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Sample records for including cross protection

  1. 25 CFR 20.403 - What do protective services include?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... allegations of child abuse and neglect, abandonment, and conditions that may require referrals (such as mental... account holder; (ii) Developing, as necessary and as permitted under 25 CFR 115, a one-time or an annual... services include? Protective services provided to a child, family or elderly person will be documented...

  2. 25 CFR 20.403 - What do protective services include?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... allegations of child abuse and neglect, abandonment, and conditions that may require referrals (such as mental... account holder; (ii) Developing, as necessary and as permitted under 25 CFR 115, a one-time or an annual... services include? Protective services provided to a child, family or elderly person will be documented...

  3. 25 CFR 20.403 - What do protective services include?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... of child abuse and neglect, abandonment, and conditions that may require referrals (such as mental or... account holder; (ii) Developing, as necessary and as permitted under 25 CFR 115, a one-time or an annual... include? Protective services provided to a child, family or elderly person will be documented in the...

  4. 25 CFR 20.403 - What do protective services include?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... allegations of child abuse and neglect, abandonment, and conditions that may require referrals (such as mental... account holder; (ii) Developing, as necessary and as permitted under 25 CFR 115, a one-time or an annual... services include? Protective services provided to a child, family or elderly person will be documented...

  5. 25 CFR 20.403 - What do protective services include?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... allegations of child abuse and neglect, abandonment, and conditions that may require referrals (such as mental... account holder; (ii) Developing, as necessary and as permitted under 25 CFR 115, a one-time or an annual... services include? Protective services provided to a child, family or elderly person will be documented...

  6. Cross-protection between experimental anti-leptospirosis bacterins.

    PubMed

    Dib, Cristina Corsi; Gonçales, Amane Paldês; de Morais, Zenaide Maria; de Souza, Gisele Oliveira; Miraglia, Fabiana; Abreu, Patricia Antonia Estima; Vasconcellos, Silvio Arruda

    2014-01-01

    We investigated the existence of cross-protection between two anti-leptospirosis monovalent experimental bacterins produced with two strains of Leptospira serogroup Pomona: Fromm strain of serovar Kennewicky, isolated from pigs in the United States, and strain GR6 of serovar Pomona isolated from pigs in Brazil. Both were added of aluminum hydroxide as an adjuvant. Experimental bacterins were tested with the hamster potency test in order to assess protection provided against the disease and against the establishment of kidney infection. Controls were polyvalent commercial vaccine produced with Leptospira strains isolated outside Brazil, which included a representative of Pomona serovar, or Sorensen solution added of aluminum hydroxide adjuvant. The challenge was performed with cross-strains of serogroup Pomona tested in accordance with international standards established for the potency test. After 21 days of the challenge, survivors were killed to evaluate the condition of Leptospira renal carrier. Experimental bacterins protected hamsters against homologous and heterologous strains, demonstrating the existence of cross-protection. The commercial vaccine protected the hamsters challenged with both strains, but there was a high proportion of animals diagnosed as renal carriers when the challenge was performed with strain GR6, isolated from pigs in Brazil. PMID:25477946

  7. Cross-protection between experimental anti-leptospirosis bacterins

    PubMed Central

    Dib, Cristina Corsi; Gonçales, Amane Paldês; de Morais, Zenaide Maria; de Souza, Gisele Oliveira; Miraglia, Fabiana; Abreu, Patricia Antonia Estima; Vasconcellos, Silvio Arruda

    2014-01-01

    We investigated the existence of cross-protection between two anti-leptospirosis monovalent experimental bacterins produced with two strains of Leptospira serogroup Pomona: Fromm strain of serovar Kennewicky, isolated from pigs in the United States, and strain GR6 of serovar Pomona isolated from pigs in Brazil. Both were added of aluminum hydroxide as an adjuvant. Experimental bacterins were tested with the hamster potency test in order to assess protection provided against the disease and against the establishment of kidney infection. Controls were polyvalent commercial vaccine produced with Leptospira strains isolated outside Brazil, which included a representative of Pomona serovar, or Sorensen solution added of aluminum hydroxide adjuvant. The challenge was performed with cross-strains of serogroup Pomona tested in accordance with international standards established for the potency test. After 21 days of the challenge, survivors were killed to evaluate the condition of Leptospira renal carrier. Experimental bacterins protected hamsters against homologous and heterologous strains, demonstrating the existence of cross-protection. The commercial vaccine protected the hamsters challenged with both strains, but there was a high proportion of animals diagnosed as renal carriers when the challenge was performed with strain GR6, isolated from pigs in Brazil. PMID:25477946

  8. Cross-protection among strains of barley yellow dwarf virus.

    PubMed

    Wen, F; Lister, R M; Fattouh, F A

    1991-04-01

    ELISA, cDNA dot blot hybridization and transmission by vector aphids were used to investigate the occurrence and degree of cross-protection produced in oat plants by virus isolates representing five strains or serotypes of barley yellow dwarf virus, namely PAV, MAV, SGV, RPV and RMV. Generally, the degree of cross-protection was positively correlated with the serological relatedness between the isolates. A high degree of cross-protection occurred between NY-MAV and MAV-PS1, two isolates of the MAV serotype; cross-protection was moderate between MAV-PS1 and either P-PAV (a Purdue isolate of the PAV serotype) or NY-SGV; cross-protection between P-PAV and NY-SGV was low. Cross-protection did not occur in other paired inoculations and did not persist in some plants, the challenge virus eventually becoming detectable. The persistence of cross-protection depended on the interval between inoculations with protecting and challenge viruses; longer inoculation intervals enhanced the persistence of cross-protection. Results obtained by ELISA and dot blot hybridization were usually consistent, indicating that cross-protection affected both viral capsid and RNA synthesis. PMID:2016594

  9. 49 CFR 1242.58 - Operating signals and interlockers, operating drawbridges, highway crossing protection (accounts...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... drawbridges, highway crossing protection (accounts XX-51-59, XX-51-60 and XX-51-61). 1242.58 Section 1242.58... Operating signals and interlockers, operating drawbridges, highway crossing protection (accounts XX-51-59, XX-51-60 and XX-51-61). Separate common expenses on the basis of total train hours (including...

  10. 49 CFR 1242.58 - Operating signals and interlockers, operating drawbridges, highway crossing protection (accounts...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... drawbridges, highway crossing protection (accounts XX-51-59, XX-51-60 and XX-51-61). 1242.58 Section 1242.58... Operating signals and interlockers, operating drawbridges, highway crossing protection (accounts XX-51-59, XX-51-60 and XX-51-61). Separate common expenses on the basis of total train hours (including...

  11. 49 CFR 1242.58 - Operating signals and interlockers, operating drawbridges, highway crossing protection (accounts...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... drawbridges, highway crossing protection (accounts XX-51-59, XX-51-60 and XX-51-61). 1242.58 Section 1242.58... Operating signals and interlockers, operating drawbridges, highway crossing protection (accounts XX-51-59, XX-51-60 and XX-51-61). Separate common expenses on the basis of total train hours (including...

  12. 49 CFR 1242.58 - Operating signals and interlockers, operating drawbridges, highway crossing protection (accounts...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... drawbridges, highway crossing protection (accounts XX-51-59, XX-51-60 and XX-51-61). 1242.58 Section 1242.58... Operating signals and interlockers, operating drawbridges, highway crossing protection (accounts XX-51-59, XX-51-60 and XX-51-61). Separate common expenses on the basis of total train hours (including...

  13. 49 CFR 1242.58 - Operating signals and interlockers, operating drawbridges, highway crossing protection (accounts...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... drawbridges, highway crossing protection (accounts XX-51-59, XX-51-60 and XX-51-61). 1242.58 Section 1242.58... Operating signals and interlockers, operating drawbridges, highway crossing protection (accounts XX-51-59, XX-51-60 and XX-51-61). Separate common expenses on the basis of total train hours (including...

  14. A DIVA vaccine for cross-protection against Salmonella

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Swine are often asymptomatic carriers of Salmonella spp., a leading cause of human bacterial foodborne disease. Vaccination against Salmonella is effective for protection of animal health and enhancement of food safety. However, current vaccines for swine may only offer limited cross-protection agai...

  15. The need to include animal protection in public health policies.

    PubMed

    Akhtar, Aysha

    2013-11-01

    Many critical public health issues require non-traditional approaches. Although many novel strategies are used, one approach not widely applied involves improving the treatment of animals. Emerging infectious diseases are pressing public health challenges that could benefit from improving the treatment of animals. Other human health issues, that overlap with animal treatment issues, and that warrant further exploration, are medical research and domestic violence. The diverse nature of these health issues and their connection with animal treatment suggest that there may be other similar intersections. Public health would benefit by including the treatment of animals as a topic of study and policy development. PMID:23803712

  16. Matrix protein 2 vaccination and protection against influenza viruses, including subtype H5N1.

    PubMed

    Tompkins, Stephen Mark; Zhao, Zi-Shan; Lo, Chia-Yun; Misplon, Julia A; Liu, Teresa; Ye, Zhiping; Hogan, Robert J; Wu, Zhengqi; Benton, Kimberly A; Tumpey, Terrence M; Epstein, Suzanne L

    2007-03-01

    Changes in influenza viruses require regular reformulation of strain-specific influenza vaccines. Vaccines based on conserved antigens provide broader protection. Influenza matrix protein 2 (M2) is highly conserved across influenza A subtypes. To evaluate its efficacy as a vaccine candidate, we vaccinated mice with M2 peptide of a widely shared consensus sequence. This vaccination induced antibodies that cross-reacted with divergent M2 peptide from an H5N1 subtype. A DNA vaccine expressing full-length consensus-sequence M2 (M2-DNA) induced M2-specific antibody responses and protected against challenge with lethal influenza. Mice primed with M2-DNA and then boosted with recombinant adenovirus expressing M2 (M2-Ad) had enhanced antibody responses that crossreacted with human and avian M2 sequences and produced T-cell responses. This M2 prime-boost vaccination conferred broad protection against challenge with lethal influenza A, including an H5N1 strain. Vaccination with M2, with key sequences represented, may provide broad protection against influenza A. PMID:17552096

  17. Mechanisms of Cross-protection by Influenza Virus M2-based Vaccines

    PubMed Central

    Lee, Yu-Na; Kim, Min-Chul; Lee, Young-Tae; Kim, Yu-Jin

    2015-01-01

    Current influenza virus vaccines are based on strain-specific surface glycoprotein hemagglutinin (HA) antigens and effective only when the predicted vaccine strains and circulating viruses are well-matched. The current strategy of influenza vaccination does not prevent the pandemic outbreaks and protection efficacy is reduced or ineffective if mutant strains emerge. It is of high priority to develop effective vaccines and vaccination strategies conferring a broad range of cross protection. The extracellular domain of M2 (M2e) is highly conserved among human influenza A viruses and has been utilized to develop new vaccines inducing cross protection against different subtypes of influenza A virus. However, immune mechanisms of cross protection by M2e-based vaccines still remain to be fully elucidated. Here, we review immune correlates and mechanisms conferring cross protection by M2e-based vaccines. Molecular and cellular immune components that are known to be involved in M2 immune-mediated protection include antibodies, B cells, T cells, alveolar macrophages, Fc receptors, complements, and natural killer cells. Better understanding of protective mechanisms by immune responses induced by M2e vaccination will help facilitate development of broadly cross protective vaccines against influenza A virus. PMID:26557805

  18. [Animal protection in constitutional law?--On the necessity of including animal protection in the constitution].

    PubMed

    Caspar, J

    1998-03-01

    The inclusion of animal protection in the constitution poses a lengthy legal-political demand, which is again being vehemently discussed at the present time. Under consideration of juristic aspects, the following treatise attempts to clarify the legal requirements which presently exist for anchoring animal protection in constitutional law. It is therefore necessary in the first instance to explain the present situation regarding animal protection law. The legal situation in this respect is marked by a fundamental collision between special democratic rights guaranteed by the constitution on the one hand, and the norms of animal protection law on the other hand, which tend to restrict these rights. Based on concrete examples taken from court decisions, it is shown that constitutional vacuum surrounding a major part of animal protection law greatly complicates or even renders impossible the application and enforcement of the latter in practice. A prerequisite for a proper legal framework for animal protection is that the different special basic democratic rights governing animal use must be counterpoised by animal protection laws backed up by the constitution. Only by this means it is possible to prevent the ineffectiveness of animal protection legislative norms in the long term. PMID:9581372

  19. Cross-protective immunity to influenza A viruses.

    PubMed

    Epstein, Suzanne L; Price, Graeme E

    2010-11-01

    Antigenic changes in influenza virus occur gradually, owing to mutations (antigenic drift), and abruptly, owing to reassortment among subtypes (antigenic shift). Availability of strain-matched vaccines often lags behind these changes, resulting in a shortfall in public health. In animal models, cross-protection by vaccines based on conserved antigens does not completely prevent infection, but greatly reduces morbidity, mortality, virus replication and, thus, viral shedding and spread. Such immunity is especially effective and long-lasting with mucosal administration. Cross-protective immunity in humans is controversial, but is suggested by some epidemiological findings. 'Universal' vaccines protective against all influenza A viruses might substantially reduce severity of infection and limit spread of disease during outbreaks. These vaccines could be used 'off the shelf' early in an outbreak or pandemic, before strain-matched vaccines are available. PMID:21087110

  20. Differential two-body compound nuclear cross section, including the width-fluctuation corrections

    SciTech Connect

    Brown, D.; Herman, M.

    2014-09-02

    We figure out the compound angular differential cross sections, following mainly Fröbrich and Lipperheide, but with the angular momentum couplings that make sense for optical model work. We include the width-fluctuation correction along with calculations.

  1. Oscillatory dynamics in a bacterial cross-protection mutualism.

    PubMed

    Yurtsev, Eugene Anatoly; Conwill, Arolyn; Gore, Jeff

    2016-05-31

    Cooperation between microbes can enable microbial communities to survive in harsh environments. Enzymatic deactivation of antibiotics, a common mechanism of antibiotic resistance in bacteria, is a cooperative behavior that can allow resistant cells to protect sensitive cells from antibiotics. Understanding how bacterial populations survive antibiotic exposure is important both clinically and ecologically, yet the implications of cooperative antibiotic deactivation on the population and evolutionary dynamics remain poorly understood, particularly in the presence of more than one antibiotic. Here, we show that two Escherichia coli strains can form an effective cross-protection mutualism, protecting each other in the presence of two antibiotics (ampicillin and chloramphenicol) so that the coculture can survive in antibiotic concentrations that inhibit growth of either strain alone. Moreover, we find that daily dilutions of the coculture lead to large oscillations in the relative abundance of the two strains, with the ratio of abundances varying by nearly four orders of magnitude over the course of the 3-day period of the oscillation. At modest antibiotic concentrations, the mutualistic behavior enables long-term survival of the oscillating populations; however, at higher antibiotic concentrations, the oscillations destabilize the population, eventually leading to collapse. The two strains form a successful cross-protection mutualism without a period of coevolution, suggesting that similar mutualisms may arise during antibiotic treatment and in natural environments such as the soil. PMID:27194723

  2. Oscillatory dynamics in a bacterial cross-protection mutualism

    PubMed Central

    Yurtsev, Eugene Anatoly; Conwill, Arolyn; Gore, Jeff

    2016-01-01

    Cooperation between microbes can enable microbial communities to survive in harsh environments. Enzymatic deactivation of antibiotics, a common mechanism of antibiotic resistance in bacteria, is a cooperative behavior that can allow resistant cells to protect sensitive cells from antibiotics. Understanding how bacterial populations survive antibiotic exposure is important both clinically and ecologically, yet the implications of cooperative antibiotic deactivation on the population and evolutionary dynamics remain poorly understood, particularly in the presence of more than one antibiotic. Here, we show that two Escherichia coli strains can form an effective cross-protection mutualism, protecting each other in the presence of two antibiotics (ampicillin and chloramphenicol) so that the coculture can survive in antibiotic concentrations that inhibit growth of either strain alone. Moreover, we find that daily dilutions of the coculture lead to large oscillations in the relative abundance of the two strains, with the ratio of abundances varying by nearly four orders of magnitude over the course of the 3-day period of the oscillation. At modest antibiotic concentrations, the mutualistic behavior enables long-term survival of the oscillating populations; however, at higher antibiotic concentrations, the oscillations destabilize the population, eventually leading to collapse. The two strains form a successful cross-protection mutualism without a period of coevolution, suggesting that similar mutualisms may arise during antibiotic treatment and in natural environments such as the soil. PMID:27194723

  3. 43 CFR 3272.12 - What environmental protection measures must I include in my utilization plan?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false What environmental protection measures... What environmental protection measures must I include in my utilization plan? (a) Describe, at a... resources; (6) Minimize air and noise pollution; and (7) Minimize hazards to public health and safety...

  4. 43 CFR 3272.12 - What environmental protection measures must I include in my utilization plan?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false What environmental protection measures... What environmental protection measures must I include in my utilization plan? (a) Describe, at a... resources; (6) Minimize air and noise pollution; and (7) Minimize hazards to public health and safety...

  5. A DIVA vaccine for cross-protection against Salmonella.

    PubMed

    Bearson, Bradley L; Bearson, Shawn M D; Kich, Jalusa D

    2016-03-01

    Swine are often asymptomatic carriers of Salmonella spp., a leading cause of human bacterial foodborne disease. Vaccination against Salmonella is effective for protecting animal health and enhancing food safety. However, with >2500 Salmonella serovars, current vaccines for swine offer limited cross-protection against heterologous serovars. Also, existing vaccines can interfere with surveillance programs that monitor the Salmonella status of swine herds. To overcome Salmonella vaccine limitations, we rationally designed and constructed an attenuated Salmonella enterica serovar Typhimurium vaccine (BBS 866) by deleting multiple small regulatory RNA (sRNA) genes (omrA, omrB, rybB, micA, and invR) in combination with an rfaH mutation. We vaccinated swine intranasally at 3-weeks of age with PBS (mock-vaccinated), BBS 866 or BBS 202 (S. Typhimurium rfaH, Bearson et al., Front Vet Sci 2014;1:9.) and challenged at 7-weeks of age with virulent S. Choleraesuis, a swine pathogen. Vaccination with BBS 866 enhanced protection against S. Choleraesuis by significantly limiting the duration of fever, weight loss, the levels of circulating INFγ, and the total number of swine with S. Choleraesuis septicemia. Vaccination with either BBS 866 or BBS 202 significantly reduced S. Choleraesuis colonization of both systemic (spleen and liver) and gastrointestinal (Peyer's Patch, Ileocecal lymph nodes, and cecum) tissues. Similar to our earlier report for BBS 202, the BBS 866 vaccine strain can be used in swine without compromising the differentiation of infected from vaccinated animals (DIVA). Therefore, the attenuated S. Typhimurium BBS 866 strain, containing mutations in rfaH and multiple sRNAs, addresses the limitations of current Salmonella vaccines by providing cross-protection against Salmonella serovars in swine without interfering with established monitoring programs for Salmonella surveillance. PMID:26836212

  6. Predicting transmission of structure-borne sound power from machines by including terminal cross-coupling

    NASA Astrophysics Data System (ADS)

    Ohlrich, Mogens

    2011-10-01

    Structure-borne sound generated by audible vibration of machines in vehicles, equipment and house-hold appliances is often a major cause of noise. Such vibration of complex machines is mostly determined and quantified by measurements. It has been found that characterization of the vibratory source strength and the prediction of power transmission to a supporting structure or the machine casing itself can be greatly simplified if all mobility cross-terms and spatial cross-coupling of source velocities can be neglected in the analysis. In many cases this gives an acceptable engineering accuracy, especially at mid- and high-frequencies. For structurally compact machines, however, the influence of cross-coupling cannot always be ignored. The present paper addresses this problem and examines the transmission of structure-borne sound power by including spatial cross-coupling between pairs of translational terminals in a global plane. This paired or bi-coupled power transmission represents the simplest case of cross-coupling. The procedure and quality of the predicted transmission using this improved technique is demonstrated experimentally for an electrical motor unit with an integrated radial fan that was mounted resiliently in a vacuum cleaner casing. It is found that cross-coupling plays a significant role, but only at frequencies below 100 Hz for the examined system.

  7. Cross-protection in nonhuman primates against Argentine hemorrhagic fever.

    PubMed Central

    Weissenbacher, M C; Coto, C E; Calello, M A; Rondinone, S N; Damonte, E B; Frigerio, M J

    1982-01-01

    The susceptibility of the marmoset Callithrix jacchus to Tacaribe virus infection was investigated to perform cross-protection studies between Junin and Tacaribe viruses. Five marmosets inoculated with Tacaribe virus failed to show any signs of disease, any alterations in erythrocyte, leukocyte, reticulocyte, and platelet counts or any changes in hematocrit or hemoglobin values. No Tacaribe virus could be recovered from blood at any time postinfection. Anti-Tacaribe neutralizing antibodies appeared 3 weeks postinfection. The five Tacaribe-infected marmosets and four noninfected controls were challenged with the pathogenic strain of Junin virus on day 60 post-Tacaribe infection. The former group showed no signs of disease, no viremia, and no challenge virus replication, whereas the control group exhibited the typical symptoms of Argentine hemorrhagic fever, high viremia, and viral titers in organs. Soon after challenge, the Tacaribe-protected marmosets synthesized neutralizing antibodies against Junin virus. These results indicate that the marmoset C. jacchus can be considered an experimental model for protection studies with arenaviruses and that the Tacaribe virus could be considered as a potential vaccine against Junin virus. PMID:6276301

  8. Cross-reactivity of designer drugs, including cathinone derivatives, in commercial enzyme-linked immunosorbent assays.

    PubMed

    Swortwood, Madeleine J; Hearn, W Lee; DeCaprio, Anthony P

    2014-01-01

    Since the introduction of synthetic heroin, designer drugs have been increasing in prevalence in the United States drug market over the past few decades. Recently, 'legal highs' sold as 'bath salts' have become a household term for one such class of designer drugs. While a number of federal and state bans have been enacted, the abuse of these designer drugs still continues. Few assays have been developed for the comprehensive detection of such compounds, so it is important to investigate how they may or may not react in presumptive screens, i.e. pre-existing commercial immunoassays. In this experiment, 16 different ELISA reagents were evaluated to determine the cross-reactivity of 30 designer drugs, including 24 phenylethylamines (including 8 cathinone derivatives), 3 piperazines, and 3 tryptamines. Cross-reactivity towards most drugs was <4% in assays targeting amphetamine or methamphetamine. Compounds such as MDA, MDMA, ethylamphetamine, and α-methyltryptamine demonstrated cross-reactivities in the range of 30-250%, but data were consistent with both manufacturer's inserts and published literature. When tested against the Randox Mephedrone/Methcathinone kit, cathinone derivatives demonstrated cross-reactivity at concentrations as low as 150 ng/ml. Since this same reagent did not cross-react with other amphetamine-like compounds, it opens the possibility to screen post-mortem specimens without the interference of putrefactive amines. All other assays demonstrated essentially no cross-reactivity towards any of the analytes evaluated. Given these results, a great need exists for more broad-range screening techniques to be applied when analyzing biological specimens by immunoassays for drugs of abuse, specifically the more recent designer drugs. PMID:23677923

  9. An X-Ray Analysis Database of Photoionization Cross Sections Including Variable Ionization

    NASA Technical Reports Server (NTRS)

    Wang, Ping; Cohen, David H.; MacFarlane, Joseph J.; Cassinelli, Joseph P.

    1997-01-01

    Results of research efforts in the following areas are discussed: review of the major theoretical and experimental data of subshell photoionization cross sections and ionization edges of atomic ions to assess the accuracy of the data, and to compile the most reliable of these data in our own database; detailed atomic physics calculations to complement the database for all ions of 17 cosmically abundant elements; reconciling the data from various sources and our own calculations; and fitting cross sections with functional approximations and incorporating these functions into a compact computer code.Also, efforts included adapting an ionization equilibrium code, tabulating results, and incorporating them into the overall program and testing the code (both ionization equilibrium and opacity codes) with existing observational data. The background and scientific applications of this work are discussed. Atomic physics cross section models and calculations are described. Calculation results are compared with available experimental data and other theoretical data. The functional approximations used for fitting cross sections are outlined and applications of the database are discussed.

  10. 43 CFR 3272.12 - What environmental protection measures must I include in my utilization plan?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false What environmental protection measures must I include in my utilization plan? 3272.12 Section 3272.12 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) GEOTHERMAL RESOURCE...

  11. Bayesian Evaluation Including Covariance Matrices of Neutron-induced Reaction Cross Sections of {sup 181}Ta

    SciTech Connect

    Leeb, H. Schnabel, G.; Srdinko, Th.; Wildpaner, V.

    2015-01-15

    A new evaluation of neutron-induced reactions on {sup 181}Ta using a consistent procedure based on Bayesian statistics is presented. Starting point of the evaluation is the description of nuclear reactions via nuclear models implemented in TALYS 1.4. A retrieval of experimental data was performed and covariance matrices of the experiments were generated from an extensive study of the corresponding literature. All reaction channels required for a transport file up to 200 MeV have been considered and the covariance matrices of cross section uncertainties for the most important channels are determined. The evaluation has been performed in one step including all available experimental data. A comparison of the evaluated cross sections and spectra with experimental data and available evaluations is performed. In general the evaluated cross section reflect our best knowledge and give a fair description of the observables. However, there are few deviations from expectation which clearly indicate the impact of the prior and the need to account for model defects. Using the results of the evaluation a complete ENDF-file similarly to those of the TENDL library is generated.

  12. Baculovirus Displaying Hemagglutinin Elicits Broad Cross-Protection against Influenza in Mice

    PubMed Central

    Seong, Baik Lin; Nguyen, Huan Huu; Chang, Jun

    2016-01-01

    The widespread influenza virus infection further emphasizes the need for novel vaccine strategies that effectively reduce the impact of epidemic as well as pandemic influenza. Conventional influenza vaccines generally induce virus neutralizing antibody responses which are specific for a few antigenically related strains within the same subtype. However, antibodies directed against the conserved stalk domain of HA could neutralize multiple subtypes of influenza virus and thus provide broad-spectrum protection. In this study, we designed and constructed a recombinant baculovirus-based vaccine, rBac-HA virus, that expresses full-length HA of pandemic H1N1 influenza virus (A/California/04/09) on the viral envelope. We demonstrated that repeated intranasal immunizations with rBac-HA virus induced HA stalk-specific antibody responses and protective immunity against homologous as well as heterosubtypic virus challenge. The adoptive transfer experiment shows that the cross-protection is conferred by the immune sera which contain HA stalk-specific antibodies. These results warrant further development of rBac-HA virus as a broad-protective vaccine against influenza. The vaccine induced protection against infection with the same subtype as well as different subtype, promising a potential universal vaccine for broad protection against different subtypes to control influenza outbreaks including pandemic. PMID:27023684

  13. Topological phases protected by reflection symmetry and cross-cap states

    NASA Astrophysics Data System (ADS)

    Cho, Gil Young; Hsieh, Chang-Tse; Morimoto, Takahiro; Ryu, Shinsei

    2015-05-01

    Twisting symmetries provides an efficient method to diagnose symmetry-protected topological (SPT) phases. In this paper, edge theories of (2+1)-dimensional topological phases protected by reflection as well as other symmetries are studied by twisting reflection symmetry, which effectively puts the edge theories on an unoriented space-time, such as the Klein bottle. A key technical step taken in this paper is the use of the so-called cross-cap states, which encode entirely the unoriented nature of space-time, and can be obtained by rearranging the space-time geometry and exchanging the role of space and time coordinates. When the system is in a nontrivial SPT phase, we find that the corresponding cross-cap state is noninvariant under the action of the symmetries of the SPT phase, but acquires an anomalous phase. This anomalous phase, with a proper definition of a reference state, on which symmetry acts trivially, reproduces the known classification of (2+1)-dimensional bosonic and fermionic SPT phases protected by reflection symmetry, including in particular the Z8 classification of topological crystalline superconductors protected by reflection and time-reversal symmetries.

  14. Cross-species infection of hepatitis E virus in a zoo-like location, including birds

    PubMed Central

    ZHANG, W.; SHEN, Q.; MOU, J.; YANG, Z. B.; YUAN, C. L.; CUI, L.; ZHU, J. G.; HUA, X. G.; XU, C. M.; HU, J.

    2008-01-01

    SUMMARY Hepatitis E virus (HEV) is a zoonotic pathogen of which several species of animals are considered to be reservoirs. Thirty-eight faecal samples, obtained from 22 species of animals including birds in a wildlife first-aid centre in Eastern China, were tested for HEV RNA. Our survey revealed that in total 28·9% (95% confidence interval 14·5–43·4) of the faecal samples from various mammals and birds were HEV RNA positive. Sequence and phylogenetic analyses of the 11 isolates demonstrated that all sequences clustered in genotype 4 with 96–100% identity to each other. In addition, serum samples from seven animal handlers have shown that five (71·4%) were seropositive. The findings imply that cross-species infection of HEV had probably occurred in this zoo-like location, and moreover, birds can be infected naturally with mammalian HEV. PMID:17961279

  15. HPV16/18 L1 VLP Vaccine Induces Cross-Neutralizing Antibodies that May Mediate Cross-Protection

    PubMed Central

    Kemp, Troy J.; Hildesheim, Allan; Safaeian, Mahboobeh; Dauner, Joseph G.; Pan, Yuanji; Porras, Carolina; Schiller, John T.; Lowy, Douglas R.; Herrero, Rolando; Pinto, Ligia A.

    2011-01-01

    Human papillomavirus (HPV) L1 VLP-based vaccines are protective against HPV vaccine-related types; however, the correlates of protection have not been defined. We observed that vaccination with Cervarix™ induced cross-neutralizing antibodies for HPV types for which evidence of vaccine efficacy has been demonstrated (HPV31/45) but not for other types (HPV52/58). In addition, HPV31/45 cross-neutralizing titers showed a significant increase with number of doses (HPV31, p<0.001; HPV45, p<0.001) and correlated with HPV16/18 neutralizing titers, respectively. These findings raise the possibility that cross-neutralizing antibodies are effectors of cross-protection observed for the HPV16/18 vaccine. PMID:21241731

  16. Substructure procedure for including tile flexibility in stress analysis of shuttle thermal protection system

    NASA Technical Reports Server (NTRS)

    Giles, G. L.

    1980-01-01

    A substructure procedure to include the flexibility of the tile in the stress analysis of the shuttle thermal protection system (TPS) is described. In this procedure, the TPS is divided into substructures of (1) the tile which is modeled by linear finite elements and (2) the SIP which is modeled as a nonlinear continuum. This procedure was applied for loading cases of uniform pressure, uniform moment, and an aerodynamic shock on various tile thicknesses. The ratios of through-the-thickness stresses in the SIP which were calculated using a flexible tile compared to using a rigid tile were found to be less than 1.05 for the cases considered.

  17. Environmental and Health Protection well inventory: Includes current and past monitoring (as of April 26, 1989)

    SciTech Connect

    Rogers, C.D.; Janssen, J.L.

    1989-10-01

    This report is an inventory of the wells contained in Environmental and Health Protection (EHP) documents since the startup of the Savannah River Site (SRS) and includes wells monitored by special request and SRS research wells. All wells listed in this inventory are monitoring wells unless otherwise indicated. The purpose of this report is as follows: to provide a historical record of the wells that EHP has monitored, to provide a document containing a list of wells that are currently in the Groundwater Monitoring Program, and to provide pertinent information about all wells listed in EHP documents

  18. Sugarcane Aphid (Hemiptera: Aphididae): Host Range and Sorghum Resistance Including Cross-Resistance From Greenbug Sources.

    PubMed

    Armstrong, J Scott; Rooney, William L; Peterson, Gary C; Villenueva, Raul T; Brewer, Michael J; Sekula-Ortiz, Danielle

    2015-04-01

    The graminous host range and sources of sorghum [Sorghum bicolor (L.) Moench.] plant resistance, including cross-resistance from greenbug, Schizaphis graminum (Rondani), were studied for the newly emerging sugarcane aphid, Melanaphis sacchari (Zehntner), in greenhouse no-choice experiments and field evaluations. The sugarcane aphid could not survive on field corn, Zea mays (L.), Teff grass, Eragrostis tef (Zucc.), proso millet, Panicum miliaceum L., barley, Hordeum vulgare L., and rye, Secale cereale L. Only sorghum genotypes served as hosts including Johnsongrass, Sorghum halepense (L.), a highly suitable noncrop host that generates high numbers of sugarcane aphid and maintains moderate phenotypic injury. The greenbug-resistant parental line RTx2783 that is resistant to greenbug biotypes C and E was resistant to sugarcane aphid in both greenhouse and field tests, while PI 55607 greenbug resistant to biotypes B, C, and E was highly susceptible. PI 55610 that is greenbug resistant to biotypes B, C, and E maintained moderate resistance to the sugarcane aphid, while greenbug-resistant PI 264453 was highly susceptible to sugarcane aphid. Two lines and two hybrids from the Texas A&M breeding program B11070, B11070, AB11055-WF1-CS1/RTx436, and AB11055-WF1-CS1/RTx437 were highly resistant to sugarcane aphid, as were parental types SC110, SC170, and South African lines Ent62/SADC, (Macia/TAM428)-LL9, (SV1*Sima/IS23250)-LG15. Tam428, a parental line that previously showed moderate resistance in South Africa and India, also showed moderate resistance in these evaluations. Overall, 9 of 20 parental sorghum entries tested for phenotypic damage in the field resulted in good resistance to the sugarcane aphid and should be utilized in breeding programs that develop agronomically acceptable sorghums for the southern regions of the United States. PMID:26470168

  19. 43 CFR 3272.12 - What environmental protection measures must I include in my utilization plan?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... surface or ground water; (4) Protect fish and wildlife; (5) Protect cultural, visual, and other natural resources; (6) Minimize air and noise pollution; and (7) Minimize hazards to public health and safety...

  20. Extending the actor-partner interdependence model to include cross-informant data.

    PubMed

    van Dulmen, Manfred H M; Goncy, Elizabeth A

    2010-12-01

    This paper illustrates an extension of the APIM technique within a path analysis framework by using cross-informant data on the outcome variable. Data for the current study were derived from a sample of young adult heterosexual couples who had been in a romantic relationship for at least four months (N = 115 couples). The findings from the current study indicate that romantic relationship satisfaction is associated with externalizing behavior problems among both females and males, but that both dyadic data and cross-informant reports are needed to understand this association. Not considering dyadic or cross-informant data may lead to different, and potentially misleading, claims. The findings from the current study provide clear evidence that incorporating cross-informant data in dyadic data analyses provides important new insights into understanding the association between romantic relationship functioning and individual outcomes. PMID:20719376

  1. Periictal and interictal headache including migraine in Dutch patients with epilepsy: a cross-sectional study.

    PubMed

    Hofstra, W A; Hageman, G; de Weerd, A W

    2015-03-01

    As early as in 1898, it was noted that there was a need to find "a plausible explanation of the long recognized affinities of migraine and epilepsy". However, results of recent studies are clearly conflicting on this matter. In this cross-sectional study, we aimed to define the prevalence and characteristics of both seizure-related and interictal headaches in patients with epilepsy (5-75years) seeking help in the tertiary epilepsy clinic SEIN in Zwolle. Using a questionnaire, subjects were surveyed on the existence of headaches including characteristics, duration, severity, and accompanying symptoms. Furthermore, details on epilepsy were retrieved from medical records (e.g., syndrome, seizure frequency, and use of drugs). Diagnoses of migraine, tension-type headache, or unclassifiable headache were made based on criteria of the International Classification of Headache Disorders. Between March and December 2013, 29 children and 226 adults were evaluated, 73% of whom indicated having current headaches, which is significantly more often when compared with the general population (p<0.001). Forty-nine percent indicated having solely interictal headache, while 29% had solely seizure-related headaches and 22% had both. Migraine occurs significantly more often in people with epilepsy in comparison with the general population (p<0.001), and the occurrence of tension-type headaches conforms to results in the general population. These results show that current headaches are a significantly more frequent problem amongst people with epilepsy than in people without epilepsy. When comparing migraine prevalence, this is significantly higher in the population of patients with epilepsy. PMID:25705827

  2. Protected zone ventilation and reduced personal exposure to airborne cross-infection.

    PubMed

    Cao, G; Nielsen, P V; Jensen, R L; Heiselberg, P; Liu, L; Heikkinen, J

    2015-06-01

    The main objective of this study was to examine the performance of protected zone ventilation (PZV) and hybrid protected zone ventilation (HPZV) to reduce the direct exposure to exhaled air from others' breathing. Experimental measurements are carried out to test the performance of PZV in a full-scale office room with two breathing thermal manikins. The measurements were performed under three configurations, including two standing manikins at different distances: 0.35, 0.5, and 1.1 m. When the supply air velocity is increased to 4 m/s in the downward plane jet, the dimensionless concentration is 40% lower than for fully mixed ventilation, which can be considered as a measure of protection from the zoning condition. The measurement results showed that in both the PZV and the HPZV system it is possible to decrease the transmission of tracer gas from one manikin to the opposite manikin; therefore, it probably would reduce the risk of air borne cross-infection between two people at the same relative positions. The results suggest that PZV and HPZV may be used to reduce the exposure of people in a protected zone from indoor pollutants emitted in a source zone. PMID:24995998

  3. Immunogenicity and Cross-Protective Efficacy Induced by Outer Membrane Proteins from Salmonella Typhimurium Mutants with Truncated LPS in Mice

    PubMed Central

    Liu, Qiong; Liu, Qing; Zhao, Xinxin; Liu, Tian; Yi, Jie; Liang, Kang; Kong, Qingke

    2016-01-01

    Lipopolysaccharide (LPS) is a major virulence factor present in the outer membrane of Salmonella enterica serovar Typhimurium (S. Typhimurium). Outer membrane proteins (OMPs) from Salmonella show high immunogenicity and provide protection against Salmonella infection, and truncated LPS alters the outer membrane composition of the cell wall. In our previous study, we demonstrated that Salmonella mutants carrying truncated LPS failed to induce strong immune responses and cross-reaction to other enteric bacteria, due to their high attenuation and low colonization in the host. Therefore, we plan to investigate whether outer membrane proteins from Salmonella mutants with truncated LPS resulting from a series of nonpolar mutations, including ∆waaC12, ∆waaF15, ∆waaG42, ∆rfaH49, ∆waaI43, ∆waaJ44, ∆waaL46, ∆wbaP45 and ∆wzy-48, affect immunogenicity and provide protection against diverse Salmonella challenge. In this study, the immunogenicity and cross-protection efficiency of purified OMPs from all mutants were investigated to explore a potential OMP vaccine to protect against homologous or heterologous serotype Salmonella challenge. The results demonstrated that OMPs from three Salmonella mutants (∆waaC12, ∆waaJ44 and ∆waaL46) induced higher immune responses and provided good protection against homologous S. Typhimurium. The OMPs from these three mutants were also selected to determine the cross-protective efficacy against homologous and heterologous serotype Salmonella. Our results indicated that the mutant ∆waaC12 can elicit higher cross-reactivity and can provide good protection against S. Choleraesuis and S. Enteritidis infection and that the cross-reactivity may be ascribed to an antigen of approximately 18.4–30 kDa. PMID:27011167

  4. Thermostable cross-protective subunit vaccine against Brucella species.

    PubMed

    Cherwonogrodzky, John W; Barabé, Nicole D; Grigat, Michelle L; Lee, William E; Poirier, Robert T; Jager, Scott J; Berger, Bradley J

    2014-12-01

    A subunit vaccine candidate was produced from Brucella suis 145 (biovar 4; expressing both the A antigen of Brucella abortus and the M antigen of Brucella melitensis). The preparation consisted mostly of polysaccharide (PS; >90% [wt/wt]; both cell-associated PS and exo-PS were combined) and a small amount of protein (1 to 3%) with no apparent nucleic acids. Vaccinated mice were protected (these had a statistically significant reduction in bacterial colonization compared to that of unvaccinated controls) when challenged with representative strains of three Brucella species most pathogenic for humans, i.e., B. abortus, B. melitensis, and B. suis. As little as 1 ng of the vaccine, without added adjuvant, protected mice against B. suis 145 infection (5 × 10(5) CFU), and a single injection of 1 μg of this subunit vaccine protected mice from B. suis 145 challenge for at least 14 months. A single immunization induced a serum IgG response to Brucella antigens that remained elevated for up to 9 weeks. The use of heat (i.e., boiling-water bath, autoclaving) in the vaccine preparation showed that it was thermostable. This method also ensured safety and security. The vaccine produced was immunogenic and highly protective against multiple strains of Brucella and represents a promising candidate for further evaluation. PMID:25320267

  5. Thermostable Cross-Protective Subunit Vaccine against Brucella Species

    PubMed Central

    Barabé, Nicole D.; Grigat, Michelle L.; Lee, William E.; Poirier, Robert T.; Jager, Scott J.; Berger, Bradley J.

