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  1. 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

    , and an effective vaccine should target conserved T- and B-cell epitopes of the virus. Conserved B-cell epitopes overlapping the CD81 receptor-binding site (CD81bs) on the E2 viral envelope glycoprotein have been reported previously and provide promising vaccine targets. In this study, we isolated 73 human m......Abs recognizing five distinct antigenic regions on the virus envelope glycoprotein complex E1E2 from an HCV-immune phage-display antibody library by using an exhaustive-panning strategy. Many of these mAbs were broadly neutralizing. In particular, the mAb AR4A, recognizing a discontinuous epitope outside the CD81......bs on the E1E2 complex, has an exceptionally broad neutralizing activity toward diverse HCV genotypes and protects against heterologous HCV challenge in a small animal model. The mAb panel will be useful for the design and development of vaccine candidates to elicit broadly neutralizing antibodies...

  2. Antiviral Therapy by HIV-1 Broadly Neutralizing and Inhibitory Antibodies

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    Zhiqing Zhang

    2016-11-01

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 infection causes acquired immune deficiency syndrome (AIDS, a global epidemic for more than three decades. HIV-1 replication is primarily controlled through antiretroviral therapy (ART but this treatment does not cure HIV-1 infection. Furthermore, there is increasing viral resistance to ART, and side effects associated with long-term therapy. Consequently, there is a need of alternative candidates for HIV-1 prevention and therapy. Recent advances have discovered multiple broadly neutralizing antibodies against HIV-1. In this review, we describe the key epitopes on the HIV-1 Env protein and the reciprocal broadly neutralizing antibodies, and discuss the ongoing clinical trials of broadly neutralizing and inhibitory antibody therapy as well as antibody combinations, bispecific antibodies, and methods that improve therapeutic efficacy by combining broadly neutralizing antibodies (bNAbs with latency reversing agents. Compared with ART, HIV-1 therapeutics that incorporate these broadly neutralizing and inhibitory antibodies offer the advantage of decreasing virus load and clearing infected cells, which is a promising prospect in HIV-1 prevention and treatment.

  3. Naturally selected hepatitis C virus polymorphisms confer broad neutralizing antibody resistance.

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    Bailey, Justin R; Wasilewski, Lisa N; Snider, Anna E; El-Diwany, Ramy; Osburn, William O; Keck, Zhenyong; Foung, Steven K H; Ray, Stuart C

    2015-01-01

    For hepatitis C virus (HCV) and other highly variable viruses, broadly neutralizing mAbs are an important guide for vaccine development. The development of resistance to anti-HCV mAbs is poorly understood, in part due to a lack of neutralization testing against diverse, representative panels of HCV variants. Here, we developed a neutralization panel expressing diverse, naturally occurring HCV envelopes (E1E2s) and used this panel to characterize neutralizing breadth and resistance mechanisms of 18 previously described broadly neutralizing anti-HCV human mAbs. The observed mAb resistance could not be attributed to polymorphisms in E1E2 at known mAb-binding residues. Additionally, hierarchical clustering analysis of neutralization resistance patterns revealed relationships between mAbs that were not predicted by prior epitope mapping, identifying 3 distinct neutralization clusters. Using this clustering analysis and envelope sequence data, we identified polymorphisms in E2 that confer resistance to multiple broadly neutralizing mAbs. These polymorphisms, which are not at mAb contact residues, also conferred resistance to neutralization by plasma from HCV-infected subjects. Together, our method of neutralization clustering with sequence analysis reveals that polymorphisms at noncontact residues may be a major immune evasion mechanism for HCV, facilitating viral persistence and presenting a challenge for HCV vaccine development.

  4. Phage Display-Derived Cross-Reactive Neutralizing Antibody against Enterovirus 71 and Coxsackievirus A16.

    Science.gov (United States)

    Zhang, Xiao; Sun, Chunyun; Xiao, Xiangqian; Pang, Lin; Shen, Sisi; Zhang, Jie; Cen, Shan; Yang, Burton B; Huang, Yuming; Sheng, Wang; Zeng, Yi

    2016-01-01

    Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are members of the Picornaviridae family and are considered the main causative agents of hand, foot and mouth disease (HFMD). In recent decades large HFMD outbreaks caused by EV71 and CVA16 have become significant public health concerns in the Asia-Pacific region. Vaccines and antiviral drugs are unavailable to prevent EV71 and CVA16 infection. In the current study, a chimeric antibody targeting a highly conserved peptide in the EV71 VP4 protein was isolated by using a phage display technique. The antibody showed cross-neutralizing capability against EV71 and CVA16 in vitro. The results suggest that this phage display-derived antibody will have great potential as a broad neutralizing antibody against EV71 and CVA16 after affinity maturation and humanization.

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

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    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. Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus

    Science.gov (United States)

    Liao, Hua-Xin; Lynch, Rebecca; Zhou, Tongqing; Gao, Feng; Alam, S. Munir; Boyd, Scott D.; Fire, Andrew Z.; Roskin, Krishna M.; Schramm, Chaim A.; Zhang, Zhenhai; Zhu, Jiang; Shapiro, Lawrence; Mullikin, James C.; Gnanakaran, S.; Hraber, Peter; Wiehe, Kevin; Kelsoe, Garnett; Yang, Guang; Xia, Shi-Mao; Montefiori, David C.; Parks, Robert; Lloyd, Krissey E.; Scearce, Richard M.; Soderberg, Kelly A.; Cohen, Myron; Kaminga, Gift; Louder, Mark K.; Tran, Lillan M.; Chen, Yue; Cai, Fangping; Chen, Sheri; Moquin, Stephanie; Du, Xiulian; Joyce, Gordon M.; Srivatsan, Sanjay; Zhang, Baoshan; Zheng, Anqi; Shaw, George M.; Hahn, Beatrice H.; Kepler, Thomas B.; Korber, Bette T.M.; Kwong, Peter D.; Mascola, John R.; Haynes, Barton F.

    2013-01-01

    Current HIV-1 vaccines elicit strain-specific neutralizing antibodies. However, cross-reactive neutralizing antibodies arise in ~20% of HIV-1-infected individuals, and details of their generation could provide a roadmap for effective vaccination. Here we report the isolation, evolution and structure of a broadly neutralizing antibody from an African donor followed from time of infection. The mature antibody, CH103, neutralized ~55% of HIV-1 isolates, and its co-crystal structure with gp120 revealed a novel loop-based mechanism of CD4-binding site recognition. Virus and antibody gene sequencing revealed concomitant virus evolution and antibody maturation. Notably, the CH103-lineage unmutated common ancestor avidly bound the transmitted/founder HIV-1 envelope glycoprotein, and evolution of antibody neutralization breadth was preceded by extensive viral diversification in and near the CH103 epitope. These data elucidate the viral and antibody evolution leading to induction of a lineage of HIV-1 broadly neutralizing antibodies and provide insights into strategies to elicit similar antibodies via vaccination. PMID:23552890

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

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    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.

  8. Molecular evolution of broadly neutralizing Llama antibodies to the CD4-binding site of HIV-1.

    Science.gov (United States)

    McCoy, Laura E; Rutten, Lucy; Frampton, Dan; Anderson, Ian; Granger, Luke; Bashford-Rogers, Rachael; Dekkers, Gillian; Strokappe, Nika M; Seaman, Michael S; Koh, Willie; Grippo, Vanina; Kliche, Alexander; Verrips, Theo; Kellam, Paul; Fassati, Ariberto; Weiss, Robin A

    2014-12-01

    To date, no immunization of humans or animals has elicited broadly neutralizing sera able to prevent HIV-1 transmission; however, elicitation of broad and potent heavy chain only antibodies (HCAb) has previously been reported in llamas. In this study, the anti-HIV immune responses in immunized llamas were studied via deep sequencing analysis using broadly neutralizing monoclonal HCAbs as a guides. Distinct neutralizing antibody lineages were identified in each animal, including two defined by novel antibodies (as variable regions called VHH) identified by robotic screening of over 6000 clones. The combined application of five VHH against viruses from clades A, B, C and CRF_AG resulted in neutralization as potent as any of the VHH individually and a predicted 100% coverage with a median IC50 of 0.17 µg/ml for the panel of 60 viruses tested. Molecular analysis of the VHH repertoires of two sets of immunized animals showed that each neutralizing lineage was only observed following immunization, demonstrating that they were elicited de novo. Our results show that immunization can induce potent and broadly neutralizing antibodies in llamas with features similar to human antibodies and provide a framework to analyze the effectiveness of immunization protocols.

  9. Association between HIV-1 coreceptor usage and resistance to broadly neutralizing antibodies.

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    Pfeifer, Nico; Walter, Hauke; Lengauer, Thomas

    2014-10-01

    Recently discovered broadly neutralizing antibodies have revitalized hopes of developing a universal vaccine against HIV-1. Mainly responsible for new infections are variants only using CCR5 for cell entry, whereas CXCR4-using variants can become dominant in later infection stages. We performed a statistical analysis on two different previously published data sets. The first data set was a panel of 199 diverse HIV-1 isolates for which IC50 neutralization titers were determined for the broadly neutralizing antibodies VRC01, VRC-PG04, PG9, and PG16. The second data set contained env sequences of viral variants extracted from HIV-1-infected humanized mice treated with the antibody PGT128 and from untreated control mice. For the panel of 199 diverse HIV-1 isolates, we found a statistically significant association between viral resistance to PG9 and PG16 and CXCR4 coreceptor usage (P = 0.0011 and P = 0.0010, respectively). Our analysis of viral variants from HIV-1-infected humanized mice under treatment with the broadly neutralizing antibody PGT128 indicated that certain antibodies might drive a viral population toward developing CXCR4 coreceptor usage capability (P = 0.0011 for the comparison between PGT128 and control measurement). These analyses highlight the importance of accounting for a possible coreceptor usage bias pertaining to the effectiveness of an HIV vaccine and to passive antibody transfer as therapeutic approach.

  10. Evolution of Neutralization Response in HIV-1 Subtype C-Infected Individuals Exhibiting Broad Cross-Clade Neutralization of HIV-1 Strains

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    Narayanaiah Cheedarla

    2018-03-01

    Full Text Available Strain-specific neutralizing antibodies develop in all human immunodeficiency virus type 1 (HIV-1-infected individuals. However, only 10–30% of infected individuals produce broadly neutralizing antibodies (bNAbs. Identification and characterization of these bNAbs and understanding their evolution dynamics are critical for obtaining useful clues for the development of an effective HIV vaccine. Very recently, we published a study in which we identified 12 HIV-1 subtype C-infected individuals from India whose plasma showed potent and broad cross-clade neutralization (BCN ability (1. In the present study, we report our findings on the evolution of host bNAb response over a period of 4 years in a subset of these individuals. Three of the five individuals (NAB033, NAB059, and NAB065 demonstrated a significant increase (p < 0.05 in potency. Interestingly, two of the three samples also showed a significant increase in CD4 binding site-specific antibody response, maintained stable CD4+ T cell counts (>350 cells/mm3 and continued to remain ART-naïve for more than 10 years after initial diagnosis, implying a strong clinical correlation with the development and evolution of broadly neutralizing antibody response against HIV-1.

  11. 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.

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

    International Nuclear Information System (INIS)

    Kubota-Koketsu, Ritsuko; Mizuta, Hiroyuki; Oshita, Masatoshi; Ideno, Shoji; Yunoki, Mikihiro; Kuhara, Motoki; Yamamoto, Naomasa; Okuno, Yoshinobu; Ikuta, Kazuyoshi

    2009-01-01

    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.

  13. Broadly-Reactive Neutralizing and Non-neutralizing Antibodies Directed against the H7 Influenza Virus Hemagglutinin Reveal Divergent Mechanisms of Protection.

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    Gene S Tan

    2016-04-01

    Full Text Available In the early spring of 2013, Chinese health authorities reported several cases of H7N9 influenza virus infections in humans. Since then the virus has established itself at the human-animal interface in Eastern China and continues to cause several hundred infections annually. In order to characterize the antibody response to the H7N9 virus we generated several mouse monoclonal antibodies against the hemagglutinin of the A/Shanghai/1/13 (H7N9 virus. Of particular note are two monoclonal antibodies, 1B2 and 1H5, that show broad reactivity to divergent H7 hemagglutinins. Monoclonal antibody 1B2 binds to viruses of the Eurasian and North American H7 lineages and monoclonal antibody 1H5 reacts broadly to virus isolates of the Eurasian lineage. Interestingly, 1B2 shows broad hemagglutination inhibiting and neutralizing activity, while 1H5 fails to inhibit hemagglutination and demonstrates no neutralizing activity in vitro. However, both monoclonal antibodies were highly protective in an in vivo passive transfer challenge model in mice, even at low doses. Experiments using mutant antibodies that lack the ability for Fc/Fc-receptor and Fc/complement interactions suggest that the protection provided by mAb 1H5 is, at least in part, mediated by the Fc-fragment of the mAb. These findings highlight that a protective response to a pathogen may not only be due to neutralizing antibodies, but can also be the result of highly efficacious non-neutralizing antibodies not readily detected by classical in vitro neutralization or hemagglutination inhibition assays. This is of interest because H7 influenza virus vaccines induce only low hemagglutination inhibiting antibody titers while eliciting robust antibody titers as measured by ELISA. Our data suggest that these binding but non-neutralizing antibodies contribute to protection in vivo.

  14. Towards HIV-1 remission: potential roles for broadly neutralizing antibodies.

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    Halper-Stromberg, Ariel; Nussenzweig, Michel C

    2016-02-01

    Current antiretroviral drug therapies do not cure HIV-1 because they do not eliminate a pool of long-lived cells harboring immunologically silent but replication-competent proviruses - termed the latent reservoir. Eliminating this reservoir and stimulating the immune response to control infection in the absence of therapy remain important but unsolved goals of HIV-1 cure research. Recently discovered broadly neutralizing antibodies (bNAbs) exhibit remarkable breadth and potency in their ability to neutralize HIV-1 in vitro, and recent studies have demonstrated new therapeutic applications for passively administered bNAbs in vivo. This Review discusses the roles bNAbs might play in HIV-1 treatment regimens, including prevention, therapy, and cure.

  15. Development of Broadly Neutralizing Antibody Mimitopes for Characterization of CRF01_AE HIV-1 Antibody Responses

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    Jesse V. Schoen

    2017-10-01

    Full Text Available Mapping humoral immune responses to HIV-1 over the course of natural infection is important in understanding epitope exposure in relation to elicitation of broadly neutralizing antibodies (bNAbs, which is considered imperative for effective vaccine design. When analyzing HIV-specific immune responses, the antibody binding profiles may be a correlate for functional antibody activity. In this study, we utilized phage display technology to identify novel mimitopes that may represent Env epitope structures bound by bNAbs directed at V1V2 and V3 domains, CD4 binding site (CD4bs and the membrane proximal external region (MPER of Env. Mimitope sequence motifs were determined for each bNAb epitope. Given the ongoing vaccine development efforts in Thailand, these mimitopes that represent CD4bs and MPER epitopes were used to map immune responses of HIV-1 CRF01_AE-infected individuals with known neutralizing responses from two distinct time periods, 1996-98 and 2012-15. The more contemporary cohort showed an increase in binding breadth with binding observed for all MPER and CD4bs mimitopes, while the older cohort showed only 75% recognition of the CD4bs mimitopes and no MPER mimotope binding. Furthermore, mimitope binding profiles correlated significantly with magnitude (p=0.0036 and breadth (p=0.0358 of neutralization of a multi-subtype Tier 1 panel of pseudoviruses. These results highlight the utility of this mimitope mapping approach for detecting human plasma IgG-specificities that target known neutralizing antibody epitopes, and may also provide an indication of the plasticity of antibody binding within HIV-1 Env neutralization determinants.

  16. Genetic signatures in the envelope glycoproteins of HIV-1 that associate with broadly neutralizing antibodies.

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    S Gnanakaran

    Full Text Available A steady increase in knowledge of the molecular and antigenic structure of the gp120 and gp41 HIV-1 envelope glycoproteins (Env is yielding important new insights for vaccine design, but it has been difficult to translate this information to an immunogen that elicits broadly neutralizing antibodies. To help bridge this gap, we used phylogenetically corrected statistical methods to identify amino acid signature patterns in Envs derived from people who have made potently neutralizing antibodies, with the hypothesis that these Envs may share common features that would be useful for incorporation in a vaccine immunogen. Before attempting this, essentially as a control, we explored the utility of our computational methods for defining signatures of complex neutralization phenotypes by analyzing Env sequences from 251 clonal viruses that were differentially sensitive to neutralization by the well-characterized gp120-specific monoclonal antibody, b12. We identified ten b12-neutralization signatures, including seven either in the b12-binding surface of gp120 or in the V2 region of gp120 that have been previously shown to impact b12 sensitivity. A simple algorithm based on the b12 signature pattern was predictive of b12 sensitivity/resistance in an additional blinded panel of 57 viruses. Upon obtaining these reassuring outcomes, we went on to apply these same computational methods to define signature patterns in Env from HIV-1 infected individuals who had potent, broadly neutralizing responses. We analyzed a checkerboard-style neutralization dataset with sera from 69 HIV-1-infected individuals tested against a panel of 25 different Envs. Distinct clusters of sera with high and low neutralization potencies were identified. Six signature positions in Env sequences obtained from the 69 samples were found to be strongly associated with either the high or low potency responses. Five sites were in the CD4-induced coreceptor binding site of gp120, suggesting an

  17. Characterization of broadly neutralizing antibody responses to HIV-1 in a cohort of long term non-progressors.

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    González, Nuria; McKee, Krisha; Lynch, Rebecca M; Georgiev, Ivelin S; Jimenez, Laura; Grau, Eulalia; Yuste, Eloísa; Kwong, Peter D; Mascola, John R; Alcamí, José

    2018-01-01

    Only a small fraction of HIV-1-infected patients develop broadly neutralizing antibodies (bNAbs), a process generally associated to chronic antigen stimulation. It has been described that rare aviremic HIV-1-infected patients can generate bNAbs but this issue remains controversial. To address this matter we have assessed bNAb responses in a large cohort of long-term non-progressors (LTNPs) with low or undetectable viremia. Samples from the LTNP cohort of the Spanish AIDS Research Network (87 elite and 42 viremic controllers) and a control population of 176 viremic typical-progressors (TPs) were screened for bNAbs using Env-recombinant viruses. bNAb specificities were studied by ELISA using mutated gp120, neutralization assays with mutated viruses, and peptide competition. Epitope specificities were also elucidated from the serum pattern of neutralization against a panel of diverse HIV-1 isolates. Broadly neutralizing sera were found among 9.3% LTNPs, both elite (7%) and viremic controllers (14%). Within the broadly neutralizing sera, CD4 binding site antibodies were detected by ELISA in 4/12 LTNPs (33%), and 16/33 of TPs (48%). Anti-MPER antibodies were detected in 6/12 LTNPs (50%) and 14/33 TPs (42%) whereas glycan-dependent HIV-1 bNAbs were more frequent in LTNPs (11/12, 92%) as compared to TPs (12/33, 36%). A good concordance between standard serum mapping and neutralization-based mapping was observed. LTNPs, both viremic and elite controllers, showed broad humoral immune responses against HIV-1, including activity against many major epitopes involved in bNAbs-mediated protection.

  18. Development of an anti-HIV vaccine eliciting broadly neutralizing antibodies.

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    Ahmed, Yousuf; Tian, Meijuan; Gao, Yong

    2017-09-12

    The extreme HIV diversity posts a great challenge on development of an effective anti-HIV vaccine. To solve this problem, it is crucial to discover an appropriate immunogens and strategies that are able to prevent the transmission of the diverse viruses that are circulating in the world. Even though there have been a number of broadly neutralizing anti-HIV antibodies (bNAbs) been discovered in recent years, induction of such antibodies to date has only been observed in HIV-1 infection. Here, in this mini review, we review the progress in development of HIV vaccine in eliciting broad immune response, especially production of bNAbs, discuss possible strategies, such as polyvalent sequential vaccination, that facilitates B cell maturation leading to bNAb response.

  19. Implementation of a quasi-realtime display of DIII-D neutral beam heating waveforms

    International Nuclear Information System (INIS)

    Phillips, J.C.

    1993-10-01

    The DIII-D neutral beam system employs eight 80 keV ion sources mounted on four beamlines to provide plasma heating to the DIII-D tokamak. The neutral beam system is capable of injecting over 20 MW of deuterium power with flexibility in terms of timing and modulation of the individual neutral beams. To maintain DIII-D's efficient tokamak shot cycle and make informed control decisions, it is important to be able to determine which beams fired, and exactly when, by the time the tokamak shot is over. Previously this information was available in centralized form only after a several minute wait. A cost-effective alternative to the traditional eight-channel storage oscilloscope has been implemented using off the shelf PC hardware and software. The system provides a real time display of injected neutral beam accelerator voltages and tokamak plasma current, as well an a summation waveform indicative of the total injected power as a function of time. The hardware consists of a Macintosh Centris 650 PC with a Motorola 68040 microprocessor. Data acquisition is accomplished using a National Instrument's 16-channel analog to digital conversion board for the Macintosh. The color displays and functionality were developed using National Instruments' LabView environment. Because the price of PCs has been decreasing rapidly and their capabilities increasing, this system is far less expensive than an eight-channel storage oscilloscope. As a flexible combination of PC and software, the system also provides much more capability than a dedicated oscilloscope, acting as the neutral beam coordinator's logbook, recording comments and availability statistics. Data such as shot number and neutral beam parameters are obtained over the local network from other computers and added to the display. Waveforms are easily archived to disk for future recall. Details of the implementation will be discussed along with samples of the displays and a description of the system's function and capabilities

  20. Implementation of a quasi-realtime display of DIII-D neutral beam heating waveforms

    Energy Technology Data Exchange (ETDEWEB)

    Phillips, J.C.

    1993-10-01

    The DIII-D neutral beam system employs eight 80 keV ion sources mounted on four beamlines to provide plasma heating to the DIII-D tokamak. The neutral beam system is capable of injecting over 20 MW of deuterium power with flexibility in terms of timing and modulation of the individual neutral beams. To maintain DIII-D`s efficient tokamak shot cycle and make informed control decisions, it is important to be able to determine which beams fired, and exactly when, by the time the tokamak shot is over. Previously this information was available in centralized form only after a several minute wait. A cost-effective alternative to the traditional eight-channel storage oscilloscope has been implemented using off the shelf PC hardware and software. The system provides a real time display of injected neutral beam accelerator voltages and tokamak plasma current, as well an a summation waveform indicative of the total injected power as a function of time. The hardware consists of a Macintosh Centris 650 PC with a Motorola 68040 microprocessor. Data acquisition is accomplished using a National Instrument`s 16-channel analog to digital conversion board for the Macintosh. The color displays and functionality were developed using National Instruments` LabView environment. Because the price of PCs has been decreasing rapidly and their capabilities increasing, this system is far less expensive than an eight-channel storage oscilloscope. As a flexible combination of PC and software, the system also provides much more capability than a dedicated oscilloscope, acting as the neutral beam coordinator`s logbook, recording comments and availability statistics. Data such as shot number and neutral beam parameters are obtained over the local network from other computers and added to the display. Waveforms are easily archived to disk for future recall. Details of the implementation will be discussed along with samples of the displays and a description of the system`s function and capabilities.

  1. Chimeric rhinoviruses displaying MPER epitopes elicit anti-HIV neutralizing responses.

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    Guohua Yi

    Full Text Available The development of an effective AIDS vaccine has been a formidable task, but remains a critical necessity. The well conserved membrane-proximal external region (MPER of the HIV-1 gp41 glycoprotein is one of the crucial targets for AIDS vaccine development, as it has the necessary attribute of being able to elicit antibodies capable of neutralizing diverse isolates of HIV.Guided by X-ray crystallography, molecular modeling, combinatorial chemistry, and powerful selection techniques, we designed and produced six combinatorial libraries of chimeric human rhinoviruses (HRV displaying the MPER epitopes corresponding to mAbs 2F5, 4E10, and/or Z13e1, connected to an immunogenic surface loop of HRV via linkers of varying lengths and sequences. Not all libraries led to viable chimeric viruses with the desired sequences, but the combinatorial approach allowed us to examine large numbers of MPER-displaying chimeras. Among the chimeras were five that elicited antibodies capable of significantly neutralizing HIV-1 pseudoviruses from at least three subtypes, in one case leading to neutralization of 10 pseudoviruses from all six subtypes tested.Optimization of these chimeras or closely related chimeras could conceivably lead to useful components of an effective AIDS vaccine. While the MPER of HIV may not be immunodominant in natural infection by HIV-1, its presence in a vaccine cocktail could provide critical breadth of protection.

  2. Service without a Smile: Comparing the Consequences of Neutral and Positive Display Rules

    Science.gov (United States)

    Trougakos, John P.; Jackson, Christine L.; Beal, Daniel J.

    2011-01-01

    We used an experimental design to examine the intrapersonal and interpersonal processes through which neutral display rules, compared to positive display rules, influence objective task performance of poll workers and ratings provided by survey respondents of the poll workers. Student participants (N = 140) were trained to adhere to 1 of the 2…

  3. Modeling neutralization kinetics of HIV by broadly neutralizing monoclonal antibodies in genital secretions coating the cervicovaginal mucosa.

    Directory of Open Access Journals (Sweden)

    Scott A McKinley

    Full Text Available Eliciting broadly neutralizing antibodies (bnAb in cervicovaginal mucus (CVM represents a promising "first line of defense" strategy to reduce vaginal HIV transmission. However, it remains unclear what levels of bnAb must be present in CVM to effectively reduce infection. We approached this complex question by modeling the dynamic tally of bnAb coverage on HIV. This analysis introduces a critical, timescale-dependent competition: to protect, bnAb must accumulate at sufficient stoichiometry to neutralize HIV faster than virions penetrate CVM and reach target cells. We developed a model that incorporates concentrations and diffusivities of HIV and bnAb in semen and CVM, kinetic rates for binding (kon and unbinding (koff of select bnAb, and physiologically relevant thicknesses of CVM and semen layers. Comprehensive model simulations lead to robust conclusions about neutralization kinetics in CVM. First, due to the limited time virions in semen need to penetrate CVM, substantially greater bnAb concentrations than in vitro estimates must be present in CVM to neutralize HIV. Second, the model predicts that bnAb with more rapid kon, almost independent of koff, should offer greater neutralization potency in vivo. These findings suggest the fastest arriving virions at target cells present the greatest likelihood of infection. It also implies the marked improvements in in vitro neutralization potency of many recently discovered bnAb may not translate to comparable reduction in the bnAb dose needed to confer protection against initial vaginal infections. Our modeling framework offers a valuable tool to gaining quantitative insights into the dynamics of mucosal immunity against HIV and other infectious diseases.

  4. Modeling neutralization kinetics of HIV by broadly neutralizing monoclonal antibodies in genital secretions coating the cervicovaginal mucosa.

    Science.gov (United States)

    McKinley, Scott A; Chen, Alex; Shi, Feng; Wang, Simi; Mucha, Peter J; Forest, M Gregory; Lai, Samuel K

    2014-01-01

    Eliciting broadly neutralizing antibodies (bnAb) in cervicovaginal mucus (CVM) represents a promising "first line of defense" strategy to reduce vaginal HIV transmission. However, it remains unclear what levels of bnAb must be present in CVM to effectively reduce infection. We approached this complex question by modeling the dynamic tally of bnAb coverage on HIV. This analysis introduces a critical, timescale-dependent competition: to protect, bnAb must accumulate at sufficient stoichiometry to neutralize HIV faster than virions penetrate CVM and reach target cells. We developed a model that incorporates concentrations and diffusivities of HIV and bnAb in semen and CVM, kinetic rates for binding (kon) and unbinding (koff) of select bnAb, and physiologically relevant thicknesses of CVM and semen layers. Comprehensive model simulations lead to robust conclusions about neutralization kinetics in CVM. First, due to the limited time virions in semen need to penetrate CVM, substantially greater bnAb concentrations than in vitro estimates must be present in CVM to neutralize HIV. Second, the model predicts that bnAb with more rapid kon, almost independent of koff, should offer greater neutralization potency in vivo. These findings suggest the fastest arriving virions at target cells present the greatest likelihood of infection. It also implies the marked improvements in in vitro neutralization potency of many recently discovered bnAb may not translate to comparable reduction in the bnAb dose needed to confer protection against initial vaginal infections. Our modeling framework offers a valuable tool to gaining quantitative insights into the dynamics of mucosal immunity against HIV and other infectious diseases.

  5. Hidden Lineage Complexity of Glycan-Dependent HIV-1 Broadly Neutralizing Antibodies Uncovered by Digital Panning and Native-Like gp140 Trimer

    Directory of Open Access Journals (Sweden)

    Linling He

    2017-08-01

    Full Text Available Germline precursors and intermediates of broadly neutralizing antibodies (bNAbs are essential to the understanding of humoral response to HIV-1 infection and B-cell lineage vaccine design. Using a native-like gp140 trimer probe, we examined antibody libraries constructed from donor-17, the source of glycan-dependent PGT121-class bNAbs recognizing the N332 supersite on the HIV-1 envelope glycoprotein. To facilitate this analysis, a digital panning method was devised that combines biopanning of phage-displayed antibody libraries, 900 bp long-read next-generation sequencing, and heavy/light (H/L-paired antibodyomics. In addition to single-chain variable fragments resembling the wild-type bNAbs, digital panning identified variants of PGT124 (a member of the PGT121 class with a unique insertion in the heavy chain complementarity-determining region 1, as well as intermediates of PGT124 exhibiting notable affinity for the native-like trimer and broad HIV-1 neutralization. In a competition assay, these bNAb intermediates could effectively compete with mouse sera induced by a scaffolded BG505 gp140.681 trimer for the N332 supersite. Our study thus reveals previously unrecognized lineage complexity of the PGT121-class bNAbs and provides an array of library-derived bNAb intermediates for evaluation of immunogens containing the N332 supersite. Digital panning may prove to be a valuable tool in future studies of bNAb diversity and lineage development.

  6. Hidden Lineage Complexity of Glycan-Dependent HIV-1 Broadly Neutralizing Antibodies Uncovered by Digital Panning and Native-Like gp140 Trimer.

    Science.gov (United States)

    He, Linling; Lin, Xiaohe; de Val, Natalia; Saye-Francisco, Karen L; Mann, Colin J; Augst, Ryan; Morris, Charles D; Azadnia, Parisa; Zhou, Bin; Sok, Devin; Ozorowski, Gabriel; Ward, Andrew B; Burton, Dennis R; Zhu, Jiang

    2017-01-01

    Germline precursors and intermediates of broadly neutralizing antibodies (bNAbs) are essential to the understanding of humoral response to HIV-1 infection and B-cell lineage vaccine design. Using a native-like gp140 trimer probe, we examined antibody libraries constructed from donor-17, the source of glycan-dependent PGT121-class bNAbs recognizing the N332 supersite on the HIV-1 envelope glycoprotein. To facilitate this analysis, a digital panning method was devised that combines biopanning of phage-displayed antibody libraries, 900 bp long-read next-generation sequencing, and heavy/light (H/L)-paired antibodyomics. In addition to single-chain variable fragments resembling the wild-type bNAbs, digital panning identified variants of PGT124 (a member of the PGT121 class) with a unique insertion in the heavy chain complementarity-determining region 1, as well as intermediates of PGT124 exhibiting notable affinity for the native-like trimer and broad HIV-1 neutralization. In a competition assay, these bNAb intermediates could effectively compete with mouse sera induced by a scaffolded BG505 gp140.681 trimer for the N332 supersite. Our study thus reveals previously unrecognized lineage complexity of the PGT121-class bNAbs and provides an array of library-derived bNAb intermediates for evaluation of immunogens containing the N332 supersite. Digital panning may prove to be a valuable tool in future studies of bNAb diversity and lineage development.

  7. Heterotypic Protection and Induction of a Broad Heterotypic Neutralization Response by Rotavirus-Like Particles

    Science.gov (United States)

    Crawford, Sue E.; Estes, Mary K.; Ciarlet, Max; Barone, Christopher; O’Neal, Christine M.; Cohen, Jean; Conner, Margaret E.

    1999-01-01

    The recognition that rotaviruses are the major cause of life-threatening diarrheal disease and significant morbidity in young children has focused efforts on disease prevention and control of these viruses. Although the correlates of protection in children remain unclear, some studies indicate that serotype-specific antibody is important. Based on this premise, current live attenuated reassortant rotavirus vaccines include the four predominant serotypes of virus. We are evaluating subunit rotavirus vaccines, 2/6/7-VLPs and 2/4/6/7-VLPs, that contain only a single VP7 of serotype G1 or G3. In mice immunized parenterally twice, G3 virus-like particles (VLPs) induced a homotypic, whereas G1 VLPs induced a homotypic and heterotypic (G3) serum neutralizing immune response. Administration of three doses of G1 or G3 VLPs induced serum antibodies that neutralized five of seven different serotype test viruses. The inclusion of VP4 in the VLPs was not essential for the induction of heterotypic neutralizing antibody in mice. To confirm these results in another species, rabbits were immunized parenterally with two doses of 2/4/6/7-VLPs containing a G3 or G1 VP7, sequentially with G3 VLPs followed by G1 (G3/G1) VLPs, or with live or psoralen-inactivated SA11. High-titer homotypic serum neutralizing antibody was induced in all rabbits, and low-level heterotypic neutralizing antibody was induced in a subset of rabbits. The rabbits immunized with the G1 or G3/G1 VLPs in QS-21 were challenged orally with live G3 ALA rotavirus. Protection levels were similar in rabbits immunized with homotypic G3 2/4/6/7-VLPs, heterotypic G1 2/4/6/7-VLPs, or G3/G1 2/4/6/7-VLPs. Therefore, G1 2/4/6/7-VLPs can induce protective immunity against a live heterotypic rotavirus challenge in an adjuvant with potential use in humans. Following challenge, broad serum heterotypic neutralizing antibody responses were detected in rabbits parenterally immunized with G1, G3/G1, or G3 VLPs but not with SA11

  8. Limited naturally occurring escape in broadly neutralizing antibody epitopes in hepatitis C glycoprotein E2 and constrained sequence usage in acute infection

    NARCIS (Netherlands)

    Rodrigo, Chaturaka; Walker, Melanie R.; Leung, Preston; Eltahla, Auda A.; Grebely, Jason; Dore, Gregory J.; Applegate, Tanya; Page, Kimberly; Dwivedi, Sunita; Bruneau, Julie; Morris, Meghan D.; Cox, Andrea L.; Osburn, William; Kim, Arthur Y.; Schinkel, Janke; Shoukry, Naglaa H.; Lauer, Georg M.; Maher, Lisa; Hellard, Margaret; Prins, Maria; Luciani, Fabio; Lloyd, Andrew R.; Bull, Rowena A.

    2017-01-01

    Broadly neutralizing antibodies have been associated with spontaneous clearance of the hepatitis C infection as well as viral persistence by immune escape. Further study of neutralizing antibody epitopes is needed to unravel pathways of resistance to virus neutralization, and to identify conserved

  9. Prediction of HIV-1 sensitivity to broadly neutralizing antibodies shows a trend towards resistance over time.

    Science.gov (United States)

    Hake, Anna; Pfeifer, Nico

    2017-10-01

    Treatment with broadly neutralizing antibodies (bNAbs) has proven effective against HIV-1 infections in humanized mice, non-human primates, and humans. Due to the high mutation rate of HIV-1, resistance testing of the patient's viral strains to the bNAbs is still inevitable. So far, bNAb resistance can only be tested in expensive and time-consuming neutralization experiments. Here, we introduce well-performing computational models that predict the neutralization response of HIV-1 to bNAbs given only the envelope sequence of the virus. Using non-linear support vector machines based on a string kernel, the models learnt even the important binding sites of bNAbs with more complex epitopes, i.e., the CD4 binding site targeting bNAbs, proving thereby the biological relevance of the models. To increase the interpretability of the models, we additionally provide a new kind of motif logo for each query sequence, visualizing those residues of the test sequence that influenced the prediction outcome the most. Moreover, we predicted the neutralization sensitivity of around 34,000 HIV-1 samples from different time points to a broad range of bNAbs, enabling the first analysis of HIV resistance to bNAbs on a global scale. The analysis showed for many of the bNAbs a trend towards antibody resistance over time, which had previously only been discovered for a small non-representative subset of the global HIV-1 population.

  10. 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.

  11. Development and characterization of novel chimeric monoclonal antibodies for broad spectrum neutralization of rabies virus.

    Directory of Open Access Journals (Sweden)

    Pan Kyeom Kim

    Full Text Available Current post-exposure prophylaxis for rabies virus infection has several limitations in terms of supply, cost, safety, and efficacy. Attempts to replace human or equine rabies immune globulins (HRIG or ERIG have been made by several companies and institutes. We developed potent monoclonal antibodies to neutralize a broad spectrum of rabies viruses by screening hybridomas received from the U.S. Centers for Disease Control and Prevention (CDC. Two kinds of chimeric human antibodies (chimeric #7 and #17 were constructed by cloning the variable regions from selected hybridomas and the constant region of a human antibody. Two antibodies were bound to antigenic site III and I/IV, respectively, and were able to neutralize 51 field isolates of rabies virus that were isolated at different times and places such as Asia, Africa, North America, South America, and Australia. These two antibodies neutralize rabies viruses with high efficacy in an in vivo test using Syrian hamster and mouse models and show low risk for adverse immunogenicity.

  12. Development and characterization of novel chimeric monoclonal antibodies for broad spectrum neutralization of rabies virus.

    Science.gov (United States)

    Kim, Pan Kyeom; Keum, Sun Ju; Osinubi, Modupe O V; Franka, Richard; Shin, Ji Young; Park, Sang Tae; Kim, Man Su; Park, Mi Jung; Lee, Soo Young; Carson, William; Greenberg, Lauren; Yu, Pengcheng; Tao, Xiaoyan; Lihua, Wang; Tang, Qing; Liang, Guodong; Shampur, Madhusdana; Rupprecht, Charles E; Chang, Shin Jae

    2017-01-01

    Current post-exposure prophylaxis for rabies virus infection has several limitations in terms of supply, cost, safety, and efficacy. Attempts to replace human or equine rabies immune globulins (HRIG or ERIG) have been made by several companies and institutes. We developed potent monoclonal antibodies to neutralize a broad spectrum of rabies viruses by screening hybridomas received from the U.S. Centers for Disease Control and Prevention (CDC). Two kinds of chimeric human antibodies (chimeric #7 and #17) were constructed by cloning the variable regions from selected hybridomas and the constant region of a human antibody. Two antibodies were bound to antigenic site III and I/IV, respectively, and were able to neutralize 51 field isolates of rabies virus that were isolated at different times and places such as Asia, Africa, North America, South America, and Australia. These two antibodies neutralize rabies viruses with high efficacy in an in vivo test using Syrian hamster and mouse models and show low risk for adverse immunogenicity.

  13. Affinity maturation in an HIV broadly neutralizing B-cell lineage through reorientation of variable domains.

    Science.gov (United States)

    Fera, Daniela; Schmidt, Aaron G; Haynes, Barton F; Gao, Feng; Liao, Hua-Xin; Kepler, Thomas B; Harrison, Stephen C

    2014-07-15

    Rapidly evolving pathogens, such as human immunodeficiency and influenza viruses, escape immune defenses provided by most vaccine-induced antibodies. Proposed strategies to elicit broadly neutralizing antibodies require a deeper understanding of antibody affinity maturation and evolution of the immune response to vaccination or infection. In HIV-infected individuals, viruses and B cells evolve together, creating a virus-antibody "arms race." Analysis of samples from an individual designated CH505 has illustrated the interplay between an antibody lineage, CH103, and autologous viruses at various time points. The CH103 antibodies, relatively broad in their neutralization spectrum, interact with the CD4 binding site of gp120, with a contact dominated by CDRH3. We show by analyzing structures of progenitor and intermediate antibodies and by correlating them with measurements of binding to various gp120s that there was a shift in the relative orientation of the light- and heavy-chain variable domains during evolution of the CH103 lineage. We further show that mutations leading to this conformational shift probably occurred in response to insertions in variable loop 5 (V5) of the HIV envelope. The shift displaced the tips of the light chain away from contact with V5, making room for the inserted residues, which had allowed escape from neutralization by the progenitor antibody. These results, which document the selective mechanism underlying this example of a virus-antibody arms race, illustrate the functional significance of affinity maturation by mutation outside the complementarity determining region surface of the antibody molecule.

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

    DEFF Research Database (Denmark)

    Law, John Lok Man; Chen, Chao; Wong, Jason

    2013-01-01

    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...

  15. Measles Virus Hemagglutinin epitopes immunogenic in natural infection and vaccination are targeted by broad or genotype-specific neutralizing monoclonal antibodies.

    Science.gov (United States)

    Muñoz-Alía, Miguel Angel; Casasnovas, José M; Celma, María Luisa; Carabaña, Juan; Liton, Paloma B; Fernandez-Muñoz, Rafael

    2017-05-15

    Measles virus (MV) remains a leading cause of vaccine-preventable deaths in children. Protection against MV is associated with neutralizing antibodies that preferentially recognize the viral hemagglutinin (MV-H), and to a lesser extent, the fusion protein (MV-F). Although MV is serologically monotypic, 24 genotypes have been identified. Here we report three neutralization epitopes conserved in the more prevalent circulating MV genotypes, two located in the MV-H receptor binding site (RBS) (antigenic site III) and a third in MV-H/MV-F interphase (antigenic site Ia) which are essential for MV multiplication. In contrast, two MV-H neutralization epitopes, showed a genotype-specific neutralization escape due to a single amino acid change, that we mapped in the "noose" antigenic site, or an enhanced neutralization epitope (antigenic site IIa). The monoclonal antibody (mAb) neutralization potency correlated with its binding affinity and was mainly driven by kinetic dissociation rate (k off ). We developed an immunoassay for mAb binding to MV-H in its native hetero-oligomeric structure with MV-F on the surface of a MV productive steady-state persistently infected (p.i.) human cell lines, and a competitive-binding assay with serum from individuals with past infection by different MV genotypes. Binding assays revealed that a broad neutralization epitope, in RBS antigenic site, a genotype specific neutralization epitopes, in noose and IIa sites, were immunogenic in natural infection and vaccination and may elicit long-lasting humoral immunity that might contribute to explain MV immunogenic stability. These results support the design of improved measles vaccines, broad-spectrum prophylactic or therapeutic antibodies and MV-used in oncolytic therapies. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Hepatitis C virus resistance to broadly neutralizing antibodies measured using replication-competent virus and pseudoparticles.

    Science.gov (United States)

    Wasilewski, Lisa N; Ray, Stuart C; Bailey, Justin R

    2016-11-01

    A better understanding of natural variation in neutralization resistance and fitness of diverse hepatitis C virus (HCV) envelope (E1E2) variants will be critical to guide rational development of an HCV vaccine. This work has been hindered by inadequate genetic diversity in viral panels and by a lack of standardization of HCV entry assays. Neutralization assays generally use lentiviral pseudoparticles expressing HCV envelope proteins (HCVpp) or chimeric full-length viruses that are replication competent in cell culture (HCVcc). There have been few systematic comparisons of specific infectivities of E1E2-matched HCVcc and HCVpp, and to our knowledge, neutralization of E1E2-matched HCVpp and HCVcc has never been compared using a diverse panel of human broadly neutralizing monoclonal antibodies (bNAbs) targeting distinct epitopes. Here, we describe an efficient method for introduction of naturally occurring E1E2 genes into a full-length HCV genome, producing replication-competent chimeric HCVcc. We generated diverse panels of E1E2-matched HCVcc and HCVpp and measured the entry-mediating fitness of E1E2 variants using the two systems. We also compared neutralization of E1E2-matched HCVcc and HCVpp by a diverse panel of human bNAbs targeting epitopes across E1E2. We found no correlation between specific infectivities of E1E2-matched HCVcc versus HCVpp, but found a very strong positive correlation between relative neutralization resistance of these same E1E2-matched HCVcc and HCVpp variants. These results suggest that quantitative comparisons of neutralization resistance of E1E2 variants can be made with confidence using either HCVcc or HCVpp, allowing the use of either or both systems to maximize diversity of neutralization panels.

  17. The effect of display movement angle, indicator type and display location on control/display stereotype strength.

    Science.gov (United States)

    Hoffmann, Errol R; Chan, Alan H S

    2017-08-01

    Much research on stereotype strength relating display and control movements for displays moving in the vertical or horizontal directions has been reported. Here we report effects of display movement angle, where the display moves at angles (relative to the vertical) of between 0° and 180°. The experiment used six different controls, four display locations relative to the operator and three types of indicator. Indicator types were included because of the strong effects of the 'scale-side principle' that are variable with display angle. A directional indicator had higher stereotype strength than a neutral indicator, and showed an apparent reversal in control/display stereotype direction beyond an angle of 90°. However, with a neutral indicator this control reversal was not present. Practitioner Summary: The effects of display moving at angles other than the four cardinal directions, types of control, location of display and types of indicator are investigated. Indicator types (directional and neutral) have an effect on stereotype strength and may cause an apparent control reversal with change of display movement angle.

  18. Variable epitope libraries: new vaccine immunogens capable of inducing broad human immunodeficiency virus type 1-neutralizing antibody response.

    Science.gov (United States)

    Charles-Niño, Claudia; Pedroza-Roldan, Cesar; Viveros, Monica; Gevorkian, Goar; Manoutcharian, Karen

    2011-07-18

    The extreme antigenic variability of human immunodeficiency virus (HIV) leads to immune escape of the virus, representing a major challenge in the design of effective vaccine. We have developed a novel concept for immunogen construction based on introduction of massive mutations within the epitopes targeting antigenically variable pathogens and diseases. Previously, we showed that these immunogens carrying large combinatorial libraries of mutated epitope variants, termed as variable epitope libraries (VELs), induce potent, broad and long lasting CD8+IFN-γ+ T-cell response. Moreover, we demonstrated that these T cells recognize more than 50% of heavily mutated variants (5 out of 10 amino acid positions were mutated in each epitope variant) of HIV-1 gp120 V3 loop-derived cytotoxic T lymphocyte epitope (RGPGRAFVTI) in mice. The constructed VELs had complexities of 10000 and 12500 individual members, generated as plasmid DNA or as M13 phage display combinatorial libraries, respectively, and with structural composition RGPGXAXXXX or XGXGXAXVXI, where X is any of 20 natural amino acids. Here, we demonstrated that sera from mice immunized with these VELs are capable of neutralizing 5 out of 10 viral isolates from Tier 2 reference panel of subtype B envelope clones, including HIV-1 isolates which are known to be resistant to neutralization by several potent monoclonal antibodies, described previously. These data indicate the feasibility of the application of immunogens based on VEL concept as an alternative approach for the development of molecular vaccines against antigenically variable pathogens. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. 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.

  20. Neutralizing Activity of Broadly Neutralizing Anti-HIV-1 Antibodies against Clade B Clinical Isolates Produced in Peripheral Blood Mononuclear Cells.

    Science.gov (United States)

    Cohen, Yehuda Z; Lorenzi, Julio C C; Seaman, Michael S; Nogueira, Lilian; Schoofs, Till; Krassnig, Lisa; Butler, Allison; Millard, Katrina; Fitzsimons, Tomas; Daniell, Xiaoju; Dizon, Juan P; Shimeliovich, Irina; Montefiori, David C; Caskey, Marina; Nussenzweig, Michel C

    2018-03-01

    Recently discovered broadly neutralizing antibodies (bNAbs) against HIV-1 demonstrate extensive breadth and potency against diverse HIV-1 strains and represent a promising approach for the treatment and prevention of HIV-1 infection. The breadth and potency of these antibodies have primarily been evaluated by using panels of HIV-1 Env-pseudotyped viruses produced in 293T cells expressing molecularly cloned Env proteins. Here we report on the ability of five bNAbs currently in clinical development to neutralize circulating primary HIV-1 isolates derived from peripheral blood mononuclear cells (PBMCs) and compare the results to those obtained with the pseudovirus panels used to characterize the bNAbs. The five bNAbs demonstrated significantly less breadth and potency against clinical isolates produced in PBMCs than against Env-pseudotyped viruses. The magnitude of this difference in neutralizing activity varied, depending on the antibody epitope. Glycan-targeting antibodies showed differences of only 3- to 4-fold, while antibody 10E8, which targets the membrane-proximal external region, showed a nearly 100-fold decrease in activity between published Env-pseudotyped virus panels and PBMC-derived primary isolates. Utilizing clonal PBMC-derived primary isolates and molecular clones, we determined that the observed discrepancy in bNAb performance is due to the increased sensitivity to neutralization exhibited by 293T-produced Env-pseudotyped viruses. We also found that while full-length molecularly cloned viruses produced in 293T cells exhibit greater sensitivity to neutralization than PBMC-derived viruses do, Env-pseudotyped viruses produced in 293T cells generally exhibit even greater sensitivity to neutralization. As the clinical development of bNAbs progresses, it will be critical to determine the relevance of each of these in vitro neutralization assays to in vivo antibody performance. IMPORTANCE Novel therapeutic and preventive strategies are needed to contain the

  1. Escherichia coli surface display of single-chain antibody VRC01 against HIV-1 infection

    International Nuclear Information System (INIS)

    Wang, Lin-Xu; Mellon, Michael; Bowder, Dane; Quinn, Meghan; Shea, Danielle; Wood, Charles; Xiang, Shi-Hua

    2015-01-01

    Human immunodeficiency virus type 1 (HIV-1) transmission and infection occur mainly via the mucosal surfaces. The commensal bacteria residing in these surfaces can potentially be employed as a vehicle for delivering inhibitors to prevent HIV-1 infection. In this study, we have employed a bacteria-based strategy to display a broadly neutralizing antibody VRC01, which could potentially be used to prevent HIV-1 infection. The VRC01 antibody mimics CD4-binding to gp120 and has broadly neutralization activities against HIV-1. We have designed a construct that can express the fusion peptide of the scFv-VRC01 antibody together with the autotransporter β-barrel domain of IgAP gene from Neisseria gonorrhoeae, which enabled surface display of the antibody molecule. Our results indicate that the scFv-VRC01 antibody molecule was displayed on the surface of the bacteria as demonstrated by flow cytometry and immunofluorescence microscopy. The engineered bacteria can capture HIV-1 particles via surface-binding and inhibit HIV-1 infection in cell culture. - Highlights: • Designed single-chain VRC01 antibody was demonstrated to bind HIV-1 envelope gp120. • Single-chain VRC01 antibody was successfully displayed on the surface of E. coli. • Engineered bacteria can absorb HIV-1 particles and prevent HIV-1 infection in cell culture

  2. Tandem bispecific broadly neutralizing antibody - a novel approach to HIV-1 treatment.

    Science.gov (United States)

    Ferrari, Guido

    2018-04-23

    The last decade has led to a significant advance in our knowledge of HIV-1 latency and immunity. However, we are still not close to finding a cure for HIV-1. Although combination antiretroviral therapy (cART) has led to increased survival, almost close to that of the general population, it is still not curative. In the current issue of the JCI, Wu et al. studied the prophylactic and therapeutic potential of an engineered tandem bispecific broadly neutralizing antibody (bs-bnAb), BiIA-SG. This bnAb's breadth and potency were highly effective in protection and treatment settings, as measured by complete viremia control following direct infusion, as well as elimination of infected cells and delay in viral rebound when delivered with a recombinant vector. These observations underscore the need for the clinical development of BiIA-SG for the prevention of HIV-1.

  3. Adenovirus Particles that Display the Plasmodium falciparum Circumsporozoite Protein NANP Repeat Induce Sporozoite-Neutralizing Antibodies in Mice

    Science.gov (United States)

    Palma, Christopher; Overstreet, Michael G.; Guedon, Jean-Marc; Hoiczyk, Egbert; Ward, Cameron; Karen, Kasey A.; Zavala, Fidel; Ketner, Gary

    2011-01-01

    Adenovirus particles can be engineered to display exogenous peptides on their surfaces by modification of viral capsid proteins, and particles that display pathogen-derived peptides can induce protective immunity. We constructed viable recombinant adenoviruses that display B-cell epitopes from the Plasmodium falciparum circumsporozoite protein (PfCSP) in the major adenovirus capsid protein, hexon. Recombinants induced high-titer antibodies against CSP when injected intraperitoneally into mice. Serum obtained from immunized mice recognized both recombinant PfCSP protein and P. falciparum sporozoites, and neutralized P. falciparum sporozoites in vitro. Replicating adenovirus vaccines have provided economical protection against adenovirus disease for over three decades. The recombinants described here may provide a path to an affordable malaria vaccine in the developing world. PMID:21199707

  4. Rapid High-Level Production of Functional HIV Broadly Neutralizing Monoclonal Antibodies in Transient Plant Expression Systems

    Science.gov (United States)

    Rosenberg, Yvonne; Sack, Markus; Montefiori, David; Forthal, Donald; Mao, Lingjun; -Abanto, Segundo Hernandez; Urban, Lori; Landucci, Gary; Fischer, Rainer; Jiang, Xiaoming

    2013-01-01

    Passive immunotherapy using anti-HIV broadly neutralizing monoclonal antibodies (mAbs) has shown promise as an HIV treatment, reducing mother-to-child-transmission (MTCT) of simian/human immunodeficiency virus (SHIV) in non-human primates and decreasing viral rebound in patients who ceased receiving anti-viral drugs. In addition, a cocktail of potent mAbs may be useful as mucosal microbicides and provide an effective therapy for post-exposure prophylaxis. However, even highly neutralizing HIV mAbs used today may lose their effectiveness if resistance occurs, requiring the rapid production of new or engineered mAbs on an ongoing basis in order to counteract the viral resistance or the spread of a certain HIV-1 clade in a particular region or patient. Plant-based expression systems are fast, inexpensive and scalable and are becoming increasingly popular for the production of proteins and monoclonal antibodies. In the present study, Agrobacterium-mediated transient transfection of plants, utilizing two species of Nicotiana, have been tested to rapidly produce high levels of an HIV 89.6PΔ140env and several well-studied anti-HIV neutralizing monoclonal antibodies (b12, 2G12, 2F5, 4E10, m43, VRC01) or a single chain antibody construct (m9), for evaluation in cell-based viral inhibition assays. The protein-A purified plant-derived antibodies were intact, efficiently bound HIV envelope, and were equivalent to, or in one case better than, their counterparts produced in mammalian CHO or HEK-293 cells in both neutralization and antibody dependent viral inhibition assays. These data indicate that transient plant-based transient expression systems are very adaptable and could rapidly generate high levels of newly identified functional recombinant HIV neutralizing antibodies when required. In addition, they warrant detailed cost-benefit analysis of prolonged incubation in plants to further increase mAb production. PMID:23533588

  5. Rapid high-level production of functional HIV broadly neutralizing monoclonal antibodies in transient plant expression systems.

    Directory of Open Access Journals (Sweden)

    Yvonne Rosenberg

    Full Text Available Passive immunotherapy using anti-HIV broadly neutralizing monoclonal antibodies (mAbs has shown promise as an HIV treatment, reducing mother-to-child-transmission (MTCT of simian/human immunodeficiency virus (SHIV in non-human primates and decreasing viral rebound in patients who ceased receiving anti-viral drugs. In addition, a cocktail of potent mAbs may be useful as mucosal microbicides and provide an effective therapy for post-exposure prophylaxis. However, even highly neutralizing HIV mAbs used today may lose their effectiveness if resistance occurs, requiring the rapid production of new or engineered mAbs on an ongoing basis in order to counteract the viral resistance or the spread of a certain HIV-1 clade in a particular region or patient. Plant-based expression systems are fast, inexpensive and scalable and are becoming increasingly popular for the production of proteins and monoclonal antibodies. In the present study, Agrobacterium-mediated transient transfection of plants, utilizing two species of Nicotiana, have been tested to rapidly produce high levels of an HIV 89.6PΔ140env and several well-studied anti-HIV neutralizing monoclonal antibodies (b12, 2G12, 2F5, 4E10, m43, VRC01 or a single chain antibody construct (m9, for evaluation in cell-based viral inhibition assays. The protein-A purified plant-derived antibodies were intact, efficiently bound HIV envelope, and were equivalent to, or in one case better than, their counterparts produced in mammalian CHO or HEK-293 cells in both neutralization and antibody dependent viral inhibition assays. These data indicate that transient plant-based transient expression systems are very adaptable and could rapidly generate high levels of newly identified functional recombinant HIV neutralizing antibodies when required. In addition, they warrant detailed cost-benefit analysis of prolonged incubation in plants to further increase mAb production.

  6. Broad antibody mediated cross-neutralization and preclinical immunogenicity of new codon-optimized HIV-1 clade CRF02_AG and G primary isolates.

    Directory of Open Access Journals (Sweden)

    Simon M Agwale

    Full Text Available Creation of an effective vaccine for HIV has been an elusive goal of the scientific community for almost 30 years. Neutralizing antibodies are assumed to be pivotal to the success of a prophylactic vaccine but previous attempts to make an immunogen capable of generating neutralizing antibodies to primary "street strain" isolates have resulted in responses of very limited breadth and potency. The objective of the study was to determine the breadth and strength of neutralizing antibodies against autologous and heterologous primary isolates in a cohort of HIV-1 infected Nigerians and to characterize envelopes from subjects with particularly broad or strong immune responses for possible use as vaccine candidates in regions predominated by HIV-1 CRF02_AG and G subtypes. Envelope vectors from a panel of primary Nigerian isolates were constructed and tested with plasma/sera from the same cohort using the PhenoSense HIV neutralizing antibody assay (Monogram Biosciences Inc, USA to assess the breadth and potency of neutralizing antibodies. The immediate goal of this study was realized by the recognition of three broadly cross-neutralizing sera: (NG2-clade CRF02_AG, NG3-clade CRF02_AG and NG9- clade G. Based on these findings, envelope gp140 sequences from NG2 and NG9, complemented with a gag sequence (Clade G and consensus tat (CRF02_AG and G antigens have been codon-optimized, synthesized, cloned and evaluated in BALB/c mice. The intramuscular administration of these plasmid DNA constructs, followed by two booster DNA immunizations, induced substantial specific humoral response against all constructs and strong cellular responses against the gag and tat constructs. These preclinical findings provide a framework for the design of candidate vaccine for use in regions where the HIV-1 epidemic is driven by clades CRF02_AG and G.

  7. Broad antibody mediated cross-neutralization and preclinical immunogenicity of new codon-optimized HIV-1 clade CRF02_AG and G primary isolates.

    Science.gov (United States)

    Agwale, Simon M; Forbi, Joseph C; Notka, Frank; Wrin, Terri; Wild, Jens; Wagner, Ralf; Wolf, Hans

    2011-01-01

    Creation of an effective vaccine for HIV has been an elusive goal of the scientific community for almost 30 years. Neutralizing antibodies are assumed to be pivotal to the success of a prophylactic vaccine but previous attempts to make an immunogen capable of generating neutralizing antibodies to primary "street strain" isolates have resulted in responses of very limited breadth and potency. The objective of the study was to determine the breadth and strength of neutralizing antibodies against autologous and heterologous primary isolates in a cohort of HIV-1 infected Nigerians and to characterize envelopes from subjects with particularly broad or strong immune responses for possible use as vaccine candidates in regions predominated by HIV-1 CRF02_AG and G subtypes. Envelope vectors from a panel of primary Nigerian isolates were constructed and tested with plasma/sera from the same cohort using the PhenoSense HIV neutralizing antibody assay (Monogram Biosciences Inc, USA) to assess the breadth and potency of neutralizing antibodies. The immediate goal of this study was realized by the recognition of three broadly cross-neutralizing sera: (NG2-clade CRF02_AG, NG3-clade CRF02_AG and NG9- clade G). Based on these findings, envelope gp140 sequences from NG2 and NG9, complemented with a gag sequence (Clade G) and consensus tat (CRF02_AG and G) antigens have been codon-optimized, synthesized, cloned and evaluated in BALB/c mice. The intramuscular administration of these plasmid DNA constructs, followed by two booster DNA immunizations, induced substantial specific humoral response against all constructs and strong cellular responses against the gag and tat constructs. These preclinical findings provide a framework for the design of candidate vaccine for use in regions where the HIV-1 epidemic is driven by clades CRF02_AG and G.

  8. Llama Antibody Fragments Recognizing Various Epitopes of the CD4bs Neutralize a Broad Range of HIV-1 Subtypes A, B and C

    Science.gov (United States)

    Aasa-Chapman, Marlèn; Gorlani, Andrea; Forsman Quigley, Anna; Hulsik, David Lutje; Chen, Lei; Weiss, Robin; de Haard, Hans; Verrips, Theo

    2012-01-01

    Many of the neutralising antibodies, isolated to date, display limited activities against the globally most prevalent HIV-1 subtypes A and C. Therefore, those subtypes are considered to be an important target for antibody-based therapy. Variable domains of llama heavy chain antibodies (VHH) have some superior properties compared with classical antibodies. Therefore we describe the application of trimeric forms of envelope proteins (Env), derived from HIV-1 of subtype A and B/C, for a prolonged immunization of two llamas. A panel of VHH, which interfere with CD4 binding to HIV-1 Env were selected with use of panning. The results of binding and competition assays to various Env, including a variant with a stabilized CD4-binding state (gp120Ds2), cross-competition experiments, maturation analysis and neutralisation assays, enabled us to classify the selected VHH into three groups. The VHH of group I were efficient mainly against viruses of subtype A, C and B′/C. The VHH of group II resemble the broadly neutralising antibody (bnmAb) b12, neutralizing mainly subtype B and C viruses, however some had a broader neutralisation profile. A representative of the third group, 2E7, had an even higher neutralization breadth, neutralizing 21 out of the 26 tested strains belonging to the A, A/G, B, B/C and C subtypes. To evaluate the contribution of certain amino acids to the potency of the VHH a small set of the mutants were constructed. Surprisingly this yielded one mutant with slightly improved neutralisation potency against 92UG37.A9 (subtype A) and 96ZM651.02 (subtype C). These findings and the well-known stability of VHH indicate the potential application of these VHH as anti-HIV-1 microbicides. PMID:22438910

  9. HIV-specific Fc effector function early in infection predicts the development of broadly neutralizing antibodies.

    Science.gov (United States)

    Richardson, Simone I; Chung, Amy W; Natarajan, Harini; Mabvakure, Batsirai; Mkhize, Nonhlanhla N; Garrett, Nigel; Abdool Karim, Salim; Moore, Penny L; Ackerman, Margaret E; Alter, Galit; Morris, Lynn

    2018-04-01

    While the induction of broadly neutralizing antibodies (bNAbs) is a major goal of HIV vaccination strategies, there is mounting evidence to suggest that antibodies with Fc effector function also contribute to protection against HIV infection. Here we investigated Fc effector functionality of HIV-specific IgG plasma antibodies over 3 years of infection in 23 individuals, 13 of whom developed bNAbs. Antibody-dependent cellular phagocytosis (ADCP), complement deposition (ADCD), cellular cytotoxicity (ADCC) and cellular trogocytosis (ADCT) were detected in almost all individuals with levels of activity increasing over time. At 6 months post-infection, individuals with bNAbs had significantly higher levels of ADCD and ADCT that correlated with antibody binding to C1q and FcγRIIa respectively. In addition, antibodies from individuals with bNAbs showed more IgG subclass diversity to multiple HIV antigens which also correlated with Fc polyfunctionality. Germinal center activity represented by CXCL13 levels and expression of activation-induced cytidine deaminase (AID) was found to be associated with neutralization breadth, Fc polyfunctionality and IgG subclass diversity. Overall, multivariate analysis by random forest classification was able to group bNAb individuals with 85% sensitivity and 80% specificity based on the properties of their antibody Fc early in HIV infection. Thus, the Fc effector function profile predicted the development of neutralization breadth in this cohort, suggesting that intrinsic immune factors within the germinal center provide a mechanistic link between the Fc and Fab of HIV-specific antibodies.

