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

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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.

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.

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

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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.

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

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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.

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

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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

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

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.

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

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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.

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

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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.

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

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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.

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

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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.

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

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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.

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...

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

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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.

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

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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.

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

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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.

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

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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.

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

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

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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.

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

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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.

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.

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

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

2017-10-25

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

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.

Electric-current Neutralization, Magnetic Shear, and Eruptive Activity in Solar Active Regions

Energy Technology Data Exchange (ETDEWEB)

Liu, Yang; Sun, Xudong [W. W. Hansen Experimental Physics Laboratory, Stanford University, Stanford, CA 94305-4085 (United States); Török, Tibor; Titov, Viacheslav S. [Predictive Science Inc., 9990 Mesa Rim Road, Suite 170, San Diego, CA 92121 (United States); Leake, James E. [NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States)

2017-09-01

The physical conditions that determine whether or not solar active regions (ARs) produce strong flares and coronal mass ejections (CMEs) are not yet well understood. Here, we investigate the association between electric-current neutralization, magnetic shear along polarity inversion lines (PILs), and eruptive activity in four ARs: two emerging and two well-developed ones. We find that the CME-producing ARs are characterized by a strongly non-neutralized total current, while the total current in the ARs that did not produce CMEs is almost perfectly neutralized. The difference in the PIL shear between these two groups is much less pronounced, which suggests that the degree of current neutralization may serve as a better proxy for assessing the ability of ARs to produce CMEs.

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

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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.

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)

Active neutral particle diagnostics for high temperature plasma

International Nuclear Information System (INIS)

Tobita, Kenji

1993-01-01

This paper describes experimental studies related to active neutral particle diagnostics in the JT-60 tokamak. Detection efficiencies of a micro-channel plate (MCP), which has widely used in plasma diagnostics, were determined for ions and neutrals. Multi-step processes for a neutral beam is predicted to enhance the beam stopping cross section in a plasma. In order to confirm the predictions, shine-through for a hydrogen and for a helium beam was measured in the JT-60 ohmic plasmas. The measurements for a hydrogen beam resulted in the cross sectional enhancement in the beam stopping. The same experiment using a helium beam indicated that the cross sectional enhancement for helium was much smaller than that for hydrogen at almost same plasma parameters. Ion temperature diagnostic using active beam scattering was developed in data processing technique, in consideration of the device function of a neutral particle analyzer and in estimation of the effect of beam ion component. Fundamental experiments for detecting helium ions in a plasma were performed using two-electron transfer reaction between a helium atomic beam and helium ions, and the energy distribution and the density of the helium ions were determined. These experiments demonstrated promise of the two-electron transfer reaction as an alpha ash detection in a burning plasma. A parasitic neutral efflux accompanied by active beam injection was investigated. (J.P.N.)

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.

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

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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.

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.

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....

Neutrality as Obstructionist in Academic Activism: Calling Bullshit

Science.gov (United States)

Rose, Barbara J.

2018-01-01

In this essay, the author uses experiences as a teacher educator and learning from a historically significant activism movement to (a) compare values in activism-centered and education-centered organizations, (b) posit ways that the concept of neutrality weakens academic activism, and (c) call for teacher education curricula and practices that…

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)

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

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

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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.

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.

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.

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

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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.

Modeling the LPS Neutralization Activity of Anti-Endotoxins

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Virapong Prachayasittikul

2009-05-01

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

Brain activation while forming memories of fearful and neutral faces in women and men.

Science.gov (United States)

Fischer, Håkan; Sandblom, Johan; Nyberg, Lars; Herlitz, Agneta; Bäckman, Lars

2007-11-01

Event-related functional MRI (fMRI) was used to assess brain activity during encoding of fearful and neutral faces in 12 women and 12 men. In a subsequent memory analysis, the authors separated successful from unsuccessful encoding of both types of faces, based on whether they were remembered or forgotten in a later recognition memory test. Overall, women and men recruited overlapping neural circuitries. Both sexes activated right-sided medial-temporal regions during successful encoding of fearful faces. Successful encoding of neutral faces was associated with left-sided lateral prefrontal and right-sided superior frontal activation in both sexes. In women, relatively greater encoding related activity for neutral faces was seen in the superior parietal and parahippocampal cortices. By contrast, men activated the left and right superior/middle frontal cortex more than women during successful encoding of the same neutral faces. These findings suggest that women and men use similar neural networks to encode facial information, with only subtle sex differences observed for neutral faces.

Feline Immunodeficiency Virus (FIV Neutralization: A Review

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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.

Broadening of neutralization activity to directly block a dominant antibody-driven SARS-coronavirus evolution pathway.

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Jianhua Sui

2008-11-01

Full Text Available Phylogenetic analyses have provided strong evidence that amino acid changes in spike (S protein of animal and human SARS coronaviruses (SARS-CoVs during and between two zoonotic transfers (2002/03 and 2003/04 are the result of positive selection. While several studies support that some amino acid changes between animal and human viruses are the result of inter-species adaptation, the role of neutralizing antibodies (nAbs in driving SARS-CoV evolution, particularly during intra-species transmission, is unknown. A detailed examination of SARS-CoV infected animal and human convalescent sera could provide evidence of nAb pressure which, if found, may lead to strategies to effectively block virus evolution pathways by broadening the activity of nAbs. Here we show, by focusing on a dominant neutralization epitope, that contemporaneous- and cross-strain nAb responses against SARS-CoV spike protein exist during natural infection. In vitro immune pressure on this epitope using 2002/03 strain-specific nAb 80R recapitulated a dominant escape mutation that was present in all 2003/04 animal and human viruses. Strategies to block this nAb escape/naturally occurring evolution pathway by generating broad nAbs (BnAbs with activity against 80R escape mutants and both 2002/03 and 2003/04 strains were explored. Structure-based amino acid changes in an activation-induced cytidine deaminase (AID "hot spot" in a light chain CDR (complementarity determining region alone, introduced through shuffling of naturally occurring non-immune human VL chain repertoire or by targeted mutagenesis, were successful in generating these BnAbs. These results demonstrate that nAb-mediated immune pressure is likely a driving force for positive selection during intra-species transmission of SARS-CoV. Somatic hypermutation (SHM of a single VL CDR can markedly broaden the activity of a strain-specific nAb. The strategies investigated in this study, in particular the use of structural

Formation of Neutral Disk-Like Zone Around the Active Hot Stars in Symbiotic Binaries

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Cariková Z.

2012-06-01

Full Text Available In this contribution we present the ionization structure in the enhanced wind from the hot star in symbiotic binaries during active phases. Rotation of the hot star leads to the compression of the outflowing material towards its equatorial plane. As a result, a neutral disk-like zone around the active hot star near the orbital plane is created. We modeled the compression of the wind and calculated the neutral disk-like zone in the enhanced wind from the hot star using the equation of the photoionization equilibrium. the presence of such neutral disk-like zones was also suggested on the basis of the modeling the spectral energy distribution of symbiotic binaries. We confront the calculated ionization structures in the enhanced wind from the hot star with the observations. the calculated column density of the neutral hydrogen atoms in the neutral disk-like zone and the emission measure of the ionized part of the wind from the hot star are in a good agreement with the quantities derived from observations during active phases. the presence of such neutral disk-like zones is transient, being connected with the active phases of symbiotic binaries. During quiescent phases, such neutral disk-like zones cannot be created because of insufficient mass-loss rate from the hot star.

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...

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.

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

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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.

Analysis of activation and shutdown contact dose rate for EAST neutral beam port

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Chen, Yuqing; Wang, Ji; Zhong, Guoqiang; Li, Jun; Wang, Jinfang; Xie, Yahong; Wu, Bin; Hu, Chundong

2017-12-01

For the safe operation and maintenance of neutral beam injector (NBI), specific activity and shutdown contact dose rate of the sample material SS316 are estimated around the experimental advanced superconducting tokamak (EAST) neutral beam port. Firstly, the neutron emission intensity is calculated by TRANSP code while the neutral beam is co-injected to EAST. Secondly, the neutron activation and shutdown contact dose rates for the neutral beam sample materials SS316 are derived by the Monte Carlo code MCNP and the inventory code FISPACT-2007. The simulations indicate that the primary radioactive nuclides of SS316 are 58Co and 54Mn. The peak contact dose rate is 8.52 × 10-6 Sv/h after EAST shutdown one second. That is under the International Thermonuclear Experimental Reactor (ITER) design values 1 × 10-5 Sv/h.

Serotonin transporter genotype (5-HTTLPR): effects of neutral and undefined conditions on amygdala activation.

Science.gov (United States)

Heinz, Andreas; Smolka, Michael N; Braus, Dieter F; Wrase, Jana; Beck, Anne; Flor, Herta; Mann, Karl; Schumann, Gunter; Büchel, Christian; Hariri, Ahmad R; Weinberger, Daniel R

2007-04-15

A polymorphism of the human serotonin transporter gene (SCL6A4) has been associated with serotonin transporter expression and with processing of aversive stimuli in the amygdala. Functional imaging studies show that during the presentation of aversive versus neutral cues, healthy carriers of the short (s) allele showed stronger amygdala activation than long (l) carriers. However, a recent report suggested that this interaction is driven by amygdala deactivation during presentation of neutral stimuli in s carriers. Functional MRI was used to assess amygdala activation during the presentation of a fixation cross or affectively aversive or neutral visual stimuli in 29 healthy men. Amygdala activation was increased in s carriers during undefined states such as the presentation of a fixation cross compared with emotionally neutral conditions. This finding suggests that s carriers show stronger amygdala reactivity to stimuli and contexts that are relatively uncertain, which we propose are stressful.

Neutral theory and the species abundance distribution: recent developments and prospects for unifying niche and neutral perspectives

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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

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.

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...

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

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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.

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

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Raul Terron-Exposito

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

Non-Cationic Proteins Are Associated with HIV Neutralizing Activity in Genital Secretions of Female Sex Workers.

Science.gov (United States)

Birse, Kenzie D M; Cole, Amy L; Hirbod, Taha; McKinnon, Lyle; Ball, Terry B; Westmacott, Garrett R; Kimani, Joshua; Plummer, Frank; Cole, Alexander M; Burgener, Adam; Broliden, Kristina

2015-01-01

Cationic proteins found in cervicovaginal secretions (CVS) are known to contribute to the early antiviral immune response against HIV-infection in vitro. We here aimed to define additional antiviral factors that are over-expressed in CVS from female sex workers at high risk of infection. CVS were collected from Kenyan HIV-seronegative (n = 34) and HIV-seropositive (n = 12) female sex workers, and were compared with those from HIV-seronegative low-risk women (n = 12). The highly exposed seronegative (HESN) sex workers were further divided into those with less (n = 22) or more (n = 12) than three years of documented sex work. Cationic protein-depleted CVS were assessed for HIV-neutralizing activity by a PBMC-based HIV-neutralizing assay, and then characterized by proteomics. HIV neutralizing activity was detected in all unprocessed CVS, however only CVS from the female sex worker groups maintained its HIV neutralizing activity after cationic protein-depletion. Differentially abundant proteins were identified in the cationic protein-depleted secretions including 26, 42, and 11 in the HESN>3 yr, HESNHIV-positive groups, respectively. Gene ontology placed these proteins into functional categories including proteolysis, oxidation-reduction, and epidermal development. The proteins identified in this study include proteins previously associated with the HESN phenotype in other cohorts as well as novel proteins not yet associated with anti-HIV activities. While cationic proteins appear to contribute to the majority of the intrinsic HIV neutralizing activity in the CVS of low-risk women, a broader range of non-cationic proteins were associated with HIV neutralizing activity in HESN and HIV-positive female sex workers. These results indicate that novel protein factors found in CVS of women with high-risk sexual practices may have inherent antiviral activity, or are involved in other aspects of anti-HIV host defense, and warrant further exploration into their mode of action.

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

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

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

The effect of electro-activation and eggshell powder on the neutralization of acid mine drainage

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Alexey Kastyuchik

2017-01-01

Full Text Available Acid mine drainage (AMD production by sulfide mine tailing (SMT is a major environmental preoccupation because it can degrade water surface quality on account of its strong acidity and advanced content of sulfide, iron (Fe and other metals and metalloids. Acid neutralization and the precipitation of metals present in AMD were carried out by electro-activation with ion-exchange membranes, which is based on the self-generation of necessary conditions for acid neutralization and metal precipitation. The treatment of SMT was carried out by using an electro-activation cell generated alkaline solution in the cathode compartment. After 60 min of electro-activation, a pHcatholyte of 7.9–9.6, depending on the experimental conditions, was obtained. The absence of Fe and other trace metal ions in the catholyte provide evidence that the electro-activation of SMT promotes the precipitation of insoluble trace metals in the cathode compartment. This approach can be applied to real conditions in combination with a pretreatment of SMT neutralization, in which biological calcareous amendments are available. Finally, the electro-activation technology of acid mine drainage may be a feasible, cost-effective approach for SMT neutralization because it focuses on sustainable development.

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...

Method of active charge and current neutralization of intense ion beams for ICF

International Nuclear Information System (INIS)

Guiragossian, Z.G.T.; Orthel, J.L.; Lemons, D.S.; Thode, L.E.

1981-01-01

Methods of generating the beam neutralization electrons with required properties are given in the context of a Light Ion Fusion Experiment (LIFE) designed accelerator. Recently derived envelope equations for neutralized and ballistically focused intense ion beams are applied to the LIFE geometry in which 10 MeV He + multiple beamlets coalesce and undergo 45:1 radial compression while beam pulses experience a 20:1 axial compression in the propagation range of 10 m. Both active and auto-neutralization methods are examined and found to produce initial electron temperatures consistent with the requirement of the envelope equation for both radial and axial adiabatic beam pulse compressions. The stability of neutralized beam propagation is also examined concerning the Pierce type electrostatic instability and for the case of LIFE beams it is found to have insignificant effect. A scaled experimental setup is presented which can serve to perform near term tests on the ballistically focused propagation of neutralized light ion beams

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.

Biological activity of sedaxane---a novel broad-spectrum fungicide for seed treatment.

Science.gov (United States)

Zeun, Ronald; Scalliet, Gabriel; Oostendorp, Michael

2013-04-01

Sedaxane is a new broad-spectrum seed treatment fungicide developed by Syngenta Crop Protection for control of seed- and soil-borne diseases in a broad range of crops. Its physicochemical properties and activity spectrum have been optimised for use as a seed treatment providing both local and systemic protection of the seed and roots of target crops. Sedaxane inhibits respiration by binding to the succinate dehydrogenase complex in the fungal mitochondrium. Its activity spectrum covers seed-borne fungi such as Ustilago nuda, Tilletia caries, Monographella nivalis and Pyrenophora graminea, as well as the soil-borne fungi Rhizoctonia solani, R. cerealis and Typhula incarnata. Under greenhouse conditions, sedaxane showed high levels and consistent protection against U. nuda, P. graminea and Rhizoctonia spp. Under field conditions, efficacy against Rhizoctonia spp. resulted in increased yield compared with the untreated check. Efficacy against snow mould has been shown under very high disease pressure conditions. The combination of sedaxane plus fludioxonil against snow mould can provide resistance management for sustainable use. The broad spectrum and high level of activity in combination with excellent crop tolerance allow the use of sedaxane as a seed treatment in a wide variety of crops. It is a potential tool for precautionary resistance management when combined with other fungicides, especially against pathogens showing a potential for resistance development, such as M. nivalis. © 2012 Society of Chemical Industry.

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)

Potent neutralization of influenza A virus by a single-domain antibody blocking M2 ion channel protein.

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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.

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

International Nuclear Information System (INIS)

Kovtun, Maxim; Kearsley, Elsabe P.; Shekhovtsova, Julia

2015-01-01

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

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.

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.

Hexon and fiber of adenovirus type 14 and 55 are major targets of neutralizing antibody but only fiber-specific antibody contributes to cross-neutralizing activity.

Science.gov (United States)

Feng, Ying; Sun, Xikui; Ye, Xianmiao; Feng, Yupeng; Wang, Jinlin; Zheng, Xuehua; Liu, Xinglong; Yi, Changhua; Hao, Mingli; Wang, Qian; Li, Feng; Xu, Wei; Li, Liang; Li, Chufang; Zhou, Rong; Chen, Ling; Feng, Liqiang

2018-05-01

Re-emerging human adenoviruses type 14 (HAdV14) and 55 (HAdV55) represent two highly virulent adenoviruses. The neutralizing antibody (nAb) responses elicited by infection or immunization remain largely unknown. Herein, we generated hexon-chimeric HAdV14 viruses harboring each single or entire hexon hyper-variable-regions (HVR) from HAdV55, and determined the neutralizing epitopes of human and mouse nAbs. In human sera, hexon-targeting nAbs are type-specific and mainly recognize HVR2, 5, and 7. Fiber-targeting nAbs are only detectable in sera cross-neutralizing HAdV14 and HAdV55 and contribute substantially to cross-neutralization. Penton-binding antibodies, however, show no significant neutralizing activities. In mice immunized with HAdV14 or HAdV55, a single immunization mainly elicited hexon-specific nAbs, which recognized HAdV14 HVR1, 2, and 7 and HAdV55 HVR1 and 2, respectively. After a booster immunization, cross-neutralizing fiber-specific nAbs became detectable. These results indicated that hexon elicits type-specific nAbs whereas fiber induces cross-neutralizing nAbs to HAdV14 and HAdV55, which are of significance in vaccine development. Copyright © 2018 Elsevier Inc. All rights reserved.

Lumbar lordosis angle and trunk and lower-limb electromyographic activity comparison in hip neutral position and external rotation during back squats.

Science.gov (United States)

Oshikawa, Tomoki; Morimoto, Yasuhiro; Kaneoka, Koji

2018-03-01

[Purpose] To compare the lumbar lordosis angle and electromyographic activities of the trunk and lower-limb muscles in the hip neutral position and external rotation during back squats. [Subjects and Methods] Ten healthy males without severe low back pain or lower-limb injury participated in this study. The lumbar lordosis angle and electromyographic activities were measured using three-dimensional motion-capture systems and surface electrodes during four back squats: parallel back squats in the hip neutral position and external rotation and full back squats in the hip neutral position and external rotation. A paired t-test was used to compare parallel and full back squats measurements in the hip neutral position and external rotation, respectively. [Results] During parallel back squats, the average lumbar lordosis angle was significantly larger in hip external rotation than in the hip neutral position. During full back squats, lumbar erector spinae and multifidus activities were significantly lower in hip external rotation than in the hip neutral position, whereas gluteus maximus activity was significantly higher in hip external rotation than in the hip neutral position. [Conclusion] The back squat in hip external rotation induced improvement of lumbar kyphosis, an increasing of the gluteus maximus activity and a decrease of both lumbar erector spinae and multifidus activities.

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

EL4 cell-based colorimetric toxin neutralization activity assays for determination of neutralizing anti-ricin antibodies.

Science.gov (United States)

Lindsey, Changhong Y; Brown, J Edward; Torabazar, Nahid R; Smith, Leonard A

2013-01-01

A recombinant ricin toxin A-chain 1-33/44-198 vaccine (RVEc), developed at the United States Army Medical Research Institute of Infectious Diseases as a vaccine candidate, is under investigation in a phase 1 clinical study. To effectively evaluate the immunogenicity of this ricin vaccine and to eliminate the use of radioactive material, an EL4 cell-based colorimetric toxin neutralization activity (TNA) assay using a CellTiter 96 AQueous One Solution Cell Proliferation Assay Reagent has been developed, optimized, and applied in the vaccine efficacy studies. The TNA assay measures the protective neutralizing anti-ricin antibodies in animal sera by determining the cell viability after ricin exposure in the assay system and comparing it to a purified mouse polyclonal antiricin IgG standard curve. The standard curve of the anti-ricin TNA assay closely fits a four-parameter logistic regression model. The unknown test sample concentration was expressed as microg/mL, but not the 50% effective concentration (EC50), which was determined by most TNA assays. The neutralizing endpoint titers, not the 50% effective dilution (ED50), of human specimens were measured with the TNA assay in support of the clinical study of the RVEc vaccine. The optimal amount of ricin toxin, EL4 cells, and concentration of standards used in the assay system was established to minimize false-negative and false-positive results of serum specimens from the nonclinical and clinical studies of RVEc. The testing conditions were adjusted to optimize assay performance. The colorimetric TNA assay replaced a radioactive TNA assay previously used in the ricin vaccine studies.

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.)

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.

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.

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)

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

Evidence for a modulation of neutral trehalase activity by Ca2+ and cAMP signaling pathways in Saccharomyces cerevisiae

Directory of Open Access Journals (Sweden)

Souza A.C.

2002-01-01

Full Text Available Saccharomyces cerevisiae neutral trehalase (encoded by NTH1 is regulated by cAMP-dependent protein kinase (PKA and by an endogenous modulator protein. A yeast strain with knockouts of CMK1 and CMK2 genes (cmk1cmk2 and its isogenic control (CMK1CMK2 were used to investigate the role of CaM kinase II in the in vitro activation of neutral trehalase during growth on glucose. In the exponential growth phase, cmk1cmk2 cells exhibited basal trehalase activity and an activation ratio by PKA very similar to that found in CMK1CMK2 cells. At diauxie, even though both cells presented comparable basal trehalase activities, cmk1cmk2 cells showed reduced activation by PKA and lower total trehalase activity when compared to CMK1CMK2 cells. To determine if CaM kinase II regulates NTH1 expression or is involved in post-translational modulation of neutral trehalase activity, NTH1 promoter activity was evaluated using an NTH1-lacZ reporter gene. Similar ß-galactosidase activities were found for CMK1CMK2 and cmk1cmk2 cells, ruling out the role of CaM kinase II in NTH1 expression. Thus, CaM kinase II should act in concert with PKA on the activation of the cryptic form of neutral trehalase. A model for trehalase regulation by CaM kinase II is proposed whereby the target protein for Ca2+/CaM-dependent kinase II phosphorylation is not the neutral trehalase itself. The possible identity of this target protein with the recently identified trehalase-associated protein YLR270Wp is discussed.

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.

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

Accelerating the peroxidase-like activity of gold nanoclusters at neutral pH for colorimetric detection of heparin and heparinase activity.

Science.gov (United States)

Hu, Lianzhe; Liao, Hong; Feng, Lingyan; Wang, Min; Fu, Wensheng

2018-04-26

The peroxidase-like catalytic activity of gold nanoclusters (NCs) is quite low around physiological pH, which greatly limits their biological applications. Herein, we found heparin can greatly accelerate the peroxidase-like activity of Au-NCs at neutral pH. The catalytic activity of Au-NCs toward the peroxidase substrate 3,3',5,5'-tetramethylbenzidine (TMB) oxidation by H2O2 was 25-fold increased in the presence of heparin at pH 7. The addition of heparin not only accelerated the initial catalytic rate of Au-NCs, but also prevented the Au-NCs from catalyst deactivation. This allows the sensitive colorimetric detection of heparin at neutral pH. In the presence of heparinase, heparin was hydrolyzed into small fragments, weakening the enhancement effect of catalytic activity. Based on this phenomenon, the sensitive colorimetric determination of heparinase in biological samples was also developed.

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.

The activity of neutral DNAase in rat tissue under radiation carcinogenesis

International Nuclear Information System (INIS)

Kerova, N.I.; Pukhova, G.G.; Chebotarev, E.E.

1984-01-01

Activity of a neutral DNA-ase and its natural inhibitor of protein nature in liver, brain and spleen of rats with malignant neoplasms, which have appeared 14-20 months after animal irradiation with fast neutrons in the dose 0.5-1.0 Gy, have been studied. Increase of free DNA-ase activity and its inhibitor with a simultaneous decrease of their ability to complexing in liver and brain supernatants is shoWn. The changes are mostly manifested in liver and in spleen they are inconsiderable and statistically unreliable

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

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...

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.

Novel α-MSH peptide analogues with broad spectrum antimicrobial activity.

Directory of Open Access Journals (Sweden)

Paolo Grieco

Full Text Available Previous investigations indicate that α-melanocyte-stimulating hormone (α-MSH and certain synthetic analogues of it exert antimicrobial effects against bacteria and yeasts. However, these molecules have weak activity in standard microbiology conditions and this hampers a realistic clinical use. The aim in the present study was to identify novel peptides with broad-spectrum antimicrobial activity in growth medium. To this purpose, the Gly10 residue in the [DNal(2'-7, Phe-12]-MSH(6-13 sequence was replaced with conventional and unconventional amino acids with different degrees of conformational rigidity. Two derivatives in which Gly10 was replaced by the residues Aic and Cha, respectively, had substantial activity against Candida strains, including C. albicans, C. glabrata, and C. krusei and against gram-positive and gram-negative bacteria. Conformational analysis indicated that the helical structure along residues 8-13 is a key factor in antimicrobial activity. Synthetic analogues of α-MSH can be valuable agents to treat infections in humans. The structural preferences associated with antimicrobial activity identified in this research can help further development of synthetic melanocortins with enhanced biological activity.

Activation of toll-like receptors and dendritic cells by a broad range of bacterial molecules

NARCIS (Netherlands)

Boele, L.C.L.; Bajramovic, J.J.; Vries, A.M.M.B.C. de; Voskamp-Visser, I.A.I.; Kaman, W.E.; Kleij, D. van der

2009-01-01

Activation of pattern recognition receptors such as Toll-like receptors (TLRs) by pathogens leads to activation and maturation of dendritic cells (DC), which orchestrate the development of the adaptive immune response. To create an overview of the effects of a broad range of pathogenic bacteria,

Relevance of southward magnetic fields in the neutral sheet to anisotropic distribution of energetic electrons and substorm activity

International Nuclear Information System (INIS)

Lui, A.T.Y.; Meng, C.

1979-01-01

The implications of southward magnetic fields at the magnetotail neutral sheet to the development of streaming anisotropy of energetic electrons and magnetospheric substorm activity are examined. Magnetic field and energetic particle measurements from the Imp 6 spacecraft, the AE index, and global auroral images from DMSP spacecraft are utilized in this study. Criteria are developed to identify events of southward magnetic fields at the neutral sheet which imply the presence of X-type magnetic neutral lines. Several features of the observations suggest that the southward magnetic fields and the implied X-type neutral lines are associated with magnetic bubbles in the neutral sheet region. It is found that the signatures of magnetic bubbles are sometimes detected in association with tailward streaming and flux enhancement of energetic electrons (47 keV< E<350keV). A cigar-shaped anisotropy in the energetic electron distribution is frequently but not always observed before the onset of tailward streaming of energetic electrons. The tailward streaming is magnetic field-aligned and occurs in the form of bursts, suggestic electrons. The tailward streaming is magnetic field-aligned and occurs in the form of bursts, suggesting that the generating process is activated somewhat quasi-periodically and is not in a steady state. Signatures of magnetic bubbles are also detected without any substantial enhancement or detectable tailward streaming of energetic electrons. By comparing Imp 6 observations with the AW index and global auroral images from DMSP spacecraft. It is found that signatures of magnetic bubbles in the neutral sheet are observed during substorms as well as during quiet geomagnetic conditions, indicating that magnetic bubbles are intrinsic features of the neutral sheet in the magnetotail regardless of substorm activity

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.

