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Sample records for engineered live attenuated

  1. Molecularly engineered live-attenuated chimeric West Nile/dengue virus vaccines protect rhesus monkeys from West Nile virus

    International Nuclear Information System (INIS)

    Pletnev, Alexander G.; St Claire, Marisa; Elkins, Randy; Speicher, Jim; Murphy, Brian R.; Chanock, Robert M.

    2003-01-01

    Two molecularly engineered, live-attenuated West Nile virus (WN) vaccine candidates were highly attenuated and protective in rhesus monkeys. The vaccine candidates are chimeric viruses (designated WN/DEN4) bearing the membrane precursor and envelope protein genes of WN on a backbone of dengue 4 virus (DEN4) with or without a deletion of 30 nucleotides (Δ30) in the 3' noncoding region of DEN4. Viremia in WN/DEN4- infected monkeys was reduced 100-fold compared to that in WN- or DEN4-infected monkeys. WN/DEN4-3'Δ30 did not cause detectable viremia, indicating that it is even more attenuated for monkeys. These findings indicate that chimerization itself and the presence of the Δ30 mutation independently contribute to the attenuation phenotype for nonhuman primates. Despite their high level of attenuation in monkeys, the chimeras induced a moderate-to-high titer of neutralizing antibodies and prevented viremia in monkeys challenged with WN. The more attenuated vaccine candidate, WN/DEN4-3'Δ30, will be evaluated first in our initial clinical studies

  2. Engineering and preclinical evaluation of attenuated nontyphoidal Salmonella strains serving as live oral vaccines and as reagent strains.

    Science.gov (United States)

    Tennant, Sharon M; Wang, Jin-Yuan; Galen, James E; Simon, Raphael; Pasetti, Marcela F; Gat, Orit; Levine, Myron M

    2011-10-01

    While nontyphoidal Salmonella (NTS) has long been recognized as a cause of self-limited gastroenteritis, it is becoming increasingly evident that multiple-antibiotic-resistant strains are also emerging as important causes of invasive bacteremia and focal infections, resulting in hospitalizations and deaths. We have constructed attenuated Salmonella enterica serovar Typhimurium and Salmonella enterica serovar Enteritidis strains that can serve as live oral vaccines and as "reagent strains" for subunit vaccine production in a safe and economical manner. Prototype attenuated vaccine strains CVD 1921 and CVD 1941, derived from the invasive wild-type strains S. Typhimurium I77 and S. Enteritidis R11, respectively, were constructed by deleting guaBA, encoding guanine biosynthesis, and clpP, encoding a master protease regulator. The clpP mutation resulted in a hyperflagellation phenotype. An additional deletion in fliD yielded reagent strains CVD 1923 and CVD 1943, respectively, which export flagellin monomers. Oral 50% lethal dose (LD₅₀) analyses showed that the NTS vaccine strains were all highly attenuated in mice. Oral immunization with CVD 1921 or CVD 1923 protected mice against lethal challenge with wild-type S. Typhimurium I77. Immunization with CVD 1941 but not CVD 1943 protected mice against lethal infection with S. Enteritidis R11. Immune responses induced by these strains included high levels of serum IgG anti-lipopolysaccharide (LPS) and anti-flagellum antibodies, with titers increasing progressively during the immunization schedule. Since S. Typhimurium and S. Enteritidis are the most common NTS serovars associated with invasive disease, these findings can pave the way for development of a highly effective, broad-spectrum vaccine against invasive NTS.

  3. A genetically engineered live-attenuated simian-human immunodeficiency virus that co-expresses the RANTES gene improves the magnitude of cellular immunity in rhesus macaques

    International Nuclear Information System (INIS)

    Shimizu, Yuya; Inaba, Katsuhisa; Kaneyasu, Kentaro; Ibuki, Kentaro; Himeno, Ai; Okoba, Masashi; Goto, Yoshitaka; Hayami, Masanori; Miura, Tomoyuki; Haga, Takeshi

    2007-01-01

    Regulated-on-activation-normal-T-cell-expressed-and-secreted (RANTES), a CC-chemokine, enhances antigen-specific T helper (Th) type-1 responses against HIV-1. To evaluate the adjuvant effects of RANTES against HIV vaccine candidate in SHIV-macaque models, we genetically engineered a live-attenuated SHIV to express the RANTES gene (SHIV-RANTES) and characterized the virus's properties in vivo. After the vaccination, the plasma viral loads were same in the SHIV-RANTES-inoculated monkeys and the parental nef-deleted SHIV (SHIV-NI)-inoculated monkeys. SHIV-RANTES provided some immunity in monkeys by remarkably increasing the antigen-specific CD4 + Th cell-proliferative response and by inducing an antigen-specific IFN-γ ELISpot response. The magnitude of the immunity in SHIV-RANTES-immunized animals, however, failed to afford greater protection against a heterologous pathogenic SHIV (SHIV-C2/1) challenge compared to control SHIV-NI-immunized animals. SHIV-RANTES immunized monkeys, elicited robust cellular CD4 + Th responses and IFN-γ ELISpot responses after SHIV-C2/1 challenge. These findings suggest that the chemokine RANTES can augment vaccine-elicited, HIV-specific CD4 + T cell responses

  4. LIVE ATTENUATED VACCINES FOR THE IMMUNOPROPHYLAXIS

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    O. A. Shamsutdinova

    2017-01-01

    Full Text Available The review focuses on the history of the production of live antiviral vaccines and their use for the prevention of infectious diseases. It was noted that before the beginning of the 20th century, only three live vaccines were developed and put into practice — against smallpox, rabies, plague. The discovery of D. Enders, T.H. Weller and F.Ch. Robins of the ability of the polio virus, and then of a number of other viruses, to reproduce in vitro in cell cultures of various types, greatly expanded the studies on the production of attenuated strains of viruses for live vaccines. The historical stages of obtaining and introducing live vaccines for the prevention of smallpox, poliomyelitis, measles, rubella, and mumps are highlighted. Arguments in favor of the use of associated vaccine preparations for the prevention of viral infections are presented. Various variants of the strategy and tactics of using live vaccines, which are used for specific prevention of viral infections in different countries, are described. The review provides information on technological methods for obtaining antiviral vaccines. The publications testifying to the development of specific reactions in immunized vaccine strains of measles, mumps, poliomyelitis and rubella viruses, such as aseptic meningitis (vaccine strains of mumps virus, acute arthritis (vaccine rubella virus strains, temperature reactions, rash (vaccine strains of the virus Measles, vaccine-associated paralytic poliomyelitis (VAPP vaccine vaccine poliovirus. It is particularly noted that the long experience of vaccine prevention both in Russia and abroad convincingly shows that the risk of developing post-vaccination complications is incommensurably lower than the risk of causing harm to health from the corresponding infections. It is concluded that despite introduction of new third and fourth generation vaccines into practice, live attenuated vaccines do not lose their significance and are used in vaccine

  5. Live attenuated S. Typhimurium vaccine with improved safety in immuno-compromised mice.

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    Balamurugan Periaswamy

    Full Text Available Live attenuated vaccines are of great value for preventing infectious diseases. They represent a delicate compromise between sufficient colonization-mediated adaptive immunity and minimizing the risk for infection by the vaccine strain itself. Immune defects can predispose to vaccine strain infections. It has remained unclear whether vaccine safety could be improved via mutations attenuating a vaccine in immune-deficient individuals without compromising the vaccine's performance in the normal host. We have addressed this hypothesis using a mouse model for Salmonella diarrhea and a live attenuated Salmonella Typhimurium strain (ssaV. Vaccination with this strain elicited protective immunity in wild type mice, but a fatal systemic infection in immune-deficient cybb(-/-nos2(-/- animals lacking NADPH oxidase and inducible NO synthase. In cybb(-/-nos2(-/- mice, we analyzed the attenuation of 35 ssaV strains carrying one additional mutation each. One strain, Z234 (ssaV SL1344_3093, was >1000-fold attenuated in cybb(-/-nos2(-/- mice and ≈100 fold attenuated in tnfr1(-/- animals. However, in wt mice, Z234 was as efficient as ssaV with respect to host colonization and the elicitation of a protective, O-antigen specific mucosal secretory IgA (sIgA response. These data suggest that it is possible to engineer live attenuated vaccines which are specifically attenuated in immuno-compromised hosts. This might help to improve vaccine safety.

  6. Engineering a Light-Attenuating Artificial Iris.

    Science.gov (United States)

    Shareef, Farah J; Sun, Shan; Kotecha, Mrignayani; Kassem, Iris; Azar, Dimitri; Cho, Michael

    2016-04-01

    Discomfort from light exposure leads to photophobia, glare, and poor vision in patients with congenital or trauma-induced iris damage. Commercial artificial iris lenses are static in nature to provide aesthetics without restoring the natural iris's dynamic response to light. A new photo-responsive artificial iris was therefore developed using a photochromic material with self-adaptive light transmission properties and encased in a transparent biocompatible polymer matrix. The implantable artificial iris was designed and engineered using Photopia, a class of photo-responsive materials (termed naphthopyrans) embedded in polyethylene. Photopia was reshaped into annular disks that were spin-coated with polydimethylsiloxane (PDMS) to form our artificial iris lens of controlled thickness. Activated by UV and blue light in approximately 5 seconds with complete reversal in less than 1 minute, the artificial iris demonstrates graded attenuation of up to 40% of visible and 60% of UV light. There optical characteristics are suitable to reversibly regulate the incident light intensity. In vitro cell culture experiments showed up to 60% cell death within 10 days of exposure to Photopia, but no significant cell death observed when cultured with the artificial iris with protective encapsulation. Nuclear magnetic resonance spectroscopy confirmed these results as there was no apparent leakage of potentially toxic photochromic material from the ophthalmic device. Our artificial iris lens mimics the functionality of the natural iris by attenuating light intensity entering the eye with its rapid reversible change in opacity and thus potentially providing an improved treatment option for patients with iris damage.

  7. Engineering a Light-Attenuating Artificial Iris

    Science.gov (United States)

    Shareef, Farah J.; Sun, Shan; Kotecha, Mrignayani; Kassem, Iris; Azar, Dimitri; Cho, Michael

    2016-01-01

    Purpose Discomfort from light exposure leads to photophobia, glare, and poor vision in patients with congenital or trauma-induced iris damage. Commercial artificial iris lenses are static in nature to provide aesthetics without restoring the natural iris's dynamic response to light. A new photo-responsive artificial iris was therefore developed using a photochromic material with self-adaptive light transmission properties and encased in a transparent biocompatible polymer matrix. Methods The implantable artificial iris was designed and engineered using Photopia, a class of photo-responsive materials (termed naphthopyrans) embedded in polyethylene. Photopia was reshaped into annular disks that were spin-coated with polydimethylsiloxane (PDMS) to form our artificial iris lens of controlled thickness. Results Activated by UV and blue light in approximately 5 seconds with complete reversal in less than 1 minute, the artificial iris demonstrates graded attenuation of up to 40% of visible and 60% of UV light. There optical characteristics are suitable to reversibly regulate the incident light intensity. In vitro cell culture experiments showed up to 60% cell death within 10 days of exposure to Photopia, but no significant cell death observed when cultured with the artificial iris with protective encapsulation. Nuclear magnetic resonance spectroscopy confirmed these results as there was no apparent leakage of potentially toxic photochromic material from the ophthalmic device. Conclusions Our artificial iris lens mimics the functionality of the natural iris by attenuating light intensity entering the eye with its rapid reversible change in opacity and thus potentially providing an improved treatment option for patients with iris damage. PMID:27116547

  8. Envelope exchange for the generation of live-attenuated arenavirus vaccines.

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    Andreas Bergthaler

    2006-06-01

    Full Text Available Arenaviruses such as Lassa fever virus cause significant mortality in endemic areas and represent potential bioterrorist weapons. The occurrence of arenaviral hemorrhagic fevers is largely confined to Third World countries with a limited medical infrastructure, and therefore live-attenuated vaccines have long been sought as a method of choice for prevention. Yet their rational design and engineering have been thwarted by technical limitations. In addition, viral genes had not been identified that are needed to cause disease but can be deleted or substituted to generate live-attenuated vaccine strains. Lymphocytic choriomeningitis virus, the prototype arenavirus, induces cell-mediated immunity against Lassa fever virus, but its safety for humans is unclear and untested. Using this virus model, we have developed the necessary methodology to efficiently modify arenavirus genomes and have exploited these techniques to identify an arenaviral Achilles' heel suitable for targeting in vaccine design. Reverse genetic exchange of the viral glycoprotein for foreign glycoproteins created attenuated vaccine strains that remained viable although unable to cause disease in infected mice. This phenotype remained stable even after extensive propagation in immunodeficient hosts. Nevertheless, the engineered viruses induced T cell-mediated immunity protecting against overwhelming systemic infection and severe liver disease upon wild-type virus challenge. Protection was established within 3 to 7 d after immunization and lasted for approximately 300 d. The identification of an arenaviral Achilles' heel demonstrates that the reverse genetic engineering of live-attenuated arenavirus vaccines is feasible. Moreover, our findings offer lymphocytic choriomeningitis virus or other arenaviruses expressing foreign glycoproteins as promising live-attenuated arenavirus vaccine candidates.

  9. Envelope Exchange for the Generation of Live-Attenuated Arenavirus Vaccines.

    Directory of Open Access Journals (Sweden)

    2006-06-01

    Full Text Available Arenaviruses such as Lassa fever virus cause significant mortality in endemic areas and represent potential bioterrorist weapons. The occurrence of arenaviral hemorrhagic fevers is largely confined to Third World countries with a limited medical infrastructure, and therefore live-attenuated vaccines have long been sought as a method of choice for prevention. Yet their rational design and engineering have been thwarted by technical limitations. In addition, viral genes had not been identified that are needed to cause disease but can be deleted or substituted to generate live-attenuated vaccine strains. Lymphocytic choriomeningitis virus, the prototype arenavirus, induces cell-mediated immunity against Lassa fever virus, but its safety for humans is unclear and untested. Using this virus model, we have developed the necessary methodology to efficiently modify arenavirus genomes and have exploited these techniques to identify an arenaviral Achilles' heel suitable for targeting in vaccine design. Reverse genetic exchange of the viral glycoprotein for foreign glycoproteins created attenuated vaccine strains that remained viable although unable to cause disease in infected mice. This phenotype remained stable even after extensive propagation in immunodeficient hosts. Nevertheless, the engineered viruses induced T cell-mediated immunity protecting against overwhelming systemic infection and severe liver disease upon wild-type virus challenge. Protection was established within 3 to 7 d after immunization and lasted for approximately 300 d. The identification of an arenaviral Achilles' heel demonstrates that the reverse genetic engineering of live-attenuated arenavirus vaccines is feasible. Moreover, our findings offer lymphocytic choriomeningitis virus or other arenaviruses expressing foreign glycoproteins as promising live-attenuated arenavirus vaccine candidates.

  10. A novel live-attenuated vaccine candidate for mayaro Fever.

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    William J Weise

    2014-08-01

    Full Text Available Mayaro virus (MAYV is an emerging, mosquito-borne alphavirus that causes a dengue-like illness in many regions of South America, and which has the potential to urbanize. Because no specific treatment or vaccine is available for MAYV infection, we capitalized on an IRES-based approach to develop a live-attenuated MAYV vaccine candidate. Testing in infant, immunocompetent as well as interferon receptor-deficient mice demonstrated a high degree of attenuation, strong induction of neutralizing antibodies, and efficacy against lethal challenge. This vaccine strain was also unable to infect mosquito cells, a major safety feature for a live vaccine derived from a mosquito-borne virus. Further preclinical development of this vaccine candidate is warranted to protect against this important emerging disease.

  11. Principles underlying rational design of live attenuated influenza vaccines

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    Jang, Yo Han

    2012-01-01

    Despite recent innovative advances in molecular virology and the developments of vaccines, influenza virus remains a serious burden for human health. Vaccination has been considered a primary countermeasure for prevention of influenza infection. Live attenuated influenza vaccines (LAIVs) are particularly attracting attention as an effective strategy due to several advantages over inactivated vaccines. Cold-adaptation, as a classical means for attenuating viral virulence, has been successfully used for generating safe and effective donor strains of LAIVs against seasonal epidemics and occasional pandemics. Recently, the advent of reverse genetics technique expedited a variety of rational strategies to broaden the pool of LAIVs. Considering the breadth of antigenic diversity of influenza virus, the pool of LAIVs is likely to equip us with better options for controlling influenza pandemics. With a brief reflection on classical attenuating strategies used at the initial stage of development of LAIVs, especially on the principles underlying the development of cold-adapted LAIVs, we further discuss and outline other attenuation strategies especially with respect to the rationales for attenuation, and their practicality for mass production. Finally, we propose important considerations for a rational vaccine design, which will provide us with practical guidelines for improving the safety and effectiveness of LAIVs. PMID:23596576

  12. Live attenuated hepatitis A vaccines developed in China

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    Xu, Zhi-Yi; Wang, Xuan-Yi

    2014-01-01

    Two live, attenuated hepatitis A vaccines, H2 and LA-1 virus strains, were developed through serial passages of the viruses in cell cultures at 32 °C and 35 °C respectively. Both vaccines were safe and immunogenic, providing protection against clinical hepatitis A in 95% of the vaccinees, with a single dose by subcutaneous injection. The vaccine recipients were not protected from asymptomatic, subclinical hepatitis A virus (HAV) infection, which induced a similar antibody response as for unvaccinated subjects. A second dose caused anamnestic response and can be used for boosting. Oral immunization of human with H2 vaccine or of marmoset with LA-1 vaccine failed, and no evidence was found for person-to-person transmission of H2 strain or for marmoset-to-marmoset transmission of LA-1 strain by close contact. H2 strain was genetically stable when passaged in marmosets, humans or cell cultures at 37 °C; 3 consecutive passages of the virus in marmosets did not cause virulence mutation. The live vaccines offer the benefits of low cost, single dose injection, long- term protection, and increased duration of immunity through subclinical infection. Improved sanitation and administration of 150 million doses of the live vaccines to children had led to a 90% reduction in the annual national incidence rate of hepatitis A in China during the 16-year period, from 1991 to 2006. Hepatitis A (HA) immunization with both live and inactivated HA vaccines was implemented in the national routine childhood immunization program in 2008 and around 92% of the 16 million annual births received the affordable live, attenuated vaccines at 18 months of age. Near elimination of the disease was achieved in a county of China for 14 years following introduction of the H2 live vaccine into the Expanded Immunization Program (EPI) in 1992. PMID:24280971

  13. Conditional live virus as a novel approach towards a safe live attenuated HIV vaccine

    NARCIS (Netherlands)

    Das, Atze T.; Zhou, Xue; Vink, Monique; Klaver, Bep; Berkhout, Ben

    2002-01-01

    To control the worldwide spread of HIV, a safe and effective prophylactic vaccine is urgently needed. Studies with the simian immunodeficiency virus demonstrated that a live attenuated virus can be effective as a vaccine, but serious concerns about the safety of such a vaccine virus have arisen. We

  14. Influenza Vaccination Strategies: Comparing Inactivated and Live Attenuated Influenza Vaccines

    Directory of Open Access Journals (Sweden)

    Saranya Sridhar

    2015-04-01

    Full Text Available Influenza is a major respiratory pathogen causing annual outbreaks and occasional pandemics. Influenza vaccination is the major method of prophylaxis. Currently annual influenza vaccination is recommended for groups at high risk of complications from influenza infection such as pregnant women, young children, people with underlying disease and the elderly, along with occupational groups such a healthcare workers and farm workers. There are two main types of vaccines available: the parenteral inactivated influenza vaccine and the intranasal live attenuated influenza vaccine. The inactivated vaccines are licensed from 6 months of age and have been used for more than 50 years with a good safety profile. Inactivated vaccines are standardized according to the presence of the viral major surface glycoprotein hemagglutinin and protection is mediated by the induction of vaccine strain specific antibody responses. In contrast, the live attenuated vaccines are licensed in Europe for children from 2–17 years of age and provide a multifaceted immune response with local and systemic antibody and T cell responses but with no clear correlate of protection. Here we discuss the immunological immune responses elicited by the two vaccines and discuss future work to better define correlates of protection.

  15. Live-Attenuated Bacterial Vectors: Tools for Vaccine and Therapeutic Agent Delivery

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    Ivan Y. C. Lin

    2015-11-01

    Full Text Available Genetically attenuated microorganisms, including pathogenic and commensal bacteria, can be engineered to carry and deliver heterologous antigens to elicit host immunity against both the vector as well as the pathogen from which the donor gene is derived. These live attenuated bacterial vectors have been given much attention due to their capacity to induce a broad range of immune responses including localized mucosal, as well as systemic humoral and/or cell-mediated immunity. In addition, the unique tumor-homing characteristics of these bacterial vectors has also been exploited for alternative anti-tumor vaccines and therapies. In such approach, tumor-associated antigen, immunostimulatory molecules, anti-tumor drugs, or nucleotides (DNA or RNA are delivered. Different potential vectors are appropriate for specific applications, depending on their pathogenic routes. In this review, we survey and summarize the main features of the different types of live bacterial vectors and discussed the clinical applications in the field of vaccinology. In addition, different approaches for using live attenuated bacterial vectors for anti-cancer therapy is discussed, and some promising pre-clinical and clinical studies in this field are outlined.

  16. Live attenuated vaccines: Historical successes and current challenges.

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    Minor, Philip D

    2015-05-01

    Live attenuated vaccines against human viral diseases have been amongst the most successful cost effective interventions in medical history. Smallpox was declared eradicated in 1980; poliomyelitis is nearing global eradication and measles has been controlled in most parts of the world. Vaccines function well for acute diseases such as these but chronic infections such as HIV are more challenging for reasons of both likely safety and probable efficacy. The derivation of the vaccines used has in general not been purely rational except in the sense that it has involved careful clinical trials of candidates and subsequent careful follow up in clinical use; the identification of the candidates is reviewed. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

  17. Live attenuated vaccines: Historical successes and current challenges

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    Minor, Philip D., E-mail: Philip.Minor@nibsc.org

    2015-05-15

    Live attenuated vaccines against human viral diseases have been amongst the most successful cost effective interventions in medical history. Smallpox was declared eradicated in 1980; poliomyelitis is nearing global eradication and measles has been controlled in most parts of the world. Vaccines function well for acute diseases such as these but chronic infections such as HIV are more challenging for reasons of both likely safety and probable efficacy. The derivation of the vaccines used has in general not been purely rational except in the sense that it has involved careful clinical trials of candidates and subsequent careful follow up in clinical use; the identification of the candidates is reviewed. - Highlights: • Live vaccines against human diseases caused by viruses have been very successful. • They have been developed by empirical clinical studies and problems identified in later use. • It can be difficult to balance ability to cause disease and ability to immunise for a strain. • There is currently no reliable basis for predicting success from pure virological studies. • Vaccinia, which eradicated smallpox, is the paradigm for all successes and issues.

  18. Live attenuated vaccines: Historical successes and current challenges

    International Nuclear Information System (INIS)

    Minor, Philip D.

    2015-01-01

    Live attenuated vaccines against human viral diseases have been amongst the most successful cost effective interventions in medical history. Smallpox was declared eradicated in 1980; poliomyelitis is nearing global eradication and measles has been controlled in most parts of the world. Vaccines function well for acute diseases such as these but chronic infections such as HIV are more challenging for reasons of both likely safety and probable efficacy. The derivation of the vaccines used has in general not been purely rational except in the sense that it has involved careful clinical trials of candidates and subsequent careful follow up in clinical use; the identification of the candidates is reviewed. - Highlights: • Live vaccines against human diseases caused by viruses have been very successful. • They have been developed by empirical clinical studies and problems identified in later use. • It can be difficult to balance ability to cause disease and ability to immunise for a strain. • There is currently no reliable basis for predicting success from pure virological studies. • Vaccinia, which eradicated smallpox, is the paradigm for all successes and issues

  19. Yellow fever live attenuated vaccine: A very successful live attenuated vaccine but still we have problems controlling the disease.

    Science.gov (United States)

    Barrett, Alan D T

    2017-10-20

    Yellow fever (YF) is regarded as the original hemorrhagic fever and has been a major public health problem for at least 250years. A very effective live attenuated vaccine, strain 17D, was developed in the 1930s and this has proved critical in the control of the disease. There is little doubt that without the vaccine, YF virus would be considered a biosafety level 4 pathogen. Significantly, YF is currently the only disease where an international vaccination certificate is required under the International Health Regulations. Despite having a very successful vaccine, there are occasional issues of supply and demand, such as that which occurred in Angola and Democratic Republic of Congo in 2016 when there was insufficient vaccine available. For the first time fractional dosing of the vaccine was approved on an emergency basis. Thus, continued vigilance and improvements in supply and demand are needed in the future. Copyright © 2017. Published by Elsevier Ltd.

  20. Preparation of live attenuated leishmania parasites by using laser technology

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    Hussain, Nabiha; Alkhouri, Hassan; Haddad, Shaden

    2018-05-01

    Leishmaniasis is a parasitic disease of humans, affecting the skin, mucosal and/or internal organs, caused by flagellate protozoa Leishmania of the Trypanosomatidae family. Leishmania would be one for which a vaccine could be developed with relative ease. Many studies mount an effective response that resolves the infection and confers solid immunity to reinfection and suggesting that infection may be a prerequisite for immunological memory. Genetically altered live attenuated parasites with controlled infectivity could achieve such immunological memory. Recent concepts include use of genetically modified live-attenuated Leishmania parasites, and proteomics approach for the search of a cross-protective leishmanial vaccine that would ideally protect against both cutaneous and visceral forms of the disease. No licensed vaccine is available till date against any form of leishmaniasis. The present study evaluated role of laser technology in development of a safe live Leishmania vaccine, a vaccine is a biological preparation that improves immunity to a particular disease, and is often made from weakened or killed forms of LPs. The parasite culture was expanded in RPMI 1640 medium with 10% fetal calf serum (FCS) and grown until stationary phase for experiments. 80 samples of leishmania promastigotes (Culture media of LPs) were exposed to Nd:YAG laser (wavelength 1064 nm, single spot or double) with different outputs powers (7w, 100 Hz, 99.03w/cm2, 0.99 J/cm2 and 8 w, 100 Hz, 113.18w/cm2 1.13J/cm2)) for suitable exposer times. The effect of semiconductor laser (wavelength 810 nm, 7w, 2000 Hz, 99.03w/cm2, 0.05 J/cm2) or (7 w, 500 Hz, 99.03 w/cm2, 0.2J/cm2) single spot or double with long exposure times. The viability of Leishmania parasites was measured using XTT method; viable parasites were decreased with long exposure times. XTT test referred both these wavelengths were effective in killing percentage of Leishmania promastigotes, the remaining were devoid flagellum that

  1. Prior DNA vaccination does not interfere with the live-attenuated measles vaccine.

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    Premenko-Lanier, Mary; Rota, Paul; Rhodes, Gary; Bellini, William; McChesney, Michael

    2004-01-26

    The currently used live-attenuated measles vaccine is very effective although maternal antibody prevents its administration prior to 6 months of age. We are investigating the ability of a DNA vaccine encoding the measles viral hemagglutinin, fusion and nucleoprotein to protect newborn infants from measles. Here, we show that a measles DNA vaccine protects juvenile macaques from pathogenic measles virus challenge and that macaques primed and boosted with this DNA vaccine have anemnestic antibody and cell-mediated responses after vaccination with a live-attenuated canine distemper-measles vaccine. Therefore, this DNA vaccine administered to newborn infants may not hinder the subsequent use of live-attenuated measles vaccine.

  2. Safety and immunogenicity of a live attenuated mumps vaccine

    Science.gov (United States)

    Liang, Yan; Ma, Jingchen; Li, Changgui; Chen, Yuguo; Liu, Longding; Liao, Yun; Zhang, Ying; Jiang, Li; Wang, Xuan-Yi; Che, Yanchun; Deng, Wei; Li, Hong; Cui, Xiaoyu; Ma, Na; Ding, Dong; Xie, Zhongping; Cui, Pingfang; Ji, Qiuyan; Wang, Jingjing; Zhao, Yuliang; Wang, Junzhi; Li, Qihan

    2014-01-01

    Background: Mumps, a communicable, acute and previously well-controlled disease, has had recent and occasional resurgences in some areas. Methods: A randomized, double-blind, controlled and multistep phase I study of an F-genotype attenuated mumps vaccine produced in human diploid cells was conducted. A total of 300 subjects were enrolled and divided into 4 age groups: 16–60 years, 5–16 years, 2–5 years and 8–24 months. The groups were immunized with one injection per subject. Three different doses of the F-genotype attenuated mumps vaccine, A (3.5 ± 0.25 logCCID50), B (4.25 ± 0.25 logCCID50) and C (5.0 ± 0.25 logCCID50), as well as a placebo control and a positive control of a licensed A-genotype vaccine (S79 strain) were used. The safety and immunogenicity of this vaccine were compared with those of the controls. Results: The safety evaluation suggested that mild adverse reactions were observed in all groups. No serious adverse event (SAE) was reported throughout the trial. The immunogenicity test showed a similar seroconversion rate of the neutralizing and ELISA antibody in the 2- to 5-year-old and 8- to 24-month-old groups compared with the seroconversion rate in the positive control. The GMT of the neutralizing anti-F-genotype virus antibodies in the vaccine groups was slightly higher than that in the positive control group. Conclusions: The F-genotype attenuated mumps vaccine evaluated in this clinical trial was demonstrated to be safe and have effective immunogenicity vs. control. PMID:24614759

  3. Engineering flesh : towards professional responsibility for 'lived bodies' in tissue engineering

    NARCIS (Netherlands)

    Derksen, M.H.G.

    2008-01-01

    Engineering Flesh. Towards professional responsibility for ‘lived bodies’ in Tissue Engineering This study analyses the work of biomedical engineers as normative work that affects people’s daily lives as bodies. In biomedical engineering, engineers study bodies as machine-like objects and develop

  4. Potency Studies of live- Attenuated Viral Vaccines Administered in ...

    African Journals Online (AJOL)

    We critically carried out a potency study in 1992 and 1997 on measles and poliovirus vaccines administered at five different vaccination centers in the metropolitan Lagos, Nigeria. using WHO guidelines on titration of live- viral vaccines, our results revealed that only 6 (16.7%) of 36 measles vaccine (MV) vials and 11 ...

  5. Immunity to Visceral Leishmaniasis Using Genetically Defined Live-Attenuated Parasites

    Directory of Open Access Journals (Sweden)

    Angamuthu Selvapandiyan

    2012-01-01

    Full Text Available Leishmaniasis is a protozoan parasitic disease endemic to the tropical and subtropical regions of the world, with three major clinical forms, self-healing cutaneous leishmaniasis (CL, mucocutaneous leishmaniasis (MCL, and visceral leishmaniasis (VL. Drug treatments are expensive and often result in the development of drug resistance. No vaccine is available against leishmaniasis. Subunit Leishmania vaccine immunization in animal models has shown some efficacy but little or none in humans. However, individuals who recover from natural infection are protected from reinfection and develop life-long protection, suggesting that infection may be a prerequisite for immunological memory. Thus, genetically altered live-attenuated parasites with controlled infectivity could achieve such memory. In this paper, we discuss development and characteristics of genetically altered, live-attenuated Leishmania donovani parasites and their possible use as vaccine candidates against VL. In addition, we discuss the challenges and other considerations in the use of live-attenuated parasites.

  6. Development of live attenuated sparfloxacin-resistant Streptococcus agalactiae polyvalent vaccines to protect Nile tilapia

    Science.gov (United States)

    To develop attenuated bacteria as potential live vaccines, sparfloxacin was used in this study to modify 40 isolates of Streptococcus agalactiae. Majority of S. agalactiae used in this study were able to develop at least 80-fold resistance to sparfloxacin. When the virulence of the sparfloxacin-resi...

  7. [A case of orchitis following vaccination with freeze-dried live attenuated mumps vaccine].

    Science.gov (United States)

    Suzuki, Masayasu; Takizawa, Akitoshi; Furuta, Akira; Yanada, Shuichi; Iwamuro, Shinya; Tashiro, Kazuya

    2002-05-01

    In Japan, freeze-dried live attenuated mumps vaccine has been used optionally since 1981. The effectiveness of mumps vaccination has been established by worldwide research since 1971. On the other hand, because of it's live activity several untoward effects have been reported. Vaccination-related mumps orchitis is a rare adverse effect of mumps vaccine. Only 9 cases of vaccination-related mumps orchitis have been reported in Japan. We describe a case of orchitis following mumps vaccination in adolescence. A 16 years-old male has admitted because of acute orchitis with high fever and painful swelling of right testis. The patient had received vaccination with freeze-dried live attenuated mumps vaccine 16 days before admission. After admission, the bed-rest had completely relieved the symptoms on 6th hospital day. The impaired testis has maintained normal size and consistency 6 months after discharge.

  8. Exploratory re-encoding of Yellow Fever Virus genome: new insights for the design of live-attenuated viruses

    OpenAIRE

    Klitting, Raphaelle; Riziki, Toilhata; Moureau, Gregory; De Lamballerie, Xavier; Piorkowski, Geraldine

    2018-01-01

    Virus attenuation by genome re-encoding is a pioneering approach for generating live-attenuated vaccine candidates. Its core principle is to introduce a large number of slightly deleterious synonymous mutations into the viral genome to produce a stable attenuation of the targeted virus. The large number of mutations introduced is supposed to guarantee the stability of the attenuated phenotype by lowering the risks of reversion and recombination for re-encoded sequences. In this prospect, iden...

  9. Updated data on effective and safe immunizations with live-attenuated vaccines for children after living donor liver transplantation.

    Science.gov (United States)

    Shinjoh, Masayoshi; Hoshino, Ken; Takahashi, Takao; Nakayama, Tetsuo

    2015-01-29

    Although immunizations using live-attenuated vaccines are not recommended for children post-liver transplant due to their theoretical risks, they will inevitably encounter vaccine-preventable viral diseases upon returning to real-life situations. The window of opportunity for vaccination is usually limited prior to transplantation because these children often have unstable disease courses. Also, vaccine immunity does not always persist after transplantation. Beginning in 2002, subcutaneous immunizations with four individual live-attenuated vaccines (measles, rubella, varicella, and mumps) to pediatric patients following living donor liver transplantation (LDLT) were performed for those who fulfilled the clinical criteria, including humoral and cell-mediated immunity. Written informed consent was collected. We included the study on 70 immunizations for 18 cases that we reported in 2008 (Shinjoh et al., 2008). A total of 196 immunizations were administered to 48 pediatric post-LDLT recipients. Of these, 144 were first immunizations and 52 were repeated immunizations following LDLT. The seroconversion rates at the first dose for measles (AIK-C), rubella (TO-336), varicella (Oka), and mumps (Hoshino) were 100% (36/36), 100% (35/35), 70% (23/33), and 75% (24/32), respectively. Antibody levels did not fall over time in patients immunized with rubella vaccine. Three mild cases of breakthrough varicella were observed. Two cases with transient parotid gland swelling were observed after mumps immunization. Two admissions because of fever at 2-3 weeks after the measles vaccine were reported but the patients had no symptoms of measles. Immunizations using selected live-attenuated vaccines were safe and effective for post-LDLT children who were not severely immunosuppressed. However, with the exception of rubella, repeated immunization may be necessary. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Preliminary development of a live attenuated canine parvovirus vaccine from an isolate of British origin.

    Science.gov (United States)

    Churchill, A E

    1987-04-04

    Canine parvovirus isolated from a case of haemorrhagic enteritis in a breeding kennel in England was passaged and cloned in cultured feline and canine cells. No significant evidence of pathogenicity was found during six serial passages of the modified virus back through young dogs. The attenuated virus was excreted by inoculated animals and spread rapidly to uninoculated animals held in contact. When high titre attenuated virus was given to the six-week-old offspring of a seropositive dam a prompt seroconversion was observed. When the attenuated virus was used as an experimental vaccine in 108 pups in an infected breeding colony a highly significant improvement was obtained in the accumulated morbidity and mortality compared with a parallel group vaccinated with modified live feline panleucopenia virus.

  11. A review of immunogenicity and tolerability of live attenuated Hepatitis A vaccine in children

    Science.gov (United States)

    Rao, Sameer; Mao, J. S.; Motlekar, Salman; Fangcheng, Zhuang; Kadhe, Ganesh

    2016-01-01

    ABSTRACT Changing epidemiology of Hepatitis A virus (HAV) has led to an increased susceptibility of adolescents and adults to the infection. Vaccination can remarkably reduce the incidence and associated morbidity of HAV infection. This review is focused on the safety and efficacy of H2 strain derived live attenuated Hepatitis A vaccine. We found the vaccine to be highly immunogenic with minimal or negligible safety issues. Moreover, a single dose of live attenuated vaccine persists a long term immune response and can be a preferred option for developing countries. In 2014, Indian Academy of Paediatrics (IAP) also updated their recommendations for H2 vaccine as a single dose as against the previous 2 dose schedule. A focused approach to include the vaccine in national immunization program should be explored. PMID:27532370

  12. Live Attenuated Influenza Vaccine Enhances Colonization of Streptococcus pneumoniae and Staphylococcus aureus in Mice

    Science.gov (United States)

    Mina, Michael J.; McCullers, Jonathan A.; Klugman, Keith P.

    2014-01-01

    ABSTRACT Community interactions at mucosal surfaces between viruses, like influenza virus, and respiratory bacterial pathogens are important contributors toward pathogenesis of bacterial disease. What has not been considered is the natural extension of these interactions to live attenuated immunizations, and in particular, live attenuated influenza vaccines (LAIVs). Using a mouse-adapted LAIV against influenza A (H3N2) virus carrying the same mutations as the human FluMist vaccine, we find that LAIV vaccination reverses normal bacterial clearance from the nasopharynx and significantly increases bacterial carriage densities of the clinically important bacterial pathogens Streptococcus pneumoniae (serotypes 19F and 7F) and Staphylococcus aureus (strains Newman and Wright) within the upper respiratory tract of mice. Vaccination with LAIV also resulted in 2- to 5-fold increases in mean durations of bacterial carriage. Furthermore, we show that the increases in carriage density and duration were nearly identical in all aspects to changes in bacterial colonizing dynamics following infection with wild-type (WT) influenza virus. Importantly, LAIV, unlike WT influenza viruses, had no effect on severe bacterial disease or mortality within the lower respiratory tract. Our findings are, to the best of our knowledge, the first to demonstrate that vaccination with a live attenuated viral vaccine can directly modulate colonizing dynamics of important and unrelated human bacterial pathogens, and does so in a manner highly analogous to that seen following wild-type virus infection. PMID:24549845

  13. Herpes Simplex Vaccines: Prospects of Live-attenuated HSV Vaccines to Combat Genital and Ocular infections

    Science.gov (United States)

    Stanfield, Brent; Kousoulas, Konstantin Gus

    2015-01-01

    Herpes simplex virus type-1 (HSV-1) and its closely related type-2 (HSV-2) viruses cause important clinical manifestations in humans including acute ocular disease and genital infections. These viruses establish latency in the trigeminal ganglionic and dorsal root neurons, respectively. Both viruses are widespread among humans and can frequently reactivate from latency causing disease. Currently, there are no vaccines available against herpes simplex viral infections. However, a number of promising vaccine approaches are being explored in pre-clinical investigations with few progressing to early phase clinical trials. Consensus research findings suggest that robust humoral and cellular immune responses may partially control the frequency of reactivation episodes and reduce clinical symptoms. Live-attenuated viral vaccines have long been considered as a viable option for generating robust and protective immune responses against viral pathogens. Varicella zoster virus (VZV) belongs to the same alphaherpesvirus subfamily with herpes simplex viruses. A live-attenuated VZV vaccine has been extensively used in a prophylactic and therapeutic approach to combat primary and recurrent VZV infection indicating that a similar vaccine approach may be feasible for HSVs. In this review, we summarize pre-clinical approaches to HSV vaccine development and current efforts to test certain vaccine approaches in human clinical trials. Also, we discuss the potential advantages of using a safe, live-attenuated HSV-1 vaccine strain to protect against both HSV-1 and HSV-2 infections. PMID:27114893

  14. Identification of sequence changes in live attenuated goose parvovirus vaccine strains developed in Asia and Europe.

    Science.gov (United States)

    Shien, J-H; Wang, Y-S; Chen, C-H; Shieh, H K; Hu, C-C; Chang, P-C

    2008-10-01

    Live attenuated vaccines have been used for control of the disease caused by goose parvovirus (GPV), but the mechanism involved in attenuation of GPV remains elusive. This report presents the complete nucleotide sequences of two live attenuated strains of GPV (82-0321V and VG32/1) that were independently developed in Taiwan and Europe, together with the parental strain of 82-0321V and a field strain isolated in Taiwan in 2006. Sequence comparisons showed that 82-0321V and VG32/1 had multiple deletions and substitutions in the inverted terminal repeats region when compared with their parental strain or the field virus, but these changes did not affect the formation of the hairpin structure essential for viral replication. Moreover, 82-0321V and VG32/1 had five amino acid changes in the non-structural protein, but these changes were located at positions distant from known functional motifs in the non-structural protein. In contrast, 82-0321V had nine changes and VG32/1 had 11 changes in their capsid proteins (VP1), and the majority of these changes occurred at positions close to the putative receptor binding sites of VP1, as predicted using the structure of adeno-associated virus 2 as the model system. Taken together, the results suggest that changes in sequence near the receptor binding sites of VP1 might be responsible for attenuation of GPV. This is the first report of complete nucleotide sequences of GPV other than the virulent B strain, and suggests a possible mechanism for attenuation of GPV.

  15. Immunogenicity and protective efficacy of a live attenuated H5N1 vaccine in nonhuman primates.

    Directory of Open Access Journals (Sweden)

    Shufang Fan

    2009-05-01

    Full Text Available The continued spread of highly pathogenic H5N1 influenza viruses among poultry and wild birds, together with the emergence of drug-resistant variants and the possibility of human-to-human transmission, has spurred attempts to develop an effective vaccine. Inactivated subvirion or whole-virion H5N1 vaccines have shown promising immunogenicity in clinical trials, but their ability to elicit protective immunity in unprimed human populations remains unknown. A cold-adapted, live attenuated vaccine with the hemagglutinin (HA and neuraminidase (NA genes of an H5N1 virus A/VN/1203/2004 (clade 1 was protective against the pulmonary replication of homologous and heterologous wild-type H5N1 viruses in mice and ferrets. In this study, we used reverse genetics to produce a cold-adapted, live attenuated H5N1 vaccine (AH/AAca that contains HA and NA genes from a recent H5N1 isolate, A/Anhui/2/05 virus (AH/05 (clade 2.3, and the backbone of the cold-adapted influenza H2N2 A/AnnArbor/6/60 virus (AAca. AH/AAca was attenuated in chickens, mice, and monkeys, and it induced robust neutralizing antibody responses as well as HA-specific CD4+ T cell immune responses in rhesus macaques immunized twice intranasally. Importantly, the vaccinated macaques were fully protected from challenge with either the homologous AH/05 virus or a heterologous H5N1 virus, A/bar-headed goose/Qinghai/3/05 (BHG/05; clade 2.2. These results demonstrate for the first time that a cold-adapted H5N1 vaccine can elicit protective immunity against highly pathogenic H5N1 virus infection in a nonhuman primate model and provide a compelling argument for further testing of double immunization with live attenuated H5N1 vaccines in human trials.

  16. Complete Genome Sequence of the Goatpox Virus Strain Gorgan Obtained Directly from a Commercial Live Attenuated Vaccine

    Science.gov (United States)

    Mathijs, Elisabeth; Vandenbussche, Frank; Haegeman, Andy; Al-Majali, Ahmad; De Clercq, Kris

    2016-01-01

    This is a report of the complete genome sequence of the goatpox virus strain Gorgan, which was obtained directly from a commercial live attenuated vaccine (Caprivac, Jordan Bio-Industries Centre). PMID:27738031

  17. No evidence of murine leukemia virus-related viruses in live attenuated human vaccines.

    Directory of Open Access Journals (Sweden)

    William M Switzer

    Full Text Available The association of xenotropic murine leukemia virus (MLV-related virus (XMRV in prostate cancer and chronic fatigue syndrome reported in previous studies remains controversial as these results have been questioned by recent data. Nonetheless, concerns have been raised regarding contamination of human vaccines as a possible source of introduction of XMRV and MLV into human populations. To address this possibility, we tested eight live attenuated human vaccines using generic PCR for XMRV and MLV sequences. Viral metagenomics using deep sequencing was also done to identify the possibility of other adventitious agents.All eight live attenuated vaccines, including Japanese encephalitis virus (JEV (SA-14-14-2, varicella (Varivax, measles, mumps, and rubella (MMR-II, measles (Attenuvax, rubella (Meruvax-II, rotavirus (Rotateq and Rotarix, and yellow fever virus were negative for XMRV and highly related MLV sequences. However, residual hamster DNA, but not RNA, containing novel endogenous gammaretrovirus sequences was detected in the JEV vaccine using PCR. Metagenomics analysis did not detect any adventitious viral sequences of public health concern. Intracisternal A particle sequences closest to those present in Syrian hamsters and not mice were also detected in the JEV SA-14-14-2 vaccine. Combined, these results are consistent with the production of the JEV vaccine in Syrian hamster cells.We found no evidence of XMRV and MLV in eight live attenuated human vaccines further supporting the safety of these vaccines. Our findings suggest that vaccines are an unlikely source of XMRV and MLV exposure in humans and are consistent with the mounting evidence on the absence of these viruses in humans.

  18. Studies of parvovirus vaccination in the dog: the performance of live attenuated feline parvovirus vaccines.

    Science.gov (United States)

    Thompson, H; McCandlish, I A; Cornwell, H J; Macartney, L; Maxwell, N S; Weipers, A F; Wills, I R; Black, J A; Mackenzie, A C

    1988-04-16

    The performance of three live attenuated feline parvovirus vaccines licensed for use in the dog was studied. At the end of the primary vaccination course 67 per cent of dogs had inadequate antibody levels (less than or equal to 32) as measured by a haemagglutination inhibition test. Interference by maternal antibody accounted for some of the failures but the fact that there was no significant difference in performance between dogs vaccinated at 12 weeks or 16 weeks of age indicated that maternal antibody was not the only factor.

  19. Titration of individual strains in trivalent live-attenuated influenza vaccine without neutralization.

    Science.gov (United States)

    Sirinonthanawech, Naraporn; Surichan, Somchaiya; Namsai, Aphinya; Puthavathana, Pilaipan; Auewarakul, Prasert; Kongchanagul, Alita

    2016-11-01

    Formulation and quality control of trivalent live-attenuated influenza vaccine requires titration of infectivity of individual strains in the trivalent mix. This is usually performed by selective neutralization of two of the three strains and titration of the un-neutralized strain in cell culture or embryonated eggs. This procedure requires standard sera with high neutralizing titer against each of the three strains. Obtaining standard sera, which can specifically neutralize only the corresponding strain of influenza viruses and is able to completely neutralize high concentration of virus in the vaccine samples, can be a problem for many vaccine manufacturers as vaccine stocks usually have very high viral titers and complete neutralization may not be obtained. Here an alternative approach for titration of individual strain in trivalent vaccine without the selective neutralization is presented. This was done by detecting individual strains with specific antibodies in an end-point titration of a trivalent vaccine in cell culture. Similar titers were observed in monovalent and trivalent vaccines for influenza A H3N2 and influenza B strains, whereas the influenza A H1N1 strain did not grow well in cell culture. Viral interference among the vaccine strains was not observed. Therefore, providing that vaccine strains grow well in cell culture, this assay can reliably determine the potency of individual strains in trivalent live-attenuated influenza vaccines. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. A single-dose live-attenuated vaccine prevents Zika virus pregnancy transmission and testis damage.

    Science.gov (United States)

    Shan, Chao; Muruato, Antonio E; Jagger, Brett W; Richner, Justin; Nunes, Bruno T D; Medeiros, Daniele B A; Xie, Xuping; Nunes, Jannyce G C; Morabito, Kaitlyn M; Kong, Wing-Pui; Pierson, Theodore C; Barrett, Alan D; Weaver, Scott C; Rossi, Shannan L; Vasconcelos, Pedro F C; Graham, Barney S; Diamond, Michael S; Shi, Pei-Yong

    2017-09-22

    Zika virus infection during pregnancy can cause congenital abnormities or fetal demise. The persistence of Zika virus in the male reproductive system poses a risk of sexual transmission. Here we demonstrate that live-attenuated Zika virus vaccine candidates containing deletions in the 3' untranslated region of the Zika virus genome (ZIKV-3'UTR-LAV) prevent viral transmission during pregnancy and testis damage in mice, as well as infection of nonhuman primates. After a single-dose vaccination, pregnant mice challenged with Zika virus at embryonic day 6 and evaluated at embryonic day 13 show markedly diminished levels of viral RNA in maternal, placental, and fetal tissues. Vaccinated male mice challenged with Zika virus were protected against testis infection, injury, and oligospermia. A single immunization of rhesus macaques elicited a rapid and robust antibody response, conferring complete protection upon challenge. Furthermore, the ZIKV-3'UTR-LAV vaccine candidates have a desirable safety profile. These results suggest that further development of ZIKV-3'UTR-LAV is warranted for humans.Zika virus infection can result in congenital disorders and cause disease in adults, and there is currently no approved vaccine. Here Shan et al. show that a single dose of a live-attenuated Zika vaccine prevents infection, testis damage and transmission to the fetus during pregnancy in different animal models.

  1. Stabilization of Live Attenuated Influenza Vaccines by Freeze Drying, Spray Drying, and Foam Drying.

    Science.gov (United States)

    Lovalenti, Phillip M; Anderl, Jeff; Yee, Luisa; Nguyen, Van; Ghavami, Behnaz; Ohtake, Satoshi; Saxena, Atul; Voss, Thomas; Truong-Le, Vu

    2016-05-01

    The goal of this research is to develop stable formulations for live attenuated influenza vaccines (LAIV) by employing the drying methods freeze drying, spray drying, and foam drying. Formulated live attenuated Type-A H1N1 and B-strain influenza vaccines with a variety of excipient combinations were dried using one of the three drying methods. Process and storage stability at 4, 25 and 37°C of the LAIV in these formulations was monitored using a TCID50 potency assay. Their immunogenicity was also evaluated in a ferret model. The thermal stability of H1N1 vaccine was significantly enhanced through application of unique formulation combinations and drying processes. Foam dried formulations were as much as an order of magnitude more stable than either spray dried or freeze dried formulations, while exhibiting low process loss and full retention of immunogenicity. Based on long-term stability data, foam dried formulations exhibited a shelf life at 4, 25 and 37°C of >2, 1.5 years and 4.5 months, respectively. Foam dried LAIV Type-B manufactured using the same formulation and process parameters as H1N1 were imparted with a similar level of stability. Foam drying processing methods with appropriate selection of formulation components can produce an order of magnitude improvement in LAIV stability over other drying methods.

  2. A modified live canine parvovirus strain with novel plaque characteristics. I. Viral attenuation and dog response.

    Science.gov (United States)

    Carmichael, L E; Joubert, J C; Pollock, R V

    1981-10-01

    A canine parvovirus (CPV) strain (C-780916) was found attenuated for pups at 80, but not after 51 serial passages in dog kidney cell (DKC) cultures. A variant viral population ('large plaque') emerged after prolonged cultivation in DKC cultures that may be associated with reduced native virulence. Dogs vaccinated with modified CPV developed high hemagglutination-inhibiting (HI) antibody titers within 4 days of incoluation and antibody persisted. Vaccinated animals shed small amounts of virus in the feces that spread to contact dogs. After five back-passages in dogs the modified strain was not pathogenic for pups and the plaque characteristics of the virus isolated from the feces were typical of the attenuated strain. The modified live CPV did not cause infection of the fetus when inoculated parenterally into pregnant bitches at various stages of gestation. It was not pathogenic for neonatal pups. These results suggest that a safe and effective live homologous (CPV) vaccine has been developed which should aid substantially in controlling CPV infection.

  3. A Reverse Genetics Approach for the Design of Methyltransferase-Defective Live Attenuated Avian Metapneumovirus Vaccines.

    Science.gov (United States)

    Zhang, Yu; Sun, Jing; Wei, Yongwei; Li, Jianrong

    2016-01-01

    Avian metapneumovirus (aMPV), also known as avian pneumovirus or turkey rhinotracheitis virus, is the causative agent of turkey rhinotracheitis and is associated with swollen head syndrome in chickens. aMPV belongs to the family Paramyxoviridae which includes many important human pathogens such as human respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and human parainfluenza virus type 3 (PIV3). The family also includes highly lethal emerging pathogens such as Nipah virus and Hendra virus, as well as agriculturally important viruses such as Newcastle disease virus (NDV). For many of these viruses, there is no effective vaccine. Here, we describe a reverse genetics approach to develop live attenuated aMPV vaccines by inhibiting the viral mRNA cap methyltransferase. The viral mRNA cap methyltransferase is an excellent target for the attenuation of paramyxoviruses because it plays essential roles in mRNA stability, efficient viral protein translation and innate immunity. We have described in detail the materials and methods used to generate recombinant aMPVs that lack viral mRNA cap methyltransferase activity. We have also provided methods to evaluate the genetic stability, pathogenesis, and immunogenicity of live aMPV vaccine candidates in turkeys.

  4. 2001 Bhuj, India, earthquake engineering seismoscope recordings and Eastern North America ground-motion attenuation relations

    Science.gov (United States)

    Cramer, C.H.; Kumar, A.

    2003-01-01

    Engineering seismoscope data collected at distances less than 300 km for the M 7.7 Bhuj, India, mainshock are compatible with ground-motion attenuation in eastern North America (ENA). The mainshock ground-motion data have been corrected to a common geological site condition using the factors of Joyner and Boore (2000) and a classification scheme of Quaternary or Tertiary sediments or rock. We then compare these data to ENA ground-motion attenuation relations. Despite uncertainties in recording method, geological site corrections, common tectonic setting, and the amount of regional seismic attenuation, the corrected Bhuj dataset agrees with the collective predictions by ENA ground-motion attenuation relations within a factor of 2. This level of agreement is within the dataset uncertainties and the normal variance for recorded earthquake ground motions.

  5. Live attenuated measles virus vaccine therapy for locally established malignant glioblastoma tumor cells

    Directory of Open Access Journals (Sweden)

    Al-Shammari AM

    2014-05-01

    Full Text Available Ahmed M Al-Shammari,1 Farah E Ismaeel,2 Shahlaa M Salih,2 Nahi Y Yaseen11Experimental Therapy Department, Iraqi Center for Cancer and Medical Genetic Researches, Mustansiriya University, 2Departments of Biotechnology, College of Science, Al-Nahrain University, Baghdad, IraqAbstract: Glioblastoma multiforme is the most aggressive malignant primary brain tumor in humans, with poor prognosis. A new glioblastoma cell line (ANGM5 was established from a cerebral glioblastoma multiforme in a 72-year-old Iraqi man who underwent surgery for an intracranial tumor. This study was carried out to evaluate the antitumor effect of live attenuated measles virus (MV Schwarz vaccine strain on glioblastoma multiforme tumor cell lines in vitro. Live attenuated MV Schwarz strain was propagated on Vero, human rhabdomyosarcoma, and human glioblastoma-multiform (ANGM5 cell lines. The infected confluent monolayer appeared to be covered with syncytia with granulation and vacuolation, as well as cell rounding, shrinkage, and large empty space with cell debris as a result of cell lysis and death. Cell lines infected with virus have the ability for hemadsorption to human red blood cells after 72 hours of infection, whereas no hemadsorption of uninfected cells is seen. Detection of MV hemagglutinin protein by monoclonal antibodies in infected cells of all cell lines by immunocytochemistry assay gave positive results (brown color in the cytoplasm of infected cells. Cell viability was measured after 72 hours of infection by 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay. Results showed a significant cytotoxic effect for MV (P≤0.05 on growth of ANGM5 and rhabdomyosarcoma cell lines after 72 hours of infection. Induction of apoptosis by MV was assessed by measuring mitochondrial membrane potentials in tumor cells after 48, 72, and 120 hours of infection. Apoptotic cells were counted, and the mean percentage of dead cells was significantly higher after 48, 72

  6. Pet ownership may attenuate loneliness among older adult primary care patients who live alone.

    Science.gov (United States)

    Stanley, Ian H; Conwell, Yeates; Bowen, Connie; Van Orden, Kimberly A

    2014-01-01

    Older adults who report feelings of loneliness are at increased risk for a range of negative physical and mental health outcomes, including early mortality. Identifying potential sources of social connectedness, such as pet ownership, could add to the understanding of how to promote health and well-being in older adults. The aim of this study is to describe the association of pet ownership and loneliness. The current study utilizes cross-sectional survey data from a sample (N = 830) of older adult primary care patients (age ≥ 60 years). Pet owners were 36% less likely than non-pet owners to report loneliness, in a model controlling for age, living status (i.e., alone vs. not alone), happy mood, and seasonal residency (adjOR = 0.64, 95% CI = 0.41-0.98, p pet ownership and living status (b = -1.60, p pet was associated with the greatest odds of reporting feelings of loneliness. The findings suggest that pet ownership may confer benefits for well-being, including attenuating feelings of loneliness and its related sequelae, among older adults who live alone.

  7. Extended Preclinical Safety, Efficacy and Stability Testing of a Live-attenuated Chikungunya Vaccine Candidate.

    Directory of Open Access Journals (Sweden)

    Kenneth S Plante

    Full Text Available We recently described a new, live-attenuated vaccine candidate for chikungunya (CHIK fever, CHIKV/IRES. This vaccine was shown to be well attenuated, immunogenic and efficacious in protecting against CHIK virus (CHIKV challenge of mice and nonhuman primates. To further evaluate its preclinical safety, we compared CHIKV/IRES distribution and viral loads in interferon-α/β receptor-incompetent A129 mice to another CHIK vaccine candidate, 181/clone25, which proved highly immunogenic but mildly reactive in human Phase I/II clinical trials. Compared to wild-type CHIK virus, (wt-CHIKV, both vaccines generated lower viral loads in a wide variety of tissues and organs, including the brain and leg muscle, but CHIKV/IRES exhibited marked restrictions in dissemination and viral loads compared to 181/clone25, and was never found outside the blood, spleen and muscle. Unlike wt-CHIKV, which caused disrupted splenic architecture and hepatic lesions, histopathological lesions were not observed in animals infected with either vaccine strain. To examine the stability of attenuation, both vaccines were passaged 5 times intracranially in infant A129 mice, then assessed for changes in virulence by comparing parental and passaged viruses for footpad swelling, weight stability and survival after subcutaneous infection. Whereas strain 181/clone25 p5 underwent a significant increase in virulence as measured by weight loss (from 30% and mortality (from 0 to 100%, CHIKV/IRES underwent no detectible change in any measure of virulence (no significant weight loss and no mortality. These data indicate greater nonclinical safety of the CHIKV/IRES vaccine candidate compared to 181/clone25, further supporting its eligibility for human testing.

  8. Development of a chimeric Zika vaccine using a licensed live-attenuated flavivirus vaccine as backbone.

    Science.gov (United States)

    Li, Xiao-Feng; Dong, Hao-Long; Wang, Hong-Jiang; Huang, Xing-Yao; Qiu, Ye-Feng; Ji, Xue; Ye, Qing; Li, Chunfeng; Liu, Yang; Deng, Yong-Qiang; Jiang, Tao; Cheng, Gong; Zhang, Fu-Chun; Davidson, Andrew D; Song, Ya-Jun; Shi, Pei-Yong; Qin, Cheng-Feng

    2018-02-14

    The global spread of Zika virus (ZIKV) and its unexpected association with congenital defects necessitates the rapid development of a safe and effective vaccine. Here we report the development and characterization of a recombinant chimeric ZIKV vaccine candidate (termed ChinZIKV) that expresses the prM-E proteins of ZIKV using the licensed Japanese encephalitis live-attenuated vaccine SA14-14-2 as the genetic backbone. ChinZIKV retains its replication activity and genetic stability in vitro, while exhibiting an attenuation phenotype in multiple animal models. Remarkably, immunization of mice and rhesus macaques with a single dose of ChinZIKV elicits robust and long-lasting immune responses, and confers complete protection against ZIKV challenge. Significantly, female mice immunized with ChinZIKV are protected against placental and fetal damage upon ZIKV challenge during pregnancy. Overall, our study provides an alternative vaccine platform in response to the ZIKV emergency, and the safety, immunogenicity, and protection profiles of ChinZIKV warrant further clinical development.

  9. The yellow fever 17D virus as a platform for new live attenuated vaccines.

    Science.gov (United States)

    Bonaldo, Myrna C; Sequeira, Patrícia C; Galler, Ricardo

    2014-01-01

    The live-attenuated yellow fever 17D virus is one of the most outstanding human vaccines ever developed. It induces efficacious immune responses at a low production cost with a well-established manufacture process. These advantages make the YF17D virus attractive as a vector for the development of new vaccines. At the beginning of vector development studies, YF17D was genetically manipulated to express other flavivirus prM and E proteins, components of the viral envelope. While these 17D recombinants are based on the substitution of equivalent YF17D genes, other antigens from unrelated pathogens have also been successfully expressed and delivered by recombinant YF17D viruses employing alternative strategies for genetic manipulation of the YF17D genome. Herein, we discuss these strategies in terms of possibilities of single epitope or larger sequence expression and the main properties of these replication-competent viral platforms.