  10. 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

  11. HIV-specific Fc effector function early in infection predicts the development of broadly neutralizing antibodies.

    Directory of Open Access Journals (Sweden)

    Simone I Richardson

    2018-04-01

    Full Text Available While the induction of broadly neutralizing antibodies (bNAbs is a major goal of HIV vaccination strategies, there is mounting evidence to suggest that antibodies with Fc effector function also contribute to protection against HIV infection. Here we investigated Fc effector functionality of HIV-specific IgG plasma antibodies over 3 years of infection in 23 individuals, 13 of whom developed bNAbs. Antibody-dependent cellular phagocytosis (ADCP, complement deposition (ADCD, cellular cytotoxicity (ADCC and cellular trogocytosis (ADCT were detected in almost all individuals with levels of activity increasing over time. At 6 months post-infection, individuals with bNAbs had significantly higher levels of ADCD and ADCT that correlated with antibody binding to C1q and FcγRIIa respectively. In addition, antibodies from individuals with bNAbs showed more IgG subclass diversity to multiple HIV antigens which also correlated with Fc polyfunctionality. Germinal center activity represented by CXCL13 levels and expression of activation-induced cytidine deaminase (AID was found to be associated with neutralization breadth, Fc polyfunctionality and IgG subclass diversity. Overall, multivariate analysis by random forest classification was able to group bNAb individuals with 85% sensitivity and 80% specificity based on the properties of their antibody Fc early in HIV infection. Thus, the Fc effector function profile predicted the development of neutralization breadth in this cohort, suggesting that intrinsic immune factors within the germinal center provide a mechanistic link between the Fc and Fab of HIV-specific antibodies.

  12. Structural Basis for Escape of Human Astrovirus from Antibody Neutralization: Broad Implications for Rational Vaccine Design

    Energy Technology Data Exchange (ETDEWEB)

    Bogdanoff, Walter A.; Perez, Edmundo I.; López, Tomás; Arias, Carlos F.; DuBois, Rebecca M. (UNAM-Mexico); (UCSC)

    2017-10-25

    ABSTRACT

    Human astroviruses are recognized as a leading cause of viral diarrhea worldwide in children, immunocompromised patients, and the elderly. There are currently no vaccines available to prevent astrovirus infection; however, antibodies developed by healthy individuals during previous infection correlate with protection from reinfection, suggesting that an effective vaccine could be developed. In this study, we investigated the molecular mechanism by which several strains of human astrovirus serotype 2 (HAstV-2) are resistant to the potent HAstV-2-neutralizing monoclonal antibody PL-2 (MAb PL-2). Sequencing of the HAstV-2 capsid genes reveals mutations in the PL-2 epitope within the capsid's spike domain. To understand the molecular basis for resistance from MAb PL-2 neutralization, we determined the 1.35-Å-resolution crystal structure of the capsid spike from one of these HAstV-2 strains. Our structure reveals a dramatic conformational change in a loop within the PL-2 epitope due to a serine-to-proline mutation, locking the loop in a conformation that sterically blocks binding and neutralization by MAb PL-2. We show that mutation to serine permits loop flexibility and recovers MAb PL-2 binding. Importantly, we find that HAstV-2 capsid spike containing a serine in this loop is immunogenic and elicits antibodies that neutralize all HAstV-2 strains. Taken together, our results have broad implications for rational selection of vaccine strains that do not contain prolines in antigenic loops, so as to elicit antibodies against diverse loop conformations.

    IMPORTANCEHuman astroviruses (HAstVs) infect nearly every person in the world during childhood and cause diarrhea, vomiting, and fever. In this study, we investigated how several strains of HAstV are resistant to a virus-neutralizing monoclonal antibody. We determined the crystal structure of the capsid protein spike domain from one of these HAstV strains and found that

  13. Broadly neutralizing antibodies for treatment and prevention of HIV-1 infection.

    Science.gov (United States)

    Cohen, Yehuda Z; Caskey, Marina

    2018-04-24

    Several anti-HIV-1 broadly neutralizing antibodies (bNAbs) with exceptional breadth and potency that target different HIV-1 envelope epitopes have been identified. bNAbs are an attractive new strategy for HIV-1 prevention and therapy, and potentially, for long-term remission or cure. Here, we discuss findings from early clinical studies that have evaluated these novel bNAbs. Phase 1 studies of bNAbs targeting two distinct HIV-1 envelope epitopes have demonstrated their favorable safety and pharmacokinetic profile. Single bNAb infusions led to significant, but transient, decline in viremia with selection of escape variants. A single bNAb also delayed viral rebound in ART-treated participants who discontinued ART. Importantly, in-vivo efficacy was related to antibody potency and to the level of preexisting resistance. Studies in animal models showed that bNAbs can clear HIV-infected cells and modulate host immune responses. These findings suggest that bNAbs may target the latent HIV reservoir in humans and could contribute to long-term remission of HIV-1 infection. bNAbs may offer advantages over traditional ART for both the prevention and treatment of HIV-1 infection. In addition, bNAbs may target the latent viral reservoir. bNAb combinations and bNAbs engineered for prolonged half-life and increased potency are currently undergoing clinical evaluation.

  14. Cleavage-Independent HIV-1 Trimers From CHO Cell Lines Elicit Robust Autologous Tier 2 Neutralizing Antibodies

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    Shridhar Bale

    2018-05-01

    Full Text Available Native flexibly linked (NFL HIV-1 envelope glycoprotein (Env trimers are cleavage-independent and display a native-like, well-folded conformation that preferentially displays broadly neutralizing determinants. The NFL platform simplifies large-scale production of Env by eliminating the need to co-transfect the precursor-cleaving protease, furin that is required by the cleavage-dependent SOSIP trimers. Here, we report the development of a CHO-M cell line that expressed BG505 NFL trimers at a high level of homogeneity and yields of ~1.8 g/l. BG505 NFL trimers purified by single-step lectin-affinity chromatography displayed a native-like closed structure, efficient recognition by trimer-preferring bNAbs, no recognition by non-neutralizing CD4 binding site-directed and V3-directed antibodies, long-term stability, and proper N-glycan processing. Following negative-selection, formulation in ISCOMATRIX adjuvant and inoculation into rabbits, the trimers rapidly elicited potent autologous tier 2 neutralizing antibodies. These antibodies targeted the N-glycan “hole” naturally present on the BG505 Env proximal to residues at positions 230, 241, and 289. The BG505 NFL trimers that did not expose V3 in vitro, elicited low-to-no tier 1 virus neutralization in vivo, indicating that they remained intact during the immunization process, not exposing V3. In addition, BG505 NFL and BG505 SOSIP trimers expressed from 293F cells, when formulated in Adjuplex adjuvant, elicited equivalent BG505 tier 2 autologous neutralizing titers. These titers were lower in potency when compared to the titers elicited by CHO-M cell derived trimers. In addition, increased neutralization of tier 1 viruses was detected. Taken together, these data indicate that both adjuvant and cell-type expression can affect the elicitation of tier 2 and tier 1 neutralizing responses in vivo.

  15. Structures of phlebovirus glycoprotein Gn and identification of a neutralizing antibody epitope.

    Science.gov (United States)

    Wu, Yan; Zhu, Yaohua; Gao, Feng; Jiao, Yongjun; Oladejo, Babayemi O; Chai, Yan; Bi, Yuhai; Lu, Shan; Dong, Mengqiu; Zhang, Chang; Huang, Guangmei; Wong, Gary; Li, Na; Zhang, Yanfang; Li, Yan; Feng, Wen-Hai; Shi, Yi; Liang, Mifang; Zhang, Rongguang; Qi, Jianxun; Gao, George F

    2017-09-05

    Severe fever with thrombocytopenia syndrome virus (SFTSV) and Rift Valley fever virus (RVFV) are two arthropod-borne phleboviruses in the Bunyaviridae family, which cause severe illness in humans and animals. Glycoprotein N (Gn) is one of the envelope proteins on the virus surface and is a major antigenic component. Despite its importance for virus entry and fusion, the molecular features of the phleboviruse Gn were unknown. Here, we present the crystal structures of the Gn head domain from both SFTSV and RVFV, which display a similar compact triangular shape overall, while the three subdomains (domains I, II, and III) making up the Gn head display different arrangements. Ten cysteines in the Gn stem region are conserved among phleboviruses, four of which are responsible for Gn dimerization, as revealed in this study, and they are highly conserved for all members in Bunyaviridae Therefore, we propose an anchoring mode on the viral surface. The complex structure of the SFTSV Gn head and human neutralizing antibody MAb 4-5 reveals that helices α6 in subdomain III is the key component for neutralization. Importantly, the structure indicates that domain III is an ideal region recognized by specific neutralizing antibodies, while domain II is probably recognized by broadly neutralizing antibodies. Collectively, Gn is a desirable vaccine target, and our data provide a molecular basis for the rational design of vaccines against the diseases caused by phleboviruses and a model for bunyavirus Gn embedding on the viral surface.

  16. High color fidelity thin film multilayer systems for head-up display use

    Science.gov (United States)

    Tsou, Yi-Jen D.; Ho, Fang C.

    1996-09-01

    Head-up display is gaining increasing access in automotive vehicles for indication and position/navigation purposes. An optical combiner, which allows the driver to receive image information from outside and inside of the automobile, is the essential part of this display device. Two multilayer thin film combiner coating systems with distinctive polarization selectivity and broad band spectral neutrality are discussed. One of the coating systems was designed to be located at the lower portion of the windshield. The coating reduced the exterior glare by approximately 45% and provided about 70% average see-through transmittance in addition to the interior information display. The other coating system was designed to be integrated with the sunshield located at the upper portion of the windshield. The coating reflected the interior information display while reducing direct sunlight penetration to 25%. Color fidelity for both interior and exterior images were maintained in both systems. This facilitated the display of full-color maps. Both coating systems were absorptionless and environmentally durable. Designs, fabrication, and performance of these coating systems are addressed.

  17. 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.

  18. Precisely Molded Nanoparticle Displaying DENV-E Proteins Induces Robust Serotype-Specific Neutralizing Antibody Responses.

    Directory of Open Access Journals (Sweden)

    Stefan W Metz

    2016-10-01

    Full Text Available Dengue virus (DENV is the causative agent of dengue fever and dengue hemorrhagic fever. The virus is endemic in over 120 countries, causing over 350 million infections per year. Dengue vaccine development is challenging because of the need to induce simultaneous protection against four antigenically distinct DENV serotypes and evidence that, under some conditions, vaccination can enhance disease due to specific immunity to the virus. While several live-attenuated tetravalent dengue virus vaccines display partial efficacy, it has been challenging to induce balanced protective immunity to all 4 serotypes. Instead of using whole-virus formulations, we are exploring the potentials for a particulate subunit vaccine, based on DENV E-protein displayed on nanoparticles that have been precisely molded using Particle Replication in Non-wetting Template (PRINT technology. Here we describe immunization studies with a DENV2-nanoparticle vaccine candidate. The ectodomain of DENV2-E protein was expressed as a secreted recombinant protein (sRecE, purified and adsorbed to poly (lactic-co-glycolic acid (PLGA nanoparticles of different sizes and shape. We show that PRINT nanoparticle adsorbed sRecE without any adjuvant induces higher IgG titers and a more potent DENV2-specific neutralizing antibody response compared to the soluble sRecE protein alone. Antigen trafficking indicate that PRINT nanoparticle display of sRecE prolongs the bio-availability of the antigen in the draining lymph nodes by creating an antigen depot. Our results demonstrate that PRINT nanoparticles are a promising platform for delivering subunit vaccines against flaviviruses such as dengue and Zika.

  19. 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.

  20. Highly-reliable operation of 638-nm broad stripe laser diode with high wall-plug efficiency for display applications

    Science.gov (United States)

    Yagi, Tetsuya; Shimada, Naoyuki; Nishida, Takehiro; Mitsuyama, Hiroshi; Miyashita, Motoharu

    2013-03-01

    Laser based displays, as pico to cinema laser projectors have gathered much attention because of wide gamut, low power consumption, and so on. Laser light sources for the displays are operated mainly in CW, and heat management is one of the big issues. Therefore, highly efficient operation is necessitated. Also the light sources for the displays are requested to be highly reliable. 638 nm broad stripe laser diode (LD) was newly developed for high efficiency and highly reliable operation. An AlGaInP/GaAs red LD suffers from low wall plug efficiency (WPE) due to electron overflow from an active layer to a p-cladding layer. Large optical confinement factor (Γ) design with AlInP cladding layers is adopted to improve the WPE. The design has a disadvantage for reliable operation because the large Γ causes high optical density and brings a catastrophic optical degradation (COD) at a front facet. To overcome the disadvantage, a window-mirror structure is also adopted in the LD. The LD shows WPE of 35% at 25°C, highest record in the world, and highly stable operation at 35°C, 550 mW up to 8,000 hours without any catastrophic optical degradation.

  1. Extra-epitopic hepatitis C virus polymorphisms confer resistance to broadly neutralizing antibodies by modulating binding to scavenger receptor B1.

    Science.gov (United States)

    El-Diwany, Ramy; Cohen, Valerie J; Mankowski, Madeleine C; Wasilewski, Lisa N; Brady, Jillian K; Snider, Anna E; Osburn, William O; Murrell, Ben; Ray, Stuart C; Bailey, Justin R

    2017-02-01

    Broadly-neutralizing monoclonal antibodies (bNAbs) may guide vaccine development for highly variable viruses including hepatitis C virus (HCV), since they target conserved viral epitopes that could serve as vaccine antigens. However, HCV resistance to bNAbs could reduce the efficacy of a vaccine. HC33.4 and AR4A are two of the most potent anti-HCV human bNAbs characterized to date, binding to highly conserved epitopes near the amino- and carboxy-terminus of HCV envelope (E2) protein, respectively. Given their distinct epitopes, it was surprising that these bNAbs showed similar neutralization profiles across a panel of natural HCV isolates, suggesting that some viral polymorphisms may confer resistance to both bNAbs. To investigate this resistance, we developed a large, diverse panel of natural HCV envelope variants and a novel computational method to identify bNAb resistance polymorphisms in envelope proteins (E1 and E2). By measuring neutralization of a panel of HCV pseudoparticles by 10 μg/mL of each bNAb, we identified E1E2 variants with resistance to one or both bNAbs, despite 100% conservation of the AR4A binding epitope across the panel. We discovered polymorphisms outside of either binding epitope that modulate resistance to both bNAbs by altering E2 binding to the HCV co-receptor, scavenger receptor B1 (SR-B1). This study is focused on a mode of neutralization escape not addressed by conventional analysis of epitope conservation, highlighting the contribution of extra-epitopic polymorphisms to bNAb resistance and presenting a novel mechanism by which HCV might persist even in the face of an antibody response targeting multiple conserved epitopes.

  2. Liquid Crystal Airborne Display

    Science.gov (United States)

    1977-08-01

    Cum.nings, J. P., et al., Properties and Limitations oe Liquid Crystals for Aircraft Displays, Honeywell Corporate Researc ."I Center, Final Report HR-72...basic module could be used to build displays for both the commercial and military! 157- marhecs, and so would establi sh a broad and sizable market ... market for the display becomes a reality; therein lies, f TABLE 16 THE COURSE OF FUTURE DISPLAY DEVELOPMENT Today 1976-77 1980 1985 Display Size 2" 1 3.2

  3. 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.

  4. Feline Immunodeficiency Virus (FIV Neutralization: A Review

    Directory of Open Access Journals (Sweden)

    Margaret J. Hosie

    2011-10-01

    Full Text Available One of the major obstacles that must be overcome in the design of effective lentiviral vaccines is the ability of lentiviruses to evolve in order to escape from neutralizing antibodies. The primary target for neutralizing antibodies is the highly variable viral envelope glycoprotein (Env, a glycoprotein that is essential for viral entry and comprises both variable and conserved regions. As a result of the complex trimeric nature of Env, there is steric hindrance of conserved epitopes required for receptor binding so that these are not accessible to antibodies. Instead, the humoral response is targeted towards decoy immunodominant epitopes on variable domains such as the third hypervariable loop (V3 of Env. For feline immunodeficiency virus (FIV, as well as the related human immunodeficiency virus-1 (HIV-1, little is known about the factors that lead to the development of broadly neutralizing antibodies. In cats infected with FIV and patients infected with HIV-1, only rarely are plasma samples found that contain antibodies capable of neutralizing isolates from other clades. In this review we examine the neutralizing response to FIV, comparing and contrasting with the response to HIV. We ask whether broadly neutralizing antibodies are induced by FIV infection and discuss the comparative value of studies of neutralizing antibodies in FIV infection for the development of more effective vaccine strategies against lentiviral infections in general, including HIV-1.

  5. Molecular clock on a neutral network.

    Science.gov (United States)

    Raval, Alpan

    2007-09-28

    The number of fixed mutations accumulated in an evolving population often displays a variance that is significantly larger than the mean (the overdispersed molecular clock). By examining a generic evolutionary process on a neutral network of high-fitness genotypes, we establish a formalism for computing all cumulants of the full probability distribution of accumulated mutations in terms of graph properties of the neutral network, and use the formalism to prove overdispersion of the molecular clock. We further show that significant overdispersion arises naturally in evolution when the neutral network is highly sparse, exhibits large global fluctuations in neutrality, and small local fluctuations in neutrality. The results are also relevant for elucidating aspects of neutral network topology from empirical measurements of the substitution process.

  6. Antibody neutralization of retargeted measles viruses

    Science.gov (United States)

    Lech, Patrycja J.; Pappoe, Roland; Nakamura, Takafumi; Tobin, Gregory J.; Nara, Peter L.; Russell, Stephen J.

    2014-01-01

    The measles virus (MV) vaccine lineage is a promising oncolytic but prior exposure to the measles vaccine or wild-type MV strains limits treatment utility due to the presence of anti-measles antibodies. MV entry can be redirected by displaying a polypeptide ligand on the Hemagglutinin (H) C-terminus. We hypothesized that retargeted MV would escape neutralization by monoclonal antibodies (mAbs) recognizing the H receptor-binding surface and be less susceptible to neutralization by human antisera. Using chimeric H proteins, with and without mutations that ablate MV receptor binding, we show that retargeted MVs escape mAbs that target the H receptor-binding surface by virtue of mutations that ablate infection via SLAM and CD46. However, C-terminally displayed domains do not mediate virus entry in the presence of human antibodies that bind to the underlying H domain. In conclusion, utility of retargeted oncolytic measles viruses does not extend to evasion of human serum neutralization. PMID:24725950

  7. Evidence for a Broad Autism Phenotype

    NARCIS (Netherlands)

    K. de Groot (Kristel); J.W. van Strien (Jan)

    2017-01-01

    textabstractThe broad autism phenotype implies the existence of a continuum ranging from individuals displaying almost no autistic traits to severely impaired diagnosed individuals. Recent studies have linked this variation in autistic traits to several domains of functioning. However, studies

  8. Walking my way? Walker gender and display format Confounds the perception of specific emotions.

    Science.gov (United States)

    Halovic, Shaun; Kroos, Christian

    2018-02-01

    Previous evidence has shown that males and females display different gait kinematics which may influence the perception of emotions displayed through the same walking gait. We therefore investigated the influence of walker gender on the perception of happiness, sadness, anger and fear displayed through walking movements. Full-light (FL), point-light (PL) and synthetically modelled point-light walkers (SW) of both genders were shown to perceivers over three experiments. Additionally, gender ambiguous synthetic walkers were shown to control for the influence of form, gender stereotypes and idiosyncratic gait movements on emotional gait perception. Each emotion was identified above chance level for both walker genders and in all display conditions though significantly less in PL and SW than in FL. The gender of the walker did not influence the pattern of identifications in FL walkers (Fear > Sad > Happy > Anger > Neutral), but did influence the identification patterns in PL (Female: [Happy = Sad = Fear = Anger] > Neutral; Male: Fear = Sad = [Happy > Anger] > Neutral) and SWs (Female: Happy = Sad = Anger = Fear = Neutral; Male: [Happy = Sad = Anger] > [Fear = Neutral]; Ambiguous: [[Happy = Sad = Anger] > Fear] = Neutral). The gender of the walker and format in which they are displayed influenced the perception of different basic emotions. The constructed SW stimuli also displayed happiness, sadness and anger with equivalent intensity in female, male and gender ambiguous walkers thus untangling the perception-expression entanglement that has plagued previous emotion perception research. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  9. 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

    2014-01-01

    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

  10. 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.

  11. A glycoconjugate antigen based on the recognition motif of a broadly neutralizing human immunodeficiency virus antibody, 2G12, is immunogenic but elicits antibodies unable to bind to the self glycans of gp120

    DEFF Research Database (Denmark)

    Astronomo, Rena D; Lee, Hing-Ken; Scanlan, Christopher N

    2008-01-01

    The glycan shield of human immunodeficiency virus type 1 (HIV-1) gp120 contributes to viral evasion from humoral immune responses. However, the shield is recognized by the HIV-1 broadly neutralizing antibody (Ab), 2G12, at a relatively conserved cluster of oligomannose glycans. The discovery of 2G......12 raises the possibility that a carbohydrate immunogen may be developed that could elicit 2G12-like neutralizing Abs and contribute to an AIDS vaccine. We have previously dissected the fine specificity of 2G12 and reported that the synthetic tetramannoside (Man(4)) that corresponds to the D1 arm...

  12. Quantitative analyses reveal distinct sensitivities of the capture of HIV-1 primary viruses and pseudoviruses to broadly neutralizing antibodies.

    Science.gov (United States)

    Kim, Jiae; Jobe, Ousman; Peachman, Kristina K; Michael, Nelson L; Robb, Merlin L; Rao, Mangala; Rao, Venigalla B

    2017-08-01

    Development of vaccines capable of eliciting broadly neutralizing antibodies (bNAbs) is a key goal to controlling the global AIDS epidemic. To be effective, bNAbs must block the capture of HIV-1 to prevent viral acquisition and establishment of reservoirs. However, the role of bNAbs, particularly during initial exposure of primary viruses to host cells, has not been fully examined. Using a sensitive, quantitative, and high-throughput qRT-PCR assay, we found that primary viruses were captured by host cells and converted into a trypsin-resistant form in less than five minutes. We discovered, unexpectedly, that bNAbs did not block primary virus capture, although they inhibited the capture of pseudoviruses/IMCs and production of progeny viruses at 48h. Further, viruses escaped bNAb inhibition unless the bNAbs were present in the initial minutes of exposure of virus to host cells. These findings will have important implications for HIV-1 vaccine design and determination of vaccine efficacy. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Doppler-shifted neutral beam line shape and beam transmission

    International Nuclear Information System (INIS)

    Kamperschroer, J.H.; Grisham, L.R.; Kokatnur, N.; Lagin, L.J.; Newman, R.A.; O'Connor, T.E.; Stevenson, T.N.; von Halle, A.

    1994-04-01

    Analysis of Doppler-shifted Balmer-α line emission from the TFTR neutral beam injection systems has revealed that the line shape is well approximated by the sum of two Gaussians, or, alternatively, by a Lorentzian. For the sum of two Gaussians, the broad portion of the distribution contains 40% of the beam power and has a divergence five times that of the narrow part. Assuming a narrow 1/e- divergence of 1.3 degrees (based on fits to the beam shape on the calorimeter), the broad part has a divergence of 6.9 degrees. The entire line shape is also well approximated by a Lorentzian with a half-maximum divergence of 0.9 degrees. Up to now, fusion neutral beam modelers have assumed a single Gaussian velocity distribution, at the extraction plane, in each direction perpendicular to beam propagation. This predicts a beam transmission efficiency from the ion source to the calorimeter of 97%. Waterflow calorimetry data, however, yield a transmission efficiency of ∼75%, a value in rough agreement with predictions of the Gaussian or Lorentzian models presented here. The broad wing of the two Gaussian distribution also accurately predicts the loss in the neutralizer. An average angle of incidence for beam loss at the exit of the neutralizer is 2.2 degrees, rather than the 4.95 degrees subtended by the center of the ion source. This average angle of incidence, which is used in computing power densities on collimators, is shown to be a function of beam divergence

  14. Isolation and characterization of broadly neutralizing human monoclonal antibodies to the e1 glycoprotein of hepatitis C virus

    DEFF Research Database (Denmark)

    Meunier, Jean-Christophe; Russell, Rodney S.; Goossens, Vera

    2008-01-01

    The relative importance of humoral and cellular immunity in the prevention or clearance of hepatitis C virus (HCV) infection is poorly understood. However, there is considerable evidence that neutralizing antibodies are involved in disease control. Here we describe the detailed analysis of human...... monoclonal antibodies (MAbs) directed against HCV glycoprotein E1, which may have the potential to control HCV infection. We have identified two MAbs that can strongly neutralize HCV-pseudotyped particles (HCVpp) bearing the envelope glycoproteins of genotypes 1a, 1b, 4a, 5a, and 6a and less strongly...... neutralize HCVpp bearing the envelope glycoproteins of genotype 2a. Genotype 3a was not neutralized. The epitopes for both MAbs were mapped to the region encompassing amino acids 313 to 327. In addition, robust neutralization was also observed against cell culture-adapted viruses of genotypes 1a and 2a...

  15. Multimeric scaffolds displaying the HIV-1 envelope MPER induce MPER-specific antibodies and cross-neutralizing antibodies when co-immunized with gp160 DNA.

    Directory of Open Access Journals (Sweden)

    Shelly J Krebs

    Full Text Available Developing a vaccine that overcomes the diversity of HIV-1 is likely to require a strategy that directs antibody (Ab responses toward conserved regions of the viral Envelope (Env. However, the generation of neutralizing Abs (NAbs targeting these regions through vaccination has proven to be difficult. One conserved region of particular interest is the membrane proximal external region (MPER of Env located within the gp41 ectodomain. In order to direct the immune response to this region, the MPER and gp41 ectodomain were expressed separately as N-terminal fusions to the E2 protein of Geobacillus stearothermophilus. The E2 protein acts as a scaffold by self-assembling into 60-mer particles, displaying up to 60 copies of the fused target on the surface. Rabbits were immunized with E2 particles displaying MPER and/or the gp41 ectodomain in conjunction with DNA encoding full-length gp160. Only vaccines including E2 particles displaying MPER elicited MPER-specific Ab responses. NAbs were elicited after two immunizations that largely targeted the V3 loop. To overcome V3 immunodominance in the DNA component, E2 particles displaying MPER were used in conjunction with gp160 DNA lacking hypervariable regions V2, V3, or combined V1V2V3. All rabbits had HIV binding Ab responses and NAbs following the second vaccination. Using HIV-2/HIV-1 MPER chimeric viruses as targets, NAbs were detected in 12/16 rabbits after three immunizations. Low levels of NAbs specific for Tier 1 and 2 viruses were observed in all groups. This study provides evidence that co-immunizing E2 particles displaying MPER and gp160 DNA can focus Ab responses toward conserved regions of Env.

  16. Conceptual Design of Industrial Process Displays

    DEFF Research Database (Denmark)

    Pedersen, C.R.; Lind, Morten

    1999-01-01

    discusses aspects of process display design taking into account both the designer's and the operator's points of view. Three aspects are emphasized: the operator tasks, the display content and the display form. The distinction between these three aspects is the basis for proposing an outline for a display......Today, process displays used in industry are often designed on the basis of piping and instrumentation diagrams without any method of ensuring that the needs of the operators are fulfilled. Therefore, a method for a systematic approach to the design of process displays is needed. This paper...... by a simple example from a plant with batch processes. Later the method is applied to develop a supervisory display for a condenser system in a nuclear power plant. The differences between the continuous plant domain of power production and the batch processes from the example are analysed and broad...

  17. Formation of broad Balmer wings in symbiotic stars

    International Nuclear Information System (INIS)

    Chang, Seok-Jun; Heo, Jeong-Eun; Hong, Chae-Lin; Lee, Hee-Won

    2016-01-01

    Symbiotic stars are binary systems composed of a hot white dwarf and a mass losing giant. In addition to many prominent emission lines symbiotic stars exhibit Raman scattered O VI features at 6825 and 7088 Å. Another notable feature present in the spectra of many symbiotics is the broad wings around Balmer lines. Astrophysical mechanisms that can produce broad wings include Thomson scattering by free electrons and Raman scattering of Ly,β and higher series by neutral hydrogen. In this poster presentation we produce broad wings around Hα and H,β adopting a Monte Carlo techinique in order to make a quantitative comparison of these two mechanisms. Thomson wings are characterized by the exponential cutoff given by the termal width whereas the Raman wings are dependent on the column density and continuum shape in the far UV region. A brief discussion is provided. (paper)

  18. Tandem bispecific neutralizing antibody eliminates HIV-1 infection in humanized mice.

    Science.gov (United States)

    Wu, Xilin; Guo, Jia; Niu, Mengyue; An, Minghui; Liu, Li; Wang, Hui; Jin, Xia; Zhang, Qi; Lam, Ka Shing; Wu, Tongjin; Wang, Hua; Wang, Qian; Du, Yanhua; Li, Jingjing; Cheng, Lin; Tang, Hang Ying; Shang, Hong; Zhang, Linqi; Zhou, Paul; Chen, Zhiwei

    2018-04-23

    The discovery of an HIV-1 cure remains a medical challenge because the virus rebounds quickly after the cessation of combination antiretroviral therapy (cART). Here, we investigate the potential of an engineered tandem bispecific broadly neutralizing antibody (bs-bnAb) as an innovative product for HIV-1 prophylactic and therapeutic interventions. We discovered that by preserving 2 single-chain variable fragment (scFv) binding domains of each parental bnAb, a single gene-encoded tandem bs-bnAb, BiIA-SG, displayed substantially improved breadth and potency. BiIA-SG neutralized all 124 HIV-1-pseudotyped viruses tested, including global subtypes/recombinant forms, transmitted/founder viruses, variants not susceptible to parental bnAbs and to many other bnAbs with an average IC50 value of 0.073 μg/ml (range HIV-1 stains. Moreover, whereas BiIA-SG delayed viral rebound in a short-term therapeutic setting when combined with cART, a single injection of adeno-associated virus-transferred (AAV-transferred) BiIA-SG gene resulted dose-dependently in prolonged in vivo expression of BiIA-SG, which was associated with complete viremia control and subsequent elimination of infected cells in humanized mice. These results warrant the clinical development of BiIA-SG as a promising bs-bnAb-based biomedical intervention for the prevention and treatment of HIV-1 infection.

  19. Identification of pleasant, neutral, and unpleasant odors in schizophrenia.

    Science.gov (United States)

    Kamath, Vidyulata; Turetsky, Bruce I; Moberg, Paul J

    2011-05-15

    Recent work on odor hedonics in schizophrenia has indicated that patients display abnormalities in hedonic judgments of odors in comparison to healthy comparison participants. In the current study, identification accuracy for pleasant, neutral, and unpleasant odors in individuals with schizophrenia and healthy controls was examined. Thirty-three schizophrenia patients (63% male) and thirty-one healthy volunteers (65% male) were recruited. The groups were well matched on age, sex, and smoking status. Participants were administered the University of Pennsylvania Smell Identification Test, which was subsequently divided into 16 pleasant, 15 neutral, and 9 unpleasant items. Analysis of identification z-scores for pleasant, neutral, and unpleasant odors revealed a significant diagnosis by valence interaction. Post-hoc analysis revealed that schizophrenia participants made more identification errors on pleasant and neutral odors compared to healthy controls, with no differences observed for unpleasant odors. No effect was seen for sex. The findings from the current investigation suggest that odor identification accuracy in patients is influenced by odor valence. This pattern of results parallels a growing body of literature indicating that patients display aberrant pleasantness ratings for pleasant odors and highlights the need for additional research on the influence of odor valence on olfactory identification performance in individuals with schizophrenia. Copyright © 2010 Elsevier Ltd. All rights reserved.

  20. TFTR neutral beam control and monitoring for DT operations

    International Nuclear Information System (INIS)

    O'Connor, T.; Kamperschroer, J.; Chu, J.

    1995-01-01

    Record fusion power output has recently been obtained in TFTR with the injection of deuterium and tritium neutral beams. This significant achievement was due in part to the controls, software, and data processing capabilities added to the neutral beam system for DT operations. Chief among these improvements was the addition of SUN workstations and large dynamic data storage to the existing Central Instrumentation Control and Data Acquisition (CICADA) system. Essentially instantaneous look back over the recent shot history has been provided for most beam waveforms and analysis results. Gas regulation controls allowing remote switchover between deuterium and tritium were also added. With these tools, comparison of the waveforms and data of deuterium and tritium for four test conditioning pulses quickly produced reliable tritium setpoints. Thereafter, all beam conditioning was performed with deuterium, thus saving the tritium supply for the important DT injection shots. The lookback capability also led to modifications of the gas system to improve reliability and to control ceramic valve leakage by backbiasing. Other features added to improve the reliability and availability of DT neutral beam operations included master beamline controls and displays, a beamline thermocouple interlock system, a peak thermocouple display, automatic gas inventory and cryo panel gas loading monitoring, beam notching controls, a display of beam/plasma interlocks, and a feedback system to control beam power based on plasma conditions

  1. Development of broad-spectrum human monoclonal antibodies for rabies post-exposure prophylaxis

    International Nuclear Information System (INIS)

    Benedictis, P. de; Minola, A.; Rota, E.; Aiello, R.; Zecchin, B.; Salomoni, A.; Foglierini, M.; Agatic, G.; Vanzetta, F.; Lavenir, R.; Lepelletier, A.; Bentley, E.; Weiss, R.; Cattoli, G.

    2016-01-01

    Full text: Currently available rabies post-exposure prophylaxis (PEP) for use in humans includes equine or human rabies immunoglobulins (RIG). The replacement of RIG with an equally or more potent and safer product is strongly encouraged due to the high costs and limited availability of existing RIG. In this study, we identified two broadly neutralizing human monoclonal antibodies that represent a valid and affordable alternative to RIG in rabies PEP. Memory B cells from four selected vaccinated donors were immortalized and monoclonal antibodies were tested for neutralizing activity and epitope specificity. Two antibodies, identified as RVC20 and RVC58 (binding to antigenic site I and III, respectively), were selected for their potency and broad-spectrum reactivity. In vitro, RVC20 and RVC58 were able to neutralize all 35 rabies virus (RABV) and 25 non-RABV lyssaviruses. They showed higher potency and breath compared to antibodies under clinical development (namely CR57, CR4098, and RAB1) and commercially available human RIG. In vivo, the RVC20–RVC58 cocktail protected Syrian hamsters from a lethal RABV challenge and did not affect the endogenous hamster post-vaccination antibody response. (author)

  2. 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.

  3. Neutralization potential as an assay of alkalinity of environmental solids

    International Nuclear Information System (INIS)

    Grube, W.E.Jr.; Ammons, J.T.

    1993-01-01

    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

  4. Neutral Community Dynamics and the Evolution of Species Interactions.

    Science.gov (United States)

    Coelho, Marco Túlio P; Rangel, Thiago F

    2018-04-01

    A contemporary goal in ecology is to determine the ecological and evolutionary processes that generate recurring structural patterns in mutualistic networks. One of the great challenges is testing the capacity of neutral processes to replicate observed patterns in ecological networks, since the original formulation of the neutral theory lacks trophic interactions. Here, we develop a stochastic-simulation neutral model adding trophic interactions to the neutral theory of biodiversity. Without invoking ecological differences among individuals of different species, and assuming that ecological interactions emerge randomly, we demonstrate that a spatially explicit multitrophic neutral model is able to capture the recurrent structural patterns of mutualistic networks (i.e., degree distribution, connectance, nestedness, and phylogenetic signal of species interactions). Nonrandom species distribution, caused by probabilistic events of migration and speciation, create nonrandom network patterns. These findings have broad implications for the interpretation of niche-based processes as drivers of ecological networks, as well as for the integration of network structures with demographic stochasticity.

  5. Neutral theory of chemical reaction networks

    International Nuclear Information System (INIS)

    Lee, Sang Hoon; Holme, Petter; Minnhagen, Petter; Bernhardsson, Sebastian; Kim, Beom Jun

    2012-01-01

    To what extent do the characteristic features of a chemical reaction network reflect its purpose and function? In general, one argues that correlations between specific features and specific functions are key to understanding a complex structure. However, specific features may sometimes be neutral and uncorrelated with any system-specific purpose, function or causal chain. Such neutral features are caused by chance and randomness. Here we compare two classes of chemical networks: one that has been subjected to biological evolution (the chemical reaction network of metabolism in living cells) and one that has not (the atmospheric planetary chemical reaction networks). Their degree distributions are shown to share the very same neutral system-independent features. The shape of the broad distributions is to a large extent controlled by a single parameter, the network size. From this perspective, there is little difference between atmospheric and metabolic networks; they are just different sizes of the same random assembling network. In other words, the shape of the degree distribution is a neutral characteristic feature and has no functional or evolutionary implications in itself; it is not a matter of life and death. (paper)

  6. 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.

  7. Two wide-angle imaging neutral-atom spectrometers

    International Nuclear Information System (INIS)

    McComas, D.J.

    1997-01-01

    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

  8. Excitation of the inner 4d shell of neutral iodine

    Energy Technology Data Exchange (ETDEWEB)

    Pettini, M; Tozzi, G P [Osservatorio Astrofisico di Arcetri, Florence (Italy); Mazzoni, M [Florence Univ. (Italy). Ist. di Astronomia

    1981-03-23

    The absorption spectrum of neutral atomic iodine has been photographed in the EUV region and three strong autoionized resonances have been identified. A broad absorption feature has been observed and is ascribed to a collective exitation of the 4d inner shell.

  9. A misleading feeling of happiness: metamemory for positive emotional and neutral pictures.

    Science.gov (United States)

    Hourihan, Kathleen L; Bursey, Elliott

    2017-01-01

    Emotional information is often remembered better than neutral information, but the emotional benefit for positive information is less consistently observed than the benefit for negative information. The current study examined whether positive emotional pictures are recognised better than neutral pictures, and further examined whether participants can predict how emotion affects picture recognition. In two experiments, participants studied a mixed list of positive and neutral pictures, and made immediate judgements of learning (JOLs). JOLs for positive pictures were consistently higher than for neutral pictures. However, recognition performance displayed an inconsistent pattern. In Experiment 1, neutral pictures were more discriminable than positive pictures, but Experiment 2 found no difference in recognition based on emotional content. Despite participants' beliefs, positive emotional content does not appear to consistently benefit picture memory.

  10. 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....

  11. Data acquisition system for PLT Neutral Beam Test Stand

    International Nuclear Information System (INIS)

    Francis, J.E. Jr.; Hammons, C.E.

    1977-01-01

    The PLT Neutral Beam Test Stand at Oak Ridge National Laboratory was constructed to test and condition powerful neutral beam sources for the Princeton Large Torus experiment at Princeton Plasma Physics Laboratory. The data acquisition system for the test stand monitors the beam characteristics and power output to determine if the beam is operating at its design specifications. The high speed of the computer system is utilized to provide near-real-time analysis of experimental data. The analysis of the data is presented as numerical tabulation and graphic display

  12. Neutral atom traps of radioactives

    International Nuclear Information System (INIS)

    Behr, J.A.

    2003-01-01

    Neutral atoms trapped with modern laser cooling techniques offer the promise of improving several broad classes of experiments with radioactive isotopes. In nuclear β decay, neutrino spectroscopy from beta-recoil coincidences, along with highly polarized samples, enable experiments to search for non-Standard Model interactions, test whether parity symmetry is maximally violated, and search for new sources of time reversal violation. Ongoing efforts at TRIUMF, Los Alamos and Berkeley will be highlighted. The traps also offer bright sources for Doppler-free spectroscopy, particularly in high-Z atoms where precision measurements could measure the strength of weak neutral nucleon-nucleon and electron-nucleon interactions. Physics with francium atoms has been vigorously pursued at Stony Brook. Several facilities plan work with radioactive atom traps; concrete plans and efforts at KVI Groningen and Legnaro will be among those summarized. Contributions to the multidisciplinary field of trace analysis will be left up to other presenters

  13. Neutral atom traps of radioactives

    CERN Document Server

    Behr, J A

    2003-01-01

    Neutral atoms trapped with modern laser cooling techniques offer the promise of improving several broad classes of experiments with radioactive isotopes. In nuclear beta decay, neutrino spectroscopy from beta-recoil coincidences, along with highly polarized samples, enable experiments to search for non-Standard Model interactions, test whether parity symmetry is maximally violated, and search for new sources of time reversal violation. Ongoing efforts at TRIUMF, Los Alamos and Berkeley will be highlighted. The traps also offer bright sources for Doppler-free spectroscopy, particularly in high-Z atoms where precision measurements could measure the strength of weak neutral nucleon-nucleon and electron-nucleon interactions. Physics with francium atoms has been vigorously pursued at Stony Brook. Several facilities plan work with radioactive atom traps; concrete plans and efforts at KVI Groningen and Legnaro will be among those summarized. Contributions to the multidisciplinary field of trace analysis will be left...

  14. Niclosamide is a proton carrier and targets acidic endosomes with broad antiviral effects.

    Science.gov (United States)

    Jurgeit, Andreas; McDowell, Robert; Moese, Stefan; Meldrum, Eric; Schwendener, Reto; Greber, Urs F

    2012-01-01

    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.

  15. 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.

  16. 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.

  17. Assessment of effects of neutrals on the power threshold for L to H transitions in DIII-D

    International Nuclear Information System (INIS)

    Owen, L.W.; Carreras, B.A.; Maingi, R.; Mioduszewski, P.K.; Carlstrom, T.N.; Groebner, R.J.

    1998-01-01

    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 results suggest that there is a missing parameter linked to the neutrals in the power threshold scaling laws

  18. Display characterization by eye: contrast ratio and discrimination throughout the grayscale

    Science.gov (United States)

    Gille, Jennifer; Arend, Larry; Larimer, James O.

    2004-06-01

    We have measured the ability of observers to estimate the contrast ratio (maximum white luminance / minimum black or gray) of various displays and to assess luminous discrimination over the tonescale of the display. This was done using only the computer itself and easily-distributed devices such as neutral density filters. The ultimate goal of this work is to see how much of the characterization of a display can be performed by the ordinary user in situ, in a manner that takes advantage of the unique abilities of the human visual system and measures visually important aspects of the display. We discuss the relationship among contrast ratio, tone scale, display transfer function and room lighting. These results may contribute to the development of applications that allow optimization of displays for the situated viewer / display system without instrumentation and without indirect inferences from laboratory to workplace.

  19. Data acquisition system for medium power neutral beam test facility

    International Nuclear Information System (INIS)

    Stewart, C.R. Jr.; Francis, J.E. Jr.; Hammons, C.E.; Dagenhart, W.K.

    1978-06-01

    The Medium Power Neutral Beam Test Facility at Oak Ridge National Laboratory was constructed in order to develop, test, and condition powerful neutral beam lines for the Princeton Large Torus experiment at Princeton Plasma Physics Laboratory. The data acquisition system for the test stand monitors source performance, beam characteristics, and power deposition profiles to determine if the beam line is operating up to its design specifications. The speed of the computer system is utilized to provide near-real-time analysis of experimental data. Analysis of the data is presented as numerical tabulation and graphic display

  20. Advanced Plasmonic Materials for Dynamic Color Display.

    Science.gov (United States)

    Shao, Lei; Zhuo, Xiaolu; Wang, Jianfang

    2018-04-01

    Plasmonic structures exhibit promising applications in high-resolution and durable color generation. Research on advanced hybrid plasmonic materials that allow dynamically reconfigurable color control has developed rapidly in recent years. Some of these results may give rise to practically applicable reflective displays in living colors with high performance and low power consumption. They will attract broad interest from display markets, compared with static plasmonic color printing, for example, in applications such as digital signage, full-color electronic paper, and electronic device screens. In this progress report, the most promising recent examples of utilizing advanced plasmonic materials for the realization of dynamic color display are highlighted and put into perspective. The performances, advantages, and disadvantages of different technologies are discussed, with emphasis placed on both the potential and possible limitations of various hybrid materials for dynamic plasmonic color display. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Soluble HIV-1 envelope immunogens derived from an elite neutralizer elicit cross-reactive V1V2 antibodies and low potency neutralizing antibodies.

    Directory of Open Access Journals (Sweden)

    Sara Carbonetti

    Full Text Available We evaluated four gp140 Envelope protein vaccine immunogens that were derived from an elite neutralizer, subject VC10042, whose plasma was able to potently neutralize a wide array of genetically distinct HIV-1 isolates. We sought to determine whether soluble Envelope proteins derived from the viruses circulating in VC10042 could be used as immunogens to elicit similar neutralizing antibody responses by vaccination. Each gp140 was tested in its trimeric and monomeric forms, and we evaluated two gp140 trimer vaccine regimens in which adjuvant was supplied at all four immunizations or at only the first two immunizations. Interestingly, all four Envelope immunogens elicited high titers of cross-reactive antibodies that recognize the variable regions V1V2 and are potentially similar to antibodies linked with a reduced risk of HIV-1 acquisition in the RV144 vaccine trial. Two of the four immunogens elicited neutralizing antibody responses that neutralized a wide array of HIV-1 isolates from across genetic clades, but those responses were of very low potency. There were no significant differences in the responses elicited by trimers or monomers, nor was there a significant difference between the two adjuvant regimens. Our study identified two promising Envelope immunogens that elicited anti-V1V2 antibodies and broad, but low potency, neutralizing antibody responses.

  2. Design and implementation of a user-friendly interface for DIII-D neutral beam automated operation

    International Nuclear Information System (INIS)

    Phillips, J.; Colleraine, A.P.; Hong, R.; Kim, J.; Lee, R.L.; Wight, J.J.

    1989-12-01

    The operational interface to the DIII-D neutral beam system, in use for the past 10 years, consisted of several interactive devices that the operator used to sequence neutral beam conditioning and plasma heating shots. Each of four independent MODCOMP Classic control computers (for four DIII-D beamlines) included a touch screen, rotary knobs, an interactive dual port terminal, and a keyboard to selectively address each of five display screens. Most of the hardware had become obsolete and repair was becoming increasingly expensive. It was clear that the hardware could be replaced with current equipment, while improving the ergonomics of control. Combined with an ongoing effort to increase the degree of automated operation and its reliability, a single microcomputer-based interface for each of the four neutral beam MODCOMP Classic control computers was developed, effectively replacing some twenty pieces of hardware. Macintosh II microcomputers were selected, with 1 megabyte of RAM and ''off-the-shelf'' input/output (I/O) consisting of a mouse, serial ports, and two monochrome high-resolution video monitors. The software is written in PASCAL and adopts standard Macintosh ''window'' techniques. From the Macintosh interface to the MODCOMP Classic, the operator can control the power supply setpoints, adjust ion source timing and synchronization, call up waveform displays on the Grinnell color display system, view the sequencing of procedures to ready a neutral beam shot, and add operator comments to an automated shot logging system. 3 refs., 2 figs

  3. 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.

  4. Challenges to the development of vaccines to hepatitis C virus that elicit neutralizing antibodies.

    Directory of Open Access Journals (Sweden)

    Heidi Edelgard Drummer

    2014-07-01

    Full Text Available Despite 20 years of research, a vaccine to prevent hepatitis C virus (HCV infection has not been developed. A vaccine to prevent HCV will need to induce broadly reactive immunity able to prevent infection by the 7 genetically and antigenically distinct genotypes circulating world-wide. Hepatitis C virus encodes two surface exposed glycoproteins, E1 and E2 that function as a heterodimer to mediate viral entry. Neutralizing antibodies (NAbs to both E1 and E2 have been described with the major NAb target being E2. The function of E2 is to attach virions to host cells via cell surface receptors that include, but is not limited to, the tetraspanin CD81 and scavenger receptor B class I. However, E2 has developed a number of immune evasion strategies to limit the effectiveness of the NAb response and possibly limit the ability of the immune system to generate potent NAbs in natural infection. Hypervariable regions that shield the underlying core domain, subdominant neutralization epitopes and glycan shielding combine to make E2 a difficult target for the immune system. This review summarizes recent information on the role of neutralizing antibodies to prevent HCV infection, the targets of the neutralizing antibody response and structural information on glycoprotein E2 in complex with neutralizing antibodies. This new information should provide a framework for the rational design of new vaccine candidates that elicit highly potent broadly reactive NAbs to prevent HCV infection.

  5. How children remember neutral and emotional pictures: boundary extension in children's scene memories.

    Science.gov (United States)

    Candel, Ingrid; Merckelbach, Harald; Houben, Katrijn; Vandyck, Inne

    2004-01-01

    Boundary extension is the tendency to remember more of a scene than was actually shown. The dominant interpretation of this memory illusion is that it originates from schemata that people construct when viewing a scene. Evidence of boundary extension has been obtained primarily with adult participants who remember neutral pictures. The current study addressed the developmental stability of this phenomenon. Therefore, we investigated whether children aged 10-12 years display boundary extension for neutral pictures. Moreover, we examined emotional scene memory. Eighty-seven children drew pictures from memory after they had seen either neutral or emotional pictures. Both their neutral and emotional drawings revealed boundary extension. Apparently, the schema construction that underlies boundary extension is a robust and ubiquitous process.

  6. Investigation of Sequence Clipping and Structural Heterogeneity of an HIV Broadly Neutralizing Antibody by a Comprehensive LC-MS Analysis

    Science.gov (United States)

    Ivleva, Vera B.; Schneck, Nicole A.; Gollapudi, Deepika; Arnold, Frank; Cooper, Jonathan W.; Lei, Q. Paula

    2018-05-01

    CAP256 is one of the highly potent, broadly neutralizing monoclonal antibodies (bNAb) designed for HIV-1 therapy. During the process development of one of the constructs, an unexpected product-related impurity was observed via microfluidics gel electrophoresis. A panel of complementary LC-MS analyses was applied for the comprehensive characterization of CAP256 which included the analysis of the intact and reduced protein, the middle-up approach, and a set of complementary peptide mapping techniques and verification of the disulfide bonds. The designed workflow allowed to identify a clip within a protruding acidic loop in the CDR-H3 region of the heavy chain, which can lead to the decrease of bNAb potency. This characterization explained the origin of the additional species reflected by the reducing gel profile. An intra-loop disulfide bond linking the two fragments was identified, which explained why the non-reducing capillary electrophoresis (CE) profile was not affected. The extensive characterization of CAP256 post-translational modifications was performed to investigate a possible cause of CE profile complexity and to illustrate other structural details related to this molecule's biological function. Two sites of the engineered Tyr sulfation were verified in the antigen-binding loop, and pyroglutamate formation was used as a tool for monitoring the extent of antibody clipping. Overall, the comprehensive LC-MS study was crucial to (1) identify the impurity as sequence clipping, (2) pinpoint the clipping location and justify its susceptibility relative to the molecular structure, (3) lead to an upstream process optimization to mitigate product quality risk, and (4) ultimately re-engineer the sequence to be clip-resistant. [Figure not available: see fulltext.

  7. A stably expressed llama single-domain intrabody targeting Rev displays broad-spectrum anti-HIV activity.

    Science.gov (United States)

    Boons, Eline; Li, Guangdi; Vanstreels, Els; Vercruysse, Thomas; Pannecouque, Christophe; Vandamme, Anne-Mieke; Daelemans, Dirk

    2014-12-01

    The HIV Rev protein mediates the transport of partially and unspliced HIV mRNA from the nucleus to the cytoplasm. Rev multimerizes on a secondary stem-loop structure present in the viral intron-containing mRNA species and recruits the cellular karyopherin CRM1 to export viral mRNAs from the nucleus to the cytoplasm. Previously we have identified a single-domain intrabody (Nb(190)), derived from a llama heavy-chain antibody, which efficiently inhibits Rev multimerization and suppresses the production of infectious virus. We recently mapped the epitope of this nanobody and demonstrated that Rev residues K20 and Y23 are crucial for interaction while residues V16, H53 and L60 are important to a lesser extent. Here, we generated cell lines stably expressing Nb(190) and assessed the capacity of these cell lines to suppress the replication of different HIV-1 subtypes. These cells stably expressing the single-domain antibody are protected from virus-induced cytopathogenic effect even in the context of high multiplicity of infection. In addition, the replication of different subtypes of group M and one strain of group O is significantly suppressed in these cell lines. Next, we analysed the natural variations of Rev amino acids in sequence samples from HIV-1 infected patients worldwide and assessed the effect of Nb(190) on the most prevalent polymorphisms occurring at the key epitope positions (K20 and Y23) in Rev. We found that Nb(190) was able to suppress the function of these Rev variants except for the K20N mutant, which was present in only 0.7% of HIV-1 sequence populations (n = 4632). Cells stably expressing the single-domain intrabody Nb(190) are protected against virus-induced cytopathogenic effect and display a selective survival advantage upon infection. In addition, Nb(190) suppresses the replication of a wide range of different HIV-1 subtypes. Large-scale sequence analysis reveals that the Nb(190) epitope positions in Rev are well conserved across major HIV-1

  8. Security alarm communication and display systems development

    International Nuclear Information System (INIS)

    Waddoups, I.G.

    1990-01-01

    Sandia National Laboratories (SNL) has, as lead Department of Energy (DOE) physical security laboratory, developed a variety of alarm communication and display systems for DOE and Department of Defense (DOD) facilities. This paper briefly describes some of the systems developed and concludes with a discussion of technology relevant to those currently designing, developing, implementing, or procuring such a system. Development activities and the rapid evolution of computers over the last decade have resulted in a broad variety of capabilities to support most security system communication and display needs. The major task in selecting a system is becoming familiar with these capabilities and finding the best match to a specific need

  9. Adenovirus Particles that Display the Plasmodium falciparum Circumsporozoite Protein NANP Repeat Induce Sporozoite-Neutralizing Antibodies in Mice

    OpenAIRE

    Palma, Christopher; Overstreet, Michael G.; Guedon, Jean-Marc; Hoiczyk, Egbert; Ward, Cameron; Karen, Kasey A.; Zavala, Fidel; Ketner, Gary

    2011-01-01

    Adenovirus particles can be engineered to display exogenous peptides on their surfaces by modification of viral capsid proteins, and particles that display pathogen-derived peptides can induce protective immunity. We constructed viable recombinant adenoviruses that display B-cell epitopes from the Plasmodium falciparum circumsporozoite protein (PfCSP) in the major adenovirus capsid protein, hexon. Recombinants induced high-titer antibodies against CSP when injected intraperitoneally into mice...

  10. Architectural Insight into Inovirus-Associated Vectors (IAVs and Development of IAV-Based Vaccines Inducing Humoral and Cellular Responses: Implications in HIV-1 Vaccines

    Directory of Open Access Journals (Sweden)

    Kyriakos A. Hassapis

    2014-12-01

    Full Text Available Inovirus-associated vectors (IAVs are engineered, non-lytic, filamentous bacteriophages that are assembled primarily from thousands of copies of the major coat protein gp8 and just five copies of each of the four minor coat proteins gp3, gp6, gp7 and gp9. Inovirus display studies have shown that the architecture of inoviruses makes all coat proteins of the inoviral particle accessible to the outside. This particular feature of IAVs allows foreign antigenic peptides to be displayed on the outer surface of the virion fused to its coat proteins and for more than two decades has been exploited in many applications including antibody or peptide display libraries, drug design, and vaccine development against infectious and non-infectious diseases. As vaccine carriers, IAVs have been shown to elicit both a cellular and humoral response against various pathogens through the display of antibody epitopes on their coat proteins. Despite their high immunogenicity, the goal of developing an effective vaccine against HIV-1 has not yet materialized. One possible limitation of previous efforts was the use of broadly neutralizing antibodies, which exhibited autoreactivity properties. In the past five years, however, new, more potent broadly neutralizing antibodies that do not exhibit autoreactivity properties have been isolated from HIV-1 infected individuals, suggesting that vaccination strategies aimed at producing such broadly neutralizing antibodies may confer protection against infection. The utilization of these new, broadly neutralizing antibodies in combination with the architectural traits of IAVs have driven the current developments in the design of an inovirus-based vaccine against HIV-1. This article reviews the applications of IAVs in vaccine development, with particular emphasis on the design of inoviral-based vaccines against HIV-1.

  11. Development and characterization of human monoclonal antibodies that neutralize multiple TGFβ isoforms.

    Science.gov (United States)

    Bedinger, Daniel; Lao, Llewelyn; Khan, Shireen; Lee, Steve; Takeuchi, Toshihiko; Mirza, Amer M

    2016-01-01

    Transforming growth factor (TGF)β levels are elevated in, and drive the progression of, numerous disease states such as advanced metastatic cancer and systemic and ocular fibrosis. There are 3 main isoforms, TGFβ1, 2, and 3. As multiple TGFβ isoforms are involved in disease processes, maximal therapeutic efficacy may require neutralization of 2 or more of the TGFβ isoforms. Fully human antibody phage display libraries were used to discover a number of antibodies that bind and neutralize various combinations of TGFβ1, 2 or 3. The primary panning did not yield any uniformly potent pan-isoform neutralizing antibodies; therefore, an antibody that displayed potent TGFβ 1, 2 inhibition, but more modest affinity versus TGFβ3, was affinity matured by shuffling with a light chain sub-library and further screening. This process yielded a high affinity pan-isoform neutralizing clone. Antibodies were analyzed and compared by binding affinity, as well as receptor and epitope competition by surface plasmon resonance methods. The antibodies were also shown to neutralize TGFβ effects in vitro in 3 assays: 1) interleukin (IL)-4 induced HT-2 cell proliferation; 2) TGFβ-mediated IL-11 release by A549 cells; and 3) decreasing SMAD2 phosphorylation in Detroit 562 cells. The antibodies' potency in these in vitro assays correlated well with their isoform-specific affinities. Furthermore, the ability of the affinity-matured clone to decrease tumor burden in a Detroit 562 xenograft study was superior to that of the parent clone. This affinity-matured antibody acts as a very potent inhibitor of all 3 main isoforms of TGFβ and may have utility for therapeutic intervention in human disease.

  12. Are "Market Neutral" Hedge Funds Really Market Neutral?

    OpenAIRE

    Andrew J. Patton

    2009-01-01

    Using a variety of different definitions of "neutrality," this study presents significant evidence against the neutrality to market risk of hedge funds in a range of style categories. I generalize standard definitions of "market neutrality," and propose five different neutrality concepts. I suggest statistical tests for each neutrality concept, and apply these tests to a database of monthly returns on 1423 hedge funds from five style categories. For the "market neutral" style, approximately o...

  13. 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

    2010-01-01

    Full Text Available 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.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.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.

  14. 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

    2001-01-01

    by 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......PA, and second step is to forms inert to uPA. With some neutralizers, the second step was associated with PAI-1 polymerization. Vitronectin reduced the susceptibility to the neutralizers. Changes in sensitivity to activity neutralization by point mutations were compatible with the various neutralizers having...

  15. 77 FR 39174 - Safety Zone, Temporary Change for Recurring Fifth Coast Guard District Fireworks Displays...

    Science.gov (United States)

    2012-07-02

    ..., Cavalier Golf & Yacht Club Independence Day Fireworks Display, Broad Bay; Virginia Beach, VA AGENCY: Coast... the Cavalier Golf & Yacht Club Independence Day Fireworks Display. This action is intended to restrict..., 2012, we published a notice of proposed rulemaking (NPRM) entitled Cavalier Golf & Yacht Club...

  16. Well separated trion and neutral excitons on superacid treated MoS{sub 2} monolayers

    Energy Technology Data Exchange (ETDEWEB)

    Cadiz, Fabian, E-mail: cadiz@insa-toulouse.fr; Tricard, Simon; Gay, Maxime; Lagarde, Delphine; Wang, Gang; Robert, Cedric; Renucci, Pierre; Urbaszek, Bernhard; Marie, Xavier [Université de Toulouse, INSA-CNRS-UPS, LPCNO, 135 Av. Rangueil, 31077 Toulouse (France)

    2016-06-20

    Developments in optoelectronics and spin-optronics based on transition metal dichalcogenide monolayers (MLs) need materials with efficient optical emission and well-defined transition energies. In as-exfoliated MoS{sub 2} MLs, the photoluminescence (PL) spectra even at low temperature consist typically of broad, overlapping contributions from neutral, charged excitons (trions) and localized states. Here, we show that in superacid treated MoS{sub 2} MLs, the PL intensity increases by up to 60 times at room temperature. The neutral and charged exciton transitions are spectrally well separated in PL and reflectivity at T = 4 K, with linewidth for the neutral exciton of 15 meV, but both transitions have similar intensities compared to the ones in as-exfoliated MLs at the same temperature. Time resolved experiments uncover picoseconds recombination dynamics analyzed separately for charged and neutral exciton emissions. Using the chiral interband selection rules, we demonstrate optically induced valley polarization for both complexes and valley coherence for only the neutral exciton.

  17. Neutralization resistance of hepatitis C virus can be overcome by recombinant human monoclonal antibodies

    DEFF Research Database (Denmark)

    Pedersen, Jannie L; Carlsen, Thomas H R; Prentoe, Jannick

    2013-01-01

    Immunotherapy and vaccine development for hepatitis C virus (HCV) will depend on broadly reactive neutralizing antibodies (NAbs). However, studies in infectious strain JFH1-based culture systems expressing patient-derived Core-NS2 proteins have suggested neutralization resistance for specific HCV...... demonstrated that the novel genotype 2 viruses as well as prototype strains J6/JFH1(2a) and J8/JFH1(2b), all with authentic envelope proteins, were resistant to neutralization by genotype 2a, 2b, 2c, 2j, 2i, and 2q patient sera. However, these patient sera had high titers of HCV-specific NAbs, because...... they efficiently reduced the infectivity of J6(2a) and J8(2b) with deleted hypervariable region 1. The genotype 2a, 2b, and 2c viruses, found resistant to polyclonal patient sera neutralization, were efficiently neutralized by two lead HMAbs (AR4A and HC84.26). Conclusion: Using novel 2a, 2b, and 2c cell...

  18. 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.

  19. Recognition of emotional facial expressions and broad autism phenotype in parents of children diagnosed with autistic spectrum disorder.

    Science.gov (United States)

    Kadak, Muhammed Tayyib; Demirel, Omer Faruk; Yavuz, Mesut; Demir, Türkay

    2014-07-01

    Research findings debate about features of broad autism phenotype. In this study, we tested whether parents of children with autism have problems recognizing emotional facial expression and the contribution of such an impairment to the broad phenotype of autism. Seventy-two parents of children with autistic spectrum disorder and 38 parents of control group participated in the study. Broad autism features was measured with Autism Quotient (AQ). Recognition of Emotional Face Expression Test was assessed with the Emotion Recognition Test, consisting a set of photographs from Ekman & Friesen's. In a two-tailed analysis of variance of AQ, there was a significant difference for social skills (F(1, 106)=6.095; p<.05). Analyses of variance revealed significant difference in the recognition of happy, surprised and neutral expressions (F(1, 106)=4.068, p=.046; F(1, 106)=4.068, p=.046; F(1, 106)=6.064, p=.016). According to our findings, social impairment could be considered a characteristic feature of BAP. ASD parents had difficulty recognizing neutral expressions, suggesting that ASD parents may have impaired recognition of ambiguous expressions as do autistic children. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. 77 FR 27156 - Safety Zone, Temporary Change for Recurring Fifth Coast Guard District Fireworks Displays...

    Science.gov (United States)

    2012-05-09

    ..., Cavalier Golf & Yacht Club Independence Day Fireworks Display, Broad Bay Virginia Beach, VA AGENCY: Coast... the safety of life on navigable waters during the Cavalier Golf & Yacht Club Independence Day..., 2012 Cavalier Golf & Yacht Club will host a fireworks display on the shoreline of the navigable waters...

  1. Antibiotic combination therapy can select for broad-spectrum multidrug resistance in Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Vestergaard, Martin; Paulander, Wilhelm; Marvig, Rasmus L.

    2016-01-01

    with the resistance evolved after single-drug exposure. Combination therapy selected for mutants that displayed broad-spectrum resistance, and a major resistance mechanism was mutational inactivation of the repressor gene mexR that regulates the multidrug efflux operon mexAB–oprM. Deregulation of this operon led...... to a broad-spectrum resistance phenotype that decreased susceptibility to the combination of drugs applied during selection as well as to unrelated antibiotic classes. Mutants isolated after single-drug exposure displayed narrow-spectrum resistance and carried mutations in the MexCD–OprJ efflux pump...... regulator gene nfxB conferring ciprofloxacin resistance, or in the gene encoding the non-essential penicillin-binding protein DacB conferring ceftazidime resistance. Reconstruction of resistance mutations by allelic replacement and in vitro fitness assays revealed that in contrast to single antibiotic use...

