Inducing Risk Neutral Preferences with Binary Lotteries

DEFF Research Database (Denmark)

Harrison, Glenn W.; Martínez-Correa, Jimmy; Swarthout, J. Todd

2013-01-01

validity of any strategic equilibrium behavior, or even the customary independence axiom. We show that subjects sampled from our population are generally risk averse when lotteries are defined over monetary outcomes, and that the binary lottery procedure does indeed induce a statistically significant shift......We evaluate the binary lottery procedure for inducing risk neutral behavior. We strip the experimental implementation down to bare bones, taking care to avoid any potentially confounding assumptions about behavior having to be made. In particular, our evaluation does not rely on the assumed...... toward risk neutrality. This striking result generalizes to the case in which subjects make several lottery choices and one is selected for payment....

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

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

Cross sections for neutrino and antineutrino neutral current interactions

International Nuclear Information System (INIS)

Bosetti, P.C.; Deden, H.; Deutschmann, M.; Fritze, P.; Graessler, H.; Hasert, F.J.; Morfin, J.; Schulte, R.; Schultze, K.; Seyfert, H.; Banerjee, S.; Barnham, K.W.J.; Beuselinck, R.; Butterworth, I.; Clayton, E.F.; Miller, D.B.; Powell, K.J.; Davis, C.L.; Grossman, P.; McGow, R.; Mulvey, J.H.; Myatt, G.; Perkins, D.H.; Pons, R.; Radojicic, O.; Renton, P.; Saitta, B.; Stenger, V.

1978-01-01

The cross sections for γ and anti γ neutral current interactions for which the hadron energy is > 15 GeV have been measured. These results, and the ratios of neutral current to charged current sections, are in agreement with the Weinberg-Salam model. Values of sin 2 thetasub(w) have been obtained both with and without the use of a parametrisation for the hadronic part of the interaction; the values are in good agreement with each other and the preferred result, that obtained by the method independent of hadronic models, is sin 2 thetasub(w) = 0.22 +- 0.05. (Auth.)

Multigenic DNA vaccine induces protective cross-reactive T cell responses against heterologous influenza virus in nonhuman primates.

Directory of Open Access Journals (Sweden)

Merika T Koday

Full Text Available Recent avian and swine-origin influenza virus outbreaks illustrate the ongoing threat of influenza pandemics. We investigated immunogenicity and protective efficacy of a multi-antigen (MA universal influenza DNA vaccine consisting of HA, M2, and NP antigens in cynomolgus macaques. Following challenge with a heterologous pandemic H1N1 strain, vaccinated animals exhibited significantly lower viral loads and more rapid viral clearance when compared to unvaccinated controls. The MA DNA vaccine induced robust serum and mucosal antibody responses but these high antibody titers were not broadly neutralizing. In contrast, the vaccine induced broadly-reactive NP specific T cell responses that cross-reacted with the challenge virus and inversely correlated with lower viral loads and inflammation. These results demonstrate that a MA DNA vaccine that induces strong cross-reactive T cell responses can, independent of neutralizing antibody, mediate significant cross-protection in a nonhuman primate model and further supports development as an effective approach to induce broad protection against circulating and emerging influenza strains.

Immunoglobulin GM and KM genes and measles vaccine-induced humoral immunity.

Science.gov (United States)

Ovsyannikova, Inna G; Larrabee, Beth R; Schaid, Daniel J; Poland, Gregory A

2017-10-04

Identifying genetic polymorphisms that explain variations in humoral immunity to live measles virus vaccine is of great interest. Immunoglobulin GM (heavy chain) and KM (light chain) allotypes are genetic markers known to be associated with susceptibility to several infectious diseases. We assessed associations between GM and KM genotypes and measles vaccine humoral immunity (neutralizing antibody titers) in a combined cohort (n=1796) of racially diverse healthy individuals (age 18-41years). We did not discover any significant associations between GM and/or KM genotypes and measles vaccine-induced neutralizing antibody titers. African-American subjects had higher neutralizing antibody titers than Caucasians (1260mIU/mL vs. 740mIU/mL, p=7.10×10 -13 ), and those titers remained statistically significant (p=1.68×10 -09 ) after adjusting for age at enrollment and time since last vaccination. There were no statistically significant sex-specific differences in measles-induced neutralizing antibody titers in our study (p=0.375). Our data indicate a surprising lack of evidence for an association between GM and KM genotypes and measles-specific neutralizing antibody titers, despite the importance of these immune response genes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Measurements of charged- and neutral-current cross sections by the CFRR collaboration

International Nuclear Information System (INIS)

Blair, R.; Barish, B.; Chu, Y.

1981-07-01

We present results on normalized charged and neutral current cross sections. The charged current results can be parameterized by a linearly rising cross section with sigma/sub ν//E = 0.719 +- 0.006 +- 0.036 x 10 -38 cm 2 /GeV and sigma/sub ν/-/E = 0.371 +- 0.004 +- 0.019 x 10 -38 cm 2 /GeV. These results are approx. 15% higher than previous measurements. Preliminary structure functions at low Q 2 are also presented. The neutral current was analyzed using the Paschos-Wolfenstein technique and yields sin 2 sigma/sub w/ = 0.243 +- 0.016

Induced mutations of rust resistance genes in wheat

International Nuclear Information System (INIS)

McIntosh, R.A.

1983-01-01

Induced mutations are being used as a tool to study genes for resistance in wheat. It was found that Pm1 can be separated from Lr20 and Sr15, but these two react like a single pleiotropic gene. Mutants were further examined in crosses and backmutations have been attempted. (author)

HIV-1 neutralizing antibodies induced by native-like envelope trimers

NARCIS (Netherlands)

Sanders, Rogier W.; van Gils, Marit J.; Derking, Ronald; Sok, Devin; Ketas, Thomas J.; Burger, Judith A.; Ozorowski, Gabriel; Cupo, Albert; Simonich, Cassandra; Goo, Leslie; Arendt, Heather; Kim, Helen J.; Lee, Jeong Hyun; Pugach, Pavel; Williams, Melissa; Debnath, Gargi; Moldt, Brian; van Breemen, Mariëlle J.; Isik, Gözde; Medina-Ramírez, Max; Back, Jaap Willem; Koff, Wayne C.; Julien, Jean-Philippe; Rakasz, Eva G.; Seaman, Michael S.; Guttman, Miklos; Lee, Kelly K.; Klasse, Per Johan; Labranche, Celia; Schief, William R.; Wilson, Ian A.; Overbaugh, Julie; Burton, Dennis R.; Ward, Andrew B.; Montefiori, David C.; Dean, Hansi; Moore, John P.

2015-01-01

A challenge for HIV-1 immunogen design is the difficulty of inducing neutralizing antibodies (NAbs) against neutralization-resistant (tier 2) viruses that dominate human transmissions. We show that a soluble recombinant HIV-1 envelope glycoprotein trimer that adopts a native conformation, BG505

Novel adenoviral vector induces T-cell responses despite anti-adenoviral neutralizing antibodies in colorectal cancer patients.

Science.gov (United States)

Morse, Michael A; Chaudhry, Arvind; Gabitzsch, Elizabeth S; Hobeika, Amy C; Osada, Takuya; Clay, Timothy M; Amalfitano, Andrea; Burnett, Bruce K; Devi, Gayathri R; Hsu, David S; Xu, Younong; Balcaitis, Stephanie; Dua, Rajesh; Nguyen, Susan; Balint, Joseph P; Jones, Frank R; Lyerly, H Kim

2013-08-01

First-generation, E1-deleted adenovirus subtype 5 (Ad5)-based vectors, although promising platforms for use as cancer vaccines, are impeded in activity by naturally occurring or induced Ad-specific neutralizing antibodies. Ad5-based vectors with deletions of the E1 and the E2b regions (Ad5 [E1-, E2b-]), the latter encoding the DNA polymerase and the pre-terminal protein, by virtue of diminished late phase viral protein expression, were hypothesized to avoid immunological clearance and induce more potent immune responses against the encoded tumor antigen transgene in Ad-immune hosts. Indeed, multiple homologous immunizations with Ad5 [E1-, E2b-]-CEA(6D), encoding the tumor antigen carcinoembryonic antigen (CEA), induced CEA-specific cell-mediated immune (CMI) responses with antitumor activity in mice despite the presence of preexisting or induced Ad5-neutralizing antibody. In the present phase I/II study, cohorts of patients with advanced colorectal cancer were immunized with escalating doses of Ad5 [E1-, E2b-]-CEA(6D). CEA-specific CMI responses were observed despite the presence of preexisting Ad5 immunity in a majority (61.3 %) of patients. Importantly, there was minimal toxicity, and overall patient survival (48 % at 12 months) was similar regardless of preexisting Ad5 neutralizing antibody titers. The results demonstrate that, in cancer patients, the novel Ad5 [E1-, E2b-] gene delivery platform generates significant CMI responses to the tumor antigen CEA in the setting of both naturally acquired and immunization-induced Ad5-specific immunity.

Evidence for neutral neutrino current coupling to right-handed quarks

International Nuclear Information System (INIS)

Allaby, J.V.; Amaldi, U.; Barbiellini, G.; Baubillier, M.; Bergsma, F.; Capone, A.; Flegel, W.; Lanceri, L.; Metcalf, M.; Nieuwenhuis, C.; Pain, R.; Panman, J.; Winter, K.; Abt, I.; Blobel, V.; Buengener, A.; Buesser, F.W.; Gall, P.D.; Hebbeker, T.; Niebergall, F.; Staehelin, P.; Borgia, B.; Diemoz, M.; Dionisi, C.; Dore, U.; Ferroni, F.; Longo, E.; Loverre, P.F.; Luminari, L.; Monacelli, P.; Morganti, S.; De Notaristefani, F.; Santacesaria, R.; Santoni, C.; Rome-1 Univ.

1989-01-01

Differential cross sections dσ/dy have been measured in semileptonic neutral- and charged-current reactions induced by neutrinos and antineutrinos. The comparison of the neutral- and the charged-current differential cross sections allows the direct determination of the chiral coupling of the neutral (νanti ν) current to left- and right-handed quarks. The result, with a value of g R 2 =0.042±0.010, is the first direct determination, with a significance of more than four standard deviations, of a non-zero value of g R . (orig.)

A Measurement of Neutrino-Induced Charged-Current Neutral Pion Production

Energy Technology Data Exchange (ETDEWEB)

Nelson, Robert H. [Univ. of Colorado, Boulder, CO (United States)

2010-01-01

This work presents the first comprehensive measurement of neutrino-induced charged-current neutral pion production (CCπ⁰) off a nuclear target. The Mini Booster Neutrino Experiment (MiniBooNE) and Booster Neutrino Beam (BNB) are discussed in detail. MiniBooNE is a high-statistics (~ 1, 000, 000 interactions) low-energy (E_vϵ 2 0.5 - 2.0 GeV) neutrino experiment located at Fermilab. The method for selecting and reconstructing CCπ⁰ events is presented. The π⁰ and μ^- are fully reconstructed in the final state allowing for the measurement of, among other things, the neutrino energy. The total observable CCπ⁰ cross-section is presented as a function of neutrino energy, along with five differential cross-sections in terms of the final state kinematics and Q². The results are combined to yield a flux-averaged total cross-section of <σ>_Φ = (9.2 ± 0.3_stat. ± 1.5_syst.) × 10^-39 cm²/CH₂ at energy 965 MeV. These measurements will aid future neutrino experiments with the prediction of their neutrino interaction rates.

High voltage series protection of neutral injectors with crossed-field tubes

International Nuclear Information System (INIS)

Hofmann, G.A.; Thomas, D.G.

1976-01-01

High voltage neutral beam injectors for fusion machines require either parallel or series protection schemes to limit fault currents in case of arcing to safe levels. The protection device is usually located between the high voltage supply and beam injector and either crowbars (parallel protection) or disconnects (series protection) the high voltage supply when a fault occurs. Because of its isolating property, series protection is preferred. The Hughes crossed-field tube is uniquely suited for series protection schemes. The tube can conduct 40 A continuously upon application of voltage (approximately 300 V) and a static magnetic field (approximately 100 G). It is also capable of interrupting currents of 1000 A within 10 μs and withstand voltage of more than 120 kV. Experiments were performed to simulate the duty of a crossed-field tube as a series protection element in a neutral injector circuit under fault conditions. Results of on-switching tests under high and low voltage and interruption of fault currents are presented. An example of a possible protection circuit with crossed-field tubes is discussed

Cross-serotype immunity induced by immunization with a conserved rhinovirus capsid protein.

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Nicholas Glanville

Full Text Available Human rhinovirus (RV infections are the principle cause of common colds and precipitate asthma and COPD exacerbations. There is currently no RV vaccine, largely due to the existence of ∼150 strains. We aimed to define highly conserved areas of the RV proteome and test their usefulness as candidate antigens for a broadly cross-reactive vaccine, using a mouse infection model. Regions of the VP0 (VP4+VP2 capsid protein were identified as having high homology across RVs. Immunization with a recombinant VP0 combined with a Th1 promoting adjuvant induced systemic, antigen specific, cross-serotype, cellular and humoral immune responses. Similar cross-reactive responses were observed in the lungs of immunized mice after infection with heterologous RV strains. Immunization enhanced the generation of heterosubtypic neutralizing antibodies and lung memory T cells, and caused more rapid virus clearance. Conserved domains of the RV capsid therefore induce cross-reactive immune responses and represent candidates for a subunit RV vaccine.

Measurement and QCD Analysis of Neutral and Charged Current Cross Sections at HERA

CERN Document Server

Adloff, C.; Andrieu, B.; Anthonis, T.; Astvatsatourov, A.; Babaev, A.; Bahr, J.; Baranov, P.; Barrelet, E.; Bartel, W.; Baumgartner, S.; Becker, J.; Beckingham, M.; Beglarian, A.; Behnke, O.; Belousov, A.; Berger, C.; Berndt, T.; Bizot, J.C.; Bohme, J.; Boudry, V.; Braunschweig, W.; Brisson, V.; Broker, H.B.; Brown, D.P.; Bruncko, D.; Busser, F.W.; Bunyatyan, A.; Burrage, A.; Buschhorn, G.; Bystritskaya, L.; Campbell, A.J.; Cao, Jun; Caron, S.; Cassol-Brunner, F.; Chekelian, V.; Clarke, D.; Collard, C.; Contreras, J.G.; Coppens, Y.R.; Coughlan, J.A.; Cousinou, M.C.; Cox, B.E.; Cozzika, G.; Cvach, J.; Dainton, J.B.; Dau, W.D.; Daum, K.; Davidsson, M.; Delcourt, B.; Delerue, N.; Demirchyan, R.; De Roeck, A.; De Wolf, E.A.; Diaconu, C.; Dingfelder, J.; Dixon, P.; Dodonov, V.; Dowell, J.D.; Dubak, A.; Duprel, C.; Eckerlin, Guenter; Eckstein, D.; Efremenko, V.; Egli, S.; Eichler, R.; Eisele, F.; Eisenhandler, E.; Ellerbrock, M.; Elsen, E.; Erdmann, M.; Erdmann, W.; Faulkner, P.J.W.; Favart, L.; Fedotov, A.; Felst, R.; Ferencei, J.; Ferron, S.; Fleischer, M.; Fleischmann, P.; Fleming, Y.H.; Flucke, G.; Flugge, G.; Fomenko, A.; Foresti, I.; Formanek, J.; Franke, G.; Frising, G.; Gabathuler, E.; Gabathuler, K.; Garvey, J.; Gassner, J.; Gayler, Joerg; Gerhards, R.; Gerlich, C.; Ghazaryan, Samvel; Goerlich, L.; Gogitidze, N.; Grab, C.; Grabski, V.; Grassler, H.; Greenshaw, T.; Grindhammer, Guenter; Haidt, D.; Hajduk, L.; Haller, J.; Heinemann, B.; Heinzelmann, G.; Henderson, R.C.W.; Hengstmann, S.; Henschel, H.; Henshaw, O.; Heremans, R.; Herrera, G.; Herynek, I.; Hildebrandt, M.; Hilgers, M.; Hiller, K.H.; Hladky, J.; Hoting, P.; Hoffmann, D.; Horisberger, R.; Hovhannisyan, A.; Ibbotson, M.; Issever, C .; Jacquet, M.; Jaffre, M.; Janauschek, L.; Janssen, X.; Jemanov, V.; Jonsson, L.; Johnson, C.; Johnson, D.P.; Jones, M.A.S.; Jung, H.; Kant, D.; Kapichine, M.; Karlsson, M.; Karschnick, O.; Katzy, J.; Keil, F.; Keller, N.; Kennedy, J.; Kenyon, I.R.; Kiesling, Christian M.; Kjellberg, P.; Klein, M.; Kleinwort, C.; Kluge, T.; Knies, G.; Koblitz, B.; Kolya, S.D.; Korbel, V.; Kostka, P.; Koutouev, R.; Koutov, A.; Kroseberg, J.; Kruger, K.; Kuhr, T.; Lamb, D.; Landon, M.P.J.; Lange, W.; Lastovicka, T.; Laycock, P.; Lebailly, E.; Lebedev, A.; Leissner, B.; Lemrani, R.; Lendermann, V.; Levonian, S.; List, B.; Lobodzinska, E.; Lobodzinski, B.; Loginov, A.; Loktionova, N.; Lubimov, V.; Luders, S.; Luke, D.; Lytkin, L.; Malden, N.; Malinovski, E.; Mangano, S.; Marage, P.; Marks, J.; Marshall, R.; Martyn, H.U.; Martyniak, J.; Maxfield, S.J.; Meer, D.; Mehta, A.; Meier, K.; Meyer, A.B.; Meyer, H.; Meyer, J.; Michine, S.; Mikocki, S.; Milstead, D.; Mohrdieck, S.; Mondragon, M.N.; Moreau, F.; Morozov, A.; Morris, J.V.; Muller, K.; Murin, P.; Nagovizin, V.; Naroska, B.; Naumann, J.; Naumann, T.; Newman, Paul R.; Niebergall, F.; Niebuhr, C.; Nix, O.; Nowak, G.; Nozicka, M.; Olivier, B.; Olsson, J.E.; Ozerov, D.; Panassik, V.; Pascaud, C.; Patel, G.D.; Peez, M.; Perez, E.; Petrukhin, A.; Phillips, J.P.; Pitzl, D.; Portheault, B.; Poschl, R.; Potachnikova, I.; Povh, B.; Rauschenberger, J.; Reimer, P.; Reisert, B.; Risler, C.; Rizvi, E.; Robmann, P.; Roosen, R.; Rostovtsev, A.; Rusakov, S.; Rybicki, K.; Sankey, D.P.C.; Sauvan, E.; Schatzel, S.; Scheins, J.; Schilling, F.P.; Schleper, P.; Schmidt, D.; Schmidt, S.; Schmitt, S.; Schneider, M.; Schoeffel, L.; Schoning, A.; Schoerner-Sadenius, Thomas; Schroder, V.; Schultz-Coulon, H.C.; Schwanenberger, C.; Sedlak, K.; Sefkow, F.; Sheviakov, I.; Shtarkov, L.N.; Sirois, Y.; Sloan, T.; Smirnov, P.; Soloviev, Y.; South, D.; Spaskov, V.; Specka, Arnd E.; Spitzer, H.; Stamen, R.; Stella, B.; Stiewe, J.; Strauch, I.; Straumann, U.; Tchetchelnitski, S.; Thompson, Graham; Thompson, P.D.; Tomasz, F.; Traynor, D.; Truoel, Peter; Tsipolitis, G.; Tsurin, I.; Turnau, J.; Turney, J.E.; Tzamariudaki, E.; Uraev, A.; Urban, Marcel; Usik, A.; Valkar, S.; Valkarova, A.; Vallee, C.; Van Mechelen, P.; Vargas Trevino, A.; Vassiliev, S.; Vazdik, Y.; Veelken, C.; Vest, A.; Vichnevski, A.; Volchinski, V.; Wacker, K.; Wagner, J.; Wallny, R.; Waugh, B.; Weber, G.; Weber, R.; Wegener, D.; Werner, C.; Werner, N.; Wessels, M.; Wiesand, S.; Winde, M.; Winter, G.G.; Wissing, C.; Wobisch, M.; Woehrling, E.E.; Wunsch, E.; Wyatt, A.C.; Zacek, J.; Zalesak, J.; Zhang, Z.; Zhokin, A.; Zomer, F.; zur Nedden, M.

2003-01-01

The inclusive e^+ p single and double differential cross sections for neutral and charged current processes are measured with the H1 detector at HERA. The data were taken in 1999 and 2000 at a centre-of-mass energy of \\sqrt{s} = 319 GeV and correspond to an integrated luminosity of 65.2 pb^-1. The cross sections are measured in the range of four-momentum transfer squared Q^2 between 100 and 30000 GeV^2 and Bjorken x between 0.0013 and 0.65. The neutral current analysis for the new e^+ p data and the earlier e^- p data taken in 1998 and 1999 is extended to small energies of the scattered electron and therefore to higher values of inelasticity y, allowing a determination of the longitudinal structure function F_L at high Q^2 (110 - 700 GeV^2). A new measurement of the structure function x F_3 is obtained using the new e^+ p and previously published e^\\pm p neutral current cross section data at high Q^2. These data together with H1 low Q^2 precision data are further used to perform new next-to-leading order QCD ...

A replicating modified vaccinia tiantan strain expressing an avian-derived influenza H5N1 hemagglutinin induce broadly neutralizing antibodies and cross-clade protective immunity in mice.

Directory of Open Access Journals (Sweden)

Haixia Xiao

Full Text Available To combat the possibility of a zoonotic H5N1 pandemic in a timely fashion, it is necessary to develop a vaccine that would confer protection against homologous and heterologous human H5N1 influenza viruses. Using a replicating modified vaccinia virus Tian Tan strain (MVTT as a vaccine vector, we constructed MVTTHA-QH and MVTTHA-AH, which expresses the H5 gene of a goose-derived Qinghai strain A/Bar-headed Goose/Qinghai/1/2005 or human-derived Anhui Strain A/Anhui/1/2005. The immunogenicity profiles of both vaccine candidates were evaluated. Vaccination with MVTTHA-QH induced a significant level of neutralizing antibodies (Nabs against a homologous strain and a wide range of H5N1 pseudoviruses (clades 1, 2.1, 2.2, 2.3.2, and 2.3.4. Neutralization tests (NT and Haemagglutination inhibition (HI antibodies inhibit the live autologous virus as well as a homologous A/Xingjiang/1/2006 and a heterologous A/Vietnam/1194/2004, representing two human isolates from clade 2.2 and clade 1, respectively. Importantly, mice vaccinated with intranasal MVTTHA-QH were completely protected from challenge with lethal dosages of A/Bar-headed Goose/Qinghai/1/2005 and the A/Viet Nam/1194/2004, respectively, but not control mice that received a mock MVTTS vaccine. However, MVTTHA-AH induced much lower levels of NT against its autologous strain. Our results suggest that it is feasible to use the H5 gene from A/Bar-headed Goose/Qinghai/1/2005 to construct an effective vaccine, when using MVTT as a vector, to prevent infections against homologous and genetically divergent human H5N1 influenza viruses.

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.

Neutral current induced reactions in the Gargamelle experiment

International Nuclear Information System (INIS)

Doninck, W. van

1976-07-01

In the heavy liquid bubble chamber Gargamelle at CERN, 3 candidates are found for the pure leptonic neutral current process anti upsilonsub(μ)e - → anti upsilon sub(μ)e - . For the inclusive semileptonic reactions upsilon N → μ - X and anti upsilon N → μ + X the ratios of the neutral current to the charged current cross sections are measured to be Rsub(upsilon) = 0.25 +- 0.04 and Rsub(anti upsilon) = 0.56 +- 0.09. These inclusive results differ from the prediction of parity conserving models by more than 3 standard deviations. All three reactions are compatible with the Weinberg-Salam-model and a value of sin 2 THETAsub(ω) near 0.3. (BJ) [de

Compilation of electron collision excitation cross sections for neutral argon

International Nuclear Information System (INIS)

Blanco, F.

1993-01-01

The present work presents a compilation and critical analysis of the available data on electron collision excitation cross sections for neutral Argon levels. This study includes: 1.- A detailed description in intermediate coupling for all the levels belonging the 20 configurations 3p5 ns (n=4to 12), np(n=4to8) and nd(n=3to8)of neutral Argon. 2.- Calculation of the electron collision excitation cross sections in Born and Born-Oppenheimer-Ochkur approximations for all the levels in the 14 configurations 3p5 ns (n=4 to 7), np (n=4 to 7) and nd (n=3 to 8). 3.- comparison and discussion of the compiled data. These are the experimental and theoretical values available from the literature, and those from this work. 4.- Analysis of the regularities and systematic behaviors in order to determine which values can be considered more reliable. It is show that the concept of one electron cross section results quite useful for this purpose. In some cases it has been possible to obtain in this way approximate analytical expressions interpolating the experimental data. 5.- All the experimental and theoretical values studied are graphically presented and compared. 6.- The last part of the work includes a listing of several general purpose programs for Atomic Physics calculations developed for this work. (Author) 35 refs

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

Directory of Open Access Journals (Sweden)

Raul Terron-Exposito

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

Electron-impact ionization of SiCl{sub 3} using an improved crossed fast-neutral-beam - electron-beam apparatus

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Mahoney, J M; Gutkin, M V; Tarnovsky, V; Becker, K [Department of Physics and Engineering Physics, Stevens Institute of Technology, Hoboken, NJ 07030 (United States)], E-mail: kbecker@poly.edu

2008-05-15

The fast-neutral-beam technique is a versatile approach to the determination of absolute cross sections for electron-impact ionization of atoms, stable molecules as well as free radicals and metastable species. A fast neutral beam of the species under study is prepared by charge-transfer neutralization of a mass-selected ion beam and the species are subsequently ionized by an electron beam. Mass- and energy-dispersive selection separates singly from multiply charged ions and parent from fragment ions and allows the determination of partial ionization cross sections. Here we describe some major improvements that were made recently to the fast-beam apparatus that has been used extensively for ionization cross section measurements for the past 15 years in our group. Experiments using well-established ionization cross sections in conjunction with extensive ion trajectory simulations were carried out to test the satisfactory performance of the modified fast-neutral-beam apparatus. We also report absolute partial cross sections for the formation of various singly charged positive ions produced by electron impact on SiCl{sub 3} for impact energies from threshold to 200 eV in the modified fast-beam apparatus.

Tetracycline inducible gene manipulation in serotonergic neurons.

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Tillmann Weber

Full Text Available The serotonergic (5-HT neuronal system has important and diverse physiological functions throughout development and adulthood. Its dysregulation during development or later in adulthood has been implicated in many neuropsychiatric disorders. Transgenic animal models designed to study the contribution of serotonergic susceptibility genes to a pathological phenotype should ideally allow to study candidate gene overexpression or gene knockout selectively in serotonergic neurons at any desired time during life. For this purpose, conditional expression systems such as the tet-system are preferable. Here, we generated a transactivator (tTA mouse line (TPH2-tTA that allows temporal and spatial control of tetracycline (Ptet controlled transgene expression as well as gene deletion in 5-HT neurons. The tTA cDNA was inserted into a 196 kb PAC containing a genomic mouse Tph2 fragment (177 kb by homologous recombination in E. coli. For functional analysis of Ptet-controlled transgene expression, TPH2-tTA mice were crossed to a Ptet-regulated lacZ reporter line (Ptet-nLacZ. In adult double-transgenic TPH2-tTA/Ptet-nLacZ mice, TPH2-tTA founder line L62-20 showed strong serotonergic β-galactosidase expression which could be completely suppressed with doxycycline (Dox. Furthermore, Ptet-regulated gene expression could be reversibly activated or inactivated when Dox was either withdrawn or added to the system. For functional analysis of Ptet-controlled, Cre-mediated gene deletion, TPH2-tTA mice (L62-20 were crossed to double transgenic Ptet-Cre/R26R reporter mice to generate TPH2-tTA/Ptet-Cre/R26R mice. Without Dox, 5-HT specific recombination started at E12.5. With permanent Dox administration, Ptet-controlled Cre-mediated recombination was absent. Dox withdrawal either postnatally or during adulthood induced efficient recombination in serotonergic neurons of all raphe nuclei, respectively. In the enteric nervous system, recombination could not be detected. We

Bibliography. Examples of literature related to the use of induced mutations in cross-breeding

International Nuclear Information System (INIS)

Micke, A.

1976-01-01

The bibliography contains about 400 references arranged alphabetically under the following 20 headings: Genetic analysis of mutants; Mutant gene combination and interaction; Pleiotropy versus linkage; Genetic background; Heterosis and overdominance; Mutations in heterozygous plants such as vegetatively propagated plants; Mutations in hybrids of self-pollinators; Distant hybridization; Increasing recombination; Alteration in the reproductive system; Alteration of photoperiodic response; Self and cross-incompatibility; Male or female sterility; Adaptability of mutants and mutant hybrids; Mutation induction in cross pollinators; Dwarfing mutant genes in cross-breeding; Protein mutants in cross-breeding; Disease resistant mutants in cross-breeding; Practical cross-breeding programmes using mutants; Spontaneous versus induced genetic diversity

Tandem-method for measurement of destruction cross-sections of neutral projectiles at intermediate and high velocities

International Nuclear Information System (INIS)

Sant'Anna, M.M.; Magnani, B.F.; Correa, R.S.; Coelho, L.F.S.

2007-01-01

We have recently presented destruction cross-section data for negative ions obtained with a technique that uses the gas stripper of a tandem accelerator as the collision target. In this work, we develop an extension of that technique to measure destruction cross-sections for neutral projectiles, important parameters to estimate neutral beam attenuation in Heavy Ion Fusion applications. Measurements for the H+N 2 collision system are used to exemplify and discuss the capabilities and limitations of the proposed experimental method

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...

Antibodies induced by vaccination with purified chick embryo cell culture vaccine (PCECV) cross-neutralize non-classical bat lyssavirus strains.

Science.gov (United States)

Malerczyk, Claudius; Selhorst, Thomas; Tordo, Noël; Moore, Susan; Müller, Thomas

2009-08-27

Tissue-culture vaccines like purified chick embryo cell vaccine (PCECV) have been shown to provide protection against classical rabies virus (RABV) via pre-exposure or post-exposure prophylaxis. A cross-neutralization study was conducted using a panel of 100 human sera, to determine, to what extent after vaccination with PCECV protection exists against non-classical bat lyssavirus strains like European bat lyssavirus (EBLV) type 1 and 2 and Australian bat lyssavirus (ABLV). Virus neutralizing antibody (VNA) concentrations against the rabies virus variants CVS-11, ABLV, EBLV-1 and EBLV-2 were determined by using a modified rapid fluorescent focus inhibition test. For ABLV and EBLV-2, the comparison to CVS-11 revealed almost identical results (100% adequate VNA concentrations >or=0.5 IU/mL; correlation coefficient r(2)=0.69 and 0.77, respectively), while for EBLV-1 more scattering was observed (97% adequate VNA concentrations; r(2)=0.50). In conclusion, vaccination with PCECV produces adequate VNA concentrations against classical RABV as well as non-classical lyssavirus strains ABLV, EBLV-1, and EBLV-2.

Neutralization of Bacterial YoeBSpn Toxicity and Enhanced Plant Growth in Arabidopsis thaliana via Co-Expression of the Toxin-Antitoxin Genes

Science.gov (United States)

Abu Bakar, Fauziah; Yeo, Chew Chieng; Harikrishna, Jennifer Ann

2016-01-01

Bacterial toxin-antitoxin (TA) systems have various cellular functions, including as part of the general stress response. The genome of the Gram-positive human pathogen Streptococcus pneumoniae harbors several putative TA systems, including yefM-yoeBSpn, which is one of four systems that had been demonstrated to be biologically functional. Overexpression of the yoeBSpn toxin gene resulted in cell stasis and eventually cell death in its native host, as well as in Escherichia coli. Our previous work showed that induced expression of a yoeBSpn toxin-Green Fluorescent Protein (GFP) fusion gene apparently triggered apoptosis and was lethal in the model plant, Arabidopsis thaliana. In this study, we investigated the effects of co-expression of the yefMSpn antitoxin and yoeBSpn toxin-GFP fusion in transgenic A. thaliana. When co-expressed in Arabidopsis, the YefMSpn antitoxin was found to neutralize the toxicity of YoeBSpn-GFP. Interestingly, the inducible expression of both yefMSpn antitoxin and yoeBSpn toxin-GFP fusion in transgenic hybrid Arabidopsis resulted in larger rosette leaves and taller plants with a higher number of inflorescence stems and increased silique production. To our knowledge, this is the first demonstration of a prokaryotic antitoxin neutralizing its cognate toxin in plant cells. PMID:27104531

Neutralization of Bacterial YoeBSpn Toxicity and Enhanced Plant Growth in Arabidopsis thaliana via Co-Expression of the Toxin-Antitoxin Genes

Directory of Open Access Journals (Sweden)

Fauziah Abu Bakar

2016-04-01

Full Text Available Bacterial toxin-antitoxin (TA systems have various cellular functions, including as part of the general stress response. The genome of the Gram-positive human pathogen Streptococcus pneumoniae harbors several putative TA systems, including yefM-yoeBSpn, which is one of four systems that had been demonstrated to be biologically functional. Overexpression of the yoeBSpn toxin gene resulted in cell stasis and eventually cell death in its native host, as well as in Escherichia coli. Our previous work showed that induced expression of a yoeBSpn toxin-Green Fluorescent Protein (GFP fusion gene apparently triggered apoptosis and was lethal in the model plant, Arabidopsis thaliana. In this study, we investigated the effects of co-expression of the yefMSpn antitoxin and yoeBSpn toxin-GFP fusion in transgenic A. thaliana. When co-expressed in Arabidopsis, the YefMSpn antitoxin was found to neutralize the toxicity of YoeBSpn-GFP. Interestingly, the inducible expression of both yefMSpn antitoxin and yoeBSpn toxin-GFP fusion in transgenic hybrid Arabidopsis resulted in larger rosette leaves and taller plants with a higher number of inflorescence stems and increased silique production. To our knowledge, this is the first demonstration of a prokaryotic antitoxin neutralizing its cognate toxin in plant cells.

Description-based reappraisal regulate the emotion induced by erotic and neutral images in a Chinese population.

Science.gov (United States)

Peng, Jiaxin; Qu, Chen; Gu, Ruolei; Luo, Yue-Jia

2012-01-01

Previous emotion-regulation research has shown that the late positive potential (LPP) is sensitive to the down-regulation of emotion; however, whether LPP is also sensitive to the up-regulation of emotion remains unclear. The present study examined the description-based reappraisal effects on the up-regulation of positive emotions induced by erotic and neutral images in a Chinese population. Self-reported ratings and event-related potential (ERP) were recorded when subjects viewed pleasant and neutral images, which were shown after either a neutral or positive description. Self-reported results showed that images following positive descriptions were rated as more pleasant compared to images following neutral descriptions. ERP results revealed that the P2, P3, and slow wave (SW) components were larger for erotic pictures than for neutral pictures, while the positive description condition yielded attenuated erotic image-induced P2, P3 and SW and increased SW induced by neutral images. The results demonstrated that description-based reappraisal, as a method of reappraisal, significantly modulates the emotional experience and ERP responses to erotic and neutral images.

Description-based reappraisal regulate the emotion induced by erotic and neutral images in a Chinese population

Directory of Open Access Journals (Sweden)

Jiaxin ePeng

2013-01-01

Full Text Available Previous emotion-regulation research has shown that the late positive potential (LPP is sensitive to the down-regulation of emotion; however, whether LPP is also sensitive to the up-regulation of emotion remains unclear. The present study examined the description-based reappraisal effects on the up-regulation of positive emotions induced by erotic and neutral images in a Chinese population. Self-reported ratings and event-related potential (ERP were recorded when subjects viewed pleasant and neutral images, which were shown after either a neutral or positive description. Self-reported results showed that images following positive descriptions were rated as more pleasant compared to images following neutral descriptions. ERP results revealed that the P2, P3, and slow wave (SW components were larger for erotic pictures than for neutral pictures, while the positive description condition yielded attenuated erotic image-induced P2, P3 and SW and increased SW induced by neutral images. The results demonstrated that description-based reappraisal, as a method of reappraisal, significantly modulates the emotional experience and ERP responses to erotic and neutral images.

Universal antibodies against the highly conserved influenza fusion peptide cross-neutralize several subtypes of influenza A virus

Energy Technology Data Exchange (ETDEWEB)

Hashem, Anwar M. [Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, ON (Canada); Department of Microbiology, Faculty of Medicine, King Abdulaziz University, Jeddah (Saudi Arabia); Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON (Canada); Van Domselaar, Gary [National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB (Canada); Li, Changgui; Wang, Junzhi [National Institute for the Control of Pharmaceutical and Biological Products, Beijing (China); She, Yi-Min; Cyr, Terry D. [Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, ON (Canada); Sui, Jianhua [Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, 44 Binney Street, Boston, MA 02115 (United States); He, Runtao [National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB (Canada); Marasco, Wayne A. [Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, 44 Binney Street, Boston, MA 02115 (United States); Li, Xuguang, E-mail: Sean.Li@hc-sc.gc.ca [Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, ON (Canada); Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON (Canada)

2010-12-10

Research highlights: {yields} The fusion peptide is the only universally conserved epitope in all influenza viral hemagglutinins. {yields} Anti-fusion peptide antibodies are universal antibodies that cross-react with all influenza HA subtypes. {yields} The universal antibodies cross-neutralize different influenza A subtypes. {yields} The universal antibodies inhibit the fusion process between the viruses and the target cells. -- Abstract: The fusion peptide of influenza viral hemagglutinin plays a critical role in virus entry by facilitating membrane fusion between the virus and target cells. As the fusion peptide is the only universally conserved epitope in all influenza A and B viruses, it could be an attractive target for vaccine-induced immune responses. We previously reported that antibodies targeting the first 14 amino acids of the N-terminus of the fusion peptide could bind to virtually all influenza virus strains and quantify hemagglutinins in vaccines produced in embryonated eggs. Here we demonstrate that these universal antibodies bind to the viral hemagglutinins in native conformation presented in infected mammalian cell cultures and neutralize multiple subtypes of virus by inhibiting the pH-dependant fusion of viral and cellular membranes. These results suggest that this unique, highly-conserved linear sequence in viral hemagglutinin is exposed sufficiently to be attacked by the antibodies during the course of infection and merits further investigation because of potential importance in the protection against diverse strains of influenza viruses.

Universal antibodies against the highly conserved influenza fusion peptide cross-neutralize several subtypes of influenza A virus

International Nuclear Information System (INIS)

Hashem, Anwar M.; Van Domselaar, Gary; Li, Changgui; Wang, Junzhi; She, Yi-Min; Cyr, Terry D.; Sui, Jianhua; He, Runtao; Marasco, Wayne A.; Li, Xuguang

2010-01-01

Research highlights: → The fusion peptide is the only universally conserved epitope in all influenza viral hemagglutinins. → Anti-fusion peptide antibodies are universal antibodies that cross-react with all influenza HA subtypes. → The universal antibodies cross-neutralize different influenza A subtypes. → The universal antibodies inhibit the fusion process between the viruses and the target cells. -- Abstract: The fusion peptide of influenza viral hemagglutinin plays a critical role in virus entry by facilitating membrane fusion between the virus and target cells. As the fusion peptide is the only universally conserved epitope in all influenza A and B viruses, it could be an attractive target for vaccine-induced immune responses. We previously reported that antibodies targeting the first 14 amino acids of the N-terminus of the fusion peptide could bind to virtually all influenza virus strains and quantify hemagglutinins in vaccines produced in embryonated eggs. Here we demonstrate that these universal antibodies bind to the viral hemagglutinins in native conformation presented in infected mammalian cell cultures and neutralize multiple subtypes of virus by inhibiting the pH-dependant fusion of viral and cellular membranes. These results suggest that this unique, highly-conserved linear sequence in viral hemagglutinin is exposed sufficiently to be attacked by the antibodies during the course of infection and merits further investigation because of potential importance in the protection against diverse strains of influenza viruses.

Antivenom Cross-Neutralization of the Venoms of Hydrophis schistosus and Hydrophis curtus, Two Common Sea Snakes in Malaysian Waters

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Choo Hock Tan

2015-02-01

Full Text Available Sea snake envenomation is a serious occupational hazard in tropical waters. In Malaysia, the beaked sea snake (Hydrophis schistosus, formerly known as Enhydrina schistosa and the spine-bellied sea snake (Hydrophis curtus, formerly known as Lapemis curtus or Lapemis hardwickii are two commonly encountered species. Australian CSL sea snake antivenom is the definitive treatment for sea snake envenomation; it is unfortunately extremely costly locally and is not widely available or adequately stocked in local hospitals. This study investigated the cross-neutralizing potential of three regionally produced anti-cobra antivenoms against the venoms of Malaysian H. schistosus and H. curtus. All three antivenoms conferred paraspecific protection from sea snake venom lethality in mice, with potency increasing in the following order: Taiwan bivalent antivenom < Thai monocled cobra monovalent antivenom < Thai neuro polyvalent antivenom (NPAV. NPAV demonstrated cross-neutralizing potencies of 0.4 mg/vial for H. schistosus venom and 0.8 mg/vial for H. curtus, which translates to a dose of less than 20 vials of NPAV to neutralize an average amount of sea snake venom per bite (inferred from venom milking. The cross-neutralization activity was supported by ELISA cross-reactivity between NPAV and the venoms of H. schistosus (58.4% and H. curtus (70.4%. These findings revealed the potential of NPAV as a second-line treatment for sea snake envenomation in the region. Further profiling of the cross-neutralization activity should address the antivenomic basis using purified toxin-based assays.

P53-dependent upregulation of neutral sphingomyelinase-2: role in doxorubicin-induced growth arrest.

Science.gov (United States)

Shamseddine, A A; Clarke, C J; Carroll, B; Airola, M V; Mohammed, S; Rella, A; Obeid, L M; Hannun, Y A

2015-10-29

Neutral sphingomyelinase-2 (nSMase2) is a ceramide-generating enzyme that has been implicated in growth arrest, apoptosis and exosome secretion. Although previous studies have reported transcriptional upregulation of nSMase2 in response to daunorubicin, through Sp1 and Sp3 transcription factors, the role of the DNA damage pathway in regulating nSMase2 remains unclear. In this study, we show that doxorubicin induces a dose-dependent induction of nSMase2 mRNA and protein with concomitant increases in nSMase activity and ceramide levels. Upregulation of nSMase2 was dependent on ATR, Chk1 and p53, thus placing it downstream of the DNA damage pathway. Moreover, overexpression of p53 was sufficient to transcriptionally induce nSMase2, without the need for DNA damage. DNA-binding mutants as well as acetylation mutants of p53 were unable to induce nSMase2, suggesting a role of nSMase2 in growth arrest. Moreover, knockdown of nSMase2 prevented doxorubicin-induced growth arrest. Finally, p53-induced nSMase2 upregulation appears to occur via a novel transcription start site upstream of exon 3. These results identify nSMase2 as a novel p53 target gene, regulated by the DNA damage pathway to induce cell growth arrest.

Enhancement of the neutral-beam stopping cross section in fusion plasmas due to multistep collision processes

International Nuclear Information System (INIS)

Boley, C.D.; Janev, R.K.; Post, D.E.

1983-10-01

Multistep processes involving excited atomic states are found to produce a substantial increase in the stopping cross section for a neutral hydrogen beam injected into a plasma, and thus to reduce the beam penetration. For typical plasma and beam parameters of current large tokamak experiments, the stopping cross-sectional enhancement is found to vary from 25% to 50% depending on the beam energy, plasma density, and impurity level. For neutral hydrogen beams with energies greater than or equal to 500 keV, envisioned in tokamak amd mirror reactor designs, the enhancement can be as large as 80 to 90%

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.

Cross-Neutralizing Antibodies in HIV-1 Individuals Infected by Subtypes B, F1, C or the B/Bbr Variant in Relation to the Genetics and Biochemical Characteristics of the env Gene.

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Dalziza Victalina de Almeida

Full Text Available Various HIV-1 env genetic and biochemical features impact the elicitation of cross-reactive neutralizing antibodies in natural infections. Thus, we aimed to investigate cross-neutralizing antibodies in individuals infected with HIV-1 env subtypes B, F1, C or the B/Bbr variant as well as env characteristics. Therefore, plasma samples from Brazilian chronically HIV-1 infected individuals were submitted to the TZM-bl neutralization assay. We also analyzed putative N-glycosylation sites (PNGLs and the size of gp120 variable domains in the context of HIV-1 subtypes prevalent in Brazil. We observed a greater breadth and potency of the anti-Env neutralizing response in individuals infected with the F1 or B HIV-1 subtypes compared with the C subtype and the variant B/Bbr. We observed greater V1 B/Bbr and smaller V4 F1 than those of other subtypes (p<0.005, however neither was there a correlation verified between the variable region length and neutralization potency, nor between PNLG and HIV-1 subtypes. The enrichment of W at top of V3 loop in weak neutralizing response viruses and the P in viruses with higher neutralization susceptibility was statistically significant (p = 0.013. Some other signatures sites were associated to HIV-1 subtype-specific F1 and B/Bbr samples might influence in the distinct neutralizing response. These results indicate that a single amino acid substitution may lead to a distinct conformational exposure or load in the association domain of the trimer of gp120 and interfere with the induction power of the neutralizing response, which affects the sensitivity of the neutralizing antibody and has significant implications for vaccine design.

Neutralization of interleukin-17A delays progression of silica-induced lung inflammation and fibrosis in C57BL/6 mice

International Nuclear Information System (INIS)

Chen, Ying; Li, Cuiying; Weng, Dong; Song, Laiyu; Tang, Wen; Dai, Wujing; Yu, Ye; Liu, Fangwei; Zhao, Ming; Lu, Chunwei; Chen, Jie

2014-01-01

Silica exposure can cause lung inflammation and fibrosis, known as silicosis. Interleukin-17A (IL-17A) and Th17 cells play a pivotal role in controlling inflammatory diseases. However, the roles of IL-17A and Th17 cells in the progress of silica-induced inflammation and fibrosis are poorly understood. This study explored the effects of IL-17A on silica-induced inflammation and fibrosis. We used an anti-mouse IL-17A antibody to establish an IL-17A-neutralized mice model, and mice were exposed to silica to establish an experimental silicosis model. We showed that IL-17A neutralization delayed neutrophil accumulation and progression of silica-induced lung inflammation and fibrosis. IL-17A neutralization reduced the percentage of Th17 in CD4 + T cells, decreased IL-6 and IL-1β expression, and increased Tregs at an early phase of silica-induced inflammation. Neutralization of IL-17A delayed silica-induced Th1/Th2 immune and autoimmune responses. These results suggest that IL-17A neutralization alleviates early stage silica-induced lung inflammation and delays progression of silica-induced lung inflammation and fibrosis. Neutralization of IL-17A suppressed Th17 cell development by decreasing IL-6 and/or IL-1β and increased Tregs at an early phase of silica-induced inflammation. Neutralization of IL-17A also delayed the Th1/Th2 immune response during silica-induced lung inflammation and fibrosis. IL-17A may play a pivotal role in the early phase of silica-induced inflammation and may mediate the Th immune response to influence silica-induced lung inflammation and fibrosis in mice. - Highlights: • Neutralization of IL-17A alleviated silica-induced lung inflammation of early stage. • Neutralization of IL-17A decreased Th17 cells and increased Tregs. • IL-17A mediated the reciprocal relationship of Th17/Tregs by IL-6 and/or IL-1β. • Neutralization of IL-17A delayed silica-induced Th1/Th2 immune response. • Neutralization of IL-17A delayed silica-induced lung

Neutralization of interleukin-17A delays progression of silica-induced lung inflammation and fibrosis in C57BL/6 mice

Energy Technology Data Exchange (ETDEWEB)

Chen, Ying; Li, Cuiying [Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, Liaoning (China); Weng, Dong [Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, Liaoning (China); Clinical Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai (China); Song, Laiyu; Tang, Wen; Dai, Wujing; Yu, Ye; Liu, Fangwei; Zhao, Ming; Lu, Chunwei [Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, Liaoning (China); Chen, Jie, E-mail: chenjie@mail.cmu.edu.cn [Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, Liaoning (China)

2014-02-15

Silica exposure can cause lung inflammation and fibrosis, known as silicosis. Interleukin-17A (IL-17A) and Th17 cells play a pivotal role in controlling inflammatory diseases. However, the roles of IL-17A and Th17 cells in the progress of silica-induced inflammation and fibrosis are poorly understood. This study explored the effects of IL-17A on silica-induced inflammation and fibrosis. We used an anti-mouse IL-17A antibody to establish an IL-17A-neutralized mice model, and mice were exposed to silica to establish an experimental silicosis model. We showed that IL-17A neutralization delayed neutrophil accumulation and progression of silica-induced lung inflammation and fibrosis. IL-17A neutralization reduced the percentage of Th17 in CD4 + T cells, decreased IL-6 and IL-1β expression, and increased Tregs at an early phase of silica-induced inflammation. Neutralization of IL-17A delayed silica-induced Th1/Th2 immune and autoimmune responses. These results suggest that IL-17A neutralization alleviates early stage silica-induced lung inflammation and delays progression of silica-induced lung inflammation and fibrosis. Neutralization of IL-17A suppressed Th17 cell development by decreasing IL-6 and/or IL-1β and increased Tregs at an early phase of silica-induced inflammation. Neutralization of IL-17A also delayed the Th1/Th2 immune response during silica-induced lung inflammation and fibrosis. IL-17A may play a pivotal role in the early phase of silica-induced inflammation and may mediate the Th immune response to influence silica-induced lung inflammation and fibrosis in mice. - Highlights: • Neutralization of IL-17A alleviated silica-induced lung inflammation of early stage. • Neutralization of IL-17A decreased Th17 cells and increased Tregs. • IL-17A mediated the reciprocal relationship of Th17/Tregs by IL-6 and/or IL-1β. • Neutralization of IL-17A delayed silica-induced Th1/Th2 immune response. • Neutralization of IL-17A delayed silica-induced lung

Photodegradable neutral-cationic brush block copolymers for nonviral gene delivery.

Science.gov (United States)

Hu, Xianglong; Li, Yang; Liu, Tao; Zhang, Guoying; Liu, Shiyong

2014-08-01

We report on the fabrication of a photodegradable gene-delivery vector based on PEO-b-P(GMA-g-PDMAEMA) neutral-cationic brush block copolymers that possess cationic poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) brushes for DNA compaction, poly(ethylene oxide) (PEO) as a hydrophilic block, and poly(glycidyl methacrylate) (PGMA) as the backbone. The PEO-b-P(GMA-g-PDMAEMA) copolymers were synthesized through the combination of reversible addition-fragmentation transfer (RAFT) polymerization and postmodification. A photocleavable PEO-based macroRAFT agent was first synthesized; next, the PEO-b-PGMA block copolymer was prepared by RAFT polymerization of GMA; this was followed by a click reaction to introduce the RAFT initiators on the side chains of the PGMA block; then, RAFT polymerization of DMAEMA afforded the PEO-b-P(GMA-g-PDMAEMA) copolymer. The obtained neutral-cationic brush block copolymer could effectively complex plasmid DNA (pDNA) into nanoparticles at an N/P ratio (i.e., the number of nitrogen residues per DNA phosphate) of 4. Upon UV irradiation, pDNA could be released owing to cleavage of the pDNA-binding cationic PDMAEMA side chains as well as the nitrobenzyl ester linkages at the diblock junction point. In addition, in vitro gene transfection results demonstrated that the polyplexes could be effectively internalized by cells with good transfection efficiency, and the UV irradiation protocol could considerably enhance the efficiency of gene transfection. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Genetics of some induced and spontaneous dwarfs of rice and their utilization in cross-breeding

International Nuclear Information System (INIS)

Siddiq, E.A.; Sadananda, A.R.; Singh, V.P.; Zaman, F.U.

1984-01-01

Genetics of induced and spontaneous dwarfs and their usefulness in crop improvement have been investigated. Genetic analysis of Jarabali Mutant, Mahsuri Mutant-1 and CRM 8-5711 reveals their dwarfness to be monogenic recessive. It appears from study of allelic relationships that dwarfism in Jarabali Mutant and CRM 8-5711 was controlled by non-allelic recessive genes sd 1 or sd 2 while in Mahsuri Mutant-1 by double recessives sd 1 and sd 2 . Study of multiple character associations with dwarfness in Jarabali Mutant suggests one group of the characters to inherit as a block and others independently. While leaf curliness is controlled by genes showing inhibitory epistasis, panicle compactness is governed by two duplicate and one inhibitory genes. Usefulness of induced and spontaneous dwarfs in cross breeding with popular tall varieties as well as high yielding dwarf varieties has been investigated in detail. Whereas some of the lines derived from crosses involving Jarabali Mutant appear promising as well-combining alternate sources of dwarfing gene, the rest arising from crosses of mutants or their derivatives with talls or improved DGWG dwarfs combine desirable agronomic features including high yield potential. (author)

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

Directory of Open Access Journals (Sweden)

Narayanaiah Cheedarla

2018-03-01

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

Dengue virus specific IgY provides protection following lethal dengue virus challenge and is neutralizing in the absence of inducing antibody dependent enhancement.

Science.gov (United States)

Fink, Ashley L; Williams, Katherine L; Harris, Eva; Alvine, Travis D; Henderson, Thomas; Schiltz, James; Nilles, Matthew L; Bradley, David S

2017-07-01

Dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are severe disease manifestations that can occur following sequential infection with different dengue virus serotypes (DENV1-4). At present, there are no licensed therapies to treat DENV-induced disease. DHF and DSS are thought to be mediated by serotype cross-reactive antibodies that facilitate antibody-dependent enhancement (ADE) by binding to viral antigens and then Fcγ receptors (FcγR) on target myeloid cells. Using genetically engineered DENV-specific antibodies, it has been shown that the interaction between the Fc portion of serotype cross-reactive antibodies and FcγR is required to induce ADE. Additionally, it was demonstrated that these antibodies were as neutralizing as their non-modified variants, were incapable of inducing ADE, and were therapeutic following a lethal, antibody-enhanced infection. Therefore, we hypothesized that avian IgY, which do not interact with mammalian FcγR, would provide a novel therapy for DENV-induced disease. We demonstrate here that goose-derived anti-DENV2 IgY neutralized DENV2 and did not induce ADE in vitro. Anti-DENV2 IgY was also protective in vivo when administered 24 hours following a lethal DENV2 infection. We were also able to demonstrate via epitope mapping that both full-length and alternatively spliced anti-DENV2 IgY recognized different epitopes, including epitopes that have not been previously identified. These observations provide evidence for the potential therapeutic applications of goose-derived anti-DENV2 IgY.

Dengue virus specific IgY provides protection following lethal dengue virus challenge and is neutralizing in the absence of inducing antibody dependent enhancement.

Directory of Open Access Journals (Sweden)

Ashley L Fink

2017-07-01

Full Text Available Dengue hemorrhagic fever (DHF and dengue shock syndrome (DSS are severe disease manifestations that can occur following sequential infection with different dengue virus serotypes (DENV1-4. At present, there are no licensed therapies to treat DENV-induced disease. DHF and DSS are thought to be mediated by serotype cross-reactive antibodies that facilitate antibody-dependent enhancement (ADE by binding to viral antigens and then Fcγ receptors (FcγR on target myeloid cells. Using genetically engineered DENV-specific antibodies, it has been shown that the interaction between the Fc portion of serotype cross-reactive antibodies and FcγR is required to induce ADE. Additionally, it was demonstrated that these antibodies were as neutralizing as their non-modified variants, were incapable of inducing ADE, and were therapeutic following a lethal, antibody-enhanced infection. Therefore, we hypothesized that avian IgY, which do not interact with mammalian FcγR, would provide a novel therapy for DENV-induced disease. We demonstrate here that goose-derived anti-DENV2 IgY neutralized DENV2 and did not induce ADE in vitro. Anti-DENV2 IgY was also protective in vivo when administered 24 hours following a lethal DENV2 infection. We were also able to demonstrate via epitope mapping that both full-length and alternatively spliced anti-DENV2 IgY recognized different epitopes, including epitopes that have not been previously identified. These observations provide evidence for the potential therapeutic applications of goose-derived anti-DENV2 IgY.