    2014-01-01

    A subunit vaccine candidate was produced from Brucella suis 145 (biovar 4; expressing both the A antigen of Brucella abortus and the M antigen of Brucella melitensis). The preparation consisted mostly of polysaccharide (PS; >90% [wt/wt]; both cell-associated PS and exo-PS were combined) and a small amount of protein (1 to 3%) with no apparent nucleic acids. Vaccinated mice were protected (these had a statistically significant reduction in bacterial colonization compared to that of unvaccinated controls) when challenged with representative strains of three Brucella species most pathogenic for humans, i.e., B. abortus, B. melitensis, and B. suis. As little as 1 ng of the vaccine, without added adjuvant, protected mice against B. suis 145 infection (5 × 105 CFU), and a single injection of 1 μg of this subunit vaccine protected mice from B. suis 145 challenge for at least 14 months. A single immunization induced a serum IgG response to Brucella antigens that remained elevated for up to 9 weeks. The use of heat (i.e., boiling-water bath, autoclaving) in the vaccine preparation showed that it was thermostable. This method also ensured safety and security. The vaccine produced was immunogenic and highly protective against multiple strains of Brucella and represents a promising candidate for further evaluation. PMID:25320267

  6. Proteomic analysis of cross protection provided between cold and osmotic stress in Listeria monocytogenes.

    PubMed

    Pittman, Joseph R; Buntyn, Joe O; Posadas, Gabriel; Nanduri, Bindu; Pendarvis, Ken; Donaldson, Janet R

    2014-04-01

    Listeria monocytogenes is a Gram-positive, foodborne pathogen responsible for approximately 28% of all food-related deaths each year in the United States. L. monocytogenes infections are linked to the consumption of minimally processed ready-to-eat (RTE) products such as cheese, deli meats, and cold-smoked finfish products. L. monocytogenes is resistant to stresses commonly encountered in the food-processing environment, including low pH, high salinity, oxygen content, and various temperatures. The purpose of this study was to determine if cells habituated at low temperatures would result in cross-protective effects against osmotic stress. We found that cells exposed to refrigerated temperatures prior to a mild salt stress treatment had increased survival in NaCl concentrations of 3%. Additionally, the longer the cells were pre-exposed to cold temperatures, the greater the increase in survival in 3% NaCl. A proteomics analysis was performed in triplicate in order to elucidate mechanisms involved in cold-stress induced cross protection against osmotic stress. Proteins involved in maintenance of the cell wall and cellular processes, such as penicillin binding proteins and osmolyte transporters, and processes involving amino acid metabolism, such as osmolyte synthesis, transport, and lipid biosynthesis, had the greatest increase in expression when cells were exposed to cold temperatures prior to salt. By gaining a better understanding of how this pathogen adapts physiologically to various environmental conditions, improvements can be made in detection and mitigation strategies. PMID:24564473

  7. Cross Section Sensitivity and Uncertainty Analysis Including Secondary Neutron Energy and Angular Distributions.

    Energy Science and Technology Software Center (ESTSC)

    1991-03-12

    Version 00 SUSD calculates sensitivity coefficients for one- and two-dimensional transport problems. Variance and standard deviation of detector responses or design parameters can be obtained using cross-section covariance matrices. In neutron transport problems, this code can perform sensitivity-uncertainty analysis for secondary angular distribution (SAD) or secondary energy distribution (SED).

  8. Investigation of Helical Cross-Flow Axis Hydrokinetic Turbines, Including Effects of Waves and Turbulence

    NASA Astrophysics Data System (ADS)

    Bachant, Peter; Wosnik, Martin

    2011-11-01

    A new test bed for hydrokinetic turbines was used to evaluate different cross-flow axis turbines, and investigate effects of waves and turbulence. Turbine thrust (drag) and mechanical power were measured in a tow tank with cross section 3.7 x 2.4m at speeds of 0.6-1.5 m/s for a Gorlov Helical Turbine (GHT) and a Lucid spherical helical turbine (LST). GHT performance was also measured in progressive waves of various periods, grid turbulence, and in a cylinder wake. Overall, the GHT performs with higher power and thrust coefficients than the LST. A 2nd law, or kinetic exergy efficiency, defined as the fraction of kinetic energy removed from the flow that is converted to usable shaft work, was measured. The distribution of energy into shaft work and turbulent kinetic energy in the wake can affect environmental transport processes and performance of turbines arrays. Progressive waves generally enhance performance of the GHT, but can lead to stall at higher tip speed ratios compared to the steady case. Grid turbulence delays dynamic stall and enables operation at lower tip speed ratios, while not decreasing maximum power coefficient. Performance in a cylinder wake is highly dependent on the cylinder's cross-stream location, ranging from benign to detrimental. The experimental observations provide insight into the physical principles of operation of cross-flow axis turbines.

  9. Extending the Actor-Partner Interdependence Model to Include Cross-Informant Data

    ERIC Educational Resources Information Center

    van Dulmen, Manfred H. M.; Goncy, Elizabeth A.

    2010-01-01

    This paper illustrates an extension of the APIM technique within a path analysis framework by using cross-informant data on the outcome variable. Data for the current study were derived from a sample of young adult heterosexual couples who had been in a romantic relationship for at least four months (N = 115 couples). The findings from the current…

  10. Extracellular vesicles including exosomes are mediators of signal transduction: Are they protective or pathogenic?

    PubMed Central

    Gangoda, Lahiru; Boukouris, Stephanie; Liem, Michael; Kalra, Hina; Mathivanan, Suresh

    2015-01-01

    Extracellular vesicles are signaling organelles that are released by many cell types and is highly conserved in both prokaryotes and eukaryotes. Based on the mechanism of biogenesis, these membranous vesicles can be classified as exosomes, shedding microvesicles and apoptotic blebs. It is becoming clearer that these extracellular vesicles mediate signal transduction in both autocrine and paracrine fashion by the transfer of proteins and RNA. Whilst the role of extracellular vesicles including exosomes in pathogenesis is well established, very little is known about their function in normal physiological conditions. Recent evidences allude that extracellular vesicles can mediate both protective and pathogenic effects depending on the precise state. In this review, we discuss the involvement of extracellular vesicle as mediators of signal transduction in neurodegenerative diseases and cancer. In addition, the role of extracellular vesicles in mediating Wnt and PI3K signaling pathways is also discussed. Additional findings on the involvement of extracellular vesicles in homeostasis and disease progression will promote a better biological understanding, advance future therapeutic and diagnostic applications. PMID:25307053

  11. Naming and outline of Dothideomycetes–2014 including proposals for the protection or suppression of generic names

    PubMed Central

    Wijayawardene, Nalin N.; Crous, Pedro W.; Kirk, Paul M.; Hawksworth, David L.; Boonmee, Saranyaphat; Braun, Uwe; Dai, Dong-Qin; D’souza, Melvina J.; Diederich, Paul; Dissanayake, Asha; Doilom, Mingkhuan; Hongsanan, Singang; Jones, E. B.Gareth; Groenewald, Johannes Z.; Jayawardena, Ruvishika; Lawrey, James D.; Liu, Jian-Kui; Lücking, Robert; Madrid, Hugo; Manamgoda, Dimuthu S.; Muggia, Lucia; Nelsen, Matthew P.; Phookamsak, Rungtiwa; Suetrong, Satinee; Tanaka, Kazuaki; Thambugala, Kasun M.; Wanasinghe, Dhanushka N.; Wikee, Saowanee; Zhang, Ying; Aptroot, André; Ariyawansa, H. A.; Bahkali, Ali H.; Bhat, D. Jayarama; Gueidan, Cécile; Chomnunti, Putarak; De Hoog, G. Sybren; Knudsen, Kerry; Li, Wen-Jing; McKenzie, Eric H. C.; Miller, Andrew N.; Phillips, Alan J. L.; Piątek, Marcin; Raja, Huzefa A.; Shivas, Roger S.; Slippers, Bernad; Taylor, Joanne E.; Tian, Qing; Wang, Yong; Woudenberg, Joyce H. C.; Cai, Lei; Jaklitsch, Walter M.

    2016-01-01

    Article 59.1, of the International Code of Nomenclature for Algae, Fungi, and Plants (ICN; Melbourne Code), which addresses the nomenclature of pleomorphic fungi, became effective from 30 July 2011. Since that date, each fungal species can have one nomenclaturally correct name in a particular classification. All other previously used names for this species will be considered as synonyms. The older generic epithet takes priority over the younger name. Any widely used younger names proposed for use, must comply with Art. 57.2 and their usage should be approved by the Nomenclature Committee for Fungi (NCF). In this paper, we list all genera currently accepted by us in Dothideomycetes (belonging to 23 orders and 110 families), including pleomorphic and nonpleomorphic genera. In the case of pleomorphic genera, we follow the rulings of the current ICN and propose single generic names for future usage. The taxonomic placements of 1261 genera are listed as an outline. Protected names and suppressed names for 34 pleomorphic genera are listed separately. Notes and justifications are provided for possible proposed names after the list of genera. Notes are also provided on recent advances in our understanding of asexual and sexual morph linkages in Dothideomycetes. A phylogenetic tree based on four gene analyses supported 23 orders and 75 families, while 35 families still lack molecular data. PMID:27284275

  12. The specific involvement of coat protein in tobacco mosaic virus cross protection.

    PubMed

    Sherwood, J L; Fulton, R W

    1982-05-01

    Nicotiana sylvestris infected by strains of tobacco mosaic virus (TMV) causing mosaic can be superinfected in the dark green leaf tissue, but not light green tissue, by necrotizing strains of TMV. The dark green tissue, however, is much less susceptible than healthy tissue, to some extent, even to unrelated viruses. The RNA of necrotizing strains of TMV was relatively more infectious than intact virus on mosaic than on healthy leaves and caused lesions in both light and dark green tissues. The same relationship was found in Nicotiana longiflora and, when the protecting strain in N. sylvestris could be used as a challenge, in Capsicum baccatum. The efficiency of superinfection by RNA was not found with viruses unrelated to TMV. When bentonite at 1 mg/ml, which is known to strip protein from TMV, was included in the inoculum of intact TMV it superinfected in the same manner as RNA. RNA of a necrotizing strain of TMV, encapsidated in brome mosaic virus protein and used as a challenge, superinfected in the same manner as RNA. When encapsidated in common TMV protein, however, it behaved as native virus. Cross protection apparently results from the prevention of uncoating of related challenge virus in light green tissue of N. sylvestris. Locally inoculated N. sylvestris leaves were insusceptible to challenge RNA or intact virus when the protecting virus was increasing. After increase ceased, RNA was more infectious than intact virus. PMID:18635142

  13. Vesicular Stomatitis Virus–Based Ebola Vaccines With Improved Cross-Protective Efficacy

    PubMed Central

    Marzi, Andrea; Ebihara, Hideki; Callison, Julie; Groseth, Allison; Williams, Kinola J.; Geisbert, Thomas W.

    2011-01-01

    For Ebola virus (EBOV), 4 different species are known: Zaire, Sudan, Côte d’Ivoire, and Reston ebolavirus. The newly discovered Bundibugyo ebolavirus has been proposed as a 5th species. So far, no cross-neutralization among EBOV species has been described, aggravating progress toward cross-species protective vaccines. With the use of recombinant vesicular stomatitis virus (rVSV)–based vaccines, guinea pigs could be protected against Zaire ebolavirus (ZEBOV) infection only when immunized with a vector expressing the homologous, but not a heterologous, EBOV glycoprotein (GP). However, infection of guinea pigs with nonadapted wild-type strains of the different species resulted in full protection of all animals against subsequent challenge with guinea pig–adapted ZEBOV, showing that cross-species protection is possible. New vectors were generated that contain EBOV viral protein 40 (VP40) or EBOV nucleoprotein (NP) as a second antigen expressed by the same rVSV vector that encodes the heterologous GP. After applying a 2-dose immunization approach, we observed an improved cross-protection rate, with 5 of 6 guinea pigs surviving the lethal ZEBOV challenge if vaccinated with rVSV-expressing SEBOV-GP and -VP40. Our data demonstrate that cross-protection between the EBOV species can be achieved, although EBOV-GP alone cannot induce the required immune response. PMID:21987743

  14. Experimental Investigation of Cross-Flow Axis Marine Hydrokinetic Turbines, Including Effects of Waves and Turbulence

    NASA Astrophysics Data System (ADS)

    Wosnik, M.; Bachant, P.

    2011-12-01

    A new test bed for Marine Hydrokinetic (MHK) turbines at the Center for Ocean Renewable Energy at the University of New Hampshire (UNH-CORE) was used to evaluate the performance of different cross-flow axis hydrokinetic turbines, and investigate the effects of waves and turbulence on these devices. The test bed was designed and built to operate in the UNH tow and wave tank, which has a cross section of 3.67m (width) x 2.44m (depth). In the present configuration, tow speeds of up to 3 m/s can be achieved for smaller turbine models, and up to 1.5 m/s for large turbine models with low gear ratio. It features a flap style wave maker at one end that is capable of producing waves with 1-5 s periods up to 0.4 m wave height. Turbine thrust (drag) and mechanical power output (torque, angular velocity) were measured at tow speeds of 0.6-1.5 m/s for two cross-flow axis MHK turbines: a Gorlov Helical Turbine (GHT) and a Lucid spherical turbine (LST). Both were provided by Lucid Energy Technologies, LLP, and have frontal areas of 1.3 (GHT) and 1.0 (LST) square meters, respectively. GHT performance was also measured in progressive waves of various periods, grid turbulence, and in the wake of a cylinder, installed upstream at various cross-stream locations. Overall, the GHT performs with higher power and thrust (drag) coefficients than the LST. A 2nd law efficiency, or kinetic exergy efficiency, was defined to calculate what fraction of the kinetic energy removed from the flow is converted to usable shaft work by each turbine. The exergy efficiency varies with tip speed ratio but approaches 90% for the optimum operating conditions for each turbine. The fraction of kinetic energy removed from the fluid that is not converted to shaft work is redistributed into turbulent kinetic energy in the wake. Quantifying the kinetic energy flowing out of the turbine is important for modeling of environmental transport processes and for predicting performance when turbines are used in arrays

  15. Cross-protection induced by Japanese encephalitis vaccines against different genotypes of Dengue viruses in mice

    PubMed Central

    Li, Jieqiong; Gao, Na; Fan, Dongying; Chen, Hui; Sheng, Ziyang; Fu, Shihong; Liang, Guodong; An, Jing

    2016-01-01

    Dengue viruses (DENVs) and Japanese encephalitis virus (JEV) are closely related mosquito-borne flaviviruses that cause very high global disease burdens. Although cross-reactivity and cross-protection within flaviviruses have been demonstrated, the effect of JEV vaccination on susceptibility to DENV infection has not been well elucidated. In this study, we found that vaccination with the JEV inactivated vaccine (INV) and live attenuated vaccine (LAV) could induce cross-immune responses and cross-protection against DENV1-4 in mice. Despite the theoretical risk of immune enhancement, no increased mortality was observed in our mouse model. Additionally, low but consistently detectable cross-neutralizing antibodies against DENV2 and DENV3 were also observed in the sera of JEV vaccine-immunized human donors. The results suggested that both JEV-LAV and JEV-INV could elicit strong cross-immunity and protection against DENVs, indicating that inoculation with JEV vaccines may influence the distribution of DENVs in co-circulated areas and that the cross-protection induced by JEV vaccines against DENVs might provide important information in terms of DENV prevention. PMID:26818736

  16. Crossed SMPS MOSFET-based protection circuit for high frequency ultrasound transceivers and transducers

    PubMed Central

    2014-01-01

    Background The ultrasonic transducer is one of the core components of ultrasound systems, and the transducer’s sensitivity is significantly related the loss of electronic components such as the transmitter, receiver, and protection circuit. In an ultrasonic device, protection circuits are commonly used to isolate the electrical noise between an ultrasound transmitter and transducer and to minimize unwanted discharged pulses in order to protect the ultrasound receiver. However, the performance of the protection circuit and transceiver obviously degrade as the operating frequency or voltage increases. We therefore developed a crossed SMPS (Switching Mode Power Supply) MOSFET-based protection circuit in order to maximize the sensitivity of high frequency transducers in ultrasound systems. The high frequency pulse signals need to trigger the transducer, and high frequency pulse signals must be received by the transducer. We therefore selected the SMPS MOSFET, which is the main component of the protection circuit, to minimize the loss in high frequency operation. The crossed configuration of the protection circuit can drive balanced bipolar high voltage signals from the pulser and transfer the balanced low voltage echo signals from the transducer. Methods The equivalent circuit models of the SMPS MOSFET-based protection circuit are shown in order to select the proper device components. The schematic diagram and operation mechanism of the protection circuit is provided to show how the protection circuit is constructed. The P-Spice circuit simulation was also performed in order to estimate the performance of the crossed MOSFET-based protection circuit. Results We compared the performance of our crossed SMPS MOSFET-based protection circuit with a commercial diode-based protection circuit. At 60 MHz, our expander and limiter circuits have lower insertion loss than the commercial diode-based circuits. The pulse-echo test is typical method to evaluate the sensitivity of

  17. EVALUATION OF TUNGSTEN ISOTOPES IN THE FAST NEUTRON RANGE INCLUDING CROSS-SECTION COVARIANCE ESTIMATION.

    SciTech Connect

    CAPOTE,R.; SIN, M.; TRKOV, A.; HERMAN, M.; CARLSON, B.V.; OBLOZINSKY, P.

    2007-04-22

    New evaluations for the tungsten isotopes {sup 180,182,183,184,186}W in the neutron energy range up to 60 MeV were produced. In the resonance range only minor adjustments to the resonance parameters were made due to a lack of adequate experimental data. Evaluations in the fast energy region were based on nuclear model calculations using the EMPIRE-2.19 code. Recently derived dispersive coupled-channel optical model potentials for W and Ta isotopes were instrumental to achieve a very good description of the available microscopic cross-section database. Model covariance data were generated with the Monte Carlo technique to produce a prior estimate for the covariance matrix. Experimental data were introduced through the GANDR system. The evaluated files were tested on selected fusion neutronics benchmarks and showed marked improvement compared to other existing evaluations.

  18. Olefin cross metathesis based de novo synthesis of a partially protected L-amicetose and a fully protected L-cinerulose derivative

    PubMed Central

    Hauke, Sylvia

    2014-01-01

    Summary Cross metathesis of a lactate derived allylic alcohol and acrolein is the entry point to a de novo synthesis of 4-benzoate protected L-amicetose and a cinerulose derivative protected at C5 and C1. PMID:24991253

  19. 10 CFR 709.26 - Protection of confidentiality of CI evaluation records to include polygraph examination records...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... include polygraph examination records and other pertinent documentation. 709.26 Section 709.26 Energy... Protection of confidentiality of CI evaluation records to include polygraph examination records and other pertinent documentation. (a) DOE owns all CI evaluation records, including polygraph examination records...

  20. 10 CFR 709.26 - Protection of confidentiality of CI evaluation records to include polygraph examination records...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... include polygraph examination records and other pertinent documentation. 709.26 Section 709.26 Energy... Protection of confidentiality of CI evaluation records to include polygraph examination records and other pertinent documentation. (a) DOE owns all CI evaluation records, including polygraph examination records...

  1. 10 CFR 709.26 - Protection of confidentiality of CI evaluation records to include polygraph examination records...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... include polygraph examination records and other pertinent documentation. 709.26 Section 709.26 Energy... Protection of confidentiality of CI evaluation records to include polygraph examination records and other pertinent documentation. (a) DOE owns all CI evaluation records, including polygraph examination records...

  2. 10 CFR 709.26 - Protection of confidentiality of CI evaluation records to include polygraph examination records...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... include polygraph examination records and other pertinent documentation. 709.26 Section 709.26 Energy... Protection of confidentiality of CI evaluation records to include polygraph examination records and other pertinent documentation. (a) DOE owns all CI evaluation records, including polygraph examination records...

  3. Cytotoxic T Cells Are the Predominant Players Providing Cross-Protective Immunity Induced by γ-Irradiated Influenza A Viruses ▿

    PubMed Central

    Furuya, Yoichi; Chan, Jennifer; Regner, Matthias; Lobigs, Mario; Koskinen, Aulikki; Kok, Tuckweng; Manavis, Jim; Li, Peng; Müllbacher, Arno; Alsharifi, Mohammed

    2010-01-01

    We previously demonstrated that a single dose of nonadjuvanted intranasal γ-irradiated influenza A virus can provide robust protection in mice against both homologous and heterosubtypic challenges, including challenge with an H5N1 avian virus strain. We investigated the mechanism behind the observed cross-protection to define which arms of the adaptive immune response are involved in mediating this protection. Studies with gene knockout mice showed the cross-protective immunity to be mediated mainly by T cells and to be dependent on the cytolytic effector molecule perforin. Adoptive transfer of memory T cells from immunized mice, but not of memory B cells, protected naïve recipients against lethal heterosubtypic influenza virus challenge. Furthermore, γ-irradiated influenza viruses induced cross-reactive Tc-cell responses but not cross-neutralizing or cross-protective antibodies. In addition, histological analysis showed reduced lung inflammation in vaccinated mice compared to that in unvaccinated controls following heterosubtypic challenge. This reduced inflammation was associated with enhanced early recruitment of T cells, both CD4+ and CD8+, and with early influenza virus-specific cytotoxic T-cell responses. Therefore, cross-protective immunity induced by vaccination with γ-irradiated influenza A virus is mediated mainly by Tc-cell responses. PMID:20164231

  4. Aerodynamic characteristics of several current helicopter tail boom cross sections including the effect of spoilers

    NASA Technical Reports Server (NTRS)

    Wilson, J. C.; Kelley, H. L.

    1986-01-01

    Aerodynamic characteristics were determined of three cylindrical shapes representative of tail boom cross sections of the U.S. Army AH-64, UH-60, and UH-1H helicopters. Forces and pressures were measured in a wind-tunnel investigation at the Langley Research Center. Data were obtained for a flow incidence range from -45 to 90 deg and a dynamic pressure range from 1.5 to 50 psf. These ranges provided data representative of full-scale Reynolds numbers and the full range of flow incidence to which these helicopter tail boom shapes would be subjected at low flight speeds. The effects of protuberances such as tail rotor drive-shaft covers and spoilers were evaluated. The data indicate that significant side loads on tail booms of helicopters can be generated and that the addition of spoilers can beneficially alter the side loads. Although an increase in vertical drag occurs, the net effect through reduction of tail rotor thrust required can be an improvement in helicopter performance.

  5. Emergence of large chiroptical responses by ligand exchange cross-linking of monolayer-protected gold clusters with chiral dithiol.

    PubMed

    Yao, Hiroshi; Yaomura, Shota

    2013-05-28

    We here present a study of cross-linking chemistry of optically inactive monothiol-protected gold clusters by chiral bidentate dithiol with two stereogenic centers, (2R,3R)-1,4-dimercapto-2,3-butanediol (L-dithiothreitol; L-DTT), and explore the impacts of the cross-linking on their chiroptical responses. The pristine protective ligand is racemic penicillamine (rac-Pen), and the products of the ligand exchange reactions include clusters containing both rac-Pen and L-DTT (partial exchange). Electrophoresis using polyacrylamide gel with a very low gel concentration (3%) can make the products separable into two components, each of which has the similar mean core diameter of 0.78 and 0.83 nm, so the difference in the relative mobility is mainly ascribed to the size of the cluster assembly. In addition, very large optical activity with the maximum anisotropy factors of about 1.0 × 10(-3) is found for the assemblies. In comparison with chiral 1,3-dithiol protection incapable of cross-linking between gold clusters, we propose that the observed optical activity is due to surface intrinsic handedness caused by a cyclic cross-linking with at least two L-DTT molecules. PMID:23635318

  6. Cross-Protection against Challenge with Puumala Virus after Immunization with Nucleocapsid Proteins from Different Hantaviruses

    PubMed Central

    de Carvalho Nicacio, Cristina; Gonzalez Della Valle, Marcelo; Padula, Paula; Björling, Ewa; Plyusnin, Alexander; Lundkvist, Åke

    2002-01-01

    Hantaviruses are rodent-borne agents that cause hemorrhagic fever with renal syndrome or hantavirus pulmonary syndrome in humans. The nucleocapsid protein (N) is relatively conserved among hantaviruses and highly immunogenic in both laboratory animals and humans, and it has been shown to induce efficient protective immunity in animal models. To investigate the ability of recombinant N (rN) from different hantaviruses to elicit cross-protection, we immunized bank voles with rN from Puumala (PUUV), Topografov (TOPV), Andes (ANDV), and Dobrava (DOBV) viruses and subsequently challenged them with PUUV. All animals immunized with PUUV and TOPV rN were completely protected. In the group immunized with DOBV rN, 7 of 10 animals were protected, while only 3 of 8 animals were protected in the group immunized with ANDV rN, which is more closely related to PUUV rN than DOBV rN. Humoral and cellular immune responses after rN immunization were also investigated. The highest cross-reactive humoral responses against PUUV antigen were detected in sera from ANDV rN-immunized animals, followed by those from TOPV rN-immunized animals, and only very low antibody cross-reactivity was observed in sera from DOBV rN-immunized animals. In proliferation assays, T lymphocytes from animals immunized with all heterologous rNs were as efficiently recalled in vitro by PUUV rN as were T lymphocytes from animals immunized with homologous protein. In summary, this study has shown that hantavirus N can elicit cross-protective immune responses against PUUV, and the results suggest a more important role for the cellular arm of the immune response than for the humoral arm in cross-protection elicited by rN. PMID:12050380

  7. The Langley thermal protection system test facility: A description including design operating boundaries

    NASA Technical Reports Server (NTRS)

    Klich, G. F.

    1976-01-01

    A description of the Langley thermal protection system test facility is presented. This facility was designed to provide realistic environments and times for testing thermal protection systems proposed for use on high speed vehicles such as the space shuttle. Products from the combustion of methane-air-oxygen mixtures, having a maximum total enthalpy of 10.3 MJ/kg, are used as a test medium. Test panels with maximum dimensions of 61 cm x 91.4 cm are mounted in the side wall of the test region. Static pressures in the test region can range from .005 to .1 atm and calculated equilibrium temperatures of test panels range from 700 K to 1700 K. Test times can be as long as 1800 sec. Some experimental data obtained while using combustion products of methane-air mixtures are compared with theory, and calibration of the facility is being continued to verify calculated values of parameters which are within the design operating boundaries.

  8. Molecular Characterization of Citrus Tristeza Virus Isolates from Mild Strain Cross Protection Experiments in Peru

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Seven isolates of Citrus tristeza virus (CTV) collected from the Topara Nursery, Lima, Peru were established as in planta cultures in Madam Vinous sweet orange in the Exotic Citrus Pathogen Quarantine Greenhouse, Beltsville, MD. Two of the isolates were collected from non-cross protected plants; Pe...

  9. 18 CFR 35.44 - Protections against affiliate cross-subsidization.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... facility, as defined by 18 CFR 292.101, made under market-based rate authority granted by the Commission... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Protections against affiliate cross-subsidization. 35.44 Section 35.44 Conservation of Power and Water Resources FEDERAL...

  10. Stability of sublethal acid stress adaptaion and induced cross protection against lauric arginate in Listeria monocytogenes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The stability of acid stress adaptation in Listeria monocytogenes and its induced cross protection effect against GRAS (generally recognized as safe) antimicrobial compounds has never been investigated before. In the present study, the acid stress adaptation in L. monocytogenes was initially induced...

  11. Iterative protecting group-free cross-coupling leading to chiral multiply arylated structures

    PubMed Central

    Crudden, Cathleen M.; Ziebenhaus, Christopher; Rygus, Jason P. G.; Ghozati, Kazem; Unsworth, Phillip J.; Nambo, Masakazu; Voth, Samantha; Hutchinson, Marieke; Laberge, Veronique S.; Maekawa, Yuuki; Imao, Daisuke

    2016-01-01

    The Suzuki–Miyaura cross-coupling is one of the most often utilized reactions in the synthesis of pharmaceutical compounds and conjugated materials. In its most common form, the reaction joins two sp2-functionalized carbon atoms to make a biaryl or diene/polyene unit. These substructures are widely found in natural products and small molecules and thus the Suzuki–Miyaura cross-coupling has been proposed as the key reaction for the automated assembly of such molecules, using protecting group chemistry to affect iterative coupling. We present herein, a significant advance in this approach, in which multiply functionalized cross-coupling partners can be employed in iterative coupling without the use of protecting groups. To accomplish this, the orthogonal reactivity of different boron substituents towards the boron-to-palladium transmetalation reaction is exploited. The approach is illustrated in the preparation of chiral enantioenriched compounds, which are known to be privileged structures in active pharmaceutical compounds. PMID:27040494

  12. Iterative protecting group-free cross-coupling leading to chiral multiply arylated structures.

    PubMed

    Crudden, Cathleen M; Ziebenhaus, Christopher; Rygus, Jason P G; Ghozati, Kazem; Unsworth, Phillip J; Nambo, Masakazu; Voth, Samantha; Hutchinson, Marieke; Laberge, Veronique S; Maekawa, Yuuki; Imao, Daisuke

    2016-01-01

    The Suzuki-Miyaura cross-coupling is one of the most often utilized reactions in the synthesis of pharmaceutical compounds and conjugated materials. In its most common form, the reaction joins two sp(2)-functionalized carbon atoms to make a biaryl or diene/polyene unit. These substructures are widely found in natural products and small molecules and thus the Suzuki-Miyaura cross-coupling has been proposed as the key reaction for the automated assembly of such molecules, using protecting group chemistry to affect iterative coupling. We present herein, a significant advance in this approach, in which multiply functionalized cross-coupling partners can be employed in iterative coupling without the use of protecting groups. To accomplish this, the orthogonal reactivity of different boron substituents towards the boron-to-palladium transmetalation reaction is exploited. The approach is illustrated in the preparation of chiral enantioenriched compounds, which are known to be privileged structures in active pharmaceutical compounds. PMID:27040494

  13. Oral Fluids as a Live-Animal Sample Source for Evaluating Cross-Reactivity and Cross-Protection following Intranasal Influenza A Virus Vaccination in Pigs

    PubMed Central

    Hughes, Holly R.; Vincent, Amy L.; Brockmeier, Susan L.; Gauger, Phillip C.; Pena, Lindomar; Santos, Jefferson; Braucher, Douglas R.; Perez, Daniel R.

    2015-01-01

    In North American swine, there are numerous antigenically distinct H1 influenza A virus (IAV) variants currently circulating, making vaccine development difficult due to the inability to formulate a vaccine that provides broad cross-protection. Experimentally, live-attenuated influenza virus (LAIV) vaccines demonstrate increased cross-protection compared to inactivated vaccines. However, there is no standardized assay to predict cross-protection following LAIV vaccination. Hemagglutination-inhibiting (HI) antibody in serum is the gold standard correlate of protection following IAV vaccination. LAIV vaccination does not induce a robust serum HI antibody titer; however, a local mucosal antibody response is elicited. Thus, a live-animal sample source that could be used to evaluate LAIV immunogenicity and cross-protection is needed. Here, we evaluated the use of oral fluids (OF) and nasal wash (NW) collected after IAV inoculation as a live-animal sample source in an enzyme-linked immunosorbent assay (ELISA) to predict cross-protection in comparison to traditional serology. Both live-virus exposure and LAIV vaccination provided heterologous protection, though protection was greatest against more closely phylogenetically related viruses. IAV-specific IgA was detected in NW and OF samples and was cross-reactive to representative IAV from each H1 cluster. Endpoint titers of cross-reactive IgA in OF from pigs exposed to live virus was associated with heterologous protection. While LAIV vaccination provided significant protection, LAIV immunogenicity was reduced compared to live-virus exposure. These data suggest that OF from pigs inoculated with wild-type IAV, with surface genes that match the LAIV seed strain, could be used in an ELISA to assess cross-protection and the antigenic relatedness of circulating and emerging IAV in swine. PMID:26291090

  14. Testing for loss of protective sensation in patients with foot ulceration: a cross-sectional study.

    PubMed

    Wood, William A; Wood, Michael A; Werter, Scott A; Menn, Joseph J; Hamilton, Scott A; Jacoby, Richard; Dellon, A Lee

    2005-01-01

    Current recommendations for the prevention of foot ulceration and amputation include screening at-risk individuals by testing for loss of protective sensation at eight sites using 10-g (5.07) nylon monofilaments. Yet measurement of the cutaneous pressure threshold to differentiate one-point from two-point static touch stimuli may allow identification of these at-risk individuals earlier in the clinical course of diabetic neuropathy. The present study tested this hypothesis using a prospective, cross-sectional, multicenter design that included sensibility testing of 496 patients with diabetic neuropathy, 17 of whom had a history of ulceration or amputation. Considering the cutaneous pressure threshold of the 5.07 Semmes-Weinstein nylon monofilament to be equivalent to the 95 g/mm(2) one-point static touch measured using the Pressure-Specified Sensory Device (Sensory Management Services LLC, Baltimore, Maryland), only 3 of these 17 patients with a history of foot ulceration or amputation would have been identified using the Semmes-Weinstein nylon monofilament screening technique. In contrast, using the Pressure-Specified Sensory Device, all 17 patients were identified as having abnormal sensibility, defined as greater than the 99% confidence limit for age, for two-point static touch on the hallux pulp. We conclude that patients at risk for foot ulceration can best be identified by actual measurement of the cutaneous sensibility of the hallux pulp. PMID:16166466

  15. Dye lasing arrangement including an optical assembly for altering the cross-section of its pumping beam and method

    DOEpatents

    O'Neil, Richard W.; Sweatt, William C.

    1992-01-01

    An optical assembly is disclosed herein along with a method of operation for use in a dye lasing arrangement, for example a dye laser oscillator or a dye amplifier, in which a continuous stream of dye is caused to flow through a given zone in a cooperating dye chamber while the zone is being illuminated by light from a pumping beam which is directed into the given zone. This in turn causes the dye therein to lase and thereby produce a new dye beam in the case of a dye laser oscillator or amplify a dye beam in the case of a dye amplifier. The optical assembly so disclosed is designed to alter the pump beam such that the beam enters the dye chamber with a different cross-sectional configuration, preferably one having a more uniform intensity profile, than its initially produced cross-sectional configuration. To this end, the assembly includes a network of optical components which first act on the beam while the latter retains its initially produced cross-sectional configuration for separating it into a plurality of predetermined segments and then recombines the separated components in a predetermined way which causes the recombined beam to have the different cross-sectional configuration.

  16. Including Adults with Intellectual Disabilities in Research: Scientists' Perceptions of Risks and Protections

    ERIC Educational Resources Information Center

    McDonald, Katherine E.; Kidney, Colleen A.; Nelms, Sandra L.; Parker, Michael R.; Kimmel, Ali; Keys, Christopher B.

    2009-01-01

    Social and cognitive characteristics of adults with intellectual disabilities (ID) place them at risk for inappropriate inclusion in or exclusion from research participation. As we grapple with how to include adults with ID in research in order to secure their right to contribute to scientific advancements and be positioned to derive benefit from…

  17. Cross-protective immune responses between genotypically distinct lineages of infectious laryngotracheitis viruses.

    PubMed

    Lee, Sang-Won; Markham, Philip F; Coppo, Mauricio J C; Legione, Alistair R; Shil, Niraj K; Quinteros, José A; Noormohammadi, Amir H; Browning, Glenn F; Hartley, Carol A; Devlin, Joanne M

    2014-03-01

    Recent phylogenetic studies have identified different genotypic lineages of infectious laryngotracheitis virus (ILTV), and these lineages can recombine in the field. The emergence of virulent recombinant field strains of ILTV by natural recombination between commercial vaccines belonging to different genotypic lineages has been reported recently. Despite the use of attenuated ILTV vaccines, these recombinant viruses were able to spread and cause disease in commercial poultry flocks, raising the question of whether the different lineages of ILTV can induce cross-protective immune responses. This study examined the capacity of the Australian-origin A20 ILTV vaccine to protect against challenge with the class 8 ILTV recombinant virus, the genome of which is predominantly derived from a heterologous genotypic lineage. Following challenge, birds vaccinated via eyedrop were protected from clinical signs of disease and pathological changes in the tracheal mucosa, although they were not completely protected from viral infection or replication. In contrast, the challenge virus induced severe clinical signs and tracheal pathology in unvaccinated birds. This is the first study to examine the ability of a vaccine from the Australian lineage to protect against challenge with a virus from a heterologous lineage. These results suggest that the two distinct genotypic lineages of ILTV can both induce cross-protection, indicating that current commercial vaccines are still likely to assist in control of ILTV in the poultry industry, in spite of the emergence of novel recombinants derived from different genotypic lineages. PMID:24758128

  18. Cross-protective immune responses elicited by a Korean variant of infectious bronchitis virus.

    PubMed

    Kim, Byoung-Yoon; Lee, Dong-Hun; Jang, Jun-Hyuk; Lim, Tae-Hyun; Choi, Soo-Won; Youn, Ha-Na; Park, Jae-Keun; Lee, Joong-Bok; Park, Seung-Yong; Choi, In-Soo; Song, Chang-Seon

    2013-09-01

    Infectious bronchitis virus (IBV) infections cause great economic losses to the poultry industry worldwide. IBVs continuously evolve by developing mutations in antigenic sites; therefore, an IBV vaccine that provides broad cross-protection can be a highly relevant and practical method in IBV control strategies. Although some IBV vaccine strains are known to provide protection against multiple IBV serotypes, in general commercially available IBV vaccine strains provide protection against antigenically related viruses but not distinct heterologous viruses. In the present study we characterized the Korean variant IBV K40/09 strain with regard to its immunogenicity and protective efficacy against seven currently circulating IBV serotypes. Three-week-old specific-pathogen-free chickens were intraocularly immunized with the IBV K40/09 strain at 10(3.5) 50% egg infective dose (EID50). Three weeks after immunization all the birds were challenged with seven different strains at 10(4.5) EID50. Chickens immunized with the IBV K40/09 strain showed significantly high levels of protection against all challenge viruses at the trachea and kidney levels. Our results suggest that IBV K40/09 could be useful to ensure IBV vaccine effectiveness owing to its cross-protective ability. Therefore, the IBV K40/09 strain merits consideration as a vaccine candidate to prevent infection as well as the spread of new IBV strains and many IBV variants that have been reported worldwide. PMID:24283135

  19. Arthritis protective regulatory potential of self–heat shock protein cross-reactive T cells

    PubMed Central

    van Eden, Willem; Wendling, Uwe; Paul, Liesbeth; Prakken, Berent; van Kooten, Peter; van der Zee, Ruurd

    2000-01-01

    Immunization with heat shock proteins has protective effects in models of induced arthritis. Analysis has shown a reduced synovial inflammation in such protected animals. Adoptive transfer and immunization with selected T cell epitopes (synthetic peptides) have indicated the protection to be mediated by T cells directed to conserved hsp epitopes. This was shown first for mycobacterial hsp60 and later for mycobacterial hsp70. Fine specificity analysis showed that such T cells were cross-reactive with the homologous self hsp. Therefore protection by microbial hsp reactive T cells can be by cross-recognition of self hsp overexpressed in the inflamed tissue. Preimmunization with hsp leads to a relative expansion of such self hsp cross-responsive T cells. The regulatory nature of such T cells may originate from mucosal tolerance maintained by commensal flora derived hsp or from partial activation through recognition of self hsp as a partial agonist (Altered Peptide Ligand) or in the absence of proper costimulation. Recently, we reported the selective upregulation of B7.2 on microbial hsp60 specific T cells in response to self hsp60. Through a preferred interaction with CTLA-4 on proinflammatory T cells this may constitute an effector mechanism of regulation. Also, regulatory T cells produced IL10. PMID:11189451

  20. Investigation of seedling yellows cross protection by mild components of the Dekopon strain of Citrus tristeza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Virulent strains of Citrus tristeza virus (CTV) can be controlled by pre-infection by mild strains of CTV which is called cross protection. However, the mode of action of cross protection is unknown and its durability unpredictable. RNA silencing is a regulatory mechanism to maintain genome integri...

  1. Cross-species protection: Schistosoma mansoni Sm-p80 vaccine confers protection against Schistosoma haematobium in hamsters and baboons.

