Yanan; Du, Binghai; Ding, Yanqin

    2015-01-01

    Brevibacillus brevis DZQ7 is a plant growth-promoting rhizobacterium (PGPR) isolated from tobacco rhizosphere. Here, we report the draft genome sequence of B. brevis DZQ7. Several functional genes related to antimicrobial activity were identified in the genome. PMID:26294619

  7. Antimicrobial activity of selected Iranian medicinal plants against a broad spectrum of pathogenic and drug multiresistant micro-organisms.

    Science.gov (United States)

    Abedini, A; Roumy, V; Mahieux, S; Gohari, A; Farimani, M M; Rivière, C; Samaillie, J; Sahpaz, S; Bailleul, F; Neut, C; Hennebelle, T

    2014-10-01

    The antimicrobial activities of 44 methanolic extracts from different parts of Iranian indigenous plant species used in traditional medicines of Iran were tested against a panel of 35 pathogenic and multiresistant bacteria and 1 yeast. The antimicrobial efficacy was determined using Müller-Hinton agar in Petri dishes seeded by a multiple inoculator and minimal inhibition concentration (MIC) method. The 21 most active extracts (MIC < 0·3 mg ml(-1) for one or several micro-organisms) were submitted to a more refined measurement. The best antibacterial activity was obtained by 10 plants. Microdilution assays allowed to determinate the MIC and MBC of the 21 most active extracts. The lowest achieved MIC value was 78 μg ml(-1), with 4 extracts. This work confirms the antimicrobial activity of assayed plants and suggests further examination to identify the chemical structure of their antimicrobial compounds. Significance and impact of the study: This study describes the antimicrobial screening of Iranian plant extracts chosen according to traditional practice against 36 microbial strains, from reference culture collections or recent clinical isolates, and enables to select 4 candidates for further chemical characterization and biological assessment: Dorema ammoniacum, Ferula assa-foetida, Ferulago contracta (seeds) and Perovskia abrotanoides (aerial parts). This may be useful in the development of potential antimicrobial agents, from easily harvested and highly sustainable plant parts. Moreover, the weak extent of cross-resistance between plant extracts and antibiotics warrants further research and may promote a strategy based on less potent but time-trained products. PMID:24888993

  8. In vitro activity of LK-157, a novel tricyclic carbapenem as broad-spectrum {beta}-lactamase inhibitor.

    Science.gov (United States)

    Paukner, Susanne; Hesse, Lars; Prezelj, Andrej; Solmajer, Tomaz; Urleb, Uros

    2009-02-01

    LK-157 is a novel tricyclic carbapenem with potent activity against class A and class C beta-lactamases. When tested against the purified TEM-1 and SHV-1 enzymes, LK-157 exhibited 50% inhibitory concentrations (IC(50)s) in the ranges of the clavulanic acid and tazobactam IC(50)s (55 nM and 151 nM, respectively). Moreover, LK-157 significantly inhibited AmpC beta-lactamase (IC(50), 62 nM), as LK-157 was >2,000-fold more potent than clavulanic acid and approximately 28-fold more active than tazobactam. The in vitro activities of LK-157 in combination with amoxicillin, piperacillin, ceftazidime, cefotaxime, ceftriaxone, cefepime, cefpirome, and aztreonam against an array of Ambler class A (TEM-, SHV-, CTX-M-, KPC-, PER-, BRO-, and PC-type)- and class C-producing bacterial strains derived from clinical settings were evaluated in synergism experiments and compared with those of clavulanic acid, tazobactam, and sulbactam. In vitro MICs against ESBL-producing strains (except CTX-M-containing strains) were reduced 2- to >256-fold, and those against AmpC-producing strains were reduced even up to >32-fold. The lowest MICs (combination of cefepime and cefpirome with a constant LK-157 concentration of 4 microg/ml, thus raising an interest for further development. LK-157 proved to be a potent beta-lactamase inhibitor, combining activity against class A and class C beta-lactamases, which is an absolute necessity for use in the clinical setting due to the worldwide increasing prevalence of bacterial strains resistant to beta-lactam antibiotics. PMID:19075067

  9. Design, synthesis, broad-spectrum antiproliferative activity, and kinase inhibitory effect of triarylpyrazole derivatives possessing arylamides or arylureas moieties.

    Science.gov (United States)

    Gamal El-Din, Mahmoud M; El-Gamal, Mohammed I; Abdel-Maksoud, Mohammed S; Yoo, Kyung Ho; Oh, Chang-Hyun

    2016-08-25

    A novel series of 1,3,4-triarylpyrazole derivatives possessing terminal arylamide or arylurea terminal moieties has been designed and synthesized. Their in vitro antiproliferative activities were investigated against a panel of 58 cell lines of nine different cancer types at the NCI, USA. The urea analogues 2b, 2c, and 2f as well as the amide derivatives 3e and 3f exerted the highest mean % inhibition values over the 58 cell line panel at 10 μM, and thus were further tested in 5-dose testing mode to determine their GI50, TGI, and LC50 values. The above mentioned compounds have shown stronger antiproliferative activities in terms of potency and efficacy upon comparing their results with Sorafenib as a reference compound. Among them, compounds 2c and 2f possessing 3,4-dichlorophenylurea terminal moiety showed the highest mean %inhibition value of about 99.85 and 104.15% respectively over the 58-cell line panel at 10 μM concentration. Also compounds 2b, 3e, and 3f exhibited mean % inhibition over 80% at 10 μM concentration. The GI50 value of compound 3e over K-562 cancer cell line was 0.75 μM. Accordingly, compound 2f was screened over seven kinases at a single-dose concentration of 10 μM to profile its kinase inhibitory activity. Interestingly, the compound showed highly inhibitory activities (90.44% and 87.71%) against BRAF (V600E) and RAF1 kinases, respectively. Its IC50 value against BRAF (V600E) was 0.77 μM. Compounds 2b, 2c, 2f, 3e, and 3f exerted high selectivity towards cancer cell lines than L132 normal lung cells. PMID:27155467

  10. Chitosan Microparticles Exert Broad-Spectrum Antimicrobial Activity against Antibiotic-Resistant Micro-organisms without Increasing Resistance.

    Science.gov (United States)

    Ma, Zhengxin; Kim, Donghyeon; Adesogan, Adegbola T; Ko, Sanghoon; Galvao, Klibs; Jeong, Kwangcheol Casey

    2016-05-01

    Antibiotic resistance is growing exponentially, increasing public health concerns for humans and animals. In the current study, we investigated the antimicrobial features of chitosan microparticles (CM), engineered from chitosan by ion gelation, seeking potential application for treating infectious disease caused by multidrug resistant microorganisms. CM showed excellent antimicrobial activity against a wide range of microorganisms, including clinically important antibiotic-resistant pathogens without raising resistant mutants in serial passage assays over a period of 15 days, which is a significantly long passage compared to tested antibiotics used in human and veterinary medicine. In addition, CM treatment did not cause cross-resistance, which is frequently observed with other antibiotics and triggers multidrug resistance. Furthermore, CM activity was examined in simulated gastrointestinal fluids that CM encounter when orally administered. Antimicrobial activity of CM was exceptionally strong to eliminate pathogens completely. CM at a concentration of 0.1 μg/mL killed E. coli O157:H7 (5 × 10(8) CFU/mL) completely in synthetic gastric fluid within 20 min. Risk assessment of CM, in an in vitro animal model, revealed that CM did not disrupt the digestibility, pH or total volatile fatty acid production, indicating that CM likely do not affect the functionality of the rumen. Given all the advantages, CM can serve as a great candidate to treat infectious disease, especially those caused by antibiotic-resistant pathogens without adverse side effects. PMID:27057922

  11. Kisameet Clay Isolated from the Central Coast of British Columbia, Canada, Demonstrates Broad-Spectrum Antimicrobial Activity.

    Science.gov (United States)

    Zhanel, George G; Karlowsky, James A

    2016-01-01

    Clay minerals are naturally occurring layered phyllosilicates which consist of fine particles and possess antimicrobial activity. In a recent article, Behroozian et al. obtained Kisameet clay (KC) from Kisameet, from the central coast of British Columbia, Canada, northwest of Vancouver and assessed its antimicrobial activity versus 16 selected ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) possessing a variety of different resistance profiles [S. Behroozian, S. L. Svensson, and J. Davies, mBio 7(1):e01842-15, 2016, http://dx.doi.org/10.1128/mBio.01842-15]. KC demonstrated complete bacterial eradication of Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Staphylococcus aureus within 24 h. For Enterobacter spp., the organisms were eradicated with 1% KC within 5 h, while for Enterococcus faecium, it took 48 h to kill all organisms. Although many questions need to be answered, these exciting findings highlight the importance of testing natural substances/products from around the globe to assess whether they possess antimicrobial activity and potential for usage as topical, oral, or systemic agents for the treatment of multidrug-resistant pathogens. PMID:26956585

  12. Mechanism for neutralizing activity by the anti-CMV gH/gL monoclonal antibody MSL-109

    Science.gov (United States)

    Fouts, Ashley E.; Comps-Agrar, Laëtitia; Stengel, Katharina F.; Ellerman, Diego; Schoeffler, Allyn J.; Warming, Søren; Eaton, Dan L.; Feierbach, Becket

    2014-01-01

    Cytomegalovirus (CMV) is a widespread opportunistic pathogen that causes birth defects when transmitted transplacentally and severe systemic illness in immunocompromised individuals. MSL-109, a human monoclonal IgG isolated from a CMV seropositive individual, binds to the essential CMV entry glycoprotein H (gH) and prevents infection of cells. Here, we suggest a mechanism for neutralization activity by MSL-109. We define a genetic basis for resistance to MSL-109 and have generated a structural model of gH that reveals the epitope of this neutralizing antibody. Using surface-based, time-resolved FRET, we demonstrate that gH/gL interacts with glycoprotein B (gB). Additionally, we detect homodimers of soluble gH/gL heterodimers and confirm this novel oligomeric assembly on full-length gH/gL expressed on the cell surface. We show that MSL-109 perturbs the dimerization of gH/gL:gH/gL, suggesting that dimerization of gH/gL may be required for infectivity. gH/gL homodimerization may be conserved between alpha- and betaherpesviruses, because both CMV and HSV gH/gL demonstrate self-association in the FRET system. This study provides evidence for a novel mechanism of action for MSL-109 and reveals a previously undescribed aspect of viral entry that may be susceptible to therapeutic intervention. PMID:24843144

  13. The structure of the broad-line region in active galactic nuclei. I. Reconstructed velocity-delay maps

    DEFF Research Database (Denmark)

    Grier, C.J.; Peterson, B.M.; Pogge, R.W.;

    2013-01-01

    of the most clearly defined velocity-delay maps to date. These maps constitute a large increase in the number of objects for which we have resolved velocity-delay maps and provide evidence supporting the reliability of reverberation-based black hole mass measurements. © 2013. The American......We present velocity-resolved reverberation results for five active galactic nuclei. We recovered velocity-delay maps using the maximum entropy method for four objects: Mrk 335, Mrk 1501, 3C 120, and PG 2130+099. For the fifth, Mrk 6, we were only able to measure mean time delays in different...

  14. Graphene oxide exhibits broad-spectrum antimicrobial activity against bacterial phytopathogens and fungal conidia by intertwining and membrane perturbation

    Science.gov (United States)

    Chen, Juanni; Peng, Hui; Wang, Xiuping; Shao, Feng; Yuan, Zhaodong; Han, Heyou

    2014-01-01

    To understand the interaction mechanism between graphene oxide (GO) and typical phytopathogens, a particular investigation was conducted about the antimicrobial activity of GO against two bacterial pathogens (P. syringae and X. campestris pv. undulosa) and two fungal pathogens (F. graminearum and F. oxysporum). The results showed that GO had a powerful effect on the reproduction of all four pathogens (killed nearly 90% of the bacteria and repressed 80% macroconidia germination along with partial cell swelling and lysis at 500 μg mL-1). A mutual mechanism is proposed in this work that GO intertwinds the bacteria and fungal spores with a wide range of aggregated graphene oxide sheets, resulting in the local perturbation of their cell membrane and inducing the decrease of the bacterial membrane potential and the leakage of electrolytes of fungal spores. It is likely that GO interacts with the pathogens by mechanically wrapping and locally damaging the cell membrane and finally causing cell lysis, which may be one of the major toxicity actions of GO against phytopathogens. The antibacterial mode proposed in this study suggests that the GO may possess antibacterial activity against more multi-resistant bacterial and fungal phytopathogens, and provides useful information about the application of GO in resisting crop diseases.To understand the interaction mechanism between graphene oxide (GO) and typical phytopathogens, a particular investigation was conducted about the antimicrobial activity of GO against two bacterial pathogens (P. syringae and X. campestris pv. undulosa) and two fungal pathogens (F. graminearum and F. oxysporum). The results showed that GO had a powerful effect on the reproduction of all four pathogens (killed nearly 90% of the bacteria and repressed 80% macroconidia germination along with partial cell swelling and lysis at 500 μg mL-1). A mutual mechanism is proposed in this work that GO intertwinds the bacteria and fungal spores with a wide range

  15. Activity of neutral endopeptidase and aminopeptidase N in mouse thymic stromal cells which bind double-positive thymocytes.

    Science.gov (United States)

    Small, M; Kaiser, M; Tse, W; Heimfeld, S; Blumberg, S

    1996-04-01

    The activity of two peptidases was determined in immortalized lines of thymic stromal cells. A line of total stromal cells (T-TG-St) was grown from transgenic mouse expressing temperature-sensitive SV40 T antigen under the control of the regulatory elements of the mouse major histocompatibility complex class I gene. From these cells we isolated a subset (DP-TG-St) that binds thymocytes which are mainly CD4+8+. We also assayed a clone of fetal thymic epithelial cells (BA/10) that binds CD4+8+ thymocytes. Both lines of double -positive cell-binding stroma exhibited strong activity of two peptidases, neutral endopeptidase (NEP; EC 3.4.24.11) and aminopeptidase N (APN; EC 3.4.11.2). In contrast, the activity of both enzymes was very low in the total thymic stromal line. Use of the specific inhibitors confirmed that these two enzymes were responsible for the activity observed but also suggested the presence of additional unidentified aminopeptidase(s) in the same stromal cells. The high activity of the two peptidases on stromal cells that bind thymocytes at the double-positive stage raises the possibility that they might contribute to the microenvironment of the developing thymocytes. PMID:8625997

  16. In Vitro Activity of Gepotidacin, a Novel Triazaacenaphthylene Bacterial Topoisomerase Inhibitor, against a Broad Spectrum of Bacterial Pathogens.

    Science.gov (United States)

    Biedenbach, D J; Bouchillon, S K; Hackel, M; Miller, L A; Scangarella-Oman, N E; Jakielaszek, C; Sahm, D F

    2016-01-01

    Gepotidacin inhibits bacterial DNA replication through a mode different from that of fluoroquinolones. Gepotidacin and comparators were tested by broth and agar dilution against clinical isolates. The in vitro activities of gepotidacin were comparable against methicillin-susceptible and -resistant Staphylococcus aureus (MSSA and MRSA, respectively) isolates (MIC90, 0.5 μg/ml). The gepotidacin MIC90s were as follows (in micrograms per milliliter) for the indicated bacteria: Streptococcus pyogenes, 0.25; Escherichia coli, 2; Moraxella catarrhalis, ≤0.06; Streptococcus pneumoniae (0.25), Haemophilus influenzae, 1; Clostridium perfringens, 0.5; and Shigella spp., 1, including levofloxacin-resistant subsets. Gepotidacin warrants further investigation for clinical development. PMID:26729499

  17. Development of FGI-106 as a broad-spectrum therapeutic with activity against members of the family Bunyaviridae

    Directory of Open Access Journals (Sweden)

    Darci R Smith

    2010-02-01

    Full Text Available Darci R Smith1, Monica Ogg1, Aura Garrison1, Abdul Yunus2, Anna Honko1, Josh Johnson1, Gene Olinger1, Lisa E Hensley1, Michael S Kinch1United States Army Medical Research Institute of Infectious Diseases (USAMRII D, Fort Detrick, MD, USA; 2Functional Genetics, Inc., Gaithersburg, MD, USAAbstract: The family Bunyaviridae is a diverse group of negative-strand RNA viruses that infect a wide range of arthropod vectors and animal hosts. Based on the continuing need for new therapeutics to treat bunyavirus infections, we evaluated the potential efficacy of FGI-106, a small-molecular compound that previously demonstrated activity against different RNA viruses. FGI-106 displayed substantial antiviral activity in cell-based assays of different bunyavirus family members, including Asian and South American hantaviruses (Hantaan virus and Andes virus, Crimean-Congo hemorrhagic fever virus, La Crosse virus, and Rift Valley fever virus. The pharmacokinetic profile of FGI-106 revealed sufficient exposure of the drug to critical target organs (lung, liver, kidney, and spleen, which are frequently the sites of bunyavirus replication. Consistent with these findings, FGI-106 treatment delivered via intraperitoneal injection prior to virus exposure was sufficient to delay the onset of Rift Valley fever virus infection in mouse-based models and to enhance survival in the face of an otherwise lethal infection. Altogether, these results suggest a potential opportunity for the use of FGI-106 to treat infections by members of the family Bunyaviridae.Keywords: Rift Valley fever virus, bunyavirus, hantavirus, antiviral, therapeutic

  18. WISE J233237.05–505643.5: A double-peaked, broad-lined active galactic nucleus with a spiral-shaped radio morphology

    International Nuclear Information System (INIS)

    We present radio continuum mapping, optical imaging, and spectroscopy of the newly discovered double-peaked, broad-lined active galactic nucleus (AGN) WISE J233237.05–505643.5 at redshift z = 0.3447. This source exhibits an FR-I and FR-II hybrid morphology, characterized by a bright core, jet, and Doppler-boosted lobe structures in Australian Telescope Compact Array continuum maps at 1.5, 5.6, and 9 GHz. Unlike most FR-II objects, W2332–5056 is hosted by a disk-like galaxy. The core has a projected 5'' linear radio feature that is perpendicular to the curved primary jet, hinting at unusual and complex activity within the inner 25 kpc. The multi-epoch, optical-near-IR photometric measurements indicate significant variability over a 3-20 yr baseline from the AGN component. Gemini South optical data show unusual double-peaked emission-line features: the centroids of the broad-lined components of Hα and Hβ are blueshifted with respect to the narrow lines and host galaxy by ∼3800 km s–1. We examine possible cases that involve single or double supermassive black holes in the system and discuss the required future investigations to disentangle the mysterious nature of this system.

  19. Nuclear Magnetic Resonance Solution Structures of Lacticin Q and Aureocin A53 Reveal a Structural Motif Conserved among Leaderless Bacteriocins with Broad-Spectrum Activity.

    Science.gov (United States)

    Acedo, Jeella Z; van Belkum, Marco J; Lohans, Christopher T; Towle, Kaitlyn M; Miskolzie, Mark; Vederas, John C

    2016-02-01

    Lacticin Q (LnqQ) and aureocin A53 (AucA) are leaderless bacteriocins from Lactococcus lactis QU5 and Staphylococcus aureus A53, respectively. These bacteriocins are characterized by the absence of an N-terminal leader sequence and are active against a broad range of Gram-positive bacteria. LnqQ and AucA consist of 53 and 51 amino acids, respectively, and have 47% identical sequences. In this study, their three-dimensional structures were elucidated using solution nuclear magnetic resonance and were shown to consist of four α-helices that assume a very similar compact, globular overall fold (root-mean-square deviation of 1.7 Å) with a highly cationic surface and a hydrophobic core. The structures of LnqQ and AucA resemble the shorter two-component leaderless bacteriocins, enterocins 7A and 7B, despite having low levels of sequence identity. Homology modeling revealed that the observed structural motif may be shared among leaderless bacteriocins with broad-spectrum activity against Gram-positive organisms. The elucidated structures of LnqQ and AucA also exhibit some resemblance to circular bacteriocins. Despite their similar overall fold, inhibition studies showed that LnqQ and AucA have different antimicrobial potency against the Gram-positive strains tested, suggesting that sequence disparities play a crucial role in their mechanisms of action. PMID:26771761

  20. WISE J233237.05–505643.5: A double-peaked, broad-lined active galactic nucleus with a spiral-shaped radio morphology

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, Chao-Wei [Infrared Processing and Analysis Center, California Institute of Technology, Pasadena, CA 91125 (United States); Jarrett, T. H. [Astronomy Department, University of Cape Town, Private Bag X3, Rondebosch 7701 (South Africa); Stern, Daniel; Assef, Roberto J.; Eisenhardt, Peter R. M.; Wu, Jingwen [Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Dr., Pasadena, CA 91109 (United States); Emonts, Bjorn [Centro de Astrobiología (INTA-CSIC), Ctra de Torrejón a Ajalvir, km 4, E-28850 Torrejón de Ardoz, Madrid (Spain); Barrows, R. Scott [Arkansas Center for Space and Planetary Sciences, University of Arkansas, Fayetteville, AR 72701 (United States); Norris, Ray P. [Australia Telescope National Facility, CSIRO Astronomy and Space Science, P.O. Box 76, Epping NSW 1710 (Australia); Lonsdale, Carol [National Radio Astronomy Observatory, 520 Edgemont Road, Charlottesville, VA 22903 (United States); Blain, Andrew W. [Department of Physics and Astronomy, University of Leicester, 1 University Road, Leicester LE1 7RH (United Kingdom); Benford, Dominic J. [NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Stalder, Brian; Stubbs, Christopher W. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); High, F. William [Kavli Institute for Cosmological Physics, University of Chicago, 5640 South Ellis Avenue, Chicago, IL 60637 (United States); Li, K. L.; Kong, Albert K. H., E-mail: Chao-Wei.Tsai@jpl.nasa.gov [Institute of Astronomy and Department of Physics, National Tsing Hua University, Hsinchu 30013, Taiwan (China)

    2013-12-10

    We present radio continuum mapping, optical imaging, and spectroscopy of the newly discovered double-peaked, broad-lined active galactic nucleus (AGN) WISE J233237.05–505643.5 at redshift z = 0.3447. This source exhibits an FR-I and FR-II hybrid morphology, characterized by a bright core, jet, and Doppler-boosted lobe structures in Australian Telescope Compact Array continuum maps at 1.5, 5.6, and 9 GHz. Unlike most FR-II objects, W2332–5056 is hosted by a disk-like galaxy. The core has a projected 5'' linear radio feature that is perpendicular to the curved primary jet, hinting at unusual and complex activity within the inner 25 kpc. The multi-epoch, optical-near-IR photometric measurements indicate significant variability over a 3-20 yr baseline from the AGN component. Gemini South optical data show unusual double-peaked emission-line features: the centroids of the broad-lined components of Hα and Hβ are blueshifted with respect to the narrow lines and host galaxy by ∼3800 km s{sup –1}. We examine possible cases that involve single or double supermassive black holes in the system and discuss the required future investigations to disentangle the mysterious nature of this system.

  1. Photomultiplication photodetectors with P3HT:fullerene-free material as the active layers exhibiting a broad response

    Science.gov (United States)

    Wang, Wenbin; Zhang, Fujun; Bai, Huitao; Li, Lingliang; Gao, Mile; Zhang, Miao; Zhan, Xiaowei

    2016-03-01

    A series of polymer photodetectors (PPDs) are fabricated based on P3HT as an electron donor and fullerene-free material DC-IDT2T as an electron acceptor. The only difference among these PPDs is the P3HT:DC-IDT2T doping weight ratios from 2 : 1 to 150 : 1. The PPDs with P3HT:DC-IDT2T (100 : 1, w/w) as the active layers exhibit champion external quantum efficiency (EQE) of 28 000% and 4000% corresponding to 390 nm and 750 nm light illumination at -20 V bias, respectively. The photomultiplication (PM) phenomenon should be attributed to the enhanced hole tunneling injection due to the interfacial band bending, which is induced by the trapped electrons in DC-IDT2T near the Al cathode. The high EQE value in the long wavelength range is due to the effect of DC-IDT2T photon harvesting and exciton dissociation on the interfacial trap-assisted hole tunneling injection. Meanwhile, the PPDs with DC-IDT2T as the electron acceptor exhibit superior stability compared with the PPDs with PC71BM as the electron acceptor.A series of polymer photodetectors (PPDs) are fabricated based on P3HT as an electron donor and fullerene-free material DC-IDT2T as an electron acceptor. The only difference among these PPDs is the P3HT:DC-IDT2T doping weight ratios from 2 : 1 to 150 : 1. The PPDs with P3HT:DC-IDT2T (100 : 1, w/w) as the active layers exhibit champion external quantum efficiency (EQE) of 28 000% and 4000% corresponding to 390 nm and 750 nm light illumination at -20 V bias, respectively. The photomultiplication (PM) phenomenon should be attributed to the enhanced hole tunneling injection due to the interfacial band bending, which is induced by the trapped electrons in DC-IDT2T near the Al cathode. The high EQE value in the long wavelength range is due to the effect of DC-IDT2T photon harvesting and exciton dissociation on the interfacial trap-assisted hole tunneling injection. Meanwhile, the PPDs with DC-IDT2T as the electron acceptor exhibit superior stability compared with the PPDs

  2. Measurement of the total active 8B solar neutrino flux at the Sudbury Neutrino Observatory with enhanced neutral current sensitivity

    International Nuclear Information System (INIS)

    The Sudbury Neutrino Observatory (SNO) has precisely determined the total active (vx)8B solar neutrino flux without assumptions about the energy dependence of the ve survival probability. The measurements were made with dissolved NaCl in the heavy water to enhance the sensitivity and signature for neutral-current interactions. The flux is found to be 5.21+-0.27 (stat)+-0.38(syst)x10-6 cm-2s-1, in agreement with previous measurements and standard solar models. A global analysis of these and other solar and reactor neutrino results yields Δm2 = 7.1+1.2-0.6 x 10-5 eV2 and θ 32.5+2.4-2.3 degrees. Maximal mixing is rejected at the equivalent of 5.4 standard deviations

  3. Measurement of the Total Active 8B Solar Neutrino Flux at the Sudbury Neutrino Observatory with Enhanced Neutral Current Sensitivity

    CERN Document Server

    Ahmed, S N; Beier, E W; Bellerive, A; Biller, S D; Boger, J; Boulay, M G; Bowler, M G; Bowles, T J; Brice, S J; Bullard, T V; Chan, Y D; Chen, M; Chen, X; Cleveland, B T; Cox, G A; Dai, X; Dalnoki-Veress, F; Doe, P J; Dosanjh, R S; Doucas, G; Dragowsky, M R; Duba, C A; Duncan, F A; Dunford, M; Dunmore, J A; Earle, E D; Elliott, S R; Evans, H C; Ewan, G T; Farine, J; Fergani, H; Fleurot, F; Formaggio, J A; Fowler, M M; Frame, K; Fulsom, B G; Gagnon, N; Graham, K; Grant, D R; Hahn, R L; Hall, J C; Hallin, A L; Hallman, E D; Hamer, A S; Handler, W B; Hargrove, C K; Harvey, P J; Hazama, R; Heeger, K M; Heintzelman, W J; Heise, J; Helmer, R L; Hemingway, R J; Hime, A; Howe, M A; Jagam, P; Jelley, N A; Klein, J R; Kos, M S; Krumins, A V; Kutter, T; Kyba, C C M; Labranche, H; Lange, R; Law, J; Lawson, I T; Lesko, K T; Leslie, J R; Levine, I; Luoma, S; MacLellan, R; Majerus, S; Mak, H B; Maneira, J; Marino, A D; McCauley, N; McDonald, A B; McGee, S; McGregor, G; Miin, C; Miknaitis, K K S; Miller, G G; Moffat, B A; Nally, C W; Nickel, B G; Noble, A J; Norman, E B; Oblath, N S; Okada, C E; Ollerhead, R W; Orrell, J L; Oser, S M; Ouellet, C V; Peeters, S J M; Poon, A W P; Robertson, B C; Robertson, R G H; Rollin, E; Rosendahl, S S E; Rusu, V L; Schwendener, M H; Simard, O; Simpson, J J; Sims, C J; Sinclair, D; Skensved, P; Smith, M W E; Starinsky, N; Stokstad, R G; Stonehill, L C; Tafirout, R; Takeuchi, Y; Tesic, G; Thomson, M; Thorman, M; Van Berg, R; Van de Water, R G; Virtue, C J; Wall, B L; Waller, D; Waltham, C E; Wan Chan Tseung, H; Wark, D L; West, N; Wilhelmy, J B; Wilkerson, J F; Wilson, J R; Wouters, J M; Yeh, M; Zuber, K

    2004-01-01

    The Sudbury Neutrino Observatory (SNO) has precisely determined the total active (nu_x) 8B solar neutrino flux without assumptions about the energy dependence of the nu_e survival probability. The measurements were made with dissolved NaCl in the heavy water to enhance the sensitivity and signature for neutral-current interactions. The flux is found to be 5.21 +/- 0.27 (stat) +/- 0.38 (syst) x10^6 cm^{-2}s^{-1}, in agreement with previous measurements and standard solar models. A global analysis of these and other solar and reactor neutrino results yields Delta m^{2} = 7.1^{+1.2}_{-0.6}x10^{-5} ev^2 and theta = 32.5^{+2.4}_{-2.3} degrees. Maximal mixing is rejected at the equivalent of 5.4 standard deviations.

  4. Serine Hydroxymethyltransferase from the Cold Adapted Microorganism Psychromonas ingrahamii: A Low Temperature Active Enzyme with Broad Substrate Specificity

    Directory of Open Access Journals (Sweden)

    Stefano Pascarella

    2012-01-01

    Full Text Available Serine hydroxymethyltransferase from the psychrophilic microorganism Psychromonas ingrahamii was expressed in Escherichia coli and purified as a His-tag fusion protein. The enzyme was characterized with respect to its spectroscopic, catalytic, and thermodynamic properties. The properties of the psychrophilic enzyme have been contrasted with the characteristics of the homologous counterpart from E. coli, which has been structurally and functionally characterized in depth and with which it shares 75% sequence identity. Spectroscopic measures confirmed that the psychrophilic enzyme displays structural properties almost identical to those of the mesophilic counterpart. At variance, the P. ingrahamii enzyme showed decreased thermostability and high specific activity at low temperature, both of which are typical features of cold adapted enzymes. Furthermore, it was a more efficient biocatalyst compared to E. coli serine hydroxymethyltransferase (SHMT particularly for side reactions. Many β-hydroxy-α-amino acids are SHMT substrates and represent important compounds in the synthesis of pharmaceuticals, agrochemicals and food additives. Thanks to these attractive properties, this enzyme could have a significant potential for biotechnological applications.

  5. Soil microbial activity and nutrients of evergreen broad-leaf forests in mid-subtropical region of China

    Institute of Scientific and Technical Information of China (English)

    Zhangquan Zeng; Silong Wang; Canming Zhang; Hong Tang; Xiquan Li; Zijian Wu; Jia Luo

    2015-01-01

    To better understand the effects of forest suc-cession on soil microbial activity, a comparison of soil microbial properties and nutrients was conducted between three forest types representing a natural forest succession chronosequence. The study compared a pine (Pinus mas-soniana) forest (PF), a pine and broadleaf mixed forest (MF) and an evergreen broadleaf forest (BF), in the Yingzuijie Biosphere Reserve, Hunan Province, China. Results showed that soil nutrients in the MF and BF plots were higher than in the PF plots. The range in microbial biomass carbon followed a similar pattern with BF having the greatest values, 522–1022 mg kg-1, followed by MF 368–569 mg kg-1, and finally, PF 193–449 mg kg-1. Soil nutrients were more strongly correlated with microbial biomass carbon than basal respiration or metabolic quo-tient. Overall, forest succession in the study site improved soil microbial properties and soil fertility, which in turn can increase primary productivity and carbon sequestration.

  6. Design status and procurement activities of the High Voltage Deck 1 and Bushing for the ITER Neutral Beam Injector

    International Nuclear Information System (INIS)

    Highlights: ► ITER Neutral Beam Injector includes several non-standard components. ► The design status of the −1 MVdc HVD1 and Bushing is described. ► The paper reports also on the integrated layout of the two components. ► Preliminary electrostatic and thermal analyses are presented. ► Procurement activities are outlined. -- Abstract: The ITER Neutral Beam Injector (NBI) power supply system includes several non-standard components, whose ratings go beyond the present industrial practice. Two of these items, to be procured by Fusion for Energy, are: 1.A −1 MVdc air-insulated Faraday cage, called High Voltage Deck 1 (HVD1), hosting the Ion Source and Extractor Power Supplies (ISEPS) and the associated diagnostics. 2.A −1 MVdc feedthrough, called HVD1-TL Bushing, aimed at connecting the HVD1 to the gas (SF6) insulated Transmission Line (TL), containing inside its High Voltage (HV) conductor all ISEPS power and control cables coming from the HVD1 to be connected to the NBI Ion Source services. The paper deals with the status of the design of the HVD1 and HVD1-TL Bushing, focusing on insulation, mechanical and thermal issues as well as on their integration with the other components of the power supply system. In particular, the insulation issue of the integrated system has been addressed by means of an electrostatic Finite Element (FE) analysis whilst a FE thermal simulation has been carried out to assess the impact of the dissipation of the proposed design of the inner conductors (ISEPS conductors) not actively cooled. Finally, the paper describes the status of procurement strategy and execution

  7. Biological activities of a neutral water-soluble agar polysaccharide prepared by agarase degradation

    Institute of Scientific and Technical Information of China (English)

    Wang Jingxue; Mou Haijin; Jiang Xiaolu; Guan Huashi

    2005-01-01

    Depolymerization of agar was performed using agarase, which was extracted from the cell-free medium of a culture of marine bacterial Alteromonas sp. nov. SY 37-12. After ethanol fractionation and lyophilization, the water-soluble agar polysaccharide (WSAP3) was collected. The anti-tumor activity of the product was determined by using Sarcoma 180 tumor in mouse. The tumor inhibition rate of WSAP3 reached 48.7% at a dose of 64mg kg-1 after 15 days treatment. WSAP3 enhanced the activities of superoxide dismutase and catalase, which suggests that WSAP3 was effective in promoting the antioxidation ability and eliminating danger from free radicals. The result of flow cytometry showed that the WSAP3 had no activities of cell cycle inhibition or apoptosis-inducing activities. The anti-oxidation of WSAP3 was further confirmed by test in vitro, which might play an important role in anti-tumor activity. The immunological regulation of WSAP3, especially its effect on the phagocytosis ratio and phagocytosis index of macrophage was also assayed in test in vivo.

  8. A novel neutral, halophile Stachybotrys microspora-based endoglucanase active impact on β-glucan.

    Science.gov (United States)

    Benhmad, Ines; Boudabbous, Manel; Yaîch, Asma; Rebai, Maryem; Gargouri, Ali

    2016-04-01

    The production of cellulases from Stachybotrys microspora strain (A19) has been improved by fed-batch fermentation on Avicel cellulose 10 mg/ml. An endoglucanase EG2 was purified to homogeneity. This cellulase has a molecular mass estimated to 50 kDa when analyzed by a denaturant gel electrophoresis. It exhibited an optimal activity at 50 °C, pH 7.0 and 0.85 M NaCl. Specifically, these results show the thermo-active, alkali-tolerant and halo-tolerant properties of EG2. In addition, this endoglucanase showed its highest activity on barley-β-glucan, compared to the CMC. Moreover, it was less active on Avicel cellulose. Furthermore, the EG2 activity was stimulated in the presence of EDTA, urea and β-mercaptoethanol whereas it was reduced in the presence of SDS. This cellulase was highly stable in the presence of organic solvents such as acetone and n-hexane. TLC showed that the main hydrolysis products from EG2 were cellobiose and glucose. This fungal endoglucanase could be potentially important in the conversion of grass-derived biomass into fermentable sugars. PMID:26861652

  9. Structural basis of the phospholipase C activity in neutral sphingomyelinase from Bacillus cereus

    International Nuclear Information System (INIS)

    Degradation of cell membrane and mucosa, of which phospholipids are major components, and production of lipid mediators are roles of phospholipases from pathogenic bacteria to grow, survive and spread in the host organism. The studies on the enzymes the important for the pathobiology of bacterial infectious disease. The crystal structure of Sphingomyelinase from Bacillus cereus revealed the structure basis of the phospholipase C and hemolysis activities in a divalent cation dependent manner. The water-bridged double divalent cations were concluded to be the catalytic architecture to the phospholipase C activity. In addition, the β-hairpin structure with aromatic amino acid residues was shown to be involved in the membrane binding of the enzyme as a part of the hemolysis activity. (author)

  10. Neutralization, by a monospecific Bothrops lanceolatus antivenom, of toxic activities induced by homologous and heterologous Bothírops snake venoms.