  2. Identification of pleasant, neutral, and unpleasant odors in schizophrenia

    OpenAIRE

    Kamath, Vidyulata; Turetsky, Bruce I.; Moberg, Paul J.

    2011-01-01

    Recent work on odor hedonics in schizophrenia has indicated that patients display abnormalities in hedonic judgments of odors in comparison to healthy comparison participants. In the current study, identification accuracy for pleasant, neutral, and unpleasant odors in individuals with schizophrenia and healthy controls was examined. Thirty-three schizophrenia patients (63% male) and thirty-one healthy volunteers (65% male) were recruited. The groups were well matched on age, sex, and smoking ...

  3. Structure of an N276-Dependent HIV-1 Neutralizing Antibody Targeting a Rare V5 Glycan Hole Adjacent to the CD4 Binding Site

    Energy Technology Data Exchange (ETDEWEB)

    Wibmer, Constantinos Kurt; Gorman, Jason; Anthony, Colin S.; Mkhize, Nonhlanhla N.; Druz, Aliaksandr; York, Talita; Schmidt, Stephen D.; Labuschagne, Phillip; Louder, Mark K.; Bailer, Robert T.; Karim, Salim S. Abdool; Mascola, John R.; Williamson, Carolyn; Moore, Penny L.; Kwong, Peter D.; Morris, Lynn (NHLS-South Africa); (NIH); (Witwatersrand); (KwaZulu-Natal)

    2016-08-31

    ABSTRACT

    All HIV-1-infected individuals develop strain-specific neutralizing antibodies to their infecting virus, which in some cases mature into broadly neutralizing antibodies. Defining the epitopes of strain-specific antibodies that overlap conserved sites of vulnerability might provide mechanistic insights into how broadly neutralizing antibodies arise. We previously described an HIV-1 clade C-infected donor, CAP257, who developed broadly neutralizing plasma antibodies targeting an N276 glycan-dependent epitope in the CD4 binding site. The initial CD4 binding site response potently neutralized the heterologous tier 2 clade B viral strain RHPA, which was used to design resurfaced gp120 antigens for single-B-cell sorting. Here we report the isolation and structural characterization of CAP257-RH1, an N276 glycan-dependent CD4 binding site antibody representative of the early CD4 binding site plasma response in donor CAP257. The cocrystal structure of CAP257-RH1 bound to RHPA gp120 revealed critical interactions with the N276 glycan, loop D, and V5, but not with aspartic acid 368, similarly to HJ16 and 179NC75. The CAP257-RH1 monoclonal antibody was derived from the immunoglobulin-variable IGHV3-33 and IGLV3-10 genes and neutralized RHPA but not the transmitted/founder virus from donor CAP257. Its narrow neutralization breadth was attributed to a binding angle that was incompatible with glycosylated V5 loops present in almost all HIV-1 strains, including the CAP257 transmitted/founder virus. Deep sequencing of autologous CAP257 viruses, however, revealed minority variants early in infection that lacked V5 glycans. These glycan-free V5 loops are unusual holes in the glycan shield that may have been necessary for initiating this N276 glycan-dependent CD4 binding site B-cell lineage.

    IMPORTANCEThe conserved CD4 binding site on gp120 is a major target for HIV-1 vaccine design, but key events in the elicitation and maturation of

  4. From Foreground to Background: How Task-Neutral Context Influences Contextual Cueing of Visual Search.

    Science.gov (United States)

    Zang, Xuelian; Geyer, Thomas; Assumpção, Leonardo; Müller, Hermann J; Shi, Zhuanghua

    2016-01-01

    Selective attention determines the effectiveness of implicit contextual learning (e.g., Jiang and Leung, 2005). Visual foreground-background segmentation, on the other hand, is a key process in the guidance of attention (Wolfe, 2003). In the present study, we examined the impact of foreground-background segmentation on contextual cueing of visual search in three experiments. A visual search display, consisting of distractor 'L's and a target 'T', was overlaid on a task-neutral cuboid on the same depth plane (Experiment 1), on stereoscopically separated depth planes (Experiment 2), or spread over the entire display on the same depth plane (Experiment 3). Half of the search displays contained repeated target-distractor arrangements, whereas the other half was always newly generated. The task-neutral cuboid was constant during an initial training session, but was either rotated by 90° or entirely removed in the subsequent test sessions. We found that the gains resulting from repeated presentation of display arrangements during training (i.e., contextual-cueing effects) were diminished when the cuboid was changed or removed in Experiment 1, but remained intact in Experiments 2 and 3 when the cuboid was placed in a different depth plane, or when the items were randomly spread over the whole display but not on the edges of the cuboid. These findings suggest that foreground-background segmentation occurs prior to contextual learning, and only objects/arrangements that are grouped as foreground are learned over the course of repeated visual search.

  5. New portable FELIX 3D display

    Science.gov (United States)

    Langhans, Knut; Bezecny, Daniel; Homann, Dennis; Bahr, Detlef; Vogt, Carsten; Blohm, Christian; Scharschmidt, Karl-Heinz

    1998-04-01

    An improved generation of our 'FELIX 3D Display' is presented. This system is compact, light, modular and easy to transport. The created volumetric images consist of many voxels, which are generated in a half-sphere display volume. In that way a spatial object can be displayed occupying a physical space with height, width and depth. The new FELIX generation uses a screen rotating with 20 revolutions per second. This target screen is mounted by an easy to change mechanism making it possible to use appropriate screens for the specific purpose of the display. An acousto-optic deflection unit with an integrated small diode pumped laser draws the images on the spinning screen. Images can consist of up to 10,000 voxels at a refresh rate of 20 Hz. Currently two different hardware systems are investigated. The first one is based on a standard PCMCIA digital/analog converter card as an interface and is controlled by a notebook. The developed software is provided with a graphical user interface enabling several animation features. The second, new prototype is designed to display images created by standard CAD applications. It includes the development of a new high speed hardware interface suitable for state-of-the- art fast and high resolution scanning devices, which require high data rates. A true 3D volume display as described will complement the broad range of 3D visualization tools, such as volume rendering packages, stereoscopic and virtual reality techniques, which have become widely available in recent years. Potential applications for the FELIX 3D display include imaging in the field so fair traffic control, medical imaging, computer aided design, science as well as entertainment.

  6. Neutralization of tier-2 viruses and epitope profiling of plasma antibodies from human immunodeficiency virus type 1 infected donors from India.

    Directory of Open Access Journals (Sweden)

    Raiees Andrabi

    Full Text Available Broadly cross neutralizing antibodies (NAbs are generated in a group of HIV-1 infected individuals during the natural infection, but little is known about their prevalence in patients infected with viral subtypes from different geographical regions. We tested here the neutralizing efficiency of plasma antibodies from 80 HIV-1 infected antiretroviral drug naive patients against a panel of subtype-B and C tier 2 viruses. We detected cross-neutralizing antibodies in approximately 19-27% of the plasma, however the subtype-C specific neutralization efficiency predominated (p = 0.004. The neutralizing activity was shown to be exclusively mediated by the immunoglobulin G (IgG fraction in the representative plasma samples. Epitope mapping of three, the most cross-neutralizing plasma (CNP AIIMS206, AIIMS239 and AIIMS249 with consensus-C overlapping envelope peptides revealed ten different binding specificities with only V3 and IDR being common. The V3 and IDR were highly antigenic regions but no correlation between their reciprocal Max50 binding titers and neutralization was observed. In addition, the neutralizing activity of CNP was not substantially reduced by V3 and gp41 peptides except a modest contribution of MPER peptide. The MPER was rarely recognized by plasma antibodies though antibody depletion and competition experiments demonstrated MPER dependent neutralization in two out of three CNP. Interestingly, the binding specificity of one of the CNP (AIIMS206 overlapped with broadly neutralizing mAb 2F5 epitope. Overall, the data suggest that, despite the low immunogenicity of HIV-1 MPER, the antibodies directed to this region may serve as crucial reagents for HIV-1 vaccine design.

  7. Real-time control and data-acquisition system for high-energy neutral-beam injectors

    International Nuclear Information System (INIS)

    Glad, A.S.; Jacobson, V.

    1981-12-01

    The need for a real-time control system and a data acquisition, processing and archiving system operating in parallel on the same computer became a requirement on General Atomic's Doublet III fusion energy project with the addition of high energy neutral beam injectors. The data acquisition processing and archiving system is driven from external events and is sequenced through each experimental shot utilizing ModComp's intertask message service. This system processes, archives and displays on operator console CRTs all physics diagnostic data related to the neutral beam injectores such as temperature, beam alignment, etc. The real-time control system is data base driven and provides periodic monitoring and control of the numerous dynamic subsystems of the neutral beam injectors such as power supplies, timing, water cooling, etc

  8. Isolation and characterization of broadly neutralizing human monoclonal antibodies to the e1 glycoprotein of hepatitis C virus

    DEFF Research Database (Denmark)

    Meunier, Jean-Christophe; Russell, Rodney S; Goossens, Vera

    2008-01-01

    monoclonal antibodies (MAbs) directed against HCV glycoprotein E1, which may have the potential to control HCV infection. We have identified two MAbs that can strongly neutralize HCV-pseudotyped particles (HCVpp) bearing the envelope glycoproteins of genotypes 1a, 1b, 4a, 5a, and 6a and less strongly...

  9. Apparatus and method for neutralizing the beam in an ion implanter

    International Nuclear Information System (INIS)

    Douglas, E.C.

    1982-01-01

    An ion implanter apparatus is described with provision for neutralizing the space charge potential of the ionic beam with a closed loop feedback system responding to the electrical charges that tend to accumulate on a target specimen. Neutralization is provided by a controllable electron source surrounding the beam. Flow of electrons to a plate radially outward of the electron source is used to derive a signal proportional to the beam ion current when the space charge potential of the beam is neutralized. The beam current signal can be used (1) to provide a read-out display for the operator; (2) to control the magnitude of the ion beam; (3) to be integrated to determine the total positive charge that enters the faraday cage of the implanter for use to control the ion beam shutter; or (4) to effect relative movement of the specimen and the beam

  10. Structure-based, targeted deglycosylation of HIV-1 gp120 and effects on neutralization sensitivity and antibody recognition

    International Nuclear Information System (INIS)

    Koch, Markus; Pancera, Marie; Kwong, Peter D.; Kolchinsky, Peter; Grundner, Christoph; Wang Liping; Hendrickson, Wayne A.; Sodroski, Joseph; Wyatt, Richard

    2003-01-01

    The human immunodeficiency virus (HIV-1) exterior envelope glycoprotein, gp120, mediates receptor binding and is the major target for neutralizing antibodies. Primary HIV-1 isolates are characteristically more resistant to broadly neutralizing antibodies, although the structural basis for this resistance remains obscure. Most broadly neutralizing antibodies are directed against functionally conserved gp120 regions involved in binding to either the primary virus receptor, CD4, or the viral coreceptor molecules that normally function as chemokine receptors. These antibodies are known as CD4 binding site (CD4BS) and CD4-induced (CD4i) antibodies, respectively. Inspection of the gp120 crystal structure reveals that although the receptor-binding regions lack glycosylation, sugar moieties lie proximal to both receptor-binding sites on gp120 and thus in proximity to both the CD4BS and the CD4i epitopes. In this study, guided by the X-ray crystal structure of gp120, we deleted four N-linked glycosylation sites that flank the receptor-binding regions. We examined the effects of selected changes on the sensitivity of two prototypic HIV-1 primary isolates to neutralization by antibodies. Surprisingly, removal of a single N-linked glycosylation site at the base of the gp120 third variable region (V3 loop) increased the sensitivity of the primary viruses to neutralization by CD4BS antibodies. Envelope glycoprotein oligomers on the cell surface derived from the V3 glycan-deficient virus were better recognized by a CD4BS antibody and a V3 loop antibody than were the wild-type glycoproteins. Absence of all four glycosylation sites rendered a primary isolate sensitive to CD4i antibody-mediated neutralization. Thus, carbohydrates that flank receptor-binding regions on gp120 protect primary HIV-1 isolates from antibody-mediated neutralization

  11. A "Trojan horse" bispecific-antibody strategy for broad protection against ebolaviruses.

    Science.gov (United States)

    Wec, Anna Z; Nyakatura, Elisabeth K; Herbert, Andrew S; Howell, Katie A; Holtsberg, Frederick W; Bakken, Russell R; Mittler, Eva; Christin, John R; Shulenin, Sergey; Jangra, Rohit K; Bharrhan, Sushma; Kuehne, Ana I; Bornholdt, Zachary A; Flyak, Andrew I; Saphire, Erica Ollmann; Crowe, James E; Aman, M Javad; Dye, John M; Lai, Jonathan R; Chandran, Kartik

    2016-10-21

    There is an urgent need for monoclonal antibody (mAb) therapies that broadly protect against Ebola virus and other filoviruses. The conserved, essential interaction between the filovirus glycoprotein, GP, and its entry receptor Niemann-Pick C1 (NPC1) provides an attractive target for such mAbs but is shielded by multiple mechanisms, including physical sequestration in late endosomes. Here, we describe a bispecific-antibody strategy to target this interaction, in which mAbs specific for NPC1 or the GP receptor-binding site are coupled to a mAb against a conserved, surface-exposed GP epitope. Bispecific antibodies, but not parent mAbs, neutralized all known ebolaviruses by coopting viral particles themselves for endosomal delivery and conferred postexposure protection against multiple ebolaviruses in mice. Such "Trojan horse" bispecific antibodies have potential as broad antifilovirus immunotherapeutics. Copyright © 2016, American Association for the Advancement of Science.

  12. On becoming neutral: effects of experimental neutralizing reconsidered.

    Science.gov (United States)

    van den Hout, M; van Pol, M; Peters, M

    2001-12-01

    Behaviour Research and Therapy 34 (1996) 889-898 found that writing out a negative thought produced anxiety and an urge to neutralize the thought, that instructing participants to neutralize the thought reduced anxiety/neutralization urge in the short run (i.e. within 2 min), but that in the control group 20 min without instruction was attended by the same reduction in anxiety/urge to neutralize ("natural decay"). The observations were made with pariticipants who scored high on "thought action fusion" and the experiment was set up as exerimental model of obsessions. We repeated the study with participants that were not selected on thought action fusion. All the findings reported by Behaviour Research and Therapy 34 (1996) 889-898 were replicated. Correlational analysis indicated that the strength of the effect was not related to scores on scales measuring "thought action fusion". Behaviour Research and Therapy 34 (1996) 889-898 did not assess whether non-neutralizing was followed by immediate reductions in distress. We did assess this and found that the larger part of the immediate reduction of distress after neutralization also occurs when no neutralization instruction is given. The effects of neutralization instructions in the present type of experiment are considerably less powerful than suggested earlier.

  13. Hemifacial Display of Emotion in the Resting State

    Directory of Open Access Journals (Sweden)

    M. K. Mandal

    1992-01-01

    Full Text Available The human face at rest displays distinguishable asymmetries with some lateralization of emotion or expression. The asymmetrical nature of the resting face was examined by preparing hemifacial composites, left–left, right–right, along with normal facial orientation. The left side and right side composites were constructed by using the lateral half of one side of the face and its mirror-reversal. The left side facial composites were found to be more emotional than the right side or normal facial orientations of neutral expressions.

  14. From foreground to background: how task-neutral context influences contextual cueing of visual search

    Directory of Open Access Journals (Sweden)

    Xuelian eZang

    2016-06-01

    Full Text Available Selective attention determines the effectiveness of implicit contextual learning (e.g., Jiang & Leung, 2005. Visual foreground-background segmentation, on the other hand, is a key process in the guidance of attention (Wolfe, 2003. In the present study, we examined the impact of foreground-background segmentation on contextual cueing of visual search in three experiments. A visual search display, consisting of distractor ‘L’s and a target ‘T’, was overlaid on a task-neutral cuboid on the same depth plane (Experiment 1, on stereoscopically separated depth planes (Experiment 2, or spread over the entire display on the same depth plane (Experiment 3. Half of the search displays contained repeated target-distractor arrangements, whereas the other half was always newly generated. The task-neutral cuboid was constant during an initial training session, but was either rotated by 90º or entirely removed in the subsequent test sessions. We found that the gains resulting from repeated presentation of display arrangements during training (i.e., contextual-cueing effects were diminished when the cuboid was changed or removed in Experiment 1, but remained intact in Experiments 2 and 3 when the cuboid was placed in a different depth plane, or when the items were randomly spread over the whole display but not on the edges of the cuboid. These findings suggest that foreground-background segmentation occurs prior to contextual learning, and only objects/arrangements that are grouped as foreground are learned over the course of repeated visual search.

  15. From Foreground to Background: How Task-Neutral Context Influences Contextual Cueing of Visual Search

    Science.gov (United States)

    Zang, Xuelian; Geyer, Thomas; Assumpção, Leonardo; Müller, Hermann J.; Shi, Zhuanghua

    2016-01-01

    Selective attention determines the effectiveness of implicit contextual learning (e.g., Jiang and Leung, 2005). Visual foreground-background segmentation, on the other hand, is a key process in the guidance of attention (Wolfe, 2003). In the present study, we examined the impact of foreground-background segmentation on contextual cueing of visual search in three experiments. A visual search display, consisting of distractor ‘L’s and a target ‘T’, was overlaid on a task-neutral cuboid on the same depth plane (Experiment 1), on stereoscopically separated depth planes (Experiment 2), or spread over the entire display on the same depth plane (Experiment 3). Half of the search displays contained repeated target-distractor arrangements, whereas the other half was always newly generated. The task-neutral cuboid was constant during an initial training session, but was either rotated by 90° or entirely removed in the subsequent test sessions. We found that the gains resulting from repeated presentation of display arrangements during training (i.e., contextual-cueing effects) were diminished when the cuboid was changed or removed in Experiment 1, but remained intact in Experiments 2 and 3 when the cuboid was placed in a different depth plane, or when the items were randomly spread over the whole display but not on the edges of the cuboid. These findings suggest that foreground-background segmentation occurs prior to contextual learning, and only objects/arrangements that are grouped as foreground are learned over the course of repeated visual search. PMID:27375530

  16. Boosting of HIV-1 neutralizing antibody responses by a distally related retroviral envelope protein

    DEFF Research Database (Denmark)

    Uchtenhagen, Hannes; Schiffner, Torben; Bowles, Emma

    2014-01-01

    Our knowledge of the binding sites for neutralizing Abs (NAb) that recognize a broad range of HIV-1 strains (bNAb) has substantially increased in recent years. However, gaps remain in our understanding of how to focus B cell responses to vulnerable conserved sites within the HIV-1 envelope glycop...

  17. One-electron capture and target ionization in He+-neutral-atom collisions

    International Nuclear Information System (INIS)

    Shevelko, V.P.; Tolstikhina, I.Yu.; Kato, D.; Tawara, H.; Song, M-.Y.; Yoon, J-.S.

    2009-12-01

    One-electron capture and target-ionization cross sections in collisions of He + ions with neutral atoms: He + + A → He + A + and He + + A → He + + A + + e, A = H, He(1s 2 , 1s2s), Ne, Ar, Kr, Xe, are calculated and compared with available experimental data over the broad energy range E = 0.1 keV/u - 10 MeV/u of He + ions. The role of the metastable states of neutral helium atoms in such collisions, which are of importance in plasma physics applications, is briefly discussed. The recommended cross section data for these processes are presented in a closed analytical form (nine-order polynomials) which can be used for a plasma modeling and diagnostics. (author)

  18. Individual differences in processing emotional images after reading disgusting and neutral sentences.

    Science.gov (United States)

    Hartigan, Alex; Richards, Anne

    2017-11-21

    The present study examined the extent to which Event Related Potentials (ERPs) evoked by disgusting, threatening and neutral photographic images were influenced by disgust propensity, disgust sensitivity and attentional control following exposure to disgusting information. Emotional cognition was manipulated by instructing participants to remember either disgusting or neutral sentences; participants in both groups then viewed emotional images while ERPs were recorded. Disgust propensity was associated with a reduced Late Positive Potential (LPP) gap between threatening and neutral stimuli (an effect driven by a rise in the LPP for neutral images) but only amongst individuals who were exposed to disgusting sentences. The typical LPP increase for disgust over neutral was reduced by attentional shifting capacity but only for individuals who were not previously exposed to disgust. There was also a persistent occipital shifted late positivity that was enhanced for disgust for the entire LPP window and was independent of exposure. Results suggest that emotion specific ERP effects can emerge within the broad unpleasant emotional category in conjunction with individual differences and prior emotional exposure. These results have important implications for the ways in which the perception of emotion is impacted by short term cognitive influences and longer term individual differences. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Endophytic Paraconiothyrium sp. from Zingiber officinale Rosc. Displays Broad-Spectrum Antimicrobial Activity by Production of Danthron.

    Science.gov (United States)

    Anisha, C; Sachidanandan, P; Radhakrishnan, E K

    2018-03-01

    The bioactivity spectrum of fungal endophytes isolated from Zingiber officinale was analyzed against clinical pathogens and against the phytopathogen Pythium myriotylum, which causes Pythium rot in ginger. One of the isolates GFM13 showed broad bioactivity against various pathogens tested including P. myriotylum. The spore suspension as well as the culture filtrate of the endophytic fungal isolate was found to effectively protect ginger rhizomes from Pythium rot. By molecular identification, the fungal endophyte was identified as Paraconiothyrium sp. The bioactive compound produced by the isolate was separated by bioactivity-guided fractionation and was identified by GC-MS as danthron, an anthraquinone derivative. PCR amplification showed the presence of non-reducing polyketide synthase gene (NR-PKS) in the endophyte GFM13, which is reported to be responsible for the synthesis of anthraquinones in fungi. This is the first report of danthron being produced as the biologically active component of Paraconiothyrium sp. Danthron is reported to have wide pharmaceutical and agronomic applications which include its use as a fungicide in agriculture. The broad-spectrum antimicrobial activity of danthron and the endophytic origin of Paraconiothyrium sp. offer immense applications of the study.

  20. OLED Display For Real Time Vision System

    OpenAIRE

    Sandhyalakshmi Narayanan; Sanjana Sridhar; Neha Deshpande; Ashwini Gaikwad

    2015-01-01

    This innovative glass design will carry an OLED based display controlled via nano Ardiuno board having Bluetooth connectivity with a Smartphone to exchange information along with onboard accelerometer. We are using a tilt angle sensor for detecting if the driver is feeling drowsy. An alcohol sensor has been used to promote the safe driving habit. The glasses will be getting latest updates about the current speed of the vehicle navigation directions nearby or approaching sign broads or service...

  1. Biomechanics of the Peacock's Display: How Feather Structure and Resonance Influence Multimodal Signaling.

    Science.gov (United States)

    Dakin, Roslyn; McCrossan, Owen; Hare, James F; Montgomerie, Robert; Amador Kane, Suzanne

    2016-01-01

    Courtship displays may serve as signals of the quality of motor performance, but little is known about the underlying biomechanics that determines both their signal content and costs. Peacocks (Pavo cristatus) perform a complex, multimodal "train-rattling" display in which they court females by vibrating the iridescent feathers in their elaborate train ornament. Here we study how feather biomechanics influences the performance of this display using a combination of field recordings and laboratory experiments. Using high-speed video, we find that train-rattling peacocks stridulate their tail feathers against the train at 25.6 Hz, on average, generating a broadband, pulsating mechanical sound at that frequency. Laboratory measurements demonstrate that arrays of peacock tail and train feathers have a broad resonant peak in their vibrational spectra at the range of frequencies used for train-rattling during the display, and the motion of feathers is just as expected for feathers shaking near resonance. This indicates that peacocks are able to drive feather vibrations energetically efficiently over a relatively broad range of frequencies, enabling them to modulate the feather vibration frequency of their displays. Using our field data, we show that peacocks with longer trains use slightly higher vibration frequencies on average, even though longer train feathers are heavier and have lower resonant frequencies. Based on these results, we propose hypotheses for future studies of the function and energetics of this display that ask why its dynamic elements might attract and maintain female attention. Finally, we demonstrate how the mechanical structure of the train feathers affects the peacock's visual display by allowing the colorful iridescent eyespots-which strongly influence female mate choice-to remain nearly stationary against a dynamic iridescent background.

  2. Non-Neutralizing Antibodies Directed against HIV and Their Functions

    Directory of Open Access Journals (Sweden)

    Luzia M. Mayr

    2017-11-01

    Full Text Available B cells produce a plethora of anti-HIV antibodies (Abs but only few of them exhibit neutralizing activity. This was long considered a profound limitation for the enforcement of humoral immune responses against HIV-1 infection, especially since these neutralizing Abs (nAbs are extremely difficult to induce. However, increasing evidence shows that additional non-neutralizing Abs play a significant role in decreasing the viral load, leading to partial and sometimes even total protection. Mechanisms suspected to participate in protection are numerous. They involve the Fc domain of Abs as well as their Fab part, and consequently the induced Ab isotype will be determinant for their functions, as well as the quantity and quality of the Fc-receptors (FcRs expressed on immune cells. Fc-mediated inhibitory functions, such as Ab-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, aggregation, and even immune activation have been proposed. However, as for nAbs, the non-neutralizing activities are limited to a subset of anti-HIV Abs. An improved in-depth characterization of the Abs displaying these functional responses is required for the development of new vaccination strategies, which aim to selectively trigger the B cells able to induce the right functional Ab combinations both at the right place and at the right time. This review summarizes our current knowledge on non-neutralizing functional inhibitory Abs and discusses the potential benefit of inducing them via vaccination. We also provide new insight into the roles of the FcγR-mediated Ab therapeutics in clinical trials for HIV diseases.

  3. Midplane neutral density profiles in the National Spherical Torus Experiment

    Energy Technology Data Exchange (ETDEWEB)

    Stotler, D. P., E-mail: dstotler@pppl.gov; Bell, R. E.; Diallo, A.; LeBlanc, B. P.; Podestà, M.; Roquemore, A. L.; Ross, P. W. [Princeton Plasma Physics Laboratory, Princeton University, P. O. Box 451, Princeton, New Jersey 08543-0451 (United States); Scotti, F. [Lawrence Livermore National Laboratory, Livermore, California 94551 (United States)

    2015-08-15

    Atomic and molecular density data in the outer midplane of NSTX [Ono et al., Nucl. Fusion 40, 557 (2000)] are inferred from tangential camera data via a forward modeling procedure using the DEGAS 2 Monte Carlo neutral transport code. The observed Balmer-β light emission data from 17 shots during the 2010 NSTX campaign display no obvious trends with discharge parameters such as the divertor Balmer-α emission level or edge deuterium ion density. Simulations of 12 time slices in 7 of these discharges produce molecular densities near the vacuum vessel wall of 2–8 × 10{sup 17 }m{sup −3} and atomic densities ranging from 1 to 7 × 10{sup 16 }m{sup −3}; neither has a clear correlation with other parameters. Validation of the technique, begun in an earlier publication, is continued with an assessment of the sensitivity of the simulated camera image and neutral densities to uncertainties in the data input to the model. The simulated camera image is sensitive to the plasma profiles and virtually nothing else. The neutral densities at the vessel wall depend most strongly on the spatial distribution of the source; simulations with a localized neutral source yield densities within a factor of two of the baseline, uniform source, case. The uncertainties in the neutral densities associated with other model inputs and assumptions are ≤50%.

  4. Operant conditioning of facial displays of pain.

    Science.gov (United States)

    Kunz, Miriam; Rainville, Pierre; Lautenbacher, Stefan

    2011-06-01

    The operant model of chronic pain posits that nonverbal pain behavior, such as facial expressions, is sensitive to reinforcement, but experimental evidence supporting this assumption is sparse. The aim of the present study was to investigate in a healthy population a) whether facial pain behavior can indeed be operantly conditioned using a discriminative reinforcement schedule to increase and decrease facial pain behavior and b) to what extent these changes affect pain experience indexed by self-ratings. In the experimental group (n = 29), the participants were reinforced every time that they showed pain-indicative facial behavior (up-conditioning) or a neutral expression (down-conditioning) in response to painful heat stimulation. Once facial pain behavior was successfully up- or down-conditioned, respectively (which occurred in 72% of participants), facial pain displays and self-report ratings were assessed. In addition, a control group (n = 11) was used that was yoked to the reinforcement plans of the experimental group. During the conditioning phases, reinforcement led to significant changes in facial pain behavior in the majority of the experimental group (p .136). Fine-grained analyses of facial muscle movements revealed a similar picture. Furthermore, the decline in facial pain displays (as observed during down-conditioning) strongly predicted changes in pain ratings (R(2) = 0.329). These results suggest that a) facial pain displays are sensitive to reinforcement and b) that changes in facial pain displays can affect self-report ratings.

  5. Confinement and βsub(p)-studies in neutral injection heated ASDEX plasmas

    International Nuclear Information System (INIS)

    Wagner, F.; Becker, G.; Behringer, K.; Campbell, D.; Eberhagen, A.; Engelhardt, W.; Fussmann, G.; Gehre, O.; Gernhardt, J.; Gierke, G. von; Haas, G.; Huang, M.; Karger, F.; Keilhacker, M.; Klueber, O.; Kornherr, M.; Lackner, K.; Lisitano, G.; Lister, G.G.; Mayer, H.M.; Meisel, D.; Mueller, E.R.; Murmann, H.; Niedermeyer, H.; Poschenrieder, W.; Rapp, H.; Roehr, H; Schneider, F.; Siller, G.; Speth, E.; Staebler, A.; Steuer, K.H.; Succi, S.; Venus, G.; Vollmer, O.

    1983-03-01

    Neutral injection experiments into limiter and divertor discharges in ASDEX are described with hydrogen and deuterium as working gas. Two operational regimes have been observed in neutral injection heated divertor discharges. One regime is characterized by deteriorated energy and particle confinement. The global energy confinement times are comparable to those of neutral injection heated limited discharges. Tthe other regime has particle and energy confinement times comparable to those of ohmic discharges with tausub(E) = 40 - 60 msec at beam powers up to 3.1 MW. This regime is further characterized by high βsub(p)-values comparable to the aspect ratio A (βsub(p) proportional 0.65 A), by good electron heating (etasub(e) proportional 2.5 x 10 13 eV cm -3 kW -1 ) and ion heating (etasub(i) proportional 4.2 x 10 13 eV cm -3 kW -1 ). In both regimes, tausub(E) increases with plasma current but there is hardly any variation with density. The differences in confinement and scaling to ohmic discharges seem to be caused by modifications of the electron loss channel. The high βsub(p)-regime develops at an injection power >=1.8 MW, anti nsub(e) >= 3 x 10 13 cm -3 and q >= 2.45, and is so far only observed in divertor discharges. There are indications that this may be due to the broad profiles with high edge temperatures which can develop in divertor discharges. An indication of broad current density profiles is given by the lack of sawtooth activity in these discharges. (orig.)

  6. Differences in pediatric vertical ground reaction force between planovalgus and neutrally aligned feet.

    Science.gov (United States)

    Pauk, Jolanta; Szymul, Joanna

    2014-01-01

    Ground reaction forces (GRF) reflect the force history of human body contact with the ground. The purpose of this study was to explore human gait abnormalities due to planovalgus by comparing vertical GRF data between individuals with planovalgus and those with neutrally aligned feet. Second we estimated associations between various measurements and vertical GRF parameters in a pediatric population. Boys and girls between the ages of 4 and 18 years (72 planovalgus feet and 74 neutrally aligned feet) took part in this study. Ground reaction forces were recorded by two Kistler platforms and normalized to body weight. Comparison of vertical GRF between planovalgus and neutrally aligned feet suggests that the first and the second peaks of vertical force (Fz1, Fz2) are most affected by planovalgus. The results also indicate that neutrally aligned feet display a different ground reaction force pattern than planovalgus, and that differences between boys and girls may be observed. The shape of the vertical GRF curve can help in clinical interpretation of abnormal gait.

  7. Biomechanics of the Peacock's Display: How Feather Structure and Resonance Influence Multimodal Signaling.

    Directory of Open Access Journals (Sweden)

    Roslyn Dakin

    Full Text Available Courtship displays may serve as signals of the quality of motor performance, but little is known about the underlying biomechanics that determines both their signal content and costs. Peacocks (Pavo cristatus perform a complex, multimodal "train-rattling" display in which they court females by vibrating the iridescent feathers in their elaborate train ornament. Here we study how feather biomechanics influences the performance of this display using a combination of field recordings and laboratory experiments. Using high-speed video, we find that train-rattling peacocks stridulate their tail feathers against the train at 25.6 Hz, on average, generating a broadband, pulsating mechanical sound at that frequency. Laboratory measurements demonstrate that arrays of peacock tail and train feathers have a broad resonant peak in their vibrational spectra at the range of frequencies used for train-rattling during the display, and the motion of feathers is just as expected for feathers shaking near resonance. This indicates that peacocks are able to drive feather vibrations energetically efficiently over a relatively broad range of frequencies, enabling them to modulate the feather vibration frequency of their displays. Using our field data, we show that peacocks with longer trains use slightly higher vibration frequencies on average, even though longer train feathers are heavier and have lower resonant frequencies. Based on these results, we propose hypotheses for future studies of the function and energetics of this display that ask why its dynamic elements might attract and maintain female attention. Finally, we demonstrate how the mechanical structure of the train feathers affects the peacock's visual display by allowing the colorful iridescent eyespots-which strongly influence female mate choice-to remain nearly stationary against a dynamic iridescent background.

  8. Using computer graphics to analyze the placement of neutral-beam injectors for the Mirror Fusion Test Facility

    International Nuclear Information System (INIS)

    Horvath, J.A.

    1977-01-01

    To optimize the neutral-beam current incident on the fusion plasma and limit the heat load on exposed surfaces of the Mirror Fusion Test Facility magnet coils, impingement of the neutral beams on the magnet structure must be minimized. Also, placement of the neutral-beam injectors must comply with specifications for neutral-current heating of the plasma and should allow maximum flexibility to accommodate alternative beam aiming patterns without significant hardware replacement or experiment down-time. Injector placements and aimings are analyzed by means of the Structural Analysis Movie Post Processor (SAMPP), a general-purpose graphics code for the display of three-dimensional finite-element models. SAMPP is used to visually assemble, disassemble, or cut away sections of the complex three-dimensional apparatus, which is represented by an assemblage of 8-node solid finite elements. The resulting picture is used to detect and quantify interactions between the structure and the neutral-particle beams

  9. Global panel of HIV-1 Env reference strains for standardized assessments of vaccine-elicited neutralizing antibodies.

    Science.gov (United States)

    deCamp, Allan; Hraber, Peter; Bailer, Robert T; Seaman, Michael S; Ochsenbauer, Christina; Kappes, John; Gottardo, Raphael; Edlefsen, Paul; Self, Steve; Tang, Haili; Greene, Kelli; Gao, Hongmei; Daniell, Xiaoju; Sarzotti-Kelsoe, Marcella; Gorny, Miroslaw K; Zolla-Pazner, Susan; LaBranche, Celia C; Mascola, John R; Korber, Bette T; Montefiori, David C

    2014-03-01

    Standardized assessments of HIV-1 vaccine-elicited neutralizing antibody responses are complicated by the genetic and antigenic variability of the viral envelope glycoproteins (Envs). To address these issues, suitable reference strains are needed that are representative of the global epidemic. Several panels have been recommended previously, but no clear answers have been available on how many and which strains are best suited for this purpose. We used a statistical model selection method to identify a global panel of reference Env clones from among 219 Env-pseudotyped viruses assayed in TZM-bl cells with sera from 205 HIV-1-infected individuals. The Envs and sera were sampled globally from diverse geographic locations and represented all major genetic subtypes and circulating recombinant forms of the virus. Assays with a panel size of only nine viruses adequately represented the spectrum of HIV-1 serum neutralizing activity seen with the larger panel of 219 viruses. An optimal panel of nine viruses was selected and augmented with three additional viruses for greater genetic and antigenic coverage. The spectrum of HIV-1 serum neutralizing activity seen with the final 12-virus panel closely approximated the activity seen with subtype-matched viruses. Moreover, the final panel was highly sensitive for detection of many of the known broadly neutralizing antibodies. For broader assay applications, all 12 Env clones were converted to infectious molecular clones using a proviral backbone carrying a Renilla luciferase reporter gene (Env.IMC.LucR viruses). This global panel should facilitate highly standardized assessments of vaccine-elicited neutralizing antibodies across multiple HIV-1 vaccine platforms in different parts of the world. An effective HIV-1 vaccine will need to overcome the extraordinary genetic variability of the virus, where most variation occurs in the viral envelope glycoproteins that are the sole targets for neutralizing antibodies. Efforts to elicit

  10. 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.

  11. Biomechanics of the Peacock’s Display: How Feather Structure and Resonance Influence Multimodal Signaling

    Science.gov (United States)

    Dakin, Roslyn; McCrossan, Owen; Hare, James F.; Montgomerie, Robert; Amador Kane, Suzanne

    2016-01-01

    Courtship displays may serve as signals of the quality of motor performance, but little is known about the underlying biomechanics that determines both their signal content and costs. Peacocks (Pavo cristatus) perform a complex, multimodal “train-rattling” display in which they court females by vibrating the iridescent feathers in their elaborate train ornament. Here we study how feather biomechanics influences the performance of this display using a combination of field recordings and laboratory experiments. Using high-speed video, we find that train-rattling peacocks stridulate their tail feathers against the train at 25.6 Hz, on average, generating a broadband, pulsating mechanical sound at that frequency. Laboratory measurements demonstrate that arrays of peacock tail and train feathers have a broad resonant peak in their vibrational spectra at the range of frequencies used for train-rattling during the display, and the motion of feathers is just as expected for feathers shaking near resonance. This indicates that peacocks are able to drive feather vibrations energetically efficiently over a relatively broad range of frequencies, enabling them to modulate the feather vibration frequency of their displays. Using our field data, we show that peacocks with longer trains use slightly higher vibration frequencies on average, even though longer train feathers are heavier and have lower resonant frequencies. Based on these results, we propose hypotheses for future studies of the function and energetics of this display that ask why its dynamic elements might attract and maintain female attention. Finally, we demonstrate how the mechanical structure of the train feathers affects the peacock’s visual display by allowing the colorful iridescent eyespots–which strongly influence female mate choice–to remain nearly stationary against a dynamic iridescent background. PMID:27119380

  12. 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.

  13. 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)

    Hu, Weibin; Chen, Aizhong; Miao, Yi; Xia, Shengli; Ling, Zhiyang; Xu, Ke; Wang, Tongyan; Xu, Ying; Cui, Jun; Wu, Hongqiang; Hu, Guiyu; Tian, Lin; Wang, Lingling; Shu, Yuelong; Ma, Xiaowei; Xu, Bianli; Zhang, Jin; Lin, Xiaojun; Bian, Chao; Sun, Bing

    2013-01-01

    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.

  14. Climate Neutral Campus Key Terms and Definitions | Climate Neutral Research

    Science.gov (United States)

    Campuses | NREL Neutral Campus Key Terms and Definitions Climate Neutral Campus Key Terms and Definitions The term climate neutral evolved along with net zero and a number of other "green" and accuracy in these areas lets research campuses know exactly how close they are to climate

  15. 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 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.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.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-protective immunity, and the potential escape evolution for EV71 still need to

  16. Directed Selection of Recombinant Human Monoclonal Antibodies to Herpes Simplex Virus Glycoproteins from Phage Display Libraries

    Science.gov (United States)

    Sanna, Pietro Paolo; Williamson, R. Anthony; de Logu, Alessandro; Bloom, Floyd E.; Burton, Dennis R.

    1995-07-01

    Human monoclonal antibodies have considerable potential in the prophylaxis and treatment of viral disease. However, only a few such antibodies suitable for clinical use have been produced to date. We have previously shown that large panels of human recombinant monoclonal antibodies against a plethora of infectious agents, including herpes simplex virus types 1 and 2, can be established from phage display libraries. Here we demonstrate that facile cloning of recombinant Fab fragments against specific viral proteins in their native conformation can be accomplished by panning phage display libraries against viral glycoproteins "captured" from infected cell extracts by specific monoclonal antibodies immobilized on ELISA plates. We have tested this strategy by isolating six neutralizing recombinant antibodies specific for herpes simplex glycoprotein gD or gB, some of which are against conformationally sensitive epitopes. By using defined monoclonal antibodies for the antigen-capture step, this method can be used for the isolation of antibodies to specific regions and epitopes within the target viral protein. For instance, monoclonal antibodies to a nonneutralizing epitope can be used in the capture step to clone antibodies to neutralizing epitopes, or antibodies to a neutralizing epitope can be used to clone antibodies to a different neutralizing epitope. Furthermore, by using capturing antibodies to more immunodominant epitopes, one can direct the cloning to less immunogenic ones. This method should be of value in generating antibodies to be used both in the prophylaxis and treatment of viral infections and in the characterization of the mechanisms of antibody protective actions at the molecular level.

  17. Complexation of metal ions with humic acid: charge neutralization model

    International Nuclear Information System (INIS)

    Kim, J.I.; Czerwinski, K.R.

    1995-01-01

    A number of different approaches are being used for describing the complexation equilibrium of actinide ions with humic or fulvic acid. The approach chosen and verified experimentally by Tu Muenchen will be discussed with notable examples from experiment. This approach is based on the conception that a given actinide ion is neutralized upon complexation with functional groups of humic or fulvic acid, e.g. carboxylic and phenolic groups, which are known as heterogeneously cross-linked polyelectrolytes. The photon energy transfer experiment with laser light excitation has shown that the actinide ion binding with the functional groups is certainly a chelation process accompanied by metal ion charge neutralization. This fact is in accordance with the experimental evidence of the postulated thermodynamic equilibrium reaction. The experimental results are found to be independent of origin of humic or fulvic acid and applicable for a broad range of pH. (authors). 23 refs., 7 figs., 1 tab

  18. Attainment of high confinement in neutral beam heated divertor discharges in the PDX tokamak

    International Nuclear Information System (INIS)

    Kaye, S.M.; Bell, M.; Bol, K.

    1983-11-01

    The PDX divertor configuration has recently been converted from an open to a closed geometry to inhibit the return of neutral gas from the divertor region to the main chamber. Since then, operation in a regime with high energy confinement in neutral beam heated discharges (ASDEX H-mode) has been routine over a wide range of operating conditions. These H-mode discharges are characterized by a sudden drop in divertor density and H/sub α/ emission and a spontaneous rise in main chamber plasma density during neutral beam injection. The confinement time is found to scale nearly linearly with plasma current, but it can be degraded due to either the presence of edge instabilities or heavy gas puffing. Detailed Thomson scattering temperature profiles show high values of Te near the plasma edge (approx. 450 eV) with sharp radial gradients (approx. 400 eV/cm) near the separatrix. Density profiles are broad and also exhibit steep gradients close to the separatrix

  19. Neutrality Versus Materiality: A Thermodynamic Theory of Neutral Surfaces

    Directory of Open Access Journals (Sweden)

    Rémi Tailleux

    2016-09-01

    Full Text Available In this paper, a theory for constructing quasi-neutral density variables γ directly in thermodynamic space is formulated, which is based on minimising the absolute value of a purely thermodynamic quantity J n . Physically, J n has a dual dynamic/thermodynamic interpretation as the quantity controlling the energy cost of adiabatic and isohaline parcel exchanges on material surfaces, as well as the dependence of in-situ density on spiciness, in a description of water masses based on γ, spiciness and pressure. Mathematically, minimising | J n | in thermodynamic space is showed to be equivalent to maximising neutrality in physical space. The physics of epineutral dispersion is also reviewed and discussed. It is argued, in particular, that epineutral dispersion is best understood as the aggregate effect of many individual non-neutral stirring events (being understood here as adiabatic and isohaline events with non-zero buoyancy, so that it is only the net displacement aggregated over many events that is approximately neutral. This new view resolves an apparent paradox between the focus in neutral density theory on zero-buoyancy motions and the overwhelming evidence that lateral dispersion in the ocean is primarily caused by non-zero buoyancy processes such as tides, residual currents and sheared internal waves. The efficiency by which a physical process contributes to lateral dispersion can be characterised by its energy signature, with those processes releasing available potential energy (negative energy cost being more efficient than purely neutral processes with zero energy cost. The latter mechanism occurs in the wedge of instability, and its source of energy is the coupling between baroclinicity, thermobaricity, and density compensated temperature/salinity anomalies. Such a mechanism, which can only exist in a salty ocean, is speculated to be important for dissipating spiciness anomalies and neutral helicity. The paper also discusses potential

  20. Younger and older adults' perception of the Wundt-Hering illusion as a function of display illumination and reflectance contrast.

    Science.gov (United States)

    Astor-Stetson, E; Lane, S

    1991-08-01

    Reflectance contrast (i.e., black as compared to grey figures on white ground) and display illumination were manipulated to vary the brightness contrast of Wundt-Hering figures. 16 college students and 16 older adults were presented with high, medium, and low reflectance contrast figures. For half the participants, display illumination was manipulated by covering the figures with a .5 yellow neutral density filter. Magnitude of the illusion increased significantly with increased reflectance contrast for college students, and college students were significantly more susceptible to the high contrast figures than were older adults. Display illumination had no effect on the performance of either group.

  1. PC-Link historical data base system MODCOMP/IBM at link for neutral particle beam operation

    International Nuclear Information System (INIS)

    Thurgood, P.

    1989-01-01

    PC-Link is a combination of hardware and software that connects an IBM PC/AT to a MODCOMP minicomputer. It is designed as an aid to the Neutral Beam operations coordinator during injection into the DIII-D tokamak project. An IBM PC/AT is linked to 4 MODCOMP realtime acquisition systems, each of which controls 2 neutral particle beam sources. At various points in the shot sequence, data is sent to the IBM PC/AT. This data can then be integrated with the data from the other sources into tables or graphics displays for use by the Beam Coordinator. In this way, the coordinator gets realtime feedback on the relative settings and performance of the sources and can observe trends within a particular source at one location. The PC-Link is used for observing relative timing information and for post shot historical archiving. The concept of the PC-Link was originally proposed several years ago. In April 1988, in-house implementation of the link software was begun. The PC-Link receives approximately 2 Kbytes of data per source per shot. This data is converted from MODCOMP format to IBM PC format and archived to disk. The last 280 shots per source are stored to disk to observe trends. The data can be displayed in a number of formats depending upon the situation. For example, prior to a shot, the beam MODCOMPs are sent timing information from the DIII-D tokamak control system. This data is echoed on the PC in a graphical representation displaying all 8 sources. At the end of the shot, the actual running times are displayed along with the requested settings. Any subset of the Historical data may be displayed either graphically or in tables for realtime comparisons between sources. 4 figs

  2. Predicting HIV-1 transmission and antibody neutralization efficacy in vivo from stoichiometric parameters.

    Directory of Open Access Journals (Sweden)

    Oliver F Brandenberg

    2017-05-01

    Full Text Available The potential of broadly neutralizing antibodies targeting the HIV-1 envelope trimer to prevent HIV-1 transmission has opened new avenues for therapies and vaccines. However, their implementation remains challenging and would profit from a deepened mechanistic understanding of HIV-antibody interactions and the mucosal transmission process. In this study we experimentally determined stoichiometric parameters of the HIV-1 trimer-antibody interaction, confirming that binding of one antibody is sufficient for trimer neutralization. This defines numerical requirements for HIV-1 virion neutralization and thereby enables mathematical modelling of in vitro and in vivo antibody neutralization efficacy. The model we developed accurately predicts antibody efficacy in animal passive immunization studies and provides estimates for protective mucosal antibody concentrations. Furthermore, we derive estimates of the probability for a single virion to start host infection and the risks of male-to-female HIV-1 transmission per sexual intercourse. Our work thereby delivers comprehensive quantitative insights into both the molecular principles governing HIV-antibody interactions and the initial steps of mucosal HIV-1 transmission. These insights, alongside the underlying, adaptable modelling framework presented here, will be valuable for supporting in silico pre-trial planning and post-hoc evaluation of HIV-1 vaccination or antibody treatment trials.

  3. Modeling of the lithium based neutralizer for ITER neutral beam injector

    Energy Technology Data Exchange (ETDEWEB)

    Dure, F., E-mail: franck.dure@u-psud.fr [LPGP, Laboratoire de Physique des Gaz et Plasmas, CNRS-Universite Paris Sud, Orsay (France); Lifschitz, A.; Bretagne, J.; Maynard, G. [LPGP, Laboratoire de Physique des Gaz et Plasmas, CNRS-Universite Paris Sud, Orsay (France); Simonin, A. [IRFM, Institut de Recherche sur la Fusion Magnetique, CEA Cadarache, 13108 Saint-Paul lez Durance (France); Minea, T. [LPGP, Laboratoire de Physique des Gaz et Plasmas, CNRS-Universite Paris Sud, Orsay (France)

    2012-04-04

    Highlights: Black-Right-Pointing-Pointer We compare different lithium based neutraliser configurations to the deuterium one. Black-Right-Pointing-Pointer We study characteristics of the secondary plasma and the propagation of the 1 MeV beam. Black-Right-Pointing-Pointer Using lithium increases the neutralisation effiency keeping correct beam focusing. Black-Right-Pointing-Pointer Using lithium also reduces the backstreaming effect in direction of the ion source. - Abstract: To achieve thermonuclear temperatures necessary to produce fusion reactions in the ITER Tokamak, additional heating systems are required. One of the main method to heat the plasma ions in ITER will be the injection of energetic neutrals (NBI). In the neutral beam injector, negative ions (D{sup -}) are electrostatically accelerated to 1 MeV, and then stripped of their extra electron via collisions with a target gas, in a structure known as neutralizer. In the current ITER specification, the target gas is deuterium. It has been recently proposed to use lithium vapor instead of deuterium as target gas in the neutralizer. This would allow to reduce the gas load in the NBI vessel and to improve the neutralization efficiency. A Particle-in-Cell Monte Carlo code has been developed to study the transport of the beams and the plasma formation in the neutralizer. A comparison between Li and D{sub 2} based neutralizers made with this code is presented here, as well as a parametric study on the geometry of the Li based neutralizer. Results demonstrate the feasibility of a Li based neutralizer, and its advantages with respect to the deuterium based one.

  4. Minor Capsid Protein L2 Polytope Induces Broad Protection against Oncogenic and Mucosal Human Papillomaviruses.

    Science.gov (United States)

    Pouyanfard, Somayeh; Spagnoli, Gloria; Bulli, Lorenzo; Balz, Kathrin; Yang, Fan; Odenwald, Caroline; Seitz, Hanna; Mariz, Filipe C; Bolchi, Angelo; Ottonello, Simone; Müller, Martin

    2018-02-15

    The amino terminus of the human papillomavirus (HPV) minor capsid protein L2 contains a major cross-neutralization epitope which provides the basis for the development of a broadly protecting HPV vaccine. A wide range of protection against different HPV types would eliminate one of the major drawbacks of the commercial, L1-based prophylactic vaccines. Previously, we have reported that insertion of the L2 epitope into a scaffold composed of bacterial thioredoxin protein generates a potent antigen inducing comprehensive protection against different animal and human papillomaviruses. We also reported, however, that although protection is broad, some oncogenic HPV types escape the neutralizing antibody response, if L2 epitopes from single HPV types are used as immunogen. We were able to compensate for this by applying a mix of thioredoxin proteins carrying L2 epitopes from HPV16, -31, and -51. As the development of a cost-efficient HPV prophylactic vaccines is one of our objectives, this approach is not feasible as it requires the development of multiple good manufacturing production processes in combination with a complex vaccine formulation. Here, we report the development of a thermostable thioredoxin-based single-peptide vaccine carrying an L2 polytope of up to 11 different HPV types. The L2 polytope antigens have excellent abilities in respect to broadness of protection and robustness of induced immune responses. To further increase immunogenicity, we fused the thioredoxin L2 polytope antigen with a heptamerization domain. In the final vaccine design, we achieve protective responses against all 14 oncogenic HPV types that we have analyzed plus the low-risk HPVs 6 and 11 and a number of cutaneous HPVs. IMPORTANCE Infections by a large number of human papillomaviruses lead to malignant and nonmalignant disease. Current commercial vaccines based on virus-like particles (VLPs) effectively protect against some HPV types but fail to do so for most others. Further, only

  5. Yeast cell surface display for lipase whole cell catalyst and its applications

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yun; Zhang, Rui; Lian, Zhongshuai; Wang, Shihui; Wright, Aaron T.

    2014-08-01

    The cell surface display technique allows for the expression of target proteins or peptides on the microbial cell surface by fusing an appropriate protein as an anchoring motif. Yeast display systems, such as Pichia pastoris, Yarowia lipolytica and Saccharomyces cerevisiae, are ideal, alternative and extensive display systems with the advantage of simple genetic manipulation and post-translational modification of expressed heterologous proteins. Engineered yeasts show high performance characteristics and variant utilizations. Herein, we comprehensively summarize the variant factors affecting lipase whole cell catalyst activity and display efficiency, including the structure and size of target proteins, screening anchor proteins, type and chain length of linkers, and the appropriate matching rules among the above-mentioned display units. Furthermore, we also address novel approaches to enhance stability and activity of recombinant lipases, such as VHb gene co-expression, multi-enzyme co-display technique, and the micro-environmental interference and self-assembly techniques. Finally, we represent the variety of applications of whole cell surface displayed lipases on yeast cells in non-aqueous phases, including synthesis of esters, PUFA enrichment, resolution of chiral drugs, organic synthesis and biofuels. We demonstrate that the lipase surface display technique is a powerful tool for functionalizing yeasts to serve as whole cell catalysts, and increasing interest is providing an impetus for broad application of this technique.

  6. Identification of a CD4-Binding-Site Antibody to HIV that Evolved Near-Pan Neutralization Breadth

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Jinghe; Kang, Byong H.; Ishida, Elise; Zhou, Tongqing; Griesman, Trevor; Sheng, Zizhang; Wu, Fan; Doria-Rose, Nicole A.; Zhang, Baoshan; McKee, Krisha; O’Dell, Sijy; Chuang, Gwo-Yu; Druz, Aliaksandr; Georgiev, Ivelin S.; Schramm, Chaim A.; Zheng, Anqi; Joyce, M.  Gordon; Asokan, Mangaiarkarasi; Ransier, Amy; Darko, Sam; Migueles, Stephen A.; Bailer, Robert T.; Louder, Mark K.; Alam, S.  Munir; Parks, Robert; Kelsoe, Garnett; Von Holle, Tarra; Haynes, Barton F.; Douek, Daniel C.; Hirsch, Vanessa; Seaman, Michael S.; Shapiro, Lawrence; Mascola, John R.; Kwong, Peter D.; Connors, Mark

    2016-11-01

    Detailed studies of the broadly neutralizing antibodies (bNAbs) that underlie the best available examples of the humoral immune response to HIV are providing important information for the development of therapies and prophylaxis for HIV-1 infection. Here, we report a CD4-binding site (CD4bs) antibody, named N6, that potently neutralized 98% of HIV-1 isolates, including 16 of 20 that were resistant to other members of its class. N6 evolved a mode of recognition such that its binding was not impacted by the loss of individual contacts across the immunoglobulin heavy chain. In addition, structural analysis revealed that the orientation of N6 permitted it to avoid steric clashes with glycans, which is a common mechanism of resistance. Thus, an HIV-1-specific bNAb can achieve potent, near-pan neutralization of HIV-1, making it an attractive candidate for use in therapy and prophylaxis.

  7. Perceptual load vs. dilution: the roles of attentional focus, stimulus category, and target predictability.

    Science.gov (United States)

    Chen, Zhe; Cave, Kyle R

    2013-01-01

    Many studies have shown that increasing the number of neutral stimuli in a display decreases distractor interference. This result has been interpreted within two different frameworks; a perceptual load account, based on a reduction in spare resources, and a dilution account, based on a degradation in distractor representation and/or an increase in crosstalk between the distractor and the neutral stimuli that contain visually similar features. In four experiments, we systematically manipulated the extent of attentional focus, stimulus category, and preknowledge of the target to examine how these factors would interact with the display set size to influence the degree of distractor processing. Display set size did not affect the degree of distractor processing in all situations. Increasing the number of neutral items decreased distractor processing only when a task induced a broad attentional focus that included the neutral stimuli, when the neutral stimuli were in the same category as the target and distractor, and when the preknowledge of the target was insufficient to guide attention to the target efficiently. These results suggest that the effect of neutral stimuli on the degree of distractor processing is more complex than previously assumed. They provide new insight into the competitive interactions between bottom-up and top-down processes that govern the efficiency of visual selective attention.

  8. Plasmons in inhomogeneously doped neutral and charged graphene nanodisks

    Energy Technology Data Exchange (ETDEWEB)

    Silveiro, Iván [ICFO-Institut de Ciencies Fotoniques, Mediterranean Technology Park, 08860 Castelldefels (Barcelona) (Spain); Javier García de Abajo, F., E-mail: javier.garciadeabajo@icfo.es [ICFO-Institut de Ciencies Fotoniques, Mediterranean Technology Park, 08860 Castelldefels (Barcelona) (Spain); ICREA-Institució Catalana de Recerca i Estudis Avançats, Passeig Lluís Companys, 23, 08010 Barcelona (Spain)

    2014-03-31

    We study plasmons in graphene nanodisks including the effect of inhomogeneity in the distribution of the doping charge. Specifically, we discuss the following two configurations: charged disks containing a fixed amount of additional carriers, which are self-consistently distributed along the surface to produce a uniform DC potential; and neutral disks exposed to a neighboring external point charge. A suitable finite-element method is elaborated to compute the charge density associated with the plasmons in the electrostatic limit. For charged disks, we find dipolar plasmons similar to those of uniformly doped graphene structures, in which the plasmon induced charge piles up near the edges. In contrast, in neutral disks placed near an external point charge, plasmons are strongly localized away from the edges. Surprisingly, a single external electron is enough to trap plasmons. The disks also display axially symmetric dark-plasmons, which can be excited through external illumination by coupling them to a neighboring metallic element. Our results have practical relevance for graphene nanophotonics under inhomogeneous doping conditions.

  9. Complexes of neutralizing and non-neutralizing affinity matured Fabs with a mimetic of the internal trimeric coiled-coil of HIV-1 gp41.

    Directory of Open Access Journals (Sweden)

    Elena Gustchina

    Full Text Available A series of mini-antibodies (monovalent and bivalent Fabs targeting the conserved internal trimeric coiled-coil of the N-heptad repeat (N-HR of HIV-1 gp41 has been previously constructed and reported. Crystal structures of two closely related monovalent Fabs, one (Fab 8066 broadly neutralizing across a wide panel of HIV-1 subtype B and C viruses, and the other (Fab 8062 non-neutralizing, representing the extremes of this series, were previously solved as complexes with 5-Helix, a gp41 pre-hairpin intermediate mimetic. Binding of these Fabs to covalently stabilized chimeric trimers of N-peptides of HIV-1 gp41 (named (CCIZN363 or 3-H has now been investigated using X-ray crystallography, cryo-electron microscopy, and a variety of biophysical methods. Crystal structures of the complexes between 3-H and Fab 8066 and Fab 8062 were determined at 2.8 and 3.0 Å resolution, respectively. Although the structures of the complexes with the neutralizing Fab 8066 and its non-neutralizing counterpart Fab 8062 were generally similar, small differences between them could be correlated with the biological properties of these antibodies. The conformations of the corresponding CDRs of each antibody in the complexes with 3-H and 5-Helix are very similar. The adaptation to a different target upon complex formation is predominantly achieved by changes in the structure of the trimer of N-HR helices, as well as by adjustment of the orientation of the Fab molecule relative to the N-HR in the complex, via rigid-body movement. The structural data presented here indicate that binding of three Fabs 8062 with high affinity requires more significant changes in the structure of the N-HR trimer compared to binding of Fab 8066. A comparative analysis of the structures of Fabs complexed to different gp41 intermediate mimetics allows further evaluation of biological relevance for generation of neutralizing antibodies, as well as provides novel structural insights into immunogen

  10. Interplay of HIV-1 phenotype and neutralizing antibody response in pathogenesis of AIDS.

    Science.gov (United States)

    Scarlatti, G; Leitner, T; Hodara, V; Jansson, M; Karlsson, A; Wahlberg, J; Rossi, P; Uhlén, M; Fenyö, E M; Albert, J

    1996-06-01

    A majority of human immunodeficiency virus type 1 (HIV-1) infected individuals display a rapid loss of CD4+ lymphocytes with fast progression towards overt acquired immunodeficiency syndrome (AIDS). However, a small proportion of individuals infected by HIV-1 remain immunologically intact for many years. In order to identify factors that might influence the pathogenesis of HIV-1 infection, 21 Italian mothers and 11 Swedish homosexual men were studied for the presence of autologous neutralizing antibodies in serum, biological phenotype of virus isolates and envelope variable region 3 (V3) sequences. The results were compared to the risk of mother-to-child transmission and progression of the disease. The presence of a neutralizing antibody response to the autologous virus as well as a virus with slow replicative capacity were linked both to low risk of mother-to-child transmission and non-progression of the disease. Patients whose peripheral blood mononuclear cells contained a mutation in the tip of the V3 loop (Arg318 to serine, lysine or leucine) significantly more often had neutralizing antibodies to autologous virus isolates containing arginine at this position. Thus, it appears that the interplay and balance between neutralizing antibody response of the host and the biological phenotype of HIV-1 strongly influence pathogenesis.

  11. Event displays highlighting the main properties of heavy flavour jets in the CMS Experiment

    CERN Multimedia

    Skovpen, Kirill

    2017-01-01

    A broad range of physics analyses at CMS rely on the efficient identification of heavy flavour jets. Identification of these objects is a challenging task, especially in the presence of a large number of multiple interactions per bunch crossing. The presented summary contains a set of graphical displays of reconstructed events in data collected by CMS in proton-proton collisions at 13 TeV in 2016. The displays highlight the main properties of heavy flavour jets in several event topologies, including QCD multijet, top quark pair, W+c and boosted H→bb.

  12. Rheological evaluation of simulated neutralized current acid waste

    International Nuclear Information System (INIS)

    Fow, C.L.; McCarthy, D.; Thornton, G.T.

    1986-06-01

    A byproduct of the Purex process is an aqueous waste stream that contains fission products. This waste stream, called current acid waste, is chemically neutralized and stored in double shell tanks on the Hanford Site. This neutralized current acid waste (NCAW) will be transported by pipe to B-Plant, a processing plant on the Hanford Site. Rheological and transport properties of NCAW slurry were evaluated. First, researchers conducted lab rheological evaluations of simulated NCAW. The results of these evaluations were then correlated with classical rheological models and scaled up to predict the performance that is likely to occur in the full-scale system. The NCAW in the tank will either be retrieved as is, i.e., no change in the concentration presently in the tank, or will be slightly concentrated before retrieval. Sluicing may be required to retrieve the solids. Three concentrations of simulated NCAW were evaluated that would simulate the different retrieval options: NCAW in the concentration that is presently in the tank; a slightly concentrated NCAW, called NCAW5.5; and equal parts of NCAW settled solids and water (simulating the sluicing stage), called NCAW1:1. The physical and rheological properties of three samples of each concentration at 25 and 100 0 C were evaluated in the laboratory. The properties displayed by NCAW and NCAW5.5 at 25 and 100 0 C allowed it to be classified as a pseudoplastic non-Newtonian fluid. NCAW1:1 at 25 and 100 0 C displayed properties of a yield-pseudoplastic non-Newtonian fluid. The classical non-Newtonian models for pseudoplastic and yield-pseudoplastic fluids were used with the laboratory data to predict the full-scale pump-pipe network parameters

  13. A distributed system of wireless signs using Gyricon electronic paper displays

    Science.gov (United States)

    Sprague, Robert A.