  10. Live Attenuated Yellow Fever 17D Vaccine: A Legacy Vaccine Still Controlling Outbreaks In Modern Day.

    Science.gov (United States)

    Collins, Natalie D; Barrett, Alan D T

    2017-03-01

    Live attenuated 17D vaccine is considered one of the safest and efficacious vaccines developed to date. This review highlights what is known and the gaps in knowledge of vaccine-induced protective immunity. Recently, the World Health Organization modifying its guidance from 10-year booster doses to one dose gives lifelong protection in most populations. Nonetheless, there are some data suggesting immunity, though protective, may wane over time in certain populations and more research is needed to address this question. Despite having an effective vaccine to control yellow fever, vaccine shortages were identified during outbreaks in 2016, eventuating the use of a fractional-dosing campaign in the Democratic Republic of the Congo. Limited studies hinder identification of the underlying mechanism(s) of vaccine longevity; however, concurrent outbreaks during 2016 provide an opportunity to evaluate vaccine immunity following fractional dosing and insights into vaccine longevity in populations where there is limited information.

  11. Development and biological properties of a new live attenuated mumps vaccine.

    Science.gov (United States)

    Saika, Shizuko; Kidokoro, Minoru; Kubonoya, Hiroko; Ito, Kozo; Ohkawa, Tokitada; Aoki, Athuko; Nagata, Noriyo; Suzuki, Kazuyoshi

    2006-01-01

    To develop a new live attenuated mumps vaccine, a wild mumps Y7 strain isolated from a patient who developed mild parotitis was treated with nitrosoguanidine and ultraviolet, followed by selection of a temperature-sensitive clone. The selected clone, Y125, showed stable temperature-sensitivity in Vero cells. Intraspinal inoculation of marmosets with the Y125 produced only minimal histopathological changes, while intracerebral inoculation of neonatal rats revealed that the Y125 did not cause hydrocephalus. Both these effects of the Y125 were similar to those of the non-neurovirulent Jeryl Lynn strain. Furthermore, subcutaneous inoculation of the Y125 induced high levels of neutralizing antibodies in all Cercopithecus monkeys examined. Although the safety and immunogenicity should be confirmed in further field trials in humans, the present results indicate that the Y125 could be a promising vaccine candidate.

  12. Safety and immunogenicity of a live attenuated Japanese encephalitis chimeric virus vaccine (IMOJEV®) in children.

    Science.gov (United States)

    Chokephaibulkit, K; Houillon, G; Feroldi, E; Bouckenooghe, A

    2016-01-01

    JE-CV (IMOJEV®, Sanofi Pasteur, France) is a live attenuated virus vaccine constructed by inserting coding sequences of the prM and E structural proteins of the Japanese encephalitis SA14-14-2 virus into the genome of yellow fever 17D virus. Primary immunization with JE-CV requires a single dose of the vaccine. This article reviews clinical trials of JE-CV in children aged up to 6 years conducted in countries across South-East Asia. Strong and persistent antibody responses were observed after single primary and booster doses, with 97% of children seroprotected up to five years after booster vaccination. Models of long-term antibody persistence predict a median duration of protection of approximately 30 years after a booster dose. The safety and reactogenicity profiles of JE-CV primary and booster doses are comparable to other widely used childhood vaccines.

  13. Live Attenuated Tularemia Vaccines for Protection Against Respiratory Challenge With Virulent F. tularensis subsp. tularensis

    Science.gov (United States)

    Jia, Qingmei; Horwitz, Marcus A.

    2018-01-01

    Francisella tularensis is the causative agent of tularemia and a Tier I bioterrorism agent. In the 1900s, several vaccines were developed against tularemia including the killed “Foshay” vaccine, subunit vaccines comprising F. tularensis protein(s) or lipoproteins(s) in an adjuvant formulation, and the F. tularensis Live Vaccine Strain (LVS); none were licensed in the U.S.A. or European Union. The LVS vaccine retains toxicity in humans and animals—especially mice—but has demonstrated efficacy in humans, and thus serves as the current gold standard for vaccine efficacy studies. The U.S.A. 2001 anthrax bioterrorism attack spawned renewed interest in vaccines against potential biowarfare agents including F. tularensis. Since live attenuated—but not killed or subunit—vaccines have shown promising efficacy and since vaccine efficacy against respiratory challenge with less virulent subspecies holarctica or F. novicida, or against non-respiratory challenge with virulent subsp. tularensis (Type A) does not reliably predict vaccine efficacy against respiratory challenge with virulent subsp. tularensis, the route of transmission and species of greatest concern in a bioterrorist attack, in this review, we focus on live attenuated tularemia vaccine candidates tested against respiratory challenge with virulent Type A strains, including homologous vaccines derived from mutants of subsp. holarctica, F. novicida, and subsp. tularensis, and heterologous vaccines developed using viral or bacterial vectors to express F. tularensis immunoprotective antigens. We compare the virulence and efficacy of these vaccine candidates with that of LVS and discuss factors that can significantly impact the development and evaluation of live attenuated tularemia vaccines. Several vaccines meet what we would consider the minimum criteria for vaccines to go forward into clinical development—safety greater than LVS and efficacy at least as great as LVS, and of these, several meet the

  14. Live, Attenuated Influenza A H5N1 Candidate Vaccines Provide Broad Cross-Protection in Mice and Ferrets

    Science.gov (United States)

    Mills, Kimberly L; Jin, Hong; Duke, Greg; Lu, Bin; Luke, Catherine J; Murphy, Brian; Swayne, David E; Kemble, George; Subbarao, Kanta

    2006-01-01

    Background Recent outbreaks of highly pathogenic influenza A H5N1 viruses in humans and avian species that began in Asia and have spread to other continents underscore an urgent need to develop vaccines that would protect the human population in the event of a pandemic. Methods and Findings Live, attenuated candidate vaccines possessing genes encoding a modified H5 hemagglutinin (HA) and a wild-type (wt) N1 neuraminidase from influenza A H5N1 viruses isolated in Hong Kong and Vietnam in 1997, 2003, and 2004, and remaining gene segments derived from the cold-adapted (ca) influenza A vaccine donor strain, influenza A/Ann Arbor/6/60 ca (H2N2), were generated by reverse genetics. The H5N1 ca vaccine viruses required trypsin for efficient growth in vitro, as predicted by the modification engineered in the gene encoding the HA, and possessed the temperature-sensitive and attenuation phenotypes specified by the internal protein genes of the ca vaccine donor strain. More importantly, the candidate vaccines were immunogenic in mice. Four weeks after receiving a single dose of 106 50% tissue culture infectious doses of intranasally administered vaccines, mice were fully protected from lethality following challenge with homologous and antigenically distinct heterologous wt H5N1 viruses from different genetic sublineages (clades 1, 2, and 3) that were isolated in Asia between 1997 and 2005. Four weeks after receiving two doses of the vaccines, mice and ferrets were fully protected against pulmonary replication of homologous and heterologous wt H5N1 viruses. Conclusions The promising findings in these preclinical studies of safety, immunogenicity, and efficacy of the H5N1 ca vaccines against antigenically diverse H5N1 vaccines provide support for their careful evaluation in Phase 1 clinical trials in humans. PMID:16968127

  15. Live, attenuated influenza A H5N1 candidate vaccines provide broad cross-protection in mice and ferrets.

    Directory of Open Access Journals (Sweden)

    Amorsolo L Suguitan

    2006-09-01

    Full Text Available Recent outbreaks of highly pathogenic influenza A H5N1 viruses in humans and avian species that began in Asia and have spread to other continents underscore an urgent need to develop vaccines that would protect the human population in the event of a pandemic.Live, attenuated candidate vaccines possessing genes encoding a modified H5 hemagglutinin (HA and a wild-type (wt N1 neuraminidase from influenza A H5N1 viruses isolated in Hong Kong and Vietnam in 1997, 2003, and 2004, and remaining gene segments derived from the cold-adapted (ca influenza A vaccine donor strain, influenza A/Ann Arbor/6/60 ca (H2N2, were generated by reverse genetics. The H5N1 ca vaccine viruses required trypsin for efficient growth in vitro, as predicted by the modification engineered in the gene encoding the HA, and possessed the temperature-sensitive and attenuation phenotypes specified by the internal protein genes of the ca vaccine donor strain. More importantly, the candidate vaccines were immunogenic in mice. Four weeks after receiving a single dose of 10(6 50% tissue culture infectious doses of intranasally administered vaccines, mice were fully protected from lethality following challenge with homologous and antigenically distinct heterologous wt H5N1 viruses from different genetic sublineages (clades 1, 2, and 3 that were isolated in Asia between 1997 and 2005. Four weeks after receiving two doses of the vaccines, mice and ferrets were fully protected against pulmonary replication of homologous and heterologous wt H5N1 viruses.The promising findings in these preclinical studies of safety, immunogenicity, and efficacy of the H5N1 ca vaccines against antigenically diverse H5N1 vaccines provide support for their careful evaluation in Phase 1 clinical trials in humans.

  16. Living bacterial sacrificial porogens to engineer decellularized porous scaffolds.

    Directory of Open Access Journals (Sweden)

    Feng Xu

    Full Text Available Decellularization and cellularization of organs have emerged as disruptive methods in tissue engineering and regenerative medicine. Porous hydrogel scaffolds have widespread applications in tissue engineering, regenerative medicine and drug discovery as viable tissue mimics. However, the existing hydrogel fabrication techniques suffer from limited control over pore interconnectivity, density and size, which leads to inefficient nutrient and oxygen transport to cells embedded in the scaffolds. Here, we demonstrated an innovative approach to develop a new platform for tissue engineered constructs using live bacteria as sacrificial porogens. E.coli were patterned and cultured in an interconnected three-dimensional (3D hydrogel network. The growing bacteria created interconnected micropores and microchannels. Then, the scafold was decellularized, and bacteria were eliminated from the scaffold through lysing and washing steps. This 3D porous network method combined with bioprinting has the potential to be broadly applicable and compatible with tissue specific applications allowing seeding of stem cells and other cell types.

  17. Production and efficacy of an attenuated live vaccine against contagious ovine ecthyma

    Directory of Open Access Journals (Sweden)

    Attilio Pini

    2008-09-01

    Full Text Available Contagious ecthyma is caused by the orf virus, a member of the family Poxviridae, genus Parapoxvirus. Morbidity in affected sheep flocks is approximately 100%, while mortality varies between 1% and 10%. A live attenuated vaccine was produced by the Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise ‘G. Caporale’. Quality control was performed in accordance with the European Pharmacopoeia. A wild virus strain was attenuated through serial passages on primary chicken embryo fibroblast tissue cultures. The virus suspension was treated according to standard procedures and freeze dried. The immunising dose was 1 ml containing 104,5TCID50, administered intramuscularly. The safety of the vaccine was successfully tested by intramuscular inoculation of 20 susceptible sheep and 20 lambs with the routine dose, 10 times the immunising dose and two normal doses administered at seven-day intervals. The efficacy of the vaccine was tested using three groups of susceptible animals. The first group included 10 lambs and the second 10 adult sheep; the animals were immunised intramuscularly with 1 ml of the reconstituted vaccine. The third group, used as controls, included five sheep and five lambs. Serological reactivity was monitored by indirect enzyme-linked immunosorbent assay (ELISA. The animals were challenged 30 days later with a pathogenic strain administered intradermally along the labial area. Vaccinated animals did not show any clinical signs of disease, whereas all the controls developed typical signs of contagious ecthyma. To confirm the efficacy of the vaccine, a field trial was conducted in four flocks affected by the disease. The trial showed that the vaccine was able to block the normal course of the disease and induce rapid recovery.

  18. Rapid strategy for screening by pyrosequencing of influenza virus reassortants--candidates for live attenuated vaccines.

    Science.gov (United States)

    Shcherbik, Svetlana V; Pearce, Nicholas C; Levine, Marnie L; Klimov, Alexander I; Villanueva, Julie M; Bousse, Tatiana L

    2014-01-01

    Live attenuated influenza vaccine viruses (LAIVs) can be generated by classical reassortment of gene segments between a cold adapted, temperature sensitive and attenuated Master Donor Virus (MDV) and a seasonal wild-type (wt) virus. The vaccine candidates contain hemagglutinin (HA) and neuraminidase (NA) genes derived from the circulating wt viruses and the remaining six genes derived from the MDV strains. Rapid, efficient selection of the viruses with 6∶2 genome compositions from the large number of genetically different viruses generated during reassortment is essential for the biannual production schedule of vaccine viruses. This manuscript describes a new approach for the genotypic analysis of LAIV reassortant virus clones based on pyrosequencing. LAIV candidate viruses were created by classical reassortment of seasonal influenza A (H3N2) (A/Victoria/361/2011, A/Ohio/02/2012, A/Texas/50/2012) or influenza A (H7N9) (A/Anhui/1/2013) wt viruses with the MDV A/Leningrad/134/17/57(H2N2). Using strain-specific pyrosequencing assays, mixed gene variations were detected in the allantoic progenies during the cloning procedure. The pyrosequencing analysis also allowed for estimation of the relative abundance of segment variants in mixed populations. This semi-quantitative approach was used for selecting specific clones for the subsequent cloning procedures. The present study demonstrates that pyrosequencing analysis is a useful technique for rapid and reliable genotyping of reassortants and intermediate clones during the preparation of LAIV candidates, and can expedite the selection of vaccine virus candidates.

  19. Rapid strategy for screening by pyrosequencing of influenza virus reassortants--candidates for live attenuated vaccines.

    Directory of Open Access Journals (Sweden)

    Svetlana V Shcherbik

    Full Text Available BACKGROUND: Live attenuated influenza vaccine viruses (LAIVs can be generated by classical reassortment of gene segments between a cold adapted, temperature sensitive and attenuated Master Donor Virus (MDV and a seasonal wild-type (wt virus. The vaccine candidates contain hemagglutinin (HA and neuraminidase (NA genes derived from the circulating wt viruses and the remaining six genes derived from the MDV strains. Rapid, efficient selection of the viruses with 6∶2 genome compositions from the large number of genetically different viruses generated during reassortment is essential for the biannual production schedule of vaccine viruses. METHODOLOGY/PRINCIPAL FINDINGS: This manuscript describes a new approach for the genotypic analysis of LAIV reassortant virus clones based on pyrosequencing. LAIV candidate viruses were created by classical reassortment of seasonal influenza A (H3N2 (A/Victoria/361/2011, A/Ohio/02/2012, A/Texas/50/2012 or influenza A (H7N9 (A/Anhui/1/2013 wt viruses with the MDV A/Leningrad/134/17/57(H2N2. Using strain-specific pyrosequencing assays, mixed gene variations were detected in the allantoic progenies during the cloning procedure. The pyrosequencing analysis also allowed for estimation of the relative abundance of segment variants in mixed populations. This semi-quantitative approach was used for selecting specific clones for the subsequent cloning procedures. CONCLUSIONS/SIGNIFICANCE: The present study demonstrates that pyrosequencing analysis is a useful technique for rapid and reliable genotyping of reassortants and intermediate clones during the preparation of LAIV candidates, and can expedite the selection of vaccine virus candidates.

  20. Development of live attenuated Streptococcus agalactiae vaccine for tilapia via continuous passage in vitro.

    Science.gov (United States)

    Li, L P; Wang, R; Liang, W W; Huang, T; Huang, Y; Luo, F G; Lei, A Y; Chen, M; Gan, X

    2015-08-01

    Fish Streptococcus agalactiae (S. agalactiae) seriously harms the world's aquaculture industry and causes huge economic losses. This study aimed to develop a potential live attenuated vaccine of S. agalactiae. Pre-screened vaccine candidate strain S. agalactiae HN016 was used as starting material to generate an attenuated strain S. agalactiae YM001 by continuous passage in vitro. The biological characteristics, virulence, and stability of YM001 were detected, and the protective efficacy of YM001 immunization in tilapia was also determined. Our results indicated that the growth, staining, characteristics of pulsed-field gel electrophoresis (PFGE) genotype, and virulence of YM001 were changed significantly as compared to the parental strain HN016. High doses of YM001 by intraperitoneal (IP) injection (1.0 × 10(9) CFU/fish) and oral gavage (1.0 × 10(10) CFU/fish) respectively did not cause any mortality and morbidity in tilapia. The relative percent survivals (RPSs) of fishes immunized with YM001 (1.0 × 10(8) CFU/fish, one time) via injection, immersion, and oral administration were 96.88, 67.22, and 71.81%, respectively, at 15 days, and 93.61, 60.56, and 53.16%, respectively, at 30 days. In all tests with 1-3 times of immunization in tilapia, the dosages at 1 × 10(8) and 1 × 10(9) CFU/fish displayed the similar best results, whereas the immunoprotection of the dosages at 1 × 10(6) and 1 × 10(7) CFU/fish declined significantly (P 0.05). The level of protective antibody elicited by oral immunization was significantly higher compared to that of the control group (P S. agalactiae strain YM001; oral immunization of tilapia with this strain produced a good immune protection. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Dose response and efficacy of a live, attenuated human rotavirus vaccine in Mexican infants.

    Science.gov (United States)

    Ruiz-Palacios, Guillermo M; Guerrero, M Lourdes; Bautista-Márquez, Aurora; Ortega-Gallegos, Hilda; Tuz-Dzib, Fernando; Reyes-González, Leticia; Rosales-Pedraza, Gustavo; Martínez-López, Julia; Castañón-Acosta, Erika; Cervantes, Yolanda; Costa-Clemens, SueAnn; DeVos, Beatrice

    2007-08-01

    Immunization against rotavirus has been proposed as the most cost-effective intervention to reduce the disease burden associated with this infection worldwide. The objective of this study was to determine the dose response, immunogenicity, and efficacy of 2 doses of an oral, attenuated monovalent G1[P8] human rotavirus vaccine in children from the same setting in Mexico, where the natural protection against rotavirus infection was studied. From June 2001 through May 2003, 405 healthy infants were randomly assigned to 1 of 3 vaccine groups (virus concentrations 10(4.7), 10(5.2), and 10(5.8) infectious units) and to a placebo group and were monitored to the age of 2 years. The vaccine/placebo was administered concurrently with diphtheria-tetanus toxoid-pertussis/hepatitis B/Haemophilus influenzae type b vaccine at 2 and 4 months of age. After the administration of the first vaccine/placebo dose, weekly home visits to collect information regarding infant health were conducted. Stool samples were collected during each gastroenteritis episode and tested for rotavirus antigen and serotype. The vaccine was well tolerated and induced a greater rate of seroconversion than observed in infants who received placebo. For the pooled vaccine groups, efficacy after 2 oral doses was 80% and 95% against any and severe rotavirus gastroenteritis, respectively. Efficacy was 100% against severe rotavirus gastroenteritis and 70% against severe gastroenteritis of any cause with the vaccine at the highest virus concentration (10(5.8) infectious units). The predominant infecting rotavirus serotype in this cohort was wild-type G1 (85%). Adverse events, including fever, irritability, loss of appetite, cough, diarrhea, and vomiting, were similar among vaccinees and placebo recipients. This new oral, live, attenuated human rotavirus vaccine was safe, immunogenic, and highly efficacious in preventing any and, more importantly, severe rotavirus gastroenteritis in healthy infants. This vaccine

  2. Correlation between live attenuated measles viral load and growth inhibition percentage in non-small cell lung cancer cell line

    Directory of Open Access Journals (Sweden)

    Rasha Fadhel Obaid

    2018-03-01

    Conclusion Live attenuated measles virus strain induced cytotoxic effect against human lung cancer cell line (A549 by induction of apoptosis as an important mechanism of anti-tumor activity, in addition, it indicates a correlation between the quantity of MV genomesand percentage of growth inhibition. This relation  has proved that measles virus had anticancer effect.

  3. Biomarkers of safety and immune protection for genetically modified live attenuated Leishmania vaccines against visceral leishmaniasis-Discovery and implications

    Directory of Open Access Journals (Sweden)

    Sreenivas eGannavaram

    2014-05-01

    Full Text Available Despite intense efforts there is no safe and efficacious vaccine against visceral leishmaniasis, which is fatal and endemic in many tropical countries. A major shortcoming in the vaccine development against blood borne parasitic agents such as Leishmania is the inadequate predictive power of the early immune responses mounted in the host against the experimental vaccines. Often immune correlates derived from in-bred animal models do not yield immune markers of protection that can be readily extrapolated to humans. The limited efficacy of vaccines based on DNA, sub-unit, heat killed parasites has led to the realization that acquisition of durable immunity against the protozoan parasites requires a controlled infection with a live attenuated organism. Recent success of irradiated malaria parasites as a vaccine candidate further strengthens this approach to vaccination. We developed several gene deletion mutants in L. donovani as potential live attenuated vaccines and reported extensively on the immunogenicity of LdCentrin1 deleted mutant in mice, hamsters and dogs. Additional limited studies using genetically modified live attenuated Leishmania parasites as vaccine candidates have been reported. However, for the live attenuated parasite vaccines, the primary barrier against widespread use remains the absence of clear biomarkers associated with protection and safety. Recent studies in evaluation of vaccines e.g., influenza and yellow fever vaccines, using systems biology tools demonstrated the power of such strategies in understanding the immunological mechanisms that underpin a protective phenotype. Applying similar tools in isolated human tissues such as PBMCs from healthy individuals infected with live attenuated parasites such as LdCen1-/- in vitro followed by human microarray hybridization experiments will enable us to understand how early vaccine-induced gene expression profiles and the associated immune responses are coordinately regulated

  4. Synthetic Biology: Engineering Living Systems from Biophysical Principles.

    Science.gov (United States)

    Bartley, Bryan A; Kim, Kyung; Medley, J Kyle; Sauro, Herbert M

    2017-03-28

    Synthetic biology was founded as a biophysical discipline that sought explanations for the origins of life from chemical and physical first principles. Modern synthetic biology has been reinvented as an engineering discipline to design new organisms as well as to better understand fundamental biological mechanisms. However, success is still largely limited to the laboratory and transformative applications of synthetic biology are still in their infancy. Here, we review six principles of living systems and how they compare and contrast with engineered systems. We cite specific examples from the synthetic biology literature that illustrate these principles and speculate on their implications for further study. To fully realize the promise of synthetic biology, we must be aware of life's unique properties. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  5. Live Attenuated Versus Inactivated Influenza Vaccine in Hutterite Children: A Cluster Randomized Blinded Trial.

    Science.gov (United States)

    Loeb, Mark; Russell, Margaret L; Manning, Vanessa; Fonseca, Kevin; Earn, David J D; Horsman, Gregory; Chokani, Khami; Vooght, Mark; Babiuk, Lorne; Schwartz, Lisa; Neupane, Binod; Singh, Pardeep; Walter, Stephen D; Pullenayegum, Eleanor

    2016-11-01

    Whether vaccinating children with intranasal live attenuated influenza vaccine (LAIV) is more effective than inactivated influenza vaccine (IIV) in providing both direct protection in vaccinated persons and herd protection in unvaccinated persons is uncertain. Hutterite colonies, where members live in close-knit, small rural communities in which influenza virus infection regularly occurs, offer an opportunity to address this question. To determine whether vaccinating children and adolescents with LAIV provides better community protection than IIV. A cluster randomized blinded trial conducted between October 2012 and May 2015 over 3 influenza seasons. (ClinicalTrials.gov: NCT01653015). 52 Hutterite colonies in Alberta and Saskatchewan, Canada. 1186 Canadian children and adolescents aged 36 months to 15 years who received the study vaccine and 3425 community members who did not. Children were randomly assigned according to community in a blinded manner to receive standard dosing of either trivalent LAIV or trivalent IIV. The primary outcome was reverse transcriptase polymerase chain reaction-confirmed influenza A or B virus in all participants (vaccinated children and persons who did not receive the study vaccine). Mean vaccine coverage among children in the LAIV group was 76.9% versus 72.3% in the IIV group. Influenza virus infection occurred at a rate of 5.3% (295 of 5560 person-years) in the LAIV group versus 5.2% (304 of 5810 person-years) in the IIV group. The hazard ratio comparing LAIV with IIV for influenza A or B virus was 1.03 (95% CI, 0.85 to 1.24). The study was conducted in Hutterite communities, which may limit generalizability. Immunizing children with LAIV does not provide better community protection against influenza than IIV. The Canadian Institutes for Health Research.

  6. Clinical development and regulatory points for consideration for second-generation live attenuated dengue vaccines.

    Science.gov (United States)

    Vannice, Kirsten S; Wilder-Smith, Annelies; Barrett, Alan D T; Carrijo, Kalinka; Cavaleri, Marco; de Silva, Aravinda; Durbin, Anna P; Endy, Tim; Harris, Eva; Innis, Bruce L; Katzelnick, Leah C; Smith, Peter G; Sun, Wellington; Thomas, Stephen J; Hombach, Joachim

    2018-03-07

    Licensing and decisions on public health use of a vaccine rely on a robust clinical development program that permits a risk-benefit assessment of the product in the target population. Studies undertaken early in clinical development, as well as well-designed pivotal trials, allow for this robust characterization. In 2012, WHO published guidelines on the quality, safety and efficacy of live attenuated dengue tetravalent vaccines. Subsequently, efficacy and longer-term follow-up data have become available from two Phase 3 trials of a dengue vaccine, conducted in parallel, and the vaccine was licensed in December 2015. The findings and interpretation of the results from these trials released both before and after licensure have highlighted key complexities for tetravalent dengue vaccines, including concerns vaccination could increase the incidence of dengue disease in certain subpopulations. This report summarizes clinical and regulatory points for consideration that may guide vaccine developers on some aspects of trial design and facilitate regulatory review to enable broader public health recommendations for second-generation dengue vaccines. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Antigenic characterization of a formalin-inactivated poliovirus vaccine derived from live-attenuated Sabin strains.

    Science.gov (United States)

    Tano, Yoshio; Shimizu, Hiroyuki; Martin, Javier; Nishimura, Yorihiro; Simizu, Bunsiti; Miyamura, Tatsuo

    2007-10-10

    A candidate inactivated poliovirus vaccine derived from live-attenuated Sabin strains (sIPV), which are used in the oral poliovirus vaccine (OPV), was prepared in a large-production scale. The modification of viral antigenic epitopes during the formalin inactivation process was investigated by capture ELISA assays using type-specific and antigenic site-specific monoclonal antibodies (MoAbs). The major antigenic site 1 was modified during the formalin inactivation of Sabin 1. Antigenic sites 1-3 were slightly modified during the formalin inactivation of Sabin 2 strain. Sites 1 and 3 were altered on inactivated Sabin 3 virus. These alterations were different to those shown by wild-type Saukett strain, used in conventional IPV (cIPV). It has been previously reported that type 1 sIPV showed higher immunogenicity to type 1 cIPV whereas types 2 and 3 sIPV induced lower level of immunogenicity than their cIPV counterparts. Our results suggest that the differences in epitope structure after formalin inactivation may account, at least in part, for the observed differences in immunogenicity between Sabin and wild-type inactivated poliovaccines.

  8. Live Attenuated Pertussis Vaccine BPZE1 Protects Baboons Against Bordetella pertussis Disease and Infection

    Science.gov (United States)

    Papin, James F.; Lecher, Sophie; Debrie, Anne-Sophie; Thalen, Marcel; Solovay, Ken; Rubin, Keith; Mielcarek, Nathalie

    2017-01-01

    Abstract Evidence suggests that the resurgence of pertussis in many industrialized countries may result from the failure of current vaccines to prevent nasopharyngeal colonization by Bordetella pertussis, the principal causative agent of whooping cough. Here, we used a baboon model to test the protective potential of the novel, live attenuated pertussis vaccine candidate BPZE1. A single intranasal/intratracheal inoculation of juvenile baboons with BPZE1 resulted in transient nasopharyngeal colonization and induction of immunoglobulin G and immunoglobulin A to all antigens tested, while causing no adverse symptoms or leukocytosis. When BPZE1-vaccinated baboons were challenged with a high dose of a highly virulent B. pertussis isolate, they were fully protected against disease, whereas naive baboons developed illness (with 1 death) and leukocytosis. Total postchallenge nasopharyngeal virulent bacterial burden of vaccinated animals was substantially reduced (0.002%) compared to naive controls, providing promising evidence in nonhuman primates that BPZE1 protects against both pertussis disease and B. pertussis infection. PMID:28535276

  9. Vaccinating high-risk children with the intranasal live-attenuated influenza vaccine: the Quebec experience.

    Science.gov (United States)

    Quach, Caroline

    2014-12-01

    Given the burden of illness associated with influenza, vaccination is recommended for individuals at high risk of complications. The live-attenuated influenza vaccine (LAIV) is administered by intranasal spray, thus directly stimulating mucosal immunity. In this review, we aimed to provide evidence for its efficacy and safety in different paediatric populations. We also share the Quebec experience of LAIV use through a publicly funded vaccination program for children with chronic, high-risk conditions. from randomized controlled trials in healthy children and in asthmatics have demonstrated superior efficacy of LAIV over the injectable vaccine (IIV). LAIV is well tolerated: its administration is associated with runny nose and nasal congestion, but not with asthma exacerbations and is well tolerated in children with cystic fibrosis, when compared to IIV. The vaccine is well accepted by children and parents and can easily be part of vaccination clinics in paediatric tertiary care centres targeting children with chronic, high-risk conditions, not leading to immunosuppression. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Biodistribution and safety of a live attenuated tetravalent dengue vaccine in the cynomolgus monkey.

    Science.gov (United States)

    Ravel, Guillaume; Mantel, Nathalie; Silvano, Jeremy; Rogue, Alexandra; Guy, Bruno; Jackson, Nicholas; Burdin, Nicolas

    2017-10-13

    The first licensed dengue vaccine is a recombinant, live, attenuated, tetravalent dengue virus vaccine (CYD-TDV; Sanofi Pasteur). This study assessed the biodistribution, shedding, and toxicity of CYD-TDV in a non-human primate model as part of the nonclinical safety assessment program for the vaccine. Cynomolgus monkeys were given one subcutaneous injection of either one human dose (5log 10 CCID 50 /serotype) of CYD-TDV or saline control. Study endpoints included clinical observations, body temperature, body weight, food consumption, clinical pathology, immunogenicity, and post-mortem examinations including histopathology. Viral load, distribution, persistence, and shedding in tissues and body fluids were evaluated by quantitative reverse transcriptase polymerase chain reaction. The subcutaneous administration of CYD-TDV was well tolerated. There were no toxicological findings other than expected minor local reactions at the injection site. A transient low level of CYD-TDV viral RNA was detected in blood and the viral genome was identified primarily at the injection site and in the draining lymph nodes following immunization. These results, together with other data from repeat-dose toxicity and neurovirulence studies, confirm the absence of toxicological concern with CYD-TDV and corroborate clinical study observations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Live Attenuated Recombinant Vaccine Protects Nonhuman Primates Against Ebola and Marburg Viruses

    National Research Council Canada - National Science Library

    Jones, Steven M; Feldmann, Heinz; Stroher, Ute; Geisbert, Joan B; Fernando, Lisa; Grolla, Allen; Klenk, Hans-Dieter; Sullivan, Nancy J; Volchkov, Viktor E; Fritz, Elizabeth A; Daddario, Kathleen M; Hensley, Lisa E; Jahrling, Peter B; Geisbert, Thomas W

    2005-01-01

    ...). Here, we developed replication-competent vaccines against EBOV and MARV based on attenuated recombinant vesicular stomatitis virus vectors expressing either the EBOV glycoprotein or MARV glycoprotein...

  12. Experimental analysis of the structure attenuation characteristics on engine noise by pseudo cylinder pressure excitation; Giji tonaiatsu kashin ni yoru engine kozo no soon tokusei hyoka

    Energy Technology Data Exchange (ETDEWEB)

    Ozawa, H; Nakada, T [Isuzu Advanced Engineering Center, Tokyo (Japan)

    1997-10-01

    The engine structure attenuation has been experimentally analyzed by the newly developed in-cylinder excitation system. It can reproduce the complete cylinder pressure in non-running engine conditions by adopting the hydraulic and the piezoelectric actuator. The structure attenuation measured in this system has a good coincidence with the ones measured in actually engine operating conditions, meanwhile the current method, which applied only high frequency components as the excitation pressure, was shown to have the unsatisfied agreement. As a result, the proposed system has been concluded to be very useful to estimate the engine noise characteristics in non-running conditions. 4 refs., 11 figs., 1 tab.

  13. Biomarkers of safety and immune protection for genetically modified live attenuated leishmania vaccines against visceral leishmaniasis - discovery and implications.

    Science.gov (United States)

    Gannavaram, Sreenivas; Dey, Ranadhir; Avishek, Kumar; Selvapandiyan, Angamuthu; Salotra, Poonam; Nakhasi, Hira L

    2014-01-01

    Despite intense efforts there is no safe and efficacious vaccine against visceral leishmaniasis, which is fatal and endemic in many tropical countries. A major shortcoming in the vaccine development against blood-borne parasitic agents such as Leishmania is the inadequate predictive power of the early immune responses mounted in the host against the experimental vaccines. Often immune correlates derived from in-bred animal models do not yield immune markers of protection that can be readily extrapolated to humans. The limited efficacy of vaccines based on DNA, subunit, heat killed parasites has led to the realization that acquisition of durable immunity against the protozoan parasites requires a controlled infection with a live attenuated organism. Recent success of irradiated malaria parasites as a vaccine candidate further strengthens this approach to vaccination. We developed several gene deletion mutants in Leishmania donovani as potential live attenuated vaccines and reported extensively on the immunogenicity of LdCentrin1 deleted mutant in mice, hamsters, and dogs. Additional limited studies using genetically modified live attenuated Leishmania parasites as vaccine candidates have been reported. However, for the live attenuated parasite vaccines, the primary barrier against widespread use remains the absence of clear biomarkers associated with protection and safety. Recent studies in evaluation of vaccines, e.g., influenza and yellow fever vaccines, using systems biology tools demonstrated the power of such strategies in understanding the immunological mechanisms that underpin a protective phenotype. Applying similar tools in isolated human tissues such as PBMCs from healthy individuals infected with live attenuated parasites such as LdCen(-/-) in vitro followed by human microarray hybridization experiments will enable us to understand how early vaccine-induced gene expression profiles and the associated immune responses are coordinately regulated in normal

  14. Biomarkers of Safety and Immune Protection for Genetically Modified Live Attenuated Leishmania Vaccines Against Visceral Leishmaniasis – Discovery and Implications

    Science.gov (United States)

    Gannavaram, Sreenivas; Dey, Ranadhir; Avishek, Kumar; Selvapandiyan, Angamuthu; Salotra, Poonam; Nakhasi, Hira L.

    2014-01-01

    Despite intense efforts there is no safe and efficacious vaccine against visceral leishmaniasis, which is fatal and endemic in many tropical countries. A major shortcoming in the vaccine development against blood-borne parasitic agents such as Leishmania is the inadequate predictive power of the early immune responses mounted in the host against the experimental vaccines. Often immune correlates derived from in-bred animal models do not yield immune markers of protection that can be readily extrapolated to humans. The limited efficacy of vaccines based on DNA, subunit, heat killed parasites has led to the realization that acquisition of durable immunity against the protozoan parasites requires a controlled infection with a live attenuated organism. Recent success of irradiated malaria parasites as a vaccine candidate further strengthens this approach to vaccination. We developed several gene deletion mutants in Leishmania donovani as potential live attenuated vaccines and reported extensively on the immunogenicity of LdCentrin1 deleted mutant in mice, hamsters, and dogs. Additional limited studies using genetically modified live attenuated Leishmania parasites as vaccine candidates have been reported. However, for the live attenuated parasite vaccines, the primary barrier against widespread use remains the absence of clear biomarkers associated with protection and safety. Recent studies in evaluation of vaccines, e.g., influenza and yellow fever vaccines, using systems biology tools demonstrated the power of such strategies in understanding the immunological mechanisms that underpin a protective phenotype. Applying similar tools in isolated human tissues such as PBMCs from healthy individuals infected with live attenuated parasites such as LdCen−/− in vitro followed by human microarray hybridization experiments will enable us to understand how early vaccine-induced gene expression profiles and the associated immune responses are coordinately regulated in normal

  15. CANINE DISTEMPER VIRUS ANTIBODY TITERS IN DOMESTIC CATS AFTER DELIVERY OF A LIVE ATTENUATED VIRUS VACCINE.

    Science.gov (United States)

    Ramsay, Edward; Sadler, Ryan; Rush, Robert; Seimon, Tracie; Tomaszewicz, Ania; Fleetwood, Ellen A; McAloose, Denise; Wilkes, Rebecca P

    2016-06-01

    Three methods for delivering a live attenuated canine distemper virus (CDV) vaccine to domestic cats ( Felis catus ) were investigated, as models for developing vaccination protocols for tigers (Panthera tigris). Twenty domestic cats were randomly divided into four treatment groups: saline injection (negative controls); and oral, intranasal, and subcutaneous vaccinates. Cats were injected with saline or a CDV vaccine (Nobivac DP, Merck) at wk 0 and 4. Blood and nasal swabs were collected at wk 0 (prior to the initial vaccination) and weekly thereafter for 9 wk. Urine samples were collected on wk 1 to 9 after initial vaccination. Forty-nine weeks following the initial vaccination series, three cats from the subcutaneous group and three cats from the intranasal group were revaccinated. Blood was collected immediately prior, and 7 and 21 days subsequent to revaccination. Nasal swabs and urine samples were collected from each cat prior to wk 49 revaccination and daily for 7 days thereafter. Nasal swabs and urine were analyzed by quantitative PCR for vaccine virus presence. Sera were tested for CDV antibodies by virus neutralization. All cats were sero-negative for CDV antibodies at the beginning of the study, and saline-injected cats remained sero-negative throughout the study. A dramatic anamnestic response was seen following wk 4 subcutaneous vaccinations, with titers peaking at wk 6 (geometric mean = 2,435.5). Following wk 49 revaccination, subcutaneous vaccinates again mounted impressive titers (wk 52 geometric mean = 2,048). Revaccination of the intranasal group cats at wk 49 produced a small increase in titers (wk 52 geometric mean = 203). CDV viral RNA was detected in six nasal swabs but no urine samples, demonstrating low viral shedding postvaccination. The strong antibody response to subcutaneous vaccination and the lack of adverse effects suggest this vaccine is safe and potentially protective against CDV infection in domestic cats.

  16. Live attenuated influenza vaccine use and safety in children and adults with asthma.

    Science.gov (United States)

    Duffy, Jonathan; Lewis, Melissa; Harrington, Theresa; Baxter, Roger; Belongia, Edward A; Jackson, Lisa A; Jacobsen, Steven J; Lee, Grace M; Naleway, Allison L; Nordin, James; Daley, Matthew F

    2017-04-01

    Live attenuated influenza vaccine (LAIV) might increase the risk of wheezing in persons with asthma or children younger than 5 years with a history of recurrent wheezing. To describe the use and assess the safety of LAIV in persons with asthma in the Vaccine Safety Datalink population. We identified persons with asthma using diagnosis codes and medication records in 7 health care organizations over 3 influenza seasons (2008-2009 through 2010-2011) and determined their influenza vaccination rates. Using the self-controlled risk interval method, we calculated the incidence rate ratio of medically attended respiratory events in the 14 days after LAIV compared with 29 to 42 days after vaccination in persons 2 through 49 years old. In our population of 6.3 million, asthma prevalence was 5.9%. Of persons with asthma, approximately 50% received any influenza vaccine but less than 1% received LAIV. The safety study included 12,354 LAIV doses (75% in children; 93% in those with intermittent or mild persistent asthma). The incidence rate ratio for inpatient and emergency department visits for lower respiratory events (including asthma exacerbation and wheezing) was 0.98 (95% confidence interval 0.63-1.51) and the incidence rate ratio for upper respiratory events was 0.94 (95% confidence interval 0.48-1.86). The risk of lower respiratory events was similar for intermittent and mild persistent asthma, across age groups, and for seasonal trivalent LAIV and 2009 H1N1 pandemic monovalent LAIV. LAIV use in asthma was mostly in persons with intermittent or mild persistent asthma. LAIV was not associated with an increased risk of medically attended respiratory adverse events. Published by Elsevier Inc.

  17. Safety of live attenuated influenza vaccine in atopic children with egg allergy.

    Science.gov (United States)

    Turner, Paul J; Southern, Jo; Andrews, Nick J; Miller, Elizabeth; Erlewyn-Lajeunesse, Michel

    2015-08-01

    Live attenuated influenza vaccine (LAIV) is an intranasal vaccine recently incorporated into the United Kingdom immunization schedule. However, it contains egg protein and, in the absence of safety data, is contraindicated in patients with egg allergy. Furthermore, North American guidelines recommend against its use in asthmatic children. We sought to assess the safety of LAIV in children with egg allergy. We performed a prospective, multicenter, open-label, phase IV intervention study involving 11 secondary/tertiary centers in the United Kingdom. Children with egg allergy (defined as a convincing clinical reaction to egg within the past 12 months and/or >95% likelihood of clinical egg allergy as per published criteria) were recruited. LAIV was administered under medical supervision, with observation for 1 hour and telephone follow-up 72 hours later. Four hundred thirty-three doses were administered to 282 children with egg allergy (median, 4.9 years; range, 2-17 years); 115 (41%) had experienced prior anaphylaxis to egg. A physician's diagnosis of asthma/recurrent wheezing was noted in 67%, and 51% were receiving regular preventer therapy. There were no systemic allergic reactions (upper 95% CI for population, 1.3%). Eight children experienced mild self-limiting symptoms, which might have been due an IgE-mediated allergic reaction. Twenty-six (9.4%; 95% CI for population, 6.2% to 13.4%) children experienced lower respiratory tract symptoms within 72 hours, including 13 with parent-reported wheeze. None of these episodes required medical intervention beyond routine treatment. In contrast to current recommendations, LAIV appears to be safe for use in children with egg allergy. Furthermore, the vaccine appears to be well tolerated in children with a diagnosis of asthma or recurrent wheeze. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Development of live attenuated Streptococcus agalactiae as potential vaccines by selecting for resistance to sparfloxacin.

    Science.gov (United States)

    Pridgeon, Julia W; Klesius, Phillip H

    2013-05-31

    To develop attenuated bacteria as potential live vaccines, sparfloxacin was used in this study to modify 40 isolates of Streptococcus agalactiae. Majority of S. agalactiae used in this study were able to develop at least 80-fold resistance to sparfloxacin. When the virulence of the sparfloxacin-resistant S. agalactiae isolates were tested in 10-12g Nile tilapia by intraperitoneal injection at dose of 2×10(7)CFU/fish, 31 were found to be avirulent to fish. Of the 31 avirulent sparfloxacin-resistant S. agalactiae isolates, 30 provided 75-100% protection to 10-12g Nile tilapia against challenges with a virulent S. agalactiae isolate Sag 50. When the virulence of the 30 sparfloxacin-resistant S. agalactiae isolates was tested in 3-5g Nile tilapia by intraperitoneal injection at dose of 2×10(7)CFU/fish, six were found to be avirulent to 3-5g Nile tilapia. Of the six avirulent sparfloxacin-resistant S. agalactiae isolates, four provided 3-5g Nile tilapia 100% protection against challenges with homologous isolates, including Sag 97-spar isolate that was non-hemolytic. However, Sag 97-spar failed to provide broad cross-protection against challenges with heterologous isolates. When Nile tilapia was vaccinated with a polyvalent vaccine consisting of 30 sparfloxacin-resistant S. agalactiae isolates at dose of 2×10(6)CFU/fish, the polyvalent vaccine provided significant (PS. agalactiae. Taken together, our results suggest that a polyvalent vaccine consisting of various strains of S. agalactiae might be essential to provide broader protection to Nile tilapia against infections caused by S. agalactiae. Published by Elsevier Ltd.

  19. Cost Effectiveness of Influenza Vaccine for U.S. Children: Live Attenuated and Inactivated Influenza Vaccine.

    Science.gov (United States)

    Shim, Eunha; Brown, Shawn T; DePasse, Jay; Nowalk, Mary Patricia; Raviotta, Jonathan M; Smith, Kenneth J; Zimmerman, Richard K

    2016-09-01

    Prior studies showed that live attenuated influenza vaccine (LAIV) is more effective than inactivated influenza vaccine (IIV) in children aged 2-8 years, supporting the Centers for Disease Control and Prevention (CDC) recommendations in 2014 for preferential LAIV use in this age group. However, 2014-2015 U.S. effectiveness data indicated relatively poor effectiveness of both vaccines, leading CDC in 2015 to no longer prefer LAIV. An age-structured model of influenza transmission and vaccination was developed, which incorporated both direct and indirect protection induced by vaccination. Based on this model, the cost effectiveness of influenza vaccination strategies in children aged 2-8 years in the U.S. was estimated. The base case assumed a mixed vaccination strategy where 33.3% and 66.7% of vaccinated children aged 2-8 years receive LAIV and IIV, respectively. Analyses were performed in 2014-2015. Using published meta-analysis vaccine effectiveness data (83% LAIV and 64% IIV), exclusive LAIV use would be a cost-effective strategy when vaccinating children aged 2-8 years, whereas IIV would not be preferred. However, when 2014-2015 U.S. effectiveness data (0% LAIV and 15% IIV) were used, IIV was likely to be preferred. The cost effectiveness of influenza vaccination in children aged 2-8 years is highly dependent on vaccine effectiveness; the vaccine type with higher effectiveness is preferred. In general, exclusive IIV use is preferred over LAIV use, as long as vaccine effectiveness is higher for IIV than for LAIV. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  20. Screening for viral extraneous agents in live-attenuated avian vaccines by using a microbial microarray and sequencing

    DEFF Research Database (Denmark)

    Olesen, Majken Lindholm; Jørgensen, Lotte Leick; Blixenkrone-Møller, Merete

    2018-01-01

    The absence of extraneous agents (EA) in the raw material used for production and in finished products is one of the principal safety elements related to all medicinal products of biological origin, such as live-attenuated vaccines. The aim of this study was to investigate the applicability...... of the Lawrence Livermore Microbial detection array version 2 (LLMDAv2) combined with whole genome amplification and sequencing for screening for viral EAs in live-attenuated vaccines and specific pathogen-free (SPF) eggs.We detected positive microarray signals for avian endogenous retrovirus EAV-HP and several...... viruses belonging to the Alpharetrovirus genus in all analyzed vaccines and SPF eggs. We used a microarray probe mapping approach to evaluate the presence of intact retroviral genomes, which in addition to PCR analysis revealed that several of the positive microarray signals were most likely due to cross...

  1. Evaluation of live attenuated S79 mumps vaccine effectiveness in mumps outbreaks: a matched case-control study.

    Science.gov (United States)

    Fu, Chuan-xi; Nie, Jun; Liang, Jian-hua; Wang, Ming

    2009-02-05

    Mumps virus infection is a potentially serious viral infection of childhood and early adulthood. In China, live attenuated S(79) mumps vaccine has been licensed for pediatric use since 1990. The objective of this study was to determine the effectiveness of live attenuated S(79) mumps vaccine against clinical mumps in outbreaks. Cases were selected from mumps outbreaks in schools in Guangzhou between 2004 and 2005. Each case was matched by gender, age and classroom. Vaccination information was obtained from Children's EPI Administrative Computerized System. Vaccine effectiveness (VE) was calculated for 1 or 2 doses of S(79) vaccine with 95% confidence intervals (CI). One hundred and ninety-four cases and 194 controls were enrolled into the study. VE of the S(79) mumps vaccine for 1 dose versus 0 confer protection 80.4% (95% CI, 60.0%-90.4%) and VEs against mumps in outbreaks for 1 dose of mumps vaccine are similar among those children aged 4-9 years and aged over 10 years old. The live attenuated S(79) mumps vaccine can be effective in preventing clinical mumps outbreaks.

  2. Cross-Protection against Marburg Virus Strains by Using a Live, Attenuated Recombinant Vaccine

    National Research Council Canada - National Science Library

    Daddario-DiCaprio, Kathleen M; Geisbert, Thomas W; Geisbert, Joan B; Stroeher, Ute; Hensley, Lisa E; Grolla, Allen; Fritz, Elizabeth A; Feldmann, Friederike; Feldmann, Heinz; Jones, Steven M

    2006-01-01

    .... MARV is also considered to have potential as a biological weapon. Recently, we reported the development of a promising attenuated, replication-competent vaccine against MARV based on recombinant vesicular stomatitis virus (VSV...

  3. Enhancement of the safety of live influenza vaccine by attenuating mutations from cold-adapted hemagglutinin

    International Nuclear Information System (INIS)

    Lee, Yoon Jae; Jang, Yo Han; Kim, Paul; Lee, Yun Ha; Lee, Young Jae; Byun, Young Ho; Lee, Kwang-Hee; Kim, Kyusik; Seong, Baik Lin

    2016-01-01

    In our previous study, X-31ca-based H5N1 LAIVs, in particular, became more virulent in mice than the X-31ca MDV, possibly by the introduction of the surface antigens of highly pathogenic H5N1 influenza virus, implying that additional attenuation is needed in this cases to increase the safety level of the vaccine. In this report we suggest an approach to further increase the safety of LAIV through additional cold-adapted mutations in the hemagglutinin. The cold-adaptation of X-31 virus resulted in four amino acid mutations in the HA. We generated a panel of 7:1 reassortant viruses each carrying the hemagglutinins with individual single amino acid mutations. We examined their phenotypes and found a major attenuating mutation, N81K. This attenuation marker conferred additional temperature-sensitive and attenuation phenotype to the LAIV. Our data indicate that the cold-adapted mutation in the HA confers additional attenuation to the LAIV strain, without compromising its productivity and immune response. - Highlights: • Cold-adaptation process induced four amino acid mutations in the HA of X-31 virus. • The four mutations in the HA also contributed to attenuation of the X-31ca virus • N81K mutation was the most significant marker for the attenuation of X-31ca virus. • Introduction of N81K mutation into H3N2 LAIV further attenuated the vaccine. • This approach provides a useful guideline for enhancing the safety of the LAIVs.

  4. Enhancement of the safety of live influenza vaccine by attenuating mutations from cold-adapted hemagglutinin

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yoon Jae [Graduate Program in Biomaterials Science and Engineering, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Vaccine Translational Research Center, Yonsei University, Seoul (Korea, Republic of); Jang, Yo Han [Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Kim, Paul; Lee, Yun Ha; Lee, Young Jae [Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Vaccine Translational Research Center, Yonsei University, Seoul (Korea, Republic of); Byun, Young Ho; Lee, Kwang-Hee; Kim, Kyusik [Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Seong, Baik Lin, E-mail: blseong@yonsei.ac.kr [Graduate Program in Biomaterials Science and Engineering, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Vaccine Translational Research Center, Yonsei University, Seoul (Korea, Republic of)

    2016-04-15

    In our previous study, X-31ca-based H5N1 LAIVs, in particular, became more virulent in mice than the X-31ca MDV, possibly by the introduction of the surface antigens of highly pathogenic H5N1 influenza virus, implying that additional attenuation is needed in this cases to increase the safety level of the vaccine. In this report we suggest an approach to further increase the safety of LAIV through additional cold-adapted mutations in the hemagglutinin. The cold-adaptation of X-31 virus resulted in four amino acid mutations in the HA. We generated a panel of 7:1 reassortant viruses each carrying the hemagglutinins with individual single amino acid mutations. We examined their phenotypes and found a major attenuating mutation, N81K. This attenuation marker conferred additional temperature-sensitive and attenuation phenotype to the LAIV. Our data indicate that the cold-adapted mutation in the HA confers additional attenuation to the LAIV strain, without compromising its productivity and immune response. - Highlights: • Cold-adaptation process induced four amino acid mutations in the HA of X-31 virus. • The four mutations in the HA also contributed to attenuation of the X-31ca virus • N81K mutation was the most significant marker for the attenuation of X-31ca virus. • Introduction of N81K mutation into H3N2 LAIV further attenuated the vaccine. • This approach provides a useful guideline for enhancing the safety of the LAIVs.

  5. Stability of live attenuated rotavirus vaccine with selected preservatives and primary containers.

    Science.gov (United States)

    Lal, Manjari; Jarrahian, Courtney; Zhu, Changcheng; Hosken, Nancy A; McClurkan, Chris L; Koelle, David M; Saxon, Eugene; Roehrig, Andrew; Zehrung, Darin; Chen, Dexiang

    2016-05-11

    Rotavirus infection, which can be prevented by vaccination, is responsible for a high burden of acute gastroenteritis disease in children, especially in low-income countries. An appropriate formulation, packaging, and delivery device for oral rotavirus vaccine has the potential to reduce the manufacturing cost of the vaccine and the logistical impact associated with introduction of a new vaccine, simplify the vaccination procedure, and ensure that the vaccine is safely and accurately delivered to children. Single-dose prefilled presentations can be easy to use; however, they are typically more expensive, can be a bottleneck during production, and occupy a greater volume per dose vis-à-vis supply chain storage and medical waste disposal, which is a challenge in low-resource settings. Multi-dose presentations used thus far have other issues, including increased wastage of vaccine and the need for separate delivery devices. In this study, the goals were to evaluate both the technical feasibility of using preservatives to develop a liquid multi-dose formulation and the primary packaging alternatives for orally delivered, liquid rotavirus vaccines. The feasibility evaluation included evaluation of commonly used preservatives for compatibility with rotavirus vaccines and stability testing of rotavirus vaccine in various primary containers, including Lameplast's plastic tubes, BD's oral dispenser version of Uniject™ (Uniject DP), rommelag's blow-fill-seal containers, and MEDInstill's multi-dose vial and pouch. These presentations were compared to a standard glass vial. The results showed that none of the preservatives tested were compatible with a live attenuated rotavirus vaccine because they had a detrimental effect on the viability of the virus. In the presence of preservatives, vaccine virus titers declined to undetectable levels within 1 month. The vaccine formulation without preservatives maintained a stability profile over 12 months in all primary containers

  6. Immunization with Live Attenuated Leishmania donovani Centrin−/− Parasites Is Efficacious in Asymptomatic Infection

    Directory of Open Access Journals (Sweden)

    Nevien Ismail

    2017-12-01

    Full Text Available Currently, there is no vaccine against visceral leishmaniasis (VL. Toward developing an effective vaccine, we have reported extensively on the immunogenicity of live attenuated LdCentrin−/− mutants in naive animal models. In VL endemic areas, asymptomatic carriers outnumber symptomatic cases of VL and are considered to be a reservoir of infection. Vaccination of asymptomatic cases represents a viable strategy to eliminate VL. Immunological correlates of protection thus derived might have limited applicability in conditions where the immunized host has prior exposure to virulent infection. To examine whether LdCen−/− parasites can induce protective immunity in experimental hosts that have low-level parasitemia from a previous exposure mimicking an asymptomatic condition, we infected C57Bl/6 mice with wild-type Leishmania donovani parasites expressing LLO epitope (LdWTLLO 103, i.v.. After 3 weeks, the mice with low levels of parasitemia were immunized with LdCen−/− parasites expressing 2W epitope (LdCen−/−2W 3 × 106 i.v. to characterize the immune responses in the same host. Antigen experienced CD4+ T cells from the asymptomatic (LdWTLLO infected LdCen−/−2W immunized, and other control groups were enriched using LLO- and 2W-specific tetramers, followed by Flow cytometric analysis. Our analysis showed that comparable CD4+ T cell proliferation and CD4+ memory T cell responses (TCM represented by CD62Lhi, CCR7+, and IL-7R+ T cell populations were induced with LdCen−/−2W in both asymptomatic and naive animals that received LdCen−/− immunization. Upon restimulation with peptide, TCM cells differentiated into effector T cells and there was no significant difference in the recall response in animals with asymptomatic infection. Following virulent challenge, comparable reduction in splenic parasite burden was observed in both asymptomatic and naive LdCen−/− immunized animals concomitant with the development of

  7. Temperature-sensitive mutations for live-attenuated Rift Valley fever vaccines: Implications from other RNA viruses

    Directory of Open Access Journals (Sweden)

    Shoko eNishiyama

    2015-08-01

    Full Text Available Rift Valley fever (RVF is a mosquito-borne zoonotic disease endemic to the African continent. RVF is characterized by high rate of abortions in ruminants and hemorrhagic fever, encephalitis or blindness in humans. RVF is caused by the Rift Valley fever virus (RVFV: genus Phlebovirus, family Bunyaviridae. Vaccination is the only known effective strategy to prevent the disease, but there are no licensed RVF vaccines available for humans. A live-attenuated vaccine candidate derived from the wild-type pathogenic Egyptian ZH548 strain, MP-12, has been conditionally licensed for veterinary use in the United States. MP-12 displays a temperature-sensitive (ts phenotype and does not replicate at 41oC. The ts mutation limits viral replication at a specific body temperature and may lead to an attenuation of the virus. Here we will review well-characterized ts mutations for RNA viruses, and further discuss the potential in designing novel live-attenuated vaccines for RVF.

  8. Towards programming languages for genetic engineering of living cells.

    Science.gov (United States)

    Pedersen, Michael; Phillips, Andrew

    2009-08-06

    Synthetic biology aims at producing novel biological systems to carry out some desired and well-defined functions. An ultimate dream is to design these systems at a high level of abstraction using engineering-based tools and programming languages, press a button, and have the design translated to DNA sequences that can be synthesized and put to work in living cells. We introduce such a programming language, which allows logical interactions between potentially undetermined proteins and genes to be expressed in a modular manner. Programs can be translated by a compiler into sequences of standard biological parts, a process that relies on logic programming and prototype databases that contain known biological parts and protein interactions. Programs can also be translated to reactions, allowing simulations to be carried out. While current limitations on available data prevent full use of the language in practical applications, the language can be used to develop formal models of synthetic systems, which are otherwise often presented by informal notations. The language can also serve as a concrete proposal on which future language designs can be discussed, and can help to guide the emerging standard of biological parts which so far has focused on biological, rather than logical, properties of parts.

  9. 78 FR 43219 - Prospective Grant of Exclusive License: Live Attenuated Dengue Tetravalent Vaccine Containing a...

    Science.gov (United States)

    2013-07-19

    ...) E-120-2001/0, Whitehead et al., ``Development of Mutations Useful for Attenuating Dengue Viruses and..., and (3) E-139-2006/0, Whitehead et al., ``Development of Dengue Vaccine Components'', Australian... August 15, 2007, Chinese Patent Application Number 200780031489.4, filed August 15, 2007, European Patent...

  10. Type III Interferon-Mediated Signaling Is Critical for Controlling Live Attenuated Yellow Fever Virus Infection In Vivo.

    Science.gov (United States)

    Douam, Florian; Soto Albrecht, Yentli E; Hrebikova, Gabriela; Sadimin, Evita; Davidson, Christian; Kotenko, Sergei V; Ploss, Alexander

    2017-08-15

    Yellow fever virus (YFV) is an arthropod-borne flavivirus, infecting ~200,000 people worldwide annually and causing about 30,000 deaths. The live attenuated vaccine strain, YFV-17D, has significantly contributed in controlling the global burden of yellow fever worldwide. However, the viral and host contributions to YFV-17D attenuation remain elusive. Type I interferon (IFN-α/β) signaling and type II interferon (IFN-γ) signaling have been shown to be mutually supportive in controlling YFV-17D infection despite distinct mechanisms of action in viral infection. However, it remains unclear how type III IFN (IFN-λ) integrates into this antiviral system. Here, we report that while wild-type (WT) and IFN-λ receptor knockout (λR -/- ) mice were largely resistant to YFV-17D, deficiency in type I IFN signaling resulted in robust infection. Although IFN-α/β receptor knockout (α/βR -/- ) mice survived the infection, mice with combined deficiencies in both type I signaling and type III IFN signaling were hypersusceptible to YFV-17D and succumbed to the infection. Mortality was associated with viral neuroinvasion and increased permeability of the blood-brain barrier (BBB). α/βR -/- λR -/- mice also exhibited distinct changes in the frequencies of multiple immune cell lineages, impaired T-cell activation, and severe perturbation of the proinflammatory cytokine balance. Taken together, our data highlight that type III IFN has critical immunomodulatory and neuroprotective functions that prevent viral neuroinvasion during active YFV-17D replication. Type III IFN thus likely represents a safeguard mechanism crucial for controlling YFV-17D infection and contributing to shaping vaccine immunogenicity. IMPORTANCE YFV-17D is a live attenuated flavivirus vaccine strain recognized as one of the most effective vaccines ever developed. However, the host and viral determinants governing YFV-17D attenuation and its potent immunogenicity are still unknown. Here, we analyzed the

  11. Human Transcriptome Response to Immunization with Live- Attenuated Venezuelan equine encephalitis Virus Vaccine (TC 83): Analysis of Whole Blood

    Science.gov (United States)

    2016-11-21

    natural killer cell 33 signaling, and B-cell development. Biomarkers were identified that differentiate between 34 vaccinees and control subjects...risk laboratory personnel.8 The first vaccine, 68 TC-83, is a live-attenuated virus developed in 1961 by serial passage of the virulent Trinidad 69...HSP90AA1), the ERK5 Signaling pathway 220 (e.g., IL6ST, NRAS, RRAS2, ATF2), the Natural Killer Cell Signaling pathway (e.g., KLRC2, 221 FYN, PRKC1

  12. Attenuation of Foot-and-Mouth Disease Virus by Engineered Viral Polymerase Fidelity.

    Science.gov (United States)

    Rai, Devendra K; Diaz-San Segundo, Fayna; Campagnola, Grace; Keith, Anna; Schafer, Elizabeth A; Kloc, Anna; de Los Santos, Teresa; Peersen, Olve; Rieder, Elizabeth

    2017-08-01

    fidelity. Recombinant FMDVs containing substitutions at 3D pol tryptophan residue 237 were genetically stable and displayed plaque phenotypes and growth kinetics similar to those of the wild-type virus in cell culture. We further demonstrate that viruses harboring either a W237F HF substitution or W237I LF and W237L LF mutations were highly attenuated in animals. Our study shows that obtaining 3D pol fidelity variants by protein engineering based on polymerase structure and function could be exploited for the development of attenuated FMDV vaccine candidates that are safer and more stable than strains obtained by selective pressure via mutagenic nucleotides or adaptation approaches. Copyright © 2017 American Society for Microbiology.