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

Search for active-sterile neutrino mixing using neutral-current interactions in NOvA

Science.gov (United States)

Adamson, P.; Aliaga, L.; Ambrose, D.; Anfimov, N.; Antoshkin, A.; Arrieta-Diaz, E.; Augsten, K.; Aurisano, A.; Backhouse, C.; Baird, M.; Bambah, B. A.; Bays, K.; Behera, B.; Bending, S.; Bernstein, R.; Bhatnagar, V.; Bhuyan, B.; Bian, J.; Blackburn, T.; Bolshakova, A.; Bromberg, C.; Brown, J.; Brunetti, G.; Buchanan, N.; Butkevich, A.; Bychkov, V.; Campbell, M.; Catano-Mur, E.; Childress, S.; Choudhary, B. C.; Chowdhury, B.; Coan, T. E.; Coelho, J. A. B.; Colo, M.; Cooper, J.; Corwin, L.; Cremonesi, L.; Cronin-Hennessy, D.; Davies, G. S.; Davies, J. P.; Derwent, P. F.; Dharmapalan, R.; Ding, P.; Djurcic, Z.; Dukes, E. C.; Duyang, H.; Edayath, S.; Ehrlich, R.; Feldman, G. J.; Frank, M. J.; Gabrielyan, M.; Gallagher, H. R.; Germani, S.; Ghosh, T.; Giri, A.; Gomes, R. A.; Goodman, M. C.; Grichine, V.; Groh, M.; Group, R.; Grover, D.; Guo, B.; Habig, A.; Hartnell, J.; Hatcher, R.; Hatzikoutelis, A.; Heller, K.; Himmel, A.; Holin, A.; Howard, B.; Hylen, J.; Jediny, F.; Judah, M.; Kafka, G. K.; Kalra, D.; Kasahara, S. M. S.; Kasetti, S.; Keloth, R.; Kolupaeva, L.; Kotelnikov, S.; Kourbanis, I.; Kreymer, A.; Kumar, A.; Kurbanov, S.; Lackey, T.; Lang, K.; Lee, W. M.; Lin, S.; Lokajicek, M.; Lozier, J.; Luchuk, S.; Maan, K.; Magill, S.; Mann, W. A.; Marshak, M. L.; Matera, K.; Matveev, V.; Méndez, D. P.; Messier, M. D.; Meyer, H.; Miao, T.; Miller, W. H.; Mishra, S. R.; Mohanta, R.; Moren, A.; Mualem, L.; Muether, M.; Mufson, S.; Murphy, R.; Musser, J.; Nelson, J. K.; Nichol, R.; Niner, E.; Norman, A.; Nosek, T.; Oksuzian, Y.; Olshevskiy, A.; Olson, T.; Paley, J.; Patterson, R. B.; Pawloski, G.; Pershey, D.; Petrova, O.; Petti, R.; Phan-Budd, S.; Plunkett, R. K.; Poling, R.; Potukuchi, B.; Principato, C.; Psihas, F.; Radovic, A.; Rameika, R. A.; Rebel, B.; Reed, B.; Rocco, D.; Rojas, P.; Ryabov, V.; Sachdev, K.; Sail, P.; Samoylov, O.; Sanchez, M. C.; Schroeter, R.; Sepulveda-Quiroz, J.; Shanahan, P.; Sheshukov, A.; Singh, J.; Singh, J.; Singh, P.; Singh, V.; Smolik, J.; Solomey, N.; Song, E.; Sousa, A.; Soustruznik, K.; Strait, M.; Suter, L.; Talaga, R. L.; Tas, P.; Thayyullathil, R. B.; Thomas, J.; Tian, X.; Tognini, S. C.; Tripathi, J.; Tsaris, A.; Urheim, J.; Vahle, P.; Vasel, J.; Vinton, L.; Vold, A.; Vrba, T.; Wang, B.; Wetstein, M.; Whittington, D.; Wojcicki, S. G.; Wolcott, J.; Yadav, N.; Yang, S.; Zalesak, J.; Zamorano, B.; Zwaska, R.; NOvA Collaboration

2017-10-01

We report results from the first search for sterile neutrinos mixing with active neutrinos through a reduction in the rate of neutral-current interactions over a baseline of 810 km between the NOvA detectors. Analyzing a 14-kton detector equivalent exposure of 6.05 ×1020 protons-on-target in the NuMI beam at Fermilab, we observe 95 neutral-current candidates at the Far Detector compared with 83.5 ±9.7 (stat ) ±9.4 (syst ) events predicted assuming mixing only occurs between active neutrino species. No evidence for νμ→νs transitions is found. Interpreting these results within a 3 +1 model, we place constraints on the mixing angles θ24<20.8 ° and θ34<31.2 ° at the 90% C.L. for 0.05 eV2≤Δ m412≤0.5 eV2 , the range of mass splittings that produce no significant oscillations over the Near Detector baseline.

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

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...

Salivary anti-coxsackievirus-B4 neutralizing activity and pattern of immune parameters in patients with type 1 diabetes: a pilot study.

Science.gov (United States)

Nekoua, Magloire Pandoua; Yessoufou, Akadiri; Alidjinou, Enagnon Kazali; Badia-Boungou, Francis; Moutairou, Kabirou; Sane, Famara; Hober, Didier

2018-05-17

Enteroviruses, especially coxsackieviruses B (CV-B), have been associated with the pathogenesis of type 1 diabetes (T1D). An anti-CV-B4 neutralizing activity in saliva of T1D patients was previously reported. Our aim was to study the association between the saliva anti-CV-B4 neutralizing activity and immune parameters in T1D patients in comparison with non-diabetic individuals. Saliva and blood samples were collected from 15 T1D patients and 8 controls. The anti-CV-B4 and anti-poliovirus type 1 (PV-1) activities of saliva and serum samples were determined by a plaque neutralization assay. Quantification of serum cytokines was performed by ELISA and the frequencies of lymphocyte subsets were evaluated using flow cytometry. The levels of salivary anti-CV-B4 neutralizing activity were higher in T1D patients than in controls (p = 0.02), whereas the serum levels of anti-CV-B4 neutralizing activity and the saliva and serum levels of anti-PV-1 neutralizing activity were not different. The proportions of effector CD4 + T cells and CD19 + B cells, but not those of CD4 + T cells, CD8 + T cells and Foxp3 + regulatory T cells, were higher in T1D patients than in controls (p = 0.02 and p = 0.01 respectively). Moreover, serum IFN-γ levels were lower in T1D patients compared to controls (p = 0.03) while IL-4 and IL-10 were not different. There was an association between saliva anti-CV-B4 activity, down-regulation of IFN-γ and B cell expansion in peripheral blood of T1D patients. The association between saliva anti-CV-B4 activity and disturbance of immune system in T1D patients deserves further investigation.

Asialoerythropoietin is a nonerythropoietic cytokine with broad neuroprotective activity in vivo

DEFF Research Database (Denmark)

Erbayraktar, Serhat; Grasso, Giovanni; Sfacteria, Alessandra

2003-01-01

Erythropoietin (EPO) is a tissue-protective cytokine preventing vascular spasm, apoptosis, and inflammatory responses. Although best known for its role in hematopoietic lineages, EPO also affects other tissues, including those of the nervous system. Enthusiasm for recombinant human erythropoietin...... importantly, asialoEPO exhibits a broad spectrum of neuroprotective activities, as demonstrated in models of cerebral ischemia, spinal cord compression, and sciatic nerve crush. These data suggest that nonerythropoietic variants of rhEPO can cross the blood-brain barrier and provide neuroprotection....

Neutralizing activities of caprine antibodies towards conserved regions of the HCV envelope glycoprotein E2

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El-Shenawy Reem

2011-08-01

Full Text Available Abstract Anti HCV vaccine is not currently available and the present antiviral therapies fail to cure approximately half of the treated HCV patients. This study was designed to assess the immunogenic properties of genetically conserved peptides derived from the C-terminal region of HVR-1 and test their neutralizing activities in a step towards developing therapeutic and/or prophylactic immunogens against HCV infection. Antibodies were generated by vaccination of goats with synthetic peptides derived from HCV E2. Viral neutralizing capacity of the generated anti E2 antibodies was tested using in vitro assays. Goats immunized with E2 synthetic peptides termed p412 [a.a 412-419], p430 [a.a 430-447] and p517 [a.a 517-531] generated high titers of antibody responses 2 to 4.5 fold higher than comparable titers of antibodies to the same epitopes in chronic HCV patients. In post infection experiments of native HCV into cultured Huh7.5 cells anti p412 and anti p 517 were proven to be neutralizing to HCV genotype 4a from patients' sera (87.5% and 75% respectively. On the contrary anti p430 exhibited weak viral neutralization capacity on the same samples (31.25%. Furthermore Ab mixes containing anti p430 exhibited reduced viral neutralization properties. From these experiments one could predict that neutralization by Abs towards different E2-epitopes varies considerably and success in the enrichment of neutralization epitope-specific antibodies may be accompanied by favorable results in combating HCV infection. Also, E2 conserved peptides p517 and p412 represent potential components of a candidate peptide vaccine against HCV infection.

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

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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.

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

Science.gov (United States)

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

2015-03-01

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

Enhanced static ground power unit based on flying capacitor based h-bridge hybrid active-neutral-point-clamped converter

DEFF Research Database (Denmark)

Abarzadeh, Mostafa; Madadi Kojabadi, Hossein; Deng, Fujin

2016-01-01

Static power converters have various applications, such as static ground power units (GPUs) for airplanes. This study proposes a new configuration of a static GPU based on a novel nine-level flying capacitor h-bridge active-neutral-point-clamped (FCHB_ANPC) converter. The main advantages of the p......Static power converters have various applications, such as static ground power units (GPUs) for airplanes. This study proposes a new configuration of a static GPU based on a novel nine-level flying capacitor h-bridge active-neutral-point-clamped (FCHB_ANPC) converter. The main advantages...

HIV-1 binding and neutralizing antibodies of injecting drug users

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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.

Characterization of a Large Panel of Rabbit Monoclonal Antibodies against HIV-1 gp120 and Isolation of Novel Neutralizing Antibodies against the V3 Loop.

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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.

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

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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.

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

Science.gov (United States)

Landt, Hermine; Ward, Martin J.; Elvis, Martin; Karovska, Margarita

2014-03-01

Here we present observational evidence that the broad emission line region (BELR) of active galactic nuclei (AGN) generally has an outer boundary. This was already clear for sources with an obvious transition between the broad and narrow components of their emission lines. We show that the narrow component of the higher-order Paschen lines is absent in all sources, revealing a broad emission line profile with a broad, flat top. This indicates that the BELR is kinematically separate from the narrow emission line region. We use the virial theorem to estimate the BELR outer radius from the flat top width of the unblended profiles of the strongest Paschen lines, Paα and Paβ, and find that it scales with the ionizing continuum luminosity roughly as expected from photoionization theory. The value of the incident continuum photon flux resulting from this relationship corresponds to that required for dust sublimation. A flat-topped broad emission line profile is produced by both a spherical gas distribution in orbital motion and an accretion disc wind if the ratio between the BELR outer and inner radius is assumed to be less than ˜100-200. On the other hand, a pure Keplerian disc can be largely excluded, since for most orientations and radial extents of the disc the emission line profile is double-horned.

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.

In vitro genotoxicity of neutral red after photo-activation and metabolic activation in the Ames test, the micronucleus test and the comet assay.

Science.gov (United States)

Guérard, Melanie; Zeller, Andreas; Singer, Thomas; Gocke, Elmar

2012-07-04

Neutral red (Nr) is relatively non-toxic and is widely used as indicator dye in many biological test systems. It absorbs visible light and is known to act as a photosensitizer, involving the generation of reactive oxygen species (type-I reaction) and singlet oxygen (type-II reaction). The mutagenicity of Nr was determined in the Ames test (with Salmonella typhimurium strains TA1535, TA97, TA98, TA98NR, TA100, and TA102) with and without metabolic activation, and with and without photo-activation on agar plates. Similarly to the situation following metabolic activation, photo-mutagenicity of Nr was seen with all Salmonella strains tested, albeit with different effects between these strains. To our knowledge, Nr is the only photo-mutagen showing such a broad action. Since the effects are also observed in strains not known to be responsive to ROS, this indicates that ROS production is not the sole mode of action that leads to photo-genotoxicity. The reactive species produced by irradiation are short-lived as pre-irradiation of an Nr solution did not produce mutagenic effects when added to the bacteria. In addition, mutagenicity in TA98 following irradiation was stronger than in the nitroreductase-deficient strain TA98NR, indicating that nitro derivatives that are transformed by bacterial nitroreductase to hydroxylamines appear to play a role in the photo-mutagenicity of Nr. Photo-genotoxicity of Nr was further investigated in the comet assay and micronucleus test in L5178Y cells. Concentration-dependent increases in primary DNA damage and in the frequency of micronuclei were observed after irradiation. Copyright © 2012 Elsevier B.V. All rights reserved.

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.

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

OpenAIRE

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

2015-01-01

Perovskite oxides (ABO[subscript 3]) have been studied extensively to promote the kinetics of the oxygen evolution reaction (OER) in alkaline electrolytes. However, developing highly active catalysts for OER at near-neutral pH is desirable for many photoelectrochemical/electrochemical devices. In this paper, we systematically studied the activity and stability of well-known perovskite oxides for OER at pH 7. Previous activity descriptors established for perovskite oxides at pH 13, such as hav...

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...

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.

Sodium ions activated phosphofructokinase leading to enhanced D-lactic acid production by Sporolactobacillus inulinus using sodium hydroxide as a neutralizing agent.

Science.gov (United States)

Zheng, Lu; Liu, Mingqing; Sun, Jiaduo; Wu, Bin; He, Bingfang

2017-05-01

Sporolactobacillus inulinus is a superior D-lactic acid-producing bacterium and proposed species for industrial production. The major pathway for D-lactic acid biosynthesis, glycolysis, is mainly regulated via the two irreversible steps catalyzed by the allosteric enzymes, phosphofructokinase (PFK) and pyruvate kinase. The activity level of PFK was significantly consistent with the cell growth and D-lactic acid production, indicating its vital role in control and regulation of glycolysis. In this study, the ATP-dependent PFK from S. inulinus was expressed in Escherichia coli and purified to homogeneity. The PFK was allosterically activated by both GDP and ADP and inhibited by phosphoenolpyruvate; the addition of activators could partly relieve the inhibition by phosphoenolpyruvate. Furthermore, monovalent cations could enhance the activity, and Na + was the most efficient one. Considering this kind activation, NaOH was investigated as the neutralizer instead of the traditional neutralizer CaCO 3 . In the early growth stage, the significant accelerated glucose consumption was achieved in the NaOH case probably for the enhanced activity of Na + -activated PFK. Using NaOH as the neutralizer at pH 6.5, the fermentation time was greatly shortened about 22 h; simultaneously, the glucose consumption rate and the D-lactic acid productivity were increased by 34 and 17%, respectively. This probably contributed to the increased pH and Na + -promoted activity of PFK. Thus, fermentations by S. inulinus using the NaOH neutralizer provide a green and highly efficient D-lactic acid production with easy subsequent purification.

Ablation centration after active eye tracker-assisted LASIK and comparison of flying-spot and broad-beam laser.

Science.gov (United States)

Lin, Jane-Ming; Chen, Wen-Lu; Chiang, Chun-Chi; Tsai, Yi-Yu

2008-04-01

To evaluate ablation centration of flying-spot LASIK, investigate the effect of patient- and surgeon-related factors on centration, and compare flying-spot and broad-beam laser results. This retrospective study comprised 173 eyes of 94 patients who underwent LASIK with the Alcon LADARVision4000 with an active eye-tracking system. The effective tracking rate of the system is 100 Hz. The amount of decentration was analyzed by corneal topography. Patient- (low, high, and extreme myopia; effect of learning) and surgeon-related (learning curve) factors influencing centration were identified. Centration was compared to the SCHWIND Multiscan broad-beam laser with a 50-Hz tracker from a previous study. Mean decentration was 0.36+/-0.18 mm (range: 0 to 0.9 mm). Centration did not differ in low, high, and extreme myopia or in patients' first and second eyes. There were no significant differences in centration between the first 50 LASIK procedures and the last 50 procedures. Comparing flying-spot and broad-beam laser results, there were no differences in centration in low myopia. However, the LADARVision4000 yielded better centration results in high and extreme myopia. The Alcon LADARVision4000 active eye tracking system provides good centration for all levels of myopic correction and better centration than the Schwind broad-beam Multiscan in eyes with high and extreme myopia.

Spraying Brassinolide improves Sigma Broad tolerance in foxtail millet (Setaria italica L.) through modulation of antioxidant activity and photosynthetic capacity.

Science.gov (United States)

Yuan, Xiang-Yang; Zhang, Li-Guang; Huang, Lei; Yang, Hui-Jie; Zhong, Yan-Ting; Ning, Na; Wen, Yin-Yuan; Dong, Shu-Qi; Song, Xi-E; Wang, Hong-Fu; Guo, Ping-Yi

2017-09-11

To explore the role of Brassinolide (BR) in improving the tolerance of Sigma Broad in foxtail millet (Setaria italica L.), effects of 0.1 mg/L of BR foliar application 24 h before 3.37 g/ha of Sigma Broad treatment at five-leaf stage of foxtail millet on growth parameters, antioxidant enzymes, malondialdehyde (MDA), chlorophyll, net photosynthetic rate (P N ), chlorophyll fluorescence and P 700 parameters were studied 7 and 15 d after herbicide treatment, respectively. Results showed that Sigma Broad significantly decreased plant height, activities of superoxide dismutase (SOD), chlorophyll content, P N , PS II effective quantum yield (Y (II)), PS II electron transport rate (ETR (II)), photochemical quantum yield of PSI(Y (I)) and PS I electron transport rate ETR (I), but significantly increased MDA. Compared to herbicide treatment, BR dramatically increased plant height, activities of SOD, Y (II), ETR (II), Y (I) and ETR (I). This study showed BR pretreatment could improve the tolerance of Sigma Broad in foxtail millet through improving the activity of antioxidant enzymes, keeping electron transport smooth, and enhancing actual photochemical efficiency of PS II and PSI.

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.

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...

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.

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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.

The neural fate of neutral information in emotion-enhanced memory.

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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.

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

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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.

Generation and characterization of tabalumab, a human monoclonal antibody that neutralizes both soluble and membrane-bound B-cell activating factor

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Manetta J

2014-08-01

Full Text Available Joseph Manetta, Holly Bina, Paul Ryan, Niles Fox, Derrick R Witcher, Kristine Kikly Biotechnology Discovery Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA Abstract: B-cell activating factor (BAFF is a B-cell survival factor with a key role in B-cell homeostasis and tolerance. Dysregulated BAFF expression may contribute to autoimmune diseases or B-cell malignancies via effects on abnormal B-lymphocyte activation, proliferation, survival, and immunoglobulin secretion. Monoclonal antibodies were generated against human BAFF, characterized for species specificity and affinity, and screened for the ability to neutralize both membrane-bound and soluble BAFF. In addition, studies were undertaken to determine the relative potency of membrane-bound and soluble BAFF. Tabalumab has a high affinity for human, cynomolgus monkey, and rabbit BAFF. No binding to mouse BAFF was detected. Tabalumab was able to neutralize soluble human, cynomolgus monkey, or rabbit BAFF with equal potency. Our data demonstrate that membrane-bound BAFF can be a more potent stimulus for B-cells than soluble BAFF, and tabalumab also neutralized membrane-bound BAFF. Tabalumab prevented BAFF from binding to BAFF receptors and demonstrated pharmacodynamic effects in human BAFF transgenic mice. Tabalumab is a high-affinity human antibody with neutralizing activity against membrane-bound and soluble BAFF. Given our findings that membrane-bound BAFF can have greater in vitro potency than soluble BAFF, neutralization of both forms of BAFF is likely to be important for optimal therapeutic effect. Keywords: autoimmunity, B-cell malignancies, B-cell survival factor, BAFF

Design of multi-megawatt actively cooled beam dumps for the Neutral-Beam Engineering Test Facility

International Nuclear Information System (INIS)

Paterson, J.A.; Koehler, G.; Wells, R.P.

1981-10-01

The Neutral Beam Engineering Test Facility will test Neutral Beam Sources up to 170 keV, 65 Amps, with 30 second beam-on times. For this application actively cooled beam dumps for both the neutral and ionized particles will be required. The dumps will be able to dissipate a wide range of power density profiles by utilizing a standard modular panel design which is incorporated into a moveable support structure. The thermal hydraulic design of the panels permit the dissipation of 2 kW/cm 2 anywhere on the panel surface. The water requirements of the dumps are optimized by restricting the flow to panel sections where the heat flux falls short of the design value. The mechanical design of the beam-dump structures is described along with tests performed on a prototype panel. The prototype tests were performed on two different panel designs, one manufactured by Mc Donnell Douglas (MDAC) the other by United Technologies (UT). The dissipation capabilities of the panels were tested at the critical regions to verify their use in the beam dump assemblies

Neutrino-heated stars and broad-line emission from active galactic nuclei

Science.gov (United States)

Macdonald, James; Stanev, Todor; Biermann, Peter L.

1991-01-01

Nonthermal radiation from active galactic nuclei indicates the presence of highly relativistic particles. The interaction of these high-energy particles with matter and photons gives rise to a flux of high-energy neutrinos. In this paper, the influence of the expected high neutrino fluxes on the structure and evolution of single, main-sequence stars is investigated. Sequences of models of neutrino-heated stars in thermal equilibrium are presented for masses 0.25, 0.5, 0.8, and 1.0 solar mass. In addition, a set of evolutionary sequences for mass 0.5 solar mass have been computed for different assumed values for the incident neutrino energy flux. It is found that winds driven by the heating due to high-energy particles and hard electromagnetic radiation of the outer layers of neutrino-bloated stars may satisfy the requirements of the model of Kazanas (1989) for the broad-line emission clouds in active galactic nuclei.

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

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

Bleaching of Neutral Cotton Seed Oil Using Organic Activated Carbon in a Batch System: Kinetics and Adsorption Isotherms

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Abba Chetima

2018-03-01

Full Text Available In the processing of cotton and neem seeds to obtain oil for diverse uses, enormous quantities of seed husk are generated as waste, which when not properly disposed of, poses environmental problems. One way of reducing this waste is to use it for the production of activated carbon (AC for its multiple applications. In this work, activated carbon was produced from cotton and neem seed husks by carbonization followed by acid activation. The prepared ACs were characterized for its porosity and surface properties as well as for its ability to bleach neutral cotton seed oil. The prepared ACs are very efficient in the decoloration process, as they removed about 96–98% of the pigments compared to 98.4% removal with commercial bleaching earth. Temperature had a pronounced effect on the bleaching of neutral cotton seed oil. Maximum adsorption was observed at 60 °C for a contact time of 45 min. The adsorption kinetics were modelled by the intra-particle and the pseudo-second order equations while the adsorption isotherms followed the Langmuir and Freundlich equations. It is concluded that the organic ACs are efficient in pigment removal from neutral cotton seed oil and therefore are potential bleaching agents for the vegetable oil industry.

Differential neutralizing activities of a single domain camelid antibody (VHH specific for ricin toxin's binding subunit (RTB.

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Cristina Herrera

Full Text Available Ricin, a member of the A-B family of ribosome-inactivating proteins, is classified as a Select Toxin by the Centers for Disease Control and Prevention because of its potential use as a biothreat agent. In an effort to engineer therapeutics for ricin, we recently produced a collection of alpaca-derived, heavy-chain only antibody VH domains (VHH or "nanobody" specific for ricin's enzymatic (RTA and binding (RTB subunits. We reported that one particular RTB-specific VHH, RTB-B7, when covalently linked via a peptide spacer to different RTA-specific VHHs, resulted in heterodimers like VHH D10/B7 that were capable of passively protecting mice against a lethal dose challenge with ricin. However, RTB-B7 itself, when mixed with ricin at a 1 ∶ 10 toxin:antibody ratio did not afford any protection in vivo, even though it had demonstrable toxin-neutralizing activity in vitro. To better define the specific attributes of antibodies associated with ricin neutralization in vitro and in vivo, we undertook a more thorough characterization of RTB-B7. We report that RTB-B7, even at 100-fold molar excess (toxin:antibody was unable to alter the toxicity of ricin in a mouse model. On the other hand, in two well-established cytotoxicity assays, RTB-B7 neutralized ricin with a 50% inhibitory concentration (IC50 that was equivalent to that of 24B11, a well-characterized and potent RTB-specific murine monoclonal antibody. In fact, RTB-B7 and 24B11 were virtually identical when compared across a series of in vitro assays, including adherence to and neutralization of ricin after the toxin was pre-bound to cell surface receptors. RTB-B7 differed from both 24B11 and VHH D10/B7 in that it was relatively less effective at blocking ricin attachment to receptors on host cells and was not able to form high molecular weight toxin:antibody complexes in solution. Whether either of these activities is important in ricin toxin neutralizing activity in vivo remains to be determined.

Maturation Pathways of Cross-Reactive HIV-1 Neutralizing Antibodies

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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

HIV-1 specific antibody titers and neutralization among chronically infected patients on long-term suppressive antiretroviral therapy (ART: a cross-sectional study.

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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.

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...

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.

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

Body mass index, metabolic factors, and striatal activation during stressful and neutral-relaxing states: an FMRI study.

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Jastreboff, Ania M; Potenza, Marc N; Lacadie, Cheryl; Hong, Kwangik A; Sherwin, Robert S; Sinha, Rajita

2011-02-01

Stress is associated with alterations in neural motivational-reward pathways in the ventral striatum (VS), hormonal/metabolic changes, and weight increases. The relationship between these different factors is not well understood. We hypothesized that body mass index (BMI) status and hormonal/metabolic factors would be associated with VS activation. We used functional magnetic resonance imaging (fMRI) to compare brain responses of overweight and obese (OW/OB: BMI ≥ 25 kg/m(2): N=27) individuals with normal weight (NW: BMI<18.5-24.9 kg/m(2): N=21) individuals during exposure to personalized stress, alcohol cue, and neutral-relaxing situations using a validated, autobiographical, script-driven, guided-imagery paradigm. Metabolic factors, including fasting plasma glucose (FPG), insulin, and leptin, were examined for their association with VS activation. Consistent with previous studies, stress and alcohol cue exposure each increased activity in cortico-limbic regions. Compared with NW individuals, OW/OB individuals showed greater VS activation in the neutral-relaxing and stress conditions. FPG was correlated with VS activation. Significant associations between VS activation and metabolic factors during stress and relaxation suggest the involvement of metabolic factors in striatal dysfunction in OW/OB individuals. This relationship may contribute to non-homeostatic feeding in obesity.

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.

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.

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.

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.

Neutral Theory and Scale-Free Neural Dynamics

Science.gov (United States)

Martinello, Matteo; Hidalgo, Jorge; Maritan, Amos; di Santo, Serena; Plenz, Dietmar; Muñoz, Miguel A.

2017-10-01

Neural tissues have been consistently observed to be spontaneously active and to generate highly variable (scale-free distributed) outbursts of activity in vivo and in vitro. Understanding whether these heterogeneous patterns of activity stem from the underlying neural dynamics operating at the edge of a phase transition is a fascinating possibility, as criticality has been argued to entail many possible important functional advantages in biological computing systems. Here, we employ a well-accepted model for neural dynamics to elucidate an alternative scenario in which diverse neuronal avalanches, obeying scaling, can coexist simultaneously, even if the network operates in a regime far from the edge of any phase transition. We show that perturbations to the system state unfold dynamically according to a "neutral drift" (i.e., guided only by stochasticity) with respect to the background of endogenous spontaneous activity, and that such a neutral dynamics—akin to neutral theories of population genetics and of biogeography—implies marginal propagation of perturbations and scale-free distributed causal avalanches. We argue that causal information, not easily accessible to experiments, is essential to elucidate the nature and statistics of neural avalanches, and that neutral dynamics is likely to play an important role in the cortex functioning. We discuss the implications of these findings to design new empirical approaches to shed further light on how the brain processes and stores information.

New Insight into the Hydrogen Evolution Reaction under Buffered Near-Neutral pH Conditions: Enthalpy and Entropy of Activation

KAUST Repository

Shinagawa, Tatsuya

2016-10-06

Electrochemical conversion of thermodynamically stable chemicals of water and carbon dioxide is regarded as a core technology for achieving sustainability in our society. In both cases, the electrochemical hydrogen evolution reaction (HER) is a key reaction, particularly at near-neutral pH. This study addresses the kinetic aspects of the HER in buffered near-neutral pH conditions using a variety of electrode materials (W, Ni, Pt, Au, and Cu) over a wide temperature range (299–346 K). When the overall performance was summarized with respect to the binding energy of the reaction intermediate species, a classic volcano-shaped relationship was obtained. Interestingly, the temperature sensitivity analysis disclosed that smaller activation energies did not always lead to higher performance in 1.5 mol L–1 K-phosphate solution (pH 5.8). Detailed analysis of the temperature- and potential-dependent parameters revealed that smaller activation energies coincided with smaller values of the pre-exponential factor in the Arrhenius’ equation (associated with the entropy of activation). Due to the trade-off relationship of enthalpy–entropy compensation in the current system, the conventional approach of mixing elements of lower and higher binding energies to the intermediate species failed: even though Ni–Cu showed lower apparent activation energy, its activity toward the HER was between that of Ni and Cu due to the lowered entropy of activation. This study demonstrates the unrevealed fundamental aspects of the HER in buffered near-neutral condition, which contributes to the rational development of efficient energy and material conversion systems.

Loss Distribution Analysis of Three-Level Active Neutral-Point-Clamped (3L-ANPC) Converter with Different PWM Strategies

DEFF Research Database (Denmark)

Zhang, Gang; Yang, Yongheng; Iannuzzo, Francesco

2016-01-01

The three-level (3L) Active Neutral-Point-Clamped (ANPC) topology has been introduced to resolve the uneven loss distribution issue in the classical 3L Neutral-Point-Clamped (NPC) topology. This Pulse-Width-Modulation (PWM) strategy is then an important means to fully explore the potential benefits...... are separated in order to improve the loss distribution among the power devices. A comparison between the proposed strategy and other major PWM strategies for the loss distribution is also carried out in this paper. Benchmarking results show that the proposed strategy has effective and superior performance...

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...

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)

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.

Evaluation of smallpox vaccines using variola neutralization.

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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.

The Myth of Neutral Judge: Overcoming Neutrality by the Cognition Theory And the Pursuit of Legal Certainty

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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.

HAMLET - A protein-lipid complex with broad tumoricidal activity.