    2006-04-01

    The proliferation of digital information is leading to a wide range of applications which make it desirable to display data easily in many locations, all changeable and updateable. The difficulty in achieving such ubiquitous displays is the cost of signage, the cost of installation, and the software and systems to control the information being sent to each of these signs. In this paper we will talk about a networked system of such signs which are made from gyricon electronic paper. Gyricon electronic paper is a reflective, bistable display which can be made in large web sheets at a reasonable price. Since it does not require a backlight nor does it require power to refresh the display image, such technology is ideal for making signs which can be run on batteries with extremely long battery life, often not needing replacement for years. The display also has a very broad illumination scattering profile which makes it readily viewable from any angle. The basic operating mechanism of the display, its manufacturing technique, and achieved performance will be described, along with the description of a networked solution using many such signs controlled with system software to identify speakers and meetings in conference rooms, hospitality suites, or classrooms in universities. Systems will also be shown which are adapted to retail pricing signage and others which can be used for large format outdoor billboards.

  14. B cell clonal lineage alterations upon recombinant HIV-1 envelope immunization of Rhesus macaques

    Science.gov (United States)

    Broadly neutralizing HIV-1 antibodies (bNAbs) isolated from infected subjects display protective potential in animal models. Their elicitation by immunization is thus highly desirable. The HIV-1 envelope glycoprotein (Env) is the sole viral target of bnAbs, but is also targeted by binding, non-neutr...

  15. Study of neutral particles

    International Nuclear Information System (INIS)

    Bartel, W.; Bulos, F.; Eisner, A.

    1975-01-01

    The range of physics problems for which a detector emphasizing neutrals is most suitable is discussed. The primary goals are the all neutrals cross section, sigma/sub o/ (e + e - → neutrals), the characterization of the neutral energy in multi-hadronic events, the search for monoenergetic photons, and good sensitivity in the difficult region of low energy photons. Those features of multi-hadronic events which are most relevant to a neutral detector were calculated using a jet model with parameters extrapolated from SPEAR energies. These distributions are presented and discussed

  16. The Effects of Transient Emotional State and Workload on Size Scaling in Perspective Displays

    Energy Technology Data Exchange (ETDEWEB)

    Tuan Q. Tran; Kimberly R. Raddatz

    2006-10-01

    Previous research has been devoted to the study of perceptual (e.g., number of depth cues) and cognitive (e.g., instructional set) factors that influence veridical size perception in perspective displays. However, considering that perspective displays have utility in high workload environments that often induce high arousal (e.g., aircraft cockpits), the present study sought to examine the effect of observers’ emotional state on the ability to perceive and judge veridical size. Within a dual-task paradigm, observers’ ability to make accurate size judgments was examined under conditions of induced emotional state (positive, negative, neutral) and high and low workload. Results showed that participants in both positive and negative induced emotional states were slower to make accurate size judgments than those not under induced emotional arousal. Results suggest that emotional state is an important factor that influences visual performance on perspective displays and is worthy of further study.

  17. ON NEUTRAL ABSORPTION AND SPECTRAL EVOLUTION IN X-RAY BINARIES

    International Nuclear Information System (INIS)

    Miller, J. M.; Cackett, E. M.; Reis, R. C.

    2009-01-01

    Current X-ray observatories make it possible to follow the evolution of transient and variable X-ray binaries across a broad range in luminosity and source behavior. In such studies, it can be unclear whether evolution in the low-energy portion of the spectrum should be attributed to evolution in the source, or instead to evolution in neutral photoelectric absorption. Dispersive spectrometers make it possible to address this problem. We have analyzed a small but diverse set of X-ray binaries observed with the Chandra High Energy Transmission Grating Spectrometer across a range in luminosity and different spectral states. The column density in individual photoelectric absorption edges remains constant with luminosity, both within and across source spectral states. This finding suggests that absorption in the interstellar medium strongly dominates the neutral column density observed in spectra of X-ray binaries. Consequently, evolution in the low-energy spectrum of X-ray binaries should properly be attributed to evolution in the source spectrum. We discuss our results in the context of X-ray binary spectroscopy with current and future X-ray missions.

  18. 3D display system using monocular multiview displays

    Science.gov (United States)

    Sakamoto, Kunio; Saruta, Kazuki; Takeda, Kazutoki

    2002-05-01

    A 3D head mounted display (HMD) system is useful for constructing a virtual space. The authors have researched the virtual-reality systems connected with computer networks for real-time remote control and developed a low-priced real-time 3D display for building these systems. We developed a 3D HMD system using monocular multi-view displays. The 3D displaying technique of this monocular multi-view display is based on the concept of the super multi-view proposed by Kajiki at TAO (Telecommunications Advancement Organization of Japan) in 1996. Our 3D HMD has two monocular multi-view displays (used as a visual display unit) in order to display a picture to the left eye and the right eye. The left and right images are a pair of stereoscopic images for the left and right eyes, then stereoscopic 3D images are observed.

  19. Structure-Based Design of Hepatitis C Virus Vaccines That Elicit Neutralizing Antibody Responses to a Conserved Epitope

    Energy Technology Data Exchange (ETDEWEB)

    Pierce, Brian G.; Boucher, Elisabeth N.; Piepenbrink, Kurt H.; Ejemel, Monir; Rapp, Chelsea A.; Thomas, William D.; Sundberg, Eric J.; Weng, Zhiping; Wang, Yang; Diamond, Michael S.

    2017-08-09

    Despite recent advances in therapeutic options, hepatitis C virus (HCV) remains a severe global disease burden, and a vaccine can substantially reduce its incidence. Due to its extremely high sequence variability, HCV can readily escape the immune response; thus, an effective vaccine must target conserved, functionally important epitopes. Using the structure of a broadly neutralizing antibody in complex with a conserved linear epitope from the HCV E2 envelope glycoprotein (residues 412 to 423; epitope I), we performed structure-based design of immunogens to induce antibody responses to this epitope. This resulted in epitope-based immunogens based on a cyclic defensin protein, as well as a bivalent immunogen with two copies of the epitope on the E2 surface. We solved the X-ray structure of a cyclic immunogen in complex with the HCV1 antibody and confirmed preservation of the epitope conformation and the HCV1 interface. Mice vaccinated with our designed immunogens produced robust antibody responses to epitope I, and their serum could neutralize HCV. Notably, the cyclic designs induced greater epitope-specific responses and neutralization than the native peptide epitope. Beyond successfully designing several novel HCV immunogens, this study demonstrates the principle that neutralizing anti-HCV antibodies can be induced by epitope-based, engineered vaccines and provides the basis for further efforts in structure-based design of HCV vaccines.

    IMPORTANCEHepatitis C virus is a leading cause of liver disease and liver cancer, with approximately 3% of the world's population infected. To combat this virus, an effective vaccine would have distinct advantages over current therapeutic options, yet experimental vaccines have not been successful to date, due in part to the virus's high sequence variability leading to immune escape. In this study, we rationally designed several vaccine immunogens based on the structure of a conserved epitope that

  20. Circular displays: control/display arrangements and stereotype strength with eight different display locations.

    Science.gov (United States)

    Chan, Alan H S; Hoffmann, Errol R

    2015-01-01

    Two experiments are reported that were designed to investigate control/display arrangements having high stereotype strengths when using circular displays. Eight display locations relative to the operator and control were tested with rotational and translational controls situated on different planes according to the Frame of Reference Transformation Tool (FORT) model of Wickens et al. (2010). (Left. No, Right! Development of the Frame of Reference Transformation Tool (FORT), Proceedings of the Human Factors and Ergonomics Society 54th Annual Meeting, 54: 1022-1026). In many cases, there was little effect of display locations, indicating the importance of the Worringham and Beringer (1998. Directional stimulus-response compatibility: a test of three alternative principles. Ergonomics, 41(6), 864-880) Visual Field principle and an extension of this principle for rotary controls (Hoffmann and Chan (2013). The Worringham and Beringer 'visual field' principle for rotary controls. Ergonomics, 56(10), 1620-1624). The initial indicator position (12, 3, 6 and 9 o'clock) had a major effect on control/display stereotype strength for many of the six controls tested. Best display/control arrangements are listed for each of the different control types (rotational and translational) and for the planes on which they are mounted. Data have application where a circular display is used due to limited display panel space and applies to space-craft, robotics operators, hospital equipment and home appliances. Practitioner Summary: Circular displays are often used when there is limited space available on a control panel. Display/control arrangements having high stereotype strength are listed for four initial indicator positions. These arrangements are best for design purposes.

  1. Mapping Determinants of Virus Neutralization and Viral Escape for Rational Design of a Hepatitis C Virus Vaccine

    Directory of Open Access Journals (Sweden)

    Mei-Le Keck

    2018-05-01

    Full Text Available Hepatitis C virus (HCV continues to spread worldwide with an annual increase of 1.75 million new infections. The number of HCV cases in the U.S. is now greater than the number of HIV cases and is increasing in young adults because of the opioid epidemic sweeping the country. HCV-related liver disease is the leading indication of liver transplantation. An effective vaccine is of paramount importance to control and prevent HCV infection. While this vaccine will need to induce both cellular and humoral immunity, this review is focused on the required antibody responses. For highly variable viruses, such as HCV, isolation and characterization of monoclonal antibodies mediating broad virus neutralization are an important guide for vaccine design. The viral envelope glycoproteins, E1 and E2, are the main targets of these antibodies. Epitopes on the E2 protein have been studied more extensively than epitopes on E1, due to higher antibody targeting that reflects these epitopes having higher degrees of immunogenicity. E2 epitopes are overall organized in discrete clusters of overlapping epitopes that ranged from high conservation to high variability. Other epitopes on E1 and E1E2 also are targets of neutralizing antibodies. Taken together, these regions are important for vaccine design. Another element in vaccine design is based on information on how the virus escapes from broadly neutralizing antibodies. Escape mutations can occur within the epitopes that are involved in antibody binding and in regions that are not involved in their epitopes, but nonetheless reduce the efficiency of neutralizing antibodies. An understanding on the specificities of a protective B cell response, the molecular locations of these epitopes on E1, E2, and E1E2, and the mechanisms, which enable the virus to negatively modulate neutralizing antibody responses to these regions will provide the necessary guidance for vaccine design.

  2. Vaccine-Elicited Tier 2 HIV-1 Neutralizing Antibodies Bind to Quaternary Epitopes Involving Glycan-Deficient Patches Proximal to the CD4 Binding Site.

    Directory of Open Access Journals (Sweden)

    Ema T Crooks

    2015-05-01

    Full Text Available Eliciting broad tier 2 neutralizing antibodies (nAbs is a major goal of HIV-1 vaccine research. Here we investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit nAbs. Unusually potent nAb titers developed in 2 of 8 rabbits immunized with virus-like particles (VLPs expressing trimers (trimer VLP sera and in 1 of 20 rabbits immunized with DNA expressing native Env trimer, followed by a protein boost (DNA trimer sera. All 3 sera neutralized via quaternary epitopes and exploited natural gaps in the glycan defenses of the second conserved region of JR-FL gp120. Specifically, trimer VLP sera took advantage of the unusual absence of a glycan at residue 197 (present in 98.7% of Envs. Intriguingly, removing the N197 glycan (with no loss of tier 2 phenotype rendered 50% or 16.7% (n = 18 of clade B tier 2 isolates sensitive to the two trimer VLP sera, showing broad neutralization via the surface masked by the N197 glycan. Neutralizing sera targeted epitopes that overlap with the CD4 binding site, consistent with the role of the N197 glycan in a putative "glycan fence" that limits access to this region. A bioinformatics analysis suggested shared features of one of the trimer VLP sera and monoclonal antibody PG9, consistent with its trimer-dependency. The neutralizing DNA trimer serum took advantage of the absence of a glycan at residue 230, also proximal to the CD4 binding site and suggesting an epitope similar to that of monoclonal antibody 8ANC195, albeit lacking tier 2 breadth. Taken together, our data show for the first time that strain-specific holes in the glycan fence can allow the development of tier 2 neutralizing antibodies to native spikes. Moreover, cross-neutralization can occur in the absence of protecting glycan. Overall, our observations provide new insights that may inform the future development of a neutralizing antibody vaccine.

  3. Neutral beam monitoring

    International Nuclear Information System (INIS)

    Fink, J.H.

    1979-01-01

    A neutral beam generated by passing accelerated ions through a walled cell containing a low energy neutral gas, such that charge exchange partially neutralizes the high energy beam, is monitored by detecting the current flowing through the cell wall produced by low energy ions which drift to the wall after the charge exchange. By segmenting the wall into radial and longitudinal segments various beam conditions are identified. (U.K.)

  4. Bunched beam neutralization

    International Nuclear Information System (INIS)

    Gammel, G.M.; Maschke, A.W.; Mobley, R.M.

    1979-01-01

    One of the steps involved in producing an intense ion beam from conventional accelerators for Heavy Ion Fusion (HIF) is beam bunching. To maintain space charge neutralized transport, neutralization must occur more quickly as the beam bunches. It has been demonstrated at BNL that a 60 mA proton beam from a 750 kV Cockcroft--Walton can be neutralized within a microsecond. The special problem in HIF is that the neutralization must occur in a time scale of nanoseconds. To study neutralization on a faster time scale, a 40 mA, 450 kV proton beam was bunched at 16 MHz. A biased Faraday cup sampled the bunched beam at the position where maximum bunching was nominally expected, about 2.5 meters from the buncher. Part of the drift region, about 1.8 meters, was occupied by a series of Gabor lenses. In addition to enhancing beam transport by transverse focussing, the background cloud of electrons in the lenses provided an extra degree of neutralization. With no lens, the best bunch factor was at least 20. Bunch factor is defined here as the ratio of the distance between bunches to the FWHM bunch length. With the lens, it was hoped that the increased plasma frequency would decrease the neutralization time and cause an increase in the bunch factor. In fact, with the lens, the instantaneous current increased about three times, but the bunch factor dropped to about 10. Even with the lens, the FWHM of the bunches at the position of maximum bunching was still comparable to or less than the oscillation period of the surrounding electron plasma. Thus, the electron density in the lens must increase before neutralization could be effective in this case, or bunching should be done at a lower frequency

  5. Galactic neutral hydrogen emission-absorption observations from Arecibo

    International Nuclear Information System (INIS)

    Dickey, J.M.; Salpeter, E.E.; Terzian, Y.

    1978-01-01

    We have observed the interstellar medium in the directions of 27 extragalactic sources at high and intermediate galactic latitudes (vertical-barb/sup ii/vertical-bar>5 0 ) at 21 cm wavelength with the upgraded Arecibo telescope (HPBW=3'.2, gainapprox.6 K Jy -1 ). The small beam greatly reduces the uncertainty in the derived on-source emission profile and increases confidence that it corresponds to the same material as the absorption spectrum. Each region has been observed for approximately 2 hours to tetect optical depths as low as 10 -2 in most cases. The data allow the derivation of optical depths, harmonic mean spin temperatures, and column densities for the neutral hydrogen as a function of velocity in the range -200 -1 (LSR) with resolution as fine as 0.25 km s -1 . Spin temperatures as high as 1000 K are evident with a significant fraction of the neutral hydrogen still hotter. The cooler material is distributed over all temperatures from 30 K to at least 800 K. At latitudes below vertical-barb/sup ii/vertical-bar 0 values for the harmonic mean temperature T/sub spin/ in the range 100 K to 300 K are most common.We have detected 66 separate absorption features, tentatively associated with neutral hydrogen clouds, with central temperatures ranging from 30 to 500 K. These features conform well to the relationship T/sub spin/=45(1-e/sup -tau/)/sup -0.5/ (K), over a broad range of values of the optical depth. The velocity distribution of these clouds shows a significant negative-velocity ''tail'' at high and intermediate latitudes. The mean square velocity of the clouds seems to depend on optical depth: v/sub rms/ is greater (approx.11 km s -1 ) for the optically thin clouds (tau -1 ). High-negative-velocity emission (v -1 ) has been detected in six directions; in two of these corresponding absorption features are evident, indicating cool neutral material

  6. An efficiently cleaved HIV-1 clade C Env selectively binds to neutralizing antibodies.

    Directory of Open Access Journals (Sweden)

    Saikat Boliar

    Full Text Available An ideal HIV-1 Env immunogen is expected to mimic the native trimeric conformation for inducing broadly neutralizing antibody responses. The native conformation is dependent on efficient cleavage of HIV-1 Env. The clade B isolate, JRFL Env is efficiently cleaved when expressed on the cell surface. Here, for the first time, we report the identification of a native clade C Env, 4-2.J41 that is naturally and efficiently cleaved on the cell surface as confirmed by its biochemical and antigenic characteristics. In addition to binding to several conformation-dependent neutralizing antibodies, 4-2.J41 Env binds efficiently to the cleavage-dependent antibody PGT151; thus validating its native cleaved conformation. In contrast, 4-2.J41 Env occludes non-neutralizing epitopes. The cytoplasmic-tail of 4-2.J41 Env plays an important role in maintaining its conformation. Furthermore, codon optimization of 4-2.J41 Env sequence significantly increases its expression while retaining its native conformation. Since clade C of HIV-1 is the prevalent subtype, identification and characterization of this efficiently cleaved Env would provide a platform for rational immunogen design.

  7. Molecular signatures of hemagglutinin stem-directed heterosubtypic human neutralizing antibodies against influenza A viruses.

    Directory of Open Access Journals (Sweden)

    Yuval Avnir

    2014-05-01

    Full Text Available Recent studies have shown high usage of the IGHV1-69 germline immunoglobulin gene for influenza hemagglutinin stem-directed broadly-neutralizing antibodies (HV1-69-sBnAbs. Here we show that a major structural solution for these HV1-69-sBnAbs is achieved through a critical triad comprising two CDR-H2 loop anchor residues (a hydrophobic residue at position 53 (Ile or Met and Phe54, and CDR-H3-Tyr at positions 98±1; together with distinctive V-segment CDR amino acid substitutions that occur in positions sparse in AID/polymerase-η recognition motifs. A semi-synthetic IGHV1-69 phage-display library screen designed to investigate AID/polη restrictions resulted in the isolation of HV1-69-sBnAbs that featured a distinctive Ile52Ser mutation in the CDR-H2 loop, a universal CDR-H3 Tyr at position 98 or 99, and required as little as two additional substitutions for heterosubtypic neutralizing activity. The functional importance of the Ile52Ser mutation was confirmed by mutagenesis and by BCR studies. Structural modeling suggests that substitution of a small amino acid at position 52 (or 52a facilitates the insertion of CDR-H2 Phe54 and CDR-H3-Tyr into adjacent pockets on the stem. These results support the concept that activation and expansion of a defined subset of IGHV1-69-encoded B cells to produce potent HV1-69-sBnAbs does not necessarily require a heavily diversified V-segment acquired through recycling/reentry into the germinal center; rather, the incorporation of distinctive amino acid substitutions by Phase 2 long-patch error-prone repair of AID-induced mutations or by random non-AID SHM events may be sufficient. We propose that these routes of B cell maturation should be further investigated and exploited as a pathway for HV1-69-sBnAb elicitation by vaccination.

  8. Identification of a conformational neutralizing epitope on the VP1 protein of type A foot-and-mouth disease virus.

    Science.gov (United States)

    Liu, Wenming; Yang, Baolin; Wang, Mingxia; Wang, Haiwei; Yang, Decheng; Ma, Wenge; Zhou, Guohui; Yu, Li

    2017-12-01

    Foot-and-mouth disease (FMD) caused by foot-and-mouth disease virus (FMDV), is a highly contagious infectious disease that affects domestic and wild cloven-hoofed animals worldwide. In recent years, outbreaks of serotype A FMD have occurred in many countries. High-affinity neutralizing antibodies against a conserved epitope could provide protective immunity against diverse subtypes of FMDV serotype A and protect against future pandemics. In this study, we generated a serotype A FMDV-specific potent neutralizing monoclonal antibody (MAb), 6C9, which recognizes a conformation-dependent epitope. MAb 6C9 potently neutralized FMDV A/XJBC/CHA/2010 with a 50% neutralization titer (NT 50 ) of 4096. Screening of a phage-displayed random 12-mer peptide library revealed that MAb 6C9 bound to phages displaying the consensus motif YxxPxGDLG, which is highly homologous to the 135 YxxPxxxxxGDLG 147 motif found in the serotype A FMDV virus-encoded structural protein VP1. To further verify the authentic epitope recognized by MAb 6C9, two FMDV A/XJBC/CHA/2010 mutant viruses, P138A and G144A, were generated using a reverse genetic system. Subsequent micro-neutralization assays and double-antibody sandwich (DAS) ELISA analyses revealed that the Pro 138 and Gly 144 residues of the conformational epitope that are recognized by 6C9 are important for MAb 6C9 binding. Importantly, the epitope 135 YxxPxxxxxGDLG 147 was highly conserved among different topotypes of serotype A FMDV strains in a sequence alignment analysis. Thus, the results of this study could have potential applications in the development of novel epitope-based vaccines and suitable a MAb-based diagnostic method for the detection of serotype A FMDV and the quantitation of antibodies against this serotype. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. PC-Link historical data base system MODCOMP/IBM at link for neutral particle beam operation

    International Nuclear Information System (INIS)

    Thurgood, P.

    1989-12-01

    ''PC-Link'' is a combination of hardware and software that connects an IBM PC/AT to a MODCOMP minicomputer. It is designed as an aid to the Neutral Beam operations coordinator during injection into the DIII-D tokamak project. An IBM PC/AT is linked to 4 MODCOMP ''realtime'' acquisition systems, each of which controls 2 neutral particle beam sources. At various points in the shot sequence, data is sent to the IBM PC/AT. This data can then be integrated with the data from the other sources into tables or graphics displays for use by the Beam Coordinator. In this way, the coordinator gets realtime feedback on the relative settings and performance of the sources and can observe trends within a particular source at one location. The PC- Link is used for observing relative timing information and for post shot historical archiving. The concept of the PC-Link was originally proposed several years ago. In April 1988, in-house implementation of the link software was begun. The PC-Link receives approximately 2 Kbytes of data per source per shot. This data is converted from MODCOMP format to IBM PC format and archived to disk. The last 280 shots per source are stored to disk to observe trends. The data can be displayed in a number of formats depending upon the situation. For example, prior to a shot, the beam MODCOMPs are sent timing information from the DIII-D tokamak control system. This data is echoed on the PC in a graphical representation displaying all 8 sources. At the end of the shot, the actual running times are displayed along with the requested settings. Any subset of the Historical data may be displayed either graphically or in tables for realtime comparisons between sources. This system is designed for realtime use, not for complete archiving purposes. This same data is also sent to a VAX computer for full integration into the archive database. This system is easily upgradable and extremely versatile. 4 figs

  10. Clinical Ethics Consultation After God: Implications for Advocacy and Neutrality.

    Science.gov (United States)

    Parker, J Clint

    2018-06-01

    In After God: Morality and Bioethics in a Secular Age, H. Tristram Engelhardt, Jr. explores the broad implications for moral reasoning once a culture has lost a God's-eye perspective. In this paper, I focus on the implications of Engelhardt's views for clinical ethics consultation. I begin by examining the question of whether clinical ethics consultants (CECs) should advocate a particular viewpoint and/or process during consultations or adopt a neutral stance. I then examine the implications of Engelhardt's views for this question. Finally, I discuss some of Engelhardt's foundational ontological, metaphysical, meta-ethical, and epistemological commitments and how these commitments connect to his views on clinical ethics consultation.

  11. A tetravalent virus-like particle vaccine designed to display domain III of dengue envelope proteins induces multi-serotype neutralizing antibodies in mice and macaques which confer protection against antibody dependent enhancement in AG129 mice.

    Directory of Open Access Journals (Sweden)

    Viswanathan Ramasamy

    2018-01-01

    Full Text Available Dengue is one of the fastest spreading vector-borne diseases, caused by four antigenically distinct dengue viruses (DENVs. Antibodies against DENVs are responsible for both protection as well as pathogenesis. A vaccine that is safe for and efficacious in all people irrespective of their age and domicile is still an unmet need. It is becoming increasingly apparent that vaccine design must eliminate epitopes implicated in the induction of infection-enhancing antibodies.We report a Pichia pastoris-expressed dengue immunogen, DSV4, based on DENV envelope protein domain III (EDIII, which contains well-characterized serotype-specific and cross-reactive epitopes. In natural infection, <10% of the total neutralizing antibody response is EDIII-directed. Yet, this is a functionally relevant domain which interacts with the host cell surface receptor. DSV4 was designed by in-frame fusion of EDIII of all four DENV serotypes and hepatitis B surface (S antigen and co-expressed with unfused S antigen to form mosaic virus-like particles (VLPs. These VLPs displayed EDIIIs of all four DENV serotypes based on probing with a battery of serotype-specific anti-EDIII monoclonal antibodies. The DSV4 VLPs were highly immunogenic, inducing potent and durable neutralizing antibodies against all four DENV serotypes encompassing multiple genotypes, in mice and macaques. DSV4-induced murine antibodies suppressed viremia in AG129 mice and conferred protection against lethal DENV-4 virus challenge. Further, neither murine nor macaque anti-DSV4 antibodies promoted mortality or inflammatory cytokine production when passively transferred and tested in an in vivo dengue disease enhancement model of AG129 mice.Directing the immune response to a non-immunodominant but functionally relevant serotype-specific dengue epitope of the four DENV serotypes, displayed on a VLP platform, can help minimize the risk of inducing disease-enhancing antibodies while eliciting effective tetravalent

  12. Plasma particle sources due to interactions with neutrals in a turbulent scrape-off layer of a toroidally confined plasma

    Science.gov (United States)

    Thrysøe, A. S.; Løiten, M.; Madsen, J.; Naulin, V.; Nielsen, A. H.; Rasmussen, J. Juul

    2018-03-01

    The conditions in the edge and scrape-off layer (SOL) of magnetically confined plasmas determine the overall performance of the device, and it is of great importance to study and understand the mechanics that drive transport in those regions. If a significant amount of neutral molecules and atoms is present in the edge and SOL regions, those will influence the plasma parameters and thus the plasma confinement. In this paper, it is displayed how neutrals, described by a fluid model, introduce source terms in a plasma drift-fluid model due to inelastic collisions. The resulting source terms are included in a four-field drift-fluid model, and it is shown how an increasing neutral particle density in the edge and SOL regions influences the plasma particle transport across the last-closed-flux-surface. It is found that an appropriate gas puffing rate allows for the edge density in the simulation to be self-consistently maintained due to ionization of neutrals in the confined region.

  13. Yeast surface display platform for rapid discovery of conformationally selective nanobodies

    DEFF Research Database (Denmark)

    McMahon, Conor; Baier, Alexander S.; Pascolutti, Roberta

    2018-01-01

    this problem, we report a fully in vitro platform for nanobody discovery based on yeast surface display. We provide a blueprint for identifying nanobodies, demonstrate the utility of the library by crystallizing a nanobody with its antigen, and most importantly, we utilize the platform to discover...... conformationally selective nanobodies to two distinct human GPCRs. To facilitate broad deployment of this platform, the library and associated protocols are freely available for nonprofit research....

  14. THE ROLL-OVER OF HELIOSPHERIC NEUTRAL HYDROGEN BELOW 100 eV: OBSERVATIONS AND IMPLICATIONS

    Energy Technology Data Exchange (ETDEWEB)

    Galli, A.; Wurz, P. [Physics Institute, University of Bern, Bern, 3012 (Switzerland); Schwadron, N. A.; Kucharek, H.; Möbius, E. [University of New Hampshire, Durham, NH 03824 (United States); Bzowski, M.; Sokół, J. M.; Kubiak, M. A. [Space Research Centre, Polish Academy of Sciences, Warsaw, 00-716 (Poland); Funsten, H. O. [Los Alamos National Laboratory, Intelligence and Space Research Division, Los Alamos, NM 87545 (United States); Fuselier, S. A.; McComas, D. J. [Southwest Research Institute, San Antonio, TX 78228 (United States)

    2016-04-20

    We present an improved analysis of the energy spectrum of energetic neutral hydrogen from the heliosheath observed with the IBEX -Lo sensor on the Interstellar Boundary EXplorer from the years 2009 to 2012. This analysis allows us to study the lowest energies between 10 and 100 eV although various background sources are more intense than the targeted signal over broad areas of the sky. The results improve our knowledge of the interaction region between our heliosphere and the interstellar plasma because these neutral atoms are direct messengers from the low-energy plasma in the heliosheath. We find a roll-over of the energy spectrum below 100 eV, which has major implications for the pressure balance of the plasma in the inner heliosheath. The results can also be compared directly with in situ observations of the Voyager 1 and 2 spacecraft.

  15. Discovery of potent broad spectrum antivirals derived from marine actinobacteria.

    Directory of Open Access Journals (Sweden)

    Avi Raveh

    Full Text Available Natural products provide a vast array of chemical structures to explore in the discovery of new medicines. Although secondary metabolites produced by microbes have been developed to treat a variety of diseases, including bacterial and fungal infections, to date there has been limited investigation of natural products with antiviral activity. In this report, we used a phenotypic cell-based replicon assay coupled with an iterative biochemical fractionation process to identify, purify, and characterize antiviral compounds produced by marine microbes. We isolated a compound from Streptomyces kaviengensis, a novel actinomycetes isolated from marine sediments obtained off the coast of New Ireland, Papua New Guinea, which we identified as antimycin A1a. This compound displays potent activity against western equine encephalitis virus in cultured cells with half-maximal inhibitory concentrations of less than 4 nM and a selectivity index of greater than 550. Our efforts also revealed that several antimycin A analogues display antiviral activity, and mechanism of action studies confirmed that these Streptomyces-derived secondary metabolites function by inhibiting the cellular mitochondrial electron transport chain, thereby suppressing de novo pyrimidine synthesis. Furthermore, we found that antimycin A functions as a broad spectrum agent with activity against a wide range of RNA viruses in cultured cells, including members of the Togaviridae, Flaviviridae, Bunyaviridae, Picornaviridae, and Paramyxoviridae families. Finally, we demonstrate that antimycin A reduces central nervous system viral titers, improves clinical disease severity, and enhances survival in mice given a lethal challenge with western equine encephalitis virus. Our results provide conclusive validation for using natural product resources derived from marine microbes as source material for antiviral drug discovery, and they indicate that host mitochondrial electron transport is a viable

  16. Both selective and neutral processes drive GC content evolution in the human genome

    Directory of Open Access Journals (Sweden)

    Cagliani Rachele

    2008-03-01

    Full Text Available Abstract Background Mammalian genomes consist of regions differing in GC content, referred to as isochores or GC-content domains. The scientific debate is still open as to whether such compositional heterogeneity is a selected or neutral trait. Results Here we analyze SNP allele frequencies, retrotransposon insertion polymorphisms (RIPs, as well as fixed substitutions accumulated in the human lineage since its divergence from chimpanzee to indicate that biased gene conversion (BGC has been playing a role in within-genome GC content variation. Yet, a distinct contribution to GC content evolution is accounted for by a selective process. Accordingly, we searched for independent evidences that GC content distribution does not conform to neutral expectations. Indeed, after correcting for possible biases, we show that intron GC content and size display isochore-specific correlations. Conclusion We consider that the more parsimonious explanation for our results is that GC content is subjected to the action of both weak selection and BGC in the human genome with features such as nucleosome positioning or chromatin conformation possibly representing the final target of selective processes. This view might reconcile previous contrasting findings and add some theoretical background to recent evidences suggesting that GC content domains display different behaviors with respect to highly regulated biological processes such as developmentally-stage related gene expression and programmed replication timing during neural stem cell differentiation.

  17. Genome-wide association study on the development of cross-reactive neutralizing antibodies in HIV-1 infected individuals.

    Directory of Open Access Journals (Sweden)

    Zelda Euler

    Full Text Available Broadly neutralizing antibodies may protect against HIV-1 acquisition. In natural infection, only 10-30% of patients have cross-reactive neutralizing humoral immunity which may relate to viral and or host factors. To explore the role of host genetic markers in the formation of cross-reactive neutralizing activity (CrNA in HIV-1 infected individuals, we performed a genome-wide association study (GWAS, in participants of the Amsterdam Cohort Studies with known CrNA in their sera. Single-nucleotide polymorphisms (SNPs with the strongest P-values are located in the major histocompatibility complex (MHC region, close to MICA (P = 7.68 × 10(-7, HLA-B (P = 6.96 × 10(-6 and in the coding region of HCP5 (P = 1.34 × 10(-5. However, none of the signals reached genome-wide significance. Our findings underline the potential involvement of genes close or within the MHC region with the development of CrNA.

  18. Genome-Wide Association Study on the Development of Cross-Reactive Neutralizing Antibodies in HIV-1 Infected Individuals

    Science.gov (United States)

    Euler, Zelda; van Gils, Marit J.; Boeser-Nunnink, Brigitte D.; Schuitemaker, Hanneke; van Manen, Daniëlle

    2013-01-01

    Broadly neutralizing antibodies may protect against HIV-1 acquisition. In natural infection, only 10–30% of patients have cross-reactive neutralizing humoral immunity which may relate to viral and or host factors. To explore the role of host genetic markers in the formation of cross-reactive neutralizing activity (CrNA) in HIV-1 infected individuals, we performed a genome-wide association study (GWAS), in participants of the Amsterdam Cohort Studies with known CrNA in their sera. Single-nucleotide polymorphisms (SNPs) with the strongest P-values are located in the major histocompatibility complex (MHC) region, close to MICA (P = 7.68×10−7), HLA-B (P = 6.96×10−6) and in the coding region of HCP5 (P = 1.34×10−5). However, none of the signals reached genome-wide significance. Our findings underline the potential involvement of genes close or within the MHC region with the development of CrNA. PMID:23372753

  19. HIV-Specific B Cell Frequency Correlates with Neutralization Breadth in Patients Naturally Controlling HIV-Infection

    Directory of Open Access Journals (Sweden)

    Angeline Rouers

    2017-07-01

    Full Text Available HIV-specific broadly neutralizing antibodies (bnAbs have been isolated from patients with high viremia but also from HIV controllers that repress HIV-1 replication. In these elite controllers (ECs, multiple parameters contribute to viral suppression, including genetic factors and immune responses. Defining the immune correlates associated with the generation of bnAbs may help in designing efficient immunotherapies. In this study, in ECs either positive or negative for the HLA-B*57 protective allele, in treated HIV-infected and HIV-negative individuals, we characterized memory B cell compartments and HIV-specific memory B cells responses using flow cytometry and ELISPOT. ECs preserved their memory B cell compartments and in contrast to treated patients, maintained detectable HIV-specific memory B cell responses. All ECs presented IgG1+ HIV-specific memory B cells but some individuals also preserved IgG2+ or IgG3+ responses. Importantly, we also analyzed the capacity of sera from ECs to neutralize a panel of HIV strains including transmitted/founder virus. 29% and 21% of HLA-B*57+ and HLA-B*57− ECs, respectively, neutralized at least 40% of the viral strains tested. Remarkably, in HLA-B*57+ ECs the frequency of HIV-Env-specific memory B cells correlated positively with the neutralization breadth suggesting that preservation of HIV-specific memory B cells might contribute to the neutralizing responses in these patients.

  20. Perceptual load vs. dilution: the roles of attentional focus, stimulus category, and target predictability

    Directory of Open Access Journals (Sweden)

    Zhe eChen

    2013-06-01

    Full Text Available Many studies have shown that increasing the number of neutral stimuli in a display decreases distractor interference. This result has been interpreted within two different frameworks; a perceptual load account, based on a reduction in spare resources, and a dilution account, based on a degradation in distractor representation and/or an increase in crosstalk between the distractor and the neutral stimuli that contain visually similar features. In four experiments, we systematically manipulated the extent of attentional focus, stimulus category, and preknowledge of the target to examine how these factors would interact with the display set size to influence the degree of distractor processing. Display set size did not affect the degree of distractor processing in all situations. Increasing the number of neutral items decreased distractor processing only when a task induced a broad attentional focus that included the neutral stimuli, when the neutral stimuli were in the same category as the target and distractor, and when the preknowledge of the target was insufficient to guide attention to the target efficiently. These results suggest that the effect of neutral stimuli on the degree of distractor processing is more complex than previously assumed. They provide new insight into the competitive interactions between bottom-up and top-down processes that govern the efficiency of visual selective attention.

  1. Binding of HIV-1 gp41-directed neutralizing and non-neutralizing fragment antibody binding domain (Fab and single chain variable fragment (ScFv antibodies to the ectodomain of gp41 in the pre-hairpin and six-helix bundle conformations.

    Directory of Open Access Journals (Sweden)

    John M Louis

    Full Text Available We previously reported a series of antibodies, in fragment antigen binding domain (Fab formats, selected from a human non-immune phage library, directed against the internal trimeric coiled-coil of the N-heptad repeat (N-HR of HIV-1 gp41. Broadly neutralizing antibodies from that series bind to both the fully exposed N-HR trimer, representing the pre-hairpin intermediate state of gp41, and to partially-exposed N-HR helices within the context of the gp41 six-helix bundle. While the affinities of the Fabs for pre-hairpin intermediate mimetics vary by only 2 to 20-fold between neutralizing and non-neutralizing antibodies, differences in inhibition of viral entry exceed three orders of magnitude. Here we compare the binding of neutralizing (8066 and non-neutralizing (8062 antibodies, differing in only four positions within the CDR-H2 binding loop, in Fab and single chain variable fragment (ScFv formats, to several pre-hairpin intermediate and six-helix bundle constructs of gp41. Residues 56 and 58 of the mini-antibodies are shown to be crucial for neutralization activity. There is a large differential (≥ 150-fold in binding affinity between neutralizing and non-neutralizing antibodies to the six-helix bundle of gp41 and binding to the six-helix bundle does not involve displacement of the outer C-terminal helices of the bundle. The binding stoichiometry is one six-helix bundle to one Fab or three ScFvs. We postulate that neutralization by the 8066 antibody is achieved by binding to a continuum of states along the fusion pathway from the pre-hairpin intermediate all the way to the formation of the six-helix bundle, but prior to irreversible fusion between viral and cellular membranes.

  2. Neutralized transport experiment

    International Nuclear Information System (INIS)

    Roy, P.K.; Yu, S.S.; Eylon, S.; Henestroza, E.; Anders, A.; Gilson, E.P.; Bieniosek, F.M.; Greenway, W.G.; Logan, B.G.; Waldron, W.L.; Shuman, D.B.; Vanecek, D.L.; Welch, D.R.; Rose, D.V.; Thoma, C.; Davidson, R.C.; Efthimion, P.C.; Kaganovich, I.; Sefkow, A.B.; Sharp, W.M.

    2005-01-01

    Experimental details on providing active neutralization of high brightness ion beam have been demonstrated for Heavy Ion Fusion program. A K + beam was extracted from a variable-perveance injector and transported through 2.4 m long quadrupole lattice for final focusing. Neutralization was provided by a localized cathode arc plasma plug and a RF volume plasma system. Effects of beam perveance, emittance, convergence focusing angle, and axial focusing position on neutralization have been investigated. Good agreement has been observed with theory and experiment throughout the study

  3. A neutral sampling formula for multiple samples and an `exact' test of neutrality

    NARCIS (Netherlands)

    Etienne, R.S.

    2007-01-01

    As the utility of the neutral theory of biodiversity is increasingly being recognized, there is also an increasing need for proper tools to evaluate the relative importance of neutral processes (dispersal limitation and stochasticity). One of the key features of neutral theory is its close link to

  4. A neutral sampling formula for multiple samples and an 'exact' test of neutrality

    NARCIS (Netherlands)

    Etienne, Rampal S.

    As the utility of the neutral theory of biodiversity is increasingly being recognized, there is also an increasing need for proper tools to evaluate the relative importance of neutral processes (dispersal limitation and stochasticity). One of the key features of neutral theory is its close link to

  5. Search for neutral leptons

    International Nuclear Information System (INIS)

    Perl, M.L.

    1984-12-01

    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

  6. Neutral currents

    International Nuclear Information System (INIS)

    Paschos, E.A.

    1977-01-01

    It is stated that over the past few years considerable progress has been made in the field of weak interactions. The existence of neutral currents involving leptons and hadrons has been established and some of the questions concerning their detailed structure have been answered. This imposes constraints on the gauge theories and has eliminated large classes of models. New questions have also been raised, one of which concerns the conservation laws obeyed by neutral currents. The wide range of investigations is impressive and is expected to continue with new results from particle, nuclear, and atomic physics. Headings include - various aspects of a gauge theory (choice of group, the symmetry breaking scheme, representation assignments for fermion fields); space-time structure; isospin structure; leptonic neutral currents; and atomic experiments. (U.K.)

  7. A human monoclonal antibody with neutralizing activity against highly divergent influenza subtypes.

    Directory of Open Access Journals (Sweden)

    Nicola Clementi

    Full Text Available The interest in broad-range anti-influenza A monoclonal antibodies (mAbs has recently been strengthened by the identification of anti-hemagglutinin (HA mAbs endowed with heterosubtypic neutralizing activity to be used in the design of "universal" prophylactic or therapeutic tools. However, the majority of the single mAbs described to date do not bind and neutralize viral isolates belonging to highly divergent subtypes clustering into the two different HA-based influenza phylogenetic groups: the group 1 including, among others, subtypes H1, H2, H5 and H9 and the group 2 including, among others, H3 subtype. Here, we describe a human mAb, named PN-SIA28, capable of binding and neutralizing all tested isolates belonging to phylogenetic group 1, including H1N1, H2N2, H5N1 and H9N2 subtypes and several isolates belonging to group 2, including H3N2 isolates from the first period of the 1968 pandemic. Therefore, PN-SIA28 is capable of neutralizing isolates belonging to subtypes responsible of all the reported pandemics, as well as other subtypes with pandemic potential. The region recognized by PN-SIA28 has been identified on the stem region of HA and includes residues highly conserved among the different influenza subtypes. A deep characterization of PN-SIA28 features may represent a useful help in the improvement of available anti-influenza therapeutic strategies and can provide new tools for the development of universal vaccinal strategies.

  8. 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.

  9. Sheet Fluorescence and Annular Analysis of Ultracold Neutral Plasmas

    International Nuclear Information System (INIS)

    Castro, J.; Gao, H.; Killian, T. C.

    2009-01-01

    Annular analysis of fluorescence imaging measurements on Ultracold Neutral Plasmas (UNPs) is demonstrated. Spatially-resolved fluorescence imaging of the strontium ions produces a spectrum that is Doppler-broadened due to the thermal ion velocity and shifted due to the ion expansion velocity. The fluorescence excitation beam is spatially narrowed into a sheet, allowing for localized analysis of ion temperatures within a volume of the plasma with small density variation. Annular analysis of fluorescence images permits an enhanced signal-to-noise ratio compared to previous fluorescence measurements done in strontium UNPs. Using this technique and analysis, plasma ion temperatures are measured and shown to display characteristics of plasmas with strong coupling such as disorder induced heating and kinetic energy oscillations.

  10. Rheological evaluation of simulated neutralized current acid waste - transuranics

    International Nuclear Information System (INIS)

    Fow, C.L.; McCarthy, D.; Thornton, G.T.; Scott, P.A.; Bray, L.A.

    1986-09-01

    At the Hanford Plutonium and Uranium Extraction Plant (PUREX), in Richland, Washington, plutonium and uranium products are recovered from irradiated fuel by a solvent extraction process. A byproduct of this process is an aqueous waste stream that contains fission products. This waste stream, called current acid waste (CAW), is chemically neutralized and stored in double shell tanks (DSTs) on the Hanford Site. This neutralized current acid waste (NCAW) will be transported by pipe to B-Plant, a processing plant located nearby. In B-Plant, the transuranic (TRU) elements in NCAW are separated from the non-TRU elements. The majority of the TRU elements in NCAW are in the solids. Therefore, the primary processing operation is to separate the NCAW solids (NCAW-TRU) from the NCAW liquid. These two waste streams will be pumped to suitable holding tanks before being further processed for permanent disposal. To ensure that the retrieval and transportation of NCAW and NCAW-TRU are successful, researchers at Pacific Northwest Laboratory (PNL) evaluated the rheological and transport properties of the slurries. This evaluation had two phases. First, researchers conducted laboratory rheological evaluations of simulated NCAW and NCAW-TRU. The results of these evaluations were then correlated with classical rheological models and scaled up to predict the performance that is likely to occur in the full-scale system. This scale-up procedure has already been successfully used to predict the critical transport properties of a slurry (Neutralized Cladding Removal Waste) with rheological properties similar to those displayed by NCAW and NCAW-TRU

  11. Plasma neutralizer for H- beams

    International Nuclear Information System (INIS)

    Grossman, M.W.

    1977-01-01

    Neutralization of H - beams by a hydrogen plasma is discussed. Optimum target thickness and maximum neutralization efficiency as a function of the fraction of the hydrogen target gas ionized is calculated for different H - beam energies. Also, the variation of neutralization efficiency with respect to target thickness for different H - beam energies is computed. The dispersion of the neutralized beam by a magnetic field for different energies and different values of B . z is found. Finally, a type of plasma jet is proposed, which may be suitable for a compact H - neutralizer

  12. Integrated Display and Environmental Awareness System - System Architecture Definition

    Science.gov (United States)

    Doule, Ondrej; Miranda, David; Hochstadt, Jake

    2017-01-01

    The Integrated Display and Environmental Awareness System (IDEAS) is an interdisciplinary team project focusing on the development of a wearable computer and Head Mounted Display (HMD) based on Commercial-Off-The-Shelf (COTS) components for the specific application and needs of NASA technicians, engineers and astronauts. Wearable computers are on the verge of utilization trials in daily life as well as industrial environments. The first civil and COTS wearable head mounted display systems were introduced just a few years ago and they probed not only technology readiness in terms of performance, endurance, miniaturization, operability and usefulness but also maturity of practice in perspective of a socio-technical context. Although the main technical hurdles such as mass and power were addressed as improvements on the technical side, the usefulness, practicality and social acceptance were often noted on the side of a broad variety of humans' operations. In other words, although the technology made a giant leap, its use and efficiency still looks for the sweet spot. The first IDEAS project started in January 2015 and was concluded in January 2017. The project identified current COTS systems' capability at minimum cost and maximum applicability and brought about important strategic concepts that will serve further IDEAS-like system development.

  13. Low level perceptual, not attentional, processes modulate distractor interference in high perceptual load displays: evidence from neglect/extinction.

    Science.gov (United States)

    Mevorach, Carmel; Tsal, Yehoshua; Humphreys, Glyn W

    2014-01-10

    According to perceptual load theory (Lavie, 2005) distractor interference is determined by the availability of attentional resources. If target processing does not exhaust resources (with low perceptual load) distractor processing will take place resulting in interference with a primary task; however, when target processing uses-up attentional capacity (with high perceptual load) interference can be avoided. An alternative account (Tsal and Benoni, 2010a) suggests that perceptual load effects can be based on distractor dilution by the mere presence of additional neutral items in high-load displays so that the effect is not driven by the amount of attention resources required for target processing. Here we tested whether patients with unilateral neglect or extinction would show dilution effects from neutral items in their contralesional (neglected/extinguished) field, even though these items do not impose increased perceptual load on the target and at the same time attract reduced attentional resources compared to stimuli in the ipsilesional field. Thus, such items do not affect the amount of attention resources available for distractor processing. We found that contralesional neutral elements can eliminate distractor interference as strongly as centrally presented ones in neglect/extinction patients, despite contralesional items being less well attended. The data are consistent with an account in terms of perceptual dilution of distracters rather than available resources for distractor processing. We conclude that distractor dilution can underlie the elimination of distractor interference in visual displays.

  14. Low level perceptual, not attentional, processes modulate distractor interference in high perceptual Load displays: evidence from neglect/extinction

    Directory of Open Access Journals (Sweden)

    Carmel eMevorach

    2014-01-01

    Full Text Available According to perceptual load theory (Lavie, 2005 distractor interference is determined by the availability of attentional resources. If target processing does not exhaust resources (with low perceptual load distractor processing will take place resulting in interference with a primary task; however when target processing uses-up attentional capacity (with high perceptual load interference can be avoided. An alternative account (Tsal & Benoni, 2010 suggests that perceptual load effects can be based on distractor dilution by the mere presence of additional neutral items in high load displays so that the effect is not driven by the amount of attention resources required for target processing. Here we tested whether patients with unilateral neglect or extinction would show dilution effects from neutral items in their contralesional (neglected/extinguished field, even though these items do not impose increased perceptual load on the target and at the same time attract reduced attentional resources compared to stimuli in the ipsilesional field. Thus, such items do not affect the amount of attention resources available for distractor processing. We found that contralesional neutral elements can eliminate distractor interference as strongly as centrally presented ones in neglect/extinction patients, despite contralesional items being less well attended. The data are consistent with an account in terms of perceptual dilution of distracters rather than available resources for distractor processing. We conclude that distractor dilution can underlie the elimination of distractor interference in visual displays.

  15. Recent improvements to the DIII-D neutral beam instrumentation and control system

    International Nuclear Information System (INIS)

    Kellman, D.H.; Hong, R.

    1997-11-01

    The DIII-D neutral beam (NB) instrumentation and control (I and C) system provides for operational control and synchronization of the eight DIII-D neutral beam injection systems, as well as for pertinent data acquisition and safety interlocking. Recently, improvements were made to the I and C system. With the replacement of the NB control computers, new signal interfacing was required to accommodate the elimination of physical operator panels, in favor of graphical user interface control pages on computer terminal screens. The program in the mode control (MC) programmable logic controller (PLC), which serves as a logic-processing interface between the NB control computers and system hardware, was modified to improve the availability of NB heating of DIII-D plasmas in the event that one or more individual beam systems suddenly become unavailable while preparing for a tokamak experimental shot sequences. An upgraded computer platform was adopted for the NB control system operator interface and new graphical user interface pages were developed to more efficiently display system status data. A failure mode of the armor tile infrared thermometers (pyrometers), which serve to terminate beam pulsing if beam shine-through overheats wall thermal shielding inside the DIII-D tokamak, was characterized such that impending failures can be detected and repairs effected to mitigate beam system down-time. The hardware that controls gas flow to the beamline neutralizer cells was upgraded to reduce susceptibility to electromagnetic interference (EMI), and interlocking was provided to terminate beam pulsing in the event of insufficient neutralizer gas flow. Motivation, implementation, and results of these improvements are presented

  16. Neutralization escape mutants define a dominant immunogenic neutralization site on hepatitis A virus

    International Nuclear Information System (INIS)

    Stapleton, J.T.; Lemon, S.M.

    1987-01-01

    Hepatitis A virus is an hepatotrophic human picornavirus which demonstrates little antigenic variability. To topologically map immunogenic sites on hepatitis A virus which elicit neutralizing antibodies, eight neutralizing monoclonal antibodies were evaluated in competition immunoassays employing radiolabeled monoclonal antibodies and HM-175 virus. Whereas two antibodies (K3-4C8 and K3-2F2) bound to intimately overlapping epitopes, the epitope bound by a third antibody (B5-B3) was distinctly different as evidenced by a lack of competition between antibodies for binding to the virus. The other five antibodies variably blocked the binding of both K3-4C8-K3-2F2 and B5-B3, suggesting that these epitopes are closely spaced and perhaps part of a single neutralization immunogenic site. Several combinations of monoclonal antibodies blocked the binding of polyclonal human convalescent antibody by greater than 96%, indicating that the neutralization epitopes bound by these antibodies are immunodominant in humans. Spontaneously arising HM-175 mutants were selected for resistance to monoclonal antibody-mediated neutralization. Neutralization resistance was associated with reduced antibody binding. These results suggest that hepatitis A virus may differ from poliovirus in possessing a single, dominant neutralization immunogenic site and therefore may be a better candidate for synthetic peptide or antiidiotype vaccine development

  17. Development of anti-infectives using phage display: biological agents against bacteria, viruses, and parasites.

    Science.gov (United States)

    Huang, Johnny X; Bishop-Hurley, Sharon L; Cooper, Matthew A

    2012-09-01

    The vast majority of anti-infective therapeutics on the market or in development are small molecules; however, there is now a nascent pipeline of biological agents in development. Until recently, phage display technologies were used mainly to produce monoclonal antibodies (MAbs) targeted against cancer or inflammatory disease targets. Patent disputes impeded broad use of these methods and contributed to the dearth of candidates in the clinic during the 1990s. Today, however, phage display is recognized as a powerful tool for selecting novel peptides and antibodies that can bind to a wide range of antigens, ranging from whole cells to proteins and lipid targets. In this review, we highlight research that exploits phage display technology as a means of discovering novel therapeutics against infectious diseases, with a focus on antimicrobial peptides and antibodies in clinical or preclinical development. We discuss the different strategies and methods used to derive, select, and develop anti-infectives from phage display libraries and then highlight case studies of drug candidates in the process of development and commercialization. Advances in screening, manufacturing, and humanization technologies now mean that phage display can make a significant contribution in the fight against clinically important pathogens.

  18. On neutral plasma oscillations

    International Nuclear Information System (INIS)

    Shadwick, B.A.; Morrison, P.J.

    1993-06-01

    We examine the conditions for the existence of spectrally stable neutral modes in a Vlasov-Poisson plasma and show that for stable equilibria of systems that have unbounded spatial domain, the only possible neutral modes are those with phase velocities that correspond to stationary inflection points of the equilibrium distribution function. It is seen that these neutral modes can possess positive or negative free energy

  19. On neutral plasma oscillations

    International Nuclear Information System (INIS)

    Shadwick, B.A.; Texas Univ., Austin; Morrison, P.J.; Texas Univ., Austin

    1994-01-01

    We examine the conditions for the existence of spectrally stable neutral modes in a Vlasov-Poisson plasma and show that for stable equilibria of systems that have unbounded spatial domain, the only possible neutral modes are those with phase velocities that correspond to stationary inflection points of the equilibrium distribution function. It is seen that these neutral modes can posses positive or negative free energy. (orig.)

  20. Automated Facial Coding Software Outperforms People in Recognizing Neutral Faces as Neutral from Standardized Datasets

    Directory of Open Access Journals (Sweden)

    Peter eLewinski

    2015-09-01

    Full Text Available Little is known about people’s accuracy of recognizing neutral faces as neutral. In this paper, I demonstrate the importance of knowing how well people recognize neutral faces. I contrasted human recognition scores of 100 typical, neutral front-up facial images with scores of an arguably objective judge – automated facial coding (AFC software. I hypothesized that the software would outperform humans in recognizing neutral faces because of the inherently objective nature of computer algorithms. Results confirmed this hypothesis. I provided the first-ever evidence that computer software (90% was more accurate in recognizing neutral faces than people were (59%. I posited two theoretical mechanisms, i.e. smile-as-a-baseline and false recognition of emotion, as possible explanations for my findings.

  1. First observations of partially neutralized and quasineutral plasmas in the Columbia Non-neutral Torus

    Science.gov (United States)

    Sarasola, Xabier; Brenner, Paul; Hahn, Michael; Pedersen, Thomas

    2009-11-01

    The Columbia Non-neutral Torus (CNT) is the first stellarator devoted to the study of pure electron, partially neutralized and positron-electron plasmas. To date, CNT usually operates with electron rich plasmas (with negligible ion density) [1], but a stellarator can also confine plasmas of arbitrary degree of neutralization. In CNT the accumulation of ions alters the equilibrium of electron plasmas and a global instability has been observed when the ion fraction exceeds 10 %. A characterization of this instability is presented in [2], analyzing its parameter dependence and spatial structure (non- resonant with rational surfaces). A new set of experiments is currently underway studying plasmas of arbitrary degree of neutralization, ranging from pure electron to quasineutral plasmas. Basic observations show that the plasma potential decouples from emitter bias when we increase the degree of the neutralization of our plasmas. Partially neutralized plasmas are also characterized by multiple mode behavior with dominant modes between 20 and 200 kHz. When the plasma becomes quasineutral, it reverts to single mode behavior. The first results on partially neutralized plasmas confined on magnetic surfaces will be presented. [1] J. Kremer, PRL 97, (2006) 095003 [2] Q. Marksteiner, PRL 100 (2008) 065002

  2. Plasma/Neutral-Beam Etching Apparatus

    Science.gov (United States)

    Langer, William; Cohen, Samuel; Cuthbertson, John; Manos, Dennis; Motley, Robert

    1989-01-01

    Energies of neutral particles controllable. Apparatus developed to produce intense beams of reactant atoms for simulating low-Earth-orbit oxygen erosion, for studying beam-gas collisions, and for etching semiconductor substrates. Neutral beam formed by neutralization and reflection of accelerated plasma on metal plate. Plasma ejected from coaxial plasma gun toward neutralizing plate, where turned into beam of atoms or molecules and aimed at substrate to be etched.

  3. From Foreground to Background: How Task-Neutral Context Influences Contextual Cueing of Visual Search

    OpenAIRE

    Zang, Xuelian; Geyer, Thomas; Assump??o, Leonardo; M?ller, Hermann J.; Shi, Zhuanghua

    2016-01-01

    Selective attention determines the effectiveness of implicit contextual learning (e.g., Jiang and Leung, 2005). Visual foreground-background segmentation, on the other hand, is a key process in the guidance of attention (Wolfe, 2003). In the present study, we examined the impact of foreground-background segmentation on contextual cueing of visual search in three experiments. A visual search display, consisting of distractor ‘L’s and a target ‘T’, was overlaid on a task-neutral cuboid on the s...

  4. Observation of Beam Driven Modes during Neutral Beam Heating on the National Spherical Torus Experiment

    International Nuclear Information System (INIS)

    Fredrickson, E.D.; Gorelenkov, E.D.; Cheng, C.Z.; Bell, R.; Darrow, D.; Johnson, D.; Kaye, S.; LeBlanc, B.; Menard, J.; Kubota, S.; Peebles, W.

    2001-01-01

    With the first injection of neutral beams on the National Spherical Torus Experiment (NSTX), a broad and complicated spectrum of coherent modes was seen between approximately 0.4 MHz and 2.5 MHz [where f(subscript ''ci'')] for deuterium is approximately 2.2 MHz. The modes have been observed with high bandwidth magnetic pick-up coils and with a reflectometer. The parametric scaling of the mode frequency with density and magnetic field is consistent with Alfvenic modes (linear in B, inversely with the square root of density). These modes have been identified as magnetosonic waves or compressional Alfven eigenmodes (CAE) excited by a cyclotron resonance with the neutral-beam ions. Modes have also been observed in the frequency range 50-150 kHz with toroidal mode numbers n = 1-5. These lower frequency modes are thought to be related to the TAE [Toroidal Alfven Eigenmode] seen commonly in tokamaks and driven by energetic fast ion populations resulting from ICRF [ion cyclotron range of frequency] and NBI [neutral-beam injection] heating. There is no clear indication of enhanced fast ion losses associated with the modes

  5. On plasma-neutral gas interaction

    International Nuclear Information System (INIS)

    Venkataramani, N.; Mattoo, S.K.

    1980-01-01

    The importance of plasma-neutral gas interaction layer has been emphasized by pointing out its application to a wide variety of physical phenomena. The interaction of a magnetised plasma stream penetrating a neutral gas cloud is discussed in the light of Alfven's critical velocity and Varma's threshold velocity on the ionising interaction. Interaction of a moving magnetised plasma with a stationary neutral gas has been studied and described. The device comprises of a plasma gun and an interaction region where neutral gas cloud is injected. The interaction region is provided with a transverse magnetic field of upto 1000 G. Several diagnostics deployed at the interaction region to make measurements on the macroscopic parameters of plasma and neutral gas are described. The parameters of discharge circuits are measured with high current and voltage probes. An interaction between a magnetised plasma stream and a neutral gas cloud is demonstrated. It is shown that this interaction does not have Varma's threshold on their relative velocity. The Alfven's critical velocity phenomenon is shown to depend on the integrated column neutral gas density that a plasma stream encounters while penetrating through it and not on the neutral gas density in the range of 10 17 -10 21 m -3 . (auth.)

  6. Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail

    Directory of Open Access Journals (Sweden)

    Takeo eKuwata

    2013-05-01

    Full Text Available The role of antibodies in protecting the host from human immunodeficiency virus type 1 (HIV-1 infection is of considerable interest, particularly because the RV144 trial results suggest that antibodies contribute to protection. Although infection of nonhuman primates with simian immunodeficiency virus (SIV is commonly used as an animal model of HIV-1 infection, the viral epitopes that elicit potent and broad neutralizing antibodies to SIV have not been identified. We isolated a monoclonal antibody (MAb B404 that potently and broadly neutralizes various SIV strains. B404 targets a conformational epitope comprising the V3 and V4 loops of Env that intensely exposed when Env binds CD4. B404-resistant variants were obtained by passaging viruses in the presence of increasing concentration of B404 in PM1/CCR5 cells. Genetic analysis revealed that the Q733stop mutation, which truncates the cytoplasmic tail of gp41, was the first major substitution in Env during passage. The maximal inhibition by B404 and other MAbs were significantly decreased against a recombinant virus with a gp41 truncation compared with the parental SIVmac316. This indicates that the gp41 truncation was associated with resistance to antibody-mediated neutralization. The infectivities of the recombinant virus with the gp41 truncation were 7900-fold, 1000-fold, and 140-fold higher than those of SIVmac316 in PM1, PM1/CCR5, and TZM-bl cells, respectively. Immunoblotting analysis revealed that the gp41 truncation enhanced the incorporation of Env into virions. The effect of the gp41 truncation on infectivity was not obvious in the HSC-F macaque cell line, although the resistance of viruses harboring the gp41 truncation to neutralization was maintained. These results suggest that viruses with a truncated gp41 cytoplasmic tail were selected by increased infectivity in human cells and by acquiring resistance to neutralizing antibody.

  7. Is an inequality-neutral flat tax reform really neutral?

    OpenAIRE

    Juan Prieto Rodríguez; Juan Gabriel Rodríguez; Rafael Salas

    2004-01-01

    . Let us assume a revenue- and inequality-neutral flat tax reform shifting from a graduated-rate tax. Is this reform really neutral in terms of the income distribution? Traditionally, there has been a bias toward the inequality analysis, forgetting other relevant aspects of the income distribution. This kind of reforms implies a set of composite transfers, both progressive and regressive, even though inequality remains unchanged. This paper shows that polarization is a useful tool for charact...

  8. Recent advances in neutral particle transport methods and codes

    International Nuclear Information System (INIS)

    Azmy, Y.Y.

    1996-01-01

    An overview of ORNL's three-dimensional neutral particle transport code, TORT, is presented. Special features of the code that make it invaluable for large applications are summarized for the prospective user. Advanced capabilities currently under development and installation in the production release of TORT are discussed; they include: multitasking on Cray platforms running the UNICOS operating system; Adjacent cell Preconditioning acceleration scheme; and graphics codes for displaying computed quantities such as the flux. Further developments for TORT and its companion codes to enhance its present capabilities, as well as expand its range of applications are disucssed. Speculation on the next generation of neutron particle transport codes at ORNL, especially regarding unstructured grids and high order spatial approximations, are also mentioned

  9. Isolation of a new broad spectrum antifungal polyene from Streptomyces sp. MTCC 5680.

    Science.gov (United States)

    Vartak, A; Mutalik, V; Parab, R R; Shanbhag, P; Bhave, S; Mishra, P D; Mahajan, G B

    2014-06-01

    A new polyene macrolide antibiotic PN00053 was isolated from the fermentation broth of Streptomyces sp. wild-type strain MTCC-5680. The producer strain was isolated from fertile mountain soil of Naldehra region, Himachal Pradesh, India. The compound PN00053 was purified through various steps of chromatographic techniques and bio-activity guided fractionation followed by its characterization using physiochemical properties, spectral data ((1) H-NMR, (13) C-NMR, HMBC, HSQC, and COSY) and MS analysis. PN00053 exhibited broad spectrum in vitro antifungal activity against strains of Aspergillus fumigatus (HMR), A. fumigatus ATCC 16424, Candida albicans (I.V.), C. albicans ATCC 14503, C. krusei GO6, C. glabrata HO4, Cryptococcus neoformans, Trichophyton sp. as well as fluconazole resistant strains C. krusei GO3 and C. glabrata HO5. It did not inhibit growth of gram positive and gram-negative bacteria, displaying its specificity against fungi. PN00053 is a novel polyene macrolide isolated from a wild strain of Streptomyces sp. PM0727240 (MTCC5680), an isolate from the mountainous rocky regions of Himachal Pradesh, India. The compound is a new derivative of the antibiotic Roflamycoin [32, 33-didehydroroflamycoin (DDHR)]. It displayed broad spectrum antifungal activity against yeast and filamentous fungi. However, it did not show any antibacterial activity. The in vitro study revealed that PN00053 has better potency as compared to clinical gold standard fluconazole. The development of pathogenic resistance against the polyenes has been seldom reported. Hence, we envisage PN00053 could be a potential antifungal lead. © 2014 The Society for Applied Microbiology.