  13. Live Zika virus chimeric vaccine candidate based on a yellow fever 17-D attenuated backbone

    OpenAIRE

    Nougairede, Antoine; Klitting, Raphaelle; Aubry, Fabien; Gilles, Magali; Touret, Franck; De Lamballerie, Xavier

    2018-01-01

    Zika virus (ZIKV) recently dispersed throughout the tropics and sub-tropics causing epidemics associated with congenital disease and neurological complications. There is currently no commercial vaccine for ZIKV. Here we describe the initial development of a chimeric virus containing the prM/E proteins of a ZIKV epidemic strain incorporated into a yellow fever 17-D attenuated backbone. Using the versatile and rapid ISA (Infectious Subgenomic Amplicons) reverse genetics method, we compared diff...

  14. Generation and Characterization of Live Attenuated Influenza A(H7N9 Candidate Vaccine Virus Based on Russian Donor of Attenuation.

    Directory of Open Access Journals (Sweden)

    Svetlana Shcherbik

    Full Text Available Avian influenza A (H7N9 virus has emerged recently and continues to cause severe disease with a high mortality rate in humans prompting the development of candidate vaccine viruses. Live attenuated influenza vaccines (LAIV are 6:2 reassortant viruses containing the HA and NA gene segments from wild type influenza viruses to induce protective immune responses and the six internal genes from Master Donor Viruses (MDV to provide temperature sensitive, cold-adapted and attenuated phenotypes.LAIV candidate A/Anhui/1/2013(H7N9-CDC-LV7A (abbreviated as CDC-LV7A, based on the Russian MDV, A/Leningrad/134/17/57 (H2N2, was generated by classical reassortment in eggs and retained MDV temperature-sensitive and cold-adapted phenotypes. CDC-LV7A had two amino acid substitutions N123D and N149D (H7 numbering in HA and one substitution T10I in NA. To evaluate the role of these mutations on the replication capacity of the reassortants in eggs, the recombinant viruses A(H7N9RG-LV1 and A(H7N9RG-LV2 were generated by reverse genetics. These changes did not alter virus antigenicity as ferret antiserum to CDC-LV7A vaccine candidate inhibited hemagglutination by homologous A(H7N9 virus efficiently. Safety studies in ferrets confirmed that CDC-LV7A was attenuated compared to wild-type A/Anhui/1/2013. In addition, the genetic stability of this vaccine candidate was examined in eggs and ferrets by monitoring sequence changes acquired during virus replication in the two host models. No changes in the viral genome were detected after five passages in eggs. However, after ten passages additional mutations were detected in the HA gene. The vaccine candidate was shown to be stable in the ferret model; post-vaccination sequence data analysis showed no changes in viruses collected in nasal washes present at day 5 or day 7.Our data indicate that the A/Anhui/1/2013(H7N9-CDC-LV7A reassortant virus is a safe and genetically stable candidate vaccine virus that is now available for

  15. Development of a human live attenuated West Nile infectious DNA vaccine: Suitability of attenuating mutations found in SA14-14-2 for WN vaccine design

    Energy Technology Data Exchange (ETDEWEB)

    Yamshchikov, Vladimir, E-mail: yaximik@gmail.com; Manuvakhova, Marina; Rodriguez, Efrain

    2016-01-15

    Direct attenuation of West Nile (WN) virus strain NY99 for the purpose of vaccine development is not feasible due to its high virulence and pathogenicity. Instead, we created highly attenuated chimeric virus W1806 with the serological identity of NY99. To further attenuate W1806, we investigated effects of mutations found in Japanese encephalitis virus vaccine SA14-14-2. WN viruses carrying all attenuating mutations lost infectivity in mammalian, but not in mosquito cells. No single reversion restored infectivity in mammalian cells, although increased infectivity in mosquito cells was observed. To identify a subset of mutations suitable for further attenuation of W1806, we analyzed effects of E{sub 138}K and K{sub 279}M changes on virulence, growth properties, and immunogenicity of derivatized W956, from which chimeric W1806 inherited its biological properties and attenuation profile. Despite strong dominant attenuating effect, introduction of only two mutations was not sufficient for attenuating W1806 to the safety level acceptable for human use. - Highlights: • Further attenuation of a WN vaccine precursor is outlined. • Effect of SA14-14-2 attenuating mutations is tested. • Mechanism of attenuation is proposed and illustrated. • The need for additional attenuating mutations is justified.

  16. Rational design of human metapneumovirus live attenuated vaccine candidates by inhibiting viral mRNA cap methyltransferase.

    Science.gov (United States)

    Zhang, Yu; Wei, Yongwei; Zhang, Xiaodong; Cai, Hui; Niewiesk, Stefan; Li, Jianrong

    2014-10-01

    The paramyxoviruses human respiratory syncytial virus (hRSV), human metapneumovirus (hMPV), and human parainfluenza virus type 3 (hPIV3) are responsible for the majority of pediatric respiratory diseases and inflict significant economic loss, health care costs, and emotional burdens. Despite major efforts, there are no vaccines available for these viruses. The conserved region VI (CR VI) of the large (L) polymerase proteins of paramyxoviruses catalyzes methyltransferase (MTase) activities that typically methylate viral mRNAs at positions guanine N-7 (G-N-7) and ribose 2'-O. In this study, we generated a panel of recombinant hMPVs carrying mutations in the S-adenosylmethionine (SAM) binding site in CR VI of L protein. These recombinant viruses were specifically defective in ribose 2'-O methylation but not G-N-7 methylation and were genetically stable and highly attenuated in cell culture and viral replication in the upper and lower respiratory tracts of cotton rats. Importantly, vaccination of cotton rats with these recombinant hMPVs (rhMPVs) with defective MTases triggered a high level of neutralizing antibody, and the rats were completely protected from challenge with wild-type rhMPV. Collectively, our results indicate that (i) amino acid residues in the SAM binding site in the hMPV L protein are essential for 2'-O methylation and (ii) inhibition of mRNA cap MTase can serve as a novel target to rationally design live attenuated vaccines for hMPV and perhaps other paramyxoviruses, such as hRSV and hPIV3. Human paramyxoviruses, including hRSV, hMPV, and hPIV3, cause the majority of acute upper and lower respiratory tract infections in humans, particularly in infants, children, the elderly, and immunocompromised individuals. Currently, there is no licensed vaccine available. A formalin-inactivated vaccine is not suitable for these viruses because it causes enhanced lung damage upon reinfection with the same virus. A live attenuated vaccine is the most promising

  17. Suppressing active replication of a live attenuated simian immunodeficiency virus vaccine does not abrogate protection from challenge

    Energy Technology Data Exchange (ETDEWEB)

    Gabriel, Benjamin; Fiebig, Uwe; Hohn, Oliver [Robert Koch-Institut, Berlin (Germany); Plesker, Roland; Coulibaly, Cheick; Cichutek, Klaus; Mühlebach, Michael D. [Paul-Ehrlich-Institut, Langen (Germany); Bannert, Norbert; Kurth, Reinhard [Robert Koch-Institut, Berlin (Germany); Norley, Stephen, E-mail: NorleyS@rki.de [Robert Koch-Institut, Berlin (Germany)

    2016-02-15

    Although safety concerns preclude the use of live attenuated HIV vaccines in humans, they provide a useful system for identifying the elusive correlates of protective immunity in the SIV/macaque animal model. However, a number of pieces of evidence suggest that protection may result from prior occupancy of susceptible target cells by the vaccine virus rather than the immune response. To address this, we developed a Nef-deletion variant of an RT-SHIV whose active replication could be shut off by treatment with RT-inhibitors. Groups of macaques were inoculated with the ∆Nef-RT-SHIV and immune responses allowed to develop before antiretroviral treatment and subsequent challenge with wild-type SIVmac239. Vaccinated animals either resisted infection fully or significantly controlled the subsequent viremia. However, there was no difference between animals undergoing replication of the vaccine virus and those without. This strongly suggests that competition for available target cells does not play a role in protection. - Highlights: • A Nef-deleted RT-SHIV was used as a live attenuated vaccine in macaques. • Vaccine virus replication was shut down to investigate its role in protection. • Ongoing vaccine virus replication did not appear to be necessary for protection. • An analysis of T- and B-cell responses failed to identify a correlate of protection.

  18. Live attenuated Francisella novicida vaccine protects against Francisella tularensis pulmonary challenge in rats and non-human primates.

    Directory of Open Access Journals (Sweden)

    Ping Chu

    2014-10-01

    Full Text Available Francisella tularensis causes the disease tularemia. Human pulmonary exposure to the most virulent form, F. tularensis subsp. tularensis (Ftt, leads to high morbidity and mortality, resulting in this bacterium being classified as a potential biothreat agent. However, a closely-related species, F. novicida, is avirulent in healthy humans. No tularemia vaccine is currently approved for human use. We demonstrate that a single dose vaccine of a live attenuated F. novicida strain (Fn iglD protects against subsequent pulmonary challenge with Ftt using two different animal models, Fischer 344 rats and cynomolgus macaques (NHP. The Fn iglD vaccine showed protective efficacy in rats, as did a Ftt iglD vaccine, suggesting no disadvantage to utilizing the low human virulent Francisella species to induce protective immunity. Comparison of specific antibody profiles in vaccinated rat and NHP sera by proteome array identified a core set of immunodominant antigens in vaccinated animals. This is the first report of a defined live attenuated vaccine that demonstrates efficacy against pulmonary tularemia in a NHP, and indicates that the low human virulence F. novicida functions as an effective tularemia vaccine platform.

  19. Suppressing active replication of a live attenuated simian immunodeficiency virus vaccine does not abrogate protection from challenge

    International Nuclear Information System (INIS)

    Gabriel, Benjamin; Fiebig, Uwe; Hohn, Oliver; Plesker, Roland; Coulibaly, Cheick; Cichutek, Klaus; Mühlebach, Michael D.; Bannert, Norbert; Kurth, Reinhard; Norley, Stephen

    2016-01-01

    Although safety concerns preclude the use of live attenuated HIV vaccines in humans, they provide a useful system for identifying the elusive correlates of protective immunity in the SIV/macaque animal model. However, a number of pieces of evidence suggest that protection may result from prior occupancy of susceptible target cells by the vaccine virus rather than the immune response. To address this, we developed a Nef-deletion variant of an RT-SHIV whose active replication could be shut off by treatment with RT-inhibitors. Groups of macaques were inoculated with the ∆Nef-RT-SHIV and immune responses allowed to develop before antiretroviral treatment and subsequent challenge with wild-type SIVmac239. Vaccinated animals either resisted infection fully or significantly controlled the subsequent viremia. However, there was no difference between animals undergoing replication of the vaccine virus and those without. This strongly suggests that competition for available target cells does not play a role in protection. - Highlights: • A Nef-deleted RT-SHIV was used as a live attenuated vaccine in macaques. • Vaccine virus replication was shut down to investigate its role in protection. • Ongoing vaccine virus replication did not appear to be necessary for protection. • An analysis of T- and B-cell responses failed to identify a correlate of protection.

  20. Comparison of immune persistence among inactivated and live attenuated hepatitis a vaccines 2 years after a single dose

    Science.gov (United States)

    Zhang, Xiaoshu; An, Jing; Tu, Aixia; Liang, Xuefeng; Cui, Fuqiang; Zheng, Hui; Tang, Yu; Liu, Jianfeng; Wang, Xuxia; Zhang, Ningjing; Li, Hui

    2016-01-01

    ABSTRACT Objective: Compare immune persistence from one dose of each of 3 different hepatitis A vaccines when given to school-age children: a domestic, live attenuated hepatitis A vaccine (H2 vaccine); a domestic inactivated hepatitis A vaccine (Healive®); and an imported, inactivated hepatitis A vaccine (Havrix®),.Methods: School-age children were randomized into 1 of 4 groups to receive a single dose of a vaccine: H2 vaccine, Healive®, Havrix®, or hepatitis B vaccine [control]. Serum samples were collected 12 and 24 months after vaccination for measurement of anti-HAV IgG using microparticle enzyme immunoassay. Seropositivity was defined as ≥ 20 mUI/ml. We compared groups on seropositivity and geometric mean concentration (GMC). Results: Seropositive rates for the H2, Healive®, Havrix®, and control groups were 64%, 94.4%, 73%, and 1.0%, respectively, 12-months post-vaccination; and 63%, 95.6%, 72%, and 1.0%, respectively 24-months post-vaccination. Seropositivity was greater for Healive® than for H2 and Havrix® at 12 months (p-values a single dose of inactivated hepatitis A vaccine and live attenuated hepatitis A vaccine. PMID:27494260

  1. Protection of macaques with diverse MHC genotypes against a heterologous SIV by vaccination with a deglycosylated live-attenuated SIV.

    Directory of Open Access Journals (Sweden)

    Chie Sugimoto

    Full Text Available HIV vaccine development has been hampered by issues such as undefined correlates of protection and extensive diversity of HIV. We addressed these issues using a previously established SIV-macaque model in which SIV mutants with deletions of multiple gp120 N-glycans function as potent live attenuated vaccines to induce near-sterile immunity against the parental pathogenic SIVmac239. In this study, we investigated the protective efficacy of these mutants against a highly pathogenic heterologous SIVsmE543-3 delivered intravenously to rhesus macaques with diverse MHC genotypes. All 11 vaccinated macaques contained the acute-phase infection with blood viral loads below the level of detection between 4 and 10 weeks postchallenge (pc, following a transient but marginal peak of viral replication at 2 weeks in only half of the challenged animals. In the chronic phase, seven vaccinees contained viral replication for over 80 weeks pc, while four did not. Neutralizing antibodies against challenge virus were not detected. Although overall levels of SIV specific T cell responses did not correlate with containment of acute and chronic viral replication, a critical role of cellular responses in the containment of viral replication was suggested. Emergence of viruses with altered fitness due to recombination between the vaccine and challenge viruses and increased gp120 glycosylation was linked to the failure to control SIV. These results demonstrate the induction of effective protective immune responses in a significant number of animals against heterologous virus by infection with deglycosylated attenuated SIV mutants in macaques with highly diverse MHC background. These findings suggest that broad HIV cross clade protection is possible, even in hosts with diverse genetic backgrounds. In summary, results of this study indicate that deglycosylated live-attenuated vaccines may provide a platform for the elucidation of correlates of protection needed for a

  2. Safety and immunogenicity of a live attenuated mumps vaccine: a phase I clinical trial.

    Science.gov (United States)

    Liang, Yan; Ma, Jingchen; Li, Changgui; Chen, Yuguo; Liu, Longding; Liao, Yun; Zhang, Ying; Jiang, Li; Wang, Xuan-Yi; Che, Yanchun; Deng, Wei; Li, Hong; Cui, Xiaoyu; Ma, Na; Ding, Dong; Xie, Zhongping; Cui, Pingfang; Ji, Qiuyan; Wang, JingJing; Zhao, Yuliang; Wang, Junzhi; Li, Qihan

    2014-01-01

    Mumps, a communicable, acute and previously well-controlled disease, has had recent and occasional resurgences in some areas. A randomized, double-blind, controlled and multistep phase I study of an F-genotype attenuated mumps vaccine produced in human diploid cells was conducted. A total of 300 subjects were enrolled and divided into 4 age groups: 16-60 years, 5-16 years, 2-5 years and 8-24 months. The groups were immunized with one injection per subject. Three different doses of the F-genotype attenuated mumps vaccine, A (3.5 ± 0.25 logCCID50), B (4.25 ± 0.25 logCCID50) and C (5.0 ± 0.25 logCCID50), as well as a placebo control and a positive control of a licensed A-genotype vaccine (S79 strain) were used. The safety and immunogenicity of this vaccine were compared with those of the controls. The safety evaluation suggested that mild adverse reactions were observed in all groups. No serious adverse event (SAE) was reported throughout the trial. The immunogenicity test showed a similar seroconversion rate of the neutralizing and ELISA antibody in the 2- to 5-year-old and 8- to 24-month-old groups compared with the seroconversion rate in the positive control. The GMT of the neutralizing anti-F-genotype virus antibodies in the vaccine groups was slightly higher than that in the positive control group. The F-genotype attenuated mumps vaccine evaluated in this clinical trial was demonstrated to be safe and have effective immunogenicity vs. control.

  3. Engineering hyporheic zones for the attenuation of urban pesticides and other stormwater trace organic contaminants

    Science.gov (United States)

    Portmann, A. C.; Halpin, B. N.; Herzog, S.; Higgins, C.; McCray, J. E.

    2017-12-01

    The hyporheic zone (HZ) is a natural bioreactor that can provide in-stream attenuation of various nonpoint source contaminants. Main contributions of nonpoint source pollution are coming from urban stormwater and agricultural runoff, which both adversely impact aquatic life. Stormwater pollutants of concern commonly include nutrients, metals, pathogens, and trace organic contaminants (TOrCs). Despite substantial water quality challenges, current stormwater management typically focuses on water quantity issues rather than pollutant removal. Furthermore, current HZ restoration best management practices do not explicitly control HZ residence times, and generally only induce localized effects. To increase hyporheic exchange and therefore improving water quality, we introduced engineered streambeds featuring modifications to subsurface hydraulic conductivity (K) and reactivity - termed Biohydrochemical Enhancements for Streamwater Treatment (BEST). BEST modifications comprise subsurface modules that employ 1) low-permeability sediments to drive hyporheic exchange and control subsurface residence times, and 2) permeable reactive geomedia to change reaction rates within the HZ. Here we present performance data collected in constructed stream experiments, comparing an all-sand control condition with a stream containing BEST modules and a mixture of 70/30 sand/woodchips (v/v). We evaluated the attenuation of a suite of TOrCs in the BEST versus the control system for two different streambed media: a coarse sand with K = 0.48 cm/s and a fine sand with K = 0.16 cm/s. The range of TOrCs investigated comprises urban pesticides and other stormwater relevant TOrCs. Benefits of applying BEST include increased exchange between streamwater and HZ water, leading to diverse redox conditions that are beneficial for aquatic organisms and will facilitate in-stream pollutant transformation. Future work will focus on tailoring the BEST design for specific pollutants, thereby controlling HZ

  4. [History of development of the live poliomyelitis vaccine from Sabin attenuated strains in 1959 and idea of poliomyelitis eradication].

    Science.gov (United States)

    Lashkevich, V A

    2013-01-01

    In 1958 Poliomyelitis Institute in Moscow and Institute of Experimental Medicine in St. Petersburg received from A. Sabin the attenuated strains of poliomyelitis virus. The characteristics of the strains were thoroughly studied by A. A. Smorodintsev and coworkers. They found that the virulence of the strains fluctuated slightly in 10 consecutive passages through the intestine of the non-immune children. A part of the Sabin material was used by A. A. Smorodintsev and M. P. Chumakov in the beginning of 1959 for immunizing approximately 40000 children in Estonia, Lithuania, and Latvia. Epidemic poliomyelitis rate in these republics decreased from approximately 1000 cases yearly before vaccination to less than 20 in the third quarter of 1959. This was a convincing proof of the efficacy and safety of the vaccine from the attenuated Sabin strains. In 1959, according to A. Sabin's recommendation, a technology of live vaccine production was developed at the Poliomyelitis Institute, and several experimental lots of vaccine were prepared. In the second part of 1959, 13.5 million children in USSR were immunized. The epidemic poliomyelitis rate decreased 3-5 times in different regions without paralytic cases, which could be attributed to the vaccination. These results were the final proof of high efficiency and safety of live poliomyelitis vaccine from the attenuated Sabin strains. Based on these results, A. Sabin and M. P. Chumakov suggested in 1960 the idea of poliomyelitis eradication using mass immunization of children with live vaccine. 72 million persons up to 20 years old were vaccinated in USSR in 1960 with a 5 times drop in the paralytic rate. 50-year-long use of live vaccine results in poliomyelitis eradication in almost all countries worldwide. More than 10 million children were rescued from the death and palsy. Poliomyelitis eradication in a few countries where it still exists depends not on medical services but is defined by the attitude of their leaders to fight

  5. Humoral immune responses of pregnant Guinea pigs Immunized with live attenuated Rhodococcus equi

    Directory of Open Access Journals (Sweden)

    Mawlood Abass Ali Al- Graibawi

    2018-02-01

    Full Text Available The potential to increase passive transfer of specific Rhodococcus equi (R.equi humoral immunity to newborn by preparturient vaccination of their dams was investigated in Pregnant Guinea pigs as a pilot study. Attenuated autogenous vaccine was prepared from a Congo red negative (CR- R.equi local isolate mixed with adjuvant (potassium alum sulphate, tested for sterility, safety and potency prior to vaccination .Two groups of pregnant G. pigs were used, the first group was vaccinated twice subcutaneously (S.C with the prepared vaccine at five and three weeks prior parturition, the second group was inoculated with adjuvant plus phosphate buffer saline (PBS twice s.c and kept as control. Offspring from the vaccinated dams had revealed high titers of specific R. equi antibody as detected by tube agglutination (TA and passive haemagglutination (PH test and showed protection against challenge dose. The results revealed that vaccination of pregnant G. pigs with the prepared attenuated vaccine was safe and efficient method to protect their offspring against experimental challenge with virulent R.equi. Vaccination was associated with increased humoral immune response in vaccinated group.

  6. Revaccination with Live Attenuated Vaccines Confer Additional Beneficial Nonspecific Effects on Overall Survival

    DEFF Research Database (Denmark)

    Benn, Christine S; Fisker, Ane B; Whittle, Hilton C

    2016-01-01

    BACKGROUND: Live vaccines against measles (MV), tuberculosis (BCG), polio (OPV) and smallpox reduce mortality more than explained by target-disease prevention. The beneficial nonspecific effects (NSEs) of MV are strongest when MV is given in presence of maternal antibodies. We therefore hypothesi......BACKGROUND: Live vaccines against measles (MV), tuberculosis (BCG), polio (OPV) and smallpox reduce mortality more than explained by target-disease prevention. The beneficial nonspecific effects (NSEs) of MV are strongest when MV is given in presence of maternal antibodies. We therefore...

  7. An effective AIDS vaccine based on live attenuated vesicular stomatitis virus recombinants.

    Science.gov (United States)

    Rose, N F; Marx, P A; Luckay, A; Nixon, D F; Moretto, W J; Donahoe, S M; Montefiori, D; Roberts, A; Buonocore, L; Rose, J K

    2001-09-07

    We developed an AIDS vaccine based on attenuated VSV vectors expressing env and gag genes and tested it in rhesus monkeys. Boosting was accomplished using vectors with glycoproteins from different VSV serotypes. Animals were challenged with a pathogenic AIDS virus (SHIV89.6P). Control monkeys showed a severe loss of CD4+ T cells and high viral loads, and 7/8 progressed to AIDS with an average time of 148 days. All seven vaccinees were initially infected with SHIV89.6P but have remained healthy for up to 14 months after challenge with low or undetectable viral loads. Protection from AIDS was highly significant (p = 0.001). VSV vectors are promising candidates for human AIDS vaccine trials because they propagate to high titers and can be delivered without injection.

  8. Genomic analysis of an attenuated Chlamydia abortus live vaccine strain reveals defects in central metabolism and surface proteins.

    Science.gov (United States)

    Burall, L S; Rodolakis, A; Rekiki, A; Myers, G S A; Bavoil, P M

    2009-09-01

    Comparative genomic analysis of a wild-type strain of the ovine pathogen Chlamydia abortus and its nitrosoguanidine-induced, temperature-sensitive, virulence-attenuated live vaccine derivative identified 22 single nucleotide polymorphisms unique to the mutant, including nine nonsynonymous mutations, one leading to a truncation of pmpG, which encodes a polymorphic membrane protein, and two intergenic mutations potentially affecting promoter sequences. Other nonsynonymous mutations mapped to a pmpG pseudogene and to predicted coding sequences encoding a putative lipoprotein, a sigma-54-dependent response regulator, a PhoH-like protein, a putative export protein, two tRNA synthetases, and a putative serine hydroxymethyltransferase. One of the intergenic mutations putatively affects transcription of two divergent genes encoding pyruvate kinase and a putative SOS response nuclease, respectively. These observations suggest that the temperature-sensitive phenotype and associated virulence attenuation of the vaccine strain result from disrupted metabolic activity due to altered pyruvate kinase expression and/or alteration in the function of one or more membrane proteins, most notably PmpG and a putative lipoprotein.

  9. Multiple antigens of Yersinia pestis delivered by live recombinant attenuated Salmonella vaccine strains elicit protective immunity against plague.

    Science.gov (United States)

    Sanapala, Shilpa; Rahav, Hannah; Patel, Hetal; Sun, Wei; Curtiss, Roy

    2016-05-05

    Based on our improved novel Salmonella vaccine delivery platform, we optimized the recombinant attenuated Salmonella typhimurium vaccine (RASV) χ12094 to deliver multiple Yersinia pestis antigens. These included LcrV196 (amino acids, 131-326), Psn encoded on pYA5383 and F1 encoded in the chromosome, their synthesis did not cause adverse effects on bacterial growth. Oral immunization with χ12094(pYA5383) simultaneously stimulated high antibody titers to LcrV, Psn and F1 in mice and presented complete protection against both subcutaneous (s.c.) and intranasal (i.n.) challenges with high lethal doses of Y. pestis CO92. Moreover, no deaths or other disease symptoms were observed in SCID mice orally immunized with χ12094(pYA5383) over a 60-day period. Therefore, the trivalent S. typhimurium-based live vaccine shows promise for a next-generation plague vaccine. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Protective efficacy of a live attenuated anti-coccidial vaccine administered to 1-day-old chickens.

    Science.gov (United States)

    Crouch, C F; Andrews, S J; Ward, R G; Francis, M J

    2003-06-01

    The efficacy of a live attenuated anti-coccidial vaccine, Paracox-5, administered to 1-day-old chicks was investigated by assessing protection against changes in weight gain following virulent challenge. Vaccinated birds were challenged independently 28 days later with each of the component species (Eimeria acervulina, Eimeria maxima, Eimeria mitis or Eimeria tenella), and protection was demonstrated against associated reduction in weight gain and lesion formation. In addition, an improvement in bird performance, in terms of feed conversion ratio, was also observed following vaccination. Furthermore, under conditions designed to more closely mimic those in the field and using hatchery spray administration, protection against a mixed virulent challenge introduced by 'seeder birds' was demonstrated evenly across a flock of broiler birds within 21 days after vaccination. These data demonstrate that Paracox-5 vaccine will protect broiler chickens against the adverse effects on performance induced by Eimeria spp.

  11. Live-attenuated tetravalent dengue vaccines: The needs and challenges of post-licensure evaluation of vaccine safety and effectiveness.

    Science.gov (United States)

    Wichmann, Ole; Vannice, Kirsten; Asturias, Edwin J; de Albuquerque Luna, Expedito José; Longini, Ira; Lopez, Anna Lena; Smith, Peter G; Tissera, Hasitha; Yoon, In-Kyu; Hombach, Joachim

    2017-10-09

    Since December 2015, the first dengue vaccine has been licensed in several Asian and Latin American countries for protection against disease from all four dengue virus serotypes. While the vaccine demonstrated an overall good safety and efficacy profile in clinical trials, some key research questions remain which make risk-benefit-assessment for some populations difficult. As for any new vaccine, several questions, such as very rare adverse events following immunization, duration of vaccine-induced protection and effectiveness when used in public health programs, will be addressed by post-licensure studies and by data from national surveillance systems after the vaccine has been introduced. However, the complexity of dengue epidemiology, pathogenesis and population immunity, as well as some characteristics of the currently licensed vaccine, and potentially also future, live-attenuated dengue vaccines, poses a challenge for evaluation through existing monitoring systems, especially in low and middle-income countries. Most notable are the different efficacies of the currently licensed vaccine by dengue serostatus at time of first vaccination and by dengue virus serotype, as well as the increased risk of dengue hospitalization among young vaccinated children observed three years after the start of vaccination in one of the trials. Currently, it is unknown if the last phenomenon is restricted to younger ages or could affect also seronegative individuals aged 9years and older, who are included in the group for whom the vaccine has been licensed. In this paper, we summarize scientific and methodological considerations for public health surveillance and targeted post-licensure studies to address some key research questions related to live-attenuated dengue vaccines. Countries intending to introduce a dengue vaccine should assess their capacities to monitor and evaluate the vaccine's effectiveness and safety and, where appropriate and possible, enhance their surveillance

  12. Development of a Live Attenuated Bivalent Oral Vaccine Against Shigella sonnei Shigellosis and Typhoid Fever.

    Science.gov (United States)

    Wu, Yun; Chakravarty, Sumana; Li, Minglin; Wai, Tint T; Hoffman, Stephen L; Sim, B Kim Lee

    2017-01-15

    Shigella sonnei and Salmonella Typhi cause significant morbidity and mortality. We exploited the safety record of the oral, attenuated S. Typhi vaccine (Ty21a) by using it as a vector to develop a bivalent oral vaccine to protect against S. sonnei shigellosis and typhoid fever. We recombineered the S. sonnei form I O-antigen gene cluster into the Ty21a chromosome to create Ty21a-Ss, which stably expresses S. sonnei form I O antigen. To enhance survivability in the acid environment of the stomach, we created an acid-resistant strain, Ty21a-AR-Ss, by inserting Shigella glutaminase-glutamate decarboxylase systems coexpressed with S. sonnei form I O-antigen gene. Mice immunized intranasally with Ty21a-AR-Ss produced antibodies against S. sonnei and S. Typhi, and survived lethal intranasal S. sonnei challenge. This paves the way for proposed good manufacturing practices manufacture and clinical trials intended to test the clinical effectiveness of Ty21a-AR-Ss in protecting against S. sonnei shigellosis and typhoid fever, as compared with the current Ty21a vaccine. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  13. Successful Latina Scientists and Engineers: Their Lived Mentoring Experiences and Career Development

    Science.gov (United States)

    San Miguel, Anitza M.; Kim, Mikyong Minsun

    2015-01-01

    Utilizing a phenomenological perspective and method, this study aimed to reveal the lived career mentoring experiences of Latinas in science and engineering and to understand how selected Latina scientists and engineers achieved high-level positions. Our in-depth interviews revealed that (a) it is important to have multiple mentors for Latinas'…

  14. Attenuation of FJ44 Turbofan Engine Noise with a Foam-Metal Liner Installed Over-the-Rotor

    Science.gov (United States)

    Sutliff, Daniel L.; Elliott, Dave M.; Jones, Michael G.; Hartley, Thomas C.

    2009-01-01

    A Williams International FJ44-3A 3000-lb thrust class turbofan engine was used as a demonstrator for a Foam-Metal Liner (FML) installed in close proximity to the fan. Two FML designs were tested and compared to the hardwall baseline. Traditional single degree-of-freedom liner designs were also evaluated to provide a comparison. Farfield acoustic levels and limited engine performance results are presented in this paper. The results show that the FML achieved up to 5 dB Acoustic Power Level (PWL) overall attenuation in the forward quadrant, equivalent to the traditional liner design. An earlier report presented the test set-up and conditions.

  15. Comparison of the live attenuated yellow fever vaccine 17D-204 strain to its virulent parental strain Asibi by deep sequencing.

    Science.gov (United States)

    Beck, Andrew; Tesh, Robert B; Wood, Thomas G; Widen, Steven G; Ryman, Kate D; Barrett, Alan D T

    2014-02-01

    The first comparison of a live RNA viral vaccine strain to its wild-type parental strain by deep sequencing is presented using as a model the yellow fever virus (YFV) live vaccine strain 17D-204 and its wild-type parental strain, Asibi. The YFV 17D-204 vaccine genome was compared to that of the parental strain Asibi by massively parallel methods. Variability was compared on multiple scales of the viral genomes. A modeled exploration of small-frequency variants was performed to reconstruct plausible regions of mutational plasticity. Overt quasispecies diversity is a feature of the parental strain, whereas the live vaccine strain lacks diversity according to multiple independent measurements. A lack of attenuating mutations in the Asibi population relative to that of 17D-204 was observed, demonstrating that the vaccine strain was derived by discrete mutation of Asibi and not by selection of genomes in the wild-type population. Relative quasispecies structure is a plausible correlate of attenuation for live viral vaccines. Analyses such as these of attenuated viruses improve our understanding of the molecular basis of vaccine attenuation and provide critical information on the stability of live vaccines and the risk of reversion to virulence.

  16. Revaccination of Guinea Pigs With the Live Attenuated Mycobacterium tuberculosis Vaccine MTBVAC Improves BCG's Protection Against Tuberculosis.

    Science.gov (United States)

    Clark, Simon; Lanni, Faye; Marinova, Dessislava; Rayner, Emma; Martin, Carlos; Williams, Ann

    2017-09-01

    The need for an effective vaccine against human tuberculosis has driven the development of different candidates and vaccination strategies. Novel live attenuated vaccines are being developed that promise greater safety and efficacy than BCG against tuberculosis. We combined BCG with the vaccine MTBVAC to evaluate whether the efficacy of either vaccine would be affected upon revaccination. In a well-established guinea pig model of aerosol infection with Mycobacterium tuberculosis, BCG and MTBVAC delivered via various prime-boost combinations or alone were compared. Efficacy was determined by a reduction in bacterial load 4 weeks after challenge. Efficacy data suggests MTBVAC-associated immunity is longer lasting than that of BCG when given as a single dose. Long and short intervals between BCG prime and MTBVAC boost resulted in improved efficacy in lungs, compared with BCG given alone. A shorter interval between MTBVAC prime and BCG boost resulted in improved efficacy in lungs, compared with BCG given alone. A longer interval resulted in protection equivalent to that of BCG given alone. These data indicate that, rather than boosting the waning efficacy of BCG, a vaccination schedule involving a combination of the 2 vaccines yielded stronger immunity to M. tuberculosis infection. This work supports development of MTBVAC use as a revaccination strategy to improve on the effects of BCG in vaccinated people living in tuberculosis-endemic countries. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  17. Restoring nervous system structure and function using tissue engineered living scaffolds

    Institute of Scientific and Technical Information of China (English)

    Laura A Struzyna; James P Harris; Kritika S Katiyar; H Isaac Chen; D KacyCullen

    2015-01-01

    Neural tissue engineering is premised on the integration of engineered living tissue with the host nervous system to directly restore lost function or to augment regenerative capacity following ner-vous system injury or neurodegenerative disease. Disconnection of axon pathways – the long-distance ifbers connecting specialized regions of the central nervous system or relaying peripheral signals – is a common feature of many neurological disorders and injury. However, functional axonal regenera-tion rarely occurs due to extreme distances to targets, absence of directed guidance, and the presence of inhibitory factors in the central nervous system, resulting in devastating effects on cognitive and sensorimotor function. To address this need, we are pursuing multiple strategies using tissue engi-neeredliving scaffolds”, which are preformed three-dimensional constructs consisting of living neural cells in a deifned, often anisotropic architecture. Living scaffolds are designed to restore function by serving as a living labeled pathway for targeted axonal regeneration – mimicking key developmental mechanisms– or by restoring lost neural circuitry via direct replacement of neurons and axonal tracts. We are currently utilizing preformed living scaffolds consisting of neuronal clusters spanned by long axonal tracts as regenerative bridges to facilitate long-distance axonal regeneration and for targeted neurosurgical reconstruction of local circuits in the brain. Although there are formidable challenges in preclinical and clinical advancement, these living tissue engineered constructs represent a promising strategy to facilitate nervous system repair and functional recovery.

  18. Restoring nervous system structure and function using tissue engineered living scaffolds

    Directory of Open Access Journals (Sweden)

    Laura A Struzyna

    2015-01-01

    Full Text Available Neural tissue engineering is premised on the integration of engineered living tissue with the host nervous system to directly restore lost function or to augment regenerative capacity following nervous system injury or neurodegenerative disease. Disconnection of axon pathways - the long-distance fibers connecting specialized regions of the central nervous system or relaying peripheral signals - is a common feature of many neurological disorders and injury. However, functional axonal regeneration rarely occurs due to extreme distances to targets, absence of directed guidance, and the presence of inhibitory factors in the central nervous system, resulting in devastating effects on cognitive and sensorimotor function. To address this need, we are pursuing multiple strategies using tissue engineered "living scaffolds", which are preformed three-dimensional constructs consisting of living neural cells in a defined, often anisotropic architecture. Living scaffolds are designed to restore function by serving as a living labeled pathway for targeted axonal regeneration - mimicking key developmental mechanisms- or by restoring lost neural circuitry via direct replacement of neurons and axonal tracts. We are currently utilizing preformed living scaffolds consisting of neuronal clusters spanned by long axonal tracts as regenerative bridges to facilitate long-distance axonal regeneration and for targeted neurosurgical reconstruction of local circuits in the brain. Although there are formidable challenges in preclinical and clinical advancement, these living tissue engineered constructs represent a promising strategy to facilitate nervous system repair and functional recovery.

  19. Type III Interferon-Mediated Signaling Is Critical for Controlling Live Attenuated Yellow Fever Virus Infection In Vivo

    Directory of Open Access Journals (Sweden)

    Florian Douam

    2017-08-01

    Full Text Available Yellow fever virus (YFV is an arthropod-borne flavivirus, infecting ~200,000 people worldwide annually and causing about 30,000 deaths. The live attenuated vaccine strain, YFV-17D, has significantly contributed in controlling the global burden of yellow fever worldwide. However, the viral and host contributions to YFV-17D attenuation remain elusive. Type I interferon (IFN-α/β signaling and type II interferon (IFN-γ signaling have been shown to be mutually supportive in controlling YFV-17D infection despite distinct mechanisms of action in viral infection. However, it remains unclear how type III IFN (IFN-λ integrates into this antiviral system. Here, we report that while wild-type (WT and IFN-λ receptor knockout (λR−/− mice were largely resistant to YFV-17D, deficiency in type I IFN signaling resulted in robust infection. Although IFN-α/β receptor knockout (α/βR−/− mice survived the infection, mice with combined deficiencies in both type I signaling and type III IFN signaling were hypersusceptible to YFV-17D and succumbed to the infection. Mortality was associated with viral neuroinvasion and increased permeability of the blood-brain barrier (BBB. α/βR−/− λR−/− mice also exhibited distinct changes in the frequencies of multiple immune cell lineages, impaired T-cell activation, and severe perturbation of the proinflammatory cytokine balance. Taken together, our data highlight that type III IFN has critical immunomodulatory and neuroprotective functions that prevent viral neuroinvasion during active YFV-17D replication. Type III IFN thus likely represents a safeguard mechanism crucial for controlling YFV-17D infection and contributing to shaping vaccine immunogenicity.

  20. Comparison of the Effectiveness of Trivalent Inactivated Influenza Vaccine and Live, Attenuated Influenza Vaccine in Preventing Influenza-Like Illness among US Service Members, 2006-2009

    Science.gov (United States)

    2012-11-26

    controlled studies. Vaccine 2012; 30:886–92. 11. Piedra PA, Gaglani MJ, Kozinetz CA, et al. Trivalent live attenuated intranasal influenza vaccine...120:e553–64. 12. Halloran ME, Piedra PA, Longini IM Jr, et al. Efficacy of trivalent, cold-adapted, influenza virus vaccine against influenza A (Fujian

  1. Cost of production of live attenuated dengue vaccines: a case study of the Instituto Butantan, Sao Paulo, Brazil.

    Science.gov (United States)

    Mahoney, R T; Francis, D P; Frazatti-Gallina, N M; Precioso, A R; Raw, I; Watler, P; Whitehead, P; Whitehead, S S

    2012-07-06

    A vaccine to prevent dengue disease is urgently needed. Fortunately, a few tetravalent candidate vaccines are in the later stages of development and show promise. But, if the cost of these candidates is too high, their beneficial potential will not be realized. The price of a vaccine is one of the most important factors affecting its ultimate application in developing countries. In recent years, new vaccines such as those for human papilloma virus and pneumococcal disease (conjugate vaccine) have been introduced with prices in developed countries exceeding $50 per dose. These prices are above the level affordable by developing countries. In contrast, other vaccines such as those against Japanese encephalitis (SA14-14-2 strain vaccine) and meningitis type A have prices in developing countries below one dollar per dose, and it is expected that their introduction and use will proceed more rapidly. Because dengue disease is caused by four related viruses, vaccines must be able to protect against all four. Although there are several live attenuated dengue vaccine candidates under clinical evaluation, there remains uncertainty about the cost of production of these tetravalent vaccines, and this uncertainty is an impediment to rapid progress in planning for the introduction and distribution of dengue vaccines once they are licensed. We have undertaken a detailed economic analysis, using standard industrial methodologies and applying generally accepted accounting practices, of the cost of production of a live attenuated vaccine, originally developed at the US National Institutes of Health (National Institute of Allergy and Infectious Diseases), to be produced at the Instituto Butantan in Sao Paulo, Brazil. We determined direct costs of materials, direct costs of personnel and labor, indirect costs, and depreciation. These were analyzed assuming a steady-state production of 60 million doses per year. Although this study does not seek to compute the price of the final

  2. Development of a human live attenuated West Nile infectious DNA vaccine: Identification of a minimal mutation set conferring the attenuation level acceptable for a human vaccine

    Energy Technology Data Exchange (ETDEWEB)

    Yamshchikov, Vladimir, E-mail: yaximik@gmail.com; Manuvakhova, Marina; Rodriguez, Efrain; Hébert, Charles

    2017-01-15

    ABSTRACT: For the development of a human West Nile (WN) infectious DNA (iDNA) vaccine, we created highly attenuated chimeric virus W1806 with the serological identity of highly virulent WN-NY99. Earlier, we attempted to utilize mutations found in the E protein of the SA14-14-2 vaccine to bring safety of W1806 to the level acceptable for human use (). Here, we analyzed effects of the SA14-14-2 changes on growth properties and neurovirulence of W1806. A set including the E138K, K279M, K439R and G447D changes was identified as the perspective subset for satisfying the target safety profile without compromising immunogenicity of the vaccine candidate. The genetic stability of the attenuated phenotype was found to be unsatisfactory being dependent on a subset of attenuating changes incorporated in W1806. Elucidation of underlying mechanisms influencing selection of pathways for restoration of the envelope protein functionality will facilitate resolution of the emerged genetic stability issue. - Highlights: •Effect of mutations in E on properties of WN1806 is determined. •A subset of attenuating mutations suitable for a human vaccine is defined. •Mechanism of attenuation is proposed and illustrated. •Underlying mechanisms of neurovirulence reversion are suggested.

  3. Engineering a Live UHD Program from the International Space Station

    Science.gov (United States)

    Grubbs, Rodney; George, Sandy

    2017-01-01

    The first-ever live downlink of Ultra-High Definition (UHD) video from the International Space Station (ISS) was the highlight of a “Super Session” at the National Association of Broadcasters (NAB) Show in April 2017. Ultra-High Definition is four times the resolution of “full HD” or “1080P” video. Also referred to as “4K”, the Ultra-High Definition video downlink from the ISS all the way to the Las Vegas Convention Center required considerable planning, pushed the limits of conventional video distribution from a space-craft, and was the first use of High Efficiency Video Coding (HEVC) from a space-craft. The live event at NAB will serve as a pathfinder for more routine downlinks of UHD as well as use of HEVC for conventional HD downlinks to save bandwidth. A similar demonstration was conducted in 2006 with the Discovery Channel to demonstrate the ability to stream HDTV from the ISS. This paper will describe the overall work flow and routing of the UHD video, how audio was synchronized even though the video and audio were received many seconds apart from each other, and how the demonstration paves the way for not only more efficient video distribution from the ISS, but also serves as a pathfinder for more complex video distribution from deep space. The paper will also describe how a “live” event was staged when the UHD video coming from the ISS had a latency of 10+ seconds. In addition, the paper will touch on the unique collaboration between the inherently governmental aspects of the ISS, commercial partners Amazon and Elemental, and the National Association of Broadcasters.

  4. Safety issues from a Phase 3 clinical trial of a live-attenuated chimeric yellow fever tetravalent dengue vaccine.

    Science.gov (United States)

    Halstead, Scott B

    2018-02-26

    A tetravalent live-attenuated 3-dose vaccine composed of chimeras of yellow fever 17D and the four dengue viruses (CYD, also called Dengvaxia) completed phase 3 clinical testing in over 35,000 children leading to a recommendation that vaccine be administered to >/ = 9 year-olds residing in highly dengue- endemic countries. When clinical trial results were assessed 2 years after the first dose, vaccine efficacy among seropositives was high, but among seronegatives efficacy was marginal. Breakthrough dengue hospitalizations of vaccinated children occurred continuously over a period of 4-5 years post 3rd dose in an age distribution suggesting these children had been vaccinated when seronegative. This surmise was validated recently when the manufacturer reported that dengue NS1 IgG antibodies were absent in sera from hospitalized vaccinated children, an observation consistent with their having received Dengvaxia when seronegative. Based upon published efficacy data and in compliance with initial published recommendations by the manufacturer and WHO the Philippine government undertook to vaccinate 800,000-plus 9 year-olds starting in April 2016. Eighteen months later, dengue hospitalizations and a deaths were reported among vaccinated children. The benefits of administering Dengvaxia predicted by the manufacturer, WHO and others derive from scoring dengue hospitalizations of vaccinated children as vaccine failures rather than as vaccine enhanced dengue disease. Recommended regimens for administration of Dengvaxia should have been structured to warn of and avoid serious adverse events.

  5. Genotyping assay for differentiation of wild-type and vaccine viruses in subjects immunized with live attenuated influenza vaccine.

    Directory of Open Access Journals (Sweden)

    Victoria Matyushenko

    Full Text Available Live attenuated influenza vaccines (LAIVs are considered as safe and effective tool to control influenza in different age groups, especially in young children. An important part of the LAIV safety evaluation is the detection of vaccine virus replication in the nasopharynx of the vaccinees, with special attention to a potential virus transmission to the unvaccinated close contacts. Conducting LAIV clinical trials in some geographical regions with year-round circulation of influenza viruses warrants the development of robust and reliable tools for differentiating vaccine viruses from wild-type influenza viruses in nasal pharyngeal wash (NPW specimens of vaccinated subjects. Here we report the development of genotyping assay for the detection of wild-type and vaccine-type influenza virus genes in NPW specimens of young children immunized with Russian-backbone seasonal trivalent LAIV using Sanger sequencing from newly designed universal primers. The new primer set allowed amplification and sequencing of short fragments of viral genes in NPW specimens and appeared to be more sensitive than conventional real-time RT-PCR protocols routinely used for the detection and typing/subtyping of influenza virus in humans. Furthermore, the new assay is capable of defining the origin of wild-type influenza virus through BLAST search with the generated sequences of viral genes fragments.

  6. Non-specific Effect of Vaccines: Immediate Protection against Respiratory Syncytial Virus Infection by a Live Attenuated Influenza Vaccine

    Directory of Open Access Journals (Sweden)

    Young J. Lee

    2018-01-01

    Full Text Available The non-specific effects (NSEs of vaccines have been discussed for their potential long-term beneficial effects beyond direct protection against a specific pathogen. Cold-adapted, live attenuated influenza vaccine (CAIV induces local innate immune responses that provide a broad range of antiviral immunity. Herein, we examined whether X-31ca, a donor virus for CAIVs, provides non-specific cross-protection against respiratory syncytial virus (RSV. The degree of RSV replication was significantly reduced when X-31ca was administered before RSV infection without any RSV-specific antibody responses. The vaccination induced an immediate release of cytokines and infiltration of leukocytes into the respiratory tract, moderating the immune perturbation caused by RSV infection. The potency of protection against RSV challenge was significantly reduced in TLR3-/- TLR7-/- mice, confirming that the TLR3/7 signaling pathways are necessary for the observed immediate and short-term protection. The results suggest that CAIVs provide short-term, non-specific protection against genetically unrelated respiratory pathogens. The additional benefits of CAIVs in mitigating acute respiratory infections for which vaccines are not yet available need to be assessed in future studies.

  7. Generation of a novel live rabies vaccine strain with a high level of safety by introducing attenuating mutations in the nucleoprotein and glycoprotein.

    Science.gov (United States)

    Nakagawa, Keisuke; Nakagawa, Kento; Omatsu, Tsutomu; Katayama, Yukie; Oba, Mami; Mitake, Hiromichi; Okada, Kazuma; Yamaoka, Satoko; Takashima, Yasuhiro; Masatani, Tatsunori; Okadera, Kota; Ito, Naoto; Mizutani, Tetsuya; Sugiyama, Makoto

    2017-10-09

    The current live rabies vaccine SAG2 is attenuated by only one mutation (Arg-to-Glu) at position 333 in the glycoprotein (G333). This fact generates a potential risk of the emergence of a pathogenic revertant by a back mutation at this position during viral propagation in the body. To circumvent this risk, it is desirable to generate a live vaccine strain highly and stably attenuated by multiple mutations. However, the information on attenuating mutations other than that at G333 is very limited. We previously reported that amino acids at positions 273 and 394 in the nucleoprotein (N273/394) (Leu and His, respectively) of fixed rabies virus Ni-CE are responsible for the attenuated phenotype by enhancing interferon (IFN)/chemokine gene expressions in infected neural cells. In this study, we found that amino acid substitutions at N273/394 (Phe-to-Leu and Tyr-to-His, respectively) attenuated the pathogenicity of the oral live vaccine ERA, which has a virulent-type Arg at G333. Then we generated ERA-N273/394-G333 attenuated by the combination of the above attenuating mutations at G333 and N273/394, and checked its safety. Similar to the ERA-G333, which is attenuated by only the mutation at G333, ERA-N273/394-G333 did not cause any symptoms in adult mice after intracerebral inoculation, indicating a low level of residual pathogenicity of ERA-N273/394-G333. Further examination revealed that infection with ERA-N273/394-G333 induces IFN-β and CXCL10 mRNA expressions more strongly than ERA-G333 infection in a neuroblastoma cell line. Importantly, we found that the ERA-N273/394-G333 stain has a lower risk for emergence of a pathogenic revertant than does the ERA-G333. These results indicate that ERA-N273/394-G333 has a potential to be a promising candidate for a live rabies vaccine strain with a high level of safety. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Evaluation of the immune response in Shitou geese (Anser anser domesticus) following immunization with GPV-VP1 DNA-based and live attenuated vaccines.

    Science.gov (United States)

    Deng, Shu-xuan; Cai, Ming-sheng; Cui, Wei; Huang, Jin-lu; Li, Mei-li

    2014-01-01

    Goose parvovirus (GPV) is a highly contagious and deadly disease for goslings and Muscovy ducklings. To compare the differences in immune response of geese immunized with GPV-VP1 DNA-based and live attenuated vaccines. Shitou geese were immunized once with either 20 μg pcDNA-GPV-VP1 DNA gene vaccine by gene gun bombardment via intramuscular injection, or 300 μg by i.m. injection, or 300 μL live attenuated vaccine by i.m. injection, whereas 300 μg pcDNA3.1 (+) i.m. or 300 μL saline i.m. were used as positive and negative controls, respectively. Each group comprised 28 animals. Peripheral blood samples were collected from 2-210 days after immunization and the proliferation of T lymphocytes, the number of CD4(+) and CD8(+) T cells and the level of IgG assessed. Statistical analysis was performed using a one-way analysis of variance with group multiple comparisons via Tukey's test. The pcDNA-GPV-VP1 DNA and attenuated vaccine induced cellular and humoral responses, and there were no differences between the 20 and 300 μg group in the responses of proliferation of T lymphocyte and the CD8(+) T-cell. However, as to CD4(+) T-cell response and humoral immunity, the 20 μg group performed better than the 300 μg group, which induced better cellular and humoral immunity than live attenuated vaccine. This study showed that it is possible to induce both cellular and humoral response using DNA-based vaccines and that the pcDNA-GPV-VP1 DNA gene vaccine induced better cellular and humoral immunity than live attenuated vaccine.

  9. Post-marketing safety surveillance for inactivated and live-attenuated Japanese encephalitis vaccines in China, 2008-2013.

    Science.gov (United States)

    Wu, Wendi; Liu, Dawei; Li, Keli; Nuorti, J Pekka; Nohynek, Hanna M; Xu, Disha; Ye, Jiakai; Zheng, Jingshan; Wang, Huaqing

    2017-06-22

    Two types of Japanese encephalitis (JE) vaccines, inactivated JE vaccine (JE-I) and live-attenuated JE vaccine (JE-L), are available and used in China. In particular, one JE-L, produced by a domestic manufacturer in China, was prequalified by WHO in 2013. We assessed the safety of JE vaccines in China during 2008-2013 using the Chinese National Adverse Events Following Immunization Information System (CNAEFIS) data. We retrieved AEFI reporting data about JE vaccines from CNAEFIS, 2008-2013, examined demographic characteristics of AEFI cases, and used administrative data on vaccine doses as denominator to calculate and compare crude reporting rates. We also used disproportionality reporting analysis between JE-I and JE-L to assess potential safety signals. A total of 34,879 AEFIs related with JE-I and JE-L were reported, with a ratio of male to female as 1.3:1; 361 (1.0%) cases were classified as serious. JE vaccines were administered concurrently with one or more other vaccines in 13,592 (39.0%) of cases. The overall AEFI reporting rates were 214.4 per million vaccination doses for JE-L and 176.9 for JE-I (rate ratio [RR]: 1.2, 95% confidence interval [CI]: 1.1-1.3) in 2010-2013. Febrile convulsions (FC) following JE-I was found as a signal of disproportionate reporting (SDR). However, there was no significant difference between the reporting rates of FC of JE-I and JE-L (0.3 per million vaccination doses for JE-L, 0.4 for JE-I, p=0.05). While our analysis did not find apparent safety concern of JE vaccines in China, further study should consider JE-I vaccines and febrile convulsion, and taking more sensitive methods to detect signals. Copyright © 2017. Published by Elsevier Ltd.

  10. Production of cell culture (MDCK) derived live attenuated influenza vaccine (LAIV) in a fully disposable platform process.

    Science.gov (United States)

    George, Meena; Farooq, Masiha; Dang, Thi; Cortes, Bernadette; Liu, Jonathan; Maranga, Luis

    2010-08-15

    The majority of influenza vaccines are manufactured using embryonated hens' eggs. The potential occurrence of a pandemic outbreak of avian influenza might reduce or even eliminate the supply of eggs, leaving the human population at risk. Also, the egg-based production technology is intrinsically cumbersome and not easily scalable to provide a rapid worldwide supply of vaccine. In this communication, the production of a cell culture (Madin-Darby canine kidney (MDCK)) derived live attenuated influenza vaccine (LAIV) in a fully disposable platform process using a novel Single Use Bioreactor (SUB) is presented. The cell culture and virus infection was maintained in a disposable stirred tank reactor with PID control of pH, DO, agitation, and temperature, similar to traditional glass or stainless steel bioreactors. The application of this technology was tested using MDCK cells grown on microcarriers in proprietary serum free medium and infection with 2006/2007 seasonal LAIV strains at 25-30 L scale. The MDCK cell growth was optimal at the agitation rate of 100 rpm. Optimization of this parameter allowed the cells to grow at a rate similar to that achieved in the conventional 3 L glass stirred tank bioreactors. Influenza vaccine virus strains, A/New Caledonia/20/99 (H1N1 strain), A/Wisconsin/67/05 (H3N2 strain), and B/Malaysia/2506/04 (B strain) were all successfully produced in SUB with peak virus titers > or =8.6 log(10) FFU/mL. This result demonstrated that more than 1 million doses of vaccine can be produced through one single run of a small bioreactor at the scale of 30 L and thus provided an alternative to the current vaccine production platform with fast turn-around and low upfront facility investment, features that are particularly useful for emerging and developing countries and clinical trial material production.

  11. Post-licensure, phase IV, safety study of a live attenuated Japanese encephalitis recombinant vaccine in children in Thailand.

    Science.gov (United States)

    Chotpitayasunondh, Tawee; Pruekprasert, Pornpimol; Puthanakit, Thanyawee; Pancharoen, Chitsanu; Tangsathapornpong, Auchara; Oberdorfer, Peninnah; Kosalaraksa, Pope; Prommalikit, Olarn; Tangkittithaworn, Suwimon; Kerdpanich, Phirangkul; Techasaensiri, Chonnamet; Korejwo, Joanna; Chuenkitmongkol, Sunate; Houillon, Guy

    2017-01-05

    Japanese encephalitis is a mosquito-borne viral disease endemic in most countries in Asia. A recombinant live, attenuated Japanese encephalitis virus vaccine, JE-CV, is licensed in 14 countries, including Thailand, for the prevention of Japanese encephalitis in adults and children. This was a prospective, phase IV, open-label, multicentre, safety study of JE-CV conducted from November 2013 to April 2015, to evaluate rare serious adverse events (AEs). JE-CV was administered to 10,000 healthy children aged 9months to vaccination. Serious AEs (SAEs), including AEs of special interest, up to 60days after administration were evaluated. Immediate Grade 3 systemic AEs up to 30min after JE-CV administration were also described. The median age of participants was 1.1years in Group 1 and 3.8years in Group 2. SAEs were reported in 204 (3.0%) participants in Group 1 and 59 (1.9%) participants in Group 2. Among a total of 294 SAEs in 263 participants, only three events occurring in two participants were considered related to vaccination. All three cases were moderate urticaria, none of which met the definition of AEs of special interest for hypersensitivity. AEs of special interest were reported in 28 (0.4%) participants in Group 1 and 4 (0.1%) participants in Group 2; none were considered related to vaccination. Febrile convulsion was the most frequently reported AE of special interest: 25 (0.4%) participants in Group 1; and 2 (vaccination. Our study did not identify any new safety concerns with JE-CV and confirms its good safety profile. This study was registered on www.clinicaltrials.gov (NCT01981967; Universal Trial Number: U1111-1127-7052). Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Varicella-Zoster Virus-Specific Cellular Immune Responses to the Live Attenuated Zoster Vaccine in Young and Older Adults.

    Science.gov (United States)

    Weinberg, Adriana; Canniff, Jennifer; Rouphael, Nadine; Mehta, Aneesh; Mulligan, Mark; Whitaker, Jennifer A; Levin, Myron J

    2017-07-15

    The incidence and severity of herpes zoster (HZ) increases with age. The live attenuated zoster vaccine generates immune responses similar to HZ. We compared the immune responses to zoster vaccine in young and older to adults to increase our understanding of the immune characteristics that may contribute to the increased susceptibility to HZ in older adults. Young (25-40 y; n = 25) and older (60-80 y; n = 33) adults had similar magnitude memory responses to varicella-zoster virus (VZV) ex vivo restimulation measured by responder cell-frequency and flow cytometry, but the responses were delayed in older compared with young adults. Only young adults had an increase in dual-function VZV-specific CD4 + and CD8 + T cell effectors defined by coexpression of IFN-γ, IL-2, and CD107a after vaccination. In contrast, older adults showed marginal increases in VZV-specific CD8 + CD57 + senescent T cells after vaccination, which were already higher than those of young adults before vaccination. An increase in VZV-stimulated CD4 + CD69 + CD57 + PD1 + and CD8 + CD69 + CD57 + PD1 + T cells from baseline to postvaccination was associated with concurrent decreased VZV-memory and CD8 + effector responses, respectively, in older adults. Blocking the PD1 pathway during ex vivo VZV restimulation increased the CD4 + and CD8 + proliferation, but not the effector cytokine production, which modestly increased with TIM-3 blockade. We conclude that high proportions of senescent and exhausted VZV-specific T cells in the older adults contribute to their poor effector responses to a VZV challenge. This may underlie their inability to contain VZV reactivation and prevent the development of HZ. Copyright © 2017 by The American Association of Immunologists, Inc.

  13. Public health impact and cost-effectiveness of intranasal live attenuated influenza vaccination of children in Germany.

    Science.gov (United States)

    Damm, Oliver; Eichner, Martin; Rose, Markus Andreas; Knuf, Markus; Wutzler, Peter; Liese, Johannes Günter; Krüger, Hagen; Greiner, Wolfgang

    2015-06-01

    In 2011, intranasally administered live attenuated influenza vaccine (LAIV) was approved in the EU for prophylaxis of seasonal influenza in 2-17-year-old children. Our objective was to estimate the potential epidemiological impact and cost-effectiveness of an LAIV-based extension of the influenza vaccination programme to healthy children in Germany. An age-structured dynamic model of influenza transmission was developed and combined with a decision-tree to evaluate different vaccination strategies in the German health care system. Model inputs were based on published literature or were derived by expert consulting using the Delphi technique. Unit costs were drawn from German sources. Under base-case assumptions, annual routine vaccination of children aged 2-17 years with LAIV assuming an uptake of 50% would prevent, across all ages, 16 million cases of symptomatic influenza, over 600,000 cases of acute otitis media, nearly 130,000 cases of community-acquired pneumonia, nearly 1.7 million prescriptions of antibiotics and over 165,000 hospitalisations over 10 years. The discounted incremental cost-effectiveness ratio was 1,228 per quality-adjusted life year gained from a broad third-party payer perspective (including reimbursed direct costs and specific transfer payments), when compared with the current strategy of vaccinating primarily risk groups with the conventional trivalent inactivated vaccine. Inclusion of patient co-payments and indirect costs in terms of productivity losses resulted in discounted 10-year cost savings of 3.4 billion. In conclusion, adopting universal influenza immunisation of healthy children and adolescents would lead to a substantial reduction in influenza-associated disease at a reasonable cost to the German statutory health insurance system. On the basis of the epidemiological and health economic simulation results, a recommendation of introducing annual routine influenza vaccination of children 2-17 years of age might be taken into

  14. The 7 C's for Creating Living Software: A Research Perspective for Quality-Oriented Software Engineering

    NARCIS (Netherlands)

    Aksit, Mehmet

    2004-01-01

    This article proposes the 7 C's for realizing quality-oriented software engineering practices. All the desired qualities of this approach are expressed in short by the term living software. The 7 C's are: Concern-oriented processes, Canonical models, Composable models, Certifiable models,

  15. Long Term Benefits for Women in a Science, Technology, Engineering, and Mathematics Living-Learning Community

    Science.gov (United States)

    Maltby, Jennifer L.; Brooks, Christopher; Horton, Marjorie; Morgan, Helen

    2016-01-01

    Science, technology, engineering and math (STEM) degrees provide opportunities for economic mobility. Yet women, underrepresented minority (URM), and first-generation college students remain disproportionately underrepresented in STEM fields. This study examined the effectiveness of a living-learning community (LLC) for URM and first-generation…

  16. Antigen-Specific lgA B Memory Cell Responses to Shigella Antigens Elicited in Volunteers Immunized with Live Attenuated Shigella flexneri 2a Oral Vaccine Candidates

    Science.gov (United States)

    2011-01-01

    167. [10] E.V. Oaks, T.L. Hale, S.B. Formal, Serum immune response to Shigella protein antigens in rhesus monkeys and humans infected with Shigella ...cell responses to Shigella antigens elicited in volunteers immunized with live attenuated Shigella flexneri 2a oral vaccine candidates J.K. Simona,b... Shigella ;. B cell memory; Immunoglobulin lgA; Mucosal immunity Abstract We studied the induction of antigen-specific lgA memory B cells (BM) in

  17. A live attenuated H7N7 candidate vaccine virus induces neutralizing antibody that confers protection from challenge in mice, ferrets and monkeys

    Science.gov (United States)

    A live attenuated H7N7 candidate vaccine virus was generated by reverse genetics using the modified hemagglutinin (HA) and neuraminidase (NA) genes of HP A/Netherlands/219/03 (NL/03) (H7N7) wild-type (wt) virus and the six internal protein genes of the cold-adapted (ca) A/Ann Arbor/6/60 ca (AA ca) (...