    PubMed

    Karmakar, Souvik; Zhang, Weidong; Ahmad, Gul; Torben, Workineh; Alam, Mayeen U; Le, Loc; Damian, Raymond T; Wolf, Roman F; White, Gary L; Carey, David W; Carter, Darrick; Reed, Steven G; Siddiqui, Afzal A

    2014-03-01

    The ability of the Schistosoma mansoni antigen, Sm-p80, to provide cross-species protection against Schistosoma haematobium challenge was evaluated in hamster and baboon models. Pronounced reduction in worm burden (48%) and in tissue egg load (64%) was observed in hamsters vaccinated with recombinant Sm-p80 admixed with glucopyranosyl lipid adjuvant-stable emulsion (GLA-SE). Similarly, in baboons, the Sm-p80/GLA-SE vaccine produced a 25% reduction in S. haematobium adult worms and decreased the egg load in the urinary bladder by 64%. A 40% and 53% reduction in fecal and urine egg output, respectively, was observed in vaccinated baboons. A balanced pro-inflammatory (Th17 and Th1) and Th2 type of response was generated after vaccination and appears indicative of augmented prophylactic efficacy. These data on cross-species protection coupled with the prophylactic, therapeutic and antifecundity efficacy against the homologous parasite, S. mansoni, reinforces Sm-p80 as a promising vaccine candidate. It is currently being prepared for GMP-compliant manufacture and for further pre-clinical development leading to human clinical trials. These results solidify the expectation that the Sm-p80 vaccine will provide relief for both the intestinal and the urinary schistosomiasis and thus will be greatly beneficial in reducing the overall burden of schistosomiasis. PMID:24397898

  2. A Multivalent and Cross-Protective Vaccine Strategy against Arenaviruses Associated with Human Disease

    PubMed Central

    Kotturi, Maya F.; Botten, Jason; Sidney, John; Bui, Huynh-Hoa; Giancola, Lori; Maybeno, Matt; Babin, Josie; Oseroff, Carla; Pasquetto, Valerie; Greenbaum, Jason A.; Peters, Bjoern; Ting, Joey; Do, Danh; Vang, Lo; Alexander, Jeff; Grey, Howard; Buchmeier, Michael J.; Sette, Alessandro

    2009-01-01

    Arenaviruses are the causative pathogens of severe hemorrhagic fever and aseptic meningitis in humans, for which no licensed vaccines are currently available. Pathogen heterogeneity within the Arenaviridae family poses a significant challenge for vaccine development. The main hypothesis we tested in the present study was whether it is possible to design a universal vaccine strategy capable of inducing simultaneous HLA-restricted CD8+ T cell responses against 7 pathogenic arenaviruses (including the lymphocytic choriomeningitis, Lassa, Guanarito, Junin, Machupo, Sabia, and Whitewater Arroyo viruses), either through the identification of widely conserved epitopes, or by the identification of a collection of epitopes derived from multiple arenavirus species. By inoculating HLA transgenic mice with a panel of recombinant vaccinia viruses (rVACVs) expressing the different arenavirus proteins, we identified 10 HLA-A02 and 10 HLA-A03-restricted epitopes that are naturally processed in human antigen-presenting cells. For some of these epitopes we were able to demonstrate cross-reactive CD8+ T cell responses, further increasing the coverage afforded by the epitope set against each different arenavirus species. Importantly, we showed that immunization of HLA transgenic mice with an epitope cocktail generated simultaneous CD8+ T cell responses against all 7 arenaviruses, and protected mice against challenge with rVACVs expressing either Old or New World arenavirus glycoproteins. In conclusion, the set of identified epitopes allows broad, non-ethnically biased coverage of all 7 viral species targeted by our studies. PMID:20019801

  3. Development of a Salmonella cross-protective vaccine for food animal production systems.

    PubMed

    Heithoff, Douglas M; House, John K; Thomson, Peter C; Mahan, Michael J

    2015-01-01

    Intensive livestock production is associated with increased Salmonella exposure, transmission, animal disease, and contamination of food and water supplies. Modified live Salmonella enterica vaccines that lack a functional DNA adenine methylase (Dam) confer cross-protection to a diversity of salmonellae in experimental models of murine, avian, ovine, and bovine models of salmonellosis. However, the commercial success of any vaccine is dependent upon the therapeutic index, the ratio of safety/efficacy. Herein, secondary virulence-attenuating mutations targeted to genes involved in intracellular and/or systemic survival were introduced into Salmonella dam vaccines to screen for vaccine candidates that were safe in the animal and the environment, while maintaining the capacity to confer cross-protective immunity to pathogenic salmonellae serotypes. Salmonella dam mgtC, dam sifA, and dam spvB vaccine strains exhibited significantly improved vaccine safety as evidenced by the failure to give rise to virulent revertants during the infective process, contrary to the parental Salmonella dam vaccine. Further, these vaccines exhibited a low grade persistence in host tissues that was associated with reduced vaccine shedding, reduced environmental persistence, and induction of cross-protective immunity to pathogenic serotypes derived from infected livestock. These data indicate that Salmonella dam double mutant vaccines are suitable for commercial applications against salmonellosis in livestock production systems. Reducing pre-harvest salmonellae load through vaccination will promote the health and productivity of livestock and reduce contamination of livestock-derived food products, while enhancing overall food safety. PMID:25448106

  4. Base excision repair enzymes protect abasic sites in duplex DNA from interstrand cross-links.

    PubMed

    Admiraal, Suzanne J; O'Brien, Patrick J

    2015-03-10

    Hydrolysis of the N-glycosyl bond between a nucleobase and deoxyribose leaves an abasic site within duplex DNA. The abasic site can react with exocyclic amines of nucleobases on the complementary strand to form interstrand DNA-DNA cross-links (ICLs). We find that several enzymes from the base excision repair (BER) pathway protect an abasic site on one strand of a DNA duplex from cross-linking with an amine on the opposing strand. Human alkyladenine DNA glycosylase (AAG) and Escherichia coli 3-methyladenine DNA glycosylase II (AlkA) accomplish this by binding tightly to the abasic site and sequestering it. AAG protects an abasic site opposite T, the product of its canonical glycosylase reaction, by a factor of ∼10-fold, as estimated from its inhibition of the reaction of an exogenous amine with the damaged DNA. Human apurinic/apyrimidinic site endonuclease 1 and E. coli endonuclease III both decrease the amount of ICL at equilibrium by generating a single-strand DNA nick at the abasic position as it is liberated from the cross-link. The reversibility of the reaction between amines and abasic sites allows BER enzymes to counter the potentially disruptive effects of this type of cross-link on DNA transactions. PMID:25679877

  5. Nature of the cross-protective antigen in subcellular vaccines of Streptococcus pneumoniae.

    PubMed Central

    Au, C C; Eisenstein, T K

    1981-01-01

    Studies have been carried out to investigate the nature of the antigen present in subcellular extracts of a rough strain of Streptococcus pneumoniae A662b which has been shown to confer protection in mice against challenge with smooth, virulent organisms of the homologous and heterologous serotypes. The finding that whole, heat-killed cells were also capable of immunizing mice against challenge with organisms of heterologous serotypes suggests that the immunogen is present on the surface of the rough pneumococcal cell. Ribosomes purified by sucrose gradient centrifugation were not protective, but material recovered in the pellet retained activity. Subcellular extracts prepared from spheroplasts with a partial absence of cell wall showed decreased protective capacity, and extracts prepared from wall-deficient protoplasts were not protective. Crude cell walls evidenced cross-serotype protection, but purified walls did not protect. These results are interpreted as suggesting that the active moiety in the subcellular vaccine is present on the surface of rough pneumococci and is either a wall antigen that must be part of a larger macromolecular complex to be immunogenic, or a substance associated with the cell wall that is present in crude, but not purified, cell wall fractions. PMID:7216442

  6. Epitope specificity determines cross-protection of a SIT-induced IgG4 antibody

    PubMed Central

    Gadermaier, E.; James, L. K.; Shamji, M. H.; Blatt, K.; Fauland, K.; Zieglmayer, P.; Garmatiuk, T.; Focke-Tejkl, M.; Villalba, M.; Beavil, R.; Keller, W.; Valent, P.; Durham, S. R.; Gould, H. J.; Flicker, S.; Valenta, R.

    2015-01-01

    Background The calcium-binding 2EF-hand protein Phl p 7 from timothy grass pollen is a highly cross-reactive pollen pan-allergen that can induce severe clinical symptoms in allergic patients. Recently, a human monoclonal Phl p 7-specific IgG4 antibody (mAb102.1F10) was isolated from a patient who had received grass pollen-specific immunotherapy (SIT). Methods We studied epitope specificity, cross-reactivity, affinity and cross-protection of mAb102.1F10 towards homologous calcium-binding pollen allergens. Sequence comparisons and molecular modelling studies were performed with ClustalW and SPADE, respectively. Surface plasmon resonance measurements were done with purified recombinant allergens. Binding and cross-reactivity of patients’ IgE and mAb102.1F10 to calcium-binding allergens and peptides thereof was studied with quantitative RAST-based methods, in ELISA, basophil activation and IgE-facilitated allergen presentation experiments. Results Allergens from Timothy grass (Phl p 7), Alder (Aln g 4), Birch (Bet v 4), Turnip rape (Bra r 1), Lamb’s quarter (Che a 3) and Olive (Ole e 3, Ole e 8) showed high sequence similarity and cross-reacted with allergic patients’ IgE. mAb102.1F10 bound the C-terminal portion of Phl p 7 in a calcium-dependent manner. It cross-reacted with high affinity with Ole e 3 whereas binding and affinity to the other allergens was low. mAb102.1F10 showed limited inhibition of patients’ IgE binding and basophil activation. Sequence comparison and surface exposure calculations identified three amino acids likely to be responsible for limited cross-reactivity. Conclusions Our results demonstrate that a small number of amino acid differences among cross-reactive allergens can reduce the affinity of binding by a SIT-induced IgG and thus limit cross-protection. PMID:26221749

  7. Protective efficacy of a bacterially produced modular capsomere presenting M2e from influenza: extending the potential of broadly cross-protecting epitopes.

    PubMed

    Wibowo, Nani; Hughes, Fiona K; Fairmaid, Emily J; Lua, Linda H L; Brown, Lorena E; Middelberg, Anton P J

    2014-06-17

    Influenza A viruses drift and shift, emerging as antigenically distinct strains that lead to epidemics and pandemics of varying severity. Even epitopes associated with broad cross-protection against different strains, such as the ectodomain of matrix protein 2 (M2e), mutate unpredictably. Vaccine protective efficacy is only ensured when the emerging virus lies within the vaccine's cross-protective domain, which is poorly defined in most situations. When virus emerges outside this domain it is essential to rapidly re-engineer the vaccine and hence re-center the cross-protective domain on the new virus. This approach of vaccine re-engineering in response to virus change is the cornerstone of the current influenza control system, based on annual prediction and/or pandemic reaction. This system could become more responsive, and perhaps preventative, if its speed could be improved. Here, we demonstrate vaccine efficacy of a rapidly manufacturable modular capsomere presenting the broadly cross-protecting M2e epitope from influenza. M2e inserted into a viral capsomere at the DNA level was expressed in Escherichia coli as a fusion protein (Wibowo et al., 2013). Immunization of mice with this modular capsomere adjuvanted with conventional aluminum hydroxide induced high (more than 10(5) endpoint titer) levels of M2e-specific antibodies that reduced disease severity and viral load in the lungs of challenged mice. The combination of rapid manufacturability of modular capsomere presented in this study, and the established cross-protective efficacy of M2e, allow rapid matching of vaccine to the circulating virus and hence rapid re-centering of the vaccine's cross-protective domain onto the virus. This approach synergizes the discussed benefits of broadly cross-protecting epitopes with rapid scale-up vaccine manufacture using microbial cell factories. PMID:24795225

  8. Mild strain cross protection of tristeza: a review of research to protect against decline on sour orange in Florida

    PubMed Central

    Lee, Richard F.; Keremane, Manjunath L.

    2013-01-01

    Tristeza, caused by Citrus tristeza virus (CTV), has long been present in Florida but outbreaks of decline on sour orange rootstock were occasional events until the late 1970s. Sour orange rootstock was valued for the high quality of fruit produced and was widely used because of its tolerance of citrus blight, a disease of unknown etiology. Research was directed towards the selection and screening of mild strains of CTV which could protect against sour orange decline strains. Following the introduction of Toxoptera citricida (also known as the brown citrus aphid) in 1995 there was a greater concern for maintaining production of existing blocks of citrus on sour orange rootstock. Availability of the CTV genome sequence around the same time as well as molecular characterization of in planta CTV populations led to the selection of mild CTV isolates which when inoculated into existing field trees, extended the productive life of the groves and enabled a more graduate replanting of trees on CTV-tolerant rootstocks. The history of CTV in Florida and the methods developed to select mild isolates for use for mild strain cross protection will be reviewed. PMID:24046764

  9. Development of Cross-Protective Influenza A Vaccines Based on Cellular Responses

    PubMed Central

    Soema, Peter Christiaan; van Riet, Elly; Kersten, Gideon; Amorij, Jean-Pierre

    2015-01-01

    Seasonal influenza vaccines provide protection against matching influenza A virus (IAV) strains mainly through the induction of neutralizing serum IgG antibodies. However, these antibodies fail to confer a protective effect against mismatched IAV. This lack of efficacy against heterologous influenza strains has spurred the vaccine development community to look for other influenza vaccine concepts, which have the ability to elicit cross-protective immune responses. One of the concepts that is currently been worked on is that of influenza vaccines inducing influenza-specific T cell responses. T cells are able to lyse infected host cells, thereby clearing the virus. More interestingly, these T cells can recognize highly conserved epitopes of internal influenza proteins, making cellular responses less vulnerable to antigenic variability. T cells are therefore cross-reactive against many influenza strains, and thus are a promising concept for future influenza vaccines. Despite their potential, there are currently no T cell-based IAV vaccines on the market. Selection of the proper antigen, appropriate vaccine formulation and evaluation of the efficacy of T cell vaccines remains challenging, both in preclinical and clinical settings. In this review, we will discuss the current developments in influenza T cell vaccines, focusing on existing protein-based and novel peptide-based vaccine formulations. Furthermore, we will discuss the feasibility of influenza T cell vaccines and their possible use in the future. PMID:26029218

  10. Environmental Protection Department`s well inventory: Includes current and past monitoring (through the second quarter of 1990)

    SciTech Connect

    Rogers, C.D.

    1990-11-01

    This report is an inventory of the wells contained in Environmental Protection Department /Environmental Monitoring Section (EPD/EMS) documents since the startup of the Savannah River Site (SRS) and includes wells monitored by special request and SRS research wells. All wells listed in this inventory are monitoring wells unless otherwise indicated. The purpose of this report is as follows: to provide a historical record of the wells that EPD/EMS has monitored, to provide a document containing a list of wells that are currently in the EPD/EMS Groundwater Monitoring Program, and to provide pertinent information about all wells listed in EPD/EMS documents

  11. A design assessment of multiwall, metallic stand-off, and RSI reusable thermal protection systems including space shuttle application

    NASA Technical Reports Server (NTRS)

    Jackson, L. R.; Dixon, S. C.

    1980-01-01

    The design and assessment of reusable surface insulation (RSI), metallic stand off and multiwall thermal protection systems (TPS) is discussed. Multiwall TPS is described in some detail, and analyses useful for design of multiwall are included. Results indicate that multiwall has the potential to satisfy the TPS design goals better than the other systems. The total mass of the stand-off TPS and of the metallic systems require less primary structure mass than the RSI system, since the nonbuckling skin criteria required for RSI may be removed. Continued development of multiwall TPS is required to verify its potential and to provide the necessary data base for design.

  12. Neutron, Proton, and Photonuclear Cross Sections for Radiation Therapy and Radiation Protection

    SciTech Connect

    Chadwick, M.B.

    1998-09-10

    The authors review recent work at Los Alamos to evaluate neutron, proton, and photonuclear cross section up to 150 MeV (to 250 MeV for protons), based on experimental data and nuclear model calculations. These data are represented in the ENDF format and can be used in computer codes to simulate radiation transport. They permit calculations of absorbed dose in the body from therapy beams, and through use of kerma coefficients allow absorbed dose to be estimated for a given neutron energy distribution. For radiation protection, these data can be used to determine shielding requirements in accelerator environments, and to calculate neutron, proton, gamma-ray, and radionuclide production. Illustrative comparisons of the evaluated cross section and kerma coefficient data with measurements are given.

  13. The Campylobacter jejuni Ferric Uptake Regulator Promotes Acid Survival and Cross-Protection against Oxidative Stress.

    PubMed

    Askoura, Momen; Sarvan, Sabina; Couture, Jean-François; Stintzi, Alain

    2016-05-01

    Campylobacter jejuni is a prevalent cause of bacterial gastroenteritis in humans worldwide. The mechanisms by which C. jejuni survives stomach acidity remain undefined. In the present study, we demonstrated that the C. jejuni ferric uptake regulator (Fur) plays an important role in C. jejuni acid survival and acid-induced cross-protection against oxidative stress. A C. jejuni Δfur mutant was more sensitive to acid than the wild-type strain. Profiling of the acid stimulon of the C. jejuni Δfur mutant allowed us to uncover Fur-regulated genes under acidic conditions. In particular, Fur was found to upregulate genes involved in flagellar and cell envelope biogenesis upon acid stress, and mutants with deletions of these genes were found to be defective in surviving acid stress. Interestingly, prior acid exposure of C. jejuni cross-protected against oxidative stress in a catalase (KatA)- and Fur-dependent manner. Western blotting and reverse transcription-quantitative PCR revealed increased expression of KatA upon acid stress. Electrophoretic mobility shift assays (EMSAs) demonstrated that the binding affinity between Fur and the katA promoter is reduced in vitro under conditions of low pH, rationalizing the higher levels of expression of katA under acidic conditions. Strikingly, the Δfur mutant exhibited reduced virulence in both human epithelial cells and the Galleria mellonella infection model. Altogether, this is the first study showing that, in addition to its role in iron metabolism, Fur is an important regulator of C. jejuni acid responses and this function cross-protects against oxidative stress. Moreover, our results clearly demonstrate Fur's important role in C. jejuni pathogenesis. PMID:26883589

  14. Studies of Seedling Yellows Amelioration of Citrus tristeza virus Strain Mixtures to Elucidate Mechanisms of Cross Protection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Citrus tristeza virus (CTV) cross-protection involves a mild strain of CTV preventing or interfering with infection or symptom expression by a severe strain. It is used to protect citrus when virulent stem pitting strains of CTV and efficient aphid vectors are endemic. However, the mode of action ...

  15. Child Protective Services: A Bibliography with Partial Annotation and Cross-Indexing -- 1976.

    ERIC Educational Resources Information Center

    Naughton, M. James; And Others

    Contained in the bibliography are citations for 1500 publications concerned with child abuse and neglect of which 700 include abstracts. Titles are listed alphabetically by author under the following broad subjects or child protective service case types: generalized abuse/neglect, generalized abuse, generalized neglect, physical abuse, physical…

  16. Cross-cultural adaptation and validation of the Protective Nursing Advocacy Scale for Brazilian nurses 1

    PubMed Central

    Tomaschewski-Barlem, Jamila Geri; Lunardi, Valéria Lerch; Barlem, Edison Luiz Devos; da Silveira, Rosemary Silva; Dalmolin, Graziele de Lima; Ramos, Aline Marcelino

    2015-01-01

    Abstract Objective: to adapt culturally and validate the Protective Nursing Advocacy Scale for Brazilian nurses. Method: methodological study carried out with 153 nurses from two hospitals in the South region of Brazil, one public and the other philanthropic. The cross-cultural adaptation of the Protective Nursing Advocacy Scale was performed according to international standards, and its validation was carried out for use in the Brazilian context, by means of factor analysis and Cronbach's alpha as measure of internal consistency. Results: by means of evaluation by a committee of experts and application of pre-test, face validity and content validity of the instrument were considered satisfactory. From the factor analysis, five constructs were identified: negative implications of the advocacy practice, advocacy actions, facilitators of the advocacy practice, perceptions that favor practice advocacy and barriers to advocacy practice. The instrument showed satisfactory internal consistency, with Cronbach's alpha values ranging from 0.70 to 0.87. Conclusion: it was concluded that the Protective Nursing Advocacy Scale - Brazilian version, is a valid and reliable instrument for use in the evaluation of beliefs and actions of health advocacy, performed by Brazilian nurses in their professional practice environment. PMID:26444169

  17. Oral fluids as a live-animal sample for evaluating cross-reactivity and cross-protection following intranasal influenza A virus vaccination in pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In North American swine there are numerous antigenically distinct influenza A virus (IAV) H1 subtypes currently circulating, making vaccine development difficult due to the inability to formulate a vaccine that provides broad cross-protection. Live-attenuated influenza virus (LAIV) vaccines provide ...

  18. Tryptophan protects hepatocytes against reactive oxygen species-dependent cell death via multiple pathways including Nrf2-dependent gene induction.

    PubMed

    Kimura, Takuya; Watanabe, Yoshifumi

    2016-05-01

    Hepatocyte apoptosis plays a key role in the pathogenesis of immune-mediated hepatitis. However, the detailed mechanisms of apoptosis signaling are still unclear and effective therapeutic drugs for hepatitis have been explored. Here, we show that tryptophan (Trp) suppressed IFN-γ-mediated hepatic apoptosis in vitro. Trp inhibited the downstream apoptotic events of mitochondria disruption, such as cell death and caspase-3 activation, while it did not influence upstream signaling including STAT1 activation and IRF1 expression. Trp suppressed reactive oxygen species (ROS) generation at the mitochondria. IFN-γ induced ROS in mitochondria by inhibiting complex I and III, but not II. This ROS generation by IFN-γ required de novo protein synthesis. Trp showed relatively weak direct scavenging activity but antagonized IFN-γ against the suppression of complex I. In addition, Trp increased the expression of the Nrf2-dependent antioxidant genes NQO1, HO-1 and GCS in hepatocytes both in vitro and in vivo. Finally, the administration of Trp in an acetaminophen-induced ROS-dependent hepatitis model suppressed the liver injury in vivo. Thus, Trp protects hepatocytes from ROS-dependent cell injury via multiple pathways. This study suggests Trp as a therapeutic antioxidant drug for hepatitis and a regulator for Nrf2-dependent genes. PMID:26795536

  19. Charged-current inclusive neutrino cross sections in the superscaling model including quasielastic, pion production and meson-exchange contributions

    NASA Astrophysics Data System (ADS)

    Ivanov, M. V.; Megias, G. D.; González-Jiménez, R.; Moreno, O.; Barbaro, M. B.; Caballero, J. A.; Donnelly, T. W.

    2016-08-01

    Charged current inclusive neutrino-nucleus cross sections are evaluated using the superscaling model for quasielastic scattering and its extension to the pion production region. The contribution of two-particle-two-hole vector meson-exchange current excitations is also considered within a fully relativistic model tested against electron scattering data. The results are compared with the inclusive neutrino-nucleus data from the T2K and SciBooNE experiments. For experiments where < {E}ν > ∼ 0.8 {{GeV}}, the three mechanisms considered in this work provide good agreement with the data. However, when the neutrino energy is larger, effects from beyond the Δ also appear to be playing a role. The results show that processes induced by vector two-body currents play a minor role in the inclusive cross sections at the kinematics considered.

  20. Protein transduction domain can enhance the humoral immunity and cross-protection of HPV16L2 peptide vaccines

    PubMed Central

    LI, LILI; GUO, YANTAO; LI, ZELIN; ZHOU, YUBAI; ZENG, YI

    2016-01-01

    Due to type-specificity, commercially available human papillomavirus (HPV) vaccines are only effective against homologous HPV serotypes, providing limited protection. Recent studies have highlighted the role of HPV minor capsid protein (known as L2) in inducing cross-protection. The N-terminal peptides of L2 contain conserved cross-response epitopes that can induce neutralizing antibodies against heterogeneous HPVs. However, when compared with L1, these peptides have lower immunogenicity, which limits the application of these vaccines. The protein transduction domain (PTD), located in the Tat protein of human immunodeficiency virus, facilitates delivery of DNA, peptides, proteins and virus particles into cells by unknown mechanisms, and has been reported to enhance immunogenicity of several antigens. In the present study, two peptides derived from the N-terminal of HPV16L2 were chosen as model antigens and constructed a series of L2 peptide vaccines by either fusing or mixing with PTD. Subsequently their immunogenicity was evaluated. The results indicated that the L2 peptides fused with PTD show considerably enhanced humoral immunity. In particular, they increased the titer of cross-neutralizing antibodies, while L2 peptides that had only been mixed with PTD induced only small cross-protection responses. Overall, the data suggest that fusion of L2 peptides with PTD significantly enhances their cross-protection and may be a promising strategy for the development of broad-spectrum HPV prophylactic vaccines. PMID:27284417

  1. An influenza viral vector Brucella abortus vaccine induces good cross-protection against Brucella melitensis infection in pregnant heifers.

    PubMed

    Tabynov, Kaissar; Ryskeldinova, Sholpan; Sansyzbay, Abylai

    2015-07-17

    Brucella melitensis can be transmitted and cause disease in cattle herds as a result of inadequate management of mixed livestock farms. Ideally, vaccines against Brucella abortus for cattle should also provide cross-protection against B. melitensis. Previously we created a novel influenza viral vector B. abortus (Flu-BA) vaccine expressing the Brucella ribosomal proteins L7/L12 or Omp16. This study demonstrated Flu-BA vaccine with adjuvant Montanide Gel01 provided 100% protection against abortion in vaccinated pregnant heifers and good cross-protection of the heifers and their calves or fetuses (90-100%) after challenge with B. melitensis 16M; the level of protection provided by Flu-BA was comparable to the commercial vaccine B. abortus S19. In terms of the index of infection and colonization of Brucella in tissues, both vaccines demonstrated significant (P=0.02 to P<0.0001) protection against B. melitensis 16M infection compared to the negative control group (PBS+Montanide Gel01). Thus, we conclude the Flu-BA vaccine provides cross-protection against B. melitensis infection in pregnant heifers. PMID:26093199

  2. Long-Lasting Cross-Protection Against Influenza A by Neuraminidase and M2e-based immunization strategies

    PubMed Central

    Schotsaert, Michael; Ysenbaert, Tine; Smet, Anouk; Schepens, Bert; Vanderschaeghe, Dieter; Stegalkina, Svetlana; Vogel, Thorsten U.; Callewaert, Nico; Fiers, Walter; Saelens, Xavier

    2016-01-01

    There is mounting evidence that in the absence of neutralizing antibodies cross-reactive T cells provide protection against pandemic influenza viruses. Here, we compared protection and CD8+ T cell responses following challenge with H1N1 2009 pandemic and H3N2 viruses of mice that had been immunized with hemagglutinin (HA), neuraminidase (NA) and the extracellular domain of matrix protein 2 (M2e) fused to a virus-like particle (VLP). Mice were challenged a first time with a sublethal dose of H1N1 2009 pandemic virus and, four weeks later, challenged again with an H3N2 virus. Mice that had been vaccinated with HA, NA, NA + M2e-VLP and HA + NA + M2e-VLP were protected against homologous H1N1 virus challenge. Challenged NA and NA + M2e-VLP vaccinated mice mounted CD8+ T cell responses that correlated with protection against secondary H3N2 challenge. HA-vaccinated mice were fully protected against challenge with homologous H1N1 2009 virus, failed to mount cross-reactive CD8+ T cells and succumbed to the second challenge with heterologous H3N2 virus. In summary, NA- and M2e-based immunity can protect against challenge with (homologous) virus without compromising the induction of robust cross-reactive CD8+ T cell responses upon exposure to virus. PMID:27072615

  3. Development and efficacy of an attenuated Vibrio harveyi vaccine candidate with cross protectivity against Vibrio alginolyticus.

    PubMed

    Hu, Yong-hua; Deng, Tian; Sun, Bo-guang; Sun, Li

    2012-06-01

    Vibrio harveyi is a Gram-negative bacterial pathogen that can infect a wide range of marine animals. In previous studies, we have reported a virulent V. harveyi strain, T4D. In the present study, an attenuated mutant of T4D, T4DM, was obtained by selection of rifampicin resistance. Compared to the wild type, T4DM was different in whole-cell protein profile and much slower in growth rate when cultured in stress conditions caused by iron depletion. Virulence analysis showed that compared to T4D, T4DM exhibited a dramatically increased median lethal dose, impaired tissue dissemination capacity, defective hemolytic activity, and significantly reduced resistance against the killing effect of host serum. To examine the potential of T4DM as a live attenuated vaccine, Japanese flounder (Paralichthys olivaceus) were vaccinated with T4DM via intraperitoneal injection or immersion. The results showed that at one and two months post-vaccination, fish administered with T4DM via both approaches, in particular that of immersion, were effectively protected against not only V. harveyi but also Vibrio alginolyticus, another important fish pathogen. Microbiological analysis showed that following immersion vaccination, T4DM was recovered from the internal organs of the vaccinated fish in a time-dependent manner within the first 6 days post-vaccination. Serum antibodies against V. harveyi and V. alginolyticus were detected in T4DM-vaccinated fish, and, compared to serum from control fish, serum from T4DM-vaccinated fish was significantly enhanced in bactericidal activity. These results indicate that T4DM is an attenuated strain with residual infectivity and that T4DM can induce effective cross-species protection against both V. harveyi and V. alginolyticus when used as a live immersion vaccine. PMID:22484605

  4. Cross-protection elicited in channel catfish (Ictalurus punctatus Rafinesque) immunized with a low dose of virulent Edwardsiella ictaluri strains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cross-protection of fingerling channel catfish (Ictalurus punctatus Rafinesque) by immersion immunization and challenge exposure to six E. ictaluri strains (AL-93-58, AL-93-75, S-94-1051, NJ #3, EILO and ATCC-33202) originating from out breaks of disease in disparate geographic locations was examine...

  5. Molecular characterization of Cirus tristeza virus isolates associated with stem pitting CTV cross-protection in Peru

    Technology Transfer Automated Retrieval System (TEKTRAN)

    During the 1970s and early 1980s, the Peruvian citrus industry was destroyed by severe Citrus tristeza virus (CTV) strains spread by the brown citrus aphid. The Topara Nursery, located 180 km south of Lima Peru, selected and identified CTV isolates that confer cross-protection against virulent stem...

  6. Leishmania donovani Nucleoside Hydrolase Terminal Domains in Cross-Protective Immunotherapy Against Leishmania amazonensis Murine Infection

    PubMed Central

    Nico, Dirlei; Gomes, Daniele Crespo; Palatnik-de-Sousa, Iam; Morrot, Alexandre; Palatnik, Marcos; Palatnik-de-Sousa, Clarisa Beatriz

    2014-01-01

    Nucleoside hydrolases of the Leishmania genus are vital enzymes for the replication of the DNA and conserved phylogenetic markers of the parasites. Leishmania donovani nucleoside hydrolase (NH36) induced a main CD4+ T cell driven protective response against L. chagasi infection in mice which is directed against its C-terminal domain. In this study, we used the three recombinant domains of NH36: N-terminal domain (F1, amino acids 1–103), central domain (F2 aminoacids 104–198), and C-terminal domain (F3 amino acids 199–314) in combination with saponin and assayed their immunotherapeutic effect on Balb/c mice previously infected with L. amazonensis. We identified that the F1 and F3 peptides determined strong cross-immunotherapeutic effects, reducing the size of footpad lesions to 48 and 64%, and the parasite load in footpads to 82.6 and 81%, respectively. The F3 peptide induced the strongest anti-NH36 antibody response and intradermal response (IDR) against L. amazonenis and a high secretion of IFN-γ and TNF-α with reduced levels of IL-10. The F1 vaccine, induced similar increases of IgG2b antibodies and IFN-γ and TNF-α levels, but no IDR and no reduction of IL-10. The multiparameter flow cytometry analysis was used to assess the immune response after immunotherapy and disclosed that the degree of the immunotherapeutic effect is predicted by the frequencies of the CD4+ and CD8+ T cells producing IL-2 or TNF-α or both. Total frequencies and frequencies of double-cytokine CD4 T cell producers were enhanced by F1 and F3 vaccines. Collectively, our multifunctional analysis disclosed that immunotherapeutic protection improved as the CD4 responses progressed from 1+ to 2+, in the case of the F1 and F3 vaccines, and as the CD8 responses changed qualitatively from 1+ to 3+, mainly in the case of the F1 vaccine, providing new correlates of immunotherapeutic protection against cutaneous leishmaniasis in mice based on T-helper TH1 and CD8+ mediated immune responses

  7. 10 CFR 709.26 - Protection of confidentiality of CI evaluation records to include polygraph examination records...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... DEPARTMENT OF ENERGY COUNTERINTELLIGENCE EVALUATION PROGRAM Safeguarding Privacy and Employee Rights § 709.26... counterintelligence evaluation, in a system of records established under the Privacy Act of 1974 (5 U.S.C. 552a). (c) DOE must afford the full privacy protection provided by law to information regarding a covered...

  8. Immunization of N terminus of enterovirus 71 VP4 elicits cross-protective antibody responses

    PubMed Central

    2013-01-01

    Background Enterovirus 71 (EV71) is major cause of hand, foot and mouth disease. Large epidemics of EV71 infection have been recently reported in the Asian-Pacific region. Currently, no vaccine is available to prevent EV71 infection. Results The peptide (VP4N20) consisting of the first 20 amino acids at the N-terminal of VP4 of EV71 genotype C4 were fused to hepatitis B core (HBcAg) protein. Expression of fusion proteins in E. coli resulted in the formation of chimeric virus-like particles (VLPs). Mice immunized with the chimeric VLPs elicited anti-VP4N20 antibody response. In vitro microneutralization experiments showed that anti-chimeric VLPs sera were able to neutralize not only EV71 of genotype C4 but also EV71 of genotype A. Neonatal mice model confirmed the neutralizing ability of anti-chimeric VLPs sera. Eiptope mapping led to the identification of a “core sequence” responsible for antibody recognition within the peptide. Conclusions Immunization of chimeric VLPs is able to elicit antibodies displaying a broad neutralizing activity against different genotypes of EV71 in vitro. The “core sequence” of EV71-VP4 is highly conserved across EV71 genotypes. The chimeric VLPs have a great potential to be a novel vaccine candidate with a broad cross-protection against different EV71 genotypes. PMID:24320792

  9. Cross-scale feedbacks and scale mismatches as influences on cultural services and the resilience of protected areas.

    PubMed

    Maciejewski, Kristine; De Vos, Alta; Cumming, Graeme S; Moore, Christine; Biggs, Duan

    2015-01-01

    Protected areas are a central strategy for achieving global conservation goals, but their continued existence depends heavily on maintaining sufficient social and political support to outweigh economic interests or other motives for land conversion. Thus, the resilience of protected areas can be considered a function of their perceived benefits to society. Nature-based tourism (NBT), a cultural ecosystem service, provides a key source of income to protected areas, facilitating a sustainable solution to conservation. The ability of tourism to generate income depends, however, on both the scales at which this cultural service is provided and the scales at which tourists respond to services on offer. This observation raises a set of location-, context-, and scale-related questions that need to be confronted before we can understand and value cultural service provision appropriately. We combine elements of resilience analysis with a systems ecology framework and apply this to NBT in protected areas to investigate cross-scale interactions and scale mismatches. We postulate that cross-scale effects can either have a positive effect on protected area resilience or lead to scale mismatches, depending on their interactions with cross-scale feedbacks. To demonstrate this, we compare spatial scales and nested levels of institutions to develop a typology of scale mismatches for common scenarios in NBT. In our new typology, the severity of a scale mismatch is expressed as the ratio of spatial scale to institutional level, producing 25 possible outcomes with differing consequences for system resilience. We predict that greater differences between interacting scales and levels, and greater magnitudes of cross-scale interactions, will lead to greater magnitudes of scale mismatch. Achieving a better understanding of feedbacks and mismatches, and finding ways of aligning spatial and institutional scales, will be critical for strengthening the resilience of protected areas that

  10. Track and Field Guide including Cross Country, Pentathlon Scoring Tables and Rules for Intercollegiate Meets and Championships with Official Rules. Janauary 1974-January 1976.

    ERIC Educational Resources Information Center

    Thompson, Donnis H., Ed.

    This guide includes information on cross country running, pentathlon scoring tables, and rules for intercollegiate meets and championships, following an introductory portion on the organization's credo and standards. The first section covers track activities for children, coaching techniques, the benefits of weight training, and some practical…

  11. Cross-protective murine graft-versus-leukemia responses to phenotypically distinct myeloid leukemia lines.

    PubMed

    Patterson, A E; Korngold, R

    2000-01-01

    -restricted tumor antigens that can elicit a cross-protective in vivo T-cell GVL response. PMID:11071259

  12. Effects of vaccination against paratuberculosis on tuberculosis in goats: diagnostic interferences and cross-protection

    PubMed Central

    2012-01-01

    Background Most countries carrying out campaigns of bovine tuberculosis (TB) eradication impose a ban on the use of mycobacterial vaccines in cattle. However, vaccination against paratuberculosis (PTB) in goats is often allowed even when its effect on TB diagnosis has not been fully evaluated. To address this issue, goat kids previously vaccinated against PTB were experimentally infected with TB. Results Evaluation of interferon-γ (IFN-γ) secretion induced by avian and bovine tuberculins (PPD) showed a predominant avian PPD-biased response in the vaccinated group from week 4 post-vaccination onward. Although 60% of the animals were bovine reactors at week 14, avian PPD-biased responses returned at week 16. After challenge with M. caprae, the IFN-γ responses radically changed to show predominant bovine PPD-biased responses from week 18 onward. In addition, cross-reactions with bovine PPD that had been observed in the vaccinated group at week 14 were reduced when using the M. tuberculosis complex-specific antigens ESAT-6/CFP-10 and Rv3615c as new DIVA (differentiation of infected and vaccinated animals) reagents, which further maintained sensitivity post-challenge. Ninety percent of the animals reacted positively to the tuberculin cervical comparative intradermal test performed at 12 weeks post-infection. Furthermore, post-mortem analysis showed reductions in tuberculous lesions and bacterial burden in some vaccinated animals, particularly expressed in terms of the degree of extrapulmonary dissemination of TB infection. Conclusions Our results suggest a degree of interference of PTB vaccination with current TB diagnostics that can be fully mitigated when using new DIVA reagents. A partial protective effect associated with vaccination was also observed in some vaccinated animals. PMID:23072619

  13. Protecting group-free, selective cross-coupling of alkyltrifluoroborates with borylated aryl bromides via photoredox/nickel dual catalysis

    PubMed Central

    Yamashita, Yohei; Tellis, John C.; Molander, Gary A.

    2015-01-01

    Orthogonal reactivity modes offer substantial opportunities for rapid construction of complex small molecules. However, most strategies for imparting orthogonality to cross-coupling reactions rely on differential protection of reactive sites, greatly reducing both atom and step economies. Reported here is a strategy for orthogonal cross-coupling wherein a mechanistically distinct activation mode for transmetalation of sp3-hybridized organoboron reagents enables C-C bond formation in the presence of various protected and unprotected sp2-hybridized organoborons. This manifold has the potential for broad application, because orthogonality is inherent to the activation mode itself. The diversification potential of this platform is shown in the rapid elaboration of a trifunctional lynchpin through various transition metal-catalyzed processes without nonproductive deprotection or functional group manipulation steps. PMID:26371299

  14. Protecting group-free, selective cross-coupling of alkyltrifluoroborates with borylated aryl bromides via photoredox/nickel dual catalysis.

    PubMed

    Yamashita, Yohei; Tellis, John C; Molander, Gary A

    2015-09-29

    Orthogonal reactivity modes offer substantial opportunities for rapid construction of complex small molecules. However, most strategies for imparting orthogonality to cross-coupling reactions rely on differential protection of reactive sites, greatly reducing both atom and step economies. Reported here is a strategy for orthogonal cross-coupling wherein a mechanistically distinct activation mode for transmetalation of sp(3)-hybridized organoboron reagents enables C-C bond formation in the presence of various protected and unprotected sp(2)-hybridized organoborons. This manifold has the potential for broad application, because orthogonality is inherent to the activation mode itself. The diversification potential of this platform is shown in the rapid elaboration of a trifunctional lynchpin through various transition metal-catalyzed processes without nonproductive deprotection or functional group manipulation steps. PMID:26371299

  15. Cross-Reactivity, Epitope Spreading, and De Novo Immune Stimulation Are Possible Mechanisms of Cross-Protection of Nonvaccine Human Papillomavirus (HPV) Types in Recipients of HPV Therapeutic Vaccines

    PubMed Central

    Greenfield, William; Moerman-Herzog, Andrea; Coleman, Hannah N.