Three-dimensional calculations of charge neutralization by neutral gas release

International Nuclear Information System (INIS)

Mandell, M.J.; Jongeward, G.A.; Katz, I.

1993-01-01

There have been numerous observations of high rocket or spacecraft potentials, both positive and negative, and both naturally and artificially induced, being neutralized during thruster firings. Two current studies, CHARGE-2B (positive polarity) and SPEAR3 (negative polarity), attempt a more systematic exploration of this phenomenon. The authors present here calculations performed in support of the SPEAR-3 program. (1) Conventional phenomenology of breakdown is applied to the three-dimensional system formed by the electrostatic potential and plume density fields. Using real cross sections, they calculate the paths along which the nozzle plume can support breakdown. This leads to a recommendation that the higher flow rate on SPEAR-3 be 2 g/s of argon, equal to the CHARGE-2B flow rate. (2) In a laboratory chamber, conditions (pressure of ∼ 2 x 10 - 5 torr) favor breakdown of the positive (electron-collecting) sheath for SPEAR-3 geometry. Three-dimensional calculations illustrate the evolution of the space charge and potential structure during the breakdown process. These calculations demonstrate the ability to apply accepted phenomenology to real systems with three dimensional electrostatic potential fields, space charge fields, and neutral density fields, including magnetic field effects and real cross-section data

Hepatitis C Virus E1 and E2 Proteins Used as Separate Immunogens Induce Neutralizing Antibodies with Additive Properties.

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Elodie Beaumont

Full Text Available Various strategies involving the use of hepatitis C virus (HCV E1 and E2 envelope glycoproteins as immunogens have been developed for prophylactic vaccination against HCV. However, the ideal mode of processing and presenting these immunogens for effective vaccination has yet to be determined. We used our recently described vaccine candidate based on full-length HCV E1 or E2 glycoproteins fused to the heterologous hepatitis B virus S envelope protein to compare the use of the E1 and E2 proteins as separate immunogens with their use as the E1E2 heterodimer, in terms of immunogenetic potential and the capacity to induce neutralizing antibodies. The specific anti-E1 and anti-E2 antibody responses induced in animals immunized with vaccine particles harboring the heterodimer were profoundly impaired with respect to those in animals immunized with particles harboring E1 and E2 separately. Moreover, the anti-E1 and anti-E2 antibodies had additive neutralizing properties that increase the cross-neutralization of heterologous strains of various HCV genotypes, highlighting the importance of including both E1 and E2 in the vaccine for an effective vaccination strategy. Our study has important implications for the optimization of HCV vaccination strategies based on HCV envelope proteins, regardless of the platform used to present these proteins to the immune system.

The potential value of the neutral comet assay and the expression of genes associated with DNA damage in assessing the radiosensitivity of tumor cells.

Science.gov (United States)

Jayakumar, Sundarraj; Bhilwade, Hari N; Pandey, Badri N; Sandur, Santosh K; Chaubey, Ramesh C

2012-10-09

The assessment of tumor radiosensitivity would be particularly useful in optimizing the radiation dose during radiotherapy. Therefore, the degree of correlation between radiation-induced DNA damage, as measured by the alkaline and the neutral comet assays, and the clonogenic survival of different human tumor cells was studied. Further, tumor radiosensitivity was compared with the expression of genes associated with the cellular response to radiation damage. Five different human tumor cell lines were chosen and the radiosensitivity of these cells was established by clonogenic assay. Alkaline and neutral comet assays were performed in γ-irradiated cells (2-8Gy; either acute or fractionated). Quantitative PCR was performed to evaluate the expression of DNA damage response genes in control and irradiated cells. The relative radiosensitivity of the cell lines assessed by the extent of DNA damage (neutral comet assay) immediately after irradiation (4Gy or 6Gy) was in agreement with radiosensitivity pattern obtained by the clonogenic assay. The survival fraction of irradiated cells showed a better correlation with the magnitude of DNA damage measured by the neutral comet assay (r=-0.9; Pcomet assay (r=-0.73; Pcomet assay was better than alkaline comet assay for assessment of radiosensitivities of tumor cells after acute or fractionated doses of irradiation. © 2012 Elsevier B.V. All rights reserved.

Measurement of neutral current e±p cross sections at high Bjorken x with the ZEUS detector

International Nuclear Information System (INIS)

Abramowicz, H.; Abt, I.; Adamczyk, L.

2013-12-01

The neutral current e ± p cross section has been measured up to values of Bjorken x≅1 with the ZEUS detector at HERA using an integrated luminosity of 187 pb -1 of e - p and 142 pb -1 of e + p collisions at √(s)=318 GeV. Differential cross sections in x and Q 2 , the exchanged boson virtuality, are presented for Q 2 ≥725 GeV 2 . An improved reconstruction method and greatly increased amount of data allows a finer binning in the high-x region of the neutral current cross section and leads to a measurement with much improved precision compared to a similar earlier analysis. The measurements are compared to Standard Model expectations based on a variety of recent parton distribution functions.

HPV-16 L1 genes with inactivated negative RNA elements induce potent immune responses

International Nuclear Information System (INIS)

Rollman, Erik; Arnheim, Lisen; Collier, Brian; Oeberg, Daniel; Hall, Haakan; Klingstroem, Jonas; Dillner, Joakim; Pastrana, Diana V.; Buck, Chris B.; Hinkula, Jorma; Wahren, Britta; Schwartz, Stefan

2004-01-01

Introduction of point mutations in the 5' end of the human papillomavirus type 16 (HPV-16) L1 gene specifically inactivates negative regulatory RNA processing elements. DNA vaccination of C57Bl/6 mice with the mutated L1 gene resulted in improved immunogenicity for both neutralizing antibodies as well as for broad cellular immune responses. Previous reports on the activation of L1 by codon optimization may be explained by inactivation of the regulatory RNA elements. The modified HPV-16 L1 DNA that induced anti-HPV-16 immunity may be seen as a complementary approach to protein subunit immunization against papillomavirus

Study of the antineutrino-induced elastic semi-leptonic neutral current reaction

International Nuclear Information System (INIS)

Racca, C.

1978-01-01

A study of the elastic neutral current reaction antiνsub(μ)p→antiνsub(μ)p has been done using Gargamelle filled with propane and the antineutrino beam of the CERN P.S. The space-time structure of the weak neutral current is discussed, the predictions of various V-A models for the ratio of neutral to charged current elastic cross-sections Rsup(antiν) are given. The experimental set-up, the scanning criteria and the program of reconstruction are described. The background due to the contamination by the reaction np→np principally is studied. Cuts are defined to resorbe these backgrounds and corrections are made for other backgrounds and losses. The results are compared with those of the reaction antiνsub(μ)p→μ + n and the ratio Rsup(antiν) is calculated. An upper limit of this ratio is given and the results are discussed [fr

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.

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.

Measurement of Neutral and Charged Current Cross Sections in Electron-Proton Collisions at High $Q^{2}$

CERN Document Server

Adloff, C.; Andrieu, B.; Anthonis, T.; Arkadov, V.; Astvatsatourov, A.; Ayyaz, I.; Babaev, A.; Bahr, J.; Baranov, P.; Barrelet, E.; Bartel, W.; Bassler, U.; Bate, P.; Beglarian, A.; Behnke, O.; Beier, C.; Belousov, A.; Benisch, T.; Berger, Christoph; Bernardi, G.; Berndt, T.; Bizot, J.C.; Boudry, V.; Braunschweig, W.; Brisson, V.; Broker, H.B.; Brown, D.P.; Bruckner, W.; Bruel, P.; Bruncko, D.; Burger, J.; Busser, F.W.; Bunyatyan, A.; Burkhardt, H.; Burrage, A.; Buschhorn, G.; Campbell, A.J.; Cao, Jun; Carli, T.; Caron, S.; Chabert, E.; Clarke, D.; Clerbaux, B.; Collard, C.; Contreras, J.G.; Coppens, Y.R.; Coughlan, J.A.; Cousinou, M.C.; Cox, B.E.; Cozzika, G.; Cvach, J.; Dainton, J.B.; Dau, W.D.; Daum, K.; Davidsson, M.; Delcourt, B.; Delerue, N.; Demirchyan, R.; De Roeck, A.; De Wolf, E.A.; Diaconu, C.; Dixon, P.; Dodonov, V.; Dowell, J.D.; Droutskoi, A.; Dubak, A.; Duprel, C.; Eckerlin, Guenter; Eckstein, D.; Efremenko, V.; Egli, S.; Eichler, R.; Eisele, F.; Eisenhandler, E.; Ellerbrock, M.; Elsen, E.; Erdmann, M.; Erdmann, W.; Faulkner, P.J.W.; Favart, L.; Fedotov, A.; Felst, R.; Ferencei, J.; Ferron, S.; Fleischer, M.; Fleming, Y.H.; Flugge, G.; Fomenko, A.; Foresti, I.; Formanek, J.; Foster, J.M.; Franke, G.; Gabathuler, E.; Gabathuler, K.; Garvey, J.; Gassner, J.; Gayler, Joerg; Gerhards, R.; Ghazarian, S.; Goerlich, L.; Gogitidze, N.; Goldberg, M.; Goodwin, C.; Grab, C.; Grassler, H.; Greenshaw, T.; Grindhammer, Guenter; Hadig, T.; Haidt, D.; Hajduk, L.; Haynes, W.J.; Heinemann, B.; Heinzelmann, G.; Henderson, R.C.W.; Hengstmann, S.; Henschel, H.; Heremans, R.; Herrera, G.; Herynek, I.; Hildebrandt, M.; Hilgers, M.; Hiller, K.H.; Hladky, J.; Hoting, P.; Hoffmann, D.; Horisberger, R.; Hurling, S.; Ibbotson, M.; Issever, C.; Jacquet, M.; Jaffre, M.; Janauschek, L.; Jansen, D.M.; Janssen, X.; Jemanov, V.; Jonsson, L.; Johnson, D.P.; Jones, M.A.S.; Jung, H.; Kastli, H.K.; Kant, D.; Kapichine, M.; Karlsson, M.; Karschnick, O.; Keil, F.; Keller, N.; Kennedy, J.; Kenyon, I.R.; Kermiche, S.; Kiesling, Christian M.; Kjellberg, P.; Klein, M.; Kleinwort, C.; Knies, G.; Koblitz, B.; Kolya, S.D.; Korbel, V.; Kostka, P.; Kotelnikov, S.K.; Koutouev, R.; Koutov, A.; Krasny, M.W.; Krehbiel, H.; Kroseberg, J.; Kruger, K.; Kupper, A.; Kuhr, T.; Kurca, T.; Lahmann, R.; Lamb, D.; Landon, M.P.J.; Lange, W.; Lastovicka, T.; Laycock, P.; Lebailly, E.; Lebedev, A.; Leissner, B.; Lemrani, R.; Lendermann, V.; Levonian, S.; Lindstroem, M.; List, B.; Lobodzinska, E.; Lobodzinski, B.; Loginov, A.; Loktionova, N.; Lubimov, V.; Luders, S.; Luke, D.; Lytkin, L.; Magnussen, N.; Mahlke-Kruger, H.; Malden, N.; Malinovski, E.; Malinovski, I.; Maracek, R.; Marage, P.; Marks, J.; Marshall, R.; Martyn, H.U.; Martyniak, J.; Maxfield, S.J.; Mehta, A.; Meier, K.; Merkel, P.; Meyer, A.B.; Meyer, H.; Meyer, J.; Meyer, P.O.; Mikocki, S.; Milstead, D.; Mkrtchyian, T.; Mohr, R.; Mohrdieck, S.; Mondragon, M.N.; Moreau, F.; Morozov, A.; Morris, J.V.; Muller, K.; Murin, P.; Nagovizin, V.; Naroska, B.; Naumann, J.; Naumann, T.; Nellen, G.; Newman, Paul R.; Nicholls, T.C.; Niebergall, F.; Niebuhr, C.; Nix, O.; Nowak, G.; Nunnemann, T.; Olsson, J.E.; Ozerov, D.; Panassik, V.; Pascaud, C.; Patel, G.D.; Perez, E.; Phillips, J.P.; Pitzl, D.; Poschl, R.; Potachnikova, I.; Povh, B.; Rabbertz, K.; Radel, G.; Rauschenberger, J.; Reimer, P.; Reisert, B.; Reyna, D.; Riess, S.; Risler, C.; Rizvi, E.; Robmann, P.; Roosen, R.; Rostovtsev, A.; Royon, C.; Rusakov, S.; Rybicki, K.; Sankey, D.P.C.; Scheins, J.; Schilling, F.P.; Schleper, P.; Schmidt, D.; Schmitt, S.; Schoeffel, L.; Schoning, A.; Schorner, T.; Schroder, V.; Schultz-Coulon, H.C.; Schwanenberger, C.; Sedlak, K.; Sefkow, F.; Chekelian, V.I.; Sheviakov, I.; Shtarkov, L.N.; Sievers, P.; Sirois, Y.; Sloan, T.; Smirnov, P.; Solochenko, V.; Solovev, Y.; Spaskov, V.; Specka, Arnd E.; Spitzer, H.; Stamen, R.; Steinhart, J.; Stella, B.; Stellberger, A.; Stiewe, J.; Straumann, U.; Struczinski, W.; Swart, M.; Tasevsky, M.; Chernyshov, V.; Chetchelnitski, S.; Thompson, Graham; Thompson, P.D.; Tobien, N.; Traynor, D.; Truoel, Peter; Tsipolitis, G.; Tsurin, I.; Turnau, J.; Turney, J.E.; Tzamariudaki, E.; Udluft, S.; Usik, A.; Valkar, S.; Valkarova, A.; Vallee, C.; Van Mechelen, P.; Vassilev, S.; Vazdik, Y.; Vichnevski, A.; Wacker, K.; Wallny, R.; Walter, T.; Waugh, B.; Weber, G.; Weber, M.; Wegener, D.; Werner, M.; White, G.; Wiesand, S.; Wilksen, T.; Winde, M.; Winter, G.G.; Wissing, C.; Wobisch, M.; Wollatz, H.; Wunsch, E.; Wyatt, A.C.; Zacek, J.; Zalesak, J.; Zhang, Z.; Zhokin, A.; Zomer, F.; Zsembery, J.; zur Nedden, M.

2001-01-01

The inclusive e^-p single and double differential cross sections for neutral and charged current processes are measured with the H1 detector at HERA, in the range of four-momentum transfer squared Q^2 between 150 and 30000 GeV^2, and Bjorken x between 0.002 and 0.65. The data were taken in 1998 and 1999 with a centre-of-mass energy of 320 GeV and correspond to an integrated luminosity of 16.4 pb^(-1). The data are compared with recent measurements of the inclusive neutral and charged current e^+p cross sections. For Q^2>1000 GeV^2 clear evidence is observed for an asymmetry between e^+p and e^-p neutral current scattering and the generalised structure function xF_3 is extracted for the first time at HERA. A fit to the charged current data is used to extract a value for the W boson propagator mass. The data are found to be in good agreement with Standard Model predictions.

Measurement of the Q2 dependence of the charged and neutral current cross sections in e±p scattering at HERA

International Nuclear Information System (INIS)

Aid, S.; Andreev, V.; Andrieu, B.

1996-03-01

The Q 2 dependence and the total cross sections for charged and neutral current processes are measured in e ± p reactions for transverse momenta of the outgoing lepton larger than 25 GeV. Comparable size of cross sections for the neutral current process and for the weak charged current process are observed above Q 2 ∼5000 GeV 2 . Using the shape and magnitude of the charged current cross section we determine a propagator mass of m W =84 -7 +10 GeV. (orig.)

Measurement of neutral current e{sup {+-}}p cross sections at high Bjorken x with the ZEUS detector

Energy Technology Data Exchange (ETDEWEB)

Abramowicz, H. [Tel Aviv Univ. (Israel). School of Physics; Max-Planck-Institute for Physics, Munich (Germany); Abt, I. [Max-Planck-Institute for Physics, Munich (Germany); Adamczyk, L. [AGH-Univ. of Science and Technology, Krakow (Poland). Faculty of Physics and Applied Computer Science; Collaboration: ZEUS Collaboration; and others

2013-12-15

The neutral current e{sup {+-}}p cross section has been measured up to values of Bjorken x{approx_equal}1 with the ZEUS detector at HERA using an integrated luminosity of 187 pb{sup -1} of e{sup -}p and 142 pb{sup -1} of e{sup +}p collisions at {radical}(s)=318 GeV. Differential cross sections in x and Q{sup 2}, the exchanged boson virtuality, are presented for Q{sup 2}{>=}725 GeV{sup 2}. An improved reconstruction method and greatly increased amount of data allows a finer binning in the high-x region of the neutral current cross section and leads to a measurement with much improved precision compared to a similar earlier analysis. The measurements are compared to Standard Model expectations based on a variety of recent parton distribution functions.

Neutralized adenovirus-immune complexes can mediate effective gene transfer via an Fc receptor-dependent infection pathway.

Science.gov (United States)

Leopold, Philip L; Wendland, Rebecca L; Vincent, Theresa; Crystal, Ronald G

2006-10-01

Neutralization of adenovirus (Ad) by anti-Ad neutralizing antibodies in serum involves formation of Ad-immune complexes that prevent the virus from interacting with target cells. We hypothesized that Ad-immune complexes likely contain viable Ad vectors which, although no longer capable of gaining access to receptors on target cells, may be able to express transgenes in cells bearing Fc receptors for immunoglobulins, i.e., that antibody-based "neutralization" of Ad vectors may be circumvented by the Fc receptor pathway. To test this hypothesis, we expressed the Fcgamma receptor IIA (FcgammaR) in A549 lung epithelial cells or human dermal fibroblasts and evaluated gene transfer in the presence of human neutralizing anti-Ad serum. FcgammaR-expressing cells bound and internalized copious amounts of Ad, with a distinct population of internalized Ad trafficking to the nucleus. The dose-response curves for inhibition of gene transfer revealed that FcgammaR-expressing cells required a more-than-10-fold higher concentration of anti-Ad serum to achieve 50% inhibition of Ad-encoded beta-galactosidase expression compared with non-FcgammaR-expressing cells. The discrepancy between neutralization of Ad during infection of FcgammaR-expressing cells and neutralization of Ad during infection of non-FcgammaR-expressing cells occurred with either heat-inactivated or non-heat-inactivated sera, was blocked by addition of purified Fc domain protein, and did not require the cytoplasmic domain of FcgammaR, suggesting that immune complex internalization proceeded via endocytosis rather than phagocytosis. FcgammaR-mediated infection by Ad-immune complexes did not require expression of the coxsackie virus-Ad receptor (CAR) since similar data were obtained when CAR-deficient human dermal fibroblasts were engineered to express FcgammaR. However, interaction of the Ad penton base with cell surface integrins contributed to the difference in neutralization between FcgammaR-expressing and non

Induced pluripotency with endogenous and inducible genes

International Nuclear Information System (INIS)

Duinsbergen, Dirk; Eriksson, Malin; Hoen, Peter A.C. 't; Frisen, Jonas; Mikkers, Harald

2008-01-01

The recent discovery that two partly overlapping sets of four genes induce nuclear reprogramming of mouse and even human cells has opened up new possibilities for cell replacement therapies. Although the combination of genes that induce pluripotency differs to some extent, Oct4 and Sox2 appear to be a prerequisite. The introduction of four genes, several of which been linked with cancer, using retroviral approaches is however unlikely to be suitable for future clinical applications. Towards developing a safer reprogramming protocol, we investigated whether cell types that express one of the most critical reprogramming genes endogenously are predisposed to reprogramming. We show here that three of the original four pluripotency transcription factors (Oct4, Klf4 and c-Myc or MYCER TAM ) induced reprogramming of mouse neural stem (NS) cells exploiting endogenous SoxB1 protein levels in these cells. The reprogrammed neural stem cells differentiated into cells of each germ layer in vitro and in vivo, and contributed to mouse development in vivo. Thus a combinatorial approach taking advantage of endogenously expressed genes and inducible transgenes may contribute to the development of improved reprogramming protocols

Cross-reactivity and neutralization of Indian King cobra (Ophiophagus hannah) venom by polyvalent and monovalent antivenoms.

Science.gov (United States)

Gowtham, Yashonandana J; Mahadeswaraswamy, Y H; Girish, K S; K, Kemparaju

2014-07-01

The venom of the largest venomous snake, the king cobra (Ophiophagus hannah), is still out of league for the production of therapeutic polyvalent antivenom nor it is characterized immunologically in the Indian subcontinent. In the present study, the king cobra venom is comparatively studied for the cross-reactivity/reactivity and toxicity neutralization by the locally available equine therapeutic polyvalent BSV and VB antivenoms, and monovalent antivenom (OH-IgG) prepared in rabbit. None of the two therapeutic antivenoms procured from two different firms showed any signs of cross-reactivity in terms of antigen-antibody precipitin lines in immunodouble diffusion assay; however, a weak and an insignificant cross-reactivity pattern was observed in ELISA and Western blot studies. Further, both BSV and VB antivenoms failed to neutralize proteolytic, hyaluronidase and phospholipase activities as well as toxic properties such as edema, myotoxicity and lethality of the venom. As expected, OH-IgG showed strong reactivity in immunodouble diffusion, ELISA and in Western blot analysis and also neutralized both enzyme activities as well as the toxic properties of the venom. Thus, the study provides insight into the likely measures that are to be taken in cases of accidental king cobra bites for which the Indian subcontinent is still not prepared for. Copyright © 2014 Elsevier B.V. All rights reserved.

A nitrogen source-dependent inducible and repressible gene expression system in the red alga Cyanidioschyzon merolae.

Directory of Open Access Journals (Sweden)

Takayuki eFujiwara

2015-08-01

Full Text Available The unicellular red alga Cyanidioschyzon merolae is a model organism for studying the basic biology of photosynthetic organisms. The C. merolae cell is composed of an extremely simple set of organelles. The genome is completely sequenced. Gene targeting and a heat-shock inducible gene expression system has been recently established. However, a conditional gene knockdown system has not been established, which is required for the examination of function of genes that are essential to cell viability and primary mutant defects. In the current study, we first evaluated the expression of a transgene from two chromosomal neutral loci located in the intergenic region between CMD184C and CMD185C, and a region upstream of the URA5.3 gene. There was no significant difference in expression between them and this result suggests that both may be used as neutral loci. We then designed an inducible and repressible gene expression by using promoters of nitrate-assimilation genes. The expression of nitrate-assimilation genes such as NR (nitrate reductase, NIR (nitrite reductase and NRT (the nitrate/nitrite transporter are reversibly regulated by their dependence on nitrogen sources. We constructed stable strains in which a cassette containing the NR, NIR or NRT promoter and sfGFP gene was inserted in a region upstream of URA5.3 and examined the efficacy of the promoters. The NR, NIR, and NRT promoters were constitutively activated in the nitrate medium, whereas their activities were extremely low in presence of ammonium. The activation of each promoter was immediately inhibited within a period of 1 hour by the addition of ammonium. Thus, a conditional knockdown system in C. merolae was successfully established. The activity varies among the promoters, and each is selectable according to the expression level of a target gene estimated by RNA-sequencing. This method is applicable to defects in genes of interest in photosynthetic organism.

Optimizing cationic and neutral lipids for efficient gene delivery at high serum content.

Science.gov (United States)

Chan, Chia-Ling; Ewert, Kai K; Majzoub, Ramsey N; Hwu, Yeu-Kuang; Liang, Keng S; Leal, Cecília; Safinya, Cyrus R

2014-01-01

Cationic liposome (CL)-DNA complexes are promising gene delivery vectors with potential application in gene therapy. A key challenge in creating CL-DNA complexes for application is that their transfection efficiency (TE) is adversely affected by serum. In particular, little is known about the effects of a high serum content on TE, even though this may provide design guidelines for application in vivo. We prepared CL-DNA complexes in which we varied the neutral lipid [1,2-dioleoyl-sn-glycerophosphatidylcholine, glycerol-monooleate (GMO), cholesterol], the headgroup charge and chemical structure of the cationic lipid, and the ratio of neutral to cationic lipid; we then measured the TE of these complexes as a function of serum content and assessed their cytotoxicity. We tested selected formulations in two human cancer cell lines (M21/melanoma and PC-3/prostate cancer). In the absence of serum, all CL-DNA complexes of custom-synthesized multivalent lipids show high TE. Certain combinations of multivalent lipids and neutral lipids, such as MVL5(5+)/GMO-DNA complexes or complexes based on the dendritic-headgroup lipid TMVLG3(8+) exhibited high TE both in the absence and presence of serum. Although their TE still dropped to a small extent in the presence of serum, it reached or surpassed that of benchmark commercial transfection reagents, particularly at a high serum content. Two-component vectors (one multivalent cationic lipid and one neutral lipid) can rival or surpass benchmark reagents at low and high serum contents (up to 50%, v/v). We propose guidelines for optimizing the serum resistance of CL-DNA complexes based on a given cationic lipid. Copyright © 2014 John Wiley & Sons, Ltd.

A measurement of the neutral current neutrino-nucleon elastic cross section at MiniBooNE

Energy Technology Data Exchange (ETDEWEB)

Cox, David Christopher [Indiana Univ., Bloomington, IN (United States)

2008-02-01

The neutral current neutrino-nucleon elastic interaction v N → v N is a fundamental process of the weak interaction ideally suited for characterizing the structure of the nucleon neutral weak current. This process comprises ~18% of neutrino events in the neutrino oscillation experiment, MiniBooNE, ranking it as the experiment's third largest process. Using ~10% of MiniBooNE's available neutrino data, a sample of these events were identified and analyzed to determine the differential cross section as a function of the momentum transfer of the interaction, Q². This is the first measurement of a differential cross section with MiniBooNE data. From this analysis, a value for the nucleon axial mass M_A was extracted to be 1.34 ± 0.25 GeV consistent with previous measurements. The integrated cross section for the Q² range 0.189 → 1.13 GeV² was calculated to be (8.8 ± 0.6(stat) ± 0.2(syst)) x 10^-40 cm².

Inclusive dijet cross sections in neutral current deep inelastic scattering at HERA

International Nuclear Information System (INIS)

Abramowicz, H.; Adamczyk, L.

2010-10-01

Single- and double-differential inclusive dijet cross sections in neutral current deep inelastic ep scattering have been measured with the ZEUS detector using an integrated luminosity of 374 pb -1 . The measurement was performed at large values of the photon virtuality, Q 2 , between 125 and 20 000 GeV 2 . The jets were reconstructed with the k T cluster algorithm in the Breit reference frame and selected by requiring their transverse energies in the Breit frame, E jet T,B , to be larger than 8 GeV. In addition, the invariant mass of the dijet system, M jj , was required to be greater than 20 GeV. The cross sections are described by the predictions of next-to-leading-order QCD. (orig.)

Measurement of charged and neutral current e-p deep inelastic scattering cross sections at high Q2

International Nuclear Information System (INIS)

Derrick, M.; Krakauer, D.; Magill, S.; Mikunas, D.; Musgrave, B.; Repond, J.; Stanek, R.; Talaga, R.L.; Zhang, H.; Ayad, R.; Bari, G.; Basile, M.; Bellagamba, L.; Boscherini, D.; Bruni, A.; Bruni, G.; Bruni, P.; Cara Romeo, G.; Castellini, G.; Chiarini, M.; Cifarelli, L.; Cindolo, F.; Contin, A.; Corradi, M.; Gialas, I.; Giusti, P.; Iacobucci, G.; Laurenti, G.; Levi, G.; Margotti, A.; Massam, T.; Nania, R.; Nemoz, C.; Palmonari, F.; Polini, A.; Sartorelli, G.; Timellini, R.; Zamora Garcia, Y.; Zichichi, A.; Bargende, A.; Crittenden, J.; Desch, K.; Diekmann, B.; Doeker, T.; Eckert, M.; Feld, L.; Frey, A.; Geerts, M.; Geitz, G.; Grothe, M.; Haas, T.; Hartmann, H.; Haun, D.; Heinloth, K.; Hilger, E.; Jakob, H.; Katz, U.F.; Mari, S.M.; Mass, A.; Mengel, S.; Mollen, J.; Paul, E.; Rembser, C.; Schattevoy, R.; Schramm, D.; Stamm, J.; Wedemeyer, R.; Campbell-Robson, S.; Cassidy, A.; Dyce, N.; Foster, B.; George, S.; Gilmore, R.; Heath, G.P.; Heath, H.F.; Llewellyn, T.J.; Morgado, C.J.S.; Norman, D.J.P.; O'Mara, J.A.; Tapper, R.J.; Wilson, S.S.; Yoshida, R.; Rau, R.R.; Arneodo, M.; Iannotti, L.; Schioppa, M.; Susinno, G.; Bernstein, A.; Caldwell, A.; Cartiglia, N.; Parsons, J.A.; Ritz, S.; Sciulli, F.; Straub, P.B.; Wai, L.; Yang, S.; Zhu, Q.; Borzemski, P.; Chwastowski, J.; Eskreys, A.; Piotrzkowski, K.; Zachara, M.; Zawiejski, L.; Adamczyk, L.; Bednarek, B.; Jelen, K.; Kisielewska, D.; Kowalski, T.; Rulikowska-Zarebska, E.; Suszycki, L.; Zajac, J.; Kotanski, A.; Przybycien, M.; Bauerdick, L.A.T.; Behrens, U.; Beier, H.; Bienlein, J.K.; Coldewey, C.; Deppe, O.; Desler, K.; Drews, G.; Flasinski, M.; Gilkinson, D.J.; Glasman, C.; Goettlicher, P.; Grosse-Knetter, J.; Gutjahr, B.; Hain, W.; Hasell, D.; Hessling, H.; Hultschig, H.; Iga, Y.; Joos, P.; Kasemann, M.; Klanner, R.; Koch, W.; Koepke, L.; Koetz, U.; Kowalski, H.; Labs, J.; Ladage, A.; Loehr, B.; Loewe, M.; Lueke, D.; Manczak, O.; Ng, J.S.T.; Nickel, S.; Notz, D.; Ohrenberg, K.; Roco, M.; Rohde, M.

1995-01-01

Deep inelastic e - p scattering has been studied in both the charged current (CC) and neutral current (NC) reactions at momentum transfers squared Q 2 above 400GeV 2 using the ZEUS detector at the HERA ep collider. The CC and NC total cross sections, the NC to CC cross section ratio, and the differential cross sections dσ/dQ 2 are presented. From the Q 2 dependence of the CC cross section, the mass term in the CC propagator is determined to be M W =76±16±13 GeV

Cellular Repair of DNA–DNA Cross-Links Induced by 1,2,3,4-Diepoxybutane

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Lisa N. Chesner

2017-05-01

Full Text Available Xenobiotic-induced interstrand DNA–DNA cross-links (ICL interfere with transcription and replication and can be converted to toxic DNA double strand breaks. In this work, we investigated cellular responses to 1,4-bis-(guan-7-yl-2,3-butanediol (bis-N7G-BD cross-links induced by 1,2,3,4-diepoxybutane (DEB. High pressure liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI+-MS/MS assays were used to quantify the formation and repair of bis-N7G-BD cross-links in wild-type Chinese hamster lung fibroblasts (V79 and the corresponding isogenic clones V-H1 and V-H4, deficient in the XPD and FANCA genes, respectively. Both V-H1 and V-H4 cells exhibited enhanced sensitivity to DEB-induced cell death and elevated bis-N7G-BD cross-links. However, relatively modest increases of bis-N7G-BD adduct levels in V-H4 clones did not correlate with their hypersensitivity to DEB. Further, bis-N7G-BD levels were not elevated in DEB-treated human clones with defects in the XPA or FANCD2 genes. Comet assays and γ-H2AX focus analyses conducted with hamster cells revealed that ICL removal was associated with chromosomal double strand break formation, and that these breaks persisted in V-H4 cells as compared to control cells. Our findings suggest that ICL repair in cells with defects in the Fanconi anemia repair pathway is associated with aberrant re-joining of repair-induced double strand breaks, potentially resulting in lethal chromosome rearrangements.

Alcohol-induced histone acetylation reveals a gene network involved in alcohol tolerance.

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Alfredo Ghezzi

Full Text Available Sustained or repeated exposure to sedating drugs, such as alcohol, triggers homeostatic adaptations in the brain that lead to the development of drug tolerance and dependence. These adaptations involve long-term changes in the transcription of drug-responsive genes as well as an epigenetic restructuring of chromosomal regions that is thought to signal and maintain the altered transcriptional state. Alcohol-induced epigenetic changes have been shown to be important in the long-term adaptation that leads to alcohol tolerance and dependence endophenotypes. A major constraint impeding progress is that alcohol produces a surfeit of changes in gene expression, most of which may not make any meaningful contribution to the ethanol response under study. Here we used a novel genomic epigenetic approach to find genes relevant for functional alcohol tolerance by exploiting the commonalities of two chemically distinct alcohols. In Drosophila melanogaster, ethanol and benzyl alcohol induce mutual cross-tolerance, indicating that they share a common mechanism for producing tolerance. We surveyed the genome-wide changes in histone acetylation that occur in response to these drugs. Each drug induces modifications in a large number of genes. The genes that respond similarly to either treatment, however, represent a subgroup enriched for genes important for the common tolerance response. Genes were functionally tested for behavioral tolerance to the sedative effects of ethanol and benzyl alcohol using mutant and inducible RNAi stocks. We identified a network of genes that are essential for the development of tolerance to sedation by alcohol.

Laser-induced fluorescence of metal-atom impurities in a neutral beam

International Nuclear Information System (INIS)

Burrell, C.F.; Pyle, R.V.; Sabetimani, Z.; Schlachter, A.S.

1984-10-01

The need to limit impurities in fusion devices to low levels is well known. We have investigated, by the technique of laser-induced fluorescence, the concentration of heavy-metal atoms in a neutral beam caused by their evaporation from the hot filaments in a conventional high-current multifilament hydrogen-ion source

Innate immune genes including a mucin-like gene, mul-1, induced by ionizing radiation in Caenorhabditis elegans.

Science.gov (United States)

Kimura, Takafumi; Takanami, Takako; Sakashita, Tetsuya; Wada, Seiichi; Kobayashi, Yasuhiko; Higashitani, Atsushi

2012-10-01

The effect of radiation on the intestine has been studied for more than one hundred years. It remains unclear, however, whether this organ uses specific defensive mechanisms against ionizing radiation. The infection with Pseudomonas aeruginosa (PA14) in Caenorhabditis elegans induces up-regulation of innate immune response genes. Here, we found that exposure to ionizing radiation also induces certain innate immune response genes such as F49F1.6 (termed mul-1), clec-4, clec-67, lys-1 and lys-2 in the intestine. Moreover, pre-treatment with ionizing radiation before seeding on PA14 lawn plate significantly increased survival rate in the nematode. We also studied transcription pathway of the mul-1 in response to ionizing radiation. Induction of mul-1 gene was highly dependent on the ELT-2 transcription factor and p38 MAPK. Moreover, the insulin/IGF-1 signal pathway works to enhance induction of this gene. The mul-1 gene showed a different induction pattern from the DNA damage response gene, ced-13, which implies that the expression of this gene might be triggered as an indirect effect of radiation. Silencing of the mul-1 gene led to growth retardation after treatment with ionizing radiation. We describe the cross-tolerance between the response to radiation exposure and the innate immune system.

Cross-sections for neutral-current neutrino-nucleus interactions applications for $^{12}$C and $^{16}$O

CERN Document Server

Jachowicz, N; Heyde, Kris L G; Ryckebusch, J

1999-01-01

We calculate cross sections for neutral current quasi-elastic neutrino-nucleus scattering within a continuum RPA model, based on a Green's function approach. As residual interaction a Skyrme force is used. The unperturbed single particle wave functions are generated using either a Woods-Saxon potential or a Hartree-Fock calculation. These calculations have interesting applications. Neutrinos play an important role in supernova nucleosynthesis. To obtain more information about these processes, cross sections are folded with a Fermi-Dirac distribution with temperatures of approximately 10$^9$ K.

Stress-induced and cue-induced craving for alcohol in heavy drinkers: Preliminary evidence of genetic moderation by the OPRM1 and CRH-BP genes.

Science.gov (United States)

Ray, Lara A

2011-01-01

Neurobiological theories of addiction have highlighted disruption in stress pathways as a central feature of addictive disorders, and pharmacological treatments targeting stress mechanisms hold great promise. This study examines genetic determinants of stress-induced and cue-induced craving in heavy drinkers by testing single-nucleotide polymorphisms (SNPs) of the corticotrophin-releasing hormone binding protein (CRH-BP) gene and the mu-opioid receptor (OPRM1) gene. This study combines guided imagery stress exposure and in vivo alcohol cue exposure in a sample of 64 (23 women) non-treatment-seeking heavy drinkers. Analyses, uncorrected for multiple comparisons, revealed that a tag SNP of the CRH-BP gene (rs10055255) moderated stress-induced craving in this sample. The same SNP predicted greater affective responses to the stress manipulation, including greater levels of subjective tension and negative mood. The Asp40 allele of the OPRM1 was associated with greater cue-induced alcohol craving following the neutral imagery condition. These initial results extend recent preclinical and clinical findings implicating the CRH-BP in stress-related alcoholism and confirm the role of the Asp40 allele of the OPRM1 gene in reward-driven alcohol phenotypes. Human laboratory models of stress and cue-induced craving may be useful in pharmacotherapy development targeting dysregulation of stress systems. Larger studies are needed to validate these preliminary findings, which should also be extended to clinical samples. Copyright © 2010 by the Research Society on Alcoholism.

Inclusive dijet cross sections in neutral current deep inelastic scattering at HERA

Energy Technology Data Exchange (ETDEWEB)

Abramowicz, H. [Tel Aviv Univ. (Israel). Raymond and Beverly Sackler Faculty of Exact Sciences; Univ. College London (United Kingdom); Cracow Univ. of Technology (Poland). Faculty of Physics, Mathematics and Applied Computer Science; Abt, I. [Max-Planck-Institut fuer Physik, Muenchen (Germany); Adamczyk, L. [AGH-Univ. of Science and Technology, Cracow (PL). Faculty of Physics and Applied Computer Science] (and others)

2010-10-15

Single- and double-differential inclusive dijet cross sections in neutral current deep inelastic ep scattering have been measured with the ZEUS detector using an integrated luminosity of 374 pb{sup -1}. The measurement was performed at large values of the photon virtuality, Q{sup 2}, between 125 and 20 000 GeV{sup 2}. The jets were reconstructed with the k{sub T} cluster algorithm in the Breit reference frame and selected by requiring their transverse energies in the Breit frame, E{sup jet}{sub T,B}, to be larger than 8 GeV. In addition, the invariant mass of the dijet system, M{sub jj}, was required to be greater than 20 GeV. The cross sections are described by the predictions of next-to-leading-order QCD. (orig.)

Are Synonymous Substitutions in Flowering Plant Mitochondria Neutral?

Science.gov (United States)

Wynn, Emily L; Christensen, Alan C

2015-10-01

Angiosperm mitochondrial genes appear to have very low mutation rates, while non-gene regions expand, diverge, and rearrange quickly. One possible explanation for this disparity is that synonymous substitutions in plant mitochondrial genes are not truly neutral and selection keeps their occurrence low. If this were true, the explanation for the disparity in mutation rates in genes and non-genes needs to consider selection as well as mechanisms of DNA repair. Rps14 is co-transcribed with cob and rpl5 in most plant mitochondrial genomes, but in some genomes, rps14 has been duplicated to the nucleus leaving a pseudogene in the mitochondria. This provides an opportunity to compare neutral substitution rates in pseudogenes with synonymous substitution rates in the orthologs. Genes and pseudogenes of rps14 have been aligned among different species and the mutation rates have been calculated. Neutral substitution rates in pseudogenes and synonymous substitution rates in genes are significantly different, providing evidence that synonymous substitutions in plant mitochondrial genes are not completely neutral. The non-neutrality is not sufficient to completely explain the exceptionally low mutation rates in land plant mitochondrial genomes, but selective forces appear to play a small role.

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

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

Directory of Open Access Journals (Sweden)

Simon M Agwale

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

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.

Copy number of the Adenomatous Polyposis Coli gene is not always neutral in sporadic colorectal cancers with loss of heterozygosity for the gene.

Science.gov (United States)

Zauber, Peter; Marotta, Stephen; Sabbath-Solitare, Marlene

2016-03-12

Changes in the number of alleles of a chromosome may have an impact upon gene expression. Loss of heterozygosity (LOH) indicates that one allele of a gene has been lost, and knowing the exact copy number of the gene would indicate whether duplication of the remaining allele has occurred. We were interested to determine the copy number of the Adenomatous Polyposis Coli (APC) gene in sporadic colorectal cancers with LOH. We selected 38 carcinomas with LOH for the APC gene region of chromosome 5, as determined by amplification of the CA repeat region within the D5S346 loci. The copy number status of APC was ascertained using the SALSA® MLPA® P043-B1 APC Kit. LOH for the DCC gene, KRAS gene mutation, and microsatellite instability were also evaluated for each tumor, utilizing standard polymerase chain reaction methods. No tumor demonstrated microsatellite instability. LOH of the DCC gene was also present in 33 of 36 (91.7%) informative tumors. A KRAS gene mutation was present in 16 of the 38 (42.1%) tumors. Twenty-four (63.2%) of the tumors were copy number neutral, 10 (26.3%) tumors demonstrated major loss, while two (5.3%) showed partial loss. Two tumors (5.3%) had copy number gain. Results of APC and DCC LOH, KRAS and microsatellite instability indicate our colorectal cancer cases were typical of sporadic cancers following the 'chromosomal instability' pathway. The majority of our colorectal carcinomas with LOH for APC gene are copy number neutral. However, one-third of our cases showed copy number loss, suggesting that duplication of the remaining allele is not required for the development of a colorectal carcinoma.

Copy number of the Adenomatous Polyposis Coli gene is not always neutral in sporadic colorectal cancers with loss of heterozygosity for the gene

International Nuclear Information System (INIS)

Zauber, Peter; Marotta, Stephen; Sabbath-Solitare, Marlene

2016-01-01

Changes in the number of alleles of a chromosome may have an impact upon gene expression. Loss of heterozygosity (LOH) indicates that one allele of a gene has been lost, and knowing the exact copy number of the gene would indicate whether duplication of the remaining allele has occurred. We were interested to determine the copy number of the Adenomatous Polyposis Coli (APC) gene in sporadic colorectal cancers with LOH. We selected 38 carcinomas with LOH for the APC gene region of chromosome 5, as determined by amplification of the CA repeat region within the D5S346 loci. The copy number status of APC was ascertained using the SALSA® MLPA® P043-B1 APC Kit. LOH for the DCC gene, KRAS gene mutation, and microsatellite instability were also evaluated for each tumor, utilizing standard polymerase chain reaction methods. No tumor demonstrated microsatellite instability. LOH of the DCC gene was also present in 33 of 36 (91.7 %) informative tumors. A KRAS gene mutation was present in 16 of the 38 (42.1 %) tumors. Twenty-four (63.2 %) of the tumors were copy number neutral, 10 (26.3 %) tumors demonstrated major loss, while two (5.3 %) showed partial loss. Two tumors (5.3 %) had copy number gain. Results of APC and DCC LOH, KRAS and microsatellite instability indicate our colorectal cancer cases were typical of sporadic cancers following the ‘chromosomal instability’ pathway. The majority of our colorectal carcinomas with LOH for APC gene are copy number neutral. However, one-third of our cases showed copy number loss, suggesting that duplication of the remaining allele is not required for the development of a colorectal carcinoma

Fixations of the HIV-1 env gene refute neutralism: New evidence for pan-selective evolution

Directory of Open Access Journals (Sweden)

Carlos Y Valenzuela

2010-01-01

Full Text Available We examined 103 nucleotide sequences of the HIV-1 env gene, sampled from 35 countries and tested: I the random (neutral distribution of the number of nucleotide changes; II the proportion of bases at molecular equilibrium; III the neutral expected homogeneity of the distribution of new fxated bases; IV the hypothesis of the neighbor infuence on the mutation rates in a site. The expected random number of fxations per site was estimated by Bose-Einstein statistics, and the expected frequencies of bases by matrices of mutation-fxation rates. The homogeneity of new fxations was analyzed using χ2 and trinomial tests for homogeneity. Fixations of the central base in trinucleotides were used to test the neighbor infuence on base substitutions. Neither the number of fxations nor the frequencies of bases ftted the expected neutral distribution. There was a highly signifcant heterogeneity in the distribution of new fxations, and several sites showed more transversions than transitions, showing that each nucleotide site has its own pattern of change. These three independent results make the neutral theory, the nearly neutral and the neighbor infuence hypotheses untenable and indicate that evolution of env is rather highly selective.

Reranking candidate gene models with cross-species comparison for improved gene prediction

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Pereira Fernando CN

2008-10-01

Full Text Available Abstract Background Most gene finders score candidate gene models with state-based methods, typically HMMs, by combining local properties (coding potential, splice donor and acceptor patterns, etc. Competing models with similar state-based scores may be distinguishable with additional information. In particular, functional and comparative genomics datasets may help to select among competing models of comparable probability by exploiting features likely to be associated with the correct gene models, such as conserved exon/intron structure or protein sequence features. Results We have investigated the utility of a simple post-processing step for selecting among a set of alternative gene models, using global scoring rules to rerank competing models for more accurate prediction. For each gene locus, we first generate the K best candidate gene models using the gene finder Evigan, and then rerank these models using comparisons with putative orthologous genes from closely-related species. Candidate gene models with lower scores in the original gene finder may be selected if they exhibit strong similarity to probable orthologs in coding sequence, splice site location, or signal peptide occurrence. Experiments on Drosophila melanogaster demonstrate that reranking based on cross-species comparison outperforms the best gene models identified by Evigan alone, and also outperforms the comparative gene finders GeneWise and Augustus+. Conclusion Reranking gene models with cross-species comparison improves gene prediction accuracy. This straightforward method can be readily adapted to incorporate additional lines of evidence, as it requires only a ranked source of candidate gene models.

Empirical phylogenies and species abundance distributions are consistent with pre-equilibrium dynamics of neutral community models with gene flow

KAUST Repository

Bonnet-Lebrun, Anne-Sophie

2017-03-17

Community characteristics reflect past ecological and evolutionary dynamics. Here, we investigate whether it is possible to obtain realistically shaped modelled communities - i.e., with phylogenetic trees and species abundance distributions shaped similarly to typical empirical bird and mammal communities - from neutral community models. To test the effect of gene flow, we contrasted two spatially explicit individual-based neutral models: one with protracted speciation, delayed by gene flow, and one with point mutation speciation, unaffected by gene flow. The former produced more realistic communities (shape of phylogenetic tree and species-abundance distribution), consistent with gene flow being a key process in macro-evolutionary dynamics. Earlier models struggled to capture the empirically observed branching tempo in phylogenetic trees, as measured by the gamma statistic. We show that the low gamma values typical of empirical trees can be obtained in models with protracted speciation, in pre-equilibrium communities developing from an initially abundant and widespread species. This was even more so in communities sampled incompletely, particularly if the unknown species are the youngest. Overall, our results demonstrate that the characteristics of empirical communities that we have studied can, to a large extent, be explained through a purely neutral model under pre-equilibrium conditions. This article is protected by copyright. All rights reserved.

Empirical phylogenies and species abundance distributions are consistent with pre-equilibrium dynamics of neutral community models with gene flow

KAUST Repository

Bonnet-Lebrun, Anne-Sophie; Manica, Andrea; Eriksson, Anders; Rodrigues, Ana S.L.

2017-01-01

Community characteristics reflect past ecological and evolutionary dynamics. Here, we investigate whether it is possible to obtain realistically shaped modelled communities - i.e., with phylogenetic trees and species abundance distributions shaped similarly to typical empirical bird and mammal communities - from neutral community models. To test the effect of gene flow, we contrasted two spatially explicit individual-based neutral models: one with protracted speciation, delayed by gene flow, and one with point mutation speciation, unaffected by gene flow. The former produced more realistic communities (shape of phylogenetic tree and species-abundance distribution), consistent with gene flow being a key process in macro-evolutionary dynamics. Earlier models struggled to capture the empirically observed branching tempo in phylogenetic trees, as measured by the gamma statistic. We show that the low gamma values typical of empirical trees can be obtained in models with protracted speciation, in pre-equilibrium communities developing from an initially abundant and widespread species. This was even more so in communities sampled incompletely, particularly if the unknown species are the youngest. Overall, our results demonstrate that the characteristics of empirical communities that we have studied can, to a large extent, be explained through a purely neutral model under pre-equilibrium conditions. This article is protected by copyright. All rights reserved.

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

Science.gov (United States)

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

2013-01-01

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

DNA vaccines expressing soluble CD4-envelope proteins fused to C3d elicit cross-reactive neutralizing antibodies to HIV-1

International Nuclear Information System (INIS)

Bower, Joseph F.; Green, Thomas D.; Ross, Ted M.

2004-01-01

DNA vaccines expressing the envelope (Env) of the human immunodeficiency virus type 1 (HIV-1) have been relatively ineffective at generating high-titer, long-lasting, neutralizing antibodies in a variety of animal models. In this study, DNA vaccines were constructed to express a fusion protein of the soluble human CD4 (sCD4) and the gp120 subunit of the HIV-1 envelope. To enhance the immunogenicity of the expressed fusion protein, three copies of the murine C3d (mC3d 3 ) were added to the carboxyl terminus of the complex. Monoclonal antibodies that recognize CD4-induced epitopes on gp120 efficiently bound to sCD4-gp120 or sCD4-gp120-mC3d 3 . In addition, both sCD4-gp120 and sCD4-gp120-mC3d 3 bound to cells expressing appropriate coreceptors in the absence of cell surface hCD4. Mice (BALB/c) vaccinated with DNA vaccines expressing either gp120-mC3d 3 or sCD4-gp120-mC3d 3 elicited antibodies that neutralized homologous virus infection. However, the use of sCD4-gp120-mC3d 3 -DNA elicited the highest titers of neutralizing antibodies that persisted after depletion of anti-hCD4 antibodies. Interestingly, only mice vaccinated with DNA expressing sCD4-gp120-mC3d 3 had antibodies that elicited cross-protective neutralizing antibodies. The fusion of sCD4 to the HIV-1 envelope exposes neutralizing epitopes that elicit broad protective immunity when the fusion complex is coupled with the molecular adjuvant, C3d

Cross neutralizing antibodies in hamsters vaccinated with leptospiral bacterins produced with three serovars of serogroup Sejroe

Directory of Open Access Journals (Sweden)

Rosana Tabata

2002-09-01

Full Text Available Three leptospiral bacterins, produced with different serovars of Serogroup Sejroe, namely the hardjo (bacterin A, wolffi (bacterin B and guaricura (bacterin C, were evaluated in male hamsters (Mesocricetus auratus by comparing the agglutinating and neutralizing antibodies titers using microscopic agglutination (MAT and in vitro growth inhibition (GIT tests. The immunization schedule was based on two 1.0 mL doses of non-diluted formalininactivated whole culture bacterin given through subcutaneous route with 10-day interval. The challenge was performed ten days after the second vaccine dose, when the animals were inoculated with 0.2 mL of non-inactivated cultures of each serovar through intraperitoneal route. On the 21st post-challenge day (PCD, all animals were bled and their sera were joined in pools (n=8 and tested by MAT and GIT. All vaccinated and control animals presented no clinical signs of leptospirosis after the challenge, but the serovar guaricura was isolated from the kidneys of control animals on the 21st PCD. The MAT results showed cross agglutinins between serovars hardjo and wolffi, and between wolffi and guaricura. The GIT results revealed the presence of cross neutralizing antibodies between serovars wolffi or guaricura against hardjo, wolffi and guaricura. It was found that the tested strain of serovar hardjo did not produce detectable levels of neutralizing antibodies, indicating its poor immunogenicity.

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

Measurement of Neutral-Current K+ Production by Neutrinos using MINERvA

Science.gov (United States)

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

2017-07-01

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

Charged-Current Neutral Pion production at SciBooNE

International Nuclear Information System (INIS)

Catala-Perez, J.

2009-01-01

SciBooNE, located in the Booster Neutrino Beam at Fermilab, collected data from June 2007 to August 2008 to accurately measure muon neutrino and anti-neutrino cross sections on carbon below 1 GeV neutrino energy. SciBooNE is studying charged current interactions. Among them, neutral pion production interactions will be the focus of this poster. The experimental signature of neutrino-induced neutral pion production is constituted by two electromagnetic cascades initiated by the conversion of the π 0 decay photons, with an additional muon in the final state for CC processes. In this poster, I will present how we reconstruct and select charged-current muon neutrino interactions producing π 0 's in SciBooNE.

Measurement of the neutral to charged current cross section ratios in neutrino and antineutrino nucleon interactions and determination of the Weinberg angle

International Nuclear Information System (INIS)

Abramowicz, H.; Groot, J.G.H. de; Hansl-Kozanecka, T.; Knobloch, J.; May, J.; Navarria, F.L.; Palazzi, P.; Para, A.; Ranjard, F.; Rothberg, J.; Schlatter, D.; Steinberger, J.; Taureg, H.; Rueden, W. von; Wahl, H.; Wotschak, J.; Duda, J.; Eisele, F.; Klasen, H.P.; Kleinknecht, K.; Lierl, H.; Pollmann, D.; Pszola, B.; Renk, B.; Willutzki, H.J.; Dydak, F.; Flottmann, T.; Geweniger, C.; Hepp, V.; Krolikowski, J.; Tittel, K.; Bloch, P.; Bloch-Devaux, B.; Guyot, C.; Loucatos, S.; Maillard, J.; Merlo, J.P.; Peyaud, B.; Rander, J.; Savoy-Navarro, A.; Turlay, R.; He, J.T.; Ruan, T.Z.; Wu, W.M.

1985-01-01

The cross section ratios of neutral and charged current interactions induced by neutrinos and antineutrinos in iron have been measured in the 200 GeV narrow-band beam at the CERN SPS. We find Rsub(ν)=0.301+-0.007 and Rsub(anti ν)=0.363+-0.015 for a hadron energy cut of 10 GeV. The results are in agreement with the standard model of electroweak interactions. In the MS renormalization scheme at the scale of the W boson mass sin 2 Osub(w)(msub(w))=0.226+-0.012 is obtained, where the error represents the experimental uncertainty. The theoretical uncertainty is estimated to be Δ sind 2 Osub(w)=+-0.006. (orig.)

Neutron-induced fission cross sections

International Nuclear Information System (INIS)

Weigmann, H.