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Ho, James C S; Nadeem, Aftab; Svanborg, Catharina

2017-01-15

HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is a tumoricidal protein-lipid complex with broad effects against cancer cells of different origin. The therapeutic potential is emphasized by a high degree of specificity for tumor tissue. Here we review early studies of HAMLET, in collaboration with the Orrenius laboratory, and some key features of the subsequent development of the HAMLET project. The early studies focused on the apoptotic response that accompanies death in HAMLET treated tumor cells and the role of mitochondria in this process. In subsequent studies, we have identified a sequence of interactions that starts with the membrane integration of HAMLET and the activation of ion fluxes followed by HAMLET internalization, progressive inhibition of MAPK kinases and GTPases and sorting of HAMLET to different cellular compartments, including the nuclei. Therapeutic efficacy of HAMLET has been demonstrated in animal models of glioblastoma, bladder cancer and intestinal cancer. In clinical studies, HAMLET has been shown to target skin papillomas and bladder cancers. The findings identify HAMLET as a new drug candidate with promising selectivity for cancer cells and a strong therapeutic potential. Copyright © 2016 Elsevier Inc. All rights reserved.

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

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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.

Holotoxin A1 Induces Apoptosis by Activating Acid Sphingomyelinase and Neutral Sphingomyelinase in K562 and Human Primary Leukemia Cells

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Seong-Hoon Yun

2018-04-01

Full Text Available Marine triterpene glycosides are attractive candidates for the development of anticancer agents. Holotoxin A1 is a triterpene glycoside found in the edible sea cucumber, Apostichopus (Stichopus japonicus. We previously showed that cladoloside C2, the 25(26-dihydro derivative of holotoxin A1, induced apoptosis in human leukemia cells by activating ceramide synthase 6. Thus, we hypothesized that holotoxin A1, which is structurally similar to cladoloside C2, might induce apoptosis in human leukemia cells through the same molecular mechanism. In this paper, we compared holotoxin A1 and cladoloside C2 for killing potency and mechanism of action. We found that holotoxin A1 induced apoptosis more potently than cladoloside C2. Moreover, holotoxin A1 induced apoptosis in K562 cells by activating caspase-8 and caspase-3, but not by activating caspase-9. During holotoxin A1-induced apoptosis, acid sphingomyelinase (SMase and neutral SMase were activated in both K562 cells and human primary leukemia cells. Specifically inhibiting acid SMase and neutral SMаse with chemical inhibitors or siRNAs significantly inhibited holotoxin A1–induced apoptosis. These results indicated that holotoxin A1 might induce apoptosis by activating acid SMase and neutral SMase. In conclusion, holotoxin A1 represents a potential anticancer agent for treating leukemia. Moreover, the aglycone structure of marine triterpene glycosides might affect the mechanism involved in inducing apoptosis.

The case for inflow of the broad-line region of active galactic nuclei

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Gaskell, C. Martin; Goosmann, René W.

2016-02-01

The high-ionization lines of the broad-line region (BLR) of thermal active galactic nuclei (AGNs) show blueshifts of a few hundred km/s to several thousand km/sec with respect to the low-ionization lines. This has long been thought to be due to the high-ionization lines of the BLR arising in a wind of which the far side of the outflow is blocked from our view by the accretion disc. Evidence for and against the disc-wind model is discussed. The biggest problem for the model is that velocity-resolved reverberation mapping repeatedly fails to show the expected kinematic signature of outflow of the BLR. The disc-wind model also cannot readily reproduce the red side of the line profiles of high-ionization lines. The rapidly falling density in an outflow makes it difficult to obtain high equivalent widths. We point out a number of major problems with associating the BLR with the outflows producing broad absorption lines. An explanation which avoids all these problems and satisfies the constraints of both the line profiles and velocity-resolved reverberation-mapping is a model in which the blueshifting is due to scattering off material spiraling inwards with an inflow velocity of half the velocity of the blueshifting. We discuss how recent reverberation mapping results are consistent with the scattering-plus-inflow model but do not support a disc-wind model. We propose that the anti-correlation of the apparent redshifting of Hβ with the blueshifting of C iv is a consequence of contamination of the red wings of Hβ by the broad wings of [O iii].

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

International Nuclear Information System (INIS)

Georgoulis, Manolis K.; Titov, Viacheslav S.; Mikić, Zoran

2012-01-01

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

Antiviral Activity of Favipiravir (T-705) against a Broad Range of Paramyxoviruses In Vitro and against Human Metapneumovirus in Hamsters.

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Jochmans, D; van Nieuwkoop, S; Smits, S L; Neyts, J; Fouchier, R A M; van den Hoogen, B G

2016-08-01

The clinical impact of infections with respiratory viruses belonging to the family Paramyxoviridae argues for the development of antiviral therapies with broad-spectrum activity. Favipiravir (T-705) has demonstrated potent antiviral activity against multiple RNA virus families and is presently in clinical evaluation for the treatment of influenza. Here we demonstrate in vitro activity of T-705 against the paramyxoviruses human metapneumovirus (HMPV), respiratory syncytial virus, human parainfluenza virus, measles virus, Newcastle disease virus, and avian metapneumovirus. In addition, we demonstrate activity against HMPV in hamsters. T-705 treatment inhibited replication of all paramyxoviruses tested in vitro, with 90% effective concentration (EC90) values of 8 to 40 μM. Treatment of HMPV-challenged hamsters with T-705 at 200 mg/kg of body weight/day resulted in 100% protection from infection of the lungs. In all treated and challenged animals, viral RNA remained detectable in the respiratory tract. The observation that T-705 treatment had a significant effect on infectious viral titers, with a limited effect on viral genome titers, is in agreement with its proposed mode of action of viral mutagenesis. However, next-generation sequencing of viral genomes isolated from treated and challenged hamsters did not reveal (hyper)mutation. Polymerase activity assays revealed a specific effect of T-705 on the activity of the HMPV polymerase. With the reported antiviral activity of T-705 against a broad range of RNA virus families, this small molecule is a promising broad-range antiviral drug candidate for limiting the viral burden of paramyxoviruses and for evaluation for treatment of infections with (re)emerging viruses, such as the henipaviruses. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Broad spectrum antimicrobial activity of melimine covalently bound to contact lenses.

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Dutta, Debarun; Cole, Nerida; Kumar, Naresh; Willcox, Mark D P

2013-01-07

To develop a stable antimicrobial contact lens, which is effective against the International Organization for Standardization (ISO) panel microorganisms, Acanthamoeba castellanii and drug resistant strains of Pseudomonas aeruginosa and Staphylococcus aureus. Melimine was covalently incorporated into etafilcon A lenses. The amount of peptide present on the lens surface was quantified using amino acid analysis. After coating, the heat stability (121°C), lens surface hydrophobicity (by captive bubble), and in vitro cytotoxicity to mouse L929 cells of the lenses were investigated. Antimicrobial activity against the micro-organisms was evaluated by viable plate count and fluorescence microscopy, measuring the proportion of cell death compared with control lenses with no melimine. The most effective concentration was determined to be 152 ± 44 μg lens(-1) melimine on the lens surface. After coating, lenses were relatively hydrophilic and were nontoxic to mammalian cells. The activity remained high after autoclaving (e.g., 3.1, 3.9, 1.2, and 1.0 log inhibition against P. aeruginosa, S. aureus, A. castellanii, and Fusarium solani, respectively). Fluorescence microscopy confirmed significantly reduced (P bacteria to melimine contact lenses. Viable count confirmed that lenses were active against all the bacteria and fungi from the ISO panel, Acanthamoeba and gave at least 2 log inhibition against all the multidrug resistant S. aureus and P. aeruginosa strains. Melimine may offer excellent potential for development as a broad spectrum antimicrobial coating for contact lenses, showing activity against all the bacterial and fungal ISO panel microorganisms, Acanthamoeba, and antibiotic resistant strains of P. aeruginosa and S. aureus.

Make the Alberta Carbon Levy Revenue Neutral

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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

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

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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.

Recombinant Sheep Pox Virus Proteins Elicit Neutralizing Antibodies.

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Chervyakova, Olga V; Zaitsev, Valentin L; Iskakov, Bulat K; Tailakova, Elmira T; Strochkov, Vitaliy M; Sultankulova, Kulyaisan T; Sandybayev, Nurlan T; Stanbekova, Gulshan E; Beisenov, Daniyar K; Abduraimov, Yergali O; Mambetaliyev, Muratbay; Sansyzbay, Abylay R; Kovalskaya, Natalia Y; Nemchinov, Lev G; Hammond, Rosemarie W

2016-06-07

The aim of this work was to evaluate the immunogenicity and neutralizing activity of sheep pox virus (SPPV; genus Capripoxvirus, family Poxviridae) structural proteins as candidate subunit vaccines to control sheep pox disease. SPPV structural proteins were identified by sequence homology with proteins of vaccinia virus (VACV) strain Copenhagen. Four SPPV proteins (SPPV-ORF 060, SPPV-ORF 095, SPPV-ORF 117, and SPPV-ORF 122), orthologs of immunodominant L1, A4, A27, and A33 VACV proteins, respectively, were produced in Escherichia coli. Western blot analysis revealed the antigenic and immunogenic properties of SPPV-060, SPPV-095, SPPV-117 and SPPV-122 proteins when injected with adjuvant into experimental rabbits. Virus-neutralizing activity against SPPV in lamb kidney cell culture was detected for polyclonal antisera raised to SPPV-060, SPPV-117, and SPPV-122 proteins. To our knowledge, this is the first report demonstrating the virus-neutralizing activities of antisera raised to SPPV-060, SPPV-117, and SPPV-122 proteins.

Recombinant Sheep Pox Virus Proteins Elicit Neutralizing Antibodies

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Olga V. Chervyakova

2016-06-01

Full Text Available The aim of this work was to evaluate the immunogenicity and neutralizing activity of sheep pox virus (SPPV; genus Capripoxvirus, family Poxviridae structural proteins as candidate subunit vaccines to control sheep pox disease. SPPV structural proteins were identified by sequence homology with proteins of vaccinia virus (VACV strain Copenhagen. Four SPPV proteins (SPPV-ORF 060, SPPV-ORF 095, SPPV-ORF 117, and SPPV-ORF 122, orthologs of immunodominant L1, A4, A27, and A33 VACV proteins, respectively, were produced in Escherichia coli. Western blot analysis revealed the antigenic and immunogenic properties of SPPV-060, SPPV-095, SPPV-117 and SPPV-122 proteins when injected with adjuvant into experimental rabbits. Virus-neutralizing activity against SPPV in lamb kidney cell culture was detected for polyclonal antisera raised to SPPV-060, SPPV-117, and SPPV-122 proteins. To our knowledge, this is the first report demonstrating the virus-neutralizing activities of antisera raised to SPPV-060, SPPV-117, and SPPV-122 proteins.

Escape from neutralization by the respiratory syncytial virus-specific neutralizing monoclonal antibody palivizumab is driven by changes in on-rate of binding to the fusion protein

International Nuclear Information System (INIS)

Bates, John T.; Keefer, Christopher J.; Slaughter, James C.; Kulp, Daniel W.; Schief, William R.; Crowe, James E.

2014-01-01

The role of binding kinetics in determining neutralizing potency for antiviral antibodies is poorly understood. While it is believed that increased steady-state affinity correlates positively with increased virus-neutralizing activity, the relationship between association or dissociation rate and neutralization potency is unclear. We investigated the effect of naturally-occurring antibody resistance mutations in the RSV F protein on the kinetics of binding to palivizumab. Escape from palivizumab-mediated neutralization of RSV occurred with reduced association rate (K on ) for binding to RSV F protein, while alteration of dissociation rate (K off ) did not significantly affect neutralizing activity. Interestingly, linkage of reduced K on with reduced potency mirrored the effect of increased K on found in a high-affinity enhanced potency palivizumab variant (motavizumab). These data suggest that association rate is the dominant factor driving neutralization potency for antibodies to RSV F protein antigenic site A and determines the potency of antibody somatic variants or efficiency of escape of viral glycoprotein variants. - Highlights: • The relationship of affinity to neutralization for virus antibodies is uncertain. • Palivizumab binds to RSV escape mutant fusion proteins, but with reduced affinity. • Association rate (K on ) correlated well with the potency of neutralization

Escape from neutralization by the respiratory syncytial virus-specific neutralizing monoclonal antibody palivizumab is driven by changes in on-rate of binding to the fusion protein

Energy Technology Data Exchange (ETDEWEB)

Bates, John T. [The Vanderbilt Vaccine Center, Departments of Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN (United States); Keefer, Christopher J. [The Vanderbilt Vaccine Center, Departments of Pediatrics, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN (United States); Slaughter, James C. [The Vanderbilt Vaccine Center, Departments of Biostatistics and Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN (United States); Kulp, Daniel W. [IAVI Neutralizing Antibody Center and Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA (United States); Schief, William R. [IAVI Neutralizing Antibody Center and Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA (United States); Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA (United States); Crowe, James E., E-mail: james.crowe@vanderbilt.edu [The Vanderbilt Vaccine Center, Departments of Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN (United States); The Vanderbilt Vaccine Center, Departments of Pediatrics, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN (United States)

2014-04-15

The role of binding kinetics in determining neutralizing potency for antiviral antibodies is poorly understood. While it is believed that increased steady-state affinity correlates positively with increased virus-neutralizing activity, the relationship between association or dissociation rate and neutralization potency is unclear. We investigated the effect of naturally-occurring antibody resistance mutations in the RSV F protein on the kinetics of binding to palivizumab. Escape from palivizumab-mediated neutralization of RSV occurred with reduced association rate (K{sub on}) for binding to RSV F protein, while alteration of dissociation rate (K{sub off}) did not significantly affect neutralizing activity. Interestingly, linkage of reduced K{sub on} with reduced potency mirrored the effect of increased K{sub on} found in a high-affinity enhanced potency palivizumab variant (motavizumab). These data suggest that association rate is the dominant factor driving neutralization potency for antibodies to RSV F protein antigenic site A and determines the potency of antibody somatic variants or efficiency of escape of viral glycoprotein variants. - Highlights: • The relationship of affinity to neutralization for virus antibodies is uncertain. • Palivizumab binds to RSV escape mutant fusion proteins, but with reduced affinity. • Association rate (K{sub on}) correlated well with the potency of neutralization.

Preferential amygdala reactivity to the negative assessment of neutral faces.

Science.gov (United States)

Blasi, Giuseppe; Hariri, Ahmad R; Alce, Guilna; Taurisano, Paolo; Sambataro, Fabio; Das, Saumitra; Bertolino, Alessandro; Weinberger, Daniel R; Mattay, Venkata S

2009-11-01

Prior studies suggest that the amygdala shapes complex behavioral responses to socially ambiguous cues. We explored human amygdala function during explicit behavioral decision making about discrete emotional facial expressions that can represent socially unambiguous and ambiguous cues. During functional magnetic resonance imaging, 43 healthy adults were required to make complex social decisions (i.e., approach or avoid) about either relatively unambiguous (i.e., angry, fearful, happy) or ambiguous (i.e., neutral) facial expressions. Amygdala activation during this task was compared with that elicited by simple, perceptual decisions (sex discrimination) about the identical facial stimuli. Angry and fearful expressions were more frequently judged as avoidable and happy expressions most often as approachable. Neutral expressions were equally judged as avoidable and approachable. Reaction times to neutral expressions were longer than those to angry, fearful, and happy expressions during social judgment only. Imaging data on stimuli judged to be avoided revealed a significant task by emotion interaction in the amygdala. Here, only neutral facial expressions elicited greater activity during social judgment than during sex discrimination. Furthermore, during social judgment only, neutral faces judged to be avoided were associated with greater amygdala activity relative to neutral faces that were judged as approachable. Moreover, functional coupling between the amygdala and both dorsolateral prefrontal (social judgment > sex discrimination) and cingulate (sex discrimination > social judgment) cortices was differentially modulated by task during processing of neutral faces. Our results suggest that increased amygdala reactivity and differential functional coupling with prefrontal circuitries may shape complex decisions and behavioral responses to socially ambiguous cues.

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

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Yunoki M

2016-07-01

Full Text Available Mikihiro Yunoki,1-3 Takeshi Kurosu,2 Ritsuko Kubota Koketsu,2,4 Kazuo Takahashi,5 Yoshinobu Okuno,4 Kazuyoshi Ikuta2,4 1Research and Development Division, Japan Blood Products Organization, Tokyo, 2Department of Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, 3Pathogenic Risk Evaluation, Graduate School of Veterinary Medicine, Rakuno Gakuen University, Hokkaido, 4Research and Development Division, The Research Foundation for Microbial Diseases of Osaka University, Kagawa, 5Osaka Prefectural Institute of Public Health, Osaka, Japan Abstract: Japanese encephalitis virus (JEV, West Nile virus (WNV, and dengue virus (DenV are causal agents of Japanese encephalitis, West Nile fever, and dengue fever, respectively. JEV is considered to be indigenized and widespread in Japan, whereas WNV and DenV are not indigenized in Japan. Globulin products seem to reflect the status of the donor population according to antivirus neutralization activity. However, the anti-JEV, -WNV, and -DenV neutralization activities of globulin products derived from donors in Japan have not been clarified. Furthermore, potential candidates for the development of an effective immunotherapeutic drug for encephalitis caused by JEV, WNV, or DenV have also not been identified. Therefore, the aim of this study was to determine the overall status of the donor population in Japan based on globulin products by evaluating anti-JEV, -WNV, and -DenV neutralizing activities of intravenous immunoglobulin. Overall, intravenous immunoglobulin products showed stable neutralizing activity against JEV but showed no or only weak activity against WNV or DenV. These results suggest that the epidemiological level against WNV and DenV in the donor population of Japan is still low, suggesting that these viruses are not yet indigenized. In addition, JEV vaccinations and/or infections in the donor population do not induce a cross-reactive antibody against WNV. Keywords

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

Science.gov (United States)

Bai, Y.; Collier, N. C.; Milestone, N. B.; Yang, C. H.

2011-06-01

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

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

International Nuclear Information System (INIS)

Zhang, Xinsheng; Wallace, Olivia L.; Domi, Arban; Wright, Kevin J.; Driscoll, Jonathan; Anzala, Omu; Sanders, Eduard J.; Kamali, Anatoli; Karita, Etienne; Allen, Susan; Fast, Pat; Gilmour, Jill; Price, Matt A.; Parks, Christopher L.

2015-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2015-08-15

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

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

Similar effectiveness of Fab and F(ab')2 antivenoms in the neutralization of hemorrhagic activity of Vipera berus snake venom in mice

OpenAIRE

Lomonte, Bruno; León Montero, Guillermo; Hanson, Lars Ake

1996-01-01

The ability of two antivenoms to Vipera spp., consisting of Fab (Therapeutic Antibodies), or of F(ab′)2 (Zagreb Institute of Immunology) antibody fragments, to neutralize the hemorrhagic activity of Vipera berus snake venom in mice, was compared. First, the neutralizing potency was determined by in vitro preincubation of venom and antivenom, followed by intradermal injection into mice and subsequent measurement of the hemorrhagic area. Both antivenoms had the same anti-hemorrhagic potency, in...

Study of iodine-iodate isotopic exchange reaction in neutral aqueous solutions by radiotracer technique

International Nuclear Information System (INIS)

Tripathi, R.; Ram, K.D.

1993-01-01

The isotopic exchange of iodine atoms in neutral aqueous solutions of iodate ions and iodine (in KI) is found to obey the rate law R = k [IO 3 - ] 0.4 [I 2 ] 1.2 at 175 o C. The addition of neutral ionic salts, e.g. KCl and KNO 3 , in the reaction mixture showed a slight catalytic effect on the exchange rate. Further, the kinetic salt effect indicated the involvement of at least one neutral species on the rate-determining step. The activation energy in neutral aqueous solutions of iodate ions and iodine is found to be 86 ± 3 kJ mol -1 , which decreases in the presence of KCl (79 ± 3 kJ mol -1 and KNO 3 (82 + 3 kJ mol -1 ). The activation parameters, viz. free energy of activation, enthalpy of activation and entropy of activation, were also calculated. Based on these results, an association-dissociation type of reaction mechanism is proposed for this exchange reaction in neutral aqueous medium, similar to that proposed earlier for iodide-iodate isotopic exchange reaction in neutral aqueous solutions, nitrate eutectic melts and iodide-iodate melts. (author)

Amygdala activation as a marker for selective attention toward neutral faces in a chronic traumatic brain injury population.

Science.gov (United States)

Young, Leanne R; Yu, Weikei; Holloway, Michael; Rodgers, Barry N; Chapman, Sandra B; Krawczyk, Daniel C

2017-09-01

There has been great interest in characterizing the response of the amygdala to emotional faces, especially in the context of social cognition. Although amygdala activation is most often associated with fearful or angry stimuli, there is considerable evidence that the response of the amygdala to neutral faces is both robust and reliable. This characteristic of amygdala function is of particular interest in the context of assessing populations with executive function deficits, such as traumatic brain injuries, which can be evaluated using fMRI attention modulation tasks that evaluate prefrontal control over representations, notably faces. The current study tested the hypothesis that the amygdala may serve as a marker of selective attention to neutral faces. Using fMRI, we gathered data within a chronic traumatic brain injury population. Blood Oxygenation Level Dependent (BOLD) signal change within the left and right amygdalae and fusiform face areas was measured while participants viewed neutral faces and scenes, under conditions requiring participants to (1) categorize pictures of faces and scenes, (2) selectively attend to either faces or scenes, or (3) attend to both faces and scenes. Findings revealed that the amygdala is an effective marker for selective attention to neutral faces and, furthermore, it was more face-specific than the fusiform face area. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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.

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

Neutrality Versus Materiality: A Thermodynamic Theory of Neutral Surfaces

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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

Chemical conditions of the Japanese neutral geothermal reservoirs

International Nuclear Information System (INIS)

Chiba, H.

1991-01-01

The aqueous speciation were calculated for fluids of seven Japanese geothermal systems. The aqueous composition as well as CO 2 partial pressure of fluid in neutral pH geothermal reservoir are controlled by silicate, calcite and anhydrite minerals. The chemical composition of neutral pH geothermal reservoir can be predictable if two parameters (e.g. temperature and one of the cation activities) are provided. (author)

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.

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.

Non-Neutralizing Antibodies Directed against HIV and Their Functions

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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.

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.

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

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.

A paralogue of the phosphomutase-like gene family in Candida glabrata, CgPmu2, gained broad-range phosphatase activity due to a small number of clustered substitutions.

Science.gov (United States)

Orlando, Kelly A; Iosue, Christine L; Leone, Sarah G; Davies, Danielle L; Wykoff, Dennis D

2015-10-15

Inorganic phosphate is required for a range of cellular processes, such as DNA/RNA synthesis and intracellular signalling. The phosphate starvation-inducible phosphatase activity of Candida glabrata is encoded by the gene CgPMU2 (C. glabrata phosphomutase-like protein). CgPMU2 is part of a three-gene family (∼75% identical) created through gene duplication in the C. glabrata clade; only CgPmu2 is a PHO-regulated broad range acid phosphatase. We identified amino acids that confer broad range phosphatase activity on CgPmu2 by creating fusions of sections of CgPMU2 with CgPMU1, a paralogue with little broad range phosphatase activity. We used site-directed mutagenesis on various fusions to sequentially convert CgPmu1 to CgPmu2. Based on molecular modelling of the Pmu proteins on to a histidine phosphatase crystal structure, clusters of amino acids were found in two distinct regions that were able to confer phosphatase activity. Substitutions in these two regions together conferred broad phosphatase activity on CgPmu1. Interestingly, one change is a histidine adjacent to the active site histidine of CgPmu2 and it exhibits a novel ability to partially replace the conserved active site histidine in CgPmu2. Additionally, a second amino acid change was able to confer nt phosphatase activity to CgPmu1, suggesting single amino acid changes neofunctionalize CgPmu2. © 2015 Authors; published by Portland Press Limited.

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

DEFF Research Database (Denmark)

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

2007-01-01

BACKGROUND: Surfactant protein D (SP-D) plays important roles in innate host defense against influenza A virus (IAV) infection. Common human polymorphisms of SP-D have been found in many human populations and associated with increased risk of certain infections. We recently reported that the Thr...... on the CRD of SP-D were found to have differing effects on antiviral activity. Using an mAb that did not interfere with antiviral activity of SP-D, we confirm that natural SP-D trimers had reduced ability to bind to IAV. In addition, the trimers had reduced ability to neutralize IAV as compared to natural...... indicate that a common human polymorphic form of SP-D may modulate host defense against IAV and give impetus to clinical studies correlating this genotype with risk for IAV infection in susceptible groups. We also show that mAbs directed against different areas on the carbohydrate recognition domain of SP...

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.

Reporter gene assay for the quantification of the activity and neutralizing antibody response to TNFα antagonists

DEFF Research Database (Denmark)

Lallemand, Christophe; Kavrochorianou, Nadia; Steenholdt, Casper

2011-01-01

A cell-based assay has been developed for the quantification of the activity of TNFα antagonists based on human erythroleukemic K562 cells transfected with a NFκB regulated firefly luciferase reporter-gene construct. Both drug activity and anti-drug neutralizing antibodies can be quantified...... with a high degree of precision within 2h, and without interference from cytokines and other factors known to activate NFκB. The assay cells also contain the Renilla luciferase reporter gene under the control of a constitutive promoter that allows TNFα-induced firefly luciferase activity to be normalized...... relative to Renilla luciferase expression. Thus, results are independent of cell number or differences in cell viability, resulting in intra and inter assay coefficients of variation of 10% or less. Normalization of results relative to the expression of an internal standard also provides a means...

Modeling of modification experiments involving neutral-gas release

International Nuclear Information System (INIS)

Bernhardt, P.A.

1983-01-01

Many experiments involve the injection of neutral gases into the upper atmosphere. Examples are critical velocity experiments, MHD wave generation, ionospheric hole production, plasma striation formation, and ion tracing. Many of these experiments are discussed in other sessions of the Active Experiments Conference. This paper limits its discussion to: (1) the modeling of the neutral gas dynamics after injection, (2) subsequent formation of ionosphere holes, and (3) use of such holes as experimental tools

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

Antibody-mediated neutralization of Ebola virus can occur by two distinct mechanisms

International Nuclear Information System (INIS)

Shedlock, Devon J.; Bailey, Michael A.; Popernack, Paul M.; Cunningham, James M.; Burton, Dennis R.; Sullivan, Nancy J.

2010-01-01

Human Ebola virus causes severe hemorrhagic fever disease with high mortality and there is no vaccine or treatment. Antibodies in survivors occur early, are sustained, and can delay infection when transferred into nonhuman primates. Monoclonal antibodies (mAbs) from survivors exhibit potent neutralizing activity in vitro and are protective in rodents. To better understand targets and mechanisms of neutralization, we investigated a panel of mAbs shown previously to react with the envelope glycoprotein (GP). While one non-neutralizing mAb recognized a GP epitope in the nonessential mucin-like domain, the rest were specific for GP1, were neutralizing, and could be further distinguished by reactivity with secreted GP. We show that survivor antibodies, human KZ52 and monkey JP3K11, were specific for conformation-dependent epitopes comprising residues in GP1 and GP2 and that neutralization occurred by two distinct mechanisms; KZ52 inhibited cathepsin cleavage of GP whereas JP3K11 recognized the cleaved, fusion-active form of GP.

Quantum Chemical Investigation on the Antioxidant Activity of Neutral and Anionic Forms of Juglone: Metal Chelation and Its Effect on Radical Scavenging Activity

Directory of Open Access Journals (Sweden)

Aymard Didier Fouegue Tamafo

2017-01-01

Full Text Available The chelation ability of divalent Mg, Ca, Fe, Co, Ni, Cu, Zn, and monovalent Cu ions by neutral and anionic forms of juglone has been investigated at DFT/B3LYP/6-31+G(d,p level of theory in gas and aqueous phases. It is noteworthy that only the 1 : 1 stoichiometry was considered herein. The effects of these metals on the radical scavenging activity of neutral juglone were evaluated via the usual descriptors of hydrogen atom transfer. According to our results, metal chelation by the two forms of juglone was spontaneous and exothermic in both media. Based on the binding energies, Cu(II ion showed the highest affinity for the ligands. QTAIM analyses identified the metal-ligand bonds as intermediate type interactions in all the chelates, except those of Ca and Mg. It was also found that the chelates were better radical scavengers than the ligands. In the gas phase, the scavenging activity of the compounds was found to be governed by direct hydrogen atom transfer, the Co(II chelate being the most reactive. In the aqueous phase also, the sequential proton loss electron transfer was preferred by all the molecules, while the Cu(II chelates were the most reactive.

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

International Nuclear Information System (INIS)

Pan, Yang; Sasaki, Tadahiro; Kubota-Koketsu, Ritsuko; Inoue, Yuji; Yasugi, Mayo; Yamashita, Akifumi; Ramadhany, Ririn; Arai, Yasuha; Du, Anariwa; Boonsathorn, Naphatsawan; Ibrahim, Madiha S.