    Science.gov (United States)

    Bogarín, G; Romero, M; Rojas, G; Lutsch, C; Casadamont, M; Lang, J; Otero, R; Gutiérrez, J M

    1999-03-01

    A monospecific Bothrops lanceolatus antivenom, currently used in Martinique, was tested for its efficacy in the neutralization of several toxic and enzymatic activities of the venoms of B. lanceolatus, B. atrox and B. asper. When tested by the i.p. route in mice, B. lanceolatus venom had an LD50 of 12.8 microg/g. In addition, it induced local tissue damage (hemorrhage, edema and myotoxicity) and showed indirect hemolytic activity, but was devoid of coagulant effect on human plasma in vitro and of defibrinating activity in mice. Antivenom was fully effective in the neutralization of lethal, hemorrhagic, edema-forming, myotoxic and indirect hemolytic effects of B. lanceolatus venom in assays involving preincubation of venom and antivenom. When tested against the venoms of B. asper and B. atrox, the antivenom completely neutralized the lethal, hemorrhagic, myotoxic and indirect hemolytic effects, and was partially effective in neutralizing edema-forming activity. In contrast, the antivenom was ineffective in the neutralization of in vitro coagulant and in vivo defibrinating effects induced by these two venoms. PMID:10080358

  11. Self-shadowing effects of slim accretion disks in active galactic nuclei: the diverse appearance of the broad-line region

    International Nuclear Information System (INIS)

    Supermassive black holes in active galactic nuclei (AGNs) undergo a wide range of accretion rates, which lead to diversity of appearance. We consider the effects of anisotropic radiation from accretion disks on the broad-line region (BLR) from the Shakura-Sunyaev regime to slim disks with super-Eddington accretion rates. The geometrically thick funnel of the inner region of slim disks produces strong self-shadowing effects that lead to very strong anisotropy of the radiation field. We demonstrate that the degree of anisotropy of the radiation fields grows with increasing accretion rate. As a result of this anisotropy, BLR clouds receive different spectral energy distributions depending on their location relative to the disk, resulting in the diverse observational appearance of the BLR. We show that the self-shadowing of the inner parts of the disk naturally produces two dynamically distinct regions of the BLR, depending on accretion rate. These two regions manifest themselves as kinematically distinct components of the broad Hβ line profile with different line widths and fluxes, which jointly account for the Lorentzian profile generally observed in narrow-line Seyfert 1 galaxies. In the time domain, these two components are expected to reverberate with different time lags with respect to the varying ionizing continuum, depending on the accretion rate and the viewing angle of the observer. The diverse appearance of the BLR due to the anisotropic ionizing energy source can be tested by reverberation mapping of Hβ and other broad emission lines (e.g., Fe II), providing a new tool to diagnose the structure and dynamics of the BLR. Other observational consequences of our model are also explored.

  12. Influence of Partial Neutralization on Catalytic Activity of Ion Exchange Resin

    Czech Academy of Sciences Publication Activity Database

    Holub, Ladislav; Hanková, Libuše; Jeřábek, Karel

    Praha, 2004. PO8. [International Conference on Polymer s and Organic Chemistry POC'04 /11./. 18.07.2004-23.07.2004, Praha] R&D Projects: GA ČR GA104/02/1104 Institutional research plan: CEZ:AV0Z4072921 Keywords : catalytic activity * exchange resin Subject RIV: CI - Industrial Chemistry, Chemical Engineering

  13. A Radial Velocity Test for Supermassive Black Hole Binaries as an Explanation for Broad, Double-Peaked Emission Lines in Active Galactic Nuclei

    CERN Document Server

    Liu, Jia; Halpern, Jules P

    2015-01-01

    One of the proposed explanations for the broad, double-peaked Balmer emission lines observed in the spectra of some active galactic nuclei (AGNs) is that they are associated with sub-parsec supermassive black hole (SMBH) binaries. Here, we test the binary broad-line region hypothesis through several decades of monitoring of the velocity structure of double-peaked H-alpha emission lines in 13 low-redshift, mostly radio-loud AGNs. This is a much larger set of objects compared to an earlier test by Eracleous et al. (1997) and we use much longer time series for the three objects studied in that paper. Although systematic changes in radial velocity can be traced in many of their lines, they are demonstrably not like those of a spectroscopic binary in a circular orbit. Any spectroscopic binary period must therefore be much longer than the span of the monitoring (assuming a circular orbit), which in turn would require black hole masses that exceed by 1-2 orders of magnitude the values obtained for these objects usin...

  14. The case for cases B and C: intrinsic hydrogen line ratios of the broad-line region of active galactic nuclei, reddenings, and accretion disc sizes

    CERN Document Server

    Gaskell, C Martin

    2016-01-01

    Low-redshift active galactic nuclei (AGNs) with extremely blue optical spectral indices are shown to have a mean, velocity-averaged, broad-line H$\\alpha$/H$\\beta$ ratio of $\\thickapprox 2.72 \\pm 0.04$, consistent with the Baker-Menzel Case B value. Comparison of a wide range of properties of the very bluest AGNs with those of a luminosity-matched subset of the Dong et al. blue AGN sample indicates that the only difference is the internal reddening. Ultraviolet fluxes are brighter for the bluest AGNs by an amount consistent with the flat AGN reddening curve of Gaskell et al. (2004). The lack of a significant difference in the GALEX (FUV--NUV) colour index strongly rules out a steep SMC-like reddening curve and also argues against an intrinsically harder spectrum. For very blue AGNs the Ly$\\alpha$/H$\\beta$ ratio is also consistent with being the Case B value. The Case B ratios provide strong support for the self-shielded broad-line model of Gaskell, Klimek & Nazarova. It is proposed that the greatly enhance...

  15. Characterization of Disopyramide derivative ADD424042 as a non-cardiotoxic neuronal sodium channel blocker with broad-spectrum anticonvulsant activity in rodent seizure models.

    Science.gov (United States)

    Król, Marek; Ufnal, Marcin; Szulczyk, Bartłomiej; Podsadni, Piotr; Drapała, Adrian; Turło, Jadwiga; Dawidowski, Maciej

    2016-01-01

    It was reported that antiarrhythmic drugs (AADs) can be useful in controlling refractory seizures in humans or in enhancing the action of antiepileptic drugs (AEDs) in animal models. Disopyramide phosphate (DISO) is an AAD that blocks sodium channels in cardiac myocytes. We evaluated a DISO derivative, 2-(2-chlorophenyl)-2-(pyridin-2-yl)acetamide (ADD424042) for its anticonvulsant activity in a battery of rodent models of epileptic seizures. The compound displayed a broad spectrum of activity in the 'classical' models as well as in the models of pharmacoresistant seizures. Furthermore, ADD424042 showed good therapeutic indices between the anticonvulsant activity and the motor impairment. On the contrary, no anticonvulsant effects but severe lethality were observed in the primary anticonvulsant testing of the parent DISO. By performing the whole-cell voltage-clamp experiments in dispersed cortical neurons we demonstrated that ADD424042 decreased the maximal amplitude of voltage-gated sodium channels with an IC50 value in nM range. Moreover, the compound enhanced use-dependent block and decreased excitability in pyramidal neurons in the current-clamp experiments in cortical slices. Importantly, we found that ADD424042 possessed either no, or very small cardiotoxic effect. In contrast to DISO, ADD424042 did not produce any apparent changes in electrocardiogram (ECG) and arterial blood pressure recordings. ADD424042 had no effect on QT and corrected QT intervals, at a dose which was 15 times higher than ED50 for the anticonvulsant effect in the MES model. Taken together, these data suggest that ADD424042 has the potential to become a lead structure for novel broadly acting AEDs with wide margin of cardiac safety. PMID:26441377

  16. Synthesis, structural characterisation and antibacterial activity of Ag{sup +}-doped fluorapatite nanomaterials prepared by neutralization method

    Energy Technology Data Exchange (ETDEWEB)

    Stanić, Vojislav, E-mail: voyo@vinca.rs [University of Belgrade, Vinča Institute of Nuclear Sciences, P.O. Box 522, 11001 Belgrade (Serbia); Radosavljević-Mihajlović, Ana S. [University of Belgrade, Vinča Institute of Nuclear Sciences, P.O. Box 522, 11001 Belgrade (Serbia); Živković-Radovanović, Vukosava [University of Belgrade, Faculty of Chemistry, P.O. Box 51, 11158 Belgrade (Serbia); Nastasijević, Branislav; Marinović-Cincović, Milena; Marković, Jelena P.; Budimir, Milica D. [University of Belgrade, Vinča Institute of Nuclear Sciences, P.O. Box 522, 11001 Belgrade (Serbia)

    2015-05-15

    Graphical abstract: - Highlights: • The neutralization method has been used for synthesis of silver-doped fluorapatite powders. • Particles of silver-doped fluorapatite samples are of nano size and homogenous in composition. • The Ag{sup +}-doped fluorapatite samples showed antibacterial effect against Kllebsiela pneumoniae, Staphylococcus aureus and Micrococcus luteus. • AFM studies showed that silver-doped sample causes considerable morphological changes of tested bacterial cells. - Abstract: Silver doped fluorapatite nanopowders were synthesised by neutralization method, which consists of dissolving Ag{sub 2}O in solution of HF and H{sub 3}PO{sub 4} and addition to suspension of Ca(OH){sub 2}. The powder XRD, SEM and FTIR studies indicated the formation of a fluorapatite nanomaterials with average length of the particles is about 80 nm and a width of about 15 nm. The FTIR studies show that carbonate content in samples is very small and carbonte ions substitute both phosphate and hydroxyl groups in the crystal structure of samples, forming AB-type fluorapatite. Antibacterial studies have demonstrated that all Ag{sup +}-doped fluorapatite samples exhibit bactericidal effect against pathogens: Staphylococcus aureus, Micrococcus luteus and Kllebsiela pneumoniae. Antibacterial activity increased with the increase of Ag{sup +} in the samples. The atomic force microscopy studies revealed extensive damage to the bacterial cell envelops in the presence of Ag{sup +}-doped fluorapatite particles which may lead to their death. The synthesized Ag{sup +}-doped fluorapatite nanomaterials are promising as antibacterial biomaterials in orthopedics and dentistry.

  17. Theoretical study of chlordecone and surface groups interaction in an activated carbon model under acidic and neutral conditions.

    Science.gov (United States)

    Gamboa-Carballo, Juan José; Melchor-Rodríguez, Kenia; Hernández-Valdés, Daniel; Enriquez-Victorero, Carlos; Montero-Alejo, Ana Lilian; Gaspard, Sarra; Jáuregui-Haza, Ulises Javier

    2016-04-01

    Activated carbons (ACs) are widely used in the purification of drinking water without almost any knowledge about the adsorption mechanisms of the persistent organic pollutants. Chlordecone (CLD, Kepone) is an organochlorinated synthetic compound that has been used mainly as agricultural insecticide. CLD has been identified and listed as a persistent organic pollutant by the Stockholm Convention. The selection of the best suited AC for this type of contaminants is mainly an empirical and costly process. A theoretical study of the influence of AC surface groups (SGs) on CLD adsorption is done in order to help understanding the process. This may provide a first selection criteria for the preparation of AC with suitable surface properties. A model of AC consisting of a seven membered ring graphene sheet (coronene) with a functional group on the edge was used to evaluate the influence of the SGs over the adsorption. Multiple Minima Hypersurface methodology (MMH) coupled with PM7 semiempirical Hamiltonian was employed in order to study the interactions of the chlordecone with SGs (hydroxyl and carboxyl) at acidic and neutral pH and different hydration conditions. Selected structures were re-optimized using CAM-B3LYP to achieve a well-defined electron density to characterize the interactions by the Quantum Theory of Atoms in Molecules approach. The deprotonated form of surface carboxyl and hydroxyl groups of AC models show the strongest interactions, suggesting a chemical adsorption. An increase in carboxylic SGs content is proposed to enhance CLD adsorption onto AC at neutral pH conditions. PMID:26945637

  18. Analysis of Non-Enzymatically Glycated Peptides: Neutral-Loss Triggered MS3 Versus Multi-Stage Activation Tandem Mass Spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Qibin; Petyuk, Vladislav A.; Schepmoes, Athena A.; Orton, Daniel J.; Monroe, Matthew E.; Yang, Feng; Smith, Richard D.; Metz, Thomas O.

    2008-10-15

    Non-enzymatic glycation of tissue proteins has important implications in the development of complications of diabetes mellitus. While electron transfer dissociation (ETD) has been shown to outperform collision-induced dissociation (CID) in sequencing glycated peptides by tandem mass spectrometry, ETD instrumentation is not yet available in all laboratories. In this study, we evaluated different advanced CID techniques (i.e., neutral-loss triggered MS3 and multi-stage activation) during LC-MSn analyses of Amadori-modified peptides enriched from human serum glycated in vitro. During neutral-loss triggered MS3 experiments, MS3 scans triggered by neutral-losses of 3 H2O or 3 H2O + HCHO produced similar results in terms of glycated peptide identifications. However, neutral losses of 3 H2O resulted in significantly more glycated peptide identifications during multi-stage activation experiments. Overall, the multi-stage activation approach produced more glycated peptide identifications, while the neutral-loss triggered MS3 approach resulted in much higher specificity. Both techniques offer a viable alternative to ETD for identifying glycated peptides when that method is unavailable.

  19. Brain Activity in Response to Trauma-specific, Negative, and Neutral Stimuli. A fMRI Study of Recent Road Traffic Accident Survivors

    Science.gov (United States)

    Nilsen, Andre S.; Blix, Ines; Leknes, Siri; Ekeberg, Øivind; Skogstad, Laila; Endestad, Tor; Østberg, Bjørn C.; Heir, Trond

    2016-01-01

    Most studies of neuro-functional patterns in trauma-exposed individuals have been conducted considerable time after the traumatic event. Hence little is known about neuro-functional processing shortly after trauma-exposure. We investigated brain activity patterns in response to trauma reminders as well as neutral and negative stimuli in individuals who had recently (within 3 weeks) been involved in a road traffic accident (RTA). Twenty-three RTA survivors and 17 non-trauma-exposed healthy controls (HCs) underwent functional MRI while viewing Trauma-specific, Negative, and Neutral pictures. Data were analyzed from four a priori regions of interest, including bilateral amygdala, subcallosal cortex, and medial prefrontal cortex. In addition, we performed a whole brain analysis and functional connectivity analysis during stimulus presentation. For both groups, Negative stimuli elicited more activity in the amygdala bilaterally than did Neutral and Trauma-specific stimuli. The whole brain analysis revealed higher activation in sensory processing related areas (bilateral occipital and temporal cortices and thalamus) as well as frontal and superior parietal areas, for the RTA group compared to HC, for Trauma-specific stimuli contrasted with Neutral stimuli. We also observed higher functional connectivity for Trauma-specific stimuli, between bilateral amygdala and somatosensory areas, for the RTA group compared to controls, when contrasted with Neutral stimuli. We argue that these results might indicate an attentional sensory processing bias toward Trauma-specific stimuli for trauma exposed individuals, a result in line with findings from the post-traumatic stress disorder literature.

  20. The first human epitope map of the alphaviral E1 and E2 proteins reveals a new E2 epitope with significant virus neutralizing activity.

    Directory of Open Access Journals (Sweden)

    Ann R Hunt

    Full Text Available BACKGROUND: Venezuelan equine encephalitis virus (VEEV is responsible for VEE epidemics that occur in South and Central America and the U.S. The VEEV envelope contains two glycoproteins E1 (mediates cell membrane fusion and E2 (binds receptor and elicits virus neutralizing antibodies. Previously we constructed E1 and E2 epitope maps using murine monoclonal antibodies (mMAbs. Six E2 epitopes (E2(c,d,e,f,g,h bound VEEV-neutralizing antibody and mapped to amino acids (aa 182-207. Nothing is known about the human antibody repertoire to VEEV or epitopes that engage human virus-neutralizing antibodies. There is no specific treatment for VEE; however virus-neutralizing mMAbs are potent protective and therapeutic agents for mice challenged with VEEV by either peripheral or aerosol routes. Therefore, fully human MAbs (hMAbs with virus-neutralizing activity should be useful for prevention or clinical treatment of human VEE. METHODS: We used phage-display to isolate VEEV-specific hFabs from human bone marrow donors. These hFabs were characterized by sequencing, specificity testing, VEEV subtype cross-reactivity using indirect ELISA, and in vitro virus neutralization capacity. One E2-specific neutralizing hFAb, F5n, was converted into IgG, and its binding site was identified using competitive ELISA with mMAbs and by preparing and sequencing antibody neutralization-escape variants. FINDINGS: Using 11 VEEV-reactive hFabs we constructed the first human epitope map for the alphaviral surface proteins E1 and E2. We identified an important neutralization-associated epitope unique to the human immune response, E2 aa115-119. Using a 9 A resolution cryo-electron microscopy map of the Sindbis virus E2 protein, we showed the probable surface location of this human VEEV epitope. CONCLUSIONS: The VEEV-neutralizing capacity of the hMAb F5 nIgG is similar to that exhibited by the humanized mMAb Hy4 IgG. The Hy4 IgG has been shown to limit VEEV infection in mice both

  1. Active Houses - development of carbon neutral buildings with healthy indoor comfort

    Energy Technology Data Exchange (ETDEWEB)

    Eriksen, Kurt Emil (VKR Holding (Denmark)). e-mail: kee@vkr-holding.com

    2009-07-01

    The European Commission and the European Parliament are calling for national strategies for low to zero carbon housing in their proposal for a revision of the EPBD; the European Commission is also recommending to include application of renewable energy sources, use of passive heating and cooling elements and shading in the design of the building and in the design of the building and to ensure indoor air quality and adequate natural light in buildings. A few Member States have already initiated targets on low energy housing, and there are several demonstration projects showing how future housing could be both zero carbon buildings and have a high indoor comfort level. The European and national strategies for low energy housing must focus on energy efficiency and CO{sub 2} reductions, but as people spend approximately 90% of their life inside buildings, future housing also needs to be developed with a focus on healthy indoor comfort. The different national standards for low energy housing have mainly been focusing on energy savings, but some new standards also focus on energy saving in combination with indoor comfort requirements, like the 'Sustainable Home standard' and BOLIG+. At the same time the German energy legislation and the EU Renewable Energy Directive are setting requirements to integrate a proportion of renewable energy into all new buildings and buildings undergoing major renovation, while others like France and England have targets to move towards energy producing houses. Therefore, a new approach, where energy efficiency, indoor climate and integration of renewable energy are included, is needed. A number of partners from the construction sector have initiated the first thoughts and, as they intend to move from passive systems to active systems, the network is named Active Houses.

  2. Central Masses and Broad-Line Region Sizes of Active Galactic Nuclei. II. A Homogeneous Analysis of a Large Reverberation-Mapping Database

    DEFF Research Database (Denmark)

    Peterson, B. M.; Ferrarese, L.; Gilbert, K. M.;

    2004-01-01

    We present improved black hole masses for 35 active galactic nuclei (AGNs) based on a complete and consistent reanalysis of broad emission-line reverberation-mapping data. From objects with multiple line measurements, we find that the highest precision measure of the virial product is obtained by...... depends critically on avoiding contaminating features, in particular the narrow components of the emission lines. We find that the precision (or random component of the error) of reverberation-based black hole mass measurements is typically around 30%, comparable to the precision attained in measurement...... of black hole masses in quiescent galaxies by gas or stellar dynamical methods. Based on results presented in a companion paper by Onken et al., we provide a zero-point calibration for the reverberation-based black hole mass scale by using the relationship between black hole mass and host...

  3. Simulation of Cl- secretion in epithelial tissues: New methodology estimating activity of electro-neutral Cl- transporter

    Directory of Open Access Journals (Sweden)

    Kouhei eSasamoto

    2015-12-01

    Full Text Available Transcellular Cl- secretion is, in general, mediated by two steps; 1 the entry step of Cl- into the cytosolic space from the basolateral space across the basolateral membrane by Cl- transporters, such as Na+-K+-2Cl- cotransporter (NKCC1, an isoform of NKCC, and 2 the releasing step of Cl- from the cytosolic space into the luminal (air space across the apical membrane via Cl- channels, such as cystic fibrosis transmembrane conductance regulator (CFTR Cl- channel. Transcellular Cl- secretion has been characterized by using various experimental techniques. For example, measurements of short-circuit currents in the Ussing chamber and patch clamp techniques provide us information on transepithelial ion movements via transcellular pathway, transepithelial conductance, activity (open probability of single channel, and whole cell currents. Although many investigators have tried to clarify roles of Cl- channels and transporters located at the apical and basolateral membranes in transcellular Cl- secretion, it is still unclear how Cl- channels/transporters contribute to transcellular Cl- secretion and are regulated by various stimuli such as Ca2+ and cAMP. In the present study, we simulate transcellular Cl- secretion using mathematical models combined with electrophysiological measurements, providing information on contribution of Cl- channels/transporters to transcellular Cl- secretion, activity of electro-neutral ion transporters and how Cl- channels/transporters are regulated.

  4. Simulation of Cl− Secretion in Epithelial Tissues: New Methodology Estimating Activity of Electro-Neutral Cl− Transporter

    Science.gov (United States)

    Sasamoto, Kouhei; Niisato, Naomi; Taruno, Akiyuki; Marunaka, Yoshinori

    2015-01-01

    Transcellular Cl− secretion is, in general, mediated by two steps; (1) the entry step of Cl− into the cytosolic space from the basolateral space across the basolateral membrane by Cl− transporters, such as Na+-K+-2Cl− cotransporter (NKCC1, an isoform of NKCC), and (2) the releasing step of Cl− from the cytosolic space into the luminal (air) space across the apical membrane via Cl− channels, such as cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel. Transcellular Cl− secretion has been characterized by using various experimental techniques. For example, measurements of short-circuit currents in the Ussing chamber and patch clamp techniques provide us information on transepithelial ion movements via transcellular pathway, transepithelial conductance, activity (open probability) of single channel, and whole cell currents. Although many investigators have tried to clarify roles of Cl− channels and transporters located at the apical and basolateral membranes in transcellular Cl− secretion, it is still unclear how Cl− channels/transporters contribute to transcellular Cl− secretion and are regulated by various stimuli such as Ca2+ and cAMP. In the present study, we simulate transcellular Cl− secretion using mathematical models combined with electrophysiological measurements, providing information on contribution of Cl− channels/transporters to transcellular Cl− secretion, activity of electro-neutral ion transporters and how Cl− channels/transporters are regulated. PMID:26779025

  5. Neutralization of the haemorrhagic activities of viperine snake venoms and venom metalloproteinases using synthetic peptide inhibitors and chelators.

    Science.gov (United States)

    Howes, J-M; Theakston, R D G; Laing, G D

    2007-04-01

    Envenoming by the West African saw-scaled viper, Echis ocellatus resembles that of most vipers, in that it results in local blistering, necrosis and sometimes life-threatening systemic haemorrhage. While effective against systemic envenoming, current antivenoms have little or no effect against local tissue damage. The major mediators of local venom pathology are the zinc-dependant snake venom metalloproteinases (SVMPs). The high degree of structural and functional homology between SVMPs and their mammalian relatives the matrix metalloproteinases (MMPs) suggests that substrate/inhibitor interactions between these subfamilies are likely to be analogous. In this study, four recently developed MMP inhibitors (MMPIs) (Marimastat, AG-3340, CGS-270 23A and Bay-12 9566) are evaluated in addition to three metal ion chelators (EDTA, TPEN and BAPTA) for their ability to inhibit the haemorrhagic activities of the medically important E. ocellatus venom and one of its haemorrhagic SVMPs, EoVMP2. As expected, the metal ion chelators significantly inhibited the haemorrhagic activities of both whole E. ocellatus venom and EoVMP2, while the synthetic MMPIs show more variation in their efficacies. These variations suggest that individual MMPIs show specificity towards SVMPs and that their application to the neutralization of local haemorrhage may require a synthetic MMPI mixture, ensuring that a close structural component for each SVMP is represented. PMID:17196631

  6. VEGF neutralizing aerosol therapy in primary pulmonary adenocarcinoma with K-ras activating-mutations.

    Science.gov (United States)

    Hervé, Virginie; Rabbe, Nathalie; Guilleminault, Laurent; Paul, Flora; Schlick, Laurène; Azzopardi, Nicolas; Duruisseaux, Michael; Fouquenet, Delphine; Montharu, Jérôme; Redini, Françoise; Paintaud, Gilles; Lemarié, Etienne; Cadranel, Jacques; Wislez, Marie; Heuzé-Vourc'h, Nathalie

    2014-01-01

    K-ras mutations promote angiogenesis in lung cancer and contribute to the drug resistance of cancer cells. It is not clear whether K-ras mutated adenocarcinomas are sensitive to anti-angiogenic therapy with monoclonal antibodies (mAbs) that target vascular endothelial growth factor (VEGF). Anti-angiogenic mAbs are usually delivered systemically, but only a small proportion reaches the lung after intravenous injection. We investigated the relevance of a non-invasive pulmonary route for the delivery of anti-VEGF mAbs in the mouse K-ras(LA1) model. We found that pulmonary delivery of these mAbs significantly reduced the number of tumor lesions and inhibited malignant progression. The antitumor effect involves the VEGFR2-dependent inhibition of blood vessel growth, which impairs tumor proliferation. Pharmacokinetic analysis of aerosolized anti-VEGF showed its low rate of passage into the bloodstream, suggesting that this delivery route is associated with reduced systemic side effects. Our findings highlight the value of the aerosol route for administration of anti-angiogenic mAbs in pulmonary adenocarcinoma with K-ras activating-mutations. PMID:25484066

  7. Neutralizing activities of human immunoglobulin derived from donors in Japan against mosquito-borne flaviviruses, Japanese encephalitis virus, West Nile virus, and dengue virus.

    Science.gov (United States)

    Yunoki, Mikihiro; Kurosu, Takeshi; Koketsu, Ritsuko Kubota; Takahashi, Kazuo; Okuno, Yoshinobu; Ikuta, Kazuyoshi

    2016-01-01

    Japanese encephalitis virus (JEV), West Nile virus (WNV), and dengue virus (DenV) are causal agents of Japanese encephalitis, West Nile fever, and dengue fever, respectively. JEV is considered to be indigenized and widespread in Japan, whereas WNV and DenV are not indigenized in Japan. Globulin products seem to reflect the status of the donor population according to antivirus neutralization activity. However, the anti-JEV, -WNV, and -DenV neutralization activities of globulin products derived from donors in Japan have not been clarified. Furthermore, potential candidates for the development of an effective immunotherapeutic drug for encephalitis caused by JEV, WNV, or DenV have also not been identified. Therefore, the aim of this study was to determine the overall status of the donor population in Japan based on globulin products by evaluating anti-JEV, -WNV, and -DenV neutralizing activities of intravenous immunoglobulin. Overall, intravenous immunoglobulin products showed stable neutralizing activity against JEV but showed no or only weak activity against WNV or DenV. These results suggest that the epidemiological level against WNV and DenV in the donor population of Japan is still low, suggesting that these viruses are not yet indigenized. In addition, JEV vaccinations and/or infections in the donor population do not induce a cross-reactive antibody against WNV. PMID:27462140

  8. Neutralizing activities of human immunoglobulin derived from donors in Japan against mosquito-borne flaviviruses, Japanese encephalitis virus, West Nile virus, and dengue virus

    Science.gov (United States)

    Yunoki, Mikihiro; Kurosu, Takeshi; Koketsu, Ritsuko Kubota; Takahashi, Kazuo; Okuno, Yoshinobu; Ikuta, Kazuyoshi

    2016-01-01

    Japanese encephalitis virus (JEV), West Nile virus (WNV), and dengue virus (DenV) are causal agents of Japanese encephalitis, West Nile fever, and dengue fever, respectively. JEV is considered to be indigenized and widespread in Japan, whereas WNV and DenV are not indigenized in Japan. Globulin products seem to reflect the status of the donor population according to antivirus neutralization activity. However, the anti-JEV, -WNV, and -DenV neutralization activities of globulin products derived from donors in Japan have not been clarified. Furthermore, potential candidates for the development of an effective immunotherapeutic drug for encephalitis caused by JEV, WNV, or DenV have also not been identified. Therefore, the aim of this study was to determine the overall status of the donor population in Japan based on globulin products by evaluating anti-JEV, -WNV, and -DenV neutralizing activities of intravenous immunoglobulin. Overall, intravenous immunoglobulin products showed stable neutralizing activity against JEV but showed no or only weak activity against WNV or DenV. These results suggest that the epidemiological level against WNV and DenV in the donor population of Japan is still low, suggesting that these viruses are not yet indigenized. In addition, JEV vaccinations and/or infections in the donor population do not induce a cross-reactive antibody against WNV. PMID:27462140

  9. Mycophenolic acid, an immunomodulator, has potent and broad-spectrum in vitro antiviral activity against pandemic, seasonal and avian influenza viruses affecting humans.

    Science.gov (United States)

    To, Kelvin K W; Mok, Ka-Yi; Chan, Andy S F; Cheung, Nam N; Wang, Pui; Lui, Yin-Ming; Chan, Jasper F W; Chen, Honglin; Chan, Kwok-Hung; Kao, Richard Y T; Yuen, Kwok-Yung

    2016-08-01

    Immunomodulators have been shown to improve the outcome of severe pneumonia. We have previously shown that mycophenolic acid (MPA), an immunomodulator, has antiviral activity against influenza A/WSN/1933(H1N1) using a high-throughput chemical screening assay. This study further investigated the antiviral activity and mechanism of action of MPA against contemporary clinical isolates of influenza A and B viruses. The 50 % cellular cytotoxicity (CC50) of MPA in Madin Darby canine kidney cell line was over 50 µM. MPA prevented influenza virus-induced cell death in the cell-protection assay, with significantly lower IC50 for influenza B virus B/411 than that of influenza A(H1N1)pdm09 virus H1/415 (0.208 vs 1.510 µM, P=0.0001). For H1/415, MPA interfered with the early stage of viral replication before protein synthesis. For B/411, MPA may also act at a later stage since MPA was active against B/411 even when added 12 h post-infection. Virus-yield reduction assay showed that the replication of B/411 was completely inhibited by MPA at concentrations ≥0.78 µM, while there was a dose-dependent reduction of viral titer for H1/415. The antiviral effect of MPA was completely reverted by guanosine supplementation. Plaque reduction assay showed that MPA had antiviral activity against eight different clinical isolates of A(H1N1), A(H3N2), A(H7N9) and influenza B viruses (IC50 <1 µM). In summary, MPA has broad-spectrum antiviral activity against human and avian-origin influenza viruses, in addition to its immunomodulatory activity. Together with a high chemotherapeutic index, the use of MPA as an antiviral agent should be further investigated in vivo. PMID:27259985

  10. The 2010 Broad Prize

    Science.gov (United States)

    Education Digest: Essential Readings Condensed for Quick Review, 2011

    2011-01-01

    A new data analysis, based on data collected as part of The Broad Prize process, provides insights into which large urban school districts in the United States are doing the best job of educating traditionally disadvantaged groups: African-American, Hispanics, and low-income students. Since 2002, The Eli and Edythe Broad Foundation has awarded The…

  11. Stepwise design, synthesis, and in vitro antifungal screening of (Z)-substituted-propenoic acid derivatives with potent broad-spectrum antifungal activity

    Science.gov (United States)

    Khedr, Mohammed A

    2015-01-01

    Fungal infections are a main reason for the high mortality rate worldwide. It is a challenge to design selective antifungal agents with broad-spectrum activity. Lanosterol 14α-demethylase is an attractive target in the design of antifungal agents. Seven compounds were selected from a number of designed compounds using a rational docking study. These compounds were synthesized and evaluated for their antifungal activity. In silico study results showed the high binding affinity to lanosterol 14α-demethylase (−24.49 and −25.83 kcal/mol) for compounds V and VII, respectively; these values were greater than those for miconazole (−18.19 kcal/mol) and fluconazole (−16.08 kcal/mol). Compound V emerged as the most potent antifungal agent among all compounds with a half maximal inhibitory concentration of 7.01, 7.59, 7.25, 31.6, and 41.6 µg/mL against Candida albicans, Candida parapsilosis, Aspergillus niger, Trichophyton rubrum, and Trichophyton mentagrophytes, respectively. The antifungal activity for most of the synthesized compounds was more potent than that of miconazole and fluconazole. PMID:26309398

  12. INTEGRAL discovery of unusually long broad-band X-ray activity from the Supergiant Fast X-ray Transient IGR J18483-0311

    CERN Document Server

    Sguera, V; Bird, A J; Bazzano, A

    2015-01-01

    We report on a broad-band X-ray study (0.5-250 keV) of the Supergiant Fast X-ray Transient IGR J18483-0311 using archival INTEGRAL data and a new targeted XMM-Newton observation. Our INTEGRAL investigation discovered for the first time an unusually long X-ray activity (3-60 keV) which continuously lasted for at least 11 days, i.e. a significant fraction (about 60%) of the entire orbital period, and spanned orbital phases corresponding to both periastron and apastron passages. This prolongated X-ray activity is at odds with the much shorter durations marking outbursts from classical SFXTs especially above 20 keV, as such it represents a departure from their nominal behavior and it adds a further extreme characteristic to the already extreme SFXT IGR J18483-0311. Our IBIS/ISGRI high energy investigation (100-250 keV) of archival outbursts activity from the source showed that the recently reported hint of a possible hard X-ray tail is not real and it is likely due to noisy background. The new XMM-Newton targeted...

  13. Neutral currents

    International Nuclear Information System (INIS)

    The evidence for the existence of weak neutral current has been a very controverted topics in the early 1970's, as well as the muon did in the 1930's. The history is very rich considering the evolution of the experimental techniques in high energy particle physics. The history of the discovery and the study of weak neutral current is reviewed. Later the quest of the intermediate vector boson continues with the decision of the community to build a large proton antiproton collider. (K.A.). 14 refs., 1 fig

  14. Effect of forage quality on intake, chewing activity, faecal particle size distribution, and digestibility of neutral detergent fibre in sheep, goats, and llamas

    DEFF Research Database (Denmark)

    Jalali, Alireza; Nørgaard, P.; Weisbjerg, Martin Riis; Nielsen, M.O.

    This study investigated the effect of forage quality on intake, eating and ruminating activities, faecal particle size distribution, and neutral detergent fibre (NDF) digestibility in three ruminating species. The experimental design included ad libitum feeding of three ruminating species with two...

  15. AGE-RELATED CHANGES IN NEUTRAL SPHINGOMYELIN-SPECIFIC PHOSPHOLIPASE C ACTIVITY IN STRIATUM, HIPPOCAMPUS, AND FRONTAL CORTEX: IMPLICATION FOR SENSITIVITY TO STRESS AND INFLAMMATION

    Science.gov (United States)

    Previous studies show the enrichment of mammalian brain with neutral sphingomyelin specific phospholipase C (ceramide-phosphocholine phosphodiesterase, EC 3.1.4.12; N-Sase). The objective of this study was to evaluate the subcellular N-Sase activity in striatum, hippocampus, and frontal cortex. Resu...

  16. Activation and deactivation of neutral palladium(II) phosphinesulfonato polymerization catalysts

    KAUST Repository

    Rünzi, Thomas

    2012-12-10

    13C-Labeled ethylene polymerization (pre)catalysts [κ2-(anisyl)2P,O]Pd(13CH3)(L) (1-13CH3-L) (L = pyridine, dmso) based on di(2-anisyl)phosphine benzenesulfonate were used to assess the degree of incorporation of 13CH3 groups into the formed polyethylenes. Polymerizations of variable reaction time reveal that ca. 60-85% of the 13C-label is found in the polymer after already 1 min polymerization time, which provides evidence that the pre-equilibration between the catalyst precursor 1-13CH3-L and the active species 1-13CH3-(ethylene) is fast with respect to chain growth. The fraction of 1-13CH3-L that initiates chain growth is likely higher than the 60-85% determined from the 13C-labeled polymer chain ends since (a) chain walking results in in-chain incorporation of the 13C-label, (b) irreversible catalyst deactivation by formation of saturated (and partially volatile) alkanes diminishes the amount of 13CH3 groups incorporated into the polymer, and (c) palladium-bound 13CH3 groups, and more general palladium-bound alkyl(polymeryl) chains, partially transfer to phosphorus by reductive elimination. NMR and ESI-MS analyses of thermolysis reactions of 1-13CH3-L provide evidence that a mixture of phosphonium salts (13CH3)xP+(aryl)4-x (2-7) is formed in the absence of ethylene. In addition, isolation and characterization of the mixed bis(chelate) palladium complex [κ2-(anisyl)2P,O]Pd[κ2-(anisyl) (13CH3)P,O] (11) by NMR and X-ray diffraction analyses from these mixtures indicate that oxidative addition of phosphonium salts to palladium(0) species is also operative. The scrambling of palladium-bound carbyls and phosphorus-bound aryls is also relevant under NMR, as well as preparative reactor polymerization conditions exemplified by the X-ray diffraction analysis of [κ2-(anisyl)2P,O] Pd[κ2-(anisyl)(CH2CH3)P,O] (12) and [κ2-(anisyl)2P,O]Pd[κ2-(anisyl) ((CH2)3CH3)P,O] (13) isolated from pressure reactor polymerization experiments. In addition, ESI-MS analyses of reactor

  17. Structure, Aggregation, and Activity of a Covalent Insulin Dimer Formed During Storage of Neutral Formulation of Human Insulin.