    2015-01-01

    Numerous versions of human papillomavirus (HPV) therapeutic vaccines designed to treat individuals with established HPV infection, including those with cervical intraepithelial neoplasia (CIN), are in development because approved prophylactic vaccines are not effective once HPV infection is established. As human papillomavirus 16 (HPV-16) is the most commonly detected type worldwide, all versions of HPV therapeutic vaccines contain HPV-16, and some also contain HPV-18. While these two HPV types are responsible for approximately 70% of cervical cancer cases, there are other high-risk HPV types known to cause malignancy. Therefore, it would be of interest to assess whether these HPV therapeutic vaccines may confer cross-protection against other high-risk HPV types. Data available from a few clinical trials that enrolled subjects with CINs regardless of the HPV type(s) present demonstrated clinical responses, as measured by CIN regression, in subjects with both vaccine-matched and nonvaccine HPV types. The currently available evidence demonstrating cross-reactivity, epitope spreading, and de novo immune stimulation as possible mechanisms of cross-protection conferred by investigational HPV therapeutic vaccines is discussed. PMID:25947147

  16. Biogenesis of influenza a virus hemagglutinin cross-protective stem epitopes.

    PubMed

    Magadán, Javier G; Altman, Meghan O; Ince, William L; Hickman, Heather D; Stevens, James; Chevalier, Aaron; Baker, David; Wilson, Patrick C; Ahmed, Rafi; Bennink, Jack R; Yewdell, Jonathan W

    2014-06-01

    Antigenic variation in the globular domain of influenza A virus (IAV) hemagglutinin (HA) precludes effective immunity to this major human pathogen. Although the HA stem is highly conserved between influenza virus strains, HA stem-reactive antibodies (StRAbs) were long considered biologically inert. It is now clear, however, that StRAbs reduce viral replication in animal models and protect against pathogenicity and death, supporting the potential of HA stem-based immunogens as drift-resistant vaccines. Optimally designing StRAb-inducing immunogens and understanding StRAb effector functions require thorough comprehension of HA stem structure and antigenicity. Here, we study the biogenesis of HA stem epitopes recognized in cells infected with various drifted IAV H1N1 strains using mouse and human StRAbs. Using a novel immunofluorescence (IF)-based assay, we find that human StRAbs bind monomeric HA in the endoplasmic reticulum (ER) and trimerized HA in the Golgi complex (GC) with similar high avidity, potentially good news for producing effective monomeric HA stem immunogens. Though HA stem epitopes are nestled among several N-linked oligosaccharides, glycosylation is not required for full antigenicity. Rather, as N-linked glycans increase in size during intracellular transport of HA through the GC, StRAb binding becomes temperature-sensitive, binding poorly to HA at 4°C and well at 37°C. A de novo designed, 65-residue protein binds the mature HA stem independently of temperature, consistent with a lack of N-linked oligosaccharide steric hindrance due to its small size. Likewise, StRAbs bind recombinant HA carrying simple N-linked glycans in a temperature-independent manner. Chemical cross-linking experiments show that N-linked oligosaccharides likely influence StRAb binding by direct local effects rather than by globally modifying the conformational flexibility of HA. Our findings indicate that StRAb binding to HA is precarious, raising the possibility that

  17. Fast and effective quantum-dots encapsulation and protection in PEO based photo-cross-linked micelles.

    PubMed

    Ferji, Khalid; Hamouda, Ines; Chassenieux, Christophe; Nadal, Brice; Dubertret, Benoit; Gaillard, Cedric; Nicol, Erwan

    2016-08-15

    Cadmium-based quantum dots (QDs) were easily, quickly and efficiently transferred from an organic medium to water without modification of their surface chemistry by the simple emulsion/solvent evaporation technique using micelles of amphiphilic diblock copolymers based on poly(ethylene oxide) and poly(2-methacryloyloxyethyl acrylate) (PEO-b-PMEA) as hosts. The resulting hybrid micelles were stabilized very rapidly by photo-cross-linking the hydrophobic core around the QDs. The encapsulation and photo-cross-linking process were shown to barely affect the photoluminescence properties. Grafting a short octyl chain at the end of the hydrophobic block enhanced both the colloidal stability of the QDs dispersed in water and prevented the quenching of their fluorescence by copper ions. Grafting a longer hexadecyl chain at the end of the PMEA block decreased the efficiency of the corona cross-linking and led to poorer stabilization and protection. PMID:27232538

  18. The Right to Be Included: Homeschoolers Combat the Structural Discrimination Embodied in Their Lawful Protection in the Czech Republic

    ERIC Educational Resources Information Center

    Kašparová, Irena

    2015-01-01

    There is a 240-year tradition of compulsory school attendance in the Czech Republic. To many, compulsory school attendance is synonymous with the right to be educated. After the collapse of communism in 1989, along with the democratization of the government, the education system was slowly opened to alternatives, including the right to educate…

  19. Identification of broadly conserved cross-species protective Leishmania antigen and its responding CD4+ T cells.

    PubMed

    Mou, Zhirong; Li, Jintao; Boussoffara, Thouraya; Kishi, Hiroyuki; Hamana, Hiroshi; Ezzati, Peyman; Hu, Chuanmin; Yi, Weijing; Liu, Dong; Khadem, Forough; Okwor, Ifeoma; Jia, Ping; Shitaoka, Kiyomi; Wang, Shufeng; Ndao, Momar; Petersen, Christine; Chen, Jianping; Rafati, Sima; Louzir, Hechmi; Muraguchi, Atsushi; Wilkins, John A; Uzonna, Jude E

    2015-10-21

    There is currently no clinically effective vaccine against leishmaniasis because of poor understanding of the antigens that elicit dominant T cell immunity. Using proteomics and cellular immunology, we identified a dominant naturally processed peptide (PEPCK335-351) derived from Leishmania glycosomal phosphoenolpyruvate carboxykinase (PEPCK). PEPCK was conserved in all pathogenic Leishmania, expressed in glycosomes of promastigotes and amastigotes, and elicited strong CD4(+) T cell responses in infected mice and humans. I-A(b)-PEPCK335-351 tetramer identified protective Leishmania-specific CD4(+) T cells at a clonal level, which comprised ~20% of all Leishmania-reactive CD4(+) T cells at the peak of infection. PEPCK335-351-specific CD4(+) T cells were oligoclonal in their T cell receptor usage, produced polyfunctional cytokines (interleukin-2, interferon-γ, and tumor necrosis factor), and underwent expansion, effector activities, contraction, and stable maintenance after lesion resolution. Vaccination with PEPCK peptide, DNA expressing full-length PEPCK, or rPEPCK induced strong durable cross-species protection in both resistant and susceptible mice. The effectiveness and durability of protection in vaccinated mice support the development of a broadly cross-species protective vaccine against different forms of leishmaniasis by targeting PEPCK. PMID:26491077

  20. mTOR modulates the antibody response to provide cross-protective immunity to lethal influenza infections

    PubMed Central

    Keating, Rachael; Hertz, Tomer; Wehenkel, Marie; Harris, Tarsha L.; Edwards, Benjamin A.; McClaren, Jennifer L.; Brown, Scott A.; Surman, Sherri; Wilson, Zachary S.; Bradley, Philip; Hurwitz, Julia; Chi, Hongbo; Doherty, Peter C.; Thomas, Paul G.; McGargill, Maureen A.

    2013-01-01

    Highly pathogenic avian influenza viruses pose a continuing global threat. Current vaccines will not protect against novel pandemic viruses. Creating “universal” vaccines has been unsuccessful because the immunological mechanisms promoting heterosubtypic immunity are incompletely defined. We show that rapamycin, an immunosuppressive drug that inhibits mTOR, promotes cross-strain protection against lethal H5N1 and H7N9 infections when administered during H3N2 virus immunization. Rapamycin reduced germinal center formation and inhibited B cell class-switching, yielding a unique repertoire of antibodies that mediated heterosubtypic protection. Our data establish a requirement for mTORC1 in B cell class-switching and demonstrate that rapamycin skews the antibody response away from high affinity variant epitopes, targeting more conserved elements of hemagglutinin. These findings have intriguing implications for influenza vaccine design. PMID:24141387

  1. Characterization of highly informative cross-species microsatellite panels for the Australian dugong (Dugong dugon) and Florida manatee (Trichechus manatus latirostris) including five novel primers.

    PubMed

    Hunter, Margaret Kellogg; Broderick, Damien; Ovenden, Jennifer R; Tucker, Kimberly Pause; Bonde, Robert K; McGuire, Peter M; Lanyon, Janet M

    2010-03-01

    The Australian dugong (Dugong dugon) and Florida manatee (Trichechus manatus latirostris) are threatened species of aquatic mammals in the order Sirenia. Sirenian conservation and management actions would benefit from a more complete understanding of genetic diversity and population structure. Generally, species-specific microsatellite markers are employed in conservation genetic studies; however, robust markers can be difficult and costly to isolate. To increase the number of available markers, dugong and manatee microsatellite primers were evaluated for cross-species amplification. Furthermore, one manatee and four dugong novel primers are reported. After polymerase chain reaction optimization, 23 (92%) manatee primers successfully amplified dugong DNA, of which 11 (48%) were polymorphic. Of the 32 dugong primers tested, 27 (84%) yielded product in the manatee, of which 17 (63%) were polymorphic. Dugong and manatee primers were compared and the most informative markers were selected to create robust and informative marker-panels for each species. These cross-species microsatellite marker-panels can be employed to assess other sirenian populations and can provide beneficial information for the protection and management of these unique mammals. PMID:21565032

  2. Pheromone dispensers, including organic polymer fibers, described in the crop protection literature: comparison of their innovation potential.

    PubMed

    Hummel, Hans E; Langner, S S; Eisinger, M-T

    2013-01-01

    parameters, they hold considerable promise for future pest control against a variety of pest insects. In combination with well known synthetic sex pheromones, they can be used for communication disruption studies. One example, the pheromone of the European grape vine moth Lobesia botrana (Lepidoptera: Tortricidae), in combination with Ecoflex fibers, has been thoroughly tested in vineyards of Freiburg, Southwest Germany, with promising results. Seven weeks of communication disruption have been achieved, long enough to cover any one of several flights of this multivoltine grape pest. Disruption effects of around 95% have been achieved which are statistically indistinguishable from positive controls tested simultaneously with Isonet LE fibers, while an untreated negative control is significantly different. Ecoflex is a cheap organic co-polyester and completely biodegradable within half a year. Thus, an extra recovery step as with some other dispensers is unnecessary. This co-polyester is also of proven non-toxicity. The extension of the seven week disruption period towards half a year (the entire duration of all 3 Lobesia flights combined) is desirable and is under additional investigation in the near future. The discovery of suitable mesofibers is protected by European and US patents. The pheromone literature appearing between 1959 and today contains more than 25,000 references. This wealth of information is immediately applicable to pest management. It has major impacts on chemical ecology and IPM. In this paper, an attempt is made to compare the systems described in the literature and to derive some predictions about their prospective innovation potential. Special emphasis is given to the new development of organic biodegradable microfibers. To this end, a new electronic searching algorithm is introduced for reviewing the entries to be found in 4 specific databases. Its prominent features will be described. Surprisingly we found no previous entries in the literature linking

  3. Conservation of the critically endangered eastern Australian population of the grey nurse shark (Carcharias taurus) through cross-jurisdictional management of a network of marine-protected areas.

    PubMed

    Lynch, Tim P; Harcourt, Robert; Edgar, Graham; Barrett, Neville

    2013-12-01

    Between 2001 and 2009, 26 marine-protected areas (MPA) were established on the east Australian seaboard, at least in part, to manage human interactions with a critically endangered population of grey nurse shark, Carcharias taurus. This network is spread across six MPA systems and includes all 19 sites outlined in the National Recovery Plan for C. taurus, though five sites remain open to some forms of fishing. The reserve network has complex cross-jurisdictional management, as the sharks occur in waters controlled by the Australian states of New South Wales (NSW) and Queensland, as well as by the Commonwealth (Federal) government. Jurisdiction is further complicated by fisheries and conservation departments both engaging in management activities within each state. This has resulted in protected area types that include IUCN category II equivalent zones in NSW, Queensland, and Commonwealth marine parks that either overlay or complement another large scaled network of protected sites called critical habitats. Across the network, seven and eight rule permutations for diving and fishing, respectively, are applied to this population of sharks. Besides sites identified by the recovery plan, additional sites have been protected as part of the general development of MPA networks. A case study at one of these sites, which historically was known to be occupied by C. taurus but had been abandoned, appears to shows re-establishment of an aggregation of juvenile and sub-adult sharks. Concurrent with the re-establishment of the aggregation, a local dive operator increased seasonal dive visitation rates at the site fourfold. As a precautionary measure, protection of abandoned sites, which includes nursery and gestating female habitats are options that may assist recovery of the east coast population of C. taurus. PMID:24213854

  4. Conservation of the Critically Endangered Eastern Australian Population of the Grey Nurse Shark ( Carcharias taurus) Through Cross-Jurisdictional Management of a Network of Marine-Protected Areas

    NASA Astrophysics Data System (ADS)

    Lynch, Tim P.; Harcourt, Robert; Edgar, Graham; Barrett, Neville

    2013-12-01

    Between 2001 and 2009, 26 marine-protected areas (MPA) were established on the east Australian seaboard, at least in part, to manage human interactions with a critically endangered population of grey nurse shark, Carcharias taurus. This network is spread across six MPA systems and includes all 19 sites outlined in the National Recovery Plan for C. taurus, though five sites remain open to some forms of fishing. The reserve network has complex cross-jurisdictional management, as the sharks occur in waters controlled by the Australian states of New South Wales (NSW) and Queensland, as well as by the Commonwealth (Federal) government. Jurisdiction is further complicated by fisheries and conservation departments both engaging in management activities within each state. This has resulted in protected area types that include IUCN category II equivalent zones in NSW, Queensland, and Commonwealth marine parks that either overlay or complement another large scaled network of protected sites called critical habitats. Across the network, seven and eight rule permutations for diving and fishing, respectively, are applied to this population of sharks. Besides sites identified by the recovery plan, additional sites have been protected as part of the general development of MPA networks. A case study at one of these sites, which historically was known to be occupied by C. taurus but had been abandoned, appears to shows re-establishment of an aggregation of juvenile and sub-adult sharks. Concurrent with the re-establishment of the aggregation, a local dive operator increased seasonal dive visitation rates at the site fourfold. As a precautionary measure, protection of abandoned sites, which includes nursery and gestating female habitats are options that may assist recovery of the east coast population of C. taurus.

  5. Chimeric porcine reproductive and respiratory syndrome virus containing shuffled multiple envelope genes confers cross-protection in pigs.

    PubMed

    Tian, Debin; Ni, Yan-Yan; Zhou, Lei; Opriessnig, Tanja; Cao, Dianjun; Piñeyro, Pablo; Yugo, Danielle M; Overend, Christopher; Cao, Qian; Lynn Heffron, C; Halbur, Patrick G; Pearce, Douglas S; Calvert, Jay G; Meng, Xiang-Jin

    2015-11-01

    The extensive genetic diversity of porcine reproductive and respiratory syndrome virus (PRRSV) strains is a major obstacle for vaccine development. We previously demonstrated that chimeric PRRSVs in which a single envelope gene (ORF3, ORF4, ORF5 or ORF6) was shuffled via DNA shuffling had an improved heterologous cross-neutralizing ability. In this study, we incorporate all of the individually-shuffled envelope genes together in different combinations into an infectious clone backbone of PRRSV MLV Fostera(®) PRRS. Five viable progeny chimeric viruses were rescued, and their growth characteristics were characterized in vitro. In a pilot pig study, two chimeric viruses (FV-SPDS-VR2,FV-SPDS-VR5) were found to induce cross-neutralizing antibodies against heterologous strains. A subsequent vaccination/challenge study in 72 pigs revealed that chimeric virus FV-SPDS-VR2 and parental virus conferred partial cross-protection when challenged with heterologous strains NADC20 or MN184B. The results have important implications for future development of an effective PRRSV vaccine that confers heterologous protection. PMID:26342466

  6. Refugee claimant's identity as cross-dresser must be considered in assessing adequacy of state protection.

    PubMed

    2008-07-01

    On 11 December 2007, the Federal Court allowed Jose Hernandez's application for judicial review of a November 2006 decision by the Refugee Protection Division of the Immigration and Refugee Board, which found that the applicant was neither a Convention refugee nor a person in need of protection. Hernandez had requested that the Board's decision be set aside and the matter referred back to a newly constituted panel of the Board for re-determination. PMID:18727196

  7. Mechanism of cross-sectoral coordination between nature protection and forestry in the Natura 2000 formulation process in Slovakia.

    PubMed

    Sarvašová, Zuzana; Sálka, Jaroslav; Dobšinská, Zuzana

    2013-09-01

    Nature protection as a policy sector is not isolated and is directly or indirectly influenced by many other sectors (e.g. forestry, water management, rural development, energy, etc.). These policy sectors are neither completely segmented nor unaffected by the decisions taken in other policy sectors. Policy formulation in nature protection is therefore also influenced by different sectors. For that reason it is inevitable to stress the need for inter-sectoral coordination to assure their policy coherence. The aim of this article is to describe the mechanism and modes of cross-sectoral coordination and to analyze the relevant actors and their interaction, using the case of the Natura 2000 formulation process in Slovakia. The European Union (EU) set up an ecological network of special protected areas, known as Natura 2000 to ensure biodiversity by conserving natural habitats and wild fauna and flora in the territory of the Member States. An optimized nature protection must therefore carefully consider existing limits and crossdisciplinary relationships at the EU, national and regional levels. The relations between forestry and biodiversity protection are analyzed using the advocacy coalition framework (ACF). The ACF is used for analyzing how two coalitions, in this case ecological and forest owners' coalitions, advocate or pursue their beliefs from the nature protection and forestry policy field. The whole process is illustrated at the regional scale on the case study of Natura 2000 sites formulation in the Slovak Republic. For better reliability and validity of research, a combination of various empiric research methods was used, supported by existing theories. So called triangulation of sociological research or triangulation of methods consists of mutual results testing of individual methodological steps through identifying corresponding political-science theories, assessing their formal points using primary and secondary document analysis and assessing their

  8. Vectors Based on Modified Vaccinia Ankara Expressing Influenza H5N1 Hemagglutinin Induce Substantial Cross-Clade Protective Immunity

    PubMed Central

    Hessel, Annett; Schwendinger, Michael; Holzer, Georg W.; Orlinger, Klaus K.; Coulibaly, Sogue; Savidis-Dacho, Helga; Zips, Marie-Luise; Crowe, Brian A.; Kreil, Thomas R.; Ehrlich, Hartmut J.; Barrett, P. Noel; Falkner, Falko G.

    2011-01-01

    Background New highly pathogenic H5N1 influenza viruses are continuing to evolve with a potential threat for an influenza pandemic. So far, the H5N1 influenza viruses have not widely circulated in humans and therefore constitute a high risk for the non immune population. The aim of this study was to evaluate the cross-protective potential of the hemagglutinins of five H5N1 strains of divergent clades using a live attenuated modified vaccinia Ankara (MVA) vector vaccine. Methodology/Principal Findings The replication-deficient MVA virus was used to express influenza hemagglutinin (HA) proteins. Specifically, recombinant MVA viruses expressing the HA genes of the clade 1 virus A/Vietnam/1203/2004 (VN/1203), the clade 2.1.3 virus A/Indonesia/5/2005 (IN5/05), the clade 2.2 viruses A/turkey/Turkey/1/2005 (TT01/05) and A/chicken/Egypt/3/2006 (CE/06), and the clade 2.3.4 virus A/Anhui/1/2005 (AH1/05) were constructed. These experimental live vaccines were assessed in a lethal mouse model. Mice vaccinated with the VN/1203 hemagglutinin-expressing MVA induced excellent protection against all the above mentioned clades. Also mice vaccinated with the IN5/05 HA expressing MVA induced substantial protection against homologous and heterologous AH1/05 challenge. After vaccination with the CE/06 HA expressing MVA, mice were fully protected against clade 2.2 challenge and partially protected against challenge of other clades. Mice vaccinated with AH1/05 HA expressing MVA vectors were only partially protected against homologous and heterologous challenge. The live vaccines induced substantial amounts of neutralizing antibodies, mainly directed against the homologous challenge virus, and high levels of HA-specific IFN-γ secreting CD4 and CD8 T-cells against epitopes conserved among the H5 clades and subclades. Conclusions/Significance The highest level of cross-protection was induced by the HA derived from the VN/1203 strain, suggesting that pandemic H5 vaccines utilizing MVA vector

  9. Immune mechanisms associated with enhanced influenza A virus disease versus cross-protection in vaccinated pigs.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vaccine associated enhanced respiratory disease (VAERD) has been described in pigs vaccinated with whole-inactivated influenza virus (WIV) following infection with heterologous influenza A virus (IAV). WIV vaccination elicits production of cross-reactive, non-neutralizing antibody to the challenge I...

  10. Preclinical Evaluation of the Pht Proteins as Potential Cross-Protective Pneumococcal Vaccine Antigens▿

    PubMed Central

    Godfroid, Fabrice; Hermand, Philippe; Verlant, Vincent; Denoël, Philippe; Poolman, Jan T.

    2011-01-01

    Current pneumococcal vaccines are composed of capsular polysaccharides (PS) of various serotypes, either as free PS or as protein-PS conjugates. The use of pneumococcus protein antigens that are able to afford protection across the majority of serotypes is envisaged as a relevant alternative and/or complement to the polysaccharides. In this context, based on several studies, the Pht protein family emerged as relevant vaccine candidates. The purpose of the present study was to evaluate the Pht protein family in several preclinical mouse models. Immunization with these antigens was compared with immunization with other pneumococcal antigens, such as CbpA, PspA, and PsaA. In a nasopharyngeal colonization model and in a lung colonization model, the Phts were found to be superior to the other candidates in terms of efficacy of protection and serotype coverage. Likewise, vaccination with PhtD allowed higher animal survival rates after lethal intranasal challenge. Finally, a passive transfer model in which natural anti-PhtD human antibodies were transferred into mice demonstrated significant protection against lethal intranasal challenge. This indicates that natural anti-PhtD human antibodies are able to protect against pneumococcal infection. Our findings, together with the serotype-independent occurrence of the Phts, designate this protein family as valid candidate antigens to be incorporated in protein-based pneumococcal vaccines. PMID:20956575

  11. Characterization of highly informative cross-species microsatellite panels for the Australian dugong (Dugong dugon) and Florida manatee (Trichechus manatus latirostris) including five novel primers

    USGS Publications Warehouse

    Hunter, Margaret Kellogg; Broderick, Damien; Ovenden, Jennifer R.; Tucker, Kimberly Pause; Bonde, Robert K.; McGuire, Peter M.; Lanyon, Janet M.

    2010-01-01

    The Australian dugong (Dugong dugon) and Florida manatee (Trichechus manatus latirostris) are threatened species of aquatic mammals in the order Sirenia. Sirenian conservation and management actions would benefit from a more complete understanding of genetic diversity and population structure. Generally, species-specific microsatellite markers are employed in conservation genetic studies; however, robust markers can be difficult and costly to isolate. To increase the number of available markers, dugong and manatee microsatellite primers were evaluated for cross-species amplification. Furthermore, one manatee and four dugong novel primers are reported. After polymerase chain reaction optimization, 23 (92%) manatee primers successfully amplified dugong DNA, of which 11 (48%) were polymorphic. Of the 32 dugong primers tested, 27 (84%) yielded product in the manatee, of which 17 (63%) were polymorphic. Dugong and manatee primers were compared and the most informative markers were selected to create robust and informative marker-panels for each species. These crossspecies microsatellite marker-panels can be employed to assess other sirenian populations and can provide beneficial information for the protection and management of these unique mammals.

  12. Yersinia pestis Caf1 Protein: Effect of Sequence Polymorphism on Intrinsic Disorder Propensity, Serological Cross-Reactivity and Cross-Protectivity of Isoforms.

    PubMed

    Kopylov, Pavel Kh; Platonov, Mikhail E; Ablamunits, Vitaly G; Kombarova, Tat'yana I; Ivanov, Sergey A; Kadnikova, Lidiya A; Somov, Aleksey N; Dentovskaya, Svetlana V; Uversky, Vladimir N; Anisimov, Andrey P

    2016-01-01

    Yersinia pestis Caf1 is a multifunctional protein responsible for antiphagocytic activity and is a key protective antigen. It is generally conserved between globally distributed Y. pestis strains, but Y. pestis subsp. microtus biovar caucasica strains circulating within populations of common voles in Georgia and Armenia were reported to carry a single substitution of alanine to serine. We investigated polymorphism of the Caf1 sequences among other Y. pestis subsp. microtus strains, which have a limited virulence in guinea pigs and in humans. Sequencing of caf1 genes from 119 Y. pestis strains belonging to different biovars within subsp. microtus showed that the Caf1 proteins exist in three isoforms, the global type Caf1NT1 (Ala48 Phe117), type Caf1NT2 (Ser48 Phe117) found in Transcaucasian-highland and Pre-Araks natural plague foci #4-7, and a novel Caf1NT3 type (Ala48 Val117) endemic in Dagestan-highland natural plague focus #39. Both minor types are the progenies of the global isoform. In this report, Caf1 polymorphism was analyzed by comparing predicted intrinsic disorder propensities and potential protein-protein interactivities of the three Caf1 isoforms. The analysis revealed that these properties of Caf1 protein are minimally affected by its polymorphism. All protein isoforms could be equally detected by an immunochromatography test for plague at the lowest protein concentration tested (1.0 ng/mL), which is the detection limit. When compared to the classic Caf1NT1 isoform, the endemic Caf1NT2 or Caf1NT3 had lower immunoreactivity in ELISA and lower indices of self- and cross-protection. Despite a visible reduction in cross-protection between all Caf1 isoforms, our data suggest that polymorphism in the caf1 gene may not allow the carriers of Caf1NT2 or Caf1NT3 variants escaping from the Caf1NT1-mediated immunity to plague in the case of a low-dose flea-borne infection. PMID:27606595

  13. Intranasal Immunization with Nontypeable Haemophilus influenzae Outer Membrane Vesicles Induces Cross-Protective Immunity in Mice

    PubMed Central

    Roier, Sandro; Leitner, Deborah R.; Iwashkiw, Jeremy; Schild-Prüfert, Kristina; Feldman, Mario F.; Krohne, Georg; Reidl, Joachim; Schild, Stefan

    2012-01-01

    Abstract Haemophilus influenzae is a Gram-negative human-restricted bacterium that can act as a commensal and a pathogen of the respiratory tract. Especially nontypeable H. influenzae (NTHi) is a major threat to public health and is responsible for several infectious diseases in humans, such as pneumonia, sinusitis, and otitis media. Additionally, NTHi strains are highly associated with exacerbations in patients suffering from chronic obstructive pulmonary disease. Currently, there is no licensed vaccine against NTHi commercially available. Thus, this study investigated the utilization of outer membrane vesicles (OMVs) as a potential vaccine candidate against NTHi infections. We analyzed the immunogenic and protective properties of OMVs derived from various NTHi strains by means of nasopharyngeal immunization and colonization studies with BALB/c mice. The results presented herein demonstrate that an intranasal immunization with NTHi OMVs results in a robust and complex humoral and mucosal immune response. Immunoprecipitation revealed the most important immunogenic proteins, such as the heme utilization protein, protective surface antigen D15, heme binding protein A, and the outer membrane proteins P1, P2, P5 and P6. The induced immune response conferred not only protection against colonization with a homologous NTHi strain, which served as an OMV donor for the immunization mixtures, but also against a heterologous NTHi strain, whose OMVs were not part of the immunization mixtures. These findings indicate that OMVs derived from NTHi strains have a high potential to act as a vaccine against NTHi infections. PMID:22880074

  14. Vaccination with Adjuvanted Recombinant Neuraminidase Induces Broad Heterologous, but Not Heterosubtypic, Cross-Protection against Influenza Virus Infection in Mice

    PubMed Central

    Wohlbold, Teddy John; Nachbagauer, Raffael; Xu, Haoming; Tan, Gene S.; Hirsh, Ariana; Brokstad, Karl A.; Cox, Rebecca J.; Palese, Peter

    2015-01-01

    ABSTRACT In an attempt to assess the cross-protective potential of the influenza virus neuraminidase (NA) as a vaccine antigen, different subtypes of recombinant NA were expressed in a baculovirus system and used to vaccinate mice prior to lethal challenge with homologous, heterologous, or heterosubtypic viruses. Mice immunized with NA of subtype N2 were completely protected from morbidity and mortality in a homologous challenge and displayed significantly reduced viral lung titers. Heterologous challenge with a drifted strain resulted in morbidity but no mortality. Similar results were obtained for challenge experiments with N1 NA. Mice immunized with influenza B virus NA (from B/Yamagata/16/88) displayed no morbidity when sublethally infected with the homologous strain and, importantly, were completely protected from morbidity and mortality when lethally challenged with the prototype Victoria lineage strain or a more recent Victoria lineage isolate. Upon analyzing the NA content in 4 different inactivated-virus vaccine formulations from the 2013-2014 season via Western blot assay and enzyme-linked immunosorbent assay quantification, we found that the amount of NA does indeed vary across vaccine brands. We also measured hemagglutinin (HA) and NA endpoint titers in pre- and postvaccination human serum samples from individuals who received a trivalent inactivated seasonal influenza vaccine from the 2004-2005 season; the induction of NA titers was statistically less pronounced than the induction of HA titers. The demonstrated homologous and heterologous protective capacity of recombinant NA suggests that supplementing vaccine formulations with a standard amount of NA may offer increased protection against influenza virus infection. PMID:25759506

  15. Lung-protective Ventilation in Patients with Brain Injury: A Multicenter Cross-sectional Study and Questionnaire Survey in China

    PubMed Central

    Luo, Xu-Ying; Hu, Ying-Hong; Cao, Xiang-Yuan; Kang, Yan; Liu, Li-Ping; Wang, Shou-Hong; Yu, Rong-Guo; Yu, Xiang-You; Zhang, Xia; Li, Bao-Shan; Ma, Zeng-Xiang; Weng, Yi-Bing; Zhang, Heng; Chen, De-Chang; Chen, Wei; Chen, Wen-Jin; Chen, Xiu-Mei; Du, Bin; Duan, Mei-Li; Hu, Jin; Huang, Yun-Feng; Jia, Gui-Jun; Li, Li-Hong; Liang, Yu-Min; Qin, Bing-Yu; Wang, Xian-Dong; Xiong, Jian; Yan, Li-Mei; Yang, Zheng-Ping; Dong, Chen-Ming; Wang, Dong-Xin; Zhan, Qing-Yuan; Fu, Shuang-Lin; Zhao, Lin; Huang, Qi-Bing; Xie, Ying-Guang; Huang, Xiao-Bo; Zhang, Guo-Bin; Xu, Wang-Bin; Xu, Yuan; Liu, Ya-Ling; Zhao, He-Ling; Sun, Rong-Qing; Sun, Ming; Cheng, Qing-Hong; Qu, Xin; Yang, Xiao-Feng; Xu, Ming; Shi, Zhong-Hua; Chen, Han; He, Xuan; Yang, Yan-Lin; Chen, Guang-Qiang; Sun, Xiu-Mei; Zhou, Jian-Xin

    2016-01-01

    Background: Over the years, the mechanical ventilation (MV) strategy has changed worldwide. The aim of the present study was to describe the ventilation practices, particularly lung-protective ventilation (LPV), among brain-injured patients in China. Methods: This study was a multicenter, 1-day, cross-sectional study in 47 Intensive Care Units (ICUs) across China. Mechanically ventilated patients (18 years and older) with brain injury in a participating ICU during the time of the study, including traumatic brain injury, stroke, postoperation with intracranial tumor, hypoxic-ischemic encephalopathy, intracranial infection, and idiopathic epilepsy, were enrolled. Demographic data, primary diagnoses, indications for MV, MV modes and settings, and prognoses on the 60th day were collected. Multivariable logistic analysis was used to assess factors that might affect the use of LPV. Results: A total of 104 patients were enrolled in the present study, 87 (83.7%) of whom were identified with severe brain injury based on a Glasgow Coma Scale ≤8 points. Synchronized intermittent mandatory ventilation (SIMV) was the most frequent ventilator mode, accounting for 46.2% of the entire cohort. The median tidal volume was set to 8.0 ml/kg (interquartile range [IQR], 7.0–8.9 ml/kg) of the predicted body weight; 50 (48.1%) patients received LPV. The median positive end-expiratory pressure (PEEP) was set to 5 cmH2O (IQR, 5–6 cmH2O). No PEEP values were higher than 10 cmH2O. Compared with partially mandatory ventilation, supportive and spontaneous ventilation practices were associated with LPV. There were no significant differences in mortality and MV duration between patients subjected to LPV and those were not. Conclusions: Among brain-injured patients in China, SIMV was the most frequent ventilation mode. Nearly one-half of the brain-injured patients received LPV. Patients under supportive and spontaneous ventilation were more likely to receive LPV. Trial Registration: Clinical

  16. Cross-protection of Lactococcus lactis-displayed HA2 subunit against homologous and heterologous influenza A viruses in mice.

    PubMed

    Lei, Han; Peng, Xiaojue; Zhao, Daxian; Jiao, Huifeng; Ouyang, Jiexiu

    2015-12-01

    Current influenza vaccines provide strain-specific protection against homologous subtypes and need to be updated annually. Therefore, it is essential to develop a universal vaccine that would induce broadly cross-protective immunity against homologous and heterologous influenza A viruses. The highly conserved HA2 subunit is a promising candidate for developing a universal influenza vaccine. Here, we hypothesized that the HA2 subunit could be displayed on the surface of Lactococcus lactis (L. lactis), using Spax as an anchor protein (L. lactis/pNZ8008-Spax-HA2) and that L. lactis/pNZ8008-Spax-HA2 would have immunogenicity by oral administration without the use of adjuvant in the mouse model. To address this hypothesis, we show that oral vaccination of mice with L. lactis/pNZ8008-Spax-HA2 elicited significant humoral and mucosal immune responses. Importantly, L. lactis/pNZ8008-Spax-HA2 provided 100% protection against homologous H5N1 or heterologous H1N1 virus challenge. These results suggest that an HA2 subunit presented on the surface of L. lactis is an effective universal vaccine candidate against influenza A viruses in the poultry industry and in humans. PMID:26358264

  17. Cross Protection against Influenza A Virus by Yeast-Expressed Heterologous Tandem Repeat M2 Extracellular Proteins.

    PubMed

    Lee, Yu-Na; Kim, Min-Chul; Lee, Young-Tae; Hwang, Hye Suk; Lee, Jongsang; Kim, Cheol; Kang, Sang-Moo

    2015-01-01

    The influenza M2 ectodomain (M2e) is well conserved across human influenza A subtypes, but there are few residue changes among avian and swine origin influenza A viruses. We expressed a tandem repeat construct of heterologous M2e sequences (M2e5x) derived from human, swine, and avian origin influenza A viruses using the yeast expression system. Intramuscular immunization of mice with AS04-adjuvanted M2e5x protein vaccines was effective in inducing M2e-specific antibodies reactive to M2e peptide and native M2 proteins on the infected cells with human, swine, or avian influenza virus, mucosal and systemic memory cellular immune responses, and cross-protection against H3N2 virus. Importantly, M2e5x immune sera were found to confer protection against different subtypes of H1N1 and H5N1 influenza A viruses in naïve mice. Also, M2e5x-immune complexes of virus-infected cells stimulated macrophages to secrete cytokines via Fc receptors, indicating a possible mechanism of protection. The present study provides evidence that M2e5x proteins produced in yeast cells could be developed as a potential universal influenza vaccine. PMID:26366729

  18. Cross Protection against Influenza A Virus by Yeast-Expressed Heterologous Tandem Repeat M2 Extracellular Proteins

    PubMed Central

    Lee, Yu-Na; Kim, Min-Chul; Lee, Young-Tae; Hwang, Hye Suk; Lee, Jongsang; Kim, Cheol; Kang, Sang-Moo

    2015-01-01

    The influenza M2 ectodomain (M2e) is well conserved across human influenza A subtypes, but there are few residue changes among avian and swine origin influenza A viruses. We expressed a tandem repeat construct of heterologous M2e sequences (M2e5x) derived from human, swine, and avian origin influenza A viruses using the yeast expression system. Intramuscular immunization of mice with AS04-adjuvanted M2e5x protein vaccines was effective in inducing M2e-specific antibodies reactive to M2e peptide and native M2 proteins on the infected cells with human, swine, or avian influenza virus, mucosal and systemic memory cellular immune responses, and cross-protection against H3N2 virus. Importantly, M2e5x immune sera were found to confer protection against different subtypes of H1N1 and H5N1 influenza A viruses in naïve mice. Also, M2e5x-immune complexes of virus-infected cells stimulated macrophages to secrete cytokines via Fc receptors, indicating a possible mechanism of protection. The present study provides evidence that M2e5x proteins produced in yeast cells could be developed as a potential universal influenza vaccine. PMID:26366729

  19. A Kinetic Modeling study on the Oxidation of Primary Reference Fuel?Toluene Mixtures Including Cross Reactions between Aromatics and Aliphatics

    SciTech Connect

    Sakai, Y; Miyoshi, A; Koshi, M; Pitz, W J

    2008-01-09

    A detailed chemical kinetic model for the mixtures of Primary Reference Fuel (PRF: n-heptane and iso-octane) and toluene has been proposed. This model is divided into three parts; a PRF mechanism [T. Ogura et al., Energy & Fuels 21 (2007) 3233-3239], toluene sub-mechanism and cross reactions between PRF and toluene. Toluene sub-mechanism includes the low temperature kinetics relevant to engine conditions. A chemical kinetic mechanism proposed by Pitz et al. [Proc. the 2nd Joint Meeting of the U.S. Combust. Institute (2001)] was used as a starting model and modified by updating rate coefficients. Theoretical estimations of rate coefficients were performed for toluene and benzyl radical reactions important at low temperatures. Cross-reactions between alkane, alkene, and aromatics were also included in order to account for the acceleration by the addition of toluene into iso-octane recently found in the shock tube study of the ignition delay [Y. Sakai et al, SAE 2007-01-4014 (2007)]. Validations of the model were performed with existing shock tube and flow tube data. The model well predicts the ignition characteristics of toluene and PRF/Toluene mixtures under the wide range of temperatures (500-1700 K) and pressures (2-50 atm). It is found that reactions of benzyl radical with oxygen molecule determine the reactivity of toluene at low temperature. Although the effect of toluene addition to iso-octane is not fully resolved, the reactions of alkene with benzyl radical have the possibility to account for the kinetic interactions between PRF and toluene.

  20. "Protect Your Loved Ones From Fataki": Discouraging Cross-Generational Sex in Tanzania.

    PubMed

    Kaufman, Michelle R; Tsang, Samantha W; Mooney, Alyssa; McCartney-Melstad, Anna; Mushi, Adiel K; Kamala, Benjamin

    2016-06-01

    The Fataki campaign aired in Tanzania via radio from 2008 to 2011 to address cross-generational sex, a major driver of HIV in the region. The campaign sought to incite social disapproval of men who engage in such relationships, generate dialogue around the issue, and encourage community interventions in these relationships through social learning. Using qualitative methods, we explored campaign reactions, use of the term Fataki to describe men in relationships with much younger women, and the nature of discussions spurred by the campaign. We conducted focus group discussions and individual interviews in Iringa and Pwani regions with young women, older men, and community leaders. Results showed that the Fataki term was widely used and had negative connotations reflecting social disapproval of men who participate in such relationships. Dialogue spurred by the campaign, primarily directed toward young women, focused on reasons for avoiding these relationships. We conclude with suggestions for relevant future interventions. PMID:25918112

  1. Cross-Protection against Lethal H5N1 Challenge in Ferrets with an Adjuvanted Pandemic Influenza Vaccine

    PubMed Central

    Baras, Benoît; Stittelaar, Koert J.; Simon, James H.; Thoolen, Robert J. M. M.; Mossman, Sally P.; Pistoor, Frank H. M.; van Amerongen, Geert; Wettendorff, Martine A.; Hanon, Emmanuel; Osterhaus, Albert D. M. E.

    2008-01-01

    Background Unprecedented spread between birds and mammals of highly pathogenic avian influenza viruses (HPAI) of the H5N1 subtype has resulted in hundreds of human infections with a high fatality rate. This has highlighted the urgent need for the development of H5N1 vaccines that can be produced rapidly and in sufficient quantities. Potential pandemic inactivated vaccines will ideally induce substantial intra-subtypic cross-protection in humans to warrant the option of use, either prior to or just after the start of a pandemic outbreak. In the present study, we evaluated a split H5N1 A/H5N1/Vietnam/1194/04, clade 1 candidate vaccine, adjuvanted with a proprietary oil-in- water emulsion based Adjuvant System proven to be well-tolerated and highly immunogenic in the human (Leroux-Roels et al. (2007) The Lancet 370:580–589), for its ability to induce intra-subtypic cross-protection against clade 2 H5N1/A/Indonesia/5/05 challenge in ferrets. Methodology and Principal Findings All ferrets in control groups receiving non-adjuvanted vaccine or adjuvant alone failed to develop specific or cross-reactive neutralizing antibodies and all died or had to be euthanized within four days of virus challenge. Two doses of adjuvanted split H5N1 vaccine containing ≥1.7 µg HA induced neutralizing antibodies in the majority of ferrets to both clade 1 (17/23 (74%) responders) and clade 2 viruses (14/23 (61%) responders), and 96% (22/23) of vaccinees survived the lethal challenge. Furthermore lung virus loads and viral shedding in the upper respiratory tract were reduced in vaccinated animals relative to controls suggesting that vaccination might also confer a reduced risk of viral transmission. Conclusion These protection data in a stringent challenge model in association with an excellent clinical profile highlight the potential of this adjuvanted H5N1 candidate vaccine as an effective tool in pandemic preparedness. PMID:18167560

  2. Critical role of TLR7 signaling in the priming of cross-protective cytotoxic T lymphocyte responses by a whole inactivated influenza virus vaccine.