2014-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-07-18

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

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

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.

Binding neutral information to emotional contexts: Brain dynamics of long-term recognition memory.

Science.gov (United States)

Ventura-Bort, Carlos; Löw, Andreas; Wendt, Julia; Moltó, Javier; Poy, Rosario; Dolcos, Florin; Hamm, Alfons O; Weymar, Mathias

2016-04-01

There is abundant evidence in memory research that emotional stimuli are better remembered than neutral stimuli. However, effects of an emotionally charged context on memory for associated neutral elements is also important, particularly in trauma and stress-related disorders, where strong memories are often activated by neutral cues due to their emotional associations. In the present study, we used event-related potentials (ERPs) to investigate long-term recognition memory (1-week delay) for neutral objects that had been paired with emotionally arousing or neutral scenes during encoding. Context effects were clearly evident in the ERPs: An early frontal ERP old/new difference (300-500 ms) was enhanced for objects encoded in unpleasant compared to pleasant and neutral contexts; and a late central-parietal old/new difference (400-700 ms) was observed for objects paired with both pleasant and unpleasant contexts but not for items paired with neutral backgrounds. Interestingly, objects encoded in emotional contexts (and novel objects) also prompted an enhanced frontal early (180-220 ms) positivity compared to objects paired with neutral scenes indicating early perceptual significance. The present data suggest that emotional--particularly unpleasant--backgrounds strengthen memory for items encountered within these contexts and engage automatic and explicit recognition processes. These results could help in understanding binding mechanisms involved in the activation of trauma-related memories by neutral cues.

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

Neutralization of toxicological activities of medically-relevant Bothrops snake venoms and relevant toxins by two polyvalent bothropic antivenoms produced in Peru and Brazil.

Science.gov (United States)

Estevao-Costa, Maria I; Gontijo, Silea S; Correia, Barbara L; Yarleque, Armando; Vivas-Ruiz, Dan; Rodrigues, Edith; Chávez-Olortegui, Carlos; Oliveira, Luciana S; Sanchez, Eladio F

2016-11-01

Snakebite envenoming is a neglected public pathology, affecting especially rural communities or isolated areas of tropical and subtropical Latin American countries. The parenteral administration of antivenom is the mainstay and the only validated treatment of snake bite envenoming. Here, we assess the efficacy of polyspecific anti-Bothrops serum (α-BS) produced in the Instituto Nacional de Salud (INS, Peru) and at the Fundação Ezequiel Dias (FUNED, Brazil), to neutralize the main toxic activities induced by five medically-relevant venoms of: Bothrops atrox, B. barnetti, and B. pictus from Peru, and the Brazilian B. jararaca and B. leucurus, all of them inhabiting different geographical locations. Protein electrophoretic patterns of these venoms showed significant differences in composition, number and intensity of bands. Another goal was to evaluate the efficacy and safety of lyophilized α-BS developed at INS to neutralize the detrimental effects of these venoms using in vivo and in vitro assays. The availability of lyophilized α-BS has relevant significance in its distribution to distant rural communities where the access to antivenom in health facilities is more difficult. Despite the fact that different antigen mixtures were used for immunization during antivenom production, our data showed high toxin-neutralizing activity of α-BS raised against Bothrops venoms. Moreover, the antivenom cross-reacted even against venoms not included in the immunization mixture. Furthermore, we have evaluated the efficacy of both α-BS to neutralize key toxic compounds belonging to the predominant protein families of Bothrops snakes. Most significantly, both α-BS cross-specifically neutralized the main toxicological activities e.g. lethality and hemorrhage induced by these venoms. Thus, our data indicate that both α-BS are equally effective to treat snake bite victims inflicted by Bothrops snakes particularly B. atrox, responsible for the largest numbers of human

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.

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.

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.

Improvement of activated carbons as oxygen reduction catalysts in neutral solutions by ammonia gas treatment and their performance in microbial fuel cells

KAUST Repository

Watson, Valerie J.; Nieto Delgado, Cesar; Logan, Bruce E.

2013-01-01

Commercially available activated carbon (AC) powders from different precursor materials (peat, coconut shell, coal, and hardwood) were treated with ammonia gas at 700 C to improve their performance as oxygen reduction catalysts in neutral p

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.)

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

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

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.

Duo-Active-Neutral-Point-Clamped Multilevel Converter: An Exploration of the Fundamental Topology and Experimental Verification

DEFF Research Database (Denmark)

Dargahi, Vahid; Corzine, Keith A.; Enslin, Johan H.

2018-01-01

For medium-voltage (MV) industrial applications such as the HVDC and adjustable-speed ac-motor drives, the multilevel voltage-source converters are deemed the predominant topologies. One of the promising derived-topologies from the neutral-point-clamped (NPC) configuration is the active NPC (ANPC......) structure with an improved balanced lossdistribution performance. This paper introduces duo-ANPC (D-ANPC) converter topology, which is controlled with a new modulation technique. The suggested control method regulates the flying capacitor (FC) voltages naturally at their reference values and preserves...

Charge exchange measurements of MHD activity during neutral beam injection in the Princeton Large Torus and the Poloidal Divertor Experiment

International Nuclear Information System (INIS)

Goldston, R.J.; Kaita, R.; Beiersdorfer, P.; Gammel, G.; Herndon, D.L.; McCune, D.C.; Meyerhofer, D.D.

1987-01-01

The horizontally scanning, multi-angle charge exchange analysers on the Princeton Large Torus (PLT) and the Poloidal Divertor Experiment (PDX) were used to study the effects of MHD activity on the background ion distribution function and on the beam ion slowing-down process during high power neutral injection. Sawtooth oscillations were observed in the fast ion flux on PLT and PDX, and measurements with neutral beams providing local neutral density enhancement indicated that the ions were transported radially when these events occurred. With near-perpendicular injection in PDX, at the lower toroidal fields necessary to maximize the plasma beta, repetitive bursts of greatly enhanced charge exchange flux were observed. These were associated with the 'fishbone' MHD instability, and a substantial depletion of the perpendicular slowing-down spectrum below the injection energy was seen. A simple phenomenological model for this loss mechanism was developed, and its use in simulation codes has been successful in providing good agreement with the experimental data. The behaviour and characteristics of this model are well matched by direct theoretical calculations. (author)

Charge-exchange measurements of MHD activity during neutral beam injection in the Princeton Large Torus and the Poloidal Divertor Experiment

International Nuclear Information System (INIS)

Goldston, R.J.; Kaita, R.; Beiersdorfer, P.; Gammel, G.; Herndon, D.L.; McCune, D.C.; Meyerhofer, D.D.

1986-07-01

The horizontally scanning, multiangle charge-exchange analyzers on the Princeton Large Torus (PLT) and the Poloidal Divertor Experiment (PDX) were used to study the effects of MHD activity on the background ion distribution function and on the beam ion slowing-down process during high-power neutral injection. Sawtooth oscillations were observed in the fast ion flux on PLT and PDX, and measurements with neutral beams providing local neutral density enhancement indicate that ions are transported radially when these events occur. With near-perpendicular injection in PDX, at the lower toroidal fields necessary to maximize beta, rapid, repetitive bursts of greatly enhanced charge-exchange flux were observed. These are associated with the ''fishbone'' MHD instability, and a substantial depletion of the perpendicular slowing-down spectrum below the injection energy was seen. A simple phenomenological model for this loss mechanism was developed, and its use in simulation codes has been successful in providing good agreement with the data. The behavior and characteristics of this model are well matched by the direct theoretical calculations

A Lactobacillus plantarum Esterase Active on a Broad Range of Phenolic Esters

Science.gov (United States)

Esteban-Torres, María; Landete, José María; Reverón, Inés; Santamaría, Laura; de las Rivas, Blanca

2015-01-01

Lactobacillus plantarum is the lactic acid bacterial species most frequently found in the fermentation of food products of plant origin on which phenolic compounds are abundant. L. plantarum strains showed great flexibility in their ability to adapt to different environments and growth substrates. Of 28 L. plantarum strains analyzed, only cultures from 7 strains were able to hydrolyze hydroxycinnamic esters, such as methyl ferulate or methyl caffeate. As revealed by PCR, only these seven strains possessed the est_1092 gene. When the est_1092 gene was introduced into L. plantarum WCFS1 or L. lactis MG1363, their cultures acquired the ability to degrade hydroxycinnamic esters. These results support the suggestion that Est_1092 is the enzyme responsible for the degradation of hydroxycinnamic esters on the L. plantarum strains analyzed. The Est_1092 protein was recombinantly produced and biochemically characterized. Surprisingly, Est_1092 was able to hydrolyze not only hydroxycinnamic esters, since all the phenolic esters assayed were hydrolyzed. Quantitative PCR experiments revealed that the expression of est_1092 was induced in the presence of methyl ferulate, an hydroxycinnamic ester, but was inhibited on methyl gallate, an hydroxybenzoic ester. As Est_1092 is an enzyme active on a broad range of phenolic esters, simultaneously possessing feruloyl esterase and tannase activities, its presence on some L. plantarum strains provides them with additional advantages to survive and grow on plant environments. PMID:25746986

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.

What does brain response to neutral faces tell us about major depression? evidence from machine learning and fMRI.

Science.gov (United States)

Oliveira, Leticia; Ladouceur, Cecile D; Phillips, Mary L; Brammer, Michael; Mourao-Miranda, Janaina

2013-01-01

A considerable number of previous studies have shown abnormalities in the processing of emotional faces in major depression. Fewer studies, however, have focused specifically on abnormal processing of neutral faces despite evidence that depressed patients are slow and less accurate at recognizing neutral expressions in comparison with healthy controls. The current study aimed to investigate whether this misclassification described behaviourally for neutral faces also occurred when classifying patterns of brain activation to neutral faces for these patients. TWO INDEPENDENT DEPRESSED SAMPLES: (1) Nineteen medication-free patients with depression and 19 healthy volunteers and (2) Eighteen depressed individuals and 18 age and gender-ratio-matched healthy volunteers viewed emotional faces (sad/neutral; happy/neutral) during an fMRI experiment. We used a new pattern recognition framework: first, we trained the classifier to discriminate between two brain states (e.g. viewing happy faces vs. viewing neutral faces) using data only from healthy controls (HC). Second, we tested the classifier using patterns of brain activation of a patient and a healthy control for the same stimuli. Finally, we tested if the classifier's predictions (predictive probabilities) for emotional and neutral face classification were different for healthy controls and depressed patients. Predictive probabilities to patterns of brain activation to neutral faces in both groups of patients were significantly lower in comparison to the healthy controls. This difference was specific to neutral faces. There were no significant differences in predictive probabilities to patterns of brain activation to sad faces (sample 1) and happy faces (samples 2) between depressed patients and healthy controls. Our results suggest that the pattern of brain activation to neutral faces in depressed patients is not consistent with the pattern observed in healthy controls subject to the same stimuli. This difference in

What does brain response to neutral faces tell us about major depression? evidence from machine learning and fMRI.

Directory of Open Access Journals (Sweden)

Leticia Oliveira

Full Text Available A considerable number of previous studies have shown abnormalities in the processing of emotional faces in major depression. Fewer studies, however, have focused specifically on abnormal processing of neutral faces despite evidence that depressed patients are slow and less accurate at recognizing neutral expressions in comparison with healthy controls. The current study aimed to investigate whether this misclassification described behaviourally for neutral faces also occurred when classifying patterns of brain activation to neutral faces for these patients.TWO INDEPENDENT DEPRESSED SAMPLES: (1 Nineteen medication-free patients with depression and 19 healthy volunteers and (2 Eighteen depressed individuals and 18 age and gender-ratio-matched healthy volunteers viewed emotional faces (sad/neutral; happy/neutral during an fMRI experiment. We used a new pattern recognition framework: first, we trained the classifier to discriminate between two brain states (e.g. viewing happy faces vs. viewing neutral faces using data only from healthy controls (HC. Second, we tested the classifier using patterns of brain activation of a patient and a healthy control for the same stimuli. Finally, we tested if the classifier's predictions (predictive probabilities for emotional and neutral face classification were different for healthy controls and depressed patients.Predictive probabilities to patterns of brain activation to neutral faces in both groups of patients were significantly lower in comparison to the healthy controls. This difference was specific to neutral faces. There were no significant differences in predictive probabilities to patterns of brain activation to sad faces (sample 1 and happy faces (samples 2 between depressed patients and healthy controls.Our results suggest that the pattern of brain activation to neutral faces in depressed patients is not consistent with the pattern observed in healthy controls subject to the same stimuli. This

ACDOS1: a computer code to calculate dose rates from neutron activation of neutral beamlines and other fusion-reactor components

International Nuclear Information System (INIS)

Keney, G.S.

1981-08-01

A computer code has been written to calculate neutron induced activation of neutral-beam injector components and the corresponding dose rates as a function of geometry, component composition, and time after shutdown. The code, ACDOS1, was written in FORTRAN IV to calculate both activity and dose rates for up to 30 target nuclides and 50 neutron groups. Sufficient versatility has also been incorporated into the code to make it applicable to a variety of general activation problems due to neutrons of energy less than 20 MeV

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.

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.

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.

Community composition and cellulase activity of cellulolytic bacteria from forest soils planted with broad-leaved deciduous and evergreen trees.

Science.gov (United States)

Yang, Jiang-Ke; Zhang, Jing-Jing; Yu, Heng-Yu; Cheng, Jian-Wen; Miao, Li-Hong

2014-02-01

Cellulolytic bacteria in forest soil provide carbon sources to improve the soil fertility and sustain the nutrient balance of the forest ecological system through the decomposition of cellulosic remains. These bacteria can also be utilized for the biological conversion of biomass into renewable biofuels. In this study, the community compositions and activities of cellulolytic bacteria in the soils of forests planted with broad-leaved deciduous (Chang Qing Garden, CQG) and broad-leaved evergreen (Forest Park, FP) trees in Wuhan, China were resolved through restriction fragment length polymorphism (RFLP) and sequencing analysis of the 16S rRNA gene. All of the isolates exhibited 35 RFLP fingerprint patterns and were clustered into six groups at a similarity level of 50 %. The phylogeny analysis based on the 16S rRNA gene sequence revealed that these RFLP groups could be clustered into three phylogenetic groups and further divided into six subgroups at a higher resolution. Group I consists of isolates from Bacillus cereus, Bacillus subtilis complex (I-A) and from Paenibacillus amylolyticus-related complex (I-B) and exhibited the highest cellulase activity among all of the cellulolytic bacteria isolates. Cluster II consists of isolates belonging to Microbacterium testaceum (II-A), Chryseobacterium indoltheticum (II-B), and Flavobacterium pectinovorum and the related complex (II-C). Cluster III consists of isolates belonging to Pseudomonas putida-related species. The community shift with respect to the plant species and the soil properties was evidenced by the phylogenetic composition of the communities. Groups I-A and I-B, which account for 36.0 % of the cellulolytic communities in the CQG site, are the dominant groups (88.4 %) in the FP site. Alternatively, the ratio of the bacteria belonging to group III (P. putida-related isolates) shifted from 28.0 % in CQG to 4.0 % in FP. The soil nutrient analysis revealed that the CQG site planted with deciduous broad

In vitro neutralization of the scorpion, Buthus tamulus venom toxicity.

Science.gov (United States)

Venkateswarlu, Y; Janakiram, B; Reddy, G R

1988-01-01

Scorpion (Buthus tamulus) venom was subjected to neutralization by treating the venom with various chemicals such as hydrochloric acid, sodium hydroxide, thiourea, formaldehyde, zinc sulphate, acetic acid and trichloroacetic acid. The venom was also subjected to heat treatment. The levels of total protein, free amino acids and protease activity in neutralized venom decreased significantly. The decrease in venom protein and free amino acids was in proportion to the duration of the heat treatment and the concentration of chemicals used except zinc sulphate, sodium hydroxide and thiourea. Protease activity of neutralized venom samples also showed a decrease except with zinc sulphate which enhanced the enzyme activity. Intramuscular injection of formaldehyde, trichlcroacetic acid and heat treated venoms into albino rats produced low mortality while thiourea and zinc sulphate were not effective in reducing the mortality. Hydrochloric acid and acetic acid treated venoms reduced the mortality by 50% with a decrease in the symptoms of envenomation. The changes were attributed to the denaturing of venom protein by chemical and heat treatments.

Antibody-dependent cellular cytotoxicity and neutralizing activity in sera of HIV-1-infected mothers and their children.

Science.gov (United States)

Broliden, K; Sievers, E; Tovo, P A; Moschese, V; Scarlatti, G; Broliden, P A; Fundaro, C; Rossi, P

1993-01-01

The prognostic and protective role of antibodies mediating cellular cytotoxicity (ADCC) and neutralization was evaluated in sera of HIV-1-infected mothers and their consecutively followed children. The presence and titres of ADCC mediating and/or neutralizing antibodies in maternal sera did not predict HIV-1 infection in their respective children. No significant difference in the sera from the children was seen when comparing the presence of neutralizing antibodies between the uninfected and infected children. Stratification of the infected group according to clinical status revealed differences. Only one of 24 AIDS patients had a high neutralizing titre against IIIB. Four patients had a very low titre and the remaining had no detectable neutralizing antibodies at all. In contrast, 10/17 infected non-AIDS children had neutralizing antibodies. Similarly, no significant difference was seen when comparing the presence of ADCC-mediating antibodies between the uninfected and the infected group of children. However, a significantly higher frequency of ADCC was seen in the seropositive non-AIDS children compared with the AIDS children. This study clearly shows that the presence of antibodies mediating ADCC and neutralization in infected children, 0-2 years old, is associated with a better clinical status and delayed disease progression. PMID:8324904

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

DEFF Research Database (Denmark)

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

2004-01-01

We present improved black hole masses for 35 active galactic nuclei (AGNs) based on a complete and consistent reanalysis of broad emission-line reverberation-mapping data. From objects with multiple line measurements, we find that the highest precision measure of the virial product is obtained...

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.

Effects of acute psychosocial stress on neural activity to emotional and neutral faces in a face recognition memory paradigm.

Science.gov (United States)

Li, Shijia; Weerda, Riklef; Milde, Christopher; Wolf, Oliver T; Thiel, Christiane M

2014-12-01

Previous studies have shown that acute psychosocial stress impairs recognition of declarative memory and that emotional material is especially sensitive to this effect. Animal studies suggest a central role of the amygdala which modulates memory processes in hippocampus, prefrontal cortex and other brain areas. We used functional magnetic resonance imaging (fMRI) to investigate neural correlates of stress-induced modulation of emotional recognition memory in humans. Twenty-seven healthy, right-handed, non-smoker male volunteers performed an emotional face recognition task. During encoding, participants were presented with 50 fearful and 50 neutral faces. One hour later, they underwent either a stress (Trier Social Stress Test) or a control procedure outside the scanner which was followed immediately by the recognition session inside the scanner, where participants had to discriminate between 100 old and 50 new faces. Stress increased salivary cortisol, blood pressure and pulse, and decreased the mood of participants but did not impact recognition memory. BOLD data during recognition revealed a stress condition by emotion interaction in the left inferior frontal gyrus and right hippocampus which was due to a stress-induced increase of neural activity to fearful and a decrease to neutral faces. Functional connectivity analyses revealed a stress-induced increase in coupling between the right amygdala and the right fusiform gyrus, when processing fearful as compared to neutral faces. Our results provide evidence that acute psychosocial stress affects medial temporal and frontal brain areas differentially for neutral and emotional items, with a stress-induced privileged processing of emotional stimuli.

Application of neutral electrolyzed water to disinfection of alginate impression.

Science.gov (United States)

Nagamatsu, Yuki; Chen, Ker-Kong; Nagamatsu, Hiroshi; Kozono, Yoshio; Shimizu, Hiroshi

2016-01-01

Neutral electrolyzed water was developed with new concepts of long-term good durability and minimum corrosiveness to metal in addition to its excellent bactericidal activities similar to acid type of electrolyzed waters. The present study examined the bactericidal effects of the neutral electrolyzed water on disinfection of the alginate impression of a dental arch model contaminated by bacteria. Only 1-min immersion in neutral electrolyzed water could sufficiently disinfect the alginate impression including the metallic tray under ultrasonic with no significant differences from acid electrolyzed waters. No bactericidal effects were found in any electrolyzed water when used as mixing water. Considering the advantages and disadvantages of each electrolyzed water in a comprehensive way, it was suggested that neutral electrolyzed water may be the most appropriate for the disinfection of alginate impression.

Neutral beam injector for 475 keV MARS sloshing ions

International Nuclear Information System (INIS)

Goebel, D.M.; Hamilton, G.W.

1983-01-01

A neutral beam injector system which produces 5 MW of 475 keV D 0 neutrals continuously on target has been designed. The beamline is intended to produce the sloshing ion distribution required in the end plug region of the conceptual MARS tandem mirror commercial reactor. The injector design utilizes the LBL self-extraction negative ion source and Transverse Field Focusing (TFF) accelerator to generate a long, ribbon ion beam. A laser photodetachment neutralizer strips over 90% of the negative ions. Magnetic and neutron shield designs are included to exclude the fringe fields of the end plug and provide low activation by the neutron flux from the target plasma. The use of a TFF accelerator and photodetachment neutralizer produces a total system electrical efficiency of about 63% for this design

Glucose administration enhances fMRI brain activation and connectivity related to episodic memory encoding for neutral and emotional stimuli.

Science.gov (United States)

Parent, Marise B; Krebs-Kraft, Desiree L; Ryan, John P; Wilson, Jennifer S; Harenski, Carla; Hamann, Stephan

2011-04-01

Glucose enhances memory in a variety of species. In humans, glucose administration enhances episodic memory encoding, although little is known regarding the neural mechanisms underlying these effects. Here we examined whether elevating blood glucose would enhance functional MRI (fMRI) activation and connectivity in brain regions associated with episodic memory encoding and whether these effects would differ depending on the emotional valence of the material. We used a double-blind, within-participants, crossover design in which either glucose (50g) or a saccharin placebo were administered before scanning, on days approximately 1 week apart. We scanned healthy young male participants with fMRI as they viewed emotionally arousing negative pictures and emotionally neutral pictures, intermixed with baseline fixation. Free recall was tested at 5 min after scanning and again after 1 day. Glucose administration increased activation in brain regions associated with successful episodic memory encoding. Glucose also enhanced activation in regions whose activity was correlated with subsequent successful recall, including the hippocampus, prefrontal cortex, and other regions, and these effects differed for negative vs. neutral stimuli. Finally, glucose substantially increased functional connectivity between the hippocampus and amygdala and a network of regions previously implicated in successful episodic memory encoding. These findings fit with evidence from nonhuman animals indicating glucose modulates memory by selectively enhancing neural activity in brain regions engaged during memory tasks. Our results highlight the modulatory effects of glucose and the importance of examining both regional changes in activity and functional connectivity to fully characterize the effects of glucose on brain function and memory. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

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

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

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.)

Stochastic demand patterns for Markov service facilities with neutral and active periods

International Nuclear Information System (INIS)

Csenki, Attila

2009-01-01

In an earlier paper, a closed form expression was obtained for the joint interval reliability of a Markov system with a partitioned state space S=U union D, i.e. for the probability that the system will reside in the set of up states U throughout the union of some specific disjoint time intervals I l =[θ l ,θ l +ζ l ],l=1,...,k. The deterministic time intervals I l formed a demand pattern specifying the desired active periods. In the present paper, we admit stochastic demand patterns by assuming that the lengths of the active periods, ζ l , as well as the lengths of the neutral periods, θ l -(θ l-1 +ζ l-1 ), are random. We explore two mechanisms for modelling random demand: (1) by alternating renewal processes; (2) by sojourn times of some continuous time Markov chain with a partitioned state space. The first construction results in an expression in terms of a revised version of the moment generating functions of the sojourns of the alternating renewal process. The second construction involves the probability that a Markov chain follows certain patterns of visits to some groups of states and yields an expression using Kronecker matrix operations. The model of a small computer system is analysed to exemplify the ideas

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.

A Lactobacillus plantarum esterase active on a broad range of phenolic esters.

Science.gov (United States)

Esteban-Torres, María; Landete, José María; Reverón, Inés; Santamaría, Laura; de las Rivas, Blanca; Muñoz, Rosario

2015-05-01

Lactobacillus plantarum is the lactic acid bacterial species most frequently found in the fermentation of food products of plant origin on which phenolic compounds are abundant. L. plantarum strains showed great flexibility in their ability to adapt to different environments and growth substrates. Of 28 L. plantarum strains analyzed, only cultures from 7 strains were able to hydrolyze hydroxycinnamic esters, such as methyl ferulate or methyl caffeate. As revealed by PCR, only these seven strains possessed the est_1092 gene. When the est_1092 gene was introduced into L. plantarum WCFS1 or L. lactis MG1363, their cultures acquired the ability to degrade hydroxycinnamic esters. These results support the suggestion that Est_1092 is the enzyme responsible for the degradation of hydroxycinnamic esters on the L. plantarum strains analyzed. The Est_1092 protein was recombinantly produced and biochemically characterized. Surprisingly, Est_1092 was able to hydrolyze not only hydroxycinnamic esters, since all the phenolic esters assayed were hydrolyzed. Quantitative PCR experiments revealed that the expression of est_1092 was induced in the presence of methyl ferulate, an hydroxycinnamic ester, but was inhibited on methyl gallate, an hydroxybenzoic ester. As Est_1092 is an enzyme active on a broad range of phenolic esters, simultaneously possessing feruloyl esterase and tannase activities, its presence on some L. plantarum strains provides them with additional advantages to survive and grow on plant environments. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Effect of Thermospheric Neutral Density upon Inner Trapped-belt Proton Flux

Science.gov (United States)

Wilson, Thomas L.; Lodhi, M. A. K.; Diaz, Abel B.

2007-01-01

We wish to point out that a secular change in the Earth's atmospheric neutral density alters charged-particle lifetime in the inner trapped radiation belts, in addition to the changes recently reported as produced by greenhouse gases. Heretofore, changes in neutral density have been of interest primarily because of their effect on the orbital drag of satellites. We extend this to include the orbital lifetime of charged particles in the lower radiation belts. It is known that the charged-belt population is coupled to the neutral density of the atmosphere through changes induced by solar activity, an effect produced by multiple scattering off neutral and ionized atoms along with ionization loss in the thermosphere where charged and neutral populations interact. It will be shown here that trapped-belt flux J is bivariant in energy E and thermospheric neutral density , as J(E,rho). One can conclude that proton lifetimes in these belts are also directly affected by secular changes in the neutral species populating the Earth s thermosphere. This result is a consequence of an intrinsic property of charged-particle flux, that flux is not merely a function of E but is dependent upon density rho when a background of neutrals is present.

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

Nef decreases HIV-1 sensitivity to neutralizing antibodies that target the membrane-proximal external region of TMgp41.

Directory of Open Access Journals (Sweden)

Rachel P J Lai

2011-12-01

Full Text Available Primate lentivirus nef is required for sustained virus replication in vivo and accelerated progression to AIDS. While exploring the mechanism by which Nef increases the infectivity of cell-free virions, we investigated a functional link between Nef and Env. Since we failed to detect an effect of Nef on the quantity of virion-associated Env, we searched for qualitative changes by examining whether Nef alters HIV-1 sensitivity to agents that target distinct features of Env. Nef conferred as much as 50-fold resistance to 2F5 and 4E10, two potent neutralizing monoclonal antibodies (nAbs that target the membrane proximal external region (MPER of TMgp41. In contrast, Nef had no effect on HIV-1 neutralization by MPER-specific nAb Z13e1, by the peptide inhibitor T20, nor by a panel of nAbs and other reagents targeting gp120. Resistance to neutralization by 2F5 and 4E10 was observed with Nef from a diverse range of HIV-1 and SIV isolates, as well as with HIV-1 virions bearing Env from CCR5- and CXCR4-tropic viruses, clade B and C viruses, or primary isolates. Functional analysis of a panel of Nef mutants revealed that this activity requires Nef myristoylation but that it is genetically separable from other Nef functions such as the ability to enhance virus infectivity and to downregulate CD4. Glycosylated-Gag from MoMLV substituted for Nef in conferring resistance to 2F5 and 4E10, indicating that this activity is conserved in a retrovirus that does not encode Nef. Given the reported membrane-dependence of MPER-recognition by 2F5 and 4E10, in contrast to the membrane-independence of Z13e1, the data here is consistent with a model in which Nef alters MPER recognition in the context of the virion membrane. Indeed, Nef and Glycosylated-Gag decreased the efficiency of virion capture by 2F5 and 4E10, but not by other nAbs. These studies demonstrate that Nef protects lentiviruses from one of the most broadly-acting classes of neutralizing antibodies. This newly

Cupiennin 1a exhibits a remarkably broad, non-stereospecific cytolytic activity on bacteria, protozoan parasites, insects, and human cancer cells.