1991-01-01

In the history of fission research, neutron-induced fission has always played the most important role. The practical importance of neutron-induced fission rests upon the fact that additional neutrons are produced in the fission process, and thus a chain reaction becomes possible. The practical applications of neutron-induced fission will not be discussed in this chapter, but only the physical properties of one of its characteristics, namely (n,f) cross sections. The most important early summaries on the subject are the monograph edited by Michaudon which also deals with the practical applications, the earlier review article on fission by Michaudon, and the review by Bjornholm and Lynn, in which neutron-induced fission receives major attention. This chapter will attempt to go an intermediate way between the very detailed theoretical treatment in the latter review and the cited monograph which emphasizes the applied aspects and the techniques of fission cross-section measurements. The more recent investigations in the field will be included. Section II will survey the properties of cross sections for neutron-induced fission and also address some special aspects of the experimental methods applied in their measurement. Section Ill will deal with the formal theory of neutron-induced nuclear reactions for the resolved resonance region and the region of statistical nuclear reactions. In Section IV, the fission width, or fission transmission coefficient, will be discussed in detail. Section V will deal with the broader structures due to incompletely damped vibrational resonances, and in particular will address the special case of thorium and neighboring isotopes. Finally, Section VI will briefly discuss parity violation effects in neutron-induced fission. 74 refs., 14 figs., 3 tabs

Regulation of gene expression in roots of the pH-sensitive Vaccinium corymbosum and the pH-tolerant Vaccinium arboreum in response to near neutral pH stress using RNA-Seq.

Science.gov (United States)

Payá-Milans, Miriam; Nunez, Gerardo H; Olmstead, James W; Rinehart, Timothy A; Staton, Margaret

2017-08-07

Blueberries are one of the few horticultural crops adapted to grow in acidic soils. Neutral to basic soil pH is detrimental to all commonly cultivated blueberry species, including Vaccinium corymbosum (VC). In contrast, the wild species V. arboreum (VA) is able to tolerate a wider range of soil pH. To assess the molecular mechanisms involved in near neutral pH stress response, plants from pH-sensitive VC (tetraploid) and pH-tolerant VA (diploid) were grown at near neutral pH 6.5 and at the preferred pH of 4.5. Transcriptome sequencing of root RNA was performed for 4 biological replications per species x pH level interaction, for a total of 16 samples. Reads were mapped to the reference genome from diploid V. corymbosum, transforming ~55% of the reads to gene counts. A quasi-likelihood F test identified differential expression due to pH stress in 337 and 4867 genes in VA and VC, respectively. Both species shared regulation of genes involved in nutrient homeostasis and cell wall metabolism. VA and VC exhibited differential regulation of signaling pathways related to abiotic/biotic stress, cellulose and lignin biosynthesis, and nutrient uptake. The specific responses in VA likely facilitate tolerance to higher soil pH. In contrast, response in VC, despite affecting a greater number of genes, is not effective overcoming the stress induced by pH. Further inspection of those genes with differential expression that are specific in VA may provide insight on the mechanisms towards tolerance.

Neutral Sphingomyelinase Behaviour in Hippocampus Neuroinflammation of MPTP-Induced Mouse Model of Parkinson’s Disease and in Embryonic Hippocampal Cells

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Samuela Cataldi

2017-01-01

Full Text Available Neutral sphingomyelinase is known to be implicated in growth arrest, differentiation, proliferation, and apoptosis. Although previous studies have reported the involvement of neutral sphingomyelinase in hippocampus physiopathology, its behavior in the hippocampus during Parkinson’s disease remains undetected. In this study, we show an upregulation of inducible nitric oxide synthase and a downregulation of neutral sphingomyelinase in the hippocampus of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP- induced mouse model of Parkinson’s disease. Moreover, the stimulation of neutral sphingomyelinase activity with vitamin 1,25-dihydroxyvitamin D3 reduces specifically saturated fatty acid sphingomyelin by making sphingomyelin a less rigid molecule that might influence neurite plasticity. The possible biological relevance of the increase of neutral sphingomyelinase in Parkinson’s disease is discussed.

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

Study of ν+N→ν+N+π and isospin analysis of the hadronic neutral current

International Nuclear Information System (INIS)

Longuemare, C.

1978-04-01

Experimental results are presented on neutrino induced single pion production in the bubble chamber Gargamelle filled with a light propane-freon mixture and exposed to the CERN PS neutrino beam. After corrections for reinteractions in the target nuclei, the neutrino neutral current cross section and the branching ratios are determined. The isospin structure of the hadronic neutral current is analysed. The conclusions are compatible with the Weinberg-Salam theory for weak and electromagnetic interactions. The isoscalar component of the neutral current is observed at the level of two standard deviations. The charged to neutral current ratio may be intepreted with the one pion production model of Adler in the framework of the above theory [fr

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.

Neutral polymorphisms in putative housekeeping genes and tandem repeats unravels the population genetics and evolutionary history of Plasmodium vivax in India.

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Surendra K Prajapati

Full Text Available The evolutionary history and age of Plasmodium vivax has been inferred as both recent and ancient by several studies, mainly using mitochondrial genome diversity. Here we address the age of P. vivax on the Indian subcontinent using selectively neutral housekeeping genes and tandem repeat loci. Analysis of ten housekeeping genes revealed a substantial number of SNPs (n = 75 from 100 P. vivax isolates collected from five geographical regions of India. Neutrality tests showed a majority of the housekeeping genes were selectively neutral, confirming the suitability of housekeeping genes for inferring the evolutionary history of P. vivax. In addition, a genetic differentiation test using housekeeping gene polymorphism data showed a lack of geographical structuring between the five regions of India. The coalescence analysis of the time to the most recent common ancestor estimate yielded an ancient TMRCA (232,228 to 303,030 years and long-term population history (79,235 to 104,008 of extant P. vivax on the Indian subcontinent. Analysis of 18 tandem repeat loci polymorphisms showed substantial allelic diversity and heterozygosity per locus, and analysis of potential bottlenecks revealed the signature of a stable P. vivax population, further corroborating our ancient age estimates. For the first time we report a comparable evolutionary history of P. vivax inferred by nuclear genetic markers (putative housekeeping genes to that inferred from mitochondrial genome diversity.

Neutral polymorphisms in putative housekeeping genes and tandem repeats unravels the population genetics and evolutionary history of Plasmodium vivax in India.

Science.gov (United States)

Prajapati, Surendra K; Joshi, Hema; Carlton, Jane M; Rizvi, M Alam

2013-01-01

The evolutionary history and age of Plasmodium vivax has been inferred as both recent and ancient by several studies, mainly using mitochondrial genome diversity. Here we address the age of P. vivax on the Indian subcontinent using selectively neutral housekeeping genes and tandem repeat loci. Analysis of ten housekeeping genes revealed a substantial number of SNPs (n = 75) from 100 P. vivax isolates collected from five geographical regions of India. Neutrality tests showed a majority of the housekeeping genes were selectively neutral, confirming the suitability of housekeeping genes for inferring the evolutionary history of P. vivax. In addition, a genetic differentiation test using housekeeping gene polymorphism data showed a lack of geographical structuring between the five regions of India. The coalescence analysis of the time to the most recent common ancestor estimate yielded an ancient TMRCA (232,228 to 303,030 years) and long-term population history (79,235 to 104,008) of extant P. vivax on the Indian subcontinent. Analysis of 18 tandem repeat loci polymorphisms showed substantial allelic diversity and heterozygosity per locus, and analysis of potential bottlenecks revealed the signature of a stable P. vivax population, further corroborating our ancient age estimates. For the first time we report a comparable evolutionary history of P. vivax inferred by nuclear genetic markers (putative housekeeping genes) to that inferred from mitochondrial genome diversity.

A crossing programme with mutants in peas: Utilization of a gene bank and a computer system

International Nuclear Information System (INIS)

Blixt, S.

1976-01-01

A gene bank for peas was established at Weibullsholm in 1930, comprising about 1500 lines and including a great number of spontaneous and induced mutants. A Wang 2200 computair system is used in the maintenance and utilization of the gene bank information. The system at present provides programs for establishing and maintaining data-files for lines and crosses, statistical programs for linkage calculations, and technical aids in growing and classifying the material. The system is very promising and can be handled without previous experience of computer work. This system is used in the planning of a specific plant breeding project, PMX and search for material to be used in the project. The PMX project as a whole aims at adapting the pea better to monoculture and to a highly mechanized agriculture, as well as at improving its nutritional value. The material used in the project up to now is four modern varieties, two primitive varieties, two cross-recombinants, one ecotype, three spontaneous mutants and five induced mutants. (author)

Measurement of plasma production and neutralization in gas neutralizers

International Nuclear Information System (INIS)

Maor, D.; Meron, M.; Johnson, B.; Jones, K.; Agagu, A.; Hu, B.

1986-01-01

In order to satisfy the need of experimental data for the designing of gas neutralizers we have started a project aimed at measuring all relevant cross sections for the charge exchange of H - , H 0 and H + projectiles, as well as the cross sections for the production of ions in the target. The expected results of these latter measurements are shown schematically

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.

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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.

Exertional and CrossFit-Induced Rhabdomyolysis.

Science.gov (United States)

Meyer, Michelle; Sundaram, Sneha; Schafhalter-Zoppoth, Ingeborg

2017-07-14

Few publications of exercise-induced rhabomyolysis currently exist in the medical literature besides case reports. However, this condition can be severe, resulting in hospitalization and IV fluid administration to prevent serious sequelae. This report describes a case of exercise-induced rhabdomyolysis caused by a CrossFit workout. A 31-year-old female presented with 2 days of bilateral upper extremity pain and soreness, which began 2 days after she completed a CrossFit workout. Workup revealed an elevated creatine phosphokinase (CPK) of 18 441 U/L, consistent with exercise-induced rhabdomyolysis, and elevated liver function tests and elevated D-dimer, although her renal function was normal. She was hospitalized for 2 days and treated with IV fluids. This case report demonstrates that CrossFit exercises can lead to rhabdomyolysis, highlighting a condition that may be underdiagnosed and underreported.

Direct measurements of neutral density depletion by two-photon absorption laser-induced fluorescence spectroscopy

International Nuclear Information System (INIS)

Aanesland, A.; Liard, L.; Leray, G.; Jolly, J.; Chabert, P.

2007-01-01

The ground state density of xenon atoms has been measured by spatially resolved laser-induced fluorescence spectroscopy with two-photon excitation in the diffusion chamber of a magnetized Helicon plasma. This technique allows the authors to directly measure the relative variations of the xenon atom density without any assumptions. A significant neutral gas density depletion was measured in the core of the magnetized plasma, in agreement with previous theoretical and experimental works. It was also found that the neutral gas density was depleted near the radial walls

Dual neutral particle induced transmutation in CINDER2008

Energy Technology Data Exchange (ETDEWEB)

Martin, W.J., E-mail: wjmarti@sandia.gov [Sandia National Laboratories, Albuquerque, NM 87185 (United States); University of New Mexico, Albuquerque, NM 87131 (United States); Oliveira, C.R.E. de; Hecht, A.A. [University of New Mexico, Albuquerque, NM 87131 (United States)

2014-12-11

Although nuclear transmutation methods for fission have existed for decades, the focus has been on neutron-induced reactions. Recent novel concepts have sought to use both neutrons and photons for purposes such as active interrogation of cargo to detect the smuggling of highly enriched uranium, a concept that would require modeling the transmutation caused by both incident particles. As photonuclear transmutation has yet to be modeled alongside neutron-induced transmutation in a production code, new methods need to be developed. The CINDER2008 nuclear transmutation code from Los Alamos National Laboratory is extended from neutron applications to dual neutral particle applications, allowing both neutron- and photon-induced reactions for this modeling with a focus on fission. Following standard reaction modeling, the induced fission reaction is understood as a two-part reaction, with an entrance channel to the excited compound nucleus, and an exit channel from the excited compound nucleus to the fission fragmentation. Because photofission yield data—the exit channel from the compound nucleus—are sparse, neutron fission yield data are used in this work. With a different compound nucleus and excitation, the translation to the excited compound state is modified, as appropriate. A verification and validation of these methods and data has been performed. This has shown that the translation of neutron-induced fission product yield sets, and their use in photonuclear applications, is appropriate, and that the code has been extended correctly. - Highlights: • The CINDER2008 transmutation code was modified to include photon-induced transmutation tracking. • A photonuclear interaction library was created to allow CINDER2008 to track photonuclear interactions. • Photofission product yield data sets were created using fission physics similarities with neutron-induced fission.

Inducement of radionuclides targeting therapy by gene transfection

International Nuclear Information System (INIS)

Luo Quanyong

2001-01-01

The author presents an overview of gene transfection methods to genetically induce tumor cells to express enhanced levels of cell surface antigens and receptors to intake radiolabeled antibody and peptide targeting and thus increase their therapeutic effect in radiotherapy. The current research include inducement of radioimmunotherapy through CEA gene transfection, inducement of iodine-131 therapy by sodium iodide symporter gene transfection and inducement of MIBG therapy by noradrenaline transporter gene transfection. These studies raise the prospect that gene-therapy techniques could be used to enable the treatment of a wide range of tumors with radiopharmaceuticals of established clinical acceptability

Determination of neutral current couplings from neutrino-induced semi-inclusive pion and inclusive reactions

International Nuclear Information System (INIS)

Hung, P.Q.

1977-01-01

It is shown that by looking at data from neutrino-induced semi-inclusive pion and inclusive reactions on isoscalar targets along, one can determine completely the neutral current couplings. Predictions for various models are also presented. (Auth.)

Acute Vhl gene inactivation induces cardiac HIF-dependent erythropoietin gene expression.

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Marta Miró-Murillo

Full Text Available Von Hippel Lindau (Vhl gene inactivation results in embryonic lethality. The consequences of its inactivation in adult mice, and of the ensuing activation of the hypoxia-inducible factors (HIFs, have been explored mainly in a tissue-specific manner. This mid-gestation lethality can be also circumvented by using a floxed Vhl allele in combination with an ubiquitous tamoxifen-inducible recombinase Cre-ER(T2. Here, we characterize a widespread reduction in Vhl gene expression in Vhl(floxed-UBC-Cre-ER(T2 adult mice after dietary tamoxifen administration, a convenient route of administration that has yet to be fully characterized for global gene inactivation. Vhl gene inactivation rapidly resulted in a marked splenomegaly and skin erythema, accompanied by renal and hepatic induction of the erythropoietin (Epo gene, indicative of the in vivo activation of the oxygen sensing HIF pathway. We show that acute Vhl gene inactivation also induced Epo gene expression in the heart, revealing cardiac tissue to be an extra-renal source of EPO. Indeed, primary cardiomyocytes and HL-1 cardiac cells both induce Epo gene expression when exposed to low O(2 tension in a HIF-dependent manner. Thus, as well as demonstrating the potential of dietary tamoxifen administration for gene inactivation studies in UBC-Cre-ER(T2 mouse lines, this data provides evidence of a cardiac oxygen-sensing VHL/HIF/EPO pathway in adult mice.

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

QCD analysis of neutral and charged current cross sections and search for contact interactions at HERA

Energy Technology Data Exchange (ETDEWEB)

Pirumov, Hayk

2013-11-15

A QCD analysis of the inclusive deep inelastic ep scattering cross section measured by the H1 experiment at HERA is presented. The data correspond to a total integrated luminosity of about 0.5 fb{sup -1} and covers a kinematic range of 0.5 GeV{sup 2} - 30000 GeV{sup 2} in the negative four-momentum transfer Q{sup 2} and 3 . 10{sup -5} - 0.65 in Bjorken x. The performed QCD analysis of the double differential neutral and charged current cross sections results in a set of parton distribution functions H1PDF 2012. The precise data from HERA II period in the kinematic region of high Q{sup 2} considerably improve the accuracy of the PDFs at the high x. In addition a search for signs of new physics using single differential neutral current cross section measurements at high Q{sup 2} is performed. The observed good agreement of the analysed data with the Standard Model predictions allows to set constraints on various new physics models within the framework of contact interactions. Limits are derived on the compositeness scale for general contact interactions, on the ratio of mass to the Yukawa coupling for heavy leptoquark models, on the effective Plank-mass scale in the large extra dimension models and on the quark radius.

Down-Regulation of Gene Expression by RNA-Induced Gene Silencing

Science.gov (United States)

Travella, Silvia; Keller, Beat

Down-regulation of endogenous genes via post-transcriptional gene silencing (PTGS) is a key to the characterization of gene function in plants. Many RNA-based silencing mechanisms such as post-transcriptional gene silencing, co-suppression, quelling, and RNA interference (RNAi) have been discovered among species of different kingdoms (plants, fungi, and animals). One of the most interesting discoveries was RNAi, a sequence-specific gene-silencing mechanism initiated by the introduction of double-stranded RNA (dsRNA), homologous in sequence to the silenced gene, which triggers degradation of mRNA. Infection of plants with modified viruses can also induce RNA silencing and is referred to as virus-induced gene silencing (VIGS). In contrast to insertional mutagenesis, these emerging new reverse genetic approaches represent a powerful tool for exploring gene function and for manipulating gene expression experimentally in cereal species such as barley and wheat. We examined how RNAi and VIGS have been used to assess gene function in barley and wheat, including molecular mechanisms involved in the process and available methodological elements, such as vectors, inoculation procedures, and analysis of silenced phenotypes.

New relations between lN-scattering cross sections and neutral current parameters

International Nuclear Information System (INIS)

Bednyakov, V.A.; Kovalenko, S.G.

1989-01-01

New relations which connect cross sections with neutral current parameters have been obtained in deep inelastic and (quasi-)elastic ν(ν-bar)N, e ± (μ ± )N scattering. The relations are independent of the structure functions and formfactors of the nucleon. A known example is the Paschos-Wolfenstein relation in ν(ν-bar)N scattering. The relations have been obtained with allowance for the contribution of the extra Z' bozon which makes it possible to use them both for extractions of the standard model parameters (ρ, sin 2 Θ W ) and for the search for some manifestations of new physics. 21 refs.; 1 tab

Development of JFH1-based cell culture systems for hepatitis C virus genotype 4a and evidence for cross-genotype neutralization

DEFF Research Database (Denmark)

Scheel, Troels Kasper Høyer; Gottwein, Judith Margarete; Jensen, Tina Birk

2008-01-01

in serial passages. Sequence analysis of recovered viruses and subsequent reverse genetic studies revealed a vital dependence on one or two NS2 mutations, depending on the 4a/2a junction. Infectivity of ED43/JFH1 viruses was CD81 dependent. The genotype 4 cell culture systems permit functional analyses...... as well as drug and vaccine research on an increasingly important genotype in the Middle East, Africa, and Europe. We also developed genotype 1a intergenotypic recombinants from H77C with vital mutations in NS3. Using H77C/JFH1 and ED43/JFH1 viruses, we demonstrated high homologous neutralizing antibody...... titers in 1a and 4a patient sera, respectively. Furthermore, availability of JFH1 viruses with envelope proteins of the six major HCV genotypes permitted cross-neutralization studies; 1a and 4a serum cross-neutralized 1a, 4a, 5a, and 6a but not 2a and 3a viruses. Thus, the JFH1 intergenotypic...

Discovery of human scFvs that cross-neutralize the toxic effects of B. jararacussu and C. d. terrificus venoms.

Science.gov (United States)

Silva, Luciano C; Pucca, Manuela B; Pessenda, Gabriela; Campos, Lucas B; Martinez, Edson Z; Cerni, Felipe A; Barbosa, José E

2018-01-01

Accidents involving venomous snakes are a public health problem worldwide, causing a large number of deaths per year. In Brazil, the majority of accidents are caused by the Bothrops and Crotalus genera, which are responsible for approximately 80% of severe envenoming cases. The cross-neutralization of snake venoms by antibodies is an important issue for development of more effective treatments. Our group has previously reported the construction of human monoclonal antibody fragments towards Bothrops jararacussu and Crotalus durissus terrificus' venoms. This study aimed to select human single-chain variable fragments (scFvs) that recognize both bothropic and crotalic crude venoms following venoms neutralizing capacity in vitro and in vivo. The cross-reactivity of Cro-Bothrumabs were demonstrated by ELISA and in vitro and in vivo experiments showed that a combination of scFvs neutralizes in vitro toxic activities (e.g. indirect hemolysis and plasma-clotting) of crotalic and bothropic venoms as well as prolonged survival time of envenomed animals. Our results may contribute to the development of the first human polyvalent antivenom against Bothrops jararacussu and Crotalus durissus terrificus venoms, overcoming some undesirable effects caused by conventional serotherapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Measurement of charged and neutral current e-p deep inelastic scattering cross sections at high Q2

International Nuclear Information System (INIS)

Derrick, M.; Krakauer, D.; Magill, S.

1995-03-01

Deep inelastic e - p scattering has been studied in both the charged current (CC) and neutral current (NC) reactions at momentum transfers squared, Q 2 , between 400 GeV 2 and the kinematic limit of 87500 GeV 2 using the ZEUS detector at the HERA ep collider. The CC and NC total cross sections, the NC to CC cross section ratio, and the differential cross sections, dσ/dQ 2 , are presented. For Q 2 ∝M W 2 , where M W is the mass of the W boson, the CC and NC cross sections have comparable magnitudes, demonstrating the equal strengths of the weak and electromagnetic interactions at high Q 2 . The Q 2 dependence of the CC cross section determines the mass term in the CC propagator to be M W =76±16±13 GeV. (orig.)

Cross-reactive neutralizing antibody responses to enterovirus 71 infections in young children: implications for vaccine development.

Directory of Open Access Journals (Sweden)

Mei-Liang Huang

Full Text Available BACKGROUND: Recently, enterovirus 71 (EV71 has caused life-threatening outbreaks involving neurological and cardiopulmonary complications in Asian children with unknown mechanism. EV71 has one single serotype but can be phylogenetically classified into 3 main genogroups (A, B and C and 11 genotypes (A, B1∼B5 and C1∼C5. In Taiwan, nationwide EV71 epidemics with different predominant genotypes occurred in 1998 (C2, 2000-2001 (B4, 2004-2005 (C4, and 2008 (B5. In this study, sera were collected to measure cross-reactive neutralizing antibody titers against different genotypes. METHODS: We collected historical sera from children who developed an EV71 infection in 1998, 2000, 2005, 2008, or 2010 and measured cross-reactive neutralizing antibody titers against all 11 EV71 genotypes. In addition, we aligned and compared the amino acid sequences of P1 proteins of the tested viruses. RESULTS: Serology data showed that children infected with genogroups B and C consistently have lower neutralizing antibody titers against genogroup A (>4-fold difference. The sequence comparisons revealed that five amino acid signatures (N143D in VP2; K18R, H116Y, D167E, and S275A in VP1 are specific for genogroup A and may be related to the observed antigenic variations. CONCLUSIONS: This study documented antigenic variations among different EV71 genogroups and identified potential immunodominant amino acid positions. Enterovirus surveillance and vaccine development should monitor these positions.

Study on radiation-inducible genes

Energy Technology Data Exchange (ETDEWEB)

Lim, Sang Yong; Kim, Dong Ho; Joe, Min Ho; Park, Hae Jun; Song, Hyu Npa

2012-01-15

Radiation-inducible genes of E. coli, which is a model strain for bacterial study, and Salmonella, which is a typical strain for pathogenic bacteria were compared through omic analysis. Heat shock response genes and prophage genes were induced by radiation in Salmonella, not in E. coli. Among prophage genes tested, STM2628 showed the highest activation by radiation, and approximately 1 kb promoter region was turned out to be necessary for radiation response. To screen an artificial promoter showing activation by 2 Gy, the high-throughput screening method using fluorescent MUG substrate was established. The use of bacteria as anticancer agents has attracted interest. In this study, we tried to develop tumor targeting bacteria in which the radiation-inducible promoter activate a transgene encoding a cytotoxic protein. To do this, a tumor-targeting hfq Salmonella mutant strain was constructed, and we found that its virulence decreased. For outward secretion of anticancer protein produced inside bacteria, the signal peptide of SspH1 was determined and the signal peptide was proven to be able to secrete an anticancer protein. Tumor xenograft mouse model was secured, which can be used for efficiency evaluation of bacterial tumor therapy.

Study on radiation-inducible genes

International Nuclear Information System (INIS)

Lim, Sang Yong; Kim, Dong Ho; Joe, Min Ho; Park, Hae Jun; Song, Hyu Npa

2012-01-01

Radiation-inducible genes of E. coli, which is a model strain for bacterial study, and Salmonella, which is a typical strain for pathogenic bacteria were compared through omic analysis. Heat shock response genes and prophage genes were induced by radiation in Salmonella, not in E. coli. Among prophage genes tested, STM2628 showed the highest activation by radiation, and approximately 1 kb promoter region was turned out to be necessary for radiation response. To screen an artificial promoter showing activation by 2 Gy, the high-throughput screening method using fluorescent MUG substrate was established. The use of bacteria as anticancer agents has attracted interest. In this study, we tried to develop tumor targeting bacteria in which the radiation-inducible promoter activate a transgene encoding a cytotoxic protein. To do this, a tumor-targeting hfq Salmonella mutant strain was constructed, and we found that its virulence decreased. For outward secretion of anticancer protein produced inside bacteria, the signal peptide of SspH1 was determined and the signal peptide was proven to be able to secrete an anticancer protein. Tumor xenograft mouse model was secured, which can be used for efficiency evaluation of bacterial tumor therapy

Human rotavirus strains bearing VP4 gene P[6] allele recovered from asymptomatic or symptomatic infections share similar, if not identical, VP4 neutralization specificities

International Nuclear Information System (INIS)

Hoshino, Yasutaka; Jones, Ronald W.; Ross, Jerri; Santos, Norma; Kapikian, Albert Z.

2003-01-01

A rotavirus VP4 gene P[6] allele has been documented in a number of countries to be characteristically associated with an endemic predominantly asymptomatic infection in neonates in maternity hospital nurseries. The mechanisms underlying the endemicity and asymptomatic nature of such neonatal infections remain unknown. Rotavirus strains sharing this same P genotype, however, have more recently been recovered from an increasing number of symptomatic diarrheal episodes in infants and young children in various parts of the world. Previously, we have shown that an asymptomatic P[6] rotavirus neonatal infection is not associated with a unique VP7 (G) serotype but may occur in conjunction with various G types. Although amino acid sequence comparisons of the VP4 gene between selected 'asymptomatic' and 'symptomatic' P[6] rotavirus strains have been reported and yielded information concerning their VP4 genotypes, serotypic comparisons of the outer capsid spike protein VP4 of such viruses have not been studied systematically by two-way cross-neutralizations. We determined the VP4 neutralization specificities of four asymptomatic and four symptomatic P[6] strains: two each of asymptomatic and symptomatic strains by two-way tests, and two each of additional asymptomatic and symptomatic strains by one-way tests. Both asymptomatic and symptomatic P[6] strains were shown to bear similar, if not identical, VP4 neutralization specificities. Thus, P[6] rotavirus strains causing asymptomatic or symptomatic infections did not appear to belong to unique P (VP4) serotypes. In addition, a close VP4 serotypic relationship between human P[6] rotavirus strains and the porcine P[6] rotavirus Gottfried strain was confirmed

A cross-reacting material CRM197 conjugate vaccine induces diphtheria toxin neutralizing antibody response in children and adolescents infected or not with HIV.

Science.gov (United States)

Silva, Giselle P; Santos, Rafaela S; Pereira-Manfro, Wânia F; Ferreira, Bianca; Barreto, Daniella M; Frota, Ana Cristina C; Hofer, Cristina B; Milagres, Lucimar G

2017-07-05

Anti-diphtheria antibody levels decrease with aging, and frequent booster vaccinations are required to maintain herd immunity. We analyzed the diphtheria toxin neutralizing antibody (DT-Nab) response induced by a conjugate vaccine (meningococcal C polysaccharide-CRM 197 ) in HIV-vertically infected (HI) children and adolescents and healthy controls (HC) with matched age. We report the association of DT-Nab with the bactericidal antibodies to serogroup C meningococcus (MenC). Before vaccination, 21 HI patients (50%) had no protection against diphtheria (≤0.01IU/ml of antibody) and only 8 (19%) showed complete protection (≥0.1IU/ml). About half of the HC (56%) had complete protection before immunization and 6 subjects (12%) had no protection against diphtheria. After one and two vaccine injections, 96% of HC and 64% of HI vaccinees, respectively, showed full protection against diphtheria. These data indicate that CRM 197 was able to induce primary and/or booster response in both groups of individuals. Copyright © 2017 Elsevier Ltd. All rights reserved.

Characterization of the alkaline/neutral invertase gene in Dendrobium officinale and its relationship with polysaccharide accumulation.

Science.gov (United States)

Gao, F; Cao, X F; Si, J P; Chen, Z Y; Duan, C L

2016-05-06

Dendrobium officinale is one of the most well-known traditional Chinese medicines, and polysaccharide is its main active ingredient. Many studies have investigated the synthesis and accumulation mechanisms of polysaccharide, but until recently, little was known about the molecular mechanism of how polysaccharide is synthesized because no related genes have been cloned. In this study, we cloned an alkaline/neutral invertase gene from D. officinale (DoNI) by the rapid amplification of cDNA ends (RACE) method. DoNI was 2231 bp long and contained an open reading frame that predicted a 62.8-kDa polypeptide with 554-amino acid residues. An alkaline/neutral invertase conserved domain was predicted from this deduced amino acid sequence, and DoNI had a similar deduced amino acid sequence to Setaria italica and Oryza brachyantha. We also found that DoNI expression in different tissues was closely related to DoNI activity, and more importantly, polysaccharide level. Our results indicate that DoNI is associated with polysaccharide accumulation in D. officinale.

Intra and Interspecific Variations of Gene Expression Levels in Yeast Are Largely Neutral: (Nei Lecture, SMBE 2016, Gold Coast).

Science.gov (United States)

Yang, Jian-Rong; Maclean, Calum J; Park, Chungoo; Zhao, Huabin; Zhang, Jianzhi

2017-09-01

It is commonly, although not universally, accepted that most intra and interspecific genome sequence variations are more or less neutral, whereas a large fraction of organism-level phenotypic variations are adaptive. Gene expression levels are molecular phenotypes that bridge the gap between genotypes and corresponding organism-level phenotypes. Yet, it is unknown whether natural variations in gene expression levels are mostly neutral or adaptive. Here we address this fundamental question by genome-wide profiling and comparison of gene expression levels in nine yeast strains belonging to three closely related Saccharomyces species and originating from five different ecological environments. We find that the transcriptome-based clustering of the nine strains approximates the genome sequence-based phylogeny irrespective of their ecological environments. Remarkably, only ∼0.5% of genes exhibit similar expression levels among strains from a common ecological environment, no greater than that among strains with comparable phylogenetic relationships but different environments. These and other observations strongly suggest that most intra and interspecific variations in yeast gene expression levels result from the accumulation of random mutations rather than environmental adaptations. This finding has profound implications for understanding the driving force of gene expression evolution, genetic basis of phenotypic adaptation, and general role of stochasticity in evolution. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Measurements of the neutral current e{sup {+-}}p cross sections using longitudinally polarised lepton beams at HERA II

Energy Technology Data Exchange (ETDEWEB)

Nikiforov, A.

2007-01-18

This thesis presents inclusive e{sup {+-}}p single and double differential cross sections for neutral current deep inelastic scattering measured as functions of the four-momentum transfer squared Q{sup 2} and the Bjorken variable x in interactions of longitudinally polarised leptons with unpolarised protons using the H1 detector at HERA II. An overview of the phenomenology of deep inelastic scattering is given and the experimental apparatus as well as the measurement and analysis procedures are described. The analysis is based on e{sup +}p data taken in 2003-04 and e{sup -}p data taken in 2005 at a centre-of-mass energy of {radical}(s)=318 GeV, with integrated luminosities of 47.6 pb{sup -1} and 98.4 pb{sup -1} for the e{sup +}p and e{sup -}p samples, respectively. The cross sections are measured in the range of 200neutral current interactions and to determine the structure function xF{sub 3}. The new HERA II data are combined together with previously published data from HERA I to determine the structure function xF{sub 3} with improved precision. Furthermore, this measurement is combined with the corresponding ZEUS measurement to provide the most accurate measurement of the interference structure function xF{sup {gamma}}{sup Z}{sub 3}, which is sensitive to the valence quark distributions down to low values of x. The data on polarised cross section asymmetries A{sup {+-}} are also combined with the ZEUS data. This leads to the first observation of parity violation in neutral current e{sup {+-}}p scattering at distances down to 10{sup -18} m. The data are well described by the Standard Model predictions. (orig.)

Measurement of neutral current cross sections at high Bjorken-x with the ZEUS detector at HERA

International Nuclear Information System (INIS)

Chekanov, S.; Derrick, M.; Magill, S.

2006-07-01

A new method is employed to measure the neutral current cross section up to Bjorken-x values of one with the ZEUS detector at HERA using an integrated luminosity of 65.1 pb -1 for e + p collisions and 16.7 pb -1 for e - p collisions at √(s)=318 GeV and 38.6 pb -1 for e + p collisions at √(s)=300 GeV. Cross sections have been extracted for Q 2 ≥648 GeV 2 and are compared to predictions using different parton density functions. For the highest x bins, the data have a tendency to lie above the expectations using recent parton density function parametrizations. (orig.)

Nearly neutral evolution in IFNL3 gene retains the immune function to detect and clear the viral infection in HCV.

Science.gov (United States)

Singh, Pratichi; Dass, J Febin Prabhu

2018-05-07

IFNL3 gene plays a crucial role in immune defense against viruses. It induces the interferon stimulated genes (ISGs) with antiviral properties by activating the JAK-STAT pathway. In this study, we investigated the evolutionary force involved in shaping the IFNL3 gene to perform its downstream function as a regulatory gene in HCV clearance. We have selected 25 IFNL3 coding sequences with human gene as a reference sequence and constructed a phylogeny. Furthermore, rate of variation, substitution saturation test, phylogenetic informativeness and differential selection were also analysed. The codon evolution result suggests that nearly neutral mutation is the key pattern in shaping the IFNL3 evolution. The results were validated by subjecting the human IFNL3 protein variants to that of the native through a molecular dynamics simulation study. The molecular dynamics simulation clearly depicts the negative impact on the reported variants in human IFNL3 protein. However, these detrimental mutations (R157Q and R157W) were shown to be negatively selected in the evolutionary study of the mammals. Hence, the variation revealed a mild impact on the IFNL3 function and may be removed from the population through negative selection due to its high functional constraints. In a nutshell, our study may contribute the overall evidence in phylotyping and structural transformation that takes place in the non-synonymous substitutions of IFNL3 protein. Substantially, our obtained theoretical knowledge will lay the path to extend the experimental validation in HCV clearance. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

Directory of Open Access Journals (Sweden)

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.

Prediction of Protection against Asian Enterovirus 71 Outbreak Strains by Cross-neutralizing Capacity of Serum from Dutch Donors, The Netherlands

Science.gov (United States)

Koen, Gerrit; van Eijk, Hetty; Koekkoek, Sylvie M.; de Jong, Menno D.; Wolthers, Katja C.

2016-01-01

Outbreaks of human enterovirus 71 (EV-71) in Asia are related to high illness and death rates among children. To gain insight into the potential threat for the population of Europe, we determined the neutralizing activity in intravenous immunoglobulin (IVIg) batches and individual serum samples from donors in the Netherlands against EV-71 strains isolated in Europe and in Asia. All IVIg batches and 41%, 79%, and 65% of serum samples from children ≤5 years of age, women of childbearing age, and HIV-positive men, respectively, showed high neutralizing activity against a Dutch C1 strain, confirming widespread circulation of EV-71 in the Netherlands. Asian B3–4 and C4 strains were efficiently cross-neutralized, predicting possible protection against extensive circulation and associated outbreaks of those types in Europe. However, C2 and C5 strains that had few mutations in the capsid region consistently escaped neutralization, emphasizing the importance of monitoring antigenic diversity among circulating EV-71 strains. PMID:27533024

Prediction of Protection against Asian Enterovirus 71 Outbreak Strains by Cross-neutralizing Capacity of Serum from Dutch Donors, The Netherlands.

Science.gov (United States)

van der Sanden, Sabine M G; Koen, Gerrit; van Eijk, Hetty; Koekkoek, Sylvie M; de Jong, Menno D; Wolthers, Katja C

2016-09-01

Outbreaks of human enterovirus 71 (EV-71) in Asia are related to high illness and death rates among children. To gain insight into the potential threat for the population of Europe, we determined the neutralizing activity in intravenous immunoglobulin (IVIg) batches and individual serum samples from donors in the Netherlands against EV-71 strains isolated in Europe and in Asia. All IVIg batches and 41%, 79%, and 65% of serum samples from children ≤5 years of age, women of childbearing age, and HIV-positive men, respectively, showed high neutralizing activity against a Dutch C1 strain, confirming widespread circulation of EV-71 in the Netherlands. Asian B3-4 and C4 strains were efficiently cross-neutralized, predicting possible protection against extensive circulation and associated outbreaks of those types in Europe. However, C2 and C5 strains that had few mutations in the capsid region consistently escaped neutralization, emphasizing the importance of monitoring antigenic diversity among circulating EV-71 strains.

Light-induced cross-linking and post-cross-linking modification of polyglycidol.

Science.gov (United States)

Marquardt, F; Bruns, M; Keul, H; Yagci, Y; Möller, M

2018-02-08

The photoinduced radical generation process has received renewed interest due to its economic and ecological appeal. Herein the light-induced cross-linking of functional polyglycidol and its post-cross-linking modification are presented. Linear polyglycidol was first functionalized with a tertiary amine in a two-step reaction. Dimethylaminopropyl functional polyglycidol was cross-linked in a UV-light mediated reaction with camphorquinone as a type II photoinitiator. The cross-linked polyglycidol was further functionalized by quaternization with various organoiodine compounds. Aqueous dispersions of the cross-linked polymers were investigated by means of DLS and zeta potential measurements. Polymer films were evaluated by DSC and XPS.

Ratio of neutral-current to charged-current cross sections for inclusive neutrino interactions in hydrogen

International Nuclear Information System (INIS)

Harris, F.A.; Berge, J.P.; Bogert, D.V.; Cence, R.J.; Coffin, T.C.; Cundy, D.C.; Diamond, R.N.; DiBianca, F.A.; French, H.T.; Hanft, R.; Kochowski, C.; Louis, W.C.; Lynch, G.R.; Malko, J.; Marriner, J.P.; Nezrick, F.A.; Parker, S.I.; Peters, M.W.; Peterson, V.Z.; Roe, B.P.; Ross, R.T.; Scott, W.G.; Seidl, A.A.; Smart, W.; Stenger, V.J.; Stevenson, M.L.; Vander Velde, J.C.

1977-01-01

The ratio of neutral-current to charged-current cross sections is determined from a sample of events obtained in an exposure of the Fermilab 15-ft hydrogen bubble chamber to a high-energy, horn-focused neutrino beam. For evens with three or more prongs and with visible hadron momentum above 10 GeV/c, the ratio is 0.40 +- 0.14. A Monte Carlo calculation assuming the Weinberg-Salam model is used to correct for excluded events, yielding R/sub NC/CC/ = 0.48 +- 0.17

Cross-organism learning method to discover new gene functionalities.

Science.gov (United States)

Domeniconi, Giacomo; Masseroli, Marco; Moro, Gianluca; Pinoli, Pietro

2016-04-01

Knowledge of gene and protein functions is paramount for the understanding of physiological and pathological biological processes, as well as in the development of new drugs and therapies. Analyses for biomedical knowledge discovery greatly benefit from the availability of gene and protein functional feature descriptions expressed through controlled terminologies and ontologies, i.e., of gene and protein biomedical controlled annotations. In the last years, several databases of such annotations have become available; yet, these valuable annotations are incomplete, include errors and only some of them represent highly reliable human curated information. Computational techniques able to reliably predict new gene or protein annotations with an associated likelihood value are thus paramount. Here, we propose a novel cross-organisms learning approach to reliably predict new functionalities for the genes of an organism based on the known controlled annotations of the genes of another, evolutionarily related and better studied, organism. We leverage a new representation of the annotation discovery problem and a random perturbation of the available controlled annotations to allow the application of supervised algorithms to predict with good accuracy unknown gene annotations. Taking advantage of the numerous gene annotations available for a well-studied organism, our cross-organisms learning method creates and trains better prediction models, which can then be applied to predict new gene annotations of a target organism. We tested and compared our method with the equivalent single organism approach on different gene annotation datasets of five evolutionarily related organisms (Homo sapiens, Mus musculus, Bos taurus, Gallus gallus and Dictyostelium discoideum). Results show both the usefulness of the perturbation method of available annotations for better prediction model training and a great improvement of the cross-organism models with respect to the single-organism ones

Screening of hypoxia-inducible genes in sporadic ALS.

LENUS (Irish Health Repository)

Cronin, Simon

2008-10-01

Genetic variations in two hypoxia-inducible angiogenic genes, VEGF and ANG, have been linked with sporadic amyotrophic lateral sclerosis (SALS). Common variations in these genes may reduce the levels or functioning of their products. VEGF and ANG belong to a larger group of angiogenic genes that are up-regulated under hypoxic conditions. We hypothesized that common genetic variation across other members of this group may also predispose to sporadic ALS. To screen other hypoxia-inducible angiogenic genes for association with SALS, we selected 112 tagging single nucleotide polymorphisms (tgSNPs) that captured the common genetic variation across 16 VEGF-like and eight ANG-like hypoxia-inducible genes. Screening for association was performed in 270 Irish individuals with typical SALS and 272 ethnically matched unrelated controls. SNPs showing association in the Irish phase were genotyped in a replication sample of 281 Swedish sporadic ALS patients and 286 Swedish controls. Seven markers showed association in the Irish. The one modest replication signal observed in the Swedish replication sample, at rs3801158 in the gene inhibin beta A, was for the opposite allele vs. the Irish cohort. We failed to detect association of common variation across 24 candidate hypoxia-inducible angiogenic genes with SALS.

Neutron-induced capture cross sections via the surrogate reaction method

International Nuclear Information System (INIS)

Boutoux, G.; Jurado, B.; Aiche, M.; Barreau, G.; Capellan, N.; Companis, I.; Czajkowski, S.; Dassie, D.; Haas, B.; Mathieu, L.; Meot, V.; Bail, A.; Bauge, E.; Daugas, J. M.; Faul, T.; Gaudefroy, L.; Morel, P.; Pillet, N.; Roig, O.; Romain, P.; Taieb, J.; Theroine, C.; Burke, J.T.; Companis, I.; Derkx, X.; Gunsing, F.; Matea, I.; Tassan-Got, L.; Porquet, M.G.; Serot, O.

2011-01-01

The surrogate reaction method is an indirect way of determining cross sections for nuclear reactions that proceed through a compound nucleus. This technique enables neutron-induced cross sections to be extracted for nuclear reactions on short-lived unstable nuclei that otherwise can not be measured. This technique has been successfully applied to determine the neutron-induced fission cross sections of several short-lived nuclei. In this work, we investigate whether this powerful technique can also be used to determine of neutron-induced capture cross sections. For this purpose we use the surrogate reaction 174 Yb( 3 He, pγ) 176 Lu to infer the well known 175 Lu(n, γ) cross section and compare the results with the directly measured neutron-induced data. This surrogate experiment has been performed in March 2010. The experimental technique used and the first preliminary results will be presented. (authors)

Measurement of neutral current cross sections at high Bjorken-x with the ZEUS detector at HERA

Energy Technology Data Exchange (ETDEWEB)

Chekanov, S.; Derrick, M.; Magill, S. [Argonne National Laboratory, Argonne, IL (US)] (and others)

2006-07-15

A new method is employed to measure the neutral current cross section up to Bjorken-x values of one with the ZEUS detector at HERA using an integrated luminosity of 65.1 pb{sup -1} for e{sup +}p collisions and 16.7 pb{sup -1} for e{sup -}p collisions at {radical}(s)=318 GeV and 38.6 pb{sup -1} for e{sup +}p collisions at {radical}(s)=300 GeV. Cross sections have been extracted for Q{sup 2}{>=}648 GeV{sup 2} and are compared to predictions using different parton density functions. For the highest x bins, the data have a tendency to lie above the expectations using recent parton density function parametrizations. (orig.)

Total scattering cross sections and interatomic potentials for neutral hydrogen and helium on some noble gases

International Nuclear Information System (INIS)

Ruzic, D.N.; Cohen, S.A.

1985-04-01

Measurements of energy-dependent scattering cross sections for 30 to 1800 eV D incident on He, Ne, Ar, and Kr, and for 40 to 850 eV He incident on He, Ar, and Kr are presented. They are determined by using the charge-exchange efflux from the Princeton Large Torus tokamak as a source of D or He. These neutrals are passed through a gas-filled scattering cell and detected by a time-of-flight spectrometer. The cross section for scattering greater than the effective angle of the apparatus (approx. =20 mrad) is found by measuring the energy-dependent attenuation of D or He as a function of pressure in the scattering cell. The interatomic potential is extracted from the data

Neutralization of H-- in energetic collisions with multiply charged ions

International Nuclear Information System (INIS)

Melchert, F.; Benner, M.; Kruedener, S.; Schulze, R.; Meuser, S.; Huber, K.; Salzborn, E.; Uskov, D.B.; Presnyakov, L.P.

1995-01-01

Employing the crossed-beam technique, we have measured absolute cross sections for neutralization of H -- ions in collisions with multiply charged ions Ne q+ (q≤4) and Ar q+ , Xe q+ (q≤8) at center-of-mass energies ranging from 20 to 200 keV. . . It is found that th cross sections are independent of the target ion species. The data are in excellent agreement with quantum calculations. A universal scaling law for the neutralization cross section is given

Negative ion formation and neutralization processes, (1)

International Nuclear Information System (INIS)

Sugiura, Toshio

1982-01-01

This review has been made preliminary for the purpose of contribute to the plasma heating by ''negative ion based neutral beam injection'' in the magnetic confinement fusion reactor. A compilation includes the survey of the general processes of negative ion formation, the data of the cross section of H - ion formation and the neutralization of H - ion, and some of new processes of H - ion formation. The data of cross section are mainly experimental, but partly include the results of theoretical calculation. (author)

X-ray induced DNA double strand break production and repair in mammalian cells as measured by neutral filter elution

Energy Technology Data Exchange (ETDEWEB)

Bradley, M O; Kohn, K W [National Institutes of Health, Bethesda, MD (USA)

1979-10-01

A neutral filter elution method was used for detecting DNA double strand breaks in mouse L1210 cells after X-ray. The assay detected the number of double strand breaks induced by as little as 1000 rad of X-ray. The rate of DNA elution through the filters under neutral conditions increased with X-ray dose. Certain conditions for deproteinization, pH, and filter type were shown to increase the assay's sensitivity. Hydrogen peroxide and Bleomycin also induced apparent DNA double strand breaks, although the ratios of double to single strand breaks varied from those produced by X-ray. The introduction of double strand cuts by HpA I restriction endonuclease in DNA lysed on filters resulted in a rapid rate of elution under neutral conditions, implying that the method can detect double strand breaks if they exist in the DNA. The eluted DNA banded with a double stranded DNA marker in cesium chloride. This evidence suggested that the assay detected DNA double strand breaks. L1210 cells were shown to rejoin most of the DNA double strand breaks induced by 5-10 krad of X-ray with a half-time of about 40 minutes. (author).

Unpolarized neutral current e{sup {+-}}p cross section measurements at the H1 experiment, HERA

Energy Technology Data Exchange (ETDEWEB)

Habib, Shiraz Z.

2009-11-15

Measurements of the unpolarized inclusive neutral current reduced cross section in e{sup {+-}}p scattering at a center of mass energy {radical}(s) {approx_equal} 319 GeV are presented. The data was collected by the H1 detector during the HERA II running phase, after the 2000 luminosity upgrade, and corresponds to an integrated luminosity of 145 pb{sup -1} and 167 pb{sup -1} for the e{sup -}p and e{sup +}p periods respectively. The cross section measurements were made for the negative four-momentum transfer squared range 65{<=} Q{sup 2}{<=}30000 GeV{sup 2} and Bjorken-x range 0.00085{<=}x{<=}0.65. Dedicated measurements at inelasticity y=0.75 and Q{sup 2}{<=}800 GeV{sup 2} are also made. The details of the analysis are presented here. The cross section measurements presented here are found to agree with previously published data as well as predictions determined from various NLO QCD fits. Scaling violation of the F{sub 2} structure function as well differences between the e{sup -} and e{sup +} cross sections at high Q{sup 2} due to the xF{sub 3} structure function have been observed. The cross sections in the range Q{sup 2}{<=}800 GeV{sup 2} at inelasticity y=0.75 suggest non-zero values of the longitudinal structure function F{sub L}. (orig.)

Investigating Gene Function in Cereal Rust Fungi by Plant-Mediated Virus-Induced Gene Silencing.

Science.gov (United States)

Panwar, Vinay; Bakkeren, Guus

2017-01-01

Cereal rust fungi are destructive pathogens, threatening grain production worldwide. Targeted breeding for resistance utilizing host resistance genes has been effective. However, breakdown of resistance occurs frequently and continued efforts are needed to understand how these fungi overcome resistance and to expand the range of available resistance genes. Whole genome sequencing, transcriptomic and proteomic studies followed by genome-wide computational and comparative analyses have identified large repertoire of genes in rust fungi among which are candidates predicted to code for pathogenicity and virulence factors. Some of these genes represent defence triggering avirulence effectors. However, functions of most genes still needs to be assessed to understand the biology of these obligate biotrophic pathogens. Since genetic manipulations such as gene deletion and genetic transformation are not yet feasible in rust fungi, performing functional gene studies is challenging. Recently, Host-induced gene silencing (HIGS) has emerged as a useful tool to characterize gene function in rust fungi while infecting and growing in host plants. We utilized Barley stripe mosaic virus-mediated virus induced gene silencing (BSMV-VIGS) to induce HIGS of candidate rust fungal genes in the wheat host to determine their role in plant-fungal interactions. Here, we describe the methods for using BSMV-VIGS in wheat for functional genomics study in cereal rust fungi.

Photoproduction of neutral pions off protons

NARCIS (Netherlands)

Crede, V.; Sparks, N.; Wilson, A.; Anisovich, A. V.; Bacelar, J. C. S.; Bantes, R.; Bartholomy, O.; Bayadilov, D.; Beck, R.; Beloglazov, Y. A.; Castelijns, R.; Dutz, H.; Elsner, D.; Ewald, R.; Frommberger, F.; Funke, Chr; Gregor, R.; Gridnev, A.; Gutz, E.; Hillert, W.; Hoffmeister, P.; Jaegle, I.; Junkersfeld, J.; Kalinowsky, H.; Kammer, S.; Klein, Frank; Klein, Friedrich; Klempt, E.; Kotulla, M.; Krusche, B.; Löhner, H.; Lopatin, I. V.; Lugert, S.; Menze, D.; Mertens, T.; Messchendorp, J. G.; Metag, V.; Nanova, M.; Nikonov, V. A.; Novinski, D.; Novotny, R.; Ostrick, M.; Pant, L. M.; van Pee, H.; Pfeiffer, M.; Roy, A.; Sarantsev, A. V.; Schadmand, S.; Schmidt, C.; Schmieden, H.; Schoch, B.; Shende, S.; Sokhoyan, V.; Suele, A.; Sumachev, V. V.; Szczepanek, T.; Thoma, U.; Trnka, D.; Varma, R.; Walther, D.; Wendel, Ch

2011-01-01

Photoproduction of neutral pions has been studied with the CBELSA/TAPS detector in the reaction gamma p -> p pi(0) for photon energies between 0.85 and 2.50 GeV. The pi(0) mesons are observed in their dominant neutral decay mode: pi(0) -> gamma gamma. For the first time, the differential cross

A semi-empirical concept for the calculation of electron-impact ionization cross sections of neutral and ionized fullerenes

International Nuclear Information System (INIS)

Deutsch, H.; Scheier, P.; Maerk, T.D.; Becker, K.

2002-01-01

A semi-empirical approach to the calculation of cross section functions (absolute value and energy dependence) for the electron-impact ionization of several neutral and ionized fullerenes C 60 n+ (n =0-3) was developed, for which reliable experimental data have been reported. In particular, it is proposed a modification of the simplistic assumption that the ionization cross section of a cluster/fullerene is given as the product of the monomer ionization cross section and a factor m a , where 'm' is the number of monomers in the ensemble and 'a' is a constant. A comparison between these calculations and the available experimental data reveals good agreement for n = 0,103. In the case of ionization of C 60 2+ (n = 2) the calculation lies significantly below the measured cross section which it was interpret as an indication that additional indirect ionization processes are present for this charge state. (nevyjel)

Measurement of the neutral to charged current cross section ratios for neutrino and antineutrino interactions on protons

International Nuclear Information System (INIS)

Jones, G.T.; Jones, R.W.L.; Kennedy, B.W.; O'Neale, S.W.; Hoffmann, E.; Hamisi, F.; Miller, D.B.; Mobayyen, M.M.; Corrigan, G.; Myatt, G.; Radojicic, D.; Retter, M.L.; Saitta, B.; Shotton, P.N.; Towers, S.J.; Bullock, F.W.; Burke, S.; Fitch, P.J.

1986-01-01

The ratios R vp and R vp of the neutral current to charged current cross sections for neutrino and antineutrino interactions on protons have been measured in BEBC. The beam was the CERN SPS 400 GeV wideband beam. The bubble chamber, equipped with the standard External Muon Identifier, was surrounded with an additional plane of wire chambers (Internal Picket Fence), which was added to improve neutral current event identification. For a total transverse momentum of the charged hadrons above 0.45 GeV/c and a charged multiplicity of at least 3, it was found that R vp =0.384±0.024±0.015 and R vp =0.338±0.014±0.016, corresponding to a value of sin 2 θ w (M w ) MS of 0.225±0.030. Combining the results from hydrogen and an isoscalar target, the differences of the neutral current chiral coupling constants were found to be u L 2 -d L 2 =-0.080±0.043±0.012 and u R 2 -d R 2 =0.021±0.055±0.028. (orig.)

Measurement of the neutral to charged current cross section ratios for neutrino and and antineutrino interactions on protons

Science.gov (United States)

Jones, G. T.; Jones, R. W. L.; Kennedy, B. W.; O'Neale, S. W.; Hoffmann, E.; Haidt, D.; Klein, H.; Mittendorfer, J.; Morrison, D. R. O.; Schmid, P.; Wachsmuth, H.; Hamisi, F.; Miller, D. B.; Mobayyen, M. M.; Aderholz, M.; Deck, L.; Schmitz, N.; Wittek, W.; Corrigan, G.; Myatt, G.; Radojicic, D.; Retter, M. L.; Saitta, B.; Shotton, P. N.; Towers, S. J.; Bullock, F. W.; Burke, S.; Fitch, P. J.; Birmingham-Bonn-CERN-Imperial College-München(MPI)-Oxford-University College Collaboration

1986-10-01

The ratios Rvp and Rvp of the neutral current to charged current cross sections for neutrino and antineutrino interactions on protons have been measured in BEBC. The beam was the CERN SPS 400 GeV wideband beam. The bubble chamber, equipped with the standard External Muon Identifier, was surrounded with an additional plane of wire chambers (Internal Picket Fence), which was added to improve neutral current event identification. For a total transverse momentum of the charged hadrons above 0.45 GeV/ c and a charged multiplicity of at least 3, it was found that R vp = 0.384 ± 0.015 and R vp = 0.338 ± 0.014 ± 0.016, corresponding to a value of sin 2θ w(M woverlineMSof 0.225 ± 0.030 . Combining the results from hydrogen and an isoscalar target, the differences of the neutral current chiral coupling constants were found to be u2l- d2L = -0.080 ± 0.043 ± 0.012 and u2R- d2R = 0.021±0.055±0.028.

Neutral heavy lepton production in e+-e- collisions

International Nuclear Information System (INIS)

Ragiadakos, C.