    PubMed

    Budimir, Natalija; de Haan, Aalzen; Meijerhof, Tjarko; Waijer, Simke; Boon, Louis; Gostick, Emma; Price, David A; Wilschut, Jan; Huckriede, Anke

    2013-01-01

    Current influenza vaccines fail to induce protection against antigenically distinct virus strains. Accordingly, there is a need for the development of cross-protective vaccines. Previously, we and others have shown that vaccination with whole inactivated virus (WIV) induces cross-protective cellular immunity in mice. To probe the mechanistic basis for this finding, we investigated the role of TLR7, a receptor for single-stranded RNA, in induction of cross-protection. Vaccination of TLR7-/- mice with influenza WIV failed to protect against a lethal heterosubtypic challenge; in contrast, wild-type mice were fully protected. The lack of protection in TLR7-/- mice was associated with high viral load and a relative paucity of influenza-specific CD8+ cytotoxic T lymphocyte (CTL) responses. Dendritic cells (DCs) from TLR7-/- mice were unable to cross-present WIV-derived antigen to influenza-specific CTLs in vitro. Similarly, TLR7-/- DCs failed to mature and become activated in response to WIV, as determined by the assessment of surface marker expression and cytokine production. Plasmacytoid DCs (pDCs) derived from wild-type mice responded directly to WIV while purified conventional DCs (cDCs) did not respond to WIV in isolation, but were responsive in mixed pDC/cDC cultures. Depletion of pDCs prior to and during WIV immunization resulted in reduced numbers of influenza-specific CTLs and impaired protection from heterosubtypic challenge. Thus, TLR7 plays a critical role in the induction of cross-protective immunity upon vaccination with WIV. The initial target cells for WIV appear to be pDCs which by direct or indirect mechanisms promote activation of robust CTL responses against conserved influenza epitopes. PMID:23658804

  3. Critical Role of TLR7 Signaling in the Priming of Cross-Protective Cytotoxic T Lymphocyte Responses by a Whole Inactivated Influenza Virus Vaccine

    PubMed Central

    Budimir, Natalija; de Haan, Aalzen; Meijerhof, Tjarko; Waijer, Simke; Boon, Louis; Gostick, Emma; Price, David A.; Wilschut, Jan; Huckriede, Anke

    2013-01-01

    Current influenza vaccines fail to induce protection against antigenically distinct virus strains. Accordingly, there is a need for the development of cross-protective vaccines. Previously, we and others have shown that vaccination with whole inactivated virus (WIV) induces cross-protective cellular immunity in mice. To probe the mechanistic basis for this finding, we investigated the role of TLR7, a receptor for single-stranded RNA, in induction of cross-protection. Vaccination of TLR7−/− mice with influenza WIV failed to protect against a lethal heterosubtypic challenge; in contrast, wild-type mice were fully protected. The lack of protection in TLR7−/− mice was associated with high viral load and a relative paucity of influenza-specific CD8+ cytotoxic T lymphocyte (CTL) responses. Dendritic cells (DCs) from TLR7−/− mice were unable to cross-present WIV-derived antigen to influenza-specific CTLs in vitro. Similarly, TLR7−/− DCs failed to mature and become activated in response to WIV, as determined by the assessment of surface marker expression and cytokine production. Plasmacytoid DCs (pDCs) derived from wild-type mice responded directly to WIV while purified conventional DCs (cDCs) did not respond to WIV in isolation, but were responsive in mixed pDC/cDC cultures. Depletion of pDCs prior to and during WIV immunization resulted in reduced numbers of influenza-specific CTLs and impaired protection from heterosubtypic challenge. Thus, TLR7 plays a critical role in the induction of cross-protective immunity upon vaccination with WIV. The initial target cells for WIV appear to be pDCs which by direct or indirect mechanisms promote activation of robust CTL responses against conserved influenza epitopes. PMID:23658804

  4. Living conditions, including life style, in primary-care patients with nonacute, nonspecific spinal pain compared with a population-based sample: a cross-sectional study

    PubMed Central

    Lindell, Odd; Johansson, Sven-Erik; Strender, Lars-Erik

    2010-01-01

    Background Nonspecific spinal pain (NSP), comprising back and/or neck pain, is one of the leading disorders behind long-term sick-listing, including disability pensions. Early interventions to prevent long-term sick-listing require the identification of patients at risk. The aim of this study was to compare living conditions associated with long-term sick-listing for NSP in patients with nonacute NSP, with a nonpatient population-based sample. Nonacute NSP is pain that leads to full-time sick-listing >3 weeks. Methods One hundred and twenty-five patients with nonacute NSP, 2000–2004, were included in a randomized controlled trial in Stockholm County with the objective of comparing cognitive–behavioral rehabilitation with traditional primary care. For these patients, a cross-sectional study was carried out with baseline data. Living conditions were compared between the patients and 338 nonpatients by logistic regression. The conditions from univariate analyses were included in a multivariate analysis. The nonsignificant variables were excluded sequentially to yield a model comprising only the significant factors (P < 0.05). The results are shown as odds ratios (OR) with 95% confidence intervals. Results In the univariate analyses, 13 of the 18 living conditions had higher odds for the patients with a dominance of physical work strains and Indication of alcohol over-consumption, odds ratio (OR) 14.8 (95% confidence interval [CI] 3.2–67.6). Five conditions qualified for the multivariate model: High physical workload, OR 13.7 (CI 5.9–32.2); Hectic work tempo, OR 8.4 (CI 2.5–28.3); Blue-collar job, OR 4.5 (CI 1.8–11.4); Obesity, OR 3.5 (CI 1.2–10.2); and Low education, OR 2.7 (CI 1.1–6.8). Conclusions As most of the living conditions have previously been insufficiently studied, our findings might contribute a wider knowledge of risk factors for long-term sick-listing for NSP. As the cross-sectional design makes causal conclusions impossible, our study

  5. Altered bone material properties in HLA-B27 rats include reduced mineral to matrix ratio and altered collagen cross-links.

    PubMed

    Gamsjaeger, Sonja; Srivastava, Apurva K; Wergedal, Jon E; Zwerina, Jochen; Klaushofer, Klaus; Paschalis, Eleftherios P; Tatakis, Dimitris N

    2014-11-01

    Spondyloarthropathy and inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease, are often associated with severe osteopenia/osteoporosis in both children and adults. HLA-B27 transgenic rats present a phenotype that includes severe colitis and severely accelerated alveolar bone loss. The purpose of this study was to evaluate long bone density status, systemic bone metabolic markers, and intrinsic bone material properties in HLA-B27 transgenic (TG) rats, and compare them with those of age- and sex-matched wild-type (WT) animals. The results indicate that in the HLA-B27 rat, an animal susceptible to both alveolar bone loss (ABL) and long bone osteopenia, there is a statistically significant negative correlation between ABL and long bone bone mineral density (BMD), as well as mineral/matrix ratio at active bone-forming trabecular surfaces. The TG animals had a lower mineral/matrix ratio and higher relative proteoglycan and advanced glycation end product (ϵ-N-Carboxymethyl-L-lysine) content and pyridinoline/divalent collagen cross-link ratio compared with WT. These results may provide better understanding of the interrelationship between osteoporosis and oral bone loss, the underlying causes of the inferior bone strength in the HLA-B27 transgenic animals, and could prove to be a useful model in the elucidation of the pathophysiology of spondyloarthropathy and IBD-associated osteopenia/osteoporosis and in the evaluation of pharmacological intervention(s) against such conditions. PMID:24771481

  6. An in vitro attenuated strain of Histomonas meleagridis provides cross-protective immunity in turkeys against heterologous virulent isolates.

    PubMed

    Sulejmanovic, T; Bilic, I; Hess, M; Liebhart, D

    2016-01-01

    In the current study, cross-protective immunity induced by a well-defined clonal strain of Histomonas meleagridis, attenuated by prolonged in vitro cultivation against different clonal heterologous isolates of the same parasite was investigated. For this purpose, 86 turkey poults were assigned to groups consisting of 9-10 birds. Birds of four groups were vaccinated on their 1st day of life followed by re-vaccination on their 14th day of life when the remaining turkeys were left untreated. The challenge was performed using four strains of H. meleagridis that were isolated from chickens or turkeys from different outbreaks of histomonosis in Europe and three of them showed diversities in their genome. Hence, every strain used for the challenge was applied to a group of vaccinated and a group of non-vaccinated birds while birds of the negative control group were sham inoculated. Non-vaccinated birds suffered from severe histomonosis due to the challenge with fatalities reaching from 5 to 10 turkeys per group. Vaccinated birds did not contract clinical signs of the disease following challenge and the increase in weight was unaffected compared to birds of the negative control group. A significant difference in lesion scores was recorded between vaccinated and non-vaccinated groups, with very few instances of liver involvement in the former groups. Livers of vaccinated birds that were without recordable macroscopic lesions were also found negative by immunohistochemical investigation. According to the data obtained, the present study demonstrates, for the first time, the cross-protective capability of a tentative vaccine strain of H. meleagridis attenuated in vitro against heterologous virulent isolates of different origin. PMID:26542637

  7. Welcome to the wild west: protecting access to cross border fertility care in the United States.

    PubMed

    Mutcherson, Kimberley M

    2012-01-01

    As has been the case with other types of medical tourism, the phenomenon of cross border fertility care ("CBFC") has sparked concern about the lack of global or even national harmonization in the regulation of the fertility industry. The diversity of laws around the globe leads would-be parents to forum shop for a welcoming place to make babies. Focusing specifically on the phenomenon of travel to the United States, this Article takes up the question of whether there should be any legal barriers to those who come to the United States seeking CBFC. In part, CBFC suffers from the same general concerns raised about the use of fertility treatment in general, but it is possible to imagine a subset of arguments that would lead to forbidding or at least discouraging people from coming to the United States for CBFC, either as a matter of law or policy. This paper stands in opposition to any such effort and contemplates the moral and ethical concerns about CBFC and how, and if, those concerns warrant expression in law. Part I describes the conditions that lead some couples and individuals to leave their home countries to access fertility treatments abroad and details why the United States, with its comparatively liberal regulation of ART, has become a popular CBFC destination for travelers from around the world. Part II offers and refutes arguments supporting greater domestic control over those who seek to satisfy their desires for CBFC in the United States by reasserting the importance of the right of procreation while also noting appropriate concerns about justice and equality in the market for babies. Part III continues the exploration of justice by investigating the question of international cooperation in legislating against perceived wrongs. This Part concludes that consistent legislation across borders is appropriate where there is consensus about the wrong of an act, but it is unnecessary and inappropriate where there remain cultural conflicts about certain

  8. Protection against human and porcine enterotoxigenic strains of Escherichia coli in rats immunized with a cross-linked toxoid vaccine.

    PubMed Central

    Klipstein, F A; Engert, R F; Clements, J D; Houghten, R A

    1983-01-01

    To compare their relative immunogenicities, we used synthetically produced Escherichia coli heat-stable toxin coupled to a protein carrier and the B subunit of porcine heat-labile toxin separately in graded dosages to immunize rats. Equivalent antigen unit dosages of each toxin raised approximately the same level of mucosal immunoglobulin A (IgA) antitoxin response and degree of protection against a challenge with respective heat-stable- or heat-labile-toxin-producing viable bacteria. Conjugation conditions were identified, therefore, which yielded a vaccine of these toxins, cross-linked by the carbodiimide reaction, that consisted of equal antigenic proportions of each toxin component as determined by enzyme-linked immunosorbent assay and expressed in antigen units. The dose-related response to immunization with this vaccine was the same as the response to its components given separately. The toxicity of the heat-stable toxin component was reduced greater than 600-fold. Immunization with optimal antigen unit dosages of the vaccine gave greater than or equal to sixfold increases in mucosal IgA antitoxin titers and provided significant (P less than 0.001) protection against challenge with heterologous serotypes of viable strains, of either human or porcine origin, that produce heat-stable or heat-labile toxin or both. PMID:6343245

  9. Effect of inactivation method on the cross-protective immunity induced by whole 'killed' influenza A viruses and commercial vaccine preparations.

    PubMed

    Furuya, Yoichi; Regner, Matthias; Lobigs, Mario; Koskinen, Aulikki; Müllbacher, Arno; Alsharifi, Mohammed

    2010-06-01

    We have recently shown that intranasal (i.n.) administration of gamma-irradiated A/PR/8 [A/Puerto Rico/8/34 (H1N1)] protects mice against lethal avian influenza A/Vietnam/1203/2004 (H5N1) and other heterosubtypic influenza A infections. Here, we used gamma-irradiated, formalin- and UV-inactivated A/PC [A/Port Chalmers/1/73 (H3N2)] virus preparations and compared their ability to induce both homologous and heterosubtypic protective immunity. Our data show that, in contrast to i.n. vaccination with formalin- or UV-inactivated virus, or the present commercially available trivalent influenza vaccine, a single dose of gamma-ray-inactivated A/PC (gamma-A/PC) conferred significant protection in mice against both homologous and heterosubtypic virus challenges. A multiple immunization regime was required for formalin-inactivated virus preparations to induce protective immunity against a homotypic virus challenge, but did not induce influenza A strain cross-protective immunity. The highly immunogenic gamma-A/PC, but not formalin- or UV-inactivated A/PC, nor the currently available subvirion vaccine, elicited cytotoxic T-cell responses that are most likely responsible for the cross-protective and long-lasting immunity against highly lethal influenza A infections in mice. Finally, freeze-drying of gamma-A/PC did not affect the ability to induce cross-protective immunity. PMID:20147516

  10. Induction of Heterosubtypic Cross-Protection against Influenza by a Whole Inactivated Virus Vaccine: The Role of Viral Membrane Fusion Activity

    PubMed Central

    Budimir, Natalija; Huckriede, Anke; Meijerhof, Tjarko; Boon, Louis; Gostick, Emma; Price, David A.; Wilschut, Jan; de Haan, Aalzen

    2012-01-01

    Background The inability of seasonal influenza vaccines to effectively protect against infection with antigenically drifted viruses or newly emerging pandemic viruses underlines the need for development of cross-reactive influenza vaccines that induce immunity against a variety of virus subtypes. Therefore, potential cross-protective vaccines, e.g., whole inactivated virus (WIV) vaccine, that can target conserved internal antigens such as the nucleoprotein (NP) and/or matrix protein (M1) need to be explored. Methodology/Principal Findings In the current study we show that a WIV vaccine, through induction of cross-protective cytotoxic T lymphocytes (CTLs), protects mice from heterosubtypic infection. This protection was abrogated after depletion of CD8+ cells in vaccinated mice, indicating that CTLs were the primary mediators of protection. Previously, we have shown that different procedures used for virus inactivation influence optimal activation of CTLs by WIV, most likely by affecting the membrane fusion properties of the virus. Specifically, inactivation with formalin (FA) severely compromises fusion activity of the virus, while inactivation with β-propiolactone (BPL) preserves fusion activity. Here, we demonstrate that vaccination of mice with BPL-inactivated H5N1 WIV vaccine induces solid protection from lethal heterosubtypic H1N1 challenge. By contrast, vaccination with FA-inactivated WIV, while preventing death after lethal challenge, failed to protect against development of disease and severe body weight loss. Vaccination with BPL-inactivated WIV, compared to FA-inactivated WIV, induced higher levels of specific CD8+ T cells in blood, spleen and lungs, and a higher production of granzyme B in the lungs upon H1N1 virus challenge. Conclusion/Significance The results underline the potential use of WIV as a cross-protective influenza vaccine candidate. However, careful choice of the virus inactivation procedure is important to retain membrane fusion activity

  11. Celastrus and its bioactive celastrol protect against bone damage in autoimmune arthritis by modulating osteoimmune cross-talk.

    PubMed

    Nanjundaiah, Siddaraju M; Venkatesha, Shivaprasad H; Yu, Hua; Tong, Li; Stains, Joseph P; Moudgil, Kamal D

    2012-06-22

    Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by bone erosion and cartilage destruction in the joints. Many of the conventional antiarthritic drugs are effective in suppressing inflammation, but they do not offer protection against bone damage. Furthermore, the prolonged use of these drugs is associated with severe adverse reactions. Thus, new therapeutic agents that can control both inflammation and bone damage but with minimal side effects are sought. Celastrus is a Chinese herb that has been used for centuries in folk medicine for the treatment of various inflammatory diseases. However, its utility for protection against inflammation-induced bone damage in arthritis and the mechanisms involved therein have not been examined. We tested celastrus and its bioactive component celastrol for this attribute in the adjuvant-induced arthritis model of RA. The treatment of arthritic rats with celastrus/celastrol suppressed inflammatory arthritis and reduced bone and cartilage damage in the joints as demonstrated by histology and bone histomorphometry. The protective effects against bone damage are mediated primarily via the inhibition of defined mediators of osteoclastic bone remodeling (e.g. receptor activator of nuclear factor-κB ligand (RANKL)), the deviation of RANKL/osteoprotegerin ratio in favor of antiosteoclastic activity, and the reduction in osteoclast numbers. Furthermore, both the upstream inducers (proinflammatory cytokines) and the downstream effectors (MMP-9) of the osteoclastogenic mediators were altered. Thus, celastrus and celastrol controlled inflammation-induced bone damage by modulating the osteoimmune cross-talk. These natural products deserve further consideration and evaluation as adjuncts to conventional therapy for RA. PMID:22549786

  12. Cross-protective vaccine efficacy of the bivalent HPV vaccine against HPV31 is associated with humoral immune responses

    PubMed Central

    Safaeian, Mahboobeh; Kemp, Troy J.; Pan, David Yuanji; Porras, Carolina; Rodriguez, Ana Cecilia; Schiffman, Mark; Cortes, Bernal; Katki, Hormuzd; Wacholder, Sholom; Schiller, John T.; Gonzalez, Paula; Penrose, Kerri; Lowy, Douglas R.; Quint, Wim; van Doorn, Leen-Jan; Herrero, Rolando; Hildesheim, Allan; Pinto, Ligia A.

    2013-01-01

    Background: We investigated the role of antibody responses as potential mechanism for the cross-protective vaccine-efficacies (VE) observed from randomized clinical trials of the HPV16/18 bivalent vaccine. Results: HPV31 cases had lower HPV16 antibody levels than controls (OR4th quartile compared with 1st quartile = 0.63; 95%CI: 0.36–1.08; p-trend = 0.03). HPV31 cases were also less likely to have detectable HPV31 neutralization, and HPV16 avidity than controls. No statistically significant differences by HPV18 antibody or HPV45 neutralization were observed among HPV45 cases and controls. Protection against HPV58 was not associated with any of the markers, confirming the specificity of our findings. Methods: Samples are from three-dose HPV vaccine recipients from the Costa Rica HPV16/18 vaccine trial. Women with a new HPV31, HPV45, or HPV58 infections over four years of follow-up were compared with randomly selected control women—with no new infection with HPV31/45/58—with respect to HPV16 and HPV18 antibody, HPV31, HPV45, and HPV58 neutralization, and HPV16 avidity. Conclusions: High HPV16 levels and avidity, and the ability to neutralize HPV31 were associated with protection against newly detected HPV31 infections, suggesting that the partial VE demonstrated for HPV31 is likely to be mediated at least in part through antibodies induced by HPV16/18 vaccination. PMID:23571174

  13. Potential Enhancements to the Cross-track Infrared Sounder (CrIS) Ground Test, Data Downlink and Processing for Climate Monitoring including Trace Gas Retrievals

    NASA Astrophysics Data System (ADS)

    Farrow, S. V.; Christensen, T.; Hagan, D. E.

    2009-12-01

    Together with ATMS, the Cross-track Infrared Sounder (CrIS) sensor is a critical payload for National Polar-orbiting Operational Environmental Satellite System (NPOESS) and will first fly on the NPOESS Preparatory Project (NPP) mission, the risk reduction flight for NPOESS. NPOESS is the next generation weather and climate monitoring system for the Department of Defense and National Oceanic and Atmospheric Administration (NOAA), being developed under contract by Northrop Grumman Aerospace Systems. The paper describes potential changes to the program baseline to make CrIS data useful for climate monitoring, including trace gas retrievals such as CO2. Specifically, these are changes to ground calibration tests, changes to the Sensor Data Record (SDR) algorithm, and changes in the spacecraft interface to downlink all of the spectral channels the sensor produces. These changes are presented to promote discussion in the science community of an alternative to achieving some of the key requirements of NASA's OCO mission, which was to monitor CO2, but was destroyed during launch.

  14. A global-local higher order theory including interlaminar stress continuity and C0 plate bending element for cross-ply laminated composite plates

    NASA Astrophysics Data System (ADS)

    Zhen, Wu; Wanji, Chen

    2010-04-01

    A C0-type global-local higher order theory including interlaminar stress continuity is proposed for the cross-ply laminated composite and sandwich plates in this paper, which is able to a priori satisfy the continuity conditions of transverse shear stresses at interfaces. Moreover, total number of unknowns involved in the model is independent of number of layers. Compared to other higher-order theories satisfying the continuity conditions of transverse shear stresses at interfaces, merit of the proposed model is that the first derivatives of transverse displacement w have been taken out from the in-plane displacement fields, so that the C0 interpolation functions is only required during its finite element implementation. To verify the present model, a C0 three-node triangular element is used for bending analysis of laminated composite and sandwich plates. It ought to be shown that all variables involved in present model are discretized by only using linear interpolation functions within an element. Numerical results show that the C0 plate element based on the present theory may accurately calculate transverse shear stresses without any postprocessing, and the present results agree well with those obtained from the C1-type higher order theory. Compared with the C1 plate bending element, the present finite element is simple, convenient to use and accurate enough.

  15. Determinants of Gastroesophageal Reflux Disease, Including Hookah Smoking and Opium Use– A Cross-Sectional Analysis of 50,000 Individuals

    PubMed Central

    Islami, Farhad; Nasseri-Moghaddam, Siavosh; Pourshams, Akram; Poustchi, Hossein; Semnani, Shahryar; Kamangar, Farin; Etemadi, Arash; Merat, Shahin; Khoshnia, Masoud; Dawsey, Sanford M.; Pharoah, Paul D.; Brennan, Paul; Abnet, Christian C.; Boffetta, Paolo; Malekzadeh, Reza

    2014-01-01

    Background Gastroesophageal reflux disease (GERD) is a common cause of discomfort and morbidity worldwide. However, information on determinants of GERD from large-scale studies in low- to medium-income countries is limited. We investigated the factors associated with different measures of GERD symptoms, including frequency, patient-perceived severity, and onset time. Methods We performed a cross-sectional analysis of the baseline data from a population-based cohort study of ∼50,000 individuals in in Golestan Province, Iran. GERD symptoms in this study included regurgitation and/or heartburn. Results Approximately 20% of participants reported at least weekly symptoms. Daily symptoms were less commonly reported by men, those of Turkmen ethnicity, and nass chewers. On the other hand, age, body mass index, alcohol drinking, cigarette smoking, opium use, lower socioeconomic status, and lower physical activity were associated with daily symptoms. Most of these factors showed similar associations with severe symptoms. Women with higher BMI and waist to hip ratio were more likely to report frequent and severe GERD symptoms. Hookah smoking (OR 1.34, 95% CI 1.02–1.75) and opium use (OR 1.70, 95% CI 1.55–1.87) were associated with severe symptoms, whereas nass chewing had an inverse association (OR 0.87, 95% CI 0.76–0.99). After exclusion of cigarette smokers, hookah smoking was still positively associated and nass chewing was inversely associated with GERD symptoms (all frequencies combined). Conclusion GERD is common in this population. The associations of hookah and opium use and inverse association of nass use with GERD symptoms are reported for the first time. Further studies are required to investigate the nature of these associations. Other determinants of GERD were mostly comparable to those reported elsewhere. PMID:24586635

  16. Protection from Secondary Dengue Virus Infection in a Mouse Model Reveals the Role of Serotype Cross-reactive B and T cells1,2

    PubMed Central

    Zompi, Simona; Santich, Brian H.; Beatty, P. Robert; Harris, Eva

    2011-01-01

    The four dengue virus (DENV) serotypes cause dengue fever (DF) and dengue hemorrhagic fever/dengue shock syndrome. Although severe disease has been associated with heterotypic secondary DENV infection, most secondary DENV infections are asymptomatic or result in classic DF. The role of cross-reactive immunity in mediating cross-protection against secondary heterotypic DENV infection is not well-understood. DENV infection of interferon-α/β and -γ receptor-deficient (AG129) mice reproduces key features of human disease. We previously demonstrated a role in cross-protection for pre-existing cross-reactive antibodies, maintained by long-lived plasma cells (LLPCs). Here we use a sequential infection model, infecting AG129 mice with DENV-1 followed by DENV-2 6–8 weeks later. We find that increased DENV-specific avidity during acute secondary heterotypic infection is mediated by cross-reactive memory B cells, as evidenced by increased numbers of DENV-1-specific cells by ELISPOT and higher avidity against DENV-1 of supernatants from polyclonally-stimulated splenocytes isolated from mice experiencing secondary DENV-2 infection. However, increased DENV-specific avidity is not associated with increased DENV-specific neutralization, which appears to be mediated by naïve B cells. Adoptive transfer of DENV-1-immune B and T cells into naïve mice prior to secondary DENV-2 infection delayed mortality. Mice depleted of T cells developed signs of disease but recovered after secondary DENV infection. Overall, we found that protective cross-reactive antibodies are secreted by both LLPCs and memory B cells and that both cross-reactive B cells and T cells provide protection against a secondary heterotypic DENV infection. Understanding the protective immunity that develops naturally against DENV infection may help design future vaccines. PMID:22131327

  17. Cell culture (Vero) derived whole virus (H5N1) vaccine based on wild-type virus strain induces cross-protective immune responses

    PubMed Central

    Kistner, Otfried; Howard, Keith; Spruth, Martin; Wodal, Walter; Brühl, Peter; Gerencer, Marijan; Crowe, Brian A.; Savidis-Dacho, Helga; Livey, Ian; Reiter, Manfred; Mayerhofer, Ines; Tauer, Christa; Grillberger, Leopold; Mundt, Wolfgang; Falkner, Falko G.; Barrett, P. Noel

    2007-01-01

    The rapid spread and the transmission to humans of avian influenza virus (H5N1) has induced world-wide fears of a new pandemic and raised concerns over the ability of standard influenza vaccine production methods to rapidly supply sufficient amounts of an effective vaccine. We report here on a robust and flexible strategy which uses wild-type virus grown in a continuous cell culture (Vero) system to produce an inactivated whole virus vaccine. Candidate vaccines based on clade 1 and clade 2 influenza H5N1 strains were developed and demonstrated to be highly immunogenic in animal models. The vaccines induce cross-neutralising antibodies, highly cross-reactive T-cell responses and are protective in a mouse challenge model not only against the homologous virus but against other H5N1 strains, including those from another clade. These data indicate that cell culture-grown, whole virus vaccines, based on the wild-type virus, allow the rapid high yield production of a candidate pandemic vaccine. PMID:17614165

  18. Polyvalent DNA vaccines expressing HA antigens of H5N1 influenza viruses with an optimized leader sequence elicit cross-protective antibody responses.

    PubMed

    Wang, Shixia; Hackett, Anthony; Jia, Na; Zhang, Chunhua; Zhang, Lu; Parker, Chris; Zhou, An; Li, Jun; Cao, Wu-Chun; Huang, Zuhu; Li, Yan; Lu, Shan

    2011-01-01

    Highly pathogenic avian influenza A (HPAI) H5N1 viruses are circulating among poultry populations in parts of Asia, Africa, and the Middle East, and have caused human infections with a high mortality rate. H5 subtype hemagglutinin (HA) has evolved into phylogenetically distinct clades and subclades based on viruses isolated from various avian species. Since 1997, humans have been infected by HPAI H5N1 viruses from several clades. It is, therefore, important to develop strategies to produce protective antibody responses against H5N1 viruses from multiple clades or antigenic groups. In the current study, we optimized the signal peptide design of DNA vaccines expressing HA antigens from H5N1 viruses. Cross reactivity analysis using sera from immunized rabbits showed that antibody responses elicited by a polyvalent formulation, including HA antigens from different clades, was able to elicit broad protective antibody responses against multiple key representative H5N1 viruses across different clades. Data presented in this report support the development of a polyvalent DNA vaccine strategy against the threat of a potential H5N1 influenza pandemic. PMID:22205966

  19. Deriving site-specific soil clean-up values for metals and metalloids: Rationale for including protection of soil microbial processes

    PubMed Central

    Kuperman, Roman G; Siciliano, Steven D; Römbke, Jörg; Oorts, Koen

    2014-01-01

    Although it is widely recognized that microorganisms are essential for sustaining soil fertility, structure, nutrient cycling, groundwater purification, and other soil functions, soil microbial toxicity data were excluded from the derivation of Ecological Soil Screening Levels (Eco-SSL) in the United States. Among the reasons for such exclusion were claims that microbial toxicity tests were too difficult to interpret because of the high variability of microbial responses, uncertainty regarding the relevance of the various endpoints, and functional redundancy. Since the release of the first draft of the Eco-SSL Guidance document by the US Environmental Protection Agency in 2003, soil microbial toxicity testing and its use in ecological risk assessments have substantially improved. A wide range of standardized and nonstandardized methods became available for testing chemical toxicity to microbial functions in soil. Regulatory frameworks in the European Union and Australia have successfully incorporated microbial toxicity data into the derivation of soil threshold concentrations for ecological risk assessments. This article provides the 3-part rationale for including soil microbial processes in the development of soil clean-up values (SCVs): 1) presenting a brief overview of relevant test methods for assessing microbial functions in soil, 2) examining data sets for Cu, Ni, Zn, and Mo that incorporated soil microbial toxicity data into regulatory frameworks, and 3) offering recommendations on how to integrate the best available science into the method development for deriving site-specific SCVs that account for bioavailability of metals and metalloids in soil. Although the primary focus of this article is on the development of the approach for deriving SCVs for metals and metalloids in the United States, the recommendations provided in this article may also be applicable in other jurisdictions that aim at developing ecological soil threshold values for protection of

  20. Occurrence and impact of negative behaviour, including domestic violence and abuse, in men attending UK primary care health clinics: a cross-sectional survey

    PubMed Central

    Hester, M; Ferrari, G; Jones, S K; Williamson, E; Bacchus, L J; Peters, T J; Feder, G

    2015-01-01

    Objective To measure the experience and perpetration of negative behaviour, including domestic violence and abuse (DVA), and investigate its associations with health conditions and behaviours in men attending general practice. Design Cross-sectional questionnaire-based study conducted between September 2010 and June 2011. Setting 16 general practices in the south west of England. Participants Male patients aged 18 or older, attending alone, who could read and write English. A total of 1403 of eligible patients (58%) participated in the survey and 1368 (56%) completed the questions relevant to this paper. 97% of respondents reported they were heterosexual. Main outcome measures Lifetime occurrence of negative behaviour consistent with DVA, perceived health impact of negative behaviours, associations with anxiety and depression symptoms, and cannabis use in the past 12 months and binge drinking. Results 22.7% (95% CI 20.2% to 24.9%) of men reported ever experiencing negative behaviour (feeling frightened, physically hurt, forced sex, ask permission) from a partner. All negative behaviours were associated with a twofold to threefold increased odds of anxiety and depression symptoms in men experiencing or perpetrating negative behaviours or both. 34.9% (95% CI 28.7% to 41.7%) of men who reported experiencing negative behaviour from a partner, and 30.8% (95% CI 23.7% to 37.8%) of men who perpetrated negative behaviours said they had been in a domestically violent or abusive relationship. No associations with problematic drinking were found; there was a weak association with cannabis use. Conclusions DVA is experienced or perpetrated by a large minority of men presenting to general practice, and these men were more likely to have current symptoms of depression and anxiety. Presentation of anxiety or depression to clinicians may be an indicator of male experience or perpetration of DVA victimisation. PMID:25991450

  1. Physiological and transcriptional responses and cross protection of Lactobacillus plantarum ZDY2013 under acid stress.

    PubMed

    Huang, Renhui; Pan, Mingfang; Wan, Cuixiang; Shah, Nagendra P; Tao, Xueying; Wei, Hua

    2016-02-01

    Acid tolerance responses (ATR) in Lactobacillus plantarum ZDY2013 were investigated at physiological and molecular levels. A comparison of composition of cell membrane fatty acids (CMFA) between acid-challenged and unchallenged cells showed that acid adaptation evoked a significantly higher percentage of saturated fatty acids and cyclopropane fatty acids in acid-challenged than in unchallenged cells. In addition, reverse transcription-quantitative PCR analysis in acid-adapted cells at different pH values (ranging from 3.0 to 4.0) indicated that several genes were differently regulated, including those related to proton pumps, amino acid metabolism, sugar metabolism, and class I and class III stress response pathways. Expression of genes involved in fatty acid synthesis and production of alkali was significantly upregulated. Upon exposure to pH 4.5 for 2 h, a higher survival rate (higher viable cell count) of Lactobacillus plantarum ZDY2013 was achieved following an additional challenge to 40 mM hydrogen peroxide for 60 min, but no difference in survival rate of cells was found with further challenge to heat, ethanol, or salt. Therefore, we concluded that the physiological and metabolic changes of acid-treated cells of Lactobacillus plantarum ZDY2013 help the cells resist damage caused by acid, and further initiated global response signals to bring the whole cell into a state of defense to other stress factors, especially hydrogen peroxide. PMID:26627851

  2. Supplementation of H1N1pdm09 split vaccine with heterologous tandem repeat M2e5x virus-like particles confers improved cross-protection in ferrets.

    PubMed

    Music, Nedzad; Reber, Adrian J; Kim, Min-Chul; York, Ian A; Kang, Sang-Moo

    2016-01-20

    Current influenza vaccines induce strain-specific immunity to the highly variable hemagglutinin (HA) protein. It is therefore a high priority to develop vaccines that induce broadly cross-protective immunity to different strains of influenza. Since influenza A M2 proteins are highly conserved among different strains, five tandem repeats of the extracellular peptide of M2 in a membrane-anchored form on virus-like particles (VLPs) have been suggested to be a promising candidate for universal influenza vaccine. In this study, ferrets were intramuscularly immunized with 2009 H1N1 split HA vaccine ("Split") alone, influenza split vaccine supplemented with M2e5x VLP ("Split+M2e5x"), M2e5x VLP alone ("M2e5x"), or mock immunized. Vaccine efficacy was measured serologically and by protection against a serologically distinct viral challenge. Ferrets immunized with Split+M2e5x induced HA strain specific and conserved M2e immunity. Supplementation of M2e5x VLP to split vaccination significantly increased the immunogenicity of split vaccine compared to split alone. The Split+M2e5x ferret group showed evidence of cross-reactive protection, including faster recovery from weight loss, and reduced inflammation, as inferred from changes in peripheral leukocyte subsets, compared to mock-immunized animals. In addition, ferrets immunized with Split+M2e5x shed lower viral nasal-wash titers than the other groups. Ferrets immunized with M2e5x alone also show some protective effects, while those immunized with split vaccine alone induced no protective effects compared to mock-immunized ferrets. These studies suggest that supplementation of split vaccine with M2e5x-VLP may provide broader and improved cross-protection than split vaccine alone. PMID:26709639

  3. Cross-protection of newly emerging HPAI H5 viruses by neutralizing human monoclonal antibodies: A viable alternative to oseltamivir.

    PubMed

    Ren, Huanhuan; Wang, Guiqin; Wang, Shuangshuang; Chen, Honglin; Chen, Zhiwei; Hu, Hongxing; Cheng, Genhong; Zhou, Paul

    2016-01-01

    Newly emerging highly pathogenic avian influenza (HPAI) H5N2, H5N3, H5N5, H5N6, H5N8 and H5N9 viruses have been spreading in poultry and wild birds. The H5N6 viruses have also caused 10 human infections with 4 fatal cases in China. Here, we assessed the cross-neutralization and cross-protection of human and mouse monoclonal antibodies against 2 viruses: a HPAI H5N8 virus, A/chicken/Netherlands/14015526/2014 (NE14) and a HPAI H5N6 virus, A/Sichuan/26221/2014 (SC14). The former was isolated from an infected chicken in Netherlands in 2014 and the latter was isolated from an infected human patient in Sichuan, China. We show that antibodies FLA5.10, FLD21.140, 100F4 and 65C6, but not AVFluIgG01, AVFluIgG03, S139/1 and the VRC01 control, potently cross-neutralize the H5N8 NE14 and H5N6 SC14 viruses. Furthermore, we show that a single injection of >1 mg/kg of antibody 100F4 at 4 hours before, or 20 mg/kg antibody 100F4 at 72 hours after, a lethal dose of H5N8 NE14 enables mice to withstand the infection. Finally, we show that a single injection of 0.5 or 1 mg/kg antibody 100F4 prophylactically or 10 mg/kg 100F4 therapeutically outperforms a 5-day course of 10 mg/kg/day oseltamivir treatment against lethal H5N8 NE14 or H5N6 SC14 infection in mice. Our results suggest that further preclinical evaluation of human monoclonal antibodies against newly emerging H5 viruses is warranted. PMID:27167234

  4. Variations in risk and protective factors for life satisfaction and mental wellbeing with deprivation: a cross-sectional study

    PubMed Central

    2012-01-01

    Background Improving life satisfaction (LS) and mental wellbeing (MWB) is important for better public health. Like other health issues, LS and MWB are closely related to deprivation (i.e. lack of resources). Developing public health measures that reduce inequalities in wellbeing requires an understanding of how factors associated with high and low LS and MWB vary with deprivation. Here, we examine such variations and explore which public health measures are likely to improve wellbeing while reducing related inequalities. Methods A self-administered questionnaire measuring LS and MWB was used with a cross-sectional sample of adults from the North West of England (n = 15,228). Within deprivation tertiles, analyses examined how demographics, health status, employment, relationships and behaviours (alcohol, tobacco, physical exercise) were associated with LS and MWB. Results Deprivation was strongly related to low LS and MWB with, for instance, 17.1 % of the most deprived tertile having low LS compared to 8.9 % in the most affluent. After controlling for confounders, across all deprivation tertiles, better self-assessed health status and being in a relationship were protective against low LS and MWB. Unemployment increased risks of low LS across all tertiles but only risks of low MWB in the deprived tertile. For this tertile, South Asian ethnicity and higher levels of exercise were protective against low MWB. In the middle tertile retired individuals had a reduced risk of low MWB and an increased chance of high LS even in comparison to those in employment. Alcohol’s impact on LS was limited to the most deprived tertile where heavy drinkers were at most risk of poor outcomes. Conclusions In this study, positive outcomes for LS and MWB were strongly associated with lower deprivation and good health status. Public health measures already developed to promote these issues are likely to improve LS and MWB. Efforts to increase engagement in exercise are also likely

  5. Cross-priming of long lived protective CD8+ T cells against Trypanosoma cruzi infection: importance of a TLR9 agonist and CD4+ T cells.