    Science.gov (United States)

    Hjorth, Christian Fogt; Norrman, Mathias; Wahlund, Per-Olof; Benie, Andrew J; Petersen, Bent O; Jessen, Christian M; Pedersen, Thomas Å; Vestergaard, Kirsten; Steensgaard, Dorte B; Pedersen, Jan Skov; Naver, Helle; Hubálek, František; Poulsen, Christian; Otzen, Daniel

    2016-04-01

    A specific covalently linked dimeric species of insulin high molecular weight products (HMWPs), formed during prolonged incubation of a neutral pharmaceutical formulation of human insulin, were characterized in terms of tertiary structure, self-association, biological activity, and fibrillation properties. The dimer was formed by a covalent link between A21Asn and B29Lys. It was analyzed using static and dynamic light scattering and small-angle X-ray scattering to evaluate its self-association behavior. The tertiary structure was obtained using nuclear magnetic resonance and X-ray crystallography. The biological activity of HMWP was determined using 2 in vitro assays, and its influence on fibrillation was investigated using Thioflavin T assays. The dimer's tertiary structure was nearly identical to that of the noncovalent insulin dimer, and it was able to form hexamers in the presence of zinc. The dimer exhibited reduced propensity for self-association in the absence of zinc but significantly postponed the onset of fibrillation in insulin formulations. Consistent with its dimeric state, the tested species of HMWP showed little to no biological activity in the used assays. This study is the first detailed characterization of a specific type of human insulin HMWP formed during storage of a marketed pharmaceutical formulation. These results indicate that this specific type of HMWP is unlikely to antagonize the physical stability of the formulation, as HMWP retained a tertiary structure similar to the noncovalent dimer and participated in hexamer assembly in the presence of zinc. In addition, increasing amounts of HMWP reduce the rate of insulin fibrillation. PMID:26921119

  18. Comparison of Catalytic Activities of Carbon Supported Pt and Pt-Ru Catalysts for Methanol Oxidation in Neutral and Basic Media by Cyclic Voltammetry

    OpenAIRE

    KHAN, Abdul Sattar Ali; Ahmed, Riaz; MIRZA, Muhammad Latif

    2008-01-01

    The catalytic activities of an equal amount of 3 different carbon supported catalysts containing 10% Pt, 20% Pt + 10% Ru, and 30% Pt were evaluated in neutral and basic media for methanol oxidation by cyclic voltammetry. The prominent oxidation peak for methanol appeared in the forward anodic sweep at around 1.0 V in neutral medium, while in basic medium it appeared at significantly lower potential close to 0.2 V. The peak current for methanol oxidation was higher on a catalyst contai...

  19. Analysis of memory B cell responses and isolation of novel monoclonal antibodies with neutralizing breadth from HIV-1-infected individuals.

    Directory of Open Access Journals (Sweden)

    Davide Corti

    Full Text Available BACKGROUND: The isolation of human monoclonal antibodies (mAbs that neutralize a broad spectrum of primary HIV-1 isolates and the characterization of the human neutralizing antibody B cell response to HIV-1 infection are important goals that are central to the design of an effective antibody-based vaccine. METHODS AND FINDINGS: We immortalized IgG(+ memory B cells from individuals infected with diverse clades of HIV-1 and selected on the basis of plasma neutralization profiles that were cross-clade and relatively potent. Culture supernatants were screened using various recombinant forms of the envelope glycoproteins (Env in multiple parallel assays. We isolated 58 mAbs that were mapped to different Env surfaces, most of which showed neutralizing activity. One mAb in particular (HJ16 specific for a novel epitope proximal to the CD4 binding site on gp120 selectively neutralized a multi-clade panel of Tier-2 HIV-1 pseudoviruses, and demonstrated reactivity that was comparable in breadth, but distinct in neutralization specificity, to that of the other CD4 binding site-specific neutralizing mAb b12. A second mAb (HGN194 bound a conserved epitope in the V3 crown and neutralized all Tier-1 and a proportion of Tier-2 pseudoviruses tested, irrespective of clade. A third mAb (HK20 with broad neutralizing activity, particularly as a Fab fragment, recognized a highly conserved epitope in the HR-1 region of gp41, but showed striking assay-dependent selectivity in its activity. CONCLUSIONS: This study reveals that by using appropriate screening methods, a large proportion of memory B cells can be isolated that produce mAbs with HIV-1 neutralizing activity. Three of these mAbs show unusual breadth of neutralization and therefore add to the current panel of HIV-1 neutralizing antibodies with potential for passive protection and template-based vaccine design.

  20. Lignosulfonic acid exhibits broadly anti-HIV-1 activity--potential as a microbicide candidate for the prevention of HIV-1 sexual transmission.

    Directory of Open Access Journals (Sweden)

    Min Qiu

    Full Text Available Some secondary metabolites from plants show to have potent inhibitory activities against microbial pathogens, such as human immunodeficiency virus (HIV, herpes simplex virus (HSV, Treponema pallidum, Neisseria gonorrhoeae, etc. Here we report that lignosulfonic acid (LSA, a polymeric lignin derivative, exhibits potent and broad activity against HIV-1 isolates of diverse subtypes including two North America strains and a number of Chinese clinical isolates values ranging from 21.4 to 633 nM. Distinct from other polyanions, LSA functions as an entry inhibitor with multiple targets on viral gp120 as well as on host receptor CD4 and co-receptors CCR5/CXCR4. LSA blocks viral entry as determined by time-of-drug addiction and cell-cell fusion assays. Moreover, LSA inhibits CD4-gp120 interaction by blocking the binding of antibodies specific for CD4-binding sites (CD4bs and for the V3 loop of gp120. Similarly, LSA interacts with CCR5 and CXCR4 via its inhibition of specific anti-CCR5 and anti-CXCR4 antibodies, respectively. Interestingly, the combination of LSA with AZT and Nevirapine exhibits synergism in viral inhibition. For the purpose of microbicide development, LSA displays low in vitro cytotoxicity to human genital tract epithelial cells, does not stimulate NF-κB activation and has no significant up-regulation of IL-1α/β and IL-8 as compared with N-9. Lastly, LSA shows no adverse effect on the epithelial integrity and the junctional protein expression. Taken together, our findings suggest that LSA can be a potential candidate for tropical microbicide.

  1. A natural component from Euphorbia humifusa Willd displays novel, broad-spectrum anti-influenza activity by blocking nuclear export of viral ribonucleoprotein.

    Science.gov (United States)

    Chang, So Young; Park, Ji Hoon; Kim, Young Ho; Kang, Jong Seong; Min, Ji-Young

    2016-03-01

    The need to develop anti-influenza drugs with novel antiviral mechanisms is urgent because of the rapid rate of antigenic mutation and the emergence of drug-resistant viruses. We identified a novel anti-influenza molecule by screening 861 plant-derived natural components using a high-throughput image-based assay that measures inhibition of the influenza virus infection. 1,3,4,6-tetra-O-galloyl-β-D-glucopyranoside (TGBG) from Euphorbia humifusa Willd showed broad-spectrum anti-influenza activity against two seasonal influenza A strains, A/California/07/2009 (H1N1) and A/Perth/16/2009 (H3N2), and seasonal influenza B strain B/Florida/04/2006. We investigated the mode of action of TGBG using neuraminidase activity inhibition and time-of-addition assays, which evaluate the viral release and entry steps, respectively. We found that TGBG exhibits a novel antiviral mechanism that differs from the FDA-approved anti-influenza drugs oseltamivir which inhibits viral release, and amantadine which inhibits viral entry. Immunofluorescence assay demonstrated that TGBG significantly inhibits nuclear export of influenza nucleoproteins (NP) during the early stages of infection causing NP to accumulate in the nucleus. In addition, influenza-induced activation of the Akt signaling pathway was suppressed by TGBG in a dose-dependent manner. These data suggest that a putative mode of action of TGBG involves inhibition of viral ribonucleoprotein (vRNP) export from the nucleus to the cytoplasm consequently disrupting the assembly of progeny virions. In summary, TGBG has potential as novel anti-influenza therapeutic with a novel mechanism of action. PMID:26850850

  2. Design of Thermostable Beta-Propeller Phytases with Activity over a Broad Range of pHs and Their Overproduction by Pichia pastoris▿

    Science.gov (United States)

    Viader-Salvadó, José M.; Gallegos-López, Juan A.; Carreón-Treviño, J. Gerardo; Castillo-Galván, Miguel; Rojo-Domínguez, Arturo; Guerrero-Olazarán, Martha

    2010-01-01

    Thermostable phytases, which are active over broad pH ranges, may be useful as feed additives, since they can resist the temperatures used in the feed-pelleting process. We designed new beta-propeller phytases, using a structure-guided consensus approach, from a set of amino acid sequences from Bacillus phytases and engineered Pichia pastoris strains to overproduce the enzymes. The recombinant phytases were N-glycosylated, had the correct amino-terminal sequence, showed activity over a pH range of 2.5 to 9, showed a high residual activity after 10 min of heat treatment at 80°C and pH 5.5 or 7.5, and were more thermostable at pH 7.5 than a recombinant form of phytase C from Bacillus subtilis (GenBank accession no. AAC31775). A structural analysis suggested that the higher thermostability may be due to a larger number of hydrogen bonds and to the presence of P257 in a surface loop. In addition, D336 likely plays an important role in the thermostability of the phytases at pH 7.5. The recombinant phytases showed higher thermostability at pH 5.5 than at pH 7.5. This difference was likely due to a different protein total charge at pH 5.5 from that at pH 7.5. The recombinant beta-propeller phytases described here may have potential as feed additives and in the pretreatment of vegetable flours used as ingredients in animal diets. PMID:20693453

  3. Neutral Current $\

    CERN Document Server

    Chauhan, S; Singh, S K

    2011-01-01

    We calculate cross sections for the neutral current induced neutrino/antineutrino reaction from $^{208}Pb$ target and applied it to study Supernova neutrino event rates. The calculations are done in local density approximation taking into account Pauli blocking, Fermi motion effects and renormalization of weak transition strengths in the nuclear medium. The numerical results for the neutrino nucleus total cross sections have been averaged over the various Supernova neutrino/antineutrino fluxes available in literature.

  4. Constraining UV continuum slopes of active galactic nuclei with cloudy models of broad-line region extreme-ultraviolet emission lines

    Energy Technology Data Exchange (ETDEWEB)

    Moloney, Joshua [CASA, Department of Astrophysical and Planetary Sciences, University of Colorado, Boulder, CO 80309 (United States); Michael Shull, J., E-mail: joshua.moloney@colorado.edu, E-mail: michael.shull@colorado.edu [Also at Institute of Astronomy, University of Cambridge, Cambridge CB3 0HA, UK. (United Kingdom)

    2014-10-01

    Understanding the composition and structure of the broad-line region (BLR) of active galactic nuclei (AGNs) is important for answering many outstanding questions in supermassive black hole evolution, galaxy evolution, and ionization of the intergalactic medium. We used single-epoch UV spectra from the Cosmic Origins Spectrograph (COS) on the Hubble Space Telescope to measure EUV emission-line fluxes from four individual AGNs with 0.49 ≤ z ≤ 0.64, two AGNs with 0.32 ≤ z ≤ 0.40, and a composite of 159 AGNs. With the CLOUDY photoionization code, we calculated emission-line fluxes from BLR clouds with a range of density, hydrogen ionizing flux, and incident continuum spectral indices. The photoionization grids were fit to the observations using single-component and locally optimally emitting cloud (LOC) models. The LOC models provide good fits to the measured fluxes, while the single-component models do not. The UV spectral indices preferred by our LOC models are consistent with those measured from COS spectra. EUV emission lines such as N IV λ765, O II λ833, and O III λ834 originate primarily from gas with electron temperatures between 37,000 K and 55,000 K. This gas is found in BLR clouds with high hydrogen densities (n {sub H} ≥ 10{sup 12} cm{sup –3}) and hydrogen ionizing photon fluxes (Φ{sub H} ≥ 10{sup 22} cm{sup –2} s{sup –1}).

  5. Effects of dissolved hydrogen and elastic and plastic deformation on active dissolution of pipeline steel in anaerobic groundwater of near-neutral pH

    International Nuclear Information System (INIS)

    The mechano-electrochemical effects of deformation and hydrogen on active dissolution of pipeline steel in near-neutral pH groundwater are described. Thermodynamic analysis shows that the free energy increment due to elastic deformation is insufficient to alter active dissolution rate remarkably. The synergistic effect of stress field and dissolved hydrogen on active dissolution (corrosion) is negligible. The effect of plastic deformation on corrosion relies heavily on the heterogeneity of dislocation structures formed in the deformation. The plastic deformation cannot significantly change the corrosion rate at the open circuit potential. There is good agreement between these theoretical predictions and experimental observations, indicating that the stress corrosion cracking of pipeline steel in the anaerobic groundwater of near-neutral pH is unlikely to be related to the hydrogen-facilitated anodic dissolution mechanism

  6. Effects of dissolved hydrogen and elastic and plastic deformation on active dissolution of pipeline steel in anaerobic groundwater of near-neutral pH

    Energy Technology Data Exchange (ETDEWEB)

    Lu, B.T. [Department of Chemical and Materials Engineering, University of Alberta, Edmonton, Alta., T6G 2G6 (Canada); Luo, J.L. [Department of Chemical and Materials Engineering, University of Alberta, Edmonton, Alta., T6G 2G6 (Canada)], E-mail: jingli.luo@ualberta.ca; Norton, P.R. [Department of Chemistry, University of Western Ontario, London, Ont., N6A 5B7 (Canada); Ma, H.Y. [Department of Chemistry, Shandong University, Jinan, Shandong 250100 (China)

    2009-01-15

    The mechano-electrochemical effects of deformation and hydrogen on active dissolution of pipeline steel in near-neutral pH groundwater are described. Thermodynamic analysis shows that the free energy increment due to elastic deformation is insufficient to alter active dissolution rate remarkably. The synergistic effect of stress field and dissolved hydrogen on active dissolution (corrosion) is negligible. The effect of plastic deformation on corrosion relies heavily on the heterogeneity of dislocation structures formed in the deformation. The plastic deformation cannot significantly change the corrosion rate at the open circuit potential. There is good agreement between these theoretical predictions and experimental observations, indicating that the stress corrosion cracking of pipeline steel in the anaerobic groundwater of near-neutral pH is unlikely to be related to the hydrogen-facilitated anodic dissolution mechanism.

  7. Synthesis, Characterization, and In Vitro and In Vivo Evaluations of 4-(N-Docosahexaenoyl 2′, 2′-Difluorodeoxycytidine with Potent and Broad-Spectrum Antitumor Activity

    Directory of Open Access Journals (Sweden)

    Youssef W. Naguib

    2016-01-01

    Full Text Available In this study, a new compound, 4-(N-docosahexaenoyl 2′, 2′-difluorodeoxycytidine (DHA-dFdC, was synthesized and characterized. Its antitumor activity was evaluated in cell culture and in mouse models of pancreatic cancer. DHA-dFdC is a poorly soluble, pale yellow waxy solid, with a molecular mass of 573.3 Da and a melting point of about 96°C. The activation energy for the degradation of DHA-dFdC in an aqueous Tween 80–based solution is 12.86 kcal/mol, whereas its stability is significantly higher in the presence of vitamin E. NCI-60 DTP Human Tumor Cell Line Screening revealed that DHA-dFdC has potent and broad-spectrum antitumor activity, especially in leukemia, renal, and central nervous system cancer cell lines. In human and murine pancreatic cancer cell lines, the IC50 value of DHA-dFdC was up to 105-fold lower than that of dFdC. The elimination of DHA-dFdC in mouse plasma appeared to follow a biexponential model, with a terminal phase t1/2 of about 58 minutes. DHA-dFdC significantly extended the survival of genetically engineered mice that spontaneously develop pancreatic ductal adenocarcinoma. In nude mice with subcutaneously implanted human Panc-1 pancreatic tumors, the antitumor activity of DHA-dFdC was significantly stronger than the molar equivalent of dFdC alone, DHA alone, or the physical mixture of them (1:1, molar ratio. DHA-dFdC also significantly inhibited the growth of Panc-1 tumors orthotopically implanted in the pancreas of nude mice, whereas the molar equivalent dose of dFdC alone did not show any significant activity. DHA-dFdC is a promising compound for the potential treatment of cancers in organs such as the pancreas.

  8. Search for active neutrino disappearance using neutral-current interactions in the MINOS long-baseline experiment

    International Nuclear Information System (INIS)

    We have measured the rates and spectra of neutral-current neutrino interactions in the MINOS detectors, which are separated by 734 km. A depletion in the rate at the far site would indicate mixing between νμ and a sterile particle. The depletion of the total neutral-current event rate at the far site is limited to be below 17% at 90% confidence level without νe appearance. Assuming oscillations occur at a single mass-squared splitting, a fit to the neutral- and charged-current energy spectra shows the fraction of νμ oscillating to a sterile neutrino is 0.28-0.28+0.25(stat.+syst.). Including νe appearance at the current experimental upper bound limits the depletion to be below 21% at 90% confidence level and the fit fraction of νμ oscillating to a sterile neutrino is 0.43-0.27+0.23(stat.+syst.)

  9. A COMPARATIVE STUDY OF OPTICAL/ULTRAVIOLET VARIABILITY OF NARROW-LINE SEYFERT 1 AND BROAD-LINE SEYFERT 1 ACTIVE GALACTIC NUCLEI

    International Nuclear Information System (INIS)

    The ensemble optical/ultraviolet (UV) variability of narrow-line Seyfert 1 (NLS1)-type active galactic nuclei (AGNs) is investigated, based on a sample selected from the Sloan Digital Sky Survey (SDSS) Stripe 82 region with multi-epoch photometric scanning data. As a comparison, a control sample of broad-line Seyfert 1 (BLS1)-type AGNs is also incorporated. To quantify properly the intrinsic variation amplitudes and their uncertainties, a novel method of parametric maximum likelihood is introduced that has, as we argued, certain virtues over previously used methods. The majority of NLS1-type AGNs exhibit significant variability on timescales from about 10 days to a few years with, however, smaller amplitudes on average compared to BLS1-type AGNs. About 20 NLS1-type AGNs that show relatively large variations are presented and may deserve future monitoring observations, for instance, reverberation mapping. The averaged structure functions of variability, constructed using the same maximum likelihood method, show remarkable similarity in shape for the two types of AGNs on timescales longer than about 10 days, which can be approximated by a power law or an exponential function. This, along with other similar properties, such as the wavelength-dependent variability, is indicative of a common dominant mechanism responsible for the long-term optical/UV variability of both NLS1- and BLS1-type AGNs. Toward the short timescales, however, there is tentative evidence that the structure function of NLS1-type AGNs continues to decline, whereas that of BLS1-type AGNs flattens with some residual variability on timescales of days. If this can be confirmed, it may suggest that an alternative mechanism, such as X-ray reprocessing, starts to dominate in BLS1-type AGNs, but not in NLS1-type AGNs, on such timescales.

  10. ACDOS1: a computer code to calculate dose rates from neutron activation of neutral beamlines and other fusion-reactor components

    International Nuclear Information System (INIS)

    A computer code has been written to calculate neutron induced activation of neutral-beam injector components and the corresponding dose rates as a function of geometry, component composition, and time after shutdown. The code, ACDOS1, was written in FORTRAN IV to calculate both activity and dose rates for up to 30 target nuclides and 50 neutron groups. Sufficient versatility has also been incorporated into the code to make it applicable to a variety of general activation problems due to neutrons of energy less than 20 MeV

  11. A New Derivative of Valproic Acid Amide Possesses a Broad-spectrum Antiseizure Profile and Unique Activity Against Status Epilepticus and Organophosphate Neuronal Damage

    Science.gov (United States)

    White, H. Steve; Alex, Anitha B.; Pollock, Amanda; Hen, Naama; Shekh-Ahmad, Tawfeeq; Wilcox, Karen S.; McDonough, John H.; Stables, James P.; Kaufmann, Dan; Yagen, Boris; Bialer, Meir

    2011-01-01

    displayed anticonvulsant activity in the rat pilocarpine model of SE. Thirty minutes after the induction of SE, the calculated rat-ED50 for SPD against convulsive SE in this model was 84mg/kg. SPD was not neuroprotective in the organotypic hippocampal slice preparation; however, it did display hippocampal neuroprotection in both SE models and cognitive sparing in the MWM which was associated with its antiseizure effect against pilocarpine-induced SE. When administered 20 and 40min after SE onset, SPD (100-174mg/kg) produced long-lasting efficacy (e.g., 4-8hr) against soman-induced convulsive and electrographic SE in both rats and guinea pigs. SPD-ED50 values in guinea pigs were 67mg/kg and 92mg/kg at when administered at SE onset or 40min after SE onset, respectively. Assuming linear PK, the PK-PD results (rats) suggests that effective SPD plasma levels ranged between 8-40mg/L (20 min post onset of soman-induced seizures) and 12-50mg/L (40 min post onset of soman-induced seizures). The time to peak (tmax) pharmacodynamic effect (PD-tmax) occurred after the PK-tmax thereby suggesting that SPD undergoes slow distribution to extra-plasmatic sites likely responsible for SPD’s antiseizure activity. Significance The results demonstrate that SPD is a broad-spectrum antiseizure compound that blocks SE induced by pilocarpine and soman and affords in vivo neuroprotection that is associated with cognitive sparing. Its activity against SE is superior to diazepam in terms of rapid onset, potency and its effect on animal mortality and functional improvement. PMID:22150444

  12. Cochlear microphonic broad tuning curves

    Science.gov (United States)

    Ayat, Mohammad; Teal, Paul D.; Searchfield, Grant D.; Razali, Najwani

    2015-12-01

    It is known that the cochlear microphonic voltage exhibits much broader tuning than does the basilar membrane motion. The most commonly used explanation for this is that when an electrode is inserted at a particular point inside the scala media, the microphonic potentials of neighbouring hair cells have different phases, leading to cancelation at the electrodes location. In situ recording of functioning outer hair cells (OHCs) for investigating this hypothesis is exceptionally difficult. Therefore, to investigate the discrepancy between the tuning curves of the basilar membrane and those of the cochlear microphonic, and the effect of phase cancellation of adjacent hair cells on the broadness of the cochlear microphonic tuning curves, we use an electromechanical model of the cochlea to devise an experiment. We explore the effect of adjacent hair cells (i.e., longitudinal phase cancellation) on the broadness of the cochlear microphonic tuning curves in different locations. The results of the experiment indicate that active longitudinal coupling (i.e., coupling with active adjacent outer hair cells) only slightly changes the broadness of the CM tuning curves. The results also demonstrate that there is a π phase difference between the potentials produced by the hair bundle and the soma near the place associated with the characteristic frequency based on place-frequency maps (i.e., the best place). We suggest that the transversal phase cancellation (caused by the phase difference between the hair bundle and the soma) plays a far more important role than longitudinal phase cancellation in the broadness of the cochlear microphonic tuning curves. Moreover, by increasing the modelled longitudinal resistance resulting the cochlear microphonic curves exhibiting sharper tuning. The results of the simulations suggest that the passive network of the organ of Corti determines the phase difference between the hair bundle and soma, and hence determines the sharpness of the

  13. Modified iron-carbon as heterogeneous electro-Fenton catalyst for organic pollutant degradation in near neutral pH condition: Characterization, degradation activity and stability

    International Nuclear Information System (INIS)

    Polytetrafluoroethylene (PTFE) was firstly used to modify the surface characteristics of Fe-C particles and acted as catalyst to degrade 2,4-dichlorophenol (2,4-DCP) by heterogeneous electro-Fenton (EF) in near neutral pH condition. Fe-C particles before and after PTFE modification, and after 15 times consecutive degradations were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and energy dispersive X-ray (EDX) spectrometry. The modified Fe-C exhibited a good activity for degradation of 120 mg/L 2,4-DCP in near neutral pH condition, achieving over 95% removal efficiency within 120 min under the conditions of Fe-C 6 g/L, current intensity 100 mA and initial pH 6.7. In this heterogeneous EF system, a significant synergetic effect between anodic oxidation and single Fe-C micro-electrolysis was obtained, which attributed to the effective EF oxidation at favorable acidic pH condition that triggered by anodic oxidation. 15 times consecutive runs demonstrated the 2,4-DCP degradation efficiency was stable while the iron leaching ratio was relatively low. Account for the catalytic activity, life span and inexpensive cost, the PTFE modified Fe-C was potential for industrial application as a good electro-Fenton catalyst to abate biorefractory pollutants in neutral pH condition

  14. Production and characterization of a broad-specificity polyclonal antibody for O,O-diethyl organophosphorus pesticides and a quantitative structure-activity relationship study of antibody recognition

    Science.gov (United States)

    Polyclonal antibody (PAb) with broad-specificity for O,O-diethyl organophosphorus pesticides (OPs) against a generic hapten, 4-(diethoxyphosphoro thioyloxy) benzoic acid, was produced. The obtained PAb showed high sensitivity to seven commonly used O,O-diethyl OPs in a competitive indirect enzyme-l...

  15. Learning from the 2009 H1N1 pandemic: prospects for more broadly effective influenza vaccines

    Institute of Scientific and Technical Information of China (English)

    Ethan C. Settembre; Philip R. Dormitzer; Rino Rappuoli

    2011-01-01

    Calls to develop a universal influenza vaccine have increased in the wake of the 2009 H1 N1 influenza pandemic. This demand comes at a time when analyses of the human antibody repertoire, informed by structures of complexes between broadly neutralizing antibodies and influenza hemagglutinin, have revealed the target of a class of broadly neutralizing antibodies. Recent studies suggest a path forward to more broadly protective influenza vaccines.%@@ Calls to develop a universal influenza vaccine have increased in the wake of the 2009 H1 N1 influenza pandemic.This demand comes at a time when analyses of the human antibody repertoire, informed by structures of complexes between broadly neutralizing antibodies and influenza hemagglutinin, have revealed the target of a class of broadly neutralizing antibodies.Recent studies suggest a path forward to more broadly protective influenza vaccines.

  16. Neutral currents

    International Nuclear Information System (INIS)

    A short survey of the new experimental data on weak neutral currents is given, followed by a comparison with modern theoretical models. Cross sections of the anti νsub(e)e → anti νsub(e)e, anti νsub(μ)e→ νsub(μ)e, νp → νp and anti νp → anti νp elastic scattering as well as inclusive cross sections of the ν+N → ν+X and anti ν+N → anti ν+X deep inelastic scattering are presented. On the basis of the comparison the Weinberg-Salam model is concluded to be in a good agreement with the shape of the cross sections. Six-quark vector models appear to be ruled out. The five-quark model due to Achiman, Koller and Walsh and two versions of the Gursey-Sikivie model satisfactorily account for the observed data in shape and in magnitude

  17. The Myth of Neutral Taxation

    OpenAIRE

    Murray N. Rothbard

    1981-01-01

    Economists have long believed that government’s tax and expendi- ture policy either is, or can readily be made to be, neutral to the market. Free-market economists have advocated such neutrality of government, and even economists favoring redistributive actions by government have believed that the service activities and the re- distributive activities of government can easily be distinguished, at least in concept. The purpose of this paper is to examine the nature and implications of fiscal...

  18. Effects of neutral particle beam on nano-crystalline silicon thin films, with application to thin film transistor backplane for flexible active matrix organic light emitting diodes

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Jin Nyoung; Song, Byoung Chul; Lee, Dong Hyeok [Dept. of Display and Semiconductor Physics, Korea University, Chungnam (Korea, Republic of); Yoo, Suk Jae; Lee, Bonju [National Fusion Research Institute, 52, Yuseong-Gu, Deajeon, 305-333 (Korea, Republic of); Hong, MunPyo, E-mail: goodmoon@korea.ac.kr [Dept. of Display and Semiconductor Physics, Korea University, Chungnam (Korea, Republic of)

    2011-08-01

    A novel deposition process for nano-crystalline silicon (nc-Si) thin films was developed using neutral beam assisted chemical vapor deposition (NBaCVD) technology for the application of the thin film transistor (TFT) backplane of flexible active matrix organic light emitting diode (AMOLED). During the formation of a nc-Si thin film, the energetic particles enhance nano-sized crystalline rather microcrystalline Si in thin films. Neutral Particle Beam (NPB) affects the crystallinity in two ways: (1) NPB energy enhances nano-crystallinity through kinetic energy transfer and chemical annealing, and (2) heavier NPB (such as Ar) induces damage and amorphization through energetic particle impinging. Nc-Si thin film properties effectively can be changed by the reflector bias. As increase of NPB energy limits growing the crystalline, the performance of TFT supports this NPB behavior. The results of nc-Si TFT by NBaCVD demonstrate the technical potentials of neutral beam based processes for achieving high stability and reduced leakage in TFT backplanes for AMOLEDs.

  19. Iron-Carbonyl-Catalyzed Redox-Neutral [4+2] Annulation of N-H Imines and Internal Alkynes by C-H Bond Activation.

    Science.gov (United States)

    Jia, Teng; Zhao, Chongyang; He, Ruoyu; Chen, Hui; Wang, Congyang

    2016-04-18

    Stoichiometric C-H bond activation of arenes mediated by iron carbonyls was reported by Pauson as early as in 1965, yet the catalytic C-H transformations have not been developed. Herein, an iron-catalyzed annulation of N-H imines and internal alkynes to furnish cis-3,4-dihydroisoquinolines is described, and represents the first iron-carbonyl-catalyzed C-H activation reaction of arenes. Remarkablely, this is also the first redox-neutral [4+2] annulation of imines and alkynes proceeding by C-H activation. The reaction also features only cis stereoselectivity and excellent atom economy as neither base, nor external ligand, nor additive is required. Experimental and theoretical studies reveal an oxidative addition mechanism for C-H bond activation to afford a dinuclear ferracycle and a synergetic diiron-promoted H-transfer to the alkyne as the turnover-determining step. PMID:27002210

  20. Role of individual phosphorylation sites for the 14-3-3-protein-dependent activation of yeast neutral trehalase Nth1

    Czech Academy of Sciences Publication Activity Database

    Veisová, Dana; Macáková, Eva; Řežábková, Lenka; Šulc, Miroslav; Vácha, Petr; Sychrová, Hana; Obšil, T.; Obšilová, Veronika

    2012-01-01

    Roč. 443, č. 3 (2012), s. 663-670. ISSN 0264-6021 R&D Projects: GA ČR(CZ) GAP207/11/0455; GA AV ČR(CZ) IAA500110801 Grant ostatní: Univerzita Karlova(CZ) 350111 Institutional research plan: CEZ:AV0Z50110509; CEZ:AV0Z50200510 Keywords : 14-3-3 protein * Bmh * neutral trehalase (Nth1) * enzymatic activity * phosphorylation * Saccharomyces cerevisiae Subject RIV: CE - Biochemistry Impact factor: 4.654, year: 2012

  1. The MK III actively cooled duct liner for the JET neutral beam line: Thermo-mechanical performance and lifetime estimation

    International Nuclear Information System (INIS)

    This paper describes the analyses performed to investigate and validate the proposed design for the updated JET MKIII duct side liner, which will replace the present inertial cooled one in the frame of the EP2 neutral beam enhancement project. The thermal-hydraulic and thermo-mechanical performance of a duct liner's generic module, under various loading scenarios has been assessed. Due to difference in scale between a generic liner module length and the relevant load bearing section thickness (∼1.2 m against 4 mm) two different scale FE models have been assessed, the first ones to evaluate the overall reactions and displacements and the others to calculate concentrated stresses in the most loaded sections. Conformity to ITER design criteria has been verified for both monotonic and cyclic loads. The effects of fatigue have been considered and an operational life of 8.5 years is predicted for the liner

  2. [In vitro and in vivo activity of a combination of clavulanic acid and amoxicillin against Klebsiella pneumoniae producing extended broad-spectrum betalactamase (CTX-1, SHV-3, SHV-4)].

    Science.gov (United States)

    Migueres, M L; Ronco, E; Guenounou, M; Philippon, A

    1989-05-01

    In vitro activity of an aminopenicillin (amoxicillin or ampicillin) combined with a betalactamase inhibitor (clavulanic acid or sulbactam, 2 mg/l) was examined against 39 strains of K. pneumoniae producing 3 types of extended broad spectrum betalactamases (CTX-1, SHV-3, SHV-4). Clavulanic acid produces the best synergistic effect. The in vivo activity of Augmentin (amoxicillin + clavulanic acid), 1 g once or twice a day, during 10 +/- 3 days was evaluated on 10 cases urinary tract infections in paraplegic patients. After 3 days, no leucocyturia was observed and bacteria were no more detected. The inhibitory effect of clavulanic acid for the extended broad-spectrum betalactamases shows that such an association could be probably chosen as well for treatment urinary infection. PMID:2674869

  3. Immune Response to Recombinant Capsid Proteins of Adenovirus in Humans: Antifiber and Anti-Penton Base Antibodies Have a Synergistic Effect on Neutralizing Activity

    Science.gov (United States)

    Gahéry-Ségard, Hanne; Farace, Françoise; Godfrin, Dominique; Gaston, Jesintha; Lengagne, Renée; Tursz, Thomas; Boulanger, Pierre; Guillet, Jean-Gérard

    1998-01-01

    Replication-deficient adenovirus used in humans for gene therapy induces a strong immune response to the vector, resulting in transient recombinant protein expression and the blocking of gene transfer upon a second administration. Therefore, in this study we examined in detail the capsid-specific humoral immune response in sera of patients with lung cancer who had been given one dose of a replication-defective adenovirus. We analyzed the immune response to the three major components of the viral capsid, hexon (Hx), penton base (Pb), and fiber (Fi). A longitudinal study of the humoral response assayed on adenovirus particle-coated enzyme-linked immunosorbent assay plates showed that patients had preexisting immunity to adenovirus prior to the administration of adenovirus–β-gal. The level of the response increased in three patients after adenovirus administration and remained at a maximum after three months. One patient had a strong immune response to adenovirus prior to treatment, and this response was unaffected by adenovirus administration. Sera collected from the patients were assayed for recognition of each individual viral capsid protein to determine more precisely the molecular basis of the humoral immune response. Clear differences existed in the humoral response to the three major components of the viral capsid in serum from humans. Sequential appearance of these antibodies was observed: anti-Fi antibodies appeared first, followed by anti-Pb antibodies and then by anti-Hx antibodies. Moreover, anti-Fi antibodies preferentially recognized the native trimeric form of Fi protein, suggesting that they recognized conformational epitopes. Our results showed that sera with no neutralizing activity contained only anti-Fi antibodies. In contrast, neutralizing activity was only obtained with sera containing anti-Fi and anti-Pb antibodies. More importantly, we showed that anti-native Fi and anti-Pb antibodies had a synergistic effect on neutralization. The

  4. The broad-spectrum metalloproteinase inhibitor BB-94 inhibits growth, HER3 and Erk activation in fulvestrant-resistant breast cancer cell lines

    DEFF Research Database (Denmark)

    Kirkegaard, Tove; Yde, Christina Westmose; Kveiborg, Marie; Lykkesfeldt, Anne E

    2014-01-01

    consequently increased cell growth. In this study, we investigated the importance of HER receptors, in particular HER3, and HER ligand shedding for growth and signaling in human MCF-7 breast cancer cells and MCF-7-derived sublines resistant to the antiestrogen fulvestrant. The HER3/HER4 ligand heregulin 1β...... induced phosphorylation of HER3, Akt and Erk, and partly rescued fulvestrant-inhibited growth of MCF-7 cells. HER3 ligands were found to be produced and shed from the fulvestrant-resistant cells as conditioned medium from fulvestrant-resistant MCF-7 cells induced phosphorylation of HER3 and Akt in MCF-7...... cells. This was prevented by treatment of resistant cells with the metalloproteinase inhibitor TAPI-2. Only the broad-spectrum metalloproteinase inhibitor BB-94, and not the more selective inhibitors GM6001 or TAPI-2, which inhibited shedding of the HER ligands produced by the fulvestrant...

  5. Improved volatile fatty acids anaerobic production from waste activated sludge by pH regulation: Alkaline or neutral pH?