Science.gov (United States)

Kuhn-Nentwig, Lucia; Willems, Jean; Seebeck, Thomas; Shalaby, Tarek; Kaiser, Marcel; Nentwig, Wolfgang

2011-01-01

Cupiennin 1a, a cytolytic peptide isolated from the venom of the spider Cupiennius salei, exhibits broad membranolytic activity towards bacteria, trypanosomes, and plasmodia, as well as human blood and cancer cells. In analysing the cytolytic activity of synthesised all-D: - and all-L: -cupiennin 1a towards pro- and eukaryotic cells, a stereospecific mode of membrane destruction could be excluded. The importance of negatively charged sialic acids on the outer leaflet of erythrocytes for the binding and haemolytic activity of L: -cupiennin 1a was demonstrated. Reducing the overall negative charges of erythrocytes by partially removing their sialic acids or by protecting them with tri- or pentalysine results in reduced haemolytic activity of the peptide.

Trivalent combination vaccine induces broad heterologous immune responses to norovirus and rotavirus in mice.

Directory of Open Access Journals (Sweden)

Kirsi Tamminen

Full Text Available Rotavirus (RV and norovirus (NoV are the two major causes of viral gastroenteritis (GE in children worldwide. We have developed an injectable vaccine design to prevent infection or GE induced with these enteric viruses. The trivalent combination vaccine consists of NoV capsid (VP1 derived virus-like particles (VLPs of GI-3 and GII-4 representing the two major NoV genogroups and tubular RV recombinant VP6 (rVP6, the most conserved and abundant RV protein. Each component was produced in insect cells by a recombinant baculovirus expression system and combined in vitro. The vaccine components were administered intramuscularly to BALB/c mice either separately or in the trivalent combination. High levels of NoV and RV type specific serum IgGs with high avidity (>50% as well as intestinal IgGs were detected in the immunized mice. Cross-reactive IgG antibodies were also elicited against heterologous NoV VLPs not used for immunization (GII-4 NO, GII-12 and GI-1 VLPs and to different RVs from cell cultures. NoV-specific serum antibodies blocked binding of homologous and heterologous VLPs to the putative receptors, histo-blood group antigens, suggesting broad NoV neutralizing activity of the sera. Mucosal antibodies of mice immunized with the trivalent combination vaccine inhibited RV infection in vitro. In addition, cross-reactive T cell immune responses to NoV and RV-specific antigens were detected. All the responses were sustained for up to six months. No mutual inhibition of the components in the trivalent vaccine combination was observed. In conclusion, the NoV GI and GII VLPs combination induced broader cross-reactive and potentially neutralizing immune responses than either of the VLPs alone. Therefore, trivalent vaccine might induce protective immune responses to the vast majority of circulating NoV and RV genotypes.

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

Influence of Partial Neutralization on Catalytic Activity of Ion Exchange Resin

Czech Academy of Sciences Publication Activity Database

Holub, Ladislav; Jeřábek, Karel

2005-01-01

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

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

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.)

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.

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

Directory of Open Access Journals (Sweden)

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.

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

Highly Oriented Growth of Catalytically Active Zeolite ZSM‐5 Films with a Broad Range of Si/Al Ratios

OpenAIRE

Fu, Donglong; Schmidt, Joel E.; Ristanović, Zoran; Chowdhury, Abhishek Dutta; Meirer, Florian; Weckhuysen, Bert M.

2017-01-01

Abstract Highly b‐oriented zeolite ZSM‐5 films are critical for applications in catalysis and separations and may serve as models to study diffusion and catalytic properties in single zeolite channels. However, the introduction of catalytically active Al3+ usually disrupts the orientation of zeolite films. Herein, using structure‐directing agents with hydroxy groups, we demonstrate a new method to prepare highly b‐oriented zeolite ZSM‐5 films with a broad range of Si/Al ratios (Si/Al=45 to ∞)...

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.

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.

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

Theoretical Study of Phosphoethanolamine: A Synthetic Anticancer Agent with Broad Antitumor Activity

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Vitor Prates Lorenzo

2016-01-01

Full Text Available Cancer is a major public health problem with limited success of available treatments, pointing to the need for new strategies to be developed. Phosphoethanolamine exhibits broad antitumor activity in a variety of tumor cells and potent inhibitor effects on tumor progress in vivo. Once-used organophosphates inhibit acetylcholinesterase (AChE, resulting in toxic effects to the user. As this group is present in phosphoethanolamine, we perform prediction of the in silico metabolism of phosphoethanolamine and submit this series to a docking study on AChE. A total of 10 metabolites were indicated by the prediction, including ammonia and hydroxylamine, which were not included in the study. Using a group of 8 organophosphorus whose pIC50 values ranged from 5.92 to 9.47 as template, we observed that no compound present in the phosphoethanolamine series had a binding energy lower than that of organophosphorus, suggesting that the series has low inhibitory power on AChE. In light of this, we conclude that phosphoethanolamine and its predicted metabolites do not significantly inhibit AChE to cause a cholinergic crisis. This finding highlights the importance of investigating this compound as lead for potential anticancer agents.

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

KAUST Repository

Khan, Mohammed Zahed Mustafa

2014-08-01

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

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

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.)

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

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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.

Neutral current induced neutrino oscillations in a supernova

CERN Document Server

Kusenko, A; Kusenko, Alexander; Segre, Gino

1997-01-01

Neutral currents induced matter oscillations of electroweak-active (anti-)neutrinos to sterile neutrinos can explain the observed motion of pulsars. In contrast to a recently proposed explanation of the pulsar birth velocities based on the electron to tau (muon) neutrino oscillations [hep-ph/9606428], the heaviest neutrino (either active or sterile) would have to have mass of order several keV.

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...

Neutralization-reionization study of the allyloxide anion

Czech Academy of Sciences Publication Activity Database

Schröder, Detlef; Schwarz, H.; Roithová, J.

2011-01-01

Roč. 301, 1/3 (2011), s. 84-89 ISSN 1387-3806 Grant - others:European Research Coucil(XE) AdG HORIZOMS Institutional research plan: CEZ:AV0Z40550506 Keywords : allyloxy radical * C-H activation * neutralization-reionization mass spectrometry Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.549, year: 2011

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,...

Role of individual phosphorylation sites for the 14-3-3-protein-dependent activation of yeast neutral trehalase Nth1

Czech Academy of Sciences Publication Activity Database

Veisová, Dana; Macáková, Eva; Řežábková, Lenka; Šulc, Miroslav; Vácha, Petr; Sychrová, Hana; Obšil, T.; Obšilová, Veronika

2012-01-01

Roč. 443, č. 3 (2012), s. 663-670 ISSN 0264-6021 R&D Projects: GA ČR(CZ) GAP207/11/0455; GA AV ČR(CZ) IAA500110801 Grant - others:Univerzita Karlova(CZ) 350111 Institutional research plan: CEZ:AV0Z50110509; CEZ:AV0Z50200510 Keywords : 14-3-3 protein * Bmh * neutral trehalase (Nth1) * enzymatic activity * phosphorylation * Saccharomyces cerevisiae Subject RIV: CE - Biochemistry Impact factor: 4.654, year: 2012

Achieving Carbon Neutrality in the Global Aluminum Industry

Science.gov (United States)

Das, Subodh

2012-02-01

In the 21st century, sustainability is widely regarded as the new corporate culture, and leading manufacturing companies (Toyota, GE, and Alcoa) and service companies (Google and Federal Express) are striving towards carbon neutrality. The current carbon footprint of the global aluminum industry is estimated at 500 million metric tonnes carbon dioxide equivalent (CO2eq), representing about 1.7% of global emissions from all sources. For the global aluminum industry, carbon neutrality is defined as a state where the total "in-use" CO2eq saved from all products in current use, including incremental process efficiency improvements, recycling, and urban mining activities, equals the CO2eq expended to produce the global output of aluminum. This paper outlines an integrated and quantifiable plan for achieving "carbon neutrality" in the global aluminum industry by advocating five actionable steps: (1) increase use of "green" electrical energy grid by 8%, (2) reduce process energy needs by 16%, (3) deploy 35% of products in "in-use" energy saving applications, (4) divert 6.1 million metric tonnes/year from landfills, and (5) mine 4.5 million metric tonnes/year from aluminum-rich "urban mines." Since it takes 20 times more energy to make aluminum from bauxite ore than to recycle it from scrap, the global aluminum industry could set a reasonable, self-imposed energy/carbon neutrality goal to incrementally increase the supply of recycled aluminum by at least 1.05 metric tonnes for every tonne of incremental production via primary aluminum smelter capacity. Furthermore, the aluminum industry can and should take a global leadership position by actively developing internationally accepted and approved carbon footprint credit protocols.

Characterization of human monoclonal antibodies that neutralize multiple poliovirus serotypes.

Science.gov (United States)

Puligedda, Rama Devudu; Kouiavskaia, Diana; Al-Saleem, Fetweh H; Kattala, Chandana Devi; Nabi, Usman; Yaqoob, Hamid; Bhagavathula, V Sandeep; Sharma, Rashmi; Chumakov, Konstantin; Dessain, Scott K

2017-10-04

Following the eradication of wild poliovirus (PV), achieving and maintaining a polio-free status will require eliminating potentially pathogenic PV strains derived from the oral attenuated vaccine. For this purpose, a combination of non-cross-resistant drugs, such as small molecules and neutralizing monoclonal antibodies (mAbs), may be ideal. We previously isolated chimpanzee and human mAbs capable of neutralizing multiple PV types (cross-neutralization). Here, we describe three additional human mAbs that neutralize types 1 and 2 PV and one mAb that neutralizes all three types. Most bind conformational epitopes and have unusually long heavy chain complementarity determining 3 domains (HC CDR3). We assessed the ability of the mAbs to neutralize A12 escape mutant PV strains, and found that the neutralizing activities of the mAbs were disrupted by different amino acid substitutions. Competitive binding studies further suggested that the specific mAb:PV interactions that enable cross-neutralization differ among mAbs and serotypes. All of the cloned mAbs bind PV in the vicinity of the "canyon", a circular depression around the 5-fold axis of symmetry through which PV recognizes its cellular receptor. We were unable to generate escape mutants to two of the mAbs, suggesting that their epitopes are important for the PV life cycle. These data indicate that PV cross-neutralization involves binding to highly conserved structures within the canyon that binds to the cellular receptor. These may be facilitated by the long HC CDR3 domains, which may adopt alternative binding configurations. We propose that the human and chimpanzee mAbs described here could have potential as anti-PV therapeutics. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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

High-Latitude Neutral Mass Density Maxima

Science.gov (United States)

Huang, C. Y.; Huang, Y.; Su, Y.-J.; Huang, T.; Sutton, E. K.

2017-10-01

Recent studies have reported that thermospheric effects due to solar wind driving can be observed poleward of auroral latitudes. In these papers, the measured neutral mass density perturbations appear as narrow, localized maxima in the cusp and polar cap. They conclude that Joule heating below the spacecraft is the cause of the mass density increases, which are sometimes associated with local field-aligned current structures, but not always. In this paper we investigate neutral mass densities measured by accelerometers on the CHAllenging Minisatellite Payload (CHAMP) and Gravity Recovery and Climate Experiment (GRACE) spacecraft from launch until years 2010 (CHAMP) and 2012 (GRACE), approximately 10 years of observations from each satellite. We extract local maxima in neutral mass densities over the background using a smoothing window with size of one quarter of the orbit. The maxima have been analyzed for each year and also for the duration of each set of satellite observations. We show where they occur, under what solar wind conditions, and their relation to magnetic activity. The region with the highest frequency of occurrence coincides approximately with the cusp and mantle, with little direct evidence of an auroral zone source. Our conclusions agree with the "hot polar cap" observations that have been reported and studied in the past.

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.

THE DIFFERENCES IN THE TORUS GEOMETRY BETWEEN HIDDEN AND NON-HIDDEN BROAD LINE ACTIVE GALACTIC NUCLEI

Energy Technology Data Exchange (ETDEWEB)

Ichikawa, Kohei; Ueda, Yoshihiro [Department of Astronomy, Kyoto University, Kitashirakawa-Oiwake-cho, Sakyo-ku, Kyoto 606-8502 (Japan); Packham, Christopher; Lopez-Rodriguez, Enrique; Alsip, Crystal D. [Department of Physics and Astronomy, University of Texas at San Antonio, One UTSA Circle, San Antonio, TX 78249 (United States); Almeida, Cristina Ramos; Ramos, Andrés Asensio; González-Martín, Omaira [Instituto de Astrofísica de Canarias, C/Vía Láctea, s/n, E-38205 La Laguna, Tenerife (Spain); Alonso-Herrero, Almudena [Instituto de Física de Cantabria, CSIC-Universidad de Cantabria, E-39005 Santander (Spain); Díaz-Santos, Tanio [Spitzer Science Center, California Institute of Technology, MS 220-6, Pasadena, CA 91125 (United States); Elitzur, Moshe [Department of Physics and Astronomy, University of Kentucky, Lexington, KY 40506-0055 (United States); Hönig, Sebastian F. [School of Physics and Astronomy, University of Southampton, Southampton SO17 1BJ (United Kingdom); Imanishi, Masatoshi [Subaru Telescope, 650 North A’ohoku Place, Hilo, HI 96720 (United States); Levenson, Nancy A. [Gemini Observatory, Southern Operations Center, c/o AURA, Casilla 603, La Serena (Chile); Mason, Rachel E. [Gemini Observatory, Northern Operations Center, 670 N. A’ohoku Place, Hilo, HI 96720 (United States); Perlman, Eric S., E-mail: ichikawa@kusastro.kyoto-u.ac.jp [Department of Physics and Space Sciences, 150 W. University Blvd., Florida Institute of Technology, Melbourne, FL 32901 (United States)

2015-04-20

We present results from the fitting of infrared (IR) spectral energy distributions of 21 active galactic nuclei (AGNs) with clumpy torus models. We compiled high spatial resolution (∼0.3–0.7 arcsec) mid-IR (MIR) N-band spectroscopy, Q-band imaging, and nuclear near- and MIR photometry from the literature. Combining these nuclear near- and MIR observations, far-IR photometry, and clumpy torus models enables us to put constraints on the torus properties and geometry. We divide the sample into three types according to the broad line region (BLR) properties: type-1s, type-2s with scattered or hidden broad line region (HBLR) previously observed, and type-2s without any published HBLR signature (NHBLR). Comparing the torus model parameters gives us the first quantitative torus geometrical view for each subgroup. We find that NHBLR AGNs have smaller torus opening angles and larger covering factors than HBLR AGNs. This suggests that the chance to observe scattered (polarized) flux from the BLR in NHBLR could be reduced by the dual effects of (a) less scattering medium due to the reduced scattering volume given the small torus opening angle and (b) the increased torus obscuration between the observer and the scattering region. These effects give a reasonable explanation for the lack of observed HBLR in some type-2 AGNs.

Improved Active-Neutral-Point-Clamped (I-ANPC) Multilevel Converter: Fundamental Circuit Topology, Innovative Modulatioin Technique, and Experimental Validation

DEFF Research Database (Denmark)

Dargahi, Vahid; Corzine, Keith A.; Enslin, Johan H.

2018-01-01

For medium-voltage (MV) high-power industrial applications including HVDC and variable-speed motor drives, multilevel converters are deemed predominant topology. One of the promising derived-topologies from neutral-point-clamped (NPC) configuration is active NPC (ANPC) inverter that offers improved......-capacitor (FC) and four switches such as the insulated-gate bipolar transistors (IGBTs). The I-ANPC converter has considerable advantages over the classic multilevel inverters that makes it a preferable topology for MV applications. The substantial reduction in the number of cells in comparison with classic...

The effect of quenched disorder in neutral theories

International Nuclear Information System (INIS)

Borile, Claudio; Maritan, Amos; Muñoz, Miguel A

2013-01-01

We study systems with two symmetric absorbing states, such as the voter model and its variations, which have been broadly used as minimal neutral models in genetics, population ecology, sociology, etc. We analyze the effects of a key ingredient inevitably present in most real applications: random-field-like quenched disorder. In accord with simulations and previous findings, coexistence between the two competing states/opinions turns out to be strongly favored by disorder in the standard voter model; actually, a disorder-induced phase transition is generated for any finite system size in the presence of an arbitrarily small spontaneous-inversion rate (preventing absorbing states from being stable). For nonlinear versions of the voter model a general theory (by Al Hammal et al) explains that the spontaneous breaking of the up/down symmetry and an absorbing state phase transition can occur either together or separately, giving rise to two different scenarios. Here, we show that the presence of quenched disorder in nonlinear voter models does not allow the separation of the up–down (Ising-like) symmetry breaking from the active-to-absorbing phase transition in low-dimensional systems: both phenomena can occur only simultaneously, as a consequence of the well-known Imry–Ma argument generalized to these non-equilibrium problems. When the two phenomena occur in unison, resulting in a genuinely non-equilibrium (‘generalized voter’) transition, the Imry–Ma argument is violated and the symmetry can be spontaneously broken even in low dimensions. (paper)

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

Directory of Open Access Journals (Sweden)

Ann R Hunt

2010-07-01

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

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

Directory of Open Access Journals (Sweden)

Wence Jiao

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

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

Neutralizing activities of ethanolic extracts of six plants traditionally used in Guatemala as antidotes for the envenomation caused by the snake Bothrops asper

Directory of Open Access Journals (Sweden)

Patricia Saravia-Otten

2015-07-01

Full Text Available Many plants are reported to be used in Guatemalan traditional medicine as antidotes against various effects of the snakebite; however, very few attempts have been made to evaluate their neutralizing capacity in controlled experiments. Six plants (Acacia hindsii, Cissampelos pareira; Hamelia patens, Piper peltatum, Sansevieria hyacinthoides and Aristolochia maxima were evaluated in vitro for their ability to neutralize phospholipase A2(PLA2 and proteolytic effects of the venom of Bothrops asper, the snake responsible for approximately half of the snakebite envenomations in Central America. These effects are indicatives of the ability of B. asper venom to produce myotoxicity, hemorrhage and inflammation. Plants were collected, dried and extracted by maceration with ethanol. After pre-incubation of several amounts of each extract with a challenge dose of venom, S. hyacinthoides demonstrated a low neutralizing capacity (< DE 50 of the PLA2 effect (13.90 ± 6.41%; C. pareira (32.98 ± 5.51% and P. peltatum (24.52 ± 7.45% neutralized less than 50% of the proteolytic effect. The results suggest that neither of the tested plants should be used individually to treat the main effects of B. asper envenomation. However, the three low-active extracts might be potentiated when used in mixtures composed of several plants, as prepared by traditional healers. Given the complexity of the venom components and the multiple pathologic effects produced by B. asper envenomation, more tests are required to fully investigate the ability of this plants to neutralize the coagulant, fibrin(ogenolytic, edematizing and myotoxic effects of the venom.

Neural representation of anxiety and personality during exposure to anxiety-provoking and neutral scenes from scary movies.

Science.gov (United States)

Straube, Thomas; Preissler, Sandra; Lipka, Judith; Hewig, Johannes; Mentzel, Hans-Joachim; Miltner, Wolfgang H R

2010-01-01

Some people search for intense sensations such as being scared by frightening movies while others do not. The brain mechanisms underlying such inter-individual differences are not clear. Testing theoretical models, we investigated neural correlates of anxiety and the personality trait sensation seeking in 40 subjects who watched threatening and neutral scenes from scary movies during functional magnetic resonance imaging. Threat versus neutral scenes induced increased activation in anterior cingulate cortex, insula, thalamus, and visual areas. Movie-induced anxiety correlated positively with activation in dorsomedial prefrontal cortex, indicating a role for this area in the subjective experience of being scared. Sensation seeking-scores correlated positively with brain activation to threat versus neutral scenes in visual areas and in thalamus and anterior insula, i.e. regions involved in the induction and representation of arousal states. For the insula and thalamus, these outcomes were partly due to an inverse relation between sensation seeking scores and brain activation during neutral film clips. These results support models predicting cerebral hypoactivation in high sensation seekers during neutral stimulation, which may be compensated by more intense sensations such as watching scary movies. 2009 Wiley-Liss, Inc.

Research and development at the Marshall Space Flight Center Neutral Buoyancy Simulator

Science.gov (United States)

Kulpa, Vygantas P.

1987-01-01

The Neutral Buoyancy Simulator (NBS), a facility designed to imitate zero-gravity conditions, was used to test the Experimental Assembly of Structures in Extravehicular Activity (EASE) and the Assembly Concept for Construction of Erectable Space Structures (ACCESS). Neutral Buoyancy Simulator applications and operations; early space structure research; development of the EASE/ACCESS experiments; and improvement of NBS simulation are summarized.

Broad-line high-excitation gas in the elliptical galaxy NGC5128

International Nuclear Information System (INIS)

Phillips, M.M.; Taylor, K.; Axon, D.J.; Atherton, P.D.; Hook, R.N.

1984-01-01

A faint, but extensive component of broad-line ionized gas has been discovered in the peculiar giant elliptical galaxy NGC5128. This component has a radically different spatial distribution from the well-studied rotating photoionized gas associated with the dust lane although the velocity fields of the two components are similar. The origin of the broad-line gas is considered as its possible relation to the active nucleus and the X-ray jet discussed. (author)

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…

Socioeconomic evaluation of broad-scale land management strategies.

Science.gov (United States)

Lisa K. Crone; Richard W. Haynes

2001-01-01

This paper examines the socioeconomic effects of alternative management strategies for Forest Service and Bureau of Land Management lands in the interior Columbia basin. From a broad-scale perspective, there is little impact or variation between alternatives in terms of changes in total economic activity or social conditions in the region. However, adopting a finer...

Proteolytische activiteit bij neutrale pH in rundermilt

NARCIS (Netherlands)

Marrink, Jan

1969-01-01

Intracellular enzymes, hydrolysing proteins optimally at acid pH values (acid proteases), have been studied in detail by several investigators. The existence of proteolytic activity at neutral pH in animal tissue extracts, on the other hand, has often been mentioned, but with few reports on the

Immunization with Clinical HIV-1 Env Proteins Induces Broad Antibody Dependent Cellular Cytotoxicity-Mediating Antibodies in a Rabbit Vaccination Model.

Science.gov (United States)

Karlsson, Ingrid; Borggren, Marie; Jensen, Sanne Skov; Heyndrickx, Leo; Stewart-Jones, Guillaume; Scarlatti, Gabriella; Fomsgaard, Anders

2017-11-17

The induction of both neutralizing antibodies and non-neutralizing antibodies with effector functions, for example, antibody-dependent cellular cytotoxicity (ADCC), is desired in the search for effective vaccines against HIV-1. In the pursuit of novel immunogens capable of inducing an efficient antibody response, rabbits were immunized with selected antigens using different prime-boost strategies. We immunized 35 different groups of rabbits with Env antigens from clinical HIV-1 subtypes A and B, including immunization with DNA alone, protein alone, and DNA prime with protein boost. The rabbit sera were screened for ADCC activity using a GranToxiLux-based assay with human peripheral blood mononuclear cells as effector cells and CEM.NKR CCR5 cells coated with HIV-1 envelope as target cells. The groups with the highest ADCC activity were further characterized for cross-reactivity between HIV-1 subtypes. The immunogen inducing the most potent and broadest ADCC response was a trimeric gp140. The ADCC activity was highest against the HIV-1 subtype corresponding to the immunogen. The ADCC activity did not necessarily reflect neutralizing activity in the pseudovirus-TZMbl assay, but there was an overall correlation between the two antiviral activities. We present a rabbit vaccination model and an assay suitable for screening HIV-1 vaccine candidates for the induction of ADCC-mediating antibodies in addition to neutralizing antibodies. The antigens and/or immunization strategies capable of inducing antibodies with ADCC activity did not necessarily induce neutralizing activity and vice versa. Nevertheless, we identified vaccine candidates that were able to concurrently induce both types of responses and that had ADCC activity that was cross-reactive between different subtypes. When searching for an effective vaccine candidate, it is important to evaluate the antibody response using a model and an assay measuring the desired function.

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...

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

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.

[Virus strain specific serum neutralizing antibodies in children and adolescents immunized with a Russian mumps vaccine].

Science.gov (United States)

Otrashevskaia, E V; Krasil'nikov, I V; Ignat'ev, G M

2010-01-01

Postvaccination immunity was studied in the children and teenagers without a history of clinical mumps infection, who had been immunized with the Leningrad-3 mumps vaccine. The level of specific lgG in ELISA and that and spectrum of their neutralizing activity against a vaccine strain and three heterologous mumps virus (MV) strains (genotypes A, C, and H) were measured. The investigation included 151 sera from the vaccinees aged 3 to 17 years, possessing the detectable specific IgG titers in ELISA and the detectable neutralizing titers against the vaccine strain. 97.4% of the vaccinees had neutralizing activity against 1-3 heterologous MV strains. A preponderance of neutralizing titers against heterologous MV strains by 1-log2 in some sera (6.5-32.5 depending on age) was most likely to suggest that the vaccinees' had been in contact with these virus strains in the past. In our investigation, a combination of positive IgG titers and neutralizing titers against the vaccine strain 2-log2 or higher provided the protection of the vaccinated children and teenagers against the symptomatic infection. There was a pronounced buster effect of the second immunization and a drop in the neutralizing activity of the sera from the vaccinated children and adolescents over time after the first and second immunization.

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.

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

International Nuclear Information System (INIS)

Peters, Diane E.; Hoover, Benjamin; Cloud, Loretta Grey; Liu, Shihui; Molinolo, Alfredo A.; Leppla, Stephen H.; Bugge, Thomas H.

2014-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-09-01

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

Neutral-current detection in the Sudbury Neutrino Observatory

International Nuclear Information System (INIS)

Bowles, T.J.; Doe, P.J.; Fowler, M.M.; Hime, A.; Robertson, R.G.H.; Thornewell, P.M.; Wilhelmy, J.B.; Wilkerson, J.F.; Wouters, J.M.

1993-01-01

The Sudbury Neutrino Observatory (SNO) will have the capability of detecting all active species of neutrinos with energies greater than 2.2 MeV by the neutral-current disintegration of deuterium. The comparison of this rate with the rate of inverse beta decay of the deuteron will yield a nearly model-independent answer to the question of whether electron neutrinos from the sun oscillate into mu or tau neutrinos. The signal of a neutral-current interaction is the liberation of a free neutron in the heavy-water detector, and we discuss a technique employing 3 He proportional counters for registering these neutrons, particularly from the standpoint of the ultra-low backgrounds needed

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

Viper and cobra venom neutralization by beta-sitosterol and stigmasterol isolated from the root extract of Pluchea indica Less. (Asteraceae).

Science.gov (United States)

Gomes, A; Saha, Archita; Chatterjee, Ipshita; Chakravarty, A K

2007-09-01

We reported previously that the methanolic root extract of the Indian medicinal plant Pluchea indica Less. (Asteraceae) could neutralize viper venom-induced action [Alam, M.I., Auddy, B., Gomes, A., 1996. Viper venom neutralization by Indian medicinal plant (Hemidesmus indicus and P. indica) root extracts. Phytother. Res. 10, 58-61]. The present study reports the neutralization of viper and cobra venom by beta-sitosterol and stigmasterol isolated from the root extract of P. indica Less. (Asteraceae). The active fraction (containing the major compound beta-sitosterol and the minor compound stigmasterol) was isolated and purified by silica gel column chromatography and the structure was determined using spectroscopic analysis (EIMS, (1)H NMR, (13)C NMR). Anti-snake venom activity was studied in experimental animals. The active fraction was found to significantly neutralize viper venom-induced lethal, hemorrhagic, defibrinogenation, edema and PLA(2) activity. Cobra venom-induced lethality, cardiotoxicity, neurotoxicity, respiratory changes and PLA(2) activity were also antagonized by the active component. It potentiated commercial snake venom antiserum action against venom-induced lethality in male albino mice. The active fraction could antagonize venom-induced changes in lipid peroxidation and superoxide dismutase activity. This study suggests that beta-sitosterol and stigmasterol may play an important role, along with antiserum, in neutralizing snake venom-induced actions.

Expanded therapeutic potential in activity space of next-generation 5-nitroimidazole antimicrobials with broad structural diversity

Science.gov (United States)

Miyamoto, Yukiko; Kalisiak, Jarosław; Korthals, Keith; Lauwaet, Tineke; Cheung, Dae Young; Lozano, Ricardo; Cobo, Eduardo R.; Upcroft, Peter; Upcroft, Jacqueline A.; Berg, Douglas E.; Gillin, Frances D.; Fokin, Valery V.; Sharpless, K. Barry; Eckmann, Lars

2013-01-01

Metronidazole and other 5-nitroimidazoles (5-NI) are among the most effective antimicrobials available against many important anaerobic pathogens, but evolving resistance is threatening their long-term clinical utility. The common 5-NIs were developed decades ago, yet little 5-NI drug development has since taken place, leaving the true potential of this important drug class unexplored. Here we report on a unique approach to the modular synthesis of diversified 5-NIs for broad exploration of their antimicrobial potential. Many of the more than 650 synthesized compounds, carrying structurally diverse functional groups, have vastly improved activity against a range of microbes, including the pathogenic protozoa Giardia lamblia and Trichomonas vaginalis, and the bacterial pathogens Helicobacter pylori, Clostridium difficile, and Bacteroides fragilis. Furthermore, they can overcome different forms of drug resistance, and are active and nontoxic in animal infection models. These findings provide impetus to the development of structurally diverse, next-generation 5-NI drugs as agents in the antimicrobial armamentarium, thus ensuring their future viability as primary therapeutic agents against many clinically important infections. PMID:24101497

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...