  18. Inhibitory effect of live-attenuated Listeria monocytogenes-based vaccines expressing MIA gene on malignant melanoma.

    Science.gov (United States)

    Qian, Yue; Zhang, Na; Jiang, Ping; Chen, Siyuan; Chu, Shujuan; Hamze, Firas; Wu, Yan; Luo, Qin; Feng, Aiping

    2012-08-01

    Listeria monocytogenes (LM), a Gram-positive facultative intracellular bacterium, can be used as an effective exogenous antigen expression vector in tumor-target therapy. But for successful clinical application, it is necessary to construct attenuated LM stain that is safe yet retains the potency of LM based on the full virulent pathogen. In this study, attenuated LM and recombinants of LM expressing melanoma inhibitory activity (MIA) were constructed successfully. The median lethal dose (LD(50)) and invasion efficiency of attenuated LM strains were detected. The recombinants were utilized for immunotherapy of animal model of B16F10 melanoma. The level of MIA mRNA expression in tumor tissue was detected by using real-time polymerase chain reaction (PCR) with specific sequence, meanwhile the anti-tumor immune response was assayed by flow cytometric analysis and enzyme-linked immunosorbent spot (ELISPOT) assay. The results showed the toxicity and invasiveness of attenuated LM were decreased as compared with LM, and attenuated LM expressing MIA, especially the double-genes attenuated LM recombinant, could significantly induce anti-tumor immune response and inhibit tumor growth. This study implicates attenuated LM may be a safer and more effective vector for immunotherapy of melanoma.

  19. Live attenuated measles vaccine expressing HIV-1 Gag virus like particles covered with gp160ΔV1V2 is strongly immunogenic

    International Nuclear Information System (INIS)

    Guerbois, Mathilde; Moris, Arnaud; Combredet, Chantal; Najburg, Valerie; Ruffie, Claude; Fevrier, Michele; Cayet, Nadege; Brandler, Samantha; Schwartz, Olivier; Tangy, Frederic

    2009-01-01

    Although a live attenuated HIV vaccine is not currently considered for safety reasons, a strategy inducing both T cells and neutralizing antibodies to native assembled HIV-1 particles expressed by a replicating virus might mimic the advantageous characteristics of live attenuated vaccine. To this aim, we generated a live attenuated recombinant measles vaccine expressing HIV-1 Gag virus-like particles (VLPs) covered with gp160ΔV1V2 Env protein. The measles-HIV virus replicated efficiently in cell culture and induced the intense budding of HIV particles covered with Env. In mice sensitive to MV infection, this recombinant vaccine stimulated high levels of cellular and humoral immunity to both MV and HIV with neutralizing activity. The measles-HIV virus infected human professional antigen-presenting cells, such as dendritic cells and B cells, and induced efficient presentation of HIV-1 epitopes and subsequent activation of human HIV-1 Gag-specific T cell clones. This candidate vaccine will be next tested in non-human primates. As a pediatric vaccine, it might protect children and adolescents simultaneously from measles and HIV.

  20. Evaluation of the thermal stability of a novel strain of live-attenuated mumps vaccine (RS-12 strain) lyophilized in different stabilizers.

    Science.gov (United States)

    Jamil, Razieh Kamali; Taqavian, Mohammad; Sadigh, Zohreh-Azita; Shahkarami, Mohammad-Kazem; Esna-Ashari, Fatemeh; Hamkar, Rasool; Hosseini, Seyedeh-Marzieh; Hatami, Alireza

    2014-04-01

    The stability of live-attenuated viral vaccines is important for immunization efficacy. Here, the thermostabilities of lyophilized live-attenuated mumps vaccine formulations in two different stabilizers, a trehalose dihydrate-based stabilizer and a stabilizer containing sucrose, human serum albumin and sorbitol were investigated using accelerated stability tests at 4°C, 25°C and 37°C at time points between 4h (every 4h for the first 24h) and 1 week. Even under the harshest storage conditions of 37°C for 1 week, the 50% cell culture infective dose (CCID50) determined from titrations in Vero cells dropped by less than 10-fold using each stabilizer formulation and thus complied with the World Health Organization's requirements for the potency of live-attenuated mumps vaccines. However, as the half-life of the RS-12 strain mumps virus infectivity was lengthened substantially at elevated temperatures using the trehalose dihydrate (TD)-based stabilizer, this stabilizer is recommended for vaccine use. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Safety Overview of a Recombinant Live-Attenuated Tetravalent Dengue Vaccine: Pooled Analysis of Data from 18 Clinical Trials.

    Directory of Open Access Journals (Sweden)

    Sophia Gailhardou

    2016-07-01

    Full Text Available A recombinant live attenuated tetravalent dengue vaccine (CYD-TDV has been shown to be efficacious in preventing virologically-confirmed dengue disease, severe dengue disease and dengue hospitalization in children aged 2-16 years in Asia and Latin America. We analyzed pooled safety data from 18 phase I, II and III clinical trials in which the dengue vaccine was administered to participants aged 2-60 years, including long-term safety follow-up in three efficacy trials. The participants were analyzed according to their age at enrollment. The percentage of participants aged 2-60 years reporting ≥1 solicited injection-site or systemic reactions was slightly higher in the CYD-TDV group than in the placebo group. The most common solicited injection-site reactions were pain. Headache and malaise were the most common solicited systemic reactions. In both groups 0.3% of participants discontinued for safety reasons. The most common unsolicited adverse events were injection-site reactions, gastrointestinal disorders, and infections. Reactogenicity did not increase with successive doses of CYD-TDV. The frequency and nature of SAEs occurring within 28 days of any dose were similar in the CYD-TDV and placebo groups and were common medical conditions that could be expected as a function of age. Baseline dengue virus serostatus did not appear to influence the safety profile. No vaccine-related anaphylactic reactions, neurotropic events or viscerotropic events were reported. In year 3 after dose 1, an imbalance for dengue hospitalization, including for severe dengue, observed in participants aged <9 years in the CYD-TDV group compared with the placebo group was not observed for participants aged ≥9 years. In Year 4, this imbalance in participants aged <9 years was less marked, giving an overall lower risk of dengue hospitalization or severe dengue from dose 1 to Year 4 in the CYD-TDV group. These results have contributed to the definition of the target

  2. Evaluation of synthetic infection-enhancing lipopeptides as adjuvants for a live-attenuated canine distemper virus vaccine administered intra-nasally to ferrets.

    Science.gov (United States)

    Nguyen, D Tien; Ludlow, Martin; van Amerongen, Geert; de Vries, Rory D; Yüksel, Selma; Verburgh, R Joyce; Osterhaus, Albert D M E; Duprex, W Paul; de Swart, Rik L

    2012-07-20

    Inactivated paramyxovirus vaccines have been associated with hypersensitivity responses upon challenge infection. For measles and canine distemper virus (CDV) safe and effective live-attenuated virus vaccines are available, but for human respiratory syncytial virus and human metapneumovirus development of such vaccines has proven difficult. We recently identified three synthetic bacterial lipopeptides that enhance paramyxovirus infections in vitro, and hypothesized these could be used as adjuvants to promote immune responses induced by live-attenuated paramyxovirus vaccines. Here, we tested this hypothesis using a CDV vaccination and challenge model in ferrets. Three groups of six animals were intra-nasally vaccinated with recombinant (r) CDV(5804P)L(CCEGFPC) in the presence or absence of the infection-enhancing lipopeptides Pam3CSK4 or PHCSK4. The recombinant CDV vaccine virus had previously been described to be over-attenuated in ferrets. A group of six animals was mock-vaccinated as control. Six weeks after vaccination all animals were challenged with a lethal dose of rCDV strain Snyder-Hill expressing the red fluorescent protein dTomato. Unexpectedly, intra-nasal vaccination of ferrets with rCDV(5804P)L(CCEGFPC) in the absence of lipopeptides resulted in good immune responses and protection against lethal challenge infection. However, in animals vaccinated with lipopeptide-adjuvanted virus significantly higher vaccine virus loads were detected in nasopharyngeal lavages and peripheral blood mononuclear cells. In addition, these animals developed significantly higher CDV neutralizing antibody titers compared to animals vaccinated with non-adjuvanted vaccine. This study demonstrates that the synthetic cationic lipopeptides Pam3CSK4 and PHCSK4 not only enhance paramyxovirus infection in vitro, but also in vivo. Given the observed enhancement of immunogenicity their potential as adjuvants for other live-attenuated paramyxovirus vaccines should be considered

  3. Gaming, texting, learning? Teaching engineering ethics through students' lived experiences with technology.

    Science.gov (United States)

    Voss, Georgina

    2013-09-01

    This paper examines how young peoples' lived experiences with personal technologies can be used to teach engineering ethics in a way which facilitates greater engagement with the subject. Engineering ethics can be challenging to teach: as a form of practical ethics, it is framed around future workplace experience in a professional setting which students are assumed to have no prior experience of. Yet the current generations of engineering students, who have been described as 'digital natives', do however have immersive personal experience with digital technologies; and experiential learning theory describes how students learn ethics more successfully when they can draw on personal experience which give context and meaning to abstract theories. This paper reviews current teaching practices in engineering ethics; and examines young people's engagement with technologies including cell phones, social networking sites, digital music and computer games to identify social and ethical elements of these practices which have relevance for the engineering ethics curricula. From this analysis three case studies are developed to illustrate how facets of the use of these technologies can be drawn on to teach topics including group work and communication; risk and safety; and engineering as social experimentation. Means for bridging personal experience and professional ethics when teaching these cases are discussed. The paper contributes to research and curriculum development in engineering ethics education, and to wider education research about methods of teaching 'the net generation'.

  4. A new course and textbook on Physical Models of Living Systems, for science and engineering undergraduates

    Science.gov (United States)

    Nelson, Philip

    2015-03-01

    I'll describe an intermediate-level course on ``Physical Models of Living Systems.'' The only prerequisite is first-year university physics and calculus. The course is a response to rapidly growing interest among undergraduates in a broad range of science and engineering majors. Students acquire several research skills that are often not addressed in traditional courses: Basic modeling skills Probabilistic modeling skills Data analysis methods Computer programming using a general-purpose platform like MATLAB or Python Dynamical systems, particularly feedback control. These basic skills, which are relevant to nearly any field of science or engineering, are presented in the context of case studies from living systems, including: Virus dynamics Bacterial genetics and evolution of drug resistance Statistical inference Superresolution microscopy Synthetic biology Naturally evolved cellular circuits. Work supported by NSF Grants EF-0928048 and DMR-0832802.

  5. Rational design of a live attenuated dengue vaccine: 2'-o-methyltransferase mutants are highly attenuated and immunogenic in mice and macaques.

    Directory of Open Access Journals (Sweden)

    Roland Züst

    Full Text Available Dengue virus is transmitted by Aedes mosquitoes and infects at least 100 million people every year. Progressive urbanization in Asia and South-Central America and the geographic expansion of Aedes mosquito habitats have accelerated the global spread of dengue, resulting in a continuously increasing number of cases. A cost-effective, safe vaccine conferring protection with ideally a single injection could stop dengue transmission. Current vaccine candidates require several booster injections or do not provide protection against all four serotypes. Here we demonstrate that dengue virus mutants lacking 2'-O-methyltransferase activity are highly sensitive to type I IFN inhibition. The mutant viruses are attenuated in mice and rhesus monkeys and elicit a strong adaptive immune response. Monkeys immunized with a single dose of 2'-O-methyltransferase mutant virus showed 100% sero-conversion even when a dose as low as 1,000 plaque forming units was administrated. Animals were fully protected against a homologous challenge. Furthermore, mosquitoes feeding on blood containing the mutant virus were not infected, whereas those feeding on blood containing wild-type virus were infected and thus able to transmit it. These results show the potential of 2'-O-methyltransferase mutant virus as a safe, rationally designed dengue vaccine that restrains itself due to the increased susceptibility to the host's innate immune response.

  6. THE ATTENUATING EFFECT OF EMPOWERMENT ON IPV-RELATED PTSD SYMPTOMS IN BATTERED WOMEN LIVING IN DOMESTIC VIOLENCE SHELTERS

    Science.gov (United States)

    Perez, Sara; Johnson, Dawn M.; Wright, Caroline Vaile

    2010-01-01

    Intimate partner violence (IPV) is associated with significant psychological distress, including posttraumatic stress disorder (PTSD). However, factors that attenuate the impact of IPV on PTSD remain largely unknown. Using hierarchical regression, this investigation explored the impact of resource acquisition and empowerment on the relationship between IPV and PTSD. Empowerment demonstrated greater relative importance over resource acquisition. Specifically, empowerment was found to attenuate the impact of IPV severity on PTSD at low and moderate levels of violence. The importance of fostering empowerment and addressing PTSD in addition to provision of resources in battered women is discussed. PMID:22411301

  7. An engineered S1P chaperone attenuates hypertension and ischemic injury.

    Science.gov (United States)

    Swendeman, Steven L; Xiong, Yuquan; Cantalupo, Anna; Yuan, Hui; Burg, Nathalie; Hisano, Yu; Cartier, Andreane; Liu, Catherine H; Engelbrecht, Eric; Blaho, Victoria; Zhang, Yi; Yanagida, Keisuke; Galvani, Sylvain; Obinata, Hideru; Salmon, Jane E; Sanchez, Teresa; Di Lorenzo, Annarita; Hla, Timothy

    2017-08-15

    Endothelial dysfunction, a hallmark of vascular disease, is restored by plasma high-density lipoprotein (HDL). However, a generalized increase in HDL abundance is not beneficial, suggesting that specific HDL species mediate protective effects. Apolipoprotein M-containing HDL (ApoM + HDL), which carries the bioactive lipid sphingosine 1-phosphate (S1P), promotes endothelial function by activating G protein-coupled S1P receptors. Moreover, HDL-bound S1P is limiting in several inflammatory, metabolic, and vascular diseases. We report the development of a soluble carrier for S1P, ApoM-Fc, which activated S1P receptors in a sustained manner and promoted endothelial function. In contrast, ApoM-Fc did not modulate circulating lymphocyte numbers, suggesting that it specifically activated endothelial S1P receptors. ApoM-Fc administration reduced blood pressure in hypertensive mice, attenuated myocardial damage after ischemia/reperfusion injury, and reduced brain infarct volume in the middle cerebral artery occlusion model of stroke. Our proof-of-concept study suggests that selective and sustained targeting of endothelial S1P receptors by ApoM-Fc could be a viable therapeutic strategy in vascular diseases. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  8. Modeling and Forecasting of Depletion of Additives in Car Engine Oils Using Attenuated Total Reflectance Fast Transform Infrared Spectroscopy

    Directory of Open Access Journals (Sweden)

    Ronald Nguele

    2014-11-01

    Full Text Available On average, additives make up to 7% of a typical lubricant base. Commonly, they are blended with lube oils to enhance specific features thereby improving their qualities. Ultimately, additives participate in the performance of car engine oils. Using an analytical tool, attenuated total reflectance fast transform infrared spectroscopy, various grades of car engine oils, at different mileages, were analyzed. Sulfate oxidation and wear were found to trigger chemical processes which, in the long run, cause lubricant degradation while carbonyl oxidation was observed to occur only at a slow rate. Based upon data obtained from infrared spectra and using a curve fitting technique, mathematical equations predicting the theoretical rates of chemical change due to the aforementioned processes were examined. Additive depletions were found to obey exponential regression rather than polynomial. Moreover, breakpoint (breakpoint is used here to denote the initiation of deterioration of additives and critical mileage (critical mileage defines the distance at which the lubricant is chemically unusable of both samples were determined.

  9. Cold-adapted live attenuated influenza vaccines developed in Russia: Can they contribute to meeting the needs for influenza control in other countries?

    International Nuclear Information System (INIS)

    Kendal, Alan P.

    1997-01-01

    It is now more than 30 years since the first cold-adapted influenza viruses were developed in Russia as potential live, attenuated vaccines. In the past 15-20 years considerable experience has been gained from Russian and joint Russian-US laboratory and clinical studies with type A monovalent and bivalent vaccines prepared with genetic reassortant viruses derived from one of these cold-adapted viruses in particular, A/Leningrad/134/57. More recent experiences include use of trivalent cold-adapted vaccines with a type B component. The overall high level of safety of individual and combined vaccines in pre-school and school-aged children, with illness reductions in open field trials equivalent to that seen with inactivated vaccines, is such as to suggest that practical measures might now be justified to facilitate expansion of the use of these vaccines to other countries. It is proposed that further experimentation with the Russian cold-adapted live attenuated vaccines should be focused on issues that will relate to the public health perspective, i.e. selection of the single best candidate type A and B vaccines for intense study using as criteria their potential for meeting licensing requirements outside Russia, and documenting the clinical protective efficacy of a single vaccine dose compared to two doses as studied until now. Resolution of these issues is important to ensure that costs for future live vaccine production, control, and utilization will be kept at lowest levels so that expanded use of live vaccines will have maximum cost-benefit and affordability. To guide those interested in these issues, examples are given of populations for whom a licensed live cold-adapted vaccine might be considered, together with indications of extra data needed to fully validate each suggested use

  10. Major histocompatibility complex-linked immune response of young chickens vaccinated with an attenuated live infectious bursal disease virus vaccine followed by an infection

    DEFF Research Database (Denmark)

    Juul-Madsen, Helle; Nielsen, O.L.; Krogh-Maibom, T.

    2002-01-01

    The influence of the MHC on infectious bursal disease virus (IBDV) vaccine response in chickens was investigated in three different chicken lines containing four different MHC haplotypes. Two MHC haplotypes were present in all three lines with one haplotype (1319) shared between the lines. Line I...... further contains the BW1 haplotype isolated from a Red jungle Fowl. Line 131 further contains the B131 haplotype isolated from a meat-type chicken, Finally, Line 21 further contains the international B21 haplotype. The chickens were vaccinated with live attenuated commercial IBDV vaccine at 3 wk of age...

  11. A live attenuated cold-adapted influenza A H7N3 virus vaccine provides protection against homologous and heterologous H7 viruses in mice and ferrets

    International Nuclear Information System (INIS)

    Joseph, Tomy; McAuliffe, Josephine; Lu, Bin; Vogel, Leatrice; Swayne, David; Jin, Hong; Kemble, George; Subbarao, Kanta

    2008-01-01

    The appearance of human infections caused by avian influenza A H7 subtype viruses underscores their pandemic potential and the need to develop vaccines to protect humans from viruses of this subtype. A live attenuated H7N3 virus vaccine was generated by reverse genetics using the HA and NA genes of a low pathogenicity A/chicken/BC/CN-6/04 (H7N3) virus and the six internal protein genes of the cold-adapted A/Ann Arbor/6/60 ca (H2N2) virus. The reassortant H7N3 BC 04 ca vaccine virus was temperature sensitive and showed attenuation in mice and ferrets. Intranasal immunization with one dose of the vaccine protected mice and ferrets when challenged with homologous and heterologous H7 viruses. The reassortant H7N3 BC 04 ca vaccine virus showed comparable levels of attenuation, immunogenicity and efficacy in mice and ferret models. The safety, immunogenicity, and efficacy of this vaccine in mice and ferrets support the evaluation of this vaccine in clinical trials

  12. Engineering CRISPR interference system in Klebsiella pneumoniae for attenuating lactic acid synthesis.

    Science.gov (United States)

    Wang, Jingxuan; Zhao, Peng; Li, Ying; Xu, Lida; Tian, Pingfang

    2018-04-05

    Klebsiella pneumoniae is a promising industrial species for bioproduction of bulk chemicals such as 1,3-propanediol, 2,3-butanediol and 3-hydroxypropionic acid (3-HP). However, lactic acid is a troublesome by-product when optimizing for 3-HP production. Therefore, it is highly desirable to minimize lactic acid. Here, we show that lactic acid synthesis can be largely blocked by an engineered CRISPR interference (CRISPRi) system in K. pneumoniae. EGFP was recruited as a reporter of this CRISPRi system. Fluorescence assay of this CRISPRi system showed that enhanced green fluorescent protein (EGFP) expression level was repressed by 85-90%. To further test this CRISPRi system, guide RNAs were designed to individually or simultaneously target four lactate-producing enzyme genes. Results showed that all lactate-producing enzyme genes were significantly repressed. Notably, D-lactate dehydrogenase (ldhA) was shown to be the most influential enzyme for lactic acid formation in micro-aerobic conditions, as inhibiting ldhA alone led to lactic acid level similar to simultaneously repressing four genes. In shake flask cultivation, the strain coexpressing puuC (an aldehyde dehydrogenase catalyzing 3-hydroxypropionaldehyde to 3-HP) and dCas9-sgRNA inhibiting ldhA produced 1.37-fold 3-HP relative to the reference strain. Furthermore, in bioreactor cultivation, this CRISPRi strain inhibiting ldhA produced 36.7 g/L 3-HP, but only generated 1 g/L lactic acid. Clearly, this engineered CRISPRi system largely simplified downstream separation of 3-HP from its isomer lactic acid, an extreme challenge for 3-HP bioprocess. This study offers a deep understanding of lactic acid metabolism in diverse species, and we believe that this CRISPRi system will facilitate biomanufacturing and functional genome studies of K. pneumoniae or beyond.

  13. Development of a dual-protective live attenuated vaccine against H5N1 and H9N2 avian influenza viruses by modifying the NS1 gene.

    Science.gov (United States)

    Choi, Eun-hye; Song, Min-Suk; Park, Su-Jin; Pascua, Philippe Noriel Q; Baek, Yun Hee; Kwon, Hyeok-il; Kim, Eun-Ha; Kim, Semi; Jang, Hyung-Kwan; Poo, Haryoung; Kim, Chul-Joong; Choi, Young Ki

    2015-07-01

    An increasing number of outbreaks of avian influenza H5N1 and H9N2 viruses in poultry have caused serious economic losses and raised concerns for human health due to the risk of zoonotic transmission. However, licensed H5N1 and H9N2 vaccines for animals and humans have not been developed. Thus, to develop a dual H5N1 and H9N2 live-attenuated influenza vaccine (LAIV), the HA and NA genes from a virulent mouse-adapted avian H5N2 (A/WB/Korea/ma81/06) virus and a recently isolated chicken H9N2 (A/CK/Korea/116/06) virus, respectively, were introduced into the A/Puerto Rico/8/34 backbone expressing truncated NS1 proteins (NS1-73, NS1-86, NS1-101, NS1-122) but still possessing a full-length NS gene. Two H5N2/NS1-LAIV viruses (H5N2/NS1-86 and H5N2/NS1-101) were highly attenuated compared with the full-length and remaining H5N2/NS-LAIV viruses in a mouse model. Furthermore, viruses containing NS1 modifications were found to induce more IFN-β activation than viruses with full-length NS1 proteins and were correspondingly attenuated in mice. Intranasal vaccination with a single dose (10(4.0) PFU/ml) of these viruses completely protected mice from a lethal challenge with the homologous A/WB/Korea/ma81/06 (H5N2), heterologous highly pathogenic A/EM/Korea/W149/06 (H5N1), and heterosubtypic highly virulent mouse-adapted H9N2 viruses. This study clearly demonstrates that the modified H5N2/NS1-LAIV viruses attenuated through the introduction of mutations in the NS1 coding region display characteristics that are desirable for live attenuated vaccines and hold potential as vaccine candidates for mammalian hosts.

  14. Vaccination of children with a live-attenuated, intranasal influenza vaccine – analysis and evaluation through a Health Technology Assessment

    Directory of Open Access Journals (Sweden)

    Andersohn, Frank

    2014-10-01

    Full Text Available [english] Background: Influenza is a worldwide prevalent infectious disease of the respiratory tract annually causing high morbidity and mortality in Germany. Influenza is preventable by vaccination and this vaccination is so far recommended by the (STIKO as a standard vaccination for people from the age of 60 onwards. Up to date a parenterally administered trivalent inactivated vaccine (TIV has been in use almost exclusively. Since 2011 however a live-attenuated vaccine (LAIV has been approved additionally. Consecutively, since 2013 the STIKO recommends LAIV (besides TIV for children from 2 to 17 years of age, within the scope of vaccination by specified indications. LAIV should be preferred administered in children from 2 to 6 of age. The objective of this Health Technology Assessment (HTA is to address various research issues regarding the vaccination of children with LAIV. The analysis was performed from a medical, epidemiological and health economic perspective, as well as from an ethical, social and legal point of view.Method: An extensive systematic database research was performed to obtain relevant information. In addition a supplementary research by hand was done. Identified literature was screened in two passes by two independent reviewers using predefined inclusion and exclusion criteria. Included literature was evaluated in full-text using acknowledged standards. Studies were graded with the highest level of evidence (1++, if they met the criteria of Results: For the medical section, the age of the study participants ranges from 6 months to 17 years. Regarding study efficacy, in children aged 6 months to ≤7 years, LAIV is superior to placebo as well as to a vac-cination with TIV (Relative Risk Reduction – RRR – of laboratory confirmed influenza infection approx. 80% and 50%, respectively. In children aged >7 to 17 years (= 18th year of their lives, LAIV is superior to a vaccination with TIV (RRR 32%. For this age group, no

  15. Online quantitative monitoring of live cell engineered cartilage growth using diffuse fiber-optic Raman spectroscopy.

    Science.gov (United States)

    Bergholt, Mads S; Albro, Michael B; Stevens, Molly M

    2017-09-01

    Tissue engineering (TE) has the potential to improve the outcome for patients with osteoarthritis (OA). The successful clinical translation of this technique as part of a therapy requires the ability to measure extracellular matrix (ECM) production of engineered tissues in vitro, in order to ensure quality control and improve the likelihood of tissue survival upon implantation. Conventional techniques for assessing the ECM content of engineered cartilage, such as biochemical assays and histological staining are inherently destructive. Raman spectroscopy, on the other hand, represents a non-invasive technique for in situ biochemical characterization. Here, we outline current roadblocks in translational Raman spectroscopy in TE and introduce a comprehensive workflow designed to non-destructively monitor and quantify ECM biomolecules in large (>3 mm), live cell TE constructs online. Diffuse near-infrared fiber-optic Raman spectra were measured from live cell cartilaginous TE constructs over a 56-day culturing period. We developed a multivariate curve resolution model that enabled quantitative biochemical analysis of the TE constructs. Raman spectroscopy was able to non-invasively quantify the ECM components and showed an excellent correlation with biochemical assays for measurement of collagen (R 2  = 0.84) and glycosaminoglycans (GAGs) (R 2  = 0.86). We further demonstrated the robustness of this technique for online prospective analysis of live cell TE constructs. The fiber-optic Raman spectroscopy strategy developed in this work offers the ability to non-destructively monitor construct growth online and can be adapted to a broad range of TE applications in regenerative medicine toward controlled clinical translation. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Early protection events in swine immunized with an experimental live attenuated classical swine fever marker vaccine, FlagT4G.

    Directory of Open Access Journals (Sweden)

    Lauren G Holinka

    Full Text Available Prophylactic vaccination using live attenuated classical swine fever (CSF vaccines has been a very effective method to control the disease in endemic regions and during outbreaks in previously disease-free areas. These vaccines confer effective protection against the disease at early times post-vaccination although the mechanisms mediating the protection are poorly characterized. Here we present the events occurring after the administration of our in-house developed live attenuated marker vaccine, FlagT4Gv. We previously reported that FlagT4Gv intramuscular (IM administered conferred effective protection against intranasal challenge with virulent CSFV (BICv as early as 7 days post-vaccination. Here we report that FlagT4Gv is able to induce protection against disease as early as three days post-vaccination. Immunohistochemical testing of tissues from FlagT4Gv-inoculated animals showed that tonsils were colonized by the vaccine virus by day 3 post-inoculation. There was a complete absence of BICv in tonsils of FlagT4Gv-inoculated animals which had been intranasal (IN challenged with BICv 3 days after FlagT4Gv infection, confirming that FlagT4Gv inoculation confers sterile immunity. Analysis of systemic levels of 19 different cytokines in vaccinated animals demonstrated an increase of IFN-α three days after FlagT4Gv inoculation compared with mock infected controls.

  17. Live Cell Analysis and Mathematical Modeling Identify Determinants of Attenuation of Dengue Virus 2'-O-Methylation Mutant.

    Directory of Open Access Journals (Sweden)

    Bianca Schmid

    2015-12-01

    Full Text Available Dengue virus (DENV is the most common mosquito-transmitted virus infecting ~390 million people worldwide. In spite of this high medical relevance, neither a vaccine nor antiviral therapy is currently available. DENV elicits a strong interferon (IFN response in infected cells, but at the same time actively counteracts IFN production and signaling. Although the kinetics of activation of this innate antiviral defense and the timing of viral counteraction critically determine the magnitude of infection and thus disease, quantitative and kinetic analyses are lacking and it remains poorly understood how DENV spreads in IFN-competent cell systems. To dissect the dynamics of replication versus antiviral defense at the single cell level, we generated a fully viable reporter DENV and host cells with authentic reporters for IFN-stimulated antiviral genes. We find that IFN controls DENV infection in a kinetically determined manner that at the single cell level is highly heterogeneous and stochastic. Even at high-dose, IFN does not fully protect all cells in the culture and, therefore, viral spread occurs even in the face of antiviral protection of naïve cells by IFN. By contrast, a vaccine candidate DENV mutant, which lacks 2'-O-methylation of viral RNA is profoundly attenuated in IFN-competent cells. Through mathematical modeling of time-resolved data and validation experiments we show that the primary determinant for attenuation is the accelerated kinetics of IFN production. This rapid induction triggered by mutant DENV precedes establishment of IFN-resistance in infected cells, thus causing a massive reduction of virus production rate. In contrast, accelerated protection of naïve cells by paracrine IFN action has negligible impact. In conclusion, these results show that attenuation of the 2'-O-methylation DENV mutant is primarily determined by kinetics of autocrine IFN action on infected cells.

  18. Association of the Host Immune Response with Protection Using a Live Attenuated African Swine Fever Virus Model.

    Science.gov (United States)

    Carlson, Jolene; O'Donnell, Vivian; Alfano, Marialexia; Velazquez Salinas, Lauro; Holinka, Lauren G; Krug, Peter W; Gladue, Douglas P; Higgs, Stephen; Borca, Manuel V

    2016-10-22

    African swine fever (ASF) is a lethal hemorrhagic disease of swine caused by a double-stranded DNA virus, ASF virus (ASFV). There is no vaccine to prevent the disease and current control measures are limited to culling and restricting animal movement. Swine infected with attenuated strains are protected against challenge with a homologous virulent virus, but there is limited knowledge of the host immune mechanisms generating that protection. Swine infected with Pretoriuskop/96/4 (Pret4) virus develop a fatal severe disease, while a derivative strain lacking virulence-associated gene 9GL (Pret4Δ9GL virus) is completely attenuated. Swine infected with Pret4Δ9GL virus and challenged with the virulent parental virus at 7, 10, 14, 21, and 28 days post infection (dpi) showed a progressive acquisition of protection (from 40% at 7 dpi to 80% at 21 and 28 dpi). This animal model was used to associate the presence of host immune response (ASFV-specific antibody and interferon (IFN)-γ responses, or specific cytokine profiles) and protection against challenge. With the exception of ASFV-specific antibodies in survivors challenged at 21 and 28 dpi, no association between the parameters assessed and protection could be established. These results, encompassing data from 65 immunized swine, underscore the complexity of the system under study, suggesting that protection relies on the concurrence of different host immune mechanisms.

  19. Association of the Host Immune Response with Protection Using a Live Attenuated African Swine Fever Virus Model

    Directory of Open Access Journals (Sweden)

    Jolene Carlson

    2016-10-01

    Full Text Available African swine fever (ASF is a lethal hemorrhagic disease of swine caused by a double-stranded DNA virus, ASF virus (ASFV. There is no vaccine to prevent the disease and current control measures are limited to culling and restricting animal movement. Swine infected with attenuated strains are protected against challenge with a homologous virulent virus, but there is limited knowledge of the host immune mechanisms generating that protection. Swine infected with Pretoriuskop/96/4 (Pret4 virus develop a fatal severe disease, while a derivative strain lacking virulence-associated gene 9GL (Pret4Δ9GL virus is completely attenuated. Swine infected with Pret4Δ9GL virus and challenged with the virulent parental virus at 7, 10, 14, 21, and 28 days post infection (dpi showed a progressive acquisition of protection (from 40% at 7 dpi to 80% at 21 and 28 dpi. This animal model was used to associate the presence of host immune response (ASFV-specific antibody and interferon (IFN-γ responses, or specific cytokine profiles and protection against challenge. With the exception of ASFV-specific antibodies in survivors challenged at 21 and 28 dpi, no association between the parameters assessed and protection could be established. These results, encompassing data from 65 immunized swine, underscore the complexity of the system under study, suggesting that protection relies on the concurrence of different host immune mechanisms.

  20. Use of the live attenuated Japanese Encephalitis vaccine SA 14-14-2 in children: A review of safety and tolerability studies.

    Science.gov (United States)

    Ginsburg, Amy Sarah; Meghani, Ankita; Halstead, Scott B; Yaich, Mansour

    2017-10-03

    Japanese encephalitis (JE) is the leading cause of viral neurological disease and disability in Asia. Some 50-80% of children with clinical JE die or have long-term neurologic sequelae. Since there is no cure, human vaccination is the only effective long-term control measure, and the World Health Organization recommends that at-risk populations receive a safe and effective vaccine. Four different types of JE vaccines are currently available: inactivated mouse brain-derived vaccines, inactivated Vero cell vaccines, live attenuated SA 14-14-2 vaccines and a live recombinant (chimeric) vaccine. With the rapidly increasing demand for and availability and use of JE vaccines, countries face an important decision in the selection of a JE vaccine. This article provides a comprehensive review of the available safety literature for the live attenuated SA 14-14-2 JE vaccine (LAJEV), the most widely used new generation JE vaccine. With well-established effectiveness data, a single dose of LAJEV protects against clinical JE disease for at least 5 years, providing a long duration of protection compared with inactivated mouse brain-derived vaccines. Since 1988, about 700 million doses of the LAJEV have been distributed globally. Our review found that LAJEV is well tolerated across a wide age range and can safely be given to children as young as 8 months of age. While serious adverse events attributable to LAJEV have been reported, independent experts have not found sufficient evidence for causality based on the available data.

  1. A live-attenuated HSV-2 ICP0 virus elicits 10 to 100 times greater protection against genital herpes than a glycoprotein D subunit vaccine.

    Directory of Open Access Journals (Sweden)

    William P Halford

    2011-03-01

    Full Text Available Glycoprotein D (gD-2 is the entry receptor of herpes simplex virus 2 (HSV-2, and is the immunogen in the pharmaceutical industry's lead HSV-2 vaccine candidate. Efforts to prevent genital herpes using gD-2 subunit vaccines have been ongoing for 20 years at a cost in excess of $100 million. To date, gD-2 vaccines have yielded equivocal protection in clinical trials. Therefore, using a small animal model, we sought to determine if a live-attenuated HSV-2 ICP0⁻ virus would elicit better protection against genital herpes than a gD-2 subunit vaccine. Mice immunized with gD-2 and a potent adjuvant (alum+monophosphoryl lipid A produced high titers of gD-2 antibody. While gD-2-immunized mice possessed significant resistance to HSV-2, only 3 of 45 gD-2-immunized mice survived an overwhelming challenge of the vagina or eyes with wild-type HSV-2 (MS strain. In contrast, 114 of 115 mice immunized with a live HSV-2 ICP0⁻ virus, 0ΔNLS, survived the same HSV-2 MS challenges. Likewise, 0ΔNLS-immunized mice shed an average 125-fold less HSV-2 MS challenge virus per vagina relative to gD-2-immunized mice. In vivo imaging demonstrated that a luciferase-expressing HSV-2 challenge virus failed to establish a detectable infection in 0ΔNLS-immunized mice, whereas the same virus readily infected naïve and gD-2-immunized mice. Collectively, these results suggest that a HSV-2 vaccine might be more likely to prevent genital herpes if it contained a live-attenuated HSV-2 virus rather than a single HSV-2 protein.

  2. Quantification of live Lactobacillus acidophilus in mixed populations of live and killed by application of attenuated reflection Fourier transform infrared spectroscopy combined with chemometrics.

    Science.gov (United States)

    Toziou, Peristera-Maria; Barmpalexis, Panagiotis; Boukouvala, Paraskevi; Verghese, Susan; Nikolakakis, Ioannis

    2018-05-30

    Since culture-based methods are costly and time consuming, alternative methods are investigated for the quantification of probiotics in commercial products. In this work ATR- FTIR vibration spectroscopy was applied for the differentiation and quantification of live Lactobacillus (La 5) in mixed populations of live and killed La 5, in the absence and in the presence of enteric polymer Eudragit ® L 100-55. Suspensions of live (La 5_L) and killed in acidic environment bacillus (La 5_K) were prepared and binary mixtures of different percentages were used to grow cell cultures for colony counting and spectral analysis. The increase in the number of colonies with added%La 5_L to the mixture was log-linear (r 2  = 0.926). Differentiation of La 5_L from La 5_K was possible directly from the peak area at 1635 cm -1 (amides of proteins and peptides) and a linear relationship between%La 5_L and peak area in the range 0-95% was obtained. Application of partial least squares regression (PLSR) gave reasonable prediction of%La 5_L (RMSEp = 6.48) in binary mixtures of live and killed La 5 but poor prediction (RMSEp = 11.75) when polymer was added to the La 5 mixture. Application of artificial neural networks (ANNs) improved greatly the predictive ability for%La 5_L both in the absence and in the presence of polymer (RMSEp = 8.11 × 10 -8 for La 5 only mixtures and RMSEp = 8.77 × 10 -8 with added polymer) due to their ability to express in the calibration models more hidden spectral information than PLSR. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. A hybrid bio-jetting approach for directly engineering living cells

    International Nuclear Information System (INIS)

    Kwok, Albert; Irvine, Scott; Arumuganathar, Sumathy; Jayasinghe, Suwan N; McEwan, Jean R

    2008-01-01

    This paper reports developments on a hybrid cell-engineering protocol coupling both bio-electrosprays and aerodynamically assisted bio-jets for process-handling living cells. The current work demonstrates the ability to couple these two cell-jetting protocols for handling a wide range of cells for deposition. The post-treated cells are assessed for their viability by way of flow cytometry, which illustrates a significant population of viable cells post-treatment in comparison to those controls. This work is the first example of coupling these two protocols for the process handling of living cells. The hybrid protocol demonstrates the achievement of stable cone jetting of a cellular suspension in the single-needle configuration which was previously unachieved with single-needle bio-electrosprays. Furthermore the living cells explored in these investigations expressed GFP, thus demonstrating the ability to couple gene therapy with this hybrid protocol. Hence, this approach could one day be explored for building biologically viable tissues incorporating a therapeutic payload for combating a range of cellular/tissue-based pathologies

  4. Longitudinal study to assess the safety and efficacy of a live-attenuated SHIV vaccine in long term immunized rhesus macaques

    International Nuclear Information System (INIS)

    Yankee, Thomas M.; Sheffer, Darlene; Liu Zhengian; Dhillon, Sukhbir; Jia Fenglan; Chebloune, Yahia; Stephens, Edward B.; Narayan, Opendra

    2009-01-01

    Live-attenuated viruses derived from SIV and SHIV have provided the most consistent protection against challenge with pathogenic viruses, but concerns regarding their long-term safety and efficacy have hampered their clinical usefulness. We report a longitudinal study in which we evaluated the long-term safety and efficacy of ΔvpuSHIV PPC , a live virus vaccine derived from SHIV PPC . Macaques were administered two inoculations of ΔvpuSHIV PPC , three years apart, and followed for eight years. None of the five vaccinated macaques developed an AIDS-like disease from the vaccine. At eight years, macaques were challenged with pathogenic SIV and SHIV. None of the four macaques with detectable cellular-mediated immunity prior to challenge had detectable viral RNA in the plasma. This study demonstrates that multiple inoculations of a live vaccine virus can be used safely and can significantly extend the efficacy of the vaccine, as compared to a single inoculation, which is efficacious for approximately three years

  5. Long-Term Safety and Immunogenicity of a Tetravalent Live-Attenuated Dengue Vaccine and Evaluation of a Booster Dose Administered to Healthy Thai Children.

    Science.gov (United States)

    Watanaveeradej, Veerachai; Simasathien, Sriluck; Mammen, Mammen P; Nisalak, Ananda; Tournay, Elodie; Kerdpanich, Phirangkul; Samakoses, Rudiwilai; Putnak, Robert J; Gibbons, Robert V; Yoon, In-Kyu; Jarman, Richard G; De La Barrera, Rafael; Moris, Philippe; Eckels, Kenneth H; Thomas, Stephen J; Innis, Bruce L

    2016-06-01

    We evaluated the safety and immunogenicity of two doses of a live-attenuated, tetravalent dengue virus vaccine (F17/Pre formulation) and a booster dose in a dengue endemic setting in two studies. Seven children (7- to 8-year-olds) were followed for 1 year after dose 2 and then given a booster dose (F17/Pre formulation), and followed for four more years (Child study). In the Infant study, 49 2-year-olds, vaccinated as infants, were followed for approximately 3.5 years after dose 2 and then given a booster dose (F17) and followed for one additional year. Two clinically notable events were observed, both in dengue vaccine recipients in the Infant study: 1 case of dengue approximately 2.7 years after dose 2 and 1 case of suspected dengue after booster vaccinations. The booster vaccinations had a favorable safety profile in terms of reactogenicity and adverse events reported during the 1-month follow-up periods. No vaccine-related serious adverse events were reported during the studies. Neutralizing antibodies against dengue viruses 1-4 waned during the 1-3 years before boosting, which elicited a short-lived booster response but did not provide a long-lived, multivalent antibody response in most subjects. Overall, this candidate vaccine did not elicit a durable humoral immune response. © The American Society of Tropical Medicine and Hygiene.

  6. Single-cycle immunodeficiency viruses provide strategies for uncoupling in vivo expression levels from viral replicative capacity and for mimicking live-attenuated SIV vaccines

    International Nuclear Information System (INIS)

    Kuate, Seraphin; Stahl-Hennig, Christiane; Haaft, Peter ten; Heeney, Jonathan; Ueberla, Klaus

    2003-01-01

    To reduce the risks associated with live-attenuated immunodeficiency virus vaccines, single-cycle immunodeficiency viruses (SCIVs) were developed by primer complementation and production of the vaccine in the absence of vif in a vif-independent cell line. After a single intravenous injection of SCIVs into rhesus monkeys, peak viral RNA levels of 10 3 to 10 4 copies/ml plasma were observed, indicating efficient expression of SCIV in the vaccinee. After booster immunizations with SCIVs, SIV-specific humoral and cellular immune responses were observed. Although the vaccine doses used in this pilot study could not protect vaccinees from subsequent intravenous challenge with pathogenic SIVmac239, our results demonstrate that the novel SCIV approach allows us to uncouple in vivo expression levels from the viral replicative capacity facilitating the analysis of the relationship between viral expression levels or viral genes and immune responses induced by SIV

  7. Memory T-cell immune response in healthy young adults vaccinated with live attenuated influenza A (H5N2) vaccine.

    Science.gov (United States)

    Chirkova, T V; Naykhin, A N; Petukhova, G D; Korenkov, D A; Donina, S A; Mironov, A N; Rudenko, L G

    2011-10-01

    Cellular immune responses of both CD4 and CD8 memory/effector T cells were evaluated in healthy young adults who received two doses of live attenuated influenza A (H5N2) vaccine. The vaccine was developed by reassortment of nonpathogenic avian A/Duck/Potsdam/1402-6/68 (H5N2) and cold-adapted A/Leningrad/134/17/57 (H2N2) viruses. T-cell responses were measured by standard methods of intracellular cytokine staining of gamma interferon (IFN-γ)-producing cells and a novel T-cell recognition of antigen-presenting cells by protein capture (TRAP) assay based on the trogocytosis phenomenon, namely, plasma membrane exchange between interacting immune cells. TRAP enables the detection of activated trogocytosis-positive T cells after virus stimulation. We showed that two doses of live attenuated influenza A (H5N2) vaccine promoted both CD4 and CD8 T-memory-cell responses in peripheral blood of healthy young subjects in the clinical study. Significant differences in geometric mean titers (GMTs) of influenza A (H5N2)-specific IFN-γ(+) cells were observed at day 42 following the second vaccination, while peak levels of trogocytosis(+) T cells were detected earlier, on the 21st day after the second vaccination. The inverse correlation of baseline levels compared to postvaccine fold changes in GMTs of influenza-specific CD4 and CD8 T cells demonstrated that baseline levels of these specific cells could be considered a predictive factor of vaccine immunogenicity.

  8. Clinical protection against caprine herpesvirus 1 genital infection by intranasal administration of a live attenuated glycoprotein E negative bovine herpesvirus 1 vaccine

    Directory of Open Access Journals (Sweden)

    Meurens François

    2007-12-01

    Full Text Available Abstract Background Caprine herpesvirus 1 (CpHV-1 is responsible of systemic diseases in kids and genital diseases leading to abortions in goats. CpHV-1 is widespread and especially in Mediterranean countries as Greece, Italy and Spain. CpHV-1 is antigenically and genetically closely related to bovine herpesvirus 1 (BoHV-1. Taking into account the biological properties shared by these two viruses, we decided in the current study to assess the protection of a live attenuated glycoprotein E (gE negative BoHV-1 vaccine against a genital CpHV-1 infection in goats. Results The vaccine was inoculated intranasally twice three weeks apart followed by a subsequent CpHV-1 intravaginal challenge which is the natural route of infection in three goats. To analyse the safety and the efficacy of this marker vaccine, two groups of three goats served as controls: one immunised with a virulent CpHV-1 and one uninoculated until the challenge. Goats were clinically monitored and all sampling procedures were carried out in a blind manner. The vaccine did not induce any undesirable local or systemic reaction and goats did not excrete gE-negative BoHV-1. After challenge, a significant reduction in disease severity was observed in immunised goats. Moreover, goats immunised with either gE-negative BoHV-1 or CpHV-1 exhibited a significant reduction in the length and the peak of viral excretion. Antibodies neutralising both BoHV-1 and CpHV-1 were raised in immunised goats. Conclusion Intranasal application of a live attenuated gE-negative BoHV-1 vaccine is able to afford a clinical protection and a reduction of virus excretion in goats challenged by a CpHV-1 genital infection.

  9. Effects of mud sedimentation on lugworm ecosystem engineering

    NARCIS (Netherlands)

    Montserrat, F.; Suykerbuyk, W.; Al-Busaidi, R.; Bouma, T.J.; Van der Wal, D.; Herman, P.M.J.

    2011-01-01

    Benthic ecosystem engineering organisms attenuate hydrodynamic or biogeochemical stress to ameliorate living conditions. Bioturbating infauna, like the lugworm Arenicola marina, determine intertidal process dynamics by maintaining the sediment oxygenated and sandy. Maintaining the permeability of

  10. CD8 Knockout Mice Are Protected from Challenge by Vaccination with WR201, a Live Attenuated Mutant of Brucella melitensis

    Directory of Open Access Journals (Sweden)

    Samuel L. Yingst

    2013-01-01

    Full Text Available CD8+ T cells have been reported to play an important role in defense against B. abortus infection in mouse models. In the present report, we use CD8 knockout mice to further elucidate the role of these cells in protection from B. melitensis infection. Mice were immunized orally by administration of B. melitensis WR201, a purine auxotrophic attenuated vaccine strain, then challenged intranasally with B. melitensis 16M. In some experiments, persistence of WR201 in the spleens of CD8 knockout mice was slightly longer than that in the spleens of normal mice. However, development of anti-LPS serum antibody, antigen-induced production of γ-interferon (IFN-γ by immune splenic lymphocytes, protection against intranasal challenge, and recovery of nonimmunized animals from intranasal challenge were similar between normal and knockout animals. Further, primary Brucella infection was not exacerbated in perforin knockout and Fas-deficient mice and these animals’ anti-Brucella immune responses were indistinguishable from those of normal mice. These results indicate that CD8+ T cells do not play an essential role as either cytotoxic cells or IFN-γ producers, yet they do participate in a specific immune response to immunization and challenge in this murine model of B. melitensis infection.

  11. Engineering Hyporheic Zones to Attenuate Heavy Metals in Constructed Urban Streams: Performance Data from Constructed Stream Flumes

    Science.gov (United States)

    Halpin, B. N.; Portmann, A. C.; Herzog, S.; Higgins, C.; McCray, J. E.

    2017-12-01

    Urban stormwater runoff is a major cause of water quality impairment along ocean shorelines and in rivers, lakes and estuaries across the United States. In addition to pathogens, nutrients, and organic contaminants, a variety of heavy metals are commonly found at elevated concentrations in urban runoff. Although such metals occur in both dissolved and particulate-bound phases, conventional stormwater controls are typically designed to remove suspended solids, while dissolved phase contaminants remain largely untreated. To address this gap in available stormwater controls, a novel technology, termed Biohydrochemical Enhancements for Streamwater Treatment (BEST), has been developed based on inspiration from the natural hyporheic zone (HZ). BEST utilizes a series of alternating streambed permeabilities to drive efficient surface water-HZ exchange. This is combined with reactive and/or sorptive streambed geomedia designed to remove dissolved phase contaminants from constructed urban drainage channels. Previous research at the Colorado School of Mines has shown that a 15-meter flume modified with BEST exhibits greater hyporheic exchange than an all-sand control flume, though both flumes provided greater contaminant attenuation than a selection of actual urban streams. This study again utilized the 15-meter flumes at Colorado School of Mines to evaluate two configurations of BEST for removal of heavy metals commonly found in stormwater runoff, including cadmium, copper, nickel, lead and zinc. In both BEST configurations, the geomedia consisted of a 30/70 (v/v) mix of woodchips and sand, with one configuration using coarse sand (K=0.48 cm/s) and the other using finer sand (K=0.16 cm/s). Both configurations were compared to an all-sand control. To evaluate metals removal, a suite of aqueous metals solution was spiked into each flume, and aqueous concentrations of the five metals of interest were monitored in both the surface and pore water over 24 hours. Differences in

  12. Exploration of the lived experiences of undergraduate science, technology, engineering, and mathematics minority students

    Science.gov (United States)

    Snead-McDaniel, Kimberly

    An expanding ethnicity gap exists in the number of students pursuing science, technology, engineering, and mathematics (STEM) careers in the United States. The National Action Council for Minorities in Engineering revealed that the number of minorities pursuing STEM degrees and careers has declined over the past few years. The specific origins of this trend are not quite evident; one variable to consider is that undergraduate minority students are failing in STEM disciplines at various levels of education from elementary to postsecondary. The failure of female and minority students to enter STEM disciplines in higher education have led various initiatives to establish programs to promote STEM disciplines among these groups. Additional funding for minority STEM programs have led to a increase in undergraduate minority students entering STEM disciplines, but the minority students' graduation rate in STEM disciplines is approximately 7% lower than the graduation of nonminority students in STEM disciplines. This phenomenological qualitative research study explores the lived experiences of underrepresented minority undergraduate college students participating in an undergraduate minority-mentoring program. The following nine themes emerged from the study: (a) competitiveness, (b) public perception, (c) dedication, (d) self-perception, (e) program activities, (f) time management, (g) exposure to career and graduate opportunities, (h) rigor in the curriculum, and (i) peer mentoring. The themes provided answers and outcomes to better support a stronger minority representation in STEM disciplines.

  13. Directed Evolution to Engineer Monobody for FRET Biosensor Assembly and Imaging at Live-Cell Surface.

    Science.gov (United States)

    Limsakul, Praopim; Peng, Qin; Wu, Yiqian; Allen, Molly E; Liang, Jing; Remacle, Albert G; Lopez, Tyler; Ge, Xin; Kay, Brian K; Zhao, Huimin; Strongin, Alex Y; Yang, Xiang-Lei; Lu, Shaoying; Wang, Yingxiao

    2018-04-19

    Monitoring enzymatic activities at the cell surface is challenging due to the poor efficiency of transport and membrane integration of fluorescence resonance energy transfer (FRET)-based biosensors. Therefore, we developed a hybrid biosensor with separate donor and acceptor that assemble in situ. The directed evolution and sequence-function analysis technologies were integrated to engineer a monobody variant (PEbody) that binds to R-phycoerythrin (R-PE) dye. PEbody was used for visualizing the dynamic formation/separation of intercellular junctions. We further fused PEbody with the enhanced CFP and an enzyme-specific peptide at the extracellular surface to create a hybrid FRET biosensor upon R-PE capture for monitoring membrane-type-1 matrix metalloproteinase (MT1-MMP) activities. This biosensor revealed asymmetric distribution of MT1-MMP activities, which were high and low at loose and stable cell-cell contacts, respectively. Therefore, directed evolution and rational design are promising tools to engineer molecular binders and hybrid FRET biosensors for monitoring molecular regulations at the surface of living cells. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. Tissue engineering by self-assembly and bio-printing of living cells

    Energy Technology Data Exchange (ETDEWEB)

    Jakab, Karoly; Marga, Francoise; Forgacs, Gabor [Department of Physics and Astronomy, University of Missouri, Columbia, MO 65211 (United States); Norotte, Cyrille [Department of Biology, University of Missouri, Columbia, MO 65211 (United States); Murphy, Keith [Organovo, Inc., 5871 Oberlin Drive, San Diego, CA 92121 (United States); Vunjak-Novakovic, Gordana, E-mail: forgacsg@missouri.ed [Department of Biomedical Engineering, Columbia University, New York, NY 10032 (United States)

    2010-06-15

    Biofabrication of living structures with desired topology and functionality requires the interdisciplinary effort of practitioners of the physical, life and engineering sciences. Such efforts are being undertaken in many laboratories around the world. Numerous approaches are pursued, such as those based on the use of natural or artificial scaffolds, decellularized cadaveric extracellular matrices and, most lately, bioprinting. To be successful in this endeavor, it is crucial to provide in vitro micro-environmental clues for the cells resembling those in the organism. Therefore, scaffolds, populated with differentiated cells or stem cells, of increasing complexity and sophistication are being fabricated. However, no matter how sophisticated scaffolds are, they can cause problems stemming from their degradation, eliciting immunogenic reactions and other a priori unforeseen complications. It is also being realized that ultimately the best approach might be to rely on the self-assembly and self-organizing properties of cells and tissues and the innate regenerative capability of the organism itself, not just simply prepare tissue and organ structures in vitro followed by their implantation. Here we briefly review the different strategies for the fabrication of three-dimensional biological structures, in particular bioprinting. We detail a fully biological, scaffoldless, print-based engineering approach that uses self-assembling multicellular units as bio-ink particles and employs early developmental morphogenetic principles, such as cell sorting and tissue fusion. (topical review)

  15. Tissue engineering by self-assembly and bio-printing of living cells

    International Nuclear Information System (INIS)

    Jakab, Karoly; Marga, Francoise; Forgacs, Gabor; Norotte, Cyrille; Murphy, Keith; Vunjak-Novakovic, Gordana

    2010-01-01

    Biofabrication of living structures with desired topology and functionality requires the interdisciplinary effort of practitioners of the physical, life and engineering sciences. Such efforts are being undertaken in many laboratories around the world. Numerous approaches are pursued, such as those based on the use of natural or artificial scaffolds, decellularized cadaveric extracellular matrices and, most lately, bioprinting. To be successful in this endeavor, it is crucial to provide in vitro micro-environmental clues for the cells resembling those in the organism. Therefore, scaffolds, populated with differentiated cells or stem cells, of increasing complexity and sophistication are being fabricated. However, no matter how sophisticated scaffolds are, they can cause problems stemming from their degradation, eliciting immunogenic reactions and other a priori unforeseen complications. It is also being realized that ultimately the best approach might be to rely on the self-assembly and self-organizing properties of cells and tissues and the innate regenerative capability of the organism itself, not just simply prepare tissue and organ structures in vitro followed by their implantation. Here we briefly review the different strategies for the fabrication of three-dimensional biological structures, in particular bioprinting. We detail a fully biological, scaffoldless, print-based engineering approach that uses self-assembling multicellular units as bio-ink particles and employs early developmental morphogenetic principles, such as cell sorting and tissue fusion. (topical review)

  16. Exploring Host-Microbiome Interactions using an in Silico Model of Biomimetic Robots and Engineered Living Cells

    OpenAIRE

    Keith C. Heyde; Warren C. Ruder

    2015-01-01

    The microbiome?s underlying dynamics play an important role in regulating the behavior and health of its host. In order to explore the details of these interactions, we created an in silico model of a living microbiome, engineered with synthetic biology, that interfaces with a biomimetic, robotic host. By analytically modeling and computationally simulating engineered gene networks in these commensal communities, we reproduced complex behaviors in the host. We observed that robot movements de...

  17. A live-attenuated and an inactivated chimeric porcine circovirus (PCV)1-2 vaccine are both effective at inducing a humoral immune response and reducing PCV2 viremia and intrauterine infection in female swine of breeding age.

    Science.gov (United States)

    Hemann, Michelle; Beach, Nathan M; Meng, Xiang-Jin; Wang, Chong; Halbur, Patrick G; Opriessnig, Tanja

    2014-01-01

    The objective of this pilot study was to determine the efficacy of inactivated (1 or 2 dose) and live-attenuated chimeric porcine circovirus (PCV)1-2 vaccines in sows using the PCV2-spiked semen model. Thirty-five sows were randomly divided into 6 groups: negative and positive controls, 1 dose inactivated PCV1-2 vaccine challenged (1-VAC-PCV2), 2 dose inactivated PCV1-2 vaccine challenged (2-VAC-PCV2), 1 dose live-attenuated PCV1-2 vaccine unchallenged (1-LIVE-VAC), and 1 dose live-attenuated PCV1-2 vaccine challenged (1-LIVE-VAC-PCV2). The inactivated PCV1-2 vaccine induced higher levels of PCV2-specific antibodies in dams. All vaccination strategies provided good protection against PCV2 viremia in dams, whereas the majority of the unvaccinated sows were viremic. Four of the 35 dams became pregnant: a negative control, a positive control, a 2-VAC-PCV2 sow, and a 1-LIVE-VAC-PCV2 sow. The PCV2 DNA was detected in 100%, 67%, and 29% of the fetuses obtained from the positive control, inactivated vaccinated, or live-attenuated vaccinated dams, respectively. The PCV2 antigen in hearts was only detectable in the positive control litter (23% of the fetuses). The PCV1-2 DNA was detected in 29% of the fetuses in the litter from the 1-LIVE-VAC-PCV2 dam. Under the conditions of this pilot study, both vaccines protected against PCV2 viremia in breeding age animals; however, vertical transmission was not prevented.

  18. Two studies evaluating the safety and immunogenicity of a live, attenuated Shigella flexneri 2a vaccine (SC602) and excretion of vaccine organisms in North American volunteers.

    Science.gov (United States)

    Katz, David E; Coster, Trinka S; Wolf, Marcia K; Trespalacios, Fernando C; Cohen, Dani; Robins, Guy; Hartman, Antoinette B; Venkatesan, Malabi M; Taylor, David N; Hale, Thomas L

    2004-02-01

    We report the first community-based evaluation of Shigella flexneri 2a strain SC602, a live, oral vaccine strain attenuated by deletion of the icsA (virG) plasmid virulence gene, given at 10(4) CFU. The primary objectives of this trial were to determine the safety and immunogenicity of the vaccine and to determine the duration of colonization. Four of 34 volunteers experienced transient fevers, and three reported diarrhea during the first 3 days of the study. Half of the volunteers mounted a positive serum immunoglobulin A (IgA) response to S. flexneri lipopolysaccharide. All but one of the volunteers excreted the vaccine in their stools for 1 to 33 days, and this excretion was often intermittent. Data from the community-based study were supplemented with an inpatient trial in which three volunteers received 10(3) and nine received 10(4) CFU. All volunteers who received 10(3) CFU excreted SC602 and had an IgA antibody-secreting cell response. Two of these had a serum IgA response. Six of the nine volunteers who received 10(4) CFU excreted SC602. One vaccinee had a transient fever and two met the definition of diarrhea. Six volunteers that received 10(4) CFU had an antibody-secreting cell response, and four had a serum IgA response. SC602 has now been tested at 10(4) CFU in a total of 58 volunteers. The cumulative results of these clinical trials, reported here and previously (Coster et al., Infect. Immun. 67:3437-3443, 1999), have demonstrated that SC602 is a substantially attenuated candidate vaccine that can evoke protection against the most severe symptoms of shigellosis in a stringent human challenge model of disease.

  19. Mucosal immunization with live attenuated Francisella novicida U112ΔiglB protects against pulmonary F. tularensis SCHU S4 in the Fischer 344 rat model.