    Science.gov (United States)

    Ma, Huijun; Chen, Xingchun; Liu, He; Liu, Hongbo; Fu, Bo

    2016-02-01

    In this study, the anaerobic fermentation was carried out for volatile fatty acids (VFAs) production at different pH (between 7.0 and 10.0) conditions with untreated sludge and heat-alkaline pretreated waste activated sludge. In the fermentation with untreated sludge, the extent of hydrolysis of organic matters and extent of acidification at alkaline pH are 54.37% and 30.37%, respectively, resulting in the highest VFAs yield at 235.46mg COD/gVS of three pH conditions. In the fermentation with heat-alkaline pretreated sludge, the acidification rate and VFAs yield at neutral pH are 30.98% and 240.14mg COD/gVS, respectively, which are higher than that at other pH conditions. With the glucose or bovine serum albumin as substrate for VFAs production, the neutral pH showed a higher VFAs concentration than the alkaline pH condition. The results of terminal restriction fragment length polymorphism (T-RFLP) analysis indicated that the alkaline pH caused low microbial richness. Based on the results in this study, we demonstrated that the alkaline pH is favor of hydrolysis of organic matter in sludge while neutral pH improved the acidogenesis for the VFAs production from sludge. Our finding is obvious different to the previous research and helpful for the understanding of how heat-alkaline pretreatment and alkaline fermentation influence the VFAs production, and beneficial to the development of VFAs production process. PMID:26652215

  6. Ebola virus-like particles produced in insect cells exhibit dendritic cell stimulating activity and induce neutralizing antibodies

    International Nuclear Information System (INIS)

    Recombinant baculoviruses (rBV) expressing Ebola virus VP40 (rBV-VP40) or GP (rBV-GP) proteins were generated. Infection of Sf9 insect cells by rBV-VP40 led to assembly and budding of filamentous particles from the cell surface as shown by electron microscopy. Ebola virus-like particles (VLPs) were produced by coinfection of Sf9 cells with rBV-VP40 and rBV-GP, and incorporation of Ebola GP into VLPs was demonstrated by SDS-PAGE and Western blot analysis. Recombinant baculovirus infection of insect cells yielded high levels of VLPs, which were shown to stimulate cytokine secretion from human dendritic cells similar to VLPs produced in mammalian cells. The immunogenicity of Ebola VLPs produced in insect cells was evaluated by immunization of mice. Analysis of antibody responses showed that most of the GP-specific antibodies were of the IgG2a subtype, while no significant level of IgG1 subtype antibodies specific for GP was induced, indicating the induction of a Th1-biased immune response. Furthermore, sera from Ebola VLP immunized mice were able to block infection by Ebola GP pseudotyped HIV virus in a single round infection assay, indicating that a neutralizing antibody against the Ebola GP protein was induced. These results show that production of Ebola VLPs in insect cells using recombinant baculoviruses represents a promising approach for vaccine development against Ebola virus infection

  7. Improvement of activated carbons as oxygen reduction catalysts in neutral solutions by ammonia gas treatment and their performance in microbial fuel cells

    KAUST Repository

    Watson, Valerie J.

    2013-11-01

    Commercially available activated carbon (AC) powders from different precursor materials (peat, coconut shell, coal, and hardwood) were treated with ammonia gas at 700 C to improve their performance as oxygen reduction catalysts in neutral pH solutions used in microbial fuel cells (MFCs). The ammonia treated ACs exhibited better catalytic performance in rotating ring-disk electrode tests than their untreated precursors, with the bituminous based AC most improved, with an onset potential of Eonset = 0.12 V (untreated, Eonset = 0.08 V) and n = 3.9 electrons transferred in oxygen reduction (untreated, n = 3.6), and the hardwood based AC (treated, E onset = 0.03 V, n = 3.3; untreated, Eonset = -0.04 V, n = 3.0). Ammonia treatment decreased oxygen content by 29-58%, increased nitrogen content to 1.8 atomic %, and increased the basicity of the bituminous, peat, and hardwood ACs. The treated coal based AC cathodes had higher maximum power densities in MFCs (2450 ± 40 mW m-2) than the other AC cathodes or a Pt/C cathode (2100 ± 1 mW m-2). These results show that reduced oxygen abundance and increased nitrogen functionalities on the AC surface can increase catalytic performance for oxygen reduction in neutral media. © 2013 Elsevier B.V. All rights reserved.

  8. Improvement of activated carbons as oxygen reduction catalysts in neutral solutions by ammonia gas treatment and their performance in microbial fuel cells

    Science.gov (United States)

    Watson, Valerie J.; Nieto Delgado, Cesar; Logan, Bruce E.

    2013-11-01

    Commercially available activated carbon (AC) powders from different precursor materials (peat, coconut shell, coal, and hardwood) were treated with ammonia gas at 700 °C to improve their performance as oxygen reduction catalysts in neutral pH solutions used in microbial fuel cells (MFCs). The ammonia treated ACs exhibited better catalytic performance in rotating ring-disk electrode tests than their untreated precursors, with the bituminous based AC most improved, with an onset potential of Eonset = 0.12 V (untreated, Eonset = 0.08 V) and n = 3.9 electrons transferred in oxygen reduction (untreated, n = 3.6), and the hardwood based AC (treated, Eonset = 0.03 V, n = 3.3; untreated, Eonset = -0.04 V, n = 3.0). Ammonia treatment decreased oxygen content by 29-58%, increased nitrogen content to 1.8 atomic %, and increased the basicity of the bituminous, peat, and hardwood ACs. The treated coal based AC cathodes had higher maximum power densities in MFCs (2450 ± 40 mW m-2) than the other AC cathodes or a Pt/C cathode (2100 ± 1 mW m-2). These results show that reduced oxygen abundance and increased nitrogen functionalities on the AC surface can increase catalytic performance for oxygen reduction in neutral media.

  9. On the disappearance of broad-line region in low-luminosity active galactic nuclei: the role of the outflows from advection dominated accretion flows

    CERN Document Server

    Cao, Xinwu

    2010-01-01

    The broad-line region (BLR) disappears in many low-luminosity AGNs, the reason of which is still controversial. The BLRs in AGNs are believed to be associated with the outflows from the accretion disks. Most of the low-luminosity AGNs (LLAGNs) contain advection dominated accretion flows (ADAFs), which are very hot and have a positive Bernoulli parameter. ADAFs are therefore associated with strong outflows. We estimate the cooling of the outflows from the ADAFs, and find that the gases in such hot outflows always cannot be cooled efficiently by bremsstrahlung radiation. The ADAF may co-exist with the standard disk, i.e., the inner ADAF connects to the outer thin accretion disk at radius R_tr, in the sources accreting at slightly lower than the critical rate. For the ADAFs with >0.001 L_edd, a secondary small inner cold disk is suggested to co-exist with the ADAF due to the condensation process. We estimate the Compton cooling of the outflow, of which the soft seed photons either come from the outer cold disk o...

  10. Squalamine as a broad-spectrum systemic antiviral agent with therapeutic potential.

    Science.gov (United States)

    Zasloff, Michael; Adams, A Paige; Beckerman, Bernard; Campbell, Ann; Han, Ziying; Luijten, Erik; Meza, Isaura; Julander, Justin; Mishra, Abhijit; Qu, Wei; Taylor, John M; Weaver, Scott C; Wong, Gerard C L

    2011-09-20

    Antiviral compounds that increase the resistance of host tissues represent an attractive class of therapeutic. Here, we show that squalamine, a compound previously isolated from the tissues of the dogfish shark (Squalus acanthias) and the sea lamprey (Petromyzon marinus), exhibits broad-spectrum antiviral activity against human pathogens, which were studied in vitro as well as in vivo. Both RNA- and DNA-enveloped viruses are shown to be susceptible. The proposed mechanism involves the capacity of squalamine, a cationic amphipathic sterol, to neutralize the negative electrostatic surface charge of intracellular membranes in a way that renders the cell less effective in supporting viral replication. Because squalamine can be readily synthesized and has a known safety profile in man, we believe its potential as a broad-spectrum human antiviral agent should be explored. PMID:21930925

  11. In Vitro Activities of Antibiotics Alone and in Combination against Brucella melitensis at Neutral and Acidic pHs

    OpenAIRE

    Akova, Murat; Gür, Deniz; Livermore, David M; Kocagöz, Tanil; Akalin, H. Erdal

    1999-01-01

    Brucellae survive acidic pHs in phagolysosomes. Azithromycin, streptomycin, and quinolones were active against Brucella melitensis at pH 7.0 but not at pH 5.0; rifampin and doxycycline retained activity at pH 5.0. Regardless of pH, azithromycin-rifampin and ofloxacin-rifampin showed less synergy than established streptomycin-doxycycline and rifampin-doxycycline combinations.

  12. Neutralization of pharmacological and toxic activities of Bothrops jararacussu snake venom and isolated myotoxins by Serjania erecta methanolic extract and its fractions

    Directory of Open Access Journals (Sweden)

    RS Fernandes

    2011-01-01

    Full Text Available Most of the snakebites recorded in Brazil are caused by the Bothrops genus. Given that the local tissue damage caused by this genus cannot be treated by antivenom therapy, numerous studies are focusing on supplementary alternatives, such as the use of medicinal plants. Serjania erecta has already demonstrated anti-inflammatory, antiseptic and healing properties. In the current study, the aerial parts of S. erecta were extracted with methanol, then submitted to chromatographic fractionation on a Sephadex LH20 column and eluted with methanol, which resulted in four main fractions. The crude extract and fractions neutralized the toxic activities of Bothrops jararacussu snake venom and isolated myotoxins (BthTX-I and II. Results showed that phospholipase A2, fibrinogenolytic, myotoxic and hemorrhagic activities were inhibited by the extract. Moreover, the myotoxic and edematous activities induced by BthTX-I, and phospholipase A2 activity induced by BthTX-II, were inhibited by the extract of S. erecta and its fraction. The clotting time on bovine plasma was significantly prolonged by the inhibitory action of fractions SF3 and SF4. This extract is a promising source of natural inhibitors, such as flavonoids and tannins, which act by forming complexes with metal ions and proteins, inhibiting the action of serineproteases, metalloproteases and phospholipases A2.

  13. Effect of the scan rate on the kinetic parameters of active dissolution and passivation of iron in a neutral solution

    International Nuclear Information System (INIS)

    The effect of polarization rate (V = 0.2-100 mV/s) of a rotating disk-like electrode (with rotation rate v = 6000 rot/min) on kinetics of active anodic dissolution and active-passive transition of Armco iron in deaerated borate duffer solution with 7.40 pH is studied by the method of cyclic volt-amperometry. It is shown that in the whole V range studied without diffusion limitations the rate of active dissolution and formation of a primary passivating film is determined by slow electrochemical stages of electron transport, and a cyclic volt-ampere curve is a nonstationary thermodynamically nonequilibrium one. A linear growth of current at anodic maximum and a positive shift of its potential with a lg V increase are observed

  14. A single substitution in 5'-untranslated region of plcB is involved in enhanced broad-range phospholipase C activity in Listeria monocytogenes strain H4

    Institute of Scientific and Technical Information of China (English)

    Fan Bai; Jianshun Chen; Qiaomiao Chen; Xiaokai Luo; Weihuan Fang; Lingli Jiang

    2011-01-01

    To examine whether the in vitro phospholipase activity in Listeria monocytogenes strain H4 was due to two nucleotide mutations (C to T at position -26 and A to G at position + 1) in plcB or resulted from regulatory activation, two mutants H4-plcB-ml (single mutation at position -26) and H4-plcB-m2 (substitution at both positions) were constructed by site-directed mutagenesis. It was found that the two mutants had significantly lower transcription of plcB than their parent strain H4 and did not show phospho-Hpase activity on the egg yolk agar, implying that the apparent phospholipase activity of strain H4 could be related to single substitution at position -26 ofplcB, most probably by its 5t-untranslated region (5'-UTR) regulation mechanism. Tn917-based transposon mutagenesis generated eight L. monocytogenes mutants lacking phospholipase activity among 560 mutant candidates. Seven mutants had transposon insertion into prfA (encoding positive regulatory factor A) open reading frame, whereas only one mutant (WF-L127) was inserted into the P1 promoter region ofprfA (prfAP1). Transcription of major virulence genes was significantly lower in both types of mutants than in their parent strain H4. Disruption of prfAP1 in WFL127 abolished its phospholipase C activity but did not change its hemolytic phenotype, indicating that plcB was more dependent on prfA regulation than hly. Taken together, this study presents some evidence for the regulation ofplcB expression by its 5'-UTR mechanism.

  15. A Comparative Study on Activated Carbons Derived from a Broad Range of Agro-industrial Wastes in Removal of Large-Molecular-Size Organic Pollutants in Aqueous Phase

    Czech Academy of Sciences Publication Activity Database

    Cruz, G.J.F.; Matějová, Lenka; Pirilä, M.; Ainassari, K.; Canepa, C.A.; Solis, J.; Cruz, J.F.; Šolcová, Olga; Keiski, R.L.

    2015-01-01

    Roč. 226, č. 7 (2015), s. 214. ISSN 0049-6979 Grant ostatní: NUT(PE) 1217-2013/UNT-R; CNCTIT(PE) 002/PE/2012 Institutional support: RVO:67985858 Keywords : agro-industrial biomass * activated carbon * adsorption Subject RIV: CI - Industrial Chemistry, Chemical Engineering Impact factor: 1.554, year: 2014

  16. Glucose Administration Enhances fMRI Brain Activation and Connectivity Related to Episodic Memory Encoding for Neutral and Emotional Stimuli

    Science.gov (United States)

    Parent, Marise B.; Krebs-Kraft, Desiree L.; Ryan, John P.; Wilson, Jennifer S.; Harenski, Carla; Hamann, Stephan

    2011-01-01

    Glucose enhances memory in a variety of species. In humans, glucose administration enhances episodic memory encoding, although little is known regarding the neural mechanisms underlying these effects. Here we examined whether elevating blood glucose would enhance functional MRI (fMRI) activation and connectivity in brain regions associated with…

  17. Connectivity of neutral networks and structural conservation in protein evolution

    OpenAIRE

    Bastolla, Ugo; Porto, Markus; Roman, H. Eduardo; Vendruscolo, Michele

    2001-01-01

    Protein structures are much more conserved than sequences during evolution. Based on this observation, we investigate the consequences of structural conservation on protein evolution. We study seven of the most studied protein folds, finding out that an extended neutral network in sequence space is associated to each of them. Within our model, neutral evolution leads to a non-Poissonian substitution process, due to the broad distribution of connectivities in neutral networks. The observation ...

  18. Generation and reactivity of putative support systems, Ce-Al neutral binary oxide nanoclusters: CO oxidation and C–H bond activation

    International Nuclear Information System (INIS)

    Both ceria (CeO2) and alumina (Al2O3) are very important catalyst support materials. Neutral binary oxide nanoclusters (NBONCs), CexAlyOz, are generated and detected in the gas phase and their reactivity with carbon monoxide (CO) and butane (C4H10) is studied. The very active species CeAlO4• can react with CO and butane via O atom transfer (OAT) and H atom transfer (HAT), respectively. Other CexAlyOz NBONCs do not show reactivities toward CO and C4H10. The structures, as well as the reactivities, of CexAlyOz NBONCs are studied theoretically employing density functional theory (DFT) calculations. The ground state CeAlO4• NBONC possesses a kite-shaped structure with an OtCeObObAlOt configuration (Ot, terminal oxygen; Ob, bridging oxygen). An unpaired electron is localized on the Ot atom of the AlOt moiety rather than the CeOt moiety: this Ot centered radical moiety plays a very important role for the reactivity of the CeAlO4• NBONC. The reactivities of Ce2O4, CeAlO4•, and Al2O4 toward CO are compared, emphasizing the importance of a spin-localized terminal oxygen for these reactions. Intramolecular charge distributions do not appear to play a role in the reactivities of these neutral clusters, but could be important for charged isoelectronic BONCs. DFT studies show that the reaction of CeAlO4• with C4H10 to form the CeAlO4H•C4H9• encounter complex is barrierless. While HAT processes have been previously characterized for cationic and anionic oxide clusters, the reported study is the first observation of a HAT process supported by a ground state neutral oxide cluster. Mechanisms for catalytic oxidation of CO over surfaces of AlxOy/MmOn or MmOn/AlxOy materials are proposed consistent with the presented experimental and theoretical results

  19. Broad range of inhibiting action of novel camphor-based compound with anti-hemagglutinin activity against influenza viruses in vitro and in vivo.

    Science.gov (United States)

    Zarubaev, V V; Garshinina, A V; Tretiak, T S; Fedorova, V A; Shtro, A A; Sokolova, A S; Yarovaya, O I; Salakhutdinov, N F

    2015-08-01

    Influenza virus continues to remain one of the leading human respiratory pathogens causing significant morbidity and mortality around the globe. Due to short-term life cycle and high rate of mutations influenza virus is able to rapidly develop resistance to clinically available antivirals. This makes necessary the search and development of new drugs with different targets and mechanisms of activity. Here we report anti-influenza activity of camphor derivative 1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene-aminoethanol (camphecene). In in vitro experiments it inhibited influenza viruses A(H1, H1pdm09, H3 and H5 subtypes) and B with EC50's lying in micromolar range. Due to low cytotoxicity it resulted in high selectivity indices (74-661 depending on the virus). This effect did not depend on susceptibility or resistance of the viruses to adamantane derivatives amantadine and rimantadine. The compound appeared the most effective when added at the early stages of viral life cycle (0-2h p.i.). In direct hemagglutinin inhibition tests camphecene was shown to decrease the activity of HA's of influenza viruses A and B. The activity of camphecene was further confirmed in experiments with influenza virus-infected mice, in which, being used orally by therapeutic schedule (once a day, days 1-5 p.i.) it decreased specific mortality of animals infected with both influenza A and B viruses (highest indices of protection 66.7% and 88.9%, respectively). Taken together, these results are encouraging for further development of camphecene-based drug(s) and for exploration of camphor derivatives as highly prospective group of potential antivirals. PMID:26072310

  20. MRJP1-containing glycoproteins isolated from honey, a novel antibacterial drug candidate with broad spectrum activity against multi-drug resistant clinical isolates

    Directory of Open Access Journals (Sweden)

    Katrina eBrudzynski

    2015-07-01

    Full Text Available The emergence of extended- spectrum β-lactamase (ESBL is the underlying cause of growing antibiotic resistance among Gram-negative bacteria to β-lactam antibiotics. We recently reported the discovery of honey glycoproteins (glps that exhibited a rapid, concentration-dependent antibacterial activity against both Gram-positive Bacillus subtilis and Gram-negative Escherichia coli that resembled action of cell wall-active β-lactam drugs. Glps showed sequence identity with the Major Royal Jelly Protein 1 (MRJP1 precursor that harbors three antimicrobial peptides: Jelleins 1, 2 and 4. Here, we used semi-quantitative radial diffusion assay and broth microdilution assay to evaluate susceptibility of a number of multi-drug resistant (MDR clinical isolates to the MRJP1-contaning honey glycoproteins. The MDR bacterial strains comprised 3 MRSA, 4 Pseudomonas aeruginosa, 2 Klebsiella pneumoniae, 2 VRE and 5 Extended-spectrum beta-lactamase (ESBL identified as 1 Proteus mirabilis, 3 Escherichia coli and 1 Escherichia coli NDM. Their resistance to different classes of antibiotics was confirmed using automated system Vitek 2. MDR isolates differred in their susceptibility to glps with MIC90 values ranging from 4.8μg/ml against B. subtilis to 14.4μg/ml against ESBL K. pneumoniae, Klebsiella spp ESBL and E. coli and up to 33μg/ml against highly resistant strains of P. aeruginosa. Glps isolated from different honeys showed a similar ability to overcome bacterial resistance to β-lactams suggesting that (a their mode of action is distinct from other classes of β-lactams and that (b the common glps structure was the lead structure responsible for the activity. The results of the current study together with our previous evidence of a rapid bactericidal activity of glps demonstrate that glps possess suitable characteristics to be considered a novel antibacterial drug candidate.

  1. Expression Patterns, Activities and Carbohydrate-Metabolizing Regulation of Sucrose Phosphate Synthase, Sucrose Synthase and Neutral Invertase in Pineapple Fruit during Development and Ripening

    Science.gov (United States)

    Zhang, Xiu-Mei; Wang, Wei; Du, Li-Qing; Xie, Jiang-Hui; Yao, Yan-Li; Sun, Guang-Ming

    2012-01-01

    Differences in carbohydrate contents and metabolizing-enzyme activities were monitored in apical, medial, basal and core sections of pineapple (Ananas comosus cv. Comte de paris) during fruit development and ripening. Fructose and glucose of various sections in nearly equal amounts were the predominant sugars in the fruitlets, and had obvious differences until the fruit matured. The large rise of sucrose/hexose was accompanied by dramatic changes in sucrose phosphate synthase (SPS) and sucrose synthase (SuSy) activities. By contrast, neutral invertase (NI) activity may provide a mechanism to increase fruit sink strength by increasing hexose concentrations. Furthermore, two cDNAs of Ac-sps (accession no. GQ996582) and Ac-ni (accession no. GQ996581) were first isolated from pineapple fruits utilizing conserved amino-acid sequences. Homology alignment reveals that the amino acid sequences contain some conserved function domains. Transcription expression analysis of Ac-sps, Ac-susy and Ac-ni also indicated distinct patterns related to sugar accumulation and composition of pineapple fruits. It suggests that differential expressions of multiple gene families are necessary for sugar metabolism in various parts and developmental stages of pineapple fruit. A cycle of sucrose breakdown in the cytosol of sink tissues could be mediated through both Ac-SuSy and Ac-NI, and Ac-NI could be involved in regulating crucial steps by generating sugar signals to the cells in a temporally and spatially restricted fashion. PMID:22949808

  2. Increased titers of neutralizing antibodies after immunization with both envelope proteins of the porcine endogenous retroviruses (PERVs

    Directory of Open Access Journals (Sweden)

    Denner Joachim

    2012-11-01

    Full Text Available Abstract Despite enormous difficulties to induce antibodies neutralizing HIV-1, especially broadly neutralizing antibodies directed against the conserved membrane proximal external region (MPER of the transmembrane envelope protein, such antibodies can be easily induced in the case of gammaretroviruses, among them the porcine endogenous retroviruses (PERVs. In addition to neutralizing antibodies directed against the transmembrane envelope protein p15E, neutralizing antibodies were also induced by immunization with the surface envelope protein gp70. PERVs represent a special risk for xenotransplantation using pig tissues or organs since they are integrated in the genome of all pigs and infect human cells and a vaccine may protect from transmission to the recipient. To investigate the effect of simultaneous immunization with both proteins in detail, a study was performed in hamsters. Gp70 and p15E of PERV were produced in E. coli, purified and used for immunization. All animals developed binding antibodies against the antigens used for immunization. Sera from animals immunized with p15E recognized epitopes in the MPER and the fusion peptide proximal region (FPPR of p15E. One MPER epitope showed a sequence homology to an epitope in the MPER of gp41 of HIV-1 recognized by broadly neutralizing antibodies found in HIV infected individuals. Neutralizing antibodies were detected in all sera. Most importantly, sera from animals immunized with gp70 had a higher neutralizing activity when compared with the sera from animals immunized with p15E and sera from animals immunized with gp70 together with p15E had a higher neutralizing activity compared with sera from animals immunized with each antigen alone. These immunization studies are important for the development of vaccines against other retroviruses including the human immunodeficiency virus HIV-1.

  3. Integrating Hot and Cool Intelligences: Thinking Broadly about Broad Abilities

    Directory of Open Access Journals (Sweden)

    W. Joel Schneider

    2016-01-01

    Full Text Available Although results from factor-analytic studies of the broad, second-stratum abilities of human intelligence have been fairly consistent for decades, the list of broad abilities is far from complete, much less understood. We propose criteria by which the list of broad abilities could be amended and envision alternatives for how our understanding of the hot intelligences (abilities involving emotionally-salient information and cool intelligences (abilities involving perceptual processing and logical reasoning might be integrated into a coherent theoretical framework.

  4. The HEPT Analogue WPR-6 Is Active against a Broad Spectrum of Nonnucleoside Reverse Transcriptase Drug-Resistant HIV-1 Strains of Different Serotypes.

    Science.gov (United States)

    Xu, Weisi; Zhao, Jianxiong; Sun, Jianping; Yin, Qianqian; Wang, Yan; Jiao, Yang; Liu, Junyi; Jiang, Shibo; Shao, Yiming; Wang, Xiaowei; Ma, Liying

    2015-08-01

    Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are important components of the highly active antiretroviral therapy (HAART) used to treat human immunodeficiency type 1 virus (HIV-1). However, because of the emergence of drug resistance and the adverse effects of current anti-HIV drugs, it is essential to develop novel NNRTIs with an excellent safety profile, improved activity against NNRTI-resistant viruses, and enhanced activity against clinical isolates of different subtypes. Here, we have identified 1-[(benzyloxy)methyl]-6-(3,5-dimethylbenzyl)-5-iodopyrimidine-2,4(1H,3H)-dione (WPR-6), a novel NNRTI with a 50% effective concentration (EC50) of 2 to 4 nM against laboratory-adapted HIV-1 strain SF33 and an EC50 of 7 to 14 nM against nucleoside reverse transcriptase inhibitor-resistant HIV-1 strain 7391 with a therapeutic index of >1 × 10(4). A panel of five representative clinical virus isolates of different subtypes circulating predominantly in China was highly sensitive to WPR-6, with EC50s ranging from 1 to 6 nM. In addition, WPR-6 showed excellent antiviral potency against the most prevalent NNRTI-resistant viruses containing the K103N and Y181C mutations. To determine whether WPR-6 selects for novel resistant mutants, in vitro resistance selection was conducted with laboratory-adapted HIV-1 strain SF33 on MT-4 cells. The results demonstrated that V106I and Y188L were the two dominant NNRTI-associated resistance mutations detected in the breakthrough viruses. Taken together, these in vitro data indicate that WPR-6 has greater efficacy than the reference HEPT analogue TNK651 and the marketed drug nevirapine against HIV-1. However, to develop it as a new NNRTI, further improvement of its pharmacological properties is warranted. PMID:26055365

  5. A simple protocol for the michael addition of indoles with electron deficient olefins catalysed by TBAHS in aqueous media and their broad spectrum antibacterial activity

    Indian Academy of Sciences (India)

    M Damodiran; R Senthil Kumar; P M Sivakumar; Mukesh Doble; Paramasivan T Perumal

    2009-01-01

    Tetrabutylammonium hydrogen sulfate catalysed addition of indoles to electron deficient olefins in water generated the corresponding Michael adducts in good to excellent yield. The Michael addition of indole occurred regioselectively at position 3 and the -alkylated products have not been observed. The synthesized compounds were tested for their antibacterial activity against four microorganisms namely, E. coli NCIM 2931, S. aureus NCIM 5021, P. vulgaris NCIM 2813, P. aeruginosa NCIM 5029 by micro dilution method. These compounds showed MIC (Minimum Inhibitory Concentration) values in the range of 0.16-2.67 M.

  6. Evidence for neutral-current diffractive neutral pion production from hydrogen in neutrino interactions on hydrocarbon

    CERN Document Server

    Wolcott, J; Altinok, O; Bercellie, A; Betancourt, M; Bodek, A; Bravar, A; Budd, H; Cai, T; Carneiro, M F; Chvojka, J; Devan, J; Dytman, S A; Diaz, G A; Eberly, B; Endress, E; Felix, J; Fields, L; Galindo, R; Gallagher, H; Golan, T; Gran, R; Harris, D A; Higuera, A; Hurtado, K; Kiveni, M; Kleykamp, J; Kordosky, M; Le, T; Maher, E; Manly, S; Mann, W A; Marshall, C M; Caicedo, D A Martinez; McFarland, K S; McGivern, C L; McGowan, A M; Messerly, B; Miller, J; Mislivec, A; Morfin, J G; Mousseau, J; Naples, D; Nelson, J K; Norrick, A; Nuruzzaman,; Paolone, V; Park, J; Patrick, C E; Perdue, G N; Rakotondravohitra, L; Ramirez, M A; Ray, H; Ren, L; Rimal, D; Rodrigues, P A; Ruterbories, D; Schellman, H; Schmitz, D W; Salinas, C J Solano; Sanchez, S F; Tagg, N; Tice, B G; Valencia, E; Walton, T; Wospakrik, M; Zhang, D

    2016-01-01

    The MINERvA experiment observes an excess of events containing electromagnetic showers relative to the expectation from Monte Carlo simulations in neutral-current neutrino interactions with mean beam energy of 4.5 GeV on a hydrocarbon target. The excess is characterized and found to be consistent with neutral-current neutral pion production with a broad energy distribution peaking at 7 GeV and a total cross section of 0.26 +- 0.02 (stat) +- 0.08 (sys) x 10^{-39} cm^{2}. The angular distribution, electromagnetic shower energy, and spatial distribution of the energy depositions of the excess are consistent with expectations from neutrino neutral-current diffractive neutral pion production from hydrogen in the hydrocarbon target. These data comprise the first direct experimental observation and constraint for a reaction that poses an important background process in neutrino oscillation experiments searching for muon neutrino to electron neutrino oscillations.

  7. Plasma Redshift in the Broad Line Region

    CERN Document Server

    Hansen, Peter M

    2013-01-01

    Astronomical properties of the broad line emission region (BLR) of active galactic nuclei (AGN) and quasi-stellar objects (QSO) are used to formulate a model of dynamic and electromagnetic scattering characteristics. The results of this modeling show that the observed redshift of these objects may be more complex than that from recession alone due to ionization or plasma effects.

  8. Potent neutralization of VEGF biological activities with a fully human antibody Fab fragment directed against VEGF receptor 2

    International Nuclear Information System (INIS)

    Compelling evidence suggest that vascular endothelial growth factor (VEGF) and its receptors, especially receptor 2 (VEGFR2, or kinase insert domain-containing receptor, KDR), play a critical role in angiogenesis under both physiological and pathological conditions, including cancer and angiogenic retinopathies such as age-related macular degeneration (AMD). To this end, inhibition of angiogenesis with antagonists to either VEGF or KDR has yielded significant therapeutic efficacy both in preclinical studies in animal models and in clinical trials in patients with cancer and AMD. We previously reported the identification of a high affinity, fully human anti-KDR antibody fragment, 1121B Fab, through a highly stringent affinity maturation process with a Fab originally isolated from a naive human antibody phage display library. In this study, we demonstrate that 1121B Fab is able to strongly block KDR/VEGF interaction, resulting in potent inhibition of an array of biological activities of VEGF, including activation of the receptor and its signaling pathway, intracellular calcium mobilization, and migration and proliferation of endothelial cells. Taken together, our data lend strong support to the further development of 1121B Fab fragment as an anti-angiogenesis agent in both cancer and angiogenic retinopathies

  9. THE SWIFT BAT SURVEY DETECTS TWO OPTICAL BROAD LINE, X-RAY HEAVILY OBSCURED ACTIVE GALAXIES: NVSS 193013+341047 AND IRAS 05218–1212

    International Nuclear Information System (INIS)

    The Swift Burst Alert Telescope (BAT) is discovering interesting new objects while monitoring the sky in the 14-195 keV band. Here we present the X-ray properties and spectral energy distributions (SEDs) for two unusual active galactic nucleus sources. Both NVSS 193013+341047 and IRAS 05218–1212 are absorbed, Compton-thin, but heavily obscured (NH ∼ 1023 cm–2), X-ray sources at redshifts <0.1. The SEDs reveal these galaxies to be very red, with high extinction in the optical and UV. A similar SED is seen for the extremely red objects (EROs) detected in the higher redshift universe. This suggests that these unusual BAT-detected sources are a low-redshift (z << 1) analog to EROs, which recent evidence suggests are a class of the elusive type II quasars. Studying the multi-wavelength properties of these sources may reveal the properties of their high-redshift counterparts.

  10. The Swift BAT Survey Detects Two Optical Broad Line, X-Ray Heavily Obscured Active Galaxies: NVSS 193013+341047 and IRAS 05218-1212

    Science.gov (United States)

    Hogg, J. Drew; Winter, Lisa M.; Mushotzky, Richard F.; Reynolds, Christopher S.; Trippe, Margaret

    2012-06-01

    The Swift Burst Alert Telescope (BAT) is discovering interesting new objects while monitoring the sky in the 14-195 keV band. Here we present the X-ray properties and spectral energy distributions (SEDs) for two unusual active galactic nucleus sources. Both NVSS 193013+341047 and IRAS 05218-1212 are absorbed, Compton-thin, but heavily obscured (N H ~ 1023 cm-2), X-ray sources at redshifts red, with high extinction in the optical and UV. A similar SED is seen for the extremely red objects (EROs) detected in the higher redshift universe. This suggests that these unusual BAT-detected sources are a low-redshift (z Lt 1) analog to EROs, which recent evidence suggests are a class of the elusive type II quasars. Studying the multi-wavelength properties of these sources may reveal the properties of their high-redshift counterparts.

  11. Functional characterization of flax fatty acid desaturase FAD2 and FAD3 isoforms expressed in yeast reveals a broad diversity in activity.

    Science.gov (United States)

    Radovanovic, Natasa; Thambugala, Dinushika; Duguid, Scott; Loewen, Evelyn; Cloutier, Sylvie

    2014-07-01

    With 45 % or more oil content that contains more than 55 % alpha linolenic (LIN) acid, linseed (Linum usitatissimum L.) is one of the richest plant sources of this essential fatty acid. Fatty acid desaturases 2 (FAD2) and 3 (FAD3) are the main enzymes responsible for the Δ12 and Δ15 desaturation in planta. In linseed, the oilseed morphotype of flax, two paralogous copies, and several alleles exist for each gene. Here, we cloned three alleles of FAD2A, four of FAD2B, six of FAD3A, and seven of FAD3B into a pYES vector and transformed all 20 constructs and an empty construct in yeast. The transformants were induced in the presence of oleic (OLE) acid substrate for FAD2 constructs and linoleic (LIO) acid for FAD3. Conversion rates of OLE acid into LIO acid and LIO acid into LIN acid were measured by gas chromatography. Conversion rate of FAD2 exceeded that of FAD3 enzymes with FAD2B having a conversion rate approximately 10 % higher than FAD2A. All FAD2 isoforms were active, but significant differences existed between isoforms of both FAD2 enzymes. Two FAD3A and three FAD3B isoforms were not functional. Some nonfunctional enzymes resulted from the presence of nonsense mutations causing premature stop codons, but FAD3B-C and FAD3B-F seem to be associated with single amino acid changes. The activity of FAD3A-C was more than fivefold greater than the most common isoform FAD3A-A, while FAD3A-F was fourfold greater. Such isoforms could be incorporated into breeding lines to possibly further increase the proportion of LIN acid in linseed. PMID:24522837

  12. Neutral theory and the species abundance distribution: recent developments and prospects for unifying niche and neutral perspectives.

    Science.gov (United States)

    Matthews, Thomas J; Whittaker, Robert J

    2014-06-01

    Published in 2001, The Unified Neutral Theory of Biodiversity and Biogeography (UNTB) emphasizes the importance of stochastic processes in ecological community structure, and has challenged the traditional niche-based view of ecology. While neutral models have since been applied to a broad range of ecological and macroecological phenomena, the majority of research relating to neutral theory has focused exclusively on the species abundance distribution (SAD). Here, we synthesize the large body of work on neutral theory in the context of the species abundance distribution, with a particular focus on integrating ideas from neutral theory with traditional niche theory. First, we summarize the basic tenets of neutral theory; both in general and in the context of SADs. Second, we explore the issues associated with neutral theory and the SAD, such as complications with fitting and model comparison, the underlying assumptions of neutral models, and the difficultly of linking pattern to process. Third, we highlight the advances in understanding of SADs that have resulted from neutral theory and models. Finally, we focus consideration on recent developments aimed at unifying neutral- and niche-based approaches to ecology, with a particular emphasis on what this means for SAD theory, embracing, for instance, ideas of emergent neutrality and stochastic niche theory. We put forward the argument that the prospect of the unification of niche and neutral perspectives represents one of the most promising future avenues of neutral theory research. PMID:25360266

  13. Human immunodeficiency virus type 1 mutants that escape neutralization by human monoclonal antibody IgG1b12. off.

    OpenAIRE

    Mo, H; Stamatatos, L; Ip, J E; Barbas, C F; Parren, P W; Burton, D R; Moore, J. P.; Ho, D D

    1997-01-01

    IgG1b12, a human monoclonal antibody (MAb) to an epitope overlapping the CD4-binding site on gp120, has broad and potent neutralizing activity against most primary human immunodeficiency virus type 1 (HIV-1) isolates. To assess whether and how escape mutants resistant to IgG1b12 can be generated, we cultured primary HIV-1 strain JRCSF in its presence. An escape mutant emerged which was approximately 100-fold more resistant to neutralization by IgG1b12. Both virion-associated and solubilized g...