1977-01-01

The cross-sections of the weak production of different kinds of neutral heavy leptons in e + -e - collisions are calculated and their signatures are studied. A possible electromagnetic production of neutral heavy leptons is also considered

Neutralized ion beam modification of cellulose membranes for study of ion charge effect on ion-beam-induced DNA transfer

Science.gov (United States)

Prakrajang, K.; Sangwijit, K.; Anuntalabhochai, S.; Wanichapichart, P.; Yu, L. D.

2012-02-01

Low-energy ion beam biotechnology (IBBT) has recently been rapidly developed worldwide. Ion-beam-induced DNA transfer is one of the important applications of IBBT. However, mechanisms involved in this application are not yet well understood. In this study plasma-neutralized ion beam was applied to investigate ion charge effect on induction of DNA transfer. Argon ion beam at 7.5 keV was neutralized by RF-driven plasma in the beam path and then bombarded cellulose membranes which were used as the mimetic plant cell envelope. Electrical properties such as impedance and capacitance of the membranes were measured after the bombardment. An in vitro experiment on plasmid DNA transfer through the cellulose membrane was followed up. The results showed that the ion charge input played an important role in the impedance and capacitance changes which would affect DNA transfer. Generally speaking, neutral particle beam bombardment of biologic cells was more effective in inducing DNA transfer than charged ion beam bombardment.

Global Gene Expression Analysis of Cross-Protected Phenotype of Pectobacterium atrosepticum.

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Vladimir Gorshkov

Full Text Available The ability to adapt to adverse conditions permits many bacterial species to be virtually ubiquitous and survive in a variety of ecological niches. This ability is of particular importance for many plant pathogenic bacteria that should be able to exist, except for their host plants, in different environments e.g. soil, water, insect-vectors etc. Under some of these conditions, bacteria encounter absence of nutrients and persist, acquiring new properties related to resistance to a variety of stress factors (cross-protection. Although many studies describe the phenomenon of cross-protection and several regulatory components that induce the formation of resistant cells were elucidated, the global comparison of the physiology of cross-protected phenotype and growing cells has not been performed. In our study, we took advantage of RNA-Seq technology to gain better insights into the physiology of cross-protected cells on the example of a harmful phytopathogen, Pectobacterium atrosepticum (Pba that causes crop losses all over the world. The success of this bacterium in plant colonization is related to both its virulence potential and ability to persist effectively under various stress conditions (including nutrient deprivation retaining the ability to infect plants afterwards. In our previous studies, we showed Pba to be advanced in applying different adaptive strategies that led to manifestation of cell resistance to multiple stress factors. In the present study, we determined the period necessary for the formation of cross-protected Pba phenotype under starvation conditions, and compare the transcriptome profiles of non-adapted growing cells and of adapted cells after the cross-protective effect has reached the maximal level. The obtained data were verified using qRT-PCR. Genes that were expressed differentially (DEGs in two cell types were classified into functional groups and categories using different approaches. As a result, we portrayed

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.

Search for an explanation for neutralization rates of atomic ion-ion reactions

Science.gov (United States)

Miller, Thomas M.; Wiens, Justin P.; Shuman, Nicholas S.; Viggiano, Albert A.

2016-09-01

We have measured well over a hundred rate coefficients k for cation-anion mutual neutralization reactions at thermal energies. For molecular ions, the k at 300 K tend not to vary more than a factor of two or three, presumably because a great many neutral states cross the incoming Coulombic potential energy curve. Atomic-atomic systems, for which there are few favorable curve crossings between the neutral and Coulombic curves, show variation of at least a factor of 60 in the measured k values at 300 K. For reactions involving the noble-gas cations, we assume that the final state is the lowest excited state of the neutral, plus the ground state of the neutralized anion, because otherwise the crossing distance R is so small that the curve-crossing probability is nil. We plotted measured k values (in cm3/s) vs the distance R (in bohr) at which the neutral and Coulombic curves cross, the found that the data are fairly well fit by a power law for k, 10-4R - 2 . 8 . The question is, is there a physical explanation for the observed dependence on R? We will discuss the data and the expectations of Landau-Zener theory. Supported by Air Force Office of Scientific Research (AFOSR-2303EP).

Measurement of high-Q2 neutral current deep inelastic e-p scattering cross sections with a longitudinally polarised electron beam at HERA

International Nuclear Information System (INIS)

Chekanov, S.; Derrick, M.; Magill, S.

2008-12-01

Measurements of the neutral current cross sections for deep inelastic scattering in e - p collisions at HERA with a longitudinally polarised electron beam are presented. The single-differential cross-sections dσ/dQ 2 , dσ/dx and dσ/dy and the double-differential cross sections in Q 2 and x are measured in the kinematic region y 2 > 185GeV 2 for both positively and negatively polarised electron beams and for each polarisation state separately. The measurements are based on an integrated luminosity of 169.9 pb -1 taken with the ZEUS detector in 2005 and 2006 at a centre-of-mass energy of 318GeV. The structure functions xF 3 and xF 3 γZ are determined by combining the e - p results presented in this paper with previously measured e + p neutral current data. The asymmetry parameter A - is used to demonstrate the parity violating effects of electroweak interactions at large spacelike photon virtuality. The measurements agree well with the predictions of the Standard Model. (orig.)

Two Photon Absorption Laser Induced Fluorescence for Neutral Hydrogen Profile Measurements

Energy Technology Data Exchange (ETDEWEB)

Scime, Earl E. [West Virginia Univ., Morgantown, WV (United States)

2016-09-23

The magnitude and spatial dependence of neutral density in magnetic confinement fusion experiments is a key physical parameter, particularly in the plasma edge. Modeling codes require precise measurements of the neutral density to calculate charge-exchange power losses and drag forces on rotating plasmas. However, direct measurements of the neutral density are problematic. In this work, we proposed to construct a laser-based diagnostic capable of providing spatially resolved measurements of the neutral density in the edge of plasma in the DIII-D tokamak. The diagnostic concept is based on two-photon absorption laser induced fluorescence (TALIF). By injecting two beams of 205 nm light (co or counter propagating), ground state hydrogen (or deuterium or tritium) can be excited from the n = 1 level to the n = 3 level at the location where the two beams intersect. Individually, the beams experience no absorption, and therefore have no difficulty penetrating even dense plasmas. After excitation, a fraction of the hydrogen atoms decay from the n = 3 level to the n = 2 level and emit photons at 656 nm (the H_α line). Calculations based on the results of previous TALIF experiments in magnetic fusion devices indicated that a laser pulse energy of approximately 3 mJ delivered in 5 ns would provide sufficient signal-to-noise for detection of the fluorescence. In collaboration with the DIII-D engineering staff and experts in plasma edge diagnostics for DIII-D from Oak Ridge National Laboratory (ORNL), WVU researchers designed a TALIF system capable of providing spatially resolved measurements of neutral deuterium densities in the DIII-D edge plasma. The laser systems were specified, purchased, and assembled at WVU. The TALIF system was tested on a low-power hydrogen discharge at WVU and the plan was to move the instrument to DIII-D for installation in collaboration with ORNL researchers. After budget cuts at DIII-D, the DIII-D facility declined to support

Two Photon Absorption Laser Induced Fluorescence for Neutral Hydrogen Profile Measurements

International Nuclear Information System (INIS)

Scime, Earl E.

2016-01-01

The magnitude and spatial dependence of neutral density in magnetic confinement fusion experiments is a key physical parameter, particularly in the plasma edge. Modeling codes require precise measurements of the neutral density to calculate charge-exchange power losses and drag forces on rotating plasmas. However, direct measurements of the neutral density are problematic. In this work, we proposed to construct a laser-based diagnostic capable of providing spatially resolved measurements of the neutral density in the edge of plasma in the DIII-D tokamak. The diagnostic concept is based on two-photon absorption laser induced fluorescence (TALIF). By injecting two beams of 205 nm light (co or counter propagating), ground state hydrogen (or deuterium or tritium) can be excited from the n = 1 level to the n = 3 level at the location where the two beams intersect. Individually, the beams experience no absorption, and therefore have no difficulty penetrating even dense plasmas. After excitation, a fraction of the hydrogen atoms decay from the n = 3 level to the n = 2 level and emit photons at 656 nm (the H α line). Calculations based on the results of previous TALIF experiments in magnetic fusion devices indicated that a laser pulse energy of approximately 3 mJ delivered in 5 ns would provide sufficient signal-to-noise for detection of the fluorescence. In collaboration with the DIII-D engineering staff and experts in plasma edge diagnostics for DIII-D from Oak Ridge National Laboratory (ORNL), WVU researchers designed a TALIF system capable of providing spatially resolved measurements of neutral deuterium densities in the DIII-D edge plasma. The laser systems were specified, purchased, and assembled at WVU. The TALIF system was tested on a low-power hydrogen discharge at WVU and the plan was to move the instrument to DIII-D for installation in collaboration with ORNL researchers. After budget cuts at DIII-D, the DIII-D facility declined to support installation on their

A multi-subunit Chlamydia vaccine inducing neutralizing antibodies and strong IFN-γ(+) CMI responses protects against a genital infection in minipigs

DEFF Research Database (Denmark)

Bøje, Sarah; Olsen, Anja Weinreich; Erneholm, Karin

2016-01-01

Chlamydia is the most widespread sexually transmitted bacterial disease and a prophylactic vaccine is highly needed. Ideally, this vaccine is required to induce a combined response of Th1 cell-mediated immune (CMI) response in concert with neutralizing antibodies. Using a novel Göttingen minipig...... animal model, we evaluated the immunogenicity and efficacy of a multi-subunit vaccine formulated in the strong Th1-inducing adjuvant CAF01. We evaluated a mixture of two fusion proteins (Hirep1 and CTH93) designed to promote either neutralizing antibodies or cell-mediated immunity, respectively. Hirep1...

Identification and characterization of a novel gene differentially expressed in zebrafish cross-subfamily cloned embryos

Directory of Open Access Journals (Sweden)

Wang Ya-Ping

2008-03-01

Full Text Available Abstract Background Cross-species nuclear transfer has been shown to be a potent approach to retain the genetic viability of a certain species near extinction. However, most embryos produced by cross-species nuclear transfer were compromised because that they were unable to develop to later stages. Gene expression analysis of cross-species cloned embryos will yield new insights into the regulatory mechanisms involved in cross-species nuclear transfer and embryonic development. Results A novel gene, K31, was identified as an up-regulated gene in fish cross-subfamily cloned embryos using SSH approach and RACE method. K31 complete cDNA sequence is 1106 base pairs (bp in length, with a 342 bp open reading frame (ORF encoding a putative protein of 113 amino acids (aa. Comparative analysis revealed no homologous known gene in zebrafish and other species database. K31 protein contains a putative transmembrane helix and five putative phosphorylation sites but without a signal peptide. Expression pattern analysis by real time RT-PCR and whole-mount in situ hybridization (WISH shows that it has the characteristics of constitutively expressed gene. Sub-cellular localization assay shows that K31 protein can not penetrate the nuclei. Interestingly, over-expression of K31 gene can cause lethality in the epithelioma papulosum cyprinid (EPC cells in cell culture, which gave hint to the inefficient reprogramming events occurred in cloned embryos. Conclusion Taken together, our findings indicated that K31 gene is a novel gene differentially expressed in fish cross-subfamily cloned embryos and over-expression of K31 gene can cause lethality of cultured fish cells. To our knowledge, this is the first report on the determination of novel genes involved in nucleo-cytoplasmic interaction of fish cross-subfamily cloned embryos.

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...

Identification of novel light-induced genes in the suprachiasmatic nucleus

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Piontkivska Helen

2007-11-01

Full Text Available Abstract Background The transmission of information about the photic environment to the circadian clock involves a complex array of neurotransmitters, receptors, and second messenger systems. Exposure of an animal to light during the subjective night initiates rapid transcription of a number of immediate-early genes in the suprachiasmatic nucleus of the hypothalamus. Some of these genes have known roles in entraining the circadian clock, while others have unknown functions. Using laser capture microscopy, microarray analysis, and quantitative real-time PCR, we performed a comprehensive screen for changes in gene expression immediately following a 30 minute light pulse in suprachiasmatic nucleus of mice. Results The results of the microarray screen successfully identified previously known light-induced genes as well as several novel genes that may be important in the circadian clock. Newly identified light-induced genes include early growth response 2, proviral integration site 3, growth-arrest and DNA-damage-inducible 45 beta, and TCDD-inducible poly(ADP-ribose polymerase. Comparative analysis of promoter sequences revealed the presence of evolutionarily conserved CRE and associated TATA box elements in most of the light-induced genes, while other core clock genes generally lack this combination of promoter elements. Conclusion The photic signalling cascade in the suprachiasmatic nucleus activates an array of immediate-early genes, most of which have unknown functions in the circadian clock. Detected evolutionary conservation of CRE and TATA box elements in promoters of light-induced genes suggest that the functional role of these elements has likely remained the same over evolutionary time across mammalian orders.

UV laser-induced cross-linking in peptides

Science.gov (United States)

Leo, Gabriella; Altucci, Carlo; Bourgoin-Voillard, Sandrine; Gravagnuolo, Alfredo M.; Esposito, Rosario; Marino, Gennaro; Costello, Catherine E.; Velotta, Raffaele; Birolo, Leila

2013-01-01

RATIONALE The aim of this study was to demonstrate, and to characterize by high resolution mass spectrometry, that it is possible to preferentially induce covalent cross-links in peptides by using high energy femtosecond UV laser pulses. The cross-link is readily formed only when aromatic amino acids are present in the peptide sequence. METHODS Three peptides, xenopsin, angiotensin I, interleukin, individually or in combination, were exposed to high energy femtosecond UV laser pulses, either alone or in the presence of spin trapping molecules, the reaction products being characterized by high resolution mass spectrometry. RESULTS High resolution mass spectrometry and spin trapping strategies showed that cross-linking occurs readily, proceeds via a radical mechanism, and is the highly dominant reaction, proceeding without causing significant photo-damage in the investigated range of experimental parameters. CONCLUSIONS High energy femtosecond UV laser pulses can be used to induce covalent cross-links between aromatic amino acids in peptides, overcoming photo-oxidation processes, that predominate as the mean laser pulse intensity approaches illumination conditions achievable with conventional UV light sources. PMID:23754800

Measurement of neutral current deep inelastic e+p scattering cross sections with longitudinally polarized positrons with ZEUS at HERA

International Nuclear Information System (INIS)

Wlasenko, Michal

2009-05-01

Measurements of neutral current deep inelastic scattering of protons colliding with longitudinally polarized positrons, performed with data recorded in years 2006 and 2007 with the ZEUS detector, corresponding to an integrated luminosity of L=113.3 pb -1 , are presented. The single-differential cross sections dσ/dQ 2 , dσ/dx, dσ/dy and the double-differential reduced cross section σ were measured in the kinematic region of 185 2 2 and y + and the generalized structure function x F 3 were extracted. All measurements agree well with the predictions of the Standard Model. (orig.)

Fitness Effects of Network Non-Linearity Induced by Gene Expression Noise

Science.gov (United States)

Ray, Christian; Cooper, Tim; Balazsi, Gabor

2012-02-01

In the non-equilibrium dynamics of growing microbial cells, metabolic enzymes can create non-linearities in metabolite concentration because of non-linear degradation (utilization): an enzyme can saturate in the process of metabolite utilization. Increasing metabolite production past the saturation point then results in an ultrasensitive metabolite response. If the production rate of a metabolite depends on a second enzyme or other protein-mediated process, uncorrelated gene expression noise can thus cause transient metabolite concentration bursts. Such bursts are physiologically unnecessary and may represent a source of selection against the ultrasensitive switch, especially if the fluctuating metabolic intermediate is toxic. Selection may therefore favor correlated gene expression fluctuations for enzymes in the same pathway, such as by same-operon membership in bacteria. Using a modified experimental lac operon system, we are undertaking a combined theoretical-experimental approach to demonstrate that (i) the lac operon has an implicit ultrasensitive switch that we predict is avoided by gene expression correlations induced by same-operon membership; (ii) bacterial growth rates are sensitive to crossing the ultrasensitive threshold. Our results suggest that correlations in intrinsic gene expression noise are exploited by evolution to ameliorate the detrimental effects of nonlinearities in metabolite concentrations.

Pichia pastoris-Expressed Bivalent Virus-Like Particulate Vaccine Induces Domain III-Focused Bivalent Neutralizing Antibodies without Antibody-Dependent Enhancement in Vivo

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Rahul Shukla

2018-01-01

Full Text Available Dengue, a significant public health problem in several countries around the world, is caused by four different serotypes of mosquito-borne dengue viruses (DENV-1, -2, -3, and -4. Antibodies to any one DENV serotype which can protect against homotypic re-infection, do not offer heterotypic cross-protection. In fact, cross-reactive antibodies may augment heterotypic DENV infection through antibody-dependent enhancement (ADE. A recently launched live attenuated vaccine (LAV for dengue, which consists of a mixture of four chimeric yellow-fever/dengue vaccine viruses, may be linked to the induction of disease-enhancing antibodies. This is likely related to viral interference among the replicating viral strains, resulting in an unbalanced immune response, as well as to the fact that the LAV encodes prM, a DENV protein documented to elicit ADE-mediating antibodies. This makes it imperative to explore the feasibility of alternate ADE risk-free vaccine candidates. Our quest for a non-replicating vaccine centered on the DENV envelope (E protein which mediates virus entry into the host cell and serves as an important target of the immune response. Serotype-specific neutralizing epitopes and the host receptor recognition function map to E domain III (EDIII. Recently, we found that Pichia pastoris-expressed DENV E protein, of all four serotypes, self-assembled into virus-like particles (VLPs in the absence of prM. Significantly, these VLPs displayed EDIII and elicited EDIII-focused DENV-neutralizing antibodies in mice. We now report the creation and characterization of a novel non-replicating recombinant particulate vaccine candidate, produced by co-expressing the E proteins of DENV-1 and DENV-2 in P. pastoris. The two E proteins co-assembled into bivalent mosaic VLPs (mVLPs designated as mE1E2bv VLPs. The mVLP, which preserved the serotype-specific antigenic integrity of its two component proteins, elicited predominantly EDIII-focused homotypic virus-neutralizing

Evidence for the Production of Neutral Mesons by Photons

CERN Document Server

Steinberger, J; Panofsky, Wolfgang Kurt Hermann

1950-01-01

In the bombardment of nuclei by 330-Mev x-rays, multiple gamma-rays are emitted. From their angular correlation it is deduced that they are emitted in pairs in the disintegration of neutral particles moving with relativistic velocities and therefore of intermediate mass. The neutral mesons are produced with cross sections similar to those for the charged mesons and with an angular distribution peaked more in the forward direction. The production cross section in hydrogen and the production cross section per nucleon in C and Be are comparable.

Structural and Functional Characterization of Anti-A33 Antibodies Reveal a Potent Cross-Species Orthopoxviruses Neutralizer.

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Michael H Matho

2015-09-01

Full Text Available Vaccinia virus A33 is an extracellular enveloped virus (EEV-specific type II membrane glycoprotein that is essential for efficient EEV formation and long-range viral spread within the host. A33 is a target for neutralizing antibody responses against EEV. In this study, we produced seven murine anti-A33 monoclonal antibodies (MAbs by immunizing mice with live VACV, followed by boosting with the soluble A33 homodimeric ectodomain. Five A33 specific MAbs were capable of neutralizing EEV in the presence of complement. All MAbs bind to conformational epitopes on A33 but not to linear peptides. To identify the epitopes, we have adetermined the crystal structures of three representative neutralizing MAbs in complex with A33. We have further determined the binding kinetics for each of the three antibodies to wild-type A33, as well as to engineered A33 that contained single alanine substitutions within the epitopes of the three crystallized antibodies. While the Fab of both MAbs A2C7 and A20G2 binds to a single A33 subunit, the Fab from MAb A27D7 binds to both A33 subunits simultaneously. A27D7 binding is resistant to single alanine substitutions within the A33 epitope. A27D7 also demonstrated high-affinity binding with recombinant A33 protein that mimics other orthopoxvirus strains in the A27D7 epitope, such as ectromelia, monkeypox, and cowpox virus, suggesting that A27D7 is a potent cross-neutralizer. Finally, we confirmed that A27D7 protects mice against a lethal challenge with ectromelia virus.

Altered Gene Expression Profile in Mouse Bladder Cancers Induced by Hydroxybutyl(butylnitrosamine

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Ruisheng Yao

2004-09-01

Full Text Available A variety of genetic alterations and gene expression changes are involved in the pathogenesis of bladder tumor. To explore these changes, oligonucleotide array analysis was performed on RNA obtained from carcinogen-induced mouse bladder tumors and normal mouse bladder epithelia using Affymetrix (Santa Clara, CA MGU74Av2 GeneChips. Analysis yielded 1164 known genes that were changed in the tumors. Certain of the upregulated genes included EGFR-Ras signaling genes, transcription factors, cell cycle-related genes, and intracellular signaling cascade genes. However, downregulated genes include mitogen-activated protein kinases, cell cycle checkpoint genes, Rab subfamily genes, Rho subfamily genes, and SH2 and SH3 domains-related genes. These genes are involved in a broad range of different pathways including control of cell proliferation, differentiation, cell cycle, signal transduction, and apoptosis. Using the pathway visualization tool GenMAPP, we found that several genes, including TbR-l, STAT1, Smad1, Smad2, Jun, NFκB, and so on, in the TGF-β signaling pathway and p115 RhoGEF, RhoGDl3, MEKK4A/MEKK4B, P13KA, and JNK in the G13 signaling pathway were differentially expressed in the tumors. In summary, we have determined the expression profiles of genes differentially expressed during mouse bladder tumorigenesis. Our results suggest that activation of the EGFR-Ras pathway, uncontrolled cell cycle, aberrant transcription factors, and G13 and TGF-β pathways are involved, and the cross-talk between these pathways seems to play important roles in mouse bladder tumorigenesis.

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...

Scattering angle-integrated (total) and magnetic sublevel cross-sections and degree of linear polarization for electron and proton induced excitation [HeI (1snp) sup 1 P sup 0 (n=2-5)] of helium

CERN Document Server

Merabet, H; Hanni, J; Bailey, M; Godunov, A L; McGuire, J H; Fursa, D V; Bray, I; Bartschat, K; Tseng, H C; Lin, C D

2003-01-01

Experimental scattering-angle-integrated (total) cross-sections sigma-bar, (scattering) angle-integrated magnetic sublevel cross-sections sigma-bar sub M sub sub L , and degree of linear polarization data have been measured in the extreme ultraviolet (EUV) wavelength region following decay of HeI (1snp) sup 1 P sup 0 (n=2-5) states induced by electron and proton impact on a neutral helium target. These measurements are compared with a first Born approach as well as more sophisticated theoretical calculations. Specifically, theoretical values for electron impact include convergent close-coupling (CCC) and R-matrix with pseudo states (RMPS) methods in addition to first Born (Born 1) approximation while proton induced excitation cross-sections are compared with atomic-orbital close-coupling (AOCC) and first Born predictions.

Enterovirus 71 Neutralizing Antibodies Seroepidemiological Research among Children in Guangzhou, China between 2014 and 2015: A Cross-Sectional Study.

Science.gov (United States)

Zhang, Dingmei; Chen, Yan; Chen, Xiashi; He, Zhenjian; Zhu, Xun; Hao, Yuantao

2017-03-20

A hand-foot-mouth disease outbreak occurred in 2014 around Guangdong. The purpose of this study was investigating the status and susceptibility of infectious neutralizing antibodies to enterovirus 71 among children so as to provide scientific evidence for the population immunity level of hand-foot-mouth disease and prepare for enterovirus 71 vaccination implementation. Serum specimens were collected from children in communities from January 2014 to March 2015 in Guangzhou. A total of 197 serum samples from children 1-5 years old were collected for this cross-sectional study via non-probabilistic sampling from the database of Chinese National Science and Technique Major Project. Neutralization activity was measured via micro neutralization test in vitro. The positive rate of enterovirus 71 neutralizing antibodies was 59.4%, whereas the geometric mean titre was 1:12.7. A statistically significant difference in true positive rates was found between different age groups but not between different genders. Being the most susceptible population of hand-foot-mouth disease, children under 3 years of age are more likely to be infected with enterovirus 71, and the immunity of children increases with increasing age. Further cohort studies should be conducted, and measures for prevention and vaccination should be taken.

Enterovirus 71 Neutralizing Antibodies Seroepidemiological Research among Children in Guangzhou, China between 2014 and 2015: A Cross-Sectional Study

Directory of Open Access Journals (Sweden)

Dingmei Zhang

2017-03-01

Full Text Available A hand-foot-mouth disease outbreak occurred in 2014 around Guangdong. The purpose of this study was investigating the status and susceptibility of infectious neutralizing antibodies to enterovirus 71 among children so as to provide scientific evidence for the population immunity level of hand-foot-mouth disease and prepare for enterovirus 71 vaccination implementation. Serum specimens were collected from children in communities from January 2014 to March 2015 in Guangzhou. A total of 197 serum samples from children 1–5 years old were collected for this cross-sectional study via non-probabilistic sampling from the database of Chinese National Science and Technique Major Project. Neutralization activity was measured via micro neutralization test in vitro. The positive rate of enterovirus 71 neutralizing antibodies was 59.4%, whereas the geometric mean titre was 1:12.7. A statistically significant difference in true positive rates was found between different age groups but not between different genders. Being the most susceptible population of hand–foot–mouth disease, children under 3 years of age are more likely to be infected with enterovirus 71, and the immunity of children increases with increasing age. Further cohort studies should be conducted, and measures for prevention and vaccination should be taken.

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.)

A Measurement of the Neutrino Neutral Current π⁰ Cross Section at MiniBooNE

Energy Technology Data Exchange (ETDEWEB)

Raaf, Jennifer Lynne [Univ. of Cincinnati, OH (United States)

2005-01-01

The MiniBooNE neutrino beam and detector at Fermilab are used to study the production of neutral current π⁰ events. The cross sections for neutrino interactions with mineral oil (CH₂) are reported for resonantly produced and coherently produced single π⁰ events. We measure a resonant single π⁰ cross section of σ(v_μ N π⁰) = (0.0129 ± 0.0011(stat.) ± 0.0043(syst.)) x 10^-36 cm²/CH₂ at a mean neutrino energy of 1.26 GeV. We measure a coherent single π⁰ cross section of σ(v_μ A → v_μ A π⁰) = (0.00077 ± 0.00016 (stat.) ± 0.00036 (syst.)) x 10^-36 cm²/CH₂ at mean neutrino energy 1.12 GeV.

Genomic Analysis Reveals Contrasting PIFq Contribution to Diurnal Rhythmic Gene Expression in PIF-Induced and -Repressed Genes.

Science.gov (United States)

Martin, Guiomar; Soy, Judit; Monte, Elena

2016-01-01

Members of the PIF quartet (PIFq; PIF1, PIF3, PIF4, and PIF5) collectively contribute to induce growth in Arabidopsis seedlings under short day (SD) conditions, specifically promoting elongation at dawn. Their action involves the direct regulation of growth-related and hormone-associated genes. However, a comprehensive definition of the PIFq-regulated transcriptome under SD is still lacking. We have recently shown that SD and free-running (LL) conditions correspond to "growth" and "no growth" conditions, respectively, correlating with greater abundance of PIF protein in SD. Here, we present a genomic analysis whereby we first define SD-regulated genes at dawn compared to LL in the wild type, followed by identification of those SD-regulated genes whose expression depends on the presence of PIFq. By using this sequential strategy, we have identified 349 PIF/SD-regulated genes, approximately 55% induced and 42% repressed by both SD and PIFq. Comparison with available databases indicates that PIF/SD-induced and PIF/SD-repressed sets are differently phased at dawn and mid-morning, respectively. In addition, we found that whereas rhythmicity of the PIF/SD-induced gene set is lost in LL, most PIF/SD-repressed genes keep their rhythmicity in LL, suggesting differential regulation of both gene sets by the circadian clock. Moreover, we also uncovered distinct overrepresented functions in the induced and repressed gene sets, in accord with previous studies in other examined PIF-regulated processes. Interestingly, promoter analyses showed that, whereas PIF/SD-induced genes are enriched in direct PIF targets, PIF/SD-repressed genes are mostly indirectly regulated by the PIFs and might be more enriched in ABA-regulated genes.

Cross-species global and subset gene expression profiling identifies genes involved in prostate cancer response to selenium

Directory of Open Access Journals (Sweden)

Dhir Rajiv

2004-08-01

Full Text Available Abstract Background Gene expression technologies have the ability to generate vast amounts of data, yet there often resides only limited resources for subsequent validation studies. This necessitates the ability to perform sorting and prioritization of the output data. Previously described methodologies have used functional pathways or transcriptional regulatory grouping to sort genes for further study. In this paper we demonstrate a comparative genomics based method to leverage data from animal models to prioritize genes for validation. This approach allows one to develop a disease-based focus for the prioritization of gene data, a process that is essential for systems that lack significant functional pathway data yet have defined animal models. This method is made possible through the use of highly controlled spotted cDNA slide production and the use of comparative bioinformatics databases without the use of cross-species slide hybridizations. Results Using gene expression profiling we have demonstrated a similar whole transcriptome gene expression patterns in prostate cancer cells from human and rat prostate cancer cell lines both at baseline expression levels and after treatment with physiologic concentrations of the proposed chemopreventive agent Selenium. Using both the human PC3 and rat PAII prostate cancer cell lines have gone on to identify a subset of one hundred and fifty-four genes that demonstrate a similar level of differential expression to Selenium treatment in both species. Further analysis and data mining for two genes, the Insulin like Growth Factor Binding protein 3, and Retinoic X Receptor alpha, demonstrates an association with prostate cancer, functional pathway links, and protein-protein interactions that make these genes prime candidates for explaining the mechanism of Selenium's chemopreventive effect in prostate cancer. These genes are subsequently validated by western blots showing Selenium based induction and using

Expression of the neutral protease gene from a thermophilic Bacillus sp BT1 strain in Bacillus subtilis and its natural host : Identification of a functional promoter

NARCIS (Netherlands)

Vecerek, B; Venema, G

The expression of the neutral protease gene (npr) from the thermophilic Bacillus sp. BT1 strain was studied in its natural host and in mesophilic Bacillus subtilis. In the thermophilic BT1 strain, the transcription of the protease gene is initiated from its own promoter, just 5' to the gene. In

238U subthreshold neutron induced fission cross section

International Nuclear Information System (INIS)

Difilippo, F.C.; Perez, R.B.; De Saussure, G.; Olsen, D.K.; Ingle, R.W.

1976-01-01

High resolution measurements of the 238 U neutron induced fission cross section are reported for neutron energies between 600 eV and 2 MeV. The average subthreshold fission cross section between 10 and 100 keV was found to be 44 +- 6 μb

Ozone-induced gene expression occurs via ethylene-dependent and -independent signalling.

Science.gov (United States)

Grimmig, Bernhard; Gonzalez-Perez, Maria N; Leubner-Metzger, Gerhard; Vögeli-Lange, Regina; Meins, Fred; Hain, Rüdiger; Penuelas, Josep; Heidenreich, Bernd; Langebartels, Christian; Ernst, Dieter; Sandermann, Heinrich

2003-03-01

Recent studies suggest that ethylene is involved in signalling ozone-induced gene expression. We show here that application of ozone increased glucuronidase (GUS) expression of chimeric reporter genes regulated by the promoters of the tobacco class I beta-1,3-glucanases (GLB and Gln2) and the grapevine resveratrol synthase (Vst1) genes in transgenic tobacco leaves. 5'-deletion analysis of the class I beta-1,3-glucanase promoter revealed that ozone-induced gene regulation is mainly mediated by the distal enhancer region containing the positively acting ethylene-responsive element (ERE). In addition, application of 1-methylcyclopropene (1-MCP), an inhibitor of ethylene action, blocked ozone-induced class I beta-1,3-glucanase promoter activity. Enhancer activity and ethylene-responsiveness depended on the integrity of the GCC boxes, cis-acting elements present in the ERE of the class I beta-1,3-glucanase and the basic-type pathogenesis-related PR-1 protein (PRB-1b) gene promoters. The minimal PRB-1b promoter containing only the ERE with intact GCC boxes, was sufficient to confer 10-fold ozone inducibility to a GUS-reporter gene, while a substitution mutation in the GCC box abolished ozone responsiveness. The ERE region of the class I beta-1,3-glucanase promoter containing two intact GCC boxes confered strong ozone inducibility to a minimal cauliflower mosaic virus (CaMV) 35S RNA promoter, whereas two single-base substitution in the GCC boxes resulted in a complete loss of ozone inducibility. Taken together, these datastrongly suggest that ethylene is signalling ozone-induced expression of class I beta-l,3-glucanase and PRB-1b genes. Promoter analysis of the stilbene synthase Vst1 gene unravelled different regions for ozone and ethylene-responsiveness. Application of 1-MCP blocked ethylene-induced Vst1 induction, but ozone induction was not affected. This shows that ozone-induced gene expression occurs via at least two different signalling mechanisms and suggests an

Oral immunization with rotavirus VP7 expressed in transgenic potatoes induced high titers of mucosal neutralizing IgA

International Nuclear Information System (INIS)

Wu Yuzhang; Li Jintao; Mou Zhirong; Fei Lei; Ni Bing; Geng Miao; Jia Zhengcai; Zhou Wei; Zou Liyun; Tang Yan

2003-01-01

Rotaviruses (RV) are a common cause of severe diarrhea in young children, resulting in nearly one million deaths worldwide annually. Rotavirus VP7 was the rotavirus neutralizing protein. Previous study reported that VP7 DNA vaccine can induce high levels of IgG in mice but cannot protect mice against challenge (Choi, A.H., Basu, M., Rae, M.N., McNeal, M.M., Ward, R.L., 1998. Virology 250, 230-240). We found that rotavirus VP7 could maintain its neutralizing immunity when it was transformed into the potato genome. Mice immunized with the transformed tubers successfully elicited serum IgG and mucosal IgA specific for VP7. The mucosal IgA titer was as high as 1000, while serum IgG titer was only 600. Neutralizing assays indicated that IgA could neutralize rotavirus. These results indicate the potential usefulness of plants for production and delivery of edible rotavirus vaccines

Heterosis and inbreeding depression for panicle characters in crosses involving induced mutants of aromatic rice

International Nuclear Information System (INIS)

Hasib, K.M.

2001-01-01

Twelve crosses of aromatic rice utilizing four γ-ray induced mutants 88-8-3 and 33-9-15 of Tulaipanja and 124-17-4 and 21-6-1 of Gobindabhog and three basmati varieties were evaluated for heterosis and inbreeding depression for different panicle characters. All the hybrids except the two hybrids of 124-17-4 with Pakistan Basmati and Pusa Basmati I manifested significantly positive heterosis for grain yield panicle -1 . High magnitude of heterosis coupled with positive inbreeding depression for panicle length, secondary branches panicle -1 , spikelet number panicle -1 , panicle weight and grain yield panicle -1 in several crosses indicating the presence of nonadditive gene action. The results indicate the scope of exploiting heterosis in aromatic rice. (author)

Measurement of high-Q2 neutral current cross-sections with longitudinally polarised positrons with the ZEUS detector

International Nuclear Information System (INIS)

Stewart, Trevor P.

2012-07-01

The cross sections for neutral current (NC) deep inelastic scattering (DIS) in e + p collisions with a longitudinally polarised positron beam are measured at high momentum transfer squared (Q 2 >185 GeV 2 ) at the ZEUS detector at HERA. The HERA accelerator provides e ± p collisions at a centre-of-mass energy of 318 GeV, which allows the weak contribution to the NC process to be studied at high Q 2 . The measurements are based on a data sample with an integrated luminosity of 135.5 pb -1 collected with the ZEUS detector in 2006 and 2007. The single differential NC cross sections dσ/dQ 2 , dσ/dx and dσ/dy and the reduced cross section σ are measured. The structure function xF 3 is determined by combining the e + p NC reduced cross sections with the previously measured e - p measurements. The interference structure function xF 3 γZ is extracted at Q 2 =1500 GeV 2 . The cross-section asymmetry between the positive and negative polarisation of the positron beam is measured and the parity violation effects of the electroweak interaction are observed. The predictions of the Standard Model of particle physics agree well with the measurements. (orig.)

Laser-induced positive ion and neutral atom/molecule emissions from single-crystal CaHPO4 center dot 2H20: The role of electron-beam-induced defects

International Nuclear Information System (INIS)

Dawes, Mary L.; Hess, Wayne P.; Kawaguchi, Yuji; Langford, S C.; Dickinson, J. Tom

1998-01-01

We examine laser-induced ion and neutral emissions from single-crystal CaHPO4 center dot 2H2O (brushite), a wide-band-gap, hydrated inorganic single crystal, with 248-nm excimer laser radiation. Both laser-induced ion and neutral emissions are several orders magnitude higher following exposure to 2keV electrons at current densities of 200 uA/cm2 and doses of 1 C/cm2. In addition to intense Ca+ signals, electron-irradiated surfaces yield substantial CaO+, PO+, and P+ signals. As-grown and as-cleaved brushite show only weak neutral O2 and Ca emissions, whereas electron-irradiated surfaces yield enhanced O2, Ca, PO, PO2, and P emissions. Electron irradiation (i) significantly heats the sample, leading to thermal dehydration (CaHPO4 formation) and pyrolysis (Ca2P2O7 formation)and (ii) chemically reduces the surface via electron stimulated desorption. The thermal effects are accompanied by morphological changes, including recrystallization. Although complex, these changes lead to high defect densities, which are responsible for the dramatic enhancements in the observed laser desorption

Integrative characterization of the venom of the coral snake Micrurus dumerilii (Elapidae) from Colombia: Proteome, toxicity, and cross-neutralization by antivenom.

Science.gov (United States)

Rey-Suárez, Paola; Núñez, Vitelbina; Fernández, Julián; Lomonte, Bruno

2016-03-16

In Colombia, nearly 2.8% of the 4200 snakebite accidents recorded annually are inflicted by coral snakes (genus Micrurus). Micrurus dumerilii has a broad distribution in this country, especially in densely populated areas. The proteomic profile of its venom was here studied by a bottom-up approach combining RP-HPLC, SDS-PAGE and MALDI-TOF/TOF. Venom proteins were assigned to eleven families, the most abundant being phospholipases A2 (PLA2; 52.0%) and three-finger toxins (3FTx; 28.1%). This compositional profile shows that M. dumerilii venom belongs to the 'PLA2-rich' phenotype, in the recently proposed dichotomy for Micrurus venoms. Enzymatic and toxic venom activities correlated with protein family abundances. Whole venom induced a conspicuous myotoxic, cytotoxic and anticoagulant effect, and was mildly edematogenic and proteolytic, whereas it lacked hemorrhagic activity. Some 3FTxs and PLA2s reproduced the lethal effect of venom. A coral snake antivenom to Micrurus nigrocinctus demonstrated significant cross-recognition of M. dumerilii venom proteins, and accordingly, ability to neutralize its lethal effect. The combined compositional, functional, and immunological data here reported for M. dumerilii venom may contribute to a better understanding of these envenomings, and support the possible use of anti-M. nigrocinctus coral snake antivenom in their treatment. Coral snakes represent a highly diversified group of elapids in the New World, with nearly 70 species within the genus Micrurus. Owing to their scarce yields, the biochemical composition and toxic activities of coral snake venoms have been less well characterized than those of viperid species. In this work, an integrative view of the venom of M. dumerilii, a medically relevant coral snake from Colombia, was obtained by a combined proteomic, functional, and immunological approach. The venom contains proteins from at least eleven families, with a predominance of phospholipases A2 (PLA2), followed by three

Comparison of toxicity neutralization-, ELISA- and PCR tests for typing of Clostridium perfringens and detection of the enterotoxin gene by PCR

DEFF Research Database (Denmark)

Møller, Kristian; Ahrens, Peter

1996-01-01

A polymerase chain reaction (PCR) was developed for the specific amplification of a part of each of the five Clostridium perfringens toxin genes: alpha (alpha), beta (beta), epsilon (epsilon), iota (iota), and enterotoxin (CPE). While the toxicity neutralization test (TNT) only showed limited...

Evidence for parity nonconservation in the weak neutral current

International Nuclear Information System (INIS)

Benvenuti, A.; Cline, D.; Messing, F.; Ford, W.; Imlay, R.; Ling, T.Y.; Mann, A.K.; Reeder, D.D.; Rubbia, C.; Stefanski, R.; Sulak, L.; Wanderer, P.

1976-01-01

Measurements of R/sup nu/ and R/sup nu-bar/, the ratios of neutral current to charged current ν and nu-bar cross sections, yield neutral current rates for ν and nu-bar that are consistent with a pure V-A interaction but 3 standard deviations from pure V or pure A, indicating the presence of parity nonconservation in the weak neutral current

Negative ion formation and neutralization processes, (2)

International Nuclear Information System (INIS)

Sugiura, Toshio

1982-09-01

This review is 2nd part of the report published at January 1982 (JAERI-M-9902). A compilation includes the survey of the data of the cross sections of H - and D - ion formations and the neutralization of these ions. This is also presented new information about the photosensitization by laser beam in dissociative-resonance electron capture of sulfur hexafluoride reported by Chen et al., for reference to enhancement of D - ions in discharge. For neutralization, the data of mutual neutralization and photodetachment are also presented. (author)

International Network for Comparison of HIV Neutralization Assays: The NeutNet Report II

NARCIS (Netherlands)

Heyndrickx, Leo; Heath, Alan; Sheik-Khalil, Enas; Alcami, Jose; Bongertz, Vera; Jansson, Marianne; Malnati, Mauro; Montefiori, David; Moog, Christiane; Morris, Lynn; Osmanov, Saladin; Polonis, Victoria; Ramaswamy, Meghna; Sattentau, Quentin; Tolazzi, Monica; Schuitemaker, Hanneke; Willems, Betty; Wrin, Terri; Fenyö, Eva Maria; Scarlatti, Gabriella

2012-01-01

Background: Neutralizing antibodies provide markers for vaccine-induced protective immunity in many viral infections. By analogy, HIV-1 neutralizing antibodies induced by immunization may well predict vaccine effectiveness. Assessment of neutralizing antibodies is therefore of primary importance,

Transition probability of the 5971-A line in neutral uranium from collision-induced fluorescence spectroscopy

International Nuclear Information System (INIS)

Gagne, J.M.; Mongeau, B.; Demers, Y.; Pianarosa, P.

1981-01-01

From collision-induced fluorescence spectroscopy measurements, we have determined the transition probability Aof the 5971-A transition in neutral uranium. Our value, A 5971 = (5.9 +- 1.8) x 10 5 sec -1 , is, within experimental error, in good agreement with the previous determination of Corliss, A 5971 = (7.3 +- 3.0) x 10 5 sec -1 [J. Res. Nat. Bur. Stand. Sect. A 80,1 (1976)

A multi-subunit Chlamydia vaccine inducing neutralizing antibodies and strong IFN-γ(+) CMI responses protects against a genital infection in minipigs

DEFF Research Database (Denmark)

Bøje, Sarah; Olsen, Anja Weinreich; Erneholm, Karin

2016-01-01

Chlamydia is the most widespread sexually transmitted bacterial disease and a prophylactic vaccine is highly needed. Ideally, this vaccine is required to induce a combined response of Th1 cell-mediated immune (CMI) response in concert with neutralizing antibodies. Using a novel Göttingen minipig...... trachomatis SvD bacteria (UV-SvD/CAF01) or CAF01. The Hirep1+CTH93/CAF01 vaccine induced a strong CMI response against the vaccine antigens and high titers of antibodies, particularly against the VD4 region of MOMP. Sera from Hirep1+CTH93/CAF01 immunized pigs neutralized C. trachomatis SvD and SvF infectivity...

Low doses of neutrons induce changes in gene expression

International Nuclear Information System (INIS)

Woloschak, G.E.; Chang-Liu, C.M.; Panozzo, J.; Libertin, C.R.

1993-01-01

Studies were designed to identify genes induced following low-dose neutron but not following γ-ray exposure in fibroblasts. Our past work had shown differences in the expression of β-protein kinase C and c-fos genes, both being induced following γ-ray but not neutron exposure. We have identified two genes that are induced following neutron, but not γ-ray, exposure: Rp-8 (a gene induced by apoptosis) and the long terminal repeat (LTR) of the human immunodeficiency (HIV). Rp-8 mRNA induction was demonstrated in Syrian hamster embryo fibroblasts and was found to be induced in cells exposed to neutrons administered at low (0.5 cGy/min) and at high dose rate (12 cGy/min). The induction of transcription from the LTR of HIV was demonstrated in HeLa cells bearing a transfected construct of the chloramphenicol acetyl transferase (CAT) gene driven by the HIV-LTR promoter. Measures of CAT activity and CAT transcripts following irradiation demonstrated an unresponsiveness to γ rays over a broad range of doses. Twofold induction of the HIV-LTR was detected following neutron exposure (48 cGy) administered at low (0.5 cGy/min) but not high (12 cGy/min) dose rates. Ultraviolet-mediated HIV-LTR induction was inhibited by low-dose-rate neutron exposure

Neutral axis as damage sensitive feature

International Nuclear Information System (INIS)

Sigurdardottir, D H; Glisic, B

2013-01-01

Structural health monitoring (SHM) is the process of continuously or periodically measuring structural parameters and the transformation of the collected data into information on real structural conditions. The centroid of stiffness is a universal parameter and its position in a cross-section can be evaluated for any load-carrying beam structure as the position of the neutral axis under conveniently chosen loads. Thus, a change in the position of the neutral axis within a cross-section can indicate a change in the position of the centroid of stiffness, i.e., unusual structural behaviors. This paper proposes a novel monitoring method based on deterministic and probabilistic determination of the position of the neutral axis under conveniently chosen conditions. Therefore, the method proposed in this paper is potentially applicable to a large variety of beam-like structures. Data from two existing structures were used to validate the method and assess its performance: Streicker Bridge at Princeton University and the US202/NJ23 highway overpass in Wayne, NJ. The results show that the neutral axis location is varying even when damage is not present. Reasons for this variation are determined and the accuracy in the evaluation assessed. This paper concludes that the position of the neutral axis can be evaluated with sufficient accuracy using static and dynamic strain measurements performed on appropriate time-scales and indicates its potential to be used as a damage sensitive feature. (paper)

Neutral axis as damage sensitive feature

Science.gov (United States)

Sigurdardottir, D. H.; Glisic, B.

2013-07-01

Structural health monitoring (SHM) is the process of continuously or periodically measuring structural parameters and the transformation of the collected data into information on real structural conditions. The centroid of stiffness is a universal parameter and its position in a cross-section can be evaluated for any load-carrying beam structure as the position of the neutral axis under conveniently chosen loads. Thus, a change in the position of the neutral axis within a cross-section can indicate a change in the position of the centroid of stiffness, i.e., unusual structural behaviors. This paper proposes a novel monitoring method based on deterministic and probabilistic determination of the position of the neutral axis under conveniently chosen conditions. Therefore, the method proposed in this paper is potentially applicable to a large variety of beam-like structures. Data from two existing structures were used to validate the method and assess its performance: Streicker Bridge at Princeton University and the US202/NJ23 highway overpass in Wayne, NJ. The results show that the neutral axis location is varying even when damage is not present. Reasons for this variation are determined and the accuracy in the evaluation assessed. This paper concludes that the position of the neutral axis can be evaluated with sufficient accuracy using static and dynamic strain measurements performed on appropriate time-scales and indicates its potential to be used as a damage sensitive feature.

A small antigenic determinant of the Chikungunya virus E2 protein is sufficient to induce neutralizing antibodies which are partially protective in mice.

Directory of Open Access Journals (Sweden)

Christopher Weber

2015-04-01

Full Text Available The mosquito-borne Chikungunya virus (CHIKV causes high fever and severe joint pain in humans. It is expected to spread in the future to Europe and has recently reached the USA due to globalization, climate change and vector switch. Despite this, little is known about the virus life cycle and, so far, there is no specific treatment or vaccination against Chikungunya infections. We aimed here to identify small antigenic determinants of the CHIKV E2 protein able to induce neutralizing immune responses.E2 enables attachment of the virus to target cells and a humoral immune response against E2 should protect from CHIKV infections. Seven recombinant proteins derived from E2 and consisting of linear and/or structural antigens were created, and were expressed in and purified from E. coli. BALB/c mice were vaccinated with these recombinant proteins and the mouse sera were screened for neutralizing antibodies. Whereas a linear N-terminally exposed peptide (L and surface-exposed parts of the E2 domain A (sA alone did not induce neutralizing antibodies, a construct containing domain B and a part of the β-ribbon (called B+ was sufficient to induce neutralizing antibodies. Furthermore, domain sA fused to B+ (sAB+ induced the highest amount of neutralizing antibodies. Therefore, the construct sAB+ was used to generate a recombinant modified vaccinia virus Ankara (MVA, MVA-CHIKV-sAB+. Mice were vaccinated with MVA-CHIKV-sAB+ and/or the recombinant protein sAB+ and were subsequently challenged with wild-type CHIKV. Whereas four vaccinations with MVA-CHIKV-sAB+ were not sufficient to protect mice from a CHIKV infection, protein vaccination with sAB+ markedly reduced the viral titers of vaccinated mice.The recombinant protein sAB+ contains important structural antigens for a neutralizing antibody response in mice and its formulation with appropriate adjuvants might lead to a future CHIKV vaccine.

Cloning and Characterizing Genes Involved in Monoterpene Induced Mammary Tumor Regression.

Science.gov (United States)

1996-10-01

AD GRANT NUMBER DAMDI7-94-J-4041 TITLE: Cloning and Characterizing Genes Involved in Monoterpene Induced Mammary Tumor Regression PRINCIPAL...October 1996 Annual (1 Sep 95 - 31 Aug 96) 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Cloning and Characterizing Genes Involved in Monoterpene Induced... Monoterpene -induced/repressed genes were identified in regressing rat mammary carcinomas treated with dietary limonene using a newly developed method

Determination of the differential cross-section in hadronic e+e--annihilation events with hard, isolated, neutral particles

International Nuclear Information System (INIS)

Makowsky, M.

1982-10-01

Hadronic e + e - -annihilation events have been measured, by the CELLO-detector at PETRA at the center of mass energy Esub(cm) = 34 GeV and Esub(cm) = 22 GeV. Those events with hard, isolated, neutral particles are selected and explored. At Esub(cm) = 34 GeV the predominant source of these isolated photons is found to be initial state bremsstrahlung of the e + e - -annihilation. The measured photon distributions as function of its energy and the total cross section are investigated. The agreement with QED-predictions is good. (orig.) [de

Characterizing Peptide Neutral Losses Induced by Negative Electron-Transfer Dissociation (NETD)

Science.gov (United States)

Rumachik, Neil G.; McAlister, Graeme C.; Russell, Jason D.; Bailey, Derek J.; Wenger, Craig D.; Coon, Joshua J.

2012-01-01

We implemented negative electron-transfer dissociation (NETD) on a hybrid ion trap/Orbitrap mass spectrometer to conduct ion/ion reactions using peptide anions and radical reagent cations. In addition to sequence-informative ladders of a•- and x-type fragment ions, NETD generated intense neutral loss peaks corresponding to the entire or partial side-chain cleavage from amino acids constituting a given peptide. Thus, a critical step towards the characterization of this recently introduced fragmentation technique is a systematic study of synthetic peptides to identify common neutral losses and preferential fragmentation pathways. Examining 46 synthetic peptides with high mass accuracy and high resolution analysis permitted facile determination of the chemical composition of each neutral loss. We identified 19 unique neutral losses from 14 amino acids and three modified amino acids, and assessed the specificity and sensitivity of each neutral loss using a database of 1542 confidently identified peptides generated from NETD shotgun experiments employing high-pH separations and negative electrospray ionization. As residue-specific neutral losses indicate the presence of certain amino acids, we determined that many neutral losses have potential diagnostic utility. We envision this catalogue of neutral losses being incorporated into database search algorithms to improve peptide identification specificity and to further advance characterization of the acidic proteome. PMID:22290482

Beam-induced pressure variations in a TFTR neutral-beam injector

International Nuclear Information System (INIS)

Willis, J.E.; Berkner, K.H.

1981-10-01

In neutral-beam injection systems either all or part of the gas flow into the neutralizer comes from the plasma source. When the beam is switched on, ions from the plasma source, which used to contribute to the gas flow, are converted to an energetic beam and are pumped away: hence reducing the gas input to the neutralizer. The large volume of the neutralizer and its high conductance damp out rapid changes; for example, when the gas to the source is first turned on, there is a 230 msec exponential rise time associated with pressure in the neutralizer. The neutralizer in turn acts as a source of gas to the first chamber and the first chamber to the second and so on. Beam dumps become additional sources of gas in the second chamber and target tank as gas molecules are collisionally desorbed from the surface of the dump. A simple analytical model (the equivalent of an electrical RC circuit) of the volumes and conductances of the system has been used to describe the pressure variations. The use of time dependent sources terms in the model gives an estimate of the desorption rate from the dumps and its time variation during a beam pulse

Interplay of foot-and-mouth disease virus, antibodies and plasmacytoid dendritic cells: virus opsonization under non-neutralizing conditions results in enhanced interferon-alpha responses

Directory of Open Access Journals (Sweden)

Lannes Nils

2012-08-01

Full Text Available Abstract Foot-and-mouth disease virus (FMDV is a highly infectious member of the Picornaviridae inducing an acute disease of cloven-hoofed species. Vaccine-induced immune protection correlates with the presence of high levels of neutralizing antibodies but also opsonising antibodies have been proposed as an important mechanism of the immune response contributing to virus clearance by macrophages and leading to the production of type-I interferon (IFN by plasmacytoid dendritic cells (pDC. The present study demonstrates that the opsonising antibody titres mediating enhanced IFN-α responses in pDC were similar to neutralizing titres, when antigenically related viruses from the same serotype were employed. However, sera cross-reacted also with non-neutralized isolates of multiple serotypes, when tested in this assay. Both uncomplexed virus and immune complexed virus stimulated pDC via Toll-like receptor 7. An additional finding of potential importance for strain-specific differences in virulence and/or immunogenicity was that pDC activation by FMDV strongly differed between viral isolates. Altogether, our results indicate that opsonising antibodies can have a broader reactivity than neutralizing antibodies and may contribute to antiviral responses induced against antigenically distant viruses.

Cross-field Mobility in a Pure Electron Plasma

International Nuclear Information System (INIS)

Fossum, E.C.; King, L.B.

2006-01-01

An electron trapping apparatus was constructed in order to study electron dynamics in the defining electric and magnetic field of a Hall-effect thruster. The approach presented here decouples the cross-field mobility from plasma effects by conducting measurements on a pure electron plasma in a highly controlled environment. Dielectric walls are removed completely eliminating all wall effect; thus, electrons are confined solely by a radial magnetic field and a crossed, independently-controlled, axial electric field that induces the closed-drift azimuthal Hall current. Electron trajectories and cross-field mobility were examined in response to electric and magnetic field strength and background neutral density

Specitic gene alterations in radiation-induced tumorigenesis

Energy Technology Data Exchange (ETDEWEB)

Ahn, Joo Mee; Kang, Chang Mo; Lee, Seung Sook; Cho, Chul Koo; Bae, Sang Woo; Lee, Su Jae; Lee, Yun Sil [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

2004-07-01

To identify a set of genes involved in the development of radiation-induced tumorigenesis, we used DNA microarrays consisting of 1,176 mouse genes and compared expression profiles of radioresistant cells, designated NIH3T3-R1 and -R4. These cells were tumorigenic in a nude mouse grafting system, as compared to the parental NIH3T3 cells. Expressions of MDM2, CDK6 and CDC25B were found to increase more than 3-fold. Entactin protein levels were downregulated in NIH3T3-R1 and -R4 cells. Changes in expression genes were confirmed by reverse transcription-PCR or western blotting. When these genes were transfected to NIH3T3 cells, the CDC25B and MDM2 overexpressing NIH3T3 cells showed radioresistance, while 2 CDK6 overexpressing cells did not. In the case of entactin overexpressing NIH3T3-R1 or R-4 cells were still radioresistant. Furthermore, the CDC25B and MDM2 overexpressing cells grafted to nude mice, were tumorigenic. NIH3T3-R1 and R4 cells showed increased radiation-induced apoptosis, accompanied by faster growth rate, rather than and earlier radiation-induced G2/M phase arrest, suggesting that the radioresistance of NIH3T3-R1 and R4 cells was due to faster growth rate, rather than induction of apoptosis. In the case of MDM2 and CDC25B overexpressing cells, similar phenomena, such as increased apoptosis and faster growth rate, were shown. The above results, therefore, demonstrate involvement of CDC25B and MDM2 overexpression in radiation-induced tumorigenesis and provide novel targets for detection of radiation-induced carcinogenesis.