    Directory of Open Access Journals (Sweden)

    Aimee L Signarovitz

    Full Text Available The need for an efficacious vaccine against Francisella tularensis is a consequence of its low infectious dose and high mortality rate if left untreated. This study sought to characterize a live attenuated subspecies novicida-based vaccine strain (U112ΔiglB in an established second rodent model of pulmonary tularemia, namely the Fischer 344 rat using two distinct routes of vaccination (intratracheal [i.t.] and oral. Attenuation was verified by comparing replication of U112ΔiglB with wild type parental strain U112 in F344 primary alveolar macrophages. U112ΔiglB exhibited an LD(50>10(7 CFU compared to the wild type (LD(50 = 5 × 10(6 CFU i.t.. Immunization with 10(7 CFU U112ΔiglB by i.t. and oral routes induced antigen-specific IFN-γ and potent humoral responses both systemically (IgG2a>IgG1 in serum and at the site of mucosal vaccination (respiratory/intestinal compartment. Importantly, vaccination with U112ΔiglB by either i.t. or oral routes provided equivalent levels of protection (50% survival in F344 rats against a subsequent pulmonary challenge with ~25 LD(50 (1.25 × 10(4 CFU of the highly human virulent strain SCHU S4. Collectively, these results provide further evidence on the utility of a mucosal vaccination platform with a defined subsp. novicida U112ΔiglB vaccine strain in conferring protective immunity against pulmonary tularemia.

  20. Efficacy of Live-Attenuated H9N2 Influenza Vaccine Candidates Containing NS1 Truncations against H9N2 Avian Influenza Viruses

    Directory of Open Access Journals (Sweden)

    Sujuan Chen

    2017-06-01

    Full Text Available H9N2 avian influenza virus is a zoonotic agent with a broad host range that can contribute genetic information to H5 or H7N9 subtype viruses, which are significant threats to both humans and birds. Thus, there is a great need for a vaccine to control H9N2 avian influenza. Three mutant viruses of an H9N2 virus A/chicken/Taixing/10/2010 (rTX-NS1-73, rTX-NS1-100, and rTX-NS1-128 were constructed with different NS1 gene truncations and confirmed by western blot analysis. The genetic stability, pathogenicity, transmissibility, and host immune responses toward these mutants were evaluated. The mutant virus rTX-NS1-128 exhibited the most attenuated phenotype and lost transmissibility. The expression levels of interleukin 12 in the nasal and tracheal tissues from chickens immunized with rTX-NS1-128 were significantly upregulated on day 3 post-immunization and the IgA and IgG antibody levels were significantly increased on days 7, 14, and 21 post-immunization when compared to chickens that received an inactivated vaccine. rTX-NS1-128 also protected chickens from challenge by homologous and heterologous H9N2 avian influenza viruses. The results indicate that rTX-NS1-128 can be used as a potential live-attenuated vaccine against H9N2 avian influenza.

  1. An attempt to model the relationship between MMI attenuation and engineering ground-motion parameters using artificial neural networks and genetic algorithms

    Directory of Open Access Journals (Sweden)

    G-A. Tselentis

    2010-12-01

    Full Text Available Complex application domains involve difficult pattern classification problems. This paper introduces a model of MMI attenuation and its dependence on engineering ground motion parameters based on artificial neural networks (ANNs and genetic algorithms (GAs. The ultimate goal of this investigation is to evaluate the target-region applicability of ground-motion attenuation relations developed for a host region based on training an ANN using the seismic patterns of the host region. This ANN learning is based on supervised learning using existing data from past earthquakes. The combination of these two learning procedures (that is, GA and ANN allows us to introduce a new method for pattern recognition in the context of seismological applications. The performance of this new GA-ANN regression method has been evaluated using a Greek seismological database with satisfactory results.

  2. The live attenuated chimeric vaccine rWN/DEN4Δ30 is well-tolerated and immunogenic in healthy flavivirus-naïve adult volunteers.

    Science.gov (United States)

    Durbin, Anna P; Wright, Peter F; Cox, Amber; Kagucia, Wangeci; Elwood, Daniel; Henderson, Susan; Wanionek, Kimberli; Speicher, Jim; Whitehead, Stephen S; Pletnev, Alexander G

    2013-11-19

    WNV has become the leading vector-borne cause of meningoencephalitis in the United States. Although the majority of WNV infections result in asymptomatic illness, approximately 20% of infections result in West Nile fever and 1% in West Nile neuroinvasive disease (WNND), which causes encephalitis, meningitis, or flaccid paralysis. The elderly are at particular risk for WNND, with more than half the cases occurring in persons older than sixty years of age. There is no licensed treatment for WNND, nor is there any licensed vaccine for humans for the prevention of WNV infection. The Laboratory of Infectious Diseases at the National Institutes of Health has developed a recombinant live attenuated WNV vaccine based on chimerization of the wild-type WNV NY99 genome with that of the live attenuated DENV-4 candidate vaccine rDEN4Δ30. The genes encoding the prM and envelope proteins of DENV-4 were replaced with those of WNV NY99 and the resultant virus was designated rWN/DEN4Δ30. The vaccine was evaluated in healthy flavivirus-naïve adult volunteers age 18-50 years in two separate studies, both of which are reported here. The first study evaluated 10³ or 10⁴ PFU of the vaccine given as a single dose; the second study evaluated 10⁵ PFU of the vaccine given as two doses 6 months apart. The vaccine was well-tolerated and immunogenic at all three doses, inducing seroconversion to WNV NY99 in 74% (10³ PFU), 75% (10⁴ PFU), and 55% (10⁵ PFU) of subjects after a single dose. A second 10⁵ PFU dose of rWN/DEN4Δ30 given 6 months after the first dose increased the seroconversion rate 89%. Based on the encouraging results from these studies, further evaluation of the candidate vaccine in adults older than 50 years of age is planned. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Construction of a Streptococcus agalactiae phoB mutant and evaluation of its potential as an attenuated modified live vaccine in golden pompano, Trachinotus ovatus.

    Science.gov (United States)

    Cai, Xiaohui; Wang, Bei; Peng, Yinhui; Li, Yuan; Lu, Yishan; Huang, Yucong; Jian, Jichang; Wu, Zaohe

    2017-04-01

    Streptococcus agalactiae is a Gram-positive pathogen that can survive inside professional phagocytes and nonphagocytic cells to cause septicemia and meningoencephalitis in freshwater and marine fish. However, vaccines based on extracellular products (ECP) and formalin-killed whole S. agalactiae cells, as well as subunit vaccine are unable to protect fish from infection by variant serotypes S. agalactiae. The search for live attenuated vaccine with highly conserved and virulent-related genes is essential for producing a vaccine to help understand and control streptococcosis In this study, the phoB gene was cloned from pathogenic S. agalactiae TOS01 strain and the mutant strain SAΔphoB was constructed via allelic exchange mutagenesis. The results showed that the deduced amino acid of S. agalactiae TOS01 shares high similarities with other Streptococcus spp. and has high conserved response regulator receiver domain (REC) and DNA-binding effector domain of two-component system response regulators (Trans_reg_C). Cell adherence and invasion assays, challenge experiments and histopathological changes post-vaccination were performed and observed, the results showed that the mutant strain SAΔphoB has a lower adherence and invasion rate and less virulent than the wild type strain in golden pompano, and it doesn't induce clinical symptoms and obvious pathological changes in golden pompano, thereby indicating that the deletion of phoB affects the virulence and infectious capacity of S. agalactiae. Golden pompano vaccinated via intraperitoneal injection SAΔphoB had the relative percent survival value of 93.1% after challenge with TOS01, demonstrating its high potential as an effective attenuated live vaccine candidate. Real-time PCR assays showed that the SAΔphoB was able to enhance the expression of immune-related genes, including MHC-I, MyD88, IL-22 and IL-10 after vaccination, indicating that the SAΔphoB is able to induce humoral and cell-mediated immune response

  4. Living in a Materials World: Materials Science Engineering Professional Development for K-12 Educators

    Energy Technology Data Exchange (ETDEWEB)

    Anne Seifert; Louis Nadelson

    2011-06-01

    Advances in materials science are fundamental to technological developments and have broad societal impacs. For example, a cellular phone is composed of a polymer case, liquid crystal displays, LEDs, silicon chips, Ni-Cd batteries, resistors, capacitors, speakers, microphones all of which have required advances in materials science to be compacted into a phone which is typically smaller than a deck of cards. Like many technological developments, cellular phones have become a ubiquitous part of society, and yet most people know little about the materials science associated with their manufacture. The probable condition of constrained knowledge of materials science was the motivation for developing and offering a 20 hour fourday course called 'Living in a Materials World.' In addition, materials science provides a connection between our every day experiences and the work of scientists and engineers. The course was offered as part of a larger K-12 teacher professional development project and was a component of a week-long summer institute designed specifically for upper elementary and middle school teachers which included 20 hour content strands, and 12 hours of plenary sessions, planning, and collaborative sharing. The focus of the institute was on enhancing teacher content knowledge in STEM, their capacity for teaching using inquiry, their comfort and positive attitudes toward teaching STEM, their knowledge of how people learn, and strategies for integrating STEM throughout the curriculum. In addition to the summer institute the participating teachers were provided with a kit of about $300 worth of materials and equipment to use to implement the content they learned in their classrooms. As part of this professional development project the participants were required to design and implement 5 lesson plans with their students this fall and report on the results, as part of the continuing education course associated with the project. 'Living in a

  5. Peru-15 (Choleragarde(®)), a live attenuated oral cholera vaccine, is safe and immunogenic in human immunodeficiency virus (HIV)-seropositive adults in Thailand.

    Science.gov (United States)

    Ratanasuwan, W; Kim, Y H; Sah, B K; Suwanagool, S; Kim, D R; Anekthananon, A; Lopez, A L; Techasathit, W; Grahek, S L; Clemens, J D; Wierzba, T F

    2015-09-11

    Many areas with endemic and epidemic cholera report significant levels of HIV transmission. According to the World Health Organization (WHO), over 95% of reported cholera cases occur in Africa, which also accounts for nearly 70% of people living with HIV/AIDS globally. Peru-15, a promising single dose live attenuated oral cholera vaccine (LA-OCV), was previously found to be safe and immunogenic in cholera endemic areas. However, no data on the vaccine's safety among HIV-seropositive adults had been collected. This study was a double-blinded, individually randomized, placebo-controlled trial enrolling HIV-seropositive adults, 18-45 years of age, conducted in Bangkok, Thailand, to assess the safety of Peru-15 in a HIV-seropositive cohort. 32 HIV infected subjects were randomized to receive either a single oral dose of the Peru-15 vaccine with a buffer or a placebo (buffer only). No serious adverse events were reported during the follow-up period in either group. The geometric mean fold (GMF) rise in V. cholerae O1 El Tor specific antibody titers between baseline and 7 days after dosing was 32.0 (pcholerae was isolated from the stool of one vaccinee, and found to be genetically identical to the Peru-15 vaccine strain. There were no significant changes in HIV viral load or CD4 T-cell counts between vaccine and placebo groups. Peru-15 was shown to be safe and immunogenic in HIV-seropositive Thai adults. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Enrollment in YFV Vaccine Trial: An Evaluation of Recruitment Outcomes Associated with a Randomized Controlled Double-Blind Trial of a Live Attenuated Yellow Fever Vaccine.

    Science.gov (United States)

    Frew, Paula M; Shapiro, Eve T; Lu, Lu; Edupuganti, Srilatha; Keyserling, Harry L; Mulligan, Mark J

    2013-04-15

    This investigation evaluated several factors associated with diverse participant enrollment of a clinical trial assessing safety, immunogenicity, and comparative viremia associated with administration of 17-D live, attenuated yellow fever vaccine given alone or in combination with human immune globulin. We obtained baseline participant information (e.g., sociodemographic, medical) and followed recruitment outcomes from 2005 to 2007. Of 355 potential Yellow Fever vaccine study participants, 231 cases were analyzed. Strong interest in study participation was observed among racial and ethnically diverse persons with 36.34% eligible following initial study screening, resulting in 18.75% enrollment. The percentage of white participants increased from 63.66% (prescreened sample) to 81.25% (enrollment group). The regression model was significant with white race as a predictor of enrollment (OR=2.744, 95% CI=1.415-5.320, p=0.003).In addition, persons were more likely to enroll via direct outreach and referral mechanisms compared to mass advertising (OR=2.433, 95% CI=1.102-5.369). The findings indicate that racially diverse populations can be recruited to vaccine clinical trials, yet actual enrollment may not reflect that diversity.

  7. Interferon alpha inhibits replication of a live-attenuated porcine reproductive and respiratory syndrome virus vaccine preventing development of an adaptive immune response in swine.

    Science.gov (United States)

    Brockmeier, Susan L; Loving, Crystal L; Eberle, Kirsten C; Hau, Samantha J; Buckley, Alexandra; Van Geelen, Albert; Montiel, Nestor A; Nicholson, Tracy; Lager, Kelly M

    2017-12-01

    Type I interferons, such as interferon alpha (IFN-α), contribute to innate antiviral immunity by promoting production of antiviral mediators and are also involved in promoting an adaptive immune response. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most devastating and costly viruses to the swine industry world-wide and has been shown to induce a meager IFN-α response. Previously we administered porcine IFN-α using a replication-defective adenovirus vector (Ad5-IFN-α) at the time of challenge with virulent PRRSV and demonstrated an increase in the number of virus-specific IFNγ secreting cells, indicating that the presence of IFN-α at the time of infection can alter the adaptive immune responses to PRRSV. In the current experiment, we explored the use of IFN-α as an adjuvant administered with live-attenuated PRRSV vaccine as a method to enhance immune response to the vaccine. Unlike the previous studies with fully virulent virus, one injection of the Ad5-IFN-α abolished replication of the vaccine virus and as a result there was no detectible adaptive immune response. Although IFN-α did not have the desired adjuvant effect, the results further highlight the use of IFN-α as a treatment for PRRSV infection. Published by Elsevier B.V.

  8. Effectiveness of Japanese encephalitis SA 14-14-2 live attenuated vaccine among Indian children: Retrospective 1:4 matched case-control study.

    Science.gov (United States)

    Tandale, Babasaheb V; Khan, Siraj A; Kushwaha, Komal P; Rahman, Helina; Gore, Milind M

    2018-04-24

    We estimate the effectiveness of Japanese encephalitis (JE) SA 14-14-2 live-attenuated vaccination single dose campaign among children aged 1-15 years in India during 2006-07. Acute encephalitis syndrome (AES) cases hospitalized following vaccination campaigns during the years 2006-08 were investigated retrospectively. The laboratory-confirmed JE cases were detected from the surveillance laboratories based on anti-JE IgM antibody by ELISA or viral RNA detection by RT-PCR in sera or cerebrospinal fluid. Consent was sought from parents or guardians. Four community controls were chosen randomly per case during house-to-house survey employing individual matching on age, gender and residence during the risk period. Vaccination history was enquired from the child's guardian and verified from vaccination card at home or records at health centre. Conditional logistic regression was conducted on matched case-control sets. We studied 149 cases and matched 596 controls. Vaccination effectiveness was 43.8% (95% CI, 1.9-67.8) based on vaccination card or record. However, effectiveness was 72.2% (95% CI, 56.2-82.4) based on parental history or card/record. Vaccination effectiveness in Assam state was higher than in Uttar Pradesh state. We concluded that the single subcutaneous dose of SA 14-14-2 JE vaccine provided moderate effectiveness in Indian children. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Development of Automatic Live Linux Rebuilding System with Flexibility in Science and Engineering Education and Applying to Information Processing Education

    Science.gov (United States)

    Sonoda, Jun; Yamaki, Kota

    We develop an automatic Live Linux rebuilding system for science and engineering education, such as information processing education, numerical analysis and so on. Our system is enable to easily and automatically rebuild a customized Live Linux from a ISO image of Ubuntu, which is one of the Linux distribution. Also, it is easily possible to install/uninstall packages and to enable/disable init daemons. When we rebuild a Live Linux CD using our system, we show number of the operations is 8, and the rebuilding time is about 33 minutes on CD version and about 50 minutes on DVD version. Moreover, we have applied the rebuilded Live Linux CD in a class of information processing education in our college. As the results of a questionnaires survey from our 43 students who used the Live Linux CD, we obtain that the our Live Linux is useful for about 80 percents of students. From these results, we conclude that our system is able to easily and automatically rebuild a useful Live Linux in short time.

  10. Safety and immunogenicity in man of a cell culture derived trivalent live attenuated seasonal influenza vaccine: a Phase I dose escalating study in healthy volunteers.

    Science.gov (United States)

    Heldens, Jacco; Hulskotte, Ellen; Voeten, Theo; Breedveld, Belinda; Verweij, Pierre; van Duijnhoven, Wilbert; Rudenko, Larissa; van Damme, Pierre; van den Bosch, Han

    2014-09-03

    Live attenuated influenza vaccine (LAIV) offers the promise of inducing a variety of immune responses thereby conferring protection to circulating field strains. LAIVs are based on cold adapted and temperature sensitive phenotypes of master donor viruses (MDVs) containing the surface glycoprotein genes of seasonal influenza strains. Two types of MDV lineages have been described, the Ann Arbor lineages and the A/Leningrad/17 and B/USSR/60 lineages. Here the safety and immunogenicity of a Madin Darby Canine Kidney - cell culture based, intranasal LAIV derived from A/Leningrad/17 and B/USSR, was evaluated in healthy influenza non-naive volunteers 18-50 years of age. In a double-blind, randomized, placebo-controlled design, single escalating doses of 1×10(5), 1×10(6), or 1×10(7) tissue culture infectious dose 50% (TCID50) of vaccine containing each of the three influenza virus re-assortants recommended by the World Health Organization for the 2008-2009 season were administered intranasally. A statistically significant geometric mean increase in hemagglutination inhibition titer was reached for influenza strain A/H3N2 after immunization with all doses of LAIV. For the A/H1N1 and B strains, the GMI in HI titer did not increase for any of the doses. Virus neutralization antibody titers showed a similar response pattern. A dose-response effect could not be demonstrated for any of the strains, neither for the HI antibody nor for the VN antibody responses. No influenza like symptoms, no nasal congestions, no rhinorrhea, or other influenza related upper respiratory tract symptoms were observed. In addition, no difference in the incidence or nature of adverse events was found between vaccine and placebo treated subjects. Overall, the results indicated that the LAIV for nasal administration is immunogenic (i.e. able to provoke an immune response) and safe both from the perspective of the attenuated virus and the MDCK cell line from which it was derived, and it warrants

  11. Lipopolysaccharide-specific memory B cell responses to an attenuated live cholera vaccine are associated with protection against Vibrio cholerae infection.

    Science.gov (United States)

    Haney, Douglas J; Lock, Michael D; Gurwith, Marc; Simon, Jakub K; Ishioka, Glenn; Cohen, Mitchell B; Kirkpatrick, Beth D; Lyon, Caroline E; Chen, Wilbur H; Sztein, Marcelo B; Levine, Myron M; Harris, Jason B

    2018-05-11

    The single-dose live attenuated vaccine CVD 103-HgR protects against experimental Vibrio cholerae infection in cholera-naïve adults for at least 6 months after vaccination. While vaccine-induced vibriocidal seroconversion is associated with protection, vibriocidal titers decline rapidly from their peak 1-2 weeks after vaccination. Although vaccine-induced memory B cells (MBCs) might mediate sustained protection in individuals without detectable circulating antibodies, it is unknown whether oral cholera vaccination induces a MBC response. In a study that enrolled North American adults, we measured lipopolysaccharide (LPS)- and cholera toxin (CtxB)-specific MBC responses to PXVX0200 (derived from the CVD 103-HgR strain) and assessed stool volumes following experimental Vibrio cholerae infection. We then evaluated the association between vaccine-induced MBC responses and protection against cholera. There was a significant increase in % CT-specific IgG, % LPS-specific IgG, and % LPS-specific IgA MBCs which persisted 180 days after vaccination as well as a significant association between vaccine-induced increase in % LPS-specific IgA MBCs and lower post-challenge stool volume (r = -0.56, p < 0.001). Oral cholera vaccination induces antigen-specific MBC responses, and the anamnestic LPS-specific responses may contribute to long-term protection and provide correlates of the duration of vaccine-induced protection. NCT01895855. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  12. A single dose of live-attenuated 638 Vibrio cholerae oral vaccine is safe and immunogenic in adult volunteers in Mozambique

    Directory of Open Access Journals (Sweden)

    Hilda María García

    2011-12-01

    Full Text Available A placebo-controlled randomized, double-blind, clinical trial was carried out to assess the safety, reactogenicity, and immunogenicity of the lyophilized vaccine candidate against cholera derived from the live attenuated 638 Vibrio cholerae O1 El Tor Ogawa strain. One hundred and twenty presumably healthy female and male adult volunteers aged between 18 and 50 years were included. They were from Maputo, Mozambique a cholera endemic area, where, in addition, human immunodeficiency virus (HIV seroprevalence is from 20 to 30%. A dose of 2 x 10 9 colony forming units (CFU was given to 80 subjects and other 40 received only vaccine lyoprotectors as a placebo control. Out-patient follow-up of adverse events was carried out during the following 30 days after vaccination. The immune response was evaluated by the estimation of seroconversion rate and the geometric mean titer (GMT of vibriocidal antibodies in the sera from volunteers that was collected previously, and at days 14 and 21 after immunization. No serious adverse events were reported. The adverse events found in the vaccine group were similar to those of the placebo groups. They were independent from the detection of antibodies against HIV-1, HIV-2, hepatitis (H A; HC and hepatitis B surface antigen. The presence of helminthes did not modify the incidence of adverse events. The 638 vaccine strain was isolated in 37 (46.25% vaccinated volunteer's feces. The peak of the GMT of vibriocidal antibodies in the vaccine group was 9056 versus 39 in the placebo group at 14 days with a total seroconversion of 97.4% at 21 days. The 638 vaccine candidate is safe and immunogenic in a cholera endemic region.

  13. The oral, live attenuated enterotoxigenic Escherichia coli vaccine ACE527 reduces the incidence and severity of diarrhea in a human challenge model of diarrheal disease.

    Science.gov (United States)

    Darsley, Michael J; Chakraborty, Subhra; DeNearing, Barbara; Sack, David A; Feller, Andrea; Buchwaldt, Charlotte; Bourgeois, A Louis; Walker, Richard; Harro, Clayton D

    2012-12-01

    An oral, live attenuated, three-strain recombinant bacterial vaccine, ACE527, was demonstrated to generate strong immune responses to colonization factor and toxin antigens of enterotoxigenic Escherichia coli (ETEC) in human volunteers. The vaccine was safe and well tolerated at doses of up to 10(11) CFU, administered in each of two doses given 21 days apart. These observations have now been extended in a phase 2b study with a total of 70 subjects. Fifty-six of these subjects were challenged 28 days after the second dose of vaccine with the highly virulent ETEC strain H10407 to obtain preliminary indicators of efficacy against disease and to support further development of the vaccine for both travelers and infants in countries where ETEC is endemic. The vaccine had a significant impact on intestinal colonization by the challenge strain, as measured by quantitative fecal culture 2 days after challenge, demonstrating the induction of a functional immune response to the CFA/I antigen. The incidence and severity of diarrhea were also reduced in vaccinees as measured by a number of secondary and ad hoc endpoints, although the 27% reduction seen in the primary endpoint, moderate to severe diarrhea, was not statistically significant. Together, these observations support the hypothesis that the ACE527 vaccine has a dual mode of action, targeting both colonization factors and the heat-labile enterotoxin (LT), and suggest that it should be further developed for more advanced trials to evaluate its impact on the burden of ETEC disease in field settings.

  14. Pan-Influenza A Protection by Prime-Boost Vaccination with Cold-Adapted Live-Attenuated Influenza Vaccine in a Mouse Model.

    Science.gov (United States)

    Jang, Yo Han; Kim, Joo Young; Byun, Young Ho; Son, Ahyun; Lee, Jeong-Yoon; Lee, Yoon Jae; Chang, Jun; Seong, Baik Lin

    2018-01-01

    Influenza virus infections continually pose a major public health threat with seasonal epidemics and sporadic pandemics worldwide. While currently licensed influenza vaccines provide only strain-specific protection, antigenic drift and shift occasionally render the viruses resistant to the host immune responses, which highlight the need for a vaccine that provides broad protection against multiple subtypes. In this study, we suggest a vaccination strategy using cold-adapted, live attenuated influenza vaccines (CAIVs) to provide a broad, potent, and safe cross-protection covering antigenically distinct hemagglutinin (HA) groups 1 and 2 influenza viruses. Using a mouse model, we tested different prime-boost combinations of CAIVs for their ability to induce humoral and T-cell responses, and protective efficacy against H1 and H5 (HA group 1) as well as H3 and H7 (HA group 2) influenza viruses. Notably, even in the absence of antibody-mediated neutralizing activity or HA inhibitory activity in vitro , CAIVs provided a potent protection against heterologous and heterosubtypic lethal challenges in vivo . Heterologous combination of prime (H1)-boost (H5) vaccine strains showed the most potent cross-protection efficacy. In vivo depletion experiments demonstrated not only that T cells and natural killer cells contributed to the cross-protection, but also the involvement of antibody-dependent mechanisms for the cross-protection. Vaccination-induced antibodies did not enhance the infectivity of heterologous viruses, and prime vaccination did not interfere with neutralizing antibody generation by the boost vaccination, allaying vaccine safety concerns associated with heterogeneity between the vaccines and challenge strains. Our data show that CAIV-based strategy can serve as a simple but powerful option for developing a "truly" universal influenza vaccine providing pan-influenza A protection, which has not been achieved yet by other vaccine strategies. The promising results

  15. Pan-Influenza A Protection by Prime–Boost Vaccination with Cold-Adapted Live-Attenuated Influenza Vaccine in a Mouse Model

    Science.gov (United States)

    Jang, Yo Han; Kim, Joo Young; Byun, Young Ho; Son, Ahyun; Lee, Jeong-Yoon; Lee, Yoon Jae; Chang, Jun; Seong, Baik Lin

    2018-01-01

    Influenza virus infections continually pose a major public health threat with seasonal epidemics and sporadic pandemics worldwide. While currently licensed influenza vaccines provide only strain-specific protection, antigenic drift and shift occasionally render the viruses resistant to the host immune responses, which highlight the need for a vaccine that provides broad protection against multiple subtypes. In this study, we suggest a vaccination strategy using cold-adapted, live attenuated influenza vaccines (CAIVs) to provide a broad, potent, and safe cross-protection covering antigenically distinct hemagglutinin (HA) groups 1 and 2 influenza viruses. Using a mouse model, we tested different prime–boost combinations of CAIVs for their ability to induce humoral and T-cell responses, and protective efficacy against H1 and H5 (HA group 1) as well as H3 and H7 (HA group 2) influenza viruses. Notably, even in the absence of antibody-mediated neutralizing activity or HA inhibitory activity in vitro, CAIVs provided a potent protection against heterologous and heterosubtypic lethal challenges in vivo. Heterologous combination of prime (H1)–boost (H5) vaccine strains showed the most potent cross-protection efficacy. In vivo depletion experiments demonstrated not only that T cells and natural killer cells contributed to the cross-protection, but also the involvement of antibody-dependent mechanisms for the cross-protection. Vaccination-induced antibodies did not enhance the infectivity of heterologous viruses, and prime vaccination did not interfere with neutralizing antibody generation by the boost vaccination, allaying vaccine safety concerns associated with heterogeneity between the vaccines and challenge strains. Our data show that CAIV-based strategy can serve as a simple but powerful option for developing a “truly” universal influenza vaccine providing pan-influenza A protection, which has not been achieved yet by other vaccine strategies. The promising

  16. Immunogenicity and Safety of the HZ/su Adjuvanted Herpes Zoster Subunit Vaccine in Adults Previously Vaccinated With a Live Attenuated Herpes Zoster Vaccine.

    Science.gov (United States)

    Grupping, Katrijn; Campora, Laura; Douha, Martine; Heineman, Thomas C; Klein, Nicola P; Lal, Himal; Peterson, James; Vastiau, Ilse; Oostvogels, Lidia

    2017-12-12

    Protection against herpes zoster (HZ) induced by the live attenuated zoster vaccine Zostavax (ZVL) wanes within 3-7 years. Revaccination may renew protection. We assessed whether (re)vaccination with the adjuvanted HZ subunit vaccine candidate (HZ/su) induced comparable immune responses in previous ZVL recipients and ZVL-naive individuals (HZ-NonVac). In an open-label, multicenter study, adults ≥65 years of age, vaccinated with ZVL ≥5 years previously (HZ-PreVac), were matched to ZVL-naive adults (HZ-NonVac). Participants received 2 doses of HZ/su 2 months apart. The primary objective of noninferiority of the humoral immune response 1 month post-dose 2 was considered demonstrated if the upper limit of the 95% confidence interval (CI) of the adjusted anti-glycoprotein E geometric mean concentration (GMC) ratio of HZ-NonVac over HZ-PreVac was <1.5. HZ/su cellular immunogenicity, reactogenicity, and safety were also assessed. In 430 participants, humoral immune response to HZ/su was noninferior in HZ-PreVac compared with HZ-NonVac (adjusted GMC ratio, 1.04 [95% CI, .92-1.17]). Cellular immunogenicity, reactogenicity, and safety appeared to be comparable between groups. HZ/su was well-tolerated, with no safety concerns raised within 1 month post-dose 2. HZ/su induces a strong immune response irrespective of prior vaccination with ZVL, and may be an attractive option to revaccinate prior ZVL recipients. NCT02581410. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  17. The epidemiological impact of childhood influenza vaccination using live-attenuated influenza vaccine (LAIV) in Germany: predictions of a simulation study

    Science.gov (United States)

    2014-01-01

    Background Routine annual influenza vaccination is primarily recommended for all persons aged 60 and above and for people with underlying chronic conditions in Germany. Other countries have already adopted additional childhood influenza immunisation programmes. The objective of this study is to determine the potential epidemiological impact of implementing paediatric influenza vaccination using intranasally administered live-attenuated influenza vaccine (LAIV) in Germany. Methods A deterministic age-structured model is used to simulate the population-level impact of different vaccination strategies on the transmission dynamics of seasonal influenza in Germany. In our base-case analysis, we estimate the effects of adding a LAIV-based immunisation programme targeting children 2 to 17 years of age to the existing influenza vaccination policy. The data used in the model is based on published evidence complemented by expert opinion. Results In our model, additional vaccination of children 2 to 17 years of age with LAIV leads to the prevention of 23.9 million influenza infections and nearly 16 million symptomatic influenza cases within 10 years. This reduction in burden of disease is not restricted to children. About one third of all adult cases can indirectly be prevented by LAIV immunisation of children. Conclusions Our results demonstrate that vaccinating children 2–17 years of age is likely associated with a significant reduction in the burden of paediatric influenza. Furthermore, annual routine childhood vaccination against seasonal influenza is expected to decrease the incidence of influenza among adults and older people due to indirect effects of herd protection. In summary, our model provides data supporting the introduction of a paediatric influenza immunisation programme in Germany. PMID:24450996

  18. Homeostatic properties of Lactobacillus jensenii engineered as a live vaginal anti-HIV microbicide.

    Science.gov (United States)

    Yamamoto, Hidemi S; Xu, Qiang; Fichorova, Raina N

    2013-01-08

    Vaginal probiotics are investigated as a binary strategy for prevention of bacterial vaginosis and HIV. We applied an innovative experimental model using primary and immortalized human cervical and vaginal epithelial cells to assess the functional properties of Lactobacillus jensenii, a predominant constituent of the healthy vaginal microbiome, engineered to express the HIV-1 entry inhibitor modified cyanovirin-N (mCV-N). In this model bacteria colonize the epithelial cells over a period of 24-72 h. Staurosporine and the Toll-like receptor 2/6 ligand macrophage-activating lipopeptide-2 (MALP-2) serve as positive controls for apoptosis and proinflammatory activation, respectively. In 24-hour intervals, the colonized epithelium is assessed microscopically, supernatants are collected for measurement of soluble immunoinflammatory mediators and production of CV-N, and cells are lysed for assessment of: 1) apoptosis by cleaved versus total caspase-3 assay; 2) NF-κB activation by a luciferase reporter assay; or 3) epithelia-associated colony forming units (CFU) in Brucella agar. Wild type (WT) L. jensenii 1153 consistently colonized cervical and vaginal cells in the absence of epithelial damage and apoptosis. The bioengineered derivatives expressing mCV-N or control plasmids showed the same stable colonization pattern, which was reproducible between technologists and bacterial batches (CFU coefficient of variation <10% within and between experiments and epithelial cell types). MALP-2 activated NF-κB and caused fold-increased levels of proinflammatory mediators with clinically established significance in the cervicovaginal environment (IL-1α, IL-1β, IL-6, TNF-α, IL-8, RANTES, MIP-3α, and ICAM-1), measured by a multiplex electrochemiluminescence assay. At the same time levels of protective anti-inflammatory mediators interleukin 1 receptor antagonist (IL-1RA) and secretory leukocyte protease inhibitor (SLPI), both measured by ELISA, remained constant (IL-1RA) or

  19. A live-attenuated chimeric PCV2 vaccine based on subtype 2b is transmitted to contact pigs but is not upregulated by concurrent infection with PPV and PRRSV and is efficacious in a triple challenge co-infection model

    Science.gov (United States)

    The objective of this study was to determine the safety and efficacy of a new live-attenuated chimeric PCV1/2b vaccine. Forty-six, 21-day-old, PCV2-naïve pigs were randomly assigned to one of six groups (Negative controls, positive controls, Vac-0, Vac-0-PCV2, Contact-PCV2, Vac-28-PCV2). All pigs we...

  20. Exploration of the Lived Experiences of Undergraduate Science, Technology, Engineering, and Mathematics Minority Students

    Science.gov (United States)

    Snead-McDaniel, Kimberly

    2010-01-01

    An expanding ethnicity gap exists in the number of students pursuing science, technology, engineering, and mathematics (STEM) careers in the United States. The National Action Council for Minorities in Engineering revealed that the number of minorities pursuing STEM degrees and careers has declined over the past few years. The specific origins of…

  1. Public health impact and cost effectiveness of mass vaccination with live attenuated human rotavirus vaccine (RIX4414) in India: model based analysis.

    Science.gov (United States)

    Rose, Johnie; Hawthorn, Rachael L; Watts, Brook; Singer, Mendel E

    2009-09-25

    To examine the public health impact of mass vaccination with live attenuated human rotavirus vaccine (RIX4414) in a birth cohort in India, and to estimate the cost effectiveness and affordability of such a programme. Decision analytical Markov model encompassing all direct medical costs. Infection risk and severity depended on age, number of previous infections, and vaccination history; probabilities of use of inpatient and outpatient health services depended on symptom severity. Published clinical, epidemiological, and economic data. When possible, parameter estimates were based on data specific for India. Population Simulated Indian birth cohort followed for five years. Decrease in rotavirus gastroenteritis episodes (non-severe and severe), deaths, outpatient visits, and admission to hospital; incremental cost effectiveness ratio of vaccination expressed as net cost in 2007 rupees per life year saved. In the base case, vaccination prevented 28,943 (29.7%) symptomatic episodes, 6981 (38.2%) severe episodes, 164 deaths (41.0%), 7178 (33.3%) outpatient visits, and 812 (34.3%) admissions to hospital per 100,000 children. Vaccination cost 8023 rupees (about pound100, euro113, $165) per life year saved, less than India's per capita gross domestic product, a common criterion for cost effectiveness. The net programme cost would be equivalent to 11.6% of the 2006-7 budget of the Indian Department of Health and Family Welfare. Model results were most sensitive to variations in access to outpatient care for those with severe symptoms. If this parameter was increased to its upper limit, the incremental cost effectiveness ratio for vaccination still fell between one and three times the per capita gross domestic product, meeting the World Health Organization's criterion for "cost effective" interventions. Uncertainty analysis indicated a 94.7% probability that vaccination would be cost effective according to a criterion of one times per capita gross domestic product per life

  2. Safety of Russian-backbone seasonal trivalent, live-attenuated influenza vaccine in a phase II randomized placebo-controlled clinical trial among children in urban Bangladesh.

    Science.gov (United States)

    Ortiz, Justin R; Goswami, Doli; Lewis, Kristen D C; Sharmeen, Amina Tahia; Ahmed, Moshtaq; Rahman, Mustafizur; Rahman, Mohammed Z; Feser, Jodi; Neuzil, Kathleen M; Brooks, W Abdullah

    2015-06-26

    Live-attenuated influenza vaccines (LAIVs) have the potential to be affordable, effective, and logistically feasible for immunization of children in low-resource settings. We conducted a phase II, randomized, double-blind, parallel group, placebo-controlled trial on the safety of the Russian-backbone, seasonal trivalent LAIV among children aged 24 through 59 months in Dhaka, Bangladesh in 2012. After vaccination, we monitored participants for six months with weekly home visits and study clinic surveillance for solicited and unsolicited adverse events, protocol-defined wheezing illness (PDWI), and serious adverse events (SAEs), including all cause hospitalizations. Three hundred children were randomized and administered LAIV (n=150) or placebo (n=150). No immediate post-vaccination reactions occurred in either group. Solicited reactions were similar between vaccine and placebo groups during the first 7 days post-vaccination and throughout the entire trial. There were no statistically significant differences in participants experiencing PDWI between LAIV and placebo groups throughout the trial (n=13 vs. n=16, p=0.697). Of 131 children with a history of medical treatment or hospitalization for asthma or wheezing at study entry, 65 received LAIV and 66 received placebo. Among this subset, there was no statistical difference in PDWI occurring throughout the trial between the LAIV or placebo groups (7.7% vs. 19.7%, p=0.074). While there were no related SAEs, LAIV recipients had six unrelated SAEs and placebo recipients had none. These SAEs included three due to traumatic injury and bone fracture, and one each due to accidental overdose of paracetamol, abdominal pain, and acute gastroenteritis. None of the participants with SAEs had laboratory-confirmed influenza, wheezing illness, or other signs of acute respiratory illness at the time of their events. In this randomized, controlled trial among 300 children aged 24 through 59 months in urban Bangladesh, Russian

  3. Safety and immunogenicity of a live attenuated RSV vaccine in healthy RSV-seronegative children 5 to 24 months of age.

    Directory of Open Access Journals (Sweden)

    Elissa Malkin

    Full Text Available Despite substantial morbidity associated with respiratory syncytial virus (RSV infection, there is no licensed vaccine. MEDI-559 is a live attenuated intranasal vaccine candidate being developed for prevention of lower respiratory illness due to RSV in young children. This randomized, placebo-controlled study evaluated safety of MEDI-559 in healthy, RSV-seronegative children. MEDI-559 or placebo was administered on 3 occasions, 2 months apart. Primary safety was based on solicited symptoms (SSs and adverse events (AEs collected for 28 days after each dose. Nasal wash samples were collected 3 times after each dose (days 7-10, 12-18, 28-34 and at sick visits. Serum was collected for measuring antibody immune responses to RSV prior to first vaccination and 28 days post final dose. Long-term safety was monitored for 365 days from first dose. SSs were mild and frequent (MEDI-559 84%; placebo 91%; most common SSs were runny/stuffy nose, cough, and irritability/fussiness. AEs occurred in 67% MEDI-559 and 57% placebo recipients: most common AE was upper respiratory tract infection (MEDI-559 35%; placebo 23%. Higher incidence of medically attended lower respiratory illness within 28 days after dosing occurred in the MEDI-559 arm compared to placebo (none associated with vaccine virus shedding. There was no evidence of enhanced RSV disease. Vaccine virus was detected only in MEDI-559 recipients; shedding occurred in 56%subjects, primarily post dose 1. A functional immune response was observed in 59% and 9% MEDI-559 and placebo recipients, respectively, by an RSV microneutralization assay. Vaccine take, assessed by proportion that shed vaccine-type virus or had a seroresponse against RSV, was seen in 95% MEDI-559 subjects. MEDI-559 is therefore biologically active and immunogenic in this seronegative pediatric population. Although the frequency of SSs and AEs was not considered clinically significant, the increase in medically attended lower respiratory

  4. In a randomized trial, the live attenuated tetravalent dengue vaccine TV003 is well-tolerated and highly immunogenic in subjects with flavivirus exposure prior to vaccination.

    Directory of Open Access Journals (Sweden)

    Stephen S Whitehead

    2017-05-01

    Full Text Available Infection caused by the four serotypes of dengue virus (DENV-1-4 is a leading cause of mosquito-borne disease. Clinically-severe dengue disease is more common when secondary dengue infection occurs following prior infection with a heterologous dengue serotype. Other flaviviruses such as yellow fever virus, Japanese encephalitis virus, and Zika virus, can also elicit antibodies which are cross-reactive to DENV. As candidate dengue vaccines become available in endemic settings and for individuals who have received other flavivirus vaccines, it is important to examine vaccine safety and immunogenicity in these flavivirus-experienced populations. We performed a randomized, controlled trial of the National Institutes of Health live attenuated tetravalent dengue vaccine candidate (TV003 in fifty-eight individuals with prior exposure to flavivirus infection or vaccine. As in prior studies of this vaccine in flavivirus-naive volunteers, flavivirus-experienced subjects received two doses of vaccine six months apart and were followed closely for clinical events, laboratory changes, viremia, and neutralizing antibody titers. TV003 was well tolerated with few adverse events other than rash, which was predominately mild. Following one dose, 87% of vaccinees had an antibody response to all four serotypes (tetravalent response, suggesting a robust immune response. In addition, 76% of vaccinees were viremic; mean peak titers ranged from 0.68–1.1 log10 PFU/mL and did not differ by serotype. The second dose of TV003 was not associated with viremia, rash, or a sustained boost in antibody titers indicating that a single dose of the vaccine is likely sufficient to prevent viral replication and thus protect against disease. In comparison to the viremia and neutralizing antibody response elicited by TV003 in flavivirus-naïve subjects from prior studies, we found that subjects who were flavivirus-exposed prior to vaccination exhibited slightly higher DENV-3 viremia

  5. Assessment of Public Health and Economic Impact of Intranasal Live-Attenuated Influenza Vaccination of Children in France Using a Dynamic Transmission Model.

    Science.gov (United States)

    Gerlier, L; Lamotte, M; Grenèche, S; Lenne, X; Carrat, F; Weil-Olivier, C; Damm, O; Schwehm, M; Eichner, M

    2017-04-01

    We estimated the epidemiological and economic impact of extending the French influenza vaccination programme from at-risk/elderly (≥65 years) only to healthy children (2-17 years). A deterministic, age-structured, dynamic transmission model was used to simulate the transmission of influenza in the French population, using the current vaccination coverage with trivalent inactivated vaccine (TIV) in at-risk/elderly individuals (current strategy) or gradually extending the vaccination to healthy children (aged 2-17 years) with intranasal, quadrivalent live-attenuated influenza vaccine (QLAIV) from current uptake up to 50% (evaluated strategy). Epidemiological, medical resource use and cost data were taken from international literature and country-specific information. The model was calibrated to the observed numbers of influenza-like illness visits/year. The 10-year number of symptomatic cases of confirmed influenza and direct medical costs ('all-payer') were calculated for the 0-17- (direct and indirect effects) and ≥18-year-old (indirect effect). The incremental cost-effectiveness ratio (ICER) was calculated for the total population, using a 4% discount rate/year. Assuming 2.3 million visits/year and 1960 deaths/year, the model calibration yielded an all-year average basic reproduction number (R 0 ) of 1.27. In the population aged 0-17 years, QLAIV prevented 865,000 influenza cases/year (58.4%), preventing 10-year direct medical expenses of €374 million. In those aged ≥18 years with unchanged TIV coverage, 1.2 million cases/year were averted (27.6%) via indirect effects (additionally prevented expenses, €457 million). On average, 613 influenza-related deaths were averted annually overall. The ICER was €18,001/life-year gained. The evaluated strategy had a 98% probability of being cost-effective at a €31,000/life-year gained threshold. The model demonstrated strong direct and indirect benefits of protecting healthy children against influenza with

  6. Cost-effectiveness analysis of intranasal live attenuated vaccine (LAIV versus injectable inactivated influenza vaccine (TIV for Canadian children and adolescents

    Directory of Open Access Journals (Sweden)

    Tarride JE

    2012-10-01

    Full Text Available Jean-Eric Tarride,1,2 Natasha Burke,1,2 Camilla Von Keyserlingk,1,2 Daria O'Reilly,1,2 Feng Xie,1,2 Ron Goeree1,21Programs for Assessment of Technology in Health (PATH Research Institute, St Joseph's Healthcare Hamilton, Hamilton, 2Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, CanadaBackground: Influenza affects all age groups and is common in children. Between 15% and 42% of preschool- and school-aged children experience influenza each season. Recently, intranasal live attenuated influenza vaccine, trivalent (LAIV has been approved in Canada.Objective: The objective of this study was to determine the cost-effectiveness of LAIV compared with that of the injectable inactivated influenza vaccine, trivalent (TIV in Canadian children and adolescents from both a payer (eg. Ministry of Health perspective and a societal perspective.Methods: A cost-effectiveness model comparing LAIV and TIV in children aged 24–59 months old was supplemented by primary (ie, a survey of 144 Canadian physicians and secondary (eg, literature data to model children aged 2–17 years old. Parameter uncertainty was addressed through univariate and probability analyses.Results: Although LAIV increased vaccination costs when compared to TIV, LAIV reduced the number of influenza cases and lowered the number of hospitalizations, emergency room visits, outpatient visits, and parents’ days lost from work. The estimated offsets in direct and societal costs saved were CAD$4.20 and CAD$35.34, respectively, per vaccinated child aged 2–17 years old. When costs and outcomes were considered, LAIV when compared to TIV, was the dominant strategy. At a willingness to pay of CAD$50,000 per quality adjusted life year gained, or CAD$100,000 per quality adjusted life year gained, the probabilistic results indicated that the probability of LAIV being cost-effective was almost 1.Conclusions: LAIV reduces the burden

  7. WHO informal consultation on quality, safety and efficacy specifications for live attenuated rotavirus vaccines Mexico City, Mexico, 8-9 February 2005.

    Science.gov (United States)

    Wood, David

    2005-12-01

    Rotavirus vaccines are at an advanced stage of development but there are as yet no WHO recommendations on production and quality control to provide regulatory guidance. A meeting of experts was convened by WHO and PAHO/AMRO to review the scientific basis for production and quality control of rotavirus vaccines, and to discuss specific measures to assure the safety and efficacy of rotavirus vaccines. The meeting was attended by 25 experts from 14 countries, drawn from academia, public health, national regulatory authorities and vaccine producers. It was agreed that existing guidance for other live virus vaccines provides a very good basis for product characterization, especially for source materials and control of production. The basis for attenuation of current vaccines or vaccine candidates is not known but, at least for the vaccines based on the Jennerian approach of using animal (bovine) rotaviruses, is likely to be multigenic. The risk of intussusception in humans is influenced by genetic background and age. Recent analyzes of large vaccine safety trials found that certain strains of vaccine virus were not associated with intussusception, although in these trials the first dose of vaccine was not administered to children over 3 months of age. Since age is a risk factor for intussusception, this may suggest that early delivery of the first dose of vaccine is desirable. However, maternal antibodies may mitigate against early delivery of the first vaccine dose. Factors which could affect vaccine efficacy or safety include strain diversity, malnutrition, other enteric infections, parasitic infection or immune suppression. It was concluded that data from clinical trials conducted in one part of the world would not necessarily be predictive of vaccine efficacy in other places. It was agreed that in nonclinical evaluations there was a need to use oral dosing for toxicity studies and, because rotavirus is non-neurovirulent, that there was no need for an animal

  8. Using Synthetic Biology to Engineer Living Cells That Interface with Programmable Materials.

    Science.gov (United States)

    Heyde, Keith C; Scott, Felicia Y; Paek, Sung-Ho; Zhang, Ruihua; Ruder, Warren C

    2017-03-09

    We have developed an abiotic-biotic interface that allows engineered cells to control the material properties of a functionalized surface. This system is made by creating two modules: a synthetically engineered strain of E. coli cells and a functionalized material interface. Within this paper, we detail a protocol for genetically engineering selected behaviors within a strain of E. coli using molecular cloning strategies. Once developed, this strain produces elevated levels of biotin when exposed to a chemical inducer. Additionally, we detail protocols for creating two different functionalized surfaces, each of which is able to respond to cell-synthesized biotin. Taken together, we present a methodology for creating a linked, abiotic-biotic system that allows engineered cells to control material composition and assembly on nonliving substrates.

  9. Engineering and exploitation of a fluorescent HIV-1 gp120 for live cell CD4 binding assays

    International Nuclear Information System (INIS)

    Costantini, Lindsey M.; Irvin, Susan C.; Kennedy, Steven C.; Guo, Feng; Goldstein, Harris; Herold, Betsy C.; Snapp, Erik L.

    2015-01-01

    The HIV-1 envelope glycoprotein, gp120, binds the host cell receptor, CD4, in the initial step of HIV viral entry and infection. This process is an appealing target for the development of inhibitory drugs and neutralizing antibodies. To study gp120 binding and intracellular trafficking, we engineered a fluorescent fusion of the humanized gp120 JRFL HIV-1 variant and GFP. Gp120-sfGFP is glycosylated with human sugars, robustly expressed, and secreted from cultured human cells. Protein dynamics, quality control, and trafficking can be visualized in live cells. The fusion protein can be readily modified with different gp120 variants or fluorescent proteins. Finally, secreted gp120-sfGFP enables a sensitive and easy binding assay that can quantitatively screen potential inhibitors of gp120-CD4 binding on live cells via fluorescence imaging or laser scanning cytometry. This adaptable research tool should aid in studies of gp120 cell biology and the development of novel anti-HIV drugs. - Highlights: • Development of fluorescent protein labeled HIV-1 envelope gp120. • Imaging of gp120 dynamics and trafficking in live cells. • Quantitative visual assay of antibody-mediated inhibition of gp120 binding to CD4 on live cells

  10. Engineering and exploitation of a fluorescent HIV-1 gp120 for live cell CD4 binding assays

    Energy Technology Data Exchange (ETDEWEB)

    Costantini, Lindsey M. [Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Irvin, Susan C. [Department of Pediatrics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Kennedy, Steven C. [Department of Pediatrics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Guo, Feng [Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Goldstein, Harris; Herold, Betsy C. [Department of Pediatrics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Snapp, Erik L., E-mail: erik-lee.snapp@einstein.yu.edu [Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States)

    2015-02-15

    The HIV-1 envelope glycoprotein, gp120, binds the host cell receptor, CD4, in the initial step of HIV viral entry and infection. This process is an appealing target for the development of inhibitory drugs and neutralizing antibodies. To study gp120 binding and intracellular trafficking, we engineered a fluorescent fusion of the humanized gp120 JRFL HIV-1 variant and GFP. Gp120-sfGFP is glycosylated with human sugars, robustly expressed, and secreted from cultured human cells. Protein dynamics, quality control, and trafficking can be visualized in live cells. The fusion protein can be readily modified with different gp120 variants or fluorescent proteins. Finally, secreted gp120-sfGFP enables a sensitive and easy binding assay that can quantitatively screen potential inhibitors of gp120-CD4 binding on live cells via fluorescence imaging or laser scanning cytometry. This adaptable research tool should aid in studies of gp120 cell biology and the development of novel anti-HIV drugs. - Highlights: • Development of fluorescent protein labeled HIV-1 envelope gp120. • Imaging of gp120 dynamics and trafficking in live cells. • Quantitative visual assay of antibody-mediated inhibition of gp120 binding to CD4 on live cells.

  11. A new approximation of the dispersion relations occurring in the sound-attenuation problem of turbofan aircraft engines

    Directory of Open Access Journals (Sweden)

    Robert SZABO

    2011-12-01

    Full Text Available The dispersion relations, appearing in the analysis of the stability of a gas flow in a straight acoustically-lined duct with respect to perturbations produced by a time harmonic source, beside the wave number and complex frequency contain the solution of a boundary value problem of the Pridmore-Brown equation depending on the wave number and frequency. For this reason, in practice the dispersion relations are rarely simple enough for carried out the zeros. The determination of zeros of these dispersion relations is crucial for the prediction of the perturbation attenuation or amplification. In this paper an approximation of the dispersion relations is given. Our approach preserves the general character of the mean flow, the general Pridmore-Brown equation and it’s only in the shear flow that we replace the exact solution of the boundary value problem with its Taylor polynomial approximate. In this way new approximate dispersion relations are obtained which zero’s can be found by computer.

  12. Conceptual Engineering Method for Attenuating He Ion Interactions on First Wall Components in the Fusion Test Facility (FTF) Employing a Low-Pressure Noble Gas

    International Nuclear Information System (INIS)

    Gentile, C.A.; Blanchard, W.R.; Kozub, T.; Priniski, C.; Zatz, I.; Obenschain, S.

    2009-01-01

    It has been shown that post detonation energetic helium ions can drastically reduce the useful life of the (dry) first wall of an IFE reactor due to the accumulation of implanted helium. For the purpose of attenuating energetic helium ions from interacting with first wall components in the Fusion Test Facility (FTF) target chamber, several concepts have been advanced. These include magnetic intervention (MI), deployment of a dynamically moving first wall, use of a sacrificial shroud, designing the target chamber large enough to mitigate the damage caused by He ions on the target chamber wall, and the use of a low pressure noble gas resident in the target chamber during pulse power operations. It is proposed that employing a low-pressure (∼ 1 torr equivalent) noble gas in the target chamber will thermalize energetic helium ions prior to interaction with the wall. The principle benefit of this concept is the simplicity of the design and the utilization of (modified) existing technologies for pumping and processing the noble ambient gas. Although the gas load in the system would be increased over other proposed methods, the use of a 'gas shield' may provide a cost effective method of greatly extending the first wall of the target chamber. An engineering study has been initiated to investigate conceptual engineering methods for implementing a viable gas shield strategy in the FTF.

  13. Five Women in Science, Technology, Engineering, and Mathematics Majors: A Portraiture of Their Lived Experiences

    Science.gov (United States)

    Torcivia, Patrice Prusko

    2012-01-01

    Numerous studies have addressed science, technology, engineering and mathematics (STEM) and their relation to education and gender ranging from elementary school pedagogy to career choices for traditional-aged college students. Little research has addressed nontraditional female students returning to the university to in the STEM fields. This…

  14. The Long-Term Safety, Public Health Impact, and Cost-Effectiveness of Routine Vaccination with a Recombinant, Live-Attenuated Dengue Vaccine (Dengvaxia): A Model Comparison Study.

    Science.gov (United States)

    Flasche, Stefan; Jit, Mark; Rodríguez-Barraquer, Isabel; Coudeville, Laurent; Recker, Mario; Koelle, Katia; Milne, George; Hladish, Thomas J; Perkins, T Alex; Cummings, Derek A T; Dorigatti, Ilaria; Laydon, Daniel J; España, Guido; Kelso, Joel; Longini, Ira; Lourenco, Jose; Pearson, Carl A B; Reiner, Robert C; Mier-Y-Terán-Romero, Luis; Vannice, Kirsten; Ferguson, Neil

    2016-11-01

    Large Phase III trials across Asia and Latin America have recently demonstrated the efficacy of a recombinant, live-attenuated dengue vaccine (Dengvaxia) over the first 25 mo following vaccination. Subsequent data collected in the longer-term follow-up phase, however, have raised concerns about a potential increase in hospitalization risk of subsequent dengue infections, in particular among young, dengue-naïve vaccinees. We here report predictions from eight independent modelling groups on the long-term safety, public health impact, and cost-effectiveness of routine vaccination with Dengvaxia in a range of transmission settings, as characterised by seroprevalence levels among 9-y-olds (SP9). These predictions were conducted for the World Health Organization to inform their recommendations on optimal use of this vaccine. The models adopted, with small variations, a parsimonious vaccine mode of action that was able to reproduce quantitative features of the observed trial data. The adopted mode of action assumed that vaccination, similarly to natural infection, induces transient, heterologous protection and, further, establishes a long-lasting immunogenic memory, which determines disease severity of subsequent infections. The default vaccination policy considered was routine vaccination of 9-y-old children in a three-dose schedule at 80% coverage. The outcomes examined were the impact of vaccination on infections, symptomatic dengue, hospitalised dengue, deaths, and cost-effectiveness over a 30-y postvaccination period. Case definitions were chosen in accordance with the Phase III trials. All models predicted that in settings with moderate to high dengue endemicity (SP9 ≥ 50%), the default vaccination policy would reduce the burden of dengue disease for the population by 6%-25% (all simulations: -3%-34%) and in high-transmission settings (SP9 ≥ 70%) by 13%-25% (all simulations: 10%- 34%). These endemicity levels are representative of the participating sites in

  15. The Long-Term Safety, Public Health Impact, and Cost-Effectiveness of Routine Vaccination with a Recombinant, Live-Attenuated Dengue Vaccine (Dengvaxia: A Model Comparison Study.

    Directory of Open Access Journals (Sweden)

    Stefan Flasche

    2016-11-01

    Full Text Available Large Phase III trials across Asia and Latin America have recently demonstrated the efficacy of a recombinant, live-attenuated dengue vaccine (Dengvaxia over the first 25 mo following vaccination. Subsequent data collected in the longer-term follow-up phase, however, have raised concerns about a potential increase in hospitalization risk of subsequent dengue infections, in particular among young, dengue-naïve vaccinees. We here report predictions from eight independent modelling groups on the long-term safety, public health impact, and cost-effectiveness of routine vaccination with Dengvaxia in a range of transmission settings, as characterised by seroprevalence levels among 9-y-olds (SP9. These predictions were conducted for the World Health Organization to inform their recommendations on optimal use of this vaccine.The models adopted, with small variations, a parsimonious vaccine mode of action that was able to reproduce quantitative features of the observed trial data. The adopted mode of action assumed that vaccination, similarly to natural infection, induces transient, heterologous protection and, further, establishes a long-lasting immunogenic memory, which determines disease severity of subsequent infections. The default vaccination policy considered was routine vaccination of 9-y-old children in a three-dose schedule at 80% coverage. The outcomes examined were the impact of vaccination on infections, symptomatic dengue, hospitalised dengue, deaths, and cost-effectiveness over a 30-y postvaccination period. Case definitions were chosen in accordance with the Phase III trials. All models predicted that in settings with moderate to high dengue endemicity (SP9 ≥ 50%, the default vaccination policy would reduce the burden of dengue disease for the population by 6%-25% (all simulations: -3%-34% and in high-transmission settings (SP9 ≥ 70% by 13%-25% (all simulations: 10%- 34%. These endemicity levels are representative of the

  16. Hydroxysafflor yellow A of Carthamus tinctorius attenuates lung injury of aged rats exposed to gasoline engine exhaust by down-regulating platelet activation.

    Science.gov (United States)

    Wang, Chaoyun; Wang, Chunhua; Ma, Chunlei; Huang, Qingxian; Sun, Hongliu; Zhang, Xiaomin; Bai, Xianyong

    2014-02-15

    Long-term inhalation of gasoline engine exhaust (GEE) increases the risk of respiratory disease. Studies have suggested involvement of platelets in the development of some lung diseases. Hydroxysafflor yellow A (HSYA), a flavonoid compound, prevents hemostasis. Therefore, we investigated its effects on GEE-induced lung injury, and role of platelets in injury. Sixty-week-old male Sprague-Dawley rats were exposed to GEE for 4h/day for 6 weeks, and then grouped as follows: control, GEE, GEE+HSYA, GEE+HSYA+GW9662, and GEE+GW9662. Arterial oxygen tension (PaO2), carbon dioxide tension (PaCO2), pH, and the PaO2/fraction of inspired oxygen ratio (PaO2/FiO2) in the blood were detected using a blood gas analyzer. Wet/dry lung weight ratio, total protein in bronchoalveolar lavage fluid (BALF), and cytokine concentrations in serum and BALF were determined. Furthermore, cyclic adenosine monophosphate (cAMP) level and expression levels of target proteins were analyzed. Platelets were counted and their state was evaluated. HSYA attenuated GEE-mediated decreases in PaO2, PaO2/FiO2, platelet cAMP level, protein kinase A (PKA) activity, and peroxisome proliferator-activated receptor γ (PPARγ) expression. HSYA also attenuated GEE-mediated increases in lung permeability, cytokine levels in serum and BALF, plasma platelet count, and ADP-mediated platelet aggregation. Moreover, it suppressed GEE-induced increases in the expression of adhesion molecules and proinflammatory cytokines in platelets and lung tissue. Therefore, HSYA is therapeutically effective for GEE-mediated lung injury and acts by enhancing PKA activity and inhibiting platelet activation. Copyright © 2013 Elsevier GmbH. All rights reserved.

  17. Biothermodynamics of live cells: a tool for biotechnology and biochemical engineering

    Science.gov (United States)

    von Stockar, Urs

    2010-12-01

    The aim of this contribution is to review the application of thermodynamics to live cultures of microbial and other cells and to explore to what extent this may be put to practical use. A major focus is on energy dissipation effects in industrially relevant cultures, both in terms of heat and Gibbs energy dissipation. The experimental techniques for calorimetric measurements in live cultures are reviewed and their use for monitoring and control is discussed. A detailed analysis of the dissipation of Gibbs energy in chemotrophic growth shows that it reflects the entropy production by metabolic processes in the cells and thus also the driving force for growth and metabolism. By splitting metabolism conceptually up into catabolism and biosynthesis, it can be shown that this driving force decreases as the growth yield increases. This relationship is demonstrated by using experimental measurements on a variety of microbial strains. On the basis of these data, several literature correlations were tested as tools for biomass yield prediction. The prediction of other culture performance characteristics, including product yields for biorefinery planning, energy yields for biofuel manufacture, maximum growth rates, maintenance requirements, and threshold concentrations is also briefly reviewed.