  10. Plasma particle sources due to interactions with neutrals in a turbulent scrape-off layer of a toroidally confined plasma

    DEFF Research Database (Denmark)

    Thrysøe, Alexander Simon; Løiten, M.; Madsen, J.

    2018-01-01

    The conditions in the edge and scrape-off layer (SOL) of magnetically confined plasmas determine the overall performance of the device, and it is of great importance to study and understand the mechanics that drive transport in those regions. If a significant amount of neutral molecules and atoms...... is present in the edge and SOL regions, those will influence the plasma parameters and thus the plasma confinement. In this paper, it is displayed how neutrals, described by a fluid model, introduce source terms in a plasma drift-fluid model due to inelastic collisions. The resulting source terms...... are included in a four-field drift fluid model, and it is shown how an increasing neutral particle density in the edge and SOL regions influences the plasma particle transport across the lastclosed-flux-surface. It is found that an appropriate gas puffing rate allows for the edge density in the simulation...

  11. Neutral Buoyancy Laboratory (NBL)

    Data.gov (United States)

    Federal Laboratory Consortium — The Neutral Buoyancy Laboratory (NBL) is an astronaut training facility and neutral buoyancy pool operated by NASA and located at the Sonny Carter Training Facility,...

  12. A Supercluster of Neutralizing Epitopes at the Interface of Ricin’s Enzymatic (RTA and Binding (RTB Subunits

    Directory of Open Access Journals (Sweden)

    Amanda Y. Poon

    2017-11-01

    Full Text Available As part of an effort to engineer ricin antitoxins and immunotherapies, we previously produced and characterized a collection of phage-displayed, heavy chain-only antibodies (VHHs from alpacas that had been immunized with ricin antigens. In our initial screens, we identified nine VHHs directed against ricin toxin’s binding subunit (RTB, but only one, JIZ-B7, had toxin-neutralizing activity. Linking JIZ-B7 to different VHHs against ricin’s enzymatic subunit (RTA resulted in several bispecific antibodies with potent toxin-neutralizing activity in vitro and in vivo. JIZ-B7 may therefore be an integral component of a future VHH-based neutralizing agent (VNA for ricin toxin. In this study, we now localize, using competitive ELISA, JIZ-B7’s epitope to a region of RTB’s domain 2 sandwiched between the high-affinity galactose/N-acetylgalactosamine (Gal/GalNAc-binding site and the boundary of a neutralizing hotspot on RTA known as cluster II. Analysis of additional RTB (n = 8- and holotoxin (n = 4-specific VHHs from a recent series of screens identified a “supercluster” of neutralizing epitopes at the RTA-RTB interface. Among the VHHs tested, toxin-neutralizing activity was most closely associated with epitope proximity to RTA, and not interference with RTB’s ability to engage Gal/GalNAc receptors. We conclude that JIZ-B7 is representative of a larger group of potent toxin-neutralizing antibodies, possibly including many described in the literature dating back several decades, that recognize tertiary and possibly quaternary epitopes located at the RTA-RTB interface and that target a region of vulnerability on ricin toxin.

  13. Proceedings of the LAMPF workshop on photon and neutral meson physics at intermediate energies

    International Nuclear Information System (INIS)

    Baer, H.W.; Crannell, H.; Peterson, R.J.

    1987-12-01

    This volume contains the Proceedings of the Workshop on ''Photon and Neutral-Meson, Physics at Intermediate Energies,'' held at Los Alamos, New Mexico, January 7 to 9, 1987. The purpose of this workshop was to bring together scientists working in the areas of electromagnetic, heavy-ion, and light hadron physics to discuss both the physics that could be addressed and potential capabilities of new, large intermediate-energy photon detectors. Based on the papers contained in these proceedings, it appears clear that there are a number of important areas that could be addressed with a much higher resolution neutral meson detector. It is also clear that the technical capability for building a neutral meson detector for energies up to 4 GeV with solid angle of approximately 10 mrs and resolution of a few hundred keV now exists. It also appears entirely reasonable to construct such a detector to be easily transportable so that it would become a national facility, available for use at a number of different laboratories. From the many interesting papers presented and from the broad representation of physicists from laboratories in Asia, Canada, Europe, Japan, and the United States, there appears to be a strong case for proceeding with the construction of such a detector

  14. A small sized time-of-flight mass spectrometer for simultaneous measurement of neutral and ionic species effusing from plasma, 1

    International Nuclear Information System (INIS)

    Horiuchi, Yukihiko

    1986-01-01

    A principle for simultaneous and real time measurement of neutral and ionic species effusing from plasma by using a time-of-flight mass spectrometer is proposed. A simple, small sized time-of-flight mass spectrometer combined with a dc glow discharge tube and an ion sampling electrode system for the simultaneous measurement on the basis of the proposed plinciple, has been constructed and tested. Details of the experimental setup including the geometry and the electronic hardware are described. It is shown that mass spectra of neutrals and ions from the positive column of the argon dc glow discharge are successfully observed on a single oscilloscope display. (author)

  15. Actively paranoid patients with schizophrenia over attribute anger to neutral faces.

    Science.gov (United States)

    Pinkham, Amy E; Brensinger, Colleen; Kohler, Christian; Gur, Raquel E; Gur, Ruben C

    2011-02-01

    Previous investigations of the influence of paranoia on facial affect recognition in schizophrenia have been inconclusive as some studies demonstrate better performance for paranoid relative to non-paranoid patients and others show that paranoid patients display greater impairments. These studies have been limited by small sample sizes and inconsistencies in the criteria used to define groups. Here, we utilized an established emotion recognition task and a large sample to examine differential performance in emotion recognition ability between patients who were actively paranoid (AP) and those who were not actively paranoid (NAP). Accuracy and error patterns on the Penn Emotion Recognition test (ER40) were examined in 132 patients (64 NAP and 68 AP). Groups were defined based on the presence of paranoid ideation at the time of testing rather than diagnostic subtype. AP and NAP patients did not differ in overall task accuracy; however, an emotion by group interaction indicated that AP patients were significantly worse than NAP patients at correctly labeling neutral faces. A comparison of error patterns on neutral stimuli revealed that the groups differed only in misattributions of anger expressions, with AP patients being significantly more likely to misidentify a neutral expression as angry. The present findings suggest that paranoia is associated with a tendency to over attribute threat to ambiguous stimuli and also lend support to emerging hypotheses of amygdala hyperactivation as a potential neural mechanism for paranoid ideation. Copyright © 2010 Elsevier B.V. All rights reserved.

  16. Impaired nutrient signaling and body weight control in a Na+ neutral amino acid cotransporter (Slc6a19)-deficient mouse.

    Science.gov (United States)

    Bröer, Angelika; Juelich, Torsten; Vanslambrouck, Jessica M; Tietze, Nadine; Solomon, Peter S; Holst, Jeff; Bailey, Charles G; Rasko, John E J; Bröer, Stefan

    2011-07-29

    Amino acid uptake in the intestine and kidney is mediated by a variety of amino acid transporters. To understand the role of epithelial neutral amino acid uptake in whole body homeostasis, we analyzed mice lacking the apical broad-spectrum neutral (0) amino acid transporter B(0)AT1 (Slc6a19). A general neutral aminoaciduria was observed similar to human Hartnup disorder which is caused by mutations in SLC6A19. Na(+)-dependent uptake of neutral amino acids into the intestine and renal brush-border membrane vesicles was abolished. No compensatory increase of peptide transport or other neutral amino acid transporters was detected. Mice lacking B(0)AT1 showed a reduced body weight. When adapted to a standard 20% protein diet, B(0)AT1-deficient mice lost body weight rapidly on diets containing 6 or 40% protein. Secretion of insulin in response to food ingestion after fasting was blunted. In the intestine, amino acid signaling to the mammalian target of rapamycin (mTOR) pathway was reduced, whereas the GCN2/ATF4 stress response pathway was activated, indicating amino acid deprivation in epithelial cells. The results demonstrate that epithelial amino acid uptake is essential for optimal growth and body weight regulation.

  17. European display scene

    Science.gov (United States)

    Bartlett, Christopher T.

    2000-08-01

    The manufacture of Flat Panel Displays (FPDs) is dominated by Far Eastern sources, particularly in Active Matrix Liquid Crystal Displays (AMLCD) and Plasma. The United States has a very powerful capability in micro-displays. It is not well known that Europe has a very active research capability which has lead to many innovations in display technology. In addition there is a capability in display manufacturing of organic technologies as well as the licensed build of Japanese or Korean designs. Finally, Europe has a display systems capability in military products which is world class.

  18. Effect of display location on control-display stereotype strength for translational and rotational controls with linear displays.

    Science.gov (United States)

    Chan, Alan H S; Hoffmann, Errol R

    2015-01-01

    Experiments were designed to investigate the effects of control type and display location, relative to the operator, on the strength of control/display stereotypes. The Worringham and Beringer Visual Field principle and an extension of this principle for rotary controls (Hoffmann E.R., and Chan A.H.S. 2013). "The Worringham and Beringer 'Visual Field' Principle for Rotary Controls. Ergonomics." 56 (10): 1620-1624) indicated that, for a number of different control types (rotary and lever) on different planes, there should be no significant effect of the display location relative to the seated operator. Past data were surveyed and stereotype strengths listed. Experiments filled gaps where data are not available. Six different control types and seven display locations were used, as in the Frame of Reference Transformation Tool (FORT) model of Wickens et al. (Wickens, C.D., Keller, J.W., and Small, R.L. (2010). "Left. No, Right! Development of the Frame of Reference Transformation Tool (FORT)." Proceedings of the Human Factors and Ergonomics Society 54th Annual Meeting September 2010, 54: 1022-1026). Control/display arrangements with high stereotype strengths were evaluated yielding data for designers of complex control/display arrangements where the control and display are in different planes and for where the operator is moving. It was found possible to predict display/control arrangements with high stereotype strength, based on past data. Practitioner Summary: Controls and displays in complex arrangements need to have high compatibility. These experiments provide arrangements for six different controls (rotary and translational) and seven different display locations relative to the operator.

  19. Neutral currents

    International Nuclear Information System (INIS)

    Aubert, B.

    1994-11-01

    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

  20. OLED Display For Real Time Vision System

    Directory of Open Access Journals (Sweden)

    Sandhyalakshmi Narayanan

    2015-08-01

    Full Text Available This innovative glass design will carry an OLED based display controlled via nano Ardiuno board having Bluetooth connectivity with a Smartphone to exchange information along with onboard accelerometer. We are using a tilt angle sensor for detecting if the driver is feeling drowsy. An alcohol sensor has been used to promote the safe driving habit. The glasses will be getting latest updates about the current speed of the vehicle navigation directions nearby or approaching sign broads or services like petrol pumps. Itll also display information like incoming calls or received messages. All this information will be obtained through a Smartphone connected via Bluetooth. Also the car mileage can be monitored with help of fuel sensor as the consumption of fuel is directly related to it. Abnormalities if detected will be immediately notified in the glasses. Also the angle of the tilt angle sensor can be defined and set by the user according to his needs. Also the main idea of using OLED glasses is that it is organic thereby helps in reducing the carbon footprint and is quite slim. Therefore it can be easily mounted on the specs without making it heavy. Also they higher level of flexibility and have low power drain and energy consumption

  1. Differences in Allelic Frequency and CDRH3 Region Limit the Engagement of HIV Env Immunogens by Putative VRC01 Neutralizing Antibody Precursors

    Directory of Open Access Journals (Sweden)

    Christina Yacoob

    2016-11-01

    Full Text Available Elicitation of broadly neutralizing antibodies remains a long-standing goal of HIV vaccine research. Although such antibodies can arise during HIV-1 infection, gaps in our knowledge of their germline, pre-immune precursor forms, as well as on their interaction with viral Env, limit our ability to elicit them through vaccination. Studies of broadly neutralizing antibodies from the VRC01-class provide insight into progenitor B cell receptors (BCRs that could develop into this class of antibodies. Here, we employed high-throughput heavy chain variable region (VH/light chain variable region (VL deep sequencing, combined with biophysical, structural, and modeling antibody analyses, to interrogate circulating potential VRC01-progenitor BCRs in healthy individuals. Our study reveals that not all humans are equally predisposed to generate VRC01-class antibodies, not all predicted progenitor VRC01-expressing B cells can bind to Env, and the CDRH3 region of germline VRC01 antibodies influence their ability to recognize HIV-1. These findings will be critical to the design of optimized immunogens that should consider CDRH3 interactions.

  2. Displays in scintigraphy

    International Nuclear Information System (INIS)

    Todd-Pokropek, A.E.; Pizer, S.M.

    1977-01-01

    Displays have several functions: to transmit images, to permit interaction, to quantitate features and to provide records. The main characteristics of displays used for image transmission are their resolution, dynamic range, signal-to-noise ratio and uniformity. Considerations of visual acuity suggest that the display element size should be much less than the data element size, and in current practice at least 256X256 for a gamma camera image. The dynamic range for image transmission should be such that at least 64 levels of grey (or equivalent) are displayed. Scanner displays are also considered, and in particular, the requirements of a whole-body camera are examined. A number of display systems and devices are presented including a 'new' heated object colour display system. Interaction with displays is considered, including background subtraction, contrast enhancement, position indication and region-of-interest generation. Such systems lead to methods of quantitation, which imply knowledge of the expected distributions. Methods for intercomparing displays are considered. Polaroid displays, which have for so long dominated the field, are in the process of being replaced by stored image displays, now that large cheap memories exist which give an equivalent image quality. The impact of this in nuclear medicine is yet to be seen, but a major effect will be to enable true quantitation. (author)

  3. Make the Alberta Carbon Levy Revenue Neutral

    Directory of Open Access Journals (Sweden)

    Kenneth J. McKenzie

    2016-04-01

    Full Text Available The new carbon levy of $30 per tonne, announced in November 2015 as part of the report issued by the Alberta government’s Climate Leadership Panel, is a positive move in the direction of pricing carbon emissions. The levy is expected to generate $3 billion in net revenue by 2018, and possibly as much as $5 billion by 2030. While there is some discussion in the report of what should be done with the revenues generated by the carbon levy, it is somewhat vague on the details, leaving a number of options open to the government. The purpose of this briefing paper is to argue that the revenues from the carbon levy should be used to lower existing taxes – the carbon tax should be revenue neutral, generating no new net revenue for the government. The basic argument is that the carbon levy can be viewed through two lenses. The first lens is the imposition of a price on carbon emissions which (at least partly reflects the social costs of emissions. Viewed through this price lens, the carbon levy plays an important role in incenting firms and individuals to change their behaviour and move towards less carbon intensive activities. The second lens is the role of a carbon tax as a part of the broad revenue system. Viewed through this tax lens, a carbon tax is not a very good, or efficient, way of generating revenue. The reason for this is somewhat nuanced, but the basic idea is that the carbon tax is applied to a narrower base than broader-based taxes. Broad based taxes generally impose lower costs on the economy than narrow based taxes. Moreover, carbon taxes interact with other taxes in the economy, exacerbating the economic costs associated with those taxes. And those costs are quite high – research shows that the total cost to the economy of raising an additional $1 in revenue through the corporate income tax in Alberta is $3.79; for the personal income tax the cost is $1.71. These taxes therefore impose higher costs on the economy than they raise

  4. Public support for neonatal screening for Pompe disease, a broad-phenotype condition

    Directory of Open Access Journals (Sweden)

    Weinreich Stephanie

    2012-03-01

    Full Text Available Abstract Background Neonatal screening for Pompe disease has been introduced in Taiwan and a few U.S. states, while other jurisdictions including some European countries are piloting or considering this screening. First-tier screening flags both classic infantile and late-onset Pompe disease, which challenges current screening criteria. Previously, advocacy groups have sometimes supported expanded neonatal screening more than professional experts, while neutral citizens' views were unknown. This study aimed to measure support for neonatal screening for Pompe disease in the general public and to compare it to support among (parents of patients with this condition. The study was done in the Netherlands, where newborns are not currently screened for Pompe disease. Newborn screening is not mandatory in the Netherlands but current uptake is almost universal. Methods A consumer panel (neutral group and (parents of patients with Pompe disease (Pompe group were sent information and a questionnaire. Responses were analyzed of 555 neutral and 58 Pompe-experienced informants who had demonstrated sufficient understanding. Results 87% of the neutral group and 88% of the Pompe group supported the introduction of screening (95% CI of difference -10 to 7%. The groups were similar in their moral reasoning about screening and acceptance of false positives, but the Pompe-experienced group expected greater benefit from neonatal detection of late-onset disease. Multivariate regression analysis controlling for demographics confirmed that approval of the introduction of screening was independent of having (a child with Pompe disease. Furthermore, respondents with university education, regardless of whether they have (a child with Pompe disease, were more likely to be reluctant about the introduction of screening than those with less education, OR for approval 0.29 (95% CI 0.18 to 0.49, p Conclusions This survey suggests a rather high level of support for newborn

  5. Monocular display unit for 3D display with correct depth perception

    Science.gov (United States)

    Sakamoto, Kunio; Hosomi, Takashi

    2009-11-01

    A study of virtual-reality system has been popular and its technology has been applied to medical engineering, educational engineering, a CAD/CAM system and so on. The 3D imaging display system has two types in the presentation method; one is a 3-D display system using a special glasses and the other is the monitor system requiring no special glasses. A liquid crystal display (LCD) recently comes into common use. It is possible for this display unit to provide the same size of displaying area as the image screen on the panel. A display system requiring no special glasses is useful for a 3D TV monitor, but this system has demerit such that the size of a monitor restricts the visual field for displaying images. Thus the conventional display can show only one screen, but it is impossible to enlarge the size of a screen, for example twice. To enlarge the display area, the authors have developed an enlarging method of display area using a mirror. Our extension method enables the observers to show the virtual image plane and to enlarge a screen area twice. In the developed display unit, we made use of an image separating technique using polarized glasses, a parallax barrier or a lenticular lens screen for 3D imaging. The mirror can generate the virtual image plane and it enlarges a screen area twice. Meanwhile the 3D display system using special glasses can also display virtual images over a wide area. In this paper, we present a monocular 3D vision system with accommodation mechanism, which is useful function for perceiving depth.

  6. 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…

  7. Authentic display of a cholera toxin epitope by chimeric type 1 fimbriae: effects of insert position and host background

    DEFF Research Database (Denmark)

    Stentebjerg-Olesen, B; Pallesen, L; Jensen, LB

    1997-01-01

    The potential of the major structural protein of type 1 fimbriae as a display system for heterologous sequences was tested. As a reporter-epitope, a heterologous sequence mimicking a neutralizing epitope of the cholera toxin B chain was inserted, in one or two copies, into four different positions...... in the fimA gene. This was carried out by introduction of new restriction sites by PCR-mediated site-directed mutagenesis of fimA in positions predicted to correspond to optimally surface-located regions of the subunit protein. Subsequently, the synthetic cholera-toxin-encoding DNA segment was inserted....... Several of the chosen positions seemed amenable even for large foreign inserts; the chimeric proteins were exposed on the bacterial surface and the cholera toxin epitope was authentically displayed, i.e. it was recognized on bacteria by specific antiserum. Display of chimeric fimbriae was tested...

  8. Human monoclonal antibodies to a novel cluster of conformational epitopes on HCV E2 with resistance to neutralization escape in a genotype 2a isolate

    DEFF Research Database (Denmark)

    Keck, Zhen-yong; Xia, Jinming; Wang, Yong

    2012-01-01

    The majority of broadly neutralizing antibodies to hepatitis C virus (HCV) are against conformational epitopes on the E2 glycoprotein. Many of them recognize overlapping epitopes in a cluster, designated as antigenic domain B, that contains residues G530 and D535. To gain information on other reg...

  9. Phenomenology of neutral current interactions

    International Nuclear Information System (INIS)

    Sakurai, J.J.

    1978-01-01

    Neutral-current interactions are discussed within a rather general phenomenological framework without commitment to any particular theoretical model. Three points are kept in mind: what various experiments really measure; the performing of complete experiments to determine the neutral-current couplings; and the testing of models in an objective, emotionally uninvolved manner. The following topics are considered: neutrino-electron scattering, hadronic currents and models, neutrino-induced inclusive hadronic reactions, neutrino-induced exclusive hadronic reactions, and neutral-current phenomena without neutrinos. In conclusion, what has actually been learned about neutral-current interactions is summarized. 9 figures, 2 tables

  10. Development of a broad-spectrum antiviral with activity against Ebola virus.

    Science.gov (United States)

    Aman, M Javad; Kinch, Michael S; Warfield, Kelly; Warren, Travis; Yunus, Abdul; Enterlein, Sven; Stavale, Eric; Wang, Peifang; Chang, Shaojing; Tang, Qingsong; Porter, Kevin; Goldblatt, Michael; Bavari, Sina

    2009-09-01

    We report herein the identification of a small molecule therapeutic, FGI-106, which displays potent and broad-spectrum inhibition of lethal viral hemorrhagic fevers pathogens, including Ebola, Rift Valley and Dengue Fever viruses, in cell-based assays. Using mouse models of Ebola virus, we further demonstrate that FGI-106 can protect animals from an otherwise lethal infection when used either in a prophylactic or therapeutic setting. A single treatment, administered 1 day after infection, is sufficient to protect animals from lethal Ebola virus challenge. Cell-based assays also identified inhibitory activity against divergent virus families, which supports a hypothesis that FGI-106 interferes with a common pathway utilized by different viruses. These findings suggest FGI-106 may provide an opportunity for targeting viral diseases.

  11. 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.

  12. Host-Primed Ebola Virus GP Exposes a Hydrophobic NPC1 Receptor-Binding Pocket, Revealing a Target for Broadly Neutralizing Antibodies.

    Science.gov (United States)

    Bornholdt, Zachary A; Ndungo, Esther; Fusco, Marnie L; Bale, Shridhar; Flyak, Andrew I; Crowe, James E; Chandran, Kartik; Saphire, Erica Ollmann

    2016-02-23

    The filovirus surface glycoprotein (GP) mediates viral entry into host cells. Following viral internalization into endosomes, GP is cleaved by host cysteine proteases to expose a receptor-binding site (RBS) that is otherwise hidden from immune surveillance. Here, we present the crystal structure of proteolytically cleaved Ebola virus GP to a resolution of 3.3 Å. We use this structure in conjunction with functional analysis of a large panel of pseudotyped viruses bearing mutant GP proteins to map the Ebola virus GP endosomal RBS at molecular resolution. Our studies indicate that binding of GP to its endosomal receptor Niemann-Pick C1 occurs in two distinct stages: the initial electrostatic interactions are followed by specific interactions with a hydrophobic trough that is exposed on the endosomally cleaved GP1 subunit. Finally, we demonstrate that monoclonal antibodies targeting the filovirus RBS neutralize all known filovirus GPs, making this conserved pocket a promising target for the development of panfilovirus therapeutics. Ebola virus uses its glycoprotein (GP) to enter new host cells. During entry, GP must be cleaved by human enzymes in order for receptor binding to occur. Here, we provide the crystal structure of the cleaved form of Ebola virus GP. We demonstrate that cleavage exposes a site at the top of GP and that this site binds the critical domain C of the receptor, termed Niemann-Pick C1 (NPC1). We perform mutagenesis to find parts of the site essential for binding NPC1 and map distinct roles for an upper, charged crest and lower, hydrophobic trough in cleaved GP. We find that this 3-dimensional site is conserved across the filovirus family and that antibody directed against this site is able to bind cleaved GP from every filovirus tested and neutralize viruses bearing those GPs. Copyright © 2016 Bornholdt et al.

  13. Is a neutral expression also a neutral stimulus? A study with functional magnetic resonance.

    Science.gov (United States)

    Carvajal, Fernando; Rubio, Sandra; Serrano, Juan M; Ríos-Lago, Marcos; Alvarez-Linera, Juan; Pacheco, Lara; Martín, Pilar

    2013-08-01

    Although neutral faces do not initially convey an explicit emotional message, it has been found that individuals tend to assign them an affective content. Moreover, previous research has shown that affective judgments are mediated by the task they have to perform. Using functional magnetic resonance imaging in 21 healthy participants, we focus this study on the cerebral activity patterns triggered by neutral and emotional faces in two different tasks (social or gender judgments). Results obtained, using conjunction analyses, indicated that viewing both emotional and neutral faces evokes activity in several similar brain areas indicating a common neural substrate. Moreover, neutral faces specifically elicit activation of cerebellum, frontal and temporal areas, while emotional faces involve the cuneus, anterior cingulated gyrus, medial orbitofrontal cortex, posterior superior temporal gyrus, precentral/postcentral gyrus and insula. The task selected was also found to influence brain activity, in that the social task recruited frontal areas while the gender task involved the posterior cingulated, inferior parietal lobule and middle temporal gyrus to a greater extent. Specifically, in the social task viewing neutral faces was associated with longer reaction times and increased activity of left dorsolateral frontal cortex compared with viewing facial expressions of emotions. In contrast, in the same task emotional expressions distinctively activated the left amygdale. The results are discussed taking into consideration the fact that, like other facial expressions, neutral expressions are usually assigned some emotional significance. However, neutral faces evoke a greater activation of circuits probably involved in more elaborate cognitive processing.

  14. Automated Calculation of DIII-D Neutral Beam Availability

    International Nuclear Information System (INIS)

    Phillips, J.C.; Hong, R.M.; Scoville, B.G.

    1999-01-01

    The neutral beam systems for the DIII-D tokamak are an extremely reliable source of auxiliary plasma heating, capable of supplying up to 20 MW of injected power, from eight separate beam sources into each tokamak discharge. The high availability of these systems for tokamak operations is sustained by careful monitoring of performance and following up on failures. One of the metrics for this performance is the requested injected power profile as compared to the power profile delivered for a particular pulse. Calculating this was a relatively straightforward task, however innovations such as the ability to modulate the beams and more recently the ability to substitute an idle beam for one which has failed during a plasma discharge, have made the task very complex. For example, with this latest advance it is possible for one or more beams to have failed, yet the delivered power profile may appear perfect. Availability used to be manually calculated. This paper presents the methods and algorithms used to produce a system which performs the calculations based on information concerning the neutral beam and plasma current waveforms, along with post-discharge information from the Plasma Control System, which has the ability to issue commands for beams in real time. Plots representing both the requested and actual power profiles, along with statistics, are automatically displayed and updated each shot, on a web-based interface viewable both at DIII-D and by our remote collaborators using no-cost software

  15. ORNL positive ion neutral beam program

    International Nuclear Information System (INIS)

    Whealton, J.H.; Haselton, H.H.; Barber, G.C.

    1978-01-01

    The neutral beam group at Oak Ridge National Laboratory has constructed neutral beam generators for the ORMAK and PLT devices, is presently constructing neutral beam devices for the ISX and PDX devices, and is contemplating the construction of neutral beam systems for the advanced TNS device. These neutral beam devices stem from the pioneering work on ion sources of G. G. Kelley and O. B. Morgan. We describe the ion sources under development at this Laboratory, the beam optics exhibited by these sources, as well as some theoretical considerations, and finally the remainder of the beamline design

  16. Hidden Broad-line Regions in Seyfert 2 Galaxies: From the Spectropolarimetric Perspective

    International Nuclear Information System (INIS)

    Du, Pu; Wang, Jian-Min; Zhang, Zhi-Xiang

    2017-01-01

    The hidden broad-line regions (BLRs) in Seyfert 2 galaxies, which display broad emission lines (BELs) in their polarized spectra, are a key piece of evidence in support of the unified model for active galactic nuclei (AGNs). However, the detailed kinematics and geometry of hidden BLRs are still not fully understood. The virial factor obtained from reverberation mapping of type 1 AGNs may be a useful diagnostic of the nature of hidden BLRs in type 2 objects. In order to understand the hidden BLRs, we compile six type 2 objects from the literature with polarized BELs and dynamical measurements of black hole masses. All of them contain pseudobulges. We estimate their virial factors, and find the average value is 0.60 and the standard deviation is 0.69, which agree well with the value of type 1 AGNs with pseudobulges. This study demonstrates that (1) the geometry and kinematics of BLR are similar in type 1 and type 2 AGNs of the same bulge type (pseudobulges), and (2) the small values of virial factors in Seyfert 2 galaxies suggest that, similar to type 1 AGNs, BLRs tend to be very thick disks in type 2 objects.

  17. 78 FR 20119 - Broad Stakeholder Survey

    Science.gov (United States)

    2013-04-03

    ... DEPARTMENT OF HOMELAND SECURITY [Docket No. DHS-2012-0042] Broad Stakeholder Survey AGENCY... concerning the Broad Stakeholder Survey. DHS previously published this ICR in the Federal Register on August... across the Nation. The Broad Stakeholder Survey is designed to gather stakeholder feedback on the...

  18. Broad band exciplex dye lasers

    International Nuclear Information System (INIS)

    Dienes, A.; Shank, C.V.; Trozzolo, A.M.

    1975-01-01

    The disclosure is concerned with exciplex dye lasers, i.e., lasers in which the emitting species is a complex formed only from a constituent in an electronically excited state. Noting that an exciplex laser, favorable from the standpoint of broad tunability, results from a broad shift in the peak emission wavelength for the exciplex relative to the unreacted species, a desirable class resulting in such broad shift is described. Preferred classes of laser media utilizing specified resonant molecules are set forth. (auth)

  19. The Bootstrap Current and Neutral Beam Current Drive in DIII-D

    International Nuclear Information System (INIS)

    Politzer, P.A.

    2005-01-01

    Noninductive current drive is an essential part of the implementation of the DIII-D Advanced Tokamak program. For an efficient steady-state tokamak reactor, the plasma must provide close to 100% bootstrap fraction (f bs ). For noninductive operation of DIII-D, current drive by injection of energetic neutral beams [neutral beam current drive (NBCD)] is also important. DIII-D experiments have reached ∼80% bootstrap current in stationary discharges without inductive current drive. The remaining current is ∼20% NBCD. This is achieved at β N [approximately equal to] β p > 3, but at relatively high q 95 (∼10). In lower q 95 Advanced Tokamak plasmas, f bs ∼ 0.6 has been reached in essentially noninductive plasmas. The phenomenology of high β p and β N plasmas without current control is being studied. These plasmas display a relaxation oscillation involving repetitive formation and collapse of an internal transport barrier. The frequency and severity of these events increase with increasing β, limiting the achievable average β and causing modulation of the total current as well as the pressure. Modeling of both bootstrap and NBCD currents is based on neoclassical theory. Measurements of the total bootstrap and NBCD current agree with calculations. A recent experiment based on the evolution of the transient voltage profile after an L-H transition shows that the more recent bootstrap current models accurately describe the plasma behavior. The profiles and the parametric dependences of the local neutral beam-driven current density have not yet been compared with theory

  20. Invisible Display in Aluminum

    DEFF Research Database (Denmark)

    Prichystal, Jan Phuklin; Hansen, Hans Nørgaard; Bladt, Henrik Henriksen

    2005-01-01

    Bang & Olufsen a/s has been working with ideas for invisible integration of displays in metal surfaces. Invisible integration of information displays traditionally has been possible by placing displays behind transparent or semitransparent materials such as plastic or glass. The wish for an integ......Bang & Olufsen a/s has been working with ideas for invisible integration of displays in metal surfaces. Invisible integration of information displays traditionally has been possible by placing displays behind transparent or semitransparent materials such as plastic or glass. The wish...... for an integrated display in a metal surface is often ruled by design and functionality of a product. The integration of displays in metal surfaces requires metal removal in order to clear the area of the display to some extent. The idea behind an invisible display in Aluminum concerns the processing of a metal...

  1. Gas cell neutralizers (Fundamental principles)

    International Nuclear Information System (INIS)

    Fuehrer, B.

    1985-06-01

    Neutralizing an ion-beam of the size and energy levels involved in the neutral-particle-beam program represents a considerable extension of the state-of-the-art of neutralizer technology. Many different mediums (e.g., solid, liquid, gas, plasma, photons) can be used to strip the hydrogen ion of its extra electron. A large, multidisciplinary R and D effort will no doubt be required to sort out all of the ''pros and cons'' of these various techniques. The purpose of this particular presentation is to discuss some basic configurations and fundamental principles of the gas type of neutralizer cell. Particular emphasis is placed on the ''Gasdynamic Free-Jet'' neutralizer since this configuration has the potential of being much shorter than other type of gas cells (in the beam direction) and it could operate in nearly a continuous mode (CW) if necessary. These were important considerations in the ATSU design which is discussed in some detail in the second presentation entitled ''ATSU Point Design''

  2. New Modulation Strategy to Balance the Neutral-Point Voltage for Three-Level Neutral-Clamped Inverter Systems

    DEFF Research Database (Denmark)

    Choi, Uimin; Lee, June-Seok; Lee, Kyo-Beum

    2014-01-01

    This paper proposes a new modulation strategy that balances the neutral-point voltage for three-level neutral-clamped inverter systems. The proposed modulation replaces the P-type or N-type small switching states with other switching states that do not affect the neutral-point voltage. The zero...... and medium switching states are employed to help the neutral-point voltage balancing. This method little bit increases the switching events and output total harmonic distortion. However, this method has a strong balancing ability at all regions. Further, it is very simple to implement in both space vector...

  3. How Objective a Neutral Word Is? A Neutrosophic Approach for the Objectivity Degrees of Neutral Words

    Directory of Open Access Journals (Sweden)

    Mihaela Colhon

    2017-11-01

    Full Text Available In the latest studies concerning the sentiment polarity of words, the authors mostly consider the positive and negative constructions, without paying too much attention to the neutral words, which can have, in fact, significant sentiment degrees. More precisely, not all the neutral words have zero positivity or negativity scores, some of them having quite important nonzero scores for these polarities. At this moment, in the literature, a word is considered neutral if its positive and negative scores are equal, which implies two possibilities: (1 zero positive and negative scores; (2 nonzero, but equal positive and negative scores. It is obvious that these cases represent two different categories of neutral words that must be treated separately by a sentiment analysis task. In this paper, we present a comprehensive study about the neutral words applied to English as is developed with the aid of SentiWordNet 3.0: the publicly available lexical resource for opinion mining. We designed our study in order to provide an accurate classification of the so-called “neutral words” described in terms of sentiment scores and using measures from neutrosophy theory. The intended scope is to fill the gap concerning the neutrality aspect by giving precise measurements for the words’ objectivity.

  4. Advanced Colorimetry of Display Systems: Tetra-Chroma3 Display Unit

    Directory of Open Access Journals (Sweden)

    J. Kaiser

    2005-06-01

    Full Text Available High-fidelity color image reproduction is one of the key issues invisual telecommunication systems, for electronic commerce,telemedicine, digital museum and so on. All colorimetric standards ofdisplay systems are up to the present day trichromatic. But, from theshape of a horseshoe-area of all existing colors in the CIE xychromaticity diagram it follows that with three real reproductivelights, the stated area in the CIE xy chromaticity diagram cannot beoverlaid. The expansion of the color gamut of a display device ispossible in a few ways. In this paper, the way of increasing the numberof primaries is studied. The fourth cyan primary is added to threeconventional ones to enlarge the color gamut of reproduction towardscyans and yellow-oranges. The original method of color management forthis new display unit is introduced. In addition, the color gamut ofthe designed additive-based display is successfully compared with thecolor gamut of a modern subtractive-based system. A display with morethan three primary colors is called a multiprimary color display. Thevery advantageous property of such display is the possibility todisplay metameric colors.

  5. Broad T-cell receptor repertoire in T-lymphocytes derived from human induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Chia-Wei Chang

    Full Text Available Human induced pluripotent stem cells (hiPSCs have enormous potential for the treatment of inherited and acquired disorders. Recently, antigen-specific T lymphocytes derived from hiPSCs have been reported. However, T lymphocyte populations with broad T cell receptor (TCR diversity have not been generated. We report that hiPSCs derived from skin biopsy are capable of producing T lymphocyte populations with a broad TCR repertoire. In vitro T cell differentiation follows a similar developmental program as observed in vivo, indicated by sequential expression of CD7, intracellular CD3 and surface CD3. The γδ TCR locus is rearranged first and is followed by rearrangement of the αβ locus. Both γδ and αβ T cells display a diverse TCR repertoire. Upon activation, the cells express CD25, CD69, cytokines (TNF-α, IFN-γ, IL-2 and cytolytic proteins (Perforin and Granzyme-B. These results suggest that most, if not all, mechanisms required to generate functional T cells with a broad TCR repertoire are intact in our in vitro differentiation protocol. These data provide a foundation for production of patient-specific T cells for the treatment of acquired or inherited immune disorders and for cancer immunotherapy.

  6. Neutral-beam-heating applications and development

    International Nuclear Information System (INIS)

    Menon, M.M.

    1981-01-01

    The technique of heating the plasma in magnetically confined fusion devices by the injection of intense beams of neutral atoms is described. The basic principles governing the physics of neutral beam heating and considerations involved in determining the injection energy, power, and pulse length required for a fusion reactor are discussed. The pertinent experimental results from various fusion devices are surveyed to illustrate the efficacy of this technique. The second part of the paper is devoted to the technology of producing the neutral beams. A state-of-the-art account o the development of neutral injectors is presented, and the prospects for utilizing neutral injection to heat the plasma in a fusion reactor are examined

  7. Expression and surface display of Cellulomonas endoglucanase in the ethanologenic bacterium Zymobacter palmae

    Energy Technology Data Exchange (ETDEWEB)

    Kojima, Motoki; Akahoshi, Tomohiro; Okamoto, Kenji; Yanase, Hideshi [Tottori Univ. (Japan). Dept. of Chemistry and Biotechnology

    2012-11-15

    In order to reduce the cost of bioethanol production from lignocellulosic biomass, we developed a tool for cell surface display of cellulolytic enzymes on the ethanologenic bacterium Zymobacter palmae. Z. palmae is a novel ethanol-fermenting bacterium capable of utilizing a broad range of sugar substrates, but not cellulose. Therefore, to express and display heterologous cellulolytic enzymes on the Z. palmae cell surface, we utilized the cell-surface display motif of the Pseudomonas ice nucleation protein Ina. The gene encoding Ina from Pseudomonas syringae IFO3310 was cloned, and its product was comprised of three functional domains: an N-terminal domain, a central domain with repeated amino acid residues, and a C-terminal domain. The N-terminal domain of Ina was shown to function as the anchoring motif for a green fluorescence protein fusion protein in Escherichia coli. To express a heterologous cellulolytic enzyme extracellularly in Z. palmae, we fused the N-terminal coding sequence of Ina to the coding sequence of an N-terminal-truncated Cellulomonas endoglucanase. Z. palmae cells carrying the fusion endoglucanase gene were shown to degrade carboxymethyl cellulose. Although a portion of the expressed fusion endoglucanase was released from Z. palmae cells into the culture broth, we confirmed the display of the protein on the cell surface by immunofluorescence microscopy. The results indicate that the N-terminal anchoring motif of Ina from P. syringae enabled the translocation and display of the heterologous cellulase on the cell surface of Z. palmae. (orig.)

  8. Neutral-point current modeling and control for Neutral-Point Clamped three-level converter drive with small DC-link capacitors

    DEFF Research Database (Denmark)

    Maheshwari, Ram Krishan; Munk-Nielsen, Stig; Busquets-Monge, Sergio

    2011-01-01

    A Neutral-Point-Clamped (NPC) three-level inverter with small DC-link capacitors is presented in this paper. This inverter requires zero average neutral-point current for stable neutral-point potential. A simple carrier based modulation strategy is proposed for achieving zero average neutral...... drive with only 14 μF DC-link capacitors. A fast and stable performance of the neutral-point voltage controller is achieved and verified by experiments....

  9. Net neutrality and audiovisual services

    OpenAIRE

    van Eijk, N.; Nikoltchev, S.

    2011-01-01

    Net neutrality is high on the European agenda. New regulations for the communication sector provide a legal framework for net neutrality and need to be implemented on both a European and a national level. The key element is not just about blocking or slowing down traffic across communication networks: the control over the distribution of audiovisual services constitutes a vital part of the problem. In this contribution, the phenomenon of net neutrality is described first. Next, the European a...

  10. Microlaser-based displays

    Science.gov (United States)

    Bergstedt, Robert; Fink, Charles G.; Flint, Graham W.; Hargis, David E.; Peppler, Philipp W.

    1997-07-01

    Laser Power Corporation has developed a new type of projection display, based upon microlaser technology and a novel scan architecture, which provides the foundation for bright, extremely high resolution images. A review of projection technologies is presented along with the limitations of each and the difficulties they experience in trying to generate high resolution imagery. The design of the microlaser based projector is discussed along with the advantage of this technology. High power red, green, and blue microlasers have been designed and developed specifically for use in projection displays. These sources, in combination with high resolution, high contrast modulator, produce a 24 bit color gamut, capable of supporting the full range of real world colors. The new scan architecture, which reduces the modulation rate and scan speeds required, is described. This scan architecture, along with the inherent brightness of the laser provides the fundamentals necessary to produce a 5120 by 4096 resolution display. The brightness and color uniformity of the display is excellent, allowing for tiling of the displays with far fewer artifacts than those in a traditionally tiled display. Applications for the display include simulators, command and control centers, and electronic cinema.

  11. Cross-neutralization of antibodies induced by vaccination with Purified Chick Embryo Cell Vaccine (PCECV) against different Lyssavirus species.

    Science.gov (United States)

    Malerczyk, Claudius; Freuling, Conrad; Gniel, Dieter; Giesen, Alexandra; Selhorst, Thomas; Müller, Thomas

    2014-01-01

    Rabies is a neglected zoonotic disease caused by viruses belonging to the genus lyssavirus. In endemic countries of Asia and Africa, where the majority of the estimated 60,000 human rabies deaths occur, it is mainly caused by the classical rabies virus (RABV) transmitted by dogs. Over the last decade new species within the genus lyssavirus have been identified. Meanwhile 15 (proposed or classified) species exist, including Australian bat lyssavirus (ABLV), European bat lyssavirus (EBLV-1 and -2), Duvenhage virus (DUVV), as well as Lagos bat virus (LBV) and Mokola virus (MOKV) and recently identified novel species like Bokeloh bat lyssavirus (BBLV), Ikoma bat lyssavirus (IKOV) or Lleida bat lyssavirus (LLBV). The majority of these lyssavirus species are found in bat reservoirs and some have caused human infection and deaths. Previous work has demonstrated that Purified Chick Embryo Cell Rabies Vaccine (PCECV) not only induces immune responses against classical RABV, but also elicits cross-neutralizing antibodies against ABLV, EBLV-1 and EBLV-2. Using the same serum samples as in our previous study, this study extension investigated cross-neutralizing activities of serum antibodies measured by rapid fluorescent focus inhibition test (RFFIT) against selected other non-classical lyssavirus species of interest, namely DUVV and BBLV, as well as MOKV and LBV. Antibodies developed after vaccination with PCECV have neutralizing capability against BBLV and DUVV in the same range as against ABLV and EBLV-1 and -2. As expected, for the phylogenetically more distant species LBV no cross-neutralizing activity was found. Interestingly, 15 of 94 serum samples (16%) with a positive neutralizing antibody titer against RABV displayed specific cross-neutralizing activity (65-fold lower than against RABV) against one specific MOKV strain (Ethiopia isolate), which was not seen against a different strain (Nigeria isolate). Cross-neutralizing activities partly correlate with the

  12. Electromagnetic trapping of neutral atoms

    International Nuclear Information System (INIS)

    Metcalf, H.J.

    1986-01-01

    Cooling and trapping of neutral atoms is a new branch of applied physics that has potential for application in many areas. The authors present an introduction to laser cooling and magnetic trapping. Some basic ideas and fundamental limitations are discussed, and the first successful experiments are reviewed. Trapping a neutral object depends on the interaction between an inhomogeneous electromagnetic field and a multiple moment that results in the exchange of kinetic for potential energy. In neutral atom traps, the potential energy must be stored as internal atomic energy, resulting in two immediate and extremely important consequences. First, the atomic energy levels will necessarily shift as the atoms move in the trap, and, second, practical traps for ground state neutral atoms atr necessarily very shallow compared to thermal energy. This small depth also dictates stringent vacuum requirements because a trapped atom cannot survive a single collision with a thermal energy background gas molecule. Neutral trapping, therefore, depends on substantial cooling of a thermal atomic sample and is inextricably connected with the cooling process

  13. Plasma neutralizers for H- or D- beams

    International Nuclear Information System (INIS)

    Berkner, K.H.; Pyle, R.V.; Savas, S.E.; Stalder, K.R.

    1980-10-01

    Plasma neutralizers can produce higher conversion efficiencies than are obtainable with gas neutralizers for the production of high-energy neutral beams from negative hydrogen ions. Little attention has been paid to experimental neutralizer studies because of the more critical problems connected with the development of negative-ion sources. With the prospect of accelerating ampere dc beams from extrapolatable ion sources some time next year, we are re-examining plasma neutralizers. Some basic considerations, two introductory experiments, and a next-step experiment are described

  14. Ion-beam Plasma Neutralization Interaction Images

    Energy Technology Data Exchange (ETDEWEB)

    Igor D. Kaganovich; Edward Startsev; S. Klasky; Ronald C. Davidson

    2002-04-09

    Neutralization of the ion beam charge and current is an important scientific issue for many practical applications. The process of ion beam charge and current neutralization is complex because the excitation of nonlinear plasma waves may occur. Computer simulation images of plasma neutralization of the ion beam pulse are presented.

  15. Ion-beam Plasma Neutralization Interaction Images

    International Nuclear Information System (INIS)

    Igor D. Kaganovich; Edward Startsev; S. Klasky; Ronald C. Davidson

    2002-04-01

    Neutralization of the ion beam charge and current is an important scientific issue for many practical applications. The process of ion beam charge and current neutralization is complex because the excitation of nonlinear plasma waves may occur. Computer simulation images of plasma neutralization of the ion beam pulse are presented

  16. Handbook of display technology

    CERN Document Server

    Castellano, Joseph A

    1992-01-01

    This book presents a comprehensive review of technical and commercial aspects of display technology. It provides design engineers with the information needed to select proper technology for new products. The book focuses on flat, thin displays such as light-emitting diodes, plasma display panels, and liquid crystal displays, but it also includes material on cathode ray tubes. Displays include a large number of products from televisions, auto dashboards, radios, and household appliances, to gasoline pumps, heart monitors, microwave ovens, and more.For more information on display tech

  17. Glycans Flanking the Hypervariable Connecting Peptide between the A and B Strands of the V1/V2 Domain of HIV-1 gp120 Confer Resistance to Antibodies That Neutralize CRF01_AE Viruses

    Science.gov (United States)

    O’Rourke, Sara M.; Sutthent, Ruengpung; Phung, Pham; Mesa, Kathryn A.; Frigon, Normand L.; To, Briana; Horthongkham, Navin; Limoli, Kay; Wrin, Terri; Berman, Phillip W.

    2015-01-01

    Understanding the molecular determinants of sensitivity and resistance to neutralizing antibodies is critical for the development of vaccines designed to prevent HIV infection. In this study, we used a genetic approach to characterize naturally occurring polymorphisms in the HIV envelope protein that conferred neutralization sensitivity or resistance. Libraries of closely related envelope genes, derived from virus quasi-species, were constructed from individuals infected with CRF01_AE viruses. The libraries were screened with plasma containing broadly neutralizing antibodies, and neutralization sensitive and resistant variants were selected for sequence analysis. In vitro mutagenesis allowed us to identify single amino acid changes in three individuals that conferred resistance to neutralization by these antibodies. All three mutations created N-linked glycosylation sites (two at N136 and one at N149) proximal to the hypervariable connecting peptide between the C-terminus of the A strand and the N-terminus of the B strand in the four-stranded V1/V2 domain β-sheet structure. Although N136 has previously been implicated in the binding of broadly neutralizing monoclonal antibodies, this glycosylation site appears to inhibit the binding of neutralizing antibodies in plasma from HIV-1 infected subjects. Previous studies have reported that the length of the V1/V2 domain in transmitted founder viruses is shorter and possesses fewer glycosylation sites compared to viruses isolated from chronic infections. Our results suggest that vaccine immunogens based on recombinant envelope proteins from clade CRF01_AE viruses might be improved by inclusion of envelope proteins that lack these glycosylation sites. This strategy might improve the efficacy of the vaccines used in the partially successful RV144 HIV vaccine trial, where the two CRF01_AE immunogens (derived from the A244 and TH023 isolates) both possessed glycosylation sites at N136 and N149. PMID:25793890

  18. Liquid crystal display

    International Nuclear Information System (INIS)

    Takami, K.

    1981-01-01

    An improved liquid crystal display device is described which can display letters, numerals and other necessary patterns in the night time using a minimized amount of radioactive material. To achieve this a self-luminous light source is placed in a limited region corresponding to a specific display area. (U.K.)

  19. INFORMATION DISPLAY: CONSIDERATIONS FOR DESIGNING COMPUTER-BASED DISPLAY SYSTEMS

    International Nuclear Information System (INIS)

    O'HARA, J.M.; PIRUS, D.; BELTRATCCHI, L.

    2004-01-01

    This paper discussed the presentation of information in computer-based control rooms. Issues associated with the typical displays currently in use are discussed. It is concluded that these displays should be augmented with new displays designed to better meet the information needs of plant personnel and to minimize the need for interface management tasks (the activities personnel have to do to access and organize the information they need). Several approaches to information design are discussed, specifically addressing: (1) monitoring, detection, and situation assessment; (2) routine task performance; and (3) teamwork, crew coordination, collaborative work

  20. Identification of antigenic regions on VP2 of African horsesickness virus serotype 3 by using phage-displayed epitope libraries.

    Science.gov (United States)

    Bentley, L; Fehrsen, J; Jordaan, F; Huismans, H; du Plessis, D H

    2000-04-01

    VP2 is an outer capsid protein of African horsesickness virus (AHSV) and is recognized by serotype-discriminatory neutralizing antibodies. With the objective of locating its antigenic regions, a filamentous phage library was constructed that displayed peptides derived from the fragmentation of a cDNA copy of the gene encoding VP2. Peptides ranging in size from approximately 30 to 100 amino acids were fused with pIII, the attachment protein of the display vector, fUSE2. To ensure maximum diversity, the final library consisted of three sub-libraries. The first utilized enzymatically fragmented DNA encoding only the VP2 gene, the second included plasmid sequences, while the third included a PCR step designed to allow different peptide-encoding sequences to recombine before ligation into the vector. The resulting composite library was subjected to immunoaffinity selection with AHSV-specific polyclonal chicken IgY, polyclonal horse immunoglobulins and a monoclonal antibody (MAb) known to neutralize AHSV. Antigenic peptides were located by sequencing the DNA of phages bound by the antibodies. Most antigenic determinants capable of being mapped by this method were located in the N-terminal half of VP2. Important binding areas were mapped with high resolution by identifying the minimum overlapping areas of the selected peptides. The MAb was also used to screen a random 17-mer epitope library. Sequences that may be part of a discontinuous neutralization epitope were identified. The amino acid sequences of the antigenic regions on VP2 of serotype 3 were compared with corresponding regions on three other serotypes, revealing regions with the potential to discriminate AHSV serotypes serologically.

  1. Water migration of macroelements in coniferous-broad-leaved forests of Sikhote-Alin

    Directory of Open Access Journals (Sweden)

    N. K. Kozhevnikova

    2017-06-01

    Full Text Available In the paper, the natural water chemical composition spatial variability studies results in the mountain forest catchment are presented. It’s shown that the catchment biotic components’ impact upon water chemical composition is detected even at input as atmospheric precipitation. The input fluxes are acid, sulfate ones with high ratio of hydrogen, potassium and dissolved organic matter. Diversity of ecotopic conditions determines the further transformation of natural water chemical composition. The role of tree crowns in the transformation increases while the crown closure and stands’ age increase. According to macrocomponents transformation and rain acidity neutralization, forest associations form the sequence: mixed > coniferous > young deciduous ones. Dissolved organic carbon (DOC, potassium and calcium become the main components of water chemical composition, while sulfates dominate among anions. For vegetation period, 9–11 kg/ha of sulfates come below tree crown. Biogenic elements transport is gradually limited in soil profile at the migration stage. Sulfate-potassium composition throughfall in spruce-fir and secondary forests community transforms into sulfate-sodium-calcium. Hydrocarbonates predominate in soil water in broad-leaved-pine type of forest, and potassium output decreases 10 times. Geochemical type of river water keeps features of chemical composition of soil drained by river section. Negligible output of sulfates, hydrocarbonates and calcium from ecosystem is established for the headwaters. Negative balance of hydrocarbonates and calcium is compensated by significant input of these components with throughfall at catchments with predominantly pine-broad-leaved forest types.

  2. Tax Neutrality on International Capital Investments

    Directory of Open Access Journals (Sweden)

    Gizem KAPUCU

    2017-07-01

    Full Text Available The tax policies which states follow with regard to developing technology and capital investments with raising mobility due to globalism are need to be discussed in its legal basis. The principle of tax neutrality has the aim of being legal foundation for these policies. According to this, the neutrality principle in taxation of international capital investments is provided with two measures, namely; not effecting the investment decision and not discriminate between investments. In this paper, initially focused on the conceptual framework and the foundations of the tax neutrality principle and later capital export neutrality and capital import neutrality are considered and explained with regard to international capital movements. Moreover, conformity and diversion to the principle of the current situation and regulations in OECD, EU and Turkey are examined.

  3. Anhedonia reflects impairment in making relative value judgments between positive and neutral stimuli in schizophrenia.

    Science.gov (United States)

    Strauss, Gregory P; Visser, Katherine Frost; Keller, William R; Gold, James M; Buchanan, Robert W

    2018-02-27

    Anhedonia (i.e., diminished capacity to experience pleasure) has traditionally been viewed as a core symptom of schizophrenia (SZ). However, modern laboratory-based studies suggest that this definition may be incorrect, as hedonic capacity may be intact. Alternative conceptualizations have proposed that anhedonia may reflect an impairment in generating mental representations of affective value that are needed to guide decision-making and initiate motivated behavior. The current study evaluated this hypothesis in 42 outpatients with SZ and 19 healthy controls (CN) who completed two tasks: (a) an emotional experience task that required them to indicate how positive, negative, and calm/excited they felt in response to a single emotional or neutral photograph; (b) a relative value judgment task where they selected which of 2 photographs they preferred. Results indicated that SZ and CN reported similar levels of positive emotion and arousal in response to emotional and neutral stimuli; however, SZ reported higher negative affect for neutral and pleasant stimuli than CN. In the relative value judgment task, CN displayed clear preference for stimuli differing in valence; however, SZ showed less distinct preferences for positive over neutral stimuli. Findings suggest that although in-the-moment experiences of positive emotion to singular stimuli may be intact in SZ, the ability to make relative value judgments that are needed to guide decision-making is impaired. Original conceptualizations of anhedonia as a diminished capacity for pleasure in SZ may be inaccurate; anhedonia may more accurately reflect a deficit in relative value judgment that results from impaired value representation. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. The Net Neutrality Debate: The Basics

    Science.gov (United States)

    Greenfield, Rich

    2006-01-01

    Rich Greenfield examines the basics of today's net neutrality debate that is likely to be an ongoing issue for society. Greenfield states the problems inherent in the definition of "net neutrality" used by Common Cause: "Network neutrality is the principle that Internet users should be able to access any web content they choose and…

  5. MICROLENSING OF QUASAR BROAD EMISSION LINES: CONSTRAINTS ON BROAD LINE REGION SIZE

    Energy Technology Data Exchange (ETDEWEB)

    Guerras, E.; Mediavilla, E. [Instituto de Astrofisica de Canarias, Via Lactea S/N, La Laguna E-38200, Tenerife (Spain); Jimenez-Vicente, J. [Departamento de Fisica Teorica y del Cosmos, Universidad de Granada, Campus de Fuentenueva, E-18071 Granada (Spain); Kochanek, C. S. [Department of Astronomy and the Center for Cosmology and Astroparticle Physics, The Ohio State University, 4055 McPherson Lab, 140 West 18th Avenue, Columbus, OH 43221 (United States); Munoz, J. A. [Departamento de Astronomia y Astrofisica, Universidad de Valencia, E-46100 Burjassot, Valencia (Spain); Falco, E. [Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Motta, V. [Departamento de Fisica y Astronomia, Universidad de Valparaiso, Avda. Gran Bretana 1111, Valparaiso (Chile)

    2013-02-20

    We measure the differential microlensing of the broad emission lines between 18 quasar image pairs in 16 gravitational lenses. We find that the broad emission lines are in general weakly microlensed. The results show, at a modest level of confidence (1.8{sigma}), that high ionization lines such as C IV are more strongly microlensed than low ionization lines such as H{beta}, indicating that the high ionization line emission regions are more compact. If we statistically model the distribution of microlensing magnifications, we obtain estimates for the broad line region size of r{sub s} = 24{sup +22} {sub -15} and r{sub s} = 55{sup +150} {sub -35} lt-day (90% confidence) for the high and low ionization lines, respectively. When the samples are divided into higher and lower luminosity quasars, we find that the line emission regions of more luminous quasars are larger, with a slope consistent with the expected scaling from photoionization models. Our estimates also agree well with the results from local reveberation mapping studies.

  6. IDEA: Interactive Display for Evolutionary Analyses.

    Science.gov (United States)

    Egan, Amy; Mahurkar, Anup; Crabtree, Jonathan; Badger, Jonathan H; Carlton, Jane M; Silva, Joana C

    2008-12-08

    The availability of complete genomic sequences for hundreds of organisms promises to make obtaining genome-wide estimates of substitution rates, selective constraints and other molecular evolution variables of interest an increasingly important approach to addressing broad evolutionary questions. Two of the programs most widely used for this purpose are codeml and baseml, parts of the PAML (Phylogenetic Analysis by Maximum Likelihood) suite. A significant drawback of these programs is their lack of a graphical user interface, which can limit their user base and considerably reduce their efficiency. We have developed IDEA (Interactive Display for Evolutionary Analyses), an intuitive graphical input and output interface which interacts with PHYLIP for phylogeny reconstruction and with codeml and baseml for molecular evolution analyses. IDEA's graphical input and visualization interfaces eliminate the need to edit and parse text input and output files, reducing the likelihood of errors and improving processing time. Further, its interactive output display gives the user immediate access to results. Finally, IDEA can process data in parallel on a local machine or computing grid, allowing genome-wide analyses to be completed quickly. IDEA provides a graphical user interface that allows the user to follow a codeml or baseml analysis from parameter input through to the exploration of results. Novel options streamline the analysis process, and post-analysis visualization of phylogenies, evolutionary rates and selective constraint along protein sequences simplifies the interpretation of results. The integration of these functions into a single tool eliminates the need for lengthy data handling and parsing, significantly expediting access to global patterns in the data.

  7. Neutral particle kinetics in fusion devices

    International Nuclear Information System (INIS)

    Tendler, M.; Heifetz, D.

    1986-05-01

    The theory of neutral particle kinetics treats the transport of mass, momentum, and energy in a plasma due to neutral particles which themselves are unaffected by magnetic fields. This transport affects the global power and particle balances in fusion devices, as well as profile control and plasma confinement quality, particle and energy fluxes onto device components, performance of pumping systems, and the design of diagnostics and the interpretation of their measurements. This paper reviews the development of analytic, numerical, and Monte Carlo methods of solving the time-independent Boltzmann equation describing neutral kinetics. These models for neutral particle behavior typically use adaptations of techniques developed originally for computing neutron transport, due to the analogy between the two phenomena, where charge-exchange corresponds to scattering and ionization to absorption. Progress in the field depends on developing multidimensional analytic methods, and obtaining experimental data for the physical processes of wall reflection, the neutral/plasma interaction, and for processes in fusion devices which are directly related to neutral transport, such as H/sub α/ emission rates, plenum pressures, and charge-exchange emission spectra

  8. Neutral particle kinetics in fusion devices

    Energy Technology Data Exchange (ETDEWEB)

    Tendler, M.; Heifetz, D.

    1986-05-01

    The theory of neutral particle kinetics treats the transport of mass, momentum, and energy in a plasma due to neutral particles which themselves are unaffected by magnetic fields. This transport affects the global power and particle balances in fusion devices, as well as profile control and plasma confinement quality, particle and energy fluxes onto device components, performance of pumping systems, and the design of diagnostics and the interpretation of their measurements. This paper reviews the development of analytic, numerical, and Monte Carlo methods of solving the time-independent Boltzmann equation describing neutral kinetics. These models for neutral particle behavior typically use adaptations of techniques developed originally for computing neutron transport, due to the analogy between the two phenomena, where charge-exchange corresponds to scattering and ionization to absorption. Progress in the field depends on developing multidimensional analytic methods, and obtaining experimental data for the physical processes of wall reflection, the neutral/plasma interaction, and for processes in fusion devices which are directly related to neutral transport, such as H/sub ..cap alpha../ emission rates, plenum pressures, and charge-exchange emission spectra.

  9. Neutral beam program

    International Nuclear Information System (INIS)

    Anon.

    1979-01-01

    The structure of the beam injection program for the Doublet-3 device is discussed. The design considerations for the beam line and design parameters for the Doublet-3 ion souce are given. Major components of the neutral beam injector system are discussed in detail. These include the neutralizer, magnetic shielding, reflecting magnets, vacuum system, calorimeter and beam dumps, and drift duct. The planned location of the two-injector system for Doublet-3 is illustrated and site preparation is considered. The status of beamline units 1 and 2 and the future program schedule are discussed

  10. 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

  11. Dust in the Diffuse Neutral Interstellar Medium

    Science.gov (United States)

    Sofia, Ulysses J.

    2008-05-01

    Studies of interstellar dust have always relied heavily upon Laboratory Astrophysics for interpretation. Laboratory values, in the broad sense that includes theory, are needed for the most basic act of measuring interstellar abundances, to the more complex determination of what grains are responsible for particular extinction. The symbiotic relationship between astronomical observations and Laboratory Astrophysics has prompted both fields to move forward, especially in the era of high-resolution ultraviolet spectroscopy when new elemental species could be interpreted and observations were able to show the limits of laboratory determinations. Thanks to this synergy, we currently have a good idea of the quantity of the most abundant elements incorporated into dust in diffuse neutral interstellar clouds: carbon, oxygen, iron, silicon and magnesium. Now the task is to figure out how, chemically and physically, those elements are integrated into interstellar grains. We can do this by comparing extinction curves to grain populations in radiative transfer models. The limitation at the present time is the availability of optical constants in the infrared through ultraviolet for species that are likely to exist in dust, i.e., those that are easy to form in the physical environments around stars and in molecular clouds. Extinction in some lines of sight can be fit within current abundance limits and with the optical constants that are available. However the inability to reproduce other extinction curves suggests that optical constants can be improved, either in quality for compounds that have been measured, or quantity in the sense of providing data for more materials. This talk will address the current state and the future of dust studies in the diffuse neutral interstellar medium. This work is supported by the grant HST-AR-10979.01-A from the Space Telescope Science Institute to Whitman College.

  12. ORNL neutral-beam program in 1978

    International Nuclear Information System (INIS)

    Whealton, J.H.

    1982-12-01

    This report was presented at the ion source workshop held at Culham Laboratory, Abingdon, Oxfordshire, in 1978. Because the proceedings of that conference are unavailable, and because the material in this report is still not to be found elsewhere, it is issued as a laboratory report. The neutral beam group at Oak Ridge National Laboratory has constructed neutral beam generators for the ORMAK and PLT devices, is presently constructing neutral beam devices for the ISX and PDX devices, and is contemplating the construction of neutral beam systems for the advanced TNS device. These neutral beam devices stem from the pioneering work on ion sources of G.G. Kelley and O.B. Morgan. We describe the ion sources under development at this laboratory, the beam optics exhibited by these sources, as well as some theoretical considerations, and finally the remainder of the beamline design

  13. Neutral-beam current drive in tokamaks

    International Nuclear Information System (INIS)

    Devoto, R.S.