Measurement of neutrino induced charged current neutral pion production cross section at SciBooNE

Energy Technology Data Exchange (ETDEWEB)

Catala-Perez, Juan [Univ. of Valencia (Spain)

2014-01-01

SciBooNE is a neutrino scattering experiment located in the Booster Neutrino Beam at Fermilab. It collected data from June 2007 to August 2008 to accurately measure muon neutrino and anti-neutrino cross sections on carbon around 1 GeV neutrino energy. In this thesis we present the results on the measurement of the muon neutrino cross section resulting in a μ^- plus a single π⁰ final state (CC- π⁰ channel). The present work will show the steps taken to achieve this result: from the reconstruction improvements to the background extraction. The flux-averaged CC - π⁰ production cross section measurement obtained in this thesis < σCC- π⁰ > Φ = (5.6 ± 1.9_fit ± 0.7_beam ± 0.5_int - 0.7_det) × 10^-40 cm²/N at an average energy of 0.89 GeV is found to agree well both with the expectation from the Monte Ca

The impacts of neutralized acid mine drainage contaminated water on the expression of selected endocrine-linked genes in juvenile Mozambique tilapia Oreochromis mossambicus exposed in vivo.

Science.gov (United States)

Truter, Johannes Christoff; va Wyk, Johannes Hendrik; Oberholster, Paul Johan; Botha, Anna-Maria

2014-02-01

Acid mine drainage (AMD) is a global environmental concern due to detrimental impacts on river ecosystems. Little is however known regarding the biological impacts of neutralized AMD on aquatic vertebrates despite excessive discharge into watercourses. The aim of this investigation was to evaluate the endocrine modulatory potential of neutralized AMD, using molecular biomarkers in the teleost fish Oreochromis mossambicus in exposure studies. Surface water was collected from six locations downstream of a high density sludge (HDS) AMD treatment plant and a reference site unimpacted by AMD. The concentrations of 28 elements, including 22 metals, were quantified in the exposure water in order to identify potential links to altered gene expression. Relatively high concentrations of manganese (~ 10mg/l), nickel (~ 0.1mg/l) and cobalt (~ 0.03 mg/l) were detected downstream of the HDS plant. The expression of thyroid receptor-α (trα), trβ, androgen receptor-1 (ar1), ar2, glucocorticoid receptor-1 (gr1), gr2, mineralocorticoid receptor (mr) and aromatase (cyp19a1b) was quantified in juvenile fish after 48 h exposure. Slight but significant changes were observed in the expression of gr1 and mr in fish exposed to water collected directly downstream of the HDS plant, consisting of approximately 95 percent neutralized AMD. The most pronounced alterations in gene expression (i.e. trα, trβ, gr1, gr2, ar1 and mr) was associated with water collected further downstream at a location with no other apparent contamination vectors apart from the neutralized AMD. The altered gene expression associated with the "downstream" locality coincided with higher concentrations of certain metals relative to the locality adjacent to the HDS plant which may indicate a causative link. The current study provides evidence of endocrine disruptive activity associated with neutralized AMD contamination in regard to alterations in the expression of key genes linked to the thyroid, interrenal and

Nitric oxide-induced interstrand cross-links in DNA.

Science.gov (United States)

Caulfield, Jennifer L; Wishnok, John S; Tannenbaum, Steven R

2003-05-01

The DNA damaging effects of nitrous acid have been extensively studied, and the formation of interstrand cross-links have been observed. The potential for this cross-linking to occur through a common nitrosating intermediate derived from nitric oxide is investigated here. Using a HPLC laser-induced fluorescence (LIF) system, the amount of interstrand cross-link formed on nitric oxide treatment of the 5'-fluorescein-labeled oligomer ATATCGATCGATAT was determined. This self-complimentary sequence contains two 5'-CG sequences, which is the preferred site for nitrous acid-induced cross-linking. Nitric oxide was delivered to an 0.5 mM oligomer solution at 15 nmol/mL/min to give a final nitrite concentration of 652 microM. The resulting concentration of the deamination product, xanthine, in this sample was found to be 211 +/- 39 nM, using GC/MS, and the amount of interstrand cross-link was determined to be 13 +/- 2.5 nM. Therefore, upon nitric oxide treatment, the cross-link is found at approximately 6% of the amount of the deamination product. Using this system, detection of the cross-link is also possible for significantly lower doses of nitric oxide, as demonstrated by treatment of the same oligomer with NO at a rate of 18 nmol/mL/min resulting in a final nitrite concentration of 126 microM. The concentration of interstrand cross-link was determined to be 3.6 +/- 0.1 nM in this sample. Therefore, using the same dose rate, when the total nitric oxide concentration delivered drops by a factor of approximately 5, the concentration of cross-link drops by a factor of about 4-indicating a qausi-linear response. It may now be possible to predict the number of cross-links in a small genome based on the number of CpG sequences and the yield of xanthine derived from nitrosative deamination.

Light-dependent expression of flg22-induced defense genes in Arabidopsis

Directory of Open Access Journals (Sweden)

Satoshi eSano

2014-10-01

Full Text Available Chloroplasts have been reported to generate retrograde immune signals that activate defense gene expression in the nucleus. However, the roles of light and photosynthesis in plant immunity remain largely elusive. In this study, we evaluated the effects of light on the expression of defense genes induced by flg22, a peptide derived from bacterial flagellins which acts as a potent elicitor in plants. Whole-transcriptome analysis of flg22-treated Arabidopsis thaliana seedlings under light and dark conditions for 30 min revealed that a number of (30% genes strongly induced by flg22 (>4.0 require light for their rapid expression, whereas flg22-repressed genes include a significant number of genes that are down-regulated by light. Furthermore, light is responsible for the flg22-induced accumulation of salicylic acid, indicating that light is indispensable for basal defense responses in plants. To elucidate the role of photosynthesis in defense, we further examined flg22-induced defense gene expression in the presence of specific inhibitors of photosynthetic electron transport: 3-(3,4-dichlorophenyl-1,1-dimethylurea (DCMU and 2,5-dibromo-3-methyl-6-isopropyl-benzoquinone (DBMIB. Light-dependent expression of defense genes was largely suppressed by DBMIB, but only partially suppressed by DCMU. These findings suggest that photosynthetic electron flow plays a role in controling the light-dependent expression of flg22-inducible defense genes.

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.

An elm EST database for identifying leaf beetle egg-induced defense genes

Directory of Open Access Journals (Sweden)

Büchel Kerstin

2012-06-01

Full Text Available Abstract Background Plants can defend themselves against herbivorous insects prior to the onset of larval feeding by responding to the eggs laid on their leaves. In the European field elm (Ulmus minor, egg laying by the elm leaf beetle ( Xanthogaleruca luteola activates the emission of volatiles that attract specialised egg parasitoids, which in turn kill the eggs. Little is known about the transcriptional changes that insect eggs trigger in plants and how such indirect defense mechanisms are orchestrated in the context of other biological processes. Results Here we present the first large scale study of egg-induced changes in the transcriptional profile of a tree. Five cDNA libraries were generated from leaves of (i untreated control elms, and elms treated with (ii egg laying and feeding by elm leaf beetles, (iii feeding, (iv artificial transfer of egg clutches, and (v methyl jasmonate. A total of 361,196 ESTs expressed sequence tags (ESTs were identified which clustered into 52,823 unique transcripts (Unitrans and were stored in a database with a public web interface. Among the analyzed Unitrans, 73% could be annotated by homology to known genes in the UniProt (Plant database, particularly to those from Vitis, Ricinus, Populus and Arabidopsis. Comparative in silico analysis among the different treatments revealed differences in Gene Ontology term abundances. Defense- and stress-related gene transcripts were present in high abundance in leaves after herbivore egg laying, but transcripts involved in photosynthesis showed decreased abundance. Many pathogen-related genes and genes involved in phytohormone signaling were expressed, indicative of jasmonic acid biosynthesis and activation of jasmonic acid responsive genes. Cross-comparisons between different libraries based on expression profiles allowed the identification of genes with a potential relevance in egg-induced defenses, as well as other biological processes, including signal transduction

An elm EST database for identifying leaf beetle egg-induced defense genes.

Science.gov (United States)

Büchel, Kerstin; McDowell, Eric; Nelson, Will; Descour, Anne; Gershenzon, Jonathan; Hilker, Monika; Soderlund, Carol; Gang, David R; Fenning, Trevor; Meiners, Torsten

2012-06-15

Plants can defend themselves against herbivorous insects prior to the onset of larval feeding by responding to the eggs laid on their leaves. In the European field elm (Ulmus minor), egg laying by the elm leaf beetle ( Xanthogaleruca luteola) activates the emission of volatiles that attract specialised egg parasitoids, which in turn kill the eggs. Little is known about the transcriptional changes that insect eggs trigger in plants and how such indirect defense mechanisms are orchestrated in the context of other biological processes. Here we present the first large scale study of egg-induced changes in the transcriptional profile of a tree. Five cDNA libraries were generated from leaves of (i) untreated control elms, and elms treated with (ii) egg laying and feeding by elm leaf beetles, (iii) feeding, (iv) artificial transfer of egg clutches, and (v) methyl jasmonate. A total of 361,196 ESTs expressed sequence tags (ESTs) were identified which clustered into 52,823 unique transcripts (Unitrans) and were stored in a database with a public web interface. Among the analyzed Unitrans, 73% could be annotated by homology to known genes in the UniProt (Plant) database, particularly to those from Vitis, Ricinus, Populus and Arabidopsis. Comparative in silico analysis among the different treatments revealed differences in Gene Ontology term abundances. Defense- and stress-related gene transcripts were present in high abundance in leaves after herbivore egg laying, but transcripts involved in photosynthesis showed decreased abundance. Many pathogen-related genes and genes involved in phytohormone signaling were expressed, indicative of jasmonic acid biosynthesis and activation of jasmonic acid responsive genes. Cross-comparisons between different libraries based on expression profiles allowed the identification of genes with a potential relevance in egg-induced defenses, as well as other biological processes, including signal transduction, transport and primary metabolism

The majority of inducible DNA repair genes in Mycobacterium tuberculosis are induced independently of RecA.

Science.gov (United States)

Rand, Lucinda; Hinds, Jason; Springer, Burkhard; Sander, Peter; Buxton, Roger S; Davis, Elaine O

2003-11-01

In many species of bacteria most inducible DNA repair genes are regulated by LexA homologues and are dependent on RecA for induction. We have shown previously by analysing the induction of recA that two mechanisms for the induction of gene expression following DNA damage exist in Mycobacterium tuberculosis. Whereas one of these depends on RecA and LexA in the classical way, the other mechanism is independent of both of these proteins and induction occurs in the absence of RecA. Here we investigate the generality of each of these mechanisms by analysing the global response to DNA damage in both wild-type M. tuberculosis and a recA deletion strain of M. tuberculosis using microarrays. This revealed that the majority of the genes that were induced remained inducible in the recA mutant stain. Of particular note most of the inducible genes with known or predicted functions in DNA repair did not depend on recA for induction. Amongst these are genes involved in nucleotide excision repair, base excision repair, damage reversal and recombination. Thus, it appears that this novel mechanism of gene regulation is important for DNA repair in M. tuberculosis.

Neutral mutation as the source of genetic variation in life history traits.

Science.gov (United States)

Brcić-Kostić, Krunoslav

2005-08-01

The mechanism underlying the maintenance of adaptive genetic variation is a long-standing question in evolutionary genetics. There are two concepts (mutation-selection balance and balancing selection) which are based on the phenotypic differences between alleles. Mutation - selection balance and balancing selection cannot properly explain the process of gene substitution, i.e. the molecular evolution of quantitative trait loci affecting fitness. I assume that such loci have non-essential functions (small effects on fitness), and that they have the potential to evolve into new functions and acquire new adaptations. Here I show that a high amount of neutral polymorphism at these loci can exist in real populations. Consistent with this, I propose a hypothesis for the maintenance of genetic variation in life history traits which can be efficient for the fixation of alleles with very small selective advantage. The hypothesis is based on neutral polymorphism at quantitative trait loci and both neutral and adaptive gene substitutions. The model of neutral - adaptive conversion (NAC) assumes that neutral alleles are not neutral indefinitely, and that in specific and very rare situations phenotypic (relative fitness) differences between them can appear. In this paper I focus on NAC due to phenotypic plasticity of neutral alleles. The important evolutionary consequence of NAC could be the increased adaptive potential of a population. Loci responsible for adaptation should be fast evolving genes with minimally discernible phenotypic effects, and the recent discovery of genes with such characteristics implicates them as suitable candidates for loci involved in adaptation.

Identification of distinct genes associated with seawater aspiration-induced acute lung injury by gene expression profile analysis

Science.gov (United States)

Liu, Wei; Pan, Lei; Zhang, Minlong; Bo, Liyan; Li, Congcong; Liu, Qingqing; Wang, Li; Jin, Faguang

2016-01-01

Seawater aspiration-induced acute lung injury (ALI) is a syndrome associated with a high mortality rate, which is characterized by severe hypoxemia, pulmonary edema and inflammation. The present study is the first, to the best of our knowledge, to analyze gene expression profiles from a rat model of seawater aspiration-induced ALI. Adult male Sprague-Dawley rats were instilled with seawater (4 ml/kg) in the seawater aspiration-induced ALI group (S group) or with distilled water (4 ml/kg) in the distilled water negative control group (D group). In the blank control group (C group) the rats' tracheae were exposed without instillation. Subsequently, lung samples were examined by histopathology; total protein concentration was detected in bronchoalveolar lavage fluid (BALF); lung wet/dry weight ratios were determined; and transcript expression was detected by gene sequencing analysis. The results demonstrated that histopathological alterations, pulmonary edema and total protein concentrations in BALF were increased in the S group compared with in the D group. Analysis of differential gene expression identified up and downregulated genes in the S group compared with in the D and C groups. A gene ontology analysis of the differential gene expression revealed enrichment of genes in the functional pathways associated with neutrophil chemotaxis, immune and defense responses, and cytokine activity. Kyoto Encyclopedia of Genes and Genomes analysis revealed that the cytokine-cytokine receptor interaction pathway was one of the most important pathways involved in seawater aspiration-induced ALI. In conclusion, activation of the cytokine-cytokine receptor interaction pathway may have an essential role in the progression of seawater aspiration-induced ALI, and the downregulation of tumor necrosis factor superfamily member 10 may enhance inflammation. Furthermore, IL-6 may be considered a biomarker in seawater aspiration-induced ALI. PMID:27509884

Preferential repair of ionizing radiation-induced damage in the transcribed strand of an active human gene is defective in Cockayne syndrome

International Nuclear Information System (INIS)

Leadon, S.A.; Copper, P.K.

1993-01-01

Cells from patients with Cockayne syndrome (CS), which are sensitive to killing by UV although overall damage removal appears normal, are specifically defective in repair of UV damage in actively transcribe genes. Because several CS strains display cross-sensitivity to killing by ionizing radiation, the authors examined whether ionizing radiation-induced damage in active genes is preferentially repaired by normal cells and whether the radiosensitivity of CS cells can be explained by a defect in this process. They found that ionizing radiation-induced damage was repaired more rapidly in the transcriptionally active metallothionein IIA (MTIIA) gene than in the inactive MTIIB gene or in the genome overall in normal cells as a result of faster repair on the transcribed strand of MTIIA. Cells of the radiosensitive CS strain CS1AN are completely defective in this strand-selective repair of ionizing radiation-induced damage, although their overall repair rate appears normal. CS3BE cells, which are intermediate in radiosensitivity, do exhibit more rapid repair of the transcribed strand but at a reduced rate compared to normal cells. Xeroderma pigmentosum complementation group A cells, which are hypersensitive to UV light because of a defect in the nucleotide excision repair pathway but do not show increased sensitivity to ionizing radiation, preferentially repair ionizing radiation-induced damage on the transcribed strand of MTIIA. Thus, the ability to rapidly repair ionizing radiation-induced damage in actively transcribing genes correlates with cell survival. The results extend the generality of preferential repair in active genes to include damage other than bulky lesions

Neutron-induced cross sections of short-lived nuclei via the surrogate reaction method

Directory of Open Access Journals (Sweden)

Morel P.

2011-10-01

Full Text Available The measurement of neutron-induced cross sections of short-lived nuclei is extremely difficult due to the radioactivity of the samples. The surrogate reaction method is an indirect way of determining cross sections for nuclear reactions that proceed through a compound nucleus. This method presents the advantage that the target material can be stable or less radioactive than the material required for a neutron-induced measurement. We have successfully used the surrogate reaction method to extract neutron-induced fission cross sections of various short-lived actinides. In this work, we investigate whether this technique can be used to determine neutron-induced capture cross sections in the rare-earth region.

Neutron-induced cross sections of short-lived nuclei via the surrogate reaction method

Directory of Open Access Journals (Sweden)

Tassan-Got L.

2012-02-01

Full Text Available The measurement of neutron-induced cross sections of short-lived nuclei is extremely difficult due to the radioactivity of the samples. The surrogate reaction method is an indirect way of determining cross sections for nuclear reactions that proceed through a compound nucleus. This method presents the advantage that the target material can be stable or less radioactive than the material required for a neutron-induced measurement. We have successfully used the surrogate reaction method to extract neutron-induced fission cross sections of various short-lived actinides. In this work, we investigate whether this technique can be used to determine neutron-induced capture cross sections in the rare-earth region.

Determination of the D/T fuel mixture using two-photon laser induced fluorescence in combination with neutral beam injection

International Nuclear Information System (INIS)

Voslamber, D.; Mandl, W.

1997-08-01

Doppler-free two-photon induced fluorescence in the Lyman-α lines of H, D and T has been suggested previously as a local and isotope-selective diagnostic of the intrinsic neutral hydrogen densities in magnetically confined fusion plasmas. In the present paper it is shown that the diagnostic potential of this method is significantly increased if it is combined with neutral atom beams whose characteristics are such that efficient production of thermal ground state atoms via charge exchange reactions is achieved. Considerably deeper plasma regions than just the plasma edge can thus be probed and local, isotope-selective information is obtained on the more relevant ions rather than on the neutrals. Additional diagnostic possibilities, e.g. those arising from the spectroscopic investigation of the beam particles themselves, are also discussed. (author)

Detecting population structure in a high gene-flow species, Atlantic herring (Clupea harengus): direct, simultaneous evaluation of neutral vs putatively selected loci

DEFF Research Database (Denmark)

André, C.; Larsson, L. C.; Laikre, L.

2010-01-01

In many marine fish species, genetic population structure is typically weak because populations are large, evolutionarily young and have a high potential for gene flow. We tested whether genetic markers influenced by natural selection are more efficient than the presumed neutral genetic markers t...

Identification of GIG1, a GlcNAc-induced gene in Candida albicans needed for normal sensitivity to the chitin synthase inhibitor nikkomycin Z.

Science.gov (United States)

Gunasekera, Angelo; Alvarez, Francisco J; Douglas, Lois M; Wang, Hong X; Rosebrock, Adam P; Konopka, James B

2010-10-01

The amino sugar N-acetylglucosamine (GlcNAc) is known to be an important structural component of cells from bacteria to humans, but its roles in cell signaling are less well understood. GlcNAc induces two pathways in the human fungal pathogen Candida albicans. One activates cyclic AMP (cAMP) signaling, which stimulates the formation of hyphal cells and the expression of virulence genes, and the other pathway induces genes needed to catabolize GlcNAc. Microarray analysis of gene expression was carried out under four different conditions in order to characterize the transcriptional changes induced by GlcNAc. The most highly induced genes include those that encode a GlcNAc transporter (NGT1) and the GlcNAc catabolic enzymes (HXK1, DAC1, and NAG1). GlcNAc also activated most of the genes whose expression is increased when cells are triggered with other stimuli to form hyphae. Surprisingly, GlcNAc also induced a subset of genes that are regulated by galactose (GAL1, GAL7, and GAL10), which may be due to cross talk between signaling pathways. A novel GlcNAc-induced gene, GIG1, which is not essential for GlcNAc catabolism or the induction of hyphae, was identified. However, a Gig1-green fluorescent protein (GFP) fusion protein was specifically induced by GlcNAc, and not by other sugars. Gig1-GFP localized to the cytoplasm, where GlcNAc metabolism occurs. Significantly, a gig1Δ mutant displayed increased resistance to nikkomycin Z, which inhibits chitin synthase from converting UDP-GlcNAc into cell wall chitin. Gig1 is highly conserved in fungi, especially those that contain GlcNAc catabolic genes. These results implicate Gig1 in GlcNAc metabolism.

High-throughput pseudovirion-based neutralization assay for analysis of natural and vaccine-induced antibodies against human papillomaviruses.

Directory of Open Access Journals (Sweden)

Peter Sehr

Full Text Available A highly sensitive, automated, purely add-on, high-throughput pseudovirion-based neutralization assay (HT-PBNA with excellent repeatability and run-to-run reproducibility was developed for human papillomavirus types (HPV 16, 18, 31, 45, 52, 58 and bovine papillomavirus type 1. Preparation of 384 well assay plates with serially diluted sera and the actual cell-based assay are separated in time, therefore batches of up to one hundred assay plates can be processed sequentially. A mean coefficient of variation (CV of 13% was obtained for anti-HPV 16 and HPV 18 titers for a standard serum tested in a total of 58 repeats on individual plates in seven independent runs. Natural antibody response was analyzed in 35 sera from patients with HPV 16 DNA positive cervical intraepithelial neoplasia grade 2+ lesions. The new HT-PBNA is based on Gaussia luciferase with increased sensitivity compared to the previously described manual PBNA (manPBNA based on secreted alkaline phosphatase as reporter. Titers obtained with HT-PBNA were generally higher than titers obtained with the manPBNA. A good linear correlation (R(2 = 0.7 was found between HT-PBNA titers and anti-HPV 16 L1 antibody-levels determined by a Luminex bead-based GST-capture assay for these 35 sera and a Kappa-value of 0.72, with only 3 discordant sera in the low titer range. In addition to natural low titer antibody responses the high sensitivity of the HT-PBNA also allows detection of cross-neutralizing antibodies induced by commercial HPV L1-vaccines and experimental L2-vaccines. When analyzing the WHO international standards for HPV 16 and 18 we determined an analytical sensitivity of 0.864 and 1.105 mIU, respectively.

Human Papillomavirus neutralizing and cross-reactive antibodies induced in HIV-positive subjects after vaccination with quadrivalent and bivalent HPV vaccines

DEFF Research Database (Denmark)

Faust, Helena; Nielsen, Lars Toft; Sehr, Peter

2016-01-01

Ninety-one HIV-infected individuals (61 men and 30 women) were randomized to vaccination either with quadrivalent (Gardasil™) or bivalent (Cervarix™) HPV vaccine. Neutralizing and specific HPV-binding serum antibodies were measured at baseline and 12 months after the first vaccine dose. Presence...... of neutralizing and binding antibodies had good agreement (average Kappa for HPV types 6, 11, 16, 18, 31, 33 and 45 was 0.65). At baseline, 88% of subjects had antibodies against at least one genital HPV. Following vaccination with Cervarix™, all subjects became seropositive for HPV16 and 18. After Gardasil......™ vaccination, 96% of subjects seroconverted for HPV16 and 73% for HPV18. Levels of HPV16-specific antibodies were 10IU in 85% of study subjects after vaccination. Antibodies against non-vaccine HPV types appeared after Gardasil...

Image Guidance and Assessment of Radiation Induced Gene Therapy

National Research Council Canada - National Science Library

Pelizzari, Charles

2004-01-01

Image guidance and assessment techniques are being developed for combined radiation/gene therapy, which utilizes a radiation-inducible gene promoter to cause expression of tumor necrosis factor alpha...

Measurement of high-Q{sup 2} neutral current deep inelastic e{sup -}p scattering cross sections with a longitudinally polarised electron beam at HERA

Energy Technology Data Exchange (ETDEWEB)

Chekanov, S.; Derrick, M.; Magill, S. [Argonne National Lab., Argonne, IL (US)] (and others)

2008-12-15

Measurements of the neutral current cross sections for deep inelastic scattering in e{sup -}p collisions at HERA with a longitudinally polarised electron beam are presented. The single-differential cross-sections d{sigma}/dQ{sup 2}, d{sigma}/dx and d{sigma}/dy and the double-differential cross sections in Q{sup 2} and x are measured in the kinematic region y < 0.9 and Q{sup 2} > 185GeV{sup 2} for both positively and negatively polarised electron beams and for each polarisation state separately. The measurements are based on an integrated luminosity of 169.9 pb{sup -1} taken with the ZEUS detector in 2005 and 2006 at a centre-of-mass energy of 318GeV. The structure functions xF{sub 3} and xF{sub 3}{sup {gamma}}{sup Z} are determined by combining the e{sup -}p results presented in this paper with previously measured e{sup +}p neutral current data. The asymmetry parameter A{sup -} is used to demonstrate the parity violating effects of electroweak interactions at large spacelike photon virtuality. The measurements agree well with the predictions of the Standard Model. (orig.)

Measurement of high-Q{sup 2} neutral current deep inelastic e{sup +}p scattering cross sections with a longitudinally polarised positron beam at HERA

Energy Technology Data Exchange (ETDEWEB)

Abramowicz, H. [Tel Aviv Univ. (Israel). School of Physics; Max Planck Institute for Physics, Munich (Germany); Abt, I. [Max Planck Institute for Physics, Munich (Germany); Adamczyk, L. [AGH-Univ. of Science and Technology, Krakow (Poland). Faculty of Physics and Applied Computer Science] [and others; Collaboration: ZEUS Collaboration

2012-08-15

Measurements of neutral current cross sections for deep inelastic scattering in e{sup +}p collisions at HERA with a longitudinally polarised positron beam are presented. The single-differential cross-sections d{sigma}/dQ{sup 2}, d{sigma}/dx and d{sigma}/dy and the reduced cross-section {sigma} were measured in the kinematic region Q{sup 2}>185 GeV{sup 2} and y<0.9, where Q{sup 2} is the four-momentum transfer squared, x the Bjorken scaling variable, and y the inelasticity of the interaction. The measurements were performed separately for positively and negatively polarised positron beams. The measurements are based on an integrated luminosity of 135.5 pb{sup -1} collected with the ZEUS detector in 2006 and 2007 at a centre-of-mass energy of 318 GeV. The structure functions F{sub 3} and F{sup {gamma}Z}{sub 3} were determined by combining the e{sup +}p results presented in this paper with previously published e{sup -}p neutral current results. The asymmetry parameter A{sup +} is used to demonstrate the parity violation predicted in electroweak interactions. The measurements are well described by the predictions of the Standard Model.

Characterization of cross-section correction to charge exchange recombination spectroscopy rotation measurements using co- and counter-neutral-beam views.

Science.gov (United States)

Solomon, W M; Burrell, K H; Feder, R; Nagy, A; Gohil, P; Groebner, R J

2008-10-01

Measurements of rotation using charge exchange recombination spectroscopy can be affected by the energy dependence of the charge exchange cross section. On DIII-D, the associated correction to the rotation can exceed 100 kms at high temperatures. In reactor-relevant low rotation conditions, the correction can be several times larger than the actual plasma rotation and therefore must be carefully validated. New chords have been added to the DIII-D CER diagnostic to view the counter-neutral-beam line. The addition of these views allows determination of the toroidal rotation without depending on detailed atomic physics calculations, while also allowing experimental characterization of the atomic physics. A database of rotation comparisons from the two views shows that the calculated cross-section correction can adequately describe the measurements, although there is a tendency for "overcorrection." In cases where accuracy better than about 15% is desired, relying on calculation of the cross-section correction may be insufficient.

Estimating Collisionally-Induced Escape Rates of Light Neutrals from Early Mars

Science.gov (United States)

Gacesa, M.; Zahnle, K. J.

2016-12-01

Collisions of atmospheric gases with hot oxygen atoms constitute an important non-thermal mechanism of escape of light atomic and molecular species at Mars. In this study, we present revised theoretical estimates of non-thermal escape rates of neutral O, H, He, and H2 based on recent atmospheric density profiles obtained from the NASA Mars Atmosphere and Volatile Evolution (MAVEN) mission and related theoretical models. As primary sources of hot oxygen, we consider dissociative recombination of O2+ and CO2+ molecular ions. We also consider hot oxygen atoms energized in primary and secondary collisions with energetic neutral atoms (ENAs) produced in charge-exchange of solar wind H+ and He+ ions with atmospheric gases1,2. Scattering of hot oxygen and atmospheric species of interest is modeled using fully-quantum reactive scattering formalism3. This approach allows us to construct distributions of vibrationally and rotationally excited states and predict the products' emission spectra. In addition, we estimate formation rates of excited, translationally hot hydroxyl molecules in the upper atmosphere of Mars. The escape rates are calculated from the kinetic energy distributions of the reaction products using an enhanced 1D model of the atmosphere for a range of orbital and solar parameters. Finally, by considering different scenarios, we estimate the influence of these escape mechanisms on the evolution of Mars's atmosphere throughout previous epochs and their impact on the atmospheric D/H ratio. M.G.'s research was supported by an appointment to the NASA Postdoctoral Program at the NASA Ames Research Center, administered by Universities Space Research Association under contract with NASA. 1N. Lewkow and V. Kharchenko, "Precipitation of Energetic Neutral Atoms and Escape Fluxes induced from the Mars Atmosphere", Astroph. J., 790, 98 (2014) 2M. Gacesa, N. Lewkow, and V. Kharchenko, "Non-thermal production and escape of OH from the upper atmosphere of Mars", arXiv:1607

Changes in gene expression linked to methamphetamine-induced dopaminergic neurotoxicity.

Science.gov (United States)

Xie, Tao; Tong, Liqiong; Barrett, Tanya; Yuan, Jie; Hatzidimitriou, George; McCann, Una D; Becker, Kevin G; Donovan, David M; Ricaurte, George A

2002-01-01

The purpose of these studies was to examine the role of gene expression in methamphetamine (METH)-induced dopamine (DA) neurotoxicity. First, the effects of the mRNA synthesis inhibitor, actinomycin-D, and the protein synthesis inhibitor, cycloheximide, were examined. Both agents afforded complete protection against METH-induced DA neurotoxicity and did so independently of effects on core temperature, DA transporter function, or METH brain levels, suggesting that gene transcription and mRNA translation play a role in METH neurotoxicity. Next, microarray technology, in combination with an experimental approach designed to facilitate recognition of relevant gene expression patterns, was used to identify gene products linked to METH-induced DA neurotoxicity. This led to the identification of several genes in the ventral midbrain associated with the neurotoxic process, including genes for energy metabolism [cytochrome c oxidase subunit 1 (COX1), reduced nicotinamide adenine dinucleotide ubiquinone oxidoreductase chain 2, and phosphoglycerate mutase B], ion regulation (members of sodium/hydrogen exchanger and sodium/bile acid cotransporter family), signal transduction (adenylyl cyclase III), and cell differentiation and degeneration (N-myc downstream-regulated gene 3 and tau protein). Of these differentially expressed genes, we elected to further examine the increase in COX1 expression, because of data implicating energy utilization in METH neurotoxicity and the known role of COX1 in energy metabolism. On the basis of time course studies, Northern blot analyses, in situ hybridization results, and temperature studies, we now report that increased COX1 expression in the ventral midbrain is linked to METH-induced DA neuronal injury. The precise role of COX1 and other genes in METH neurotoxicity remains to be elucidated.

JC virus induces altered patterns of cellular gene expression: Interferon-inducible genes as major transcriptional targets

International Nuclear Information System (INIS)

Verma, Saguna; Ziegler, Katja; Ananthula, Praveen; Co, Juliene K.G.; Frisque, Richard J.; Yanagihara, Richard; Nerurkar, Vivek R.

2006-01-01

Human polyomavirus JC (JCV) infects 80% of the population worldwide. Primary infection, typically occurring during childhood, is asymptomatic in immunocompetent individuals and results in lifelong latency and persistent infection. However, among the severely immunocompromised, JCV may cause a fatal demyelinating disease, progressive multifocal leukoencephalopathy (PML). Virus-host interactions influencing persistence and pathogenicity are not well understood, although significant regulation of JCV activity is thought to occur at the level of transcription. Regulation of the JCV early and late promoters during the lytic cycle is a complex event that requires participation of both viral and cellular factors. We have used cDNA microarray technology to analyze global alterations in gene expression in JCV-permissive primary human fetal glial cells (PHFG). Expression of more than 400 cellular genes was altered, including many that influence cell proliferation, cell communication and interferon (IFN)-mediated host defense responses. Genes in the latter category included signal transducer and activator of transcription 1 (STAT1), interferon stimulating gene 56 (ISG56), myxovirus resistance 1 (MxA), 2'5'-oligoadenylate synthetase (OAS), and cig5. The expression of these genes was further confirmed in JCV-infected PHFG cells and the human glioblastoma cell line U87MG to ensure the specificity of JCV in inducing this strong antiviral response. Results obtained by real-time RT-PCR and Western blot analyses supported the microarray data and provide temporal information related to virus-induced changes in the IFN response pathway. Our data indicate that the induction of an antiviral response may be one of the cellular factors regulating/controlling JCV replication in immunocompetent hosts and therefore constraining the development of PML

Identifying Candidate Reprogramming Genes in Mouse Induced Pluripotent Stem Cells.

Science.gov (United States)

Gao, Fang; Li, Jingyu; Zhang, Heng; Yang, Xu; An, Tiezhu

2017-08-01

Factor-based induced reprogramming approaches have tremendous potential for human regenerative medicine, but the efficiencies of these approaches are still low. In this study, we analyzed the global transcriptional profiles of mouse induced pluripotent stem cells (miPSCs) and mouse embryonic stem cells (mESCs) from seven different labs and present here the first successful clustering according to cell type, not by lab of origin. We identified 2131 different expression genes (DEs) as candidate pluripotency-associated genes by comparing mESCs/miPSCs with somatic cells and 720 DEs between miPSCs and mESCs. Interestingly, there was a significant overlap between the two DE sets. Therefore, we defined the overlap DEs as "consensus DEs" including 313 miPSC-specific genes expressed at a higher level in miPSCs versus mESCs and 184 mESC-specific genes in total and reasoned that these may contribute to the differences in pluripotency between mESCs and miPSCs. A classification of "consensus DEs" according to their different expression levels between somatic cells and mESCs/miPSCs shows that 86% of the miPSC-specific genes are more highly expressed in somatic cells, while 73% of mESC-specific genes are highly expressed in mESCs/miPSCs, indicating that the miPSCs have not efficiently silenced the expression pattern of the somatic cells from which they are derived and failed to completely induce the genes with high expression levels in mESCs. We further revealed a strong correlation between oocyte-enriched factors and insufficiently induced mESC-specific genes and identified 11 hub genes via network analysis. In light of these findings, we postulated that these key hub genes might not only drive somatic cell nuclear transfer (SCNT) reprogramming but also augment the efficiency and quality of miPSC reprogramming.

Neutral sheet crossings in the distant magnetotail

International Nuclear Information System (INIS)

Heikkila, W.J.; Slavin, J.A.; Smith, E.J.; Baker, D.N.; Zwickl, R.D.

1985-01-01

We have analyzed the magnetic field data from ISEE-3 in the distant magnetotail for 18 crossings of the cross-tail current sheet (or so-called natural sheet) to determine the direction of the normal component B/sub z/. The crossings occurred near the middle of the aberrated magnetotail (0 0.4 nT), consistent with closed field lines connected to the earth. In 3 cases B/sub z/ was very close to zero; in several instances there was structure in B/sub y/, suggesting localized currents with x or z directions. One may have been a magnetopause crossing. The strong preponderance of northward B/sub z/ favors a model of the magnetotail which is dominated by boundary layer plasma, flowing tailward on closed magnetic field lines, which requires the existence of an electric field in the sense from dusk to dawn. 37 refs., 15 figs., 1 tab

Collisional-radiative model for neutral helium in plasma. Excitation cross section and singlet-triplet wavefunction mixing

Energy Technology Data Exchange (ETDEWEB)

Goto, Motoshi [National Inst. for Fusion Science, Toki, Gifu (Japan); Fujimoto, Takashi

1997-10-01

We have revised the collisional-radiative (CR) model code of neutral helium (T. Fujimoto, JQSRT 21, 1979). The spin-orbit interaction gives rise to mixing of the wavefunctions of the singlet and triplet states. The degree of the mixing depends on the magnetic field, and at the field strength of the level-anticrossings complete mixing, or complete breakdown of the L-S coupling scheme, occurs. We have approximately incorporated this effect into the code. We have reviewed the excitation cross section data for electron impacts. For transitions starting from the ground state, the recent assessment by the group led by Dr. de Heer is judged satisfactory. For transitions from the metastable levels the assessment by the same group appears rather conservative; there remains a question about the cross section values near the threshold. For transitions between different-l levels within the same multiplicity and same n, a semi-empirical formula based on the Born cross section gives a good agreement with experiment. Proton impacts are also considered for these transitions. We compare the new cross sections with those used in the original version. These cross sections for transitions starting from the metastable levels are fitted by analytical formulas and the parameter values are given. We also give parameter values for the excitation rate coefficient for these transitions as well as for transitions starting from the ground state. With all the above revisions incorporated into the CR model code, we have calculated the energy loss rates and the line intensity ratios for the purpose of plasma diagnostics, where the effect of a magnetic field is noted. The calculated population distribution over excited levels are compared with experiment, and a tentative conclusion is drawn concerning the excitation cross section from the metastable level. (author)

A heterologous prime-boost Ebola virus vaccine regimen induces durable neutralizing antibody response and prevents Ebola virus-like particle entry in mice.

Science.gov (United States)

Chen, Tan; Li, Dapeng; Song, Yufeng; Yang, Xi; Liu, Qingwei; Jin, Xia; Zhou, Dongming; Huang, Zhong

2017-09-01

Ebola virus (EBOV) is one of the most virulent pathogens known to humans. Neutralizing antibodies play a major role in the protection against EBOV infections. Thus, an EBOV vaccine capable of inducing a long-lasting neutralizing antibody response is highly desirable. We report here that a heterologous prime-boost vaccine regimen can elicit durable EBOV-neutralizing antibody response in mice. A chimpanzee serotype 7 adenovirus expressing EBOV GP (denoted AdC7-GP) was generated and used for priming. A truncated version of EBOV GP1 protein (denoted GP1t) was produced at high levels in Drosophila S2 cells and used for boosting. Mouse immunization studies showed that the AdC7-GP prime/GP1t boost vaccine regimen was more potent in eliciting neutralizing antibodies than either the AdC7-GP or GP1t alone. Neutralizing antibodies induced by the heterologous prime-boost regimen sustained at high titers for at least 18 weeks after immunization. Significantly, in vivo challenge studies revealed that the entry of reporter EBOV-like particles was efficiently blocked in mice receiving the heterologous prime-boost regimen even at 18 weeks after the final dose of immunization. These results suggest that this novel AdC7-GP prime/GP1t boost regimen represents an EBOV vaccine approach capable of establishing long-term protection, and therefore warrants further development. Copyright © 2017 Elsevier B.V. All rights reserved.

Specific gene mutations induced by heavy ions

International Nuclear Information System (INIS)

Freeling, M.; Karoly, C.W.; Cheng, D.S.K.

1980-01-01

This report summarizes our heavy-ion research rationale, progress, and plans for the near future. The major project involves selecting a group of maize Adh1 mutants induced by heavy ions and correlating their altered behavior with altered DNA nucleotide sequences and sequence arrangements. This research requires merging the techniques of classical genetics and recombinant DNA technology. Our secondary projects involve (1) the use of the Adh gene in the fruit fly, Drosophila melanogaster, as a second system with which to quantify the sort of specific gene mutants induced by heavy ions as compared to x rays, and (2) the development of a maize Adh1 pollen in situ monitor for environmental mutagens

Nuclear fission and neutron-induced fission cross-sections

Energy Technology Data Exchange (ETDEWEB)

James, G.D.; Lynn, J.E.; Michaudon, A.; Rowlands, J.; de Saussure, G.

1981-01-01

A general presentation of current knowledge of the fission process is given with emphasis on the low energy fission of actinide nuclei and neutron induced fission. The need for and the required accuracy of fission cross section data in nuclear energy programs are discussed. A summary is given of the steps involved in fission cross section measurement and the range of available techniques. Methods of fission detection are described with emphasis on energy dependent changed and detector efficiency. Examples of cross section measurements are given and data reduction is discussed. The calculation of fission cross sections is discussed and relevant nuclear theory including the formation and decay of compound nuclei and energy level density is introduced. A description of a practical computation of fission cross sections is given.

Epithelial Cell Gene Expression Induced by Intracellular Staphylococcus aureus

Directory of Open Access Journals (Sweden)

Xianglu Li

2009-01-01

Full Text Available HEp-2 cell monolayers were cocultured with intracellular Staphylococcus aureus, and changes in gene expression were profiled using DNA microarrays. Intracellular S. aureus affected genes involved in cellular stress responses, signal transduction, inflammation, apoptosis, fibrosis, and cholesterol biosynthesis. Transcription of stress response and signal transduction-related genes including atf3, sgk, map2k1, map2k3, arhb, and arhe was increased. In addition, elevated transcription of proinflammatory genes was observed for tnfa, il1b, il6, il8, cxcl1, ccl20, cox2, and pai1. Genes involved in proapoptosis and fibrosis were also affected at transcriptional level by intracellular S. aureus. Notably, intracellular S. aureus induced strong transcriptional down-regulation of several cholesterol biosynthesis genes. These results suggest that epithelial cells respond to intracellular S. aureus by inducing genes affecting immunity and in repairing damage caused by the organism, and are consistent with the possibility that the organism exploits an intracellular environment to subvert host immunity and promote colonization.

Can one distinguish τ-neutrinos from antineutrinos in neutral-current pion production processes?

International Nuclear Information System (INIS)

Hernandez, E.; Nieves, J.; Valverde, M.

2007-01-01

A potential way to distinguish τ-neutrinos from antineutrinos, below the τ-production threshold, but above the pion production one, is presented. It is based on the different behavior of the neutral-current pion production off the nucleon, depending on whether it is induced by neutrinos or antineutrinos. This procedure for distinguishing τ-neutrinos from antineutrinos neither relies on any nuclear model, nor it is affected by any nuclear effect (distortion of the outgoing nucleon waves, etc.). We show that neutrino-antineutrino asymmetries occur both in the totally integrated cross sections and in the pion azimuthal differential distributions. To define the asymmetries for the latter distributions we just rely on Lorentz-invariance. All these asymmetries are independent of the lepton family and can be experimentally measured by using electron or muon neutrinos, due to the lepton family universality of the neutral-current neutrino interaction. Nevertheless and to estimate their size, we have also used the chiral model of [E. Hernandez, J. Nieves, M. Valverde, hep-ph/0701149] at intermediate energies. Results are really significant since the differences between neutrino and antineutrino induced reactions are always large in all physical channels

Identification of GIG1, a GlcNAc-Induced Gene in Candida albicans Needed for Normal Sensitivity to the Chitin Synthase Inhibitor Nikkomycin Z▿§

Science.gov (United States)

Gunasekera, Angelo; Alvarez, Francisco J.; Douglas, Lois M.; Wang, Hong X.; Rosebrock, Adam P.; Konopka, James B.

2010-01-01

The amino sugar N-acetylglucosamine (GlcNAc) is known to be an important structural component of cells from bacteria to humans, but its roles in cell signaling are less well understood. GlcNAc induces two pathways in the human fungal pathogen Candida albicans. One activates cyclic AMP (cAMP) signaling, which stimulates the formation of hyphal cells and the expression of virulence genes, and the other pathway induces genes needed to catabolize GlcNAc. Microarray analysis of gene expression was carried out under four different conditions in order to characterize the transcriptional changes induced by GlcNAc. The most highly induced genes include those that encode a GlcNAc transporter (NGT1) and the GlcNAc catabolic enzymes (HXK1, DAC1, and NAG1). GlcNAc also activated most of the genes whose expression is increased when cells are triggered with other stimuli to form hyphae. Surprisingly, GlcNAc also induced a subset of genes that are regulated by galactose (GAL1, GAL7, and GAL10), which may be due to cross talk between signaling pathways. A novel GlcNAc-induced gene, GIG1, which is not essential for GlcNAc catabolism or the induction of hyphae, was identified. However, a Gig1-green fluorescent protein (GFP) fusion protein was specifically induced by GlcNAc, and not by other sugars. Gig1-GFP localized to the cytoplasm, where GlcNAc metabolism occurs. Significantly, a gig1Δ mutant displayed increased resistance to nikkomycin Z, which inhibits chitin synthase from converting UDP-GlcNAc into cell wall chitin. Gig1 is highly conserved in fungi, especially those that contain GlcNAc catabolic genes. These results implicate Gig1 in GlcNAc metabolism. PMID:20675577

Measurement of high-Q{sup 2} neutral current cross-sections with longitudinally polarised positrons with the ZEUS detector

Energy Technology Data Exchange (ETDEWEB)

Stewart, Trevor P.

2012-07-15

The cross sections for neutral current (NC) deep inelastic scattering (DIS) in e{sup +}p collisions with a longitudinally polarised positron beam are measured at high momentum transfer squared (Q{sup 2}>185 GeV{sup 2}) at the ZEUS detector at HERA. The HERA accelerator provides e{sup {+-}}p collisions at a centre-of-mass energy of 318 GeV, which allows the weak contribution to the NC process to be studied at high Q{sup 2}. The measurements are based on a data sample with an integrated luminosity of 135.5 pb{sup -1} collected with the ZEUS detector in 2006 and 2007. The single differential NC cross sections d{sigma}/dQ{sup 2}, d{sigma}/dx and d{sigma}/dy and the reduced cross section {sigma} are measured. The structure function xF{sub 3} is determined by combining the e{sup +}p NC reduced cross sections with the previously measured e{sup -}p measurements. The interference structure function xF{sub 3}{sup {gamma}Z} is extracted at Q{sup 2}=1500 GeV{sup 2}. The cross-section asymmetry between the positive and negative polarisation of the positron beam is measured and the parity violation effects of the electroweak interaction are observed. The predictions of the Standard Model of particle physics agree well with the measurements. (orig.)

High-energy Neutron-induced Fission Cross Sections of Natural Lead and Bismuth-209

CERN Document Server

Tarrio, D; Carrapico, C; Eleftheriadis, C; Leeb, H; Calvino, F; Herrera-Martinez, A; Savvidis, I; Vlachoudis, V; Haas, B; Koehler, P; Vannini, G; Oshima, M; Le Naour, C; Gramegna, F; Wiescher, M; Pigni, M T; Audouin, L; Mengoni, A; Quesada, J; Becvar, F; Plag, R; Cennini, P; Mosconi, M; Rauscher, T; Couture, A; Capote, R; Sarchiapone, L; Vlastou, R; Domingo-Pardo, C; Dillmann, I; Pavlopoulos, P; Karamanis, D; Krticka, M; Jericha, E; Ferrari, A; Martinez, T; Trubert, D; Oberhummer, H; Karadimos, D; Plompen, A; Isaev, S; Terlizzi, R; Cortes, G; Cox, J; Cano-Ott, D; Pretel, C; Colonna, N; Berthoumieux, E; Vaz, P; Heil, M; Lopes, I; Lampoudis, C; Walter, S; Calviani, M; Gonzalez-Romero, E; Embid-Segura, M; Stephan, C; Igashira, M; Papachristodoulou, C; Aerts, G; Tavora, L; Berthier, B; Rudolf, G; Andrzejewski, J; Villamarin, D; Ferreira-Marques, R; Tain, J L; O'Brien, S; Reifarth, R; Kadi, Y; Neves, F; Poch, A; Kerveno, M; Rubbia, C; Lazano, M; Dahlfors, M; Wisshak, K; Salgado, J; Dridi, W; Ventura, A; Andriamonje, S; Assimakopoulos, P; Santos, C; Voss, F; Ferrant, L; Patronis, N; Chiaveri, E; Guerrero, C; Perrot, L; Vicente, M C; Lindote, A; Praena, J; Baumann, P; Kappeler, F; Rullhusen, P; Furman, W; David, S; Marrone, S; Tassan-Got, L; Gunsig, F; Alvarez-Velarde, F; Massimi, C; Mastinu, P; Pancin, J; Papadopoulos, C; Tagliente, G; Haight, R; Chepel, V; Kossionides, E; Badurek, G; Marganiec, J; Lukic, S; Pavlik, A; Goncalves, I; Duran, I; Alvarez, H; Abbondanno, U; Fujii, K; Milazzo, P M; Moreau, C

2011-01-01

The CERN Neutron Time-Of-Flight (n\\_TOF) facility is well suited to measure small neutron-induced fission cross sections, as those of subactinides. The cross section ratios of (nat)Pb and (209)Bi relative to (235)U and (238)U were measured using PPAC detectors. The fragment coincidence method allows to unambiguously identify the fission events. The present experiment provides the first results for neutron-induced fission up to 1 GeV for (nat)Pb and (209)Bi. A good agreement with previous experimental data below 200 MeV is shown. The comparison with proton-induced fission indicates that the limiting regime where neutron-induced and proton-induced fission reach equal cross section is close to 1 GeV.

Altered Stress-Induced Regulation of Genes in Monocytes in Adults with a History of Childhood Adversity.

Science.gov (United States)

Schwaiger, Marion; Grinberg, Marianna; Moser, Dirk; Zang, Johannes C S; Heinrichs, Markus; Hengstler, Jan G; Rahnenführer, Jörg; Cole, Steve; Kumsta, Robert

2016-09-01

Exposure to serious or traumatic events early in life can lead to persistent alterations in physiological stress response systems, including enhanced cross talk between the neuroendocrine and immune system. These programming effects may be mechanistically involved in mediating the effects of adverse childhood experience on disease risk in adulthood. We investigated hormonal and genome-wide mRNA expression responses in monocytes to acute stress exposure, in a sample of healthy adults (n=30) with a history of early childhood adversity, and a control group (n=30) without trauma experience. The early adversity group showed altered hypothalamus-pituitary-adrenal axis responses to stress, evidenced by lower ACTH and cortisol responses. Analyses of gene expression patterns showed that stress-responsive transcripts were enriched for genes involved in cytokine activity, cytokine-cytokine receptor interaction, chemokine activity, and G-protein coupled receptor binding. Differences between groups in stress-induced regulation of gene transcription were observed for genes involved in steroid binding, hormone activity, and G-protein coupled receptor binding. Transcription factor binding motif analysis showed an increased activity of pro-inflammatory upstream signaling in the early adversity group. We also identified transcripts that were differentially correlated with stress-induced cortisol increases between the groups, enriched for genes involved in cytokine-cytokine receptor interaction and glutamate receptor signaling. We suggest that childhood adversity leads to persistent alterations in transcriptional control of stress-responsive pathways, which-when chronically or repeatedly activated-might predispose individuals to stress-related psychopathology.

Glycation induces formation of amyloid cross-beta structure in albumin.

Science.gov (United States)

Bouma, Barend; Kroon-Batenburg, Loes M J; Wu, Ya-Ping; Brünjes, Bettina; Posthuma, George; Kranenburg, Onno; de Groot, Philip G; Voest, Emile E; Gebbink, Martijn F B G

2003-10-24

Amyloid fibrils are components of proteinaceous plaques that are associated with conformational diseases such as Alzheimer's disease, transmissible spongiform encephalopathies, and familial amyloidosis. Amyloid polypeptides share a specific quarternary structure element known as cross-beta structure. Commonly, fibrillar aggregates are modified by advanced glycation end products (AGE). In addition, AGE formation itself induces protein aggregation. Both amyloid proteins and protein-AGE adducts bind multiligand receptors, such as receptor for AGE, CD36, and scavenger receptors A and B type I, and the serine protease tissue-type plasminogen activator (tPA). Based on these observations, we hypothesized that glycation induces refolding of globular proteins, accompanied by formation of cross-beta structure. Using transmission electron microscopy, we demonstrate here that glycated albumin condensates into fibrous or amorphous aggregates. These aggregates bind to amyloid-specific dyes Congo red and thioflavin T and to tPA. In contrast to globular albumin, glycated albumin contains amino acid residues in beta-sheet conformation, as measured with circular dichroism spectropolarimetry. Moreover, it displays cross-beta structure, as determined with x-ray fiber diffraction. We conclude that glycation induces refolding of initially globular albumin into amyloid fibrils comprising cross-beta structure. This would explain how glycated ligands and amyloid ligands can bind to the same multiligand "cross-beta structure" receptors and to tPA.

Candidate gene identification of ovulation-inducing genes by RNA sequencing with an in vivo assay in zebrafish.

Directory of Open Access Journals (Sweden)

Wanlada Klangnurak

Full Text Available We previously reported the microarray-based selection of three ovulation-related genes in zebrafish. We used a different selection method in this study, RNA sequencing analysis. An additional eight up-regulated candidates were found as specifically up-regulated genes in ovulation-induced samples. Changes in gene expression were confirmed by qPCR analysis. Furthermore, up-regulation prior to ovulation during natural spawning was verified in samples from natural pairing. Gene knock-out zebrafish strains of one of the candidates, the starmaker gene (stm, were established by CRISPR genome editing techniques. Unexpectedly, homozygous mutants were fertile and could spawn eggs. However, a high percentage of unfertilized eggs and abnormal embryos were produced from these homozygous females. The results suggest that the stm gene is necessary for fertilization. In this study, we selected additional ovulation-inducing candidate genes, and a novel function of the stm gene was investigated.

Radiation-induced pulmonary gene expression changes are attenuated by the CTGF antibody Pamrevlumab.

Science.gov (United States)

Sternlicht, Mark D; Wirkner, Ute; Bickelhaupt, Sebastian; Lopez Perez, Ramon; Tietz, Alexandra; Lipson, Kenneth E; Seeley, Todd W; Huber, Peter E

2018-01-18

Fibrosis is a delayed side effect of radiation therapy (RT). Connective tissue growth factor (CTGF) promotes the development of fibrosis in multiple settings, including pulmonary radiation injury. To better understand the cellular interactions involved in RT-induced lung injury and the role of CTGF in these responses, microarray expression profiling was performed on lungs of irradiated and non-irradiated mice, including mice treated with the anti-CTGF antibody pamrevlumab (FG-3019). Between group comparisons (Welch's t-tests) and principal components analyses were performed in Genespring. At the mRNA level, the ability of pamrevlumab to prolong survival and ameliorate RT-induced radiologic, histologic and functional lung deficits was correlated with the reversal of a clear enrichment in mast cell, macrophage, dendritic cell and mesenchymal gene signatures. Cytokine, growth factor and matrix remodeling genes that are likely to contribute to RT pneumonitis and fibrosis were elevated by RT and attenuated by pamrevlumab, and likely contribute to the cross-talk between enriched cell-types in injured lung. CTGF inhibition had a normalizing effect on select cell-types, including immune cells not typically regarded as being regulated by CTGF. These results suggest that interactions between RT-recruited cell-types are critical to maintaining the injured state; that CTGF plays a key role in this process; and that pamrevlumab can ameliorate RT-induced lung injury in mice and may provide therapeutic benefit in other immune and fibrotic disorders.