  14. Molecular cloning of the large subunit of the high-Ca2+-requiring form of human Ca2+-activated neutral protease

    International Nuclear Information System (INIS)

    A nearly full-length cDNA clone for the large subunit of high-Ca2+-requiring Ca2+-activated neutral protease (mCANP) from human tissues has been isolated. The deduced protein, determined for the first time as an mCANP, has essentially the same structural features as those revealed previously for the large subunits of the low-Ca2+-requiring form (μCANP). Namely, the protein, comprising 700 amino acid residues, is characterized by four domains, containing a cysteine protease like domain and a Ca2+-binding domain. The overall amino acid sequence similarities of the mCANP large subunit with those of human μCANP and chicken CANP are 62% and 66%, respectively. These values are slightly lower than that observed between μCANP and chicken CANP (70%). Local sequence similarities vary with the domain, 73-78% in the cysteine protease like domain and 48-65% in the Ca2+-binding domain. These results suggest that CANPs with different Ca2+ sensitivities share a common evolutionary origin and that their regulatory mechanisms are similar except for the Ca2+ concentrations required for activation

  15. THE SWIFT BAT SURVEY DETECTS TWO OPTICAL BROAD LINE, X-RAY HEAVILY OBSCURED ACTIVE GALAXIES: NVSS 193013+341047 AND IRAS 05218-1212

    Energy Technology Data Exchange (ETDEWEB)

    Hogg, J. Drew; Winter, Lisa M. [Department of Astrophysical and Planetary Sciences, University of Colorado, UCB 391, Boulder, CO 80309 (United States); Mushotzky, Richard F.; Reynolds, Christopher S.; Trippe, Margaret, E-mail: james.hogg@colorado.edu, E-mail: lisa.winter@colorado.edu [Department of Astronomy, University of Maryland, College Park, MD 20742 (United States)

    2012-06-20

    The Swift Burst Alert Telescope (BAT) is discovering interesting new objects while monitoring the sky in the 14-195 keV band. Here we present the X-ray properties and spectral energy distributions (SEDs) for two unusual active galactic nucleus sources. Both NVSS 193013+341047 and IRAS 05218-1212 are absorbed, Compton-thin, but heavily obscured (N{sub H} {approx} 10{sup 23} cm{sup -2}), X-ray sources at redshifts <0.1. The SEDs reveal these galaxies to be very red, with high extinction in the optical and UV. A similar SED is seen for the extremely red objects (EROs) detected in the higher redshift universe. This suggests that these unusual BAT-detected sources are a low-redshift (z << 1) analog to EROs, which recent evidence suggests are a class of the elusive type II quasars. Studying the multi-wavelength properties of these sources may reveal the properties of their high-redshift counterparts.

  16. Supermassive Black Holes with High Accretion Rates in Active Galactic Nuclei. V. A New Size-Luminosity Scaling Relation for the Broad-Line Region

    CERN Document Server

    Du, Pu; Zhang, Zhi-Xiang; Huang, Ying-Ke; Wang, Kai; Hu, Chen; Qiu, Jie; Li, Yan-Rong; Fan, Xu-Liang; Fang, Xiang-Er; Bai, Jin-Ming; Bian, Wei-Hao; Yuan, Ye-Fei; Ho, Luis C; Wang, Jian-Min

    2016-01-01

    This paper reports results of the third-year campaign of monitoring super-Eddington accreting massive black holes (SEAMBHs) in active galactic nuclei (AGNs) between 2014-2015. Ten new targets were selected from quasar sample of Sloan Digital Sky Survey (SDSS), which are generally more luminous than the SEAMBH candidates in last two years. H$\\beta$ lags ($\\tau_{_{\\rm H\\beta}}$) in five of the 10 quasars have been successfully measured in this monitoring season. We find that the lags are generally shorter, by large factors, than those of objects with same optical luminosity, in light of the well-known $R_{_{\\rm H\\beta}}-L_{5100}$ relation. The five quasars have dimensionless accretion rates of $\\dot{\\mathscr{M}}=10-10^3$. Combining measurements of the previous SEAMBHs, we find that the reduction of H$\\beta$ lags tightly depends on accretion rates, $\\tau_{_{\\rm H\\beta}}/\\tau_{_{R-L}}\\propto\\dot{\\mathscr{M}}^{-0.42}$, where $\\tau_{_{R-L}}$ is the H$\\beta$ lag from the normal $R_{_{\\rm H\\beta}}-L_{5100}$ relation....

  17. Broad screening of the legume family for variability in seed insecticidal activities and for the occurrence of the A1b-like knottin peptide entomotoxins.

    Science.gov (United States)

    Louis, Sandrine; Delobel, Bernard; Gressent, Frédéric; Duport, Gabrielle; Diol, Ousmane; Rahioui, Isabelle; Charles, Hubert; Rahbé, Yvan

    2007-02-01

    Pea albumin 1b (PA1b) is a small sulphur-rich peptide from pea seeds, also named leginsulin because of the binding characteristics of its soybean orthologue. Its insecticidal properties were discovered more recently. By using a combination of molecular, biochemical and specific insect bioassays on seed extracts, we characterised genes from numerous Papilionoideae, but not from Caesalpinioideae or Mimosoideae, although the last group harboured species with partially positive cues (homologous biological activities). The A1b defence peptide family, therefore, appears to have evolved relatively late in the legume lineage, maybe from the sophoroid group (e.g. Styphnolobium japonicum). However, unambiguous sequence information is restricted to a group of tribes within the subfamily Papilionoideae (Psoraleae, Millettieae, Desmodieae, Hedysareae, Phaseoleae, Vicieae, and the now clearly polyphyletic "Trifolieae" and "Galegeae"). Recent diversification by gene duplications has occurred in many species, or longer ago in some lineages (Medicago truncatula), as well as probable gene or expression losses at different taxonomic levels (Loteae, Vigna subterranea). PMID:17222873

  18. Simulations of the broad visual field imaging camera from the Eclair mission - modelling the intern regions of the galaxy active nuclei

    International Nuclear Information System (INIS)

    The first part of this work deals with the Eclair mission, dedicated to the study of the prompt multi-wavelength emission of gamma-ray bursts (GRB). The performance of the wide-field X-γ spectro-imager onboard Eclair is computed with Monte-Carlo simulations. The sensitivity to GRB detections depends principally on the background level in the camera. Simulations show that from a sample of hundred GRB detected in the camera's field of view, 47% and 61% of these GRB should be located with a precision better than 10 and 20 arc-minutes respectively in 1.024 seconds. The second part concerns the photo-ionization code Titan. This code computes the radiative transfer in taking into account the interconnection between matter and radiation. We show that the computation of the radiative transfer 'in a full way' is important to take into account the effects of radiative transfer and therefore to have a proper interpretation of active galactic nuclei (AGN) spectra. A set of spectroscopic diagnostics has been found from theoretical studies using Titan and the He-like line triplets. These diagnostics allow us to determine the density, the total column density and the ionisation parameters of the observed photo-ionized media, by measuring the fluxes and the continuous radiative recombination of the He-like triplets

  19. Canine distemper virus neutralization activity is low in human serum and it is sensitive to an amino acid substitution in the hemagglutinin protein.

    Science.gov (United States)

    Zhang, Xinsheng; Wallace, Olivia L; Domi, Arban; Wright, Kevin J; Driscoll, Jonathan; Anzala, Omu; Sanders, Eduard J; Kamali, Anatoli; Karita, Etienne; Allen, Susan; Fast, Pat; Gilmour, Jill; Price, Matt A; Parks, Christopher L

    2015-08-01

    Serum was analyzed from 146 healthy adult volunteers in eastern Africa to evaluate measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb) prevalence and potency. MV plaque reduction neutralization test (PRNT) results indicated that all sera were positive for MV nAbs. Furthermore, the 50% neutralizing dose (ND50) for the majority of sera corresponded to antibody titers induced by MV vaccination. CDV nAbs titers were low and generally were detected in sera with high MV nAb titers. A mutant CDV was generated that was less sensitive to neutralization by human serum. The mutant virus genome had 10 nucleotide substitutions, which coded for single amino acid substitutions in the fusion (F) and hemagglutinin (H) glycoproteins and two substitutions in the large polymerase (L) protein. The H substitution occurred in a conserved region involved in receptor interactions among morbilliviruses, implying that this region is a target for cross-reactive neutralizing antibodies. PMID:25880113

  20. Tetra-O-Methyl Nordihydroguaiaretic Acid Broadly Suppresses Cancer Metabolism and Synergistically Induces Strong Anticancer Activity in Combination with Etoposide, Rapamycin and UCN-01.

    Science.gov (United States)

    Kimura, Kotohiko; Huang, Ru Chih C

    2016-01-01

    The ability of Tetra-O-methyl nordihydroguaiaretic acid (M4N) to induce rapid cell death in combination with Etoposide, Rapamycin, or UCN-01 was examined in LNCaP cells, both in cell culture and animal experiments. Mice treated with M4N drug combinations with either Etoposide or Rapamycin showed no evidence of tumor and had a 100% survival rate 100 days after tumor implantation. By comparison all other vehicles or single drug treated mice failed to survive longer than 30 days after implantation. This synergistic improvement of anticancer effect was also confirmed in more than 20 cancer cell lines. In LNCaP cells, M4N was found to reduce cellular ATP content, and suppress NDUFS1 expression while inducing hyperpolarization of mitochondrial membrane potential. M4N-treated cells lacked autophagy with reduced expression of BNIP3 and ATG5. To understand the mechanisms of this anticancer activity of M4N, the effect of this drug on three cancer cell lines (LNCaP, AsPC-1, and L428 cells) was further examined via transcriptome and metabolomics analyses. Metabolomic results showed that there were reductions of 26 metabolites essential for energy generation and/or production of cellular components in common with these three cell lines following 8 hours of M4N treatment. Deep RNA sequencing analysis demonstrated that there were sixteen genes whose expressions were found to be modulated following 6 hours of M4N treatment similarly in these three cell lines. Six out of these 16 genes were functionally related to the 26 metabolites described above. One of these up-regulated genes encodes for CHAC1, a key enzyme affecting the stress pathways through its degradation of glutathione. In fact M4N was found to suppress glutathione content and induce reactive oxygen species production. The data overall indicate that M4N has profound specific negative impacts on a wide range of cancer metabolisms supporting the use of M4N combination for cancer treatments. PMID:26886430

  1. Tetra-O-Methyl Nordihydroguaiaretic Acid Broadly Suppresses Cancer Metabolism and Synergistically Induces Strong Anticancer Activity in Combination with Etoposide, Rapamycin and UCN-01.

    Directory of Open Access Journals (Sweden)

    Kotohiko Kimura

    Full Text Available The ability of Tetra-O-methyl nordihydroguaiaretic acid (M4N to induce rapid cell death in combination with Etoposide, Rapamycin, or UCN-01 was examined in LNCaP cells, both in cell culture and animal experiments. Mice treated with M4N drug combinations with either Etoposide or Rapamycin showed no evidence of tumor and had a 100% survival rate 100 days after tumor implantation. By comparison all other vehicles or single drug treated mice failed to survive longer than 30 days after implantation. This synergistic improvement of anticancer effect was also confirmed in more than 20 cancer cell lines. In LNCaP cells, M4N was found to reduce cellular ATP content, and suppress NDUFS1 expression while inducing hyperpolarization of mitochondrial membrane potential. M4N-treated cells lacked autophagy with reduced expression of BNIP3 and ATG5. To understand the mechanisms of this anticancer activity of M4N, the effect of this drug on three cancer cell lines (LNCaP, AsPC-1, and L428 cells was further examined via transcriptome and metabolomics analyses. Metabolomic results showed that there were reductions of 26 metabolites essential for energy generation and/or production of cellular components in common with these three cell lines following 8 hours of M4N treatment. Deep RNA sequencing analysis demonstrated that there were sixteen genes whose expressions were found to be modulated following 6 hours of M4N treatment similarly in these three cell lines. Six out of these 16 genes were functionally related to the 26 metabolites described above. One of these up-regulated genes encodes for CHAC1, a key enzyme affecting the stress pathways through its degradation of glutathione. In fact M4N was found to suppress glutathione content and induce reactive oxygen species production. The data overall indicate that M4N has profound specific negative impacts on a wide range of cancer metabolisms supporting the use of M4N combination for cancer treatments.

  2. Bacillus polymachus sp. nov., with a broad range of antibacterial activity, isolated from forest topsoil samples by using a modified culture method.

    Science.gov (United States)

    Nguyen, Tuan Manh; Kim, Jaisoo

    2015-02-01

    A new, modified culture method that utilizes a transwell plate with a 0.4 µm pore-size microporous membrane was developed. This system allows only trace nutrients from the soil into the liquid culture through the microporous membrane. The method is a more powerful tool for the discovery of novel species from soils than are traditional methods. Such newly identified species could potentially produce useful metabolites. A bacterial strain, T515(T), was isolated using this modified culture method. Growth of strain T515(T) occurred at pH 4-9 in a temperature range between 20 °C and 40 °C and in the presence of 0-2 % (w/v) NaCl on R2A agar. Colonies on the agar plates were tiny, white, and convex after 5 days incubation at 28 °C. Comparative analysis of the nearly full-length 16S rRNA gene sequence of strain T515(T) revealed close pairwise similarity with species of the genus Bacillus, and strain T515(T) was most closely related to Bacillus panaciterrae Gsoil 1517(T) (96.7 %) and Bacillus funiculus NAF001(T) (96.0 %). The major quinone of strain T515(T) was menaquinone-7 (MK-7) and the major fatty acids were iso-C15 : 0 (45.5 %), anteiso-C15 : 0 (23.2 %) and C16 : 0 (10.9 %). The predominant polar lipids were diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. Strain T515(T) was sensitive to streptomycin and tetracycline, but resistant to rifampicin (0.125 µg ml(-1)), ampicillin (0.5 µg ml(-1)) and chloramphenicol (1 µg ml(-1)). The strain showed antimicrobial activities against the six strains tested: Bacillus subtilis KEMB 51201-001, Staphylococcus aureus KEMB 4659, Pseudomonas aeruginosa KACC 10185, Staphylococcus epidermidis KACC 13234, Paenibacillus larvae KACC 14031 and Escherichia coli KEMB 212-234. Based on these results, strain T515(T) represents a novel species of the genus Bacillus with the proposed name, Bacillus polymachus sp. nov. The type strain is T515(T) ( = KEMB 9005-168(T) = KACC 18242(T) = NBRC 110614(T)). PMID

  3. Niclosamide is a proton carrier and targets acidic endosomes with broad antiviral effects.

    Directory of Open Access Journals (Sweden)

    Andreas Jurgeit

    Full Text Available Viruses use a limited set of host pathways for infection. These pathways represent bona fide antiviral targets with low likelihood of viral resistance. We identified the salicylanilide niclosamide as a broad range antiviral agent targeting acidified endosomes. Niclosamide is approved for human use against helminthic infections, and has anti-neoplastic and antiviral effects. Its mode of action is unknown. Here, we show that niclosamide, which is a weak lipophilic acid inhibited infection with pH-dependent human rhinoviruses (HRV and influenza virus. Structure-activity studies showed that antiviral efficacy and endolysosomal pH neutralization co-tracked, and acidification of the extracellular medium bypassed the virus entry block. Niclosamide did not affect the vacuolar H(+-ATPase, but neutralized coated vesicles or synthetic liposomes, indicating a proton carrier mode-of-action independent of any protein target. This report demonstrates that physico-chemical interference with host pathways has broad range antiviral effects, and provides a proof of concept for the development of host-directed antivirals.

  4. Investigation of an Immunoassay with Broad Specificity to Quinolone Drugs by Genetic Algorithm with Linear Assignment of Hypermolecular Alignment of Data Sets and Advanced Quantitative Structure-Activity Relationship Analysis.

    Science.gov (United States)

    Chen, Jiahong; Lu, Ning; Shen, Xing; Tang, Qiushi; Zhang, Chijian; Xu, Jun; Sun, Yuanming; Huang, Xin-An; Xu, Zhenlin; Lei, Hongtao

    2016-04-01

    A polyclonal antibody against the quinolone drug pazufloxacin (PAZ) but with surprisingly broad specificity was raised to simultaneously detect 24 quinolones (QNs). The developed competitive indirect enzyme-linked immunosorbent assay (ciELISA) exhibited limits of detection (LODs) for the 24 QNs ranging from 0.45 to 15.16 ng/mL, below the maximum residue levels (MRLs). To better understand the obtained broad specificity, a genetic algorithm with linear assignment of hypermolecular alignment of data sets (GALAHAD) was used to generate the desired pharmacophore model and superimpose the QNs, and then advanced comparative molecular field analysis (CoMFA) and advanced comparative molecular similarity indices analysis (CoMSIA) models were employed to study the three-dimensional quantitative structure-activity relationship (3D QSAR) between QNs and the antibody. It was found that the QNs could interact with the antibody with different binding poses, and cross-reactivity was mainly positively correlated with the bulky substructure containing electronegative atom at the 7-position, while it was negatively associated with the large bulky substructure at the 1-position of QNs. PMID:26982746

  5. Hydrophobin fusion of an influenza virus hemagglutinin allows high transient expression in Nicotiana benthamiana, easy purification and immune response with neutralizing activity.

    Directory of Open Access Journals (Sweden)

    Nicolas Jacquet

    Full Text Available The expression of recombinant hemagglutinin in plants is a promising alternative to the current egg-based production system for the influenza vaccines. Protein-stabilizing fusion partners have been developed to overcome the low production yields and the high downstream process costs associated with the plant expression system. In this context, we tested the fusion of hydrophobin I to the hemagglutinin ectodomain of the influenza A (H1N1pdm09 virus controlled by the hybrid En2PMA4 transcriptional promoter to rapidly produce high levels of recombinant antigen by transient expression in agro-infiltrated Nicotiana benthamiana leaves. The fusion increased the expression level by a factor of ∼ 2.5 compared to the unfused protein allowing a high accumulation level of 8.6% of the total soluble proteins. Hemagglutinin was located in ER-derived protein bodies and was successfully purified by combining an aqueous-two phase partition system and a salting out step. Hydrophobin interactions allowed the formation of high molecular weight hemagglutinin structures, while unfused proteins were produced as monomers. Purified protein was shown to be biologically active and to induce neutralizing antibodies after mice immunization. Hydrophobin fusion to influenza hemagglutinin might therefore be a promising approach for rapid, easy, and low cost production of seasonal or pandemic influenza vaccines in plants.

  6. CO2 Neutral Active Houses

    NARCIS (Netherlands)

    Bazzu, M.J.

    2012-01-01

    This "designers' manual" is made during the TIDO-course AR0531 Smart & Bioclimatic Design. Since buildings are one of the main sources of energy consumption, a global adoption of a highly efficient solution would significantly lower energy consumption and environmental impact. The concept of the Pa

  7. Search for neutral leptons

    International Nuclear Information System (INIS)

    At present we know of three kinds of neutral leptons: the electron neutrino, the muon neutrino, and the tau neutrino. This paper reviews the search for additional neutral leptons. The method and significance of a search depends upon the model used for the neutral lepton being sought. Some models for the properties and decay modes of proposed neutral leptons are described. Past and present searches are reviewed. The limits obtained by some completed searches are given, and the methods of searches in progress are described. Future searches are discussed. 41 references

  8. A Broad View of Macroeconomic Stability

    OpenAIRE

    José Antonio Ocampo

    2005-01-01

    This paper recommends a broad concept of macroeconomic stability, whereby “sound macroeconomic frameworks” include not only price stability and sound fiscal policies, but also a well-functioning real economy, sustainable debt ratios and healthy public and private sector balance sheets. These multiple dimensions imply using multiple policy instruments. The paper elaborates a framework for developing countries that involves active use of counter-cyclical macroeconomic policies (exchange rate, m...

  9. Harnessing the protective potential of HIV-1 neutralizing antibodies [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    S Abigail Smith

    2016-01-01

    Full Text Available Recent biological, structural, and technical advances are converging within the HIV-1 vaccine field to harness the power of antibodies for prevention and therapy. Numerous monoclonal antibodies with broad neutralizing activity against diverse HIV-1 isolates have now been identified, revealing at least five sites of vulnerability on the envelope (Env glycoproteins. While there are practical and technological barriers blocking a clear path from broadly neutralizing antibodies (bNAb to a protective vaccine, this is not a dead end. Scientists are revisiting old approaches with new technology, cutting new trails through unexplored territory, and paving new roads in the hopes of preventing HIV-1 infection. Other promising avenues to capitalize on the power of bNAbs are also being pursued, such as passive antibody immunotherapy and gene therapy approaches. Moreover, non-neutralizing antibodies have inhibitory activities that could have protective potential, alone or in combination with bNAbs. With a new generation of bNAbs, and a clinical trial that associated antibodies with reduced acquisition, the field is closer than ever to developing strategies to use antibodies against HIV-1.

  10. Degradation of 32 emergent contaminants by UV and neutral photo-fenton in domestic wastewater effluent previously treated by activated sludge.

    Science.gov (United States)

    De la Cruz, N; Giménez, J; Esplugas, S; Grandjean, D; de Alencastro, L F; Pulgarín, C

    2012-04-15

    This study focuses on the removal of 32 selected micropollutants (pharmaceuticals, corrosion inhibitors and biocides/pesticides) found in an effluent coming from a municipal wastewater treatment plant (MWTP) based on activated sludge. Dissolved organic matter was present, with an initial total organic carbon of 15.9 mg L(-1), and a real global quantity of micropollutants of 29.5 μg L(-1). The treatments tested on the micropollutants removal were: UV-light emitting at 254 nm (UV(254)) alone, dark Fenton (Fe(2+,3+)/H(2)O(2)) and photo-Fenton (Fe(2+,3+)/H(2)O(2)/light). Different irradiation sources were used for the photo-Fenton experiences: UV(254) and simulated sunlight. Iron and H(2)O(2) concentrations were also changed in photo-Fenton experiences in order to evaluate its influence on the degradation. All the experiments were developed at natural pH, near neutral. Photo-Fenton treatments employing UV(254), 50 mg L(-1) of H(2)O(2), with and without adding iron (5 mg L(-1) of Fe(2+) added or 1.48 mg L(-1) of total iron already present) gave the best results. Global percentages of micropollutants removal achieved were 98 and a 97% respectively, after 30 min of treatments. As the H(2)O(2) concentration increased (10, 25 and 50 mg L(-1)), best degradations were observed. UV(254), Fenton, and photo-Fenton under simulated sunlight gave less promising results with lower percentages of removal. The highlight of this paper is to point out the possibility of the micropollutants degradation in spite the presence of DOM in much higher concentrations. PMID:22305640

  11. Potent neutralization of influenza A virus by a single-domain antibody blocking M2 ion channel protein.

    Directory of Open Access Journals (Sweden)

    Guowei Wei

    Full Text Available Influenza A virus poses serious health threat to humans. Neutralizing antibodies against the highly conserved M2 ion channel is thought to offer broad protection against influenza A viruses. Here, we screened synthetic Camel single-domain antibody (VHH libraries against native M2 ion channel protein. One of the isolated VHHs, M2-7A, specifically bound to M2-expressed cell membrane as well as influenza A virion, inhibited replication of both amantadine-sensitive and resistant influenza A viruses in vitro, and protected mice from a lethal influenza virus challenge. Moreover, M2-7A showed blocking activity for proton influx through M2 ion channel. These pieces of evidence collectively demonstrate for the first time that a neutralizing antibody against M2 with broad specificity is achievable, and M2-7A may have potential for cross protection against a number of variants and subtypes of influenza A viruses.

  12. A new EV71 VP3 epitope in norovirus P particle vector displays neutralizing activity and protection in vivo in mice.

    Science.gov (United States)

    Jiang, Liping; Fan, Rongjun; Sun, Shiyang; Fan, Peihu; Su, Weiheng; Zhou, Yan; Gao, Feng; Xu, Fei; Kong, Wei; Jiang, Chunlai

    2015-11-27

    Enterovirus 71 (EV71) and Coxsackievirus A16 (CVA16), as the main agents causing hand, foot and mouth disease (HFMD), have become a serious public health concern in the Asia-Pacific region. Recently, various neutralizing B cell epitopes of EV71 were identified as targets for promising vaccine candidates. Structural studies of Picornaviridae indicated that potent immunodominant epitopes typically lie in the hypervariable loop of capsid surfaces. However, cross-neutralizing antibodies and cross-protection between EV71 and CVA16 have not been observed. Therefore, we speculated that divergent sequences of the two viruses are key epitopes for inducing protective neutralizing responses. In this study, we selected 10 divergent epitope candidates based on alignment of the EV71 and CVA16 P1 amino acid sequences using the Multalin interface page, and these epitopes are conserved among all subgenotypes of EV71. Simultaneously, by utilizing the norovirus P particle as a novel vaccine delivery carrier, we identified the 71-6 epitope (amino acid 176-190 of VP3) as a conformational neutralizing epitope against EV71 in an in vitro micro-neutralization assay as well as an in vivo protection assay in mice. Altogether, these results indicated that the incorporation of the 71-6 epitope into the norovirus P domain can provide a promising candidate for an effective synthetic peptide-based vaccine against EV71. PMID:26529072

  13. Overview of neutral beam injector technology developments at universities

    International Nuclear Information System (INIS)

    Activities of universities on the neutral beam injector developments have been overviewed. The subjects consist of NBI construction, components developments and system analyses, which are intensively studied at universities. Although neutral beam injector technologies are present day top topics, however, still a lot of efforts with flexible ideas are necessary to realize reactor relevant neutral beam injector system. (author)

  14. Broad Diphotons from Narrow States

    CERN Document Server

    An, Haipeng; Zhang, Yue

    2015-01-01

    ATLAS and CMS have each reported a modest diphoton excess consistent with the decay of a broad resonance at ~ 750 GeV. We show how this signal can arise in a weakly coupled theory comprised solely of narrow width particles. In particular, if the decaying particle is produced off-shell, then the associated diphoton resonance will have a broad, adjustable width. We present simplified models which explain the diphoton excess through the three-body decay of a scalar or fermion. Our minimal ultraviolet completion is a weakly coupled and renormalizable theory of a singlet scalar plus a heavy vector-like quark and lepton. The smoking gun of this mechanism is an asymmetric diphoton peak recoiling against missing transverse energy, jets, or leptons.

  15. The neutral losses from C{sub 60}{sup +x} by neutralization-reionization mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    McHale, K.J.; Poice, M.J.; Wesdemiotis, C. [Univ. of Akron, OH (United States)

    1994-12-31

    The most obvious shortcoming of mass spectrometry is the fact that only ions can be detected. However, since the development of neutralization-reionization mass spectrometry (NRMS), neutrals produced by unimolecular reactions in the gas phase can also be observed. One particular case where NRMS is useful is for the determination of the neutral losses from Buckminsterfullerene ions. Due to the high symmetry of Buckminsterfullerene and its very regular pattern of dissociation, as seen in the EI and collisionally activated dissociation (CAD) spectra, the problem of whether the neutrals produced from C{sub 60}{sup +x} ions are sequential C{sub 2} losses or larger C{sub 2n} (n=1,2,3,4,{hor_ellipsis}) clusters has not been solved. Here, the NRMS technique of neutral fragment reionization (N,R) is used to investigate the neutral CAD fragments from C{sub 60}{sup +x}.

  16. Initiation of immune tolerance-controlled HIV gp41 neutralizing B cell lineages.

    Science.gov (United States)

    Zhang, Ruijun; Verkoczy, Laurent; Wiehe, Kevin; Munir Alam, S; Nicely, Nathan I; Santra, Sampa; Bradley, Todd; Pemble, Charles W; Zhang, Jinsong; Gao, Feng; Montefiori, David C; Bouton-Verville, Hilary; Kelsoe, Garnett; Larimore, Kevin; Greenberg, Phillip D; Parks, Robert; Foulger, Andrew; Peel, Jessica N; Luo, Kan; Lu, Xiaozhi; Trama, Ashley M; Vandergrift, Nathan; Tomaras, Georgia D; Kepler, Thomas B; Moody, M Anthony; Liao, Hua-Xin; Haynes, Barton F

    2016-04-27

    Development of an HIV vaccine is a global priority. A major roadblock to a vaccine is an inability to induce protective broadly neutralizing antibodies (bnAbs). HIV gp41 bnAbs have characteristics that predispose them to be controlled by tolerance. We used gp41 2F5 bnAb germline knock-in mice and macaques vaccinated with immunogens reactive with germline precursors to activate neutralizing antibodies. In germline knock-in mice, bnAb precursors were deleted, with remaining anergic B cells capable of being activated by germline-binding immunogens to make gp41-reactive immunoglobulin M (IgM). Immunized macaques made B cell clonal lineages targeted to the 2F5 bnAb epitope, but 2F5-like antibodies were either deleted or did not attain sufficient affinity for gp41-lipid complexes to achieve the neutralization potency of 2F5. Structural analysis of members of a vaccine-induced antibody lineage revealed that heavy chain complementarity-determining region 3 (HCDR3) hydrophobicity was important for neutralization. Thus, gp41 bnAbs are controlled by immune tolerance, requiring vaccination strategies to transiently circumvent tolerance controls. PMID:27122615

  17. Initiation of immune tolerance–controlled HIV gp41 neutralizing B cell lineages

    Science.gov (United States)

    Zhang, Ruijun; Verkoczy, Laurent; Wiehe, Kevin; Alam, S. Munir; Nicely, Nathan I.; Santra, Sampa; Bradley, Todd; Pemble, Charles W.; Zhang, Jinsong; Gao, Feng; Montefiori, David C.; Bouton-Verville, Hilary; Kelsoe, Garnett; Larimore, Kevin; Greenberg, Phillip D.; Parks, Robert; Foulger, Andrew; Peel, Jessica N.; Luo, Kan; Lu, Xiaozhi; Trama, Ashley M.; Vandergrift, Nathan; Tomaras, Georgia D.; Kepler, Thomas B.; Moody, M. Anthony; Liao, Hua-Xin; Haynes, Barton F.

    2016-01-01

    Development of an HIV vaccine is a global priority. A major roadblock to a vaccine is an inability to induce protective broadly neutralizing antibodies (bnAbs). HIV gp41 bnAbs have characteristics that predispose them to be controlled by tolerance. We used gp41 2F5 bnAb germline knock-in mice and macaques vaccinated with immunogens reactive with germline precursors to activate neutralizing antibodies. In germline knock-in mice, bnAb precursors were deleted, with remaining anergic B cells capable of being activated by germline-binding immunogens to make gp41-reactive immunoglobulin M (IgM). Immunized macaques made B cell clonal lineages targeted to the 2F5 bnAb epitope, but 2F5-like antibodies were either deleted or did not attain sufficient affinity for gp41-lipid complexes to achieve the neutralization potency of 2F5. Structural analysis of members of a vaccine-induced antibody lineage revealed that heavy chain complementarity-determining region 3 (HCDR3) hydrophobicity was important for neutralization. Thus, gp41 bnAbs are controlled by immune tolerance, requiring vaccination strategies to transiently circumvent tolerance controls. PMID:27122615

  18. Hexachlorobenzene-induced alterations on neutral and acidic sphingomyelinases and serine palmitoyltransferase activities. A time course study in two strains of rats.

    Science.gov (United States)

    Billi de Catabbi, S C; Setton-Advruj, C P; Sterin-Speziale, N; San Martín de Viale, L C; Cochón, A C

    2000-08-21

    Hexachlorobenzene (HCB) induces porphyria both in humans and rodents, and hepatocarcinoma in rodents. In a previous work we observed that HCB produces a continuous decrease in hepatic sphingomyelin (SM) content in Wistar rats. A distinguishing characteristic of sphingolipids breakdown products is their participation in anti-proliferative and apoptotic processes and in the suppression of oncogenesis. As a first step to elucidate the role of SM decrease in the hepatotoxicity induced by HCB, the present study evaluates the metabolic causes of the continuous decrease in hepatic SM content observed in Wistar rats with HCB intoxication, and its relation with porphyria development. For this purpose, the time-course (3, 7, 15, 21 and 28 days) of the effects of HCB on hepatic SM levels and on some of the enzymes of SM synthesis (serine palmitoyltransferase, SPT) and catabolism (sphingomyelinases, SMases) was followed, using two strains of rats differing in their susceptibility to acquire porphyria: Chbb THOM (low) and Wistar (high). HCB (1 g kg(-1) b.w. per day) was administered by gastric intubation as an aqueous suspension. After 5 days of HCB treatment, animals were allowed a 2-day recovery period without HCB administration. Two phases in the HCB-induced damages to sphingolipid metabolism were observed. The first stage (7 days of treatment), common to both strains of rats, was characterized by a decrease in hepatic SM levels (17-25%) and in SPT activity (50-43%), while strain differences were found for the later stage. In Chbb THOM rats, hepatic SM content was restored to normal values concomitantly with an increase in SPT activity (44%, at day 28), and without any increase in SM catabolism. In addition, the level of the other phospholipids was not altered. In Wistar rats, hepatic SM levels decreased continuously throughout the experiment, accompanied by increases in SPT, acidic sphingomyelinase (A-SMase) and neutral sphingomyelinase (N-SMase) activities (86, 28.5 and 78

  19. A niche for neutrality.

    Science.gov (United States)

    Adler, Peter B; Hillerislambers, Janneke; Levine, Jonathan M

    2007-02-01

    Ecologists now recognize that controversy over the relative importance of niches and neutrality cannot be resolved by analyzing species abundance patterns. Here, we use classical coexistence theory to reframe the debate in terms of stabilizing mechanisms (niches) and fitness equivalence (neutrality). The neutral model is a special case where stabilizing mechanisms are absent and species have equivalent fitness. Instead of asking whether niches or neutral processes structure communities, we advocate determining the degree to which observed diversity reflects strong stabilizing mechanisms overcoming large fitness differences or weak stabilization operating on species of similar fitness. To answer this question, we propose combining data on per capita growth rates with models to: (i) quantify the strength of stabilizing processes; (ii) quantify fitness inequality and compare it with stabilization; and (iii) manipulate frequency dependence in growth to test the consequences of stabilization and fitness equivalence for coexistence. PMID:17257097

  20. Ultracold Neutral Plasmas

    OpenAIRE

    Killian, T. C.; Pattard, T.; Pohl, T.; Rost, J. M.

    2006-01-01

    Ultracold neutral plasmas, formed by photoionizing laser-cooled atoms near the ionization threshold, have electron temperatures in the 1-1000 kelvin range and ion temperatures from tens of millikelvin to a few kelvin. They represent a new frontier in the study of neutral plasmas, which traditionally deals with much hotter systems, but they also blur the boundaries of plasma, atomic, condensed matter, and low temperature physics. Modelling these plasmas challenges computational techniques and ...

  1. The neutral comet assay

    International Nuclear Information System (INIS)

    The single-cell gel electrophoresis (or comet) assay is a rapid and sensitive fluorescence microscopic method that is used for the detection of DNA damage at the individual cell level. Comet assay under neutral conditions allows the detection of DNA double-strand breaks, considered to the biologically relevant radiation-induced lesion. In this report we describe modifications of the neutral comet method and its use for studying DNA damage and its repair in irradiated human lymphocytes. (author)

  2. Relativistic redshifts in quasar broad lines

    International Nuclear Information System (INIS)

    The broad emission lines commonly seen in quasar spectra have velocity widths of a few percent of the speed of light, so special- and general-relativistic effects have a significant influence on the line profile. We have determined the redshift of the broad Hβ line in the quasar rest frame (determined from the core component of the [O III] line) for over 20,000 quasars from the Sloan Digital Sky Survey Data Release 7 quasar catalog. The mean redshift as a function of line width is approximately consistent with the relativistic redshift that is expected if the line originates in a randomly oriented Keplerian disk that is obscured when the inclination of the disk to the line of sight exceeds ∼30°-45°, consistent with simple active galactic nucleus unification schemes. This result also implies that the net line-of-sight inflow/outflow velocities in the broad-line region are much less than the Keplerian velocity when averaged over a large sample of quasars with a given line width.

  3. Broad spectrum antibiotic compounds and use thereof

    Energy Technology Data Exchange (ETDEWEB)

    Koglin, Alexander; Strieker, Matthias

    2016-07-05

    The discovery of a non-ribosomal peptide synthetase (NRPS) gene cluster in the genome of Clostridium thermocellum that produces a secondary metabolite that is assembled outside of the host membrane is described. Also described is the identification of homologous NRPS gene clusters from several additional microorganisms. The secondary metabolites produced by the NRPS gene clusters exhibit broad spectrum antibiotic activity. Thus, antibiotic compounds produced by the NRPS gene clusters, and analogs thereof, their use for inhibiting bacterial growth, and methods of making the antibiotic compounds are described.