    PubMed

    de Alencar, Bruna C G; Araújo, Adriano F S; Penido, Marcus L O; Gazzinelli, Ricardo T; Rodrigues, Mauricio M

    2007-08-10

    We recently described that vaccination of mice with a glutathione S transferase fusion protein representing amino acids 261-500 of the Amastigote Surface Protein-2 efficiently cross-primed protective CD8+ T cells against a lethal challenge with the human protozoan parasite Trypanosoma cruzi. In this study, we initially established that this protective immunity was long lived. Subsequently, we studied the importance of TLR9 agonist CpG ODN 1826, TLR4 and CD4+ T cells for the generation of these protective CD8+ T cells. We found that: (i) the TLR9 agonist CpG ODN 1826 improved the efficiency of protective immunity; (ii) TLR4 is not relevant for priming of specific CD8+ T cells; (iii) CD4+ T cells are critical for priming of memory/protective CD8+ T cells. PMID:17629597

  6. Proton pump inhibitors protect mice from acute systemic inflammation and induce long-term cross-tolerance

    PubMed Central

    Balza, E; Piccioli, P; Carta, S; Lavieri, R; Gattorno, M; Semino, C; Castellani, P; Rubartelli, A

    2016-01-01

    Incidence of sepsis is increasing, representing a tremendous burden for health-care systems. Death in acute sepsis is attributed to hyperinflammatory responses, but the underlying mechanisms are still unclear. We report here that proton pump inhibitors (PPIs), which block gastric acid secretion, selectively inhibited tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) secretion by Toll-like receptor (TLR)-activated human monocytes in vitro, in the absence of toxic effects. Remarkably, the oversecretion of IL-1β that represents a hallmark of monocytes from patients affected by cryopyrin-associated periodic syndrome is also blocked. Based on these propaedeutic experiments, we tested the effects of high doses of PPIs in vivo in the mouse model of endotoxic shock. Our data show that a single administration of PPI protected mice from death (60% survival versus 5% of untreated mice) and decreased TNF-α and IL-1β systemic production. PPIs were efficacious even when administered after lipopolysaccharide (LPS) injection. PPI-treated mice that survived developed a long-term cross-tolerance, becoming resistant to LPS- and zymosan-induced sepsis. In vitro, their macrophages displayed impaired TNF-α and IL-1β to different TLR ligands. PPIs also prevented sodium thioglycollate-induced peritoneal inflammation, indicating their efficacy also in a non-infectious setting independent of TLR stimulation. Lack of toxicity and therapeutic effectiveness make PPIs promising new drugs against sepsis and other severe inflammatory conditions. PMID:27441656

  7. Biodegradable nanoparticle-entrapped vaccine induces cross-protective immune response against a virulent heterologous respiratory viral infection in pigs.

    PubMed

    Dwivedi, Varun; Manickam, Cordelia; Binjawadagi, Basavaraj; Joyappa, Dechamma; Renukaradhya, Gourapura J

    2012-01-01

    Biodegradable nanoparticle-based vaccine development research is unexplored in large animals and humans. In this study, we illustrated the efficacy of nanoparticle-entrapped UV-killed virus vaccine against an economically important respiratory viral disease of pigs called porcine reproductive and respiratory syndrome virus (PRRSV). We entrapped PLGA [poly (lactide-co-glycolides)] nanoparticles with killed PRRSV antigens (Nano-KAg) and detected its phagocytosis by pig alveolar macrophages. Single doses of Nano-KAg vaccine administered intranasally to pigs upregulated innate and PRRSV specific adaptive responses. In a virulent heterologous PRRSV challenge study, Nano-KAg vaccine significantly reduced the lung pathology and viremia, and the viral load in the lungs. Immunologically, enhanced innate and adaptive immune cell population and associated cytokines with decreased secretion of immunosuppressive mediators were observed at both mucosal sites and blood. In summary, we demonstrated the benefits of intranasal delivery of nanoparticle-based viral vaccine in eliciting cross-protective immune response in pigs, a potential large animal model. PMID:23240064

  8. Proton pump inhibitors protect mice from acute systemic inflammation and induce long-term cross-tolerance.

    PubMed

    Balza, E; Piccioli, P; Carta, S; Lavieri, R; Gattorno, M; Semino, C; Castellani, P; Rubartelli, A

    2016-01-01

    Incidence of sepsis is increasing, representing a tremendous burden for health-care systems. Death in acute sepsis is attributed to hyperinflammatory responses, but the underlying mechanisms are still unclear. We report here that proton pump inhibitors (PPIs), which block gastric acid secretion, selectively inhibited tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) secretion by Toll-like receptor (TLR)-activated human monocytes in vitro, in the absence of toxic effects. Remarkably, the oversecretion of IL-1β that represents a hallmark of monocytes from patients affected by cryopyrin-associated periodic syndrome is also blocked. Based on these propaedeutic experiments, we tested the effects of high doses of PPIs in vivo in the mouse model of endotoxic shock. Our data show that a single administration of PPI protected mice from death (60% survival versus 5% of untreated mice) and decreased TNF-α and IL-1β systemic production. PPIs were efficacious even when administered after lipopolysaccharide (LPS) injection. PPI-treated mice that survived developed a long-term cross-tolerance, becoming resistant to LPS- and zymosan-induced sepsis. In vitro, their macrophages displayed impaired TNF-α and IL-1β to different TLR ligands. PPIs also prevented sodium thioglycollate-induced peritoneal inflammation, indicating their efficacy also in a non-infectious setting independent of TLR stimulation. Lack of toxicity and therapeutic effectiveness make PPIs promising new drugs against sepsis and other severe inflammatory conditions. PMID:27441656

  9. Design and Validation of a Novel Method to Measure Cross-Sectional Area of Neck Muscles Included during Routine MR Brain Volume Imaging

    PubMed Central

    Kilgour, Alixe H. M.; Subedi, Deepak; Gray, Calum D.; Deary, Ian J.; Lawrie, Stephen M.; Wardlaw, Joanna M.; Starr, John M.

    2012-01-01

    Introduction Low muscle mass secondary to disease and ageing is an important cause of excess mortality and morbidity. Many studies include a MR brain scan but no peripheral measure of muscle mass. We developed a technique to measure posterior neck muscle cross-sectional area (CSA) on volumetric MR brain scans enabling brain and muscle size to be measured simultaneously. Methods We performed four studies to develop and test: feasibility, inter-rater reliability, repeatability and external validity. We used T1-weighted MR brain imaging from young and older subjects, obtained on different scanners, and collected mid-thigh MR data. Results After developing the technique and demonstrating feasibility, we tested it for inter-rater reliability in 40 subjects. Intraclass correlation coefficients (ICC) between raters were 0.99 (95% confidence intervals (CI) 0.98–1.00) for the combined group (trapezius, splenius and semispinalis), 0.92 (CI 0.85–0.96) for obliquus and 0.92 (CI 0.85–0.96) for sternocleidomastoid. The first unrotated principal component explained 72.2% of total neck muscle CSA variance and correlated positively with both right (r = 0.52, p = .001) and left (r = 0.50, p = .002) grip strength. The 14 subjects in the repeatability study had had two MR brain scans on three different scanners. The ICC for between scanner variation for total neck muscle CSA was high at 0.94 (CI 0.86–0.98). The ICCs for within scanner variations were also high, with values of 0.95 (CI 0.86–0.98), 0.97 (CI 0.92–0.99) and 0.96 (CI 0.86–0.99) for the three scanners. The external validity study found a correlation coefficient for total thigh CSA and total neck CSA of 0.88. Discussion We present a feasible, valid and reliable method for measuring neck muscle CSA on T1-weighted MR brain scans. Larger studies are needed to validate and apply our technique with subjects differing in age, ethnicity and geographical location. PMID:22509305

  10. Memory T Cells Generated by Prior Exposure to Influenza Cross React with the Novel H7N9 Influenza Virus and Confer Protective Heterosubtypic Immunity

    PubMed Central

    McMaster, Sean R.; Gabbard, Jon D.; Koutsonanos, Dimitris G.; Compans, Richard W.; Tripp, Ralph A.; Tompkins, S. Mark; Kohlmeier, Jacob E.

    2015-01-01

    Influenza virus is a source of significant health and economic burden from yearly epidemics and sporadic pandemics. Given the potential for the emerging H7N9 influenza virus to cause severe respiratory infections and the lack of exposure to H7 and N9 influenza viruses in the human population, we aimed to quantify the H7N9 cross-reactive memory T cell reservoir in humans and mice previously exposed to common circulating influenza viruses. We identified significant cross-reactive T cell populations in humans and mice; we also found that cross-reactive memory T cells afforded heterosubtypic protection by reducing morbidity and mortality upon lethal H7N9 challenge. In context with our observation that PR8-primed mice have limited humoral cross-reactivity with H7N9, our data suggest protection from H7N9 challenge is indeed mediated by cross-reactive T cell populations established upon previous priming with another influenza virus. Thus, pre-existing cross-reactive memory T cells may limit disease severity in the event of an H7N9 influenza virus pandemic. PMID:25671696

  11. A VLP Vaccine Induces Broad-Spectrum Cross-Protective Antibody Immunity against H5N1 and H1N1 Subtypes of Influenza A Virus

    PubMed Central

    Wu, Chia-Ying; Yeh, Yi-Chun; Chan, Jia-Tsrong; Yang, Yu-Chih; Yang, Ji-Rong; Liu, Ming-Tsan; Wu, Ho-Sheng; Hsiao, Pei-Wen

    2012-01-01

    The recent threats of influenza epidemics and pandemics have prioritized the development of a universal vaccine that offers protection against a wider variety of influenza infections. Here, we demonstrate a genetically modified virus-like particle (VLP) vaccine, referred to as H5M2eN1-VLP, that increased the antigenic content of NA and induced rapid recall of antibody against HA2 after viral infection. As a result, H5M2eN1-VLP vaccination elicited a broad humoral immune response against multiple viral proteins and caused significant protection against homologous RG-14 (H5N1) and heterologous A/California/07/2009 H1N1 (CA/07) and A/PR/8/34 H1N1 (PR8) viral lethal challenges. Moreover, the N1-VLP (lacking HA) induced production of a strong NA antibody that also conferred significant cross protection against H5N1 and heterologous CA/07 but not PR8, suggesting the protection against N1-serotyped viruses can be extended from avian-origin to CA/07 strain isolated in humans, but not to evolutionally distant strains of human-derived. By comparative vaccine study of an HA-based VLP (H5N1-VLP) and NA-based VLPs, we found that H5N1-VLP vaccination induced specific and strong protective antibodies against the HA1 subunit of H5, thus restricting the breadth of cross-protection. In summary, we present a feasible example of direction of VLP vaccine immunity toward NA and HA2, which resulted in cross protection against both seasonal and pandemic influenza strains, that could form the basis for future design of a better universal vaccine. PMID:22879951

  12. Screening of antimicrobial agents for in vitro radiation protection and mitigation capacity, including those used in supportive care regimens for bone marrow transplant recipients.

    PubMed

    Epperly, Michael W; Franicola, Darcy; Shields, Donna; Rwigema, Jean-Claude; Stone, Brandon; Zhang, Xichen; McBride, William; Georges, George; Wipf, Peter; Greenberger, Joel S

    2010-01-01

    Antibiotic and antifungal agents used in supportive care regimens for bone marrow transplantation recipients contribute to a significant dose-modifying effect of otherwise lethal total body irradiation. To determine whether drugs used in supportive care and other commonly used antibiotics such as tetracycline function as radiation protectors or damage mitigators in vitro, 13 drugs were tested for radiation protection and radiation damage mitigation of 32D cl 3 hematopoietic progenitor cells in clonagenic survival curves in vitro. Antibiotic/Antifungal agents including cilastatin, amikacin, ceftazidine, vancomycin, tetracycline, doxycycline, ciprofloxacin, metronidazole, methacycline, minocycline, meclocycline, oxytetracycline and rolitetracycline were added in 1, 10, or 100 micromolar concentrations to murine interleukin-3-dependent hematopoietic progenitor cell line 32D cl 3 cells either before or after irradiation of 0 to 8 Gy. Control irradiated 32D cl 3 cells showed radiosensitivity comparable to freshly explanted mouse marrow hematopoietic progenitor cells (D(0) 1.1+/-0.1 Gy, N 1.5+/-0.4). Positive control GS-nitroxide JP4-039 (known radiation mitigator) treated 32D cl 3 cells were radioresistant (D(0) 1.2+/-0.1, N 5.8+/-2.4 (p=0.009)). Of the 13 drugs tested, tetracycline was found to be a significant radiation mitigator (D(0) 0.9+/-0.1, N 13.9+/-0.4 (p=0.0027)). Thus, the radiation dose-modifying effect of some antibiotics, but not those currently used in the supportive care (antibiotic/antifungal regimens) for marrow transplant patients, may act as radiation damage mitigators for hematopoietic cells as well as decreasing the growth and inflammatory response to microbial pathogens. PMID:20133970

  13. Cross-Protection of Influenza A Virus Infection by a DNA Aptamer Targeting the PA Endonuclease Domain

    PubMed Central

    Yuan, Shuofeng; Zhang, Naru; Singh, Kailash; Shuai, Huiping; Chu, Hin; Zhou, Jie; Chow, Billy K. C.

    2015-01-01

    Amino acid residues in the N-terminal of the PA subunit (PAN) of the influenza A virus polymerase play critical roles in endonuclease activity, protein stability, and viral RNA (vRNA) promoter binding. In addition, PAN is highly conserved among different subtypes of influenza virus, which suggests PAN to be a desired target in the development of anti-influenza agents. We selected DNA aptamers targeting the intact PA protein or the PAN domain of an H5N1 virus strain using systematic evolution of ligands by exponential enrichment (SELEX). The binding affinities of selected aptamers were measured, followed by an evaluation of in vitro endonuclease inhibitory activity. Next, the antiviral effects of enriched aptamers against influenza A virus infections were examined. A total of three aptamers targeting PA and six aptamers targeting PAN were selected. Our data demonstrated that all three PA-selected aptamers neither inhibited endonuclease activity nor exhibited antiviral efficacy, whereas four of the six PAN-selected aptamers inhibited both endonuclease activity and H5N1 virus infection. Among the four effective aptamers, one exhibited cross-protection against infections of H1N1, H5N1, H7N7, and H7N9 influenza viruses, with a 50% inhibitory concentration (IC50) of around 10 nM. Notably, this aptamer was identified at the 5th round but disappeared after the 10th round of selection, suggesting that the identification and evaluation of aptamers at early rounds of selection may be highly helpful for screening effective aptamers. Overall, our study provides novel insights for screening and developing effective aptamers for use as anti-influenza drugs. PMID:25918143

  14. Evaluation of Cross-Protection of a Lineage 1 West Nile Virus Inactivated Vaccine against Natural Infections from a Virulent Lineage 2 Strain in Horses, under Field Conditions

    PubMed Central

    Chaintoutis, Serafeim C.; Diakakis, Nikolaos; Papanastassopoulou, Maria; Banos, Georgios

    2015-01-01

    Although experimental data regarding cross-protection of horse West Nile virus (WNV) vaccines against lineage 2 infections exist, the cross-protective efficacy of these vaccines under field conditions has not been demonstrated. This study was conducted to evaluate the capability of an inactivated lineage 1 vaccine (Equip WNV) to protect against natural infections from the Nea Santa-Greece-2010 lineage 2 strain. In total, 185 WNV-seronegative horses in Thessaloniki, Greece, were selected during 2 consecutive years (2011 and 2012); 140 were immunized, and 45 were used as controls. Horses were examined for signs compatible with WNV infection. Neutralizing antibody titers against the Greek strain and the PaAn001/France lineage 1 strain were determined in immunized horses. WNV circulation was detected during both years in the study area. It was estimated that 37% and 27% of the horses were infected during 2011 and 2012, respectively. Three control animals developed clinical signs, and the WNV diagnosis was confirmed. Signs related to WNV infection were not observed in the vaccinated animals. The nonvaccinated animals had a 7.58% ± 1.82% higher chance of exhibiting signs than immunized animals (P < 0.05). Neutralizing antibodies raised against both strains in all immunized horses were detectable 1 month after the initial vaccination course. The cross-protective capacity of the lowest titer (1:40) was evident in 19 animals which were subsequently infected and did not exhibit signs. Neutralizing antibodies were detectable until the annual booster, when strong anamnestic responses were observed (geometrical mean titer ratio [GMTR] for lineage 1 of 30.2; GMTR for lineage 2 of 27.5). The results indicate that Equip WNV is capable of inducing cross-protection against natural infections from a virulent lineage 2 WNV strain in horses. PMID:26178384

  15. Neuraminidase-Inhibiting Antibody Is a Correlate of Cross-Protection against Lethal H5N1 Influenza Virus in Ferrets Immunized with Seasonal Influenza Vaccine

    PubMed Central

    Brown, Lorena E.; Barr, Ian G.; Gilbertson, Brad; Lowther, Sue; Kachurin, Anatoly; Kachurina, Olga; Klippel, Jessica; Bodle, Jesse; Pearse, Martin; Middleton, Deborah

    2013-01-01

    In preparing for the threat of a pandemic of avian H5N1 influenza virus, we need to consider the significant delay (4 to 6 months) necessary to produce a strain-matched vaccine. As some degree of cross-reactivity between seasonal influenza vaccines and H5N1 virus has been reported, this was further explored in the ferret model to determine the targets of protective immunity. Ferrets were vaccinated with two intramuscular inoculations of trivalent inactivated split influenza vaccine or subcomponent vaccines, with and without adjuvant, and later challenged with a lethal dose of A/Vietnam/1203/2004 (H5N1) influenza virus. We confirmed that vaccination with seasonal influenza vaccine afforded partial protection against lethal H5N1 challenge and showed that use of either AlPO4 or Iscomatrix adjuvant with the vaccine resulted in complete protection against disease and death. The protection was due exclusively to the H1N1 vaccine component, and although the hemagglutinin contributed to protection, the dominant protective response was targeted toward the neuraminidase (NA) and correlated with sialic acid cleavage-inhibiting antibody titers. Purified heterologous NA formulated with Iscomatrix adjuvant was also protective. These results suggest that adjuvanted seasonal trivalent vaccine could be used as an interim measure to decrease morbidity and mortality from H5N1 prior to the availability of a specific vaccine. The data also highlight that an inducer of cross-protective immunity is the NA, a protein whose levels are not normally monitored in vaccines and whose capacity to induce immunity in recipients is not normally assessed. PMID:23283953

  16. A mechanism for the dynamo terms to sustain closed-flux current, including helicity balance, by driving current which crosses the magnetic field

    SciTech Connect

    Jarboe, T. R.; Nelson, B. A.; Sutherland, D. A.

    2015-07-15

    An analysis of imposed dynamo current drive (IDCD) [T.R. Jarboe et al., Nucl. Fusion 52 083017 (2012)] reveals: (a) current drive on closed flux surfaces seems possible without relaxation, reconnection, or other flux-surface-breaking large events; (b) the scale size of the key physics may be smaller than is often computationally resolved; (c) helicity can be sustained across closed flux; and (d) IDCD current drive is parallel to the current which crosses the magnetic field to produce the current driving force. In addition to agreeing with spheromak data, IDCD agrees with selected tokamak data.

  17. Emerging importance of mismatch repair components including UvrD helicase and their cross-talk with the development of drug resistance in malaria parasite.

    PubMed

    Ahmad, Moaz; Tuteja, Renu

    2014-12-01

    Human malaria is an important parasitic infection responsible for a significant number of deaths worldwide, particularly in tropical and subtropical regions. The recent scenario has worsened mainly because of the emergence of drug-resistant malaria parasites having the potential to spread across the world. Drug-resistant parasites possess a defective mismatch repair (MMR); therefore, it is essential to explore its mechanism in detail to determine the underlying cause. Recently, artemisinin-resistant parasites have been reported to exhibit nonsynonymous single nucleotide polymorphisms in genes involved in MMR pathways such as MutL homolog (MLH) and UvrD. Plasmodium falciparum MLH is an endonuclease required to restore the defective MMR in drug-resistant W2 strain of P. falciparum. Although the role of helicases in eukaryotic MMR has been questioned, the identification and characterization of the UvrD helicase and their cross-talk with MLH in P. falciparum suggests the possible involvement of UvrD in MMR. A comparative genome-wide analysis revealed the presence of the UvrD helicase in Plasmodium species, while it is absent in human host. Therefore, PfUvrD may emerge as a suitable drug target to control malaria. This review study is focused on recent developments in MMR biochemistry, emerging importance of the UvrD helicase, possibility of its involvement in MMR and the emerging cross-talk between MMR components and drug resistance in malaria parasite. PMID:25771870

  18. Method for Calculation of Laminar Heat Transfer in Air Flow Around Cylinders of Arbitrary Cross Section (including Large Temperature Differences and Transpiration Cooling)

    NASA Technical Reports Server (NTRS)

    Eckert, E R; Livingood, John N B

    1953-01-01

    The solution of heat-transfer problems has become vital for many aeronautical applications. The shapes of objects to be cooled can often be approximated by cylinders of various cross sections with flow normal to the axis as, for instance heat transfer on gas-turbine blades and on air foils heated for deicing purposes. A laminar region always exists near the stagnation point of such objects. A method previously presented by E. R. G. Eckert permits the calculation of local heat transfer around the periphery of cylinders of arbitrary cross section in the laminar region for flow of a fluid with constant property values with an accuracy sufficient for engineering purposes. The method is based on exact solutions of the boundary-layer equations for incompressible wedge-type flow and on the postulate that at any point on the cylinder the boundary-layer growth is the same as that on a wedge with comparable flow conditions. This method is extended herein to take into account the influence of large temperature differences between the cylinder wall and the flow as well as the influence of transpiration cooling when the same medium as the outside flow is used as coolant.

  19. CROSS-DISCIPLINARY PHYSICS AND RELATED AREAS OF SCIENCE AND TECHNOLOGY: A new mammalian circadian oscillator model including the cAMP module

    NASA Astrophysics Data System (ADS)

    Wang, Jun-Wei; Zhou, Tian-Shou

    2009-12-01

    In this paper, we develop a new mathematical model for the mammalian circadian clock, which incorporates both transcriptional/translational feedback loops (TTFLs) and a cAMP-mediated feedback loop. The model shows that TTFLs and cAMP signalling cooperatively drive the circadian rhythms. It reproduces typical experimental observations with qualitative similarities, e.g. circadian oscillations in constant darkness and entrainment to light-dark cycles. In addition, it can explain the phenotypes of cAMP-mutant and Rev-erbα-/--mutant mice, and help us make an experimentally-testable prediction: oscillations may be rescued when arrhythmic mice with constitutively low concentrations of cAMP are crossed with Rev-erbα-/- mutant mice. The model enhances our understanding of the mammalian circadian clockwork from the viewpoint of the entire cell.

  20. FUNDAMENTAL AREAS OF PHENOMENOLOGY (INCLUDING APPLICATIONS): Lattice Boltzmann Simulation of the Cross Flow Over a Cantilevered and Longitudinally Vibrating Circular Cylinder

    NASA Astrophysics Data System (ADS)

    Xia, Yong; Lu, De-Tang; Liu, Yang; Xu, You-Sheng

    2009-03-01

    The multiple-relaxation-time lattice Boltzmann method (MRT-LBM) is implemented to numerically simulate the cross flow over a longitudinal vibrating circular cylinder. This research is carried out on a three-dimensional (3D) finite cantilevered cylinder to investigate the effect of forced vibration on the wake characteristics and the 3D effect of a cantilevered cylinder. To meet the accuracy of this method, the present calculation is carried out at a low Reynolds number Re = 100, as well as to make the vibration obvious, we make the vibration strong enough. The calculation results indicate that the vibration has significant influence on the wake characteristics. When the vibrating is big enough, our early works show that the 2D vortex shedding would be locked up by vibration. Contrarily, this phenomenon would not appear in the present 3D case because of the end effect of the cantilevered cylinder.

  1. Genetic analyses of the FRNK motif function of Turnip mosaic virus uncover multiple and potentially interactive pathways of cross-protection.

    PubMed

    Kung, Yi-Jung; Lin, Pin-Chun; Yeh, Shyi-Dong; Hong, Syuan-Fei; Chua, Nam-Hai; Liu, Li-Yu; Lin, Chan-Pin; Huang, Yu-Hsin; Wu, Hui-Wen; Chen, Chin-Chih; Lin, Shih-Shun

    2014-09-01

    Cross-protection triggered by a mild strain of virus acts as a prophylaxis to prevent subsequent infections by related viruses in plants; however, the underling mechanisms are not fully understood. Through mutagenesis, we isolated a mutant strain of Turnip mosaic virus (TuMV), named Tu-GK, that contains an Arg182Lys substitution in helper component-proteinase (HC-Pro(K)) that confers complete cross-protection against infection by a severe strain of TuMV in Nicotiana benthamiana, Arabidopsis thaliana Col-0, and the Arabidopsis dcl2-4/dcl4-1 double mutant defective in DICER-like ribonuclease (DCL)2/DCL4-mediated silencing. Our analyses showed that HC-Pro(K) loses the ability to interfere with microRNA pathways, although it retains a partial capability for RNA silencing suppression triggered by DCL. We further showed that Tu-GK infection triggers strong salicylic acid (SA)-dependent and SA-independent innate immunity responses. Our data suggest that DCL2/4-dependent and -independent RNA silencing pathways are involved, and may crosstalk with basal innate immunity pathways, in host defense and in cross-protection. PMID:24804808

  2. rBCG30-induced immunity and cross-protection against Mycobacterium leprae challenge are enhanced by boosting with the Mycobacterium tuberculosis 30-kilodalton antigen 85B.

    PubMed

    Gillis, Thomas P; Tullius, Michael V; Horwitz, Marcus A

    2014-09-01

    Leprosy remains a major global health problem and typically occurs in regions in which tuberculosis is endemic. Vaccines are needed that protect against both infections and do so better than the suboptimal Mycobacterium bovis BCG vaccine. Here, we evaluated rBCG30, a vaccine previously demonstrated to induce protection superior to that of BCG against Mycobacterium tuberculosis and Mycobacterium bovis challenge in animal models, for efficacy against Mycobacterium leprae challenge in a murine model of leprosy. rBCG30 overexpresses the M. tuberculosis 30-kDa major secretory protein antigen 85B, which is 85% homologous with the M. leprae homolog (r30ML). Mice were sham immunized or immunized intradermally with BCG or rBCG30 and challenged 2.5 months later by injection of viable M. leprae into each hind footpad. After 7 months, vaccine efficacy was assessed by enumerating the M. leprae bacteria per footpad. Both BCG and rBCG30 induced significant protection against M. leprae challenge. In the one experiment in which a comparison between BCG and rBCG30 was feasible, rBCG30 induced significantly greater protection than did BCG. Immunization of mice with purified M. tuberculosis or M. leprae antigen 85B also induced protection against M. leprae challenge but less so than BCG or rBCG30. Notably, boosting rBCG30 with M. tuberculosis antigen 85B significantly enhanced r30ML-specific immune responses, substantially more so than boosting BCG, and significantly augmented protection against M. leprae challenge. Thus, rBCG30, a vaccine that induces improved protection against M. tuberculosis, induces cross-protection against M. leprae that is comparable or potentially superior to that induced by BCG, and boosting rBCG30 with antigen 85B further enhances immune responses and protective efficacy. PMID:25001602

  3. A Vibrio cholerae ghost-based subunit vaccine induces cross-protective chlamydial immunity that is enhanced by CTA2B, the nontoxic derivative of cholera toxin

    PubMed Central

    Ekong, Eno E.; Okenu, Daniel N.; Mania-Pramanik, Jayanti; He, Qing; Igietseme, Joseph U.; Ananaba, Godwin A.; Lyn, Deborah; Black, Carolyn; Eko, Francis O.

    2011-01-01

    The Vibrio cholerae ghost (rVCG) platform is an effective carrier and delivery system for designing efficacious Chlamydia vaccines. We investigated whether CTA2B, the nontoxic derivative of cholera toxin, can augment protective immunity conferred by an rVCG-based chlamydial vaccine and enhance cross-protection against heterologous chlamydial strains. An rVCG vaccine coexpressing chlamydial major outer membrane protein and CTA2B was genetically constructed and antigens were targeted to the inner membrane of V. cholerae before ghost production by gene E-mediated lysis. Effective immunomodulation by CTA2B was demonstrated by the ability of the vaccine construct to enhance the activation and maturation of dendritic cells in vitro. Also, C57BL/6 mice immunized via mucosal and systemic routes showed increased specific mucosal and systemic antibody and T-helper type-1 (Th1) responses, irrespective of the route. The enhanced production of IFN-γ, but not IL-4 by genital mucosal and splenic T cells, indicated a predominantly Th1 response. Clearance of the Chlamydia muridarum vaginal infection was significantly enhanced by codelivery of the vaccine with CTA2B, with the intravaginal route showing a moderate advantage. These results indicate that the rVCG-based vaccine is capable of inducing cross-protection against heterologous chlamydial serovars and that incorporation of mucosal adjuvants, such as CTA2B in the rVCG delivery platform, may enhance protective immunity. PMID:19040663

  4. Inactivated porcine reproductive and respiratory syndrome virus vaccine adjuvanted with Montanide™ Gel 01 ST elicits virus-specific cross-protective inter-genotypic response in piglets.

    PubMed

    Tabynov, Kairat; Sansyzbay, Abylay; Tulemissova, Zhanara; Tabynov, Kaissar; Dhakal, Santosh; Samoltyrova, Aigul; Renukaradhya, Gourapura J; Mambetaliyev, Muratbay

    2016-08-30

    The efficacy of a novel BEI-inactivated porcine reproductive and respiratory syndrome virus (PRRSV) candidate vaccine in pigs, developed at RIBSP Republic of Kazakhstan and delivered with an adjuvant Montanide™ Gel 01 ST (D/KV/ADJ) was compared with a commercial killed PRRSV vaccine (NVDC-JXA1, C/KV/ADJ) used widely in swine herds of the Republic of Kazakhstan. Clinical parameters (body temperature and respiratory disease scores), virological and immunological profiles [ELISA and virus neutralizing (VN) antibody titers], macroscopic lung lesions and viral load in the lungs (quantitative real-time PCR and cell culture assay) were assessed in vaccinated and both genotype 1 and 2 PRRSV challenged pigs. Our results showed that the commercial vaccine failed to protect pigs adequately against the clinical disease, viremia and lung lesions caused by the challenged field isolates, Kazakh strains of PRRSV type 1 and type 2 genotypes. In contrast, clinical protection, absence of viremia and lung lesions in D/KV/ADJ vaccinated pigs was associated with generation of VN antibodies in both homologous vaccine strain LKZ/2010 (PRRSV type 2) and a heterogeneous type 1 PRRSV strain (CM/08) challenged pigs. Thus, our data indicated the induction of cross-protective VN antibodies by D/KV/ADJ vaccine, and importantly demonstrated that an inactivated PRRSV vaccine could also induce cross-protective response across the viral genotype. PMID:27527768

  5. The kinase mTOR modulates the antibody response to provide cross-protective immunity to lethal infection with influenza virus.

    PubMed

    Keating, Rachael; Hertz, Tomer; Wehenkel, Marie; Harris, Tarsha L; Edwards, Benjamin A; McClaren, Jennifer L; Brown, Scott A; Surman, Sherri; Wilson, Zachary S; Bradley, Philip; Hurwitz, Julia; Chi, Hongbo; Doherty, Peter C; Thomas, Paul G; McGargill, Maureen A

    2013-12-01

    Highly pathogenic avian influenza viruses pose a continuing global threat. Current vaccines will not protect against newly evolved pandemic viruses. The creation of 'universal' vaccines has been unsuccessful because the immunological mechanisms that promote heterosubtypic immunity are incompletely defined. We found here that rapamycin, an immunosuppressive drug that inhibits the kinase mTOR, promoted cross-strain protection against lethal infection with influenza virus of various subtypes when administered during immunization with influenza virus subtype H3N2. Rapamycin reduced the formation of germinal centers and inhibited class switching in B cells, which yielded a unique repertoire of antibodies that mediated heterosubtypic protection. Our data established a requirement for the mTORC1 complex in B cell class switching and demonstrated that rapamycin skewed the antibody response away from high-affinity variant epitopes and targeted more conserved elements of hemagglutinin. Our findings have implications for the design of a vaccine against influenza virus. PMID:24141387

  6. Cross-linking of anaplasma marginale outer membrane proteins enhances immunogenicity, but is not required for protection from challenge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bacterial outer membrane proteins are the primary targets of a protective immune response. The specific characteristics of outer membrane-based immunogens, in terms of antigen content and context that are required for protective immunity remain unknown for a wide variety of bacterial pathogens. Usin...

  7. Heterologous protection elicited by candidate monomeric recombinant HIV-1 gp120 vaccine in the absence of cross neutralising antibodies in a macaque model

    PubMed Central

    2012-01-01

    Background Current data suggest that an efficacious human immunodeficiency virus type 1 (HIV-1) vaccine should elicit both adaptive humoral and cell mediated immune responses. Such a vaccine will also need to protect against infection from a range of heterologous viral variants. Here we have developed a simian-human immunodeficiency virus (SHIV) based model in cynomolgus macaques to investigate the breadth of protection conferred by HIV-1W61D recombinant gp120 vaccination against SHIVsbg and SHIVSF33 challenge, and to identify correlates of protection. Results High titres of anti-envelope antibodies were detected in all vaccinees. The antibodies reacted with both the homologous HIV-1W61D and heterologous HIV-1IIIB envelope rgp120 which has an identical sequence to the SHIVsbg challenge virus. Significant titres of virus neutralising antibodies were detected against SHIVW61D expressing an envelope homologous with the vaccine, but only limited cross neutralisation against SHIVsbg, SHIV-4 and SHIVSF33 was observed. Protection against SHIVsbg infection was observed in vaccinated animals but none was observed against SHIVSF33 challenge. Transfer of immune sera from vaccinated macaques to naive recipients did not confer protection against SHIVsbg challenge. In a follow-up study, T cell proliferative responses detected after immunisation with the same vaccine against a single peptide present in the second conserved region 2 of HIV-1 W61D and HIV-1 IIIB gp120, but not SF33 gp120. Conclusions Following extended vaccination with a HIV-1 rgp120 vaccine, protection was observed against heterologous virus challenge with SHIVsbg, but not SHIVSF33. Protection did not correlate with serological responses generated by vaccination, but might be associated with T cell proliferative responses against an epitope in the second constant region of HIV-1 gp120. Broader protection may be obtained with recombinant HIV-1 envelope based vaccines formulated with adjuvants that generate

  8. o-nitrobenzyl photolabile protecting groups with red-shifted absorption: syntheses and uncaging cross-sections for one- and two-photon excitation.

    PubMed

    Aujard, Isabelle; Benbrahim, Chouaha; Gouget, Marine; Ruel, Odile; Baudin, Jean-Bernard; Neveu, Pierre; Jullien, Ludovic

    2006-09-01

    We evaluated the o-nitrobenzyl platform for designing photolabile protecting groups with red-shifted absorption that could be photolyzed upon one- and two-photon excitation. Several synthetic pathways to build different conjugated o-nitrobenzyl backbones, as well as to vary the benzylic position, are reported. Relative to the reference 4,5-dimethoxy-2-nitrobenzyl group, several o-nitrobenzyl derivatives exhibit a large and red-shifted one-photon absorption within the near-UV range. Uncaging after one-photon excitation was studied by measuring UV-visible absorption and steady-state fluorescence emission on model caged ethers and esters. In the whole series investigated, the caged substrates were released cleanly upon photolysis. Quantum yields of uncaging after one-photon absorption lie within the 0.1-1 % range. We observed that these drop as the maximum wavelength absorption of the o-nitrobenzyl protecting group is increased. A new method based on fluorescence correlation spectroscopy (FCS) after two-photon excitation was used to measure the action uncaging cross section for two-photon excitation. The series of o-nitrobenzyl caged fluorescent coumarins investigated exhibit values within the 0.1-0.01 Goeppert-Mayer (GM) range. Such results are in line with the low quantum yields of uncaging associated with cross-sections of 1-50 GM for two-photon absorption. Although the cross-sections for one- and two-photon absorption of o-nitrobenzyl photolabile protecting groups can be readily improved, we emphasize the difficulty in enlarging the corresponding action uncaging cross-sections in view of the observed trend of their quantum yield of uncaging. PMID:16763952

  9. Impact of IgM Antibodies on Cross-Protection against Pneumococcal Serogroups 6 and 19 after Immunization with 7-Valent Pneumococcal Conjugate Vaccine in Children.

    PubMed

    Cho, Hye-Kyung; Park, In Ho; Burton, Robert L; Kim, Kyung-Hyo

    2016-06-01

    Although it is well known that pneumococcal conjugate vaccines provide cross-protection against some vaccine-related serotypes, these mechanisms are still unclear. This study was performed to investigate the role of cross-protective IgM antibodies against vaccine-related serotypes 6A, 6C, and 19A induced in children aged 12-23 months after immunization with 7-valent pneumococcal conjugate vaccine (PCV7). We obtained serum samples from 18 Korean children aged 12-23 months after a PCV7 booster immunization. The serum IgG and IgM concentrations of serotypes 6B and 19F were measured by enzyme-linked immunosorbent assay (ELISA) in serum. The opsonic indices (OIs) against vaccine serotypes 6B and 19F and vaccine-related serotypes 6A, 6C, and 19A were determined by an opsonophagocytic killing assay (OPA) in IgM-depleted and control serum. Both IgG and IgM antibodies in ELISA and opsonic indices in OPA against serotypes 6B and 19F were demonstrated in the immune serum. IgM depletion decreased the OIs against vaccine serotypes 6B (geometric means of OIs (GMIs) of 3,009 vs. 1,396, 38% reduction) and 19F (1,117 vs. 750, 36% reduction). In addition, IgM depletion markedly decreased the OIs against vaccine-related serotypes 6A (GMIs of 961 vs. 329, 70% reduction), 6C (432 vs. 185, 72% reduction), and 19A (301 vs. 166, 58% reduction). The booster immunization PCV7 induced protective antibodies in the form of both IgG and IgM isotypes. IgM antibodies contributed to eliciting cross-protection against vaccine-related serotypes as well as against vaccine serotypes. PMID:27247505

  10. Impact of IgM Antibodies on Cross-Protection against Pneumococcal Serogroups 6 and 19 after Immunization with 7-Valent Pneumococcal Conjugate Vaccine in Children

    PubMed Central

    Burton, Robert L.

    2016-01-01

    Although it is well known that pneumococcal conjugate vaccines provide cross-protection against some vaccine-related serotypes, these mechanisms are still unclear. This study was performed to investigate the role of cross-protective IgM antibodies against vaccine-related serotypes 6A, 6C, and 19A induced in children aged 12-23 months after immunization with 7-valent pneumococcal conjugate vaccine (PCV7). We obtained serum samples from 18 Korean children aged 12-23 months after a PCV7 booster immunization. The serum IgG and IgM concentrations of serotypes 6B and 19F were measured by enzyme-linked immunosorbent assay (ELISA) in serum. The opsonic indices (OIs) against vaccine serotypes 6B and 19F and vaccine-related serotypes 6A, 6C, and 19A were determined by an opsonophagocytic killing assay (OPA) in IgM-depleted and control serum. Both IgG and IgM antibodies in ELISA and opsonic indices in OPA against serotypes 6B and 19F were demonstrated in the immune serum. IgM depletion decreased the OIs against vaccine serotypes 6B (geometric means of OIs (GMIs) of 3,009 vs. 1,396, 38% reduction) and 19F (1,117 vs. 750, 36% reduction). In addition, IgM depletion markedly decreased the OIs against vaccine-related serotypes 6A (GMIs of 961 vs. 329, 70% reduction), 6C (432 vs. 185, 72% reduction), and 19A (301 vs. 166, 58% reduction). The booster immunization PCV7 induced protective antibodies in the form of both IgG and IgM isotypes. IgM antibodies contributed to eliciting cross-protection against vaccine-related serotypes as well as against vaccine serotypes. PMID:27247505

  11. A Chimeric 18L1-45RG1 Virus-Like Particle Vaccine Cross-Protects against Oncogenic Alpha-7 Human Papillomavirus Types

    PubMed Central

    Huber, Bettina; Schellenbacher, Christina; Jindra, Christoph; Fink, Dieter; Shafti-Keramat, Saeed; Kirnbauer, Reinhard

    2015-01-01

    Persistent infection with oncogenic human papillomaviruses (HPV) types causes all cervical and a subset of other anogenital and oropharyngeal carcinomas. Four high-risk (hr) mucosal types HPV16, 18, 45, or 59 cause almost all cervical adenocarcinomas (AC), a subset of cervical cancer (CxC). Although the incidence of cervical squamous cell carcinoma (SCC) has dramatically decreased following introduction of Papanicolaou (PAP) screening, the proportion of AC has relatively increased. Cervical SCC arise mainly from the ectocervix, whereas AC originate primarily from the endocervical canal, which is less accessible to obtain viable PAP smears. Licensed (bivalent and quadrivalent) HPV vaccines comprise virus-like particles (VLP) of the most important hr HPV16 and 18, self-assembled from the major capsid protein L1. Due to mainly type-restricted efficacy, both vaccines do not target 13 additional hr mucosal types causing 30% of CxC. The papillomavirus genus alpha species 7 (α7) includes a group of hr types of which HPV18, 45, 59 are proportionally overrepresented in cervical AC and only partially (HPV18) targeted by current vaccines. To target these types, we generated a chimeric vaccine antigen that consists of a cross-neutralizing epitope (homologue of HPV16 RG1) of the L2 minor capsid protein of HPV45 genetically inserted into a surface loop of HPV18 L1 VLP (18L1-45RG1). Vaccination of NZW rabbits with 18L1-45RG1 VLP plus alum-MPL adjuvant induced high-titer neutralizing antibodies against homologous HPV18, that cross-neutralized non-cognate hr α7 types HPV39, 45, 68, but not HPV59, and low risk HPV70 in vitro, and induced a robust L1-specific cellular immune response. Passive immunization protected mice against experimental vaginal challenge with pseudovirions of HPV18, 39, 45 and 68, but not HPV59 or the distantly related α9 type HPV16. 18L1-45RG1 VLP might be combined with our previously described 16L1-16RG1 VLP to develop a second generation bivalent vaccine

  12. ASCORBATE PEROXIDASE6 protects Arabidopsis desiccating and germinating seeds from stress and mediates cross talk between reactive oxygen species, abscisic acid, and auxin.