Detecting the neutral top-pion at e+e- colliders

International Nuclear Information System (INIS)

Wang Xuelei; Yang Yueling; Li Bingzhong

2004-01-01

We investigate some processes of the associated production of a neutral top-pion Π t 0 with a pair of fermions (e + e - →ff-barΠ t 0 ) in the context of top-color-assisted technicolor (TC2) theory in the future e + e - colliders. The studies show that the largest cross sections of the processes e + e - →f ' f ' Π t 0 (f ' =u,d,c,s,μ,τ) could only reach the level of 0.01 fb; we can hardly detect a neutral top-pion through these processes. For the processes e + e - →e + e - Π t 0 , e + e - →tt-barΠ t 0 , and e + e - →bb-barΠ t 0 , the cross sections of these processes are at the level of a few fb for the favorable parameters, and a few tens, even hundreds, of neutral top-pion events can be produced at future e + e - colliders each year through these processes. With the clean background of the flavor-changing tc-bar channel, the top-pion events can possibly be detected at the planned high luminosity e + e - colliders. Therefore, such neutral top-pion production processes provide a useful way to detect a neutral top-pion and test the TC2 model directly

Molecular Characterization of a stress-induced NAC Gene ...

Indian Academy of Sciences (India)

lenovo

1Cotton Research Center, Shandong Academy of Agricultural Sciences, Jinan 250100, China. 2College of Life ... Running title: GhSNAC3 gene in Cotton ... Quantitative RT-PCR analysis indicated that GhSNAC3 was induced by high salinity, drought ..... simple and general method for transferring genes into plants. Science ...

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

Science.gov (United States)

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

2015-08-01

Serum was analyzed from 146 healthy adult volunteers in eastern Africa to evaluate measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb) prevalence and potency. MV plaque reduction neutralization test (PRNT) results indicated that all sera were positive for MV nAbs. Furthermore, the 50% neutralizing dose (ND50) for the majority of sera corresponded to antibody titers induced by MV vaccination. CDV nAbs titers were low and generally were detected in sera with high MV nAb titers. A mutant CDV was generated that was less sensitive to neutralization by human serum. The mutant virus genome had 10 nucleotide substitutions, which coded for single amino acid substitutions in the fusion (F) and hemagglutinin (H) glycoproteins and two substitutions in the large polymerase (L) protein. The H substitution occurred in a conserved region involved in receptor interactions among morbilliviruses, implying that this region is a target for cross-reactive neutralizing antibodies. Copyright © 2015 Elsevier Inc. All rights reserved.

Measurement of neutral current deep inelastic e{sup +}p scattering cross sections with longitudinally polarized positrons with ZEUS at HERA

Energy Technology Data Exchange (ETDEWEB)

Wlasenko, Michal

2009-05-15

Measurements of neutral current deep inelastic scattering of protons colliding with longitudinally polarized positrons, performed with data recorded in years 2006 and 2007 with the ZEUS detector, corresponding to an integrated luminosity of L=113.3 pb{sup -1}, are presented. The single-differential cross sections d{sigma}/dQ{sup 2}, d{sigma}/dx, d{sigma}/dy and the double-differential reduced cross section {sigma} were measured in the kinematic region of 185

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

Directory of Open Access Journals (Sweden)

Johannes S Gach

Full Text Available The majority of potent and broadly neutralizing antibodies against HIV-1 have been isolated from untreated patients with acute or chronic infection. To assess the extent of HIV-1 specific antibody response and neutralization after many years of virologic suppression from potent combination ART, we examined antibody binding titers and neutralization of 51 patients with chronic HIV-1 infection on suppressive ART for at least three years. In this cross-sectional analysis, we found high antibody titers against gp120, gp41, and the membrane proximal external region (MPER in 59%, 43%, and 27% of patients, respectively. We observed significantly higher endpoint binding titers for gp120 and gp41 for patients with >10 compared to ≤ 10 years of detectable HIV RNA. Additionally, we observed higher median gp120 and gp41 antibody titers in patients with HIV RNA 10 years of detectable HIV RNA (8/20 [40.0%] versus 3/31 [9.7%] for ≤ 10 years, p = 0.02 and a trend toward greater neutralization in patients with ≤ 5 years of HIV RNA 5 years, p = 0.08. All patients with neutralizing activity mediated successful phagocytosis of VLPs by THP-1 cells after antibody opsonization. Our findings of highly specific antibodies to several structural epitopes of HIV-1 with antibody effector functions and neutralizing activity after long-term suppressive ART, suggest continuous antigenic stimulation and evolution of HIV-specific antibody response occurs before and after suppression with ART. These patients, particularly those with slower HIV progression and more time with detectable viremia prior to initiation of suppressive ART, are a promising population to identify and further study functional antibodies against HIV-1.

Evaluation of smallpox vaccines using variola neutralization.

Science.gov (United States)

Damon, Inger K; Davidson, Whitni B; Hughes, Christine M; Olson, Victoria A; Smith, Scott K; Holman, Robert C; Frey, Sharon E; Newman, Frances; Belshe, Robert B; Yan, Lihan; Karem, Kevin

2009-08-01

The search for a 'third'-generation smallpox vaccine has resulted in the development and characterization of several vaccine candidates. A significant barrier to acceptance is the absence of challenge models showing induction of correlates of protective immunity against variola virus. In this light, virus neutralization provides one of few experimental methods to show specific 'in vitro' activity of vaccines against variola virus. Here, we provide characterization of the ability of a modified vaccinia virus Ankara vaccine to induce variola virus-neutralizing antibodies, and we provide comparison with the neutralization elicited by standard Dryvax vaccination.

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.

Concurrent synthesis and release of nod-gene-inducing flavonoids from alfalfa roots

International Nuclear Information System (INIS)

Maxwell, C.A.; Phillips, D.A.

1990-01-01

Flavonoid signals from alfalfa (Medicago sativa L.) induce transcription of nodulation (nod) genes in Rhizobium meliloti. Alfalfa roots release three major nod-gene inducers: 4',7-dihydroxyflavanone, 4',7-dihydroxyflavone, and 4,4'-dihydroxy-2'-methoxychalcone. The objective of the present study was to define temporal relationships between synthesis and exudation for those flavonoids. Requirements for concurrent flavonoid biosynthesis were assessed by treating roots of intact alfalfa seedlings with [U- 14 C]-L-phenylalanine in the presence or absence of the phenylalanine ammonia-lyase inhibitor L-2-aminoxy-3-phenylpropionic acid (AOPP). In the absence of AOPP, each of the three flavonoids in exudates contained 14 C. In the presence of AOPP, 14 C labeling and release of all the exuded nod-gene inducers were reduced significantly. AOPP inhibited labeling and release of the strongest nod-gene inducer, methoxychalcone, by more than 90%. The release process responsible for exudation of nod-gene inducers appears to be specific rather than a general phenomenon such as a sloughing off of cells during root growth

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.

Photorhabdus luminescens genes induced upon insect infection

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Jung Kirsten

2008-05-01

Full Text Available Abstract Background Photorhabdus luminescens is a Gram-negative luminescent enterobacterium and a symbiote to soil nematodes belonging to the species Heterorhabditis bacteriophora. P.luminescens is simultaneously highly pathogenic to insects. This bacterium exhibits a complex life cycle, including one symbiotic stage characterized by colonization of the upper nematode gut, and a pathogenic stage, characterized by release from the nematode into the hemocoel of insect larvae, resulting in rapid insect death caused by bacterial toxins. P. luminescens appears to sense and adapt to the novel host environment upon changing hosts, which facilitates the production of factors involved in survival within the host, host-killing, and -exploitation. Results A differential fluorescence induction (DFI approach was applied to identify genes that are up-regulated in the bacterium after infection of the insect host Galleria mellonella. For this purpose, a P. luminescens promoter-trap library utilizing the mCherry fluorophore as a reporter was constructed, and approximately 13,000 clones were screened for fluorescence induction in the presence of a G. mellonella larvae homogenate. Since P. luminescens has a variety of regulators that potentially sense chemical molecules, like hormones, the screen for up-regulated genes or operons was performed in vitro, excluding physicochemical signals like oxygen, temperature or osmolarity as variables. Clones (18 were obtained exhibiting at least 2.5-fold induced fluorescence and regarded as specific responders to insect homogenate. In combination with a bioinformatics approach, sequence motifs were identified in these DNA-fragments that are similar to 29 different promoters within the P. luminescens genome. By cloning each of the predicted promoters upstream of the reporter gene, induction was verified for 27 promoters in vitro, and for 24 promoters in viable G. mellonella larvae. Among the validated promoters are some known

Neutral currents, supernovae neutrinos, and nucleosynthesis

International Nuclear Information System (INIS)

Haxton, W.C.

1988-01-01

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

Adaptive genetic markers discriminate migratory runs of Chinook salmon (Oncorhynchus tshawytscha) amid continued gene flow.

Science.gov (United States)

O'Malley, Kathleen G; Jacobson, Dave P; Kurth, Ryon; Dill, Allen J; Banks, Michael A

2013-12-01

Neutral genetic markers are routinely used to define distinct units within species that warrant discrete management. Human-induced changes to gene flow however may reduce the power of such an approach. We tested the efficiency of adaptive versus neutral genetic markers in differentiating temporally divergent migratory runs of Chinook salmon (Oncorhynchus tshawytscha) amid high gene flow owing to artificial propagation and habitat alteration. We compared seven putative migration timing genes to ten microsatellite loci in delineating three migratory groups of Chinook in the Feather River, CA: offspring of fall-run hatchery broodstock that returned as adults to freshwater in fall (fall run), spring-run offspring that returned in spring (spring run), and fall-run offspring that returned in spring (FRS). We found evidence for significant differentiation between the fall and federally listed threatened spring groups based on divergence at three circadian clock genes (OtsClock1b, OmyFbxw11, and Omy1009UW), but not neutral markers. We thus demonstrate the importance of genetic marker choice in resolving complex life history types. These findings directly impact conservation management strategies and add to previous evidence from Pacific and Atlantic salmon indicating that circadian clock genes influence migration timing.

Identification of a variant antigenic neutralizing epitope in hypervariable region 1 of avian leukosis virus subgroup J.

Science.gov (United States)

Hou, Minbo; Zhou, Defang; Li, Gen; Guo, Huijun; Liu, Jianzhu; Wang, Guihua; Zheng, Qiankun; Cheng, Ziqiang

2016-03-08

Avian leukosis virus subgroup J (ALV-J) is a hypervariable oncogenic retrovirus that causes great economic loss in poultry. Antigenic variations in the variable regions make the development of an effective vaccine a challenging task. In the present study, we identified a variant antigenic neutralizing epitope using reverse vaccinology methods. First, we predicted the B-cell epitopes in gp85 gene of ALV-J strains by DNAman and bioinformatics. Fourteen candidate epitopes were selected and linked in tandem with glycines or serines as a multi-epitope gene. The expressed protein of multi-epitope gene can induce high-titer antibody that can recognize nature ALV-J and neutralize the infectivity of ALV-J strains. Next, we identified a high effective epitope using eight overlapping fragments of gp85 gene reacting with mAb 2D5 and anti-multi-epitope sera. The identified epitope contained one of the predicted epitopes and localized in hyervariable region 1 (hr1), indicating a variant epitope. To better understand if the variants of the epitope have a good antigenicity, we synthesized four variants to react with mAb 2D5 and anti-ALV-J sera. The result showed that all variants could react with the two kinds of antibodies though they showed different antigenicity, while could not react with ALV-J negative sera. Thus, the variant antigenic neutralizing epitope was determined as 137-LRDFIA/E/TKWKS/GDDL/HLIRPYVNQS-158. The result shows a potential use of this variant epitopes as a novel multi-epitope vaccine against ALV-J in poultry. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Quantification of Lyssavirus-Neutralizing Antibodies Using Vesicular Stomatitis Virus Pseudotype Particles.

Science.gov (United States)

Moeschler, Sarah; Locher, Samira; Conzelmann, Karl-Klaus; Krämer, Beate; Zimmer, Gert

2016-09-16

Rabies is a highly fatal zoonotic disease which is primarily caused by rabies virus (RABV) although other members of the genus Lyssavirus can cause rabies as well. As yet, 14 serologically and genetically diverse lyssaviruses have been identified, mostly in bats. To assess the quality of rabies vaccines and immunoglobulin preparations, virus neutralization tests with live RABV are performed in accordance with enhanced biosafety standards. In the present work, a novel neutralization test is presented which takes advantage of a modified vesicular stomatitis virus (VSV) from which the glycoprotein G gene has been deleted and replaced by reporter genes. This single-cycle virus was trans-complemented with RABV envelope glycoprotein. Neutralization of this pseudotype virus with RABV reference serum or immune sera from vaccinated mice showed a strong correlation with the rapid fluorescent focus inhibition test (RFFIT). Importantly, pseudotype viruses containing the envelope glycoproteins of other lyssaviruses were neutralized by reference serum to a significantly lesser extent or were not neutralized at all. Taken together, a pseudotype virus system has been successfully developed which allows the safe, fast, and sensitive detection of neutralizing antibodies directed against different lyssaviruses.

Quantification of Lyssavirus-Neutralizing Antibodies Using Vesicular Stomatitis Virus Pseudotype Particles

Directory of Open Access Journals (Sweden)

Sarah Moeschler

2016-09-01

Full Text Available Rabies is a highly fatal zoonotic disease which is primarily caused by rabies virus (RABV although other members of the genus Lyssavirus can cause rabies as well. As yet, 14 serologically and genetically diverse lyssaviruses have been identified, mostly in bats. To assess the quality of rabies vaccines and immunoglobulin preparations, virus neutralization tests with live RABV are performed in accordance with enhanced biosafety standards. In the present work, a novel neutralization test is presented which takes advantage of a modified vesicular stomatitis virus (VSV from which the glycoprotein G gene has been deleted and replaced by reporter genes. This single-cycle virus was trans-complemented with RABV envelope glycoprotein. Neutralization of this pseudotype virus with RABV reference serum or immune sera from vaccinated mice showed a strong correlation with the rapid fluorescent focus inhibition test (RFFIT. Importantly, pseudotype viruses containing the envelope glycoproteins of other lyssaviruses were neutralized by reference serum to a significantly lesser extent or were not neutralized at all. Taken together, a pseudotype virus system has been successfully developed which allows the safe, fast, and sensitive detection of neutralizing antibodies directed against different lyssaviruses.

TGF-β-induced IκB-ζ controls Foxp3 gene expression

Energy Technology Data Exchange (ETDEWEB)

MaruYama, Takashi, E-mail: ta-maru@umin.ac.jp [Laboratory of Cell Recognition and Response, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980-8578 (Japan); School of Medicine, Gifu University, Gifu 501-1194 (Japan)

2015-08-21

Inhibitor of kappa B (IκB)-ζ, a member of the nuclear IκB family of proteins, is induced by the transforming growth factor (TGF)-β signaling pathway and plays a pivotal role in maintaining the balance of T helper (Th) cell subsets. IκB-ζ deficiency results in reduced percentages of Th17 cells and increased percentages of Th1 cells. In this study, the effects of IκB-ζ deficiency on T-cell subsets were examined further. The data showed that IκB-ζ-deficient T cells had a high capacity for generation of regulatory T cells (Tregs) when T cells were cultured under TGF-β stimulation in the presence of cytokine-neutralizing antibodies. Mechanistically, IκB-ζ itself negatively regulated activation of the Foxp3 promoter in a nuclear factor of kappaB-dependent manner. Thus, this study showed that IκB-ζ controlled Treg differentiation. - Highlights: • IκB-ζ-deficient T cells exhibited increased generation of Foxp3{sup +} Tregs. • IκB-ζ played a key role in Foxp3 gene expression. • Retroviral overexpression of IκB-ζ was achieved in T cells.

TGF-β-induced IκB-ζ controls Foxp3 gene expression

International Nuclear Information System (INIS)

MaruYama, Takashi

2015-01-01

Inhibitor of kappa B (IκB)-ζ, a member of the nuclear IκB family of proteins, is induced by the transforming growth factor (TGF)-β signaling pathway and plays a pivotal role in maintaining the balance of T helper (Th) cell subsets. IκB-ζ deficiency results in reduced percentages of Th17 cells and increased percentages of Th1 cells. In this study, the effects of IκB-ζ deficiency on T-cell subsets were examined further. The data showed that IκB-ζ-deficient T cells had a high capacity for generation of regulatory T cells (Tregs) when T cells were cultured under TGF-β stimulation in the presence of cytokine-neutralizing antibodies. Mechanistically, IκB-ζ itself negatively regulated activation of the Foxp3 promoter in a nuclear factor of kappaB-dependent manner. Thus, this study showed that IκB-ζ controlled Treg differentiation. - Highlights: • IκB-ζ-deficient T cells exhibited increased generation of Foxp3 + Tregs. • IκB-ζ played a key role in Foxp3 gene expression. • Retroviral overexpression of IκB-ζ was achieved in T cells

Identification of salt-stress induced differentially expressed genes in ...

African Journals Online (AJOL)

Identification of salt-stress induced differentially expressed genes in barley leaves using the annealingcontrol- primer-based GeneFishing technique. S Lee, K Lee, K Kim, GJ Choi, SH Yoon, HC Ji, S Seo, YC Lim, N Ahsan ...

Soil microbial community responses to acid exposure and neutralization treatment.

Science.gov (United States)

Shin, Doyun; Lee, Yunho; Park, Jeonghyun; Moon, Hee Sun; Hyun, Sung Pil

2017-12-15

Changes in microbial community induced by acid shock were studied in the context of potential release of acids to the environment due to chemical accidents. The responses of microbial communities in three different soils to the exposure to sulfuric or hydrofluoric acid and to the subsequent neutralization treatment were investigated as functions of acid concentration and exposure time by using 16S-rRNA gene based pyrosequencing and DGGE (Denaturing Gradient Gel Electrophoresis). Measurements of soil pH and dissolved ion concentrations revealed that the added acids were neutralized to different degrees, depending on the mineral composition and soil texture. Hydrofluoric acid was more effectively neutralized by the soils, compared with sulfuric acid at the same normality. Gram-negative ß-Proteobacteria were shown to be the most acid-sensitive bacterial strains, while spore-forming Gram-positive Bacilli were the most acid-tolerant. The results of this study suggest that the Gram-positive to Gram-negative bacterial ratio may serve as an effective bio-indicator in assessing the impact of the acid shock on the microbial community. Neutralization treatments helped recover the ratio closer to their original values. The findings of this study show that microbial community changes as well as geochemical changes such as pH and dissolved ion concentrations need to be considered in estimating the impact of an acid spill, in selecting an optimal remediation strategy, and in deciding when to end remedial actions at the acid spill impacted site. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cross-pollination of research findings, although uncommon, may accelerate discovery of human disease genes

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Duda Marlena

2012-11-01

Full Text Available Abstract Background Technological leaps in genome sequencing have resulted in a surge in discovery of human disease genes. These discoveries have led to increased clarity on the molecular pathology of disease and have also demonstrated considerable overlap in the genetic roots of human diseases. In light of this large genetic overlap, we tested whether cross-disease research approaches lead to faster, more impactful discoveries. Methods We leveraged several gene-disease association databases to calculate a Mutual Citation Score (MCS for 10,853 pairs of genetically related diseases to measure the frequency of cross-citation between research fields. To assess the importance of cooperative research, we computed an Individual Disease Cooperation Score (ICS and the average publication rate for each disease. Results For all disease pairs with one gene in common, we found that the degree of genetic overlap was a poor predictor of cooperation (r2=0.3198 and that the vast majority of disease pairs (89.56% never cited previous discoveries of the same gene in a different disease, irrespective of the level of genetic similarity between the diseases. A fraction (0.25% of the pairs demonstrated cross-citation in greater than 5% of their published genetic discoveries and 0.037% cross-referenced discoveries more than 10% of the time. We found strong positive correlations between ICS and publication rate (r2=0.7931, and an even stronger correlation between the publication rate and the number of cross-referenced diseases (r2=0.8585. These results suggested that cross-disease research may have the potential to yield novel discoveries at a faster pace than singular disease research. Conclusions Our findings suggest that the frequency of cross-disease study is low despite the high level of genetic similarity among many human diseases, and that collaborative methods may accelerate and increase the impact of new genetic discoveries. Until we have a better

A novel mutation in PNPLA2 leading to neutral lipid storage disease with myopathy.

Science.gov (United States)

Ash, Daniel B; Papadimitriou, Dimitra; Hays, Arthur P; Dimauro, Salvatore; Hirano, Michio

2012-09-01

Mutations in PNPLA2, a gene encoding adipose triglyceride lipase, lead to neutral lipid storage disease with myopathy. To report the clinical and molecular features of a case of neutral lipid storage disease with myopathy resulting from a novel mutation in PNPLA2. Case report. University hospital. A 65-year-old man with progressive muscle weakness and high serum creatine kinase levels. Direct sequencing of the PNPLA2 gene. Identification of a novel homozygous mutation in the patient's PNPLA2 gene confirmed the suspected diagnosis of neutral lipid storage disease with myopathy. Screening of the PNPLA2 gene should be considered for patients presenting with high levels of creatine kinase, progressive muscle weakness, and systemic lipid accumulation. The presence of Jordans anomaly can be a strong diagnostic clue.

Study on radiation-inducible genes

Energy Technology Data Exchange (ETDEWEB)

Lim, Sang Yong; Kim, Dong Ho; Joe, Min Ho; Song, Hyu Npa

2012-01-15

Transcription of previously identified radiation-inducible genes, uscA and cyoA, was examined responding to radiation. The putative promoter regions of both genes were cloned into pRS415 vector containing lacZ, and the core promoter region necessary for radiation response were determined through promoter deletion method. To investigate the role of uscA, which is assumed to be small RNA related with radiation response, a deletion mutant strain of uscA was constructed. However, uscA deletion did not affect bacterial survival against radiation exposure. The use of bacteria as anticancer agents has attracted interest. In this study, we tried to develop tumor targeting bacteria in which the radiation-inducible promoter activate a transgene encoding a cytotoxic protein. For outward secretion of anticancer protein produced inside bacteria, the N-terminal 140 amino acid of SspH1 was found to function as a secretion signal peptide. To create an attenuated tumor-targeting bacteria, Salmonella ptsI mutant strain was constructed, and we found that its virulence decreased. Finally, the tumor-targeting ability of ptsI mutant was verified by the use of in-vivo imaging analysis.

Study on radiation-inducible genes

International Nuclear Information System (INIS)

Lim, Sang Yong; Kim, Dong Ho; Joe, Min Ho; Song, Hyu Npa

2012-01-01

Transcription of previously identified radiation-inducible genes, uscA and cyoA, was examined responding to radiation. The putative promoter regions of both genes were cloned into pRS415 vector containing lacZ, and the core promoter region necessary for radiation response were determined through promoter deletion method. To investigate the role of uscA, which is assumed to be small RNA related with radiation response, a deletion mutant strain of uscA was constructed. However, uscA deletion did not affect bacterial survival against radiation exposure. The use of bacteria as anticancer agents has attracted interest. In this study, we tried to develop tumor targeting bacteria in which the radiation-inducible promoter activate a transgene encoding a cytotoxic protein. For outward secretion of anticancer protein produced inside bacteria, the N-terminal 140 amino acid of SspH1 was found to function as a secretion signal peptide. To create an attenuated tumor-targeting bacteria, Salmonella ptsI mutant strain was constructed, and we found that its virulence decreased. Finally, the tumor-targeting ability of ptsI mutant was verified by the use of in-vivo imaging analysis

Compilation of electron collision excitation cross sections for neutral argon; Compilacion de resultados de secciones eficaces de excitacion para niveles del Argon neutro

Energy Technology Data Exchange (ETDEWEB)

Blanco, F

1993-07-01

The present work presents a compilation and critical analysis of the available data on electron collision excitation cross sections for neutral Argon levels. This study includes: 1.- A detailed description in intermediate coupling for all the levels belonging the 20 configurations 3p5 ns (n=4to 12), np(n=4to8) and nd(n=3to8)of neutral Argon. 2.- Calculation of the electron collision excitation cross sections in Born and Born-Oppenheimer-Ochkur approximations for all the levels in the 14 configurations 3p5 ns (n=4 to 7), np (n=4 to 7) and nd (n=3 to 8). 3.- comparison and discussion of the compiled data. These are the experimental and theoretical values available from the literature, and those from this work. 4.- Analysis of the regularities and systematic behaviors in order to determine which values can be considered more reliable. It is show that the concept of one electron cross section results quite useful for this purpose. In some cases it has been possible to obtain in this way approximate analytical expressions interpolating the experimental data. 5.- All the experimental and theoretical values studied are graphically presented and compared. 6.- The last part of the work includes a listing of several general purpose programs for Atomic Physics calculations developed for this work. (Author) 35 refs.

Tamoxifen-elicited uterotrophy: cross-species and cross-ligand analysis of the gene expression program

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Forgacs Agnes L

2009-04-01

Full Text Available Abstract Background Tamoxifen (TAM is a well characterized breast cancer drug and selective estrogen receptor modulator (SERM which also has been associated with a small increase in risk for uterine cancers. TAM's partial agonist activation of estrogen receptor has been characterized for specific gene promoters but not at the genomic level in vivo.Furthermore, reducing uncertainties associated with cross-species extrapolations of pharmaco- and toxicogenomic data remains a formidable challenge. Results A comparative ligand and species analysis approach was conducted to systematically assess the physiological, morphological and uterine gene expression alterations elicited across time by TAM and ethynylestradiol (EE in immature ovariectomized Sprague-Dawley rats and C57BL/6 mice. Differential gene expression was evaluated using custom cDNA microarrays, and the data was compared to identify conserved and divergent responses. 902 genes were differentially regulated in all four studies, 398 of which exhibit identical temporal expression patterns. Conclusion Comparative analysis of EE and TAM differentially expressed gene lists suggest TAM regulates no unique uterine genes that are conserved in the rat and mouse. This demonstrates that the partial agonist activities of TAM extend to molecular targets in regulating only a subset of EE-responsive genes. Ligand-conserved, species-divergent expression of carbonic anhydrase 2 was observed in the microarray data and confirmed by real time PCR. The identification of comparable temporal phenotypic responses linked to related gene expression profiles demonstrates that systematic comparative genomic assessments can elucidate important conserved and divergent mechanisms in rodent estrogen signalling during uterine proliferation.

Identification and Application of Neutralizing Epitopes of Human Adenovirus Type 55 Hexon Protein

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Xingui Tian

2015-10-01

Full Text Available Human adenovirus type 55 (HAdV55 is a newly identified re-emergent acute respiratory disease (ARD pathogen with a proposed recombination of hexon gene between HAdV11 and HAdV14 strains. The identification of the neutralizing epitopes is important for the surveillance and vaccine development against HAdV55 infection. In this study, four type-specific epitope peptides of HAdV55 hexon protein, A55R1 (residues 138 to 152, A55R2 (residues 179 to 187, A55R4 (residues 247 to 259 and A55R7 (residues 429 to 443, were predicted by multiple sequence alignment and homology modeling methods, and then confirmed with synthetic peptides by enzyme-linked immunosorbent assay (ELISA and neutralization tests (NT. Finally, the A55R2 was incorporated into human adenoviruses 3 (HAdV3 and a chimeric adenovirus rAd3A55R2 was successfully obtained. The chimeric rAd3A55R2 could induce neutralizing antibodies against both HAdV3 and HAdV55. This current study will contribute to the development of novel adenovirus vaccine candidate and adenovirus structural analysis.

Identification and Application of Neutralizing Epitopes of Human Adenovirus Type 55 Hexon Protein

Science.gov (United States)

Tian, Xingui; Ma, Qiang; Jiang, Zaixue; Huang, Junfeng; Liu, Qian; Lu, Xiaomei; Luo, Qingming; Zhou, Rong

2015-01-01

Human adenovirus type 55 (HAdV55) is a newly identified re-emergent acute respiratory disease (ARD) pathogen with a proposed recombination of hexon gene between HAdV11 and HAdV14 strains. The identification of the neutralizing epitopes is important for the surveillance and vaccine development against HAdV55 infection. In this study, four type-specific epitope peptides of HAdV55 hexon protein, A55R1 (residues 138 to 152), A55R2 (residues 179 to 187), A55R4 (residues 247 to 259) and A55R7 (residues 429 to 443), were predicted by multiple sequence alignment and homology modeling methods, and then confirmed with synthetic peptides by enzyme-linked immunosorbent assay (ELISA) and neutralization tests (NT). Finally, the A55R2 was incorporated into human adenoviruses 3 (HAdV3) and a chimeric adenovirus rAd3A55R2 was successfully obtained. The chimeric rAd3A55R2 could induce neutralizing antibodies against both HAdV3 and HAdV55. This current study will contribute to the development of novel adenovirus vaccine candidate and adenovirus structural analysis. PMID:26516903

UV-induced cross-linking of abscisic acid to binding proteins

International Nuclear Information System (INIS)

Cornelussen, M.H.M.; Karssen, C.M.; Loon, L.C. van

1995-01-01

Conditions for UV-induced cross-linking of abscisic acid (ABA) through its enone chromophore to binding proteins were evaluated. The effects of a UV-light band between 260 and 530 nm on both unconjugated and protein-conjugated ABA, as well as on anti-ABA antibodies as models of ABA-binding proteins were determined. UV irradiation caused both isomerization and photolysis of ABA, but increasing the lower irradiation boundary to 345 nm strongly reduced photolysis and largely prevented isomerization. When conjugated to alkaline phosphatase (AP), ABA remained stable when using either a 320 or a 345 nm filter. At these wavelengths both binding of ABA to antibodies as well as AP enzymatic activity were maintained. UV-induced cross-linking of monoclonal anti-ABA antibodies to immobilized ABA was analysed by immunoassays. Optimal cross-linking was achieved after a 5 min irradiation period at 0°, using a long pass, cut-on filter to quench wavelengths below 290 nm. This cross-linking faithfully reflected cognate binding activity. (author)

Deletion of circadian gene Per1 alleviates acute ethanol-induced hepatotoxicity in mice

International Nuclear Information System (INIS)

Wang, Tao; Yang, Ping; Zhan, Yibei; Xia, Lin; Hua, Zichun; Zhang, Jianfa

2013-01-01

The severity of ethanol-induced liver injury is associated with oxidative stress and lipid accumulation in the liver. Core circadian clock is known to mediate antioxidative enzyme activity and lipid metabolism. However, the link between circadian clock and ethanol-induced hepatotoxicity remains unclear. Here we showed that extents of acute ethanol-induced liver injury and steatosis in mice exhibit circadian variations consistent with hepatic expression of Period (Per) genes. Mice lacking clock gene Per1 displayed less susceptible to ethanol-induced liver injury, as evidenced by lower serum transaminase activity and less severe histopathological changes. Ethanol-induced lipid peroxidation was alleviated in Per1−/− mice. However, Per1 deletion had no effect on antioxidants depletion caused by ethanol administration. Ethanol-induced triglycerides (TG) accumulation in the serum and liver was significantly decreased in Per1−/− mice compared with that in wild-type (WT) mice. Analysis of gene expression in the liver revealed peroxisome proliferators activated receptor-gamma (PPARγ) and its target genes related to TG synthesis are remarkably down-regulated in Per1−/− mice. HepG2 cells were treated with ethanol at 150 mM for 3 days. Per1 overexpression augmented lipid accumulation after treatment with ethanol in HepG2 cells, but had no effect on ethanol-induced oxidative stress. Expression of genes related to lipogenesis, including PPARγ and its target genes, was up-regulated in cells overexpressing Per1. In conclusion, these results indicated that circadian rhythms of ethanol-induced hepatotoxicity are controlled by clock gene Per1, and deletion of Per1 protected mice from ethanol-induced liver injury by decreasing hepatic lipid accumulation

Charging induced emission of neutral atoms from NaCl nanocube corners

International Nuclear Information System (INIS)

Ceresoli, Davide; Zykova-Timan, Tatyana; Tosatti, Erio

2008-01-01

Detachment of neutral cations/anions from solid alkali halides can in principle be provoked by donating/subtracting electrons to the surface of alkali halide crystals, but generally constitutes a very endothermic process. However, the amount of energy required for emission is smaller for atoms located in less favorable positions, such as surface steps and kinks. For a corner ion in an alkali halide cube the binding is the weakest, so it should be easier to remove that atom, once it is neutralized. We carried out first principles density functional calculations and simulations of neutral and charged NaCl nanocubes, to establish the energetics of extraction of neutralized corner ions. Following hole donation (electron removal) we find that detachment of neutral Cl corner atoms will require a limited energy of about 0.8 eV. Conversely, following the donation of an excess electron to the cube, a neutral Na atom is extractable from the corner at the lower cost of about 0.6 eV. Since the cube electron affinity level (close to that a NaCl(100) surface state, which we also determine) is estimated to lie about 1.8 eV below vacuum, the overall energy balance upon donation to the nanocube of a zero-energy electron from vacuum will be exothermic. The atomic and electronic structure of the NaCl(100) surface, and of the nanocube Na and Cl corner vacancies are obtained and analyzed as a byproduct

Rain-induced cross-polarization effects on satellite ...

African Journals Online (AJOL)

Rain-induced cross-polarization effects on satellite telecommunication in some tropical location. ... The PDF file you selected should load here if your Web browser has a PDF reader plug-in installed (for example, a recent version of Adobe Acrobat Reader). If you would like more information about how to print, save, and ...

Structure of the neutral capsular polysaccharide of Acinetobacter baumannii NIPH146 that carries the KL37 capsule gene cluster.

Science.gov (United States)

Arbatsky, Nikolay P; Shneider, Mikhail M; Kenyon, Johanna J; Shashkov, Alexander S; Popova, Anastasiya V; Miroshnikov, Konstantin A; Volozhantsev, Nikolay V; Knirel, Yuriy A

2015-09-02

Capsular polysaccharide (CPS) was isolated from Acinetobacter baumannii NIPH146, and the following structure of branched pentasaccharide repeating unit was established by sugar analyses along with 1D and 2D NMR spectroscopy: In comparison to most other known capsular polysaccharides of A. baumannii, the CPS studied is neutral and lacks any specific monosaccharide component. The synthesis, assembly and export of this structure could be attributed to genes in a novel capsule biosynthesis gene cluster, designated KL37, which was found in the NIPH146 genome. The CPS of A. baumannii NIPH146 shares the α-d-Galp-(1→6)-β-d-Glcp-(1→3)-d-GalpNAc-(1→ trisaccharide fragment with the CPS units of several A. baumannii strains, including ATCC 17978 and LUH 5537 that carry the KL3 and KL22 gene clusters, respectively. KL37 contains two genes for glycosyltransferases that are related to two glycosyltransferase genes present in both KL3 and KL22, and the encoded proteins could be tentatively assigned to linkages between sugars in the CPS repeat. Copyright © 2015 Elsevier Ltd. All rights reserved.

Precision measurement of the cross section of charged-current and neutral current processes at large Q2 at HERA with the polarized-electron beam

International Nuclear Information System (INIS)

Tran, Trong Hieu

2010-03-01

The inclusive cross sections for both charged and neutral current processes have been measured in interactions of longitudinally polarized electrons (positrons) with unpolarized protons using the full data samples collected by H1 at HERA-II. The data taken at a center-of-mass energy of 319 GeV correspond to an integrated luminosity of 149.1 pb -1 and 180.0 pb -1 for e - p and e + p collisions, representing an increase in statistics of a factor of 10 and 2, respectively, over the data from HERA-I. The measured double differential cross sections d 2 σ/dxdQ 2 cover more than two orders of magnitude in both Q 2 , the negative four-momentum transfer squared, up to 30000 GeV 2 , and Bjorken x, down to 0.003. The cross section data are compared to predictions of the Standard Model which is able to provide a good description of the data. The polarization asymmetry as a function of Q 2 is measured with improved precision, confirming the previous observation of P violation effect in neutral current ep scattering at distances down to 10 -18 m. The total cross sections of the charged current process, for Q 2 > 400 GeV 2 and inelasticity y ± beams and different polarization values. Together with the corresponding cross section obtained from the previously published unpolarized data, the polarization dependence of the charged current cross section is measured and found to be in agreement with the Standard Model prediction with the absence of right-handed charged current. The cross sections are combined with previously published data from H1 to obtain the most precise unpolarized measurements. These are used to extract the structure function xF 3 γZ which is sensitive to the valence quark distributions down to low x values. The new cross sections have also been used in a combined electroweak and QCD fit to significantly improve the light quark couplings to the Z-boson than those obtained based on the HERA-I data alone. (orig.)

Cross-correlation cosmography with intensity mapping of the neutral hydrogen 21 cm emission

Science.gov (United States)

Pourtsidou, A.; Bacon, D.; Crittenden, R.

2015-11-01

The cross-correlation of a foreground density field with two different background convergence fields can be used to measure cosmographic distance ratios and constrain dark energy parameters. We investigate the possibility of performing such measurements using a combination of optical galaxy surveys and neutral hydrogen (HI) intensity mapping surveys, with emphasis on the performance of the planned Square Kilometre Array (SKA). Using HI intensity mapping to probe the foreground density tracer field and/or the background source fields has the advantage of excellent redshift resolution and a longer lever arm achieved by using the lensing signal from high redshift background sources. Our results show that, for our best SKA-optical configuration of surveys, a constant equation of state for dark energy can be constrained to ≃8 % for a sky coverage fsky=0.5 and assuming a σ (ΩDE)=0.03 prior for the dark energy density parameter. We also show that using the cosmic microwave background as the second source plane is not competitive, even when considering a COrE-like satellite.

Expression and Association of SCD Gene Polymorphisms and Fatty Acid Compositions in Chicken Cross

Directory of Open Access Journals (Sweden)

A. Furqon

2017-12-01

Full Text Available Stearoyl-CoA desaturase (SCD is an integral membrane protein of endoplasmic reticulum (ER that catalyzes the rate limiting step in the monounsaturated fatty acids from saturated fatty acids. Selection for fatty acids traits based on molecular marker assisted selection is needed to increase a value of chicken meat. This study was designed to analyze expression and associations of SCD gene polymorphisms with fatty acid traits in F2 kampung-broiler chicken cross. A total of 62 F2 kampung-broiler chicken cross (29 males and 33 females were used in this study. Fatty acid traits were measured at 26 weeks of age. Samples were divided into two groups based on fatty acid traits (the highest and the lowest. Primers in exon 2 region were designed from the genomic chicken sequence. The SNP g.37284A>G was detected and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP method was then used to genotype. The expression of SCD gene was analyzed using quantitative real time PCR (qRT-PCR. The result showed that there were three genotypes (AA, AG, and GG found in this study. The SCD|AciI polymorphism was significantly associated with palmitoleic acid (C16:1, fatty acids total and saturated fatty acid in 26 weeks old of F2 kampung-broiler chicken cross (P<0.05. The SCD gene was expressed for polyunsaturated fatty acids in liver tissue in two groups of chickens. In conclusion, the SCD gene could be a candidate gene that affects fatty acids traits in F2 kampung-broiler chicken cross.

Mutant genes in pea breeding

International Nuclear Information System (INIS)

Swiecicki, W.K.

1990-01-01

Full text: Mutations of genes Dpo (dehiscing pods) and A (anthocyanin synthesis) played a role in pea domestication. A number of other genes were important in cultivar development for 3 types of usage (dry seeds, green vegetable types, fodder), e.g. fn, fna, le, p, v, fas and af. New genes (induced and spontaneous), are important for present ideotypes and are registered by the Pisum Genetics Association (PGA). Comparison of a pea variety ideotype with the variation available in gene banks shows that breeders need 'new' features. In mutation induction experiments, genotype, mutagen and method of treatment (e.g. combined or fractionated doses) are varied for broadening the mutation spectrum and selecting more genes of agronomic value. New genes are genetically analysed. In Poland, some mutant varieties with the gene afila were registered, controlling lodging by a shorter stem and a higher number of internodes. Really non-lodging pea varieties could strongly increase seed yield. But the probability of detecting a major gene for lodging resistance is low. Therefore, mutant genes with smaller influence on plant architecture are sought, to combine their effect by crossing. Promising seem to be the genes rogue, reductus and arthritic as well as a number of mutant genes not yet genetically identified. The gene det for terminal inflorescence - similarly to Vicia faba - changes plant development. Utilisation of assimilates and ripening should be better. Improvement of harvest index should give higher seed yield. A number of genes controlling disease resistance are well known (eg. Fw, Fnw, En, mo and sbm). Important in mass screening of resistance are closely linked gene markers. Pea gene banks collect respective lines, but mutants induced in highly productive cultivars would be better. Inducing gene markers sometimes seems to be easier than transfer by crossing. Mutation induction in pea breeding is probably more important because a high number of monogenic features are

Effect of gene-targeted mutation in TNF receptor (p55) on contact hypersensitivity and ultraviolet B-induced immunosuppression

Energy Technology Data Exchange (ETDEWEB)

Kondo, Seiji; Wang, Binghe; Fujisawa, Hiroshi [Univ. of Toronto, Ontario (Canada)] [and others

1995-10-15

Tumor necrosis factor {alpha} (TNF-{alpha}) is a pleiotropic proinflammatory cytokine. TNF-{alpha} has been implicated in the pathogenesis of delayed-type hypersensitivity reactions such as allergic contact hypersensitivity and has been suggested as a mediator of ultraviolet B (UVB)-induced immunosuppression. Conflicting reports, however, exist concerning the effects of TNF-{alpha} on contact hypersensitivity (CHS). To determine the role of TNF-{alpha} in the generation and regulation of CHS, gene-targeted mutant mice lacking TNF-receptor (p55) gene (TNF-R1(-) mice) were treated with dinitrofluorobenzene (DNFB) to induce CHS. TNF-R1(-) mice showed significant hyperresponsiveness in CHS (152.8 {+-} 20.9%, p < 0.025) compared with normal syngeneic mice (C57BL/6) assessed by ear swelling. To determine whether UVB can induce suppression in TNF-R1(-) mice, mice were irradiated on the shaved abdomen with 96 ml/cm{sup 2} UVB and 3 days later they were painted with 0.5% DNFB (sensitization dose), followed 5 days later with 0.2% DNFB to the left ear (challenge dose). Significant suppression of CHS was observed both locally (sensitization on irradiated site) and systemically (sensitization on unirradiated site) in UVB-irradiated TNF-R1(-) mice as well as in normal mice. To rule out possible signaling through p75 TNF-R, the mice were treated with anti-TNF-{alpha} Ab (V1q), which can neutralize any TNF effects through either receptor. V1q had no effect on these phenomena observed in TNF-R1(-) mice. These results suggest that TNF-{alpha} plays a regulatory role in CHS but is not required to induce UVB-mediated immunosuppression. 45 refs., 5 figs.

Direct measurement of the concentration of metastable ions produced from neutral gas particles using laser-induced fluorescence

Science.gov (United States)

Chu, Feng; Skiff, Fred; Berumen, Jorge; Mattingly, Sean; Hood, Ryan

2017-10-01

Extensive information can be obtained on wave-particle interactions and wave fields by direct measurement of perturbed ion distribution functions using laser-induced fluorescence (LIF). For practical purposes, LIF is frequently performed on metastables that are produced from neutral gas particles and existing ions in other electronic states. We numerically simulate the ion velocity distribution measurement and wave-detection process using a Lagrangian model for the LIF signal. The results show that under circumstances where the metastable ion population is coming directly from the ionization of neutrals (as opposed to the excitation of ground-state ions), the velocity distribution will only faithfully represent processes which act on the ion dynamics in a time shorter than the metastable lifetime. Therefore, it is important to know the ratio of metastable population coming from neutrals to that from existing ions to correct the LIF measurements of plasma ion temperature and electrostatic waves. In this paper, we experimentally investigate the ratio of these two populations by externally launching an ion acoustic wave and comparing the wave amplitudes that are measured with LIF and a Langmuir probe using a lock-in amplifier. DE-FG02-99ER54543.

Microarray-based screening of differentially expressed genes in glucocorticoid-induced avascular necrosis

Science.gov (United States)

Huang, Gangyong; Wei, Yibing; Zhao, Guanglei; Xia, Jun; Wang, Siqun; Wu, Jianguo; Chen, Feiyan; Chen, Jie; Shi, Jingshen

2017-01-01

The underlying mechanisms of glucocorticoid (GC)-induced avascular necrosis of the femoral head (ANFH) have yet to be fully understood, in particular the mechanisms associated with the change of gene expression pattern. The present study aimed to identify key genes with a differential expression pattern in GC-induced ANFH. E-MEXP-2751 microarray data were downloaded from the ArrayExpress database. Differentially expressed genes (DEGs) were identified in 5 femoral head samples of steroid-induced ANFH rats compared with 5 placebo-treated rat samples. Gene Ontology (GO) and pathway enrichment analyses were performed upon these DEGs. A total 93 DEGs (46 upregulated and 47 downregulated genes) were identified in GC-induced ANFH samples. These DEGs were enriched in different GO terms and pathways, including chondrocyte differentiation and detection of chemical stimuli. The enrichment map revealed that skeletal system development was interconnected with several other GO terms by gene overlap. The literature mined network analysis revealed that 5 upregulated genes were associated with femoral necrosis, including parathyroid hormone receptor 1 (PTHR1), vitamin D (1,25-Dihydroxyvitamin D3) receptor (VDR), collagen, type II, α1, proprotein convertase subtilisin/kexin type 6 and zinc finger protein 354C (ZFP354C). In addition, ZFP354C and VDR were identified to transcription factors. Furthermore, PTHR1 was revealed to interact with VDR, and α-2-macroglobulin (A2M) interacted with fibronectin 1 (FN1) in the PPI network. PTHR1 may be involved in GC-induced ANFH via interacting with VDR. A2M may also be involved in the development of GC-induced ANFH through interacting with FN1. An improved understanding of the molecular mechanisms underlying GC-induced ANFH may provide novel targets for diagnostics and therapeutic treatment. PMID:28393228

Microarray‑based screening of differentially expressed genes in glucocorticoid‑induced avascular necrosis.

Science.gov (United States)

Huang, Gangyong; Wei, Yibing; Zhao, Guanglei; Xia, Jun; Wang, Siqun; Wu, Jianguo; Chen, Feiyan; Chen, Jie; Shi, Jingshen

2017-06-01

The underlying mechanisms of glucocorticoid (GC)‑induced avascular necrosis of the femoral head (ANFH) have yet to be fully understood, in particular the mechanisms associated with the change of gene expression pattern. The present study aimed to identify key genes with a differential expression pattern in GC‑induced ANFH. E‑MEXP‑2751 microarray data were downloaded from the ArrayExpress database. Differentially expressed genes (DEGs) were identified in 5 femoral head samples of steroid‑induced ANFH rats compared with 5 placebo‑treated rat samples. Gene Ontology (GO) and pathway enrichment analyses were performed upon these DEGs. A total 93 DEGs (46 upregulated and 47 downregulated genes) were identified in GC‑induced ANFH samples. These DEGs were enriched in different GO terms and pathways, including chondrocyte differentiation and detection of chemical stimuli. The enrichment map revealed that skeletal system development was interconnected with several other GO terms by gene overlap. The literature mined network analysis revealed that 5 upregulated genes were associated with femoral necrosis, including parathyroid hormone receptor 1 (PTHR1), vitamin D (1,25‑Dihydroxyvitamin D3) receptor (VDR), collagen, type II, α1, proprotein convertase subtilisin/kexin type 6 and zinc finger protein 354C (ZFP354C). In addition, ZFP354C and VDR were identified to transcription factors. Furthermore, PTHR1 was revealed to interact with VDR, and α‑2‑macroglobulin (A2M) interacted with fibronectin 1 (FN1) in the PPI network. PTHR1 may be involved in GC‑induced ANFH via interacting with VDR. A2M may also be involved in the development of GC‑induced ANFH through interacting with FN1. An improved understanding of the molecular mechanisms underlying GC‑induced ANFH may provide novel targets for diagnostics and therapeutic treatment.

Photosensitized UVA-Induced Cross-Linking between Human DNA Repair and Replication Proteins and DNA Revealed by Proteomic Analysis

Science.gov (United States)

2016-01-01

Long wavelength ultraviolet radiation (UVA, 320–400 nm) interacts with chromophores present in human cells to induce reactive oxygen species (ROS) that damage both DNA and proteins. ROS levels are amplified, and the damaging effects of UVA are exacerbated if the cells are irradiated in the presence of UVA photosensitizers such as 6-thioguanine (6-TG), a strong UVA chromophore that is extensively incorporated into the DNA of dividing cells, or the fluoroquinolone antibiotic ciprofloxacin. Both DNA-embedded 6-TG and ciprofloxacin combine synergistically with UVA to generate high levels of ROS. Importantly, the extensive protein damage induced by these photosensitizer+UVA combinations inhibits DNA repair. DNA is maintained in intimate contact with the proteins that effect its replication, transcription, and repair, and DNA–protein cross-links (DPCs) are a recognized reaction product of ROS. Cross-linking of DNA metabolizing proteins would compromise these processes by introducing physical blocks and by depleting active proteins. We describe a sensitive and statistically rigorous method to analyze DPCs in cultured human cells. Application of this proteomics-based analysis to cells treated with 6-TG+UVA and ciprofloxacin+UVA identified proteins involved in DNA repair, replication, and gene expression among those most vulnerable to cross-linking under oxidative conditions. PMID:27654267

Plasticity-Related Gene Expression During Eszopiclone-Induced Sleep.

Science.gov (United States)

Gerashchenko, Dmitry; Pasumarthi, Ravi K; Kilduff, Thomas S

2017-07-01

Experimental evidence suggests that restorative processes depend on synaptic plasticity changes in the brain during sleep. We used the expression of plasticity-related genes to assess synaptic plasticity changes during drug-induced sleep. We first characterized sleep induced by eszopiclone in mice during baseline conditions and during the recovery from sleep deprivation. We then compared the expression of 18 genes and two miRNAs critically involved in synaptic plasticity in these mice. Gene expression was assessed in the cerebral cortex and hippocampus by the TaqMan reverse transcription polymerase chain reaction and correlated with sleep parameters. Eszopiclone reduced the latency to nonrapid eye movement (NREM) sleep and increased NREM sleep amounts. Eszopiclone had no effect on slow wave activity (SWA) during baseline conditions but reduced the SWA increase during recovery sleep (RS) after sleep deprivation. Gene expression analyses revealed three distinct patterns: (1) four genes had higher expression either in the cortex or hippocampus in the group of mice with increased amounts of wakefulness; (2) a large proportion of plasticity-related genes (7 out of 18 genes) had higher expression during RS in the cortex but not in the hippocampus; and (3) six genes and the two miRNAs showed no significant changes across conditions. Even at a relatively high dose (20 mg/kg), eszopiclone did not reduce the expression of plasticity-related genes during RS period in the cortex. These results indicate that gene expression associated with synaptic plasticity occurs in the cortex in the presence of a hypnotic medication. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Measurement of the neutral to charged current cross section ratios for neutrino and antineutrino interactions on protons

International Nuclear Information System (INIS)

Mobayyen, M.

1986-01-01

The ratios R νp and R a ntiν a ntip of the neutral current to charged current cross sections for neutrino and antineutrino interactions on protons have been measured in BEBC. For a total transverse momentum of the charged hadrons above 0.45 GeV/c and a charged multiplicity of at least 3, it was found that R νp = 0.384±0.024±0.015 and R a ntiν a nti p = 0.338±0.014±0.016, corresponding to a value of sin 2 θ W (M W ) a nti M a nti S of 0.225±0.030. 20 refs

Locating a modifier gene of Ovum mutant through crosses between ...

Indian Academy of Sciences (India)

modifier gene of Om in the B6 background. [Tan J., Song ... should be half the rate of those from the normal crosses,. B6 (+/+) ... the genetic background of the B6 strain. The purpose of .... Smirnov test (P > 0.05) and the reproductive rate of N2.

An alphavirus vector overcomes the presence of neutralizing antibodies and elevated numbers of Tregs to induce immune responses in humans with advanced cancer.

Science.gov (United States)

Morse, Michael A; Hobeika, Amy C; Osada, Takuya; Berglund, Peter; Hubby, Bolyn; Negri, Sarah; Niedzwiecki, Donna; Devi, Gayathri R; Burnett, Bruce K; Clay, Timothy M; Smith, Jonathan; Lyerly, H Kim

2010-09-01

Therapeutic anticancer vaccines are designed to boost patients' immune responses to tumors. One approach is to use a viral vector to deliver antigen to in situ DCs, which then activate tumor-specific T cell and antibody responses. However, vector-specific neutralizing antibodies and suppressive cell populations such as Tregs remain great challenges to the efficacy of this approach. We report here that an alphavirus vector, packaged in virus-like replicon particles (VRP) and capable of efficiently infecting DCs, could be repeatedly administered to patients with metastatic cancer expressing the tumor antigen carcinoembryonic antigen (CEA) and that it overcame high titers of neutralizing antibodies and elevated Treg levels to induce clinically relevant CEA-specific T cell and antibody responses. The CEA-specific antibodies mediated antibody-dependent cellular cytotoxicity against tumor cells from human colorectal cancer metastases. In addition, patients with CEA-specific T cell responses exhibited longer overall survival. These data suggest that VRP-based vectors can overcome the presence of neutralizing antibodies to break tolerance to self antigen and may be clinically useful for immunotherapy in the setting of tumor-induced immunosuppression.

Progress report on the neutral beam radiation hardening study

International Nuclear Information System (INIS)

Lee, J.D.; Condit, R.H.; Hoenig, C.L.; Wilcox, T.P.; Erickson, J.

1978-01-01

A neutral beam injector as presently conceived directly views the plasma it is sustaining. In turn the injector is exposed to the primary fusion neutrons plus secondary neutrons and gammas streaming back up the neutral beam duct. The intent of this work is to examine representative beam lines to see how performance and lifetimes could be affected by this radiation environment and to determine how unacceptable effects could be alleviated. Potential radiation induced problems addressed in this report have been limited to: (1) overheating of cryopanels and insulators, (2) gamma flux induced electrical conductivity increase of insulators, and (3) neutron and gamma fluence induced damage to insulator materials

Editing Transgenic DNA Components by Inducible Gene Replacement in Drosophila melanogaster

Science.gov (United States)

Lin, Chun-Chieh; Potter, Christopher J.