  4. The fission yeast mitotic activator cdc25 and sucrose induce early flowering synergistically in the day-neutral Nicotiana tabacum cv. Samsun

    Czech Academy of Sciences Publication Activity Database

    Teichmanová, M.; Mašková, P.; Vojvodová, P.; Krekule, Jan; Francis, D.; Lipavská, H.

    2007-01-01

    Roč. 176, č. 4 (2007), s. 804-812. ISSN 0028-646X Grant ostatní: Grantová agentura UK(CZ) 133/2000 Institutional research plan: CEZ:AV0Z50380511 Source of funding: V - iné verejné zdroje Keywords : cdc25 gene * cell cycle regulation * day neutral tobacco Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.249, year: 2007

  5. Common acute lymphoblastic leukemia antigen (CALLA) is active neutral endopeptidase 24.11 ("enkephalinase"): direct evidence by cDNA transfection analysis.

    OpenAIRE

    Shipp, M A; Vijayaraghavan, J.; Schmidt, E V; Masteller, E L; D'Adamio, L; Hersh, L.B.; Reinherz, E L

    1989-01-01

    The common acute lymphoblastic leukemia antigen (CALLA) is a 749-amino acid type II integral membrane protein expressed by most acute lymphoblastic leukemias, certain other lymphoid malignancies with an immature phenotype, and normal lymphoid progenitors. A computer search against the most recent GenBank release (no. 56) indicates that human CALLA cDNA encodes a protein nearly identical to the rat and rabbit neutral endopeptidase 24.11 ("enkephalinase;" EC 3.4.24.11). This zinc metalloendopep...

  6. Ghost imaging with broad distance

    Institute of Scientific and Technical Information of China (English)

    段德洋; 张路; 杜少将; 夏云杰

    2015-01-01

    We present a scheme that is able to achieve the ghost imaging with broad distance. The physical nature of our scheme is that the different wavelength beams are separated in free space by an optical media according to the slow light or dispersion principle. Meanwhile, the equality of the optical distance of the two light arms is not violated. The photon correlation is achieved by the rotating ground glass plate (RGGP) and spatial light modulator (SLM), respectively. Our work shows that a monochromic ghost image can be obtained in the case of RGGP. More importantly, the position (or distance) of the object can be ascertained by the color of the image. Thus, the imaging and ranging processes are combined as one process for the first time to the best of our knowledge. In the case of SLM, we can obtain a colored image regardless of where the object is.

  7. Ultracold neutral plasmas.

    Science.gov (United States)

    Killian, Thomas C

    2007-05-01

    Ultracold neutral plasmas occupy an exotic regime of plasma physics in which electrons form a swarming, neutralizing background for ions that sluggishly move in a correlated manner. Strong interactions between the charged particles give rise to surprising dynamics such as oscillations of the average kinetic energy during equilibration and extremely fast recombination. Such phenomena offer stimulating and challenging problems for computational scientists, and the physics can be applied to other environments, such as the interior of gas giant planets and plasmas created by short-pulse laser irradiation of solid, liquid, and cluster targets. PMID:17478712

  8. Magnetohydrodynamic stability of broad line region clouds

    CERN Document Server

    Krause, Martin; Burkert, Andreas

    2012-01-01

    Hydrodynamic stability has been a longstanding issue for the cloud model of the broad line region in active galactic nuclei. We argue that the clouds may be gravitationally bound to the supermassive black hole. If true, stabilisation by thermal pressure alone becomes even more difficult. We further argue that if magnetic fields should be present in such clouds at a level that could affect the stability properties, they need to be strong enough to compete with the radiation pressure on the cloud. This would imply magnetic field values of a few Gauss for a sample of Active Galactic Nuclei we draw from the literature. We then investigate the effect of several magnetic configurations on cloud stability in axi-symmetric magnetohydrodynamic simulations. For a purely azimuthal magnetic field which provides the dominant pressure support, the cloud first gets compressed by the opposing radiative and gravitational forces. The pressure inside the cloud then increases, and it expands vertically. Kelvin-Helmholtz and colu...

  9. Role of the EF-hand-like Motif in the 14-3-3 Protein- mediated Activation of Yeast Neutral Trehalase Nth1

    Czech Academy of Sciences Publication Activity Database

    Kopecká, Miroslava; Košek, Dalibor; Kukačka, Zdeněk; Řežábková, Lenka; Man, Petr; Novák, Petr; Obšil, T.; Obšilová, Veronika

    2014-01-01

    Roč. 289, č. 20 (2014), s. 13948-13961. ISSN 0021-9258 R&D Projects: GA ČR(CZ) GAP207/11/0455 Grant ostatní: Univerzita Karlova(CZ) 644313; Univerzita Karlova(CZ) 800413 Institutional support: RVO:67985823 ; RVO:61388971 Keywords : calcium * enzyme mechanisms * mass spectrometry (MS) * protein cross-linking * protein structure * 14-3-3 * Bmh * H/D exchange * neutral trehalase * SAXS Subject RIV: CE - Biochemistry Impact factor: 4.573, year: 2014

  10. ITER neutral beam system

    International Nuclear Information System (INIS)

    The Neutral Beam (NB) system for the International Thermonuclear Experimental Reactor (ITER) has reached a high degree of integration with the tokamak and with the rest of the plant. Operational requirements and maintainability have been considered in the design. The paper considers the integration with the tokamak, discusses design improvements which appear necessary and finally notes R and D progress in key areas. (author)

  11. CO2-Neutral Fuels

    Science.gov (United States)

    Goede, Adelbert; van de Sanden, Richard

    2016-06-01

    Mimicking the biogeochemical cycle of System Earth, synthetic hydrocarbon fuels are produced from recycled CO2 and H2O powered by renewable energy. Recapturing CO2 after use closes the carbon cycle, rendering the fuel cycle CO2 neutral. Non-equilibrium molecular CO2 vibrations are key to high energy efficiency.

  12. Issues in neutral currents

    International Nuclear Information System (INIS)

    The experimental results on low energy confirming the structure of the effective Lagrangian of the weak neutral current processes as predicted by the Salam-Weinberg model are reviewed. Some possible modifications of the effective Lagrangian and the feasibility of their experimental verification are also considered. (P.L.)

  13. Bleach Neutralizes Mold Allergens

    Science.gov (United States)

    Science Teacher, 2005

    2005-01-01

    Researchers at National Jewish Medical and Research Center have demonstrated that dilute bleach not only kills common household mold, but may also neutralize the mold allergens that cause most mold-related health complaints. The study, published in the Journal of Allergy and Clinical Immunology, is the first to test the effect on allergic…

  14. Mod en neutral seksualitet!

    DEFF Research Database (Denmark)

    Leer, Jonatan

    2013-01-01

    Towards a Neutral Sexuality! or Roland Barthes as a Queer Thinker? This article argues that the work of Roland Barthes has interesting perspectives in common with the queer theory. This argument will be put forward by using his concept of ‘the neutral’ that Barthes defines as “that which outplays...

  15. Ghost imaging with broad distance

    Science.gov (United States)

    Duan, De-Yang; Zhang, Lu; Du, Shao-Jiang; Xia, Yun-Jie

    2015-10-01

    We present a scheme that is able to achieve the ghost imaging with broad distance. The physical nature of our scheme is that the different wavelength beams are separated in free space by an optical media according to the slow light or dispersion principle. Meanwhile, the equality of the optical distance of the two light arms is not violated. The photon correlation is achieved by the rotating ground glass plate (RGGP) and spatial light modulator (SLM), respectively. Our work shows that a monochromic ghost image can be obtained in the case of RGGP. More importantly, the position (or distance) of the object can be ascertained by the color of the image. Thus, the imaging and ranging processes are combined as one process for the first time to the best of our knowledge. In the case of SLM, we can obtain a colored image regardless of where the object is. Project supported by the National Natural Science Foundation of China (Grant Nos. 61178012, 11204156, 11304179, and 11247240), the Specialized Research Fund for the Doctoral Program of Higher Education of China (Grant Nos. 20133705110001 and 20123705120002), the Scientific Research Foundation for Outstanding Young Scientists of Shandong Province, China (Grant No. BS2013DX034), and the Natural Science Foundation of Shandong Province, China (Grant No. ZR2012FQ024).

  16. Autonomous mine detection system (AMDS) neutralization payload module

    Science.gov (United States)

    Majerus, M.; Vanaman, R.; Wright, N.

    2010-04-01

    The Autonomous Mine Detection System (AMDS) program is developing a landmine and explosive hazards standoff detection, marking, and neutralization system for dismounted soldiers. The AMDS Capabilities Development Document (CDD) has identified the requirement to deploy three payload modules for small robotic platforms: mine detection and marking, explosives detection and marking, and neutralization. This paper addresses the neutralization payload module. There are a number of challenges that must be overcome for the neutralization payload module to be successfully integrated into AMDS. The neutralizer must meet stringent size, weight, and power (SWaP) requirements to be compatible with a small robot. The neutralizer must be effective against a broad threat, to include metal and plastic-cased Anti-Personnel (AP) and Anti-Tank (AT) landmines, explosive devices, and Unexploded Explosive Ordnance (UXO.) It must adapt to a variety of threat concealments, overburdens, and emplacement methods, to include soil, gravel, asphalt, and concrete. A unique neutralization technology is being investigated for adaptation to the AMDS Neutralization Module. This paper will describe review this technology and how the other two payload modules influence its design for minimizing SWaP. Recent modeling and experimental efforts will be included.

  17. Maturation Pathways of Cross-Reactive HIV-1 Neutralizing Antibodies

    Directory of Open Access Journals (Sweden)

    Dimiter S. Dimitrov

    2009-11-01

    Full Text Available Several human monoclonal antibodies (hmAbs and antibody fragments, including the best characterized in terms of structure-function b12 and Fab X5, exhibit relatively potent and broad HIV-1 neutralizing activity. However, the elicitation of b12 or b12-like antibodies in vivo by vaccine immunogens based on the HIV-1 envelope glycoprotein (Env has not been successful. B12 is highly divergent from the closest corresponding germline antibody while X5 is less divergent. We have hypothesized that the relatively high degree of specific somatic hypermutations may preclude binding of the HIV-1 envelope glycoprotein (Env to closest germline antibodies, and that identifying antibodies that are intermediates in the pathways to maturation could help design novel vaccine immunogens to guide the immune system for their enhanced elicitation. In support of this hypothesis we have previously found that a germline-like b12 (monovalent and bivalent scFv as an Fc fusion protein or IgG lacks measurable binding to an Env as measured by ELISA with a sensitivity in the μM range [1]; here we present evidence confirming and expanding these findings for a panel of Envs. In contrast, a germline-like scFv X5 bound Env with high (nM affinity. To begin to explore the maturation pathways of these antibodies we identified several possible b12 intermediate antibodies and tested their neutralizing activity. These intermediate antibodies neutralized only some HIV-1 isolates and with relatively weak potency. In contrast, germline-like scFv X5 neutralized a subset of the tested HIV-1 isolates with comparable efficiencies to that of the mature X5. These results could help explain the relatively high immunogenicity of the coreceptor binding site on gp120 and the abundance of CD4-induced (CD4i antibodies in HIV-1-infected patients (X5 is a CD4i antibody as well as the maturation pathway of X5. They also can help identify antigens that can bind specifically to b12 germline and

  18. 77 FR 50144 - Broad Stakeholder Survey

    Science.gov (United States)

    2012-08-20

    ... SECURITY Broad Stakeholder Survey AGENCY: National Protection and Programs Directorate, DHS. ACTION: 60-day... comments concerning the Broad Stakeholder Survey. DATES: Comments are encouraged and will be accepted until... across the Nation. The Broad Stakeholder Survey is designed to gather stakeholder feedback on...

  19. 76 FR 34087 - Broad Stakeholder Survey

    Science.gov (United States)

    2011-06-10

    ... SECURITY Broad Stakeholder Survey AGENCY: National Protection and Programs Directorate, DHS. ACTION: 60-day... comments concerning the Broad Stakeholder Survey. DATES: Comments are encouraged and will be accepted until.... The Broad Stakeholder Survey is designed to gather stakeholder feedback on the effectiveness of...

  20. 78 FR 20119 - Broad Stakeholder Survey

    Science.gov (United States)

    2013-04-03

    ... SECURITY Broad Stakeholder Survey AGENCY: National Protection and Programs Directorate, DHS. ACTION: 30-day... soliciting comments concerning the Broad Stakeholder Survey. DHS previously published this ICR in the Federal... responders across the Nation. The Broad Stakeholder Survey is designed to gather stakeholder feedback on...

  1. Neutral muonic helium(3)

    International Nuclear Information System (INIS)

    Neutral muonic helium, He++μ-e-, can be considered in two pieces. The (He++μ-)+-system is a hydrogenic ion halfway in size between an atom and a nucleus. It acts like a singly charged pseudo-nucleus to the electron surrounding it. The whole system appears like one hydrogen inside another. Neutral muonic helium can be formed in the ground state in which the coupling of the magnetic moments gives rise to a hyperfine structure (hfs). 3He++μ-e- has three spin one half particles interact without any restrictions by the Pauli exclusion principle. The level diagram of the ground state is shown. There is a large muonic hfs splitting corresponding to the He++μ- ion to be in one of the two spin states with total spin quantum number G = 0 and G = 1. To measure the atomic hfs superimposed on the G = 1 triplet state is the aim of this experiment. (Auth.)

  2. Ultracold Neutral Plasmas

    CERN Document Server

    Killian, T C; Pohl, T; Rost, J M

    2006-01-01

    Ultracold neutral plasmas, formed by photoionizing laser-cooled atoms near the ionization threshold, have electron temperatures in the 1-1000 kelvin range and ion temperatures from tens of millikelvin to a few kelvin. They represent a new frontier in the study of neutral plasmas, which traditionally deals with much hotter systems, but they also blur the boundaries of plasma, atomic, condensed matter, and low temperature physics. Modelling these plasmas challenges computational techniques and theories of non-equilibrium systems, so the field has attracted great interest from the theoretical and computational physics communities. By varying laser intensities and wavelengths it is possible to accurately set the initial plasma density and energy, and charged-particle-detection and optical diagnostics allow precise measurements for comparison with theoretical predictions. Recent experiments using optical probes demonstrated that ions in the plasma equilibrate in a strongly coupled fluid phase. Strongly coupled pla...

  3. Rabbits immunized with Epstein-Barr virus gH/gL or gB recombinant proteins elicit higher serum virus neutralizing activity than gp350.

    Science.gov (United States)

    Cui, Xinle; Cao, Zhouhong; Chen, Quanyi; Arjunaraja, Swadhinya; Snow, Andrew L; Snapper, Clifford M

    2016-07-25

    Epstein-Barr virus (EBV) is the primary cause of infectious mononucleosis and has been strongly implicated in the etiology of multiple epithelial and lymphoid cancers, such as nasopharyngeal carcinoma, gastric carcinoma, Hodgkin lymphoma, Burkitt lymphoma, non-Hodgkin lymphoma and post-transplant lymphoproliferative disorder. There is currently no licensed prophylactic vaccine for EBV. Most efforts to develop prophylactic vaccines have focused on EBV gp350, which binds to CD21/CD35 to gain entry into B cells, and is a major target of serum neutralizing antibody in EBV seropositive humans. However, a recombinant monomeric gp350 protein failed to prevent EBV infection in a phase II clinical trial. Thus, alternative or additional target antigens may be necessary for a successful prophylactic vaccine. EBV gH/gL and gB proteins coordinately mediate EBV fusion and entry into B cells and epithelial cells, strongly suggesting that vaccination with these proteins might elicit antibodies that will prevent EBV infection. We produced recombinant trimeric and monomeric EBV gH/gL heterodimeric proteins and a trimeric EBV gB protein, in addition to tetrameric and monomeric gp350(1-470) proteins, in Chinese hamster ovary cells. We demonstrated that vaccination of rabbits with trimeric and monomeric gH/gL, trimeric gB, and tetrameric gp350(1-470) induced serum EBV-neutralizing titers, using cultured human B cells, that were >100-fold, 20-fold, 18-fold, and 4-fold higher, respectively, than monomeric gp350(1-470). These data strongly suggest a role for testing EBV gH/gL and EBV gB in a future prophylactic vaccine to prevent EBV infection of B cells, as well as epithelial cells. PMID:27291087

  4. Neutral atom traps.

    Energy Technology Data Exchange (ETDEWEB)

    Pack, Michael Vern

    2008-12-01

    This report describes progress in designing a neutral atom trap capable of trapping sub millikelvin atom in a magnetic trap and shuttling the atoms across the atom chip from a collection area to an optical cavity. The numerical simulation and atom chip design are discussed. Also, discussed are preliminary calculations of quantum noise sources in Kerr nonlinear optics measurements based on electromagnetically induced transparency. These types of measurements may be important for quantum nondemolition measurements at the few photon limit.

  5. Neutral beams for mirrors

    International Nuclear Information System (INIS)

    An important demonstration of negative ion technology is proposed for FY92 in the MFTF-α+T, an upgrade of the Mirror Fusion Test Facility at the Lawrence Livermore National Laboratory. This facility calls for 200-keV negative ions to form neutral beams that generate sloshing ions in the reactor end plugs. Three different beam lines are considered for this application. Their advantages and disadvantages are discussed

  6. Gargamelle: neutral current event

    CERN Multimedia

    1973-01-01

    This event shows real tracks of particles from the 1200 litre Gargamelle bubble chamber that ran on the PS from 1970 to 1976 and on the SPS from 1976 to 1979. In this image a neutrino passes close to a nucleon and reemerges as a neutrino. Such events are called neutral curent, as they are mediated by the Z0 boson which has no electric charge.

  7. Eliciting neutralizing antibodies against the membrane proximal external region of HIV-1 Env by chimeric live attenuated influenza A virus vaccines.

    Science.gov (United States)

    Zang, Yang; Du, Dongchuan; Li, Na; Su, Weiheng; Liu, Xintao; Zhang, Yan; Nie, Jianhui; Wang, Youchun; Kong, Wei; Jiang, Chunlai

    2015-07-31

    Despite significant efforts directed toward research on HIV-1 vaccines, a truly effective immunogen has not been achieved. However, the broadly neutralizing antibodies (BnAbs) 2F5 and 4E10, targeting the highly conserved membrane proximal external region (MPER) of HIV-1, are two promising tools for vaccine development. Here we engrafted the MPER into the linker domain between the trimeric core structure and the transmembrane domain of influenza A virus HA2 to investigate the potential of such chimeric viruses to elicit HIV-1 neutralizing antibodies. In the context of proliferating attenuated influenza A viruses, these HIV-1 neutralizing antibody epitopes could be continuously expressed and mimicked their native conformation to induce humoral immune responses. While MPER-specific antibodies could be detected in serum of guinea pigs vaccinated with the chimeric viruses, they exhibited only weakly neutralizing activities. These antisera from vaccinated animals neutralized viruses of clades B and BC (tier 1), but not of clades AE (tier 1) and C (tier 2). These results suggest that influenza A virus can be used as a vehicle for displaying MPER and inducing BnAbs, but it provides limited protection against HIV-1 infection. In the future development of HIV-1 vaccines by rational design, a more effective live virus vector or multiple antigens should be chosen to facilitate the process of neutralizing antibody maturation. PMID:26126669

  8. Conformational Masking and Receptor-Dependent Unmasking of Highly Conserved Env Epitopes Recognized by Non-Neutralizing Antibodies That Mediate Potent ADCC against HIV-1.

    Science.gov (United States)

    Lewis, George K; Finzi, Andrés; DeVico, Anthony L; Pazgier, Marzena

    2015-09-01

    The mechanism of antibody-mediated protection is a major focus of HIV-1 vaccine development and a significant issue in the control of viremia. Virus neutralization, Fc-mediated effector function, or both, are major mechanisms of antibody-mediated protection against HIV-1, although other mechanisms, such as virus aggregation, are known. The interplay between virus neutralization and Fc-mediated effector function in protection against HIV-1 is complex and only partially understood. Passive immunization studies using potent broadly neutralizing antibodies (bnAbs) show that both neutralization and Fc-mediated effector function provides the widest dynamic range of protection; however, a vaccine to elicit these responses remains elusive. By contrast, active immunization studies in both humans and non-human primates using HIV-1 vaccine candidates suggest that weakly neutralizing or non-neutralizing antibodies can protect by Fc-mediated effector function, albeit with a much lower dynamic range seen for passive immunization with bnAbs. HIV-1 has evolved mechanisms to evade each type of antibody-mediated protection that must be countered by a successful AIDS vaccine. Overcoming the hurdles required to elicit bnAbs has become a major focus of HIV-1 vaccine development. Here, we discuss a less studied problem, the structural basis of protection (and its evasion) by antibodies that protect only by potent Fc-mediated effector function. PMID:26393642

  9. Study of Zweig's rule using phi mesons in a broad band neutral beam

    International Nuclear Information System (INIS)

    A study of Zweig's rule using phi mesons in a high energy photon beam was performed. Measurement of the ratio sigma(γA → phi ππA)/sigma(γA → ωππA) = 0.10 +- 0.02 is taken as evidence that there is not as strong suppression as could be expected. Other ratios show strange particle production down from nonstrange particle production by a factor of twelve. Decays involving phi mesons are studied, and the only candidate seen is a four sigma effect in the mode two phis with a mass 2.15 GeV. F meson, charm pseudo-scalar meson and exotic vector mesons which might decay into phis are not seen. The phi prime is not seen with an upper limit sigma(γA → phi'A)B(phi' → K+K-π+π-) < 6 nb per nucleon

  10. Human broadly neutralizing antibodies to the envelope glycoprotein complex of hepatitis C virus

    DEFF Research Database (Denmark)

    Giang, Erick; Dorner, Marcus; Prentoe, Jannick C;

    2012-01-01

    Hepatitis C virus (HCV) infects ∼2% of the world's population. It is estimated that there are more than 500,000 new infections annually in Egypt, the country with the highest HCV prevalence. An effective vaccine would help control this expanding global health burden. HCV is highly variable, and a...

  11. AGN Broad Line Regions Scale with Bolometric Luminosity

    CERN Document Server

    Trippe, Sascha

    2015-01-01

    The masses of supermassive black holes in active galactic nuclei (AGN) can be derived spectroscopically via virial mass estimators based on selected broad optical/ultraviolet emission lines. These estimates commonly use the line width as a proxy for the gas speed and the monochromatic continuum luminosity as a proxy for the radius of the broad line region. However, if the size of the broad line region scales with bolometric rather than monochromatic AGN luminosity, mass estimates based on different emission lines will show a systematic discrepancy which is a function of the color of the AGN continuum. This has actually been observed in mass estimates based on H-alpha / H-beta and C IV lines, indicating that AGN broad line regions indeed scale with bolometric luminosity. Given that this effect seems to have been overlooked as yet, currently used single-epoch mass estimates are likely to be biased.

  12. Identification of the Broad Solar Emission Features Near 117 nm

    CERN Document Server

    Avrett, E H; Loeser, R; Avrett, Eugene H.; Kurucz, Robert L.; Loeser, Rudolf

    2006-01-01

    Wilhelm et al. have recently called attention to the unidentified broad emission features near 117 nm in the solar spectrum. They discuss the observed properties of these features in detail but do not identify the source of this emission. We show that the broad autoionizing transitions of neutral sulfur are responsible for these emission features. Autoionizing lines of \\ion{S}{i} occur throughout the spectrum between Lyman alpha and the Lyman limit. Sulfur is a normal contributor to stellar spectra. We use non-LTE chromospheric model calculations with line data from the Kurucz 2004 \\ion{S}{i} line list to simulate the solar spectrum in the range 116 to 118 nm. We compare the results with SUMER disk-center observations from Curdt et al. and limb observations from Wilhelm et al. Our calculations generally agree with the SUMER observations of the broad autoionizing \\ion{S}{i} emission features, the narrow \\ion{S}{i} emission lines, and the continuum in this wavelength region, and agree with basic characteristics...

  13. A new balancing three level three dimensional space vector modulation strategy for three level neutral point clamped four leg inverter based shunt active power filter controlling by nonlinear back stepping controllers.

    Science.gov (United States)

    Chebabhi, Ali; Fellah, Mohammed Karim; Kessal, Abdelhalim; Benkhoris, Mohamed F

    2016-07-01

    In this paper is proposed a new balancing three-level three dimensional space vector modulation (B3L-3DSVM) strategy which uses a redundant voltage vectors to realize precise control and high-performance for a three phase three-level four-leg neutral point clamped (NPC) inverter based Shunt Active Power Filter (SAPF) for eliminate the source currents harmonics, reduce the magnitude of neutral wire current (eliminate the zero-sequence current produced by single-phase nonlinear loads), and to compensate the reactive power in the three-phase four-wire electrical networks. This strategy is proposed in order to gate switching pulses generation, dc bus voltage capacitors balancing (conserve equal voltage of the two dc bus capacitors), and to switching frequency reduced and fixed of inverter switches in same times. A Nonlinear Back Stepping Controllers (NBSC) are used for regulated the dc bus voltage capacitors and the SAPF injected currents to robustness, stabilizing the system and to improve the response and to eliminate the overshoot and undershoot of traditional PI (Proportional-Integral). Conventional three-level three dimensional space vector modulation (C3L-3DSVM) and B3L-3DSVM are calculated and compared in terms of error between the two dc bus voltage capacitors, SAPF output voltages and THDv, THDi of source currents, magnitude of source neutral wire current, and the reactive power compensation under unbalanced single phase nonlinear loads. The success, robustness, and the effectiveness of the proposed control strategies are demonstrated through simulation using Sim Power Systems and S-Function of MATLAB/SIMULINK. PMID:27018144

  14. Isolation and purification of a neutral alpha(1,2)-mannosidase from Trypanosoma cruzi.

    Science.gov (United States)

    Bonay, P; Fresno, M

    1999-05-01

    Trypanosoma cruzi is an obligatory intracellular protozoan parasite that causes Chagas' disease in humans. Although a fair amount is known about the biochemistry of certain trypanosomes, very little is known about the enzymic complement of synthesis and processing of glycoproteins and/or functions of the subcellular organelles in this parasite. There have been very few reports on the presence of acid and neutral hydrolases in Trypanosoma cruzi. Here we report the first purification and characterization of a neutral mannosidase from the epimastigote stage of Trypanosoma cruzi. The neutral mannosidase was purified nearly 800-fold with an 8% recovery to apparent homogeneity from a CHAPS extract of epimastigotes by the following procedures: (1) metal affinity chromatography on Co+2-Sepharose, (2) anion exchange, and (3) hydroxylapatite. The purified enzyme has a native molecular weight of 150-160 kDa and is apparently composed of two subunits of 76 kDa. The purified enzyme exhibits a broad pH profile with a maximum at pH 5.9-6.3. It is inhibited by swainsonine (Ki, 0.1 microM), D-mannono-delta-lactam (Ki, 20 microM), kifunensine (Ki, 60 microM) but not significantly by deoxymannojirimycin. The enzyme is activated by Co2+and Ni2+and strongly inhibited by EDTA and Fe2+. The purified enzyme is active against p-nitrophenyl alpha-D-mannoside (km = 87 microM). High-mannose Man9GlcNAc substrate was hydrolyzed by the purified enzyme to Man7GlcNAc at pH 6.1. The purified enzyme does not show activity against alpha1,3- or alpha1,6-linked mannose residues. Antibodies against the recently purified lysosomal alpha-mannosidase from T.cruzi did not react with the neutral mannosidase reported here. PMID:10207175

  15. Doublet III vacuum vessel neutral beam armor

    International Nuclear Information System (INIS)

    The evolution of the Doublet III neutral beam armor is followed from the initial design of a radiation cooled metallic tile to the present actively cooled graphite design. Results of the thermal and stress analyses that dictated the present design are reviewed

  16. Characterization and epitope mapping of monoclonal antibodies raised against rat hepatitis E virus capsid protein: An evaluation of their neutralizing activity in a cell culture system.

    Science.gov (United States)

    Kobayashi, Tominari; Takahashi, Masaharu; Tanggis; Mulyanto; Jirintai, Suljid; Nagashima, Shigeo; Nishizawa, Tsutomu; Okamoto, Hiroaki

    2016-07-01

    Hepatitis E virus (HEV) is the causative agent of acute hepatitis. Rat HEV is a recently discovered virus related to, but distinct from, human HEV. Since laboratory rats can be reproducibly infected with rat HEV and a cell culture system has been established for rat HEV, this virus may be used as a surrogate virus for human HEV, enabling studies on virus replication and mechanism of infection. However, monoclonal antibodies (MAbs) against rat HEV capsid (ORF2) protein are not available. In this study, 12 murine MAbs were generated against a recombinant ORF2 protein of rat HEV (rRatHEV-ORF2: amino acids 101-644) and were classified into at least six distinct groups by epitope mapping and a cross-reactivity analysis with human HEV ORF2 proteins. Two non-cross-reactive MAbs recognizing the protruding (P) domain detected both non-denatured and denatured rRatHEV-ORF2 protein and efficiently captured cell culture-produced rat HEV particles that had been treated with deoxycholate and trypsin, but not those without prior treatment. In addition, these two MAbs were able to efficiently neutralize replication of cell culture-generated rat HEV particles without lipid membranes (but not those with lipid membranes) in a cell culture system, similar to human HEV. PMID:26992654

  17. Nonexotic Neutral Gauge Bosons

    OpenAIRE

    Appelquist, Thomas; Dobrescu, Bogdan A.; Hopper, Adam R.

    2002-01-01

    We study theoretical and experimental constraints on electroweak theories including a new color-singlet and electrically-neutral gauge boson. We first note that the electric charges of the observed fermions imply that any such Z' boson may be described by a gauge theory in which the Abelian gauge groups are the usual hypercharge along with another U(1) component in a kinetic-diagonal basis. Assuming that the observed quarks and leptons have generation-independent U(1) charges, and that no new...

  18. Neutralization potential as an assay of alkalinity of environmental solids

    International Nuclear Information System (INIS)

    The method to determine neutralizing equivalence of agricultural limestone has been applied to quantify the amount of bases present in a broad diversity of mineral materials, solid reagents, and products involved in environmental processes. The capacity to neutralize native or imposed acidity must be known in many processes in order to preserve near-neutral material. The standard method for assaying agricultural limestones was adapted to quantify native alkalinity in calcareous rocks exposed by coal surface mining. Data from these analyses continue to provide the surface mining industry and regulating agencies with a measure of the extent to which acidic mine drainage may be neutralized by the natural components of surrounding rock strata and disturbed materials. This approach to determine base content has also been applied to commercially available industrial byproducts added to soils or wastes. Kiln dust, fly ash, sludge, and other additives have been evaluated routinely to measure their alkalinity contribution and also batch-to-batch uniformity. The application of this technique to monitor amounts of reagents added to neutralize acid waste materials by adding alkalis is discussed. Use of this procedure to evaluate different materials is documented with exemplary data. Results of analyses of a broad variety of rock and soil materials, amended soils, soil additives or amendments, industrial waste byproducts, sludge, and treated wastes are presented. Utility of the procedure for routine quality control in soil treatment, amendment uniformity, and product analysis is discussed

  19. Characterization of a Large Panel of Rabbit Monoclonal Antibodies against HIV-1 gp120 and Isolation of Novel Neutralizing Antibodies against the V3 Loop.

    Directory of Open Access Journals (Sweden)

    Yali Qin

    Full Text Available We recently reported the induction of potent, cross-clade neutralizing antibodies (nAbs against Human Immunodeficiency Virus type-1 (HIV-1 in rabbits using gp120 based on an M-group consensus sequence. To better characterize these antibodies, 93 hybridomas were generated, which represent the largest panel of monoclonal antibodies (mAbs ever generated from a vaccinated rabbit. The single most frequently recognized epitope of the isolated mAbs was at the very C-terminal end of the protein (APTKAKRRVVEREKR, followed by the V3 loop. A total of seven anti-V3 loop mAbs were isolated, two of which (10A3 and 10A37 exhibited neutralizing activity. In contrast to 10A3 and most other anti-V3 loop nAbs, 10A37 was atypical with its epitope positioned more towards the C-terminal half of the loop. To our knowledge, 10A37 is the most potent and broadly neutralizing anti-V3 loop mAb induced by vaccination. Interestingly, all seven anti-V3 loop mAbs competed with PGT121, suggesting a possibility that early induction of potent anti-V3 loop antibodies could prevent induction of more broadly neutralizing PGT121-like antibodies that target the conserved base of the V3 loop stem.

  20. Tracing the neutral gas environments of young radio AGN with ASKAP

    CERN Document Server

    Allison, J R; Moss, V A; Harvey-Smith, L; Heywood, I; Indermuehle, B T; McConnell, D; Sault, R J; Whiting, M T

    2015-01-01

    At present neutral atomic hydrogen (HI) gas in galaxies at redshifts above $z \\sim 0.3$ (the extent of 21-cm emission surveys in individual galaxies) and below $z \\sim 1.7$ (where the Lyman-$\\alpha$ line is not observable with ground-based telescopes) has remained largely unexplored. The advent of precursor telescopes to the Square Kilometre Array will allow us to conduct the first systematic radio-selected 21-cm absorption surveys for HI over these redshifts. While HI absorption is a tracer of the reservoir of cold neutral gas in galaxies available for star formation, it can also be used to reveal the extreme kinematics associated with jet-driven neutral outflows in radio-loud active galactic nuclei. Using the six-antenna Boolardy Engineering Test Array of the Australian Square Kilometre Array Pathfinder, we have demonstrated that in a single frequency tuning we can detect HI absorption over a broad range of redshifts between $z = 0.4$ and $1.0$. As part of our early science and commissioning program, we are...

  1. A broad view of arsenic.

    Science.gov (United States)

    Jones, F T

    2007-01-01

    In the mind of the general public, the words "arsenic" and "poison" have become almost synonymous. Yet, As is a natural metallic element found in low concentrations in virtually every part of the environment, including foods. Mining and smelting activities are closely associated with As, and the largest occurrence of As contamination in the United States is near the gold mines of northern Nevada. Inhabitants of Bangladesh and surrounding areas have been exposed to water that is naturally and heavily contaminated with As, causing what the World Health Organization has described as the worst mass poisoning in history. Although readily absorbed by humans, most inorganic As (>90%) is rapidly cleared from the blood with a half-life of 1 to 2 h, and 40 to 70% of the As intake is absorbed, metabolized, and excreted within 48 h. Arsenic does not appreciably bioaccumulate, nor does it biomagnify in the food chain. The United States has for some time purchased more As than any other country in the world, but As usage is waning, and further reductions appear likely. Arsenic is used in a wide variety of industrial applications, from computers to fireworks. All feed additives used in US poultry feeds must meet the strict requirements of the US Food and Drug Administration Center for Veterinary Medicine (Rockville, MD) before use. Although some public health investigators have identified poultry products as a potentially significant source of total As exposure for Americans, studies consistently demonstrate that <1% of samples tested are above the 0.5 ppm limit established by the US Food and Drug Administration Center for Veterinary Medicine. Although laboratory studies have demonstrated the possibility that As in poultry litter could pollute ground waters, million of tons of litter have been applied to the land, and no link has been established between litter application and As contamination of ground water. Yet, the fact that <2% of the United States population is involved in

  2. Commentary: Ownership Neutrality and Practical Complications

    OpenAIRE

    Shay, Stephen E.

    2009-01-01

    In "Reconsidering the Taxation of Foreign Income," Jim Hines analyzes the consequences of taxing, as opposed to exempting, active foreign business income by comparing the expected effects on capital ownership of a "pure" worldwide income taxation system with the effects on capital ownership of a "pure" territorial taxation regime. Consistent with his earlier work, Hines asserts that a capital ownership neutrality analysis supports exempting foreign active business income from home country res...

  3. Comparison of Search Engines Non-Neutral and Neutral Behaviors

    OpenAIRE

    COUCHENEY, Pierre; Maillé, Patrick; Tuffin, Bruno

    2012-01-01

    Network neutrality has recently attracted a lot of attention but search neutrality is also becoming a vivid subject of discussion because a non-neutral search may prevent some relevant content from being accessed by users. We propose in this paper to model two situations of a non-neutral search engine behavior, which can rank the link propositions according to the pro t a search can generate for it instead of just relevance: the case when the search engine owns some content, and the case when...