    PubMed

    Chen, Changming; Letnik, Ilya; Hacham, Yael; Dobrev, Petre; Ben-Daniel, Bat-Hen; Vanková, Radomíra; Amir, Rachel; Miller, Gad

    2014-09-01

    A seed's ability to properly germinate largely depends on its oxidative poise. The level of reactive oxygen species (ROS) in Arabidopsis (Arabidopsis thaliana) is controlled by a large gene network, which includes the gene coding for the hydrogen peroxide-scavenging enzyme, cytosolic ASCORBATE PEROXIDASE6 (APX6), yet its specific function has remained unknown. In this study, we show that seeds lacking APX6 accumulate higher levels of ROS, exhibit increased oxidative damage, and display reduced germination on soil under control conditions and that these effects are further exacerbated under osmotic, salt, or heat stress. In addition, ripening APX6-deficient seeds exposed to heat stress displayed reduced germination vigor. This, together with the increased abundance of APX6 during late stages of maturation, indicates that APX6 activity is critical for the maturation-drying phase. Metabolic profiling revealed an altered activity of the tricarboxylic acid cycle, changes in amino acid levels, and elevated metabolism of abscisic acid (ABA) and auxin in drying apx6 mutant seeds. Further germination assays showed an impaired response of the apx6 mutants to ABA and to indole-3-acetic acid. Relative suppression of abscisic acid insensitive3 (ABI3) and ABI5 expression, two of the major ABA signaling downstream components controlling dormancy, suggested that an alternative signaling route inhibiting germination was activated. Thus, our study uncovered a new role for APX6, in protecting mature desiccating and germinating seeds from excessive oxidative damage, and suggested that APX6 modulate the ROS signal cross talk with hormone signals to properly execute the germination program in Arabidopsis. PMID:25049361

  13. ASCORBATE PEROXIDASE6 Protects Arabidopsis Desiccating and Germinating Seeds from Stress and Mediates Cross Talk between Reactive Oxygen Species, Abscisic Acid, and Auxin1[C][W][OPEN

    PubMed Central

    Chen, Changming; Letnik, Ilya; Hacham, Yael; Dobrev, Petre; Ben-Daniel, Bat-Hen; Vanková, Radomíra; Amir, Rachel; Miller, Gad

    2014-01-01

    A seed’s ability to properly germinate largely depends on its oxidative poise. The level of reactive oxygen species (ROS) in Arabidopsis (Arabidopsis thaliana) is controlled by a large gene network, which includes the gene coding for the hydrogen peroxide-scavenging enzyme, cytosolic ASCORBATE PEROXIDASE6 (APX6), yet its specific function has remained unknown. In this study, we show that seeds lacking APX6 accumulate higher levels of ROS, exhibit increased oxidative damage, and display reduced germination on soil under control conditions and that these effects are further exacerbated under osmotic, salt, or heat stress. In addition, ripening APX6-deficient seeds exposed to heat stress displayed reduced germination vigor. This, together with the increased abundance of APX6 during late stages of maturation, indicates that APX6 activity is critical for the maturation-drying phase. Metabolic profiling revealed an altered activity of the tricarboxylic acid cycle, changes in amino acid levels, and elevated metabolism of abscisic acid (ABA) and auxin in drying apx6 mutant seeds. Further germination assays showed an impaired response of the apx6 mutants to ABA and to indole-3-acetic acid. Relative suppression of abscisic acid insensitive3 (ABI3) and ABI5 expression, two of the major ABA signaling downstream components controlling dormancy, suggested that an alternative signaling route inhibiting germination was activated. Thus, our study uncovered a new role for APX6, in protecting mature desiccating and germinating seeds from excessive oxidative damage, and suggested that APX6 modulate the ROS signal cross talk with hormone signals to properly execute the germination program in Arabidopsis. PMID:25049361

  14. Hydrogel microspheres for stabilization of an antioxidant enzyme: effect of emulsion cross-linking of a dual polysaccharide system on the protection of enzyme activity.

    PubMed

    Tang, Deh-Wei; Yu, Shu-Huei; Wu, Wen-Shin; Hsieh, Hao-Ying; Tsai, Yi-Chin; Mi, Fwu-Long

    2014-01-01

    Catalase is an antioxidant enzyme abundant in natural resources. However, the enzyme is usually inactivated by gastric acid and digestive enzymes after oral ingestion. In this study, carboxymethyl chitosan (CM-chitosan) and hyaluronic acid (HA) conjugate hydrogel microspheres have been prepared by an emulsion cross-linking technique to retain the activity of catalase in simulated gastrointestinal (GI) fluids. Cross-linking reduced the swelling capability and increased the resistance toward hyaluronidase digestion of prepared HA-CM-chitosan hydrogel microspheres. Catalase entrapped in the hydrogel microspheres exhibited superior stability over a wide pH range (pH 2.0 and 6.0-8.0) as compared to the native enzyme. The entrapped catalase was also protected against degradation by digestive enzymes. Following the treatments, the catalase-loaded microspheres, in contrast to native catalase, could effectively decrease the intracellular H2O2 level and protect HT-29 colonic epithelial cells against H2O2-induced oxidative damage to preserve cell viability. These results suggested that the HA-CM-chitosan hydrogel microspheres can be used for entrapment, protection and intestinal delivery of catalase for H2O2 scavenging. PMID:24055882

  15. Interspecies difference in placement of developing teeth and its relationship with cross-sectional geometry of the mandibular symphysis in four primate species including modern humans.

    PubMed

    Fukase, Hitoshi

    2012-02-01

    The form of the anthropoid mandibular symphysis has recently been addressed in association with spatial requirements for the forming anterior teeth. To evaluate potential relationships between the symphyseal shape and teeth further, the growth patterns of the symphyseal region and the positioning of the tooth crypts were examined using CT data, comparing four primate species (modern humans, chimpanzees, Japanese monkeys, and hamadryas baboons) with varied symphyseal curvature and tooth size. First, results showed that interspecies differences in overall mandibular shape including symphyseal inclination and bicanine width are consistently expressed throughout postnatal ontogeny, although local symphyseal configurations related to the superior transverse torus (STT) tended to change considerably during growth in chimpanzees. Second, the four species were found to exhibit differentiated formation positions of the incisor and canine crypts. In particular, I2 developed between I1 and C in humans with a broad bicanine space and small teeth, whereas it was positioned posterior to I1 and above C in the cercopithecines with an extremely narrow bicanine space. In chimpanzees, despite the large bicanine width, I1 and I2 grew with a large antero-posterior overlap owing to their large size. These results indicate that the dental positioning is determined in concert with the size balance of the available mandibular space and forming teeth. Finally, the positions/contours of I2 crypt were shown to correspond strongly with the STT across the taxa. This suggests that interspecies differences in symphyseal shape should be interpreted partially by the species-specific positional relationships of the developing anterior teeth. PMID:22120684

  16. Cross-Reactive, Cell-Mediated Immunity and Protection of Chickens from Lethal H5N1 Influenza Virus Infection in Hong Kong Poultry Markets

    PubMed Central

    Seo, Sang Heui; Webster, Robert G.

    2001-01-01

    In 1997, avian H5N1 influenza virus transmitted from chickens to humans resulted in 18 confirmed infections. Despite harboring lethal H5N1 influenza viruses, most chickens in the Hong Kong poultry markets showed no disease signs. At this time, H9N2 influenza viruses were cocirculating in the markets. We investigated the role of H9N2 influenza viruses in protecting chickens from lethal H5N1 influenza virus infections. Sera from chickens infected with an H9N2 influenza virus did not cross-react with an H5N1 influenza virus in neutralization or hemagglutination inhibition assays. Most chickens primed with an H9N2 influenza virus 3 to 70 days earlier survived the lethal challenge of an H5N1 influenza virus, but infected birds shed H5N1 influenza virus in their feces. Adoptive transfer of T lymphocytes or CD8+ T cells from inbred chickens (B2/B2) infected with an H9N2 influenza virus to naive inbred chickens (B2/B2) protected them from lethal H5N1 influenza virus. In vitro cytotoxicity assays showed that T lymphocytes or CD8+ T cells from chickens infected with an H9N2 influenza virus recognized target cells infected with either an H5N1 or H9N2 influenza virus in a dose-dependent manner. Our findings indicate that cross-reactive cellular immunity induced by H9N2 influenza viruses protected chickens from lethal infection with H5N1 influenza viruses in the Hong Kong markets in 1997 but permitted virus shedding in the feces. Our findings are the first to suggest that cross-reactive cellular immunity can change the outcome of avian influenza virus infection in birds in live markets and create a situation for the perpetuation of H5N1 influenza viruses. PMID:11222674

  17. Adjuvanted poly(lactic-co-glycolic) acid nanoparticle-entrapped inactivated porcine reproductive and respiratory syndrome virus vaccine elicits cross-protective immune response in pigs

    PubMed Central

    Binjawadagi, Basavaraj; Dwivedi, Varun; Manickam, Cordelia; Ouyang, Kang; Wu, Yun; Lee, Ly James; Torrelles, Jordi B; Renukaradhya, Gourapura J

    2014-01-01

    Porcine reproductive and respiratory syndrome (PRRS), caused by the PRRS virus (PRRSV), is an economically devastating disease, causing daily losses of approximately $3 million to the US pork industry. Current vaccines have failed to completely prevent PRRS outbreaks. Recently, we have shown that poly(lactic-co-glycolic) acid (PLGA) nanoparticle-entrapped inactivated PRRSV vaccine (NP-KAg) induces a cross-protective immune response in pigs. To further improve its cross-protective efficacy, the NP-KAg vaccine formulation was slightly modified, and pigs were coadministered the vaccine twice intranasally with a potent adjuvant: Mycobacterium tuberculosis whole-cell lysate. In vaccinated virulent heterologous PRRSV-challenged pigs, the immune correlates in the blood were as follows: 1) enhanced PRRSV-specific antibody response with enhanced avidity of both immunoglobulin (Ig)-G and IgA isotypes, associated with augmented virus-neutralizing antibody titers; 2) comparable and increased levels of virus-specific IgG1 and IgG2 antibody subtypes and production of high levels of both T-helper (Th)-1 and Th2 cytokines, indicative of a balanced Th1–Th2 response; 3) suppressed immunosuppressive cytokine response; 4) increased frequency of interferon-γ+ lymphocyte subsets and expanded population of antigen-presenting cells; and most importantly 5) complete clearance of detectable replicating challenged heterologous PRRSV and close to threefold reduction in viral ribonucleic acid load detected in the blood. In conclusion, intranasal delivery of adjuvanted NP-KAg vaccine formulation to growing pigs elicited a broadly cross-protective immune response, showing the potential of this innovative vaccination strategy to prevent PRRS outbreaks in pigs. A similar approach to control other respiratory diseases in food animals and humans appears to be feasible. PMID:24493925

  18. Characterization of a novel citrus tristeza virus genotype within three cross-protecting source GFMS12 sub-isolates in South Africa by means of Illumina sequencing.

    PubMed

    Zablocki, Olivier; Pietersen, Gerhard

    2014-08-01

    Tristeza disease (caused by citrus tristeza virus, CTV) is currently controlled in South Africa by means of cross-protection. In this study, we characterized the CTV populations of three grapefruit mild strain 12 (GFMS12) single-aphid-transmission-derived sub-isolates at the whole-genome level using Illumina sequencing technology. A novel South African isolate (CT-ZA3, of the T68 genotype) was shown to be the dominant genotype in all GFMS12 sub-isolates tested, along with reads unique to various other genotypes occurring as minor components. Uncertainty remains as to the significance of these minor components. PMID:24623089

  19. Heterosubtypic Neutralizing Monoclonal Antibodies Cross-Protective against H5N1 and H1N1 Recovered from Human IgM+ Memory B Cells

    PubMed Central

    Throsby, Mark; van den Brink, Edward; Jongeneelen, Mandy; Poon, Leo L. M.; Alard, Philippe; Cornelissen, Lisette; Bakker, Arjen; Cox, Freek; van Deventer, Els; Guan, Yi; Cinatl, Jindrich; ter Meulen, Jan; Lasters, Ignace; Carsetti, Rita; Peiris, Malik; de Kruif, John; Goudsmit, Jaap

    2008-01-01

    Background The hemagglutinin (HA) glycoprotein is the principal target of protective humoral immune responses to influenza virus infections but such antibody responses only provide efficient protection against a narrow spectrum of HA antigenic variants within a given virus subtype. Avian influenza viruses such as H5N1 are currently panzootic and pose a pandemic threat. These viruses are antigenically diverse and protective strategies need to cross protect against diverse viral clades. Furthermore, there are 16 different HA subtypes and no certainty the next pandemic will be caused by an H5 subtype, thus it is important to develop prophylactic and therapeutic interventions that provide heterosubtypic protection. Methods and Findings Here we describe a panel of 13 monoclonal antibodies (mAbs) recovered from combinatorial display libraries that were constructed from human IgM+ memory B cells of recent (seasonal) influenza vaccinees. The mAbs have broad heterosubtypic neutralizing activity against antigenically diverse H1, H2, H5, H6, H8 and H9 influenza subtypes. Restriction to variable heavy chain gene IGHV1-69 in the high affinity mAb panel was associated with binding to a conserved hydrophobic pocket in the stem domain of HA. The most potent antibody (CR6261) was protective in mice when given before and after lethal H5N1 or H1N1 challenge. Conclusions The human monoclonal CR6261 described in this study could be developed for use as a broad spectrum agent for prophylaxis or treatment of human or avian influenza infections without prior strain characterization. Moreover, the CR6261 epitope could be applied in targeted vaccine strategies or in the design of novel antivirals. Finally our approach of screening the IgM+ memory repertoire could be applied to identify conserved and functionally relevant targets on other rapidly evolving pathogens. PMID:19079604

  20. Evaluation of the Cross-Protective Efficacy of a Chimeric Porcine Reproductive and Respiratory Syndrome Virus Constructed Based on Two Field Strains

    PubMed Central

    Shabir, Nadeem; Khatun, Amina; Nazki, Salik; Kim, Bumseok; Choi, Eun-Jin; Sun, Dong; Yoon, Kyoung-Jin; Kim, Won-Il

    2016-01-01

    One of the major hurdles to porcine reproductive and respiratory syndrome (PRRS) vaccinology is the limited or no cross-protection conferred by current vaccines. To overcome this challenge, a PRRS chimeric virus (CV) was constructed using an FL12-based cDNA infectious clone in which open reading frames (ORFs) 3–4 and ORFs 5–6 were replaced with the two Korean field isolates K08-1054 and K07-2273,respectively. This virus was evaluated as a vaccine candidate to provide simultaneous protection against two genetically distinct PRRS virus (PRRSV) strains. Thirty PRRS-negative three-week-old pigs were divided into five groups and vaccinated with CV, K08-1054, K07-2273, VR-2332, or a mock inoculum. At 25 days post-vaccination (dpv), the pigs in each group were divided further into two groups and challenged with either K08-1054 or K07-2273. All of the pigs were observed until 42 dpv and were euthanized for pathological evaluation. Overall, the CV-vaccinated group exhibited higher levels of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and interleukin-12 (IL-12) expression and of serum virus-neutralizing antibodies compared with the other groups after vaccination and also demonstrated better protection levels against both viruses compared with the challenge control group. Based on these results, it was concluded that CV might be an effective vaccine model that can confer a broader range of cross-protection to various PRRSV strains. PMID:27556483

  1. Evaluation of the Cross-Protective Efficacy of a Chimeric Porcine Reproductive and Respiratory Syndrome Virus Constructed Based on Two Field Strains.

    PubMed

    Shabir, Nadeem; Khatun, Amina; Nazki, Salik; Kim, Bumseok; Choi, Eun-Jin; Sun, Dong; Yoon, Kyoung-Jin; Kim, Won-Il

    2016-01-01

    One of the major hurdles to porcine reproductive and respiratory syndrome (PRRS) vaccinology is the limited or no cross-protection conferred by current vaccines. To overcome this challenge, a PRRS chimeric virus (CV) was constructed using an FL12-based cDNA infectious clone in which open reading frames (ORFs) 3-4 and ORFs 5-6 were replaced with the two Korean field isolates K08-1054 and K07-2273,respectively. This virus was evaluated as a vaccine candidate to provide simultaneous protection against two genetically distinct PRRS virus (PRRSV) strains. Thirty PRRS-negative three-week-old pigs were divided into five groups and vaccinated with CV, K08-1054, K07-2273, VR-2332, or a mock inoculum. At 25 days post-vaccination (dpv), the pigs in each group were divided further into two groups and challenged with either K08-1054 or K07-2273. All of the pigs were observed until 42 dpv and were euthanized for pathological evaluation. Overall, the CV-vaccinated group exhibited higher levels of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and interleukin-12 (IL-12) expression and of serum virus-neutralizing antibodies compared with the other groups after vaccination and also demonstrated better protection levels against both viruses compared with the challenge control group. Based on these results, it was concluded that CV might be an effective vaccine model that can confer a broader range of cross-protection to various PRRSV strains. PMID:27556483

  2. Assessment of personal protective equipment use among farmers in eastern North Carolina: a cross-sectional study.

    PubMed

    Kearney, Gregory D; Xu, Xiaohui; Balanay, Jo Anne G; Allen, Daniel L; Rafferty, Ann P

    2015-01-01

    Agriculture consistently ranks among the top hazardous occupations, accounting for a significant number of injuries and fatalities in the workplace. Eastern North Carolina has a significant number of small, independent, family-run, owned, and operated farms. However, little is known about perception, behavior, training, accessibility, or purchasing personal protective equipment (PPE) for safety among farmers in the region. In this study, telephone interviews were conducted among participating farmers between March and June 2012 (N = 129). Univariate and bivariate analyses were conducted to examine associations between PPE behavior and workplace hazards, health-related concerns, and wearing and purchasing PPE. Findings indicated that personal behavior of wearing hearing protection devices (HPDs) and protection from the sun among farmers was low. However, a relatively high percentage of farmers reported wearing PPE when working with agricultural chemicals. Most farmers received training from agricultural extension offices. The findings indicate that, in general, farmers are well aware of the risks associated with occupational hazards and recognize concern for health and safety protection in the workplace. Transitioning these concerns into preventative action remains a challenge and priority for the agricultural health professional. PMID:25635742

  3. Informing Food Protection Education: A Project to Define and Classify Resources for a Cross-Disciplinary Expert Community

    ERIC Educational Resources Information Center

    Schenck-Hamlin, Donna; Pierquet, Jennifer; McClellan, Chuck

    2011-01-01

    In the wake of the September 2001 attacks, the U.S. government founded the Department of Homeland Security (DHS) with responsibility to develop a National Infrastructure Protection Plan for securing critical infrastructures and key resources. DHS established interdisciplinary networks of academic expertise administered through Centers of…

  4. Cross protection against fowl cholera disease with the use of recombinant Pasteurella multocida FHAB2 peptides vaccine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It has been demonstrated that fhaB2 (filamentous hemagglutinin) is an important virulence factor for P. multocida in development of fowl cholera disease and that recombinant FHAB2 peptides derived from P. multocida, Pm-1059, protect turkeys against Pm-1059 challenge. To test the hypothesis that rFHA...

  5. Toll-Like Receptor 2- and 6-Mediated Stimulation by Macrophage-Activating Lipopeptide 2 Induces Lipopolysaccharide (LPS) Cross Tolerance in Mice, Which Results in Protection from Tumor Necrosis Factor Alpha but in Only Partial Protection from Lethal LPS Doses

    PubMed Central

    Deiters, Ursula; Gumenscheimer, Marina; Galanos, Chris; Mühlradt, Peter F.

    2003-01-01

    Patients or experimental animals previously exposed to lipopolysaccharide (LPS) become tolerant to further LPS challenge. We investigated the potential of the macrophage-activating lipopeptide 2 (MALP-2) to induce in vivo cross tolerance to tumor necrosis factor alpha (TNF-α) and LPS. MALP-2-induced tolerance could be of practical interest, as MALP-2 proved much less pyrogenic in rabbits than LPS. Whereas LPS signals via Toll-like receptor 4 (TLR4), MALP-2 uses TLR2 and TLR6. LPS-mediated cytokine release was studied in mice pretreated with intraperitoneal injections of MALP-2. No biologically active TNF-α could be detected in the serum of MALP-2-treated animals when challenged with LPS 24 or 72 h later, whereas suppression of LPS-dependent interleukin (IL)-6 lasted for only 24 h. Protection from lethal TNF-α shock was studied in galactosamine-treated mice. Dose dependently, MALP-2 prevented death from lethal TNF-α doses in TLR4−/− but not in TLR2−/− mice, with protection lasting from 5 to 24 h. To assay protection from LPS, mice were pretreated with MALP-2 doses of up to 10 μg. Five and 24 h later, the animals were simultaneously sensitized and challenged by intravenous coinjection of galactosamine and a lethal dose of 50 ng of LPS. There was only limited protection (four of seven mice survived) when mice were challenged 5 h after MALP-2 pretreatment, and no protection when mice were challenged at later times. The high effectiveness of MALP-2 in suppressing TNF-α, the known ways of biological inactivation, and low pyrogenicity make MALP-2 a potential candidate for clinical use. PMID:12874325

  6. An H5N1-based matrix protein 2 ectodomain tetrameric peptide vaccine provides cross-protection against lethal infection with H7N9 influenza virus

    PubMed Central

    Leung, Ho-Chuen; Chan, Chris Chung-Sing; Poon, Vincent Kwok-Man; Zhao, Han-Jun; Cheung, Chung-Yan; Ng, Fai; Huang, Jian-Dong; Zheng, Bo-Jian

    2015-01-01

    In March 2013, a patient infected with a novel avian influenza A H7N9 virus was reported in China. Since then, there have been 458 confirmed infection cases and 177 deaths. The virus contains several human-adapted markers, indicating that H7N9 has pandemic potential. The outbreak of this new influenza virus highlighted the need for the development of universal influenza vaccines. Previously, we demonstrated that a tetrameric peptide vaccine based on the matrix protein 2 ectodomain (M2e) of the H5N1 virus (H5N1-M2e) could protect mice from lethal infection with different clades of H5N1 and 2009 pandemic H1N1 influenza viruses. In this study, we investigated the cross-protection of H5N1-M2e against lethal infection with the new H7N9 virus. Although five amino acid differences existed at positions 13, 14, 18, 20, and 21 between M2e of H5N1 and H7N9, H5N1-M2e vaccination with either Freund's adjuvant or the Sigma adjuvant system (SAS) induced a high level of anti-M2e antibody, which cross-reacted with H7N9-M2e peptide. A mouse-adapted H7N9 strain, A/Anhui/01/2013m, was used for lethal challenge in animal experiments. H5N1-M2e vaccination provided potent cross-protection against lethal challenge of the H7N9 virus. Reduced viral replication and histopathological damage of mouse lungs were also observed in the vaccinated mice. Our results suggest that the tetrameric H5N1-M2e peptide vaccine could protect against different subtypes of influenza virus infections. Therefore, this vaccine may be an ideal candidate for developing a universal vaccine to prevent the reemergence of avian influenza A H7N9 virus and the emergence of potential novel reassortants of influenza virus. PMID:26038770

  7. CD4+ T Cells Recognizing PE/PPE Antigens Directly or via Cross Reactivity Are Protective against Pulmonary Mycobacterium tuberculosis Infection.

    PubMed

    Sayes, Fadel; Pawlik, Alexandre; Frigui, Wafa; Gröschel, Matthias I; Crommelynck, Samuel; Fayolle, Catherine; Cia, Felipe; Bancroft, Gregory J; Bottai, Daria; Leclerc, Claude; Brosch, Roland; Majlessi, Laleh

    2016-07-01

    Mycobacterium tuberculosis (Mtb), possesses at least three type VII secretion systems, ESX-1, -3 and -5 that are actively involved in pathogenesis and host-pathogen interaction. We recently showed that an attenuated Mtb vaccine candidate (Mtb Δppe25-pe19), which lacks the characteristic ESX-5-associated pe/ppe genes, but harbors all other components of the ESX-5 system, induces CD4+ T-cell immune responses against non-esx-5-associated PE/PPE protein homologs. These T cells strongly cross-recognize the missing esx-5-associated PE/PPE proteins. Here, we characterized the fine composition of the functional cross-reactive Th1 effector subsets specific to the shared PE/PPE epitopes in mice immunized with the Mtb Δppe25-pe19 vaccine candidate. We provide evidence that the Mtb Δppe25-pe19 strain, despite its significant attenuation, is comparable to the WT Mtb strain with regard to: (i) its antigenic repertoire related to the different ESX systems, (ii) the induced Th1 effector subset composition, (iii) the differentiation status of the Th1 cells induced, and (iv) its particular features at stimulating the innate immune response. Indeed, we found significant contribution of PE/PPE-specific Th1 effector cells in the protective immunity against pulmonary Mtb infection. These results offer detailed insights into the immune mechanisms underlying the remarkable protective efficacy of the live attenuated Mtb Δppe25-pe19 vaccine candidate, as well as the specific potential of PE/PPE proteins as protective immunogens. PMID:27467705

  8. Attempts to enhance cross-protection against porcine reproductive and respiratory syndrome viruses using chimeric viruses containing structural genes from two antigenically distinct strains.

    PubMed

    Sun, Dong; Khatun, Amina; Kim, Won-Il; Cooper, Vickie; Cho, Yong-Il; Wang, Chong; Choi, Eun-Jin; Yoon, Kyoung-Jin

    2016-08-01

    Due to significant antigenic variations between field isolates of porcine reproductive and respiratory syndrome virus (PRRSV), suboptimal cross-protection between different viruses impedes the effective control of PRRS via vaccination. Our previous study showed that chimeric viruses containing mixed structural genes from two distinct strains (VR2332 and JA142) of PRRSV were highly susceptible to the viral neutralizing activity of antisera generated against both parental strains. In this study, three chimeric viruses (JAP5, JAP56 and JAP2-6) were constructed by replacing ORF5, ORFs 5 and 6, and ORFs 2-6 of VR2332 with the corresponding genes of JA142, respectively, and their ability to confer cross-protection against challenge with the VR2332 and JA142 strains was evaluated in vivo. A total of 114 pigs were divided into 6 groups, and each group was intramuscularly injected with one of the 3 chimeric viruses (n=16 pigs per group), VR2332 (n=24), JA142 (n=24), or sham inoculum (n=18). At 44days post-inoculation (dpi), these pigs were further divided into 15 groups (n=6 or 8 pigs per group) and intranasally challenged with VR2332, JA142, or sham inoculum. All pigs inoculated with one of the chimeric viruses prior to challenge had lower viremia levels than the challenge control pigs. Prior inoculation with JAP56 markedly decreased viremia to nearly undetectable levels in pigs challenged with either VR2332 or JA142. These results suggest that chimeric viruses harboring mixed structural genes from two distinct PRRSV strains can provide protection against both donor viruses. PMID:27406935

  9. CD4+ T Cells Recognizing PE/PPE Antigens Directly or via Cross Reactivity Are Protective against Pulmonary Mycobacterium tuberculosis Infection

    PubMed Central

    Sayes, Fadel; Pawlik, Alexandre; Frigui, Wafa; Gröschel, Matthias I.; Crommelynck, Samuel; Fayolle, Catherine; Cia, Felipe; Bancroft, Gregory J.; Bottai, Daria; Leclerc, Claude; Brosch, Roland; Majlessi, Laleh

    2016-01-01

    Mycobacterium tuberculosis (Mtb), possesses at least three type VII secretion systems, ESX-1, -3 and -5 that are actively involved in pathogenesis and host-pathogen interaction. We recently showed that an attenuated Mtb vaccine candidate (Mtb Δppe25-pe19), which lacks the characteristic ESX-5-associated pe/ppe genes, but harbors all other components of the ESX-5 system, induces CD4+ T-cell immune responses against non-esx-5-associated PE/PPE protein homologs. These T cells strongly cross-recognize the missing esx-5-associated PE/PPE proteins. Here, we characterized the fine composition of the functional cross-reactive Th1 effector subsets specific to the shared PE/PPE epitopes in mice immunized with the Mtb Δppe25-pe19 vaccine candidate. We provide evidence that the Mtb Δppe25-pe19 strain, despite its significant attenuation, is comparable to the WT Mtb strain with regard to: (i) its antigenic repertoire related to the different ESX systems, (ii) the induced Th1 effector subset composition, (iii) the differentiation status of the Th1 cells induced, and (iv) its particular features at stimulating the innate immune response. Indeed, we found significant contribution of PE/PPE-specific Th1 effector cells in the protective immunity against pulmonary Mtb infection. These results offer detailed insights into the immune mechanisms underlying the remarkable protective efficacy of the live attenuated Mtb Δppe25-pe19 vaccine candidate, as well as the specific potential of PE/PPE proteins as protective immunogens. PMID:27467705

  10. Intentions to perform non-pharmaceutical protective behaviors during influenza outbreaks in Sweden: a cross-sectional study following a mass vaccination campaign.

    PubMed

    Timpka, Toomas; Spreco, Armin; Gursky, Elin; Eriksson, Olle; Dahlström, Örjan; Strömgren, Magnus; Ekberg, Joakim; Pilemalm, Sofie; Karlsson, David; Hinkula, Jorma; Holm, Einar

    2014-01-01

    Failure to incorporate the beliefs and attitudes of the public into theoretical models of preparedness has been identified as a weakness in strategies to mitigate infectious disease outbreaks. We administered a cross-sectional telephone survey to a representative sample (n = 443) of the Swedish adult population to examine whether self-reported intentions to improve personal hygiene and increase social distancing during influenza outbreaks could be explained by trust in official information, self-reported health (SF-8), sociodemographic factors, and determinants postulated in protection motivation theory, namely threat appraisal and coping appraisal. The interviewees were asked to make their appraisals for two scenarios: a) an influenza with low case fatality and mild lifestyle impact; b) severe influenza with high case fatality and serious disturbances of societal functions. Every second respondent (50.0%) reported high trust in official information about influenza. The proportion that reported intentions to take deliberate actions to improve personal hygiene during outbreaks ranged between 45-85%, while less than 25% said that they intended to increase social distancing. Multiple logistic regression models with coping appraisal as the explanatory factor most frequently contributing to the explanation of the variance in intentions showed strong discriminatory performance for staying home while not ill (mild outbreaks: Area under the curve [AUC] 0.85 (95% confidence interval 0.82;0.89), severe outbreaks AUC 0.82 (95% CI 0.77;0.85)) and acceptable performance with regard to avoiding public transportation (AUC 0.78 (0.74;0.82), AUC 0.77 (0.72;0.82)), using handwash products (AUC 0.70 (0.65;0.75), AUC 0.76 (0.71;0.80)), and frequently washing hands (AUC 0.71 (0.66;0.76), AUC 0.75 (0.71;0.80)). We conclude that coping appraisal was the explanatory factor most frequently included in statistical models explaining self-reported intentions to carry out non

  11. Intentions to Perform Non-Pharmaceutical Protective Behaviors during Influenza Outbreaks in Sweden: A Cross-Sectional Study following a Mass Vaccination Campaign

    PubMed Central

    Timpka, Toomas; Spreco, Armin; Gursky, Elin; Eriksson, Olle; Dahlström, Örjan; Strömgren, Magnus; Ekberg, Joakim; Pilemalm, Sofie; Karlsson, David; Hinkula, Jorma; Holm, Einar

    2014-01-01

    Failure to incorporate the beliefs and attitudes of the public into theoretical models of preparedness has been identified as a weakness in strategies to mitigate infectious disease outbreaks. We administered a cross-sectional telephone survey to a representative sample (n = 443) of the Swedish adult population to examine whether self-reported intentions to improve personal hygiene and increase social distancing during influenza outbreaks could be explained by trust in official information, self-reported health (SF-8), sociodemographic factors, and determinants postulated in protection motivation theory, namely threat appraisal and coping appraisal. The interviewees were asked to make their appraisals for two scenarios: a) an influenza with low case fatality and mild lifestyle impact; b) severe influenza with high case fatality and serious disturbances of societal functions. Every second respondent (50.0%) reported high trust in official information about influenza. The proportion that reported intentions to take deliberate actions to improve personal hygiene during outbreaks ranged between 45–85%, while less than 25% said that they intended to increase social distancing. Multiple logistic regression models with coping appraisal as the explanatory factor most frequently contributing to the explanation of the variance in intentions showed strong discriminatory performance for staying home while not ill (mild outbreaks: Area under the curve [AUC] 0.85 (95% confidence interval 0.82;0.89), severe outbreaks AUC 0.82 (95% CI 0.77;0.85)) and acceptable performance with regard to avoiding public transportation (AUC 0.78 (0.74;0.82), AUC 0.77 (0.72;0.82)), using handwash products (AUC 0.70 (0.65;0.75), AUC 0.76 (0.71;0.80)), and frequently washing hands (AUC 0.71 (0.66;0.76), AUC 0.75 (0.71;0.80)). We conclude that coping appraisal was the explanatory factor most frequently included in statistical models explaining self-reported intentions to carry out non

  12. Microneedle delivery of an M2e-TLR5 ligand fusion protein to skin confers broadly cross-protective influenza immunity.

    PubMed

    Wang, Bao-Zhong; Gill, Harvinder S; He, Cheng; Ou, Changbo; Wang, Li; Wang, Ying-Chun; Feng, Hao; Zhang, Han; Prausnitz, Mark R; Compans, Richard W

    2014-03-28

    Influenza vaccines with broad cross-protection are urgently needed to prevent an emerging influenza pandemic. A fusion protein of the Toll-like receptor (TLR) 5-agonist domains from flagellin and multiple repeats of the conserved extracellular domain of the influenza matrix protein 2 (M2e) was constructed, purified and evaluated as such a vaccine. A painless vaccination method suitable for possible self-administration using coated microneedle arrays was investigated for skin-targeted delivery of the fusion protein in a mouse model. The results demonstrate that microneedle immunization induced strong humoral as well as mucosal antibody responses and conferred complete protection against homo- and heterosubtypic lethal virus challenges. Protective efficacy with microneedles was found to be significantly better than that seen with conventional intramuscular injection, and comparable to that observed with intranasal immunization. Because of its advantages for administration, safety and storage, microneedle delivery of M2e-flagellin fusion protein is a promising approach for an easy-to-administer universal influenza vaccine. PMID:24417966

  13. Microneedle delivery of an M2e-TLR5 ligand fusion protein to skin confers broadly cross-protective influenza immunity

    PubMed Central

    Wang, Bao-Zhong; Gill, Harvinder S.; He, Cheng; Ou, Changbo; Wang, Li; Wang, Ying-Chun; Feng, Hao; Zhang, Han; Prausnitz, Mark R.; Compans, Richard W.

    2014-01-01

    Influenza vaccines with broad cross-protection are urgently needed to prevent an emerging influenza pandemic. A fusion protein of the TLR5-agonist domains from flagellin and multiple repeats of the conserved extracellular domain of the influenza matrix protein 2 (M2e) was constructed, purified and evaluated as such a vaccine. A painless vaccination method suitable for possible self-administration using coated microneedle arrays was investigated for skin-targeted delivery of the fusion protein in a mouse model. The results demonstrate that microneedle immunization induced strong humoral as well as mucosal antibody responses and conferred complete protection against homo- and heterosubtypic lethal virus challenges. Protective efficacy with microneedles was found to be significantly better than that seen with conventional intramuscular injection, and comparable to that observed with intranasal immunization. Because of its advantages for administration, safety and storage, microneedle delivery of M2e-flagellin fusion protein is a promising approach for an easy-to-administer universal influenza vaccine. PMID:24417966

  14. Brominated 7-hydroxycoumarin-4-ylmethyls: Photolabile protecting groups with biologically useful cross-sections for two photon photolysis

    PubMed Central

    Furuta, Toshiaki; Wang, Samuel S.-H.; Dantzker, Jami L.; Dore, Timothy M.; Bybee, Wendy J.; Callaway, Edward M.; Denk, Winfried; Tsien, Roger Y.

    1999-01-01

    Photochemical release (uncaging) of bioactive messengers with three-dimensional spatial resolution in light-scattering media would be greatly facilitated if the photolysis could be powered by pairs of IR photons rather than the customary single UV photons. The quadratic dependence on light intensity would confine the photolysis to the focus point of the laser, and the longer wavelengths would be much less affected by scattering. However, previous caged messengers have had very small cross sections for two-photon excitation in the IR region. We now show that brominated 7-hydroxycoumarin-4-ylmethyl esters and carbamates efficiently release carboxylates and amines on photolysis, with one- and two-photon cross sections up to one or two orders of magnitude better than previously available. These advantages are demonstrated on neurons in brain slices from rat cortex and hippocampus excited by glutamate uncaged from N-(6-bromo-7-hydroxycoumarin-4-ylmethoxycarbonyl)-l-glutamate (Bhc-glu). Conventional UV photolysis of Bhc-glu requires less than one-fifth the intensities needed by one of the best previous caged glutamates, γ-(α-carboxy-2-nitrobenzyl)-l-glutamate (CNB-glu). Two-photon photolysis with raster-scanned femtosecond IR pulses gives the first three-dimensionally resolved maps of the glutamate sensitivity of neurons in intact slices. Bhc-glu and analogs should allow more efficient and three-dimensionally localized uncaging and photocleavage, not only in cell biology and neurobiology but also in many technological applications. PMID:9990000

  15. Cross-protective efficacy of Leishmania infantum LiHyD protein against tegumentary leishmaniasis caused by Leishmania major and Leishmania braziliensis species.