  18. The Soyuz launch vehicle the two lives of an engineering triumph

    CERN Document Server

    Lardier, Christian

    2013-01-01

    The Soyuz launch vehicle has had a long and illustrious history. Built as the world's first intercontinental missile, it took the first man into space in April 1961, before becoming the workhorse of Russian spaceflight, launching satellites, interplanetary probes, every cosmonaut from Gagarin onwards, and, now, the multinational crews of the International Space Station. This remarkable book gives a complete and accurate description of the two lives of Soyuz, chronicling the cooperative space endeavor of Europe and Russia. First, it takes us back to the early days of astronautics, when technology served politics. From archives found in the Soviet Union the authors describe the difficulty of designing a rocket in the immediate post-war period. Then, in Soyuz's golden age, it launched numerous scientific missions and manned flights which were publicized worldwide while the many more numerous military missions were kept highly confidential! The second part of the book tells the contemporary story of the second li...

  19. [Methods of substances and organelles introduction in living cell for cell engineering technologies].

    Science.gov (United States)

    Nikitin, V A

    2007-01-01

    We have presented the classification of more than 40 methods of genetic material, substances and organelles introduction into a living cell. Each of them has its characteristic advantages, disadvantages and limitations with respect to cell viability, transfer efficiency, general applicability, and technical requirements. It this article we have enlarged on the description of our developments of several new and improved approaches, methods and devices of the direct microinjection into a single cell and cell microsurgery with the help of glass micropipettes. The problem of low efficiency of mammalian cloning is discussed with emphasis on the necessity of expertizing of each step of single cell reconstruction to begin with microsurgical manipulations and necessity of the development of such methods of single cell resonstruction that could minimize the possible damage of the cell.

  20. Characterization of a vraG Mutant in a Genetically Stable Staphylococcus aureus Small-Colony Variant and Preliminary Assessment for Use as a Live-Attenuated Vaccine against Intrammamary Infections.

    Directory of Open Access Journals (Sweden)

    Julie Côté-Gravel

    Full Text Available Staphylococcus aureus is a leading cause of bovine intramammary infections (IMIs that can evolve into difficult-to-treat chronic mastitis. To date, no vaccine formulation has shown high protective efficacy against S. aureus IMI, partly because this bacterium can efficiently evade the immune system. For instance, S. aureus small colony variants (SCVs have intracellular abilities and can persist without producing invasive infections. As a first step towards the development of a live vaccine, this study describes the elaboration of a novel attenuated mutant of S. aureus taking advantage of the SCV phenotype. A genetically stable SCV was created through the deletion of the hemB gene, impairing its ability to adapt and revert to the invasive phenotype. Further attenuation was obtained through inactivation of gene vraG (SACOL0720 which we previously showed to be important for full virulence during bovine IMIs. After infection of bovine mammary epithelial cells (MAC-T, the double mutant (ΔvraGΔhemB was less internalized and caused less cell destruction than that seen with ΔhemB and ΔvraG, respectively. In a murine IMI model, the ΔvraGΔhemB mutant was strongly attenuated, with a reduction of viable counts of up to 5-log10 CFU/g of mammary gland when compared to the parental strain. A complete clearance of ΔvraGΔhemB from glands was observed whereas mortality rapidly (48h occurred with the wild-type strain. Immunization of mice using subcutaneous injections of live ΔvraGΔhemB raised a strong immune response as judged by the high total IgG titers measured against bacterial cell extracts and by the high IgG2a/IgG1 ratio observed against the IsdH protein. Also, ΔvraGΔhemB had sufficient common features with bovine mastitis strains so that the antibody response also strongly recognized strains from a variety of mastitis associated spa types. This double mutant could serve as a live-attenuated component in vaccines to improve cell-mediated immune

  1. Live recombinant BHV/BRSV vaccine

    NARCIS (Netherlands)

    Keil, G.M.; Rijsewijk, F.A.M.

    1998-01-01

    The present invention refers to synthetic Bovine Respiratory Syncytium virus genes. Also the invention relates to live attenuated Bovine Herpesvirus recombinants carrying such synthetic genes. Furthermore, the invention relates to vaccines based on these live attenuated recombinants, for the

  2. Oral vaccination with LcrV from Yersinia pestis KIM delivered by live attenuated Salmonella enterica serovar Typhimurium elicits a protective immune response against challenge with Yersinia pseudotuberculosis and Yersinia enterocolitica.

    Science.gov (United States)

    Branger, Christine G; Torres-Escobar, Ascención; Sun, Wei; Perry, Robert; Fetherston, Jacqueline; Roland, Kenneth L; Curtiss, Roy

    2009-08-27

    The use of live recombinant attenuated Salmonella vaccines (RASV) synthesizing Yersinia proteins is a promising approach for controlling infection by Yersinia species. In this study, we constructed attenuated Salmonella strains which synthesize a truncated form of LcrV, LcrV196 and evaluated the immune response and protective efficacy elicited by these strains in mice against two other major species of Yersinia: Yersinia pseudotuberculosis and Yersinia enterocolitica. Surprisingly, we found that the RASV strain alone was sufficient to afford nearly full protection against challenge with Y. pseudotuberculosis, indicating the likelihood that Salmonella produces immunogenic cross-protective antigens. In contrast, lcrV196 expression was required for protection against challenge with Y. enterocolitica strain 8081, but was not sufficient to achieve significant protection against challenge with Y. enterocolitica strain WA, which expressed a divergent form of lcrV. Nevertheless, we are encouraged by these findings to continue pursuing our long-term goal of developing a single vaccine to protect against all three human pathogenic species of Yersinia.

  3. Engineered core-shell magnetic nanoparticle for MR dual-modal tracking and safe magnetic manipulation of ependymal cells in live rodents

    Science.gov (United States)

    Peng, Yung-Kang; Lui, Cathy N. P.; Chen, Yu-Wei; Chou, Shang-Wei; Chou, Pi-Tai; Yung, Ken K. L.; Edman Tsang, S. C.

    2018-01-01

    Tagging recognition group(s) on superparamagnetic iron oxide is known to aid localisation (imaging), stimulation and separation of biological entities using magnetic resonance imaging (MRI) and magnetic agitation/separation (MAS) techniques. Despite the wide applicability of iron oxide nanoparticles in T 2-weighted MRI and MAS, the quality of the images and safe manipulation of the exceptionally delicate neural cells in a live brain are currently the key challenges. Here, we demonstrate the engineered manganese oxide clusters-iron oxide core-shell nanoparticle as an MR dual-modal contrast agent for neural stem cells (NSCs) imaging and magnetic manipulation in live rodents. As a result, using this engineered nanoparticle and associated technologies, identification, stimulation and transportation of labelled potentially multipotent NSCs from a specific location of a live brain to another by magnetic means for self-healing therapy can therefore be made possible.

  4. Concomitant or sequential administration of live attenuated Japanese encephalitis chimeric virus vaccine and yellow fever 17D vaccine: randomized double-blind phase II evaluation of safety and immunogenicity.

    Science.gov (United States)

    Nasveld, Peter E; Marjason, Joanne; Bennett, Sonya; Aaskov, John; Elliott, Suzanne; McCarthy, Karen; Kanesa-Thasan, Niranjan; Feroldi, Emmanuel; Reid, Mark

    2010-11-01

    A randomized, double-blind, study was conducted to evaluate the safety, tolerability and immunogenicity of a live attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) co-administered with live attenuated yellow fever vaccine (YF-17D strain; Stamaril®, Sanofi Pasteur) or administered successively. Participants (n = 108) were randomized to receive: YF followed by JE-CV 30 days later, JE followed by YF 30 days later, or the co-administration of JE and YF followed or preceded by placebo 30 days later or earlier. Placebo was used in a double-dummy fashion to ensure masking. Neutralizing antibody titers against JE-CV, YF-17D and selected wild-type JE strains was determined using a 50% serum-dilution plaque reduction neutralization test. Seroconversion was defined as the appearance of a neutralizing antibody titer above the assay cut-off post-immunization when not present pre-injection at day 0, or a least a four-fold rise in neutralizing antibody titer measured before the pre-injection day 0 and later post vaccination samples. There were no serious adverse events. Most adverse events (AEs) after JE vaccination were mild to moderate in intensity, and similar to those reported following YF vaccination. Seroconversion to JE-CV was 100% and 91% in the JE/YF and YF/JE sequential vaccination groups, respectively, compared with 96% in the co-administration group. All participants seroconverted to YF vaccine and retained neutralizing titers above the assay cut-off at month six. Neutralizing antibodies against JE vaccine were detected in 82-100% of participants at month six. These results suggest that both vaccines may be successfully co-administered simultaneously or 30 days apart.

  5. Focal attenuation of specific electroencephalographic power over the right parahippocampal region during transcerebral copper screening in living subjects and hemispheric asymmetric voltages in fixed brain tissue.

    Science.gov (United States)

    Rouleau, Nicolas; Lehman, Brendan; Persinger, Michael A

    2016-08-01

    Covering the heads of human volunteers with a toque lined with copper mesh compared to no mesh resulted in significant diminishments in quantitative electroencephalographic power within theta and beta-gamma bands over the right caudal hemisphere. The effect was most evident in women compared to men. The significant attenuation of power was verified by LORETA (low resolution electromagnetic tomography) within the parahippocampal region of the right hemisphere. Direct measurements of frequency-dependent voltages of coronal section preserved in ethanol-formalin-acetic acid from our human brain collection revealed consistently elevated power (0.2μV(2)Hz(-1)) in right hemispheric structures compared to left. The discrepancy was most pronounced in the grey (cortical) matter of the right parahippocampal region. Probing the superficial convexities of the cerebrum in an unsectioned human brain demonstrated rostrocaudal differences in hemispheric spectral power density asymmetries, particularly over caudal and parahippocampal regions, which were altered as a function of the chemical and spatial contexts imposed upon the tissue. These results indicate that the heterogeneous response of the human cerebrum to covering of the head by a thin conductor could reflect an intrinsic structure and unique electrical property of the (entorhinal) cortices of the right caudal hemisphere that persists in fixed tissue. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Comparison of egg and high yielding MDCK cell-derived live attenuated influenza virus for commercial production of trivalent influenza vaccine: in vitro cell susceptibility and influenza virus replication kinetics in permissive and semi-permissive cells.

    Science.gov (United States)

    Hussain, Althaf I; Cordeiro, Melissa; Sevilla, Elizabeth; Liu, Jonathan

    2010-05-14

    Currently MedImmune manufactures cold-adapted (ca) live, attenuated influenza vaccine (LAIV) from specific-pathogen free (SPF) chicken eggs. Difficulties in production scale-up and potential exposure of chicken flocks to avian influenza viruses especially in the event of a pandemic influenza outbreak have prompted evaluation and development of alternative non-egg based influenza vaccine manufacturing technologies. As part of MedImmune's effort to develop the live attenuated influenza vaccine (LAIV) using cell culture production technologies we have investigated the use of high yielding, cloned MDCK cells as a substrate for vaccine production by assessing host range and virus replication of influenza virus produced from both SPF egg and MDCK cell production technologies. In addition to cloned MDCK cells the indicator cell lines used to evaluate the impact of producing LAIV in cells on host range and replication included two human cell lines: human lung carcinoma (A549) cells and human muco-epidermoid bronchiolar carcinoma (NCI H292) cells. The influenza viruses used to infect the indicators cell lines represented both the egg and cell culture manufacturing processes and included virus strains that composed the 2006-2007 influenza seasonal trivalent vaccine (A/New Caledonia/20/99 (H1N1), A/Wisconsin/67/05 (H3N2) and B/Malaysia/2506/04). Results from this study demonstrate remarkable similarity between influenza viruses representing the current commercial egg produced and developmental MDCK cell produced vaccine production platforms. MedImmune's high yielding cloned MDCK cells used for the cell culture based vaccine production were highly permissive to both egg and cell produced ca attenuated influenza viruses. Both the A549 and NCI H292 cells regardless of production system were less permissive to influenza A and B viruses than the MDCK cells. Irrespective of the indicator cell line used the replication properties were similar between egg and the cell produced

  7. Safety and immunogenicity of an oral DNA vaccine encoding Sip of Streptococcus agalactiae from Nile tilapia Oreochromis niloticus delivered by live attenuated Salmonella typhimurium.

    Science.gov (United States)

    Huang, L Y; Wang, K Y; Xiao, D; Chen, D F; Geng, Y; Wang, J; He, Y; Wang, E L; Huang, J L; Xiao, G Y

    2014-05-01

    Attenuated Salmonella typhimurium SL7207 was used as a carrier for a reconstructed DNA vaccine against Streptococcus agalactiae. A 1.02 kb DNA fragment, encoding for a portion of the surface immunogenic protein (Sip) of S. agalactiae was inserted into pVAX1. The recombinant plasmid pVAX1-sip was transfected in EPC cells to detect the transient expression by an indirect immunofluorescence assay, together with Western blot analysis. The pVAX1-sip was transformed by electroporation into SL7207. The stability of pVAX1-sip into Salmonella was over 90% after 50 generations with antibiotic selection in vitro while remained stable over 80% during 35 generations under antibiotic-free conditions. The LD50 of SL/pVAX1-sip was 1.7 × 10(11) CFU/fish by intragastric administration which indicated a quite low virulence. Tilapias were inoculated orally at 10(8) CFU/fish, the recombinant bacteria were found present in intestinal tract, spleens and livers and eventually eliminated from the tissues 4 weeks after immunization. Fish immunized at 10(7), 10(8) and 10(9) CFU/fish with different immunization times caused various levels of serum antibody and an effective protection against lethal challenge with the wild-type strain S. agalactiae. Integration studies showed that the pVAX1-sip did not integrate with tilapia chromosomes. The DNA vaccine SL/pVAX1-sip was proved to be safe and effective in protecting tilapias against S. agalactiae infection. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Measured attenuation correction methods

    International Nuclear Information System (INIS)

    Ostertag, H.; Kuebler, W.K.; Doll, J.; Lorenz, W.J.

    1989-01-01

    Accurate attenuation correction is a prerequisite for the determination of exact local radioactivity concentrations in positron emission tomography. Attenuation correction factors range from 4-5 in brain studies to 50-100 in whole body measurements. This report gives an overview of the different methods of determining the attenuation correction factors by transmission measurements using an external positron emitting source. The long-lived generator nuclide 68 Ge/ 68 Ga is commonly used for this purpose. The additional patient dose from the transmission source is usually a small fraction of the dose due to the subsequent emission measurement. Ring-shaped transmission sources as well as rotating point or line sources are employed in modern positron tomographs. By masking a rotating line or point source, random and scattered events in the transmission scans can be effectively suppressed. The problems of measured attenuation correction are discussed: Transmission/emission mismatch, random and scattered event contamination, counting statistics, transmission/emission scatter compensation, transmission scan after administration of activity to the patient. By using a double masking technique simultaneous emission and transmission scans become feasible. (orig.)

  9. Evaluation of live attenuated H7N3 and H7N7 vaccine viruses for their receptor binding preferences, immunogenicity in ferrets and cross reactivity to the novel H7N9 virus.

    Directory of Open Access Journals (Sweden)

    Qi Xu

    Full Text Available Live attenuated influenza vaccine (LAIV candidates of the H7 subtype, A/Netherlands/219/03 (H7N7, NL03 ca and A/chicken/British Columbia/CN-6/2004 (H7N3, BC04 ca, were evaluated for their receptor binding specificity and immunogenicity in ferrets. The BC04 ca virus exhibited α2,3-SA and α2,6-SA dual receptor binding preference while the NL03 ca virus preferentially bound to α2,3-SA. Substitution of the Q226 and G228 (Q-G by the L226 and S228 (L-S residues in the HA improved binding to α2,6-SA for NL03 ca. The vaccine viruses with L-S retained the attenuation phenotype. NL03 L-S ca replicated more efficiently than the original NL03 ca virus in the upper respiratory tract of ferrets, and induced higher levels of humoral and cellular immune responses. Prior vaccination with seasonal LAIV reduced H7-specific antibody responses, but did not reduce the H7N7 vaccine mediated protection against a heterologous H7N3 BC04 wt virus infection in ferrets. In addition, the H7N3 and H7N7 vaccine immunized ferret sera cross reacted with the newly emerged H7N9 virus. These data, in combination with the safety data from previously conducted Phase 1 studies, suggest that these vaccines may have a role in responding to the threat posed by the H7N9 virus.

  10. The cold adapted and temperature sensitive influenza A/Ann Arbor/6/60 virus, the master donor virus for live attenuated influenza vaccines, has multiple defects in replication at the restrictive temperature

    International Nuclear Information System (INIS)

    Chan, Winnie; Zhou, Helen; Kemble, George; Jin Hong

    2008-01-01

    We have previously determined that the temperature sensitive (ts) and attenuated (att) phenotypes of the cold adapted influenza A/Ann Arbor/6/60 strain (MDV-A), the master donor virus for the live attenuated influenza A vaccines (FluMist), are specified by the five amino acids in the PB1, PB2 and NP gene segments. To understand how these loci control the ts phenotype of MDV-A, replication of MDV-A at the non-permissive temperature (39 deg. C) was compared with recombinant wild-type A/Ann Arbor/6/60 (rWt). The mRNA and protein synthesis of MDV-A in the infected MDCK cells were not significantly reduced at 39 deg. C during a single-step replication, however, vRNA synthesis was reduced and the nuclear-cytoplasmic export of viral RNP (vRNP) was blocked. In addition, the virions released from MDV-A infected cells at 39 deg. C exhibited irregular morphology and had a greatly reduced amount of the M1 protein incorporated. The reduced M1 protein incorporation and vRNP export blockage correlated well with the virus ts phenotype because these defects could be partially alleviated by removing the three ts loci from the PB1 gene. The virions and vRNPs isolated from the MDV-A infected cells contained a higher level of heat shock protein 70 (Hsp70) than those of rWt, however, whether Hsp70 is involved in thermal inhibition of MDV-A replication remains to be determined. Our studies demonstrate that restrictive replication of MDV-A at the non-permissive temperature occurs in multiple steps of the virus replication cycle

  11. Engineering Multifunctional Living Paints: Thin, Convectively-Assembled Biocomposite Coatings of Live Cells and Colloidal Latex Particles Deposited by Continuous Convective-Sedimentation Assembly

    Science.gov (United States)

    Jenkins, Jessica Shawn

    Advanced composite materials could be revolutionized by the development of methods to incorporate living cells into functional materials and devices. This could be accomplished by continuously and rapidly depositing thin ordered arrays of adhesive colloidal latex particles and live cells that maintain stability and preserve microbial reactivity. Convective assembly is one method of rapidly assembling colloidal particles into thin (advantages over thicker randomly ordered composites, including enhanced cell stability and increased reactivity through minimized diffusion resistance to nutrients and reduced light scattering. This method can be used to precisely deposit live bacteria, cyanobacteria, yeast, and algae into biocomposite coatings, forming reactive biosensors, photoabsorbers, or advanced biocatalysts. This dissertation developed new continuous deposition and coating characterization methods for fabricating and characterizing 90 hours) photohydrogen production under anoxygenic conditions. Nutrient reduction slows cell division, minimizing coating outgrowth, and promotes photohydrogen generation, improving coating reactivity. Scanning electron microscopy of microstructure revealed how coating reactivity can be controlled by the size and distribution of the nanopores in the biocomposite layers. Variations in colloid microsphere size and suspension composition do not affect coating reactivity, but both parameters alter coating microstructure. Porous paper coated with thin coatings of colloidal particles and cells to enable coatings to be used in a gas-phase without dehydration may offer higher volumetric productivity for hydrogen production. Future work should focus on optimization of cell density, light intensity, media cycling, and acetate concentration.

  12. Clinical Efficacy, Safety, and Immunogenicity of a Live Attenuated Tetravalent Dengue Vaccine (CYD-TDV in Children: A Systematic Review with Meta-analysis

    Directory of Open Access Journals (Sweden)

    Moffat Malisheni

    2017-08-01

    Full Text Available BackgroundDengue hemorrhagic fever is the leading cause of hospitalization and death in children living in Asia and Latin America. There is an urgent need for an effective and safe dengue vaccine to reduce morbidity and mortality in this high-risk population given the lack of dengue specific treatment at present. This review aims to determine the efficacy, safety, and immunogenicity of CYD-TDV vaccine in children.MethodsThis is a systematic review including meta-analysis of randomized controlled clinical trial data from Embase, Medline, the Cochrane Library, Web of Science, and ClinicalTrials.gov. Studies that assessed CYD-TDV vaccine efficacy [(1 − RR*100], safety (RR, and immunogenicity (weighted mean difference in children were included in this study. Random effects model was employed to analyze patient-level data extracted from primary studies.ResultsThe overall efficacy of CYD-TDV vaccine was 54% (40–64, while serotype-specific efficacy was 77% (66–85 for DENV4, 75% (65–82 for DENV3, 50% (36–61 for DENV1, and 34% (14–49 for DENV2. 15% (−174–74 vaccine efficacy was obtained for the unknown serotype. Meta-analysis of included studies with longer follow-up time (25 months revealed that CYD-TDV vaccine significantly increased the risk of injection site reactions (RR = 1.1: 1.04–1.17; p-value = 0.001. Immunogenicity (expressed as geometric mean titers in descending order was 439.7 (331.7–547.7, 323 (247 – 398.7, 144.1 (117.9–170.2, and 105 (88.7–122.8 for DENV3, DENV2, DENV1, and DENV4, respectively.ConclusionCYD-TDV vaccine is effective and immunogenic in children overall. Reduced efficacy of CYD-TDV vaccine against DENV2 notoriously known for causing severe dengue infection and dengue outbreaks cause for serious concern. Post hoc meta-analysis of long-term follow-up data (≥25 months from children previously vaccinated with CYD-TDV vaccine is needed to make a conclusion regarding CYD-TDV vaccine

  13. Safety and infectivity of two doses of live-attenuated recombinant cold-passaged human parainfluenza type 3 virus vaccine rHPIV3cp45 in HPIV3-seronegative young children.

    Science.gov (United States)

    Englund, Janet A; Karron, Ruth A; Cunningham, Coleen K; Larussa, Philip; Melvin, Ann; Yogev, Ram; Handelsman, Ed; Siberry, George K; Thumar, Bhavanji; Schappell, Elizabeth; Bull, Catherine V; Chu, Helen Y; Schaap-Nutt, Anne; Buchholz, Ursula; Collins, Peter L; Schmidt, Alexander C

    2013-11-19

    Human parainfluenza virus type 3 (HPIV3) is a common cause of upper and lower respiratory tract illness in infants and young children. Live-attenuated cold-adapted HPIV3 vaccines have been evaluated in infants but a suitable interval for administration of a second dose of vaccine has not been defined. HPIV3-seronegative children between the ages of 6 and 36 months were randomized 2:1 in a blinded study to receive two doses of 10⁵ TCID₅₀ (50% tissue culture infectious dose) of live-attenuated, recombinant cold-passaged human PIV3 vaccine (rHPIV3cp45) or placebo 6 months apart. Serum antibody levels were assessed prior to and approximately 4-6 weeks after each dose. Vaccine virus infectivity, defined as detection of vaccine-HPIV3 in nasal wash and/or a≥4-fold rise in serum antibody titer, and reactogenicity were assessed on days 3, 7, and 14 following immunization. Forty HPIV3-seronegative children (median age 13 months; range 6-35 months) were enrolled; 27 (68%) received vaccine and 13 (32%) received placebo. Infectivity was detected in 25 (96%) of 26 evaluable vaccinees following doses 1 and 9 of 26 subject (35%) following dose 2. Among those who shed virus, the median duration of viral shedding was 12 days (range 6-15 days) after dose 1 and 6 days (range 3-8 days) after dose 2, with a mean peak log₁₀ viral titer of 3.4 PFU/mL (SD: 1.0) after dose 1 compared to 1.5 PFU/mL (SD: 0.92) after dose 2. Overall, reactogenicity was mild, with no difference in rates of fever and upper respiratory infection symptoms between vaccine and placebo groups. rHPIV3cp45 was immunogenic and well-tolerated in seronegative young children. A second dose administered 6 months after the initial dose was restricted in those previously infected with vaccine virus; however, the second dose boosted antibody responses and induced antibody responses in two previously uninfected children. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Intramuscular Immunization of Mice with the Live-Attenuated Herpes Simplex Virus 1 Vaccine Strain VC2 Expressing Equine Herpesvirus 1 (EHV-1) Glycoprotein D Generates Anti-EHV-1 Immune Responses in Mice.

    Science.gov (United States)

    Liu, Shiliang A; Stanfield, Brent A; Chouljenko, Vladimir N; Naidu, Shan; Langohr, Ingeborg; Del Piero, Fabio; Ferracone, Jacqueline; Roy, Alma A; Kousoulas, Konstantin G

    2017-06-15

    Vaccination remains the best option to combat equine herpesvirus 1 (EHV-1) infection, and several different strategies of vaccination have been investigated and developed over the past few decades. Herein, we report that the live-attenuated herpes simplex virus 1 (HSV-1) VC2 vaccine strain, which has been shown to be unable to enter into neurons and establish latency in mice, can be utilized as a vector for the heterologous expression of EHV-1 glycoprotein D (gD) and that the intramuscular immunization of mice results in strong antiviral humoral and cellular immune responses. The VC2-EHV-1-gD recombinant virus was constructed by inserting an EHV-1 gD expression cassette under the control of the cytomegalovirus immediate early promoter into the VC2 vector in place of the HSV-1 thymidine kinase (UL23) gene. The vaccines were introduced into mice through intramuscular injection. Vaccination with both the VC2-EHV-1-gD vaccine and the commercially available vaccine Vetera EHV XP 1/4 (Vetera; Boehringer Ingelheim Vetmedica) resulted in the production of neutralizing antibodies, the levels of which were significantly higher in comparison to those in VC2- and mock-vaccinated animals ( P < 0.01 or P < 0.001). Analysis of EHV-1-reactive IgG subtypes demonstrated that vaccination with the VC2-EHV-1-gD vaccine stimulated robust IgG1 and IgG2a antibodies after three vaccinations ( P < 0.001). Interestingly, Vetera-vaccinated mice produced significantly higher levels of IgM than mice in the other groups before and after challenge ( P < 0.01 or P < 0.05). Vaccination with VC2-EHV-1-gD stimulated strong cellular immune responses, characterized by the upregulation of both interferon- and tumor necrosis factor-positive CD4 + T cells and CD8 + T cells. Overall, the data suggest that the HSV-1 VC2 vaccine strain may be used as a viral vector for the vaccination of horses as well as, potentially, for the vaccination of other economically important animals. IMPORTANCE A novel virus

  15. Comparison of the safety and immunogenicity of live attenuated and inactivated hepatitis A vaccine in healthy Chinese children aged 18 months to 16 years: results from a randomized, parallel controlled, phase IV study.

    Science.gov (United States)

    Ma, F; Yang, J; Kang, G; Sun, Q; Lu, P; Zhao, Y; Wang, Z; Luo, J; Wang, Z

    2016-09-01

    For large-scale immunization of children with hepatitis A (HA) vaccines in China, accurately designed studies comparing the safety and immunogenicity of the live attenuated HA vaccine (HA-L) and inactivated HA vaccine (HA-I) are necessary. A randomized, parallel controlled, phase IV clinical trial was conducted with 6000 healthy children aged 18 months to 16 years. HA-L or HA-I was administered at a ratio of 1: 1 to randomized selected participants. The safety and immunogenicity were evaluated. Both HA-L and HA-I were well tolerated by all participants. The immunogenicity results showed that the seroconversion rates (HA-L versus HA-I: 98.0% versus 100%, respectively, p >0.05), and geometric mean concentrations in participants negative for antibodies against HA virus IgG (anti-HAV IgG) before vaccination did not differ significantly between the two types of vaccines (HA-L versus HA-I first dose: 898.9 versus 886.2 mIU/mL, respectively, p >0.05). After administration of the booster dose of HA-I, the geometric mean concentrations of anti-HAV IgG (HA-I booster dose: 2591.2 mIU/mL) was higher than that after the first dose (p children. The effects of long-term immunogenicity after natural exposure to wild-type HA virus and the possibility of mutational shifts of the live vaccine virus in the field need to be studied in more detail. Copyright © 2016. Published by Elsevier Ltd.

  16. Development of a duplex real-time RT-qPCR assay to monitor genome replication, gene expression and gene insert stability during in vivo replication of a prototype live attenuated canine distemper virus vector encoding SIV gag.

    Science.gov (United States)

    Coleman, John W; Wright, Kevin J; Wallace, Olivia L; Sharma, Palka; Arendt, Heather; Martinez, Jennifer; DeStefano, Joanne; Zamb, Timothy P; Zhang, Xinsheng; Parks, Christopher L

    2015-03-01

    Advancement of new vaccines based on live viral vectors requires sensitive assays to analyze in vivo replication, gene expression and genetic stability. In this study, attenuated canine distemper virus (CDV) was used as a vaccine delivery vector and duplex 2-step quantitative real-time RT-PCR (RT-qPCR) assays specific for genomic RNA (gRNA) or mRNA have been developed that concurrently quantify coding sequences for the CDV nucleocapsid protein (N) and a foreign vaccine antigen (SIV Gag). These amplicons, which had detection limits of about 10 copies per PCR reaction, were used to show that abdominal cavity lymphoid tissues were a primary site of CDV vector replication in infected ferrets, and importantly, CDV gRNA or mRNA was undetectable in brain tissue. In addition, the gRNA duplex assay was adapted for monitoring foreign gene insert genetic stability during in vivo replication by analyzing the ratio of CDV N and SIV gag genomic RNA copies over the course of vector infection. This measurement was found to be a sensitive probe for assessing the in vivo genetic stability of the foreign gene insert. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Oral live attenuated human rotavirus vaccine (RotarixTM offers sustained high protection against severe G9P[8] rotavirus gastroenteritis during the first two years of life in Brazilian children

    Directory of Open Access Journals (Sweden)

    Maria Cleonice A Justino

    2012-11-01

    Full Text Available In a large Phase III trial conducted in 10 Latin American countries, the safety and efficacy of the live attenuated monovalent rotavirus vaccine RIX4414 was evaluated in 15,183 healthy infants followed up during the first two years of life. Belém was the only site in Brazil included in this multicentre trial. The study in Belém included a subset of 653 infants who were followed up until 24 months of age for protection against severe rotavirus gastroenteritis. These subjects were randomly assigned in a 1:1 ratio to receive two doses of vaccine (n = 328 or two doses of placebo (n = 325 at approximately two and four months of age. Of the 653 enrolled infants, 23 dropped out during the study period. For the combined two-year period, the efficacy of RIX4414 was 72.3% [95% confidence interval (CI 37.5-89.1%] against severe rotavirus-related gastroenteritis, reaching a protection rate of 81.8% (95% CI 36.4-96.6% against circulating wild-type G9 rotavirus strains. It is concluded that two doses of RIX4414 are highly efficacious against severe rotavirus gastroenteritis in Belém during the first two years of life and provide high protection against the worldwide emergence and spread of G9P[8] strains.

  18. Evolution of Live-Attenuated HIV Vaccines

    NARCIS (Netherlands)

    Berkhout, Ben

    2011-01-01

    Despite intensive research since the viral pathogen was discovered some 25 years ago, not much progress has been reported on the development of a safe vaccine that protects against human immunodeficiency virus type 1. A vaccine approach that has been abandoned because its safety cannot be guaranteed

  19. Observational study on immune response to yellow fever and measles vaccines in 9 to 15-month old children. Is it necessary to wait 4 weeks between two live attenuated vaccines?

    Science.gov (United States)

    Michel, R; Berger, F; Ravelonarivo, J; Dussart, P; Dia, M; Nacher, M; Rogier, S; Moua, D; Sarr, F D; Diop, O M; Sall, A A; Baril, L

    2015-05-11

    The use of 2 live attenuated vaccines (LAV) is recommended to be simultaneous or after an interval of at least four weeks between injections. The primary objective of this study was to compare the humoral response to yellow fever (YF) and measles vaccines among children vaccinated against these two diseases, either simultaneously or separated by an interval of 7-28 days. A prospective, multicenter observational study was conducted among children aged 9-15 months. The primary endpoint was the occurrence of positive yellow fever antibodies after YF vaccine by estimating the titers of neutralizing antibodies from venous blood samples. Children vaccinated against YF 7-28 days after receiving the vaccine against measles (test group) were compared with children vaccinated the same day against these two diseases (referent group). Analysis was performed on 284 children. Of them, fifty-four belonged to the test group. Measles serology was positive in 91.7% of children. Neutralizing antibodies against YF were detected in 90.7% of the test group and 92.9 of the referent group (p=0.6). In addition, quantitative analysis of the immune response did not show a lower response to YF vaccination when it took place 1-28 days after measles vaccination. In 1965, Petralli showed a lower response to the smallpox vaccine when injected 4-20 days after measles vaccination. Since then, recommendations are to observe an interval of four weeks between LAV not injected on the same day. Other published studies failed to show a significant difference in the immune response to a LAV injected 1-28 days after another LAV. These results suggest that the usual recommendations for immunization with two LAV may not be correct. In low income countries, the current policy should be re-evaluated. This re-evaluation should also be applied to travelers to yellow fever endemic countries. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Uptake and impact of a new live attenuated influenza vaccine programme in England: early results of a pilot in primary school-age children, 2013/14 influenza season.

    Science.gov (United States)

    Pebody, R G; Green, H K; Andrews, N; Zhao, H; Boddington, N; Bawa, Z; Durnall, H; Singh, N; Sunderland, A; Letley, L; Ellis, J; Elliot, A J; Donati, M; Smith, G E; de Lusignan, S; Zambon, M

    2014-06-05

    As part of the introduction and roll-out of a universal childhood live-attenuated influenza vaccination programme, 4–11 year-olds were vaccinated in seven pilot areas in England in the 2013/14 influenza season. This paper presents the uptake and impact of the programme for a range of disease indicators. End-of-season uptake was defined as the number of children in the target population who received at least one dose of influenza vaccine. Between week 40 2013 and week 15 2014, cumulative disease incidence per 100,000 population (general practitioner consultations for influenza-like illness and laboratory-confirmed influenza hospitalisations), cumulative influenza swab positivity in primary and secondary care and cumulative proportion of emergency department respiratory attendances were calculated. Indicators were compared overall and by age group between pilot and non-pilot areas. Direct impact was defined as reduction in cumulative incidence based on residence in pilot relative to non-pilot areas in 4–11 year-olds. Indirect impact was reduction between pilot and non-pilot areas in 11 year-olds. Overall vaccine uptake of 52.5% (104,792/199,475) was achieved. Although influenza activity was low, a consistent, though not statistically significant, decrease in cumulative disease incidence and influenza positivity across different indicators was seen in pilot relative to non-pilot areas in both targeted and non-targeted age groups, except in older age groups, where no difference was observed for secondary care indicators.

  1. Safety and immunogenicity of live-attenuated Japanese encephalitis SA 14-14-2 vaccine co-administered with measles vaccine in 9-month-old infants in Sri Lanka.

    Science.gov (United States)

    Wijesinghe, Pushpa Ranjan; Abeysinghe, M R Nihal; Yoksan, Sutee; Yao, Yafu; Zhou, Benli; Zhang, Lei; Yaich, Mansour; Neuzil, Kathleen M; Victor, John C

    2014-08-20

    To facilitate introduction of live attenuated SA 14-14-2 Japanese encephalitis vaccine (LJEV) into the National Immunization Programme of Sri Lanka, we evaluated the safety and immunogenicity of co-administration of LJEV and measles vaccine at 9 months of age. Serum immune responses were evaluated post-vaccination on days 28, 180, and 365 using JE neutralization test and anti-measles IgG ELISA. 278 infants received one dose of LJEV and measles vaccine. Of these, 257 were eligible for the per-protocol analysis. On Day 0, 14 infants (5.5%) were seropositive for JE, but none were seropositive for measles. At Day 28, seropositivity rates were 90.7% (95% CI, 86.4-93.9%) for JE and 84.8% (95% CI, 79.8-89.0%) for measles. The geometric mean titer for JE neutralizing antibodies was 111 (95% CI, 90-135), and the geometric mean concentration (GMC) for anti-measles IgG was 375 mI U/mL (95% CI, 351-400 mI U/mL). Over the next year, JE neutralizing antibody responses declined only slightly, with seropositivity at 87.4% (95% CI, 82.6-91.2%) at Day 365. In contrast, measles antibody levels continued to increase over time. Seropositivity for anti-measles IgG reached 97.2% (95% CI, 94.4-98.9%) at Day 365, and the GMC rose to 1202 mI U/mL (95% CI, 1077-1341 mI U/mL). Co-administration of LJEV and measles vaccine was also safe. Most adverse reactions were mild, and no serious adverse events were related to study vaccinations. The safety and immunogenicity of LJEV co-administered with measles vaccine in Sri Lankan infants is similar to that seen in other populations, and our results support use of LJEV at 9 months of age. Live SA 14-14-2 vaccine is now prequalified by the WHO for use in infants in Asia, and other countries may wish to introduce LJEV to combat this devastating disease. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Live recombinant BHV/BRSV vaccine

    OpenAIRE

    Keil, G.M.; Rijsewijk, F.A.M.

    1998-01-01

    The present invention refers to synthetic Bovine Respiratory Syncytium virus genes. Also the invention relates to live attenuated Bovine Herpesvirus recombinants carrying such synthetic genes. Furthermore, the invention relates to vaccines based on these live attenuated recombinants, for the protection of cattle against both Bovine herpesvirus infection and against Bovine Respiratory Syncytium virus infection. Also the invention relates to methods for the preparation of such live attenuated r...

  3. A Live-Attenuated Chimeric Porcine Circovirus Type 2 (PCV2) Vaccine Is Transmitted to Contact Pigs but Is Not Upregulated by Concurrent Infection with Porcine Parvovirus (PPV) and Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) and Is Efficacious in a PCV2b-PRRSV-PPV Challenge Model▿

    OpenAIRE

    Opriessnig, T.; Shen, H. G.; Pal, N.; Ramamoorthy, S.; Huang, Y. W.; Lager, K. M.; Beach, N. M.; Halbur, P. G.; Meng, X. J.

    2011-01-01

    The live chimeric porcine circovirus type 2 (PCV2) vaccine with the capsid gene of the emerging subtype 2b cloned in the genomic backbone of the nonpathogenic PCV1 is attenuated in vivo and induces protective immunity against PCV2. To further determine the safety and efficacy of this experimental vaccine, we tested for evidence of pig-to-pig transmission by commingling nonvaccinated and vaccinated pigs, determined potential upregulation by simultaneous vaccination and infection with porcine p...

  4. Man as a living bioreactor: Long-term histological aspects of a mandibular replacement engineered in the patient's own body.

    Science.gov (United States)

    Naujokat, H; Açil, Y; Gülses, A; Birkenfeld, F; Wiltfang, J

    2018-05-26

    In 2016, we reported the world's first reconstruction of a mandibular discontinuity defect using a custom-made bone transplant that had been prefabricated in the gastrocolic omentum using tissue engineering strategies. However, the tissue of an engineered human neomandible has not been evaluated histologically until now. The current study assessed the long-term histological characteristics of biopsies of the neomandible 9months after transplantation. Histological analysis showed an increased amount of vital mineralized bone tissue after 10months, in comparison to biopsies obtained earlier. The engineered bone covered the surface of the bone substitute material but also grew out typical structures of cancellous bone tissue without a core of BioOss. The amount of induced bone tissue was 32% in the biopsy. In addition, the soft tissue showed an alignment of the connective tissue fibres parallel to the trabecular bone. Increasing time and mechanical forces at the mandible led to an increased amount of mineralized tissue and remodelling of the connective tissue fibres after transplantation. Further research should focus on developing advanced scaffold materials, as the outer titanium mesh cage leads to complications. Copyright © 2018 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  5. Efficacy and safety of an oral live attenuated human rotavirus vaccine against rotavirus gastroenteritis during the first 2 years of life in Latin American infants: a randomised, double-blind, placebo-controlled phase III study.

    Science.gov (United States)

    Linhares, Alexandre C; Velázquez, F Raúl; Pérez-Schael, Irene; Sáez-Llorens, Xavier; Abate, Hector; Espinoza, Felix; López, Pío; Macías-Parra, Mercedes; Ortega-Barría, Eduardo; Rivera-Medina, Doris Maribel; Rivera, Luis; Pavía-Ruz, Noris; Nuñez, Ernesto; Damaso, Silvia; Ruiz-Palacios, Guillermo M; De Vos, Béatrice; O'Ryan, Miguel; Gillard, Paul; Bouckenooghe, Alain

    2008-04-05

    Peak incidence of rotavirus gastroenteritis is seen in infants between 6 and 24 months of age. We therefore aimed to assess the 2-year efficacy and safety of an oral live attenuated human rotavirus vaccine for prevention of severe gastroenteritis in infants. 15 183 healthy infants aged 6-13 weeks from ten Latin American countries randomly assigned in a 1 to 1 ratio to receive two oral doses of RIX4414 or placebo at about 2 and 4 months of age in a double-blind, placebo-controlled phase III study were followed up until about 2 years of age. Primary endpoint was vaccine efficacy from 2 weeks after dose two until 1 year of age. Treatment allocation was concealed from investigators and parents of participating infants. Efficacy follow-up for gastroenteritis episodes was undertaken from 2 weeks after dose two until about 2 years of age. Analysis was according to protocol. This study is registered with ClinicalTrials.gov, number NCT00140673 (eTrack444563-023). 897 infants were excluded from the according-to-protocol analysis. Fewer cases (protavirus gastroenteritis were recorded for the combined 2-year period in the RIX4414 group (32 [0.4%] of 7205; 95% CI 0.3-0.6) than in the placebo group (161 [2.3%] of 7081; 1.9-2.6), resulting in a vaccine efficacy of 80.5% (71.3-87.1) to 82.1% (64.6-91.9) against wild-type G1, 77.5% (64.7-86.2) against pooled non-G1 strains, and 80.5% (67.9-88.8) against pooled non-G1 P[8] strains. Vaccine efficacy for hospital admission for rotavirus gastroenteritis was 83.0% (73.1-89.7) and for admission for diarrhoea of any cause was 39.3% (29.1-48.1). No cases of intussusception were reported during the second year of follow-up. Two doses of RIX4414 were effective against severe rotavirus gastroenteritis during the first 2 years of life in a Latin American setting. Inclusion of RIX4414 in routine paediatric immunisations should reduce the burden of rotavirus gastroenteritis worldwide.

  6. Predicted Attenuation Relation and Observed Ground Motion of Gorkha Nepal Earthquake of 25 April 2015

    Science.gov (United States)

    Singh, R. P.; Ahmad, R.

    2015-12-01

    A comparison of recent observed ground motion parameters of recent Gorkha Nepal earthquake of 25 April 2015 (Mw 7.8) with the predicted ground motion parameters using exitsing attenuation relation of the Himalayan region will be presented. The recent earthquake took about 8000 lives and destroyed thousands of poor quality of buildings and the earthquake was felt by millions of people living in Nepal, China, India, Bangladesh, and Bhutan. The knowledge of ground parameters are very important in developing seismic code of seismic prone regions like Himalaya for better design of buildings. The ground parameters recorded in recent earthquake event and aftershocks are compared with attenuation relations for the Himalayan region, the predicted ground motion parameters show good correlation with the observed ground parameters. The results will be of great use to Civil engineers in updating existing building codes in the Himlayan and surrounding regions and also for the evaluation of seismic hazards. The results clearly show that the attenuation relation developed for the Himalayan region should be only used, other attenuation relations based on other regions fail to provide good estimate of observed ground motion parameters.

  7. Ligand-directed tosyl chemistry for in situ native protein labeling and engineering in living systems: from basic properties to applications.

    Science.gov (United States)

    Tsukiji, Shinya; Hamachi, Itaru

    2014-08-01

    The ability to introduce any chemical probe to any endogenous target protein in its native environment, that is in cells and in vivo, is anticipated to provide various new exciting tools for biological and biomedical research. Although still at the prototype stage, the ligand-directed tosyl (LDT) chemistry is a novel type of affinity labeling technique that we developed for such a dream. This chemistry allows for modifying native proteins by various chemical probes with high specificity in various biological settings ranging from in vitro (in test tubes) to in living cells and in vivo. Since the first report, the list of proteins that are successfully labeled by the LDT chemistry has been increasing. A growing number of studies have demonstrated its utility to create semisynthetic proteins directly in cellular contexts. The in situ generated semisynthetic proteins are applicable for various types of analysis and imaging of intracellular biological processes. In this review, we summarize the basic properties of the LDT chemistry and its applications toward in situ engineering and analysis of native proteins in living systems. Current limitations and future challenges of this area are also described. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Mechanistic understanding of the cysteine capping modifications of antibodies enables selective chemical engineering in live mammalian cells.

    Science.gov (United States)

    Zhong, Xiaotian; He, Tao; Prashad, Amar S; Wang, Wenge; Cohen, Justin; Ferguson, Darren; Tam, Amy S; Sousa, Eric; Lin, Laura; Tchistiakova, Lioudmila; Gatto, Scott; D'Antona, Aaron; Luan, Yen-Tung; Ma, Weijun; Zollner, Richard; Zhou, Jing; Arve, Bo; Somers, Will; Kriz, Ronald

    2017-04-20

    Protein modifications by intricate cellular machineries often redesign the structure and function of existing proteins to impact biological networks. Disulfide bond formation between cysteine (Cys) pairs is one of the most common modifications found in extracellularly-destined proteins, key to maintaining protein structure. Unpaired surface cysteines on secreted mammalian proteins are also frequently found disulfide-bonded with free Cys or glutathione (GSH) in circulation or culture, the mechanism for which remains unknown. Here we report that these so-called Cys-capping modifications take place outside mammalian cells, not in the endoplasmic reticulum (ER) where oxidoreductase-mediated protein disulfide formation occurs. Unpaired surface cysteines of extracellularly-arrived proteins such as antibodies are uncapped upon secretion before undergoing disulfide exchange with cystine or oxidized GSH in culture medium. This observation has led to a feasible way to selectively modify the nucleophilic thiol side-chain of cell-surface or extracellular proteins in live mammalian cells, by applying electrophiles with a chemical handle directly into culture medium. These findings provide potentially an effective approach for improving therapeutic conjugates and probing biological systems. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. The LCLS Gas Attenuator Revisited

    International Nuclear Information System (INIS)

    Ryutov, D

    2005-01-01

    In the report ''X-ray attenuation cell'' [1] a preliminary analysis of the gas attenuator for the Linac Coherent Light Source (LCLS) was presented. This analysis was carried out for extremely stringent set of specifications. In particular, a very large diameter for the unobstructed beam was set (1 cm) to accommodate the spontaneous radiation; the attenuator was supposed to cover the whole range of energies of the coherent radiation, from 800 eV to 8000 eV; the maximum attenuation was set at the level of 10 4 ; the use of solid attenuators was not allowed, as well as the use of rotating shutters. The need to reach a sufficient absorption at the high-energy end of the spectrum predetermined the choice of Xe as the working gas (in order to have a reasonable absorption at a not-too-high pressure). A sophisticated differential pumping system that included a Penning-type ion pump was suggested in order to minimize the gas leak into the undulator/accelerator part of the facility. A high cost of xenon meant also that an efficient (and expensive) gas-recovery system would have to be installed. The main parameter that determined the high cost and the complexity of the system was a large radius of the orifice. The present viewpoint allows for much smaller size of the orifice, r 0 = 1.5 mm. (1) The use of solid attenuators is also allowed (R.M. Bionta, private communication). It is, therefore, worthwhile to reconsider various parameters of the gas attenuator for these much less stringent conditions. This brief study should be considered as a physics input for the engineering design. As a working gas we consider now the argon, which, on the one hand, provides a reasonable absorption lengths and, on the other hand, is inexpensive enough to be exhausted into the atmosphere (no recovery). The absorption properties of argon are illustrated by Fig.1 where the attenuation factor A is shown for various beam energies, based on Ref. [2]. The other relevant parameters for argon are

  10. Tracer attenuation in groundwater

    Science.gov (United States)

    Cvetkovic, Vladimir

    2011-12-01

    The self-purifying capacity of aquifers strongly depends on the attenuation of waterborne contaminants, i.e., irreversible loss of contaminant mass on a given scale as a result of coupled transport and transformation processes. A general formulation of tracer attenuation in groundwater is presented. Basic sensitivities of attenuation to macrodispersion and retention are illustrated for a few typical retention mechanisms. Tracer recovery is suggested as an experimental proxy for attenuation. Unique experimental data of tracer recovery in crystalline rock compare favorably with the theoretical model that is based on diffusion-controlled retention. Non-Fickian hydrodynamic transport has potentially a large impact on field-scale attenuation of dissolved contaminants.

  11. Utilisation of ISA Reverse Genetics and Large-Scale Random Codon Re-Encoding to Produce Attenuated Strains of Tick-Borne Encephalitis Virus within Days.

    Science.gov (United States)

    de Fabritus, Lauriane; Nougairède, Antoine; Aubry, Fabien; Gould, Ernest A; de Lamballerie, Xavier

    2016-01-01

    Large-scale codon re-encoding is a new method of attenuating RNA viruses. However, the use of infectious clones to generate attenuated viruses has inherent technical problems. We previously developed a bacterium-free reverse genetics protocol, designated ISA, and now combined it with large-scale random codon-re-encoding method to produce attenuated tick-borne encephalitis virus (TBEV), a pathogenic flavivirus which causes febrile illness and encephalitis in humans. We produced wild-type (WT) and two re-encoded TBEVs, containing 273 or 273+284 synonymous mutations in the NS5 and NS5+NS3 coding regions respectively. Both re-encoded viruses were attenuated when compared with WT virus using a laboratory mouse model and the relative level of attenuation increased with the degree of re-encoding. Moreover, all infected animals produced neutralizing antibodies. This novel, rapid and efficient approach to engineering attenuated viruses could potentially expedite the development of safe and effective new-generation live attenuated vaccines.

  12. ASSESSING AEROBIC NATURAL ATTENUATION OF TRICHLOROETHENE AT FOUR DOE SITES

    International Nuclear Information System (INIS)

    Koelsch, Michael C.; Starr, Robert C.; Sorenson, Kent S. Jr.

    2005-01-01

    A 3-year Department of Energy Environmental Science Management Program (EMSP) project is currently investigating natural attenuation of trichloroethane (TCE) in aerobic groundwater. This presentation summarizes the results of a screening process to identify TCE plumes at DOE facilities that are suitable for assessing the rate of TCE cometabolism under aerobic conditions. In order to estimate aerobic degradation rates, plumes had to meet the following criteria: TCE must be present in aerobic groundwater, a conservative co-contaminant must be present and have approximately the same source as TCE, and the groundwater velocity must be known. A total of 127 TCE plumes were considered across 24 DOE sites. The four sites retained for the assessment were: (1) Brookhaven National Laboratory, OU III; (2) Paducah Gaseous Diffusion Plant, Northwest Plume; (3) Rocky Flats Environmental Technology Site, Industrialized Area--Southwest Plume and 903 Pad South Plume; and (4) Savannah River Site, A/M Area Plume. For each of these sites, a co-contaminant derived from the same source area as TCE was used as a nonbiodegrading tracer. The tracer determined the extent to which concentration decreases in the plume can be accounted for solely by abiotic processes such as dispersion and dilution. Any concentration decreases not accounted for by these processes must be explained by some other natural attenuation mechanism. Thus, ''half-lives'' presented herein are in addition to attenuation that occurs due to hydrologic mechanisms. This ''tracer-corrected method'' has previously been used at the DOE's Idaho National Engineering and Environmental Laboratory in conjunction with other techniques to document the occurrence of intrinsic aerobic cometabolism. Application of this method to other DOE sites is the first step to determining whether this might be a significant natural attenuation mechanism on a broader scale. Application of the tracer-corrected method to data from the Brookhaven

  13. Engineering Obsolescence

    DEFF Research Database (Denmark)

    Cohn, Marisa

    2014-01-01

    Editor's Note: In this contribution to the series on Hackers, Makers, and Engineers, she tells us about her research on relationships to technological change in a long-lived NASA-ESA software infrastructure project. Her research considers how people live alongside technological change, inhabit...

  14. Repeating Spatial-Temporal Motifs of CA3 Activity Dependent on Engineered Inputs from Dentate Gyrus Neurons in Live Hippocampal Networks.

    Science.gov (United States)

    Bhattacharya, Aparajita; Desai, Harsh; DeMarse, Thomas B; Wheeler, Bruce C; Brewer, Gregory J

    2016-01-01

    Anatomical and behavioral studies, and in vivo and slice electrophysiology of the hippocampus suggest specific functions of the dentate gyrus (DG) and the CA3 subregions, but the underlying activity dynamics and repeatability of information processing remains poorly understood. To approach this problem, we engineered separate living networks of the DG and CA3 neurons that develop connections through 51 tunnels for axonal communication. Growing these networks on top of an electrode array enabled us to determine whether the subregion dynamics were separable and repeatable. We found spontaneous development of polarized propagation of 80% of the activity in the native direction from DG to CA3 and different spike and burst dynamics for these subregions. Spatial-temporal differences emerged when the relationships of target CA3 activity were categorized with to the number and timing of inputs from the apposing network. Compared to times of CA3 activity when there was no recorded tunnel input, DG input led to CA3 activity bursts that were 7× more frequent, increased in amplitude and extended in temporal envelope. Logistic regression indicated that a high number of tunnel inputs predict CA3 activity with 90% sensitivity and 70% specificity. Compared to no tunnel input, patterns of >80% tunnel inputs from DG specified different patterns of first-to-fire neurons in the CA3 target well. Clustering dendrograms revealed repeating motifs of three or more patterns at up to 17 sites in CA3 that were importantly associated with specific spatial-temporal patterns of tunnel activity. The number of these motifs recorded in 3 min was significantly higher than shuffled spike activity and not seen above chance in control networks in which CA3 was apposed to CA3 or DG to DG. Together, these results demonstrate spontaneous input-dependent repeatable coding of distributed activity in CA3 networks driven by engineered inputs from DG networks. These functional configurations at measured times

  15. Booster vaccination with safe, modified, live-attenuated mutants of Brucella abortus strain RB51 vaccine confers protective immunity against virulent strains of B. abortus and Brucella canis in BALB/c mice.

    Science.gov (United States)

    Truong, Quang Lam; Cho, Youngjae; Kim, Kiju; Park, Bo-Kyoung; Hahn, Tae-Wook

    2015-11-01

    Brucella abortus attenuated strain RB51 vaccine (RB51) is widely used in prevention of bovine brucellosis. Although vaccination with this strain has been shown to be effective in conferring protection against bovine brucellosis, RB51 has several drawbacks, including residual virulence for animals and humans. Therefore, a safe and efficacious vaccine is needed to overcome these disadvantages. In this study, we constructed several gene deletion mutants (ΔcydC, ΔcydD and ΔpurD single mutants, and ΔcydCΔcydD and ΔcydCΔpurD double mutants) of RB51 with the aim of increasing the safety of the possible use of these mutants as vaccine candidates. The RB51ΔcydC, RB51ΔcydD, RB51ΔpurD, RB51ΔcydCΔcydD and RB51ΔcydCΔpurD mutants exhibited significant attenuation of virulence when assayed in murine macrophages in vitro or in BALB/c mice. A single intraperitoneal immunization with RB51ΔcydC, RB51ΔcydD, RB51ΔcydCΔcydD or RB51ΔcydCΔpurD mutants was rapidly cleared from mice within 3 weeks, whereas the RB51ΔpurD mutant and RB51 were detectable in spleens until 4 and 7 weeks, respectively. Vaccination with a single dose of RB51 mutants induced lower protective immunity in mice than did parental RB51. However, a booster dose of these mutants provided significant levels of protection in mice against challenge with either the virulent homologous B. abortus strain 2308 or the heterologous Brucella canis strain 26. In addition, these mutants were found to induce a mixed but T-helper-1-biased humoral and cellular immune response in immunized mice. These data suggest that immunization with a booster dose of attenuated RB51 mutants provides an attractive strategy to protect against either bovine or canine brucellosis.

  16. [PERSPECTIVES OF DEVELOPMENT OF LIVE RECOMBINANT ANTHRAX VACCINES BASED ON OPPORTUNISTIC AND APATHOGENIC MICROORGANISMS].

    Science.gov (United States)

    Popova, P Yu; Mikshis, N I

    2016-01-01

    Live genetic engineering anthrax vaccines on the platform of avirulent and probiotic micro-organisms are a safe and adequate alternative to preparations based on attenuated Bacillus anthracis strains. Mucosal application results in a direct contact of the vaccine preparations with mucous membranes in those organs arid tissues of the macro-organisms, that are exposed to the pathogen in the first place, resulting in a development of local and systemic immune response. Live recombinant anthrax vaccines could be used both separately as well as in a prime-boost immunization scheme. The review focuses on immunogenic and protective properties of experimental live genetic engineering prearations, created based on members of geni of Salmonella, Lactobacillus and adenoviruses.

  17. Attenuation correction for SPECT

    International Nuclear Information System (INIS)

    Hosoba, Minoru

    1986-01-01

    Attenuation correction is required for the reconstruction of a quantitative SPECT image. A new method for detecting body contours, which are important for the correction of tissue attenuation, is presented. The effect of body contours, detected by the newly developed method, on the reconstructed images was evaluated using various techniques for attenuation correction. The count rates in the specified region of interest in the phantom image by the Radial Post Correction (RPC) method, the Weighted Back Projection (WBP) method, Chang's method were strongly affected by the accuracy of the contours, as compared to those by Sorenson's method. To evaluate the effect of non-uniform attenuators on the cardiac SPECT, computer simulation experiments were performed using two types of models, the uniform attenuator model (UAM) and the non-uniform attenuator model (NUAM). The RPC method showed the lowest relative percent error (%ERROR) in UAM (11 %). However, 20 to 30 percent increase in %ERROR was observed for NUAM reconstructed with the RPC, WBP, and Chang's methods. Introducing an average attenuation coefficient (0.12/cm for Tc-99m and 0.14/cm for Tl-201) in the RPC method decreased %ERROR to the levels for UAM. Finally, a comparison between images, which were obtained by 180 deg and 360 deg scans and reconstructed from the RPC method, showed that the degree of the distortion of the contour of the simulated ventricles in the 180 deg scan was 15 % higher than that in the 360 deg scan. (Namekawa, K.)

  18. Landing gear noise attenuation

    Science.gov (United States)

    Moe, Jeffrey W. (Inventor); Whitmire, Julia (Inventor); Kwan, Hwa-Wan (Inventor); Abeysinghe, Amal (Inventor)

    2011-01-01

    A landing gear noise attenuator mitigates noise generated by airframe deployable landing gear. The noise attenuator can have a first position when the landing gear is in its deployed or down position, and a second position when the landing gear is in its up or stowed position. The noise attenuator may be an inflatable fairing that does not compromise limited space constraints associated with landing gear retraction and stowage. A truck fairing mounted under a truck beam can have a compliant edge to allow for non-destructive impingement of a deflected fire during certain conditions.

  19. A live-attenuated chimeric porcine circovirus type 2 (PCV2) vaccine is transmitted to contact pigs but is not upregulated by concurrent infection with porcine parvovirus (PPV) and porcine reproductive and respiratory syndrome virus (PRRSV) and is efficacious in a PCV2b-PRRSV-PPV challenge model.

    Science.gov (United States)

    Opriessnig, T; Shen, H G; Pal, N; Ramamoorthy, S; Huang, Y W; Lager, K M; Beach, N M; Halbur, P G; Meng, X J

    2011-08-01

    The live chimeric porcine circovirus type 2 (PCV2) vaccine with the capsid gene of the emerging subtype 2b cloned in the genomic backbone of the nonpathogenic PCV1 is attenuated in vivo and induces protective immunity against PCV2. To further determine the safety and efficacy of this experimental vaccine, we tested for evidence of pig-to-pig transmission by commingling nonvaccinated and vaccinated pigs, determined potential upregulation by simultaneous vaccination and infection with porcine parvovirus (PPV) and porcine reproductive and respiratory syndrome virus (PRRSV), and determined vaccine efficacy by challenging pigs 4 weeks after vaccination with PCV2b, PRRSV, and PPV. Forty-six 21-day-old, PCV2-naïve pigs were randomly assigned to one of six groups. Twenty-nine of 46 pigs were challenged with PCV2b, PRRSV, and PPV at day 28, 8/46 remained nonvaccinated and nonchallenged and served as negative controls, and 9/46 remained nonchallenged and served as vaccination controls. All animals were necropsied at day 49. PCV1-PCV2 viremia was detected in nonvaccinated contact pigs commingled with vaccinated pigs, indicating pig-to-pig transmission; however, PCV1-PCV2 DNA levels remained low in all vaccinated and contact pigs regardless of concurrent infection. Finally, vaccination 28 days before challenge resulted in significantly (P attenuated chimeric PCV2 vaccine, although transmissible to contact pigs, remains attenuated in pigs concurrently infected with PRRSV and PPV and induces protective immunity against PCV2b when it is administered 28 days before PCV2 exposure.

  20. A Live-Attenuated Chimeric Porcine Circovirus Type 2 (PCV2) Vaccine Is Transmitted to Contact Pigs but Is Not Upregulated by Concurrent Infection with Porcine Parvovirus (PPV) and Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) and Is Efficacious in a PCV2b-PRRSV-PPV Challenge Model▿

    Science.gov (United States)

    Opriessnig, T.; Shen, H. G.; Pal, N.; Ramamoorthy, S.; Huang, Y. W.; Lager, K. M.; Beach, N. M.; Halbur, P. G.; Meng, X. J.