  4. HIV-1 binding and neutralizing antibodies of injecting drug users

    Directory of Open Access Journals (Sweden)

    E.P. Ouverney

    2005-09-01

    Full Text Available Previous studies have demonstrated a stronger seroreactivity against some synthetic peptides responsible for inducing neutralizing antibodies in injecting drug users (IDU compared to that of individuals sexually infected with HIV-1 (S, but the effectiveness in terms of the neutralizing ability of these antibodies has not been evaluated. Our objective was to study the humoral immune response of IDU by determining the specificity of their antibodies and the presence of neutralizing antibodies. The neutralization capacity against the HIV-1 isolate MN (genotype B, the primary HIV-1 isolate 95BRRJ021 (genotype F, and the seroreactivity with peptides known to induce neutralizing antibodies, from the V2 and V3 loops of different HIV-1 subtypes, were analyzed. Seroreactivity indicates that IDU plasma are more likely to recognize a broader range of peptides than S plasma, with significantly higher titers, especially of V3 peptides. Similar neutralization frequencies of the MN isolate were observed in plasma of the IDU (16/47 and S (20/60 groups in the 1:10 dilution. The neutralization of the 95BRRJ021 isolate was more frequently observed for plasma from the S group (15/23 than from the IDU group (15/47, P = 0.0108. No correlation between neutralization and seroreactivity with the peptides tested was observed. These results suggest that an important factor responsible for the extensive and broad humoral immune response observed in IDU is their infection route. There was very little difference in neutralizing antibody response between the IDU and S groups despite their differences in seroreactivity and health status.

  5. Broad Prize: Do the Successes Spread?

    Science.gov (United States)

    Samuels, Christina A.

    2011-01-01

    When the Broad Prize for Urban Education was created in 2002, billionaire philanthropist Eli Broad said he hoped the awards, in addition to rewarding high-performing school districts, would foster healthy competition; boost the prestige of urban education, long viewed as dysfunctional; and showcase best practices. Over the 10 years the prize has…

  6. Antihypertensive neutral lipid

    Energy Technology Data Exchange (ETDEWEB)

    Snyder, F.L.; Blank, M.L.

    1986-06-17

    A method is described for treating a warm-blooded animal comprising administering to the animal a neutral glycerolipid with a 12 to 20 carbon alkyl group at the sn-1 position, a short carbon chain acyl group at the sn-2 position and a hydroxyl group at the sn-3 position in an amount sufficient to lower the arterial blood pressure of the animal. A method is also described for treating a warm-blooded animal comprising administering a composition consisting essentially of a 1-alkyl-2-acetyl (or propionyl)-sn glycerol in combination with a 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine, wherein the 1-alkyl groups contain 12 to 20 carbon atoms, dissolved in an inert pharmaceutically acceptable solvent in amounts sufficient to lower the arterial blood pressure of the animal.

  7. Children and trauma : a broad perspective on exposure and recovery

    NARCIS (Netherlands)

    Alisic, E.

    2011-01-01

    The purpose of this dissertation was to generate a broad overview of children’s exposure to and recovery from trauma in order to promote theory building and the design of prevention and intervention activities. First, a general population study was conducted in 1770 primary school children. They fil

  8. Trivalent combination vaccine induces broad heterologous immune responses to norovirus and rotavirus in mice.

    Directory of Open Access Journals (Sweden)

    Kirsi Tamminen

    Full Text Available Rotavirus (RV and norovirus (NoV are the two major causes of viral gastroenteritis (GE in children worldwide. We have developed an injectable vaccine design to prevent infection or GE induced with these enteric viruses. The trivalent combination vaccine consists of NoV capsid (VP1 derived virus-like particles (VLPs of GI-3 and GII-4 representing the two major NoV genogroups and tubular RV recombinant VP6 (rVP6, the most conserved and abundant RV protein. Each component was produced in insect cells by a recombinant baculovirus expression system and combined in vitro. The vaccine components were administered intramuscularly to BALB/c mice either separately or in the trivalent combination. High levels of NoV and RV type specific serum IgGs with high avidity (>50% as well as intestinal IgGs were detected in the immunized mice. Cross-reactive IgG antibodies were also elicited against heterologous NoV VLPs not used for immunization (GII-4 NO, GII-12 and GI-1 VLPs and to different RVs from cell cultures. NoV-specific serum antibodies blocked binding of homologous and heterologous VLPs to the putative receptors, histo-blood group antigens, suggesting broad NoV neutralizing activity of the sera. Mucosal antibodies of mice immunized with the trivalent combination vaccine inhibited RV infection in vitro. In addition, cross-reactive T cell immune responses to NoV and RV-specific antigens were detected. All the responses were sustained for up to six months. No mutual inhibition of the components in the trivalent vaccine combination was observed. In conclusion, the NoV GI and GII VLPs combination induced broader cross-reactive and potentially neutralizing immune responses than either of the VLPs alone. Therefore, trivalent vaccine might induce protective immune responses to the vast majority of circulating NoV and RV genotypes.

  9. Effects of detergent on calcium-activated neutral proteinase (CANP) of neural and non-neural tissues in rat. A comparative study

    International Nuclear Information System (INIS)

    Homogenates of brain, liver, kidney, heart and skeletal muscle of rat were prepared in 0.32 M-sucrose containing 2 mM EDTA. The CANP activity was assayed using 14C-azocasein as substrate in 50 mM Tris acetate buffer, pH 7.4, 0.1% Triton X-100 and 5 mM-β-mercaptoethanol, with and without CaCl2. Addition to CNS membranes of other non-ionic detergents including sodium deoxycholate, β-D-thiogluco-pyranoside, and cetyltrimethyl-ammonium bromide activated the enzyme to varying extent depending on the detergent concentration. The ionic detergent sodium dodecyl sulfate abolished CANP activity completely in all preparations and this effect could not be reversed by non-ionic detergents. The most interesting feature of the Triton X-100 effect was a ten-fold increase of CNS CANP activity whereas non-neural CANP was not at all induced by Triton. CNS CANP was found mainly in the particulate fraction and only 30% in cytosol. In contrast, non-neural CANP was present mainly in cytosol. These results suggest that the bulk of CANP is membrane bound in CNS and differs from other tissue where it remains cytosolic

  10. CO2-neutral fuels

    Science.gov (United States)

    Goede, A. P. H.

    2015-08-01

    The need for storage of renewable energy (RE) generated by photovoltaic, concentrated solar and wind arises from the fact that supply and demand are ill-matched both geographically and temporarily. This already causes problems of overcapacity and grid congestion in countries where the fraction of RE exceeds the 20% level. A system approach is needed, which focusses not only on the energy source, but includes conversion, storage, transport, distribution, use and, last but not least, the recycling of waste. Furthermore, there is a need for more flexibility in the energy system, rather than relying on electrification, integration with other energy systems, for example the gas network, would yield a system less vulnerable to failure and better adapted to requirements. For example, long-term large-scale storage of electrical energy is limited by capacity, yet needed to cover weekly to seasonal demand. This limitation can be overcome by coupling the electricity net to the gas system, considering the fact that the Dutch gas network alone has a storage capacity of 552 TWh, sufficient to cover the entire EU energy demand for over a month. This lecture explores energy storage in chemicals bonds. The focus is on chemicals other than hydrogen, taking advantage of the higher volumetric energy density of hydrocarbons, in this case methane, which has an approximate 3.5 times higher volumetric energy density. More importantly, it allows the ready use of existing gas infrastructure for energy storage, transport and distribution. Intermittent wind electricity generated is converted into synthetic methane, the Power to Gas (P2G) scheme, by splitting feedstock CO2 and H2O into synthesis gas, a mixture of CO and H2. Syngas plays a central role in the synthesis of a range of hydrocarbon products, including methane, diesel and dimethyl ether. The splitting is accomplished by innovative means; plasmolysis and high-temperature solid oxygen electrolysis. A CO2-neutral fuel cycle is

  11. CO2-neutral fuels

    Directory of Open Access Journals (Sweden)

    Goede A. P. H.

    2015-01-01

    Full Text Available The need for storage of renewable energy (RE generated by photovoltaic, concentrated solar and wind arises from the fact that supply and demand are ill-matched both geographically and temporarily. This already causes problems of overcapacity and grid congestion in countries where the fraction of RE exceeds the 20% level. A system approach is needed, which focusses not only on the energy source, but includes conversion, storage, transport, distribution, use and, last but not least, the recycling of waste. Furthermore, there is a need for more flexibility in the energy system, rather than relying on electrification, integration with other energy systems, for example the gas network, would yield a system less vulnerable to failure and better adapted to requirements. For example, long-term large-scale storage of electrical energy is limited by capacity, yet needed to cover weekly to seasonal demand. This limitation can be overcome by coupling the electricity net to the gas system, considering the fact that the Dutch gas network alone has a storage capacity of 552 TWh, sufficient to cover the entire EU energy demand for over a month. This lecture explores energy storage in chemicals bonds. The focus is on chemicals other than hydrogen, taking advantage of the higher volumetric energy density of hydrocarbons, in this case methane, which has an approximate 3.5 times higher volumetric energy density. More importantly, it allows the ready use of existing gas infrastructure for energy storage, transport and distribution. Intermittent wind electricity generated is converted into synthetic methane, the Power to Gas (P2G scheme, by splitting feedstock CO2 and H2O into synthesis gas, a mixture of CO and H2. Syngas plays a central role in the synthesis of a range of hydrocarbon products, including methane, diesel and dimethyl ether. The splitting is accomplished by innovative means; plasmolysis and high-temperature solid oxygen electrolysis. A CO2-neutral fuel

  12. The quasi-neutral limit in optimal semiconductor design

    OpenAIRE

    Pinnau, Rene; Totzeck, Claudia; Tse, Oliver

    2015-01-01

    We study the quasi-neutral limit in an optimal semiconductor design problem constrained by a nonlinear, nonlocal Poisson equation modelling the drift diffusion equations in thermal equilibrium. While a broad knowledge on the asymptotic links between the different models in the semiconductor model hierarchy exists, there are so far no results on the corresponding optimization problems available. Using a variational approach we end up with a bi-level optimization problem, which is thoroughly an...

  13. Application Neutrality and a Paradox of Side Payments

    CERN Document Server

    Altman, Eitan; Kesidis, George

    2010-01-01

    The ongoing debate over "net neutrality" covers a broad set of issues related to the regulation of public networks. This paper contains two separate contributions: (a) an extension of the quadratic-utility framework we proposed in a previous paper to study the impact of side payments in a system involving pluralities of access and content providers; and (b) a variation of this model to deal with the question of application neutrality. Our analysis of the generalized framework (a) reveals an interesting "paradox" that did not occur with monopolistic players: side payments handicap the providers who perceive them. Application neutrality (b) refers to price discrimination: ISPs charging consumers different fees depending on their use of the network (web surfing, VoIP, file sharing, etc.). We analyze the consequences of such discrimination for a simple two-application setting.

  14. The merits of neutral theory

    NARCIS (Netherlands)

    Alonso, David; Etienne, Rampal S.; McKane, Alan J.

    2006-01-01

    Hubbell's neutral theory of biodiversity has challenged the classic niche-based view of ecological community structure. Although there have been many attempts to falsify Hubbell's theory, we argue that falsification should not lead to rejection, because there is more to the theory than neutrality al

  15. Self-neutralizing well acidizing

    Energy Technology Data Exchange (ETDEWEB)

    Richardson, E.A.; Scheuerman, R.F.

    1974-07-30

    A process for acidizing a subterranean region by contacting it with an acidic solution is improved by dissolving in the solution a pH-increasing reactant that subsequently adjusts the pH of the solution to a selected relatively neutral value. Urea is an example of the acid neutralizer. (10 claims)

  16. Cross-clade neutralizing antibodies against HIV-1 induced in rabbits by focusing the immune response on a neutralizing epitope

    International Nuclear Information System (INIS)

    Studies were performed to induce cross-clade neutralizing antibodies (Abs) by testing various combinations of prime and boost constructs that focus the immune response on structurally-conserved epitopes in the V3 loop of HIV-1 gp120. Rabbits were immunized with gp120 DNA containing a V3 loop characterized by the GPGR motif at its tip, and/or with gp120 DNA with a V3 loop carrying the GPGQ motif. Priming was followed by boosts with V3-fusion proteins (V3-FPs) carrying the V3 sequence from a subtype B virus (GPGR motif), and/or with V3 sequences from subtypes A and C (GPGQ motif). The broadest and most consistent neutralizing responses were generated when using a clade C gp120 DNA prime and with the V3B-FP boost. Immune sera displayed neutralizing activity in three assays against pseudoviruses and primary isolates from subtypes A, AG, B, C, and D. Polyclonal Abs in the immune rabbit sera neutralized viruses that were not neutralized by pools of human anti-V3 monoclonal Abs. Greater than 80% of the neutralizing Abs were specific for V3, showing that the immune response could be focused on a neutralizing epitope and that vaccine-induced anti-V3 Abs have cross-clade neutralizing activity.

  17. Broad spectrum anthelmintic potential of Cassia plants

    Institute of Scientific and Technical Information of China (English)

    Suman Kundu; Saptarshi Roy; Larisha Mawkhleing Lyndem

    2014-01-01

    Objective: To study the in vitro anthelmintic efficacy of Cassia alata (C. alata), Cassia(C. angustifolia) and Cassia occidentalis (C. occidentalis). angustifolia Methods: Crude ethanol extract from leaves of the three plants were prepared in rotary evaporator and different concentrations (10, 20 and 40 mg/mL) of leaf extracts were used for treatment on different representatives of helminthes (Heterakis gallinarum, Raillietina tetragona and Catatropis sp.) from domestic fowl (Gallus gallus domesticus). Loss of motility and death were monitored frequently.Results: C. alata showed early paralysis in all worms treated followed by C. angustifolia. C. occidentalis in combination with C. alata together caused early paralysis in all treated worms than the combination of C. alata with C. angustfolia. While Heterakis gallinarum in control survived for (81.33±2.07) h, treated worms lost their motility at (5.71±0.10) h, (6.60±0.86) h and (13.95±0.43) h with C. angustifolia, C. alata and C. occidentalis respectively at a concentration of 40 mg/mL which showed better efficacy than albendazole. Catatropis sp. survival period was (26.49±1.38) h in control, but with plant treatment, it lost its motility in just (0.57±0.08) h, (1.00±0.12) h and (1.47±0.40) h at 40 mg/mL concentration of C. alata, C. angustifolia and C. occidentalis respectively.Raillietina tetragona on the other hand became paralysed at (1.68±0.27) h, (2.95±0.29) h and (4.13±0.31) h with above concentrations treated with three plants respectively, however in control it survived up to (81.93±4.71) h.Conclusions:This present study indicated broad spectrum vermifugal activity of all plants tested.

  18. Emotionally Neutral Stimuli Are Not Neutral in Schizophrenia: A Mini Review of Functional Neuroimaging Studies

    Science.gov (United States)

    Potvin, Stéphane; Tikàsz, Andràs; Mendrek, Adrianna

    2016-01-01

    Reliable evidence shows that schizophrenia patients tend to experience negative emotions when presented with emotionally neutral stimuli. Similarly, several functional neuroimaging studies show that schizophrenia patients have increased activations in response to neutral material. However, results are heterogeneous. Here, we review the functional neuroimaging studies that have addressed this research question. Based on the 36 functional neuroimaging studies that we retrieved, it seems that the increased brain reactivity to neutral stimuli is fairly common in schizophrenia, but that the regions involved vary considerably, apart from the amygdala. Prefrontal and cingulate sub-regions and the hippocampus may also be involved. By contrasts, results in individuals at risk for psychosis are less consistent. In schizophrenia patients, results are less consistent in the case of studies using non-facial stimuli, explicit processing paradigms, and/or event-related designs. This means that human faces may convey subtle information (e.g., trustworthiness) other than basic emotional expressions. It also means that the aberrant brain reactivity to neutral stimuli is less likely to occur when experimental paradigms are too cognitively demanding as well as in studies lacking statistical power. The main hypothesis proposed to account for this increased brain reactivity to neutral stimuli is the aberrant salience hypothesis of psychosis. Other investigators propose that the aberrant brain reactivity to neutral stimuli in schizophrenia results from abnormal associative learning, untrustworthiness judgments, priming effects, and/or reduced habituation to neutral stimuli. In the future, the effects of antipsychotics on this aberrant brain reactivity will need to be determined, as well as the potential implication of sex/gender. PMID:27445871

  19. Emotionally Neutral Stimuli Are Not Neutral in Schizophrenia: A Mini Review of Functional Neuroimaging Studies.

    Science.gov (United States)

    Potvin, Stéphane; Tikàsz, Andràs; Mendrek, Adrianna

    2016-01-01

    Reliable evidence shows that schizophrenia patients tend to experience negative emotions when presented with emotionally neutral stimuli. Similarly, several functional neuroimaging studies show that schizophrenia patients have increased activations in response to neutral material. However, results are heterogeneous. Here, we review the functional neuroimaging studies that have addressed this research question. Based on the 36 functional neuroimaging studies that we retrieved, it seems that the increased brain reactivity to neutral stimuli is fairly common in schizophrenia, but that the regions involved vary considerably, apart from the amygdala. Prefrontal and cingulate sub-regions and the hippocampus may also be involved. By contrasts, results in individuals at risk for psychosis are less consistent. In schizophrenia patients, results are less consistent in the case of studies using non-facial stimuli, explicit processing paradigms, and/or event-related designs. This means that human faces may convey subtle information (e.g., trustworthiness) other than basic emotional expressions. It also means that the aberrant brain reactivity to neutral stimuli is less likely to occur when experimental paradigms are too cognitively demanding as well as in studies lacking statistical power. The main hypothesis proposed to account for this increased brain reactivity to neutral stimuli is the aberrant salience hypothesis of psychosis. Other investigators propose that the aberrant brain reactivity to neutral stimuli in schizophrenia results from abnormal associative learning, untrustworthiness judgments, priming effects, and/or reduced habituation to neutral stimuli. In the future, the effects of antipsychotics on this aberrant brain reactivity will need to be determined, as well as the potential implication of sex/gender. PMID:27445871

  20. Continuous Viral Escape and Selection by Autologous Neutralizing Antibodies in Drug-Naïve Human Immunodeficiency Virus Controllers▿

    OpenAIRE

    Mahalanabis, Madhumita; Jayaraman, Pushpa; Miura, Toshiyuki; Pereyra, Florencia; Chester, E. Michael; Richardson, Barbra; Walker, Bruce; Haigwood, Nancy L.

    2008-01-01

    We assessed differences in the character and specificity of autologous neutralizing antibodies (ANAbs) against individual viral variants of the quasispecies in a cohort of drug-naïve subjects with long-term controlled human immunodeficiency virus type 1 (HIV-1) infection and moderate levels of broad heterologous neutralizing antibodies (HNAb). Functional plasma virus showed continuous env evolution despite a short time frame and low levels of viral replication. Neutralization-sensitive varian...

  1. BROAD PHONEME CLASSIFICATION USING SIGNAL BASED FEATURES

    Directory of Open Access Journals (Sweden)

    Deekshitha G

    2014-12-01

    Full Text Available Speech is the most efficient and popular means of human communication Speech is produced as a sequence of phonemes. Phoneme recognition is the first step performed by automatic speech recognition system. The state-of-the-art recognizers use mel-frequency cepstral coefficients (MFCC features derived through short time analysis, for which the recognition accuracy is limited. Instead of this, here broad phoneme classification is achieved using features derived directly from the speech at the signal level itself. Broad phoneme classes include vowels, nasals, fricatives, stops, approximants and silence. The features identified useful for broad phoneme classification are voiced/unvoiced decision, zero crossing rate (ZCR, short time energy, most dominant frequency, energy in most dominant frequency, spectral flatness measure and first three formants. Features derived from short time frames of training speech are used to train a multilayer feedforward neural network based classifier with manually marked class label as output and classification accuracy is then tested. Later this broad phoneme classifier is used for broad syllable structure prediction which is useful for applications such as automatic speech recognition and automatic language identification.

  2. Salivary agglutinin and lung scavenger receptor cysteine-rich glycoprotein 340 have broad anti-influenza activities and interactions with surfactant protein D that vary according to donor source and sialylation

    DEFF Research Database (Denmark)

    Hartshorn, Kevan L.; Ligtenberg, Antoon; White, Mitchell R.; van Eijk, Martin; Hartshorn, Max; Pemberton, Lily; Holmskov, Uffe; Crouch, Erika

    2006-01-01

    salivary gp-340 are identical in protein sequence, salivary gp-340 from one donor had significantly greater antiviral activity against avian-like IAV strains which preferentially bind sialic acids in alpha(2,3) linkage. A greater density of alpha(2,3)-linked sialic acids was present on the salivary gp-340...... from this donor as compared with salivary gp-340 from another donor or several preparations of lung gp-340. Hence, the specificity of sialic acid linkages on gp-340 is an important determinant of anti-IAV activity. Gp-340 binds to SP-D (surfactant protein D), and we previously showed that lung gp-340...

  3. Giant Broad Line Regions in Dwarf Seyferts

    CERN Document Server

    Devereux, Nick

    2015-01-01

    High angular resolution spectroscopy obtained with the Hubble Space Telescope (HST) has revealed a remarkable population of galaxies hosting dwarf Seyfert nuclei with an unusually large broad-line region (BLR). These objects are remarkable for two reasons. Firstly, the size of the BLR can, in some cases, rival those seen in the most luminous quasars. Secondly, the size of the BLR is not correlated with the central continuum luminosity, an observation that distinguishes them from their reverberating counterparts. Collectively, these early results suggest that non-reverberating dwarf Seyferts are a heterogeneous group and not simply scaled versions of each other. Careful inspection reveals broad H Balmer emission lines with single peaks, double peaks, and a combination of the two, suggesting that the broad emission lines are produced in kinematically distinct regions centered on the black hole (BH). Because the gravitational field strength is already known for these objects, by virtue of knowing their BH mass, ...

  4. Spectral Decomposition of Broad-Line AGNs and Host Galaxies

    CERN Document Server

    Vanden Berk, Daniel E; Yip, C W; Schneider, D P; Connolly, A J; Burton, R E; Jester, S; Hall, P B; Szalay, A S; Brinkmann, J; Berk, Daniel E. Vanden; Shen, Jiajian; Yip, Ching-Wa; Schneider, Donald P.; Connolly, Andrew J.; Burton, Ross E.; Jester, Sebastian; Hall, Patrick B.; Szalay, Alex S.; Brinkmann, John

    2005-01-01

    Using an eigenspectrum decomposition technique, we separate the host galaxy from the broad line active galactic nucleus (AGN) in a set of 4666 spectra from the Sloan Digital Sky Survey (SDSS), from redshifts near zero up to about 0.75. The decomposition technique uses separate sets of galaxy and quasar eigenspectra to efficiently and reliably separate the AGN and host spectroscopic components. The technique accurately reproduces the host galaxy spectrum, its contributing fraction, and its classification. We show how the accuracy of the decomposition depends upon S/N, host galaxy fraction, and the galaxy class. Based on the eigencoefficients, the sample of SDSS broad-line AGN host galaxies spans a wide range of spectral types, but the distribution differs significantly from inactive galaxies. In particular, post-starburst activity appears to be much more common among AGN host galaxies. The luminosities of the hosts are much higher than expected for normal early-type galaxies, and their colors become increasing...

  5. HIV-1 specific antibody titers and neutralization among chronically infected patients on long-term suppressive antiretroviral therapy (ART: a cross-sectional study.

    Directory of Open Access Journals (Sweden)

    Johannes S Gach

    Full Text Available The majority of potent and broadly neutralizing antibodies against HIV-1 have been isolated from untreated patients with acute or chronic infection. To assess the extent of HIV-1 specific antibody response and neutralization after many years of virologic suppression from potent combination ART, we examined antibody binding titers and neutralization of 51 patients with chronic HIV-1 infection on suppressive ART for at least three years. In this cross-sectional analysis, we found high antibody titers against gp120, gp41, and the membrane proximal external region (MPER in 59%, 43%, and 27% of patients, respectively. We observed significantly higher endpoint binding titers for gp120 and gp41 for patients with >10 compared to ≤ 10 years of detectable HIV RNA. Additionally, we observed higher median gp120 and gp41 antibody titers in patients with HIV RNA 10 years of detectable HIV RNA (8/20 [40.0%] versus 3/31 [9.7%] for ≤ 10 years, p = 0.02 and a trend toward greater neutralization in patients with ≤ 5 years of HIV RNA 5 years, p = 0.08. All patients with neutralizing activity mediated successful phagocytosis of VLPs by THP-1 cells after antibody opsonization. Our findings of highly specific antibodies to several structural epitopes of HIV-1 with antibody effector functions and neutralizing activity after long-term suppressive ART, suggest continuous antigenic stimulation and evolution of HIV-specific antibody response occurs before and after suppression with ART. These patients, particularly those with slower HIV progression and more time with detectable viremia prior to initiation of suppressive ART, are a promising population to identify and further study functional antibodies against HIV-1.

  6. Detection and Quantized Conductance of Neutral Atoms Near a Charged Carbon Nanotube

    OpenAIRE

    Ristroph, Trygve; Goodsell, Anne; Golovchenko, Jene Andrew; Hau, Lene V.

    2005-01-01

    We describe a novel single atom detector that uses the high electric field surrounding a charged single-walled carbon nanotube to attract and subsequently field-ionize neutral atoms. A theoretical study of the field-ionization tunneling rates for atomic trajectories in the attractive potential near a nanowire shows that a broadly applicable, high spatial resolution, low-power, neutral-atom detector with nearly 100% efficiency is realizable with present-day technology. Calculations also show t...

  7. Expression of apical Na(+)-L-glutamine co-transport activity, B(0)-system neutral amino acid co-transporter (B(0)AT1) and angiotensin-converting enzyme 2 along the jejunal crypt-villus axis in young pigs fed a liquid formula

    Science.gov (United States)

    Gut apical amino acid (AA) transport activity is high at birth and during suckling, thus being essential to maintain luminal nutrient-dependent mucosal growth through providing AA as essential metabolic fuel, substrates and nutrient stimuli for cellular growth. Because system-B(0) Na(+)-neutral AA c...

  8. Hybrid grating reflector with high reflectivity and broad bandwidth

    DEFF Research Database (Denmark)

    Taghizadeh, Alireza; Park, Gyeong Cheol; Mørk, Jesper; Chung, Il-Sug

    2014-01-01

    We suggest a new type of grating reflector denoted hybrid grating (HG) which shows large reflectivity in a broad wavelength range and has a structure suitable for realizing a vertical cavity laser with ultra-small modal volume. The properties of the grating reflector are investigated numerically......). By using an active III-V layer, a laser can be realized where the gain region is integrated into the mirror itself...

  9. High-throughput discovery of broad-spectrum peptide antibiotics

    OpenAIRE

    Rathinakumar, Ramesh; Wimley, William C.

    2010-01-01

    Membrane-permeabilizing peptide antibiotics are an underutilized weapon in the battle against drug-resistant microorganisms. This is true, in part, because of the bottleneck caused by the lack of explicit design principles and the paucity of simple high-throughput methods for selection. In this work, we characterize the requirements for broad-spectrum antimicrobial activity by membrane permeabilization and find that different microbial membranes have very different susceptibilities to permeab...

  10. Shareholder, stakeholder-owner or broad stakeholder maximization

    DEFF Research Database (Denmark)

    Mygind, Niels

    2004-01-01

    including the shareholders of a company. Although it may be the ultimate goal for Corporate Social Responsibility to achieve this kind of maximization, broad stakeholder maximization is quite difficult to give a precise definition. There is no one-dimensional measure to add different stakeholder benefits...... defined by other stakeholders' interests. These constraints vary for dif-ferent stakeholder owners and new standards for Corporate Social Responsibility and more active political consumers will strengthen these constraints....

  11. The Economics of Net Neutrality

    OpenAIRE

    Hahn, Robert W.; Wallsten, Scott

    2006-01-01

    This essay examines the economics of "net neutrality" and broadband Internet access. We argue that mandating net neutrality would be likely to reduce economic welfare. Instead, the government should focus on creating competition in the broadband market by liberalizing more spectrum and reducing entry barriers created by certain local regulations. In cases where a broadband provider can exercise market power the government should use its antitrust enforcement authority to police anticompetitiv...

  12. Neutral theory in community ecology

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    One of the central goals of community ecology is to understand the forces that maintain species diversity within communities. The traditional niche-assembly theory asserts that species live together in a community only when they differ from one another in resource uses. But this theory has some difficulties in explaining the diversity often observed in specie-rich communities such as tropical forests. As an alternative to the niche theory, Hubbell and other ecologists introduced a neutral model. Hubbell argues that the number of species in a community is controlled by species extinction and immigration or speciation of new species. Assuming that all individuals of all species in a trophically similar com-munity are ecologically equivalent, Hubbell's neutral theory predicts two important statistical distributions. One is the asymptotic log-series distribution for the metacommunities under point mutation speciation, and the other is the zero-sum multinomial distribution for both local communities under dispersal limitation and metacommunities under random fission speciation. Unlike the niche-assembly theory, the neutral theory takes similarity in species and individuals as a starting point for investigating species diversity. Based on the fundamental processes of birth, death, dispersal and spe-ciation, the neutral theory provided the first mechanistic explanation of species abundance distribution commonly observed in natural communities. Since the publication of the neutral theory, there has been much discussion about it, pro and con. In this paper, we summarize recent progress in the assumption, prediction and speciation mode of the neutral theory, including progress in the theory itself, tests about the assumption of the theory, prediction and speciation mode at the metacommunity level. We also suggest that the most important task in the future is to bridge the niche-assembly theory and the neutral theory, and to add species differences to the neutral theory and

  13. Cold ion-neutral reactions

    OpenAIRE

    Hall, Felix Henry Joynson

    2013-01-01

    Cold ion-neutral reactive processes were studied in an hybrid trap down to average collision energies /k_B > 20 mK. The atomic ion-neutral systems Ca^+ + Rb and Ba^+ + Rb were studied, and the results interpreted with high-level quantum chemical and quantum scattering calculations. Three reactive processes were found to be in competition, namely non-radiative charge transfer induced by non-adiabatic couplings between potential energy surfaces, radiative charge transfer, and radiative associat...

  14. Vendor neutral archive in PACS

    Directory of Open Access Journals (Sweden)

    Tapesh Kumar Agarwal

    2012-01-01

    Full Text Available An archive is a location containing a collection of records, documents, or other materials of historical importance. An integral part of Picture Archiving and Communication System (PACS is archiving. When a hospital needs to migrate a PACS vendor, the complete earlier data need to be migrated in the format of the newly procured PACS. It is both time and money consuming. To address this issue, the new concept of vendor neutral archive (VNA has emerged. A VNA simply decouples the PACS and workstations at the archival layer. This is achieved by developing an application engine that receives, integrates, and transmits the data using the different syntax of a Digital Imaging and Communication in Medicine (DICOM format. Transferring the data belonging to the old PACS to a new one is performed by a process called migration of data. In VNA, a number of different data migration techniques are available to facilitate transfer from the old PACS to the new one, the choice depending on the speed of migration and the importance of data. The techniques include simple DICOM migration, prefetch-based DICOM migration, medium migration, and the expensive non-DICOM migration. "Vendor neutral" may not be a suitable term, and "architecture neutral," "PACS neutral," "content neutral," or "third-party neutral" are probably better and preferred terms. Notwithstanding this, the VNA acronym has come to stay in both the medical IT user terminology and in vendor nomenclature, and radiologists need to be aware of its impact in PACS across the globe.

  15. Broad resonances and beta-decay

    DEFF Research Database (Denmark)

    Riisager, K.; Fynbo, H. O. U.; Hyldegaard, S.;

    2015-01-01

    Beta-decay into broad resonances gives a distorted lineshape in the observed energy spectrum. Part of the distortion arises from the phase space factor, but we show that the beta-decay matrix element may also contribute. Based on a schematic model for p-wave continuum neutron states it is argued...

  16. Structural Constraints of Vaccine-Induced Tier-2 Autologous HIV Neutralizing Antibodies Targeting the Receptor-Binding Site

    Directory of Open Access Journals (Sweden)

    Todd Bradley

    2016-01-01

    Full Text Available Antibodies that neutralize autologous transmitted/founder (TF HIV occur in most HIV-infected individuals and can evolve to neutralization breadth. Autologous neutralizing antibodies (nAbs against neutralization-resistant (Tier-2 viruses are rarely induced by vaccination. Whereas broadly neutralizing antibody (bnAb-HIV-Envelope structures have been defined, the structures of autologous nAbs have not. Here, we show that immunization with TF mutant Envs gp140 oligomers induced high-titer, V5-dependent plasma neutralization for a Tier-2 autologous TF evolved mutant virus. Structural analysis of autologous nAb DH427 revealed binding to V5, demonstrating the source of narrow nAb specificity and explaining the failure to acquire breadth. Thus, oligomeric TF Envs can elicit autologous nAbs to Tier-2 HIVs, but induction of bnAbs will require targeting of precursors of B cell lineages that can mature to heterologous neutralization.

  17. Study of the active filter for the cancellation of currents of the neutral in three-phase systems; Estudio del filtro activo para la cancelacion de corrientes de neutro en sistemas trifasicos

    Energy Technology Data Exchange (ETDEWEB)

    Diaz Saldierna, Luis Humberto

    2004-05-15

    The proliferation of the so called nonlinear loads has increased in a considerable way in the last years. These loads generate non sine waveforms in the current that consume, producing effects such as low power factor, generation of reactive power and harmonics, to mention some of them. Another problem shows up when an unbalance of loads exists in the three-phase systems with connection to the neutral (star connection); the unbalance generates circulation of currents through the neutral conductor, which can get to be of equal to greater magnitude than the phase currents; these are problems that degrade the quality of the supply and the consumption of electrical energy. Solutions such as the passive filters and active filters are used to face this kind of problems. The passive filters are used to attenuate the harmonics of current of more significant magnitude in three-phase systems non-connected to the neutral (delta connection), nevertheless the passive filters have considerable limitations, because they cannot compensate unbalance, and it is necessary a filter for every harmonic and its performance is adequate for constant loads. The active filters can be used to correct the power factor, since they can get to filter most of the LF harmonics, compensate the loads unbalance and the reactive power flow. In this work a study is made on the neutral currents associated to the active power and harmonic currents in the three-phase systems of four wires, the most active filters are chosen as a solution. The objective of the thesis is to analyze and to construct an active filter of current for the attenuation of current harmonics and the compensation of the load unbalance existing in a three-phase of four wires. The thesis document comprises five chapters and three appendixes, as it is next described: In chapter I a short introduction is presented on the problems and possible solutions of the same ones. In chapter II an analysis is made on the harmonic distortion and the

  18. Modeling of modification experiments involving neutral-gas release

    International Nuclear Information System (INIS)

    Many experiments involve the injection of neutral gases into the upper atmosphere. Examples are critical velocity experiments, MHD wave generation, ionospheric hole production, plasma striation formation, and ion tracing. Many of these experiments are discussed in other sessions of the Active Experiments Conference. This paper limits its discussion to: (1) the modeling of the neutral gas dynamics after injection, (2) subsequent formation of ionosphere holes, and (3) use of such holes as experimental tools

  19. Identification and characterization of a broadly cross-reactive HIV-1 human monoclonal antibody that binds to both gp120 and gp41.

    Directory of Open Access Journals (Sweden)

    Mei-Yun Zhang

    Full Text Available Identification of broadly cross-reactive HIV-1-neutralizing antibodies (bnAbs may assist vaccine immunogen design. Here we report a novel human monoclonal antibody (mAb, designated m43, which co-targets the gp120 and gp41 subunits of the HIV-1 envelope glycoprotein (Env. M43 bound to recombinant gp140 s from various primary isolates, to membrane-associated Envs on transfected cells and HIV-1 infected cells, as well as to recombinant gp120 s and gp41 fusion intermediate structures containing N-trimer structure, but did not bind to denatured recombinant gp140 s and the CD4 binding site (CD4bs mutant, gp120 D368R, suggesting that the m43 epitope is conformational and overlaps the CD4bs on gp120 and the N-trimer structure on gp41. M43 neutralized 34% of the HIV-1 primary isolates from different clades and all the SHIVs tested in assays based on infection of peripheral blood mononuclear cells (PBMCs by replication-competent virus, but was less potent in cell line-based pseudovirus assays. In contrast to CD4, m43 did not induce Env conformational changes upon binding leading to exposure of the coreceptor binding site, enhanced binding of mAbs 2F5 and 4E10 specific for the membrane proximal external region (MPER of gp41 Envs, or increased gp120 shedding. The overall modest neutralization activity of m43 is likely due to the limited binding of m43 to functional Envs which could be increased by antibody engineering if needed. M43 may represent a new class of bnAbs targeting conformational epitopes overlapping structures on both gp120 and gp41. Its novel epitope and possibly new mechanism(s of neutralization could helpdesign improved vaccine immunogens and candidate therapeutics.