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)

Forgetting emotional and neutral words: an ERP study.

Science.gov (United States)

Brandt, Karen R; Nielsen, Maria Kragh; Holmes, Amanda

2013-03-21

Previous research has demonstrated that emotional material is more likely to be remembered than neutral material (Hamann, 2001). The present study employed the item-method of directed forgetting in order to examine whether emotionally negative words are not only easier to remember, but also harder to forget. Event-related potentials (ERPs) were additionally measured in order to investigate the processes of selective rehearsal and active inhibition in directed forgetting. The results demonstrated directed forgetting effects for both neutral and negative words, with a stronger effect for negative items. Late positive potentials (LPPs) for 'to-be-remembered' (TBR) relative to 'to-be-forgotten' (TBF) cues were enhanced when the cues followed negative in comparison to neutral words, indicating the greater selective rehearsal of TBR negative items. Frontal positivities to TBF relative to TBR cues were not modulated by word valence, indicating that inhibitory processes were unaffected by emotion. Taken together, the present research demonstrates for the first time that, not only are emotionally negative words prone to the same directed forgetting effects as neutral words, but that these effects are in fact enhanced for negative words and due to increased selective rehearsal of TBR negative items. The discrepancies between the present findings and those of previous studies are discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

Peters, Diane E; Hoover, Benjamin; Cloud, Loretta Grey; Liu, Shihui; Molinolo, Alfredo A; Leppla, Stephen H; Bugge, Thomas H

2014-09-01

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

Lack of protection following passive transfer of polyclonal highly functional low-dose non-neutralizing antibodies.

Directory of Open Access Journals (Sweden)

Anne-Sophie Dugast

Full Text Available Recent immune correlates analysis from the RV144 vaccine trial has renewed interest in the role of non-neutralizing antibodies in mediating protection from infection. While neutralizing antibodies have proven difficult to induce through vaccination, extra-neutralizing antibodies, such as those that mediate antibody-dependent cellular cytotoxicity (ADCC, are associated with long-term control of infection. However, while several non-neutralizing monoclonal antibodies have been tested for their protective efficacy in vivo, no studies to date have tested the protective activity of naturally produced polyclonal antibodies from individuals harboring potent ADCC activity. Because ADCC-inducing antibodies are highly enriched in elite controllers (EC, we passively transferred highly functional non-neutralizing polyclonal antibodies, purified from an EC, to assess the potential impact of polyclonal non-neutralizing antibodies on a stringent SHIV-SF162P3 challenge in rhesus monkeys. Passive transfer of a low-dose of ADCC inducing antibodies did not protect from infection following SHIV-SF162P3 challenge. Passively administered antibody titers and gp120-specific, but not gp41-specific, ADCC and antibody induced phagocytosis (ADCP were detected in the majority of the monkeys, but did not correlate with post infection viral control. Thus these data raise the possibility that gp120-specific ADCC activity alone may not be sufficient to control viremia post infection but that other specificities or Fc-effector profiles, alone or in combination, may have an impact on viral control and should be tested in future passive transfer experiments.

Snake venom neutralization by Indian medicinal plants (Vitex negundo and Emblica officinalis) root extracts.

Science.gov (United States)

Alam, M I; Gomes, A

2003-05-01

The methanolic root extracts of Vitex negundo Linn. and Emblica officinalis Gaertn. were explored for the first time for antisnake venom activity. The plant (V. negundo and E. officinalis) extracts significantly antagonized the Vipera russellii and Naja kaouthia venom induced lethal activity both in in vitro and in vivo studies. V. russellii venom-induced haemorrhage, coagulant, defibrinogenating and inflammatory activity was significantly neutralized by both plant extracts. No precipitating bands were observed between the plant extract and snake venom. The above observations confirmed that the plant extracts possess potent snake venom neutralizing capacity and need further investigation.

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''

Neutralizing and non-neutralizing monoclonal antibodies against dengue virus E protein derived from a naturally infected patient

Directory of Open Access Journals (Sweden)

Isern Sharon

2010-02-01

Full Text Available Abstract Background Antibodies produced in response to infection with any of the four serotypes of dengue virus generally provide homotypic immunity. However, prior infection or circulating maternal antibodies can also mediate a non-protective antibody response that can enhance the course of disease in a subsequent heterotypic infection. Naturally occurring human monoclonal antibodies can help us understand the protective and pathogenic roles of the humoral immune system in dengue virus infection. Results Epstein-Barr Virus (EBV transformation of B cells isolated from the peripheral blood of a human subject with previous dengue infection was performed. B cell cultures were screened by ELISA for antibodies to dengue (DENV envelope (E protein. ELISA positive cultures were cloned by limiting dilution. Three IgG1 human monoclonal antibodies (HMAbs were purified and their binding specificity to E protein was verified by ELISA and biolayer interferometry. Neutralization and enhancement assays were conducted in epithelial and macrophage-like cell lines, respectively. All three HMAbs bound to E from at least two of the four DENV serotypes, one of the HMAbs was neutralizing, and all were able to enhance DENV infection. Conclusions HMAbs against DENV can be successfully generated by EBV transformation of B cells from patients at least two years after naturally acquired DENV infections. These antibodies show different patterns of cross-reactivity, neutralizing, and enhancement activity.

Cross-reactivity and phospholipase A2 neutralization of anti-irradiated Bothrops jararaca venom antibodies

International Nuclear Information System (INIS)

Spencer, P.J.; Nascimento, N. do; Paula, R.A. de; Cardi, B.A.; Rogero, J.R.

1995-01-01

The detoxified Bothrops jararaca venom, immunized rabbits with the toxoid obtained and investigated cross-reactivity of the antibodies obtained against autologous and heterelogous venoms was presented. It was also investigated the ability of the IgGs, purified by affinity chromatography, from those sera to neutralize phospholipase. A 2 , an ubiquous enzyme in animal venoms. Results indicate that venom irradiation leads to an attenuation of toxicity of 84%. Cross-reactivity was investigated by ELISA and Western blot and all venoms were reactive to the antibodies. On what refers to phospholipase A 2 activity neutralization, the antibodies neutralized autologous venoms efficiently and, curiously, other venoms from the same genus were not neutralized, while Lachesis muta venom, a remote related specier, was neutralized by this serum. These data suggest that irradiation preserve important epitopes for induction of neutralizing antibodies and that these epitopes are not shared by all venoms assayed. (author). 8 refs, 2 figs, 3 tabs

Antibody-Mediated Neutralization of the Exotoxin Mycolactone, the Main Virulence Factor Produced by Mycobacterium ulcerans.

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Jean-Pierre Dangy

2016-06-01

Full Text Available Mycolactone, the macrolide exotoxin produced by Mycobacterium ulcerans, causes extensive tissue destruction by inducing apoptosis of host cells. In this study, we aimed at the production of antibodies that could neutralize the cytotoxic activities of mycolactone.Using the B cell hybridoma technology, we generated a series of monoclonal antibodies with specificity for mycolactone from spleen cells of mice immunized with the protein conjugate of a truncated synthetic mycolactone derivative. L929 fibroblasts were used as a model system to investigate whether these antibodies can inhibit the biological effects of mycolactone. By measuring the metabolic activity of the fibroblasts, we found that anti-mycolactone mAbs can completely neutralize the cytotoxic activity of mycolactone.The toxin neutralizing capacity of anti-mycolactone mAbs supports the concept of evaluating the macrolide toxin as vaccine target.

Practicing for space underwater: inventing neutral buoyancy training, 1963-1968.

Science.gov (United States)

Neufeld, Michael J; Charles, John B

2015-01-01

Neutral buoyancy's value was far from obvious when human spaceflight began in 1961. Starting in 1964, Environmental Research Associates, a tiny company in the suburbs of Baltimore, developed the key innovations in an obscure research project funded by NASA's Langley Research Center. The new Houston center dismissed it until a mid-1966 EVA crisis, after which it rapidly took over. In parallel, NASA Marshall Space Flight Center developed many of the same techniques, as did many large aerospace corporations, yet the long-run technological impact of corporate activity was near zero. Because ERA and Marshall's pioneering activities led to the two long-running NASA training centers at Houston and Huntsville, those two organizations deserve primary credit for the construction of the neutral buoyancy technological system. Published by Elsevier Ltd.

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...

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

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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.

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

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....

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

Energy Technology Data Exchange (ETDEWEB)

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

2015-05-15

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

Unusual broad-line Mg II emitters among luminous galaxies in the baryon oscillation spectroscopic survey

International Nuclear Information System (INIS)

Roig, Benjamin; Blanton, Michael R.; Ross, Nicholas P.

2014-01-01

Many classes of active galactic nuclei (AGNs) have been observed and recorded since the discovery of Seyfert galaxies. In this paper, we examine the sample of luminous galaxies in the Baryon Oscillation Spectroscopic Survey. We find a potentially new observational class of AGNs, one with strong and broad Mg II λ2799 line emission, but very weak emission in other normal indicators of AGN activity, such as the broad-line Hα, Hβ, and the near-ultraviolet AGN continuum, leading to an extreme ratio of broad Hα/Mg II flux relative to normal quasars. Meanwhile, these objects' narrow-line flux ratios reveal AGN narrow-line regions with levels of activity consistent with the Mg II fluxes and in agreement with that of normal quasars. These AGN may represent an extreme case of the Baldwin effect, with very low continuum and high equivalent width relative to typical quasars, but their ratio of broad Mg II to broad Balmer emission remains very unusual. They may also be representative of a class of AGN where the central engine is observed indirectly with scattered light. These galaxies represent a small fraction of the total population of luminous galaxies (≅ 0.1%), but are more likely (about 3.5 times) to have AGN-like nuclear line emission properties than other luminous galaxies. Because Mg II is usually inaccessible for the population of nearby galaxies, there may exist a related population of broad-line Mg II emitters in the local universe which is currently classified as narrow-line emitters (Seyfert 2 galaxies) or low ionization nuclear emission-line regions.

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

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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.

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...

Induction of human immunodeficiency virus neutralizing antibodies using fusion complexes.

Science.gov (United States)

Zipeto, Donato; Matucci, Andrea; Ripamonti, Chiara; Scarlatti, Gabriella; Rossolillo, Paola; Turci, Marco; Sartoris, Silvia; Tridente, Giuseppe; Bertazzoni, Umberto

2006-05-01

Human immunodeficiency virus-1 (HIV-1) infects cells by membrane fusion that is mediated by the envelope proteins gp120/gp41 and the cellular receptors CD4 and CCR5. During this process, some conserved viral epitopes are temporarily exposed and may induce a neutralizing antibody response when fixed in the fusogenic conformation. These transient structures are conserved and may be effective antigens for use in an anti-HIV-1 vaccine. In this study we tested different conditions of preparation of fusion complexes inducing neutralizing antibodies against both R5 and X4 tropic HIV-1 strains. Cell lines expressing HIV-1 gp120/gp41 and CD4-CCR5 were prepared and conditions for producing fusion complexes were tested. Complexes produced at different temperature and fixative combinations were used to immunize mice. Results indicated that (a) fusion complexes prepared at either 21 degrees C, 30 degrees C or 37 degrees C were immunogenic and induced neutralizing antibodies against both R5 and X4 HIV-1 heterologous isolates; (b) after extensive purification of antibodies there was no cytotoxic effect; (c) complexes prepared at 37 degrees C were more immunogenic and induced higher titers of neutralizing antibodies than complexes prepared at either 21 degrees C or 30 degrees C; (d) the fixative used did not affect the titer of neutralizing antibodies except for glutaraldehyde which was ineffective; (e) the neutralizing activity was retained after CD4-CCR5 antibody removal. The production of higher titers of neutralizing antibody with fusion complexes prepared at 37 degrees C, as compared to lower temperatures, may be related to the induction of antibodies against many different conformation intermediates that subsequently act synergistically at different steps in the fusion process.

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

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

International Nuclear Information System (INIS)

Smith, J.W.H.; Westreich, P.; Abdellatif, H.; Filbee-Dexter, P.; Smith, A.J.; Wood, T.E.; Croll, L.M.; Reynolds, J.H.; Dahn, J.R.

2010-01-01

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

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

[Advance in research on regulatory mechanism and functions of neutral sphingomyelinse 2].

Science.gov (United States)

Zhang, Lan; Guo, Jun

2013-10-01

Neutral sphingomyelinase 2 (nSMase2), which located mainly on the plasma membrane, hydrolyzes sphingomyelin into ceramide and plays an important role in the physiological and pathological regulation of cell apoptosis, cell growth arrest, and inflammation. nSMase2 is also involved in the development of Alzheimer's disease and the bone growth.Under neutral pH and the presence of Ca(2+), Mg(2+), and Mn(+), the activity of nSMase2 is induced by oxidative stress through phosphorylation. Furthermore, the induced interaction of anionic phospholipids and the signaling molecules like receptor for activated C-kinase 1/embryonic ectodermal development with nSMase2 are also crucial mechanisms of protein activation. In the review, recent research advances in the structure and function of nSMase2 and its underlying mechanisms are summarized.

Cross-neutralization between three mumps viruses & mapping of haemagglutinin-neuraminidase (HN epitopes

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Sunil R Vaidya

2016-01-01

Full Text Available Background & objectives: The reports from the countries where mumps vaccine is given as routine immunization suggest differences in mumps virus neutralizing antibody titres when tested with vaccine and wild type viruses. Such reports are unavailable from countries like India where mumps vaccine is not included in routine immunization. We, therefore, undertook this study to understand the cross-neutralization activity of Indian mumps viruses. Methods: By using commercial mumps IgG enzyme immunoassay (EIA and a rapid focus reduction neutralization test (FRNT, a panel of serum samples was tested. The panel consisted of 14 acute and 14 convalescent serum samples collected during a mumps outbreak and 18 archived serum samples. Two wild types (genotypes C and G and Leningrad-Zagreb vaccine strain (genotype N were used for the challenge experiments and FRNT titres were determined and further compared. The HN protein sequence of three mumps viruses was analyzed for the presence of key epitopes. Results: All serum samples effectively neutralized mumps virus wild types and a vaccine strain. However, significantly lower FRNT titres were noted to wild types than to vaccine strain (P<0.05. The comparison between EIA and FRNT results revealed 95.6 per cent agreement. No amino acid changes were seen in the epitopes in the Indian wild type strains. All potential N-linked glycosylation sites were observed in Indian strains. Interpretation & conclusions:Good cross-neutralization activity was observed for three mumps virus strains, however, higher level of FRNT titres was detected for mumps virus vaccine strain compared to Indian wild type isolates.

Cross-neutralization between three mumps viruses & mapping of haemagglutinin-neuraminidase (HN) epitopes.

Science.gov (United States)

Vaidya, Sunil R; Dvivedi, Garima M; Jadhav, Santoshkumar M

2016-01-01

The reports from the countries where mumps vaccine is given as routine immunization suggest differences in mumps virus neutralizing antibody titres when tested with vaccine and wild type viruses. Such reports are unavailable from countries like India where mumps vaccine is not included in routine immunization. We, therefore, undertook this study to understand the cross-neutralization activity of Indian mumps viruses. By using commercial mumps IgG enzyme immunoassay (EIA) and a rapid focus reduction neutralization test (FRNT), a panel of serum samples was tested. The panel consisted of 14 acute and 14 convalescent serum samples collected during a mumps outbreak and 18 archived serum samples. Two wild types (genotypes C and G) and Leningrad-Zagreb vaccine strain (genotype N) were used for the challenge experiments and FRNT titres were determined and further compared. The HN protein sequence of three mumps viruses was analyzed for the presence of key epitopes. All serum samples effectively neutralized mumps virus wild types and a vaccine strain. However, significantly lower FRNT titres were noted to wild types than to vaccine strain (P<0.05). The comparison between EIA and FRNT results revealed 95.6 per cent agreement. No amino acid changes were seen in the epitopes in the Indian wild type strains. All potential N-linked glycosylation sites were observed in Indian strains. Good cross-neutralization activity was observed for three mumps virus strains, however, higher level of FRNT titres was detected for mumps virus vaccine strain compared to Indian wild type isolates.

Functionalized carbon nanotube based hybrid electrochemical capacitors using neutral bromide redox-active electrolyte for enhancing energy density

Science.gov (United States)

Tang, Xiaohui; Lui, Yu Hui; Chen, Bolin; Hu, Shan

2017-06-01

A hybrid electrochemical capacitor (EC) with enhanced energy density is realized by integrating functionalized carbon nanotube (FCNT) electrodes with redox-active electrolyte that has a neutral pH value (1 M Na2SO4 and 0.5 M KBr mixed aqueous solution). The negative electrode shows an electric double layer capacitor-type behavior. On the positive electrode, highly reversible Br-/Br3- redox reactions take place, presenting a battery-type behavior, which contributes to increase the capacitance of the hybrid cell. The voltage window of the whole cell is extended up to 1.5 V because of the high over-potentials of oxygen and hydrogen evolution reactions in the neutral electrolyte. Compared with raw CNT, the FCNT has better wettability in the aqueous electrolyte and contributes to increase the electric double layer capacitance of the cell. As a result, the maximum energy density of 28.3 Wh kg-1 is obtained from the hybrid EC at 0.5 A g-1 without sacrificing its power density, which is around 4 times larger than that of the electrical double layer capacitor constructed by FCNT electrodes and 1 M Na2SO4 electrolyte. Moreover, the discharge capacity retained 86.3% of its initial performance after 10000 cycles of galvanostatic charge and discharge test (10 A/g), suggesting its long life cycle even at high current loading.

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.

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

eCD4-Ig variants that more potently neutralize HIV-1.

Science.gov (United States)

Fetzer, Ina; Gardner, Matthew R; Davis-Gardner, Meredith E; Prasad, Neha R; Alfant, Barnett; Weber, Jesse A; Farzan, Michael

2018-03-28

The HIV-1 entry inhibitor eCD4-Ig is a fusion of CD4-Ig and a coreceptor-mimetic peptide. eCD4-Ig is markedly more potent than CD4-Ig, with neutralization efficiencies approaching those of HIV-1 broadly neutralizing antibodies (bNAbs). However, unlike bNAbs, eCD4-Ig neutralizes all HIV-1, HIV-2 and SIV isolates that it has been tested against, suggesting that it may be useful in clinical settings where antibody escape is a concern. Here we characterize three new eCD4-Ig variants, each with different architectures and each utilizing D1.22, a stabilized form of CD4 domain 1. These variants were 10- to 20-fold more potent than our original eCD4-Ig variant, with a construct bearing four D1.22 domains (eD1.22-HL-Ig) exhibiting the greatest potency. However, this variant mediated less efficient antibody-dependent cell-mediated cytotoxicity (ADCC) activity than eCD4-Ig itself or several other eCD4-Ig variants, including the smallest variant (eD1.22-Ig). A variant with the same architecture as original eCD4-Ig (eD1.22-D2-Ig) showed modestly higher thermal stability and best prevented promotion of infection of CCR5-positive, CD4-negative cells. All three variants, and eCD4-Ig itself, mediated more efficient shedding of the HIV-1 envelope glycoprotein gp120 than did CD4-Ig. Finally, we show that only three D1.22 mutations contributed to the potency of eD1.22-D2-Ig, and that introduction of these changes into eCD4-Ig resulted in a variant 9-fold more potent than eCD4-Ig and 2-fold more potent than eD1.22-D2-Ig. These studies will assist in developing eCD4-Ig variants with properties optimized for prophylaxis, therapy, and cure applications. IMPORTANCE HIV-1 bNAbs have properties different from antiretroviral compounds. Specifically, antibodies can enlist immune effector cells to eliminate infected cells, whereas antiretroviral compounds simply interfere with various steps in the viral lifecycle. Unfortunately, HIV-1 is adept at evading antibody recognition, limiting the

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

EVA Development and Verification Testing at NASA's Neutral Buoyancy Laboratory

Science.gov (United States)

Jairala, Juniper C.; Durkin, Robert; Marak, Ralph J.; Sipila, Stepahnie A.; Ney, Zane A.; Parazynski, Scott E.; Thomason, Arthur H.

2012-01-01

As an early step in the preparation for future Extravehicular Activities (EVAs), astronauts perform neutral buoyancy testing to develop and verify EVA hardware and operations. Neutral buoyancy demonstrations at NASA Johnson Space Center's Sonny Carter Training Facility to date have primarily evaluated assembly and maintenance tasks associated with several elements of the International Space Station (ISS). With the retirement of the Shuttle, completion of ISS assembly, and introduction of commercial players for human transportation to space, evaluations at the Neutral Buoyancy Laboratory (NBL) will take on a new focus. Test objectives are selected for their criticality, lack of previous testing, or design changes that justify retesting. Assembly tasks investigated are performed using procedures developed by the flight hardware providers and the Mission Operations Directorate (MOD). Orbital Replacement Unit (ORU) maintenance tasks are performed using a more systematic set of procedures, EVA Concept of Operations for the International Space Station (JSC-33408), also developed by the MOD. This paper describes the requirements and process for performing a neutral buoyancy test, including typical hardware and support equipment requirements, personnel and administrative resource requirements, examples of ISS systems and operations that are evaluated, and typical operational objectives that are evaluated.

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

International Nuclear Information System (INIS)

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

1980-07-01

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

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.

Behavioral and neural indices of affective coloring for neutral social stimuli

Science.gov (United States)

Schaefer, Stacey M; Lapate, Regina C; Schoen, Andrew J; Gresham, Lauren K; Mumford, Jeanette A; Davidson, Richard J

2018-01-01

Abstract Emotional processing often continues beyond the presentation of emotionally evocative stimuli, which can result in affective biasing or coloring of subsequently encountered events. Here, we describe neural correlates of affective coloring and examine how individual differences in affective style impact the magnitude of affective coloring. We conducted functional magnetic resonance imaging in 117 adults who passively viewed negative, neutral and positive pictures presented 2 s prior to neutral faces. Brain responses to neutral faces were modulated by the valence of preceding pictures, with greater activation for faces following negative (vs positive) pictures in the amygdala, dorsomedial and lateral prefrontal cortex, ventral visual cortices, posterior superior temporal sulcus, and angular gyrus. Three days after the magnetic resonance imaging scan, participants rated their memory and liking of previously encountered neutral faces. Individuals higher in trait positive affect and emotional reappraisal rated faces as more likable when preceded by emotionally arousing (negative or positive) pictures. In addition, greater amygdala responses to neutral faces preceded by positively valenced pictures were associated with greater memory for these faces 3 days later. Collectively, these results reveal individual differences in how emotions spill over onto the processing of unrelated social stimuli, resulting in persistent and affectively biased evaluations of such stimuli. PMID:29447377

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.

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…

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.

Effects of neutral particle beam on nano-crystalline silicon thin films, with application to thin film transistor backplane for flexible active matrix organic light emitting diodes

International Nuclear Information System (INIS)

Jang, Jin Nyoung; Song, Byoung Chul; Lee, Dong Hyeok; Yoo, Suk Jae; Lee, Bonju; Hong, MunPyo

2011-01-01

A novel deposition process for nano-crystalline silicon (nc-Si) thin films was developed using neutral beam assisted chemical vapor deposition (NBaCVD) technology for the application of the thin film transistor (TFT) backplane of flexible active matrix organic light emitting diode (AMOLED). During the formation of a nc-Si thin film, the energetic particles enhance nano-sized crystalline rather microcrystalline Si in thin films. Neutral Particle Beam (NPB) affects the crystallinity in two ways: (1) NPB energy enhances nano-crystallinity through kinetic energy transfer and chemical annealing, and (2) heavier NPB (such as Ar) induces damage and amorphization through energetic particle impinging. Nc-Si thin film properties effectively can be changed by the reflector bias. As increase of NPB energy limits growing the crystalline, the performance of TFT supports this NPB behavior. The results of nc-Si TFT by NBaCVD demonstrate the technical potentials of neutral beam based processes for achieving high stability and reduced leakage in TFT backplanes for AMOLEDs.

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

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.

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

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.

The Columbia Non-neutral Torus

International Nuclear Information System (INIS)

Pedersen, Thomas Sunn

2009-01-01

Final report for the Columbia Non-neutral Torus. This details the results from the design, construction and initial operation of the Columbia Non-neutral Torus. During the duration of this grant, I designed, built, and operated the Columbia Nonneutral Torus, the world's lowest aspect ratio stellarator, and arguably, the world's simplest stellarator. This demonstrates the ease and robustness of the chosen stellarator design and allowed us to commence the investigation of the physics of non-neutral plasmas confined on magnetic surfaces. These plasmas are unique in many ways and had not previously been studied in a stellarator. Our first results showed that it is possible to confine and study a relatively cold pure electron plasma in a stellarator. We confirmed that the plasma is stable, and that the plasma is reasonably well confined in a stellarator configuration. These results were published in Physics of Plasmas (2006) and Physical Review Letters (2006). They enabled the existing program which is resolving the underlying transport processes in a classical stellarator with intense self-electric fields and enable the next phase of operation, electron-positron plasma physics. During the period of this grant, two students were trained in experimental plasma physics and both received their PhD degrees shortly after the grant terminated. One student is now employed in the financial services industry, the other is a postdoctoral associate at Los Alamos National Laboratory. The chief goals were to build and begin operation of the Columbia Non-neutral Torus. These goals were achieved in the third year of funding. The development of diagnostic methods and the confirmation of stable equilibria were also achieved during the grant period. In summary, the main scientific goals were all met. The main educational goals were also met, as the experiment became the training ground not only for the two aforementioned graduate students but also for a number of undergraduate students

Children and trauma : a broad perspective on exposure and recovery

NARCIS (Netherlands)

Alisic, E.

2011-01-01

The purpose of this dissertation was to generate a broad overview of children’s exposure to and recovery from trauma in order to promote theory building and the design of prevention and intervention activities. First, a general population study was conducted in 1770 primary school children. They

Hepatitis C virus epitope exposure and neutralization by antibodies is affected by time and temperature

DEFF Research Database (Denmark)

Sabo, Michelle C; Luca, Vincent C; Ray, Stuart C

2012-01-01

A recent study with flaviviruses suggested that structural dynamics of the virion impact antibody neutralization via exposure of ostensibly cryptic epitopes. To determine whether this holds true for the distantly related hepatitis C virus (HCV), whose neutralizing epitopes may be obscured...... by a glycan shield, apolipoprotein interactions, and the hypervariable region on the E2 envelope protein, we assessed how time and temperature of pre-incubation altered monoclonal antibody (MAb) neutralization of HCV. Notably, several MAbs showed increased inhibitory activity when pre-binding was performed...

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

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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.

Neutral Polymeric Micelles for RNA Delivery

Science.gov (United States)

Lundy, Brittany B.; Convertine, Anthony; Miteva, Martina; Stayton, Patrick S.

2013-01-01

RNA interference (RNAi) drugs have significant therapeutic potential but delivery systems with appropriate efficacy and toxicity profiles are still needed. Here, we describe a neutral, ampholytic polymeric delivery system based on conjugatable diblock polymer micelles. The diblock copolymer contains a hydrophilic poly[N-(2-hydroxypropyl) methacrylamide-co-N-(2-(pyridin-2- yldisulfanyl)ethyl)methacrylamide) (poly[HPMA-co-PDSMA]) segment to promote aqueous stability and facilitate thiol-disulfide exchange reactions, and a second ampholytic block composed of propyl acrylic acid (PAA), dimethylaminoethyl methacrylate (DMAEMA), and butyl methacrylate (BMA). The poly[(HPMA-co-PDSMA)-b-(PAA-co-DMAEMA-co-BMA)] was synthesized using Reversible Addition-Fragmentation chain Transfer (RAFT) polymerization with an overall molecular weight of 22,000 g/mol and a PDI of 1.88. Dynamic light scattering and fluorescence measurements indicated that the diblock copolymers self-assemble under aqueous conditions to form polymeric micelles with a hydrodynamic radius and critical micelle concentration of 25 nm and 25 μg/mL respectively. Red blood cell hemolysis experiments show that the neutral hydrophilic micelles have potent membrane destabilizing activity at endosomal pH values. Thiolated siRNA targeting glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was directly conjugated to the polymeric micelles via thiol exchange reactions with the pyridal disulfide groups present in the micelle corona. Maximum silencing activity in HeLa cells was observed at a 1:10 molar ratio of siRNA to polymer following a 48 h incubation period. Under these conditions 90 % mRNA knockdown and 65 % and protein knockdown of at 48 h was achieved with negligible toxicity. In contrast the polymeric micelles lacking a pH-responsive endosomalytic segment demonstrated negligible mRNA and protein knockdown under these conditions. The potent mRNA knockdown and excellent biocompatibility of the neutral siRNA conjugates

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

Active thermal fine laser tuning in a broad spectral range and optical properties of cholesteric liquid crystal.