    2011-01-01

    The live chimeric porcine circovirus type 2 (PCV2) vaccine with the capsid gene of the emerging subtype 2b cloned in the genomic backbone of the nonpathogenic PCV1 is attenuated in vivo and induces protective immunity against PCV2. To further determine the safety and efficacy of this experimental vaccine, we tested for evidence of pig-to-pig transmission by commingling nonvaccinated and vaccinated pigs, determined potential upregulation by simultaneous vaccination and infection with porcine parvovirus (PPV) and porcine reproductive and respiratory syndrome virus (PRRSV), and determined vaccine efficacy by challenging pigs 4 weeks after vaccination with PCV2b, PRRSV, and PPV. Forty-six 21-day-old, PCV2-naïve pigs were randomly assigned to one of six groups. Twenty-nine of 46 pigs were challenged with PCV2b, PRRSV, and PPV at day 28, 8/46 remained nonvaccinated and nonchallenged and served as negative controls, and 9/46 remained nonchallenged and served as vaccination controls. All animals were necropsied at day 49. PCV1-PCV2 viremia was detected in nonvaccinated contact pigs commingled with vaccinated pigs, indicating pig-to-pig transmission; however, PCV1-PCV2 DNA levels remained low in all vaccinated and contact pigs regardless of concurrent infection. Finally, vaccination 28 days before challenge resulted in significantly (P attenuated chimeric PCV2 vaccine, although transmissible to contact pigs, remains attenuated in pigs concurrently infected with PRRSV and PPV and induces protective immunity against PCV2b when it is administered 28 days before PCV2 exposure. PMID:21653745

  1. Genetically attenuated P36p-deficient Plasmodium berghei sporozoites confer long-lasting and partial cross-species protection

    NARCIS (Netherlands)

    Douradinha, Bruno; van Dijk, Melissa R.; Ataide, Ricardo; van Gemert, Geert-Jan; Thompson, Joanne; Franetich, Jean-Francois; Mazier, Dominique; Luty, Adrian J. F.; Sauerwein, Robert; Janse, Chris J.; Waters, Andrew P.; Mota, Maria M.

    2007-01-01

    Immunisation with live, radiation-attenuated sporozoites (RAS) or genetically attenuated sporozoites (GAS) of rodent plasmodial parasites protects against subsequent challenge infections. We recently showed that immunisation with Plasinodium berghei GAS that lack the microneme protein P36p protects

  2. Comparison of the efficacy of Neethling lumpy skin disease virus and x10RM65 sheep-pox live attenuated vaccines for the prevention of lumpy skin disease - The results of a randomized controlled field study.

    Science.gov (United States)

    Ben-Gera, J; Klement, E; Khinich, E; Stram, Y; Shpigel, N Y

    2015-09-11

    Lumpy skin disease (LSD) is a viral disease of cattle and buffalo, caused by a Capripox virus. A field study was performed during an LSD epidemic which occurred in 2012-2013 in Israel, in order to assess the efficacy of two commercial vaccines for protection against LSD. Fifteen dairy herds, vaccinated 2-5 months prior to study onset with a single dose of 10(2.5) TCID50 of RM65 attenuated sheep-pox vaccine, and not affected previously, were enrolled in the study. 4694 cows were randomized to be either vaccinated with a 10(3.5) TCID50/dose of RM65 vaccine (x10RM65) or with a same dose of an attenuated Neethling LSD virus vaccine. A case of LSD was defined as the appearance of at least 5 lesions typical to LSD and a severe case was defined if this sign was accompanied by either fever (>39.5°C) or/and a 20% reduction in milk production. Deep lesion biopsies and blood samples were collected from 64.5% of the cases in an attempt to detect DNA of LSD virus by PCR and to differentiate between the wild strain and the vaccine Neethling strain. Seventy-six cows were affected by LSD in 8 herds with an incidence of 0.3-5.7%. Mantel-Haenszel relative risk (RRMH) for LSD morbidity at least 15 days after vaccination in x10RM65 vs. Neethling was 2.635 (CI95%=1.44-4.82) and 11.2 (2.3-54.7) for severe morbidity. RRMH for laboratory confirmed cases was 4.28 (1.59-11.53). An incidence of 0.38% (9/2356) of Neethling associated disease was observed among Neethling vaccinated cows while no such disease occurred in x10RM65 vaccinated cows. We conclude that the Neethling vaccine is significantly more effective than x10RM65 in preventing LSD morbidity, though it might cause a low incidence of Neethling associated disease. No transmission of the Neethling strain to non-Neethling vaccinated cows was observed in this study. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Intramuscular Immunization of Mice with a Live-Attenuated Triple Mutant of Yersinia pestis CO92 Induces Robust Humoral and Cell-Mediated Immunity To Completely Protect Animals against Pneumonic Plague.

    Science.gov (United States)

    Tiner, Bethany L; Sha, Jian; Ponnusamy, Duraisamy; Baze, Wallace B; Fitts, Eric C; Popov, Vsevolod L; van Lier, Christina J; Erova, Tatiana E; Chopra, Ashok K

    2015-12-01

    Earlier, we showed that the Δlpp ΔmsbB Δail triple mutant of Yersinia pestis CO92 with deleted genes encoding Braun lipoprotein (Lpp), an acyltransferase (MsbB), and the attachment invasion locus (Ail), respectively, was avirulent in a mouse model of pneumonic plague. In this study, we further evaluated the immunogenic potential of the Δlpp ΔmsbB Δail triple mutant and its derivative by different routes of vaccination. Mice were immunized via the subcutaneous (s.c.) or the intramuscular (i.m.) route with two doses (2 × 10(6) CFU/dose) of the above-mentioned triple mutant with 100% survivability of the animals. Upon subsequent pneumonic challenge with 70 to 92 50% lethal doses (LD(50)) of wild-type (WT) strain CO92, all of the mice survived when immunization occurred by the i.m. route. Since Ail has virulence and immunogenic potential, a mutated version of Ail devoid of its virulence properties was created, and the genetically modified ail replaced the native ail gene on the chromosome of the Δlpp ΔmsbB double mutant, creating a Δlpp ΔmsbB::ailL2 vaccine strain. This newly generated mutant was attenuated similarly to the Δlpp ΔmsbB Δail triple mutant when administered by the i.m. route and provided 100% protection to animals against subsequent pneumonic challenge. Not only were the two above-mentioned mutants cleared rapidly from the initial i.m. site of injection in animals with no histopathological lesions, the immunized mice did not exhibit any disease symptoms during immunization or after subsequent exposure to WT CO92. These two mutants triggered balanced Th1- and Th2-based antibody responses and cell-mediated immunity. A substantial increase in interleukin-17 (IL-17) from the T cells of vaccinated mice, a cytokine of the Th17 cells, further augmented their vaccine potential. Thus, the Δlpp ΔmsbB Δail and Δlpp ΔmsbB::ailL2 mutants represent excellent vaccine candidates for plague, with the latter mutant still retaining Ail immunogenicity but

  4. Engineering nanoparticle-coated bacteria as oral DNA vaccines for cancer immunotherapy.

    Science.gov (United States)

    Hu, Qinglian; Wu, Min; Fang, Chun; Cheng, Changyong; Zhao, Mengmeng; Fang, Weihuan; Chu, Paul K; Ping, Yuan; Tang, Guping

    2015-04-08

    Live attenuated bacteria are of increasing importance in biotechnology and medicine in the emerging field of cancer immunotherapy. Oral DNA vaccination mediated by live attenuated bacteria often suffers from low infection efficiency due to various biological barriers during the infection process. To this end, we herein report, for the first time, a new strategy to engineer cationic nanoparticle-coated bacterial vectors that can efficiently deliver oral DNA vaccine for efficacious cancer immunotherapy. By coating live attenuated bacteria with synthetic nanoparticles self-assembled from cationic polymers and plasmid DNA, the protective nanoparticle coating layer is able to facilitate bacteria to effectively escape phagosomes, significantly enhance the acid tolerance of bacteria in stomach and intestines, and greatly promote dissemination of bacteria into blood circulation after oral administration. Most importantly, oral delivery of DNA vaccines encoding autologous vascular endothelial growth factor receptor 2 (VEGFR2) by this hybrid vector showed remarkable T cell activation and cytokine production. Successful inhibition of tumor growth was also achieved by efficient oral delivery of VEGFR2 with nanoparticle-coated bacterial vectors due to angiogenesis suppression in the tumor vasculature and tumor necrosis. This proof-of-concept work demonstrates that coating live bacterial cells with synthetic nanoparticles represents a promising strategy to engineer efficient and versatile DNA vaccines for the era of immunotherapy.

  5. Radiofrequency attenuator and method

    Science.gov (United States)

    Warner, Benjamin P [Los Alamos, NM; McCleskey, T Mark [Los Alamos, NM; Burrell, Anthony K [Los Alamos, NM; Agrawal, Anoop [Tucson, AZ; Hall, Simon B [Palmerston North, NZ

    2009-01-20

    Radiofrequency attenuator and method. The attenuator includes a pair of transparent windows. A chamber between the windows is filled with molten salt. Preferred molten salts include quarternary ammonium cations and fluorine-containing anions such as tetrafluoroborate (BF.sub.4.sup.-), hexafluorophosphate (PF.sub.6.sup.-), hexafluoroarsenate (AsF.sub.6.sup.-), trifluoromethylsulfonate (CF.sub.3SO.sub.3.sup.-), bis(trifluoromethylsulfonyl)imide ((CF.sub.3SO.sub.2).sub.2N.sup.-), bis(perfluoroethylsulfonyl)imide ((CF.sub.3CF.sub.2SO.sub.2).sub.2N.sup.-) and tris(trifluoromethylsulfonyl)methide ((CF.sub.3SO.sub.2).sub.3C.sup.-). Radicals or radical cations may be added to or electrochemically generated in the molten salt to enhance the RF attenuation.

  6. Attenuation coefficients of soils

    International Nuclear Information System (INIS)

    Martini, E.; Naziry, M.J.

    1989-01-01

    As a prerequisite to the interpretation of gamma-spectrometric in situ measurements of activity concentrations of soil radionuclides the attenuation of 60 to 1332 keV gamma radiation by soil samples varying in water content and density has been investigated. A useful empirical equation could be set up to describe the dependence of the mass attenuation coefficient upon photon energy for soil with a mean water content of 10%, with the results comparing well with data in the literature. The mean density of soil in the GDR was estimated at 1.6 g/cm 3 . This value was used to derive the linear attenuation coefficients, their range of variation being 10%. 7 figs., 5 tabs. (author)

  7. Computer-controlled attenuator.

    Science.gov (United States)

    Mitov, D; Grozev, Z

    1991-01-01

    Various possibilities for applying electronic computer-controlled attenuators for the automation of physiological experiments are considered. A detailed description is given of the design of a 4-channel computer-controlled attenuator, in two of the channels of which the output signal can change by a linear step, in the other two channels--by a logarithmic step. This, together with the existence of additional programmable timers, allows to automate a wide range of studies in different spheres of physiology and psychophysics, including vision and hearing.

  8. Natural attenuation of herbicides

    DEFF Research Database (Denmark)

    Tuxen, Nina; Højberg, Anker Lajer; Broholm, Mette Martina

    2002-01-01

    A field injection experiment in a sandy, aerobic aquifer showed that two phenoxy acids MCPP (mecoprop) and dichlorprop were degraded within I in downgradient of the injection wells after an apparent lag period. The plume development and microbial measurements indicated that microbial growth gover....... The observations may be important for application of natural attenuation as a remedy in field scale systems....

  9. Photon attenuation by intensifying screens

    International Nuclear Information System (INIS)

    Holje, G.

    1983-01-01

    The photon attenuation by intensifying screens of different chemical composition has been determined. The attenuation of photons between 20 keV and 120 keV was measured by use of a multi-channel analyzer and a broad bremsstrahlung distribution. The attenuation by the intensifying screens was hereby determined simultaneously at many different monoenergetic photon energies. Experimentally determined attenuations were found to agree well with attenuation calculated from mass attenuation coefficients. The attenuation by the screens was also determined at various bremsstrahlung distributions, simulating those occurring behind the patient in various diagnostic X-ray examinations. The high attenuation in some of the intensifying screens form the basis for an analysis of the construction of asymmetric screen pairs. Single screen systems are suggested as a favourable alternative to thick screen pair systems. (Author)

  10. Healthy Living

    Science.gov (United States)

    ... Health Menu Topics Environment & Health Healthy Living Pollution Reduce, Reuse, Recycle Science – How It Works The Natural World Games ... Lessons Topics Expand Environment & Health Healthy Living Pollution Reduce, Reuse, Recycle Science – How It Works The Natural World Games ...

  11. Enhanced Attenuation: Chlorinated Organics

    Science.gov (United States)

    2008-04-01

    attenuation capacity of the aquifer downgradient from the source (e.g., permeable reactive barriers or phytoremediation ) Selection of EA remedies should be...prevalence and/or mobility of nitrate and sulfate compounds and/or metals such as iron, manganese, chromium, copper, and arsenic . Furthermore, in...ranging from very aggressive source destruction and removal methods to less energy-intensive methods, such as phytoremediation . In many cases, it

  12. Assisted Living

    Science.gov (United States)

    ... it, too. Back to top What is the Cost for Assisted Living? Although assisted living costs less than nursing home ... Primarily, older persons or their families pay the cost of assisted living. Some health and long-term care insurance policies ...

  13. Control algorithms for dynamic attenuators

    Energy Technology Data Exchange (ETDEWEB)

    Hsieh, Scott S., E-mail: sshsieh@stanford.edu [Department of Radiology, Stanford University, Stanford, California 94305 and Department of Electrical Engineering, Stanford University, Stanford, California 94305 (United States); Pelc, Norbert J. [Department of Radiology, Stanford University, Stanford California 94305 and Department of Bioengineering, Stanford University, Stanford, California 94305 (United States)

    2014-06-15

    Purpose: The authors describe algorithms to control dynamic attenuators in CT and compare their performance using simulated scans. Dynamic attenuators are prepatient beam shaping filters that modulate the distribution of x-ray fluence incident on the patient on a view-by-view basis. These attenuators can reduce dose while improving key image quality metrics such as peak or mean variance. In each view, the attenuator presents several degrees of freedom which may be individually adjusted. The total number of degrees of freedom across all views is very large, making many optimization techniques impractical. The authors develop a theory for optimally controlling these attenuators. Special attention is paid to a theoretically perfect attenuator which controls the fluence for each ray individually, but the authors also investigate and compare three other, practical attenuator designs which have been previously proposed: the piecewise-linear attenuator, the translating attenuator, and the double wedge attenuator. Methods: The authors pose and solve the optimization problems of minimizing the mean and peak variance subject to a fixed dose limit. For a perfect attenuator and mean variance minimization, this problem can be solved in simple, closed form. For other attenuator designs, the problem can be decomposed into separate problems for each view to greatly reduce the computational complexity. Peak variance minimization can be approximately solved using iterated, weighted mean variance (WMV) minimization. Also, the authors develop heuristics for the perfect and piecewise-linear attenuators which do not requirea priori knowledge of the patient anatomy. The authors compare these control algorithms on different types of dynamic attenuators using simulated raw data from forward projected DICOM files of a thorax and an abdomen. Results: The translating and double wedge attenuators reduce dose by an average of 30% relative to current techniques (bowtie filter with tube current

  14. Control algorithms for dynamic attenuators

    International Nuclear Information System (INIS)

    Hsieh, Scott S.; Pelc, Norbert J.

    2014-01-01

    Purpose: The authors describe algorithms to control dynamic attenuators in CT and compare their performance using simulated scans. Dynamic attenuators are prepatient beam shaping filters that modulate the distribution of x-ray fluence incident on the patient on a view-by-view basis. These attenuators can reduce dose while improving key image quality metrics such as peak or mean variance. In each view, the attenuator presents several degrees of freedom which may be individually adjusted. The total number of degrees of freedom across all views is very large, making many optimization techniques impractical. The authors develop a theory for optimally controlling these attenuators. Special attention is paid to a theoretically perfect attenuator which controls the fluence for each ray individually, but the authors also investigate and compare three other, practical attenuator designs which have been previously proposed: the piecewise-linear attenuator, the translating attenuator, and the double wedge attenuator. Methods: The authors pose and solve the optimization problems of minimizing the mean and peak variance subject to a fixed dose limit. For a perfect attenuator and mean variance minimization, this problem can be solved in simple, closed form. For other attenuator designs, the problem can be decomposed into separate problems for each view to greatly reduce the computational complexity. Peak variance minimization can be approximately solved using iterated, weighted mean variance (WMV) minimization. Also, the authors develop heuristics for the perfect and piecewise-linear attenuators which do not requirea priori knowledge of the patient anatomy. The authors compare these control algorithms on different types of dynamic attenuators using simulated raw data from forward projected DICOM files of a thorax and an abdomen. Results: The translating and double wedge attenuators reduce dose by an average of 30% relative to current techniques (bowtie filter with tube current

  15. Control algorithms for dynamic attenuators.

    Science.gov (United States)

    Hsieh, Scott S; Pelc, Norbert J

    2014-06-01

    The authors describe algorithms to control dynamic attenuators in CT and compare their performance using simulated scans. Dynamic attenuators are prepatient beam shaping filters that modulate the distribution of x-ray fluence incident on the patient on a view-by-view basis. These attenuators can reduce dose while improving key image quality metrics such as peak or mean variance. In each view, the attenuator presents several degrees of freedom which may be individually adjusted. The total number of degrees of freedom across all views is very large, making many optimization techniques impractical. The authors develop a theory for optimally controlling these attenuators. Special attention is paid to a theoretically perfect attenuator which controls the fluence for each ray individually, but the authors also investigate and compare three other, practical attenuator designs which have been previously proposed: the piecewise-linear attenuator, the translating attenuator, and the double wedge attenuator. The authors pose and solve the optimization problems of minimizing the mean and peak variance subject to a fixed dose limit. For a perfect attenuator and mean variance minimization, this problem can be solved in simple, closed form. For other attenuator designs, the problem can be decomposed into separate problems for each view to greatly reduce the computational complexity. Peak variance minimization can be approximately solved using iterated, weighted mean variance (WMV) minimization. Also, the authors develop heuristics for the perfect and piecewise-linear attenuators which do not require a priori knowledge of the patient anatomy. The authors compare these control algorithms on different types of dynamic attenuators using simulated raw data from forward projected DICOM files of a thorax and an abdomen. The translating and double wedge attenuators reduce dose by an average of 30% relative to current techniques (bowtie filter with tube current modulation) without

  16. Living Technology

    DEFF Research Database (Denmark)

    2010-01-01

    This book is aimed at anyone who is interested in learning more about living technology, whether coming from business, the government, policy centers, academia, or anywhere else. Its purpose is to help people to learn what living technology is, what it might develop into, and how it might impact...... our lives. The phrase 'living technology' was coined to refer to technology that is alive as well as technology that is useful because it shares the fundamental properties of living systems. In particular, the invention of this phrase was called for to describe the trend of our technology becoming...... increasingly life-like or literally alive. Still, the phrase has different interpretations depending on how one views what life is. This book presents nineteen perspectives on living technology. Taken together, the interviews convey the collective wisdom on living technology's power and promise, as well as its...

  17. Software engineering

    CERN Document Server

    Sommerville, Ian

    2016-01-01

    For courses in computer science and software engineering The Fundamental Practice of Software Engineering Software Engineering introduces readers to the overwhelmingly important subject of software programming and development. In the past few years, computer systems have come to dominate not just our technological growth, but the foundations of our world's major industries. This text seeks to lay out the fundamental concepts of this huge and continually growing subject area in a clear and comprehensive manner. The Tenth Edition contains new information that highlights various technological updates of recent years, providing readers with highly relevant and current information. Sommerville's experience in system dependability and systems engineering guides the text through a traditional plan-based approach that incorporates some novel agile methods. The text strives to teach the innovators of tomorrow how to create software that will make our world a better, safer, and more advanced place to live.

  18. Development of an attenuated live heartwater vaccine for use in ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    ... it requires ultra-cold storage (-196° C), intravenous administration by veterinary health professionals, ... It is expected that by the end of the project, the production process of the new heartwater vaccine will ... Agricultural Research Council.

  19. Immunogenicity and safety of a live attenuated varicella vaccine in ...

    African Journals Online (AJOL)

    children were vaccinated, of whom 189 (44,5%) completed the study. ... varicella vaccination.. Results. The vaccine was safe and well tolerated. No local symptoms were ... of varicella (e.g. encephalitis, pneumonia, scars); inhibition of the spread of the .... intestinal disorders, respiratory infections, measles and conjunctivitis) ...

  20. Simulation on the shock attenuation behavior of coupled RHA and ...

    African Journals Online (AJOL)

    This paper presents the shock attenuation behavior of engineering materials namely Rolled Homogenous Armor (RHA) and sandwich composite when subject to blast loadings. Blast loading on sandwich composite structure and monolithic material are investigated using LSDYNA 3D with Arbitrary LagrangianEulerian ...

  1. Seringas hipodérmicas descartáveis versus reutilizáveis: estudo de possíveis efeitos sobre o vírus da vacina viva, atenuada contra o sarampo Disposable versus reusable hypodermic syringes: study of feasible effects upon the virus of the live, attenuated measles vaccine

    Directory of Open Access Journals (Sweden)

    Edda de Rizzo

    1986-12-01

    Full Text Available Objetivou-se verificar entre seringas hipodérmicas descartáveis e reutilizáveis qual interfere mais com o vírus vivo presente na vacina contra o sarampo. Vacinas pertencentes a dois lotes foram reconstituídas com os dois tipos de seringas, de modo a formarem dois pools distintos, mantidos à temperatura de +2 a+8°C e protegidos da luz. De cada lote foram realizadas, no mínimo, seis titulações em paralelo, com amostragem a cada hora, de zero a seis horas após reconstituição. A análise estatística dos resultados obtidos nas titulações, feita pelo sistema de retas de regressão demonstrou que embora as vacinas manipuladas com ambos os tipos de seringas apresentassem um decréscimo de título estatisticamente significativo com o decorrer das horas, ele foi bem mais acentuado para as vacinas reconstituídas com seringas reutilizáveis. A menor interferência das descartáveis no título da vacina viva, atenuada contra o sarampo, demonstrou que a preconização e uso desse tipo de seringas pela Secretaria de Estado da Saúde de São Paulo é o ideal e recomendável, por preservar mais a vacina desde a reconstituição até sua administração e, conseqüentemente, a sua eficácia na prevenção dessa infecção.The study was performed in the State of S.Paulo, SP, Brazil, with the purpose of finding out whether reusable (glass and disposable hypodermic syringes used for administration of live attenuated measles vaccines would interfere with their virus. At least six different experiments using two distinct lots of vaccines were carried out. Each time, a lot was reconstituted with reusable and disposable syringes in parallel to form separate pools from which samples were collected hourly from zero to the sixtieth hour after reconstitution for virus titration in monolayers of Vero cells. The straight line regression system chosen for the analysis of the results demonstrated that although vaccines reconstituted with both types of syringes

  2. Live Well

    Science.gov (United States)

    ... Health Conditions Live Well Mental Health Substance Use Smoking Healthy Diet Physical Activity Family Planning Living with HIV: Travel ... to his or her health and well-being. Smoking - Tobacco use is the ... year. Healthy Diet - No matter your HIV status, healthy eating is ...

  3. Healthy living

    Science.gov (United States)

    ... living URL of this page: //medlineplus.gov/ency/article/002393.htm Healthy living To use the sharing features on this page, please enable JavaScript. Good health habits can allow you to avoid illness and improve your quality of life. The following steps will help you ...

  4. Moving Real Exergaming Engines on the Web: The webFitForAll Case Study in an Active and Healthy Ageing Living Lab Environment.

    Science.gov (United States)

    Konstantinidis, Evdokimos I; Bamparopoulos, Giorgos; Bamidis, Panagiotis D

    2017-05-01

    Exergames have been the subject of research and technology innovations for a number of years. Different devices and technologies have been utilized to train the body and the mind of senior people or different patient groups. In the past, we presented FitForAll, the protocol efficacy of which was proven through widely taken (controlled) pilots with more than 116 seniors for a period of two months. The current piece of work expands this and presents the first truly web exergaming platform, which is solely based on HTML5 and JavaScript without any browser plugin requirements. The adopted architecture (controller application communication framework) combines a unified solution for input devices such as MS Kinect and Wii Balance Βoard which may seamlessly be exploited through standard physical exercise protocols (American College of Sports Medicine guidelines) and accommodate high detail logging; this allows for proper pilot testing and usability evaluations in ecologically valid Living Lab environments. The latter type of setups is also used herein for evaluating the web application with more than a dozen of real elderly users following quantitative approaches.

  5. Living PSA

    International Nuclear Information System (INIS)

    Evans, M.G.K.

    1997-01-01

    The aim of this presentation is to gain an understanding of the requirements for a PSA to be considered a Living PSA. The presentation is divided into the following topics: Definition; Planning/Documentation; Task Performance; Maintenance; Management. 4 figs

  6. Ultrasonic attenuation in superconducting zinc

    International Nuclear Information System (INIS)

    Auluck, S.

    1978-01-01

    The differences in the Zn ultrasonic attenuation data of different workers are analyzed. The superconducting energy gaps deduced from our analysis of the ultrasonic-attenuation data of Cleavelin and Marshall are consistent with the gaps deduced from the knowledge of the Fermi surface and the electron-phonon mass enhancement factor

  7. Properties of sound attenuation around a two-dimensional underwater vehicle with a large cavitation number

    International Nuclear Information System (INIS)

    Ye Peng-Cheng; Pan Guang

    2015-01-01

    Due to the high speed of underwater vehicles, cavitation is generated inevitably along with the sound attenuation when the sound signal traverses through the cavity region around the underwater vehicle. The linear wave propagation is studied to obtain the influence of bubbly liquid on the acoustic wave propagation in the cavity region. The sound attenuation coefficient and the sound speed formula of the bubbly liquid are presented. Based on the sound attenuation coefficients with various vapor volume fractions, the attenuation of sound intensity is calculated under large cavitation number conditions. The result shows that the sound intensity attenuation is fairly small in a certain condition. Consequently, the intensity attenuation can be neglected in engineering. (paper)

  8. Assisted Living

    Science.gov (United States)

    ... a resident's needs depends as much on the philosophy and services of the assisted living facility as it does on the quality of care. The Administration on Aging, a part of the U.S. Department of Health and Human Services (HHS), offers these suggestions to help you ...

  9. Easier living?

    DEFF Research Database (Denmark)

    Høholt, Stine

    2005-01-01

    I ph.d.-projektet: "Easier Living? Streamline design og den æstetiserede livsverden" analyseres 1930'ernes Streamline-bevægelse, som tilhører den amerikanske modernisme inden for industrielt produktdesign. Bevægelsens glatte, strømlinede produkter bliver med deres enorme udbredelse det historiske...

  10. Austrian Lives

    OpenAIRE

    Bischof, Günter; Plasser, Fritz; Maltschnig, Eva

    2012-01-01

    Writing biographies for a long time had been a male hegemonic project. Ever since Plutarch and Sueton composed their vitae of the greats of classical antiquity, to the medieval obsession with the hagiographies of holy men (and a few women) and saints, Vasari's lives of great Renaissance artists, down to the French encyclopedists, Dr. Johnson and Lytton Strachey, as well as Ranke and Droysen the genre of biographical writing has become increasingly more refined. In the twentieth century male p...

  11. Attenuation in Superconducting Circular Waveguides

    Directory of Open Access Journals (Sweden)

    K. H. Yeap

    2016-09-01

    Full Text Available We present an analysis on wave propagation in superconducting circular waveguides. In order to account for the presence of quasiparticles in the intragap states of a superconductor, we employ the characteristic equation derived from the extended Mattis-Bardeen theory to compute the values of the complex conductivity. To calculate the attenuation in a circular waveguide, the tangential fields at the boundary of the wall are first matched with the electrical properties (which includes the complex conductivity of the wall material. The matching of fields with the electrical properties results in a set of transcendental equations which is able to accurately describe the propagation constant of the fields. Our results show that although the attenuation in the superconducting waveguide above cutoff (but below the gap frequency is finite, it is considerably lower than that in a normal waveguide. Above the gap frequency, however, the attenuation in the superconducting waveguide increases sharply. The attenuation eventually surpasses that in a normal waveguide. As frequency increases above the gap frequency, Cooper pairs break into quasiparticles. Hence, we attribute the sharp rise in attenuation to the increase in random collision of the quasiparticles with the lattice structure.

  12. Functional living biointerfaces to direct cell-material interaction

    OpenAIRE

    Rodrigo Navarro, Aleixandre

    2016-01-01

    [EN] This thesis deals with the development of a living biointerface between synthetic substrates and living cells to engineer cell-material interactions for tissue engineering purposes. This living biointerface is made of Lactococcus lactis, a non-pathogenic lactic bacteria widely used as starter in the dairy industry and, recently, in the expression of heterologous proteins in applications such as oral vaccine delivery or membrane-bound expression of proteins. L. lactis has been engine...

  13. Living Lands

    DEFF Research Database (Denmark)

    Christensen, Suna Møller

    2015-01-01

    , hunters attended to questions like safe-journeying on ice or the role of natural surroundings in children’s education, in ways revealing a relational perception of ‘nature’ and dissolving culture-nature dualisms. Hunters’ experiences in living the land afforded children a dwelling position from which...... to grow with the features of the land. Framed this way, ‘nature’ was regarded as part of the social world. I suggest that learning among Arctic hunters is social and twofold. First, we can learn how human-environment relations influence individual life trajectories. Secondly, ‘nature’ as part...

  14. Lively package

    International Nuclear Information System (INIS)

    Jaremko, G.

    1997-01-01

    Progress on the Lloydminster Heavy Oil Interpretive Centre, sponsored by the Lloydminster Oilfield Technical Society and expected to open in late 1998, was discussed. Some $150,000 of the $750,000 budget is already in the bank, and another $150,000 is in the pipeline. The Centre will be added to an existing and well-established visitor's site. It is reported to contain a lively and imaginatively-designed exhibit package, and promises to become a combination of educational tool and tourist attraction for the town of Lloydminster, Saskatchewan, in the heart of heavy oil country

  15. Engineering Encounters: Engineering Adaptations

    Science.gov (United States)

    Gatling, Anne; Vaughn, Meredith Houle

    2015-01-01

    Engineering is not a subject that has historically been taught in elementary schools, but with the emphasis on engineering in the "Next Generation Science Standards," curricula are being developed to explicitly teach engineering content and design. However, many of the scientific investigations already conducted with students have…

  16. Josephson tunnel junction microwave attenuator

    DEFF Research Database (Denmark)

    Koshelets, V. P.; Shitov, S. V.; Shchukin, A. V.

    1993-01-01

    A new element for superconducting electronic circuitry-a variable attenuator-has been proposed, designed, and successfully tested. The principle of operation is based on the change in the microwave impedance of a superconductor-insulator-superconductor (SIS) Josephson tunnel junction when dc biased...... at different points in the current-voltage characteristic. Both numerical calculations based on the Tien-Gordon theory and 70-GHz microwave experiments have confirmed the wide dynamic range (more than 15-dB attenuation for one stage) and the low insertion loss in the ''open'' state. The performance of a fully...

  17. Swine dysentery: protection of pigs by oral and parenteral immunisation with attenuated Treponema hyodysenteriae.

    Science.gov (United States)

    Hudson, M J; Alexander, T J; Lysons, R J; Prescott, J F

    1976-11-01

    An attenuated strain of Treponema hyodysenteriae was used to immunise 18 pigs in three experiments. Live attenuated spirochaetes were dosed orally and injected intra-peritoneally, and killed spirochaetes were injected intramuscularly with adjuvant. The vaccinated pigs, which developed high serum agglutination titres against T hyodysenteriae, and 18 unvaccinated litter-mates were repeatedly challenged with virulent T hyodysenteriae. Nine vaccinated pigs and 16 control pigs developed typical swine dysentery.

  18. Gain attenuation of gated framing camera

    International Nuclear Information System (INIS)

    Xiao Shali; Liu Shenye; Cao Zhurong; Li Hang; Zhang Haiying; Yuan Zheng; Wang Liwei

    2009-01-01

    The theoretic model of framing camera's gain attenuation is analyzed. The exponential attenuation curve of the gain along the pulse propagation time is simulated. An experiment to measure the coefficient of gain attenuation based on the gain attenuation theory is designed. Experiment result shows that the gain follows an exponential attenuation rule with a quotient of 0.0249 nm -1 , the attenuation coefficient of the pulse is 0.00356 mm -1 . The loss of the pulse propagation along the MCP stripline is the leading reason of gain attenuation. But in the figure of a single stripline, the gain dose not follow the rule of exponential attenuation completely, instead, there is a gain increase at the stripline bottom. That is caused by the reflection of the pulse. The reflectance is about 24.2%. Combining the experiment and theory, which design of the stripline MCP can improved the gain attenuation. (authors)

  19. Numerical simulation of several impact attenuator design for a formula student car

    Science.gov (United States)

    Sinaga, Farlian Rizky; Ubaidillah, Kurniawan, Krishna Eka; Fadhil, Muhamad Ivan; Cahyono, Sukmaji Indro; Idris, Muhamad Hafiz

    2018-02-01

    In the Formula Society of Automotive Engineer (SAE), safety is a vigorous factor. One of the safety components in the Formula SAE car is the impact attenuator. The purpose of this study is to get the impact attenuator design with the best ability to absorb kinetic energy from several existing designs, through numerical approaches, for estimating conditions against dynamic impacts. Material of impact attenuator use combination of aluminum and Zirconium G350. The simulation was caried out by crashing the impact with the rigid wall, to find the deformation that occurs and the energies are absorbed. The impact attenuator design to be simulated should be optimized to meet some parameters in the SAE Formula. The result of impact attenuator simulation should be able to absorb energy of 7350 joules at move 7 m/s and deformation at bulkhead less than 25.4 mm.

  20. Modeling of 830 nm FSO Link Attenuation in Fog or Wind Turbulence

    Czech Academy of Sciences Publication Activity Database

    Pešek, J.; Fišer, Ondřej; Svoboda, Jaroslav; Schejbal, V.

    2010-01-01

    Roč. 19, č. 2 (2010), s. 237-241 ISSN 1210-2512 R&D Projects: GA ČR GA102/08/0851; GA MŠk OC09027 Institutional research plan: CEZ:AV0Z30420517 Keywords : Free space optics propagation * fog attenuation, * wind turbulence attenuation * turbulent energy Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering Impact factor: 0.503, year: 2010 http://www.radioeng.cz/fulltexts/2010/10_02_237_241.pdf

  1. Students' Perception of Live Lectures' Inherent Disadvantages

    Science.gov (United States)

    Petrovic, Juraj; Pale, Predrag

    2015-01-01

    This paper aims to provide insight into various properties of live lectures from the perspective of sophomore engineering students. In an anonymous online survey conducted at the Faculty of Electrical Engineering and Computing, University of Zagreb, we investigated students' opinions regarding lecture attendance, inherent disadvantages of live…

  2. Transient attenuation in optical fibers

    International Nuclear Information System (INIS)

    Hopkins, A.A.; Kelly, R.E.; Looney, L.D.; Lyons, P.B.

    1984-01-01

    Low and high energy pulsed electron beams were used to generate radiation-induced transient attenuation in high-OH, Suprasil core, PCS fibers, demonstrating the energy dependence of the radiation damage and recovery mechanisms. A radiation resistant low-OH fiber was studied and its performance contrasted to that of high-OH materials. Several fibers with differing core compositions were also studied

  3. A Generalized Correction for Attenuation.

    Science.gov (United States)

    Petersen, Anne C.; Bock, R. Darrell

    Use of the usual bivariate correction for attenuation with more than two variables presents two statistical problems. This pairwise method may produce a covariance matrix which is not at least positive semi-definite, and the bivariate procedure does not consider the possible influences of correlated errors among the variables. The method described…

  4. Compact plasmonic variable optical attenuator

    DEFF Research Database (Denmark)

    Leosson, Kristjan; Rosenzveig, Tiberiu; Hermannsson, Pétur Gordon

    2008-01-01

    We demonstrate plasmonic nanowire-based thermo-optic variable optical attenuators operating in the 1525-1625 nm wavelength range. The devices have a footprint as low as 1 mm, extinction ratio exceeding 40 dB, driving voltage below 3 V, and full modulation bandwidth of 1 kHz. The polarization...

  5. Attenuation of Vrancea events revisited

    International Nuclear Information System (INIS)

    Radulian, M.; Popa, M.; Grecu, B.; Panza, G.F.

    2003-11-01

    New aspects of the frequency-dependent attenuation of the seismic waves traveling from Vrancea subcrustal sources toward NW (Transylvanian Basin) and SE (Romanian Plain) are evidenced by the recent experimental data made available by the CALIXTO'99 tomography experiment. The observations validate the previous theoretical computations performed for the assessment, by means of a deterministic approach, of the seismic hazard in Romania. They reveal an essential aspect of the seismic ground motion attenuation, that has important implications on the probabilistic assessment of seismic hazard from Vrancea intermediate-depth earthquakes. The attenuation toward NW is shown to be a much stronger frequency-dependent effect than the attenuation toward SE and the seismic hazard computed by the deterministic approach fits satisfactorily well the observed ground motion distribution in the low-frequency band (< 1 Hz). The apparent contradiction with the historically-based intensity maps arises mainly from a systematic difference in the vulnerability (buildings eigenperiod) of the buildings in the intra- and extra-Carpathians regions. (author)

  6. American Society of Civil Engineers | ASCE

    Science.gov (United States)

    Membership Your New Membership: Getting Started Member Value Civil Engineering Salaries Manage Your Account Vote Now Education & Careers Training & Courses Getting Licensed & Certified Live Exam Reviews Specialty Certifications Civil Engineering Body of Knowledge Volunteer Opportunities Jobs Ethics

  7. Engineered Muscle Actuators: Cells and Tissues

    National Research Council Canada - National Science Library

    Dennis, Robert G; Herr, Hugh; Parker, Kevin K; Larkin, Lisa; Arruda, Ellen; Baar, Keith

    2007-01-01

    .... Our primary objectives were to engineer living skeletal muscle actuators in culture using integrated bioreactors to guide tissue development and to maintain tissue contractility, to achieve 50...

  8. Living arrangements and mental health in Finland

    Science.gov (United States)

    Joutsenniemi, Kaisla; Martelin, Tuija; Martikainen, Pekka; Pirkola, Sami; Koskinen, Seppo

    2006-01-01

    Background Non‐married persons are known to have poor mental health compared with married persons. Health differences between marital status groups may largely arise from corresponding differences in interpersonal social bonds. However, official marital status mirrors the social reality of persons to a decreasing extent, and living arrangements may be a better measure of social bonds. Little is known about mental health in different living arrangement groups. This study aims to establish the extent and determinants of mental health differences by living arrangement in terms of psychological distress (GHQ) and DSM‐IV psychiatric disorders (CIDI). Methods Data were used from the nationally representative cross sectional health 2000 survey, conducted in 2000–1 in Finland. Altogether 4685 participants (80%) aged 30–64 years were included in these analyses; comprehensive information was available on measures of mental health and living arrangements. Living arrangements were measured as follows: married, cohabiting, living with other(s) than a partner, and living alone. Results Compared with the married, persons living alone and those living with other(s) than a partner were approximately twice as likely to have anxiety or depressive disorders. Cohabiters did not differ from the married. In men, psychological distress was similarly associated with living arrangements. Unemployment, lack of social support, and alcohol consumption attenuated the excess psychological distress and psychiatric morbidity of persons living alone and of those living with other(s) than a partner by about 10%–50% each. Conclusions Living arrangements are strongly associated with mental health, particularly among men. Information on living arrangements, social support, unemployment, and alcohol use may facilitate early stage recognition of poor mental health in primary health care. PMID:16698975

  9. Outdoor FSO Communications Under Fog: Attenuation Modeling and Performance Evaluation

    KAUST Repository

    Esmail, Maged Abdullah

    2016-07-18

    Fog is considered to be a primary challenge for free space optics (FSO) systems. It may cause attenuation that is up to hundreds of decibels per kilometer. Hence, accurate modeling of fog attenuation will help telecommunication operators to engineer and appropriately manage their networks. In this paper, we examine fog measurement data coming from several locations in Europe and the United States and derive a unified channel attenuation model. Compared with existing attenuation models, our proposed model achieves a minimum of 9 dB, which is lower than the average root-mean-square error (RMSE). Moreover, we have investigated the statistical behavior of the channel and developed a probabilistic model under stochastic fog conditions. Furthermore, we studied the performance of the FSO system addressing various performance metrics, including signal-to-noise ratio (SNR), bit-error rate (BER), and channel capacity. Our results show that in communication environments with frequent fog, FSO is typically a short-range data transmission technology. Therefore, FSO will have its preferred market segment in future wireless fifth-generation/sixth-generation (5G/6G) networks having cell sizes that are lower than a 1-km diameter. Moreover, the results of our modeling and analysis can be applied in determining the switching/thresholding conditions in highly reliable hybrid FSO/radio-frequency (RF) networks.

  10. Enhanced Attenuation Technologies: Passive Soil Vapor Extraction

    Energy Technology Data Exchange (ETDEWEB)

    Vangelas, K.; Looney, B.; Kamath, R.; Adamson, D.; Newell, C.

    2010-03-15

    Passive soil vapor extraction (PSVE) is an enhanced attenuation (EA) approach that removes volatile contaminants from soil. The extraction is driven by natural pressure gradients between the subsurface and atmosphere (Barometric Pumping), or by renewable sources of energy such as wind or solar power (Assisted PSVE). The technology is applicable for remediating sites with low levels of contamination and for transitioning sites from active source technologies such as active soil vapor extraction (ASVE) to natural attenuation. PSVE systems are simple to design and operate and are more cost effective than active systems in many scenarios. Thus, PSVE is often appropriate as an interim-remedial or polishing strategy. Over the past decade, PSVE has been demonstrated in the U.S. and in Europe. These demonstrations provide practical information to assist in selecting, designing and implementing the technology. These demonstrations indicate that the technology can be effective in achieving remedial objectives in a timely fashion. The keys to success include: (1) Application at sites where the residual source quantities, and associated fluxes to groundwater, are relatively low; (2) Selection of the appropriate passive energy source - barometric pumping in cases with a deep vadose zone and barrier (e.g., clay) layers that separate the subsurface from the atmosphere and renewable energy assisted PSVE in other settings and where higher flow rates are required. (3) Provision of sufficient access to the contaminated vadose zones through the spacing and number of extraction wells. This PSVE technology report provides a summary of the relevant technical background, real-world case study performance, key design and cost considerations, and a scenario-based cost evaluation. The key design and cost considerations are organized into a flowchart that dovetails with the Enhanced Attenuation: Chlorinated Organics Guidance of the Interstate Technology and Regulatory Council (ITRC). The PSVE

  11. Engineering Encounters: Reverse Engineering

    Science.gov (United States)

    McGowan, Veronica Cassone; Ventura, Marcia; Bell, Philip

    2017-01-01

    This column presents ideas and techniques to enhance your science teaching. This month's issue shares information on how students' everyday experiences can support science learning through engineering design. In this article, the authors outline a reverse-engineering model of instruction and describe one example of how it looked in our fifth-grade…

  12. SEISMIC ATTENUATION FOR RESERVOIR CHARACTERIZATION

    Energy Technology Data Exchange (ETDEWEB)

    Joel Walls; M.T. Taner; Gary Mavko; Jack Dvorkin

    2002-01-01

    In Section 1 of this first report we will describe the work we are doing to collect and analyze rock physics data for the purpose of modeling seismic attenuation from other measurable quantities such as porosity, water saturation, clay content and net stress. This work and other empirical methods to be presented later, will form the basis for ''Q pseudo-well modeling'' that is a key part of this project. In Section 2 of this report, we will show the fundamentals of a new method to extract Q, dispersion, and attenuation from field seismic data. The method is called Gabor-Morlet time-frequency decomposition. This technique has a number of advantages including greater stability and better time resolution than spectral ratio methods.

  13. Macroseismic intensity attenuation in Iran

    Science.gov (United States)

    Yaghmaei-Sabegh, Saman

    2018-01-01

    Macroseismic intensity data plays an important role in the process of seismic hazard analysis as well in developing of reliable earthquake loss models. This paper presents a physical-based model to predict macroseismic intensity attenuation based on 560 intensity data obtained in Iran in the time period 1975-2013. The geometric spreading and energy absorption of seismic waves have been considered in the proposed model. The proposed easy to implement relation describes the intensity simply as a function of moment magnitude, source to site distance and focal depth. The prediction capability of the proposed model is assessed by means of residuals analysis. Prediction results have been compared with those of other intensity prediction models for Italy, Turkey, Iran and central Asia. The results indicate the higher attenuation rate for the study area in distances less than 70km.

  14. ENHANCEMENTS TO NATURAL ATTENUATION: SELECTED CASE STUDIES

    Energy Technology Data Exchange (ETDEWEB)

    Vangelas, K; W. H. Albright, W; E. S. Becvar, E; C. H. Benson, C; T. O. Early, T; E. Hood, E; P. M. Jardine, P; M. Lorah, M; E. Majche, E; D. Major, D; W. J. Waugh, W; G. Wein, G; O. R. West, O

    2007-05-15

    In 2003 the US Department of Energy (DOE) embarked on a project to explore an innovative approach to remediation of subsurface contaminant plumes that focused on introducing mechanisms for augmenting natural attenuation to achieve site closure. Termed enhanced attenuation (EA), this approach has drawn its inspiration from the concept of monitored natural attenuation (MNA).

  15. Comparison of the nucleotide sequence of wild-type hepatitis - A virus and its attenuated candidate vaccine derivative

    International Nuclear Information System (INIS)

    Cohen, J.I.; Rosenblum, B.; Ticehurst, J.R.; Daemer, R.; Feinstone, S.; Purcell, R.H.

    1987-01-01

    Development of attenuated mutants for use as vaccines is in progress for other viruses, including influenza, rotavirus, varicella-zoster, cytomegalovirus, and hepatitis-A virus (HAV). Attenuated viruses may be derived from naturally occurring mutants that infect human or nonhuman hosts. Alternatively, attenuated mutants may be generated by passage of wild-type virus in cell culture. Production of attenuated viruses in cell culture is a laborious and empiric process. Despite previous empiric successes, understanding the molecular basis for attenuation of vaccine viruses could facilitate future development and use of live-virus vaccines. Comparison of the complete nucleotide sequences of wild-type (virulent) and vaccine (attenuated) viruses has been reported for polioviruses and yellow fever virus. Here, the authors compare the nucleotide sequence of wild-type HAV HM-175 with that of a candidate vaccine derivative

  16. Effects of attenuation map accuracy on attenuation-corrected micro-SPECT images

    NARCIS (Netherlands)

    Wu, C.; Gratama van Andel, H.A.; Laverman, P.; Boerman, O.C.; Beekman, F.J.

    2013-01-01

    Background In single-photon emission computed tomography (SPECT), attenuation of photon flux in tissue affects quantitative accuracy of reconstructed images. Attenuation maps derived from X-ray computed tomography (CT) can be employed for attenuation correction. The attenuation coefficients as well

  17. Applicability of monitored natural attenuation at radioactively contaminated sites

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2006-01-15

    grouped into three categories: non-intervention, containment and removal. This report discusses in detail the necessary prerequisites, processes involved and applicability of non-intervention as a strategy for dealing with radioactive contamination. Particular emphasis is put on modelling tools as integral elements of monitored natural attenuation (MNA). It provides a comprehensive critique of, and explores the limits of, the applicability of MNA. While MNA is de facto relied upon in many instances where contamination cannot be completely removed from an engineered repository, it is emphasized that non-intervention is not equivalent to a 'do nothing' option. In order to rely on MNA safely, a thorough understanding of the site and the migration behaviour of the contaminants in the given environment is needed. This is gained from a comprehensive site investigation. This report complements other recent reports on remediation techniques and strategies with a less invasive concept. An extensive body of references including relevant web sites will help the reader to find more detailed or more up-to-date information.

  18. Applicability of monitored natural attenuation at radioactively contaminated sites

    International Nuclear Information System (INIS)

    2006-01-01

    grouped into three categories: non-intervention, containment and removal. This report discusses in detail the necessary prerequisites, processes involved and applicability of non-intervention as a strategy for dealing with radioactive contamination. Particular emphasis is put on modelling tools as integral elements of monitored natural attenuation (MNA). It provides a comprehensive critique of, and explores the limits of, the applicability of MNA. While MNA is de facto relied upon in many instances where contamination cannot be completely removed from an engineered repository, it is emphasized that non-intervention is not equivalent to a 'do nothing' option. In order to rely on MNA safely, a thorough understanding of the site and the migration behaviour of the contaminants in the given environment is needed. This is gained from a comprehensive site investigation. This report complements other recent reports on remediation techniques and strategies with a less invasive concept. An extensive body of references including relevant web sites will help the reader to find more detailed or more up-to-date information

  19. [Living better or living longer].

    Science.gov (United States)

    Sauvy, A

    1987-01-01

    It has been just 2 centuries since France began to struggle seriously against mortality and excess fertility. Life expectancy, which for millenia had been under 30 years at birth, began to increase because of the discovery of effective treatments, improved production and standards of living, and access of large numbers of persons to health care. France, in the 2nd half of the 18th century, became the first country in which fertility regulation was achieved on a wide scale. The failure of England, a country of similar culture, to follow suit until a century later remains unexplained. After World War II, simple and fairly inexpensive means of mortality control, such as vaccines and water purifiers, became widely distributed throughout the developing world. These countries, which traditionally had mortality rates of 35 or 40/1000 and fertility of 40-45/1000, experienced rapid declines in mortality rates while their fertility remained constant or even increased. Because antinatal techniques diffused so much more slowly, the equilibrium of births and deaths was disturbed as rates of increase of 2 or 3% per year became common. Although the inhabitants of poor countries were not concerned, perhaps through ignorance of what was occurring, the rich countries were alarmed by the increase. Their principal objective became to spread contraception in the poor countries. The available methods at the time, however, were none too reliable. When oral contraceptive pills became available, fertility dropped to very low levels in Europe but such factors as cost and illiteracy discouraged use in many underdeveloped countries. Fertility declined in a few insular states such as Hong Kong, Taiwan, and Singapore even before the appearance of pills. Life expectancies in developing countries except a few in Africa have increased since World War II and are now higher than in Europe at the turn of the century. "Health for all by the year 2000" is an astonishing slogan for a serious

  20. Reeds diesel engine troubleshooting handbook

    CERN Document Server

    Pickthall, Barry

    2013-01-01

    Most diesel engines will develop a problem at some point in their lives, but armed with the right knowledge a skipper needn't worry. The Reeds Diesel Engine Troubleshooting Handbook is a compact, pocket-sized guide to finding solutions to all of the most common engine problems, and many of the less common ones too. The perfect format for quick reference on board, this book will help skippers fix troublesome engines themselves, avoiding costly engineer fees if the problem is simple to sort out, or enabling an emergency patch-up for a more serious problem until they can get back to port. Each to

  1. Experiment evaluation of impact attenuator for a racing car under static load

    Science.gov (United States)

    Imanullah, Fahmi; Ubaidillah, Prasojo, Arfi Singgih; Wirawan, Adhe Aji

    2018-02-01

    The automotive world is a world where one of the factors that must be considered carefully is the safety aspect. In the formula student car one of the safety factor in the form of impact attenuator. Impact attenuator is used as anchoring when a collision occurs in front of the vehicle. In the rule of formula society of automotive engineer (FSAE) student, impact attenuator is required to absorb the energy must meet or exceed 7350 Joules with a slowdown in speed not exceeding 20 g average and peak of 40 g. The student formula participants are challenged to pass the boundaries so that in designing and making the impact attenuator must pay attention to the strength and use of the minimum material so that it can minimize the expenditure. In this work, an impact attenuator was fabricated and tested using static compression. The primary goal was evaluating the actual capability of the impact attenuator for impact energy absorption. The prototype was made of aluminum alloy in a prismatic shape, and the inside wall was filled with rooftop plastic slices and polyurethane hard foam. The compression test has successfully carried out, and the load versus displacement data could be used in calculating energy absorption capability. The result of the absorbent energy of the selected impact attenuator material. Impact attenuator full polyurethane absorbed energy reach 6380 Joule. For impact attenuator with aluminum polyurethane with a slashed rooftop material as section absorbed energy reach 6600 Joule. Impact attenuator with Aluminum Polyurethane with aluminum orange peel partitions absorbed energy reach 8800 Joule. From standard student formula, energy absorbed in this event must meet or exceed 7350 Joules that meet aluminum polyurethane with aluminum orange peel partitions with the ability to absorb 8800 Joule.

  2. Engineer Ethics

    International Nuclear Information System (INIS)

    Lee, Dae Sik; Kim, Yeong Pil; Kim, Yeong Jin

    2003-03-01

    This book tells of engineer ethics such as basic understanding of engineer ethics with history of engineering as a occupation, definition of engineering and specialized job and engineering, engineer ethics as professional ethics, general principles of ethics and its limitation, ethical theory and application, technique to solve the ethical problems, responsibility, safety and danger, information engineer ethics, biotechnological ethics like artificial insemination, life reproduction, gene therapy and environmental ethics.

  3. Biomedical Engineering Education in Perspective

    Science.gov (United States)

    Gowen, Richard J.

    1973-01-01

    Discusses recent developments in the health care industry and their impact on the future of biomedical engineering education. Indicates that a more thorough understanding of the complex functions of the living organism can be acquired through the application of engineering techniques to problems of life sciences. (CC)

  4. Natural attenuation: A feasible approach to remediation of ground water pollution at landfills?

    Energy Technology Data Exchange (ETDEWEB)

    Christensen, T.H.; Bjerg, P.L.; Kjeldsen, P.

    2000-12-31

    Remediation of ground water pollution at old landfills with no engineered leachate collection system is a demanding and costly operation. It requires control of the landfill body, since the majority of the pollutants are still present in the landfilled waste for decades after the site has been closed. However, natural attenuation of the plume without removing the source is an attractive approach to managing leachate plumes. Natural attenuation has been implemented for petroleum hydrocarbon plumes and for chlorinated solvent plumes, primarily in the US. Natural attenuation has not yet gained a foothold with respect to leachate plumes, however. Based on the experiences gained from 10 years of research on two Danish landfills, it is suggested that natural attenuation is a feasible approach but is more complicated and demanding than in the case of petroleum hydrocarbons and chlorinated solvent.

  5. Chlorine signal attenuation in concrete.

    Science.gov (United States)

    Naqvi, A A; Maslehuddin, M; Ur-Rehman, Khateeb; Al-Amoudi, O S B

    2015-11-01

    The intensity of prompt gamma-ray was measured at various depths from chlorine-contaminated silica fume (SF) concrete slab concrete specimens using portable neutron generator-based prompt gamma-ray setup. The intensity of 6.11MeV chloride gamma-rays was measured from the chloride contaminated slab at distance of 15.25, 20.25, 25.25, 30.25 and 35.25cm from neutron target in a SF cement concrete slab specimens. Due to attenuation of thermal neutron flux and emitted gamma-ray intensity in SF cement concrete at various depths, the measured intensity of chlorine gamma-rays decreases non-linearly with increasing depth in concrete. A good agreement was noted between the experimental results and the results of Monte Carlo simulation. This study has provided useful experimental data for evaluating the chloride contamination in the SF concrete utilizing gamma-ray attenuation method. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. SEISMIC ATTENUATION FOR RESERVOIR CHARACTERIZATION

    Energy Technology Data Exchange (ETDEWEB)

    Joel Walls; M.T. Taner; Naum Derzhi; Gary Mavko; Jack Dvorkin

    2003-12-01

    We have developed and tested technology for a new type of direct hydrocarbon detection. The method uses inelastic rock properties to greatly enhance the sensitivity of surface seismic methods to the presence of oil and gas saturation. These methods include use of energy absorption, dispersion, and attenuation (Q) along with traditional seismic attributes like velocity, impedance, and AVO. Our approach is to combine three elements: (1) a synthesis of the latest rock physics understanding of how rock inelasticity is related to rock type, pore fluid types, and pore microstructure, (2) synthetic seismic modeling that will help identify the relative contributions of scattering and intrinsic inelasticity to apparent Q attributes, and (3) robust algorithms that extract relative wave attenuation attributes from seismic data. This project provides: (1) Additional petrophysical insight from acquired data; (2) Increased understanding of rock and fluid properties; (3) New techniques to measure reservoir properties that are not currently available; and (4) Provide tools to more accurately describe the reservoir and predict oil location and volumes. These methodologies will improve the industry's ability to predict and quantify oil and gas saturation distribution, and to apply this information through geologic models to enhance reservoir simulation. We have applied for two separate patents relating to work that was completed as part of this project.

  7. Living with endometriosis

    Science.gov (United States)

    Pelvic pain - living with endometriosis; Endometrial implant - living with endometriosis; Endometrioma - living with endometriosis ... counter pain relievers can reduce the pain of endometriosis. These include: Ibuprofen (Advil) Naproxen (Aleve) Acetaminophen (Tylenol) ...

  8. Calculation Of Pneumatic Attenuation In Pressure Sensors

    Science.gov (United States)

    Whitmore, Stephen A.

    1991-01-01

    Errors caused by attenuation of air-pressure waves in narrow tubes calculated by method based on fundamental equations of flow. Changes in ambient pressure transmitted along narrow tube to sensor. Attenuation of high-frequency components of pressure wave calculated from wave equation derived from Navier-Stokes equations of viscous flow in tube. Developed to understand and compensate for frictional attenuation in narrow tubes used to connect aircraft pressure sensors with pressure taps on affected surfaces.

  9. Estimating Rain Attenuation In Satellite Communication Links

    Science.gov (United States)

    Manning, R. M.

    1991-01-01

    Attenuation computed with help of statistical model and meteorological data. NASA Lewis Research Center Satellite Link Attenuation Model (SLAM) program QuickBASIC computer program evaluating static and dynamic statistical assessment of impact of rain attenuation on communication link established between Earth terminal and geosynchronous satellite. Application in specification, design, and assessment of satellite communication links for any terminal location in continental United States. Written in Microsoft QuickBASIC.

  10. Natural attenuation, biostimulation and bioaugmentation of landfill leachate management

    Science.gov (United States)

    Er, X. Y.; Seow, T. W.; Lim, C. K.; Ibrahim, Z.

    2018-04-01

    Landfills used for solid waste management will lead to leachate production. Proper leachate management is highly essential to be paid attention to protect the environment and living organisms’ health and safety. In this study, the remedial strategies used for leachate management were natural attenuation, biostimulation and bioaugmentation. All treatment samples were treated via 42-days combined anaerobic-aerobic treatment and the treatment efficiency was studied by measuring the removal rate of COD and ammonia nitrogen. In this study, all remedial strategies showed different degrees of contaminants removal. Lowest contaminants removal rate was achieved via bioaugmentation of B. panacihumi strain ZB1, which were 39.4% of COD and 37.6% of ammonia nitrogen removed from the leachate sample. Higher contaminants removal rate was achieved via natural attenuation and biostimulation. Native microbial population was able to remove 41% of COD and 59% of ammonia nitrogen from the leachate sample. The removal efficiency could be further improved via biostimulation to trigger microbial growth and decontamination rate. Through biostimulation, 58% of COD and 51.8% of ammonia nitrogen were removed from the leachate sample. In conclusion, natural attenuation and biostimulation should be the main choice for leachate management to avoid any unexpected impacts due to introduction of exogenous species.

  11. Engineering opportunities in nuclear engineering

    International Nuclear Information System (INIS)

    Walton, D.G.

    1980-01-01

    The pattern of education and training of Nuclear Engineers in the UK is outlined under the headings; degree courses for professional engineers, postgraduate courses, education of technician engineers. Universities which offer specific courses are stated and useful addresses listed. (UK)

  12. Basic live sound reinforcement a practical guide for starting live audio

    CERN Document Server

    Biederman, Raven

    2013-01-01

    Access and interpret manufacturer spec information, find shortcuts for plotting measure and test equations, and learn how to begin your journey towards becoming a live sound professional. Land and perform your first live sound gigs with this guide that gives you just the right amount of information. Don't get bogged down in details intended for complex and expensive equipment and Madison Square Garden-sized venues. Basic Live Sound Reinforcement is a handbook for audio engineers and live sound enthusiasts performing in small venues from one-mike coffee shops to clubs. With their combined ye

  13. Evolutionary characteristics of morbilliviruses during serial passages in vitro: Gradual attenuation of virus virulence.

    Science.gov (United States)

    Liu, Fuxiao; Wu, Xiaodong; Li, Lin; Zou, Yanli; Liu, Shan; Wang, Zhiliang

    2016-08-01

    The genus Morbillivirus is classified into the family Paramyxoviridae, and is composed of 6 members, namely measles virus (MV), rinderpest virus (RPV), peste-des-petits-ruminants virus (PPRV), canine distemper virus (CDV), phocine distemper virus (PDV) and cetacean morbillivirus (CeMV). The MV, RPV, PPRV and CDV have been successfully attenuated through their serial passages in vitro for the production of live vaccines. It has been demonstrated that the morbilliviral virulence in animals was progressively attenuated with their consecutive passages in vitro. However, only a few reports were involved in explanation of an attenuation-related mechanism on them until many years after the establishment of a quasispecies theory. RNA virus quasispecies arise from rapid evolution of viruses with high mutation rate during genomic replication, and play an important role in gradual loss of viral virulence by serial passages. Here, we overviewed the development of live-attenuated vaccine strains against morbilliviruses by consecutive passages in vitro, and further discussed a related mechanism concerning the relationship between virulence attenuation and viral evolution. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. [The gentic principles for the design of live Salmonella vaccines].

    Science.gov (United States)

    Petrovskaia, V G; Marakusha, B I; Bondarenko, V M

    1996-01-01

    The presently known methods of obtaining Salmonella vaccine strains are characterized, their advantages and drawbacks are noted. Great importance of the genetic safety of Salmonella attenuated strains to be controlled is emphasized, taking into account that they are also used as carrier strains for obtaining hybrid and gene-engineering (vector) vaccines carrying immunogenicity factors of other species of pathogenic microorganisms.

  15. Allergy, living and learning

    DEFF Research Database (Denmark)

    Chivato, T; Valovirta, E; Dahl, R

    2012-01-01

    Allergy Living and Learning (ALL) is a European initiative designed to increase knowledge and understanding of people living with allergies in order to improve respiratory allergy care.......Allergy Living and Learning (ALL) is a European initiative designed to increase knowledge and understanding of people living with allergies in order to improve respiratory allergy care....