    1986-01-01

    The theory of neutral-beam current drive in tokamaks is reviewed. Experiments are discussed where neutral beams have been used to drive current directly and also indirectly through neoclassical effects. Application of the theory to an experimental test reactor is described. It is shown that neutral beams formed from negative ions accelerated to 500 to 700 keV are needed for this device

  14. Neutral-beam current drive in tokamaks

    International Nuclear Information System (INIS)

    Devoto, R.S.

    1987-01-01

    The theory of neutral-beam current drive in tokamaks is reviewed. Experiments are discussed where neutral beams have been used to drive current directly and also indirectly through neoclassical effects. Application of the theory to an experimental test reactor is described. It is shown that neutral beams formed from negative ions accelerated to 500-700 keV are needed for this device

  15. Adjuvant-Mediated Epitope Specificity and Enhanced Neutralizing Activity of Antibodies Targeting Dengue Virus Envelope Protein

    Directory of Open Access Journals (Sweden)

    Denicar Lina Nascimento Fabris Maeda

    2017-09-01

    Full Text Available The heat-labile toxins (LT produced by enterotoxigenic Escherichia coli display adjuvant effects to coadministered antigens, leading to enhanced production of serum antibodies. Despite extensive knowledge of the adjuvant properties of LT derivatives, including in vitro-generated non-toxic mutant forms, little is known about the capacity of these adjuvants to modulate the epitope specificity of antibodies directed against antigens. This study characterizes the role of LT and its non-toxic B subunit (LTB in the modulation of antibody responses to a coadministered antigen, the dengue virus (DENV envelope glycoprotein domain III (EDIII, which binds to surface receptors and mediates virus entry into host cells. In contrast to non-adjuvanted or alum-adjuvanted formulations, antibodies induced in mice immunized with LT or LTB showed enhanced virus-neutralization effects that were not ascribed to a subclass shift or antigen affinity. Nonetheless, immunosignature analyses revealed that purified LT-adjuvanted EDIII-specific antibodies display distinct epitope-binding patterns with regard to antibodies raised in mice immunized with EDIII or the alum-adjuvanted vaccine. Notably, the analyses led to the identification of a specific EDIII epitope located in the EF to FG loop, which is involved in the entry of DENV into eukaryotic cells. The present results demonstrate that LT and LTB modulate the epitope specificity of antibodies generated after immunization with coadministered antigens that, in the case of EDIII, was associated with the induction of neutralizing antibody responses. These results open perspectives for the more rational development of vaccines with enhanced protective effects against DENV infections.

  16. Ionized and Neutral Outflows in the QUEST QSOs

    Science.gov (United States)

    Veilleux, Sylvain

    2011-10-01

    The role of galactic winds in gas-rich mergers is of crucial importance to understand galaxy and SMBH evolution. In recent months, our group has had three major scientific breakthroughs in this area: {1} The discovery with Herschel of massive molecular {OH-absorbing} outflows in several ULIRGs, including the nearest quasar, Mrk 231. {2} The independent discovery from mm-wave interferometric observations in the same object of a spatially resolved molecular {CO-emitting} wind with estimated mass outflow rate 3x larger than the star formation rate and spatially coincident with blueshifted neutral {Na ID-absorbing} gas in optical long-slit spectra. {3} The unambiguous determination from recent Gemini/IFU observations that the Na ID outflow in this object is wide-angle, thus driven by a QSO wind rather than a jet. This powerful outflow may be the long-sought "smoking gun" of quasar mechanical feedback purported to transform gas-rich mergers. However, our Herschel survey excludes all FIR-faint {UV-bright} "classic" QSOs by necessity. So here we propose a complementary FUV absorption-line survey of all FIR-bright -and- FIR-faint QSOs from the same parent sample. New {19 targets} and archival {11} spectra will be used to study, for the first time, the gaseous environments of QSOs as a function of host properties and age across the merger sequence ULIRG -> QSO. These data will allow us to distinguish between ionized & neutral quasar-driven outflows, starburst-driven winds, and tidal debris around the mergers. They will also be uniquely suited for a shallow but broad study of the warm & warm-hot intergalactic media, complementary to on-going surveys that are deeper but narrower.

  17. Neutral beam in ALVAND IIC tokamak

    International Nuclear Information System (INIS)

    Ghrannevisse, M.; Moradshahi, M.; Avakian, M.

    1992-01-01

    Neutral beams have a wide application in tokamak experiments. It used to heat; fuel; adjust electric potentials in plasmas and diagnose particles densities and momentum distributions. It may be used to sustain currents in tokamaks to extend the pulse length. A 5 KV; 500 mA ion source has been constructed by plasma physics group, AEOI and it used to produce plasma and study the plasma parameters. Recently this ion source has been neutralized and it adapted to a neutral beam source; and it used to heat a cylindrical DC plasma and the plasma of ALVAND IIC Tokamak which is a small research tokamak with a minor radius of 12.6 cm, and a major radius of 45.5 cm. In this paper we report the neutralization of the ion beam and the results obtained by injection of this neutral beam into plasmas. (author) 2 refs., 4 figs

  18. Structural Basis for Differential Neutralization of Ebolaviruses

    Directory of Open Access Journals (Sweden)

    John M. Dye

    2012-04-01

    Full Text Available There are five antigenically distinct ebolaviruses that cause hemorrhagic fever in humans or non-human primates (Ebola virus, Sudan virus, Reston virus, Taï Forest virus, and Bundibugyo virus. The small handful of antibodies known to neutralize the ebolaviruses bind to the surface glycoprotein termed GP1,2. Curiously, some antibodies against them are known to neutralize in vitro but not protect in vivo, whereas other antibodies are known to protect animal models in vivo, but not neutralize in vitro. A detailed understanding of what constitutes a neutralizing and/or protective antibody response is critical for development of novel therapeutic strategies. Here, we show that paradoxically, a lower affinity antibody with restricted access to its epitope confers better neutralization than a higher affinity antibody against a similar epitope, suggesting that either subtle differences in epitope, or different characteristics of the GP1,2 molecules themselves, confer differential neutralization susceptibility. Here, we also report the crystal structure of trimeric, prefusion GP1,2 from the original 1976 Boniface variant of Sudan virus complexed with 16F6, the first antibody known to neutralize Sudan virus, and compare the structure to that of Sudan virus, variant Gulu. We discuss new structural details of the GP1-GP2 clamp, thermal motion of various regions in GP1,2 across the two viruses visualized, details of differential interaction of the crystallized neutralizing antibodies, and their relevance for virus neutralization.

  19. JAVA Stereo Display Toolkit

    Science.gov (United States)

    Edmonds, Karina

    2008-01-01

    This toolkit provides a common interface for displaying graphical user interface (GUI) components in stereo using either specialized stereo display hardware (e.g., liquid crystal shutter or polarized glasses) or anaglyph display (red/blue glasses) on standard workstation displays. An application using this toolkit will work without modification in either environment, allowing stereo software to reach a wider audience without sacrificing high-quality display on dedicated hardware. The toolkit is written in Java for use with the Swing GUI Toolkit and has cross-platform compatibility. It hooks into the graphics system, allowing any standard Swing component to be displayed in stereo. It uses the OpenGL graphics library to control the stereo hardware and to perform the rendering. It also supports anaglyph and special stereo hardware using the same API (application-program interface), and has the ability to simulate color stereo in anaglyph mode by combining the red band of the left image with the green/blue bands of the right image. This is a low-level toolkit that accomplishes simply the display of components (including the JadeDisplay image display component). It does not include higher-level functions such as disparity adjustment, 3D cursor, or overlays all of which can be built using this toolkit.

  20. The merits of neutral theory

    NARCIS (Netherlands)

    Alonso, D.; Etienne, R.S.; McKane, A.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

  1. Latest development of display technologies

    International Nuclear Information System (INIS)

    Gao Hong-Yue; Yao Qiu-Xiang; Liu Pan; Zheng Zhi-Qiang; Liu Ji-Cheng; Zheng Hua-Dong; Zeng Chao; Yu Ying-Jie; Sun Tao; Zeng Zhen-Xiang

    2016-01-01

    In this review we will focus on recent progress in the field of two-dimensional (2D) and three-dimensional (3D) display technologies. We present the current display materials and their applications, including organic light-emitting diodes (OLEDs), flexible OLEDs quantum dot light emitting diodes (QLEDs), active-matrix organic light emitting diodes (AMOLEDs), electronic paper (E-paper), curved displays, stereoscopic 3D displays, volumetric 3D displays, light field 3D displays, and holographic 3D displays. Conventional 2D display devices, such as liquid crystal devices (LCDs) often result in ambiguity in high-dimensional data images because of lacking true depth information. This review thus provides a detailed description of 3D display technologies. (topical review)

  2. Broad-Band Variability in Accreting Compact Objects

    Directory of Open Access Journals (Sweden)

    S. Scaringi

    2015-02-01

    Full Text Available Cataclysmic variable stars are in many ways similar to X-ray binaries. Both types of systems possess an accretion disk, which in most cases can reach the surface (or event horizon of the central compact object. The main difference is that the embedded gravitational potential well in X-ray binaries is much deeper than those found in cataclysmic variables. As a result, X-ray binaries emit most of their radiation at X-ray wavelengths, as opposed to cataclysmic variables which emit mostly at optical/ultraviolet wavelengths. Both types of systems display aperiodic broad-band variability which can be associated to the accretion disk. Here, the properties of the observed X-ray variability in XRBs are compared to those observed at optical wavelengths in CVs. In most cases the variability properties of both types of systems are qualitatively similar once the relevant timescales associated with the inner accretion disk regions have been taken into account. The similarities include the observed power spectral density shapes, the rms-flux relation as well as Fourier-dependant time lags. Here a brief overview on these similarities is given, placing them in the context of the fluctuating accretion disk model which seeks to reproduce the observed variability.

  3. Neutral evolution of mutational robustness

    NARCIS (Netherlands)

    Nimwegen, Erik van; Crutchfield, James P.; Huynen, Martijn

    1999-01-01

    We introduce and analyze a general model of a population evolving over a network of selectively neutral genotypes. We show that the population s limit distribution on the neutral network is solely determined by the network topology and given by the principal eigenvector of the network

  4. Nitrogen-neutrality: a step towards sustainability

    Science.gov (United States)

    Leip, Adrian; Leach, Allison; Musinguzi, Patrick; Tumwesigye, Trust; Olupot, Giregon; Tenywa, John Stephen; Mudiope, Joseph; Hutton, Olivia; Cordovil, Claudia M. d. S.; Bekunda, Mateete; Galloway, James

    2014-11-01

    We propose a novel indicator measuring one dimension of the sustainability of an entity in modern societies: Nitrogen-neutrality. N-neutrality strives to offset Nr releases an entity exerts on the environment from the release of reactive nitrogen (Nr) to the environment by reducing it and by offsetting the Nr releases elsewhere. N-neutrality also aims to increase awareness about the consequences of unintentional releases of nitrogen to the environment. N-neutrality is composed of two quantified elements: Nr released by an entity (e.g. on the basis of the N footprint) and Nr reduction from management and offset projects (N offset). It includes management strategies to reduce nitrogen losses before they occur (e.g., through energy conservation). Each of those elements faces specific challenges with regard to data availability and conceptual development. Impacts of Nr releases to the environment are manifold, and the impact profile of one unit of Nr release depends strongly on the compound released and the local susceptibility to Nr. As such, N-neutrality is more difficult to conceptualize and calculate than C-neutrality. We developed a workable conceptual framework for N-neutrality which was adapted for the 6th International Nitrogen Conference (N2013, Kampala, November 2013). Total N footprint of the surveyed meals at N2013 was 66 kg N. A total of US 3050 was collected from the participants and used to offset the conference’s N footprint by supporting the UN Millennium Village cluster Ruhiira in South-Western Uganda. The concept needs further development in particular to better incorporate the spatio-temporal variability of impacts and to standardize the methods to quantify the required N offset to neutralize the Nr releases impact. Criteria for compensation projects need to be sharply defined to allow the development of a market for N offset certificates.

  5. Nitrogen-neutrality: a step towards sustainability

    International Nuclear Information System (INIS)

    Leip, Adrian; Leach, Allison; Hutton, Olivia; Galloway, James; Musinguzi, Patrick; Tumwesigye, Trust; Olupot, Giregon; Stephen Tenywa, John; Mudiope, Joseph; Cordovil, Claudia M d S; Bekunda, Mateete

    2014-01-01

    We propose a novel indicator measuring one dimension of the sustainability of an entity in modern societies: Nitrogen-neutrality. N-neutrality strives to offset Nr releases an entity exerts on the environment from the release of reactive nitrogen (Nr) to the environment by reducing it and by offsetting the Nr releases elsewhere. N-neutrality also aims to increase awareness about the consequences of unintentional releases of nitrogen to the environment. N-neutrality is composed of two quantified elements: Nr released by an entity (e.g. on the basis of the N footprint) and Nr reduction from management and offset projects (N offset). It includes management strategies to reduce nitrogen losses before they occur (e.g., through energy conservation). Each of those elements faces specific challenges with regard to data availability and conceptual development. Impacts of Nr releases to the environment are manifold, and the impact profile of one unit of Nr release depends strongly on the compound released and the local susceptibility to Nr. As such, N-neutrality is more difficult to conceptualize and calculate than C-neutrality. We developed a workable conceptual framework for N-neutrality which was adapted for the 6th International Nitrogen Conference (N2013, Kampala, November 2013). Total N footprint of the surveyed meals at N2013 was 66 kg N. A total of US$ 3050 was collected from the participants and used to offset the conference’s N footprint by supporting the UN Millennium Village cluster Ruhiira in South-Western Uganda. The concept needs further development in particular to better incorporate the spatio-temporal variability of impacts and to standardize the methods to quantify the required N offset to neutralize the Nr releases impact. Criteria for compensation projects need to be sharply defined to allow the development of a market for N offset certificates. (paper)

  6. Sensitivity of HIV-1 to neutralization by antibodies against O-linked carbohydrate epitopes despite deletion of O-glycosylation signals in the V3 loop

    DEFF Research Database (Denmark)

    Hansen, J E; Jansson, B; Gram, G J

    1996-01-01

    It has been suggested that threonine or serine residues in the V3 loop of HIV-1 gp120 are glycosylated with the short-chain O-linked oligosaccharides Tn or sialosyl-Tn that function as epitopes for broadly neutralizing carbohydrate specific antibodies. In this study we examined whether mutation....... Additionally, one of these T-A mutants (T308A) also abrogated the signal for N-glycosylation at N306 inside the V3-loop. The mutant clones were compared with the wild type virus as to sensitivity to neutralization with monoclonal and polyclonal antibodies specific for the tip of the V3 loop of BRU or for the O......-linked oligosaccharides Tn or sialosyl-Tn. Deletion of the N-linked oligosaccharide at N306 increased the neutralization sensitivity to antibodies specific for the tip of the loop, which indicates that N-linked glycosylation modulates the accessibility to this immunodominant epitope. However, none of the mutants...

  7. Displays and simulators

    Science.gov (United States)

    Mohon, N.

    A 'simulator' is defined as a machine which imitates the behavior of a real system in a very precise manner. The major components of a simulator and their interaction are outlined in brief form, taking into account the major components of an aircraft flight simulator. Particular attention is given to the visual display portion of the simulator, the basic components of the display, their interactions, and their characteristics. Real image displays are considered along with virtual image displays, and image generators. Attention is given to an advanced simulator for pilot training, a holographic pancake window, a scan laser image generator, the construction of an infrared target simulator, and the Apollo Command Module Simulator.

  8. Heavy neutral leptons at FASER

    Science.gov (United States)

    Kling, Felix; Trojanowski, Sebastian

    2018-05-01

    We study the prospects for discovering heavy neutral leptons at Forward Search Experiment (FASER), the newly proposed detector at the LHC. Previous studies showed that a relatively small detector with ˜10 m length and ≲1 m2 cross sectional area can probe large unconstrained parts of parameter space for dark photons and dark Higgs bosons. In this work, we show that FASER will also be sensitive to heavy neutral leptons that have mixing angles with the active neutrinos that are up to an order of magnitude lower than current bounds. In particular, this is true for heavy neutral leptons produced dominantly in B -meson decays, in which case FASER's discovery potential is comparable to the proposed SHiP detector. We also illustrate how the search for heavy neutral leptons at FASER will be complementary to ongoing searches in high-pT experiments at the LHC and can shed light on the nature of dark matter and the process of baryogenesis in the early Universe.

  9. The Neutral Interest Rate: Estimates for Chile

    OpenAIRE

    Rodrigo Fuentes S; Fabián Gredig U.

    2008-01-01

    To estimate the neutral real interest rate for Chile, we use a variety of methods that can be classified into three categories: those derived from economic theory, the neutral rate implicit in financial assets, and statistical procedures using macroeconomic data. We conclude that the neutral rate is not constant over time, but it is closely related with—though not equivalent to—the potential GDP growth rate. The application of the different methods yields fairly similar results. The neutral r...

  10. BEAMS3D Neutral Beam Injection Model

    Energy Technology Data Exchange (ETDEWEB)

    Lazerson, Samuel

    2014-04-14

    With the advent of applied 3D fi elds in Tokamaks and modern high performance stellarators, a need has arisen to address non-axisymmetric effects on neutral beam heating and fueling. We report on the development of a fully 3D neutral beam injection (NBI) model, BEAMS3D, which addresses this need by coupling 3D equilibria to a guiding center code capable of modeling neutral and charged particle trajectories across the separatrix and into the plasma core. Ionization, neutralization, charge-exchange, viscous velocity reduction, and pitch angle scattering are modeled with the ADAS atomic physics database [1]. Benchmark calculations are presented to validate the collisionless particle orbits, neutral beam injection model, frictional drag, and pitch angle scattering effects. A calculation of neutral beam heating in the NCSX device is performed, highlighting the capability of the code to handle 3D magnetic fields.

  11. Modeling Secondary Neutral Helium in the Heliosphere

    International Nuclear Information System (INIS)

    Müller, Hans-Reinhard; Möbius, Eberhard; Wood, Brian E.

    2016-01-01

    An accurate, analytic heliospheric neutral test-particle code for helium atoms from the interstellar medium (ISM) is coupled to global heliospheric models dominated by hydrogen and protons from the solar wind and the ISM. This coupling enables the forward-calculation of secondary helium neutrals from first principles. Secondaries are produced predominantly in the outer heliosheath, upwind of the heliopause, by charge exchange of helium ions with neutral atoms. The forward model integrates the secondary production terms along neutral trajectories and calculates the combined neutral helium phase space density in the innermost heliosphere where it can be related to in-situ observations. The phase space density of the secondary component is lower than that of primary neutral helium, but its presence can change the analysis of primaries and the ISM, and can yield valuable insight into the characteristics of the plasma in the outer heliosheath. (paper)

  12. Neutral particle beam alternative concept for ITER

    International Nuclear Information System (INIS)

    Sedgley, D.; Brook, J.; Luzzi, T.; Deutsch, L.

    1989-01-01

    An analysis of an ITER neutral particle beam system is presented. The analysis covers the neutralizer, ion dumps, pumping, and geometric aspects. The US beam concept for ITER consists of three or four clusters of beamlines delivering approximately 80 MW total of 1.6-MeV deuterium to three or four reactor ports. Each cluster has three self-contained beamlines featuring plasma neutralizers and electrostatic ion dumps. In this study, each of the beamlines has two source assemblies with separate gas neutralizers and magnetic ion dumps. Deuterium is injected into the gas neutralizers by a separate system. Saddle-shaped copper coils augment the tokamak poloidal field to turn the charged particles into the ion dumps. The gas flow from the source, neutralizer, and ion dump is pumped by regenerable cryopanels. The effect of the port between the TF coils and the beam injection angle on the plasma footprint was studied

  13. Displays enabling mobile multimedia

    Science.gov (United States)

    Kimmel, Jyrki

    2007-02-01

    With the rapid advances in telecommunications networks, mobile multimedia delivery to handsets is now a reality. While a truly immersive multimedia experience is still far ahead in the mobile world, significant advances have been made in the constituent audio-visual technologies to make this become possible. One of the critical components in multimedia delivery is the mobile handset display. While such alternatives as headset-style near-to-eye displays, autostereoscopic displays, mini-projectors, and roll-out flexible displays can deliver either a larger virtual screen size than the pocketable dimensions of the mobile device can offer, or an added degree of immersion by adding the illusion of the third dimension in the viewing experience, there are still challenges in the full deployment of such displays in real-life mobile communication terminals. Meanwhile, direct-view display technologies have developed steadily, and can provide a development platform for an even better viewing experience for multimedia in the near future. The paper presents an overview of the mobile display technology space with an emphasis on the advances and potential in developing direct-view displays further to meet the goal of enabling multimedia in the mobile domain.

  14. An experimenter's history of neutral currents

    International Nuclear Information System (INIS)

    Sciulli, F.

    1979-01-01

    The history of the experimental study of neutral currents, defined as the class of weak interactions engaged in by lepton pairs of net zero charge, is traced under the headings; historical motivations, experimental searches, first positive indications, neutral currents corroborated, neutrino experiments on neutral currents and some general experimental comments. It is concluded that the neutral current does exist and predicted on the basis of gauge theory ideas, and though to connect the weak and electromagnetic interactions, its very general experimental properties are quite consistent with those ideas. Among these are flavor conserving complicated isospin structure, complicated V, A structure and a structure which depends on the type (or quantum numbers) of the target. 50 references. (UK)

  15. On Integrity of Flexible Displays

    Science.gov (United States)

    Bouten, Piet C. P.

    Nowadays two display types are dominant in the display market: the bulky cathode ray tube (CRT) and liquid crystal displays (LCD). Both types use glass as substrate material. The LCD display is the dominant player for mobile applications, in for instance mobile phones and portable computers. In the development of displays and their applications a clear interest exists to replace the rigid rectangular display cells by free-shaped, curved or even roll-up cells. These types of applications require flexible displays.

  16. Computational study of the first stage of hypersonic ion beam neutralization: The cross neutralization stage

    International Nuclear Information System (INIS)

    Pomot, C.; Dolique, J.M.

    1975-01-01

    A study is made of the first stage of evolution of a hypersonic ion beam in which thermoelectrons are emitted by a heated grid, known as the neutralizer. Downstream from the neutralizer there appears successively as a sheath a range of periodic and quasi-stationary electric field and a front where the electric field oscillates with the plasma frequency. The sheath is self-regulated. Some electrons are trapped in the periodic and stationary electric field. The characteristics of the periodic, quasi-stationary range correspond to those of both an experimental study and one-dimensional time-independent macroscopic theory. This quasi-stationary regime builds up in a time smaller than ω/subp/e -1 and is studied for a few periods ω/subP//sube/ -1 . The subsequent evolution of this state of nonequilibrium is not investigated. The experimental study has shown that, as for the neutralization of a subsonic ion beam, it leads to a field-free, homogeneous medium: a ''synthesized plasma.'' The importance of the first stage described herein, which may be called the gross neutralization stage, is due to the properties of mean neutrality in the current and in the charge insured by the regulating sheath, properties which will be preseved downstream

  17. Net neutrality and audiovisual services

    NARCIS (Netherlands)

    van Eijk, N.; Nikoltchev, S.

    2011-01-01

    Net neutrality is high on the European agenda. New regulations for the communication sector provide a legal framework for net neutrality and need to be implemented on both a European and a national level. The key element is not just about blocking or slowing down traffic across communication

  18. Energizing and depletion of neutrals by a collisional plasma

    International Nuclear Information System (INIS)

    Fruchtman, A

    2008-01-01

    Neutral depletion can significantly affect the steady state of low temperature plasmas. Recent theoretical analyses predicted previously unexpected effects of neutral depletion in both collisional and collisionless regimes. In this paper we address the effect of the energy deposited in the neutral gas by a collisional plasma. The fraction of power deposited in the neutrals is shown to be independent of the amount of power. The first case we address is of a thermalized neutral gas. It is shown that a low heat conductivity of the neutral gas is followed by a high neutral temperature that results in a high neutral depletion even if the plasma pressure is small. In the second case neutrals are accelerated through charge exchange with ions leading to what we call neutral pumping, which is equivalent to ion pumping in a collisionless plasma. Neutral depletion is found in the second case for both a closed system (no net mass flow) and an open system (a finite mass flow). A thruster that employs a collisional plasma and pumped neutrals is compared with the thruster analyzed before that employs collisionless plasma.

  19. Net Neutrality: Media Discourses and Public Perception

    Directory of Open Access Journals (Sweden)

    Christine Quail

    2010-01-01

    Full Text Available This paper analyzes media and public discourses surrounding net neutrality, with particular attention to public utility philosophy, from a critical perspective. The article suggests that further public education about net neutrality would be beneficial. The first portion of this paper provides a survey of the existing literature surrounding net neutrality, highlighting the contentious debate between market-based and public interest perspectives. In order to contextualize the debate, an overview of public utility philosophy is provided, shedding light on how the Internet can be conceptualized as a public good. Following this discussion, an analysis of mainstream media is presented, exploring how the media represents the issue of net neutrality and whether or not the Internet is discussed through the lens of public utility. To further examine how the net neutrality debate is being addressed, and to see the potential impacts of media discourses on the general public, the results of a focus group are reported and analyzed. Finally, a discussion assesses the implications of the net neutrality debate as presented through media discourses, highlighting the future of net neutrality as an important policy issue.

  20. On implicit abstract neutral nonlinear differential equations

    Energy Technology Data Exchange (ETDEWEB)

    Hernández, Eduardo, E-mail: lalohm@ffclrp.usp.br [Universidade de São Paulo, Departamento de Computação e Matemática, Faculdade de Filosofia Ciências e Letras de Ribeirão Preto (Brazil); O’Regan, Donal, E-mail: donal.oregan@nuigalway.ie [National University of Ireland, School of Mathematics, Statistics and Applied Mathematics (Ireland)

    2016-04-15

    In this paper we continue our developments in Hernández and O’Regan (J Funct Anal 261:3457–3481, 2011) on the existence of solutions for abstract neutral differential equations. In particular we extend the results in Hernández and O’Regan (J Funct Anal 261:3457–3481, 2011) for the case of implicit nonlinear neutral equations and we focus on applications to partial “nonlinear” neutral differential equations. Some applications involving partial neutral differential equations are presented.

  1. A Measurement of Coherent Neutral Pion Production in Neutrino Neutral Current Interactions in NOMAD experiment

    CERN Document Server

    Kullenberg, C T

    2009-01-01

    We present a study of exclusive neutral pion production in neutrino-nucleus Neutral Current interactions using data from the NOMAD experiment at the CERN SPS. The data correspond to $1.44 \\times 10^6$ muon-neutrino Charged Current interactions in the energy range $2.5 \\leq E_{\

  2. IDEA: Interactive Display for Evolutionary Analyses

    Directory of Open Access Journals (Sweden)

    Carlton Jane M

    2008-12-01

    Full Text Available Abstract Background The availability of complete genomic sequences for hundreds of organisms promises to make obtaining genome-wide estimates of substitution rates, selective constraints and other molecular evolution variables of interest an increasingly important approach to addressing broad evolutionary questions. Two of the programs most widely used for this purpose are codeml and baseml, parts of the PAML (Phylogenetic Analysis by Maximum Likelihood suite. A significant drawback of these programs is their lack of a graphical user interface, which can limit their user base and considerably reduce their efficiency. Results We have developed IDEA (Interactive Display for Evolutionary Analyses, an intuitive graphical input and output interface which interacts with PHYLIP for phylogeny reconstruction and with codeml and baseml for molecular evolution analyses. IDEA's graphical input and visualization interfaces eliminate the need to edit and parse text input and output files, reducing the likelihood of errors and improving processing time. Further, its interactive output display gives the user immediate access to results. Finally, IDEA can process data in parallel on a local machine or computing grid, allowing genome-wide analyses to be completed quickly. Conclusion IDEA provides a graphical user interface that allows the user to follow a codeml or baseml analysis from parameter input through to the exploration of results. Novel options streamline the analysis process, and post-analysis visualization of phylogenies, evolutionary rates and selective constraint along protein sequences simplifies the interpretation of results. The integration of these functions into a single tool eliminates the need for lengthy data handling and parsing, significantly expediting access to global patterns in the data.

  3. Design of the ITER Neutral Beam injectors

    International Nuclear Information System (INIS)

    Hemsworth, R.S.; Feist, J.; Hanada, M.; Heinemann, B.; Inoue, T.; Kuessel, E.; Kulygin, V.; Krylov, A.; Lotte, P.; Miyamoto, K.; Miyamoto, N.; Murdoch, D.; Nagase, A.; Ohara, Y.; Okumura, Y.; Pamela, J.; Panasenkov, A.; Shibata, K.; Tanii, M.

    1996-01-01

    This paper describes the Neutral Beam Injection system which is presently being designed in Europe, Japan and Russia, with co-ordination by the Joint Central Team of ITER at Naka, Japan. The proposed system consists of three negative ion based neutral injectors, delivering a total of 50 MW of 1 MeV D 0 to the ITER plasma for pulse length of ≥1000 s. The injectors each use a single caesiated volume arc discharge negative ion source, and a multi-grid, multi-aperture accelerator, to produce about 40 A of 1 MeV D - . This will be neutralized in a sub-divided gas neutralizer, which has a conversion efficiency of about 60%. The charged fraction of the beam emerging from the neutralizer is dumped in an electrostatic residual ion dump. A water cooled calorimeter can be moved into the beam path to intercept the neutral beam, allowing commissioning of the injector independent of ITER. copyright 1996 American Institute of Physics

  4. Book Display as Adult Service

    Directory of Open Access Journals (Sweden)

    Matthew S. Moore

    1997-03-01

    Full Text Available 無Book display as an adult service is defined as choosing and positioning adult books from the collection to increase their circulation. The author contrasts bookstore arrangement for sales versus library arrangement for access. The paper considers the library-as-a-whole as a display, examines the right size for an in-library display, and discusses mass displays, end-caps, on-shelf displays, and the Tiffany approach. The author proposes that an effective display depends on an imaginative, unifying theme, and that book displays are part of the joy of libraries.

  5. A Three Monoclonal Antibody Combination Potently Neutralizes Multiple Botulinum Neurotoxin Serotype E Subtypes

    Directory of Open Access Journals (Sweden)

    Consuelo Garcia-Rodriguez

    2018-03-01

    Full Text Available Human botulism is most commonly caused by botulinum neurotoxin (BoNT serotypes A, B, and E. For this work, we sought to develop a human monoclonal antibody (mAb-based antitoxin capable of binding and neutralizing multiple subtypes of BoNT/E. Libraries of yeast-displayed single chain Fv (scFv antibodies were created from the heavy and light chain variable region genes of humans immunized with pentavalent-toxoid- and BoNT/E-binding scFv isolated by Fluorescence-Activated Cell Sorting (FACS. A total of 10 scFv were isolated that bound one or more BoNT/E subtypes with nanomolar-level equilibrium dissociation constants (KD. By diversifying the V-regions of the lead mAbs and selecting for cross-reactivity, we generated three scFv that bound all four BoNT/E subtypes tested at three non-overlapping epitopes. The scFvs were converted to IgG that had KD values for the different BoNT/E subtypes ranging from 9.7 nM to 2.28 pM. An equimolar combination of the three mAbs was able to potently neutralize BoNT/E1, BoNT/E3, and BoNT/E4 in a mouse neutralization assay. The mAbs have potential utility as therapeutics and as diagnostics capable of recognizing multiple BoNT/E subtypes. A derivative of the three-antibody combination (NTM-1633 is in pre-clinical development with an investigational new drug (IND application filing expected in 2018.

  6. A Three Monoclonal Antibody Combination Potently Neutralizes Multiple Botulinum Neurotoxin Serotype E Subtypes.

    Science.gov (United States)

    Garcia-Rodriguez, Consuelo; Razai, Ali; Geren, Isin N; Lou, Jianlong; Conrad, Fraser; Wen, Wei-Hua; Farr-Jones, Shauna; Smith, Theresa J; Brown, Jennifer L; Skerry, Janet C; Smith, Leonard A; Marks, James D

    2018-03-01

    Human botulism is most commonly caused by botulinum neurotoxin (BoNT) serotypes A, B, and E. For this work, we sought to develop a human monoclonal antibody (mAb)-based antitoxin capable of binding and neutralizing multiple subtypes of BoNT/E. Libraries of yeast-displayed single chain Fv (scFv) antibodies were created from the heavy and light chain variable region genes of humans immunized with pentavalent-toxoid- and BoNT/E-binding scFv isolated by Fluorescence-Activated Cell Sorting (FACS). A total of 10 scFv were isolated that bound one or more BoNT/E subtypes with nanomolar-level equilibrium dissociation constants (K D ). By diversifying the V-regions of the lead mAbs and selecting for cross-reactivity, we generated three scFv that bound all four BoNT/E subtypes tested at three non-overlapping epitopes. The scFvs were converted to IgG that had K D values for the different BoNT/E subtypes ranging from 9.7 nM to 2.28 pM. An equimolar combination of the three mAbs was able to potently neutralize BoNT/E1, BoNT/E3, and BoNT/E4 in a mouse neutralization assay. The mAbs have potential utility as therapeutics and as diagnostics capable of recognizing multiple BoNT/E subtypes. A derivative of the three-antibody combination (NTM-1633) is in pre-clinical development with an investigational new drug (IND) application filing expected in 2018.

  7. Children's Control/Display Stereotypes.

    Science.gov (United States)

    Hoffmann, Errol R; Chan, Alan H S; Tai, Judy P C

    2018-06-01

    Objective The aim of this study was to determine control/display stereotypes for children of a range of ages and development of these stereotypes with age. Background Little is known about control/display stereotypes for children of different ages and the way in which these stereotypes develop with age. This study is part of a program to determine the need to design differentially for these age groups. Method We tested four groups of children with various tasks (age groups 5 to 7, 8 to 10, 11 to 13, 14 to 16), with about 30 in each group. Examples of common tasks were opening a bottle, turning on taps, and allocating numbers to keypads. More complex tasks involved rotating a control to move a display in a requested direction. Results Tasks with which different age groups were familiar showed no effect of age group. Different control/display arrangements generally showed an increase in stereotype strength with age, with dependence on the form of the control/display arrangement. Two-dimensional arrangements, with the control on the same plane as the display, had higher stereotype strength than three-dimensional arrangements for all age groups, suggesting an effect of familiarity with controls and displays with increasing age. Conclusion Children's control/display stereotypes do not differ greatly from those of adults, and hence, design for children older than 5 years of age, for control/display stereotypes, can be the same as that for adult populations. Application When designing devices for children, the relationship between controls and displays can be as for adult populations, for which there are considerable experimental data.

  8. Weak neutral-current interactions

    International Nuclear Information System (INIS)

    Barnett, R.M.

    1978-08-01

    The roles of each type of experiment in establishing uniquely the values of the the neutral-current couplings of u and d quarks are analyzed together with their implications for gauge models of the weak and electromagnetic interactions. An analysis of the neutral-current couplings of electrons and of the data based on the assumption that only one Z 0 boson exists is given. Also a model-independent analysis of parity violation experiments is discussed. 85 references

  9. Differential Antibody Responses to Conserved HIV-1 Neutralizing Epitopes in the Context of Multivalent Scaffolds and Native-Like gp140 Trimers.

    Science.gov (United States)

    Morris, Charles D; Azadnia, Parisa; de Val, Natalia; Vora, Nemil; Honda, Andrew; Giang, Erick; Saye-Francisco, Karen; Cheng, Yushao; Lin, Xiaohe; Mann, Colin J; Tang, Jeffrey; Sok, Devin; Burton, Dennis R; Law, Mansun; Ward, Andrew B; He, Linling; Zhu, Jiang

    2017-02-28

    Broadly neutralizing antibodies (bNAbs) have provided valuable insights into the humoral immune response to HIV-1. While rationally designed epitope scaffolds and well-folded gp140 trimers have been proposed as vaccine antigens, a comparative understanding of their antibody responses has not yet been established. In this study, we probed antibody responses to the N332 supersite and the membrane-proximal external region (MPER) in the context of heterologous protein scaffolds and native-like gp140 trimers. Ferritin nanoparticles and fragment crystallizable (Fc) regions were utilized as multivalent carriers to display scaffold antigens with grafted N332 and MPER epitopes, respectively. Trimeric scaffolds were also identified to stabilize the MPER-containing BG505 gp140.681 trimer in a native-like conformation. Following structural and antigenic evaluation, a subset of scaffold and trimer antigens was selected for immunization in BALB/c mice. Serum binding revealed distinct patterns of antibody responses to these two bNAb targets presented in different structural contexts. For example, the N332 nanoparticles elicited glycan epitope-specific antibody responses that could also recognize the native trimer, while a scaffolded BG505 gp140.681 trimer generated a stronger and more rapid antibody response to the trimer apex than its parent gp140.664 trimer. Furthermore, next-generation sequencing (NGS) of mouse splenic B cells revealed expansion of antibody lineages with long heavy-chain complementarity-determining region 3 (HCDR3) loops upon activation by MPER scaffolds, in contrast to the steady repertoires primed by N332 nanoparticles and a soluble gp140.664 trimer. These findings will facilitate the future development of a coherent vaccination strategy that combines both epitope-focused and trimer-based approaches. IMPORTANCE Both epitope-focused and trimer-based strategies are currently being explored in HIV-1 vaccine development, which aims to elicit broadly neutralizing

  10. Affinity selection of Nipah and Hendra virus-related vaccine candidates from a complex random peptide library displayed on bacteriophage virus-like particles

    Energy Technology Data Exchange (ETDEWEB)

    Peabody, David S.; Chackerian, Bryce; Ashley, Carlee; Carnes, Eric; Negrete, Oscar

    2017-01-24

    The invention relates to virus-like particles of bacteriophage MS2 (MS2 VLPs) displaying peptide epitopes or peptide mimics of epitopes of Nipah Virus envelope glycoprotein that elicit an immune response against Nipah Virus upon vaccination of humans or animals. Affinity selection on Nipah Virus-neutralizing monoclonal antibodies using random sequence peptide libraries on MS2 VLPs selected peptides with sequence similarity to peptide sequences found within the envelope glycoprotein of Nipah itself, thus identifying the epitopes the antibodies recognize. The selected peptide sequences themselves are not necessarily identical in all respects to a sequence within Nipah Virus glycoprotein, and therefore may be referred to as epitope mimics VLPs displaying these epitope mimics can serve as vaccine. On the other hand, display of the corresponding wild-type sequence derived from Nipah Virus and corresponding to the epitope mapped by affinity selection, may also be used as a vaccine.

  11. Transport of neutral atoms and molecules in TFCX

    International Nuclear Information System (INIS)

    Boley, C.D.

    1984-09-01

    The distribution of neutrals in the proposed reactor TFCX has been modeled by the 3-D Monte Carlo neutral transport code DEGAS, which has been run in conjunction with the 1-1/2-D time-dependent plasma transport code WHIST. The former code contains the best available treatment of neutral-particle physics, including a selection of wall reflection models. The latter code has a comprehensive set of plasma transport coefficients, an MHD equilibrium package, and provision for source terms such as those involving neutrals. It has a simple scrape-off model involving sound-speed flow to the neutralizer plates. The codes are run in iteration, so that the flux-surface averaged particle and energy sources due to interactions with neutrals are consistent with the plasma profiles. The design considered here has a bottom limiter with a pumping plenum. Results are given for the power balance, the mutually consistent plasma and neutral distributions set up in the edge region, the neutral density in the plenum, and the charge-exchange power deposition and erosion along the limiter

  12. Nasal Immunization Confers High Avidity Neutralizing Antibody Response and Immunity to Primary and Recurrent Genital Herpes in Guinea Pigs

    Science.gov (United States)

    Persson, Josefine; Zhang, Yuan; Olafsdottir, Thorunn A.; Thörn, Karolina; Cairns, Tina M.; Wegmann, Frank; Sattentau, Quentin J.; Eisenberg, Roselyn J.; Cohen, Gary H.; Harandi, Ali M.

    2016-01-01

    Genital herpes is one of the most prevalent sexually transmitted infections in both the developing and developed world. Following infection, individuals experience life-long latency associated with sporadic ulcerative outbreaks. Despite many efforts, no vaccine has yet been licensed for human use. Herein, we demonstrated that nasal immunization with an adjuvanted HSV-2 gD envelope protein mounts significant protection to primary infection as well as the establishment of latency and recurrent genital herpes in guinea pigs. Nasal immunization was shown to elicit specific T cell proliferative and IFN-γ responses as well as systemic and vaginal gD-specific IgG antibody (Ab) responses. Furthermore, systemic IgG Abs displayed potent HSV-2 neutralizing properties and high avidity. By employing a competitive surface plasmon resonance (SPR) analysis combined with a battery of known gD-specific neutralizing monoclonal Abs (MAbs), we showed that nasal immunization generated IgG Abs directed to two major discontinuous neutralizing epitopes of gD. These results highlight the potential of nasal immunization with an adjuvanted HSV-2 envelope protein for induction of protective immunity to primary and recurrent genital herpes. PMID:28082979

  13. Nasal Immunization Confers High Avidity Neutralizing Antibody Response and Immunity to Primary and Recurrent Genital Herpes in Guinea Pigs.

    Science.gov (United States)

    Persson, Josefine; Zhang, Yuan; Olafsdottir, Thorunn A; Thörn, Karolina; Cairns, Tina M; Wegmann, Frank; Sattentau, Quentin J; Eisenberg, Roselyn J; Cohen, Gary H; Harandi, Ali M

    2016-01-01

    Genital herpes is one of the most prevalent sexually transmitted infections in both the developing and developed world. Following infection, individuals experience life-long latency associated with sporadic ulcerative outbreaks. Despite many efforts, no vaccine has yet been licensed for human use. Herein, we demonstrated that nasal immunization with an adjuvanted HSV-2 gD envelope protein mounts significant protection to primary infection as well as the establishment of latency and recurrent genital herpes in guinea pigs. Nasal immunization was shown to elicit specific T cell proliferative and IFN-γ responses as well as systemic and vaginal gD-specific IgG antibody (Ab) responses. Furthermore, systemic IgG Abs displayed potent HSV-2 neutralizing properties and high avidity. By employing a competitive surface plasmon resonance (SPR) analysis combined with a battery of known gD-specific neutralizing monoclonal Abs (MAbs), we showed that nasal immunization generated IgG Abs directed to two major discontinuous neutralizing epitopes of gD. These results highlight the potential of nasal immunization with an adjuvanted HSV-2 envelope protein for induction of protective immunity to primary and recurrent genital herpes.

  14. Divergence at neutral and non-neutral loci in Drosophila buzzatii populations and their hybrids

    DEFF Research Database (Denmark)

    Andersen, Ditte Holm; Pertoldi, Cino; Loeschcke, Volker

    2008-01-01

    The impact of intraspecific hybridisation on fitness and morphological traits depends on the history of natural selection and genetic drift, which may have led to differently coadapted gene-complexes in the parental populations. The divergence at neutral and non-neutral loci between populations can...... populations of Drosophila buzzatii, one between populations from Argentina and the Canary Islands (separated for 200 years), and the other between populations from Argentina and Australia (separated for 80 years). We observed the highest divergence at neutral loci between the Argentinean and Canary Island...

  15. Host-Primed Ebola Virus GP Exposes a Hydrophobic NPC1 Receptor-Binding Pocket, Revealing a Target for Broadly Neutralizing Antibodies

    Directory of Open Access Journals (Sweden)

    Zachary A. Bornholdt

    2016-02-01

    Full Text Available The filovirus surface glycoprotein (GP mediates viral entry into host cells. Following viral internalization into endosomes, GP is cleaved by host cysteine proteases to expose a receptor-binding site (RBS that is otherwise hidden from immune surveillance. Here, we present the crystal structure of proteolytically cleaved Ebola virus GP to a resolution of 3.3 Å. We use this structure in conjunction with functional analysis of a large panel of pseudotyped viruses bearing mutant GP proteins to map the Ebola virus GP endosomal RBS at molecular resolution. Our studies indicate that binding of GP to its endosomal receptor Niemann-Pick C1 occurs in two distinct stages: the initial electrostatic interactions are followed by specific interactions with a hydrophobic trough that is exposed on the endosomally cleaved GP1 subunit. Finally, we demonstrate that monoclonal antibodies targeting the filovirus RBS neutralize all known filovirus GPs, making this conserved pocket a promising target for the development of panfilovirus therapeutics.

  16. Augmenting digital displays with computation

    Science.gov (United States)

    Liu, Jing

    As we inevitably step deeper and deeper into a world connected via the Internet, more and more information will be exchanged digitally. Displays are the interface between digital information and each individual. Naturally, one fundamental goal of displays is to reproduce information as realistically as possible since humans still care a lot about what happens in the real world. Human eyes are the receiving end of such information exchange; therefore it is impossible to study displays without studying the human visual system. In fact, the design of displays is rather closely coupled with what human eyes are capable of perceiving. For example, we are less interested in building displays that emit light in the invisible spectrum. This dissertation explores how we can augment displays with computation, which takes both display hardware and the human visual system into consideration. Four novel projects on display technologies are included in this dissertation: First, we propose a software-based approach to driving multiview autostereoscopic displays. Our display algorithm can dynamically assign views to hardware display zones based on multiple observers' current head positions, substantially reducing crosstalk and stereo inversion. Second, we present a dense projector array that creates a seamless 3D viewing experience for multiple viewers. We smoothly interpolate the set of viewer heights and distances on a per-vertex basis across the arrays field of view, reducing image distortion, crosstalk, and artifacts from tracking errors. Third, we propose a method for high dynamic range display calibration that takes into account the variation of the chrominance error over luminance. We propose a data structure for enabling efficient representation and querying of the calibration function, which also allows user-guided balancing between memory consumption and the amount of computation. Fourth, we present user studies that demonstrate that the ˜ 60 Hz critical flicker fusion

  17. Intense ion beam neutralization using underdense background plasma

    Energy Technology Data Exchange (ETDEWEB)

    Berdanier, William [Department of Physics, The University of Texas at Austin, Austin, Texas 78712 (United States); Princeton Plasma Physics Laboratory, Princeton University, Princeton, New Jersey 08543 (United States); Roy, Prabir K. [Lawrence Berkeley National Laboratory, Berkeley, California 94720 (United States); Kaganovich, Igor [Princeton Plasma Physics Laboratory, Princeton University, Princeton, New Jersey 08543 (United States)

    2015-01-15

    Producing an overdense background plasma for neutralization purposes with a density that is high compared to the beam density is not always experimentally possible. We show that even an underdense background plasma with a small relative density can achieve high neutralization of intense ion beam pulses. Using particle-in-cell simulations, we show that if the total plasma electron charge is not sufficient to neutralize the beam charge, electron emitters are necessary for effective neutralization but are not needed if the plasma volume is so large that the total available charge in the electrons exceeds that of the ion beam. Several regimes of possible underdense/tenuous neutralization plasma densities are investigated with and without electron emitters or dense plasma at periphery regions, including the case of electron emitters without plasma, which does not effectively neutralize the beam. Over 95% neutralization is achieved for even very underdense background plasma with plasma density 1/15th the beam density. We compare results of particle-in-cell simulations with an analytic model of neutralization and find close agreement with the particle-in-cell simulations. Further, we show experimental data from the National Drift Compression experiment-II group that verifies the result that underdense plasma can neutralize intense heavy ion beams effectively.

  18. 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.

  19. Controllability Problem of Fractional Neutral Systems: A Survey

    Directory of Open Access Journals (Sweden)

    Artur Babiarz

    2017-01-01

    Full Text Available The following article presents recent results of controllability problem of dynamical systems in infinite-dimensional space. Generally speaking, we describe selected controllability problems of fractional order systems, including approximate controllability of fractional impulsive partial neutral integrodifferential inclusions with infinite delay in Hilbert spaces, controllability of nonlinear neutral fractional impulsive differential inclusions in Banach space, controllability for a class of fractional neutral integrodifferential equations with unbounded delay, controllability of neutral fractional functional equations with impulses and infinite delay, and controllability for a class of fractional order neutral evolution control systems.

  20. Display of adenoregulin with a novel Pichia pastoris cell surface display system.

    Science.gov (United States)

    Ren, Ren; Jiang, Zhengbing; Liu, Meiyun; Tao, Xinyi; Ma, Yushu; Wei, Dongzhi

    2007-02-01

    Two Pichia pastoris cell surface display vectors were constructed. The vectors consisted of the flocculation functional domain of Flo1p with its own secretion signal sequence or the alpha-factor secretion signal sequence, a polyhistidine (6xHis) tag for detection, an enterokinase recognition site, and the insertion sites for target proteins. Adenoregulin (ADR) is a 33-amino-acid antimicrobial peptide isolated from Phyllomedusa bicolor skin. The ADR was expressed and displayed on the Pichia pastoris KM71 cell surface with the system reported. The displayed recombinant ADR fusion protein was detected by fluorescence microscopy and confocal laser scanning microscopy (CLSM). The antimicrobial activity of the recombinant adenoregulin was detected after proteolytic cleavage of the fusion protein on cell surface. The validity of the Pichia pastoris cell surface display vectors was proved by the displayed ADR.

  1. 77 FR 50144 - Broad Stakeholder Survey

    Science.gov (United States)

    2012-08-20

    ... DEPARTMENT OF HOMELAND SECURITY [Docket No. DHS-2012-0042] Broad Stakeholder Survey AGENCY... Information Collection Request: 1670-NEW. SUMMARY: The Department of Homeland Security (DHS), National... (Pub. L. 104-13, 44 U.S.C. Chapter 35). NPPD is soliciting comments concerning the Broad Stakeholder...

  2. 76 FR 34087 - Broad Stakeholder Survey

    Science.gov (United States)

    2011-06-10

    ... DEPARTMENT OF HOMELAND SECURITY [Docket No. DHS-2011-0027] Broad Stakeholder Survey AGENCY... Information Collection Request: 1670-NEW. SUMMARY: The Department of Homeland Security (DHS), National... (Pub. L. 104-13, 44 U.S.C. Chapter 35). NPPD is soliciting comments concerning the Broad Stakeholder...

  3. Method to Minimize the Low-Frequency Neutral-Point Voltage Oscillations With Time-Offset Injection for Neutral-Point-Clamped Inverters

    DEFF Research Database (Denmark)

    Choi, Ui-Min; Blaabjerg, Frede; Lee, Kyo-Beum

    2015-01-01

    time of small- and medium-voltage vectors. However, if the power factor is lower, there is a limitation to eliminate neutral-point oscillations. In this case, the proposed method can be improved by changing the switching sequence properly. Additionally, a method for neutral-point voltage balancing......This paper proposes a method to reduce the low-frequency neutral-point voltage oscillations. The neutral-point voltage oscillations are considerably reduced by adding a time offset to the three-phase turn-on times. The proper time offset is simply calculated considering the phase currents and dwell...

  4. Neutrality in mediation: an ambiguous ethical value

    OpenAIRE

    Bailey, Paul

    2014-01-01

    Mediator neutrality would appear, by definition, to be a necessary and required ethical principle for all mediators to practice. But what is meant by neutrality in mediation? Is it practically possible to be completely neutral between parties in mediation while at the same time being fair to both of them? This paper attempts to answer these two questions.

  5. Neutral-beam development plan, FY 1982-1987

    International Nuclear Information System (INIS)

    1981-09-01

    The following chapters are included: (1) status of BNL negative ion source development, (2) source development program plan, (3) status of beam transport and acceleration, (4) accelerator development program plan, (5) neutralizer concepts, (6) neutralization program plan, (7) neutral beam systems, (8) test facilities, (9) program milestones and time schedules, (10) organization and Grumman participation, and (11) funding tables

  6. ITER neutral beam system US conceptual design

    International Nuclear Information System (INIS)

    Purgalis, P.

    1990-09-01

    In this document we present the US conceptual design of a neutral beam system for International Thermonuclear Experimental Reactor (ITER). The design incorporates a barium surface conversion D - source feeding a linear array of accelerator channels. The system uses a dc accelerator with electrostatic quadrupoles for strong focusing. A high voltage power supply that is integrated with the accelerator is presented as an attractive option. A gas neutralizer is used and residual ions exiting the neutralizer are deflected to water-cooled dumps. Cryopanels are located at the accelerator exit to pump excess gas from the source and the neutralizer, and in the ion dump cavity to pump re-neutralized ions and neutralizer gas. All the above components are packaged in compact identical, independent modules which can be removed for remote maintenance. The neutral beam system delivers 75 MW of DO at 1.3 MeV, into three ports with a total of 9 modules arranged in stacks of three modules per port . To increase reliability each module is designed to deliver up to 10 MW; this allows eight modules operating at partial capacity to deliver the required power in the event one module is out of service, and provides 20% excess capacity to improve availability. Radiation protection is provided by shielding and by locating critical components in the source and accelerator 46.5 m from the torus centerline. Neutron shielding in the drift duct and neutralizer provides the added feature of limiting conductance and thus reducing gas flow to and from the torus

  7. Flat panel display - Impurity doping technology for flat panel displays

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Toshiharu [Advanced Technology Planning, Sumitomo Eaton Nova Corporation, SBS Tower 9F, 10-1, Yoga 4-chome, Setagaya-ku, 158-0097 Tokyo (Japan)]. E-mail: suzuki_tsh@senova.co.jp

    2005-08-01

    Features of the flat panel displays (FPDs) such as liquid crystal display (LCD) and organic light emitting diode (OLED) display, etc. using low temperature poly-Si (LTPS) thin film transistors (TFTs) are briefly reviewed comparing with other FPDs. The requirements for fabricating TFTs used for high performance FPDs and system on glass (SoG) are addressed. This paper focuses on the impurity doping technology, which is one of the key technologies together with crystallization by laser annealing, formation of high quality gate insulator and gate-insulator/poly-Si interface. The issues to be solved in impurity doping technology for state of the art and future TFTs are clarified.

  8. Flat panel display - Impurity doping technology for flat panel displays

    International Nuclear Information System (INIS)

    Suzuki, Toshiharu

    2005-01-01

    Features of the flat panel displays (FPDs) such as liquid crystal display (LCD) and organic light emitting diode (OLED) display, etc. using low temperature poly-Si (LTPS) thin film transistors (TFTs) are briefly reviewed comparing with other FPDs. The requirements for fabricating TFTs used for high performance FPDs and system on glass (SoG) are addressed. This paper focuses on the impurity doping technology, which is one of the key technologies together with crystallization by laser annealing, formation of high quality gate insulator and gate-insulator/poly-Si interface. The issues to be solved in impurity doping technology for state of the art and future TFTs are clarified

  9. Handbook of Visual Display Technology

    CERN Document Server

    Cranton, Wayne; Fihn, Mark

    2012-01-01

    The Handbook of Visual Display Technology is a unique work offering a comprehensive description of the science, technology, economic and human interface factors associated with the displays industry. An invaluable compilation of information, the Handbook will serve as a single reference source with expert contributions from over 150 international display professionals and academic researchers. All classes of display device are covered including LCDs, reflective displays, flexible solutions and emissive devices such as OLEDs and plasma displays, with discussion of established principles, emergent technologies, and particular areas of application. The wide-ranging content also encompasses the fundamental science of light and vision, image manipulation, core materials and processing techniques, display driving and metrology.

  10. Polymer Dispersed Liquid Crystal Displays

    Science.gov (United States)

    Doane, J. William

    The following sections are included: * INTRODUCTION AND HISTORICAL DEVELOPMENT * PDLC MATERIALS PREPARATION * Polymerization induced phase separation (PIPS) * Thermally induced phase separation (TIPS) * Solvent induced phase separation (SIPS) * Encapsulation (NCAP) * RESPONSE VOLTAGE * Dielectric and resistive effects * Radial configuration * Bipolar configuration * Other director configurations * RESPONSE TIME * DISPLAY CONTRAST * Light scattering and index matching * Incorporation of dyes * Contrast measurements * PDLC DISPLAY DEVICES AND INNOVATIONS * Reflective direct view displays * Large-scale, flexible displays * Switchable windows * Projection displays * High definition spatial light modulator * Haze-free PDLC shutters: wide angle view displays * ENVIRONMENTAL STABILITY * ACKNOWLEDGEMENTS * REFERENCES

  11. Information rich display design

    International Nuclear Information System (INIS)

    Welch, Robin; Braseth, Alf Ove; Veland, Oeystein

    2004-01-01

    This paper presents the concept Information Rich Displays. The purpose of Information Rich Displays (IRDs) is to condensate prevailing information in process displays in such a way that each display format (picture) contains more relevant information for the user. Compared to traditional process control displays, this new concept allows the operator to attain key information at a glance and at the same time allows for improved monitoring of larger portions of the process. This again allows for reduced navigation between both process and trend displays and ease the cognitive demand on the operator. This concept has been created while working on designing display prototypes for the offshore petroleum production facilities of tomorrow. Offshore installations basically consist of wells, separation trains (where oil, gas and water are separated from each other), an oil tax measurement system (where oil quality is measured and the pressure increased to allow for export), gas compression (compression of gas for export) and utility systems (water treatment, chemical systems etc.). This means that an offshore control room operator has to deal with a complex process that comprises several functionally different systems. The need for a new approach to offshore display format design is in particular based on shortcomings in today's designs related to the keyhole effect, where the display format only reveals a fraction of the whole process. Furthermore, the upcoming introduction of larger off- and on-shore operation centres will increase the size and complexity of the operators' work domain. In the light of the increased demands on the operator, the proposed IRDs aim to counter the negative effects this may have on the workload. In this work we have attempted to classify the wide range of different roles an operator can have in different situations. The information content and amount being presented to the operator in a display should be viewed in context of the roles the

  12. Active ion temperature measurement with heating neutral beam

    International Nuclear Information System (INIS)

    Miura, Yukitoshi; Matsuda, Toshiaki; Yamamoto, Shin

    1987-03-01

    When the heating neutral-beam (hydrogen beam) is injected into a deuterium plasma, the density of neutral particles is increased locally. By using this increased neutral particles, the local ion temperature is measured by the active charge-exchange method. The analyzer is the E//B type mass-separated neutral particle energy analyzer and the measured position is about one third outside of the plasma radius. The deuterium energy spectrum is Maxwellian, and the temperature is increased from 350 eV to 900 eV during heating. Since the local hydrogen to deuterium density concentration and the density of the heating neutral-beam as well as the ion temperature can be obtained good S/N ratio, the usefulness of this method during neutral-beam heating is confirmed by this experiment. (author)

  13. Facial expressions of emotion (KDEF): identification under different display-duration conditions.

    Science.gov (United States)

    Calvo, Manuel G; Lundqvist, Daniel

    2008-02-01

    Participants judged which of seven facial expressions (neutrality, happiness, anger, sadness, surprise, fear, and disgust) were displayed by a set of 280 faces corresponding to 20 female and 20 male models of the Karolinska Directed Emotional Faces database (Lundqvist, Flykt, & Ohman, 1998). Each face was presented under free-viewing conditions (to 63 participants) and also for 25, 50, 100, 250, and 500 msec (to 160 participants), to examine identification thresholds. Measures of identification accuracy, types of errors, and reaction times were obtained for each expression. In general, happy faces were identified more accurately, earlier, and faster than other faces, whereas judgments of fearful faces were the least accurate, the latest, and the slowest. Norms for each face and expression regarding level of identification accuracy, errors, and reaction times may be downloaded from www.psychonomic.org/archive/.

  14. Structural Determination of the Broadly Reactive Anti-IGHV1-69 Anti-idiotypic Antibody G6 and Its Idiotope.

    Science.gov (United States)

    Avnir, Yuval; Prachanronarong, Kristina L; Zhang, Zhen; Hou, Shurong; Peterson, Eric C; Sui, Jianhua; Zayed, Hatem; Kurella, Vinodh B; McGuire, Andrew T; Stamatatos, Leonidas; Hilbert, Brendan J; Bohn, Markus-Frederik; Kowalik, Timothy F; Jensen, Jeffrey D; Finberg, Robert W; Wang, Jennifer P; Goodall, Margaret; Jefferis, Roy; Zhu, Quan; Kurt Yilmaz, Nese; Schiffer, Celia A; Marasco, Wayne A

    2017-12-12

    The heavy chain IGHV1-69 germline gene exhibits a high level of polymorphism and shows biased use in protective antibody (Ab) responses to infections and vaccines. It is also highly expressed in several B cell malignancies and autoimmune diseases. G6 is an anti-idiotypic monoclonal Ab that selectively binds to IGHV1-69 heavy chain germline gene 51p1 alleles that have been implicated in these Ab responses and disease processes. Here, we determine the co-crystal structure of humanized G6 (hG6.3) in complex with anti-influenza hemagglutinin stem-directed broadly neutralizing Ab D80. The core of the hG6.3 idiotope is a continuous string of CDR-H2 residues starting with M53 and ending with N58. G6 binding studies demonstrate the remarkable breadth of binding to 51p1 IGHV1-69 Abs with diverse CDR-H3, light chain, and antigen binding specificities. These studies detail the broad expression of the G6 cross-reactive idiotype (CRI) that further define its potential role in precision medicine. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Structural Determination of the Broadly Reactive Anti-IGHV1-69 Anti-idiotypic Antibody G6 and Its Idiotope

    Directory of Open Access Journals (Sweden)

    Yuval Avnir

    2017-12-01

    Full Text Available The heavy chain IGHV1-69 germline gene exhibits a high level of polymorphism and shows biased use in protective antibody (Ab responses to infections and vaccines. It is also highly expressed in several B cell malignancies and autoimmune diseases. G6 is an anti-idiotypic monoclonal Ab that selectively binds to IGHV1-69 heavy chain germline gene 51p1 alleles that have been implicated in these Ab responses and disease processes. Here, we determine the co-crystal structure of humanized G6 (hG6.3 in complex with anti-influenza hemagglutinin stem-directed broadly neutralizing Ab D80. The core of the hG6.3 idiotope is a continuous string of CDR-H2 residues starting with M53 and ending with N58. G6 binding studies demonstrate the remarkable breadth of binding to 51p1 IGHV1-69 Abs with diverse CDR-H3, light chain, and antigen binding specificities. These studies detail the broad expression of the G6 cross-reactive idiotype (CRI that further define its potential role in precision medicine.

  16. 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.

  17. Kinetics of neutralization of Po-218

    International Nuclear Information System (INIS)

    Chu, K.D.

    1987-01-01

    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 mobilities of Po + and PoO 2 + 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 NO 2 or H 2 O in nitrogen. When PoO 2 + is formed, the electron transfer mechanism dominates the neutralization process. The electron is transferred to PoO 2 + from molecules with lower ionization potentials. The ionization potential of PoO 2 + is also determined to be 10.44 +/- 0.05 eV

  18. Neutral and Non-Neutral Evolution of Duplicated Genes with Gene Conversion

    Directory of Open Access Journals (Sweden)

    Jeffrey A. Fawcett

    2011-02-01

    Full Text Available Gene conversion is one of the major mutational mechanisms involved in the DNA sequence evolution of duplicated genes. It contributes to create unique patters of DNA polymorphism within species and divergence between species. A typical pattern is so-called concerted evolution, in which the divergence between duplicates is maintained low for a long time because of frequent exchanges of DNA fragments. In addition, gene conversion affects the DNA evolution of duplicates in various ways especially when selection operates. Here, we review theoretical models to understand the evolution of duplicates in both neutral and non-neutral cases. We also explain how these theories contribute to interpreting real polymorphism and divergence data by using some intriguing examples.