Science.gov (United States)

Jeong, Mi-Yun; Kwak, Keumcheol

2016-11-20

In this study, we achieved active fine laser tuning in a broad spectral range with dye-doped cholesteric liquid crystal wedge-type cells through temperature control. The spatial pitch gradient of each position of the wedge cell at room temperature was almost maintained after developing a temperature gradient. To achieve the maximum tuning range, the chiral dopant concentration, thickness, thickness gradient, and temperature gradient on the wedge cell should be matched properly. In order to understand the laser tuning mechanism for temperature change, we studied the temperature dependence of optical properties of the photonic bandgap of cholesteric liquid crystals. In our cholesteric liquid crystal samples, when temperature was increased, photonic bandgaps were shifted toward blue, while the width of the photonic bandgap was decreased, regardless of whether the helicity was left-handed or right-handed. This is mainly due to the combination of decreased refractive indices, higher molecular anisotropy of chiral molecules, and increased chiral molecular solubility. We envisage that this kind of study will prove useful in the development of practical active tunable CLC laser devices.

TPX/TFTR Neutral Beam energy absorbers

International Nuclear Information System (INIS)

Dahlgren, F.; Wright, K.; Kamperschroer, J.; Grisham, L.; Lontai, L.; Peters, C.; VonHalle, A.

1993-01-01

The present beam energy absorbing surfaces on the TFTR Neutral Beams such as Ion Dumps, Calorimeters, beam defining apertures, and scrapers, are simple water cooled copper plates which wee designed to absorb (via their thermal inertia) the incident beam power for two seconds with a five minute coal down interval between pulses. These components are not capable of absorbing the anticipated beam power loading for 1000 second TPX pulses and will have to be replaced with an actively cooled design. While several actively cooled energy absorbing designs were considered,, the hypervapotron elements currently being used on the JET beamlines were chosen due to their lower cooling water demands and reliable performance on JET

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

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

A novel reporter system for neutralizing and enhancing antibody assay against dengue virus.

Science.gov (United States)

Song, Ke-Yu; Zhao, Hui; Jiang, Zhen-You; Li, Xiao-Feng; Deng, Yong-Qiang; Jiang, Tao; Zhu, Shun-Ya; Shi, Pei-Yong; Zhang, Bo; Zhang, Fu-Chun; Qin, E-De; Qin, Cheng-Feng

2014-02-18

Dengue virus (DENV) still poses a global public health threat, and no vaccine or antiviral therapy is currently available. Antibody plays distinct roles in controlling DENV infections. Neutralizing antibody is protective against DENV infection, whereas sub-neutralizing concentration of antibody can increase DENV infection, termed antibody-dependent enhancement (ADE). Plaque-based assay represents the most widely accepted method measuring neutralizing or enhancing antibodies. In this study, a novel reporter virus-based system was developed for measuring neutralization and ADE activity. A stable Renilla luciferase reporter DENV (Luc-DENV) that can produce robust luciferase signals in BHK-21 and K562 cells were used to establish the assay and validated against traditional plaque-based assay. Luciferase value analysis using various known DENV-specific monoclonal antibodies showed good repeatability and a well linear correlation with conventional plaque-based assays. The newly developed assay was finally validated with clinical samples from infected animals and individuals. This reporter virus-based assay for neutralizing and enhancing antibody evaluation is rapid, lower cost, and high throughput, and will be helpful for laboratory detection and epidemiological investigation for DENV antibodies.

Broad-Band Visually Evoked Potentials: Re(convolution in Brain-Computer Interfacing.

Directory of Open Access Journals (Sweden)

Jordy Thielen

Full Text Available Brain-Computer Interfaces (BCIs allow users to control devices and communicate by using brain activity only. BCIs based on broad-band visual stimulation can outperform BCIs using other stimulation paradigms. Visual stimulation with pseudo-random bit-sequences evokes specific Broad-Band Visually Evoked Potentials (BBVEPs that can be reliably used in BCI for high-speed communication in speller applications. In this study, we report a novel paradigm for a BBVEP-based BCI that utilizes a generative framework to predict responses to broad-band stimulation sequences. In this study we designed a BBVEP-based BCI using modulated Gold codes to mark cells in a visual speller BCI. We defined a linear generative model that decomposes full responses into overlapping single-flash responses. These single-flash responses are used to predict responses to novel stimulation sequences, which in turn serve as templates for classification. The linear generative model explains on average 50% and up to 66% of the variance of responses to both seen and unseen sequences. In an online experiment, 12 participants tested a 6 × 6 matrix speller BCI. On average, an online accuracy of 86% was reached with trial lengths of 3.21 seconds. This corresponds to an Information Transfer Rate of 48 bits per minute (approximately 9 symbols per minute. This study indicates the potential to model and predict responses to broad-band stimulation. These predicted responses are proven to be well-suited as templates for a BBVEP-based BCI, thereby enabling communication and control by brain activity only.

Broad anti-HIV activity of the Oscillatoria agardhii agglutinin homologue lectin family.

Science.gov (United States)

Férir, Geoffrey; Huskens, Dana; Noppen, Sam; Koharudin, Leonardus M I; Gronenborn, Angela M; Schols, Dominique

2014-10-01

Oscillatoria agardhii agglutinin homologue (OAAH) proteins belong to a recently discovered lectin family. The founding member OAA and a designed hybrid OAAH (OPA) recognize similar but unique carbohydrate structures of Man-9, compared with other antiviral carbohydrate-binding agents (CBAs). These two newly described CBAs were evaluated for their inactivating properties on HIV replication and transmission and for their potential as microbicides. Various cellular assays were used to determine antiviral activity against wild-type and certain CBA-resistant HIV-1 strains: (i) free HIV virion infection in human T lymphoma cell lines and PBMCs; (ii) syncytium formation assay using persistently HIV-infected T cells and non-infected CD4+ T cells; (iii) DC-SIGN-mediated viral capture; and (iv) transmission to uninfected CD4+ T cells. OAA and OPA were also evaluated for their mitogenic properties and potential synergistic effects using other CBAs. OAA and OPA inhibit HIV replication, syncytium formation between HIV-1-infected and uninfected T cells, DC-SIGN-mediated HIV-1 capture and transmission to CD4+ target T cells, thereby rendering a variety of HIV-1 and HIV-2 clinical isolates non-infectious, independent of their coreceptor use. Both CBAs competitively inhibit the binding of the Manα(1-2)Man-specific 2G12 monoclonal antibody (mAb) as shown by flow cytometry and surface plasmon resonance analysis. The HIV-1 NL4.3(2G12res), NL4.3(MVNres) and IIIB(GRFTres) strains were equally inhibited as the wild-type HIV-1 strains by these CBAs. Combination studies indicate that OAA and OPA act synergistically with Hippeastrum hybrid agglutinin, 2G12 mAb and griffithsin (GRFT), with the exception of OPA/GRFT. OAA and OPA are unique CBAs with broad-spectrum anti-HIV activity; however, further optimization will be necessary for microbicidal application. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights

Highly Oriented Growth of Catalytically Active Zeolite ZSM-5 Films with a Broad Range of Si/Al Ratios.

Science.gov (United States)

Fu, Donglong; Schmidt, Joel E; Ristanović, Zoran; Chowdhury, Abhishek Dutta; Meirer, Florian; Weckhuysen, Bert M

2017-09-04

Highly b-oriented zeolite ZSM-5 films are critical for applications in catalysis and separations and may serve as models to study diffusion and catalytic properties in single zeolite channels. However, the introduction of catalytically active Al 3+ usually disrupts the orientation of zeolite films. Herein, using structure-directing agents with hydroxy groups, we demonstrate a new method to prepare highly b-oriented zeolite ZSM-5 films with a broad range of Si/Al ratios (Si/Al=45 to ∞). Fluorescence micro-(spectro)scopy was used to monitor misoriented microstructures, which are invisible to X-ray diffraction, and show Al 3+ framework incorporation and illustrate the differences between misoriented and b-oriented films. The methanol-to-hydrocarbons process was studied by operando UV/Vis diffuse reflectance micro-spectroscopy with on-line mass spectrometry, showing that the b-oriented zeolite ZSM-5 films are active and stable under realistic process conditions. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Antibacterial activity and safety of commercial veterinary cationic steroid antibiotics and neutral superoxidized water.

Directory of Open Access Journals (Sweden)

Benjamin E Bergstrom

Full Text Available Antibiotic resistance of bacteria common to the ocular surface is an evolving problem. Thus, novel treatment options with new modes of action are required. We investigated the antibacterial activity and safety of three commercially available topical veterinary ophthalmic products (cationic steroid antibiotics, products A and B, and a neutral superoxidized water, product C to determine their potential use as antimicrobial alternatives. The minimum inhibitory concentrations (MIC of the three products were determined against 17 antibiotic resistant bacterial clinical isolates from the ocular surface. Using a standard cytotoxicity assay, the products at varying concentrations were evaluated with a corneal fibroblast cell line and a macrophage-like cell line to determine their potential toxic effect in vitro. The commercial ophthalmic solutions, ofloxacin 0.3%, tobramycin 0.3% and gentamicin 0.3% were used as positive controls for the MIC and tobramycin 0.3% was used as positive control for the cytotoxicity assays. For the MIC, Product C showed no inhibition of growth for any organisms, while Products A and B showed inhibition of growth similar to slightly less than the positive controls. For the cytotoxicity assays, Product C exhibited minimal toxicity while Products A and B exhibited toxicity similar to the controls. In conclusion, Product C had no antibacterial activity in these assays, while Products A and B had antibacterial profiles similar to slightly less than common topical ophthalmic antibiotics and cytotoxicity profiles similar to common topical ophthalmic antibiotics. To our knowledge, this is the first report on the antibacterial activity and safety of the cationic steroid antibiotics and superoxidized water.

National negative-ion-based neutral-beam development plan

International Nuclear Information System (INIS)

Cooper, W.S.; Pyle, R.V.

1983-08-01

The plan covers facilities required, program milestones, and decision points. It includes identification of applications, experiments, theoretical research areas, development of specific technologies and reactor development and demonstration facilities required to bring about the successful application of negative-ion-based neutral beams. Particular emphasis is placed on those activities leading to use on existing plasma confinement experiments or their upgrades

The Activity of the Neutral Sphingomyelinase Is Important in T Cell Recruitment and Directional Migration

Directory of Open Access Journals (Sweden)

Lena Collenburg

2017-08-01

Full Text Available Breakdown of sphingomyelin as catalyzed by the activity of sphingomyelinases profoundly affects biophysical properties of cellular membranes which is particularly important with regard to compartmentalization of surface receptors and their signaling relay. As it is activated both upon TCR ligation and co-stimulation in a spatiotemporally controlled manner, the neutral sphingomyelinase (NSM has proven to be important in T cell activation, where it appears to play a particularly important role in cytoskeletal reorganization and cell polarization. Because these are important parameters in directional T cell migration and motility in tissues, we analyzed the role of the NSM in these processes. Pharmacological inhibition of NSM interfered with early lymph node homing of T cells in vivo indicating that the enzyme impacts on endothelial adhesion, transendothelial migration, sensing of chemokine gradients or, at a cellular level, acquisition of a polarized phenotype. NSM inhibition reduced adhesion of T cells to TNF-α/IFN-γ activated, but not resting endothelial cells, most likely via inhibiting high-affinity LFA-1 clustering. NSM activity proved to be highly important in directional T cell motility in response to SDF1-α, indicating that their ability to sense and translate chemokine gradients might be NSM dependent. In fact, pharmacological or genetic NSM ablation interfered with T cell polarization both at an overall morphological level and redistribution of CXCR4 and pERM proteins on endothelial cells or fibronectin, as well as with F-actin polymerization in response to SDF1-α stimulation, indicating that efficient directional perception and signaling relay depend on NSM activity. Altogether, these data support a central role of the NSM in T cell recruitment and migration both under homeostatic and inflamed conditions by regulating polarized redistribution of receptors and their coupling to the cytoskeleton.

Potential Adverse Effects of Broad-Spectrum Antimicrobial Exposure in the Intensive Care Unit.

Science.gov (United States)

Wiens, Jenna; Snyder, Graham M; Finlayson, Samuel; Mahoney, Monica V; Celi, Leo Anthony

2018-02-01

The potential adverse effects of empiric broad-spectrum antimicrobial use among patients with suspected but subsequently excluded infection have not been fully characterized. We sought novel methods to quantify the risk of adverse effects of broad-spectrum antimicrobial exposure among patients admitted to an intensive care unit (ICU). Among all adult patients admitted to ICUs at a single institution, we selected patients with negative blood cultures who also received ≥1 broad-spectrum antimicrobials. Broad-spectrum antimicrobials were categorized in ≥1 of 5 categories based on their spectrum of activity against potential pathogens. We performed, in serial, 5 cohort studies to measure the effect of each broad-spectrum category on patient outcomes. Exposed patients were defined as those receiving a specific category of broad-spectrum antimicrobial; nonexposed were all other patients in the cohort. The primary outcome was 30-day mortality. Secondary outcomes included length of hospital and ICU stay and nosocomial acquisition of antimicrobial-resistant bacteria (ARB) or Clostridium difficile within 30 days of admission. Among the study cohort of 1918 patients, 316 (16.5%) died within 30 days, 821 (42.8%) had either a length of hospital stay >7 days or an ICU length of stay >3 days, and 106 (5.5%) acquired either a nosocomial ARB or C. difficile . The short-term use of broad-spectrum antimicrobials in any of the defined broad-spectrum categories was not significantly associated with either primary or secondary outcomes. The prompt and brief empiric use of defined categories of broad-spectrum antimicrobials could not be associated with additional patient harm.

Arginine-rich histones have strong antiviral activity for influenza A viruses.

Science.gov (United States)

Hoeksema, Marloes; Tripathi, Shweta; White, Mitchell; Qi, Li; Taubenberger, Jeffery; van Eijk, Martin; Haagsman, Henk; Hartshorn, Kevan L

2015-10-01

While histones are best known for DNA binding and transcription-regulating properties, they also have antimicrobial activity against a broad range of potentially pathogenic organisms. Histones are abundant in neutrophil extracellular traps, where they play an important role in NET-mediated antimicrobial killing. Here, we show anti-influenza activity of histones against both seasonal H3N2 and H1N1, but not pandemic H1N1. The arginine rich histones, H3 and H4, had greater neutralizing and viral aggregating activity than the lysine rich histones, H2A and H2B. Of all core histones, histone H4 is most potent in neutralizing IAV, and incubation with IAV with histone H4 results in a decrease in uptake and viral replication by epithelial cells when measured by qRT-PCR. The antiviral activity of histone H4 is mediated principally by direct effects on viral particles. Histone H4 binds to IAV as assessed by ELISA and co-sedimentation of H4 with IAV. H4 also induces aggregation, as assessed by confocal microscopy and light transmission assays. Despite strong antiviral activity against the seasonal IAV strains, H4 was inactive against pandemic H1N1. These findings indicate a possible role for histones in the innate immune response against IAV. © The Author(s) 2015.

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.

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

Diagnostics of pre-breakdown light emission in a helium coplanar barrier discharge: the presence of neutral bremsstrahlung

Science.gov (United States)

Navrátil, Zdeněk; Morávek, Tomáš; Ráheľ, Jozef; Čech, Jan; Lalinský, Ondřej; Trunec, David

2017-05-01

Weak light emission (˜10-3 of active discharge signal; average count rate ˜ 1 photon s-1 nm-1) associated with surface charge relaxation during the dark phase of a helium diffuse coplanar barrier discharge was studied by optical emission spectroscopy, using a technique of phase-resolved single photon counting. The optical emission spectra of the dark phase contained luminescent bands of the dielectrics used (Al2O3, AlN) and spectral lines from the gas constituents (OH*, {{{N}}}2* , {{{N}}}2+* , He*, He{}2* , O*). During the charge relaxation event, a broad continuum appeared in the optical emission spectra, consisting of bremsstrahlung radiation and amplified luminescence of the dielectric barrier. The analysis presented suggests that the bremsstrahlung radiation originated from slow electrons colliding with neutral helium atoms. The fitting procedure we developed reproduced well the observed shape of the continuum. Moreover, it provided a method for the determination of electric field strength in the discharge during this particular phase. The electric field reached 1 kV cm-1 during the charge relaxation event.

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.

Glycosylation analysis of recombinant neutral protease I from Aspergillus oryzae expressed in Pichia pastoris.

Science.gov (United States)

Lei, Da; Xu, Yang; He, Qinghua; Pang, Yifeng; Chen, Bo; Xiong, Liang; Li, Yanping

2013-12-01

Neutral protease I from Aspergillus oryzae 3.042 was expressed in Pichia pastoris and its N-glycosylation properties were analyzed. After purification by nickel-affinity chromatography column, the recombinant neutral protease (rNPI) was confirmed to be N-glycosylated by periodicacid/Schiff's base staining and Endo H digestion. Moreover, the deglycosylated protein's molecular weight decreased to 43.3 kDa from 54.5 kDa analyzed by SDS-PAGE and MALDI-TOF-MS, and the hyperglycosylation extent was 21 %. The N-glycosylation site of rNPI was analyzed by nano LC-MS/MS after digesting by trypsin and Glu-C, and the unique potential site Asn41 of mature peptide was found to be glycosylated. Homology modeling of the 3D structure of rNPI indicated that the attached N-glycans hardly affected neutral protease's activity due to the great distance away from the active site of the enzyme.

Preparation of translationally cold neutral molecules.

Science.gov (United States)

Di Domenicantonio, Giulia; Bertsche, Benjamin; Osterwalder, Andreas

2011-01-01

Efforts at EPFL to obtain translationally cold neutral molecules are described. Active deceleration of polar molecules is performed by confining the molecules in moving three-dimensional electrostatic traps, and by appropriately choosing the velocity of those traps. Alternatively, cold molecules can be obtained by velocity filtering. Here, the velocity of the molecules is not changed, but instead the cold molecules are extracted from a thermal sample by using the competition between the electrostatic force and the centrifugal force inside a bent electrostatic guide for polar molecules.

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.

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

Energy Technology Data Exchange (ETDEWEB)

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

2010-08-15

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

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

Lanthanoid abundance of some neutral hot spring waters in Japan

International Nuclear Information System (INIS)

Kikawada, Yoshikazu; Oi, Takao; Honda, Teruyuki

1999-01-01

Contents of lanthanoids (Ln's) in some neutral hot spring waters as well as in acidic hot spring waters were determined by neutron activation analysis. It was found that a higher pH resulted in lower concentrations of Ln's; the value of correlation coefficient (r) between the logarithm of the concentration of Sm ([Sm]), chosen as the representative of Ln's, and the logarithm of pH was -0.90. The sum of [Al] and [Fe] was strongly correlated with [Ln]'s in the pH range of 1.3 and 8.8; the correlation was expressed as log[Sm] = 0.893 log([Al] + [Fe]) - 5.45 with the r value of 0.98. The sum of [Al] and [Fe] was thus a good measure of the Ln contents in acidic and neutral hot spring waters. The Ln abundance patterns of neutral hot spring waters with normal CO 2 concentrations had concave shapes with relative depletion in the middle-heavy Ln's and seemed to reflect the solubility of Ln carbonates. The neutral hot spring water with a high CO 2 content of 1,800 ppm showed a Ln pattern with a relative enrichment in the heavy Ln's and seemed to reflect the solubility of Ln's observed for CO 2 -rich solutions. (author)

Complete Genome Sequence of Bacillus velezensis YJ11-1-4, a Strain with Broad-Spectrum Antimicrobial Activity, Isolated from Traditional Korean Fermented Soybean Paste.

Science.gov (United States)

Lee, Hyo Jung; Chun, Byung-Hee; Jeon, Hye Hee; Kim, Yeon Bee; Lee, Se Hee

2017-11-30

Bacillus velezensis YJ11-1-4 is a strain that exhibits broad-spectrum antimicrobial activity against various pathogens. It was isolated from doenjang, a traditional Korean fermented soybean paste. The genome comprises a single circular chromosome of 4,006,637 bp with 46.42% G+C content without plasmids. Copyright © 2017 Lee et al.

Genomic insights into the broad antifungal activity, plant-probiotic properties, and their regulation, in Pseudomonas donghuensis strain SVBP6

Science.gov (United States)

Iriarte, Andrés; Valverde, Claudio Fabián

2018-01-01

Plant-growth promotion has been linked to the Pseudomonas genus since the beginning of this research field. In this work, we mined the genome of an Argentinean isolate of the recently described species P. donghuensis. Strain SVBP6, isolated from bulk soil of an agricultural plot, showed a broad antifungal activity and several other plant-probiotic activities. As this species has been recently described, and it seems like some plant-growth promoting (PGP) traits do not belong to the classical pseudomonads toolbox, we decide to explore the SVBP6 genome via an bioinformatic approach. Genome inspection confirmed our previous in vitro results about genes involved in several probiotic activities. Other genetic traits possibly involved in survival of SVBP6 in highly competitive environments, such as rhizospheres, were found. Tn5 mutagenesis revealed that the antifungal activity against the soil pathogen Macrophomina phaseolina was dependent on a functional gacS gene, from the regulatory cascade Gac-Rsm, but it was not due to volatile compounds. Altogether, our genomic analyses and in vitro tests allowed the phylogenetic assignment and provided the first insights into probiotic properties of the first P. donghuensis isolate from the Americas. PMID:29538430

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

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.

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)

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...

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...

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.

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)

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

The Freshwater Sponge Ephydatia fluviatilis Harbours Diverse Pseudomonas Species (Gammaproteobacteria, Pseudomonadales) with Broad-Spectrum Antimicrobial Activity

Science.gov (United States)

Keller-Costa, Tina; Jousset, Alexandre; van Overbeek, Leo; van Elsas, Jan Dirk; Costa, Rodrigo

2014-01-01

Bacteria are believed to play an important role in the fitness and biochemistry of sponges (Porifera). Pseudomonas species (Gammaproteobacteria, Pseudomonadales) are capable of colonizing a broad range of eukaryotic hosts, but knowledge of their diversity and function in freshwater invertebrates is rudimentary. We assessed the diversity, structure and antimicrobial activities of Pseudomonas spp. in the freshwater sponge Ephydatia fluviatilis. Polymerase Chain Reaction – Denaturing Gradient Gel Electrophoresis (PCR-DGGE) fingerprints of the global regulator gene gacA revealed distinct structures between sponge-associated and free-living Pseudomonas communities, unveiling previously unsuspected diversity of these assemblages in freshwater. Community structures varied across E. fluviatilis specimens, yet specific gacA phylotypes could be detected by PCR-DGGE in almost all sponge individuals sampled over two consecutive years. By means of whole-genome fingerprinting, 39 distinct genotypes were found within 90 fluorescent Pseudomonas isolates retrieved from E. fluviatilis. High frequency of in vitro antibacterial (49%), antiprotozoan (35%) and anti-oomycetal (32%) activities was found among these isolates, contrasting less-pronounced basidiomycetal (17%) and ascomycetal (8%) antagonism. Culture extracts of highly predation-resistant isolates rapidly caused complete immobility or lysis of cells of the protozoan Colpoda steinii. Isolates tentatively identified as P. jessenii, P. protegens and P. oryzihabitans showed conspicuous inhibitory traits and correspondence with dominant sponge-associated phylotypes registered by cultivation-independent analysis. Our findings suggest that E. fluviatilis hosts both transient and persistent Pseudomonas symbionts displaying antimicrobial activities of potential ecological and biotechnological value. PMID:24533086

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)

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

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

Losing Neutrality: The Neural Basis of Impaired Emotional Control without Sleep.

Science.gov (United States)

Simon, Eti Ben; Oren, Noga; Sharon, Haggai; Kirschner, Adi; Goldway, Noam; Okon-Singer, Hadas; Tauman, Rivi; Deweese, Menton M; Keil, Andreas; Hendler, Talma

2015-09-23

Sleep deprivation has been shown recently to alter emotional processing possibly associated with reduced frontal regulation. Such impairments can ultimately fail adaptive attempts to regulate emotional processing (also known as cognitive control of emotion), although this hypothesis has not been examined directly. Therefore, we explored the influence of sleep deprivation on the human brain using two different cognitive-emotional tasks, recorded using fMRI and EEG. Both tasks involved irrelevant emotional and neutral distractors presented during a competing cognitive challenge, thus creating a continuous demand for regulating emotional processing. Results reveal that, although participants showed enhanced limbic and electrophysiological reactions to emotional distractors regardless of their sleep state, they were specifically unable to ignore neutral distracting information after sleep deprivation. As a consequence, sleep deprivation resulted in similar processing of neutral and negative distractors, thus disabling accurate emotional discrimination. As expected, these findings were further associated with a decrease in prefrontal connectivity patterns in both EEG and fMRI signals, reflecting a profound decline in cognitive control of emotion. Notably, such a decline was associated with lower REM sleep amounts, supporting a role for REM sleep in overnight emotional processing. Altogether, our findings suggest that losing sleep alters emotional reactivity by lowering the threshold for emotional activation, leading to a maladaptive loss of emotional neutrality. Significance statement: Sleep loss is known as a robust modulator of emotional reactivity, leading to increased anxiety and stress elicited by seemingly minor triggers. In this work, we aimed to portray the neural basis of these emotional impairments and their possible association with frontal regulation of emotional processing, also known as cognitive control of emotion. Using specifically suited EEG and f

Vision, trends, gaps and a broad road map for future engineering

NARCIS (Netherlands)

Goossenaerts, J.B.M.; Possel-Dölken, F.; Popplewell, K.

2007-01-01

New challenges result from the virtualization and distribution of product development activities. This article analyzes problems of cooperative engineering as well as methods and tools for the virtual engineering of extended products. Based on these analyses, a broad road map is proposed that

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

Fast-ion transport and neutral beam current drive in ASDEX upgrade

DEFF Research Database (Denmark)

Geiger, B.; Weiland, M.; Jacobsen, Asger Schou

2015-01-01

The neutral beam current drive efficiency has been investigated in the ASDEX Upgrade tokamak by replacing on-axis neutral beams with tangential off-axis beams. A clear modification of the radial fast-ion profiles is observed with a fast-ion D-alpha diagnostic that measures centrally peaked profiles...... during on-axis injection and outwards shifted profiles during off-axis injection. Due to this change of the fast-ion population, a clear modification of the plasma current profile is predicted but not observed by a motional Stark effect diagnostic. The fast-ion transport caused by MHD activity has been...

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

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.

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.

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.

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_{\

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

Monolithic front-end preamplifiers for a broad range of calorimetry applications

Energy Technology Data Exchange (ETDEWEB)

Radeka, V.; Rescia, S. [Brookhaven National Lab., Upton, NY (United States); Manfredi, P.F.; Speziali, V. [Pavia Univ. (Italy). Dipt. di Elettronica]|[INFN--Sezzione di Milano, Milano (Italy)

1993-12-31

The present paper summarizes the salient results of a research and development activity in the area of low noise preamplifiers for different applications in calorimetry. Design target for all circuits considered here are low noise, ability to cope with broad energy ranges and radiation hardness.

The precipitation synthesis of broad-spectrum UV absorber nanoceria

International Nuclear Information System (INIS)

Nurhasanah, Iis; Sutanto, Heri; Puspaningrum, Nurul Wahyu

2013-01-01

In this paper the possibility of nanoceria as broad-spectrum UV absorber was evaluated. Nanoceria were synthesized by precipitation process from cerium nitrate solution and ammonium hydroxide as precipitant agent. Isopropanol was mixed with water as solvent to prevent hard agglomeration. The structure of resulting nanoceria was characterized by x-ray diffractometer (XRD). The transparency in the visible light and efficiency of protection in UV A region were studied using ultraviolet-visible (UV - Vis) spectrophotometer. The results show that nanoceria possess good tranparency in visible light and high UV light absorption. The critical absorption wavelenght of 368 nm was obtained which is desirable for excellent broad-spectrum protection absorbers. Moreover, analysis of photodegradation nanoceria to methylene blue solution shows poor photocatalytic activity. It indicates that nanoceria suitable for used as UV absorber in personal care products

Broad spectrum bioactive sunscreens.