  20. Emotionally neutral stimuli are not neutral in schizophrenia:A mini-review of functional neuroimaging studies

    OpenAIRE

    Stephane Potvin; Andràs Tikàsz; Adrianna Mendrek

    2016-01-01

    Reliable evidence shows that schizophrenia patients tend to experience negative emotions when presented with emotionally neutral stimuli. Similarly, several functional neuroimaging studies show that schizophrenia patients have increased activations in response to neutral material. However, results are heterogeneous. Here, we review the functional neuro-imaging studies that have addressed this research question. Based on the 36 functional neuroimaging studies that we retrieved, it seems that t...

  1. Sialylated immunoglobulin G can neutralize influenza virus infection through receptor mimicry

    Science.gov (United States)

    Zhao, Conghui; Liu, Xingmu; Zhang, Zaiping; Li, Tongfei; Sun, Ruiman; Gu, Huan; Gu, Jiang

    2016-01-01

    Influenza viruses possess a great threat to human health, but there is still no effective drug to deal with the outbreak of possible new influenza subtypes. In this study, we first fractionated sialylated immunoglobulin G (IgG), mainly Fab sialylated fraction, with sambucus nigra agglutinin affinity chromatography. We then demonstrated that sialylated IgG possessed more effective neutralizing activity against 2009 A (H1N1) subtype than that of IgG mixture, and sialosides on the Fab is crucial in this neutralization reaction as when such residues were removed with neuraminidase A digestion the blocking effect was significantly reduced. It appears that sialic acid residues attached to Fab could serve as binding moieties to receptor binding site of influenza virus. These findings indicate that sialylated IgG probably is an effective anti-influenza broad-spectrum drug utilizing its receptor mimicry to competitively inhibit the attachment of influenza viruses with sialic acid receptors on target cells. This property would be particularly useful if it can be applied to prevent newly emerged influenza virus strain infections in future epidemics. PMID:26870994

  2. Quasar Cartography: from Black Hole to Broad Line Region Scales

    CERN Document Server

    Chelouche, Doron

    2013-01-01

    A generalized approach to reverberation mapping (RM) is presented, which is applicable to broad- and narrow-band photometric data, as well as to spectroscopic observations. It is based on multivariate correlation analysis techniques and, in its present implementation, is able to identify reverberating signals across the accretion disk and the broad line region (BLR) of active galactic nuclei (AGN). Statistical tests are defined to assess the significance of time-delay measurements using this approach, and the limitations of the adopted formalism are discussed. It is shown how additional constraints on some of the parameters of the problem may be incorporated into the analysis thereby leading to improved results. When applied to a sample of 14 Seyfert 1 galaxies having good-quality high-cadence photometric data, accretion disk scales and BLR sizes are simultaneously determined, on a case-by-case basis, in most objects. The BLR scales deduced here are in good agreement with the findings of independent spectrosc...

  3. Assessment of effects of neutrals on the power threshold for L to H transitions in DIII-D

    International Nuclear Information System (INIS)

    To assess the effect of edge neutrals on the low to high confinement transition threshold, a broad range of plasma discharges has been analyzed. From this analysis, the transition power divided by the density, at constant magnetic field, appears to be a function of a single parameter measuring the neutrals' effect, This parameter cannot be uniquely identified. For instance, it may be the radial decay length of the neutral profile or the charge exchange damping rate at about r/a ∼ 0.95. This results suggest that there is a missing parameter linked to the neutrals in the power threshold scaling laws

  4. Flow over an Erodible Broad Crested Weir

    Directory of Open Access Journals (Sweden)

    Dr. K. C.Sahu

    2015-01-01

    Full Text Available The overtopping flow of water over an earthen embankment causes erosion of soil from its surfaces and the eroded surface of the embankment acts as a Broad crest weir. But the longitudinal profile of the weir goes on changing with time of erosion. Hence crest height of the weir goes changing in accelerated flow condition. In this paper, the discharge equation for this type of flow situation is established for different types of soils used in the embankment. Then, the experiments have been carried out as the analogous rigid beds of the captured eroded profiles at any time of erosion of the broad crested weir to compare the discharge equation and to study the energy loss in dislodging the soil from the surface of the weir and transporting them down stream.

  5. Broad line regions in Seyfert-1 galaxies

    International Nuclear Information System (INIS)

    To reproduce observed emission profiles of Seyfert galaxies, rotation in an accretion disk has been proposed. In this thesis, the profiles emitted by such an accretion disk are investigated. Detailed comparison with the observed profiles yields that a considerable fraction can be fitted with a power-law function, as predicted by the model. The author analyzes a series of high quality spectra of Seyfert galaxies, obtained with the 2.5m telescope at Las Campanas. He presents detailed analyses of two objects: Mkn335 and Akn120. In both cases, strong evidence is presented for the presence of two separate broad line zones. These zones are identified with an accretion disk and an outflowing wind. The disk contains gas with very high densities and emits predominantly the lower ionization lines. He reports on the discovery of very broad wings beneath the strong forbidden line 5007. (Auth.)

  6. Fourier evaluation of broad Moessbauer spectra

    International Nuclear Information System (INIS)

    It is shown by the Fourier analysis of broad Moessbauer spectra that the even part of the distribution of the dominant hyperfine interaction (hyperfine field or quadrupole splitting) can be obtained directly without using least-square fitting procedures. Also the odd part of this distribution correlated with other hyperfine parameters (e.g. isomer shift) can be directly determined. Examples for amorphous magnetic and paramagnetic iron-based alloys are presented. (author)

  7. Crx broadly modulates the pineal transcriptome

    OpenAIRE

    Rovsing, Louise; Clokie, Samuel; Bustos, Diego M.; Rohde, Kristian; Steven L Coon; Litman, Thomas; Rath, Martin F.; Møller, Morten; Klein, David C.

    2011-01-01

    Cone-rod homeobox (Crx) encodes Crx, a transcription factor expressed selectively in retinal photoreceptors and pinealocytes, the major cell type of the pineal gland. Here, the influence of Crx on the mammalian pineal gland was studied by light and electron microscopy and by use of microarray and qRTPCR technology, thereby extending previous studies on selected genes (Furukawa et al. 1999). Deletion of Crx was not found to alter pineal morphology, but was found to broadly modulate the mouse p...

  8. Toll-like receptor 9 ligand D-type oligodeoxynucleotide D35 as a broad inhibitor for influenza A virus replication that is associated with suppression of neuraminidase activity.

    Science.gov (United States)

    Yamada, Hiroshi; Nagase, Satoshi; Takahashi, Kazuo; Sakoda, Yoshihiro; Kida, Hiroshi; Okamoto, Shigefumi

    2016-05-01

    The most effective drugs available to treat influenza are neuraminidase (NA) inhibitors, which provide important additional measures for the control of influenza virus infections. However, since the emergence of NA inhibitor-resistant viruses may compromise the clinical utility of this class of anti-influenza agents, it is very important to develop new anti-influenza agents which target a different region in NA responsible for its sensitivity from that for NA inhibitors and could be used to treat NA inhibitors-resistant isolates. The oligodeoxynucleotide D35, multimerized and aggregated, suppressed replication of influenza A viruses except A/WSN/33 (WSN). The suppressive viral replication by D35 depended on G-terad and multimer formation. The range of the suppressive viral replication at the late stage, including virus assembly and release from infected cells, was much larger than that at the initial stage, viral attachment and entry. D35 suppressed NA activity of influenza A viruses. Furthermore, replacing the NA gene of A/Puerto Rico/8/34 (PR8), in which viral replication was inhibited by D35 at the late stage, with the NA gene from WSN, in which viral replication was not inhibited, eliminated the D35-dependent suppression. D35 showed an additive anti-influenza effect with oseltamivir. It was also effective in vivo. These results suggest that the influenza virus NA mainly contributes to the D35-suppressible virus release from infected cells at the late stage. In addition, because administration of D35 into the virus-infected mice suppressed viral replication and weight loss, clinical application of D35 could be considered. PMID:26923882

  9. HIV-1 Env DNA vaccine plus protein boost delivered by EP expands B- and T-cell responses and neutralizing phenotype in vivo.

    Directory of Open Access Journals (Sweden)

    Kar Muthumani

    Full Text Available An effective HIV vaccine will most likely require the induction of strong T-cell responses, broadly neutralizing antibodies (bNAbs, and the elicitation of antibody-dependent cellular cytotoxicity (ADCC. Previously, we demonstrated the induction of strong HIV/SIV cellular immune responses in macaques and humans using synthetic consensus DNA immunogens delivered via adaptive electroporation (EP. However, the ability of this improved DNA approach to prime for relevant antibody responses has not been previously studied. Here, we investigate the immunogenicity of consensus DNA constructs encoding gp140 sequences from HIV-1 subtypes A, B, C and D in a DNA prime-protein boost vaccine regimen. Mice and guinea pigs were primed with single- and multi-clade DNA via EP and boosted with recombinant gp120 protein. Sera were analyzed for gp120 binding and induction of neutralizing antibody activity. Immunization with recombinant Env protein alone induced low-titer binding antibodies with limited neutralization breath. In contrast, the synthetic DNA prime-protein boost protocol induced significantly higher antibody binding titers. Furthermore, sera from DNA prime-protein boost groups were able to neutralize a broader range of viruses in a panel of tier 1 clade B viruses as well as multiple tier 1 clade A and clade C viruses. Further investigation of synthetic DNA prime plus adaptive EP plus protein boost appears warranted.

  10. Relativistic redshifts in quasar broad lines

    CERN Document Server

    Tremaine, Scott; Liu, Xin; Loeb, Abraham

    2014-01-01

    The broad emission lines commonly seen in quasar spectra have velocity widths of a few per cent of the speed of light, so special- and general-relativistic effects have a significant influence on the line profile. We have determined the redshift of the broad H-beta line in the quasar rest frame (determined from the core component of the [OIII] line) for over 20,000 quasars from the Sloan Digital Sky Survey DR7 quasar catalog. The mean redshift as a function of line width is approximately consistent with the relativistic redshift that is expected if the line originates in a randomly oriented Keplerian disk that is obscured when the inclination of the disk to the line of sight exceeds ~30-45 degrees, consistent with simple AGN unification schemes. This result also implies that the net line-of-sight inflow/outflow velocities in the broad-line region are much less than the Keplerian velocity when averaged over a large sample of quasars with a given line width.

  11. Neutral beams for magnetic fusion

    International Nuclear Information System (INIS)

    Significant advances in forming energetic beams of neutral hydrogen and deuterium atoms have led to a breakthrough in magnetic fusion: neutral beams are now heating plasmas to thermonuclear temperatures, here at LLL and at other laboratories. For example, in our 2XIIB experiment we have injected a 500-A-equivalent current of neutral deuterium atoms at an average energy of 18 keV, producing a dense plasma (1014 particles/cm3) at thermonuclear energy (14 keV or 160 million kelvins). Currently, LLL and LBL are developing beam energies in the 80- to 120-keV range for our upcoming MFTF experiment, for the TFTR tokamak experiment at Princeton, and for the Doublet III tokamak experiment at General Atomic. These results increase our long-range prospects of producing high-intensity beams of energies in the hundreds or even thousands of kilo-electron-volts, providing us with optimistic extrapolations for realizing power-producing fusion reactors

  12. Neutral B meson flavor tagging

    CERN Document Server

    Wilson, R J

    2001-01-01

    We present an investigation of the use of net charge and kaon identification to tag the flavor of neutral B mesons. The net charge of the neutral B meson decay products is zero if all charged particles are used and slightly non-zero if only undiscriminated hadronic final states are used. The net charge of the kaons alone correctly tags the identity of the neutral meson in at least a third of all decays. We have parametrized the particle identification capability of several techniques, such as dE/dx in time projection chambers, LEP/SLC ring-imaging chambers and an enhanced BaBar DIRC. Using these parametrisations we compare the relative tagging power of each technique to that of an ideal detector. (8 refs).

  13. Areas of Active Tectonic Uplift Are Sensitive to Small Changes in Fold Orientations within a Broad Zone of Left-lateral Transpression and Shearing, Dominican Republic and Haiti (Hispaniola)

    Science.gov (United States)

    Ambrosius, I.; Mann, P.

    2014-12-01

    Previous GPS studies have shown that the island of Hispaniola is a 250 km-wide zone of active, east-west, left-lateral shearing along two major strike-slip zones: the Septentrional-Oriente fault zone through the northern part of the island and the Enriquillo-Plantain Garden fault zone (EPGFZ) through the southern part of the island. The total interplate rate distributed on both faults is 21 mm/yr. Using a high-resolution DEM, we constructed fluvial channel profiles across transpression-related folds of late Miocene to recent age in the area of central and southern Dominican Republic and Haiti to determine controls of areas of relatively high, moderate, and slow uplift inferred from fluvial channel profiles. Fold axes in this area extend for 50-150 km and exhibit two different trends: 1) folds that occupy the area of the Sierra de Neiba-Chaine des Matheux north of the Enriquillo-Cul-de-Sac Valley and EPGFZ and folds that occupy the area of the Sierra de Bahoruco-Massif de la Selle all exhibit more east-west fold axes trending 110; 2) folds that occupy the area northwest of the EPGFZ in the western Chaine des Matheux and Sierra de Neiba all exhibit fold axes with more northwest trends of 125. River channel profiles show that the second group of more northwesterly-trending fold axes show relatively higher rates of tectonic uplift based on their convex-upward river profiles. Our interpretation for regional variations in river profiles and inferred uplift is that uplift is more pronounced on fold axes trending 15 degrees more to the northwest because their axes are more oblique to the interplate direction of east-west shearing. Longterm uplift rates previously measured from a stairstep of late Quaternary coral terraces at the plunging nose of the westernmost Chaine des Matheux have been previously shown to be occurring at a rate of 0.19 mm/yr. Onland exposures of Holocene corals are found only on one locality within the southern area of folds 30 km west of the epicenter

  14. Hierarchical MoS2@MoP core-shell heterojunction electrocatalysts for efficient hydrogen evolution reaction over a broad pH range

    Science.gov (United States)

    Wu, Aiping; Tian, Chungui; Yan, Haijing; Jiao, Yanqing; Yan, Qing; Yang, Guoyu; Fu, Honggang

    2016-05-01

    A low-cost catalyst for the hydrogen evolution reaction (HER) over a broad pH range is highly desired to meet the practical needs in different areas. In this study, hierarchical flower-like MoS2@MoP core-shell heterojunctions (HF-MoSP) are designed as a promising catalyst for HER over a broad pH range. The materials are obtained by the controllable phosphidation of the hierarchical MoS2 flower (HF-MoS2) composed of thin silk belt-like sheets. The phosphidation degree, P/S ratio and work function (WF) of HF-MoSP can be tuned easily over broad range by changing the phosphidation temperature. Under optimized condition, HF-MoSP exhibits excellent electrocatalytic activity for HER with a low onset overpotential of 29 mV and η of 108 mV at 10 mA cm-2 in 0.5 M H2SO4 and retains its good activity for 30 h. In addition, the catalyst shows excellent activity in 1 M KOH with an onset overpotential of 42 mV and η of 119 mV at 10 mA cm-2. The catalysts also exhibit obvious activity in neutral, weak acid and weak alkaline conditions. The good performance is relative to the synergy of the MoP shell and MoS2 core and the high WF of HF-MoSP close to Pt, and the large SBET of HF-MoSP benefited from the hierarchical structure. This study represents the construction of the core-shell heterojunction and provides a new way to provide the low-cost and high-performance catalyst for HER.A low-cost catalyst for the hydrogen evolution reaction (HER) over a broad pH range is highly desired to meet the practical needs in different areas. In this study, hierarchical flower-like MoS2@MoP core-shell heterojunctions (HF-MoSP) are designed as a promising catalyst for HER over a broad pH range. The materials are obtained by the controllable phosphidation of the hierarchical MoS2 flower (HF-MoS2) composed of thin silk belt-like sheets. The phosphidation degree, P/S ratio and work function (WF) of HF-MoSP can be tuned easily over broad range by changing the phosphidation temperature. Under optimized

  15. ATF neutral beam injection system

    International Nuclear Information System (INIS)

    The Advanced Toroidal Facility is a stellarator torsatron being built at Oak Ridge National Laboratory to investigate improved plasma confinement schemes. Plasmas heating will be carried out predominantly by means of neutral beam injection. This paper describes the basic parameters of the injection system. Numerical calculations were done to optimize the aiming of the injectors. The results of these calculations and their implications on the neutral power to the machine are elaborated. The effects of improving the beam optics and altering the focal length on the power transmitted to the plasma are discussed

  16. Tracing the neutral gas environments of young radio AGN with ASKAP

    Science.gov (United States)

    Allison, J. R.; Sadler, E. M.; Moss, V. A.; Harvey-Smith, L.; Heywood, I.; Indermuehle, B. T.; McConnell, D.; Sault, R. J.; Whiting, M. T.

    2016-02-01

    At present neutral atomic hydrogen (H I) gas in galaxies at redshifts above {z ˜ 0.3} (the extent of 21 cm emission surveys in individual galaxies) and below {z ˜ 1.7} (where the Lyman-\\alpha line is not observable with ground-based telescopes) has remained largely unexplored. The advent of precursor telescopes to the Square Kilometre Array will allow us to conduct the first systematic radio-selected 21 cm absorption surveys for H I over these redshifts. While H I absorption is a tracer of the reservoir of cold neutral gas in galaxies available for star formation, it can also be used to reveal the extreme kinematics associated with jet-driven neutral outflows in radio-loud active galactic nuclei. Using the six-antenna Boolardy Engineering Test Array of the Australian Square Kilometre Array Pathfinder, we have demonstrated that in a single frequency tuning we can detect H I absorption over a broad range of redshifts between z = 0.4 and 1.0. As part of our early science and commissioning program, we are now carrying out a search for absorption towards a sample of the brightest GPS and CSS sources in the southern sky. These intrinsically compact sources present us with an opportunity to study the circumnuclear region of recently re-started radio galaxies, in some cases showing direct evidence of mechanical feedback through jet-driven outflows. With the sensitivity of the full ASKAP array we will be able to study the kinematics of atomic gas in a few thousand radio galaxies, testing models of radio jet feedback well beyond the nearby Universe.

  17. Neutral Atomic Carbon in Centers of Galaxies

    OpenAIRE

    Israel, F.P.; Baas, F

    2001-01-01

    We present measurements of the emission from the centers of fifteen spiral galaxies in the 3P1-3P0 [CI] fine-structure transition at 492 GHz. Observed galaxy centers range from quiescent to starburst to active. The intensities of neutral carbon, the J=2-1 transition of 13CO and the J=4-3 transition of 12CO are compared in matched beams. Most galaxy centers emit more strongly in [CI] than in 13CO, completely unlike the situation pertaining to Galactic molecular cloud regions. [CI] intensities ...

  18. The buffer effect in neutral electrolyte supercapacitors

    DEFF Research Database (Denmark)

    Thrane Vindt, Steffen; Skou, Eivind M.

    2016-01-01

    The observation that double-layer capacitors based on neutral aqueous electrolytes can have significantly wider usable potential windows than those based on acidic or alkaline electrolytes is studied. This effect is explained by a local pH change taking place at the electrode surfaces, leading to a...... of addition of a buffer to such systems. It is shown that a 56 % higher dynamic storage capacity may be achieved, simply by controlling the buffer capacity of the electrolyte. The model system used, is based on a well-known commercial activated carbon (NORIT™ A SUPRA) as the electrode material...

  19. Two wide-angle imaging neutral-atom spectrometers

    Energy Technology Data Exchange (ETDEWEB)

    McComas, D.J.

    1997-12-31

    The Two Wide-angle Imaging Neutral-atom Spectrometers (TWINS) mission provides a new capability for stereoscopically imaging the magnetosphere. By imaging the charge exchange neutral atoms over a broad energy range (1 < E , {approximately} 100 keV) using two identical instruments on two widely-spaced high-altitude, high-inclination spacecraft, TWINS will enable the 3-dimensional visualization and the resolution of large scale structures and dynamics within the magnetosphere for the first time. These observations will provide a leap ahead in the understanding of the global aspects of the terrestrial magnetosphere and directly address a number of critical issues in the ``Sun-Earth Connections`` science theme of the NASA Office of Space Science.

  20. Two wide-angle imaging neutral-atom spectrometers

    International Nuclear Information System (INIS)

    The Two Wide-angle Imaging Neutral-atom Spectrometers (TWINS) mission provides a new capability for stereoscopically imaging the magnetosphere. By imaging the charge exchange neutral atoms over a broad energy range (1 < E , ∼ 100 keV) using two identical instruments on two widely-spaced high-altitude, high-inclination spacecraft, TWINS will enable the 3-dimensional visualization and the resolution of large scale structures and dynamics within the magnetosphere for the first time. These observations will provide a leap ahead in the understanding of the global aspects of the terrestrial magnetosphere and directly address a number of critical issues in the ''Sun-Earth Connections'' science theme of the NASA Office of Space Science

  1. Money neutrality: Rethinking the myth

    Directory of Open Access Journals (Sweden)

    Issaoui Fakhri

    2015-01-01

    Full Text Available Considered as an axiomatic basis of classical, neoclassical, and monetarist theories, the long-run money neutrality assumption does not always seem to be verified. Indeed, in our view, the money, in the sense of M2, can constitute a long-run channel of growth transmission. Thus, this paper examines the long-term relationship among money supply (M2, income (GDP, and prices (CPI. The subprime crisis in 2007 has shown that the demand for money does not only meet motives of transaction, precaution, and speculation but also of fictional or quasi-fictional future demands due to the fact that they are created without real counterparts. The capacity of production systems in developed countries to respond to increases in money supply by creating more wealth, involves the assumption of money neutrality in the long-run. However, in developing countries, the excess of money supply may lead to inflation trends. The present study has confirmed the long-term non-neutrality of money supply in the USA, and its neutrality in Gabon and Morocco.

  2. ITER Neutral Beam Injection System

    International Nuclear Information System (INIS)

    A Japanese design proposal of the ITER Neutral Beam Injection System (NBS) which is consistent with the ITER common design requirements is described. The injection system is required to deliver a neutral deuterium beam of 75MW at 1.3MeV to the reactor plasma and utilized not only for plasma heating but also for current drive and current profile control. The injection system is composed of 9 modules, each of which is designed so as to inject a 1.3MeV, 10MW neutral beam. The most important point in the design is that the injection system is based on the utilization of a cesium-seeded volume negative ion source which can produce an intense negative ion beam with high current density at a low source operating pressure. The design value of the source is based on the experimental values achieved at JAERI. The utilization of the cesium-seeded volume source is essential to the design of an efficient and compact neutral beam injection system which satisfies the ITER common design requirements. The critical components to realize this design are the 1.3MeV, 17A electrostatic accelerator and the high voltage DC acceleration power supply, whose performances must be demonstrated prior to the construction of ITER NBI system. (author)

  3. Net Neutrality in the Netherlands

    NARCIS (Netherlands)

    N. van Eijk

    2014-01-01

    The Netherlands is among the first countries that have put specific net neutrality standards in place. The decision to implement specific regulation was influenced by at least three factors. The first was the prevailing social and academic debate, partly due to developments in the United States. The

  4. Neutralization kinetics for polonium-218

    International Nuclear Information System (INIS)

    In a well-defined experimental system the neutralization of polonium-218 ions was investigated as a function of the physical and chemical properties of the controlled composition atmosphere. The diffusion coefficient of polonium-218 under various concentrations of trace gas NO2 in nitrogen was measured. The mobilities of Po+ and PoO2+ are determined by combining experimental results with a computer model of the system. Three neutralization mechanisms were individually studied. The small-ion recombination rate has been found to be proportional to the square root of radon concentration. The electron-scavenging mechanism is responsible for the neutralization of Po+ in NO2 or H2O in nitrogen. When PoO2+ is formed, the electron-transfer mechanism dominates the neutralization process. The electron is transferred to PoO2+ from molecules with lower ionization potentials. The ionization molecules with lower ionization potentials. The ionization potential of PoO2+ is also determined to be 10.44 +/- 0.05 eV

  5. Neutral Models with Generalised Speciation

    NARCIS (Netherlands)

    Haegeman, Bart; Etienne, Rampal S.

    2009-01-01

    Hubbell's neutral theory claims that ecological patterns such as species abundance distributions can be explained by a stochastic model based on simple assumptions. One of these assumptions, the point mutation assumption, states that every individual has the same probability to speciate. Etienne et

  6. Two-strain competition in quasi-neutral stochastic disease dynamics

    Science.gov (United States)

    We develop a new perturbation method for studying quasi-neutral competition in a broad class of stochastic competition models, and apply it to the analysis of fixation of competing strains in two epidemic models. The first model is a two-strain generalization of the stochastic Susceptible-Infected-S...

  7. Neutralizing antibodies to hepatitis C virus in perinatally infected children followed up prospectively

    DEFF Research Database (Denmark)

    Meunier, Jean-Christophe; Bukh, Jens; Diaz, Giacomo;

    2011-01-01

    Little is known about the presence and role of neutralizing antibodies (NtAbs) in perinatal hepatitis C virus (HCV) infection. Using HCV pseudoparticles, NtAbs were studied longitudinally in 12 HCV-infected children with or without evidence of acute hepatitis during the first year of life. Broadly...

  8. Atypical and classical memory B cells produce Plasmodium falciparum neutralizing antibodies

    DEFF Research Database (Denmark)

    Muellenbeck, Matthias F; Ueberheide, Beatrix; Amulic, Borko;

    2013-01-01

    . We show at the single cell level that natural Pf infection induces the development of classical memory B cells (CM) and atypical memory B cells (AtM) that produce broadly neutralizing antibodies against blood stage Pf parasites. CM and AtM contribute to anti-Pf serum IgG production, but only AtM show...

  9. Cross-Reactive Neutralizing Humoral Immunity Does Not Protect from HIV Type 1 Disease Progression

    NARCIS (Netherlands)

    Z. Euler; M.J. van Gils; E.M. Bunnik; P. Phung; B. Schweighardt; T. Wrin; H. Schuitemaker

    2010-01-01

    Broadly reactive neutralizing antibodies are the focus of human immunodeficiency virus (HIV) type 1 vaccine design. However, only little is known about their role in acquired immunodeficiency syndrome (AIDS) pathogenesis and the factors associated with their development. Here we used a multisubtype

  10. Quality and quantity of TFH cells are critical for broad antibody development in SHIVAD8 infection.

    Science.gov (United States)

    Yamamoto, Takuya; Lynch, Rebecca M; Gautam, Rajeev; Matus-Nicodemos, Rodrigo; Schmidt, Stephen D; Boswell, Kristin L; Darko, Sam; Wong, Patrick; Sheng, Zizhang; Petrovas, Constantinos; McDermott, Adrian B; Seder, Robert A; Keele, Brandon F; Shapiro, Lawrence; Douek, Daniel C; Nishimura, Yoshiaki; Mascola, John R; Martin, Malcolm A; Koup, Richard A

    2015-07-29

    Broadly neutralizing antibodies (bNAbs) protect against HIV-1 infection, yet how they are generated during chronic infection remains unclear. It is known that T follicular helper (TFH) cells are needed to promote affinity maturation of B cells during an immune response; however, the role of TFH during HIV-1 infection is undefined within lymph node germinal centers (GCs). We use nonhuman primates to investigate the relationship in the early stage of chronic SHIVAD8 (simian-human immunodeficiency virus AD8) infection between envelope (Env)-specific TFH cells, Env-specific B cells, virus, and the generation of bNAbs during later infection. We found that both the frequency and quality of Env-specific TFH cells were associated with an expansion of Env-specific immunoglobulin G-positive GC B cells and broader neutralization across HIV clades. We also found a correlation between breadth of neutralization and the degree of somatic hypermutation in Env-specific memory B cells. Finally, we observed high viral loads and greater diversity of Env sequences in rhesus macaques that developed cross-reactive neutralization as compared to those that did not. These studies highlight the importance of boosting high-quality TFH populations as part of a robust vaccine regimen aimed at eliciting bNabs. PMID:26223303

  11. Application Neutrality and a Paradox of Side Payments

    OpenAIRE

    Altman, Eitan; Caron, Stéphane; Kesidis, George

    2010-01-01

    The ongoing debate over net neutrality covers a broad set of issues related to the regulation of public networks. In two ways, we extend an idealized usage-priced game-theoretic framework based on a common linear demand-response model. First, we study the impact of "side payments" among a plurality of Internet service (access) providers and content providers. In the non-monopolistic case, our analysis reveals an interesting "paradox" of side payments in that overall revenues are reduced for t...

  12. The broad line region in active galactic nuclei

    Directory of Open Access Journals (Sweden)

    D. Dultzin Hacyan

    2000-01-01

    Full Text Available Revisamos las limitaciones observacionales a los modelos sobre la estructura de las regiones que emiten las l neas anchas en los N ucleos Activos de Galaxias. La comparaci on entre las l neas de alta y baja ionizaci on con FWHM H 4000 km s

  13. Broadly tunable quasi-phase-matching in nonlinear metamaterials

    International Nuclear Information System (INIS)

    The ability to tune the quasi-phase-matching (QPM) frequency is a highly desirable though lacking feature of many nonlinear devices. To this end, we consider QPM in a special class of active nonlinear metamaterials (MMs), whose properties can be controlled postfabrication. By application of a tunable, periodic perturbation in the linear susceptibility (magnetic or electric) of a MM, a single nonlinear device can be constructed to operate over an exceedingly broad bandwidth. We propose a nonlinear MM for QPM second-order harmonic generation at terahertz frequencies, predicted to have a tunable bandwidth of over 100%.

  14. Antiviral drug discovery: broad-spectrum drugs from nature.

    OpenAIRE

    Martinez, J P; Sasse, F; Brönstrup, M; Diez, J; Meyerhans, A

    2015-01-01

    Covering: up to April 2014. The development of drugs with broad-spectrum antiviral activities is a long pursued goal in drug discovery. It has been shown that blocking co-opted host-factors abrogates the replication of many viruses, yet the development of such host-targeting drugs has been met with scepticism mainly due to toxicity issues and poor translation to in vivo models. With the advent of new and more powerful screening assays and prediction tools, the idea of a drug that can efficien...

  15. Spectral decomposition of broad-line agns and host galaxies

    Energy Technology Data Exchange (ETDEWEB)

    Vanden Berk, Daniel E.; Shen, Jiajian; /Penn State U., Astron. Astrophys.; Yip, Ching-Wa; /Pittsburgh U.; Schneider, Donald P.; /Penn State U., Astron. Astrophys.; Connolly,; /Pittsburgh U.; Burton, Ross E.; /Pittsburgh U. /Case Western Reserve U.; Jester, Sebastian; /Fermilab; Hall, Patrick B.; /York U., Canada; Szalay, Alex S.; /Johns Hopkins; Brinkmann, John; /Apache Point Observ.

    2005-09-01

    Using an eigenspectrum decomposition technique, we separate the host galaxy from the broad line active galactic nucleus (AGN) in a set of 4666 spectra from the Sloan Digital Sky Survey (SDSS), from redshifts near zero up to about 0.75. The decomposition technique uses separate sets of galaxy and quasar eigenspectra to efficiently and reliably separate the AGN and host spectroscopic components. The technique accurately reproduces the host galaxy spectrum, its contributing fraction, and its classification. We show how the accuracy of the decomposition depends upon S/N, host galaxy fraction, and the galaxy class. Based on the eigencoefficients, the sample of SDSS broad-line AGN host galaxies spans a wide range of spectral types, but the distribution differs significantly from inactive galaxies. In particular, post-starburst activity appears to be much more common among AGN host galaxies. The luminosities of the hosts are much higher than expected for normal early-type galaxies, and their colors become increasingly bluer than early-type galaxies with increasing host luminosity. Most of the AGNs with detected hosts are emitting at between 1% and 10% of their estimated Eddington luminosities, but the sensitivity of the technique usually does not extend to the Eddington limit. There are mild correlations among the AGN and host galaxy eigencoefficients, possibly indicating a link between recent star formation and the onset of AGN activity. The catalog of spectral reconstruction parameters is available as an electronic table.

  16. Lipochemistry of the progamic stage of a self-incompatible species: Neutral lipids and fatty acids of the secretory stigma during its glandular activity, and of the solid style, the ovary and the anther in Forsythia intermedia Zab. (Heterostylic species).

    Science.gov (United States)

    Dumas, C

    1977-01-01

    Chromatographic (thin-layer, gas column, column chromatography) analyses of neutral lipids and fatty acids of reproductive tissues of Forsythia intermedia Zab., a self-incompatible species, were performed with two objectives in mind: 1. To determine whether there is a qualitative evolution of the different classes of lipids and fatty acids that could be correlated with the three functional stages observed during previous histochemical and ultrastructural studies. The stigmatic exudate and intracellular accumulations consist mainly of neutral lipids. 2. To compare the lipid composition of the stigma (both "thrum" and "pin" forms) with that of the style, the ovary, and the anther, and to investigate the possible existence of a stigma-specific lipid compound. Stigmatic neutral lipids are found mostly in a glyceridic mixture probably containing hydrocarbons and terpenes. The fatty acids identified are between C:7 and C: 12, with the maximum unsaturated form being a C: 18. During the secretory process there is no great qualitative diference between the neutral lipids and fatty acids found in the stigmas of "thrum" and "pin" forms. Sterols are present in styles, ovaries, and anthers, but not in stigmas. They represent the only difference in the lipid composition of these various floral structures. PMID:24420636

  17. Large-scale analysis of B-cell epitopes on influenza virus hemagglutinin - implications for cross-reactivity of neutralizing antibodies

    OpenAIRE

    Jing eSun; Ulrich eKudahl; Zhiwei eCao; Christian eSimon; Reinherz, Ellis L; Vladimir eBrusic

    2014-01-01

    Influenza viruses continue to cause substantial morbidity and mortality worldwide. Fast gene mutation on surface proteins of influenza virus result in increasing resistance to current vaccines and available antiviral drugs. Broadly neutralizing antibodies represent targets for prophylactic and therapeutic treatments of influenza. We performed a systematic bioinformatics study of cross-reactivity of neutralizing antibodies against influenza virus surface glycoprotein hemagglutinin (HA). This s...

  18. Radiative lifetimes of neutral neodymium

    International Nuclear Information System (INIS)

    This work is part of an on-going study of radiative properties of rare earth neutral atoms. This work is motivated by research needs in several disparate fields including astrophysics and lighting technology. Radiative lifetimes of 100 levels of neutral neodymium are measured using the technique of time-resolved laser-induced fluorescence on a slow atomic beam. Of the 100 levels, 3 are even parity ranging in energy from 25 746 to 26 835 cm-1, and the remaining 97 are odd parity ranging from 17 787 to 27 786 cm-1. This set of Nd i lifetimes represents a significant extension to the available published data, with 51 of the 100 level lifetimes measured for the first time. These data, which are accurate to ±5%, provide the absolute normalization for a large set of measured Nd i transition probabilities.

  19. Radiative lifetimes of neutral gadolinium

    Energy Technology Data Exchange (ETDEWEB)

    Den Hartog, E A; Bilty, K A; Lawler, J E, E-mail: eadenhar@wisc.edu, E-mail: biltyka@uwec.edu, E-mail: jelawler@wisc.edu [Department of Physics, University of Wisconsin, 1150 University Ave, Madison, WI 53706 (United States)

    2011-03-14

    The current work is part of an ongoing study of radiative properties of rare earth neutral atoms motivated by research needs in several disparate fields including astrophysics, laser chemistry and lighting technology. Time-resolved laser-induced fluorescence on a slow atomic beam has been used to measure radiative lifetimes, accurate to {+-}5%, for 136 levels of neutral gadolinium. Of the 136 levels, 6 are odd parity ranging in energy from 32 929 to 36 654 cm{sup -1}, and the remaining 130 are even parity ranging from 17 750 to 34 175 cm{sup -1}. This set of Gd i lifetimes represents a significant extension to the available published data, with 93 of the 136 level lifetimes measured for the first time. These lifetimes will provide the absolute normalization for a large set of measured Gd i transition probabilities.

  20. Radiative lifetimes of neutral gadolinium

    International Nuclear Information System (INIS)

    The current work is part of an ongoing study of radiative properties of rare earth neutral atoms motivated by research needs in several disparate fields including astrophysics, laser chemistry and lighting technology. Time-resolved laser-induced fluorescence on a slow atomic beam has been used to measure radiative lifetimes, accurate to ±5%, for 136 levels of neutral gadolinium. Of the 136 levels, 6 are odd parity ranging in energy from 32 929 to 36 654 cm-1, and the remaining 130 are even parity ranging from 17 750 to 34 175 cm-1. This set of Gd i lifetimes represents a significant extension to the available published data, with 93 of the 136 level lifetimes measured for the first time. These lifetimes will provide the absolute normalization for a large set of measured Gd i transition probabilities.