  19. Neutral signature Walker-VSI metrics

    International Nuclear Information System (INIS)

    Coley, A; McNutt, D; Musoke, N; Brooks, D; Hervik, S

    2014-01-01

    We will construct explicit examples of four-dimensional neutral signature Walker (but not necessarily degenerate Kundt) spaces for which all of the polynomial scalar curvature invariants vanish. We then investigate the properties of some particular subclasses of Ricci flat spaces. We also briefly describe some four-dimensional neutral signature Einstein spaces for which all of the polynomial scalar curvature invariants are constant. (paper)

  20. Fast Neutral Pressure Measurements in NSTX

    International Nuclear Information System (INIS)

    R. Raman; H.W. Kugel; T. Provost; R. Gernhardt; T.R. Jarboe; M.G. Bell

    2002-01-01

    Several fast neutral pressure gauges have been installed on NSTX [National Spherical Torus Experiment] to measure the vessel and divertor pressure during inductive and coaxial helicity injected (CHI) plasma operations. Modified, PDX [Poloidal Divertor Experiment]-type Penning gauges have been installed on the upper and lower divertors. Neutral pressure measurements during plasma operations from these and from two shielded fast Micro ion gauges at different toroidal locations on the vessel mid-plane are described. A new unshielded ion gauge, referred to as the In-vessel Neutral Pressure (INP) gauge is under development

  1. Measurement of Neutral-Current display='inline'>K+ Production by Neutrinos using MINERvA

    Energy Technology Data Exchange (ETDEWEB)

    Marshall, C. M.; Aliaga, L.; Altinok, O.; Bellantoni, L.; Bercellie, A.; Betancourt, M.; Bodek, A.; Bravar, A.; Cai, T.; Carneiro, M. F.; da Motta, H.; Dytman, S. A.; Díaz, G. A.; Dunkman, M.; Eberly, B.; Endress, E.; Felix, J.; Fields, L.; Fine, R.; Gago, A. M.; Galindo, R.; Gallagher, H.; Ghosh, A.; Golan, T.; Gran, R.; Harris, D. A.; Higuera, A.; Hurtado, K.; Kleykamp, J.; Kordosky, M.; Le, T.; Maher, E.; Manly, S.; Mann, W. A.; Caicedo, D. A. Martinez; McFarland, K. S.; McGivern, C. L.; McGowan, A. M.; Messerly, B.; Miller, J.; Mislivec, A.; Morfín, J. G.; Mousseau, J.; Naples, D.; Nelson, J. K.; Norrick, A.; Nuruzzaman,; Paolone, V.; Patrick, C. E.; Perdue, G. N.; Ramírez, M. A.; Ransome, R. D.; Ray, H.; Ren, L.; Rimal, D.; Rodrigues, P. A.; Ruterbories, D.; Schmitz, D. W.; Solano Salinas, C. J.; Sultana, M.; Sánchez Falero, S.; Valencia, E.; Walton, T.; Wolcott, J.; Wospakrik, M.; Yaeggy, B.; Zhang, D.

    2017-07-01

    Neutral-current production of K+ by atmospheric neutrinos is a background in searches for the proton decay p→K+ν¯. Reactions such as νp→νK+Λ are indistinguishable from proton decays when the decay products of the Λ are below detection threshold. Events with K+ are identified in MINERvA by reconstructing the timing signature of a K+ decay at rest. A sample of 201 neutrino-induced neutral-current K+ events is used to measure differential cross sections with respect to the K+ kinetic energy, and the non-K+ hadronic visible energy. An excess of events at low hadronic visible energy is observed relative to the prediction of the neut event generator. Good agreement is observed with the cross section prediction of the genie generator. A search for photons from π0 decay, which would veto a neutral-current K+ event in a proton decay search, is performed, and a 2σ deficit of detached photons is observed relative to the genie prediction.

  2. Edge momentum transport by neutrals: an interpretive numerical framework

    Science.gov (United States)

    Omotani, J. T.; Newton, S. L.; Pusztai, I.; Viezzer, E.; Fülöp, T.; The ASDEX Upgrade Team

    2017-06-01

    Due to their high cross-field mobility, neutrals can contribute to momentum transport even at the low relative densities found inside the separatrix and they can generate intrinsic rotation. We use a charge-exchange dominated solution to the neutral kinetic equation, coupled to neoclassical ions, to evaluate the momentum transport due to neutrals. Numerical solutions to the drift-kinetic equation allow us to cover the full range of collisionality, including the intermediate levels typical of the tokamak edge. In the edge there are several processes likely to contribute to momentum transport in addition to neutrals. Therefore, we present here an interpretive framework that can evaluate the momentum transport through neutrals based on radial plasma profiles. We demonstrate its application by analysing the neutral angular momentum flux for an L-mode discharge in the ASDEX Upgrade tokamak. The magnitudes of the angular momentum fluxes we find here due to neutrals of 0.6-2 \\text{N} \\text{m} are comparable to the net torque on the plasma from neutral beam injection, indicating the importance of neutrals for rotation in the edge.

  3. Neutralization of wastewater from nitrite passivation

    International Nuclear Information System (INIS)

    Pawlowski, L.; Mientki, B.; Wasag, H.

    1982-01-01

    A method for neutralization of wastewater formed in nitrite passivation has been presented. The method consists of introducing urea into wastewater and acidifying it with sulphuric acid. Wastewater is neutralized with lime. After clarification, wastewater can be drained outside the plant

  4. Effect of neutral atoms on tokamak edge plasmas

    International Nuclear Information System (INIS)

    Fueloep, T.; Catto, Peter J.; Helander, P.

    2001-01-01

    Neutral atoms can significantly influence the physics of tokamak edge plasmas, e.g., by affecting the radial electric field and plasma flow there, which may, in turn, be important for plasma confinement. Earlier work [Fueloep et al., Phys. Plasmas 5, 3969 (1998)], assuming short mean-free path neutrals and Pfirsch-Schlueter ions, has shown that the ion-neutral coupling through charge-exchange affects the neoclassical flow velocity significantly. However, the mean-free path of the neutrals is not always small in comparison with the radial scale length of densities and temperatures in the edge pedestal. It is therefore desirable to determine what happens in the limit when the neutral mean-free path is comparable with the scale length. In the present work a self-similar solution for the neutral distribution function allowing for strong temperature and density variation is used, following the analysis of Helander and Krasheninnikov [Phys. Plasmas 3, 226 (1995)]. The self-similar solution is possible if the ratio of the mean-free path to the temperature and density scale length is constant throughout the edge plasma. The resulting neutral distribution function is used to investigate the neutral effects on the ion flow and electrostatic potential as this ratio varies from much less than one to order unity

  5. The value of Network Neutrality for the Internet of Tomorrow : Report of the Dynamic Coalition on Network Neutrality

    OpenAIRE

    Belli , Luca; De Filippi , Primavera

    2013-01-01

    The report explores some of the most crucial facets of Network Neutrality, underscoring its close relationship with the full enjoyment of end-users fundamental rights. The report also includes a proposal for a Model Framework on Network Neutrality that has been elaborated by the Dynamic Coalition through an open, inclusive and multi-stakeholder effort, in order to promote an efficient safeguard of the Net Neutrality principle in accordance with international human rights standards.

  6. Display of nuclear medicine imaging studies

    International Nuclear Information System (INIS)

    Singh, B.; Kataria, S.K.; Samuel, A.M.

    2002-08-01

    Nuclear medicine imaging studies involve evaluation of a large amount of image data. Digital signal processing techniques have introduced processing algorithms that increase the information content of the display. Nuclear medicine imaging studies require interactive selection of suitable form of display and pre-display processing. Static imaging study requires pre-display processing to detect focal defects. Point operations (histogram modification) along with zoom and capability to display more than one image in one screen is essential. This album mode of display is also applicable to dynamic, MUGA and SPECT data. Isometric display or 3-D graph of the image data is helpful in some cases e.g. point spread function, flood field data. Cine display is used on a sequence of images e.g. dynamic, MUGA and SPECT imaging studies -to assess the spatial movement of tracer with time. Following methods are used at the investigator's discretion for inspection of the 3-D object. 1) Display of orthogonal projections, 2) Display of album of user selected coronal/ sagital/ transverse orthogonal slices, 3) Display of three orthogonal slices through user selected point, 4) Display of a set of orthogonal slices generated in the user-selected volume, 5) Generation and display of 3-D shaded surface. 6) Generation of volume data and display along with the 3-D shaded surface, 7) Side by side display orthogonal slices of two 3-D objects. Displaying a set of two-dimensional slices of a 3-D reconstructed object through shows all the defects but lacks the 3-D perspective. Display of shaded surface lacks the ability to show the embedded defects. Volume display -combining the 3-D surface and gray level volume data is perhaps the best form of display. This report describes these forms of display along with the theory. (author)

  7. Recent DIII-D neutral beam calibration results

    International Nuclear Information System (INIS)

    Wight, J.; Hong, R.M.; Phillips, J.

    1991-10-01

    Injected DIII-D neutral beam power is estimated based on three principle quantities: the fraction of ion beam that is neutralized in the neutralizer gas cell, the beamline transmission efficiency, and the fraction of beam reionized in the drift duct. System changes in the past few years have included a new gradient grid voltage operating point, ion source arc regulation, routine deuterium operations and new neutralizer gas flow controllers. Additionally, beam diagnostics have been improved and better calibrated. To properly characterize the beams the principle quantities have been re-measured. Two diagnostics are primarily used to measure the quantities. The beamline waterflow calorimetry system measures the neutralization efficiency and the beamline transmission efficiency, and the target tile thermocouples measure the reionization loss. An additional diagnostic, the target tile pyrometer, confirmed the reionization loss measurement. Descriptions and results of these measurements will be presented. 4 refs., 5 figs., 2 tabs

  8. 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…

  9. Display technologies for augmented reality

    Science.gov (United States)

    Lee, Byoungho; Lee, Seungjae; Jang, Changwon; Hong, Jong-Young; Li, Gang

    2018-02-01

    With the virtue of rapid progress in optics, sensors, and computer science, we are witnessing that commercial products or prototypes for augmented reality (AR) are penetrating into the consumer markets. AR is spotlighted as expected to provide much more immersive and realistic experience than ordinary displays. However, there are several barriers to be overcome for successful commercialization of AR. Here, we explore challenging and important topics for AR such as image combiners, enhancement of display performance, and focus cue reproduction. Image combiners are essential to integrate virtual images with real-world. Display performance (e.g. field of view and resolution) is important for more immersive experience and focus cue reproduction may mitigate visual fatigue caused by vergence-accommodation conflict. We also demonstrate emerging technologies to overcome these issues: index-matched anisotropic crystal lens (IMACL), retinal projection displays, and 3D display with focus cues. For image combiners, a novel optical element called IMACL provides relatively wide field of view. Retinal projection displays may enhance field of view and resolution of AR displays. Focus cues could be reconstructed via multi-layer displays and holographic displays. Experimental results of our prototypes are explained.

  10. Sexual Dimorphisms of Appendicular Musculoskeletal Morphology Related to Social Display in Cuban Anolis Lizards.

    Science.gov (United States)

    Anzai, Wataru; Cádiz, Antonio; Endo, Hideki

    2015-10-01

    In Anolis lizards, sexual dimorphism has been reported in morphological and ecological traits. Males show larger body size and longer limbs related to territorial combat and courtship display with the dewlap. Although functional-anatomical traits are closely related to locomotor behaviors, differences between sexes in musculoskeletal traits on limbs remain unclear. We explored the relationships among sexual dimorphisms in musculoskeletal morphology, habitat, and locomotor traits in Anolis lizards. Specifically, we examined appendicular musculoskeletal morphology in three species of Cuban Anolis by measuring muscle mass and lengths of moment arms. Through comparisons of crossing locomotion, we found that the runner species possessed larger extensors in hindlimbs, which are advantageous for running, whereas the masses of the humeral and femoral retractors were larger in climber species, allowing these lizards to hold up their bodies and occupy tree substrates. Comparisons between the sexes showed different trends among the three species. Males of A. porcatus, which inhabit narrow branches or leaves, had stronger elbow extensors that maintain the display posture. In contrast, males of A. sagrei, which occupy broad surfaces, did not show sexual differences that affected social display. Moreover, A. bartschi indicated sexual differences despite the absence of dewlapping behavior. Our findings suggest that both sexes show fundamentally similar relationships between muscular morphology and locomotor habits to adapt arboreal or terrestrial substrates, and yet sexual dimorphism in forelimb muscles may additionally affected by male specific display with the dewlap.

  11. Negative ion based neutral beams for plasma heating

    International Nuclear Information System (INIS)

    Prelec, K.

    1978-01-01

    Neutral beam systems based on negative ions have been considered because of a high expected power efficiency. Methods for the production, acceleration and neutralization of negative ions will be reviewed and possibilities for an application in neutral beam lines explored

  12. Targets for high power neutral beams

    International Nuclear Information System (INIS)

    Kim, J.

    1980-01-01

    Stopping high-power, long-pulse beams is fast becoming an engineering challenge, particularly in neutral beam injectors for heating magnetically confined plasmas. A brief review of neutral beam target technology is presented along with heat transfer calculations for some selected target designs

  13. Next generation smart window display using transparent organic display and light blocking screen.

    Science.gov (United States)

    Kim, Gyeong Woo; Lampande, Raju; Choe, Dong Cheol; Ko, Ik Jang; Park, Jin Hwan; Pode, Ramchandra; Kwon, Jang Hyuk

    2018-04-02

    Transparent organic light emitting diodes (TOLED) have widespread applications in the next-generation display devices particularly in the large size transparent window and interactive displays. Herein, we report high performance and stable attractive smart window displays using facile process. Advanced smart window display is realized by integrating the high performance light blocking screen and highly transparent white OLED panel. The full smart window display reveals a maximum transmittance as high as 64.2% at the wavelength of 600 nm and extremely good along with tunable ambient contrast ratio (171.94:1) compared to that of normal TOLED (4.54:1). Furthermore, the performance decisive light blocking screen has demonstrated an excellent optical and electrical characteristics such as i) high transmittance (85.56% at 562nm) at light-penetrating state, ii) superior absorbance (2.30 at 562nm) in light interrupting mode, iii) high optical contrast (85.50 at 562 nm), iv) high optical stability for more than 25,000 cycle of driving, v) fast switching time of 1.9 sec, and vi) low driving voltage of 1.7 V. The experimental results of smart window display are also validated using optical simulation. The proposed smart window display technology allows us to adjust the intensity of daylight entering the system quickly and conveniently.

  14. Combinatorial Libraries As a Tool for the Discovery of Novel, Broad-Spectrum Antibacterial Agents Targeting the ESKAPE Pathogens.

    Science.gov (United States)

    Fleeman, Renee; LaVoi, Travis M; Santos, Radleigh G; Morales, Angela; Nefzi, Adel; Welmaker, Gregory S; Medina-Franco, José L; Giulianotti, Marc A; Houghten, Richard A; Shaw, Lindsey N

    2015-04-23

    Mixture based synthetic combinatorial libraries offer a tremendous enhancement for the rate of drug discovery, allowing the activity of millions of compounds to be assessed through the testing of exponentially fewer samples. In this study, we used a scaffold-ranking library to screen 37 different libraries for antibacterial activity against the ESKAPE pathogens. Each library contained between 10000 and 750000 structural analogues for a total of >6 million compounds. From this, we identified a bis-cyclic guanidine library that displayed strong antibacterial activity. A positional scanning library for these compounds was developed and used to identify the most effective functional groups at each variant position. Individual compounds were synthesized that were broadly active against all ESKAPE organisms at concentrations development of resistance, and displayed almost no toxicity when tested against human lung cells and erythrocytes. Using a murine model of peritonitis, we also demonstrate that these agents are highly efficacious in vivo.

  15. WE-D-9A-03: CSDF: A Color Extension of the Grayscale Standard Display Function

    International Nuclear Information System (INIS)

    Kimpe, T; Marchessoux, C; Rostang, J; Piepers, B; Avanaki, A; Espig, K; Xthona, A

    2014-01-01

    Purpose: Use of color images in medical imaging has increased significantly the last few years. As of today there is no agreed standard on how color information needs to be visualized on medical color displays, resulting into large variability of color appearance and it making consistency and quality assurance a challenge. This paper presents a proposal for an extension of DICOM GSDF towards color. Methods: Visualization needs for several color modalities (multimodality imaging, nuclear medicine, digital pathology, quantitative imaging applications…) have been studied. On this basis a proposal was made for desired color behavior of color medical display systems and its behavior and effect on color medical images was analyzed. Results: Several medical color modalities could benefit from perceptually linear color visualization for similar reasons as why GSDF was put in place for greyscale medical images. An extension of the GSDF (Greyscale Standard Display Function) to color is proposed: CSDF (color standard display function). CSDF is based on deltaE2000 and offers a perceptually linear color behavior. CSDF uses GSDF as its neutral grey behavior. A comparison between sRGB/GSDF and CSDF confirms that CSDF significantly improves perceptual color linearity. Furthermore, results also indicate that because of the improved perceptual linearity, CSDF has the potential to increase perceived contrast of clinically relevant color features. Conclusion: There is a need for an extension of GSDF towards color visualization in order to guarantee consistency and quality. A first proposal (CSDF) for such extension has been made. Behavior of a CSDF calibrated display has been characterized and compared with sRGB/GSDF behavior. First results indicate that CSDF could have a positive influence on perceived contrast of clinically relevant color features and could offer benefits for quantitative imaging applications. Authors are employees of Barco Healthcare

  16. Neutralizing antibodies against two HIV-1 strains in consecutively collected serum samples: cross neutralization and association to HIV-1 related disease

    DEFF Research Database (Denmark)

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

    1992-01-01

    97 sera collected during a 10-year period from 10 HIV-1 infected individuals were tested for neutralizing capacity against a virus isolate FICPH-22 obtained from a Danish AIDS patient, and the laboratory strain HTLV-IIIB. Three patterns of serum neutralizing activity were demonstrated: (a) patients...... developing high neutralizing activity against both HIV strains; (b) patients developing high neutralizing activity against the Danish virus isolate; and (c) patients developing only low titers of neutralizing antibodies (NA) against both HIV strains. The HTLV-IIIB strain was less sensitive to serum...... neutralization than the FICPH-22 isolate and the appearance of NA against HTLV-IIIB was typically lacking several years behind that against FICPH-22 indicating a broadening of the NA response over time. No difference in clinical outcome was observed comparing patients reaching high titers of NA and patients...

  17. Improved numerical calculation of the generation of a neutral beam by charge transfer between chlorine ions/neutrals and a graphite surface

    International Nuclear Information System (INIS)

    Kubota, Tomohiro; Samukawa, Seiji; Watanabe, Naoki; Ohtsuka, Shingo; Iwasaki, Takuya; Ono, Kohei; Iriye, Yasuroh

    2014-01-01

    The charge transfer process between chlorine particles (ions or neutrals) and a graphite surface on collision was investigated by using a highly stable numerical simulator based on time-dependent density functional theory to understand the generation mechanism of a high-efficiency neutral beam developed by Samukawa et al (2001 Japan. J. Appl. Phys. 40 L779). A straightforward calculation was achieved by adopting a large enough unit cell. The dependence of the neutralization efficiency on the incident energy of the particle was investigated, and the trend of the experimental result was reproduced. It was also found that doping the electrons and holes into graphite could change the charge transfer process and neutralization probability. This result suggests that it is possible to develop a neutral beam source that has high neutralization efficiency for both positive and negative ions. (paper)

  18. Visual merchandising window display

    Directory of Open Access Journals (Sweden)

    Opris (Cas. Stanila M.

    2013-12-01

    Full Text Available Window display plays a major part in the selling strategies; it does not only include the simple display of goods, nowadays it is a form of art, also having the purpose of sustaining the brand image. This article wants to reveal the tools that are essential in creating a fabulous window display. Being a window designer is not an easy job, you have to always think ahead trends, to have a sense of colour, to know how to use light to attract customers in the store after only one glance at the window. The big store window displays are theatre scenes: with expensive backgrounds, special effects and high fashion mannequins. The final role of the displays is to convince customers to enter the store and trigger the purchasing act which is the final goal of the retail activity.

  19. An experimental evaluation of alarm processing and display characteristics

    International Nuclear Information System (INIS)

    O'Hara, J.; Brown, W.; Hallbert, B.; Skraaning, G.Jr.; Persensky, J.; Wachtel, J.

    1998-01-01

    This paper describes a research program sponsored by the U.S. Nuclear Regulatory Commission to address the human factors engineering (HFE) aspects of nuclear power plant alarm systems. The overall objective of the program is to develop HFE review guidance for advanced alarm systems. As part of this program, guidance has been developed based on a broad base of technical and research literature. In the course of guidance development, aspects of alarm system design for which the technical basis was insufficient to support complete guidance development were identified. The primary purpose of the research reported in this paper was to evaluate the effects of three of these alarm system design characteristics on operator performance in order to contribute to the understanding of potential safety issues and to provide data to support the development of design review guidance in these areas. Three alarm system design characteristics studied were (1) alarm processing (degree of alarm reduction), (2) alarm availability (dynamic prioritization and suppression), and (3) alarm display (a dedicated tile format, a mixed tile and message list format, and a format in which alarm information is integrated into the process displays). A secondary purpose was to provide confirmatory evidence of selected alarm system guidance developed in an earlier phase of the project. The alarm characteristics were combined into eight separate experimental conditions. Six, two-person crews of professional nuclear power plant operators participated in the study. Following training, each crew completed 16 test trials which consisted of two trials in each of the eight experimental conditions (one with a low-complexity scenario and one with a high-complexity scenario). Measures of process performance. operator task performance, situation awareness, and workload were obtained. In addition. operator opinions and evaluations of the alarm processing and display conditions were collected. Numerous strengths

  20. Mechanical design criteria for continuously operating neutral beams

    International Nuclear Information System (INIS)

    Vosen, S.R.; Bender, D.J.; Fink, J.H.; Lee, J.D.

    1977-01-01

    A schematic of a neutral beam injector is shown. Neutral gas is injected into the ion source, where a discharge ionizes the gas. The ions are drawn from the source by an extractor grid and then accelerated to full energy by the accel grids. After acceleration the ions pass through the neutralizer cell. Once through the neutralizer cell, the beam consists of neutrals and ions. The ions traveling with the beam are space charge neutralized by background electrons. The grid which precedes the direct converter is negatively charged and acts to separate the electrons from the rest of the beam. As a result of the beam's uncompensated space charge the remaining ions spread out from the beam to be collected at the direct converter. This paper presents a generalized analysis which will be useful in determining effects of energy and particle fluxes on the long-term performance of the grids

  1. 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.

  2. Nuclear Medicine Image Display. Chapter 14

    Energy Technology Data Exchange (ETDEWEB)

    Bergmann, H. [Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna (Austria)

    2014-12-15

    The final step in a medical imaging procedure is to display the image(s) on a suitable display system where it is presented to the medical specialist for diagnostic interpretation. The display of hard copy images on X ray film or photographic film has largely been replaced today by soft copy image display systems with cathode ray tube (CRT) or liquid crystal display (LCD) monitors as the image rendering device. Soft copy display requires a high quality display monitor and a certain amount of image processing to optimize the image both with respect to the properties of the display device and to some psychophysiological properties of the human visual system. A soft copy display system, therefore, consists of a display workstation providing some basic image processing functions and the display monitor as the intrinsic display device. Display devices of lower quality may be used during intermediate steps of the acquisition and analysis of a patient study. Display monitors with a quality suitable for diagnostic reading by the specialist medical doctor are called primary devices, also known as diagnostic devices. Monitors with lower quality but good enough to be used for positioning, processing of studies, presentation of images in the wards, etc. are referred to as secondary devices or clinical devices. Nuclear medicine images can be adequately displayed even for diagnostic purposes on secondary devices. However, the increasing use of X ray images on which to report jointly with images from nuclear medicine studies, such as those generated by dual modality imaging, notably by positron emission tomography (PET)/computed tomography (CT) and single photon emission computed tomography (SPECT)/CT, requires display devices capable of visualizing high resolution grey scale images at diagnostic quality, i.e. primary display devices. Both grey scale and colour display devices are used, the latter playing an important role in the display of processed nuclear medicine images and

  3. Nuclear Medicine Image Display. Chapter 14

    International Nuclear Information System (INIS)

    Bergmann, H.

    2014-01-01

    The final step in a medical imaging procedure is to display the image(s) on a suitable display system where it is presented to the medical specialist for diagnostic interpretation. The display of hard copy images on X ray film or photographic film has largely been replaced today by soft copy image display systems with cathode ray tube (CRT) or liquid crystal display (LCD) monitors as the image rendering device. Soft copy display requires a high quality display monitor and a certain amount of image processing to optimize the image both with respect to the properties of the display device and to some psychophysiological properties of the human visual system. A soft copy display system, therefore, consists of a display workstation providing some basic image processing functions and the display monitor as the intrinsic display device. Display devices of lower quality may be used during intermediate steps of the acquisition and analysis of a patient study. Display monitors with a quality suitable for diagnostic reading by the specialist medical doctor are called primary devices, also known as diagnostic devices. Monitors with lower quality but good enough to be used for positioning, processing of studies, presentation of images in the wards, etc. are referred to as secondary devices or clinical devices. Nuclear medicine images can be adequately displayed even for diagnostic purposes on secondary devices. However, the increasing use of X ray images on which to report jointly with images from nuclear medicine studies, such as those generated by dual modality imaging, notably by positron emission tomography (PET)/computed tomography (CT) and single photon emission computed tomography (SPECT)/CT, requires display devices capable of visualizing high resolution grey scale images at diagnostic quality, i.e. primary display devices. Both grey scale and colour display devices are used, the latter playing an important role in the display of processed nuclear medicine images and

  4. Sputtering of neutral and ionic indium clusters

    International Nuclear Information System (INIS)

    Ma, Z.; Coon, S.R.; Calaway, W.F.; Pellin, M.J.; Gruen, D.M.; Von Nagy-Felsobuki, E.I.

    1993-01-01

    Secondary neutral and secondary ion cluster yields were measured during the sputtering of a polycrystalline indium surface by normally incident ∼4 keV Ar + ions. In the secondary neutral mass spectra, indium clusters as large as In 32 were observed. In the secondary ion mass spectra, indium clusters up to In 18 + were recorded. Cluster yields obtained from both the neutral and ion channel exhibited a power law dependence on the number of constituent atoms, n, in the cluster, with the exponents measured to be -5.6 and -4. 1, respectively. An abundance drop was observed at n=8, 15, and 16 in both the neutral and ion yield distributions suggesting that the stability of the ion (either secondary ion or photoion) plays a significant role in the observed distributions. In addition, our experiments suggest that unimolecular decomposition of the neutral cluster may also plays an important role in the measured yield distributions

  5. Inhibition of Neutral Red Photolysis with Different Antioxidants

    Directory of Open Access Journals (Sweden)

    Zlatan Rimpapa

    2007-02-01

    Full Text Available Neutral red is a dye the azine structure which has been used as an acido-base indicator and a dye in histochemistry. In 1960 Goldhaber introduced Neutral red into the medium of resorbing bone cultures to localize the osteoclast in the living cultures. Using time-lapse microcinematography in order to follow the osteoclasts, he reported excellent contrast could be obtained with Neutral red due to the avidity of osteoclasts for this dye. Unfortunately, however, the photodynamic effect resulting from subsequent exposure of these cultures to light precluded this approach, and again in 1963. it was observed that the death of the osteoclasts was probably due to a photodynamic effect related to the dye in the cell, the presence of oxygen and the frequent exposure of light by our time-lapse photography. VIS and UV irradiation induced photolysis of Neutral red, and from Neutral red cation produced with photons a Neutral red radical. This Neutral red radical can be inhibited with action of an antioxidant, such as melatonin, glutathione, ascorbic acid, E vitamin, etc. We developed an assay with Neutral redphotolysis which utilizes a VIS and UV irradiation technique for quantification the inhibition of photolysis with action of an antioxidant. In this method Neutral red acts double, as a free radical generator and as a photosensitizer.

  6. Soviet exoatmospheric neutral particle beam research

    International Nuclear Information System (INIS)

    Leiss, J.E.; Abrams, R.H.; Ehlers, K.W.; Farrell, J.A.; Gillespie, G.H.; Jameson, R.A.; Keefe, D.; Parker, R.K.

    1988-02-01

    This technical assessment was performed by a panel of eight U.S. scientists and engineers who are familiar with Soviet research through their own research experience, their knowledge of the published scientific literature and conference proceedings, and personal contacts with Soviet scientists and other foreign colleagues. Most of the technical components of a neutral particle beam generating system including the ion source, the accelerator, the accelerator radio frequency power supply, the beam conditioning and aiming system, and the beam neutralizer system are addressed. It does not address a number of other areas important to an exoatmospheric neutral beam system

  7. Two dimensional neutral transport analysis in tokamak plasma

    International Nuclear Information System (INIS)

    Shimizu, Katsuhiro; Azumi, Masafumi

    1987-02-01

    Neutral particle influences the particle and energy balance, and play an important role on sputtering impurity and the charge exchange loss of neutral beam injection. In order to study neutral particle behaviour including the effects of asymmetric source and divertor configuration, the two dimensional neutral transport code has been developed using the Monte-Carlo techniques. This code includes the calculation of the H α radiation intensity based on the collisional-radiation model. The particle confinement time of the joule heated plasma in JT-60 tokamak is evaluated by comparing the calculated H α radiation intensity with the experimental data. The effect of the equilibrium on the neutral density profile in high-β plasma is also investigated. (author)

  8. Structural basis for type VI secreted peptidoglycan dl-endopeptidase function, specificity and neutralization in Serratia marcescens

    Energy Technology Data Exchange (ETDEWEB)

    Srikannathasan, Velupillai; English, Grant [University of Dundee, Dundee DD1 5EH, Scotland (United Kingdom); Bui, Nhat Khai [Newcastle University, Newcastle upon Tyne NE2 4HH (United Kingdom); Trunk, Katharina; O’Rourke, Patrick E. F.; Rao, Vincenzo A. [University of Dundee, Dundee DD1 5EH, Scotland (United Kingdom); Vollmer, Waldemar [Newcastle University, Newcastle upon Tyne NE2 4HH (United Kingdom); Coulthurst, Sarah J., E-mail: s.j.coulthurst@dundee.ac.uk; Hunter, William N., E-mail: s.j.coulthurst@dundee.ac.uk [University of Dundee, Dundee DD1 5EH, Scotland (United Kingdom)

    2013-12-01

    Crystal structures of type VI secretion system-associated immunity proteins, a peptidoglycan endopeptidase and a complex of the endopeptidase and its cognate immunity protein are reported together with assays of endopeptidase activity and functional assessment. Some Gram-negative bacteria target their competitors by exploiting the type VI secretion system to extrude toxic effector proteins. To prevent self-harm, these bacteria also produce highly specific immunity proteins that neutralize these antagonistic effectors. Here, the peptidoglycan endopeptidase specificity of two type VI secretion-system-associated effectors from Serratia marcescens is characterized. These small secreted proteins, Ssp1 and Ssp2, cleave between γ-d-glutamic acid and l-meso-diaminopimelic acid with different specificities. Ssp2 degrades the acceptor part of cross-linked tetratetrapeptides. Ssp1 displays greater promiscuity and cleaves monomeric tripeptides, tetrapeptides and pentapeptides and dimeric tetratetra and tetrapenta muropeptides on both the acceptor and donor strands. Functional assays confirm the identity of a catalytic cysteine in these endopeptidases and crystal structures provide information on the structure–activity relationships of Ssp1 and, by comparison, of related effectors. Functional assays also reveal that neutralization of these effectors by their cognate immunity proteins, which are called resistance-associated proteins (Raps), contributes an essential role to cell fitness. The structures of two immunity proteins, Rap1a and Rap2a, responsible for the neutralization of Ssp1 and Ssp2-like endopeptidases, respectively, revealed two distinct folds, with that of Rap1a not having previously been observed. The structure of the Ssp1–Rap1a complex revealed a tightly bound heteromeric assembly with two effector molecules flanking a Rap1a dimer. A highly effective steric block of the Ssp1 active site forms the basis of effector neutralization. Comparisons with Ssp2–Rap2

  9. Structural basis for type VI secreted peptidoglycan dl-endopeptidase function, specificity and neutralization in Serratia marcescens

    International Nuclear Information System (INIS)

    Srikannathasan, Velupillai; English, Grant; Bui, Nhat Khai; Trunk, Katharina; O’Rourke, Patrick E. F.; Rao, Vincenzo A.; Vollmer, Waldemar; Coulthurst, Sarah J.; Hunter, William N.

    2013-01-01

    Crystal structures of type VI secretion system-associated immunity proteins, a peptidoglycan endopeptidase and a complex of the endopeptidase and its cognate immunity protein are reported together with assays of endopeptidase activity and functional assessment. Some Gram-negative bacteria target their competitors by exploiting the type VI secretion system to extrude toxic effector proteins. To prevent self-harm, these bacteria also produce highly specific immunity proteins that neutralize these antagonistic effectors. Here, the peptidoglycan endopeptidase specificity of two type VI secretion-system-associated effectors from Serratia marcescens is characterized. These small secreted proteins, Ssp1 and Ssp2, cleave between γ-d-glutamic acid and l-meso-diaminopimelic acid with different specificities. Ssp2 degrades the acceptor part of cross-linked tetratetrapeptides. Ssp1 displays greater promiscuity and cleaves monomeric tripeptides, tetrapeptides and pentapeptides and dimeric tetratetra and tetrapenta muropeptides on both the acceptor and donor strands. Functional assays confirm the identity of a catalytic cysteine in these endopeptidases and crystal structures provide information on the structure–activity relationships of Ssp1 and, by comparison, of related effectors. Functional assays also reveal that neutralization of these effectors by their cognate immunity proteins, which are called resistance-associated proteins (Raps), contributes an essential role to cell fitness. The structures of two immunity proteins, Rap1a and Rap2a, responsible for the neutralization of Ssp1 and Ssp2-like endopeptidases, respectively, revealed two distinct folds, with that of Rap1a not having previously been observed. The structure of the Ssp1–Rap1a complex revealed a tightly bound heteromeric assembly with two effector molecules flanking a Rap1a dimer. A highly effective steric block of the Ssp1 active site forms the basis of effector neutralization. Comparisons with Ssp2–Rap2

  10. Display systems for NPP control

    International Nuclear Information System (INIS)

    Rozov, S.S.

    1988-01-01

    Main trends in development of display systems used as the means for image displaying in NPP control systems are considered. It is shown that colour display devices appear to be the most universal means for concentrated data presentation. Along with digital means the display systems provide for high-speed response, sufficient for operative control of executive mechanisms. A conclusion is drawn that further development of display systems will move towards creation of large colour fields (on reflection base or with multicolour gas-discharge elements)

  11. Temporal behavior of neutral particle fluxes in TFTR [Tokamak Fusion Test Reactor] neutral beam injectors

    International Nuclear Information System (INIS)

    Kamperschroer, J.H.; Gammel, G.M.; Roquemore, A.L.

    1989-09-01

    Data from an E parallel B charge exchange neutral analyzer (CENA), which views down the axis of a neutral beamline through an aperture in the target chamber calorimeter of the TFTR neutral beam test facility, exhibit two curious effects. First, there is a turn-on transient lasting tens of milliseconds having a magnitude up to three times that of the steady-state level. Second, there is a 720 Hz, up to 20% peak-to-peak fluctuation persisting the entire pulse duration. The turn-on transient occurs as the neutralizer/ion source system reaches a new pressure equilibrium following the effective ion source gas throughput reduction by particle removal as ion beam. Widths of the transient are a function of the gas throughput into the ion source, decreasing as the gas supply rate is reduced. Heating of the neutalizer gas by the beam is assumed responsible, with gas temperature increasing as gas supply rate is decreased. At low gas supply rates, the transient is primarliy due to dynamic changes in the neutralizer line density and/or beam species composition. Light emission from the drift duct corroborate the CENA data. At high gas supply rates, dynamic changes in component divergence and/or spatial profiles of the source plasma are necessary to explain the observations. The 720 Hz fluctuation is attributed to a 3% peak-to-peak ripple of 720 Hz on the arc power supply amplified by the quadratic relationship between beam divergence and beam current. Tight collimation by CENA apertures cause it to accept a very small part of the ion source's velocity space, producing a signal linearly proportional to beam divergence. Estimated fluctuations in the peak power density delivered to the plasma under these conditions are a modest 3--8% peak to peak. The efffects of both phenomena on the injected neutral beam can be ameliorated by careful operion of the ion sources. 21 refs., 11 figs., 2 tabs

  12. Net Neutrality and Inflation of Traffic

    NARCIS (Netherlands)

    Peitz, M.; Schütt, F.

    2015-01-01

    Under strict net neutrality Internet service providers (ISPs) are required to carry data without any differentiation and at no cost to the content provider. We provide a simple framework with a monopoly ISP to evaluate different net neutrality rules. Content differs in its sensitivity to delay.

  13. Ribosome display: next-generation display technologies for production of antibodies in vitro.

    Science.gov (United States)

    He, Mingyue; Khan, Farid

    2005-06-01

    Antibodies represent an important and growing class of biologic research reagents and biopharmaceutical products. They can be used as therapeutics in a variety of diseases. With the rapid expansion of proteomic studies and biomarker discovery, there is a need for the generation of highly specific binding reagents to study the vast number of proteins encoded by the genome. Display technologies provide powerful tools for obtaining antibodies. Aside from the preservation of natural antibody repertoires, they are capable of exploiting diversity by DNA recombination to create very large libraries for selection of novel molecules. In contrast to in vivo immunization processes, display technologies allow selection of antibodies under in vitro-defined selection condition(s), resulting in enrichment of antibodies with desired properties from large populations. In addition, in vitro selection enables the isolation of antibodies against difficult antigens including self-antigens, and this can be applied to the generation of human antibodies against human targets. Display technologies can also be combined with DNA mutagenesis for antibody evolution in vitro. Some methods are amenable to automation, permitting high-throughput generation of antibodies. Ribosome display is considered as representative of the next generation of display technologies since it overcomes the limitations of cell-based display methods by using a cell-free system, offering advantages of screening larger libraries and continuously expanding new diversity during selection. Production of display-derived antibodies can be achieved by choosing one of a variety of prokaryotic and eukaryotic cell-based expression systems. In the near future, cell-free protein synthesis may be developed as an alternative for large-scale generation of antibodies.

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

  15. ITER Neutral Beam Injection System

    International Nuclear Information System (INIS)

    Ohara, Yoshihiro; Tanaka, Shigeru; Akiba, Masato

    1991-03-01

    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)

  16. Net neutrality and inflation of traffic

    NARCIS (Netherlands)

    Peitz, M.; Schütt, Florian

    Under strict net neutrality Internet service providers (ISPs) are required to carry data without any differentiation and at no cost to the content provider. We provide a simple framework with a monopoly ISP to evaluate the short-run effects of different net neutrality rules. Content differs in its

  17. Construction and Characterization of a Humanized Anti-Epstein-Barr Virus gp350 Antibody with Neutralizing Activity in Cell Culture

    Directory of Open Access Journals (Sweden)

    Jerome E. Tanner

    2018-04-01

    Full Text Available Acute Epstein-Barr virus (EBV infection in immunosuppressed transplant patients can give rise to a malignant B-cell proliferation known as post-transplant lymphoproliferative disease (PTLD. The EBV major virion surface glycoprotein (gp350 is a principal target of naturally occurring neutralizing antibodies and is viewed as the best target to prevent acute infection and PTLD in at-risk transplant recipients. We have constructed a humanized (hu version of the murine anti-gp350 neutralizing monoclonal antibody 72a1. The hu72a1 IgG1 antibody displayed no significant anti-mouse activity, recognized both gp350 and its splice variant gp220 as well as a gp350 peptide that was shown to constitute the principal EBV gp350 neutralizing epitope when tested in immunoassays. Hu72a1 antibody blocked in vitro EBV infection of B cells at a level which equaled that of a mouse-human chimeric 72a1 antibody construct. This work provides a further structural and immunological understanding of the 72a1 antibody interaction with EBV gp350, and constitutes a launch point for future anti-EBV therapeutic antibodies designed to block EBV infection and prevent PTLD while eliminating the deleterious antigenic murine features of the original 72a1 antibody.

  18. Large-screen display industry: market and technology trends for direct view and projection displays

    Science.gov (United States)

    Castellano, Joseph A.; Mentley, David E.

    1996-03-01

    Large screen information displays are defined as dynamic electronic displays that can be viewed by more than one person and are at least 2-feet wide. These large area displays for public viewing provide convenience, entertainment, security, and efficiency to the viewers. There are numerous uses for large screen information displays including those in advertising, transportation, traffic control, conference room presentations, computer aided design, banking, and military command/control. A noticeable characteristic of the large screen display market is the interchangeability of display types. For any given application, the user can usually choose from at least three alternative technologies, and sometimes from many more. Some display types have features that make them suitable for specific applications due to temperature, brightness, power consumption, or other such characteristic. The overall worldwide unit consumption of large screen information displays of all types and for all applications (excluding consumer TV) will increase from 401,109 units in 1995 to 655,797 units in 2002. On a unit consumption basis, applications in business and education represent the largest share of unit consumption over this time period; in 1995, this application represented 69.7% of the total. The market (value of shipments) will grow from DOL3.1 billion in 1995 to DOL3.9 billion in 2002. The market will be dominated by front LCD projectors and LCD overhead projector plates.

  19. Spectroscopy, Manipulation and Trapping of Neutral Atoms, Molecules, and Other Particles Using Optical Nanofibers: A Review

    Science.gov (United States)

    Morrissey, Michael J.; Deasy, Kieran; Frawley, Mary; Kumar, Ravi; Prel, Eugen; Russell, Laura; Truong, Viet Giang; Chormaic, Síle Nic

    2013-01-01

    The use of tapered optical fibers, i.e., optical nanofibers, for spectroscopy and the detection of small numbers of particles, such as neutral atoms or molecules, has been gaining interest in recent years. In this review, we briefly introduce the optical nanofiber, its fabrication, and optical mode propagation within. We discuss recent progress on the integration of optical nanofibers into laser-cooled atom and vapor systems, paying particular attention to spectroscopy, cold atom cloud characterization, and optical trapping schemes. Next, a natural extension of this work to molecules is introduced. Finally, we consider several alternatives to optical nanofibers that display some advantages for specific applications. PMID:23945738

  20. Neutral currents, supernovae neutrinos, and nucleosynthesis

    International Nuclear Information System (INIS)

    Haxton, W.C.

    1988-01-01

    The inelastic interactions of neutrinos during stellar collapse and neutron star cooling are discussed. The primary mechanism for dissipative neutrino reactions is nuclear excitation by neutral current scattering, a process not included in standard descriptions of supernovae. Charge-current and neutral current ''preheating'' of iron lying outside the shock front appears to be significant in the few milliseconds near shock breakout. This could help produce a more energetic shock. During the cooling phase, the neutral current interactions of muon and taon neutrinos appear to be responsible for some interesting nucleosynthesis. I discuss two examples the production of fluorine and neutrino-induced r-process nucleosynthesis. 26 refs., 1 fig., 3 tabs

  1. Integrating linear optimization with structural modeling to increase HIV neutralization breadth.

    Directory of Open Access Journals (Sweden)

    Alexander M Sevy

    2018-02-01

    Full Text Available Computational protein design has been successful in modeling fixed backbone proteins in a single conformation. However, when modeling large ensembles of flexible proteins, current methods in protein design have been insufficient. Large barriers in the energy landscape are difficult to traverse while redesigning a protein sequence, and as a result current design methods only sample a fraction of available sequence space. We propose a new computational approach that combines traditional structure-based modeling using the Rosetta software suite with machine learning and integer linear programming to overcome limitations in the Rosetta sampling methods. We demonstrate the effectiveness of this method, which we call BROAD, by benchmarking the performance on increasing predicted breadth of anti-HIV antibodies. We use this novel method to increase predicted breadth of naturally-occurring antibody VRC23 against a panel of 180 divergent HIV viral strains and achieve 100% predicted binding against the panel. In addition, we compare the performance of this method to state-of-the-art multistate design in Rosetta and show that we can outperform the existing method significantly. We further demonstrate that sequences recovered by this method recover known binding motifs of broadly neutralizing anti-HIV antibodies. Finally, our approach is general and can be extended easily to other protein systems. Although our modeled antibodies were not tested in vitro, we predict that these variants would have greatly increased breadth compared to the wild-type antibody.

  2. Integrating linear optimization with structural modeling to increase HIV neutralization breadth.

    Science.gov (United States)

    Sevy, Alexander M; Panda, Swetasudha; Crowe, James E; Meiler, Jens; Vorobeychik, Yevgeniy

    2018-02-01

    Computational protein design has been successful in modeling fixed backbone proteins in a single conformation. However, when modeling large ensembles of flexible proteins, current methods in protein design have been insufficient. Large barriers in the energy landscape are difficult to traverse while redesigning a protein sequence, and as a result current design methods only sample a fraction of available sequence space. We propose a new computational approach that combines traditional structure-based modeling using the Rosetta software suite with machine learning and integer linear programming to overcome limitations in the Rosetta sampling methods. We demonstrate the effectiveness of this method, which we call BROAD, by benchmarking the performance on increasing predicted breadth of anti-HIV antibodies. We use this novel method to increase predicted breadth of naturally-occurring antibody VRC23 against a panel of 180 divergent HIV viral strains and achieve 100% predicted binding against the panel. In addition, we compare the performance of this method to state-of-the-art multistate design in Rosetta and show that we can outperform the existing method significantly. We further demonstrate that sequences recovered by this method recover known binding motifs of broadly neutralizing anti-HIV antibodies. Finally, our approach is general and can be extended easily to other protein systems. Although our modeled antibodies were not tested in vitro, we predict that these variants would have greatly increased breadth compared to the wild-type antibody.

  3. Broad absorption line symbiotic stars: highly ionized species in the fast outflow from MWC 560

    Science.gov (United States)

    Lucy, Adrian B.; Knigge, Christian; Sokoloski, J. L.

    2018-04-01

    In symbiotic binaries, jets and disk winds may be integral to the physics of accretion onto white dwarfs from cool giants. The persistent outflow from symbiotic star MWC 560 (≡V694 Mon) is known to manifest as broad absorption lines (BALs), most prominently at the Balmer transitions. We report the detection of high-ionization BALs from C IV, Si IV, N V, and He II in International Ultraviolet Explorer spectra obtained on 1990 April 29 - 30, when an optical outburst temporarily erased the obscuring `iron curtain' of absorption troughs from Fe II and similar ions. The C IV and Si IV BALs reached maximum radial velocities at least 1000 km s-1 higher than contemporaneous Mg II and He II BALs; the same behaviors occur in the winds of quasars and cataclysmic variables. An iron curtain lifts to unveil high-ionization BALs during the P Cygni phase observed in some novae, suggesting by analogy a temporary switch in MWC 560 from persistent outflow to discrete mass ejection. At least three more symbiotic stars exhibit broad absorption with blue edges faster than 1500 km s-1; high-ionization BALs have been reported in AS 304 (≡V4018 Sgr), while transient Balmer BALs have been reported in Z And and CH Cyg. These BAL-producing fast outflows can have wider opening angles than has been previously supposed. BAL symbiotics are short-timescale laboratories for their giga-scale analogs, broad absorption line quasars (BALQSOs), which display a similarly wide range of ionization states in their winds.

  4. Impact of neutral density fluctuations on gas puff imaging diagnostics

    Science.gov (United States)

    Wersal, C.; Ricci, P.

    2017-11-01

    A three-dimensional turbulence simulation of the SOL and edge regions of a toroidally limited tokamak is carried out. The simulation couples self-consistently the drift-reduced two-fluid Braginskii equations to a kinetic equation for neutral atoms. A diagnostic neutral gas puff on the low-field side midplane is included and the impact of neutral density fluctuations on D_α light emission investigated. We find that neutral density fluctuations affect the D_α emission. In particular, at a radial distance from the gas puff smaller than the neutral mean free path, neutral density fluctuations are anti-correlated with plasma density, electron temperature, and D_α fluctuations. It follows that the neutral fluctuations reduce the D_α emission in most of the observed region and, therefore, have to be taken into account when interpreting the amplitude of the D_α emission. On the other hand, higher order statistical moments (skewness, kurtosis) and turbulence characteristics (such as correlation length, or the autocorrelation time) are not significantly affected by the neutral fluctuations. At distances from the gas puff larger than the neutral mean free path, a non-local shadowing effect influences the neutral density fluctuations. There, the D_α fluctuations are correlated with the neutral density fluctuations, and the high-order statistical moments and measurements of other turbulence properties are strongly affected by the neutral density fluctuations.

  5. 32 CFR 644.323 - Neutral language.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Neutral language. 644.323 Section 644.323 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Disposal § 644.323 Neutral language. Wherever the words “man”, “men”, or their related...

  6. Toxicity of binary chemical munition destruction products: methylphosphonic acid, methylphosphinic acid, 2-diisopropylaminoethanol, DF neutralent, and QL neutralent.

    Science.gov (United States)

    Watson, Rebecca E; Hafez, Ahmed M; Kremsky, Jonathan N; Bizzigotti, George O

    2007-01-01

    This paper reports the toxicity and environmental impact of neutralents produced from the hydrolysis of binary chemical agent precursor chemicals DF (methylphosphonic difluoride) and QL (2-[bis(1-methylethyl)amino]ethyl ethyl methylphosphonite). Following a literature review of the neutralent mixtures and constituents, basic toxicity tests were conducted to fill data gaps, including acute oral and dermal median lethal dose assays, the Ames mutagenicity test, and ecotoxicity tests. For methylphosphonic acid (MPA), a major constituent of DF neutralent, the acute oral LD(50) in the Sprague-Dawley rat was measured at 1888 mg/kg, and the Ames test using typical tester strains of Salmonella typhimurium and Escherichia coli was negative. The 48-h LC(50) values for pH-adjusted DF neutralent with Daphnia magna and Cyprinodon variegatus were > 2500 mg/L and 1593 mg/L, respectively. The acute oral LD(50) values in the rat for QL neutralent constituents methylphosphinic acid (MP) and 2-diisopropylaminoethanol (KB) were both determined to be 940 mg/kg, and the Ames test was negative for both. Good Laboratory Practice (GLP)-compliant ecotoxicity tests for MP and KB gave 48-h D. magna EC(50) values of 6.8 mg/L and 83 mg/L, respectively. GLP-compliant 96-h C. variegatus assays on MP and KB gave LC(50) values of 73 and 252 mg/L, respectively, and NOEC values of 22 and 108 mg/L. QL neutralent LD(50) values for acute oral and dermal toxicity tests were both > 5000 mg/kg, and the 48-h LD(50) values for D. magna and C. variegatus were 249 and 2500 mg/L, respectively. Using these data, the overall toxicity of the neutralents was assessed.

  7. Mimotopes selected by biopanning with high-titer HIV-neutralizing antibodies in plasma from Chinese slow progressors

    Directory of Open Access Journals (Sweden)

    Xiaoli Zhang

    Full Text Available OBJECTIVE: One approach to identifying HIV-1 vaccine candidates is to dissect the natural antiviral immune response in treatment-naïve individuals infected for over ten years, considered slow progressor patients (SPs. It is suspected that SP plasma has strongly neutralizing antibodies (NAb targeting specific HIV viral epitopes. METHODS: NAbs levels of 11 HIV-1-infected SPs were detected by PBMC-based neutralization assays. To investigate SP NAb epitope, this study used a biopanning approach to obtain mimotopes of HIV-1 that were recognized by SP plasma NAbs. IgG was purified from hightiter NAb SP plasma, and used as the ligand for three rounds of biopanning to select HIV-specific mimotopes from a phage-displayed random peptide library. Double-antibody sandwich ELISA, competitive inhibition assays, and peptide sequence analysis were used to evaluate the characteristics of phage-borne mimotopes. RESULTS: SPs had significantly more plasma neutralizing activity than typical progressors (TPs (p = 0.04. P2 and P9 plasma, which have highest-titer HIV-NAb, were selected as ligands for biopanning. After three rounds of biopanning, 48 phage clones were obtained, of which 22 clones were consistent with requirement, binding with HIV-1 positive plasma and unbinding with HIV-1 negative plasma. Compared with linear HIV-1 protein sequence and HIV-1 protein structure files, only 12 clones were possible linear mimotopes of NAbs. In addition, the C40 clone located in gp41 CHR was found to be a neutralizing epitope, which could inhibit pooled HIV-1 positive plasma reaction. CONCLUSION: Biopanning of serum IgG can yield mimotopes of HIV-1-related antigen epitopes. This methodology provides a basis for exploration into HIV-1-related antigen-antibody interactions and furthers NAb immunotherapy and vaccine design.

  8. Serbia's Military Neutrality: Origins, effects and challenges

    Directory of Open Access Journals (Sweden)

    Ejdus Filip

    2014-10-01

    Full Text Available Serbia is the only state in the Western Balkans that is not seeking NATO membership. In December 2007, Serbia declared military neutrality and in spite of its EU membership aspirations, developed very close relations with Moscow. The objective of this paper is threefold. First, I argue that in order to understand why Serbia declared military neutrality, one has to look both at the discursive terrain and domestic power struggles. The key narrative that was strategically used by mnemonic entrepreneurs, most importantly by the former Prime Minister Vojislav Koštunica, to legitimize military neutrality was the trauma of NATO intervention in 1999 and the ensuing secession of Kosovo. In the second part of the paper, I discuss the operational consequences of the military neutrality policy for Serbia's relations with NATO and Russia, as well as for military reform and EU accession. Finally, I spell out the challenges ahead in Serbia's neutrality policy and argue that its decision makers will increasingly be caught between pragmatic foreign policy requirements on the one hand and deeply entrenched traumatic memories on the other.

  9. Scalable Resolution Display Walls

    KAUST Repository

    Leigh, Jason; Johnson, Andrew; Renambot, Luc; Peterka, Tom; Jeong, Byungil; Sandin, Daniel J.; Talandis, Jonas; Jagodic, Ratko; Nam, Sungwon; Hur, Hyejung; Sun, Yiwen

    2013-01-01

    This article will describe the progress since 2000 on research and development in 2-D and 3-D scalable resolution display walls that are built from tiling individual lower resolution flat panel displays. The article will describe approaches and trends in display hardware construction, middleware architecture, and user-interaction design. The article will also highlight examples of use cases and the benefits the technology has brought to their respective disciplines. © 1963-2012 IEEE.

  10. Corrosion protection method by neutral treatment for boilers

    International Nuclear Information System (INIS)

    Ishikawa, Hisashige

    1978-01-01

    The corrosion protection method by neutral treatment has been applied in Europe mainly for boilers and nuclear reactors instead of existing all volatile treatment. The cause of corrosion of steel and copper in water and the effect of neutral treatment, that is the effect of protection film of magnetite in steel and cuprous oxide in copper alloy, are explained with the characteristic figure of PH, electromotive force and chemical formula. The experience of applying this neutral treatment to the Wedel thermal power plant and the system flow sheet, the water treatment equipment, relating instrumentations and the water examination are described in detail. Hydrogen peroxide is injected in this neutral treatment. The comparison between the existing water treatment and the neutral treatment and their merits and demerits are explained. (Nakai, Y.)

  11. The Myth of Neutral Judge: Overcoming Neutrality by the Cognition Theory And the Pursuit of Legal Certainty

    Directory of Open Access Journals (Sweden)

    Alyane Almeida de Araújo

    2016-11-01

    Full Text Available The  Law  scientific-rational  character  created  the  image  of  a  neutral  judge;  however, Neuroscience currently shows that the decision-making process involves activations in the prefrontal cortex along with emotions management areas. The aim of this work is to check the subsistence of the neutral judge after the cognition theory, with points of reflexion in post- positivist hermeneutics. Using the comprehensive method on bibliographic prospection, we conclude that despite the neutrality has been overcome, the search for legal certainty continues, which will be achieved through values and social purposes of the onwn normative system.

  12. X-Windows Widget for Image Display

    Science.gov (United States)

    Deen, Robert G.

    2011-01-01

    XvicImage is a high-performance XWindows (Motif-compliant) user interface widget for displaying images. It handles all aspects of low-level image display. The fully Motif-compliant image display widget handles the following tasks: (1) Image display, including dithering as needed (2) Zoom (3) Pan (4) Stretch (contrast enhancement, via lookup table) (5) Display of single-band or color data (6) Display of non-byte data (ints, floats) (7) Pseudocolor display (8) Full overlay support (drawing graphics on image) (9) Mouse-based panning (10) Cursor handling, shaping, and planting (disconnecting cursor from mouse) (11) Support for all user interaction events (passed to application) (12) Background loading and display of images (doesn't freeze the GUI) (13) Tiling of images.

  13. Study on the visibility of an electroluminescent display for automobiles; Jidoshayo EL display no shininsei

    Energy Technology Data Exchange (ETDEWEB)

    Matsumoto, N; Harada, M; Idogaki, T [Denso Corp., Aichi (Japan)

    1997-10-01

    This report explores the visibility of an Electroluminescent (EL) display for automotive use. Displays for automobiles are exposed to the direct rays of the sun and forced to operate in wide temperature range. Therefore, luminous flux density by the lighting on EL display panel and operating environment temperature must be considered for the visibility evaluation. Sensory evaluation on the visibility and physical measurements such as contrast, chromaticity difference in accordance with the viewing angle change indicate that the visibility of the EL display for automobiles is advantageous over other displays. 6 refs., 11 figs., 1 tab.

  14. Laser illuminated flat panel display

    Energy Technology Data Exchange (ETDEWEB)

    Veligdan, J.T.

    1995-12-31

    A 10 inch laser illuminated flat panel Planar Optic Display (POD) screen has been constructed and tested. This POD screen technology is an entirely new concept in display technology. Although the initial display is flat and made of glass, this technology lends itself to applications where a plastic display might be wrapped around the viewer. The display screen is comprised of hundreds of planar optical waveguides where each glass waveguide represents a vertical line of resolution. A black cladding layer, having a lower index of refraction, is placed between each waveguide layer. Since the cladding makes the screen surface black, the contrast is high. The prototype display is 9 inches wide by 5 inches high and approximately I inch thick. A 3 milliwatt HeNe laser is used as the illumination source and a vector scanning technique is employed.

  15. Neutral Red versus MTT assay of cell viability in the presence of copper compounds.

    Science.gov (United States)

    Gomez Perez, Mariela; Fourcade, Lyvia; Mateescu, Mircea Alexandru; Paquin, Joanne

    2017-10-15

    Copper is essential for numerous physiological functions, and copper compounds may display therapeutic as well as cytotoxic effects. The MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay is a standard test largely used in cytotoxicity studies. This report shows that low micromolar levels of copper compounds such as Cu(II)Urea 2 , Cu(II)Ser 2 and CuCl 2 can interfere with the MTT assay making improper the detection of formazan product of MTT reduction. Comparatively, the Neutral Red assay appears to be sensitive and showing no interference with these compounds. The lactate dehydrogenase alternative assay cannot be used because of inhibitory effect of these copper compounds on the enzyme activity. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Neutral beam development plan

    International Nuclear Information System (INIS)

    Staten, H.S.

    1980-08-01

    The national plan is presented for developing advanced injection systems for use on upgrades of existing experiments, and use on future facilities such as ETF, to be built in the late 1980's or early 90's where power production from magnetic fusion will move closer to a reality. Not only must higher power and longer pulse length systems be developed , but they must operate reliably; they must be a tool for the experimenter, not the experiment itself. Neutral beam systems handle large amounts of energy and as such, they often are as complicated as the plasma physics experiment itself. This presents a significant challenge to the neutral beam developer

  17. Photoproduction of neutral pions off protons

    NARCIS (Netherlands)

    Crede, V.; Sparks, N.; Wilson, A.; Anisovich, A. V.; Bacelar, J. C. S.; Bantes, R.; Bartholomy, O.; Bayadilov, D.; Beck, R.; Beloglazov, Y. A.; Castelijns, R.; Dutz, H.; Elsner, D.; Ewald, R.; Frommberger, F.; Funke, Chr; Gregor, R.; Gridnev, A.; Gutz, E.; Hillert, W.; Hoffmeister, P.; Jaegle, I.; Junkersfeld, J.; Kalinowsky, H.; Kammer, S.; Klein, Frank; Klein, Friedrich; Klempt, E.; Kotulla, M.; Krusche, B.; Löhner, H.; Lopatin, I. V.; Lugert, S.; Menze, D.; Mertens, T.; Messchendorp, J. G.; Metag, V.; Nanova, M.; Nikonov, V. A.; Novinski, D.; Novotny, R.; Ostrick, M.; Pant, L. M.; van Pee, H.; Pfeiffer, M.; Roy, A.; Sarantsev, A. V.; Schadmand, S.; Schmidt, C.; Schmieden, H.; Schoch, B.; Shende, S.; Sokhoyan, V.; Suele, A.; Sumachev, V. V.; Szczepanek, T.; Thoma, U.; Trnka, D.; Varma, R.; Walther, D.; Wendel, Ch

    2011-01-01

    Photoproduction of neutral pions has been studied with the CBELSA/TAPS detector in the reaction gamma p -> p pi(0) for photon energies between 0.85 and 2.50 GeV. The pi(0) mesons are observed in their dominant neutral decay mode: pi(0) -> gamma gamma. For the first time, the differential cross

  18. Gender Neutrality: Women's Friend or Foe?

    Science.gov (United States)

    Steuernagel, Trudy

    Gender neutral public policies are those that are either silent on the question of the existence of significant gender differences or incorporate a perspective which mandates that such differences be ignored. Prominent voices today contend that gender neutrality favors males and have held the male standard as the one for which women should aspire.…

  19. A safe and reliable neutralization assay based on pseudovirus to measure neutralizing antibody titer against poliovirus.

    Science.gov (United States)

    Liu, Shaohua; Song, Dongmei; Bai, Han; Lu, Weiwei; Dai, Xinxian; Hao, Chunsheng; Zhang, Zhongyang; Guo, Huijie; Zhang, Yue; Li, Xiuling

    2017-12-01

    With the promotion of inactivated poliomyelitis vaccine (IPV) and live attenuated oral poliomyelitis vaccine (OPV), the global reported cases of poliomyelitis have reduced sharply from 0.35 million in 1988 to 74 in 2015. The Polio Eradication & Endgame Strategic Plan published by WHO in 2013 included the strategy of implementation of poliovirus safe handling and containment measures to minimize the risks of facility-associated reintroduction of virus into the polio-free community to prevent the re-import of poliovirus. Toward this strategy, we produced replication-incompetent pseudovirus of poliovirus type 1, 2, 3 attenuated strains by constructing poliovirus capsid expression vectors and poliovirus replicon then transfecting HEK293T cells and developed a pseudovirus-based neutralization assay (pNA) to determine neutralizing antibody titer which is more secure, time-saving and reliable than conventional neutralization assay (cNA). By using anti-poliovirus rat serum, we demonstrated excellent correlation between neutralizing antibody titers measured by cNA and pNA. It was concluded that pNA can be a potential alternative to replace cNA as a safe and time-saving system for titer determination after live poliovirus's safekeeping. © 2017 Wiley Periodicals, Inc.

  20. ICAN: High power neutral beam generation

    International Nuclear Information System (INIS)

    Moustaizis, S.D.; Lalousis, P.; Perrakis, K.; Auvray, P.; Larour, J.; Ducret, J.E.; Balcou, P.

    2015-01-01

    During the last few years there is an increasing interest on the development of alternative high power new negative ion source for Tokamak applications. The proposed new neutral beam device presents a number of advantages with respect to: the density current, the acceleration voltage, the relative compact dimension of the negative ion source, and the coupling of a high power laser beam for photo-neutralization of the negative ion beam. Here we numerically investigate, using a multi- fluid 1-D code, the acceleration and the extraction of high power ion beam from a Magnetically Insulated Diode (MID). The diode configuration will be coupled to a high power device capable of extracting a current up to a few kA with an accelerating voltage up to MeV. An efficiency of up to 92% of the coupling of the laser beam, is required in order to obtain a high power, up to GW, neutral beam. The new high energy, high average power, high efficiency (up to 30%) ICAN fiber laser is proposed for both the plasma generation and the photo-neutralizer configuration. (authors)

  1. OLED displays and lighting

    CERN Document Server

    Koden, Mitsuhiro

    2017-01-01

    Organic light-emitting diodes (OLEDs) have emerged as the leading technology for the new display and lighting market. OLEDs are solid-state devices composed of thin films of organic molecules that create light with the application of electricity. OLEDs can provide brighter, crisper displays on electronic devices and use less power than conventional light-emitting diodes (LEDs) or liquid crystal displays (LCDs) used today. This book covers both the fundamentals and practical applications of flat and flexible OLEDs.

  2. Crystal structure and size-dependent neutralization properties of HK20, a human monoclonal antibody binding to the highly conserved heptad repeat 1 of gp41.