Science.gov (United States)

Velasco, Maria Valéria Robles; Sarruf, Fernanda Daud; Salgado-Santos, Idalina Maria Nunes; Haroutiounian-Filho, Carlos Alberto; Kaneko, Telma Mary; Baby, André Rolim

2008-11-03

The development of sunscreens containing reduced concentration of chemical UV filters, even though, possessing broad spectrum effectiveness with the use of natural raw materials that improve and infer UV absorption is of great interest. Due to the structural similarities between polyphenolic compounds and organic UV filters, they might exert photoprotection activity. The objective of the present research work was to develop bioactive sunscreen delivery systems containing rutin, Passiflora incarnata L. and Plantago lanceolata extracts associated or not with organic and inorganic UV filters. UV transmission of the sunscreen delivery system films was performed by using diffuse transmittance measurements coupling to an integrating sphere. In vitro photoprotection efficacy was evaluated according to the following parameters: estimated sun protection factor (SPF); Boot's Star Rating category; UVA/UVB ratio; and critical wavelength (lambda(c)). Sunscreen delivery systems obtained SPF values ranging from 0.972+/-0.004 to 28.064+/-2.429 and bioactive compounds interacted with the UV filters positive and negatively. This behavior may be attributed to: the composition of the delivery system; the presence of inorganic UV filter and quantitative composition of the organic UV filters; and the phytochemical composition of the P. incarnata L. and P. lanceolata extracts. Among all associations of bioactive compounds and UV filters, we found that the broad spectrum sunscreen was accomplished when 1.68% (w/w) P. incarnata L. dry extract was in the presence of 7.0% (w/w) ethylhexyl methoxycinnamate, 2.0% (w/w) benzophenone-3 and 2.0% (w/w) TiO(2). It was demonstrated that this association generated estimated SPF of 20.072+/-0.906 and it has improved the protective defense against UVA radiation accompanying augmentation of the UVA/UVB ratio from 0.49 to 0.52 and lambda(c) from 364 to 368.6nm.

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

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

International Nuclear Information System (INIS)

Boldrin, Marco; De Lorenzi, Antonio; Decamps, Hans; Grando, Luca; Simon, Muriel; Toigo, Vanni

2013-01-01

Highlights: ► ITER Neutral Beam Injector includes several non-standard components. ► The design status of the −1 MV dc HVD1 and Bushing is described. ► The paper reports also on the integrated layout of the two components. ► Preliminary electrostatic and thermal analyses are presented. ► Procurement activities are outlined. -- Abstract: The ITER Neutral Beam Injector (NBI) power supply system includes several non-standard components, whose ratings go beyond the present industrial practice. Two of these items, to be procured by Fusion for Energy, are: 1.A −1 MV dc air-insulated Faraday cage, called High Voltage Deck 1 (HVD1), hosting the Ion Source and Extractor Power Supplies (ISEPS) and the associated diagnostics. 2.A −1 MV dc feedthrough, called HVD1-TL Bushing, aimed at connecting the HVD1 to the gas (SF 6 ) insulated Transmission Line (TL), containing inside its High Voltage (HV) conductor all ISEPS power and control cables coming from the HVD1 to be connected to the NBI Ion Source services. The paper deals with the status of the design of the HVD1 and HVD1-TL Bushing, focusing on insulation, mechanical and thermal issues as well as on their integration with the other components of the power supply system. In particular, the insulation issue of the integrated system has been addressed by means of an electrostatic Finite Element (FE) analysis whilst a FE thermal simulation has been carried out to assess the impact of the dissipation of the proposed design of the inner conductors (ISEPS conductors) not actively cooled. Finally, the paper describes the status of procurement strategy and execution

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

Application in industry and energy production of active carbon/cobalt catalyst for nitrogen oxide neutralization

International Nuclear Information System (INIS)

Mekhandzhiev, D.; Nikolov, R.; Lyutskanov, L.; Dushanov, D.; Lakov, L.

1997-01-01

A new material for neutralization of nitrogen oxides is presented. Two or three metals containing catalysts with a good activity and selectivity towards NO x have been obtained. Preparation of carbon catalysts by deposition of the active phase precursor on the initial carbon material prior to activation is considered as the most promising method. An active carbon-based catalyst (AC/Co) has been synthesized Apricot shells preliminary impregnated with a water-alcohol solution of Co nitrate have been used as initial carbon material. after drying they have been subjected to one-phase steam pyrolysis using a fix-bed reactor. The catalyst thus obtained has a specific surface area (BET) of 53 m 2 g -1 , a favorable mesopore volume/total volume ratio (about 0.85) determined by nitrogen adsorption, a suitable mesopore distribution, about 70% of the mesopores being characterized by r p larger than 25 A and a high dispersion of the Co oxide phase. In addition the catalyst possesses the necessary mechanical resistance. The catalyst has exhibited a high activity with respect to NO x reduction with CO at low temperatures (at 150-250 o C which are the temperatures of industrial flue gases, nO conversion up to 60-95% occurs) and a high selectivity. No presence of H 2 O has been established over the whole temperature range (100-300 o C). An additional advantage of the catalyst is the fact that the amount of CO above 150 o C is lower than the stoichiometric which indicates parallel participation in the process of both the active phase and the support (active carbon) It is also important that the presented catalyst has a low price due to the use of waste products from agriculture and the elimination of special thermal treatment of the supported Co nitrate. There are possibilities of using of other organic wastes from agriculture as well as wastes obtained during flotation of coal. (author)

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...

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.

Neutralization of IFN-γ reverts clinical and laboratory features in a mouse model of macrophage activation syndrome.

Science.gov (United States)

Prencipe, Giusi; Caiello, Ivan; Pascarella, Antonia; Grom, Alexei A; Bracaglia, Claudia; Chatel, Laurence; Ferlin, Walter G; Marasco, Emiliano; Strippoli, Raffaele; de Min, Cristina; De Benedetti, Fabrizio

2018-04-01

The pathogenesis of macrophage activation syndrome (MAS) is not clearly understood: a large body of evidence supports the involvement of mechanisms similar to those implicated in the setting of primary hemophagocytic lymphohistiocytosis. We sought to investigate the pathogenic role of IFN-γ and the therapeutic efficacy of IFN-γ neutralization in an animal model of MAS. We used an MAS model established in mice transgenic for human IL-6 (IL-6TG mice) challenged with LPS (MAS mice). Levels of IFN-γ and IFN-γ-inducible chemokines were evaluated by using real-time PCR in the liver and spleen and by means of ELISA in plasma. IFN-γ neutralization was achieved by using the anti-IFN-γ antibody XMG1.2 in vivo. Mice with MAS showed a significant upregulation of the IFN-γ pathway, as demonstrated by increased mRNA levels of Ifng and higher levels of phospho-signal transducer and activator of transcription 1 in the liver and spleen and increased expression of the IFN-γ-inducible chemokines Cxcl9 and Cxcl10 in the liver and spleen, as well as in plasma. A marked increase in Il12a and Il12b expression was also found in livers and spleens of mice with MAS. In addition, mice with MAS had a significant increase in numbers of liver CD68 + macrophages. Mice with MAS treated with an anti-IFN-γ antibody showed a significant improvement in survival and body weight recovery associated with a significant amelioration of ferritin, fibrinogen, and alanine aminotransferase levels. In mice with MAS, treatment with the anti-IFN-γ antibody significantly decreased circulating levels of CXCL9, CXCL10, and downstream proinflammatory cytokines. The decrease in CXCL9 and CXCL10 levels paralleled the decrease in serum levels of proinflammatory cytokines and ferritin. These results provide evidence for a pathogenic role of IFN-γ in the setting of MAS. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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.

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.

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.

Applying neutral drift to the directed molecular evolution of a β-glucuronidase into a β-galactosidase: Two different evolutionary pathways lead to the same variant

Directory of Open Access Journals (Sweden)

Hale Jennifer R

2011-05-01

Full Text Available Abstract Background Directed protein evolution has been used to modify protein activity and research has been carried out to enhance the production of high quality mutant libraries. Many theoretical approaches suggest that allowing a population to undergo neutral selection may be valuable in directed evolution experiments. Findings Here we report on an investigation into the value of neutral selection in a classical model system for directed evolution, the conversion of the E. coli β-glucuronidase to a β-galactosidase activity. We find that neutral selection, i.e. selection for retaining glucuronidase activity, can efficiently identify the majority of sites of mutation that have been identified as beneficial for galactosidase activity in previous experiments. Each variant demonstrating increased galactosidase activity identified by our neutral drift experiments contained a mutation at one of four sites, T509, S557, N566 or W529. All of these sites have previously been identified using direct selection for beta galactosidase activity. Conclusions Our results are consistent with others that show that a neutral selection approach can be effective in selecting improved variants. However, we interpret our results to show that neutral selection is, in this case, not a more efficient approach than conventional directed evolution approaches. However, the neutral approach is likely to be beneficial when the resulting library can be screened for a range of related activities. More detailed statistical studies to resolve the apparent differences between this system and others are likely to be a fruitful avenue for future research.

Estimating carbon dioxide fluxes from temperate mountain grasslands using broad-band vegetation indices

Directory of Open Access Journals (Sweden)

G. Wohlfahrt

2010-02-01

Full Text Available The broad-band normalised difference vegetation index (NDVI and the simple ratio (SR were calculated from measurements of reflectance of photosynthetically active and short-wave radiation at two temperate mountain grasslands in Austria and related to the net ecosystem CO₂ exchange (NEE measured concurrently by means of the eddy covariance method. There was no significant statistical difference between the relationships of midday mean NEE with narrow- and broad-band NDVI and SR, measured during and calculated for that same time window, respectively. The skill of broad-band NDVI and SR in predicting CO₂ fluxes was higher for metrics dominated by gross photosynthesis and lowest for ecosystem respiration, with NEE in between. A method based on a simple light response model whose parameters were parameterised based on broad-band NDVI allowed to improve predictions of daily NEE and is suggested to hold promise for filling gaps in the NEE time series. Relationships of CO₂ flux metrics with broad-band NDVI and SR however generally differed between the two studied grassland sites indicting an influence of additional factors not yet accounted for.

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...

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...

Dengue-Immune Humans Have Higher Levels of Complement-Independent Enhancing Antibody than Complement-Dependent Neutralizing Antibody.

Science.gov (United States)

Yamanaka, Atsushi; Konishi, Eiji

2017-09-25

Dengue is the most important arboviral disease worldwide. We previously reported that most inhabitants of dengue-endemic countries who are naturally immune to the disease have infection-enhancing antibodies whose in vitro activity does not decrease in the presence of complement (complement-independent enhancing antibodies, or CiEAb). Here, we compared levels of CiEAb and complement-dependent neutralizing antibodies (CdNAb) in dengue-immune humans. A typical antibody dose-response pattern obtained in our assay system to measure the balance between neutralizing and enhancing antibodies showed both neutralizing and enhancing activities depending on serum dilution factor. The addition of complement to the assay system increased the activity of neutralizing antibodies at lower dilutions, indicating the presence of CdNAb. In contrast, similar dose-response curves were obtained with and without complement at higher dilutions, indicating higher levels of CiEAb than CdNAb. For experimental support for the higher CiEAb levels, a cocktail of mouse monoclonal antibodies against dengue virus type 1 was prepared. The antibody dose-response curves obtained in this assay, with or without complement, were similar to those obtained with human serum samples when a high proportion of D1-V-3H12 (an antibody exhibiting only enhancing activity and thus a model for CiEAb) was used in the cocktail. This study revealed higher-level induction of CiEAb than CdNAb in humans naturally infected with dengue viruses.

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...

The ASDEX 100 keV neutral lithium beam diagnostic gun

International Nuclear Information System (INIS)

McCormick, K.; Kick, M.

1983-04-01

The neutral lithium beam gun intended for measurement of the poloidal magnetic field and of the density gradient in the scrape-off layer of ASDEX is described, and test results over a beam energy range of 27-100 keV are presented. In the gun, lithium ions are extracted from a solid emitter (#betta#-Eurcryptite) in a Pierce-type configuration, accelerated and focused in a two-tube immersion lens, and neutralized in a charge-exchange cell using sodium. The beam can be pulsed from less than one to several seconds, depending on experimental needs. At a distance of 165 cm from the gun the neutral beam equivalent current is typically greater than 1 mA (0.16 mA) for a beam energy of 100 keV (27 keV), the beam FWHM being about 8-9 mm. It is found that to produce a particular beam with a certain ratio must be maintained between the extraction and total beam voltages, this relationship depending in turn on the emitter-extractor separation. The principal features which distinguish the ASDEX gun from that employed on W7a are the greater compactness - all the active elements, i.e. emitter, extractor, lens, deflection plates and neutralizer, are contained with 57 cm - and the vacuum vessel, which simultaneously serves as the magnetic shielding. (orig.)

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.

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

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

Automated image-based assay for evaluation of HIV neutralization and cell-to-cell fusion inhibition.

Science.gov (United States)

Sheik-Khalil, Enas; Bray, Mark-Anthony; Özkaya Şahin, Gülsen; Scarlatti, Gabriella; Jansson, Marianne; Carpenter, Anne E; Fenyö, Eva Maria

2014-08-30

Standardized techniques to detect HIV-neutralizing antibody responses are of great importance in the search for an HIV vaccine. Here, we present a high-throughput, high-content automated plaque reduction (APR) assay based on automated microscopy and image analysis that allows evaluation of neutralization and inhibition of cell-cell fusion within the same assay. Neutralization of virus particles is measured as a reduction in the number of fluorescent plaques, and inhibition of cell-cell fusion as a reduction in plaque area. We found neutralization strength to be a significant factor in the ability of virus to form syncytia. Further, we introduce the inhibitory concentration of plaque area reduction (ICpar) as an additional measure of antiviral activity, i.e. fusion inhibition. We present an automated image based high-throughput, high-content HIV plaque reduction assay. This allows, for the first time, simultaneous evaluation of neutralization and inhibition of cell-cell fusion within the same assay, by quantifying the reduction in number of plaques and mean plaque area, respectively. Inhibition of cell-to-cell fusion requires higher quantities of inhibitory reagent than inhibition of virus neutralization.

JET neutral beam duct Optical Interlock

Energy Technology Data Exchange (ETDEWEB)

Ash, A.D.; Jones, T.T.C.; Surrey, E.; Ćirić, D.; Hall, S.I.; Young, D.; Afzal, M.; Hackett, L.; Day, I.E.; King, R.

2015-10-15

Highlights: • Optical Interlocks were installed on the JET NBI system as part of the EP2 upgrade. • The system protects the JET tokamak and NBI systems from thermal load damage. • Balmer-α beam emission is used to monitor the neutral beam-line pressure. • We demonstrate an improved trip delay of 2 ms compared to 50 ms before EP2. - Abstract: The JET Neutral Beam Injection (NBI) system is the most powerful neutral beam plasma heating system currently operating. Optical Interlocks were installed on the beam lines in 2011 for the JET Enhancement Project 2 (EP2), when the heating power was increased from 23 MW to 34 MW. JET NBI has two beam lines. Each has eight positive ion injectors operating in deuterium at 80 kV–125 kV (accelerator voltage) and up to 65 A (beam current). Heating power is delivered through two ducts where the central power density can be more than 100 MW/m{sup 2}. In order to deliver this safely, the beam line pressure should be below 2 × 10{sup −5} mbar otherwise the power load on the duct from the re-ionised fraction of the beam is excessive. The new Optical Interlock monitors the duct pressure by measuring the Balmer-α beam emission (656 nm). This is proportional to the instantaneous beam flux and the duct pressure. Light is collected from a diagnostic window and focused into 1-mm diameter fibres. The Doppler shifted signal is selected using an angle-tuned interference filter. The light is measured by a photo-multiplier module with a logarithmic amplifier. The interlock activation time of 2 ms is sufficient to protect the system from a fully re-ionised beam—a significant improvement on the previous interlock. The dynamic range is sufficient to see bremsstrahlung emission from JET plasma and not saturate during plasma disruptions. For high neutron flux operations the optical fibres within the biological shield can be annealed to 350 °C. A self-test is possible by illuminating the diagnostic window with a test lamp and measuring

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.

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.

Dissociative part-dependent biopsychosocial reactions to backward masked angry and neutral faces: An fMRI study of dissociative identity disorder.

Science.gov (United States)

Schlumpf, Yolanda R; Nijenhuis, Ellert R S; Chalavi, Sima; Weder, Ekaterina V; Zimmermann, Eva; Luechinger, Roger; La Marca, Roberto; Reinders, A A T Simone; Jäncke, Lutz

2013-01-01

The Theory of Structural Dissociation of the Personality (TSDP) proposes that dissociative identity disorder (DID) patients are fixed in traumatic memories as "Emotional Parts" (EP), but mentally avoid these as "Apparently Normal Parts" of the personality (ANP). We tested the hypotheses that ANP and EP have different biopsychosocial reactions to subliminally presented angry and neutral faces, and that actors instructed and motivated to simulate ANP and EP react differently. Women with DID and matched healthy female actors (CON) were as ANP and EP (DIDanp, DIDep, CONanp, CONep) consecutively exposed to masked neutral and angry faces. Their brain activation was monitored using functional magnetic resonance imaging. The black-and-white dotted masks preceding and following the faces each had a centered colored dot, but in a different color. Participants were instructed to immediately press a button after a perceived color change. State anxiety was assessed after each run using the STAI-S. Final statistical analyses were conducted on 11 DID patients and 15 controls for differences in neural activity, and 13 DID patients and 15 controls for differences in behavior and psychometric measures. Differences between ANP and EP in DID patients and between DID and CON in the two dissociative parts of the personality were generally larger for neutral than for angry faces. The longest reaction times (RTs) existed for DIDep when exposed to neutral faces. Compared to DIDanp, DIDep was associated with more activation of the parahippocampal gyrus. Following neutral faces and compared to CONep, DIDep had more activation in the brainstem, face-sensitive regions, and motor-related areas. DIDanp showed a decreased activity all over the brain in the neutral and angry face condition. There were neither significant within differences nor significant between group differences in state anxiety. CON was not able to simulate genuine ANP and EP biopsychosocially. DID patients have dissociative

Dissociative part-dependent biopsychosocial reactions to backward masked angry and neutral faces: An fMRI study of dissociative identity disorder☆

Science.gov (United States)

Schlumpf, Yolanda R.; Nijenhuis, Ellert R.S.; Chalavi, Sima; Weder, Ekaterina V.; Zimmermann, Eva; Luechinger, Roger; La Marca, Roberto; Reinders, A.A.T. Simone; Jäncke, Lutz

2013-01-01

Objective The Theory of Structural Dissociation of the Personality (TSDP) proposes that dissociative identity disorder (DID) patients are fixed in traumatic memories as “Emotional Parts” (EP), but mentally avoid these as “Apparently Normal Parts” of the personality (ANP). We tested the hypotheses that ANP and EP have different biopsychosocial reactions to subliminally presented angry and neutral faces, and that actors instructed and motivated to simulate ANP and EP react differently. Methods Women with DID and matched healthy female actors (CON) were as ANP and EP (DIDanp, DIDep, CONanp, CONep) consecutively exposed to masked neutral and angry faces. Their brain activation was monitored using functional magnetic resonance imaging. The black-and-white dotted masks preceding and following the faces each had a centered colored dot, but in a different color. Participants were instructed to immediately press a button after a perceived color change. State anxiety was assessed after each run using the STAI-S. Final statistical analyses were conducted on 11 DID patients and 15 controls for differences in neural activity, and 13 DID patients and 15 controls for differences in behavior and psychometric measures. Results Differences between ANP and EP in DID patients and between DID and CON in the two dissociative parts of the personality were generally larger for neutral than for angry faces. The longest reaction times (RTs) existed for DIDep when exposed to neutral faces. Compared to DIDanp, DIDep was associated with more activation of the parahippocampal gyrus. Following neutral faces and compared to CONep, DIDep had more activation in the brainstem, face-sensitive regions, and motor-related areas. DIDanp showed a decreased activity all over the brain in the neutral and angry face condition. There were neither significant within differences nor significant between group differences in state anxiety. CON was not able to simulate genuine ANP and EP biopsychosocially

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

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.

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)

Inhibition of HIV Virus by Neutralizing Vhh Attached to Dual Functional Liposomes Encapsulating Dapivirine.

Science.gov (United States)

Wang, Scarlet Xiaoyan; Michiels, Johan; Ariën, Kevin K; New, Roger; Vanham, Guido; Roitt, Ivan

2016-12-01

Although highly active antiretroviral therapy (HAART) has greatly improved the life expectancy of HIV/AIDS patients, the treatment is not curative. It is a global challenge which fosters an urgent need to develop an effective drug or neutralizing antibody delivery approach for the prevention and treatment of this disease. Due to the low density of envelope spikes with restricted mobility present on the surface of HIV virus, which limit the antibody potency and allow virus mutation and escape from the immune system, it is important for a neutralizing antibody to form bivalent or multivalent bonds with the virus. Liposome constructs could fulfil this need due to the flexible mobility of the membrane with its attached antibodies and the capacity for drug encapsulation. In this study, we evaluated the neutralization activity of a range of liposome formulations in different sizes coated with anti-gp120 llama antibody fragments (Vhhs) conjugated via either non-covalent metal chelation or a covalent linkage. The non-covalent construct demonstrated identical binding affinity to HIV-1 envelope glycoprotein gp120 and neutralizing ability for HIV virus as free Vhh. Although covalently linked Vhh showed significant binding affinity to gp120, it unexpectedly had a lower neutralization potency. This may be due to the comparability in size of the viral and liposome particles restricting the number which can be bound to the liposome surface so involving only a fraction of the antibodies, whereas non-covalently attached antibodies dissociate from the surface after acting with gp120 and free the remainder to bind further viruses. Covalently conjugated Vhh might also trigger the cellular uptake of a liposome-virion complex. To explore the possible ability of the antibody-coated liposomes to have a further function, we encapsulated the hydrophobic antiviral drug dapivirine into both of the non-covalently and covalently conjugated liposome formulations, both of which revealed high

Inhibition of HIV Virus by Neutralizing Vhh Attached to Dual Functional Liposomes Encapsulating Dapivirine

Science.gov (United States)

Wang, Scarlet Xiaoyan; Michiels, Johan; Ariën, Kevin K.; New, Roger; Vanham, Guido; Roitt, Ivan

2016-07-01

Although highly active antiretroviral therapy (HAART) has greatly improved the life expectancy of HIV/AIDS patients, the treatment is not curative. It is a global challenge which fosters an urgent need to develop an effective drug or neutralizing antibody delivery approach for the prevention and treatment of this disease. Due to the low density of envelope spikes with restricted mobility present on the surface of HIV virus, which limit the antibody potency and allow virus mutation and escape from the immune system, it is important for a neutralizing antibody to form bivalent or multivalent bonds with the virus. Liposome constructs could fulfil this need due to the flexible mobility of the membrane with its attached antibodies and the capacity for drug encapsulation. In this study, we evaluated the neutralization activity of a range of liposome formulations in different sizes coated with anti-gp120 llama antibody fragments (Vhhs) conjugated via either non-covalent metal chelation or a covalent linkage. The non-covalent construct demonstrated identical binding affinity to HIV-1 envelope glycoprotein gp120 and neutralizing ability for HIV virus as free Vhh. Although covalently linked Vhh showed significant binding affinity to gp120, it unexpectedly had a lower neutralization potency. This may be due to the comparability in size of the viral and liposome particles restricting the number which can be bound to the liposome surface so involving only a fraction of the antibodies, whereas non-covalently attached antibodies dissociate from the surface after acting with gp120 and free the remainder to bind further viruses. Covalently conjugated Vhh might also trigger the cellular uptake of a liposome-virion complex. To explore the possible ability of the antibody-coated liposomes to have a further function, we encapsulated the hydrophobic antiviral drug dapivirine into both of the non-covalently and covalently conjugated liposome formulations, both of which revealed high

A RADIAL VELOCITY TEST FOR SUPERMASSIVE BLACK HOLE BINARIES AS AN EXPLANATION FOR BROAD, DOUBLE-PEAKED EMISSION LINES IN ACTIVE GALACTIC NUCLEI

Energy Technology Data Exchange (ETDEWEB)

Liu, Jia; Halpern, Jules P. [Astronomy Department, Columbia University, 550 West 120th Street, New York, NY 10027 (United States); Eracleous, Michael [Department of Astronomy and Institute for Gravitation and The Cosmos, The Pennsylvania State University, 525 Davey Lab, University Park, PA 16802 (United States)

2016-01-20

One of the proposed explanations for the broad, double-peaked Balmer emission lines observed in the spectra of some active galactic nuclei (AGNs) is that they are associated with sub-parsec supermassive black hole (SMBH) binaries. Here, we test the binary broad-line region hypothesis through several decades of monitoring of the velocity structure of double-peaked Hα emission lines in 13 low-redshift, mostly radio-loud AGNs. This is a much larger set of objects compared to an earlier test by Eracleous et al. and we use much longer time series for the three objects studied in that paper. Although systematic changes in radial velocity can be traced in many of their lines, they are demonstrably not like those of a spectroscopic binary in a circular orbit. Any spectroscopic binary period must therefore be much longer than the span of the monitoring (assuming a circular orbit), which in turn would require black hole masses that exceed by 1–2 orders of magnitude the values obtained for these objects using techniques such as reverberation mapping and stellar velocity dispersion. Moreover, the response of the double-peaked Balmer line profiles to fluctuations of the ionizing continuum and the shape of the Lyα profiles are incompatible with an SMBH binary. The binary broad-line region hypothesis is therefore disfavored. Other processes evidently shape these line profiles and cause the long-term velocity variations of the double peaks.

Differences between Doppler velocities of ions and neutral atoms in a solar prominence

Science.gov (United States)

Anan, T.; Ichimoto, K.; Hillier, A.

2017-05-01

Context. In astrophysical systems with partially ionized plasma, the motion of ions is governed by the magnetic field while the neutral particles can only feel the magnetic field's Lorentz force indirectly through collisions with ions. The drift in the velocity between ionized and neutral species plays a key role in modifying important physical processes such as magnetic reconnection, damping of magnetohydrodynamic waves, transport of angular momentum in plasma through the magnetic field, and heating. Aims: This paper aims to investigate the differences between Doppler velocities of calcium ions and neutral hydrogen in a solar prominence to look for velocity differences between the neutral and ionized species. Methods: We simultaneously observed spectra of a prominence over an active region in H I 397 nm, H I 434 nm, Ca II 397 nm, and Ca II 854 nm using a high dispersion spectrograph of the Domeless Solar Telescope at Hida observatory. We compared the Doppler velocities, derived from the shift of the peak of the spectral lines presumably emitted from optically-thin plasma. Results: There are instances when the difference in velocities between neutral atoms and ions is significant, for example 1433 events ( 3% of sets of compared profiles) with a difference in velocity between neutral hydrogen atoms and calcium ions greater than 3σ of the measurement error. However, we also found significant differences between the Doppler velocities of two spectral lines emitted from the same species, and the probability density functions of velocity difference between the same species is not significantly different from those between neutral atoms and ions. Conclusions: We interpreted the difference of Doppler velocities as being a result of the motions of different components in the prominence along the line of sight, rather than the decoupling of neutral atoms from plasma. The movie attached to Fig. 1 is available at http://www.aanda.org

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

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.

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

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

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.

Twisted Amides: From Obscurity to Broadly Useful Transition-Metal-Catalyzed Reactions by N-C Amide Bond Activation.

Science.gov (United States)

Liu, Chengwei; Szostak, Michal

2017-05-29

The concept of using amide bond distortion to modulate amidic resonance has been known for more than 75 years. Two classic twisted amides (bridged lactams) ingeniously designed and synthesized by Kirby and Stoltz to feature fully perpendicular amide bonds, and as a consequence emanate amino-ketone-like reactivity, are now routinely recognized in all organic chemistry textbooks. However, only recently the use of amide bond twist (distortion) has advanced to the general organic chemistry mainstream enabling a host of highly attractive N-C amide bond cross-coupling reactions of broad synthetic relevance. In this Minireview, we discuss recent progress in this area and present a detailed overview of the prominent role of amide bond destabilization as a driving force in the development of transition-metal-catalyzed cross-coupling reactions by N-C bond activation. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Plasma-neutral gas interaction in a tokamak divertor: effects of hydrogen molecules and plasma recombination

International Nuclear Information System (INIS)

Krasheninnikov, S.I.; Pigarov, A.Yu.; Soboleva, T.K.; Sigmar, D.J.

1997-01-01

We investigate the influence of hydrogen molecules on plasma recombination using a collisional-radiative model for multispecies hydrogen plasmas and tokamak detached divertor parameters. The rate constant found for molecular activated recombination of a plasma can be as high as 2 x 10 -10 cm 3 /s, confirming our pervious estimates. We investigate the effects of hydrogen molecules and plasma recombination on self-consistent plasma-neutral gas interactions in the recycling region of a tokamak divertor. We treat the plasma flow in a fluid approximation retaining the effects of plasma recombination and employing a Knudsen neutral transport model for a 'gas box' divertor geometry. For the model of plasma-neutral interactions we employ we find: (a) molecular activated recombination is a dominant channel of divertor plasma recombination; and (b) plasma recombination is a key element leading to a decrease in the plasma flux onto the target and substantial plasma pressure drop which are the main features of detached divertor regimes. (orig.)