2016-01-01

Gene conversions occur when genomic double-strand DNA breaks (DSBs) trigger unidirectional transfer of genetic material from a homologous template sequence. Exogenous or mutated sequence can be introduced through this homology-directed repair (HDR). We leveraged gene conversion to develop a method for genomic editing of existing transgenic insertions in Drosophila melanogaster. The clustered regularly-interspaced palindromic repeats (CRISPR)/Cas9 system is used in the homology assisted CRISPR knock-in (HACK) method to induce DSBs in a GAL4 transgene, which is repaired by a single-genomic transgenic construct containing GAL4 homologous sequences flanking a T2A-QF2 cassette. With two crosses, this technique converts existing GAL4 lines, including enhancer traps, into functional QF2 expressing lines. We used HACK to convert the most commonly-used GAL4 lines (labeling tissues such as neurons, fat, glia, muscle, and hemocytes) to QF2 lines. We also identified regions of the genome that exhibited differential efficiencies of HDR. The HACK technique is robust and readily adaptable for targeting and replacement of other genomic sequences, and could be a useful approach to repurpose existing transgenes as new genetic reagents become available. PMID:27334272

The Agricultural Antibiotic Carbadox Induces Phage-mediated Gene Transfer in Salmonella

Directory of Open Access Journals (Sweden)

Bradley L. Bearson

2014-02-01

Full Text Available Antibiotics are used for disease therapeutic or preventative effects in humans and animals, as well as for enhanced feed conversion efficiency in livestock. Antibiotics can also cause undesirable effects in microbial populations, including selection for antibiotic resistance, enhanced pathogen invasion, and stimulation of horizontal gene transfer. Carbadox is a veterinary antibiotic used in the U.S. during the starter phase of swine production for improved feed efficiency and control of swine dysentery and bacterial swine enteritis. Carbadox has been shown in vitro to induce phage-encoded Shiga toxin in Shiga toxin-producing Escherichia coli and a phage-like element transferring antibiotic resistance genes in Brachyspira hyodysenteriae, but the effect of carbadox on prophages in other bacteria is unknown. This study examined carbadox exposure on prophage induction and genetic transfer in Salmonella enterica serovar Typhimurium, a human foodborne pathogen that frequently colonizes swine without causing disease. S. Typhimurium LT2 exposed to carbadox induced prophage production, resulting in bacterial cell lysis and release of virions that were visible by electron microscopy. Carbadox induction of phage-mediated gene transfer was confirmed by monitoring the transduction of a sodCIII::neo cassette in the Fels-1 prophage from LT2 to a recipient Salmonella strain. Furthermore, carbadox frequently induced generalized transducing phages in multidrug-resistant phage type DT104 and DT120 isolates, resulting in the transfer of chromosomal and plasmid DNA that included antibiotic resistance genes. Our research indicates that exposure of Salmonella to carbadox induces prophages that can transfer virulence and antibiotic resistance genes to susceptible bacterial hosts. Carbadox-induced, phage-mediated gene transfer could serve as a contributing factor in bacterial evolution during animal production, with prophages being a reservoir for bacterial fitness

Cross-species comparison of biological themes and underlying genes on a global gene expression scale in a mouse model of colorectal liver metastasis and in clinical specimens

Directory of Open Access Journals (Sweden)

Schirmacher Peter

2008-09-01

Full Text Available Abstract Background Invasion-related genes over-expressed by tumor cells as well as by reacting host cells represent promising drug targets for anti-cancer therapy. Such candidate genes need to be validated in appropriate animal models. Results This study examined the suitability of a murine model (CT26/Balb/C of colorectal liver metastasis to represent clinical liver metastasis specimens using a global gene expression approach. Cross-species similarity was examined between pure liver, liver invasion, tumor invasion and pure tumor compartments through overlap of up-regulated genes and gene ontology (GO-based biological themes on the level of single GO-terms and of condensed GO-term families. Three out of four GO-term families were conserved in a compartment-specific way between the species: secondary metabolism (liver, invasion (invasion front, and immune response (invasion front and liver. Among the individual GO-terms over-represented in the invasion compartments in both species were "extracellular matrix", "cell motility", "cell adhesion" and "antigen presentation" indicating that typical invasion related processes are operating in both species. This was reflected on the single gene level as well, as cross-species overlap of potential target genes over-expressed in the combined invasion front compartments reached up to 36.5%. Generally, histopathology and gene expression correlated well as the highest single gene overlap was found to be 44% in syn-compartmental comparisons (liver versus liver whereas cross-compartmental overlaps were much lower (e.g. liver versus tumor: 9.7%. However, single gene overlap was surprisingly high in some cross-compartmental comparisons (e.g. human liver invasion compartment and murine tumor invasion compartment: 9.0% despite little histolopathologic similarity indicating that invasion relevant genes are not necessarily confined to histologically defined compartments. Conclusion In summary, cross

Intermediate heat exchanger tube vibration induced by cross and parallel mixed flow

International Nuclear Information System (INIS)

Kawamura, Koji

1986-01-01

The characteristics of pool type LMFBR intermediate heat exchanger (IHX) tube vibrations induced by cross and parallel mixed flow were basically investigated. Secondary coolant in IHX tube bundle is mixed flow of parallel jit flow along the tube axis through flow holes in baffle plates and cross flow. By changing these two flow rate, flow distributions vary in the tube bundle. Mixed flow also induces vibrations which cause fretting wear and fatigue of tube. It is therefore very important to evaluate the tube vibration characteristics for estimating the tube integrity. The results show that the relationships between tube vibrations and flow distributions in the tube bundle were cleared, and mixed flow induced tube vibration could be evaluated on the base of the characteristics of both parallel and cross flow induced vibration. From these investigations it could be concluded that the characteristics of tube vibration for various flow distributions can be systematically evaluated. (author)

Host-Induced Gene Silencing of Rice Blast Fungus Magnaporthe oryzae Pathogenicity Genes Mediated by the Brome Mosaic Virus.

Science.gov (United States)

Zhu, Lin; Zhu, Jian; Liu, Zhixue; Wang, Zhengyi; Zhou, Cheng; Wang, Hong

2017-09-26

Magnaporthe oryzae is a devastating plant pathogen, which has a detrimental impact on rice production worldwide. Despite its agronomical importance, some newly-emerging pathotypes often overcome race-specific disease resistance rapidly. It is thus desirable to develop a novel strategy for the long-lasting resistance of rice plants to ever-changing fungal pathogens. Brome mosaic virus (BMV)-induced RNA interference (RNAi) has emerged as a useful tool to study host-resistance genes for rice blast protection. Planta-generated silencing of targeted genes inside biotrophic pathogens can be achieved by expression of M. oryzae -derived gene fragments in the BMV-mediated gene silencing system, a technique termed host-induced gene silencing (HIGS). In this study, the effectiveness of BMV-mediated HIGS in M. oryzae was examined by targeting three predicted pathogenicity genes, MoABC1, MoMAC1 and MoPMK1 . Systemic generation of fungal gene-specific small interfering RNA (siRNA) molecules induced by inoculation of BMV viral vectors inhibited disease development and reduced the transcription of targeted fungal genes after subsequent M. oryzae inoculation. Combined introduction of fungal gene sequences in sense and antisense orientation mediated by the BMV silencing vectors significantly enhanced the efficiency of this host-generated trans-specific RNAi, implying that these fungal genes played crucial roles in pathogenicity. Collectively, our results indicated that BMV-HIGS system was a great strategy for protecting host plants against the invasion of pathogenic fungi.

Protective effects of L-selenomethionine on space radiation induced changes in gene expression.

Science.gov (United States)

Stewart, J; Ko, Y-H; Kennedy, A R

2007-06-01

Ionizing radiation can produce adverse biological effects in astronauts during space travel. Of particular concern are the types of radiation from highly energetic, heavy, charged particles known as HZE particles. The aims of our studies are to characterize HZE particle radiation induced biological effects and evaluate the effects of L-selenomethionine (SeM) on these adverse biological effects. In this study, microarray technology was used to measure HZE radiation induced changes in gene expression, as well as to evaluate modulation of these changes by SeM. Human thyroid epithelial cells (HTori-3) were irradiated (1 GeV/n iron ions) in the presence or in the absence of 5 microM SeM. At 6 h post-irradiation, all cells were harvested for RNA isolation. Gene Chip U133Av2 from Affymetrix was used for the analysis of gene expression, and ANOVA and EASE were used for a determination of the genes and biological processes whose differential expression is statistically significant. Results of this microarray study indicate that exposure to small doses of radiation from HZE particles, 10 and 20 cGy from iron ions, induces statistically significant differential expression of 196 and 610 genes, respectively. In the presence of SeM, differential expression of 77 out of 196 genes (exposure to 10 cGy) and 336 out of 610 genes (exposure to 20 cGy) is abolished. In the presence or in the absence of SeM, radiation from HZE particles induces differential expression of genes whose products have roles in the induction of G1/S arrest during the mitotic cell cycle, as well as heat shock proteins. Some of the genes, whose expressions were affected by radiation from HZE particles and were unchanged in irradiated cells treated with SeM, have been shown to have altered expression levels in cancer cells. The conclusions of this report are that radiation from HZE particles can induce differential expression of many genes, some of which are known to play roles in the same processes that have

Are Moral Disengagement, Neutralization Techniques, and Self-Serving Cognitive Distortions the Same? Developing a Unified Scale of Moral Neutralization of Aggression

Directory of Open Access Journals (Sweden)

Denis Ribeaud

2010-12-01

Full Text Available

In Vivo Imaging of Local Gene Expression Induced by Magnetic Hyperthermia

Directory of Open Access Journals (Sweden)

Olivier Sandre

2017-02-01

Full Text Available The present work aims to demonstrate that colloidal dispersions of magnetic iron oxide nanoparticles stabilized with dextran macromolecules placed in an alternating magnetic field can not only produce heat, but also that these particles could be used in vivo for local and noninvasive deposition of a thermal dose sufficient to trigger thermo-induced gene expression. Iron oxide nanoparticles were first characterized in vitro on a bio-inspired setup, and then they were assayed in vivo using a transgenic mouse strain expressing the luciferase reporter gene under transcriptional control of a thermosensitive promoter. Iron oxide nanoparticles dispersions were applied topically on the mouse skin or injected subcutaneously with Matrigel™ to generate so-called pseudotumors. Temperature was monitored continuously with a feedback loop to control the power of the magnetic field generator and to avoid overheating. Thermo-induced luciferase expression was followed by bioluminescence imaging 6 h after heating. We showed that dextran-coated magnetic iron oxide nanoparticle dispersions were able to induce in vivo mild hyperthermia compatible with thermo-induced gene expression in surrounding tissues and without impairing cell viability. These data open new therapeutic perspectives for using mild magnetic hyperthermia as noninvasive modulation of tumor microenvironment by local thermo-induced gene expression or drug release.

A Precision Measurement of the Neutral Pion Lifetime via the Primakoff Effect

Energy Technology Data Exchange (ETDEWEB)

Clinton, Eric [Univ. of Massachusetts, Amherst, MA (United States)

2007-09-01

The neutral pion radiative width has been measured to 8.411 eV ± 1.8% + 1.13% - 1.70% (lifetime = 7.826 ± 0.14 + 0.088 - 0.133 x 10^-17 s) utilizing the Primakoff effect and roughly 4.9 to 5.5 GeV photons at the Thomas Jefferson National Accelerator Facility in Newport News, VA. The Hall B Photon Tagger, the Hall B Pair Spectrometer, a state of the art Hybrid Calorimter enabled precision incident photon energy measurement, photon flux measurement, and neutral pion identification, respectively. With these and other hardware and software tools, elastic neutral pion yields were extracted from the data. A well developed and understood simulation calculated geometric and software cut efficiency curves. The simulation also provided photo-pion production response functions to fit the experimental cross sections and extract the Primakoff cross section and thus the neutral pion radiative width and lifetime. Future work includes improving understanding of the nuclear incoherent process and any other background sources of elastic neutral pions in this data.

Identification of novel senescence-associated genes in ionizing radiation-induced senescent carcinoma cells

International Nuclear Information System (INIS)

Lee, Jae Seon; Kim, Bong Cho; Han, Na Kyung; Hong, Mi Na; Park, Su Min; Yoo, Hee Jung; Chu, In Sun; Lee, Sun Hee

2009-01-01

Cellular senescence is considered as a defense mechanism to prevent tumorigenesis. Ionizing radiation (IR) induces stress-induced premature senescence as well as apoptosis in various cancer cells. Senescent cells undergo functional and morphological changes including large and flattened cell shape, senescence-associated β-galactosidase (SA-βGal) activity, and altered gene expressions. Even with the recent findings of several gene expression profiles and supporting functional data, it is obscure that mechanism of IR-induced premature senescence in cancer cells. We performed microarray analysis to identify the common regulated genes in ionizing radiation-induced prematurely senescent human carcinoma cell lines

Recent measurements of low energy charge exchange cross sections for collisions of multicharged ions on neutral atoms and molecules

International Nuclear Information System (INIS)

Havener, Charles C.

2001-01-01

At ORNL Multicharged Ion Research Facility (MIRF), charge exchange (CX) cross sections have been measured for multicharged ions (MCI) on neutral atoms and molecules. The ORNL ion-atom merged-beam apparatus was used to measure single electron capture by MCI from H at eV/amu energies. A gas cell was used to measure single and double electron capture by MCI from a variety of molecular targets at keV collision energies. The merged-beams experiment has been successful in providing benchmark total electron capture measurements for several collision systems with a variety of multicharged ions on H or D

Genetic stability of gene targeted immunoglobulin loci. I. Heavy chain isotype exchange induced by a universal gene replacement vector.

Science.gov (United States)

Kardinal, C; Selmayr, M; Mocikat, R

1996-11-01

Gene targeting at the immunoglobulin loci of B cells is an efficient tool for studying immunoglobulin expression or generating chimeric antibodies. We have shown that vector integration induced by human immunoglobulin G1 (IgG1) insertion vectors results in subsequent vector excision mediated by the duplicated target sequence, whereas replacement events which could be induced by the same constructs remain stable. We could demonstrate that the distribution of the vector homology strongly influences the genetic stability obtained. To this end we developed a novel type of a heavy chain replacement vector making use of the heavy chain class switch recombination sequence. Despite the presence of a two-sided homology this construct is universally applicable irrespective of the constant gene region utilized by the B cell. In comparison to an integration vector the frequency of stable incorporation was strongly increased, but we still observed vector excision, although at a markedly reduced rate. The latter events even occurred with circular constructs. Linearization of the construct at various sites and the comparison with an integration vector that carries the identical homology sequence, but differs in the distribution of homology, revealed the following features of homologous recombination of immunoglobulin genes: (i) the integration frequency is only determined by the length of the homology flank where the cross-over takes place; (ii) a 5' flank that does not meet the minimum requirement of homology length cannot be complemented by a sufficient 3' flank; (iii) free vector ends play a role for integration as well as for replacement targeting; (iv) truncating recombination events are suppressed in the presence of two flanks. Furthermore, we show that the switch region that was used as 3' flank is non-functional in an inverted orientation.

Transcriptome analysis of trichothecene-induced gene expression in barley.

Science.gov (United States)

Boddu, Jayanand; Cho, Seungho; Muehlbauer, Gary J

2007-11-01

Fusarium head blight, caused primarily by Fusarium graminearum, is a major disease problem on barley (Hordeum vulgare L.). Trichothecene mycotoxins produced by the fungus during infection increase the aggressiveness of the fungus and promote infection in wheat (Triticum aestivum L.). Loss-of-function mutations in the TRI5 gene in F. graminearum result in the inability to synthesize trichothecenes and in reduced virulence on wheat. We examined the impact of pathogen-derived trichothecenes on virulence and the transcriptional differences in barley spikes infected with a trichothecene-producing wild-type strain and a loss-of-function tri5 trichothecene nonproducing mutant. Disease severity, fungal biomass, and floret necrosis and bleaching were reduced in spikes inoculated with the tri5 mutant strain compared with the wild-type strain, indicating that the inability to synthesize trichothecenes results in reduced virulence in barley. We detected 63 transcripts that were induced during trichothecene accumulation, including genes encoding putative trichothecene detoxification and transport proteins, ubiquitination-related proteins, programmed cell death-related proteins, transcription factors, and cytochrome P450s. We also detected 414 gene transcripts that were designated as basal defense response genes largely independent of trichothecene accumulation. Our results show that barley exhibits a specific response to trichothecene accumulation that can be separated from the basal defense response. We propose that barley responds to trichothecene accumulation by inducing at least two general responses. One response is the induction of genes encoding trichothecene detoxification and transport activities that may reduce the impact of trichothecenes. The other response is to induce genes encoding proteins associated with ubiquitination and cell death which may promote successful establishment of the disease.

Isolation and characterization of an auxin-inducible glutathione S-transferase gene of Arabidopsis thaliana

NARCIS (Netherlands)

Kop, D.A.M. van der; Schuyer, M.; Scheres, B.J.G.; Zaal, B.J. van der; Hooykaas, P.J.J.

1996-01-01

Genes homologous to the auxin-inducible Nt103 glutathione S-transferase (GST) gene of tobacco, were isolated from a genomic library of Arabidopsis thaliana. We isolated a λ clone containing an auxin-inducible gene, At103-1a, and part of a constitutively expressed gene, At103-1b. The coding regions

Antibodies to the A27 protein of vaccinia virus neutralize and protect against infection but represent a minor component of Dryvax vaccine--induced immunity.

Science.gov (United States)

He, Yong; Manischewitz, Jody; Meseda, Clement A; Merchlinsky, Michael; Vassell, Russell A; Sirota, Lev; Berkower, Ira; Golding, Hana; Weiss, Carol D

2007-10-01

The smallpox vaccine Dryvax, which consists of replication-competent vaccinia virus, elicits antibodies that play a major role in protection. Several vaccinia proteins generate neutralizing antibodies, but their importance for protection is unknown. We investigated the potency of antibodies to the A27 protein of the mature virion in neutralization and protection experiments and the contributions of A27 antibodies to Dryvax-induced immunity. Using a recombinant A27 protein (rA27), we confirmed that A27 contains neutralizing determinants and that vaccinia immune globulin (VIG) derived from Dryvax recipients contains reactivity to A27. However, VIG neutralization was not significantly reduced when A27 antibodies were removed, and antibodies elicited by an rA27 enhanced the protection conferred by VIG in passive transfer experiments. These findings demonstrate that A27 antibodies do not represent the major fraction of neutralizing activity in VIG and suggest that immunity may be augmented by vaccines and immune globulins that include strong antibody responses to A27.

Measurement of Neutral-Current K^{+} Production by Neutrinos using MINERvA

Energy Technology Data Exchange (ETDEWEB)

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

2017-07-01

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

Conjugal transfer of aac(6')Ie-aph(2″)Ia gene from native species and mechanism of regulation and cross resistance in Enterococcus faecalis MCC3063 by real time-PCR.

Science.gov (United States)

Jaimee, G; Halami, P M

2017-09-01

High level aminoglycoside resistance (HLAR) in the lactic acid bacteria (LAB) derived from food animals is detrimental. The aim of this study was to investigate the localization and conjugal transfer of aminoglycoside resistance genes, aac(6')Ie-aph(2″)Ia and aph(3')IIIa in different Enterococcus species. The cross resistance patterns in Enterococcus faecalis MCC3063 to clinically important aminoglycosides by real time PCR were also studied. Southern hybridization experiments revealed the presence of aac(6')Ie-aph(2 ″ )Ia and aph(3')IIIa genes conferring HLAR in high molecular weight plasmids except in Lactobacillus plantarum. The plasmid encoded bifunctional aac(6')Ie-aph(2″)Ia gene was transferable from Enterococcus avium (n = 2), E. cecorum (n = 1), E. faecalis (n = 1) and Pediococcus lolii (n = 1) species into the recipient strain; E. faecalis JH2-2 by filter mating experiments thus indicating the possible risks of gene transfer into pathogenic strains. Molecular analysis of cross resistance patterns in native isolate of E. faecalis MCC3063 carrying aac(6')Ie-aph(2″)Ia and aph(3')IIIa gene was displayed by quantification of the mRNA levels in this study. For this, the culture was induced with increasing concentrations of gentamicin, kanamycin and streptomycin (2048, 4096, 8192, 16384 μg/mL) individually. The increasing concentrations of gentamicin and kanamycin induced the expression of the aac(6')Ie-aph(2″)Ia and aph(3')IIIa resistance genes, respectively. Interestingly, it was observed that induction with streptomycin triggered a significant fold increase in the expression of the aph(3')IIIa gene which otherwise was not known to modify the aminoglycoside. This is noteworthy as streptomycin was found to confer cross resistance to structurally unrelated kanamycin. Also, expression of the aph(3')IIIa gene when induced with streptomycin, revealed that bacteria harbouring this gene will be able to overcome streptomycin bactericidal action at

Fast and sensitive detection of indels induced by precise gene targeting

DEFF Research Database (Denmark)

Yang, Zhang; Steentoft, Catharina; Hauge, Camilla

2015-01-01

The nuclease-based gene editing tools are rapidly transforming capabilities for altering the genome of cells and organisms with great precision and in high throughput studies. A major limitation in application of precise gene editing lies in lack of sensitive and fast methods to detect...... and characterize the induced DNA changes. Precise gene editing induces double-stranded DNA breaks that are repaired by error-prone non-homologous end joining leading to introduction of insertions and deletions (indels) at the target site. These indels are often small and difficult and laborious to detect...

Inclusive distributions of diffractively produced neutral kaons, lambdas, and antilambdas, and upper limits on Λ/sub c/+ production in high energy γ p interactions

International Nuclear Information System (INIS)

Bhadra, S.

1985-01-01

The author has used a large acceptance spectrometer in a tagged photon beam to study the interactions of real photons with protons in a hydrogen target. In particular, this thesis presents distributions of neutral kaons, lambdas, and antilambdas from diffractive dissociation where the kinematic regions of the target and projectile fragments are clearly distinguished by using events with clean recoiling protons. This data extends the neutral strange particle production rate measurements to higher overall centre-of-mass energies than previous photoproduction experiments. Comparison to pion-induced reactions supports the hypothesis that the photon behaves primarily as a hardon. Finally, upper limits have been set on the Λ/sub c/ + cross section times the branching ratio for decay modes leading to neutral strange particles for a diffractive dissociation process

Drug-loaded nanoparticles induce gene expression in human pluripotent stem cell derivatives

Science.gov (United States)

Gajbhiye, Virendra; Escalante, Leah; Chen, Guojun; Laperle, Alex; Zheng, Qifeng; Steyer, Benjamin; Gong, Shaoqin; Saha, Krishanu

2013-12-01

Tissue engineering and advanced manufacturing of human stem cells requires a suite of tools to control gene expression spatiotemporally in culture. Inducible gene expression systems offer cell-extrinsic control, typically through addition of small molecules, but small molecule inducers typically contain few functional groups for further chemical modification. Doxycycline (DXC), a potent small molecule inducer of tetracycline (Tet) transgene systems, was conjugated to a hyperbranched dendritic polymer (Boltorn H40) and subsequently reacted with polyethylene glycol (PEG). The resulting PEG-H40-DXC nanoparticle exhibited pH-sensitive drug release behavior and successfully controlled gene expression in stem-cell-derived fibroblasts with a Tet-On system. While free DXC inhibited fibroblast proliferation and matrix metalloproteinase (MMP) activity, PEG-H40-DXC nanoparticles maintained higher fibroblast proliferation levels and MMP activity. The results demonstrate that the PEG-H40-DXC nanoparticle system provides an effective tool to controlling gene expression in human stem cell derivatives.Tissue engineering and advanced manufacturing of human stem cells requires a suite of tools to control gene expression spatiotemporally in culture. Inducible gene expression systems offer cell-extrinsic control, typically through addition of small molecules, but small molecule inducers typically contain few functional groups for further chemical modification. Doxycycline (DXC), a potent small molecule inducer of tetracycline (Tet) transgene systems, was conjugated to a hyperbranched dendritic polymer (Boltorn H40) and subsequently reacted with polyethylene glycol (PEG). The resulting PEG-H40-DXC nanoparticle exhibited pH-sensitive drug release behavior and successfully controlled gene expression in stem-cell-derived fibroblasts with a Tet-On system. While free DXC inhibited fibroblast proliferation and matrix metalloproteinase (MMP) activity, PEG-H40-DXC nanoparticles maintained

Evaluation of cross sections for neutron-induced reactions in sodium

International Nuclear Information System (INIS)

Larson, D.C.

1980-09-01

An evaluation of the neutron-induced cross sections of 23 Na has been done for the energy range from 10 -5 eV to 20 MeV. All significant cross sections are given, including differential cross sections for production of gamma rays. The recommended values are based on experimental data where available, and use results of a consistent model code analysis of available data to predict cross sections where there are no experimental data. This report describes the evaluation that was submitted to the Cross Section Evaluation Working Group (CSEWG) for consideration as a part of the Evaluated Nuclear Data File, Version V, and subsequently issued as MAT 1311. 126 references, 130 figures, 14 tables

HIV-1 binding and neutralizing antibodies of injecting drug users

Directory of Open Access Journals (Sweden)

E.P. Ouverney

2005-09-01

Full Text Available Previous studies have demonstrated a stronger seroreactivity against some synthetic peptides responsible for inducing neutralizing antibodies in injecting drug users (IDU compared to that of individuals sexually infected with HIV-1 (S, but the effectiveness in terms of the neutralizing ability of these antibodies has not been evaluated. Our objective was to study the humoral immune response of IDU by determining the specificity of their antibodies and the presence of neutralizing antibodies. The neutralization capacity against the HIV-1 isolate MN (genotype B, the primary HIV-1 isolate 95BRRJ021 (genotype F, and the seroreactivity with peptides known to induce neutralizing antibodies, from the V2 and V3 loops of different HIV-1 subtypes, were analyzed. Seroreactivity indicates that IDU plasma are more likely to recognize a broader range of peptides than S plasma, with significantly higher titers, especially of V3 peptides. Similar neutralization frequencies of the MN isolate were observed in plasma of the IDU (16/47 and S (20/60 groups in the 1:10 dilution. The neutralization of the 95BRRJ021 isolate was more frequently observed for plasma from the S group (15/23 than from the IDU group (15/47, P = 0.0108. No correlation between neutralization and seroreactivity with the peptides tested was observed. These results suggest that an important factor responsible for the extensive and broad humoral immune response observed in IDU is their infection route. There was very little difference in neutralizing antibody response between the IDU and S groups despite their differences in seroreactivity and health status.

Virus neutralizing antibody response in mice and dogs with a bicistronic DNA vaccine encoding rabies virus glycoprotein and canine parvovirus VP2.

Science.gov (United States)

Patial, Sonika; Chaturvedi, V K; Rai, A; Saini, M; Chandra, Rajesh; Saini, Y; Gupta, Praveen K

2007-05-16

A bicistronic DNA vaccine against rabies and parvovirus infection of dogs was developed by subcloning rabies glycoprotein and canine parvovirus (CPV) VP2 genes into a bicistronic vector. After characterizing the expression of both the proteins in vitro, the bicistronic DNA vaccine was injected in mice and induced immune response was compared with monocistronic DNA vaccines. There was no significant difference in ELISA and virus neutralizing (VN) antibody responses against rabies and CPV in mice immunized with either bicistronic or monocistronic DNA vaccine. Further, there was significantly similar protection in mice immunized with either bicistronic or monocistronic rabies DNA vaccine on rabies virus challenge. Similarly, dogs immunized with monocistronic and bicistronic DNA vaccines developed comparable VN antibodies against rabies and CPV. This study indicated that bicistronic DNA vaccine can be used in dogs to induce virus neutralizing immune responses against both rabies and CPV.

Timing is critical for effective glucocorticoid receptor mediated repression of the cAMP-induced CRH gene.

Directory of Open Access Journals (Sweden)

Siem van der Laan

Full Text Available Glucocorticoid negative feedback of the hypothalamus-pituitary-adrenal axis is mediated in part by direct repression of gene transcription in glucocorticoid receptor (GR expressing cells. We have investigated the cross talk between the two main signaling pathways involved in activation and repression of corticotrophin releasing hormone (CRH mRNA expression: cyclic AMP (cAMP and GR. We report that in the At-T20 cell-line the glucocorticoid-mediated repression of the cAMP-induced human CRH proximal promoter activity depends on the relative timing of activation of both signaling pathways. Activation of the GR prior to or in conjunction with cAMP signaling results in an effective repression of the cAMP-induced transcription of the CRH gene. In contrast, activation of the GR 10 minutes after onset of cAMP treatment, results in a significant loss of GR-mediated repression. In addition, translocation of ligand-activated GR to the nucleus was found as early as 10 minutes after glucocorticoid treatment. Interestingly, while both signaling cascades counteract each other on the CRH proximal promoter, they synergize on a synthetic promoter containing 'positive' response elements. Since the order of activation of both signaling pathways may vary considerably in vivo, we conclude that a critical time-window exists for effective repression of the CRH gene by glucocorticoids.

Radiation-induced gene expression in human subcutaneous fibroblasts is predictive of radiation-induced fibrosis

DEFF Research Database (Denmark)

Rødningen, Olaug Kristin; Børresen-Dale, Anne-Lise; Alsner, Jan

2008-01-01

BACKGROUND AND PURPOSE: Breast cancer patients show a large variation in normal tissue reactions after ionizing radiation (IR) therapy. One of the most common long-term adverse effects of ionizing radiotherapy is radiation-induced fibrosis (RIF), and several attempts have been made over the last...... years to develop predictive assays for RIF. Our aim was to identify basal and radiation-induced transcriptional profiles in fibroblasts from breast cancer patients that might be related to the individual risk of RIF in these patients. MATERIALS AND METHODS: Fibroblast cell lines from 31 individuals......-treated fibroblasts. Transcriptional differences in basal and radiation-induced gene expression profiles were investigated using 15K cDNA microarrays, and results analyzed by both SAM and PAM. RESULTS: Sixty differentially expressed genes were identified by applying SAM on 10 patients with the highest risk of RIF...

Liver lipid molecules induce PEPCK-C gene transcription and attenuate insulin action

International Nuclear Information System (INIS)

Chen Guoxun

2007-01-01

Cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) plays key roles in gluconeogenesis, glyceroneogenesis, and cataplerosis. Experiments were designed to examine the effects of endogenous lipid molecules from rat livers on the expression of PEPCK-C gene in primary rat hepatocytes. The lipid extracts prepared from livers of Zucker fatty, lean, and Wistar rats induced the expression levels of PEPCK-C transcripts. Insulin-mediated reduction of PEPCK-C gene expression was attenuated by the same treatment. The lipid extracts induced the relative luciferase activity of reporter gene constructs that contain a 2.2-kb 5' promoter fragment of PEPCK-C gene, but not the construct that contains only the 3' untranslated region (UTR) of its mRNA. The estimated half life of PEPCK-C transcripts in the presence of the lipid extract is the same as that in the absence of it. My results demonstrate for the first time that endogenous lipid molecules induce PEPCK-C gene transcription and attenuate insulin action in liver

Actinide neutron-induced fission cross section measurements at LANSCE

Energy Technology Data Exchange (ETDEWEB)

Tovesson, Fredrik K [Los Alamos National Laboratory; Laptev, Alexander B [Los Alamos National Laboratory; Hill, Tony S [INL

2010-01-01

Fission cross sections of a range of actinides have been measured at the Los Alamos Neutron Science Center (LANSCE) in support of nuclear energy applications in a wide energy range from sub-thermal energies up to 200 MeV. A parallel-plate ionization chamber are used to measure fission cross sections ratios relative to the {sup 235}U standard while incident neutron energies are determined using the time-of-flight method. Recent measurements include the {sup 233,238}U, {sup 239-242}Pu and {sup 243}Am neutron-induced fission cross sections. Obtained data are presented in comparison with ex isting evaluations and previous data.

Gene expression profiling distinguishes between spontaneous and radiation-induced rat mammary carcinomas

International Nuclear Information System (INIS)

Imaoka, Tatsuhiko; Nishimura, Mayumi; Kakinuma, Shizuko; Shimada, Yoshiya; Yamashita, Satoshi; Ushijima, Toshikazu

2008-01-01

The ability to distinguish between spontaneous and radiation-induced cancers in humans is expected to improve the resolution of estimated risk from low dose radiation. Mammary carcinomas were obtained from Sprague-Dawley rats that were either untreated (n=45) or acutely γ-irradiated (1 Gy; n=20) at seven weeks of age. Gene expression profiles of three spontaneous and four radiation-induced carcinomas, as well as those of normal mammary glands, were analyzed by microarrays. Differential expression of identified genes of interest was then verified by quantitative polymerase chain reaction (qPCR). Cluster analysis of global gene expression suggested that spontaneous carcinomas were distinguished from a heterogeneous population of radiation-induced carcinomas, though most gene expressions were common. We identified 50 genes that had different expression levels between spontaneous and radiogenic carcinomas. We then selected 18 genes for confirmation of the microarray data by qPCR analysis and obtained the following results: high expression of Plg, Pgr and Wnt4 was characteristic to all spontaneous carcinomas; Tnfsf11, Fgf10, Agtr1a, S100A9 and Pou3f3 showed high expression in a subset of radiation-induced carcinomas; and increased Gp2, Areg and Igf2 expression, as well as decreased expression of Ca3 and noncoding RNA Mg1, were common to all carcinomas. Thus, gene expression analysis distinguished between spontaneous and radiogenic carcinomas, suggesting possible differences in their carcinogenic mechanism. (author)

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.

Coherent and Incoherent Neutral Current Scattering for Supernova Detection

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P. C. Divari

2012-01-01

Full Text Available The total cross sections as well as the neutrino event rates are calculated in the neutral current neutrino scattering off 40Ar and 132Xe isotopes at neutrino energies (Ev<100 MeV. The individual contribution coming from coherent and incoherent channels is taking into account. An enhancement of the neutral current component is achieved via the coherent (0gs+→0gs+ channel which is dominant with respect to incoherent (0gs+→Jf one. The response of the above isotopes as a supernova neutrino detection has been considered, assuming a two parameter Fermi-Dirac distribution for the supernova neutrino energy spectra. The calculated total cross sections are tested on a gaseous spherical TPC detector dedicated for supernova neutrino detection.

Overexpression and amplification of the c-myc gene in mouse tumors induced by chemical and radiations

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Niwa, Ohtsura; Enoki, Yoshitaka; Yokoro, Kenjiro

1989-03-01

We examined expression of the c-myc gene by the dot blot hybridization of total cellular RNA from mouse primary tumors induced by chemicals and radiations. Expression of the c-myc gene was found to be elevated in 69 cases among 177 independently induced tumors of 12 different types. DNA from tumors overexpressing the myc gene was analyzed by Southern blotting. No case of rearrangement was detected. However, amplification of the c-myc gene was found in 7 cases of primary sarcomas. These included 4 cases out of 24 methylcholanthrene-induced sarcomas and 3 cases out of 7 /alpha/-tocopherol-induced sacromas. We also analyzed 8 cases of sarcomas induced by radiations, but could not find changes in the gene structure of the c-myc gene. Thus, our data indicate tumor type specificity and agent specificity of c-myc gene amplification. (author).

Tissue specific promoters improve the localization of radiation-inducible gene expression

International Nuclear Information System (INIS)

Hallahan, Dennis; Kataoka, Yasushi; Kuchibhotla, Jaya; Virudachalam, Subbu; Weichselbaum, Ralph

1996-01-01

Purpose: Site-specific activation of gene expression can be achieved by the use of a promoter that is induced by physical agents such as x-rays. The purpose of the present study was to determine whether site-specific activation of gene therapy can also be achieved within the vascular endothelium by use of radiation-inducible promoters. We studied induction of promoter-reporter gene constructs using previously identified radiation-promoters from c-jun, c-fos, Egr-1, ICAM-1, ELAM-1 after transfection into in the vascular endothelium. Methods: The following radiation-inducible genetic constructs were created: The ELAM-1 promoter fragment was cloned into pOGH to obtain the pE-sel(-587 +35)GH reporter construct. The ICAM-1 promoter fragment (-1162/+1) was cloned upstream of the CAT coding region of the pCAT-plasmid (Promega) after removal of the SV40 promoter by Bgl2/Stu1 digestion to create the pBS-CAT plasmid. The 132 to +170 bp segment of the 5' untranslated region of the c-jun promoter was cloned to the CAT reporter gene to create the -132/+170 cjun-CAT. The Egr-1 promoter fragment (-425/+75) was cloned upstream of the CAT coding region to create the pE425-CAT plasmid. Tandem repeats of the AP-1 binding site were cloned upstream of the CAT coding region (3 xTRE-CAT). Tandem repeats of the Egr binding site (EBS) were cloned upstream of the CAT coding region (EBS-CAT). Human vascular endothelial cells from both large vessel and small vessel origin (HUVEC and HMEC), as well as human tumor cell lines were transfected with plasmids -132/+170 cjun-CAT, pE425-CAT, 3 xTRE-CAT, EBS-CAT, pE-sel-GH and pBS-CAT by use of liposomes. Humor tumor cell lines included SQ20B (squamous), RIT3 (sarcoma), and HL525 (leukemia). Each plasmid was cotransfected with a plasmid containing a CMV promoter linked to the LacZ gene (1 μg). Transfected cells were treated with mock irradiation or x-rays. Cell extracts were assayed for reporter gene expression. Results: Radiation-induced gene

Epitope mapping and characterization of a novel CD4-induced human monoclonal antibody capable of neutralizing primary HIV-1 strains

International Nuclear Information System (INIS)

Xiang Shihua; Wang Liping; Abreu, Mariam; Huang, C.-C.; Kwong, Peter D.; Rosenberg, Eric; Robinson, James E.; Sodroski, Joseph

2003-01-01

Human immunodeficiency virus (HIV-1) enters target cells by binding its gp120 exterior envelope glycoprotein to CD4 and one of the chemokine receptors, CCR5 or CXCR4. CD4-induced (CD4i) antibodies bind gp120 more efficiently after CD4 binding and block the interaction with the chemokine receptor. Examples of CD4i antibodies are limited, and the prototypes of the CD4i antibodies exhibit only weak neutralizing activity against primary, clinical HIV-1 isolates. Here we report the identification of a novel antibody, E51, that exhibits CD4-induced binding to gp120 and neutralizes primary HIV-1 more efficiently than the prototypic CD4i antibodies. The E51 antibody blocks the interaction of gp120-CD4 complexes with CCR5 and binds to a highly conserved, basic gp120 element composed of the β19-strand and surrounding structures. Thus, on primary HIV-1 isolates, this gp120 region, which has been previously implicated in chemokine receptor binding, is accessible to a subset of CD4i antibodies

Oleocanthal Modulates Estradiol-Induced Gene Expression Involving Estrogen Receptor α.

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Keiler, Annekathrin Martina; Djiogue, Sefirin; Ehrhardt, Tino; Zierau, Oliver; Skaltsounis, Leandros; Halabalaki, Maria; Vollmer, Günter

2015-09-01

Oleocanthal is a bioactive compound from olive oil. It has attracted considerable attention as it is anti-inflammatory, antiproliferative, and has been shown to possess neuroprotective properties in vitro and in vivo. Delineated from its polyphenolic structure, the aim of this study was to characterize oleocanthal towards estrogenic properties. This might contribute to partly explain the beneficial effects described for the Mediterranean diet. Estrogenic properties of oleocanthal were assessed by different methods: a) stimulation of reporter gene activity in MVLN or RNDA cells either expressing estrogen receptor α or β, b) stimulation of luciferase reporter gene activity in U2OS osteosarcoma cells expressing estrogen receptor α or β, and c) elucidation of the impact on estradiol-induced gene expression in U2OS cells transduced with both estrogen receptors. Depending on the cell line origin, oleocanthal inhibited luciferase activity (MVLN, U2OS-estrogen receptor β) or weakly induced reporter gene activity at 10 µM in U2OS-estrogen receptor α cells. However, oleocanthal inhibited stimulation of luciferase activity by estradiol from both estrogen receptors. Oleocanthal, if given alone, did not stimulate gene expression in U2OS cells, but it significantly modulated the response of estradiol. Oleocanthal enhanced the effect of estradiol on the regulation of those genes, which are believed to be regulated through heterodimeric estrogen receptors. As the estrogenic response pattern of oleocanthal is rather unique, we compared the results obtained with oleacein. Oleocanthal binds to both estrogen receptors inducing estradiol-agonistic or antiagonistic effects depending on the cell line. Regarding regulation of gene expression in U2OS-estrogen receptor α/β cells, oleocanthal and oleacein enhanced estradiol-mediated regulation of heterodimer-regulated genes. Georg Thieme Verlag KG Stuttgart · New York.

Lithium ions induce prestalk-associated gene expression and inhibit prespore gene expression in Dictyostelium discoideum

NARCIS (Netherlands)

Peters, Dorien J.M.; Lookeren Campagne, Michiel M. van; Haastert, Peter J.M. van; Spek, Wouter; Schaap, Pauline

1989-01-01

We investigated the effect of Li+ on two types of cyclic AMP-regulated gene expression and on basal and cyclic AMP-stimulated inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) levels. Li+ effectively inhibits cyclic AMP-induced prespore gene expression, half-maximal inhibition occurring at about 2mM-LiCl.

Nitrate-induced genes in tomato roots. Array analysis reveals novel genes that may play a role in nitrogen nutrition.

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Wang, Y H; Garvin, D F; Kochian, L V

2001-09-01

A subtractive tomato (Lycopersicon esculentum) root cDNA library enriched in genes up-regulated by changes in plant mineral status was screened with labeled mRNA from roots of both nitrate-induced and mineral nutrient-deficient (-nitrogen [N], -phosphorus, -potassium [K], -sulfur, -magnesium, -calcium, -iron, -zinc, and -copper) tomato plants. A subset of cDNAs was selected from this library based on mineral nutrient-related changes in expression. Additional cDNAs were selected from a second mineral-deficient tomato root library based on sequence homology to known genes. These selection processes yielded a set of 1,280 mineral nutrition-related cDNAs that were arrayed on nylon membranes for further analysis. These high-density arrays were hybridized with mRNA from tomato plants exposed to nitrate at different time points after N was withheld for 48 h, for plants that were grown on nitrate/ammonium for 5 weeks prior to the withholding of N. One hundred-fifteen genes were found to be up-regulated by nitrate resupply. Among these genes were several previously identified as nitrate responsive, including nitrate transporters, nitrate and nitrite reductase, and metabolic enzymes such as transaldolase, transketolase, malate dehydrogenase, asparagine synthetase, and histidine decarboxylase. We also identified 14 novel nitrate-inducible genes, including: (a) water channels, (b) root phosphate and K(+) transporters, (c) genes potentially involved in transcriptional regulation, (d) stress response genes, and (e) ribosomal protein genes. In addition, both families of nitrate transporters were also found to be inducible by phosphate, K, and iron deficiencies. The identification of these novel nitrate-inducible genes is providing avenues of research that will yield new insights into the molecular basis of plant N nutrition, as well as possible networking between the regulation of N, phosphorus, and K nutrition.

GATA-dependent regulation of TPO-induced c-mpl gene expression during megakaryopoiesis.

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Sunohara, Masataka; Morikawa, Shigeru; Fuse, Akira; Sato, Iwao

2014-01-01

Thrombopoietin (TPO) and its receptor, c-Mpl, play the crucial role during megakaryocytopoiesis. Previously, we have shown that the promoter activity of c-mpl induced by TPO is modulated by transcription through a PKC-dependent pathway and that GATA(-77) is involved as a positive regulatory element in TPO-induced c-mpl gene expression in the megakaryoblastic CMK cells. In this research, to examine participating possibility of GATA promoter element in TPO- induced c-mpl gene expression through a PKC-independent pathway, the promoter activity of site-directed mutagenesis and the effect of potein kinase C modulator were measured by a transient transfection assay system. Together with our previous results on the TPO-induced c-mpl promoter, this study indicates destruction of -77GATA in c-mpl promoter decreased the activity by 47.3% under existence of GF109203. These results suggest that GATA promoter element plays significant role in TPO-induced c-mpl gene expression through a PKC-independent pathway.

Induced photoemission from driven nonadiabatic dynamics in an avoided crossing system

Energy Technology Data Exchange (ETDEWEB)

Arasaki, Yasuki; Mizuno, Yuta; Takatsuka, Kazuo, E-mail: kaztak@mns2.c.u-tokyo.ac.jp [Department of Basic Science, Graduate School of Arts and Sciences, The University of Tokyo, Komaba, 153-8902 Tokyo (Japan); Scheit, Simona [Department of Basic Science, Graduate School of Arts and Sciences, The University of Tokyo, Komaba, 153-8902 Tokyo (Japan); Theoretische Chemie, Universität Heidelberg, Im Neuneheimer Feld 229, 69120 Heidelberg (Germany)

2014-12-21

When vibrational dynamics on an ionic state (large dipole moment) is coupled to that on a neutral state (small dipole moment) such as at an avoided crossing in the alkali halide system, the population transfer between the states cause oscillation of the molecular dipole, leading to dipole emission. Such dynamics may be driven by an external field. We study how the coupled wavepacket dynamics is affected by the parameters (intensity, frequency) of the driving field with the aim of making use of the photoemission as an alternative detection scheme of femtosecond and subfemtosecond vibrational and electronic dynamics or as a characteristic optical source.

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

Science.gov (United States)

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

2011-01-01

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

Differential expression of ozone-induced gene during exposures to ...

African Journals Online (AJOL)

Differential expression of ozone-induced gene during exposures to salt stress in Polygonum sibiricum Laxm leaves, stem and underground stem. ... PcOZI-1 mRNA in untreated plants was detected at low levels in underground stem, leaves and at higher levels in stem. PcOZI-1 mRNA accumulation was transiently induced ...

Carbon-Starvation Induces Cross-Resistance to Thermal, Acid, and Oxidative Stress in Serratia marcescens

Science.gov (United States)

Pittman, Joseph R.; Kline, La’Kesha C.; Kenyon, William J.

2015-01-01

The broad host-range pathogen Serratia marcescens survives in diverse host and non-host environments, often enduring conditions in which the concentration of essential nutrients is growth-limiting. In such environments, carbon and energy source starvation (carbon-starvation) is one of the most common forms of stress encountered by S. marcescens. Related members of the family Enterobacteriaceae are known to undergo substantial changes in gene expression and physiology in response to the specific stress of carbon-starvation, enabling non-spore-forming cells to survive periods of prolonged starvation and exposure to other forms of stress (i.e., starvation-induced cross-resistance). To determine if carbon-starvation also results in elevated levels of cross-resistance in S. marcescens, both log-phase and carbon-starved cultures, depleted of glucose before the onset of high cell-density stationary-phase, were grown in minimal media at either 30 °C or 37 °C and were then challenged for resistance to high temperature (50 °C), low pH (pH 2.8), and oxidative stress (15 mM H2O2). In general, carbon-starved cells exhibited a higher level of resistance to thermal stress, acid stress, and oxidative stress compared to log-phase cells. The extent of carbon-starvation-induced cross-resistance was dependent on incubation temperature and on the particular strain of S. marcescens. In addition, strain- and temperature-dependent variations in long-term starvation survival were also observed. The enhanced stress-resistance of starved S. marcescens cells could be an important factor in their survival and persistence in many non-host environments and within certain host microenvironments where the availability of carbon sources is suboptimal for growth. PMID:27682115

Carbon-Starvation Induces Cross-Resistance to Thermal, Acid, and Oxidative Stress in Serratia marcescens

Directory of Open Access Journals (Sweden)

Joseph R. Pittman

2015-10-01

Full Text Available The broad host-range pathogen Serratia marcescens survives in diverse host and non-host environments, often enduring conditions in which the concentration of essential nutrients is growth-limiting. In such environments, carbon and energy source starvation (carbon-starvation is one of the most common forms of stress encountered by S. marcescens. Related members of the family Enterobacteriaceae are known to undergo substantial changes in gene expression and physiology in response to the specific stress of carbon-starvation, enabling non-spore-forming cells to survive periods of prolonged starvation and exposure to other forms of stress (i.e., starvation-induced cross-resistance. To determine if carbon-starvation also results in elevated levels of cross-resistance in S. marcescens, both log-phase and carbon-starved cultures, depleted of glucose before the onset of high cell-density stationary-phase, were grown in minimal media at either 30 °C or 37 °C and were then challenged for resistance to high temperature (50 °C, low pH (pH 2.8, and oxidative stress (15 mM H2O2. In general, carbon-starved cells exhibited a higher level of resistance to thermal stress, acid stress, and oxidative stress compared to log-phase cells. The extent of carbon-starvation-induced cross-resistance was dependent on incubation temperature and on the particular strain of S. marcescens. In addition, strain- and temperature-dependent variations in long-term starvation survival were also observed. The enhanced stress-resistance of starved S. marcescens cells could be an important factor in their survival and persistence in many non-host environments and within certain host microenvironments where the availability of carbon sources is suboptimal for growth.

Neutral Atom Diffusion in a Partially Ionized Prominence Plasma

Science.gov (United States)

Gilbert, Holly

2010-01-01

The support of solar prominences is normally described in terms of a magnetic force on the prominence plasma that balances the solar gravitational force. Because the prominence plasma is only partially ionized. it is necessary to consider in addition the support of the neutral component of the prominence plasma. This support is accomplished through a frictional interaction between the neutral and ionized components of the plasma, and its efficacy depends strongly on the degree of ionization of the plasma. More specifically, the frictional force is proportional to the relative flow of neutral and ion species, and for a sufficiently weakly ionized plasma, this flow must be relatively large to produce a frictional force that balances gravity. A large relative flow, of course, implies significant draining of neutral particles from the prominence. We evaluate the importance of this draining effect for a hydrogen-helium plasma, and consider the observational evidence for cross-field diffusion of neutral prominence material,

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.

Cross-species transcriptomic approach reveals genes in hamster implantation sites.

Science.gov (United States)

Lei, Wei; Herington, Jennifer; Galindo, Cristi L; Ding, Tianbing; Brown, Naoko; Reese, Jeff; Paria, Bibhash C

2014-12-01

The mouse model has greatly contributed to understanding molecular mechanisms involved in the regulation of progesterone (P4) plus estrogen (E)-dependent blastocyst implantation process. However, little is known about contributory molecular mechanisms of the P4-only-dependent blastocyst implantation process that occurs in species such as hamsters, guineapigs, rabbits, pigs, rhesus monkeys, and perhaps humans. We used the hamster as a model of P4-only-dependent blastocyst implantation and carried out cross-species microarray (CSM) analyses to reveal differentially expressed genes at the blastocyst implantation site (BIS), in order to advance the understanding of molecular mechanisms of implantation. Upregulation of 112 genes and downregulation of 77 genes at the BIS were identified using a mouse microarray platform, while use of the human microarray revealed 62 up- and 38 down-regulated genes at the BIS. Excitingly, a sizable number of genes (30 up- and 11 down-regulated genes) were identified as a shared pool by both CSMs. Real-time RT-PCR and in situ hybridization validated the expression patterns of several up- and down-regulated genes identified by both CSMs at the hamster and mouse BIS to demonstrate the merit of CSM findings across species, in addition to revealing genes specific to hamsters. Functional annotation analysis found that genes involved in the spliceosome, proteasome, and ubiquination pathways are enriched at the hamster BIS, while genes associated with tight junction, SAPK/JNK signaling, and PPARα/RXRα signalings are repressed at the BIS. Overall, this study provides a pool of genes and evidence of their participation in up- and down-regulated cellular functions/pathways at the hamster BIS. © 2014 Society for Reproduction and Fertility.

The progress of tumor gene-radiotherapy induced by Egr-1 promoter

International Nuclear Information System (INIS)

Guo Rui; Li Biao

2010-01-01

The promoter of early growth response gene-1 (Egr-1) is a cis-acting element of Egr-1, and its activity is regulated by inducers such as ionizing radiation, free radical. In designated gene-radiotherapy system, radiation combined with therapeutic gene (such as tumor necrosis factor-α gene, suicide gene) can spatially and temporally regulate therapeutic gene expression in the irradiated field, produced a marked effect, while little systemic toxicities were observed. The combination of radiotherapy and gene therapy is promising in tumor therapy. (authors)

Interferon induced IFIT family genes in host antiviral defense.

Science.gov (United States)

Zhou, Xiang; Michal, Jennifer J; Zhang, Lifan; Ding, Bo; Lunney, Joan K; Liu, Bang; Jiang, Zhihua

2013-01-01

Secretion of interferons (IFNs) from virus-infected cells is a hallmark of host antiviral immunity and in fact, IFNs exert their antiviral activities through the induction of antiviral proteins. The IFN-induced protein with tetratricopeptide repeats (IFITs) family is among hundreds of IFN-stimulated genes. This family contains a cluster of duplicated loci. Most mammals have IFIT1, IFIT2, IFIT3 and IFIT5; however, bird, marsupial, frog and fish have only IFIT5. Regardless of species, IFIT5 is always adjacent to SLC16A12. IFIT family genes are predominantly induced by type I and type III interferons and are regulated by the pattern recognition and the JAK-STAT signaling pathway. IFIT family proteins are involved in many processes in response to viral infection. However, some viruses can escape the antiviral functions of the IFIT family by suppressing IFIT family genes expression or methylation of 5' cap of viral molecules. In addition, the variants of IFIT family genes could significantly influence the outcome of hepatitis C virus (HCV) therapy. We believe that our current review provides a comprehensive picture for the community to understand the structure and function of IFIT family genes in response to pathogens in human, as well as in animals.

Duplication and diversification of the hypoxia-inducible IGFBP-1 gene in zebrafish.

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Hiroyasu Kamei

2008-08-01

Full Text Available Gene duplication is the primary force of new gene evolution. Deciphering whether a pair of duplicated genes has evolved divergent functions is often challenging. The zebrafish is uniquely positioned to provide insight into the process of functional gene evolution due to its amenability to genetic and experimental manipulation and because it possess a large number of duplicated genes.We report the identification and characterization of two hypoxia-inducible genes in zebrafish that are co-ortholgs of human IGF binding protein-1 (IGFBP-1. IGFBP-1 is a secreted protein that binds to IGF and modulates IGF actions in somatic growth, development, and aging. Like their human and mouse counterparts, in adult zebrafish igfbp-1a and igfbp-1b are exclusively expressed in the liver. During embryogenesis, the two genes are expressed in overlapping spatial domains but with distinct temporal patterns. While zebrafish IGFBP-1a mRNA was easily detected throughout embryogenesis, IGFBP-1b mRNA was detectable only in advanced stages. Hypoxia induces igfbp-1a expression in early embryogenesis, but induces the igfbp-1b expression later in embryogenesis. Both IGFBP-1a and -b are capable of IGF binding, but IGFBP-1b has much lower affinities for IGF-I and -II because of greater dissociation rates. Overexpression of IGFBP-1a and -1b in zebrafish embryos caused significant decreases in growth and developmental rates. When tested in cultured zebrafish embryonic cells, IGFBP-1a and -1b both inhibited IGF-1-induced cell proliferation but the activity of IGFBP-1b was significantly weaker.These results indicate subfunction partitioning of the duplicated IGFBP-1 genes at the levels of gene expression, physiological regulation, protein structure, and biological actions. The duplicated IGFBP-1 may provide additional flexibility in fine-tuning IGF signaling activities under hypoxia and other catabolic conditions.

Expression profiling and cross-species RNA interference (RNAi of desiccation-induced transcripts in the anhydrobiotic nematode Aphelenchus avenae

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Culleton Bridget A

2010-01-01

Full Text Available Abstract Background Some organisms can survive extreme desiccation by entering a state of suspended animation known as anhydrobiosis. The free-living mycophagous nematode Aphelenchus avenae can be induced to enter anhydrobiosis by pre-exposure to moderate reductions in relative humidity (RH prior to extreme desiccation. This preconditioning phase is thought to allow modification of the transcriptome by activation of genes required for desiccation tolerance. Results To identify such genes, a panel of expressed sequence tags (ESTs enriched for sequences upregulated in A. avenae during preconditioning was created. A subset of 30 genes with significant matches in databases, together with a number of apparently novel sequences, were chosen for further study. Several of the recognisable genes are associated with water stress, encoding, for example, two new hydrophilic proteins related to the late embryogenesis abundant (LEA protein family. Expression studies confirmed EST panel members to be upregulated by evaporative water loss, and the majority of genes was also induced by osmotic stress and cold, but rather fewer by heat. We attempted to use RNA interference (RNAi to demonstrate the importance of this gene set for anhydrobiosis, but found A. avenae to be recalcitrant with the techniques used. Instead, therefore, we developed a cross-species RNAi procedure using A. avenae sequences in another anhydrobiotic nematode, Panagrolaimus superbus, which is amenable to gene silencing. Of 20 A. avenae ESTs screened, a significant reduction in survival of desiccation in treated P. superbus populations was observed with two sequences, one of which was novel, while the other encoded a glutathione peroxidase. To confirm a role for glutathione peroxidases in anhydrobiosis, RNAi with cognate sequences from P. superbus was performed and was also shown to reduce desiccation tolerance in this species. Conclusions This study has identified and characterised the

Differences in gene expression profiles and signaling pathways in rhabdomyolysis-induced acute kidney injury.