    Science.gov (United States)

    Sabin, Charles; Corti, Davide; Buzon, Victor; Seaman, Mike S; Lutje Hulsik, David; Hinz, Andreas; Vanzetta, Fabrizia; Agatic, Gloria; Silacci, Chiara; Mainetti, Lara; Scarlatti, Gabriella; Sallusto, Federica; Weiss, Robin; Lanzavecchia, Antonio; Weissenhorn, Winfried

    2010-11-18

    The human monoclonal antibody (mAb) HK20 neutralizes a broad spectrum of primary HIV-1 isolates by targeting the highly conserved heptad repeat 1 (HR1) of gp41, which is transiently exposed during HIV-1 entry. Here we present the crystal structure of the HK20 Fab in complex with a gp41 mimetic 5-Helix at 2.3 Å resolution. HK20 employs its heavy chain CDR H2 and H3 loops to bind into a conserved hydrophobic HR1 pocket that is occupied by HR2 residues in the gp41 post fusion conformation. Compared to the previously described HR1-specific mAb D5, HK20 approaches its epitope with a different angle which might favor epitope access and thus contribute to its higher neutralization breadth and potency. Comparison of the neutralization activities of HK20 IgG, Fab and scFv employing both single cycle and multiple cycle neutralization assays revealed much higher potencies for the smaller Fab and scFv over IgG, implying that the target site is difficult to access for complete antibodies. Nevertheless, two thirds of sera from HIV-1 infected individuals contain significant titers of HK20-inhibiting antibodies. The breadth of neutralization of primary isolates across all clades, the higher potencies for C-clade viruses and the targeting of a distinct site as compared to the fusion inhibitor T-20 demonstrate the potential of HK20 scFv as a therapeutic tool.

  3. Are Moral Disengagement, Neutralization Techniques, and Self-Serving Cognitive Distortions the Same? Developing a Unified Scale of Moral Neutralization of Aggression

    Directory of Open Access Journals (Sweden)

    Denis Ribeaud

    2010-12-01

    Full Text Available

    Can the three concepts of Neutralization Techniques, Moral Disengagement, and Secondary Self-Serving Cognitive Distortions be conceived theoretically and empirically
    as capturing the same cognitive processes and thus be measured with one single scale of Moral Neutralization? First, we show how the different approaches overlap conceptually. Second, in Study 1, we verify that four scales derived from the three conceptions of Moral Neutralization are correlated in such a way that they can be conceived as measuring the same phenomenon. Third, building on the results of Study 1, we derive a unified scale of Moral Neutralization which specifically focuses on the neutralization of aggression and test it in a large general population sample of preadolescents (Study 2. Confirmatory factor analyses suggest a good internal consistency and acceptable cross-gender factorial invariance. Correlation analyses with related behavioral and cognitive constructs corroborate the scale’s criterion and convergent validity. In the final section we present a possible integration of Moral Neutralization in a broader framework of crime causation.

  4. Dichroic Liquid Crystal Displays

    Science.gov (United States)

    Bahadur, Birendra

    The following sections are included: * INTRODUCTION * DICHROIC DYES * Chemical Structure * Chemical and Photochemical Stability * THEORETICAL MODELLING * DEFECTS CAUSED BY PROLONGED LIGHT IRRADIATION * CHEMICAL STRUCTURE AND PHOTOSTABILITY * OTHER PARAMETERS AFFECTING PHOTOSTABILITY * CELL PREPARATION * DICHROIC PARAMETERS AND THEIR MEASUREMENTS * Order Parameter and Dichroic Ratio Of Dyes * Absorbance, Order Parameter and Dichroic Ratio Measurements * IMPACT OF DYE STRUCTURE AND LIQUID CRYSTAL HOST ON PHYSICAL PROPERTIES OF A DICHROIC MIXTURE * Order Parameter and Dichroic Ratio * EFFECT OF LENGTH OF DICHROIC DYES ON THE ORDER PARAMETER * EFFECT OF THE BREADTH OF DYE ON THE ORDER PARAMETER * EFFECT OF THE HOST ON THE ORDER PARAMETER * TEMPERATURE VARIATION OF THE ORDER PARAMETER OF DYES IN A LIQUID CRYSTAL HOST * IMPACT OF DYE CONCENTRATION ON THE ORDER PARAMETER * Temperature Range * Viscosity * Dielectric Constant and Anisotropy * Refractive Indices and Birefringence * solubility43,153-156 * Absorption Wavelength and Auxochromic Groups * Molecular Engineering of Dichroic Dyes * OPTICAL, ELECTRO-OPTICAL AND LIFE PARAMETERS * Colour And CIE Colour space120,160-166 * CIE 1931 COLOUR SPACE * CIE 1976 CHROMATICITY DIAGRAM * CIE UNIFORM COLOUR SPACES & COLOUR DIFFERENCE FORMULAE120,160-166 * Electro-Optical Parameters120 * LUMINANCE * CONTRAST AND CONTRAST RATIO * SWITCHING SPEED * Life Parameters and Failure Modes * DICHROIC MIXTURE FORMULATION * Monochrome Mixture * Black Mixture * ACHROMATIC BLACK MIXTURE FOR HEILMEIER DISPLAYS * Effect of Illuminant on Display Colour * Colour of the Field-On State * Effect of Dye Linewidth * Optimum Centroid Wavelengths * Effect of Dye Concentration * Mixture Formulation Using More Than Three Dyes * ACHROMATIC MIXTURE FOR WHITE-TAYLOR TYPE DISPLAYS * HEILMEIER DISPLAYS * Theoretical Modelling * Threshold Characteristic * Effects of Dye Concentration on Electro-optical Parameters * Effect of Cholesteric Doping * Effect of Alignment

  5. Negative ion formation and neutralization processes, (2)

    International Nuclear Information System (INIS)

    Sugiura, Toshio

    1982-09-01

    This review is 2nd part of the report published at January 1982 (JAERI-M-9902). A compilation includes the survey of the data of the cross sections of H - and D - ion formations and the neutralization of these ions. This is also presented new information about the photosensitization by laser beam in dissociative-resonance electron capture of sulfur hexafluoride reported by Chen et al., for reference to enhancement of D - ions in discharge. For neutralization, the data of mutual neutralization and photodetachment are also presented. (author)

  6. Foster Wheeler experience with biomass and other CO{sub 2}-neutral fuels in large CFBs

    Energy Technology Data Exchange (ETDEWEB)

    Zabetta, E.; Kauppinen, K.; Slotte, M. (Foster Wheeler Power Group Europe, Varkaus (Finland)), Email: edgardo.coda@fwfin.fwc.com

    2009-07-01

    Foster Wheeler is a global engineering and construction contractor and a power equipment supplier. Among other products, the company offers state-of-the-art boilers for heat and electricity generation. During the past 30 years Foster Wheeler has booked over 350 circulating fluidized bed boilers (CFBs) ranging from 7 to nearly 1000 MW{sub th}. Of these, over 50 are designed for biomass (or bio-mix) and nearly 50 for waste (or waste-mix) containing biodegradable fractions, which are considered CO{sub 2}-neutral. The biggest challenges encountered in biomass (co-)firing are the tendency towards bed agglomeration and fouling of convective heat surfaces, often associated to corrosion. Such problems are marginal with certain woody biomass, but they intensify when other biomass or waste are fired, and further grow when boilers must operate at highest efficiency while firing erratic fuel mixtures. This paper describes the designs and tools developed at Foster Wheeler to fire different types of biomass and wastes in large CFB boilers. Latest references are then described, showing the ever growing performances achievable when firing CO{sub 2}-neutral fuels, but also highlighting the challenges of boilers that must maintain high performance throughout unprecedentedly broad fuel ranges. (orig.)

  7. The neural fate of neutral information in emotion-enhanced memory.

    Science.gov (United States)

    Watts, Sarah; Buratto, Luciano G; Brotherhood, Emilie V; Barnacle, Gemma E; Schaefer, Alexandre

    2014-07-01

    In this study, we report evidence that neural activity reflecting the encoding of emotionally neutral information in memory is reduced when neutral and emotional stimuli are intermixed during encoding. Specifically, participants studied emotional and neutral pictures organized in mixed lists (in which emotional and neutral pictures were intermixed) or in pure lists (only-neutral or only-emotional pictures) and performed a recall test. To estimate encoding efficiency, we used the Dm effect, measured with event-related potentials. Recall for neutral items was lower in mixed compared to pure lists and posterior Dm activity for neutral items was reduced in mixed lists, whereas it remained robust in pure lists. These findings might be caused by an asymmetrical competition for attentional and working memory resources between emotional and neutral information, which could be a major determinant of emotional memory effects. Copyright © 2014 Society for Psychophysiological Research.

  8. Electrodermal responses to words in chronic low back pain patients: a comparison between pain descriptors, other emotional words, and neutral words.

    Science.gov (United States)

    Bonnet, Adeline; Naveteur, Janick

    2006-10-01

    This study examines the electrodermal reactivity of chronic sufferers to emotional words. The hypothesis that patients are over-sensitive to pain descriptors is tested. Electrodermal activity was recorded in 12 chronic low back pain patients and 12 healthy controls during passive viewing of words on a video monitor. These words were pain descriptors, other emotional words, and neutral words, in a pseudo-randomized order. A jingle was associated with the word occurrence. In chronic low back pain patients, skin conductance responses (SCRs) induced by pain descriptors or other emotional words were larger than SCRs induced by neutral words but they did not differ from each other. Patients presented SCRs, which were both larger and faster than those of controls, including following neutral words. There was no significant effect of word type in controls. Skin conductance level and the number of nonspecific fluctuations were larger in patients as compared with controls. The present electrodermal study suggests that chronic pain is linked to an increased reactivity to a wide range of stimuli. Emotional load amplifies the effect. This leads to recommend broad therapeutic management in chronic sufferers. Contrary to expectation derived from classical conditioning, patients did not prove over-sensitive to pain descriptors. This negative finding is discussed at methodologic, physiologic, and psychologic levels.

  9. Nogo stimuli do not receive more attentional suppression or response inhibition than neutral stimuli: evidence from the N2pc, PD and N2 components in a spatial cueing paradigm

    Directory of Open Access Journals (Sweden)

    Caroline eBarras

    2016-05-01

    Full Text Available It has been claimed that stimuli sharing the color of the nogo-target are suppressed because of the strong incentive to not process the nogo-target, but we failed to replicate this finding. Participants searched for a color singleton in the target display and indicated its shape when it was in the go color. If the color singleton in the target display was in the nogo color, they had to withhold the response. The target display was preceded by a cue display that also contained a color singleton (the cue. The cue was either in the color of the go or nogo target, or it was in an unrelated, neutral color. With cues in the go color, reaction times (RTs were shorter when the cue appeared at the same location as the target compared to when it appeared at a different location. Also, electrophysiological recordings showed that an index of attentional selection, the N2pc, was elicited by go cues. Surprisingly, we failed to replicate cueing costs for cues in the nogo color that were originally reported by Anderson and Folk (2012. Consistently, we also failed to find an electrophysiological index of attentional suppression (the PD for cues in the nogo color. Further, fronto-central ERPs to the cue display showed the same negativity for nogo and neutral stimuli relative to go stimuli, which is at odds with response inhibition and conflict monitoring accounts of the Nogo-N2. Thus, the modified cueing paradigm employed here provides little evidence that features associated with nogo-targets are suppressed at the level of attention or response selection. Rather, nogo-stimuli are efficiently ignored and attention is focused on features that require a response.

  10. Dual-functioning peptides discovered by phage display increase the magnitude and specificity of BMSC attachment to mineralized biomaterials.

    Science.gov (United States)

    Ramaraju, Harsha; Miller, Sharon J; Kohn, David H

    2017-07-01

    Design of biomaterials for cell-based therapies requires presentation of specific physical and chemical cues to cells, analogous to cues provided by native extracellular matrices (ECM). We previously identified a peptide sequence with high affinity towards apatite (VTKHLNQISQSY, VTK) using phage display. The aims of this study were to identify a human MSC-specific peptide sequence through phage display, combine it with the apatite-specific sequence, and verify the specificity of the combined dual-functioning peptide to both apatite and human bone marrow stromal cells. In this study, a combinatorial phage display identified the cell binding sequence (DPIYALSWSGMA, DPI) which was combined with the mineral binding sequence to generate the dual peptide DPI-VTK. DPI-VTK demonstrated significantly greater binding affinity (1/K D ) to apatite surfaces compared to VTK, phosphorylated VTK (VTK phos ), DPI-VTK phos , RGD-VTK, and peptide-free apatite surfaces (p biomaterial surfaces and subsequently increase cell proliferation and differentiation. These new peptides expand biomaterial design methodology for cell-based regeneration of bone defects. This strategy of combining cell and material binding phage display derived peptides is broadly applicable to a variety of systems requiring targeted adhesion of specific cell populations, and may be generalized to the engineering of any adhesion surface. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Neutral axis as damage sensitive feature

    International Nuclear Information System (INIS)

    Sigurdardottir, D H; Glisic, B

    2013-01-01

    Structural health monitoring (SHM) is the process of continuously or periodically measuring structural parameters and the transformation of the collected data into information on real structural conditions. The centroid of stiffness is a universal parameter and its position in a cross-section can be evaluated for any load-carrying beam structure as the position of the neutral axis under conveniently chosen loads. Thus, a change in the position of the neutral axis within a cross-section can indicate a change in the position of the centroid of stiffness, i.e., unusual structural behaviors. This paper proposes a novel monitoring method based on deterministic and probabilistic determination of the position of the neutral axis under conveniently chosen conditions. Therefore, the method proposed in this paper is potentially applicable to a large variety of beam-like structures. Data from two existing structures were used to validate the method and assess its performance: Streicker Bridge at Princeton University and the US202/NJ23 highway overpass in Wayne, NJ. The results show that the neutral axis location is varying even when damage is not present. Reasons for this variation are determined and the accuracy in the evaluation assessed. This paper concludes that the position of the neutral axis can be evaluated with sufficient accuracy using static and dynamic strain measurements performed on appropriate time-scales and indicates its potential to be used as a damage sensitive feature. (paper)

  12. Neutral axis as damage sensitive feature

    Science.gov (United States)

    Sigurdardottir, D. H.; Glisic, B.

    2013-07-01

    Structural health monitoring (SHM) is the process of continuously or periodically measuring structural parameters and the transformation of the collected data into information on real structural conditions. The centroid of stiffness is a universal parameter and its position in a cross-section can be evaluated for any load-carrying beam structure as the position of the neutral axis under conveniently chosen loads. Thus, a change in the position of the neutral axis within a cross-section can indicate a change in the position of the centroid of stiffness, i.e., unusual structural behaviors. This paper proposes a novel monitoring method based on deterministic and probabilistic determination of the position of the neutral axis under conveniently chosen conditions. Therefore, the method proposed in this paper is potentially applicable to a large variety of beam-like structures. Data from two existing structures were used to validate the method and assess its performance: Streicker Bridge at Princeton University and the US202/NJ23 highway overpass in Wayne, NJ. The results show that the neutral axis location is varying even when damage is not present. Reasons for this variation are determined and the accuracy in the evaluation assessed. This paper concludes that the position of the neutral axis can be evaluated with sufficient accuracy using static and dynamic strain measurements performed on appropriate time-scales and indicates its potential to be used as a damage sensitive feature.

  13. Evolutionary advantage via common action of recombination and neutrality

    Science.gov (United States)

    Saakian, David B.; Hu, Chin-Kun

    2013-11-01

    We investigate evolution models with recombination and neutrality. We consider the Crow-Kimura (parallel) mutation-selection model with the neutral fitness landscape, in which there is a central peak with high fitness A, and some of 1-point mutants have the same high fitness A, while the fitness of other sequences is 0. We find that the effect of recombination and neutrality depends on the concrete version of both neutrality and recombination. We consider three versions of neutrality: (a) all the nearest neighbor sequences of the peak sequence have the same high fitness A; (b) all the l-point mutations in a piece of genome of length l≥1 are neutral; (c) the neutral sequences are randomly distributed among the nearest neighbors of the peak sequences. We also consider three versions of recombination: (I) the simple horizontal gene transfer (HGT) of one nucleotide; (II) the exchange of a piece of genome of length l, HGT-l; (III) two-point crossover recombination (2CR). For the case of (a), the 2CR gives a rather strong contribution to the mean fitness, much stronger than that of HGT for a large genome length L. For the random distribution of neutral sequences there is a critical degree of neutrality νc, and for μmutations affect the mean-field-like and fluctuation-like factors similarly. Consequently, recombination can accelerate the non-mean-field (fluctuation) type dynamics without considerably affecting the mean-field-like factors.

  14. Heavy-atom neutral beams for tandem-mirror end plugs

    International Nuclear Information System (INIS)

    Post, D.E.; Grisham, L.R.; Santarius, J.F.; Emmert, G.A.

    1981-05-01

    The advantages of neutral beams with Z greater than or equal to 3 formed from negative ions, accelerated to 0.5 to 1.0 MeV/amu, and neutralized with high efficiency, are investigated for use in tandem mirror reactor end plugs. These beams can produce Q's of 20 to 30, and thus can replace the currently proposed 200 to 500 keV neutral proton beams presently planned for tandem mirror reactors. Thus, these Z greater than or equal to 3 neutral beams increase the potential attractiveness of tandem mirror reactors by offering a substitute for difficult high energy neutral hydrogen end plug beams

  15. Monte Carlo neutral density calculations for ELMO Bumpy Torus

    International Nuclear Information System (INIS)

    Davis, W.A.; Colchin, R.J.

    1986-11-01

    The steady-state nature of the ELMO Bumpy Torus (EBT) plasma implies that the neutral density at any point inside the plasma volume will determine the local particle confinement time. This paper describes a Monte Carlo calculation of three-dimensional atomic and molecular neutral density profiles in EBT. The calculation has been done using various models for neutral source points, for launching schemes, for plasma profiles, and for plasma densities and temperatures. Calculated results are compared with experimental observations - principally spectroscopic measurements - both for guidance in normalization and for overall consistency checks. Implications of the predicted neutral profiles for the fast-ion-decay measurement of neutral densities are also addressed

  16. Neutral beams for magnetic fusion

    International Nuclear Information System (INIS)

    Hooper, B.

    1977-01-01

    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 (10 14 particles/cm 3 ) 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

  17. Charge neutralization of small ion beam clumps

    Energy Technology Data Exchange (ETDEWEB)

    Welch, D R [Mission Research Corp., Albuquerque, NM (United States); Olson, C L; Hanson, D L [Sandia National Labs., Albuquerque, NM (United States)

    1997-12-31

    The mega-ampere currents associated with light ion fusion (LIF) require excellent charge neutralization to prevent divergence growth. As the size and space-charge potential of a beam clump or `beamlet` become small (submillimeter size and kilovolt potentials), the neutralization becomes increasingly difficult. Linear theory predicts that plasma electrons cannot neutralize potentials < {phi}{sub crit} = (1/2)m{sub e}v{sub i}{sup 2}/e, where m{sub e} is the electron mass and v{sub i} is the ion beam velocity. A non-uniform beam would, therefore, have regions with potentials sufficient to add divergence to beam clumps. The neutralization of small beamlets produced on the SABLE accelerator and in numerical simulation has supported the theory, showing a plateau in divergence growths as the potential in the beamlet exceeds {phi}{sub crit}. (author). 1 tab., 2 figs., 4 refs.

  18. Large-scale analysis of B-cell epitopes on influenza virus hemagglutinin - implications for cross-reactivity of neutralizing antibodies

    DEFF Research Database (Denmark)

    Sun, Jing; Kudahl, Ulrich J.; Simon, Christian

    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 (bnAbs) represent targets for prophylacti......, and differences between historical influenza strains, we enhance our preparedness and the ability to respond to the emerging pandemic threats....... a method to assess the likely cross-reactivity potential of bnAbs for influenza strains, either newly emerged or existing. Our method catalogs influenza strains by a new concept named discontinuous peptide, and then provide assessment of cross-reactivity. Potentially cross-reactive strains are those...

  19. Crosstalk evaluation in stereoscopic displays

    NARCIS (Netherlands)

    Wang, L.; Teunissen, C.; Tu, Yan; Chen, Li; Zhang, P.; Zhang, T.; Heynderickx, I.E.J.

    2011-01-01

    Substantial progress in liquid-crystal display and polarization film technology has enabled several types of stereoscopic displays. Despite all progress, some image distortions still exist in these 3-D displays, of which interocular crosstalk - light leakage of the image for one eye to the other eye

  20. Measurement of plasma production and neutralization in gas neutralizers

    International Nuclear Information System (INIS)

    Maor, D.; Meron, M.; Johnson, B.; Jones, K.; Agagu, A.; Hu, B.

    1986-01-01

    In order to satisfy the need of experimental data for the designing of gas neutralizers we have started a project aimed at measuring all relevant cross sections for the charge exchange of H - , H 0 and H + projectiles, as well as the cross sections for the production of ions in the target. The expected results of these latter measurements are shown schematically

  1. Evaluation of smallpox vaccines using variola neutralization.

    Science.gov (United States)

    Damon, Inger K; Davidson, Whitni B; Hughes, Christine M; Olson, Victoria A; Smith, Scott K; Holman, Robert C; Frey, Sharon E; Newman, Frances; Belshe, Robert B; Yan, Lihan; Karem, Kevin

    2009-08-01

    The search for a 'third'-generation smallpox vaccine has resulted in the development and characterization of several vaccine candidates. A significant barrier to acceptance is the absence of challenge models showing induction of correlates of protective immunity against variola virus. In this light, virus neutralization provides one of few experimental methods to show specific 'in vitro' activity of vaccines against variola virus. Here, we provide characterization of the ability of a modified vaccinia virus Ankara vaccine to induce variola virus-neutralizing antibodies, and we provide comparison with the neutralization elicited by standard Dryvax vaccination.

  2. Consortium for military LCD display procurement

    Science.gov (United States)

    Echols, Gregg

    2002-08-01

    International Display Consortium (IDC) is the joining together of display companies to combined their buying power and obtained favorable terms with a major LCD manufacturer. Consolidating the buying power and grouping the demand enables the rugged display industry of avionics, ground vehicles, and ship based display manufacturers to have unencumbered access to high performance AMLCDs while greatly reducing risk and lowering cost. With an unrestricted supply of AMLCD displays, the consortium members have total control of their risk, cost, deliveries and added value partners. Every display manufacturer desires a very close relationship with a display vender. With IDC each consortium member achieves a close relationship. Consortium members enjoy cost effective access to high performance, industry standard sized LCD panels, and modified commercial displays with 100 degree C clearing points and portrait configurations. Consortium members also enjoy proposal support, technical support and long-term support.

  3. Validation, automatic generation and use of broad phonetic transcriptions

    NARCIS (Netherlands)

    Bael, Cristophe Patrick Jan Van

    2007-01-01

    Broad phonetic transcriptions represent the pronunciation of words as strings of characters from specifically designed symbol sets. In everyday life, broad phonetic transcriptions are often used as aids to pronounce (foreign) words. In addition, broad phonetic transcriptions are often used for

  4. The innovation-enhancing effects of network neutrality

    NARCIS (Netherlands)

    Kocsis, V.; Weda, J.

    2013-01-01

    In the past decade, economists, legal experts, and policy makers have been discussing the effects of neutral network structures on - among others - innovations by content and application providers. Does network neutrality - the open and non-discriminatory functioning of the internet - provide

  5. The Framing of Network Neutrality Governance

    DEFF Research Database (Denmark)

    Perry, James

    The neutrality of the internet with regard to applications (e.g. search, social networking, email, to mention only three) has been central to innovation and growth in the knowledge-economy over the past two decades. Until recently, neutrality was built into the internet's design via its core stan...... with a critical analysis of their respective operational paradigms, the paper seeks to understand who is framing the debate, how they are doing so, and to what (systemic) effect....... generative: Useful innovations in applications of the internet could take hold easily, and it was difficult – or indeed impossible - for incumbent business interests to disrupt or sabotage them. However, this neutrality is now under threat. New technologies have given incumbent businesses the ability...

  6. Current neutralization of converging ion beams

    International Nuclear Information System (INIS)

    Mosher, D.

    1978-01-01

    It is desired to consider the problem of current neutralization of heavy ion beams traversing gas backgrounds in which the conductivity changes due to beam heating and beam convergence. The procedure is to determine Green's-function solutions to the magnetic-diffusion equation derived from Maxwell's equations and an assumed scaler-plasma conductivity sigma for the background-electron current density j/sub e/. The present calculation is more general than some previously carried out in that arbitrary time variations for the beam current j/sub b/ and conductivity are allowed and the calculation is valid for both weak and strong neutralization. Results presented here must be combined with an appropriate energy-balance equation for the heated background in order to obtain the neutralization self-consistently

  7. Truly neutral microobjects and oscillations in particle physics

    International Nuclear Information System (INIS)

    Bilenky, S.M.; Pontecorvo, B.

    1982-01-01

    Oscillation phenomena between different states of neutral elementary particles are discussed. The known kaon oscillation and the proposed neutrino, neutron and other kinds of oscillations are analysed. The proper bound states of neutral objects (neutrinos, neutrons, hydrogen atoms) are investigated in the case of small and strong violation of CP symmetry. Consequences concerning the observable masses and quantum numbers of such neutral objects are drawn. (D.Gy.)

  8. Neutral currents in semileptonic reactions

    International Nuclear Information System (INIS)

    Paschos, E.A.

    1975-05-01

    The evidence for weak neutral currents is analyzed in semileptonic reactions with special emphasis on their Lorentz and internal symmetry structure. It is found that present observations are consistent with the expectations of gauge theories, but other possibilities can not be ruled out. Of particular interest in this respect is the presence of a large isoscalar component. The excitation of the Δ-resonance by neutral currents is analyzed, and pion-nucleon mass distributions are presented. Charge asymmetries sensitive to isoscalar-isovector interferences are discussed. (U.S.)

  9. Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques.

    Science.gov (United States)

    Borggren, Marie; Vinner, Lasse; Andresen, Betina Skovgaard; Grevstad, Berit; Repits, Johanna; Melchers, Mark; Elvang, Tara Laura; Sanders, Rogier W; Martinon, Frédéric; Dereuddre-Bosquet, Nathalie; Bowles, Emma Joanne; Stewart-Jones, Guillaume; Biswas, Priscilla; Scarlatti, Gabriella; Jansson, Marianne; Heyndrickx, Leo; Grand, Roger Le; Fomsgaard, Anders

    2013-07-19

    HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb). We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques.

  10. Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques

    Directory of Open Access Journals (Sweden)

    Roger Le Grand

    2013-07-01

    Full Text Available HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb. We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques.

  11. Super high precision 200 ppi liquid crystal display series; Chokoseido 200 ppi ekisho display series

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-03-01

    In mobile equipment, in demand is a high precision liquid crystal display (LCD) having the power of expression equivalent to printed materials like magazines because of the necessity of displaying a large amount of information on a easily potable small screen. In addition, with the spread and high-quality image of digital still cameras, it is strongly desired to display photographed digital image data in high quality. Toshiba Corp., by low temperature polysilicone (p-Si) technology, commercialized the liquid crystal display series of 200 ppi (pixels per inch) precision dealing with the rise of the high-precision high-image quality LCD market. The super high precision of 200 ppi enables the display of smooth beautiful animation comparable to printed sheets of magazines and photographs. The display series are suitable for the display of various information services such as electronic books and electronic photo-viewers including internet. The screen sizes lined up are No. 4 type VGA (640x480 pixels) of a small pocket notebook size and No. 6.3 type XGA (1,024x768 pixels) of a paperback size, with a larger screen to be furthered. (translated by NEDO)

  12. Long-Run Neutrality and Superneutrality in an ARIMA Framework.

    OpenAIRE

    Fisher, Mark E; Seater, John J

    1993-01-01

    The authors formalize long-run neutrality and long-run superneutrality in the context of a bivariate ARIMA model; show how the restrictions implied by long-run neutrality and long-run superneutrality depend on the orders of integration of the variables; apply their analysis to previous work, showing how that work is related to long-run neutrality and long-run superneutrality; and provide some new evidence on long-run neutrality and long-run superneutrality. Copyright 1993 by American Economic...

  13. A Compressive Superresolution Display

    KAUST Repository

    Heide, Felix; Gregson, James; Wetzstein, Gordon; Raskar, Ramesh; Heidrich, Wolfgang

    2014-01-01

    In this paper, we introduce a new compressive display architecture for superresolution image presentation that exploits co-design of the optical device configuration and compressive computation. Our display allows for superresolution, HDR, or glasses-free 3D presentation.

  14. A Compressive Superresolution Display

    KAUST Repository

    Heide, Felix

    2014-06-22

    In this paper, we introduce a new compressive display architecture for superresolution image presentation that exploits co-design of the optical device configuration and compressive computation. Our display allows for superresolution, HDR, or glasses-free 3D presentation.

  15. Research on Stress Neutral Layer Offset in the Straightening Process

    Directory of Open Access Journals (Sweden)

    Hailian Gui

    2015-01-01

    Full Text Available The stress neutral layer offset is analyzed by theoretical and numerical calculation methods. In traditional straightening theory, the stress neutral layer was consistent with the geometric central layer. However, there is a phenomenon that the stress neutral layer has some offset with the geometric neutral layer. This offset is a very important factor for improving the precision of the straightening force. The formula of the stress neutral layer offset is obtained by a theoretical method and the change law is given by numerical calculation method. The neutral layer offset theory provides the theoretical basis for establishing the model of straightening force precisely.

  16. A General Nonlinear Fluid Model for Reacting Plasma-Neutral Mixtures

    Energy Technology Data Exchange (ETDEWEB)

    Meier, E T; Shumlak, U

    2012-04-06

    A generalized, computationally tractable fluid model for capturing the effects of neutral particles in plasmas is derived. The model derivation begins with Boltzmann equations for singly charged ions, electrons, and a single neutral species. Electron-impact ionization, radiative recombination, and resonant charge exchange reactions are included. Moments of the reaction collision terms are detailed. Moments of the Boltzmann equations for electron, ion, and neutral species are combined to yield a two-component plasma-neutral fluid model. Separate density, momentum, and energy equations, each including reaction transfer terms, are produced for the plasma and neutral equations. The required closures for the plasma-neutral model are discussed.

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

    Energy Technology Data Exchange (ETDEWEB)

    Chang, So Young; Park, Ji Hoon [Respiratory Viruses Research Laboratory, Discovery Biology Department, Institut Pasteur Korea, 16, Daewangpangyo-ro 712 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-400 (Korea, Republic of); Kim, Young Ho; Kang, Jong Seong [College of Pharmacy, Chungnam National University, Daejeon, 305-764 (Korea, Republic of); Min, Ji-Young, E-mail: jiyoung.min@ip-korea.org [Respiratory Viruses Research Laboratory, Discovery Biology Department, Institut Pasteur Korea, 16, Daewangpangyo-ro 712 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-400 (Korea, Republic of)

    2016-03-04

    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. - Highlights: • The plant-derived natural product TGBG has broad-spectrum antiviral activity against seasonal influenza A and B viruses. • TGBG has a novel anti-viral mechanism of action that from differs from the currently available anti-influenza drugs. • TGBG hinders nuclear export of the influenza virus ribonucleoprotein (v

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

    International Nuclear Information System (INIS)

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

    2016-01-01

    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. - Highlights: • The plant-derived natural product TGBG has broad-spectrum antiviral activity against seasonal influenza A and B viruses. • TGBG has a novel anti-viral mechanism of action that from differs from the currently available anti-influenza drugs. • TGBG hinders nuclear export of the influenza virus ribonucleoprotein (v

  19. JTEC panel on display technologies in Japan

    Science.gov (United States)

    Tannas, Lawrence E., Jr.; Glenn, William E.; Credelle, Thomas; Doane, J. William; Firester, Arthur H.; Thompson, Malcolm

    1992-01-01

    This report is one in a series of reports that describes research and development efforts in Japan in the area of display technologies. The following are included in this report: flat panel displays (technical findings, liquid crystal display development and production, large flat panel displays (FPD's), electroluminescent displays and plasma panels, infrastructure in Japan's FPD industry, market and projected sales, and new a-Si active matrix liquid crystal display (AMLCD) factory); materials for flat panel displays (liquid crystal materials, and light-emissive display materials); manufacturing and infrastructure of active matrix liquid crystal displays (manufacturing logistics and equipment); passive matrix liquid crystal displays (LCD basics, twisted nematics LCD's, supertwisted nematic LCD's, ferroelectric LCD's, and a comparison of passive matrix LCD technology); active matrix technology (basic active matrix technology, investment environment, amorphous silicon, polysilicon, and commercial products and prototypes); and projection displays (comparison of Japanese and U.S. display research, and technical evaluation of work).

  20. Auditors' Professional Skepticism: Neutrality versus Presumptive Doubt

    NARCIS (Netherlands)

    Groot, T.L.C.M.; Quadackers, L.M.; Wright, A.

    2014-01-01

    Although skepticism is widely viewed as essential to audit quality, there is a debate about what form is optimal. The two prevailing perspectives that have surfaced are "neutrality" and "presumptive doubt." With neutrality, auditors neither believe nor disbelieve client management. With presumptive

  1. DNA vaccines expressing soluble CD4-envelope proteins fused to C3d elicit cross-reactive neutralizing antibodies to HIV-1

    International Nuclear Information System (INIS)

    Bower, Joseph F.; Green, Thomas D.; Ross, Ted M.

    2004-01-01

    DNA vaccines expressing the envelope (Env) of the human immunodeficiency virus type 1 (HIV-1) have been relatively ineffective at generating high-titer, long-lasting, neutralizing antibodies in a variety of animal models. In this study, DNA vaccines were constructed to express a fusion protein of the soluble human CD4 (sCD4) and the gp120 subunit of the HIV-1 envelope. To enhance the immunogenicity of the expressed fusion protein, three copies of the murine C3d (mC3d 3 ) were added to the carboxyl terminus of the complex. Monoclonal antibodies that recognize CD4-induced epitopes on gp120 efficiently bound to sCD4-gp120 or sCD4-gp120-mC3d 3 . In addition, both sCD4-gp120 and sCD4-gp120-mC3d 3 bound to cells expressing appropriate coreceptors in the absence of cell surface hCD4. Mice (BALB/c) vaccinated with DNA vaccines expressing either gp120-mC3d 3 or sCD4-gp120-mC3d 3 elicited antibodies that neutralized homologous virus infection. However, the use of sCD4-gp120-mC3d 3 -DNA elicited the highest titers of neutralizing antibodies that persisted after depletion of anti-hCD4 antibodies. Interestingly, only mice vaccinated with DNA expressing sCD4-gp120-mC3d 3 had antibodies that elicited cross-protective neutralizing antibodies. The fusion of sCD4 to the HIV-1 envelope exposes neutralizing epitopes that elicit broad protective immunity when the fusion complex is coupled with the molecular adjuvant, C3d

  2. Australian Children's Understanding of Display Rules

    Science.gov (United States)

    Choy, Grace

    2009-01-01

    Cultural display rules govern the manifestation of emotional expressions. In compliance with display rules, the facial expressions displayed (i.e. apparent emotion) may be incongruent with the emotion experienced (i.e. real emotion). This study investigates Australian Caucasian children's understanding of display rules. A sample of 80 four year…

  3. The case for transparent depth display

    NARCIS (Netherlands)

    Kooi, F.L.

    2003-01-01

    Purpose: The continuing developments in display technology have resulted in the ability to present increasing amounts of data on computer displays. One of the coming break-throughs is generally believed to be the introduction of '3-D displays': displays with a true sense of depth. Though these types

  4. Efficient Means of Detecting Neutral Atoms in Space

    Science.gov (United States)

    Zinicola, W. N.

    2006-12-01

    This summer, The Society of Physics Students granted me the opportunity to participate in an internship for The National Aeronautics and Space Administration (NASA) and The University of Maryland. Our chief interest was analyzing low energy neutral atoms that were created from random interactions of ions in space plasma. From detecting these neutrals one can project a image of what the plasma's composition is, and how this plasma changes through interactions with the solar wind. Presently, low energy neutral atom detectors have poor efficiency, typically in the range of 1%. Our goal was to increase this efficiency. To detect low energy neutrals we must first convert them from neutral molecules to negatively charged ions. Once converted, these "new" negatively charged ions can be easily detected and completely analyzed giving us information about their energy, mass, and instantaneous direction. The efficiency of the detector is drastically affected by the surface used for converting these neutrals. My job was first to create thin metal conversion surfaces. Then, using an X-ray photoelectron spectrometer, analyze atomic surface composition and gather work function values. Once the work function values were known we placed the surfaces in our neutral detector and measured their conversion efficiencies. Finally, a relation between the work function of the metal surface an its conversion efficiency was generated. With this relationship accurately measured one could use this information to help give suggestions on what surface would be the best to increase our detection efficiency. If we could increase the efficiency of these low energy neutral atom detectors by even 1% we would be able to decrease the size of the detector therefore making it cheaper and more applicable for space exploration.* * A special thanks to Dr. Michael Coplan of the University of Maryland for his support and guidance through all my research.

  5. New ultraportable display technology and applications

    Science.gov (United States)

    Alvelda, Phillip; Lewis, Nancy D.

    1998-08-01

    MicroDisplay devices are based on a combination of technologies rooted in the extreme integration capability of conventionally fabricated CMOS active-matrix liquid crystal display substrates. Customized diffraction grating and optical distortion correction technology for lens-system compensation allow the elimination of many lenses and systems-level components. The MicroDisplay Corporation's miniature integrated information display technology is rapidly leading to many new defense and commercial applications. There are no moving parts in MicroDisplay substrates, and the fabrication of the color generating gratings, already part of the CMOS circuit fabrication process, is effectively cost and manufacturing process-free. The entire suite of the MicroDisplay Corporation's technologies was devised to create a line of application- specific integrated circuit single-chip display systems with integrated computing, memory, and communication circuitry. Next-generation portable communication, computer, and consumer electronic devices such as truly portable monitor and TV projectors, eyeglass and head mounted displays, pagers and Personal Communication Services hand-sets, and wristwatch-mounted video phones are among the may target commercial markets for MicroDisplay technology. Defense applications range from Maintenance and Repair support, to night-vision systems, to portable projectors for mobile command and control centers.

  6. Detection of extensive cross-neutralization between pandemic and seasonal A/H1N1 Influenza Viruses using a pseudotype neutralization assay.

    Directory of Open Access Journals (Sweden)

    Béatrice Labrosse

    Full Text Available BACKGROUND: Cross-immunity between seasonal and pandemic A/H1N1 influenza viruses remains uncertain. In particular, the extent that previous infection or vaccination by seasonal A/H1N1 viruses can elicit protective immunity against pandemic A/H1N1 is unclear. METHODOLOGY/PRINCIPAL FINDINGS: Neutralizing titers against seasonal A/H1N1 (A/Brisbane/59/2007 and against pandemic A/H1N1 (A/California/04/2009 were measured using an HIV-1-based pseudovirus neutralization assay. Using this highly sensitive assay, we found that a large fraction of subjects who had never been exposed to pandemic A/H1N1 express high levels of pandemic A/H1N1 neutralizing titers. A significant correlation was seen between neutralization of pandemic A/H1N1 and neutralization of a standard seasonal A/H1N1 strain. Significantly higher pandemic A/H1N1 neutralizing titers were measured in subjects who had received vaccination against seasonal influenza in 2008-2009. Higher pandemic neutralizing titers were also measured in subjects over 60 years of age. CONCLUSIONS/SIGNIFICANCE: Our findings reveal that the extent of protective cross-immunity between seasonal and pandemic A/H1N1 influenza viruses may be more important than previously estimated. This cross-immunity could provide a possible explanation of the relatively mild profile of the recent influenza pandemic.

  7. 46 CFR 120.376 - Grounded distribution systems (Neutral grounded).

    Science.gov (United States)

    2010-10-01

    ....376 Section 120.376 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS CARRYING MORE THAN 150 PASSENGERS OR WITH OVERNIGHT ACCOMMODATIONS FOR MORE THAN 49 PASSENGERS... distribution system having a neutral bus or conductor must have the neutral grounded. (c) The neutral or each...

  8. Bibliographic Displays in OPACs and Web Catalogs: How Well Do They Comply with Display Guidelines?

    Science.gov (United States)

    Cherry, Joan M.

    1998-01-01

    Evaluation of data from assessments of full bibliographic displays in academic library OPACs (online public access catalogs) and World Wide Web catalogs against a checklist of desirable features found that OPAC displays scored 58% and Web displays scored 60%. Discusses weaknesses, focusing on those found in the majority of the displays…

  9. A nanobody:GFP bacterial platform that enables functional enzyme display and easy quantification of display capacity

    DEFF Research Database (Denmark)

    Wendel, Sofie; Christian Fischer, Emil; Martinez, Virginia

    2016-01-01

    Background: Bacterial surface display is an attractive technique for the production of cell-anchored, functional proteins and engineering of whole-cell catalysts. Although various outer membrane proteins have been used for surface display, an easy and versatile high-throughput-compatible assay...... to displaying the nanobody alone. We used flow cytometry to analyse display capability on single-cell versus population level and found that the signal peptide of the anchor has great effect on display efficiency.Conclusions: We have developed an inexpensive and easy read-out assay for surface display using...... nanobody: GFP interactions. The assay is compatible with the most common fluorescence detection methods, including multi-well plate whole-cell fluorescence detection, SDS-PAGE in-gel fluorescence, microscopy and flow cytometry. We anticipate that the platform will facilitate future in-depth studies...

  10. Rare decays of neutral π and eta

    International Nuclear Information System (INIS)

    Poutissou, J.M.

    1983-09-01

    The decays of the pseudoscalar neutral mesons π degree and eta degree have provided a test of fundamental principles. The main branch, π degree → 2γ, was investigated in the late 60's in the context of current algebra and the decay rate calculated from the singular triangle diagram is in excellent agreement with experiment. Rare leptonic decays of the neutral pseudoscalar mesons are of interest because of the information they reveal about neutral currents or other exotic interactions between leptons and quarks. The author discusses recent information on the π degree → e + e - decay

  11. The breadth and titer of maternal HIV-1-specific heterologous neutralizing antibodies are not associated with a lower rate of mother-to-child transmission of HIV-1.

    Science.gov (United States)

    Chaillon, Antoine; Wack, Thierry; Braibant, Martine; Mandelbrot, Laurent; Blanche, Stéphane; Warszawski, Josiane; Barin, Francis

    2012-10-01

    It has been hypothesized that neutralizing antibodies (NAbs) should have broad specificity to be effective in protection against diverse HIV-1 variants. The mother-to-child transmission model of HIV-1 provides the opportunity to examine whether the breadth of maternal NAbs is associated with protection of infants from infection. Samples were obtained at delivery from 57 transmitting mothers (T) matched with 57 nontransmitting mothers (NT) enrolled in the multicenter French perinatal cohort (ANRS EPF CO1) between 1990 and 1996. Sixty-eight (59.6%) and 46 (40.4%) women were infected by B and non-B viruses, respectively. Neutralization assays were carried out with TZM-bl cells, using a panel of 10 primary isolates of 6 clades (A, B, C, F, CRF01_AE, and CRF02_AG), selected for their moderate or low sensitivity to neutralization. Neutralization breadths were not statistically different between T and NT mothers. However, a few statistically significant differences were observed, with higher frequencies or titers of NAbs toward several individual strains for NT mothers when the clade B-infected or non-clade B-infected mothers were analyzed separately. Our study confirms that the breadth of maternal NAbs is not associated with protection of infants from infection.

  12. Reconfigurable Full-Page Braille Displays

    Science.gov (United States)

    Garner, H. Douglas

    1994-01-01

    Electrically actuated braille display cells of proposed type arrayed together to form full-page braille displays. Like other braille display cells, these provide changeable patterns of bumps driven by digitally recorded text stored on magnetic tapes or in solid-state electronic memories. Proposed cells contain electrorheological fluid. Viscosity of such fluid increases in strong electrostatic field.

  13. 46 CFR 183.376 - Grounded distribution systems (neutral grounded).

    Science.gov (United States)

    2010-10-01

    ....376 Section 183.376 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER... propulsion, power, lighting, or distribution system having a neutral bus or conductor must have the neutral... generator to ground before the generator is connected to the bus, except the neutral of an emergency power...

  14. Analysis of variola and vaccinia virus neutralization assays for smallpox vaccines.

    Science.gov (United States)

    Hughes, Christine M; Newman, Frances K; Davidson, Whitni B; Olson, Victoria A; Smith, Scott K; Holman, Robert C; Yan, Lihan; Frey, Sharon E; Belshe, Robert B; Karem, Kevin L; Damon, Inger K

    2012-07-01

    Possible smallpox reemergence drives research for third-generation vaccines that effectively neutralize variola virus. A comparison of neutralization assays using different substrates, variola and vaccinia (Dryvax and modified vaccinia Ankara [MVA]), showed significantly different 90% neutralization titers; Dryvax underestimated while MVA overestimated variola neutralization. Third-generation vaccines may rely upon neutralization as a correlate of protection.

  15. Display-management system for MFTF

    International Nuclear Information System (INIS)

    Nelson, D.O.

    1981-01-01

    The Mirror Fusion Test Facility (MFTF) is controlled by 65 local control microcomputers which are supervised by a local network of nine 32-bit minicomputers. Associated with seven of the nine computers are state-of-the-art graphics devices, each with extensive local processing capability. These devices provide the means for an operator to interact with the control software running on the minicomputers. It is critical that the information the operator views accurately reflects the current state of the experiment. This information is integrated into dynamically changing pictures called displays. The primary organizational component of the display system is the software-addressable segment. The segments created by the display creation software are managed by display managers associated with each graphics device. Each display manager uses sophisticated storage management mechanisms to keep the proper segments resident in the local graphics device storage

  16. Development of KSTAR Neutral Beam Heating System

    Energy Technology Data Exchange (ETDEWEB)

    Oh, B. H.; Song, W. S.; Yoon, B. J. (and others)

    2007-10-15

    The prototype components of a neutral beam injection (NBI) system have been developed for the KSTAR, and a capability of the manufactured components has been tested. High power ion source, acceleration power supply, other ion source power supplies, neutralizer, bending magnet for ion beam separation, calorimeter, and cryo-sorption pump have been developed by using the domestic technologies and tested for a neutral beam injection of 8 MW per beamline with a pulse duration of 300 seconds. The developed components have been continuously upgraded to achieve the design requirements. The development technology of high power and long pulse neutral beam injection system has been proved with the achievement of 5.2 MW output for a short pulse length and 1.6 MW output for a pulse length of 300 seconds. Using these development technologies, the domestic NB technology has been stabilized under the development of high power ion source, NB beamline components, high voltage and current power supplies, NB diagnostics, NB system operation and control.

  17. Data display with the Q system

    International Nuclear Information System (INIS)

    Oothoudt, M.A.

    1979-01-01

    The Q data-acquisition system for PDP-11 mini-computers at the Clinton P. Anderson Meson Physics Facility (LAMPF) provides experimenters with basic tools for on-line data display. Tasks are available to plot one- and two-parameter histograms on Tektronix 4000 series storage-tube terminals. The histograms to be displayed and the display format may be selected with simple keyboard commands. A task is also available to create and display live two-parameter scatter plots for any acquired or calculated quantities. Other tasks in the system manage the display data base, list display parameters and histogram contents on hardcopy devices, and save core histograms on disk or tape for off-line analysis. 8 figures

  18. A nanobody:GFP bacterial platform that enables functional enzyme display and easy quantification of display capacity.

    Science.gov (United States)

    Wendel, Sofie; Fischer, Emil C; Martínez, Virginia; Seppälä, Susanna; Nørholm, Morten H H

    2016-05-03

    Bacterial surface display is an attractive technique for the production of cell-anchored, functional proteins and engineering of whole-cell catalysts. Although various outer membrane proteins have been used for surface display, an easy and versatile high-throughput-compatible assay for evaluating and developing surface display systems is missing. Using a single domain antibody (also called nanobody) with high affinity for green fluorescent protein (GFP), we constructed a system that allows for fast, fluorescence-based detection of displayed proteins. The outer membrane hybrid protein LppOmpA and the autotransporter C-IgAP exposed the nanobody on the surface of Escherichia coli with very different efficiency. Both anchors were capable of functionally displaying the enzyme Chitinase A as a fusion with the nanobody, and this considerably increased expression levels compared to displaying the nanobody alone. We used flow cytometry to analyse display capability on single-cell versus population level and found that the signal peptide of the anchor has great effect on display efficiency. We have developed an inexpensive and easy read-out assay for surface display using nanobody:GFP interactions. The assay is compatible with the most common fluorescence detection methods, including multi-well plate whole-cell fluorescence detection, SDS-PAGE in-gel fluorescence, microscopy and flow cytometry. We anticipate that the platform will facilitate future in-depth studies on the mechanism of protein transport to the surface of living cells, as well as the optimisation of applications in industrial biotech.

  19. International Thermonuclear Experimental Reactor (ITER) neutral beam design

    International Nuclear Information System (INIS)

    Myers, T.J.; Brook, J.W.; Spampinato, P.T.; Mueller, J.P.; Luzzi, T.E.; Sedgley, D.W.

    1990-10-01

    This report discusses the following topics on ITER neutral beam design: ion dump; neutralizer and module gas flow analysis; vacuum system; cryogenic system; maintainability; power distribution; and system cost

  20. (IAM Series No 005) Are “Market Neutral” Hedge Funds Really Market Neutral?

    OpenAIRE

    Andrew Patton

    2004-01-01

    One can consider the concept of market neutrality for hedge funds as having breadth and depth: breadth reflects the number of market risks to which a fund is neutral, while depth reflects the completeness of the neutrality of the fund to market risks. We focus on market neutrality depth, and propose five different neutrality concepts. Mean neutrality nests the standard correlation-based definition of neutrality. Variance neutrality, Value-at-Risk neutrality and tail neutrality all relate to t...

  1. Steady state neutral beam injector

    International Nuclear Information System (INIS)

    Mattoo, S.K.; Bandyopadhyay, M.; Baruah, U.K.; Bisai, N.; Chakbraborty, A.K.; Chakrapani, Ch.; Jana, M.R.; Bajpai, M.; Jaykumar, P.K.; Patel, D.; Patel, G.; Patel, P.J.; Prahlad, V.; Rao, N.V.M.; Rotti, C.; Singh, N.P.; Sridhar, B.

    2000-01-01

    Learning from operational reliability of neutral beam injectors in particular and various heating schemes including RF in general on TFTR, JET, JT-60, it has become clear that neutral beam injectors may find a greater role assigned to them for maintaining the plasma in steady state devices under construction. Many technological solutions, integrated in the present day generation of injectors have given rise to capability of producing multimegawatt power at many tens of kV. They have already operated for integrated time >10 5 S without deterioration in the performance. However, a new generation of injectors for steady state devices have to address to some basic issues. They stem from material erosion under particle bombardment, heat transfer > 10 MW/m 2 , frequent regeneration of cryopanels, inertial power supplies, data acquisition and control of large volume of data. Some of these engineering issues have been addressed to in the proposed neutral beam injector for SST-1 at our institute; the remaining shall have to wait for the inputs of the database generated from the actual experience with steady state injectors. (author)

  2. Γ-source Neutral Point Clamped Inverter

    DEFF Research Database (Denmark)

    Mo, Wei; Loh, Poh Chiang; Blaabjerg, Frede

    Transformer based Z-source inverters are recently proposed to achieve promising buck-boost capability. They have improved higher buck-boost capability, smaller size and less components count over Z-source inverters. On the other hand, neutral point clamped inverters have less switching stress...... and better output performance comparing with traditional two-level inverters. Integrating these two types of configurations can help neutral point inverters achieve enhanced votlage buck-boost capability....

  3. Plasma heating with multi-MeV neutral atom beams

    International Nuclear Information System (INIS)

    Grisham, L.R.; Post, D.E.; Mikkelsen, D.R.; Eubank, H.P.

    1981-10-01

    We explore the utility and feasibility of neutral beams of greater than or equal to 6 AMU formed from negative ions, and also of D 0 formed from D - . The negative ions would be accelerated to approx. 1 to 2 MeV/AMU and neutralized, whereupon the neutral atoms would be used to heat and, perhaps, to drive current in magnetically confined plasmas. Such beams appear feasible and offer the promise of significant advantages relative to conventional neutral beams based on positive deuterium ions at approx. 150 keV

  4. Net neutrality towards a co-regulatory solution

    CERN Document Server

    Marsden, Christopher T

    2010-01-01

    In considering market developments and policy responses to some of the most heated net-neutrality debates in Europe and the United States, Net Neutrality is the first, fully comprehensive overview of the subject. This book is also unique in providing readers with a supplementary outline of recommended policy prescriptives.

  5. Improvements in data display

    International Nuclear Information System (INIS)

    Ellis, G.W.

    1979-01-01

    An analog signal processor is described in this patent for connecting a source of analog signals to a cathode ray tube display in order to extend the dynamic range of the display. This has important applications in the field of computerised X-ray tomography since significant medical information, such as tumours in soft tissue, is often represented by minimal level changes in image density. Cathode ray tube displays are limited to approximately 15 intensity levels. Thus if both strong and weak absorption of the X-rays occurs, the dynamic range of the transmitted signals will be too large to permit small variations to be examined directly on a cathode ray display. Present tomographic image reconstruction methods are capable of quantising X-ray absorption density measurements into 256 or more distinct levels and a description is given of the electronics which enables the upper and lower range of intensity levels to be independently set and continuously varied. (UK)

  6. Crystal structure and size-dependent neutralization properties of HK20, a human monoclonal antibody binding to the highly conserved heptad repeat 1 of gp41.

    Directory of Open Access Journals (Sweden)

    Charles Sabin

    Full Text Available The human monoclonal antibody (mAb HK20 neutralizes a broad spectrum of primary HIV-1 isolates by targeting the highly conserved heptad repeat 1 (HR1 of gp41, which is transiently exposed during HIV-1 entry. Here we present the crystal structure of the HK20 Fab in complex with a gp41 mimetic 5-Helix at 2.3 Å resolution. HK20 employs its heavy chain CDR H2 and H3 loops to bind into a conserved hydrophobic HR1 pocket that is occupied by HR2 residues in the gp41 post fusion conformation. Compared to the previously described HR1-specific mAb D5, HK20 approaches its epitope with a different angle which might favor epitope access and thus contribute to its higher neutralization breadth and potency. Comparison of the neutralization activities of HK20 IgG, Fab and scFv employing both single cycle and multiple cycle neutralization assays revealed much higher potencies for the smaller Fab and scFv over IgG, implying that the target site is difficult to access for complete antibodies. Nevertheless, two thirds of sera from HIV-1 infected individuals contain significant titers of HK20-inhibiting antibodies. The breadth of neutralization of primary isolates across all clades, the higher potencies for C-clade viruses and the targeting of a distinct site as compared to the fusion inhibitor T-20 demonstrate the potential of HK20 scFv as a therapeutic tool.

  7. Energy spectrum of neutrals formed in an ion accelerator

    International Nuclear Information System (INIS)

    Fink, J.H.

    1982-01-01

    This work presents an estimate of the energy distribution of the neutrals formed in the ion beam accelerator. However it does not determine the fraction of those neutrals which leave the neutral beam injector and go on into the reactor. To do that, more details of the beam line performance are needed

  8. Targeted toxicological screening for acidic, neutral and basic substances in postmortem and antemortem whole blood using simple protein precipitation and UPLC-HR-TOF-MS

    DEFF Research Database (Denmark)

    Telving, Rasmus; Hasselstrøm, Jørgen Bo; Andreasen, Mette Findal

    2016-01-01

    -HR-TOF-MS was achieved in one injection. This method covered basic substances, substances traditionally analyzed in negative ESI (e.g., salicylic acid), small highly polar substances such as beta- and gamma-hydroxybutyric acid (BHB and GHB, respectively) and highly non-polar substances such as amiodarone. The new method......A broad targeted screening method based on broadband collision-induced dissociation (bbCID) ultra-performance liquid chromatography high-resolution time-of-flight mass spectrometry (UPLC-HR-TOF-MS) was developed and evaluated for toxicological screening of whole blood samples. The acidic, neutral...... was performed on spiked whole blood samples and authentic postmortem and antemortem whole blood samples. For most of the basic drugs, the established cut-off limits were very low, ranging from 0.25ng/g to 50ng/g. The established cut-off limits for most neutral and acidic drugs, were in the range from 50ng...

  9. Method to minimize the low-frequency neutral-point voltage oscillations with time-offset injection for neutral-point-clamped inverters

    DEFF Research Database (Denmark)

    Choi, Uimin; Lee, Kyo-Beum; Blaabjerg, Frede

    2013-01-01

    This paper proposes a method to reduce the low-frequency neutral-point voltage oscillations. The neutral-point voltage oscillations are considerably reduced by adding a time-offset to the three phase turn-on times. The proper time-offset is simply calculated considering the phase currents and dwell...

  10. Coupled plasma-neutral transport model for the scrape-off region

    International Nuclear Information System (INIS)

    Galambos, J.D.; Peng, Y.K.M.; Heifetz, D.

    1985-03-01

    Analysis of the scrape-off region requires treatment of the plasma transport along and across the field lines and inclusion of the neutral transport effects. A method for modeling the scrape-off region that is presented here uses separate models for each of these aspects that are coupled together through an iteration procedure that requires only minimal numerical effort. The method is applied here to estimate the neutral pumping rates in the pump-limiter and divertor options for a proposed deuterium-tritium (D-T) ignition experiment. High neutral recycling in the vicinity of the neutralizer plate dramatically affects pumping rates for both the pump-limiter and divertor. In both cases, the plasma flow into the channel surrounding the neutralizer plate is greatly reduced by the neutral recycling. The fraction of this flow that is pumped can be large (> 50%), but in general it is dependent on the particular geometry and plasma conditions. It is estimated that pumping speeds approximately greater than 10 5 L/s are adequate for the exhaust requirements in the pump-limiter and the divertor cases. Also, high neutral recycling on the front surface of the limiter tends to increase the neutral pumping rate

  11. Economic Features of the Internet and Network Neutrality

    OpenAIRE

    Nicholas Economides

    2015-01-01

    We discuss the issue of a possible abolition of network neutrality and the introduction of paid prioritization by residential broadband access networks.We show that, in short run analysis where bandwidth is fixed, and in the absence of congestion, network neutrality tends to maximize total surplus. When an ISP violates network neutrality and invests the extra profits to bandwidth expansion, the presence of more bandwidth alleviates the allocative distortion, and can even reverse it. We also d...

  12. Vendor neutral archive in PACS

    International Nuclear Information System (INIS)

    Agarwal, Tapesh Kumar; Sanjeev

    2012-01-01

    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

  13. Material failures observed in Doublet III neutral beamlines

    International Nuclear Information System (INIS)

    Bailey, E.W.; Colleraine, A.; Doll, D.; Grunloh, H.; Kim, J.; Langhorn, A.; Thurgood, B.

    1983-12-01

    The Doublet III neutral beam injectors consist of three separable spools two meters in diameter by four meters long overall when assembled. Contained within these spools are the neutralizers, ion dumps, deflecting magnet, calorimeter dumps, cryogenic panels and beam scraping collimators 3,7. To date three beamlines are in operation on Doublet III, and the beams have accumulated operating time of approximately 32 months, with the oldest having been in operation for 18 months. During this time operation of DIII with the neutral beam sources has demonstrated the following: 7.8 MW injected neutrals from three beamlines (6 sources), high β (4.5%), and non-circular plasma shape. The sources have also exhibited a very reliable injected shot history 4, 5, 6, 8. Material failures encountered during the operation of DIII N.B. injectors and the solutions to these failures are described. Failures include cracking of the neutralizer exit collimator due to heating cycles, failure of cyropanel support rods due to cooling cycles, failure of the sliding drive of the moveable calorimeter due to friction

  14. Altered dynamics of broad-leaved tree species in a Chinese subtropical montane mixed forest: the role of an anomalous extreme 2008 ice storm episode.

    Science.gov (United States)

    Ge, Jielin; Xiong, Gaoming; Wang, Zhixian; Zhang, Mi; Zhao, Changming; Shen, Guozhen; Xu, Wenting; Xie, Zongqiang

    2015-04-01

    Extreme climatic events can trigger gradual or abrupt shifts in forest ecosystems via the reduction or elimination of foundation species. However, the impacts of these events on foundation species' demography and forest dynamics remain poorly understood. Here we quantified dynamics for both evergreen and deciduous broad-leaved species groups, utilizing a monitoring permanent plot in a subtropical montane mixed forest in central China from 2001 to 2010 with particular relevance to the anomalous 2008 ice storm episode. We found that both species groups showed limited floristic alterations over the study period. For each species group, size distribution of dead individuals approximated a roughly irregular and flat shape prior to the ice storm and resembled an inverse J-shaped distribution after the ice storm. Furthermore, patterns of mortality and recruitment displayed disequilibrium behaviors with mortality exceeding recruitment for both species groups following the ice storm. Deciduous broad-leaved species group accelerated overall diameter growth, but the ice storm reduced evergreen small-sized diameter growth. We concluded that evergreen broad-leaved species were more susceptible to ice storms than deciduous broad-leaved species, and ice storm events, which may become more frequent with climate change, might potentially threaten the perpetuity of evergreen-dominated broad-leaved forests in this subtropical region in the long term. These results underscore the importance of long-term monitoring that is indispensible to elucidate causal links between forest dynamics and climatic perturbations.

  15. Fault detection and protection system for neutral beam generators on the Neutral Beam Engineering Test Facility (NBETF)

    International Nuclear Information System (INIS)

    deVries, G.J.; Chesley, K.L.; Owren, H.M.

    1983-12-01

    Neutral beam sources, their power supplies and instrumentation can be damaged from high voltage sparkdown or from overheating due to excessive currents. The Neutral Beam Engineering Test Facility (NBETF) in Berkeley has protective electronic hardware that senses a condition outside a safe operating range and generates a response to terminate such a fault condition. A description of this system is presented in this paper. 8 references, 2 figures, 2 tables

  16. 42 CFR 412.352 - Budget neutrality adjustment.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Budget neutrality adjustment. 412.352 Section 412.352 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... § 412.352 Budget neutrality adjustment. For FY 1992 through FY 1995, CMS will determine an adjustment to...

  17. Helmet-Mounted Display Design Guide

    Science.gov (United States)

    1997-11-03

    on openStack create menu "CSHMD" set the menuitems of "CSHMD" to "(Main Menu; References;-; Definitions;Display Criteria;Display Formats;Display Modes...34Macintosh" then put ":" into dirSep else put "V’ into dirSep put stackPathO&"Resource"&dirSep into gResPath put 0 into gXRef end openStack on

  18. Neutralizing Antibodies and Pathogenesis of Hepatitis C Virus Infection

    Directory of Open Access Journals (Sweden)

    Françoise Stoll-Keller

    2012-10-01

    Full Text Available Hepatitis C virus (HCV infection is a major cause of chronic liver disease worldwide. The interplay between the virus and host innate and adaptive immune responses determines the outcome of infection. There is increasing evidence that host neutralizing responses play a relevant role in the resulting pathogenesis. Furthermore, viral evasion from host neutralizing antibodies has been revealed to be an important contributor in leading both to viral persistence in acute liver graft infection following liver transplantation, and to chronic viral infection. The development of novel model systems to study HCV entry and neutralization has allowed a detailed understanding of the molecular mechanisms of virus-host interactions during antibody-mediated neutralization. The understanding of these mechanisms will ultimately contribute to the development of novel antiviral preventive strategies for liver graft infection and an urgently needed vaccine. This review summarizes recent concepts of the role of neutralizing antibodies in viral clearance and protection, and highlights consequences of viral escape from neutralizing antibodies in the pathogenesis of HCV infection.

  19. Next-generation phage display: integrating and comparing available molecular tools to enable cost-effective high-throughput analysis.

    Directory of Open Access Journals (Sweden)

    Emmanuel Dias-Neto

    2009-12-01

    sequencing and is proposed as the method of choice over a broad range of phage display applications in vitro, in cells, and in vivo.

  20. Ruggedized Full-Color Flexible OLED Display

    National Research Council Canada - National Science Library

    Hack, Michael

    2003-01-01

    .... The team comprised Universal Display Corporation, Princeton University, the University of Southern California, Penn State University, L3 Displays and Vitex Systems, and was led by Universal Display Corporation (PI: Michael Hack...