    PubMed

    Lage, Daniela Pagliara; Martins, Vívian Tamietti; Duarte, Mariana Costa; Costa, Lourena Emanuele; Tavares, Grasiele de Sousa Vieira; Ramos, Fernanda Fonseca; Chávez-Fumagalli, Miguel Angel; Menezes-Souza, Daniel; Roatt, Bruno Mendes; Tavares, Carlos Alberto Pereira; Coelho, Eduardo Antonio Ferraz

    2016-06-01

    Vaccination can be considered the most cost-effective strategy to control neglected diseases, but nowadays there is not an effective vaccine available against leishmaniasis. In the present study, a vaccine based on the combination of the Leishmania-specific hypothetical protein (LiHyD) with saponin was tested in BALB/c mice against infection caused by Leishmania major and Leishmania braziliensis species. This antigen was firstly identified in Leishmania infantum and showed to be protective against infection of BALB/c mice using this parasite species. The immunogenicity of rLiHyD/saponin vaccine was evaluated, and the results showed that immunized mice produced high levels of IFN-γ, IL-12 and GM-CSF after in vitro stimulation with rLiHyD, as well as by using L. major or L. braziliensis protein extracts. After challenge, vaccinated animals showed significant reductions in the infected footpad swellings, as well as in the parasite burden in the infection site, liver, spleen, and infected paws draining lymph nodes, when compared to those that were inoculated with the vaccine diluent (saline) or immunized with saponin. The immunization of rLiHyD without adjuvant was not protective against both challenges. The partial protection obtained by the rLiHyD/saponin vaccine was associated with a parasite-specific IL-12-dependent IFN-γ secretion, which was produced mainly by CD4(+) T cells. In these animals, a decrease in the parasite-mediated IL-4 and IL-10 responses, associated with the presence of high levels of LiHyD- and parasite-specific IgG2a isotype antibodies, were also observed. The present study showed that a hypothetical protein that was firstly identified in L. infantum, when combined to a Th1 adjuvant, was able to confer a cross-protection against highly infective stationary-phase promastigotes of two Leishmania species causing tegumentary leishmaniasis. PMID:26976272

  16. Protection against Lethal Enterovirus 71 Challenge in Mice by a Recombinant Vaccine Candidate Containing a Broadly Cross-Neutralizing Epitope within the VP2 EF Loop

    PubMed Central

    Xu, Longfa; He, Delei; Li, Zhiqun; Zheng, Jun; Yang, Lisheng; Yu, Miao; Yu, Hai; Chen, Yixin; Que, Yuqiong; Shih, James Wai Kuo; Liu, Gang; Zhang, Jun; Zhao, Qinjian; Cheng, Tong; Xia, Ningshao

    2014-01-01

    Human enterovirus 71 (EV71) is the main causative agent of hand, foot, and mouth disease (HFMD) and is associated with several severe neurological complications in the Asia-Pacific region. Here, we evaluated that while passive transfer of neutralizing monoclonal antibody (nMAb) against the VP2 protein protect against lethal EV71 infection in BALB/c mice. Protective nMAb were mapped to residues 141-155 of VP2 by peptide ELISA. High-resolution structural analysis showed that the epitope is part of the VP2 EF loop, which is the “puff” region that forms the “southern rim” of the canyon. Moreover, a three-dimensional structural characterization for the puff region with prior neutralizing epitopes and receptor-binding sites that can serve to inform vaccine strategies. Interestingly, using hepatitis B virus core protein (HBc) as a carrier, we demonstrated that the cross-neutralizing EV71 antibodies were induced, and the VP2 epitope immunized mice serum also conferred 100% in vivo passive protection. The mechanism of in vivo protection conferred by VP2 nMAb is in part attributed to the in vitro neutralizing titer and ability to bind authentic viral particles. Importantly, the anti-VP2(aa141-155) antibodies could inhibit the binding of human serum to EV71 virions showed that the VP2 epitope is immunodominant. Collectively, our results suggest that a broad-spectrum vaccine strategy targeting the high-affinity epitope of VP2 EF loop may elicits effective immune responses against EV71 infection. PMID:24669278

  17. A Cross-Sectional Study of Taenia solium in a Multiple Taeniid-Endemic Region Reveals Competition May be Protective

    PubMed Central

    Conlan, James V.; Vongxay, Khamphouth; Khamlome, Boualam; Dorny, Pierre; Sripa, Banchob; Elliot, Aileen; Blacksell, Stuart D.; Fenwick, Stanley; Thompson, R. C. Andrew

    2012-01-01

    We conducted cross-sectional surveys for taeniasis and cysticercosis in humans, pigs, and dogs in four northern provinces of Laos. Human cysticercosis and taeniasis prevalence was 2.2% (95% confidence interval [CI] = 1.4–3.0%) and 8.4% (95% CI = 6.9–9.9%), respectively. Eating uncooked beef, being male, province of residence, age, and ethnicity were significant risk factors for taeniasis and only province of residence was a significant risk factor for cystiercosis. Thirty-five human tapeworms were recovered during the survey and 33 (94.3%) and 2 (5.7%) were identified as Taenia saginata and T. solium, respectively. Maximum-likelihood adjusted prevalence of T. solium and T. hydatigena in pigs was 4.2% (95% CI = 0.5–7.9%) and 55.9% (95% CI = 47.5–64.3%), respectively, and T. hydatigena taeniasis in dogs was 4.8% (95% CI = 0.0–11.3%). Taenia hydatigena and T. saginata were the most prevalent taeniids in the respective pig and human populations and together may suppress T. solium transmission. PMID:22855759

  18. Workshop Two: Child Protection; Relative Values?

    ERIC Educational Resources Information Center

    Taylor, Anne Sinclair

    1996-01-01

    Presents salient features of workshop discussion examining child abuse. Topics discussed include cross-cultural definitions of abuse, prevalence rates, family-centered versus child-centered approaches, educational perspectives on child protection work, the need for international research, abuses of child protection systems, emotional demands on…

  19. Adverse life events and delinquent behavior among Kenyan adolescents: a cross-sectional study on the protective role of parental monitoring, religiosity, and self-esteem

    PubMed Central

    2014-01-01

    Background Past research provides strong evidence that adverse life events heighten the risk of delinquent behavior among adolescents. Urban informal (slum) settlements in sub-Saharan Africa are marked by extreme adversity. However, the prevalence and consequences of adverse life events as well as protective factors that can mitigate the effects of exposure to these events in slum settlements is largely understudied. We examine two research questions. First, are adverse life events experienced at the individual and household level associated with a higher likelihood of delinquent behavior among adolescents living in two slums in Nairobi, Kenya? Second, are parental monitoring, religiosity, and self-esteem protective against delinquency in a context of high adversity? Methods We used cross-sectional data from 3,064 males and females aged 12–19 years who participated in the Transitions to Adulthood Study. We examined the extent to which a composite index of adverse life events was associated with delinquent behavior (measured using a composite index derived from nine items). We also examined the direct and moderating effects of three protective factors: parental monitoring, religiosity, and self-esteem. Results Fifty-four percent of adolescents reported at least one adverse life event, while 18% reported three or more adverse events. For both males and females, adversity was positively and significantly associated with delinquency in bivariate and multivariate models. Negative associations were observed between the protective factors and delinquency. Significant adverse events × protective factor interaction terms were observed for parental monitoring (females and males), religiosity (males), and self-esteem (females). Conclusions Similar to research in high income countries, adverse life events are associated with an increased likelihood of delinquent behavior among adolescents living in urban slums in Kenya, a low-income country. However, parental monitoring

  20. A RESPIRATORY DISEASE MODEL FOR ASSESSMENT OF CLINICAL AND PATHOLOGIC CROSS-PROTECTION FOLLOWING HETEROLOGOUS ACUTE-TYPE PRRSV CHALLENGE.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Acute-type PRRS outbreaks were first observed in 1996. They are characterized by severe reproductive and respiratory clinical disease losses (including sow mortalities) in PRRSV “immune” herds (regularly vaccinated or systematically exposed). This study was designed to document and validate the inef...

  1. Cross-Protective Immunity to Leishmania amazonensis is Mediated by CD4+ and CD8+ Epitopes of Leishmania donovani Nucleoside Hydrolase Terminal Domains.

    PubMed

    Nico, Dirlei; Gomes, Daniele Crespo; Alves-Silva, Marcus Vinícius; Freitas, Elisangela Oliveira; Morrot, Alexandre; Bahia, Diana; Palatnik, Marcos; Rodrigues, Mauricio M; Palatnik-de-Sousa, Clarisa B

    2014-01-01

    The nucleoside hydrolase (NH) of Leishmania donovani (NH36) is a phylogenetic marker of high homology among Leishmania parasites. In mice and dog vaccination, NH36 induces a CD4+ T cell-driven protective response against Leishmania chagasi infection directed against its C-terminal domain (F3). The C-terminal and N-terminal domain vaccines also decreased the footpad lesion caused by Leishmania amazonensis. We studied the basis of the crossed immune response using recombinant generated peptides covering the whole NH36 sequence and saponin for mice prophylaxis against L. amazonensis. The F1 (amino acids 1-103) and F3 peptide (amino acids 199-314) vaccines enhanced the IgG and IgG2a anti-NH36 antibodies to similar levels. The F3 vaccine induced the strongest DTH response, the highest proportions of NH36-specific CD4+ and CD8+ T cells after challenge and the highest expression of IFN-γ and TNF-α. The F1 vaccine, on the other hand, induced a weaker but significant DTH response and a mild enhancement of IFN-γ and TNF-α levels. The in vivo depletion with anti-CD4 or CD8 monoclonal antibodies disclosed that cross-protection against L. amazonensis infection was mediated by a CD4+ T cell response directed against the C-terminal domain (75% of reduction of the size of footpad lesion) followed by a CD8+ T cell response against the N-terminal domain of NH36 (57% of reduction of footpad lesions). Both vaccines were capable of inducing long-term cross-immunity. The amino acid sequence of NH36 showed 93% identity to the sequence of the NH A34480 of L. amazonensis, which also showed the presence of completely conserved predicted epitopes for CD4+ and CD8+ T cells in F1 domain, and of CD4+ epitopes differing by a single amino acid, in F1 and F3 domains. The identification of the C-terminal and N-terminal domains as the targets of the immune response to NH36 in the model of L. amazonensis infection represents a basis for the rationale development of a bivalent vaccine against

  2. Sun protection

    MedlinePlus

    ... age spots are caused by exposure to the sun. The two types of sun rays that can injure the skin are ultraviolet ... changes is to protect your skin from the sun. This includes using sunscreen and other protective measures. ...

  3. Regulated delayed synthesis of lipopolysaccharide and enterobacterial common antigen of Salmonella Typhimurium enhances immunogenicity and cross-protective efficacy against heterologous Salmonella challenge.

    PubMed

    Huang, Chun; Liu, Qing; Luo, Yali; Li, Pei; Liu, Qiong; Kong, Qingke

    2016-08-01

    Lipopolysaccharide (LPS) O-antigen and enterobacterial common antigen (ECA) are two major polysaccharide structures on the surface of Salmonella enterica serovar Typhimurium. Previous studies have demonstrated that regulated truncation of LPS enhances the cross-reaction against conserved outer membrane proteins (OMPs) from enteric bacteria. We speculate that the regulation of both O-antigen and ECA may enhance the induction of immune responses against conserved OMPs from enteric bacteria. In this work we targeted rfbB and rffG genes which encode dTDP-glucose 4,6-dehydratases and share the same function in regulating O-antigen and ECA synthesis. We constructed a mutant, S496 (ΔrfbB6 ΔrffG7 ΔpagL73::TT araC PBADrfbB-3), in which rfbB gene expression was dependent on exogenously supplied arabinose during in vitro growth and achieved the simultaneous tight regulation of both LPS and ECA synthesis, as demonstrated by the LPS profile and Western blotting using antisera against LPS and ECA. When administered orally, S. Typhimurium S496 was completely attenuated for virulence but still retained the capacity to colonize and disseminate in mice. In addition, we found that oral immunization with S496 resulted in increased immune responses against OMPs from enteric bacteria and enhanced survival compared with immunization with S492 possessing ΔrfbB6 ΔrffG8 mutations when challenged with lethal doses of Salmonella Choleraesuis or Salmonella Enteritidis. These results indicate that S. Typhimurium arabinose-regulated rfbB strain S496 is a good vaccine candidate, conferring cross-protection against lethal challenge with heterologous Salmonella. PMID:27423383

  4. Inactivated Enterovirus 71 Vaccine Produced by 200-L Scale Serum-Free Microcarrier Bioreactor System Provides Cross-Protective Efficacy in Human SCARB2 Transgenic Mouse

    PubMed Central

    Wu, Chia-Ying; Lin, Yi-Wen; Kuo, Chia-Ho; Liu, Wan-Hsin; Tai, Hsiu-Fen; Pan, Chien-Hung; Chen, Yung-Tsung; Hsiao, Pei-Wen; Chan, Chi-Hsien; Chang, Ching-Chuan; Liu, Chung-Cheng; Chow, Yen-Hung; Chen, Juine-Ruey

    2015-01-01

    Epidemics and outbreaks caused by infections of several subgenotypes of EV71 and other serotypes of coxsackie A viruses have raised serious public health concerns in the Asia-Pacific region. These concerns highlight the urgent need to develop a scalable manufacturing platform for producing an effective and sufficient quantity of vaccines against deadly enteroviruses. In this report, we present a platform for the large-scale production of a vaccine based on the inactivated EV71(E59-B4) virus. The viruses were produced in Vero cells in a 200 L bioreactor with serum-free medium, and the viral titer reached 107 TCID50/mL 10 days after infection when using an MOI of 10−4. The EV71 virus particles were harvested and purified by sucrose density gradient centrifugation. Fractions containing viral particles were pooled based on ELISA and SDS-PAGE. TEM was used to characterize the morphologies of the viral particles. To evaluate the cross-protective efficacy of the EV71 vaccine, the pooled antigens were combined with squalene-based adjuvant (AddaVAX) or aluminum phosphate (AlPO4) and tested in human SCARB2 transgenic (Tg) mice. The Tg mice immunized with either the AddaVAX- or AlPO4-adjuvanted EV71 vaccine were fully protected from challenges by the subgenotype C2 and C4 viruses, and surviving animals did not show any degree of neurological paralysis symptoms or muscle damage. Vaccine treatments significantly reduced virus antigen presented in the central nervous system of Tg mice and alleviated the virus-associated inflammatory response. These results strongly suggest that this preparation results in an efficacious vaccine and that the microcarrier/bioreactor platform offers a superior alternative to the previously described roller-bottle system. PMID:26287531

  5. Inactivated Enterovirus 71 Vaccine Produced by 200-L Scale Serum-Free Microcarrier Bioreactor System Provides Cross-Protective Efficacy in Human SCARB2 Transgenic Mouse.

    PubMed

    Wu, Chia-Ying; Lin, Yi-Wen; Kuo, Chia-Ho; Liu, Wan-Hsin; Tai, Hsiu-Fen; Pan, Chien-Hung; Chen, Yung-Tsung; Hsiao, Pei-Wen; Chan, Chi-Hsien; Chang, Ching-Chuan; Liu, Chung-Cheng; Chow, Yen-Hung; Chen, Juine-Ruey

    2015-01-01

    Epidemics and outbreaks caused by infections of several subgenotypes of EV71 and other serotypes of coxsackie A viruses have raised serious public health concerns in the Asia-Pacific region. These concerns highlight the urgent need to develop a scalable manufacturing platform for producing an effective and sufficient quantity of vaccines against deadly enteroviruses. In this report, we present a platform for the large-scale production of a vaccine based on the inactivated EV71(E59-B4) virus. The viruses were produced in Vero cells in a 200 L bioreactor with serum-free medium, and the viral titer reached 10(7) TCID50/mL 10 days after infection when using an MOI of 10(-4). The EV71 virus particles were harvested and purified by sucrose density gradient centrifugation. Fractions containing viral particles were pooled based on ELISA and SDS-PAGE. TEM was used to characterize the morphologies of the viral particles. To evaluate the cross-protective efficacy of the EV71 vaccine, the pooled antigens were combined with squalene-based adjuvant (AddaVAX) or aluminum phosphate (AlPO4) and tested in human SCARB2 transgenic (Tg) mice. The Tg mice immunized with either the AddaVAX- or AlPO4-adjuvanted EV71 vaccine were fully protected from challenges by the subgenotype C2 and C4 viruses, and surviving animals did not show any degree of neurological paralysis symptoms or muscle damage. Vaccine treatments significantly reduced virus antigen presented in the central nervous system of Tg mice and alleviated the virus-associated inflammatory response. These results strongly suggest that this preparation results in an efficacious vaccine and that the microcarrier/bioreactor platform offers a superior alternative to the previously described roller-bottle system. PMID:26287531

  6. Sterilizing Immunity Elicited by Neisseria meningitidis Carriage Shows Broader Protection than Predicted by Serum Antibody Cross-Reactivity in CEACAM1-Humanized Mice

    PubMed Central

    McCaw, Shannon E.; Strobel, Lea; Frosch, Matthias

    2014-01-01

    Neisseria meningitidis asymptomatically colonizes the human upper respiratory tract but is also the cause of meningitis and severe septicemia. Carriage or disease evokes an immune response against the infecting strain. Hitherto, we have known little about the breadth of immunity induced by natural carriage of a single strain or its implications for subsequent infectious challenge. In this study, we establish that transgenic mice expressing human CEACAM1 support nasal colonization by a variety of strains of different capsular types. Next, we nasally challenged these mice with either of the N. meningitidis strains H44/76 (serogroup B, ST-32) and 90/18311 (serogroup C, ST-11), while following the induction of strain-specific immunoglobulin. When these antisera were tested for reactivity with a diverse panel of N. meningitidis strains, very low levels of antibody were detected against all meningococcal strains, yet a mutually exclusive “fingerprint” of high-level cross-reactivity toward certain strains became apparent. To test the efficacy of these responses for protection against subsequent challenge, CEACAM1-humanized mice exposed to strain 90/18311 were then rechallenged with different N. meningitidis strains. As expected, the mice were immune to challenge with the same strain and with a closely related ST-11 strain, 38VI, while H44/76 (ST-32) could still colonize these animals. Notably, however, despite the paucity of detectable humoral response against strain 196/87 (ST-32), this strain was unable to colonize the 90/18311-exposed mice. Combined, our data suggest that current approaches may underestimate the actual breadth of mucosal protection gained through natural exposure to N. meningitidis strains. PMID:25368118

  7. Exposure to low UVA doses increases KatA and KatB catalase activities, and confers cross-protection against subsequent oxidative injuries in Pseudomonas aeruginosa.

    PubMed

    Pezzoni, Magdalena; Tribelli, Paula M; Pizarro, Ramón A; López, Nancy I; Costa, Cristina S

    2016-05-01

    Solar UVA radiation is one of the main environmental stress factors for Pseudomonas aeruginosa. Exposure to high UVA doses produces lethal effects by the action of the reactive oxygen species (ROS) it generates. P. aeruginosa has several enzymes, including KatA and KatB catalases, which provide detoxification of ROS. We have previously demonstrated that KatA is essential in defending P. aeruginosa against high UVA doses. In order to analyse the mechanisms involved in the adaptation of this micro-organism to UVA, we investigated the effect of exposure to low UVA doses on KatA and KatB activities, and the physiological consequences. Exposure to UVA induced total catalase activity; assays with non-denaturing polyacrylamide gels showed that both KatA and KatB activities were increased by radiation. This regulation occurred at the transcriptional level and depended, at least partly, on the increase in H2O2 levels. We demonstrated that exposure to low UVA produced a protective effect against subsequent lethal doses of UVA, sodium hypochlorite and H2O2. Protection against lethal UVA depends on katA, whilst protection against sodium hypochlorite depends on katB, demonstrating that different mechanisms are involved in the defence against these oxidative agents, although both genes can be involved in the global cellular response. Conversely, protection against lethal doses of H2O2 could depend on induction of both genes and/or (an)other defensive factor(s). A better understanding of the adaptive response of P. aeruginosa to UVA is relevant from an ecological standpoint and for improving disinfection strategies that employ UVA or solar irradiation. PMID:26940049

  8. Increased viremia, altered immune responses, fever, and pathologic lesions following intranasal heterologous wild-type PRRSV challenge: Ident of markers associated with incomplete cross-protection in respiratory disease model

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: Investigate immune response differences associated with inadequate cross-protection against heterologous WT-PRRSv challenge in a respiratory disease model. ATTC 2332 was used to IN infect 10 Medicated Early Weaned pigs at 4 weeks of age and five pigs each were then IN challenged 6 weeks ...

  9. Vaccination with NS1-truncated H3N2 swine influenza virus primes T cells and confers cross-protection against an H1N1 heterosubtypic challenge in pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The diversity of contemporary swine influenza virus (SIV) strains impedes effective immunization of swine herds. Mucosally delivered, attenuated virus vaccines are one approach with potential to provide broad cross-protection. Reverse genetics-derived H3N2 SIV virus with truncated NS1 (NS1delta126 T...

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

    PubMed

    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. PMID:27533024

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

    PubMed Central

    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

  12. A Cross-Lagged Panel Model Examining Protective Behavioral Strategies: Are Types of Strategies Differentially Related to Alcohol Use and Consequences?

    PubMed Central

    Napper, Lucy E.; Kenney, Shannon R.; Lac, Andrew; Lewis, Leslie J.; LaBrie, Joseph W.

    2014-01-01

    Protective behavioral strategies (PBS) are skills that can be used to reduce the of risk alcohol-related negative consequences. Studies have shown that, in general, PBS are related to less alcohol consumption and fewer negative consequences; however, other studies have suggested that not all types of PBS (e.g., stopping/limiting drinking [SLD], manner of drinking [MOD] and serious harm reduction [SHR]) are equally effective at reducing alcohol risk. In addition, few studies have explored the longitudinal relationships among PBS, alcohol use and consequences. Using a sample of heavy drinking college students (N = 338), the current study examined PBS use, alcohol consumption and consequences across two time points three months apart. Cross-lagged panel models revealed that MOD predicted a reduction in alcohol use and negative consequences. SHR was longitudinally related to fewer negative consequences, but unrelated to alcohol use. SLD was not associated with drinking or consequences at follow-up. These results highlight the need for future research to examine the effects of different types of PBS and have implications for alcohol intervention programs that incorporate PBS skills training. PMID:24229842

  13. Cross-protection against European swine influenza viruses in the context of infection immunity against the 2009 pandemic H1N1 virus: studies in the pig model of influenza.

    PubMed

    Qiu, Yu; De Hert, Karl; Van Reeth, Kristien

    2015-01-01

    Pigs are natural hosts for the same influenza virus subtypes as humans and are a valuable model for cross-protection studies with influenza. In this study, we have used the pig model to examine the extent of virological protection between a) the 2009 pandemic H1N1 (pH1N1) virus and three different European H1 swine influenza virus (SIV) lineages, and b) these H1 viruses and a European H3N2 SIV. Pigs were inoculated intranasally with representative strains of each virus lineage with 6- and 17-week intervals between H1 inoculations and between H1 and H3 inoculations, respectively. Virus titers in nasal swabs and/or tissues of the respiratory tract were determined after each inoculation. There was substantial though differing cross-protection between pH1N1 and other H1 viruses, which was directly correlated with the relatedness in the viral hemagglutinin (HA) and neuraminidase (NA) proteins. Cross-protection against H3N2 was almost complete in pigs with immunity against H1N2, but was weak in H1N1/pH1N1-immune pigs. In conclusion, infection with a live, wild type influenza virus may offer substantial cross-lineage protection against viruses of the same HA and/or NA subtype. True heterosubtypic protection, in contrast, appears to be minimal in natural influenza virus hosts. We discuss our findings in the light of the zoonotic and pandemic risks of SIVs. PMID:26404790

  14. Expression and characterization of genetically engineered human immunodeficiency virus-like particles containing modified envelope glycoproteins: implications for development of a cross-protective AIDS vaccine.

    PubMed

    Rovinski, B; Haynes, J R; Cao, S X; James, O; Sia, C; Zolla-Pazner, S; Matthews, T J; Klein, M H

    1992-07-01

    Noninfectious human immunodeficiency virus type 1 (HIV-1) viruslike particles containing chimeric envelope glycoproteins were expressed in mammalian cells by using inducible promoters. We engineered four expression vectors in which a synthetic oligomer encoding gp120 residues 306 to 328 (amino acids YNKRKRIHIGP GRAFYTTKNIIG) from the V3 loop of the MN viral isolate was inserted at various positions within the endogenous HIV-1LAI env gene. Expression studies revealed that insertion of the heterologous V3(MN) loop segment at two different locations within the conserved region 2 (C2) of gp120, either 173 or 242 residues away from the N terminus of the mature subunit, resulted in the secretion of fully assembled HIV-like particles containing chimeric LAI/MN envelope glycoproteins. Both V3 loop epitopes were recognized by loop-specific neutralizing antibodies. However, insertion of the V3(MN) loop segment into other regions of gp120 led to the production of envelope-deficient viruslike particles. Immunization with HIV-like particles containing chimeric envelope proteins induced specific antibody responses against both the autologous and heterologous V3 loop epitopes, including cross-neutralizing antibodies against the HIV-1LAI and HIV-1MN isolates. This study, therefore, demonstrates the feasibility of genetically engineering optimized HIV-like particles capable of eliciting cross-neutralizing antibodies. PMID:1602531

  15. An innovative approach to induce cross-protective immunity against porcine reproductive and respiratory syndrome virus in the lungs of pigs through adjuvanted nanotechnology-based vaccination

    PubMed Central

    Binjawadagi, Basavaraj; Dwivedi, Varun; Manickam, Cordelia; Ouyang, Kang; Torrelles, Jordi B; Renukaradhya, Gourapura J

    2014-01-01

    cytokines) in the lungs were observed. In conclusion, combination of NP-KAg and soluble M. tb WCL elicits broadly cross-protective anti-PRRSV immunity in the pig respiratory system. PMID:24711701

  16. Physical activity as a protective factor against depressive symptoms in older Chinese veterans in the community: result from a national cross-sectional study

    PubMed Central

    Du, Wen-Jin; Tan, Ji-Ping; Yi, Fang; Zou, Yong-Ming; Gao, Ya; Zhao, Yi-Ming; Wang, Lu-Ning

    2015-01-01

    Background Physical activity is generally considered to be effective in reducing the prevalence of depression and promoting remission of its symptoms. However, large-scale epidemiological research on this issue is lacking in older Chinese adults. We performed a nationwide epidemiological survey to determine the relationship between physical activity and depressive symptoms in older Chinese veterans in the community, with adjustment for potential confounders. Methods A cross-sectional study was conducted in a representative sample of 9,676 community-dwelling older Chinese veterans. Depressive symptoms were identified using the Center for Epidemiological Studies Depression Scale. Physical activity was self-reported using a one-year physical activity questionnaire. Information about covariates was obtained by questionnaire-based interview. Relationships between study variables and symptoms of depression were estimated using unadjusted and adjusted analyses. Results The median age was 82.29 (interquartile range 80.25–84.60) years. In total, 81.84% of the study participants engaged in physical activity that was predominantly light in intensity. In unadjusted analyses, physical activity was associated with a significantly decreased likelihood of depressive symptoms (5.43% versus 18.83%, P<0.0001). Multivariate logistic regression with adjustment and controlling for confounders, physical activity was still inversely associated with depressive symptoms and was the only independent protective factor (odds ratio 0.57, 95% confidence interval 0.44–0.72, P<0.0001) among the associated factors in this study. In a univariate general linear model, there was a significant difference in Center for Epidemiological Studies Depression Scale score between subjects participating in active physical activity and those who did not (F=59.07, P<0.0001). Conclusion This study found an inverse relationship between physical activity and symptoms of depression in older Chinese veterans in

  17. VirR-Mediated Resistance of Listeria monocytogenes against Food Antimicrobials and Cross-Protection Induced by Exposure to Organic Acid Salts

    PubMed Central

    Kang, Jihun; Wiedmann, Martin; Boor, Kathryn J.

    2015-01-01

    Formulations of ready-to-eat (RTE) foods with antimicrobial compounds constitute an important safety measure against foodborne pathogens such as Listeria monocytogenes. While the efficacy of many commercially available antimicrobial compounds has been demonstrated in a variety of foods, the current understanding of the resistance mechanisms employed by L. monocytogenes to counteract these stresses is limited. In this study, we screened in-frame deletion mutants of two-component system response regulators associated with the cell envelope stress response for increased sensitivity to commercially available antimicrobial compounds (nisin, lauric arginate, ε-polylysine, and chitosan). A virR deletion mutant showed increased sensitivity to all antimicrobials and significantly greater loss of membrane integrity when exposed to nisin, lauric arginate, or ε-polylysine (P < 0.05). The VirR-regulated operon, dltABCD, was shown to be the key contributor to resistance against these antimicrobial compounds, whereas another VirR-regulated gene, mprF, displayed an antimicrobial-specific contribution to resistance. An experiment with a β-glucuronidase (GUS) reporter fusion with the dlt promoter indicated that nisin does not specifically induce VirR-dependent upregulation of dltABCD. Lastly, prior exposure of L. monocytogenes parent strain H7858 and the ΔvirR mutant to 2% potassium lactate enhanced subsequent resistance against nisin and ε-polylysine (P < 0.05). These data demonstrate that VirRS-mediated regulation of dltABCD is the major resistance mechanism used by L. monocytogenes against cell envelope-damaging food antimicrobials. Further, the potential for cross-protection induced by other food-related stresses (e.g., organic acids) needs to be considered when applying these novel food antimicrobials as a hurdle strategy for RTE foods. PMID:25911485

  18. VirR-Mediated Resistance of Listeria monocytogenes against Food Antimicrobials and Cross-Protection Induced by Exposure to Organic Acid Salts.

    PubMed

    Kang, Jihun; Wiedmann, Martin; Boor, Kathryn J; Bergholz, Teresa M

    2015-07-01

    Formulations of ready-to-eat (RTE) foods with antimicrobial compounds constitute an important safety measure against foodborne pathogens such as Listeria monocytogenes. While the efficacy of many commercially available antimicrobial compounds has been demonstrated in a variety of foods, the current understanding of the resistance mechanisms employed by L. monocytogenes to counteract these stresses is limited. In this study, we screened in-frame deletion mutants of two-component system response regulators associated with the cell envelope stress response for increased sensitivity to commercially available antimicrobial compounds (nisin, lauric arginate, ε-polylysine, and chitosan). A virR deletion mutant showed increased sensitivity to all antimicrobials and significantly greater loss of membrane integrity when exposed to nisin, lauric arginate, or ε-polylysine (P < 0.05). The VirR-regulated operon, dltABCD, was shown to be the key contributor to resistance against these antimicrobial compounds, whereas another VirR-regulated gene, mprF, displayed an antimicrobial-specific contribution to resistance. An experiment with a β-glucuronidase (GUS) reporter fusion with the dlt promoter indicated that nisin does not specifically induce VirR-dependent upregulation of dltABCD. Lastly, prior exposure of L. monocytogenes parent strain H7858 and the ΔvirR mutant to 2% potassium lactate enhanced subsequent resistance against nisin and ε-polylysine (P < 0.05). These data demonstrate that VirRS-mediated regulation of dltABCD is the major resistance mechanism used by L. monocytogenes against cell envelope-damaging food antimicrobials. Further, the potential for cross-protection induced by other food-related stresses (e.g., organic acids) needs to be considered when applying these novel food antimicrobials as a hurdle strategy for RTE foods. PMID:25911485

  19. Situational Awareness and Health Protective Responses to Pandemic Influenza A (H1N1) in Hong Kong: A Cross-Sectional Study

    PubMed Central

    Liao, Qiuyan; Cowling, Benjamin; Lam, Wing Tak; Ng, Man Wai; Fielding, Richard

    2010-01-01

    Background Whether information sources influence health protective behaviours during influenza pandemics or other emerging infectious disease epidemics is uncertain. Methodology Data from cross-sectional telephone interviews of 1,001 Hong Kong adults in June, 2009 were tested against theory and data-derived hypothesized associations between trust in (formal/informal) information, understanding, self-efficacy, perceived susceptibility and worry, and hand hygiene and social distancing using Structural Equation Modelling with multigroup comparisons. Principal Findings Trust in formal (government/media) information about influenza was associated with greater reported understanding of A/H1N1 cause (β = 0.36) and A/H1N1 prevention self-efficacy (β = 0.25), which in turn were associated with more hand hygiene (β = 0.19 and β = 0.23, respectively). Trust in informal (interpersonal) information was negatively associated with perceived personal A/H1N1 susceptibility (β = −0.21), which was negatively associated with perceived self-efficacy (β = −0.42) but positively associated with influenza worry (β = 0.44). Trust in informal information was positively associated with influenza worry (β = 0.16) which was in turn associated with greater social distancing (β = 0.36). Multigroup comparisons showed gender differences regarding paths from trust in formal information to understanding of A/H1N1 cause, trust in informal information to understanding of A/H1N1 cause, and understanding of A/H1N1 cause to perceived self-efficacy. Conclusions/Significance Trust in government/media information was more strongly associated with greater self-efficacy and handwashing, whereas trust in informal information was strongly associated with perceived health threat and avoidance behaviour. Risk communication should consider the effect of gender differences. PMID:20967280

  20. 40 CFR 35.3575 - Application of Federal cross-cutting authorities (cross-cutters).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Application of Federal cross-cutting authorities (cross-cutters). 35.3575 Section 35.3575 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY....3575 Application of Federal cross-cutting authorities (cross-cutters). (a) General. A number of...

  1. Matrix M H5N1 Vaccine Induces Cross-H5 Clade Humoral Immune Responses in a Randomized Clinical Trial and Provides Protection from Highly Pathogenic Influenza Challenge in Ferrets

    PubMed Central

    Cox, Rebecca J.; Major, Diane; Pedersen, Gabriel; Pathirana, Rishi D.; Hoschler, Katja; Guilfoyle, Kate; Roseby, Sarah; Bredholt, Geir; Assmus, Jörg; Breakwell, Lucy; Campitelli, Laura; Sjursen, Haakon

    2015-01-01

    Background and Methods Highly pathogenic avian influenza (HPAI) viruses constitute a pandemic threat and the development of effective vaccines is a global priority. Sixty adults were recruited into a randomized clinical trial and were intramuscularly immunized with two virosomal vaccine H5N1 (NIBRG-14) doses (21 days apart) of 30μg HA alone or 1.5, 7.5 or 30μg HA adjuvanted with Matrix M. The kinetics and longevity of the serological responses against NIBRG-14 were determined by haemagglutination inhibition (HI), single radial haemolysis (SRH), microneutralization (MN) and ELISA assays. The cross-H5 clade responses in sera were determined by HI and the antibody-secreting (ASC) cell ELISPOT assays. The protective efficacy of the vaccine against homologous HPAI challenge was evaluated in ferrets. Results The serological responses against the homologous and cross-reactive strains generally peaked one week after the second dose, and formulation with Matrix M augmented the responses. The NIBRG-14-specific seroprotection rates fell significantly by six months and were low against cross-reactive strains although the adjuvant appeared to prolong the longevity of the protective responses in some subjects. By 12 months post-vaccination, nearly all vaccinees had NIBRG-14-specific antibody titres below the protective thresholds. The Matrix M adjuvant was shown to greatly improve ASC and serum IgG responses following vaccination. In a HPAI ferret challenge model, the vaccine protected the animals from febrile responses, severe weight loss and local and systemic spread of the virus. Conclusion Our findings show that the Matrix M-adjuvanted virosomal H5N1 vaccine is a promising pre-pandemic vaccine candidate. Trial Registration ClinicalTrials.gov NCT00868218 PMID:26147369

  2. A Cross-national Comparison of Risk and Protective Factors for Adolescent Drug Use and Delinquency in the United States and the Netherlands

    PubMed Central

    Oesterle, Sabrina; Hawkins, J. David; Steketee, Majone; Jonkman, Harrie; Brown, Eric C.; Moll, Marit; Haggerty, Kevin P.

    2015-01-01

    The present study compared associations between risk and protective factors and adolescent drug use and delinquency in the Netherlands and the United States. Data were collected from students between the ages of 12 and 17 using the same school-administered survey instrument in both countries. Levels of exposure to risk and protective factors were generally similar in both countries. The same risk and protective factors shown to be associated with U.S. adolescents’ drug use and delinquency were related significantly to Dutch youth’s drug use and delinquency. One important exception was that Dutch students perceived their parents’ attitudes to be more favorable toward alcohol use; these attitudes also were more predictive of adolescents’ regular drinking in the Netherlands compared to the United States. The findings indicate that the risk and protective factors measured in this study can be important targets for prevention of health-compromising behaviors among young people in the Netherlands and the United States. PMID:26166843

  3. FUNDAMENTAL AREAS OF PHENOMENOLOGY (INCLUDING APPLICATIONS): Suppression of Nonlinear Patterning Effect in Wavelength Conversion Based on Transient Cross-Phase Modulation in Semiconductor Optical Amplifier Assisted with a Detuning Filter

    NASA Astrophysics Data System (ADS)

    Zhou, En-Bo; Zhang, Xin-Liang; Yu, Yu; Huang, De-Xiu

    2009-03-01

    Nonlinear patterning (NLP) effect in wavelength conversion based on transient cross-phase modulation (XPM) in semiconductor optical amplifier (SOA) assisted with a detuning filter is theoretically investigated. A non-adiabatic model is used to estimate the ultrafast dynamics of gain, phase and electron temperature in the SOA. Simulation results show that the NLP can be greatly suppressed by introducing an assist light, especially for the probe wavelength distant from gain peak. Furthermore, the results also indicate that the improvement is more evident for long wavelength probe light and assist light in counter-propagating configuration.

  4. A Vaccine of L2 Epitope Repeats Fused with a Modified IgG1 Fc Induced Cross-Neutralizing Antibodies and Protective Immunity against Divergent Human Papillomavirus Types

    PubMed Central

    Zhang, Ting; Liu, Yanchun; Xie, Xixiu; Wang, Zhirong; Xu, Xuemei

    2014-01-01

    Current human papillomavirus (HPV) major capsid protein L1 virus-like particles (VLPs)-based vaccines in clinic induce strong HPV type-specific neutralizing antibody responses. To develop pan-HPV vaccines, here, we show that the fusion protein E3R4 consisting of three repeats of HPV16 L2 aa 17–36 epitope (E3) and a modified human IgG1 Fc scaffold (R4) induces cross-neutralizing antibodies and protective immunity against divergent HPV types. E3R4 was expressed as a secreted protein in baculovirus expression system and could be simply purified by one step Protein A affinity chromatography with the purity above 90%. Vaccination of E3R4 formulated with Freunds adjuvant not only induced cross-neutralizing antibodies against HPV pseudovirus types 16, 18, 45, 52, 58, 6, 11 and 5 in mice, but also protected mice against vaginal challenges with HPV pseudovirus types 16, 45, 52, 58, 11 and 5 for at least eleven months after the first immunization. Moreover, vaccination of E3R4 formulated with FDA approved adjuvant alum plus monophosphoryl lipid A also induced cross-neutralizing antibodies against HPV types 16, 18 and 6 in rabbits. Thus, our results demonstrate that delivery of L2 antigen as a modified Fc-fusion protein may facilitate pan-HPV vaccine development. PMID:24802101

  5. A cationic liposome-DNA complexes adjuvant (JVRS-100) enhances the immunogenicity and cross-protective efficacy of pre-pandemic influenza A (H5N1) vaccine in ferrets.

    PubMed

    Liu, Feng; Sun, Xiangjie; Fairman, Jeffery; Lewis, David B; Katz, Jacqueline M; Levine, Min; Tumpey, Terrence M; Lu, Xiuhua

    2016-05-01

    Influenza A (H5N1) viruses continue to pose a public health threat. As inactivated H5N1 vaccines are poorly immunogenic, adjuvants are needed to improve the immunogenicity of H5N1 vaccine in humans. Here, we investigated the immunogenicity and cross-protective efficacy in ferrets of a clade 2.2-derived vaccine with addition of JVRS-100, an adjuvant consisting of cationic liposome-DNA complexes (CLDC). After the first vaccination, significantly higher levels of hemagglutination-inhibition (HAI) and neutralizing antibody titers were detected in ferrets immunized with adjuvanted vaccine compared to unadjuvanted vaccine. Following a second dose of adjuvanted vaccine, HAI antibody titers of ≥ 40 were detected against viruses from multiple H5N1 clades. HAI antibodies against newly isolated H5N2 and H5N8 viruses were also augmented by JVRS-100. Ferrets were challenged with a heterologous H5N1 virus. All ferrets that received two doses of adjuvanted vaccine exhibited mild illness, significantly reduced nasal wash virus titers and protection from lethal challenge. In contrast, ferrets that received unadjuvanted vaccine showed greater weight loss, high viral titers and 3 of 6 animals succumbed to the lethal challenge. Our results indicate that the addition of JVRS-100 to H5N1 vaccine enhanced immunogenicity and cross-protection against lethal H5N1 virus disease in ferrets. JVRS-100 warrants further investigation as a potential adjuvant for influenza vaccines. PMID:26967975

  6. 49 CFR 234.241 - Protection of insulated wire; splice in underground wire.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... underground wire. 234.241 Section 234.241 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION GRADE CROSSING SAFETY, INCLUDING... Testing Maintenance Standards § 234.241 Protection of insulated wire; splice in underground...

  7. 49 CFR 234.241 - Protection of insulated wire; splice in underground wire.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... underground wire. 234.241 Section 234.241 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION GRADE CROSSING SAFETY, INCLUDING... Testing Maintenance Standards § 234.241 Protection of insulated wire; splice in underground...

  8. 49 CFR 234.241 - Protection of insulated wire; splice in underground wire.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... underground wire. 234.241 Section 234.241 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION GRADE CROSSING SAFETY, INCLUDING... Testing Maintenance Standards § 234.241 Protection of insulated wire; splice in underground...

  9. Protective eyewear selection for interventional fluoroscopy.

    PubMed

    Sturchio, Glenn M; Newcomb, Richard D; Molella, Robin; Varkey, Prathibha; Hagen, Philip T; Schueler, Beth A

    2013-02-01

    Three protective eyewear models were evaluated to determine effectiveness in reducing radiation dose to a fluoroscopist's eyes. The performance of the protective eyewear was measured using radiation dosimeters in a fluoroscopy suite. An Eyewear Protection Factor was determined for each model in each of three exposure orientations. The protection was strongly influenced by the location of the radiation source. When the source was in front of the fluoroscopist, the lead equivalence was important. When the source was to the side of the fluoroscopist, the cross section of the side shield had a significant influence on protection. Protective eyewear selection needs to include consideration of job task and head orientation to the radiation source as well as the possibility that face shape and eyewear fit may also impact the radiation dose to the eye. PMID:23287514

  10. Occupant Protection Project

    NASA Technical Reports Server (NTRS)

    Bopp, Genie; Somers, Jeff; Granderson, Brad; Gernhardt, Mike; Currie, Nancy; Lawrence, Chuck

    2010-01-01

    Topics include occupant protection overview with a focus on crew protection during dynamic phases of flight; occupant protection collaboration; modeling occupant protection; occupant protection considerations; project approach encompassing analysis tools, injury criteria, and testing program development; injury criteria update methodology, unique effects of pressure suits and other factors; and a summary.