Science.gov (United States)

Geng, Xiaodong; Wang, Yuanda; Hong, Quan; Yang, Jurong; Zheng, Wei; Zhang, Gang; Cai, Guangyan; Chen, Xiangmei; Wu, Di

2015-01-01

Rhabdomyolysis is a threatening syndrome because it causes the breakdown of skeletal muscle. Muscle destruction leads to the release of myoglobin, intracellular proteins, and electrolytes into the circulation. The aim of this study was to investigate the differences in gene expression profiles and signaling pathways upon rhabdomyolysis-induced acute kidney injury (AKI). In this study, we used glycerol-induced renal injury as a model of rhabdomyolysis-induced AKI. We analyzed data and relevant information from the Gene Expression Omnibus database (No: GSE44925). The gene expression data for three untreated mice were compared to data for five mice with rhabdomyolysis-induced AKI. The expression profiling of the three untreated mice and the five rhabdomyolysis-induced AKI mice was performed using microarray analysis. We examined the levels of Cyp3a13, Rela, Aldh7a1, Jun, CD14. And Cdkn1a using RT-PCR to determine the accuracy of the microarray results. The microarray analysis showed that there were 1050 downregulated and 659 upregulated genes in the rhabdomyolysis-induced AKI mice compared to the control group. The interactions of all differentially expressed genes in the Signal-Net were analyzed. Cyp3a13 and Rela had the most interactions with other genes. The data showed that Rela and Aldh7a1 were the key nodes and had important positions in the Signal-Net. The genes Jun, CD14, and Cdkn1a were also significantly upregulated. The pathway analysis classified the differentially expressed genes into 71 downregulated and 48 upregulated pathways including the PI3K/Akt, MAPK, and NF-κB signaling pathways. The results of this study indicate that the NF-κB, MAPK, PI3K/Akt, and apoptotic pathways are regulated in rhabdomyolysis-induced AKI.

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

The CRO-1 gene of Saccharomyces cerevisiae controls mitotic crossing over, chromosomal stability and sporulation

International Nuclear Information System (INIS)

Esposito, M.S.; Maleas, D.T.; Bjornstad, K.A.; Holbrook, L.L.

1987-01-01

The properties of a novel temperature-sensitive recombination-defective mutant of Saccharomyces cerevisiae, cro1-1 is described. The cro1-1 mutant is the first instance of a rec mutation that reduces drastically the rates of spontaneous mitotic crossing-over events but not those of gene conversional events. The cro1-1 mutation thus provides evidence that mitotic crossing-over is dependent upon gene products that are not essential for gene conversional events. The cro1-1 mutation also results in enhanced mitotic-chromosomal instability and MATa/MATα cro1-1/cro1-1 mutants are sporulation deficient. These phenotypes indicate that the CRO1 gene modulates mitotic chromosomal integrity and is essential for normal meiosis. The cro1-1 mutant possesses Holliday junction resolvase activity, hence its recombinational defect does not involve failure to execute this putative final recombinational step. 7 refs., 1 fig., 5 tabs

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...

Neutron-induced cross-sections via the surrogate method

International Nuclear Information System (INIS)

Boutoux, G.

2011-11-01

The surrogate reaction method is an indirect way of determining neutron-induced cross sections through transfer or inelastic scattering reactions. This method presents the advantage that in some cases the target material is stable or less radioactive than the material required for a neutron-induced measurement. The method is based on the hypothesis that the excited nucleus is a compound nucleus whose decay depends essentially on its excitation energy and on the spin and parity state of the populated compound state. Nevertheless, the spin and parity population differences between the compound-nuclei produced in the neutron and transfer-induced reactions may be different. This work reviews the surrogate method and its validity. Neutron-induced fission cross sections obtained with the surrogate method are in general good agreement. However, it is not yet clear to what extent the surrogate method can be applied to infer radiative capture cross sections. We performed an experiment to determine the gamma decay probabilities for 176 Lu and 173 Yb by using the surrogate reactions 174 Yb( 3 He,pγ) 176 Lu * and 174 Yb( 3 He,αγ) 173 Yb * , respectively, and compare them with the well-known corresponding probabilities obtained in the 175 Lu(n,γ) and 172 Yb(n,γ) reactions. This experiment provides answers to understand why, in the case of gamma-decay, the surrogate method gives significant deviations compared to the corresponding neutron-induced reaction. In this work, we have also assessed whether the surrogate method can be applied to extract capture probabilities in the actinide region. Previous experiments on fission have also been reinterpreted. Thus, this work provides new insights into the surrogate method. This work is organised in the following way: in chapter 1, the theoretical aspects related to the surrogate method will be introduced. The validity of the surrogate method will be investigated by means of statistical model calculations. In chapter 2, a review on

Extracting Cross-Ontology Weighted Association Rules from Gene Ontology Annotations.

Science.gov (United States)

Agapito, Giuseppe; Milano, Marianna; Guzzi, Pietro Hiram; Cannataro, Mario

2016-01-01

Gene Ontology (GO) is a structured repository of concepts (GO Terms) that are associated to one or more gene products through a process referred to as annotation. The analysis of annotated data is an important opportunity for bioinformatics. There are different approaches of analysis, among those, the use of association rules (AR) which provides useful knowledge, discovering biologically relevant associations between terms of GO, not previously known. In a previous work, we introduced GO-WAR (Gene Ontology-based Weighted Association Rules), a methodology for extracting weighted association rules from ontology-based annotated datasets. We here adapt the GO-WAR algorithm to mine cross-ontology association rules, i.e., rules that involve GO terms present in the three sub-ontologies of GO. We conduct a deep performance evaluation of GO-WAR by mining publicly available GO annotated datasets, showing how GO-WAR outperforms current state of the art approaches.

The effect of modulators of radiation-induced G2 arrest on the repair of radiation-induced DNA damage detectable by neutral filter elution

International Nuclear Information System (INIS)

Rowley, R.; Kort, L.

1988-01-01

The influence of cycloheximide (50 μg/ml), caffeine (5 mM) and cordycepin (0.15 mM) on the repair of the damage detectable in DNA by neutral filter elution was determined. Chinese hamster ovary cells (CHO) were irradiated with X-ray doses of 20, 60 and 100 Gy then allowed to repair without drug treatment or in the presence of each drug for intervals up to 6 h. DNA damage repair proceeded in two phases. The fast component of the repair process (t 1/2 approx. 7 min) was not modified by drug treatment; the slow component (t 1/2 170 min) was unaffected by cycloheximide or cordycepin, but appeared to be inhibited by caffeine. It was concluded that: (a) the lesion which results in radiation-induced G 2 arrest is not the lesion which is detectable by neutral filter elution, and (b) the influence of caffeine on dsb repair is specific to caffeine and is not mediated by a reduction in the duration of G 2 arrest. (author)

Photoinduced Dynamics of Neutral, Cationic, and Anionic Species

DEFF Research Database (Denmark)

Stephansen, Anne Boutrup

. The investigations have primarily employed femtosecond time-resolved photoionization or photodetachment techniques. Intersystem crossing (ISC) in neutral organic species is conventionally assumed to be slow due to the spin-forbidden nature of the process; this assumption has been challenged during the past decade...

Studies on the utility of artificial mutations in plant breeding, 16: Gene analysis of male sterility induced in rice [Oryza sativa

International Nuclear Information System (INIS)

Ko, T.; Yamagata, H.

1987-01-01

Eleven male-sterile mutants were induced from a rice variety Sasanishiki by ethyleneimine and γ-ray treatments of seeds. Nine of them produced no pollen grains or only abortive ones and the other two showed extremely low pollen fertilities. The eleven mutants were crossed with the original variety. All F 1 hybrids were fertile, i.e., normal in both pollen and seed fertilities. In eight of their F 2 progenies, fertile and male-sterile plants segregated in a ratio of 3 to 1, indicating that the male sterility of the eight mutants was controlled by a single recessive gene. In one of the other three, segregation ratio suggested the participation of two recessive genes, while in the remaining two, the number of the genes responsible for male sterility could not be determined. (author)

Measurement of the neutron-induced fission cross-section of 240,242Pu

International Nuclear Information System (INIS)

Salvador-Castineira, P.; Hambsch, F.J.; Brys, T.; Oberstedt, S.; Vidali, M.; Pretel, C.

2014-01-01

Fast spectrum neutron-induced fission cross-section data for transuranic isotopes are in high demand in the nuclear data community. In particular, highly accurate data are needed for the new Generation-IV nuclear applications. The aim is to obtain precise neutron-induced fission cross-sections for 240 Pu and 242 Pu. In this context accurate data on spontaneous fission half-lives have also been measured. To minimise the total uncertainty on the fission cross-sections the detector efficiency has been studied in detail. Both isotopes have been measured using a twin Frisch-grid ionisation chamber (TFGIC) due to its superiority compared to other detector systems in view of radiation hardness, 2 x 2π solid angle coverage and very good energy resolution. (authors)

Stress analysis of neutral beam pivot point bellows for tokamak fusion test reactor

International Nuclear Information System (INIS)

Johnson, J.J.; Benda, B.J.; Tiong, L.W.

1983-01-01

The neutral beam pivot point bellows serves as an airtight flexible linkage between the torus duct and the neutral beam transition duct in Princeton University's Tokamak Fusion Test Reactor. The bellows considered here is basically rectangular in cross section with rounded corners; a unique shape. Its overall external dimensions are about 28 in. (about 711 mm) X about 35 in. (about 889 mm). The bellows is formed from 18 convolutions and is of the nested ripple type. It is about 11 in. (about 43.3 mm) in length, composed of Inconel 718, and each leaf has a thickness of 0.034 in. (.86 mm). The bellows is subjected to a series of design loading conditions -- vacuum, vacuum + 2 psi (.12 MPa), vacuum + stroke (10,000 cycles), vacuum + temperature increase + extension, extension to a stress of 120 ksi (838 MPa), and a series of rotational loading conditions induced in the bellows by alignment of the neutral beam injector. A stress analysis of the bellows was performed by the finite element method -- locations and magnitude of maximum stresses were calculated for all of the design loading conditions to check with allowable values and help guide placement of strain gauges during proof testing. A typical center convolution and end convolution were analyzed. Loading conditions were separated into symmetric and antisymmetric cases about the planes of symmetry of the cross-section. Iterative linear analyses were performed, i.e. compressive loading conditions led to predicted overlap of the leaves from linear analysis and restraints were added to prevent such overlap. This effect was found to be substantial in stress predicition and necessary to be taken into account. A total of eleven loading conditions and seven models were analyzed. The results showed peak stresses to be within allowable limits and the number of allowable cycles to be greater than the design condition

Feline Immunodeficiency Virus (FIV Neutralization: A Review

Directory of Open Access Journals (Sweden)

Margaret J. Hosie

2011-10-01

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

International network for comparison of HIV neutralization assays: the NeutNet report II.

Directory of Open Access Journals (Sweden)

Leo Heyndrickx

Full Text Available BACKGROUND: Neutralizing antibodies provide markers for vaccine-induced protective immunity in many viral infections. By analogy, HIV-1 neutralizing antibodies induced by immunization may well predict vaccine effectiveness. Assessment of neutralizing antibodies is therefore of primary importance, but is hampered by the fact that we do not know which assay(s can provide measures of protective immunity. An international collaboration (NeutNet involving 18 different laboratories previously compared different assays using monoclonal antibodies (mAbs and soluble CD4 (Phase I study. METHODS: In the present study (Phase II, polyclonal reagents were evaluated by 13 laboratories. Each laboratory evaluated nine plasmas against an 8 virus panel representing different genetic subtypes and phenotypes. TriMab, a mixture of three mAbs, was used as a positive control allowing comparison of the results with Phase I in a total of nine different assays. The assays used either uncloned virus produced in peripheral blood mononuclear cells (PBMCs (Virus Infectivity Assays, VIA, or Env (gp160-pseudotyped viruses (pseudoviruses, PSV produced in HEK293T cells from molecular clones or from uncloned virus. Target cells included PBMC and genetically engineered cell lines in either single- or multiple-cycle infection format. Infection was quantified by using a range of assay read-outs including extra- or intra-cellular p24 antigen detection, luciferase, beta-galactosidase or green fluorescent protein (GFP reporter gene expression. FINDINGS: Using TriMab, results of Phase I and Phase II were generally in agreement for six of the eight viruses tested and confirmed that the PSV assay is more sensitive than PBMC (p = 0.014. Comparisons with the polyclonal reagents showed that sensitivities were dependent on both virus and plasma. CONCLUSIONS: Here we further demonstrate clear differences in assay sensitivities that were dependent on both the neutralizing reagent and the virus

International network for comparison of HIV neutralization assays: the NeutNet report II.

Science.gov (United States)

Heyndrickx, Leo; Heath, Alan; Sheik-Khalil, Enas; Alcami, Jose; Bongertz, Vera; Jansson, Marianne; Malnati, Mauro; Montefiori, David; Moog, Christiane; Morris, Lynn; Osmanov, Saladin; Polonis, Victoria; Ramaswamy, Meghna; Sattentau, Quentin; Tolazzi, Monica; Schuitemaker, Hanneke; Willems, Betty; Wrin, Terri; Fenyö, Eva Maria; Scarlatti, Gabriella

2012-01-01

Neutralizing antibodies provide markers for vaccine-induced protective immunity in many viral infections. By analogy, HIV-1 neutralizing antibodies induced by immunization may well predict vaccine effectiveness. Assessment of neutralizing antibodies is therefore of primary importance, but is hampered by the fact that we do not know which assay(s) can provide measures of protective immunity. An international collaboration (NeutNet) involving 18 different laboratories previously compared different assays using monoclonal antibodies (mAbs) and soluble CD4 (Phase I study). In the present study (Phase II), polyclonal reagents were evaluated by 13 laboratories. Each laboratory evaluated nine plasmas against an 8 virus panel representing different genetic subtypes and phenotypes. TriMab, a mixture of three mAbs, was used as a positive control allowing comparison of the results with Phase I in a total of nine different assays. The assays used either uncloned virus produced in peripheral blood mononuclear cells (PBMCs) (Virus Infectivity Assays, VIA), or Env (gp160)-pseudotyped viruses (pseudoviruses, PSV) produced in HEK293T cells from molecular clones or from uncloned virus. Target cells included PBMC and genetically engineered cell lines in either single- or multiple-cycle infection format. Infection was quantified by using a range of assay read-outs including extra- or intra-cellular p24 antigen detection, luciferase, beta-galactosidase or green fluorescent protein (GFP) reporter gene expression. Using TriMab, results of Phase I and Phase II were generally in agreement for six of the eight viruses tested and confirmed that the PSV assay is more sensitive than PBMC (p = 0.014). Comparisons with the polyclonal reagents showed that sensitivities were dependent on both virus and plasma. Here we further demonstrate clear differences in assay sensitivities that were dependent on both the neutralizing reagent and the virus. Consistent with the Phase I study, we recommend

Repair of 8-methoxypsoralen + UVA-induced damage in specific sequences in chromosomal and episomal DNA in human cells

Energy Technology Data Exchange (ETDEWEB)

Dean, S.W.

1989-07-01

A study of the repair of DNA damage in the dihydrofolate reductase (dhfr) gene of SV40-transformed human fibroblasts after treatment with 8-methoxypsoralen (8MOP) and UVA is described. 8MOP+UVA-induced cross-links in the dhfr gene were completely repaired by 12 h in one normal and one Fanconi's anaemia (FA) group A cell line. In contrast, approximately 35% of cross-links in an episomally maintained Epstein--Barr virus derived plasmid remained unrepaired even after 48 h. Cross-linkable monoadducts in the dhfr gene were repaired more slowly than cross-links, and there was no detectable repair of cross-linkable monoadducts in the plasmid. Thus the ability of a cell to repair 8MOP+UVA-induced cross-links or cross-linkable monoadducts in an episome does not reflect its capacity to repair such lesions in genomic DNA.

Repair of 8-methoxypsoralen + UVA-induced damage in specific sequences in chromosomal and episomal DNA in human cells

International Nuclear Information System (INIS)

Dean, S.W.

1989-01-01

A study of the repair of DNA damage in the dihydrofolate reductase (dhfr) gene of SV40-transformed human fibroblasts after treatment with 8-methoxypsoralen (8MOP) and UVA is described. 8MOP+UVA-induced cross-links in the dhfr gene were completely repaired by 12 h in one normal and one Fanconi's anaemia (FA) group A cell line. In contrast, ∼35% of cross-links in an episomally maintained Epstein-Barr virus derived plasmid remained unrepaired even after 48 h. Cross-linkable monoadducts in the dhfr gene were repaired more slowly than cross-links, and there was no detectable repair of cross-linkable monoadducts in the plasmid. Thus the ability of a cell to repair 8MOP+UVA-induced cross-links or cross-linkable monoadducts in an episome does not reflect its capacity to repair such lesions in genomic DNA. (author)

Cross-section calculations for neutron-induced reactions up to 50 MeV

International Nuclear Information System (INIS)

Yamamuro, Nobuhiro.

1996-01-01

In the field of accelerator development, medium-energy reaction cross-section data for structural materials of accelerator and shielding components are required, especially for radiation protection purposes. For a d + Li stripping reaction neutron source used in materials research, neutron reaction cross sections up to 50 MeV are necessary for the design study of neutron irradiation facilities. The current version of SINCROS-II is able to calculate neutron and proton-induced reaction cross sections up to ∼ 50 MeV with some modifications and extensions of the cross-section calculation code. The production of isotopes when structural materials and other materials are bombarded with neutrons or protons is calculated using a revised code in the SINCROS-II system. The parameters used in the cross-section calculations are mainly examined with proton-induced reactions because the experimental data for neutrons above 20 MeV are rare. The status of medium mass nuclide evaluations for aluminum, silicon, chromium, manganese, and copper is presented. These data are useful to estimate the radiation and transmutation of nuclei in the materials

Molecular cytogenetics of radiation-induced gene mutations in Drosophila melanogaster

International Nuclear Information System (INIS)

Aleksandrov, I.D.; Aleksandrova, M.V.; Lapidus, I.L.; Karpovskij, A.L.

1996-01-01

The classical paradigm of spatially unrelated lesions for gene mutations and chromosomal exchange breakpoints induced by ionizing radiations in eukaryotic cells was re-examined in the experiments on the mapping of gamma-ray- or neutron-induced breakpoints in and outside of white (w) and vestigial (vg) genes of Drosophila melanogaster using the in situ hybridization of the large fragments of the genes under study with the polythene chromosomes of the relevant mutants. The results for the random sample of 60 inversion and translocation breakpoints analysed to date have shown that (i) 50% of them are mapped as the hot spots within big introns of both the genes, and (ii) 21 of 60 breaks (35%) are located outside of genes. It is important to note that 26% (16/60) of the breakpoints analysed are flanked by the deletions, the sizes of which vary from the quarter to a whole of the gene. It was found that the deletions flank both the inversion and translocation breakpoints and arise more often after action of neutrons than photons. An unexpectedly high frequency of the multiple-damaged w and vg mutants that have the gene/point mutation and additional, but separate, chromosome exchange (the so-called double- or triple-site mutants) has shown that the genetic danger of ionizing radiation is higher than usually accepted on the base of single gene/point mutation assessments. 11 refs., 3 figs

Radiation-induced gene amplification in rodent and human cells

International Nuclear Information System (INIS)

Luecke-Huhle, C.; Gloss, B.; Herrlich, P.

1990-01-01

Ionizing and UV radiations induce amplification of SV40 DNA sequences integrated in the genome of Chinese hamster cells and increase amplification of the dihydrofolate reductase (DHFR) gene during methotrexate selection in human skin fibroblasts of a patient with ataxia telangiectasia. Various types of external (60-Co-γ-rays, 241-Am-α-particles, UV) or internal radiation (caused by the decay of 125 I incorporated into DNA in form of I-UdR) were applied. By cell fusion experiments it could be shown that SV40 gene amplification is mediated by one or several diffusible trans-acting factors induced or activated in a dose dependent manner by all types of radiation. One of these factors binds to a 10 bp sequence within the minimal origin of replication of SV40. In vivo competition with an excess of a synthetic oligonucleotide comprising this sequence blocks radiation-induced amplification. (author) 25 refs.; 8 figs

Oral Gene Application Using Chitosan-DNA Nanoparticles Induces Transferable Tolerance

Science.gov (United States)

Ensminger, Stephan M.; Spriewald, Bernd M.

2012-01-01

Oral tolerance is a promising approach to induce unresponsiveness to various antigens. The development of tolerogenic vaccines could be exploited in modulating the immune response in autoimmune disease and allograft rejection. In this study, we investigated a nonviral gene transfer strategy for inducing oral tolerance via antigen-encoding chitosan-DNA nanoparticles (NP). Oral application of ovalbumin (OVA)-encoding chitosan-DNA NP (OVA-NP) suppressed the OVA-specific delayed-type hypersensitivity (DTH) response and anti-OVA antibody formation, as well as spleen cell proliferation following OVA stimulation. Cytokine expression patterns following OVA stimulation in vitro showed a shift from a Th1 toward a Th2/Th3 response. The OVA-NP-induced tolerance was transferable from donor to naïve recipient mice via adoptive spleen cell transfer and was mediated by CD4+CD25+ T cells. These findings indicate that nonviral oral gene transfer can induce regulatory T cells for antigen-specific immune modulation. PMID:22933401

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.

Precise integration of inducible transcriptional elements (PrIITE) enables absolute control of gene expression

DEFF Research Database (Denmark)

Pinto, Rita; Hansen, Lars; Hintze, John

2017-01-01

to be a limitation. Here, we report that the combined use of genome editing tools and last generation Tet-On systems can resolve these issues. Our principle is based on precise integration of inducible transcriptional elements (coined PrIITE) targeted to: (i) exons of an endogenous gene of interest (GOI) and (ii......Tetracycline-based inducible systems provide powerful methods for functional studies where gene expression can be controlled. However, the lack of tight control of the inducible system, leading to leakiness and adverse effects caused by undesirable tetracycline dosage requirements, has proven......) a safe harbor locus. Using PrIITE cells harboring a GFP reporter or CDX2 transcription factor, we demonstrate discrete inducibility of gene expression with complete abrogation of leakiness. CDX2 PrIITE cells generated by this approach uncovered novel CDX2 downstream effector genes. Our results provide...

A single amino-acid change in a highly conserved motif of gp41 elicits HIV-1 neutralization and protects against CD4 depletion.

Science.gov (United States)

Petitdemange, Caroline; Achour, Abla; Dispinseri, Stefania; Malet, Isabelle; Sennepin, Alexis; Ho Tsong Fang, Raphaël; Crouzet, Joël; Marcelin, Anne-Geneviève; Calvez, Vincent; Scarlatti, Gabriella; Debré, Patrice; Vieillard, Vincent

2013-09-01

The induction of neutralizing antibodies against conserved regions of the human immunodeficiency virus type 1 (HIV-1) envelope protein is a major goal of vaccine strategies. We previously identified 3S, a critical conserved motif of gp41 that induces the NKp44L ligand of an activating NK receptor. In vivo, anti-3S antibodies protect against the natural killer (NK) cell-mediated CD4 depletion that occurs without efficient viral neutralization. Specific substitutions within the 3S peptide motif were prepared by directed mutagenesis. Virus production was monitored by measuring the p24 production. Neutralization assays were performed with immune-purified antibodies from immunized mice and a cohort of HIV-infected patients. Expression of NKp44L on CD4(+) T cells and degranulation assay on activating NK cells were both performed by flow cytometry. Here, we show that specific substitutions in the 3S motif reduce viral infection without affecting gp41 production, while decreasing both its capacity to induce NKp44L expression on CD4(+) T cells and its sensitivity to autologous NK cells. Generation of antibodies in mice against the W614 specific position in the 3S motif elicited a capacity to neutralize cross-clade viruses, notable in its magnitude, breadth, and durability. Antibodies against this 3S variant were also detected in sera from some HIV-1-infected patients, demonstrating both neutralization activity and protection against CD4 depletion. These findings suggest that a specific substitution in a 3S-based immunogen might allow the generation of specific antibodies, providing a foundation for a rational vaccine that combine a capacity to neutralize HIV-1 and to protect CD4(+) T cells.

Cigarette smoke modulates expression of human rhinovirus-induced airway epithelial host defense genes.

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David Proud

Full Text Available Human rhinovirus (HRV infections trigger acute exacerbations of chronic obstructive pulmonary disease (COPD and asthma. The human airway epithelial cell is the primary site of HRV infection and responds to infection with altered expression of multiple genes, the products of which could regulate the outcome to infection. Cigarette smoking aggravates asthma symptoms, and is also the predominant risk factor for the development and progression of COPD. We, therefore, examined whether cigarette smoke extract (CSE modulates viral responses by altering HRV-induced epithelial gene expression. Primary cultures of human bronchial epithelial cells were exposed to medium alone, CSE alone, purified HRV-16 alone or to HRV-16+ CSE. After 24 h, supernatants were collected and total cellular RNA was isolated. Gene array analysis was performed to examine mRNA expression. Additional experiments, using real-time RT-PCR, ELISA and/or western blotting, validated altered expression of selected gene products. CSE and HRV-16 each induced groups of genes that were largely independent of each other. When compared to gene expression in response to CSE alone, cells treated with HRV+CSE showed no obvious differences in CSE-induced gene expression. By contrast, compared to gene induction in response to HRV-16 alone, cells exposed to HRV+CSE showed marked suppression of expression of a number of HRV-induced genes associated with various functions, including antiviral defenses, inflammation, viral signaling and airway remodeling. These changes were not associated with altered expression of type I or type III interferons. Thus, CSE alters epithelial responses to HRV infection in a manner that may negatively impact antiviral and host defense outcomes.

Mapping the epitopes of a neutralizing antibody fragment directed against the lethal factor of Bacillus anthracis and cross-reacting with the homologous edema factor.

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Philippe Thullier

Full Text Available The lethal toxin (LT of Bacillus anthracis, composed of the protective antigen (PA and the lethal factor (LF, plays an essential role in anthrax pathogenesis. PA also interacts with the edema factor (EF, 20% identity with LF to form the edema toxin (ET, which has a lesser role in anthrax pathogenesis. The first recombinant antibody fragment directed against LF was scFv 2LF; it neutralizes LT by blocking the interaction between PA and LF. Here, we report that scFv 2LF cross-reacts with EF and cross-neutralizes ET, and we present an in silico method taking advantage of this cross-reactivity to map the epitope of scFv 2LF on both LF and EF. This method identified five epitope candidates on LF, constituted of a total of 32 residues, which were tested experimentally by mutating the residues to alanine. This combined approach precisely identified the epitope of scFv 2LF on LF as five residues (H229, R230, Q234, L235 and Y236, of which three were missed by the consensus epitope candidate identified by pre-existing in silico methods. The homolog of this epitope on EF (H253, R254, E258, L259 and Y260 was experimentally confirmed to constitute the epitope of scFv 2LF on EF. Other inhibitors, including synthetic molecules, could be used to target these epitopes for therapeutic purposes. The in silico method presented here may be of more general interest.

Measurement of the ratios of neutral-current to charged current cross sections of neutrino and antineutrino interactions in Ne

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Bosetti, P. C.; Fritze, P.; Grässler, H.; Hasert, F. J.; Schulte, R.; Schultze, K.; Geich-Gimbel, C.; Nellen, B.; Pech, R.; Wünsch, B.; Grant, A.; Hulth, P. O.; Klein, H.; Morrison, D. R. O.; Pape, L.; Wachsmuth, H.; Vayaki, A.; Barnham, K. W. J.; Beuselinck, R.; Clayton, E. F.; Miller, D. B.; Mobayyen, M. M.; Petrides, A.; Albajar, C.; Myatt, G.; Saitta, B.; Wells, J.; Bolognese, T.; Vignaud, D.; Aachen-Bonn-CERN-Democritos-Imperial College, London-Oxford-Saclay Collaboration

1983-05-01

The ratios of neutral current to charged current cross sections of neutrino and antineutrino interactions in heavy Ne/H 2 mixture have been measured in BEBC. The beam was the CERN SPS 200 GeV/ c narrow band beam. The ratios were obtained using a cut in the transverse momentum of the hadronic system. In the standard Glashow-Salam-Weinberg model, our results correspond to the value of sin 2θw = 0.182 ± 0.020 ± 0.012. By combining this experiment with data from a hydrogen target the coupling constants uL2 and L2 are found to be 0.15 ± 0.04 and 0.19 ± 0.05, respectively.

Measurement of the ratios of neutral-current to charged current cross sections of neutrino and antineutrino interactions in Ne

International Nuclear Information System (INIS)

Bosetti, P.C.; Fritze, P.; Graessler, H.; Hasert, F.J.; Schulte, R.; Schultze, K.; Vayaki, A.; Barnham, K.W.J.; Beuselinck, R.; Clayton, E.F.; Miller, D.B.; Mobayyen, M.M.; Petrides, A.; Albajar, C.; Myatt, G.; Saitta, B.; Wells, J.

1983-01-01

The ratios of neutral current to charged current cross sections of neutrino and antineutrino interactions in heavy Ne/H 2 mixture have been measured in BEBC. The beam was the CERN SPS 200 GeV/c narrow band beam. The ratios were obtained using a cut in the transverse momentum of the hadronic system. In the standard Glashow-Salam-Weinberg model, our results correspond to the value of sin 2 THETAsub(w)=0.182+-0.020+-0.012. By combining this experiment with data from a hydrogen target the coupling constants usub(L) 2 and dsub(L) 2 are found to be 0.15+-0.04 and 0.19+-0.05, respectively. (orig.)

Bound states for a neutral particle analogous to a quantum dot induced by the non-inertial effects of the Fermi-Walker reference frame

International Nuclear Information System (INIS)

Bakke, Knut

2010-01-01

We study the appearance of bound states analogous to a quantum dot, proposed by Tan and Inkson (1996) , in the non-relativistic quantum dynamics of a neutral particle with permanent magnetic dipole moment induced by the non-inertial effects of the Fermi-Walker reference frame.

In vitro selection of mutants: Inducible gene regulation for salt tolerance

International Nuclear Information System (INIS)

Winicov, I.; Bastola, D.R.; Deutch, C.E.; Pethe, V.V.; Petrusa, L.

2001-01-01

Regulation of differentially expressed genes in plants may be involved in inducing tolerance to stress. Isogenic salt-sensitive and salt-tolerant alfalfa lines were investigated for molecular differences in their response to salt. The genes, which are differentially induced by salt in the salt-tolerant alfalfa cells and are also regulated by salt at the whole plant level, were cloned. Both transcriptional and post- transcriptional mechanisms influenced salt-induced product accumulation in the salt-tolerant alfalfa. The salt-tolerant plants doubled proline concentration rapidly in roots, while salt-sensitive plants showed a delayed response. To understand the regulatory system in the salt-tolerant alfalfa, two genes that are expressed in roots were studied. Alfin1 encodes a zinc-finger type putative DNA transcription factor conserved in alfalfa, rice and Arabidopsis, and MsPRP2 encodes a protein that serves as a cell wall- membrane linker in roots. Recombinant Alfin1 protein was selected, amplified, cloned and its consensus sequence was identified. The recombinant Alfin1 also bound specifically to fragments of the MsPRP2 promoter in vitro, containing the Alfin1 binding consensus sequence. The results show unambiguously binding specificity of Alfin1 DNA, supporting its role in gene regulation. Alfin1 function was tested in transformed alfalfa in vivo by over-expressing Alfin1 from 35S CaMV promoter. The transgenic plants appeared normal. However, plants harboring the anti-sense construct did not grow well in soil, indicating that Alfin1 expression was essential. Alfin1 over-expression in transgenic alfalfa led to enhanced levels of MsPRP2 transcript accumulation, demonstrating that Alfin1 functioned in vivo in gene regulation. Since MsPRP2 gene is also induced by salt, it is likely that Alfin1 is an important transcription factor for gene regulation in salt-tolerant alfalfa, and an excellent target for manipulation to improve salt tolerance. (author)

FORMALDEHYDE-INDUCED GENE EXPRESSION IN F344 RAT NASAL RESPIRATORY EPITHELIUM.

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Formaldehyde-induced gene expression in F344 rat nasal respiratory epithelium ABSTRACTFormaldehyde, an occupational and environmental toxicant used extensively in the manufacturing of many household and personal use products, is known to induce squamous cell carci...

Relationship between radiation induced activation of DNA repair genes and radiation induced apoptosis in human cell line A431

International Nuclear Information System (INIS)

Bom, Hee Seung; Min, Jung Jun; Kim, Kyung Keun; Choi, Keun Hee

2000-01-01

The purpose of this study was to evaluate the relationship between radiation-induced acivation of DNA repair genes and radiation induced apoptosis in A431 cell line. Five and 25 Gys of gamma radiation were given to A431 cells by a Cs-137 cell irradiator. Apoptosis was evaluated by flow cytometry using annexin V-fluorescein isothiocyanate and propidium iodide staining. The expression of DNA repair genes was evaluated by both Northern and Western blot analyses. The number of apoptotic cells increased with the increased radiation dose. It increased most significantly at 12 hours after irradiation. Expression of p53, p21, and ℎRAD50 reached the highest level at 12 hours after 5 Gy irradiation. In response to 25 Gy irradiation, ℎRAD50 and p21 were expressed maximally at 12 hours, but p53 and GADD45 genes showed the highest expression level after 12 hours. Induction of apoptosis and DNA repair by ionizing radiation were closely correlated. The peak time of inducing apoptosis and DNA repair was 12 hours in this study model. ℎRAD50, a recently discovered DNA repair gene, was also associated with radiation-induced apoptosis.=20

A comparison of neutral and immune genetic variation in Atlantic salmon, Salmo salar L. in Chilean aquaculture facilities.

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David S Portnoy

Full Text Available Genetic diversity was assessed in samples of cultured Atlantic salmon, Salmo salar L., obtained from facilities in Chile between 2005 and 2010, a period of time during which the infectious pathogens Infectious Salmon Anemia (ISA virus, Caligus rogercresseyi (sea lice, and Piscirickettsia salmonis (salmon rickettsial syndrome were common. Two panels of microsatellite markers were utilized: one with microsatellites with no known gene associations (neutral and one featuring microsatellites linked to putative immune-related genes (immune-related. Allelic richness and gene diversity across samples were significantly greater in neutral loci as compared to immune-related loci. Both diversity measures were homogeneous among samples for immune-related loci and heterogeneous among samples for neutral loci. Immune-related loci were identified as F(ST outliers in pairwise comparisons of samples at a 10-fold higher frequency than neutral loci. These results indicate that neutral and immune-related portions of the Atlantic salmon genome may have differed in response to the gauntlet of pathogens and that monitoring of specific, well characterized immune-related loci as well as neutral loci in cultured species could be useful when disease control and prevention is a goal.

Tacrolimus increases Nox4 expression in human renal fibroblasts and induces fibrosis-related genes by aberrant TGF-beta receptor signalling.

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Georg Kern

Full Text Available Chronic nephrotoxicity of immunosuppressives is one of the main limiting factors in the long-term outcome of kidney transplants, leading to tissue fibrosis and ultimate organ failure. The cytokine TGF-β is considered a key factor in this process. In the human renal fibroblast cell line TK-173, the macrolide calcineurin inhibitor tacrolimus (FK-506 induced TGF-β-like effects, manifested by increased expression of NAD(PH-oxidase 4 (Nox4, transgelin, tropomyosin 1, and procollagen α1(V mRNA after three days. The macrolide mTOR inhibitor rapamycin had similar effects, while cyclosporine A did not induce fibrose-related genes. Concentration dependence curves were sigmoid, where mRNA expression was induced already at low nanomolar levels of tacrolimus, and reached saturation at 100-300 nM. The effects were independent of extracellular TGF-β as confirmed by the use of neutralizing antibodies, and thus most likely caused by aberrant TGF-β receptor signaling, where binding of tacrolimus to the regulatory FKBP12 protein results in a "leaky" TGF-β receptor. The myofibroblast marker α-smooth muscle actin was neither induced by tacrolimus nor by TGF-β1, indicating an incomplete activation of TK-173 fibroblasts under culture conditions. Tacrolimus- and TGF-β1-induced Nox4 protein upregulation was confirmed by Western blotting, and was accompanied by a rise in intracellular H2O2 concentration. Si-RNA mediated knock-down of Nox4 expression prevented up-regulation of procollagen α1(V mRNA in tacrolimus-treated cells, but induced procollagen α1(V expression in control cells. Nox4 knock-down had no significant effect on the other genes tested. TGF-β is a key molecule in fibrosis, and the constant activation of aberrant receptor signaling by tacrolimus might contribute to the long-term development of interstitial kidney fibrosis in immunosuppressed patients. Nox4 levels possibly play a regulatory role in these processes.

Calculation of beam neutralization in the IPNS-Upgrade RCS

International Nuclear Information System (INIS)

Chae, Yong-Chul.

1995-01-01

The author calculated the neutralization of circulating beam in this report. In the calculation it is assumed that all electrons liberated from the background molecules due to the collisional processes are trapped in the potential well of the proton beam. Including the dependence of ionization cross sections on the kinetic energy of the incident particle, the author derived the empirical formula for beam neutralization as a function of time and baseline vacuum pressure, which is applicable to the one acceleration cycle of the IPNS-Upgrade RCS

Neutral and emotional episodic memory: global impairment after lorazepam or scopolamine.

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Kamboj, Sunjeev K; Curran, H Valerie

2006-11-01

Benzodiazepines and anticholinergic drugs have repeatedly been shown to impair episodic memory for emotionally neutral material in humans. However, their effect on memory for emotionally laden stimuli has been relatively neglected. We sought to investigate the effects of the benzodiazepine, lorazepam, and the anticholinergic, scopolamine, on incidental episodic memory for neutral and emotional components of a narrative memory task in humans. A double-blind, placebo-controlled independent group design was used with 48 healthy volunteers to examine the effects of these drugs on emotional and neutral episodic memory. As expected, the emotional memory advantage was retained for recall and recognition memory under placebo conditions. However, lorazepam and scopolamine produced anterograde recognition memory impairments on both the neutral and emotional components of the narrative, although floor effects were obtained for recall memory. Furthermore, compared with placebo, recognition memory for both central (gist) and peripheral (detail) aspects of neutral and emotional elements of the narrative was poorer after either drug. Benzodiazepine-induced GABAergic enhancement or scopolamine-induced cholinergic hypofunction results in a loss of the enhancing effect of emotional arousal on memory. Furthermore, lorazepam- and scopolamine-induced memory impairment for both gist (which is amygdala dependent) and detail raises the possibility that their effects on emotional memory do not depend only on the amygdala. We discuss the results with reference to potential clinical/forensic implications of processing emotional memories under conditions of globally impaired episodic memory.

Evolutionary advantage via common action of recombination and neutrality

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Saakian, David B.; Hu, Chin-Kun

2013-11-01

We investigate evolution models with recombination and neutrality. We consider the Crow-Kimura (parallel) mutation-selection model with the neutral fitness landscape, in which there is a central peak with high fitness A, and some of 1-point mutants have the same high fitness A, while the fitness of other sequences is 0. We find that the effect of recombination and neutrality depends on the concrete version of both neutrality and recombination. We consider three versions of neutrality: (a) all the nearest neighbor sequences of the peak sequence have the same high fitness A; (b) all the l-point mutations in a piece of genome of length l≥1 are neutral; (c) the neutral sequences are randomly distributed among the nearest neighbors of the peak sequences. We also consider three versions of recombination: (I) the simple horizontal gene transfer (HGT) of one nucleotide; (II) the exchange of a piece of genome of length l, HGT-l; (III) two-point crossover recombination (2CR). For the case of (a), the 2CR gives a rather strong contribution to the mean fitness, much stronger than that of HGT for a large genome length L. For the random distribution of neutral sequences there is a critical degree of neutrality νc, and for μmutations affect the mean-field-like and fluctuation-like factors similarly. Consequently, recombination can accelerate the non-mean-field (fluctuation) type dynamics without considerably affecting the mean-field-like factors.

Inactivated H7 Influenza Virus Vaccines Protect Mice despite Inducing Only Low Levels of Neutralizing Antibodies.

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Kamal, Ram P; Blanchfield, Kristy; Belser, Jessica A; Music, Nedzad; Tzeng, Wen-Pin; Holiday, Crystal; Burroughs, Ashley; Sun, Xiangjie; Maines, Taronna R; Levine, Min Z; York, Ian A

2017-10-15

Avian influenza viruses of the H7 hemagglutinin (HA) subtype present a significant public health threat, as evidenced by the ongoing outbreak of human A(H7N9) infections in China. When evaluated by hemagglutination inhibition (HI) and microneutralization (MN) assays, H7 viruses and vaccines are found to induce lower level of neutralizing antibodies (nAb) than do their seasonal counterparts, making it difficult to develop and evaluate prepandemic vaccines. We have previously shown that purified recombinant H7 HA appear to be poorly immunogenic in that they induce low levels of HI and MN antibodies. In this study, we immunized mice with whole inactivated reverse genetics reassortant (RG) viruses expressing HA and neuraminidase (NA) from 3 different H7 viruses [A/Shanghai/2/2013(H7N9), A/Netherlands/219/2003(H7N7), and A/New York/107/2003(H7N2)] or with human A(H1N1)pdm09 (A/California/07/2009-like) or A(H3N2) (A/Perth16/2009) viruses. Mice produced equivalent titers of antibodies to all viruses as measured by enzyme-linked immunosorbent assay (ELISA). However, the antibody titers induced by H7 viruses were significantly lower when measured by HI and MN assays. Despite inducing very low levels of nAb, H7 vaccines conferred complete protection against homologous virus challenge in mice, and the serum antibodies directed against the HA head region were capable of mediating protection. The apparently low immunogenicity associated with H7 viruses and vaccines may be at least partly related to measuring antibody titers with the traditional HI and MN assays, which may not provide a true measure of protective immunity associated with H7 immunization. This study underscores the need for development of additional correlates of protection for prepandemic vaccines. IMPORTANCE H7 avian influenza viruses present a serious risk to human health. Preparedness efforts include development of prepandemic vaccines. For seasonal influenza viruses, protection is correlated with antibody

Mutation of neutralizing/antibody-dependent enhancing epitope on spike protein and 7b gene of feline infectious peritonitis virus: influences of viral replication in monocytes/macrophages and virulence in cats.

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Takano, Tomomi; Tomiyama, Yoshika; Katoh, Yasuichiroh; Nakamura, Michiyo; Satoh, Ryoichi; Hohdatsu, Tsutomu

2011-03-01

We previously prepared neutralizing monoclonal antibody (MAb)-resistant (mar) mutant viruses using a laboratory strain feline infectious peritonitis virus (FIPV) 79-1146 (Kida et al., 1999). Mar mutant viruses are mutated several amino acids of the neutralizing epitope of Spike protein, compared with the parent strain, FIPV 79-1146. We clarified that MAb used to prepare mar mutant viruses also lost its activity to enhance homologous mar mutant viruses, strongly suggesting that neutralizing and antibody-dependent enhancing epitopes are present in the same region in the strain FIPV 79-1146. We also discovered that amino acid mutation in the neutralizing epitope reduced viral replication in monocytes/macrophages. We also demonstrated that the mutation or deletion of two nucleotides in 7b gene abrogate the virulence of strain FIPV 79-1146. Copyright © 2011 Elsevier B.V. All rights reserved.

Infrequent alterations of the P53 gene in rat skin cancers induced by ionising-radiation

International Nuclear Information System (INIS)

Jin, Y.; Burns, F.J.; Garte, S.J.; Hosselet, S.; New York Univ., NY

1996-01-01

Radiation carcinogenesis almost certainly involves multiple genetic alterations. Identification of such genetic alterations would provide information to help understand better the molecular mechanism or radiation carcinogenesis. The energy released by ionizing radiation has the potential to produce DNA strand breaks, major gene deletions or rearrangements, and other base damages. Alterations of the p53 gene, a common tumour suppressor gene altered in human cancers, were examined in radiation-induced rat skin cancers. Genomic DNA from a total of 33rat skin cancers induced by ionizing radiation was examined by Southern blot hybridization for abnormal restriction fragment patterns in the p53 gene. A abnormal p53 restriction pattern was found in one of 16 cancers induced by electron radiation and in one of nine cancers induced by neon ions. The genomic DNA from representative cancers, including the two with an abnormal restriction pattern was further examined by polymerase chain reaction amplification and direct sequencing in exons 5-8 of the p53 gene. The results showed that one restriction fragment length polymorphism (RFLP)-positive cancer induced by electron radiation had a partial gene deletion which was defined approximately between exons 2-8, while none of the other cancers showed sequence changes. Our results indicate that the alterations in the critical binding region of the p53 gene are infrequent in rat skin cancers induced by either electron or neon ion radiation. (Author)

Identification of an attenuated barley stripe mosaic virus for the virus-induced gene silencing of pathogenesis-related wheat genes

OpenAIRE

Buhrow, Leann M.; Clark, Shawn M.; Loewen, Michele C.

2016-01-01

Background Virus-induced gene silencing (VIGS) has become an emerging technology for the rapid, efficient functional genomic screening of monocot and dicot species. The barley stripe mosaic virus (BSMV) has been described as an effective VIGS vehicle for the evaluation of genes involved in wheat and barley phytopathogenesis; however, these studies have been obscured by BSMV-induced phenotypes and defense responses. The utility of BSMV VIGS may be improved using a BSMV genetic background which...

Neutral pion electroproduction and virtual Compton scattering on proton with four-momentum transfer squared Q2 = 1 GeV2. Measurement of cross-sections and of generalized polarizabilities

International Nuclear Information System (INIS)

Laveissiere, G.

2001-11-01

In hadronic physics, the nucleon structure and the quarks confinement are still topical issues. The neutral pion electroproduction and virtual Compton scattering (VCS) reactions allow us to access new observables that describe this structure. This work is focussed on the VCS experiment performed at Jefferson Lab in 1998. The 4 GeV electron beam is scattered off a cryogenic hydrogen target, and the scattered electron and recoiled proton are detected in coincidence in the twin hall A spectrometers. The photon (pion) is reconstructed using a missing particle technique. The data analysis allowed to extract the cross sections relative to both process at four-momentum transfer squared Q 2 = 1 GeV 2 . The VCS cross section has been extracted for the first time in the proton resonance region (W between 1.O and 2.0 GeV) through the photon electroproduction reaction. Around the pion-production threshold up to the Delta(1232) resonance region, these results lead to the measurement of the generalized polarizabilities, that describe the proton structure in the same way as the elastic form factors. Moreover, the neutral pion electroproduction cross section measurement in the resonance region has brought new constraints on the existing phenomenological models. (author)

Regulation of radiation-induced apoptosis by early growth response-1 gene in solid tumors

International Nuclear Information System (INIS)

Ahmed, M.

2003-01-01

Ionizing radiation exposure is associated with activation of certain immediate-early genes that function as transcription factors. These include members of jun or fos and early growth response (EGR) gene families. In particular, the functional role of EGR-1 in radiation-induced signaling is pivotal since the promoter of EGR-1 contains radiation-inducible CArG DNA sequences. The Egr-1 gene belongs to a family of Egr genes that includes EGR-2, EGR-3, EGR-4, EGR-α and the tumor suppressor, Wilms' tumor gene product, WT1. The Egr-1 gene product, EGR-1, is a nuclear protein that contains three zinc fingers of the C 2 H 2 subtype. The EGR-1 GC-rich consensus target sequence, 5'-GCGT/GGGGCG-3' or 5'-TCCT/ACCTCCTCC-3', has been identified in the promoter regions of transcription factors, growth factors, receptors, cell cycle regulators and pro-apoptotic genes. The gene targets mediated by Egr-1 in response to ionizing radiation include TNF-α , p53, Rb and Bax, all these are effectors of apoptosis. Based on these targets, Egr-1 is a pivotal gene that initiates early signal transduction events in response to ionizing radiation leading to either growth arrest or cell death in tumor cells. There are two potential application of Egr-1 gene in therapy of cancer. First, the Egr-1 promoter contains information for appropriate spatial and temporal expression in-vivo that can be regulated by ionizing radiation to control transcription of genes that have pro-apoptotic and suicidal function. Secondly, EGR-1 protein can eliminate 'induced-radiation resistance' by inhibiting the functions of radiation-induced pro-survival genes (NFκB activity and bcl-2 expression) and activate pro-apoptotic genes (such as bax) to confer a significant radio-sensitizing effect. Together, the reported findings from my laboratory demonstrate clearly that EGR-1 is an early central gene that confers radiation sensitivity and its pro-apoptotic functions are synergized by abrogation of induced radiation

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

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Mingshun Zhang

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

Myostatin propeptide gene delivery by gene gun ameliorates muscle atrophy in a rat model of botulinum toxin-induced nerve denervation.

Science.gov (United States)

Tsai, Sen-Wei; Tung, Yu-Tang; Chen, Hsiao-Ling; Yang, Shang-Hsun; Liu, Chia-Yi; Lu, Michelle; Pai, Hui-Jing; Lin, Chi-Chen; Chen, Chuan-Mu

2016-02-01

Muscle atrophy is a common symptom after nerve denervation. Myostatin propeptide, a precursor of myostatin, has been documented to improve muscle growth. However, the mechanism underlying the muscle atrophy attenuation effects of myostatin propeptide in muscles and the changes in gene expression are not well established. We investigated the possible underlying mechanisms associated with myostatin propeptide gene delivery by gene gun in a rat denervation muscle atrophy model, and evaluated gene expression patterns. In a rat botulinum toxin-induced nerve denervation muscle atrophy model, we evaluated the effects of wild-type (MSPP) and mutant-type (MSPPD75A) of myostatin propeptide gene delivery, and observed changes in gene activation associated with the neuromuscular junction, muscle and nerve. Muscle mass and muscle fiber size was moderately increased in myostatin propeptide treated muscles (pmyostatin propeptide gene delivery, especially the mutant-type of MSPPD75A, attenuates muscle atrophy through myogenic regulatory factors and acetylcholine receptor regulation. Our data concluded that myostatin propeptide gene therapy may be a promising treatment for nerve denervation induced muscle atrophy. Copyright © 2016 Elsevier Inc. All rights reserved.

CAR expression and inducibility of CYP2B genes in liver of rats treated with PB-like inducers

International Nuclear Information System (INIS)

Pustylnyak, Vladimir O.; Gulyaeva, Lyudmila F.; Lyakhovich, Vyacheslav V.

2005-01-01

The expression of the CAR gene and inducibility of CYP2B protein in the liver of male Wistar rats treated with phenobarbital (PB) and triphenyldioxane (TPD) were investigated. To clarify the role of phosphorylation/dephosphorylation in these processes, rats were treated with inhibitors of Ca 2+ /calmodulin-dependent kinase II (W 7 ) or protein phosphatases PP1 and PP2A (OA) before induction. Constitutive expression of the CAR gene in livers of untreated rats was detected by multiplex RT-PCR. Treatment with W 7 resulted in a 2.8-fold induction of CAR gene expression, whereas OA led to a 2.4-fold decrease of the mRNA level. The same results were obtained for CYP2B genes expression, which were increased by W 7 treatment (two-fold) and decreased by OA (2.3-fold). PB-induction did not lead to significant alteration in the level of CAR gene expression, although CYP2B genes expression was enhanced two-fold over control values. TPD caused a two-fold increase of both CAR and CYP2B mRNA levels. Both inducers reduced the effects of inhibitors on CAR gene expression. Results of EMSA showed that PB, TPD or W 7 alone induced formation of complexes of NR1 with nuclear proteins. Appearance of the complexes correlated with an increase in CYP2B expression, and their intensities were modulated by the protein kinase inhibitors. Thus, our results demonstrate that constitutive expressions of CAR as well as CYP2B during induction are regulated by phosphorylation/dephosphorylation processes

The latest development of EAST neutral beam injector

International Nuclear Information System (INIS)

Hu Chundong; Xu Yongjian

2014-01-01

As the first full superconducting non-circular cross section Tokomak in the world, EAST is used to explore the forefront physics and engineering issues on the construction of Tokomak fusion reactor. Neutral beam injection has been recognized as one of the most effective means for plasma heating. According to the research plan of the EAST physics experiment, a set of neutral beam injector (4∼8 MW, 10∼100 s)will be built and operational in 2014. The paper presents the latest development of EAST neutral beam injector and the latest experiment results of long pulse beam extraction and high power beam extraction are reported, those results show that all targets reach or almost reach the design targets. All these will lay a solid foundation for the achievement of plasma heating and current drive for EAST in 2014. (authors)

Two-photon induced collagen cross-linking in bioartificial cardiac tissue

Science.gov (United States)

Kuetemeyer, Kai; Kensah, George; Heidrich, Marko; Meyer, Heiko; Martin, Ulrich; Gruh, Ina; Heisterkamp, Alexander

2011-08-01

Cardiac tissue engineering is a promising strategy for regenerative therapies to overcome the shortage of donor organs for transplantation. Besides contractile function, the stiffness of tissue engineered constructs is crucial to generate transplantable tissue surrogates with sufficient mechanical stability to withstand the high pressure present in the heart. Although several collagen cross-linking techniques have proven to be efficient in stabilizing biomaterials, they cannot be applied to cardiac tissue engineering, as cell death occurs in the treated area. Here, we present a novel method using femtosecond (fs) laser pulses to increase the stiffness of collagen-based tissue constructs without impairing cell viability. Raster scanning of the fs laser beam over riboflavin-treated tissue induced collagen cross-linking by two-photon photosensitized singlet oxygen production. One day post-irradiation, stress-strain measurements revealed increased tissue stiffness by around 40% being dependent on the fibroblast content in the tissue. At the same time, cells remained viable and fully functional as demonstrated by fluorescence imaging of cardiomyocyte mitochondrial activity and preservation of active contraction force. Our results indicate that two-photon induced collagen cross-linking has great potential for studying and improving artificially engineered tissue for regenerative therapies.

DNA-dependent protein kinase inhibits AID-induced antibody gene conversion.

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Adam J L Cook

2007-04-01

Full Text Available Affinity maturation and class switching of antibodies requires activation-induced cytidine deaminase (AID-dependent hypermutation of Ig V(DJ rearrangements and Ig S regions, respectively, in activated B cells. AID deaminates deoxycytidine bases in Ig genes, converting them into deoxyuridines. In V(DJ regions, subsequent excision of the deaminated bases by uracil-DNA glycosylase, or by mismatch repair, leads to further point mutation or gene conversion, depending on the species. In Ig S regions, nicking at the abasic sites produced by AID and uracil-DNA glycosylases results in staggered double-strand breaks, whose repair by nonhomologous end joining mediates Ig class switching. We have tested whether nonhomologous end joining also plays a role in V(DJ hypermutation using chicken DT40 cells deficient for Ku70 or the DNA-dependent protein kinase catalytic subunit (DNA-PKcs. Inactivation of the Ku70 or DNA-PKcs genes in DT40 cells elevated the rate of AID-induced gene conversion as much as 5-fold. Furthermore, DNA-PKcs-deficiency appeared to reduce point mutation. The data provide strong evidence that double-strand DNA ends capable of recruiting the DNA-dependent protein kinase complex are important intermediates in Ig V gene conversion.