  16. Attenuation in Melting Layer of Precipitation

    NARCIS (Netherlands)

    Klaassen, W.

    1988-01-01

    A model of the melting layer is employed on radar measurements to simulate the attenuation of radio waves at 12, 20 and 30GHz. The attenuation in the melting layer is simulated to be slightly larger than that of rain with the same path length and precipitation intensity. The result appears to depend

  17. Precision Model for Microwave Rotary Vane Attenuator

    DEFF Research Database (Denmark)

    Guldbrandsen, Tom

    1979-01-01

    A model for a rotary vane attenuator is developed to describe the attenuator reflection and transmission coefficients in detail. All the parameters of the model can be measured in situ, i.e., without diassembling any part. The tranmission errors caused by internal reflections are calculated from ...

  18. Photostimulated attenuation of hypersound in superlattice

    International Nuclear Information System (INIS)

    Mensah, S.Y.; Allotey, F.K.; Adjepong, S.K.

    1992-10-01

    Photostimulated attenuation of hypersound in semiconductor superlattice has been investigated. It is shown that the attenuation coefficient depends on the phonon wave vector q in an oscillatory manner and that from this oscillation the band width Δ of superlattice can be found. (author). 14 refs, 1 fig

  19. Engineering Institute

    Science.gov (United States)

    Projects Past Projects Publications NSEC » Engineering Institute Engineering Institute Multidisciplinary engineering research that integrates advanced modeling and simulations, novel sensing systems and new home of Engineering Institute Contact Institute Director Charles Farrar (505) 665-0860 Email UCSD EI

  20. Creating living machines

    Science.gov (United States)

    Kamm, Roger D.; Bashir, Rashid

    2015-01-01

    Development of increasingly complex integrated cellular systems will be a major challenge for the next decade and beyond, as we apply the knowledge gained from the sub-disciplines of tissue engineering, synthetic biology, micro-fabrication and nanotechnology, systems biology, and developmental biology. In this prospective, we describe the current state-of-the-art in the context of differentiating source cells from more primitive, pluripotent cells, and organizing these cells into populations of a single cell type to produce the components or building blocks of higher order systems and finally, combining multiple cell types, possibly in combination with scaffolds possessing specific physical or chemical properties, to produce greater functionality. As these “living machines” increase in capabilities, exhibit emergent behavior and potentially reveal the ability for self-assembly, self-repair, and even self-replication, questions arise regarding the ethical implications of this work. Future prospects as well as ways of addressing these complex ethical questions will be addressed. PMID:24006130

  1. Ultrasound fields in an attenuating medium

    DEFF Research Database (Denmark)

    Jensen, Jørgen Arendt; Gandhi,, D; O'Brien,, W.D., Jr.

    1993-01-01

    of the rectangles and sums all contributions to arrive at the spatial impulse response for the aperture and field point. This approach makes it possible to model all transducer apertures, and the program can readily calculate the emitted, pulse-echo and continuous wave field. Attenuation is included by splitting...... it into a frequency dependent part and frequency independent part. The latter results in an attenuation factor that is multiplied onto the responses from the individual elements, and the frequency dependent part is handled by attenuating the basic one-dimensional pulse. The influence on ultrasound fields from......Ultrasound fields propagating in tissue will undergo changes in shape not only due to diffraction, but also due to the frequency dependent attenuation. Linear fields can be fairly well predicted for a non-attenuating medium like water by using the Tupholme-Stepanishen method for calculating...

  2. A replication-deficient rabies virus vaccine expressing Ebola virus glycoprotein is highly attenuated for neurovirulence

    International Nuclear Information System (INIS)

    Papaneri, Amy B.; Wirblich, Christoph; Cann, Jennifer A.; Cooper, Kurt; Jahrling, Peter B.; Schnell, Matthias J.; Blaney, Joseph E.

    2012-01-01

    We are developing inactivated and live-attenuated rabies virus (RABV) vaccines expressing Ebola virus (EBOV) glycoprotein for use in humans and endangered wildlife, respectively. Here, we further characterize the pathogenesis of the live-attenuated RABV/EBOV vaccine candidates in mice in an effort to define their growth properties and potential for safety. RABV vaccines expressing GP (RV-GP) or a replication-deficient derivative with a deletion of the RABV G gene (RVΔG-GP) are both avirulent after intracerebral inoculation of adult mice. Furthermore, RVΔG-GP is completely avirulent upon intracerebral inoculation of suckling mice unlike parental RABV vaccine or RV-GP. Analysis of RVΔG-GP in the brain by quantitative PCR, determination of virus titer, and immunohistochemistry indicated greatly restricted virus replication. In summary, our findings indicate that RV-GP retains the attenuation phenotype of the live-attenuated RABV vaccine, and RVΔG-GP would appear to be an even safer alternative for use in wildlife or consideration for human use.

  3. A replication-deficient rabies virus vaccine expressing Ebola virus glycoprotein is highly attenuated for neurovirulence

    Energy Technology Data Exchange (ETDEWEB)

    Papaneri, Amy B. [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD 21702 (United States); Wirblich, Christoph [Department of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Cann, Jennifer A.; Cooper, Kurt [Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick MD, 21702 (United States); Jahrling, Peter B. [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD 21702 (United States); Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick MD, 21702 (United States); Schnell, Matthias J., E-mail: matthias.schnell@jefferson.edu [Department of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Jefferson Vaccine Center, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Blaney, Joseph E., E-mail: jblaney@niaid.nih.gov [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD 21702 (United States)

    2012-12-05

    We are developing inactivated and live-attenuated rabies virus (RABV) vaccines expressing Ebola virus (EBOV) glycoprotein for use in humans and endangered wildlife, respectively. Here, we further characterize the pathogenesis of the live-attenuated RABV/EBOV vaccine candidates in mice in an effort to define their growth properties and potential for safety. RABV vaccines expressing GP (RV-GP) or a replication-deficient derivative with a deletion of the RABV G gene (RV{Delta}G-GP) are both avirulent after intracerebral inoculation of adult mice. Furthermore, RV{Delta}G-GP is completely avirulent upon intracerebral inoculation of suckling mice unlike parental RABV vaccine or RV-GP. Analysis of RV{Delta}G-GP in the brain by quantitative PCR, determination of virus titer, and immunohistochemistry indicated greatly restricted virus replication. In summary, our findings indicate that RV-GP retains the attenuation phenotype of the live-attenuated RABV vaccine, and RV{Delta}G-GP would appear to be an even safer alternative for use in wildlife or consideration for human use.

  4. Mechanical engineering

    CERN Document Server

    Darbyshire, Alan

    2010-01-01

    Alan Darbyshire's best-selling text book provides five-star high quality content to a potential audience of 13,000 engineering students. It explains the most popular specialist units of the Mechanical Engineering, Manufacturing Engineering and Operations & Maintenance Engineering pathways of the new 2010 BTEC National Engineering syllabus. This challenging textbook also features contributions from specialist lecturers, ensuring that no stone is left unturned.

  5. MicroRNA-Based Attenuation of Influenza Virus across Susceptible Hosts.

    Science.gov (United States)

    Waring, Barbara M; Sjaastad, Louisa E; Fiege, Jessica K; Fay, Elizabeth J; Reyes, Ismarc; Moriarity, Branden; Langlois, Ryan A

    2018-01-15

    Influenza A virus drives significant morbidity and mortality in humans and livestock. Annual circulation of the virus in livestock and waterfowl contributes to severe economic disruption and increases the risk of zoonotic transmission of novel strains into the human population, where there is no preexisting immunity. Seasonal vaccinations in humans help prevent infection and can reduce symptoms when infection does occur. However, current vaccination regimens available for livestock are limited in part due to safety concerns regarding reassortment/recombination with circulating strains. Therefore, inactivated vaccines are used instead of the more immunostimulatory live attenuated vaccines. MicroRNAs (miRNAs) have been used previously to generate attenuated influenza A viruses for use as a vaccine. Here, we systematically targeted individual influenza gene mRNAs using the same miRNA to determine the segment(s) that yields maximal attenuation potential. This analysis demonstrated that targeting of NP mRNA most efficiently ablates replication. We further increased the plasticity of miRNA-mediated attenuation of influenza A virus by exploiting a miRNA, miR-21, that is ubiquitously expressed across influenza-susceptible hosts. In order to construct this targeted virus, we used CRISPR/Cas9 to eliminate the universally expressed miR-21 from MDCK cells. miR-21-targeted viruses were attenuated in human, mouse, canine, and avian cells and drove protective immunity in mice. This strategy has the potential to enhance the safety of live attenuated vaccines in humans and zoonotic reservoirs. IMPORTANCE Influenza A virus circulates annually in both avian and human populations, causing significant morbidity, mortality, and economic burden. High incidence of zoonotic infections greatly increases the potential for transmission to humans, where no preexisting immunity or vaccine exists. There is a critical need for new vaccine strategies to combat emerging influenza outbreaks. Micro

  6. Beta attenuation transmission system (BATS)

    Energy Technology Data Exchange (ETDEWEB)

    Hagan, R.C.; Fullbright, H.J.

    1977-01-01

    The beta attenuation transmission system (BATS) is an automated radiation gauge designed for quantitative measurement of component thickness in explosive detonators. The BATS was designed and built by Group M-1, the Nondestructive Testing Group, of the Los Alamos Scientific Laboratory to measure the areal thickness, in mg/cm/sup 2/, of a cylinder of high explosive (HE) enclosed within a plastic holder. The problem is to determine the density of the HE. A /sup 90/Sr source is collimated by a 0.25 x 1.59-mm slit, and the transmitted beta-particle flux is detected by a plastic scintillator, coupled to a photomultiplier tube. The detonator is transported through the radiation beam by a leadscrew, ballnut, stepping-motor combination. Continuous analog position data are available, derived from the output from a linear-actuated potentiometer attached to the scanner. A linear electrometer amplifies the detected signal, which is then integrated for a preselected time, to obtain the desired statistical accuracy. A microprocessor (..mu..P) is used to control the scanner position and to make the data readings at the assigned positions. The data are stored, and, at the completion of the scan, are processed into the desired format. The final answer is displayed to the operator or output to a peripheral device for permanent record. The characteristics of the radiation source, the collimator, the signal detection and conditioning, and the final results are described in detail. The scanner and the microprocessor control system are briefly outlined.

  7. Transport and attenuation of radiations

    CERN Document Server

    Nimal, J C

    2003-01-01

    This article treats of the calculation methods used for the dimensioning of the protections against radiations. The method consists in determining for a given point the flux of particles coming from a source at a given time. A strong attenuation (of about some few mu Sv.h sup - sup 1) is in general expected between the source and the areas accessible to the personnel or the public. The calculation has to take into account a huge number of radiation-matter interactions and to solve the integral-differential transport equation which links the particles flux to the source. Several methods exist from the simplified physical model with numerical developments to the more or less precise resolution of the transport equation. These methods allows also the calculation of the uncertainties of equivalent dose rates, heat sources, structure damages using the data covariances (efficient cross-sections, modeling, etc..): 1 - transport equation; 2 - Monte-Carlo method; 3 - semi-numerical methods S sub N; 4 - methods based o...

  8. Plasmodium falciparum: attenuation by irradiation

    International Nuclear Information System (INIS)

    Waki, S.; Yonome, I.; Suzuki, M.

    1983-01-01

    The effect of irradiation on the in vitro growth of Plasmodium falciparum was investigated. The cultured malarial parasites at selected stages of development were exposed to gamma rays and the sensitivity of each stage was determined. The stages most sensitive to irradiation were the ring forms and the early trophozoites; late trophozoites were relatively insensitive. The greatest resistance was shown when parasites were irradiated at a time of transition from the late trophozoite and schizont stages to young ring forms. The characteristics of radiosensitive variation in the parasite cycle resembled that of mammalian cells. Growth curves of parasites exposed to doses of irradiation upto 150 gray had the same slope as nonirradiated controls but parasites which were exposed to 200 gray exhibited a growth curve which was less steep than that for parasites in other groups. Less than 10 organisms survived from the 10(6) parasites exposed to this high dose of irradiation; the possibility exists of obtaining radiation-attenuated P. falciparum

  9. Beta attenuation transmission system (BATS)

    International Nuclear Information System (INIS)

    Hagan, R.C.; Fullbright, H.J.

    1977-01-01

    The beta attenuation transmission system (BATS) is an automated radiation gauge designed for quantitative measurement of component thickness in explosive detonators. The BATS was designed and built by Group M-1, the Nondestructive Testing Group, of the Los Alamos Scientific Laboratory to measure the areal thickness, in mg/cm 2 , of a cylinder of high explosive (HE) enclosed within a plastic holder. The problem is to determine the density of the HE. A 90 Sr source is collimated by a 0.25 x 1.59-mm slit, and the transmitted beta-particle flux is detected by a plastic scintillator, coupled to a photomultiplier tube. The detonator is transported through the radiation beam by a leadscrew, ballnut, stepping-motor combination. Continuous analog position data are available, derived from the output from a linear-actuated potentiometer attached to the scanner. A linear electrometer amplifies the detected signal, which is then integrated for a preselected time, to obtain the desired statistical accuracy. A microprocessor (μP) is used to control the scanner position and to make the data readings at the assigned positions. The data are stored, and, at the completion of the scan, are processed into the desired format. The final answer is displayed to the operator or output to a peripheral device for permanent record. The characteristics of the radiation source, the collimator, the signal detection and conditioning, and the final results are described in detail. The scanner and the microprocessor control system are briefly outlined

  10. Attenuation characteristics of gypsum wallboard

    International Nuclear Information System (INIS)

    Christensen, Ralph C.; Sayeg, Joseph

    1978-01-01

    Increased cost of lead is promoting enhanced usage of common building materials for shielding in diagnostic medical and dental facilities where only a few half value layers (HVLs) are needed. We have measured attenuation of x-rays in gypsum wallboard as a function of kVp, filtration, and wallboard thickness. Our findings, obtained using a Victoreen 555 with an 0.1 DAS probe in poor geometry, are in agreement with the sparse data in the literature (Gross and McCullough (1977), Radiology 122: 825. Moos et al. (1961), Oral Surgery, Oral Medicine, and Oral Pathology 14: 569) but extend to thicker wall configurations and different kVp and filtration parameters. We conclude that gypsum wallboard as sole shielding material should be used with great caution. These findings are of value in maximizing the benefit/cost ratio for diagnostic shielding, and strengthen the conviction that, where used for shielding purposes, common building materials must be installed carefully and HVL-depth dependence considered thoroughly. (author)

  11. Summary of existing information on gamma-ray and X-ray attenuation coefficients of solutions

    DEFF Research Database (Denmark)

    Singh, K.; Gerward, Leif

    2002-01-01

    Accurate values of X-ray and gamma-ray attenuation coefficients of different chemicals are required in spectrometry as well as in many other scientific, engineering and medical disciplines involving photon radiation. The current state of knowledge of experimental and theoretical gamma-ray and X-r......-ray attenuation coefficients in aqueous solutions of salts is presented and exemplified by recent work. The results presented provide a basis for studying X-ray and gamma-ray photon interactions with ions in solution (hydrated ions) rather than ion compounds in solid form....

  12. Measured anisotropic air flow resistivity and sound attenuation of glass wool

    DEFF Research Database (Denmark)

    Tarnow, Viggo

    2002-01-01

    Department of Mechanical Engineering, Technical University of Denmark, Bygning 358, DK 2800 Lyngby, Denmark The air flow resistivity of glass wool has been measured in different directions. The glass wool was delivered from the manufacturer as slabs measuring 100×600×900 mm3, where the surface 600...... 7.75 kPa s m**2. A formula for prediction of resistivity for other densities is given. By comparing measured values of sound attenuation with results calculated from resistivity data, it is demonstrated that the measured attenuation can be predicted in a simple manner. ©2002 Acoustical Society...

  13. Investigation of multilayered nanocomposites as low energy X-Rays attenuators

    International Nuclear Information System (INIS)

    Silva, Liliane; Batista, Adriana S.M.; Nascimento, Jefferson P.; Furtado, Clascídia A.; Faria, Luiz O.

    2017-01-01

    The development of radiation attenuating materials has application in radioprotection and conditioning of short-lived waste. Polymeric materials can serve as a matrix for the dispersion of nanomaterials with good attenuation features, resulting in lightweight, conformable, flexible and easy-to-process materials. Thus, some well-known shielding materials could be used in low proportion for the formation of new materials. On the other hand, nanostructured carbon materials, such as graphene oxide (GO) and carbon nanotubes (NTCs), have been reported recently to show enhanced attenuation properties. In this sense, polymeric matrixes provide the necessary flexibility for use in various applications that require molding. For the present work, poly(vinylidene fluoride) [PVDF] homopolymers and its fluorinated copolymers were filled with nanosized metallic and graphene oxides in order to produce nanocomposites with increased low energy X-ray attenuation efficiency. Film samples of PVDF/reduced Graphene Oxide [PVDF/rGO] and Poly(vinylidene fluoride – tryfluorethylene)/Barium Oxide [P(VDF-TrFE)/BaO] were synthesized. In a second step, the samples were then sandwiched between Kapton® layers and exposed to X-rays source (8.5 keV). The samples were characterized with Scanning Electron Microscopy (SEM) and Energy Dispersive Spectroscopy (EDS). The attenuation coefficient was evaluated and compared with the attenuation of the individual constituents. It was observed an increase in the linear attenuation coefficient of the layered materials, justifying further investigation of these nanostructured composites as X-ray or gamma radiation attenuators. (author)

  14. Investigation of multilayered nanocomposites as low energy X-Rays attenuators

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Liliane; Batista, Adriana S.M.; Nascimento, Jefferson P.; Furtado, Clascídia A.; Faria, Luiz O., E-mail: asfisica@gmail.com, E-mail: adriananuclear@yahoo.com.br, E-mail: farialo@cdtn.br, E-mail: nascimentopatricio@yahoo.com.br, E-mail: clas@cdtn.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil); Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

    2017-11-01

    The development of radiation attenuating materials has application in radioprotection and conditioning of short-lived waste. Polymeric materials can serve as a matrix for the dispersion of nanomaterials with good attenuation features, resulting in lightweight, conformable, flexible and easy-to-process materials. Thus, some well-known shielding materials could be used in low proportion for the formation of new materials. On the other hand, nanostructured carbon materials, such as graphene oxide (GO) and carbon nanotubes (NTCs), have been reported recently to show enhanced attenuation properties. In this sense, polymeric matrixes provide the necessary flexibility for use in various applications that require molding. For the present work, poly(vinylidene fluoride) [PVDF] homopolymers and its fluorinated copolymers were filled with nanosized metallic and graphene oxides in order to produce nanocomposites with increased low energy X-ray attenuation efficiency. Film samples of PVDF/reduced Graphene Oxide [PVDF/rGO] and Poly(vinylidene fluoride – tryfluorethylene)/Barium Oxide [P(VDF-TrFE)/BaO] were synthesized. In a second step, the samples were then sandwiched between Kapton® layers and exposed to X-rays source (8.5 keV). The samples were characterized with Scanning Electron Microscopy (SEM) and Energy Dispersive Spectroscopy (EDS). The attenuation coefficient was evaluated and compared with the attenuation of the individual constituents. It was observed an increase in the linear attenuation coefficient of the layered materials, justifying further investigation of these nanostructured composites as X-ray or gamma radiation attenuators. (author)

  15. Living Shorelines: Assessing Geomorphic Change and Water Quality in an Urban Waterway

    Science.gov (United States)

    Huggins, A.; Schwartz, M. C.; Schmutz, P. P.

    2017-12-01

    In recent years, alternative strategies for shoreline armoring have become increasingly popular with coastal property owners. In Northwest Florida, local agencies implemented plans to attenuate wave action and reduce landward shore recession in an urban bayou by installing living shorelines. Living shorelines are constructed in the inter-tidal zones and incorporate both hard and soft structured stabilization. Generally, the hard component is fossilized oyster shells and the soft component is planted intertidal vegetation, such as Spartina alterniflora (Smooth cordgrass) and Juncus roemererianus (Black needlerush). Living shorelines were intended to comprise both ecological and societal implications by significantly slowing erosion processes for property owners, by utilizing oyster beds to improve water quality, and by fostering new ecological habitats in the marsh grasses. The issue presented with living shoreline management is long-term studies have not been carried out on these engineered systems. For this study, geospatial technology was utilized to create 3D images of terrain by interpolation of data points using a TotalStation to compute geomorphic change. Additionally, water samples were analyzed using traditional wet chemistry laboratory methods to determine total oxidized nitrogen (TON), ammonium, and orthophosphate content in water. Over a short three-month preliminary study, sediment accretion was observed primarily within the vegetation with the bulk of the erosion occurring around the oyster beds. TON was detected at levels between 10 µM and 30 µM, ammonium up to 5 µM, and orthophosphate was only detected in very low levels, consistently quality data will be used to establish baseline data for future research to determine volumetric geomorphic change,and to set a standard for water quality trends, surrounding oyster beds and vegetation in response to climatic events.

  16. Light attenuation in estuarine mangrove lakes

    Science.gov (United States)

    Frankovich, Thomas A.; Rudnick, David T.; Fourqurean, James W.

    2017-01-01

    Submerged aquatic vegetation (SAV) cover has declined in brackish lakes in the southern Everglades characterized by low water transparencies, emphasizing the need to evaluate the suitability of the aquatic medium for SAV growth and to identify the light attenuating components that contribute most to light attenuation. Underwater attenuation of downwards irradiance of photosynthetically active radiation (PAR) was determined over a three year period at 42 sites in shallow (freshwater flow into these areas may dilute CDOM concentrations and improve the salinity and light climate for SAV communities.

  17. Living Gluten Free

    Science.gov (United States)

    ... Disease" Articles Celiac Disease Changes Everything / What is Celiac Disease? / Symptoms, Diagnosis & Treatment / Four Inches and Seven Pounds… / Learning to Live Well with Celiac Disease / Living Gluten-Free Spring 2015 Issue: Volume 10 ...

  18. Modelling live forensic acquisition

    CSIR Research Space (South Africa)

    Grobler, MM

    2009-06-01

    Full Text Available This paper discusses the development of a South African model for Live Forensic Acquisition - Liforac. The Liforac model is a comprehensive model that presents a range of aspects related to Live Forensic Acquisition. The model provides forensic...

  19. Engineering Cartilage

    Science.gov (United States)

    ... Research Matters NIH Research Matters March 3, 2014 Engineering Cartilage Artistic rendering of human stem cells on ... situations has been a major goal in tissue engineering. Cartilage contains water, collagen, proteoglycans, and chondrocytes. Collagens ...

  20. Governing Engineering

    DEFF Research Database (Denmark)

    Buch, Anders

    2012-01-01

    Most people agree that our world face daunting problems and, correctly or not, technological solutions are seen as an integral part of an overall solution. But what exactly are the problems and how does the engineering ‘mind set’ frame these problems? This chapter sets out to unravel dominant...... perspectives in challenge per-ception in engineering in the US and Denmark. Challenge perception and response strategies are closely linked through discursive practices. Challenge perceptions within the engineering community and the surrounding society are thus critical for the shaping of engineering education...... and the engineering profession. Through an analysis of influential reports and position papers on engineering and engineering education the chapter sets out to identify how engineering is problematized and eventually governed. Drawing on insights from governmentality studies the chapter strives to elicit the bodies...

  1. Industrial Engineering

    DEFF Research Database (Denmark)

    Karlsson, Christer

    2015-01-01

    Industrial engineering is a discipline that is concerned with increasing the effectiveness of (primarily) manufacturing and (occasionally).......Industrial engineering is a discipline that is concerned with increasing the effectiveness of (primarily) manufacturing and (occasionally)....

  2. Governing Engineering

    DEFF Research Database (Denmark)

    Buch, Anders

    2011-01-01

    Abstract: Most people agree that our world faces daunting problems and, correctly or not, technological solutions are seen as an integral part of an overall solution. But what exactly are the problems and how does the engineering ‘mind set’ frame these problems? This chapter sets out to unravel...... dominant perspectives in challenge perception in engineering in the US and Denmark. Challenge perception and response strategies are closely linked through discursive practices. Challenge perceptions within the engineering community and the surrounding society are thus critical for the shaping...... of engineering education and the engineering profession. Through an analysis of influential reports and position papers on engineering and engineering education the chapter sets out to identify how engineering is problematized and eventually governed. Drawing on insights from governmentality studies the chapter...

  3. Computer Engineers.

    Science.gov (United States)

    Moncarz, Roger

    2000-01-01

    Looks at computer engineers and describes their job, employment outlook, earnings, and training and qualifications. Provides a list of resources related to computer engineering careers and the computer industry. (JOW)

  4. Engineering _ litteraturliste

    DEFF Research Database (Denmark)

    Sillasen, Martin Krabbe; Daugbjerg, Peer; Nielsen, Keld

    2017-01-01

    Litteraturliste udarbejdet som grundlag for artiklen ”Engineering – svaret på naturfagenes udfordringer?”......Litteraturliste udarbejdet som grundlag for artiklen ”Engineering – svaret på naturfagenes udfordringer?”...

  5. Coefficient of linear attenuation of beer for γ rays of 662 keV

    International Nuclear Information System (INIS)

    Ortiz A, M. D.; Cano S, D.; Vega C, H. R.

    2017-10-01

    The coefficient of linear attenuation of the beer was determined by means of a transmission experiment with a source of Cs 137 and a gamma ray spectrometer with a NaI(Tl) detector of 7.62 cm in diameter and 7.62 cm in height, using narrow geometry. The pulse height spectrum was accumulated for 1 minute of live time, 7 beer thicknesses (0.6 cm) were used. By means of linear regression by weighted squares we determined the linear attenuation coefficient whose value was μ = 0.0843 ± 0.0007 cm -1 . The coefficient of linear attenuation of water is 2.2% times greater than that of beer and to the geometry of the experimental arrangement. (Author)

  6. ADVANCING THE SCIENCE OF NATURAL AND ENHANCED ATTENUATION FOR CHLORINATED SOLVENTS

    Energy Technology Data Exchange (ETDEWEB)

    Looney, B; TOM O. EARLY, T; TYLER GILMORE, T; FRANCIS H. CHAPELLE, F; NORMAN H. CUTSHALL, N; JEFF ROSS, J; MARK ANKENY, M; Michael Heitkamp, M; DAVID MAJOR, D; CHARLES J. NEWELL, C; W. JODY WAUGH, W; GARY WEIN, G; Karen Vangelas, K; Karen-M Adams, K; CLAIRE H. SINK, C

    2006-12-27

    This report summarizes the results of a three-year program that addressed key scientific and technical aspects related to natural and enhanced attenuation of chlorinated organics. The results from this coordinated three-year program support a variety of technical and regulatory advancements. Scientists, regulators, engineers, end-users and stakeholders participated in the program, which was supported by the U.S. Department of Energy (DOE) and the Interstate Technology and Regulatory Council (ITRC). The overarching objective of the effort was to examine environmental remedies that are based on natural processes--remedies such as Monitored Natural Attenuation (MNA) or Enhanced Attenuation (EA). A key result of the recent effort was the general affirmation of the approaches and guidance in the original U.S. Environmental Protection Agency (EPA) chlorinated solvent MNA protocols and directives from 1998 and 1999, respectively. The research program did identify several specific opportunities for advances based on: (1) mass balance as the central framework for attenuation based remedies, (2) scientific advancements and achievements during the past ten years, (3) regulatory and policy development and real-world experience using MNA, and (4) exploration of various ideas for integrating attenuation remedies into a systematic set of ''combined remedies'' for contaminated sites. These opportunities are summarized herein and are addressed in more detail in referenced project documents and journal articles, as well as in the technical and regulatory documents being developed within the ITRC. Natural attenuation processes occur in all soil and groundwater systems and act, to varying degrees, on all contaminants. Thus, a decision to rely on natural attenuation processes as part of a site-remediation strategy does not depend on the occurrence of natural attenuation, but on its effectiveness in meeting site-specific remediation goals. Meeting these goals

  7. Seismic attenuation system for a nuclear reactor

    Energy Technology Data Exchange (ETDEWEB)

    Liszkai, Tamas; Cadell, Seth

    2018-01-30

    A system for attenuating seismic forces includes a reactor pressure vessel containing nuclear fuel and a containment vessel that houses the reactor pressure vessel. Both the reactor pressure vessel and the containment vessel include a bottom head. Additionally, the system includes a base support to contact a support surface on which the containment vessel is positioned in a substantially vertical orientation. An attenuation device is located between the bottom head of the reactor pressure vessel and the bottom head of the containment vessel. Seismic forces that travel from the base support to the reactor pressure vessel via the containment vessel are attenuated by the attenuation device in a direction that is substantially lateral to the vertical orientation of the containment vessel.

  8. Dexmedetomidine in premedication to attenuate the acute ...

    African Journals Online (AJOL)

    Background: The choice of anaesthetic agent for electroconvulsive therapy (ECT) depends on seizure duration, haemodynamic ... and infarction. To attenuate this acute ... scheduled for ECT, physical status ASA I and II, age between 18 and.

  9. Attenuation measurements in solutions of some carbohydrates

    International Nuclear Information System (INIS)

    Gagandeep; Singh, K.; Lark, B.S.; Sahota, H.S.

    2000-01-01

    The linear attenuation coefficients in aqueous solutions of three carbohydrates, glucose (C 6 H 12 O 6 ), maltose monohydrate (C 12 H 22 O 11 ·H 2 O), and sucrose (C 12 H 22 O 11 ), were determined at 81, 356, 511, 662, 1,173, and 1,332 keV by the gamma-ray transmission method in a good geometry setup. From the precisely measured densities of these solutions, mass attenuation coefficients were then obtained that varied systematically with the corresponding changes in the concentrations (g/cm 3 ) of these solutions. The experimental results were used in terms of effective atomic numbers and electron densities. A comparison between experimental and theoretical values of attenuation coefficients has proven that the study has a potential application for the determination of attenuation coefficients of solid solutes from their solutions without obtaining them in pure crystalline form

  10. Attenuation Measurements in Solutions of Some Carbohydrates

    International Nuclear Information System (INIS)

    Gagandeep; Singh, Kulwant; Lark, B.S.; Sahota, H.S.

    2000-01-01

    The linear attenuation coefficients in aqueous solutions of three carbohydrates, glucose (C 6 H 12 O 6 ), maltose monohydrate (C 12 H 22 O 11 .H 2 O), and sucrose (C 12 H 22 O 11 ), were determined at 81, 356, 511, 662, 1173, and 1332 keV by the gamma-ray transmission method in a good geometry setup. From the precisely measured densities of these solutions, mass attenuation coefficients were then obtained that varied systematically with the corresponding changes in the concentrations (g/cm 3 ) of these solutions. The experimental results were used in terms of effective atomic numbers and electron densities. A comparison between experimental and theoretical values of attenuation coefficients has proven that the study has a potential application for the determination of attenuation coefficients of solid solutes from their solutions without obtaining them in pure crystalline form

  11. Radiation-attenuated vaccine for lungworm disease

    International Nuclear Information System (INIS)

    Singh, C.M.

    1977-01-01

    The work done at the Indian Veternary Research Institute, Izatnagar, on the development of a vaccine for lungworm diseases is reported. Research work done includes: (1) studies on the epidemiology and the incidence of the lungworm infections, (ii) studies on the radiation-attenuated lungworm Dictyocaulus filaria vaccine, (iii) studies on other parasites using ionizing radiation, (iv) incidence of lungworm infection in sheep in Jammu and Kashmir State, (v) suitable dose of gamma radiation for attenuation, (vi) laboratory studies with radiation-attenuated D. filaria vaccine, (vii) serology of D. filaria infection, (viii) field trials with the radiation-attenuated vaccine, (ix) immune response of previously exposed lambs to vaccination, (x) comparative susceptibility of sheep and goats to infection with D. filaria, (xi) quantitative studies of D. filaria in lambs and (xii) production and supply of lungworm vaccine. (A.K.)

  12. Post-Retrieval Extinction Attenuates Cocaine Memories

    OpenAIRE

    Sartor, Gregory C; Aston-Jones, Gary

    2013-01-01

    Recent studies have shown that post-retrieval extinction training attenuates fear and reward-related memories in both humans and rodents. This noninvasive, behavioral approach has the potential to be used in clinical settings to treat maladaptive memories that underlie several psychiatric disorders, including drug addiction. However, few studies to date have used a post-retrieval extinction approach to attenuate addiction-related memories. In the current study, we attempted to disrupt cocaine...

  13. Electron Effective-Attenuation-Length Database

    Science.gov (United States)

    SRD 82 NIST Electron Effective-Attenuation-Length Database (PC database, no charge)   This database provides values of electron effective attenuation lengths (EALs) in solid elements and compounds at selected electron energies between 50 eV and 2,000 eV. The database was designed mainly to provide EALs (to account for effects of elastic-eletron scattering) for applications in surface analysis by Auger-electron spectroscopy (AES) and X-ray photoelectron spectroscopy (XPS).

  14. Investigation of photon attenuation coefficients for marble

    International Nuclear Information System (INIS)

    Basyigit, C; Akkurt, I; Kilincarslan, S; Akkurt, A

    2005-01-01

    The total linear attenuation coefficients μ (cm -1 ) have been obtained using the XCOM program at photon energies of 1 keV to 1 GeV for six different natural marbles produced in different places in Turkey. The individual contribution of photon interaction processes to the total linear attenuation coefficients for marble has been investigated. The calculated results were also compared with the measurements. The results obtained for marble were also compared with concrete. (note)

  15. Mechanisms of geometrical seismic attenuation

    Directory of Open Access Journals (Sweden)

    Igor B. Morozov

    2011-07-01

    Full Text Available In several recent reports, we have explained the frequency dependence of the apparent seismic quality-factor (Q observed in many studies according to the effects of geometrical attenuation, which was defined as the zero-frequency limit of the temporal attenuation coefficient. In particular, geometrical attenuation was found to be positive for most waves traveling within the lithosphere. Here, we present three theoretical models that illustrate the origin of this geometrical attenuation, and we investigate the causes of its preferential positive values. In addition, we discuss the physical basis and limitations of both the conventional and new attenuation models. For waves in media with slowly varying properties, geometrical attenuation is caused by variations in the wavefront curvature, which can be both positive (for defocusing and negative (for focusing. In media with velocity/density contrasts, incoherent reflectivity leads to geometrical-attenuation coefficients which are proportional to the mean squared reflectivity and are always positive. For «coherent» reflectivity, the geometrical attenuation is approximately zero, and the attenuation process can be described according to the concept of «scattering Q». However, the true meaning of this parameter is in describing the mean reflectivity within the medium, and not that of the traditional resonator quality factor known in mechanics. The general conclusion from these models is that non-zero and often positive levels of geometrical attenuation are common in realistic, heterogeneous media, both observationally and theoretically. When transformed into the conventional Q-factor form, this positive geometrical attenuation leads to Q values that quickly increase with frequency. These predictions show that the positive frequency-dependent Q observed in many datasets might represent artifacts of the transformations of the attenuation coefficients into Q.

  1. Effective preexposure and postexposure prophylaxis of rabies with a highly attenuated recombinant rabies virus.

    Science.gov (United States)

    Faber, Milosz; Li, Jianwei; Kean, Rhonda B; Hooper, D Craig; Alugupalli, Kishore R; Dietzschold, Bernhard

    2009-07-07

    Rabies remains an important public health problem with more than 95% of all human rabies cases caused by exposure to rabid dogs in areas where effective, inexpensive vaccines are unavailable. Because of their ability to induce strong innate and adaptive immune responses capable of clearing the infection from the CNS after a single immunization, live-attenuated rabies virus (RV) vaccines could be particularly useful not only for the global eradication of canine rabies but also for late-stage rabies postexposure prophylaxis of humans. To overcome concerns regarding the safety of live-attenuated RV vaccines, we developed the highly attenuated triple RV G variant, SPBAANGAS-GAS-GAS. In contrast to most attenuated recombinant RVs generated thus far, SPBAANGAS-GAS-GAS is completely nonpathogenic after intracranial infection of mice that are either developmentally immunocompromised (e.g., 5-day-old mice) or have inherited deficits in immune function (e.g., antibody production or type I IFN signaling), as well as normal adult animals. In addition, SPBAANGAS-GAS-GAS induces immune mechanisms capable of containing a CNS infection with pathogenic RV, thereby preventing lethal rabies encephalopathy. The lack of pathogenicity together with excellent immunogenicity and the capacity to deliver immune effectors to CNS tissues makes SPBAANGAS-GAS-GAS a promising vaccine candidate for both the preexposure and postexposure prophylaxis of rabies.

  2. Tracking the attenuation and nonbreaking dissipation of swells using altimeters

    Science.gov (United States)

    Jiang, Haoyu; Stopa, Justin E.; Wang, He; Husson, Romain; Mouche, Alexis; Chapron, Bertrand; Chen, Ge

    2016-02-01

    A method for systematically tracking swells across oceanic basins is developed by taking advantage of high-quality data from space-borne altimeters and wave model output. The evolution of swells is observed over large distances based on 202 swell events with periods ranging from 12 to 18 s. An empirical attenuation rate of swell energy of about 4 × 10-7 m-1 is estimated using these observations, and the nonbreaking energy dissipation rates of swells far away from their generating areas are also estimated using a point source model. The resulting acceptance range of nonbreaking dissipation rates is -2.5 to 5.0 × 10-7 m-1, which corresponds to a dissipation e-folding scales of at least 2000 km for steep swells, to almost infinite for small-amplitude swells. These resulting rates are consistent with previous studies using in-situ and synthetic aperture radar (SAR) observations. The frequency dispersion and angular spreading effects during swell propagation are discussed by comparing the results with other studies, demonstrating that they are the two dominant processes for swell height attenuation, especially in the near field. The resulting dissipation rates from these observations can be used as a reference for ocean engineering and wave modeling, and for related studies such as air-sea and wind-wave-turbulence interactions.

  3. Engineered nanomaterials: Exposures, hazards and risk prevention.

    Science.gov (United States)

    Nanotechnology presents the possibility of revolutionizing many aspects of our lives. People in many settings (academic, small and large industrial, and the general public) are either developing or using engineered nanomaterials (ENMs). However, understanding of the health and sa...

  4. Verification of photon attenuation characteristics for 3D printer based small animal lung model

    International Nuclear Information System (INIS)

    Lee, Se Ho; Lee, Seung Wook; Han, Su Chul; Park, Seung Woo

    2016-01-01

    Since it is difficult to measure absorbed dose to mice in vivo, replica mice are mostly used as alternative. In this study, realistic mouse phantom was fabricated by using 3D printer (object500 connex3, Stratasys, USA). Elemental inks as material of 3D printer were selected corresponding to mouse tissue. To represent lung, selected material was partially used with air layer. In order to verify material equivalent, super-flex bolus was simply compared to verify photon attenuation characteristics. In the case of lung, Hounsfield unit (HU) of the phantom were compared with a live mouse. In this study, we fabricated mouse phantom by using 3D printer, and practically verified photon attenuation characteristics. The fabricated phantom shows tissue equivalence as well as similar geometry with live mouse. As more and more growing of 3D printer technique, 3D printer based small preclinical animal phantom would increase reliability of verification of absorbed dose in small animal for preclinical study

  5. Verification of photon attenuation characteristics for 3D printer based small animal lung model

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Se Ho; Lee, Seung Wook [Pusan National University, Busan (Korea, Republic of); Han, Su Chul; Park, Seung Woo [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2016-05-15

    Since it is difficult to measure absorbed dose to mice in vivo, replica mice are mostly used as alternative. In this study, realistic mouse phantom was fabricated by using 3D printer (object500 connex3, Stratasys, USA). Elemental inks as material of 3D printer were selected corresponding to mouse tissue. To represent lung, selected material was partially used with air layer. In order to verify material equivalent, super-flex bolus was simply compared to verify photon attenuation characteristics. In the case of lung, Hounsfield unit (HU) of the phantom were compared with a live mouse. In this study, we fabricated mouse phantom by using 3D printer, and practically verified photon attenuation characteristics. The fabricated phantom shows tissue equivalence as well as similar geometry with live mouse. As more and more growing of 3D printer technique, 3D printer based small preclinical animal phantom would increase reliability of verification of absorbed dose in small animal for preclinical study.

  6. Cost-effective management of hydrocarbon plumes using monitored natural attenuation: case studies

    International Nuclear Information System (INIS)

    Borg, G.A.

    2000-01-01

    Engineered remediation of hydrocarbon plumes in groundwater at operating service station sites is expensive, disruptive, does not improve the management of risks to receptors, and does not provide certainty of outcome. When plumes are delineated, potential receptors identified and primary sources removed, monitored natural attenuation (MINA) is a cost-effective remediation option. If available, hydrocarbon concentration data from successive groundwater monitoring events showing that a plume is stable or reducing will provide enough primary evidence that natural attenuation is occurring. Where potential receptors will not be impacted in the short to medium term, MNA provides the same level of risk management as engineered remediation with much less cost, no disruption to the service station business, and with a certainty of meeting the objectives of the remediation

  7. Lg Attenuation Modeling in the Middle East

    Science.gov (United States)

    Pasyanos, M. E.; Matzel, E. M.; Walter, W. R.; Rodgers, A. J.

    2008-12-01

    We present a broadband tomographic model of Lg attenuation in the Middle East derived from source- and site-corrected amplitudes. The study region spans from Turkey through the Arabian Peninsula and Iran to Pakistan, Afghanistan, and northwest India. Absolute amplitude measurements are made on hand-selected and carefully windowed seismograms for tens of stations and thousands of crustal earthquakes resulting in excellent coverage of the region. We have modified the standard attenuation tomography technique to more explicitly define the earthquake source expression in terms of the seismic moment. This facilitates the use of the model to predict the expected amplitudes of new events, an important consideration for earthquake hazard or explosion monitoring applications. We will discuss the updated method and implications of this parameterization. A conjugate gradient method is used to tomographically invert the amplitude dataset of over 8000 paths. We solve for Q variation, as well as site and source terms, for a wide range of frequencies ranging from 0.5 -- 10 Hz. The attenuation results have a strong correlation to tectonics. Shields have low attenuation, while tectonic regions have high attenuation, with the highest attenuation at 1 Hz found in eastern Turkey. The results also compare favorably to other studies in the region made using Lg propagation efficiency, Lg/Pg amplitude ratios and two-station methods. We tomographically invert the amplitude measurements for each frequency independently. In doing so, it appears the frequency-dependence of attenuation is not compatible with the power law representation of Q(f). This research was performed under the auspices of the U.S. Department of Energy by the Lawrence Livermore National Laboratory under contract number DE-AC52-07NA27344. This is LLNL contribution LLNL-ABS-406761.

  8. Flexural wave attenuation in a sandwich beam with viscoelastic periodic cores

    Science.gov (United States)

    Guo, Zhiwei; Sheng, Meiping; Pan, Jie

    2017-07-01

    The flexural-wave attenuation performance of traditional constraint-layer damping in a sandwich beam is improved by using periodic constrained-layer damping (PCLD), where the monolithic viscoelastic core is replaced with two periodically alternating viscoelastic cores. Closed-form solutions of the wave propagation constants of the infinite periodic sandwich beam and the forced response of the corresponding finite sandwich structure are theoretically derived, providing computational support on the analysis of attenuation characteristics. In a sandwich beam with PCLD, the flexural waves can be attenuated by both Bragg scattering effect and damping effect, where the attenuation level is mainly dominated by Bragg scattering in the band-gaps and by damping in the pass-bands. Affected by these two effects, when the parameters of periodic cores are properly selected, a sandwich beam with PCLD can effectively reduce vibrations of much lower frequencies than that with traditional constrained-layer damping. The effects of the parameters of viscoelastic periodic cores on band-gap properties are also discussed, showing that the average attenuation in the desired frequency band can be maximized by tuning the length ratio and core thickness to proper values. The research in this paper could possibly provide useful information for the researches and engineers to design damping structures.

  9. Maximum likelihood estimation of the attenuated ultrasound pulse

    DEFF Research Database (Denmark)

    Rasmussen, Klaus Bolding

    1994-01-01

    The attenuated ultrasound pulse is divided into two parts: a stationary basic pulse and a nonstationary attenuation pulse. A standard ARMA model is used for the basic pulse, and a nonstandard ARMA model is derived for the attenuation pulse. The maximum likelihood estimator of the attenuated...

  10. Effective preexposure and postexposure prophylaxis of rabies with a highly attenuated recombinant rabies virus

    OpenAIRE

    Faber, Milosz; Li, Jianwei; Kean, Rhonda B.; Hooper, D. Craig; Alugupalli, Kishore R.; Dietzschold, Bernhard

    2009-01-01

    Rabies remains an important public health problem with more than 95% of all human rabies cases caused by exposure to rabid dogs in areas where effective, inexpensive vaccines are unavailable. Because of their ability to induce strong innate and adaptive immune responses capable of clearing the infection from the CNS after a single immunization, live-attenuated rabies virus (RV) vaccines could be particularly useful not only for the global eradication of canine rabies but also for late-stage r...

  11. Safety and efficacy of an attenuated Chinese QX-like infectious bronchitis virus strain as a candidate vaccine.

    Science.gov (United States)

    Zhao, Ye; Cheng, Jin-long; Liu, Xiao-yu; Zhao, Jing; Hu, Yan-xin; Zhang, Guo-zhong

    2015-10-22

    Infectious bronchitis (IB) is a highly contagious respiratory and urogenital disease of chickens caused by infectious bronchitis virus (IBV). This disease is of considerable economic importance and is primarily controlled through biosecurity and immunization with live attenuated and inactivated IB vaccines of various serotypes. In the present study, we tested the safety and efficacy of an attenuated predominant Chinese QX-like IBV strain. The results revealed that the attenuated strain has a clear decrease in pathogenicity for specific-pathogen-free (SPF) chickens compared with the parent strain. Strain YN-inoculated birds had clinical signs of varying severity with 30% mortality, while the attenuated group appeared healthy, with less tissue damage. The attenuated strain also had relatively low tissue replication rates and higher antibody levels. The superior protective efficacy of the attenuated strain was observed when vaccinated birds were challenged with a homologous or heterologous field IBV strain, indicating the potential of the attenuated YN (aYN) as a vaccine. Producing a vaccine targeting the abundant serotype in China is essential to reducing the economic impact of IB on the poultry industry. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Engineering extracellular matrix through nanotechnology.

    Science.gov (United States)

    Kelleher, Cassandra M; Vacanti, Joseph P

    2010-12-06

    The goal of tissue engineering is the creation of a living device that can restore, maintain or improve tissue function. Behind this goal is a new idea that has emerged from twentieth century medicine, science and engineering. It is preceded by centuries of human repair and replacement with non-living materials adapted to restore function and cosmetic appearance to patients whose tissues have been destroyed by disease, trauma or congenital abnormality. The nineteenth century advanced replacement and repair strategies based on moving living structures from a site of normal tissue into a site of defects created by the same processes. Donor skin into burn wounds, tendon transfers, intestinal replacements into the urinary tract, toes to replace fingers are all examples. The most radical application is that of vital organ transplantation in which a vital part such as heart, lung or liver is removed from one donor, preserved for transfer and implanted into a patient dying of end-stage organ failure. Tissue engineering and regenerative medicine have advanced a general strategy combining the cellular elements of living tissue with sophisticated biomaterials to produce living structures of sufficient size and function to improve patients' lives. Multiple strategies have evolved and the application of nanotechnology can only improve the field. In our era, by necessity, any medical advance must be successfully commercialized to allow widespread application to help the greatest number of patients. It follows that business models and regulatory agencies must adapt and change to enable these new technologies to emerge. This brief review will discuss the science of nanotechnology and how it has been applied to this evolving field. We will then briefly summarize the history of commercialization of tissue engineering and suggest that nanotechnology may be of use in breeching the barriers to commercialization although its primary mission is to improve the technology by solving some

  13. Reversion of a live porcine reproductive and respiratory virus vaccine investigated by parallel mutations

    DEFF Research Database (Denmark)

    Nielsen, Henriette S.; Oleksiewicz, Martin B; Forsberg, R

    2001-01-01

    A live attenuated porcine reproductive and respiratory syndrome (PRRS) vaccine virus has been shown to revert to virulence under field conditions. In order to identify genetic virulence determinants, ORF1 from the attenuated vaccine virus and three Danish vaccine-derived field isolates was sequen......A live attenuated porcine reproductive and respiratory syndrome (PRRS) vaccine virus has been shown to revert to virulence under field conditions. In order to identify genetic virulence determinants, ORF1 from the attenuated vaccine virus and three Danish vaccine-derived field isolates...... in the vaccine virus sequence during cell-culture adaptation. Evaluation of the remaining mutations in the ORF1 sequence revealed stronger selective pressure for amino acid conservation during spread in pigs than during vaccine production. Furthermore, it was found that the selective pressure did not change...

  14. Reversion of a live porcine reproductive and respiratory syndrome virus vaccine investigated by parallel mutations

    DEFF Research Database (Denmark)

    Nielsen, Henriette S.; Oleksiewicz, M.B.; Forsberg, R.

    2001-01-01

    A live attenuated porcine reproductive and respiratory syndrome (PRRS) vaccine virus has been shown to revert to virulence under field conditions. In order to identify genetic virulence determinants, ORF1 from the attenuated vaccine virus and three Danish vaccine-derived field isolates was sequen......A live attenuated porcine reproductive and respiratory syndrome (PRRS) vaccine virus has been shown to revert to virulence under field conditions. In order to identify genetic virulence determinants, ORF1 from the attenuated vaccine virus and three Danish vaccine-derived field isolates...... in the vaccine virus sequence during cell-culture adaptation. Evaluation of the remaining mutations in the ORF1 sequence revealed stronger selective pressure for amino acid conservation during spread in pigs than during vaccine production. Furthermore, it was found that the selective pressure did not change...

  15. Deletion of the thymidine kinase gene induces complete attenuation of the Georgia isolate of African swine fever virus

    Science.gov (United States)

    African swine fever virus (ASFV) is the etiological agent of a contagious and often lethal viral disease of domestic pigs. There are no vaccines to control Africa swine fever (ASF). Experimental vaccines have been developed using genetically modified live attenuated ASFVs obtained by specifically de...

  16. Correlation of free-space optics link attenuation with sonic temperature

    Czech Academy of Sciences Publication Activity Database

    Chládová, Zuzana; Fišer, Ondřej; Brázda, Vladimír; Svoboda, Jaroslav

    2013-01-01

    Roč. 52, č. 3 (2013) ISSN 0091-3286 R&D Projects: GA ČR(CZ) GAP102/11/1376 Institutional support: RVO:68378289 Keywords : free-space optics * atmospheric attenuation * water vapor * free-space optics design Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering Impact factor: 0.958, year: 2013 http://opticalengineering.spiedigitallibrary.org/article.aspx?articleid=1667062

  17. Vickers Attenuator. Volume 3C(VA) - Technical appraisal. Consultants' 1983 report

    Energy Technology Data Exchange (ETDEWEB)

    1986-01-01

    A report is given by a team of Consultants on the estimated cost of converting wave energy to electrical energy by a 2 GW array of Vickers Attenuator wave energy devices and delivering this to a sub-station on the west coast of Skye. Comparisons of the estimates made by the team developing the concept are presented and discrepancies discussed. A detailed engineering assessment is given.

  18. Fat Attenuation at CT in Anorexia Nervosa

    Science.gov (United States)

    Gill, Corey M.; Torriani, Martin; Murphy, Rachel; Harris, Tamara B.; Miller, Karen K.; Klibanski, Anne

    2016-01-01

    Purpose To investigate the composition, cross-sectional area (CSA), and hormonal correlates of different fat depots in women with anorexia nervosa (AN) and control subjects with normal weights to find out whether patients with AN have lower fat CSA but higher attenuation than did control subjects and whether these changes may be mediated by gonadal steroids, cortisol, and thyroid hormones. Materials and Methods This study was institutional review board approved and HIPAA compliant. Written informed consent was obtained. Forty premenopausal women with AN and 40 normal-weight women of comparable age (mean age ± standard deviation, 26 years ± 5) were studied. All individuals underwent computed tomography of the abdomen and thigh with a calibration phantom. Abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), thigh SAT, and thigh intermuscular adipose tissue CSA and attenuation were quantified. Serum estradiol, thyroid hormones, and urinary free cortisol levels were assessed. Variables were compared by using analysis of variance. Associations were examined by using linear regression analysis. Results Women with AN had higher fat attenuation than did control subjects (−100.1 to −46.7 HU vs −117.6 to −61.8 HU, P < .0001), despite lower fat CSA (2.0–62.8 cm2 vs 5.5–185.9 cm2, P < .0001). VAT attenuation but not CSA was inversely associated with lowest prior lifetime body mass index in AN (r = −0.71, P = .006). Serum estradiol levels were inversely associated with fat attenuation (r = −0.34 to −0.61, P = .03 to <.0001) and were positively associated with fat CSA of all compartments (r = 0.42–0.64, P = .007 to <.0001). Thyroxine levels and urinary free cortisol levels were positively associated with thigh SAT attenuation (r = 0.64 [P = .006] and r = 0.68 [P = .0004], respectively) and were inversely associated with abdominal SAT and VAT CSA (r = −0.44 to −0.58, P = .04 to .02). Conclusion Women with AN have differences in fat

  19. Engineering mechanics

    CERN Document Server

    Gross, Dietmar; Schröder, Jörg; Wall, Wolfgang A; Rajapakse, Nimal

    Statics is the first volume of a three-volume textbook on Engineering Mechanics. The authors, using a time-honoured straightforward and flexible approach, present the basic concepts and principles of mechanics in the clearest and simplest form possible to advanced undergraduate engineering students of various disciplines and different educational backgrounds. An important objective of this book is to develop problem solving skills in a systematic manner. Another aim of this volume is to provide engineering students as well as practising engineers with a solid foundation to help them bridge the gap between undergraduate studies on the one hand and advanced courses on mechanics and/or practical engineering problems on the other. The book contains numerous examples, along with their complete solutions. Emphasis is placed upon student participation in problem solving. The contents of the book correspond to the topics normally covered in courses on basic engineering mechanics at universities and colleges. Now in i...

  20. Invisible Engineers

    Science.gov (United States)

    Ohashi, Hideo

    Questionnaire to ask “mention three names of scientists you know” and “three names of engineers you know” was conducted and the answers from 140 adults were analyzed. The results indicated that the image of scientists is represented by Nobel laureates and that of engineers by great inventors like Thomas Edison and industry founders like Soichiro Honda. In order to reveal the image of engineers among young generation, questionnaire was conducted for pupils in middle and high schools. Answers from 1,230 pupils were analyzed and 226 names mentioned as engineers were classified. White votes reached 60%. Engineers who are neither big inventors nor company founders collected less than 1% of named votes. Engineers are astonishingly invisible from young generation. Countermeasures are proposed.

  1. Global engineering

    International Nuclear Information System (INIS)

    Plass, L.

    2001-01-01

    This article considers the challenges posed by the declining orders in the plant engineering and contracting business in Germany, the need to remain competitive, and essential preconditions for mastering the challenge. The change in engineering approach is illustrated by the building of a methanol plant in Argentina by Lurgi with the basic engineering completed in Frankfurt with involvement of key personnel from Poland, completely engineered subsystems from a Brazilian subsupplier, and detailed engineering work in Frankfurt. The production of methanol from natural gas using the LurgiMega/Methanol process is used as a typical example of the industrial plant construction sector. The prerequisites for successful global engineering are listed, and error costs in plant construction, possible savings, and process intensification are discussed

  2. Elastic wave attenuation in rocks containing fluids

    International Nuclear Information System (INIS)

    Berryman, J.G.

    1986-01-01

    The low-frequency limit of Biot's theory of fluid-saturated porous media predicts that the coefficients for viscous attenuation of shear waves and of the fast compressional wave are proportional to the fluid permeability. Although the observed attenuation is generally in qualitative agreement with the theory, the magnitude of the observed attenuation coefficient in rocks is often more than an order of magnitude higher than expected. This apparent dilemma can be resolved without invoking other attenuation mechanisms if the intrinsic permeability of the rock is inhomogeneous and varies widely in magnitude. A simple calculation of the overall behavior of a layered porous material using local-flow Biot theory shows that the effective permeability for attenuation is the mean of the constituent permeabilities while the effective permeability for fluid flow is the harmonic mean. When the range of variation in the local permeability is one or more orders of magnitude, this difference in averaging method can easily explain some of the observed discrepancies

  3. Live your questions now

    OpenAIRE

    Brownrigg, Jenny

    2016-01-01

    'Live Your Questions Now' is a case study for Cubitt Education's publication 'Aging in Public: creative practice in ageing and the public realm from across the UK', edited by Daniel Baker and published by Cubitt Gallery, Studios and Education, London in 2016. The publication was linked to Cubitt's programme 'Public Wisdom' (2011-2015). My case study is about 'Live your questions now', a group exhibition I curated in 2011 for Mackintosh Museum, The Glasgow School of Art. 'Live your questions n...

  4. Human engineering

    International Nuclear Information System (INIS)

    Yang, Seong Hwan; Park, Bum; Gang, Yeong Sik; Gal, Won Mo; Baek, Seung Ryeol; Choe, Jeong Hwa; Kim, Dae Sung

    2006-07-01

    This book mentions human engineering, which deals with introduction of human engineering, Man-Machine system like system design, and analysis and evaluation of Man-Machine system, data processing and data input, display, system control of man, human mistake and reliability, human measurement and design of working place, human working, hand tool and manual material handling, condition of working circumstance, working management, working analysis, motion analysis working measurement, and working improvement and design in human engineering.

  5. Engineering Electromagnetics

    International Nuclear Information System (INIS)

    Kim, Se Yun

    2009-01-01

    This book deals with engineering electromagnetics. It contains seven chapters, which treats understanding of engineering electromagnetics such as magnet and electron spin, current and a magnetic field and an electromagnetic wave, Essential tool for engineering electromagnetics on rector and scalar, rectangular coordinate system and curl vector, electrostatic field with coulomb rule and method of electric images, Biot-Savart law, Ampere law and magnetic force, Maxwell equation and an electromagnetic wave and reflection and penetration of electromagnetic plane wave.

  6. Information engineering

    Energy Technology Data Exchange (ETDEWEB)

    Hunt, D.N.

    1997-02-01

    The Information Engineering thrust area develops information technology to support the programmatic needs of Lawrence Livermore National Laboratory`s Engineering Directorate. Progress in five programmatic areas are described in separate reports contained herein. These are entitled Three-dimensional Object Creation, Manipulation, and Transport, Zephyr:A Secure Internet-Based Process to Streamline Engineering Procurements, Subcarrier Multiplexing: Optical Network Demonstrations, Parallel Optical Interconnect Technology Demonstration, and Intelligent Automation Architecture.

  7. Software engineering

    CERN Document Server

    Sommerville, Ian

    2010-01-01

    The ninth edition of Software Engineering presents a broad perspective of software engineering, focusing on the processes and techniques fundamental to the creation of reliable, software systems. Increased coverage of agile methods and software reuse, along with coverage of 'traditional' plan-driven software engineering, gives readers the most up-to-date view of the field currently available. Practical case studies, a full set of easy-to-access supplements, and extensive web resources make teaching the course easier than ever.

  8. Administration for Community Living

    Science.gov (United States)

    ... 15, 2017 Grants from the National Institute on Disability, Independent Living, and Rehabilitation Research ... integration, and inclusion throughout life Other ACL Sites Eldercare Locator OlderIndians. ...

  9. Living the Utopia

    DEFF Research Database (Denmark)

    Davis, John; Warring, Anette Elisabeth

    2011-01-01

    This article examines experiments in communal living in Britain and Denmark in the early 1970s, using life-story interviews from seventeen members of two British and two Danish communes. It examines communal living as a fusion of radical political principles with the practice of experimental...... collective living. It concludes that the movement's egalitarian principles of resource-sharing, gender equality and the avoidance of hierarchies were broadly achieved, even if the movement obviously did not realize its more ambitious objective of undermining the bourgeois family. Though none...... of the interviewees lives communally now, most remain faithful to the principles behind the movement....

  10. Mechanical Engineering | Classification | College of Engineering & Applied

    Science.gov (United States)

    Engineering Concentration on Ergonomics M.S. Program in Computer Science Interdisciplinary Concentration on Energy Doctoral Programs in Engineering Non-Degree Candidate Departments Biomedical Engineering Biomedical Engineering Industry Advisory Council Civil & Environmental Engineering Civil &

  11. Biomedical Engineering | Classification | College of Engineering & Applied

    Science.gov (United States)

    Engineering Concentration on Ergonomics M.S. Program in Computer Science Interdisciplinary Concentration on Energy Doctoral Programs in Engineering Non-Degree Candidate Departments Biomedical Engineering Biomedical Engineering Industry Advisory Council Civil & Environmental Engineering Civil &

  12. Materials Science & Engineering | Classification | College of Engineering &

    Science.gov (United States)

    Biomedical Engineering Concentration on Ergonomics M.S. Program in Computer Science Interdisciplinary Concentration on Energy Doctoral Programs in Engineering Non-Degree Candidate Departments Biomedical Engineering Biomedical Engineering Industry Advisory Council Civil & Environmental Engineering Civil &

  13. Electrical Engineering | Classification | College of Engineering & Applied

    Science.gov (United States)

    Engineering Concentration on Ergonomics M.S. Program in Computer Science Interdisciplinary Concentration on Energy Doctoral Programs in Engineering Non-Degree Candidate Departments Biomedical Engineering Biomedical Engineering Industry Advisory Council Civil & Environmental Engineering Civil &

  14. Engineering tribology

    CERN Document Server

    Stachowiak, Gwidon; Batchelor, A W; Batchelor, Andrew W

    2005-01-01

    As with the previous edition, the third edition of Engineering Tribology provides a thorough understanding of friction and wear using technologies such as lubrication and special materials. Tribology is a complex topic with its own terminology and specialized concepts, yet is vitally important throughout all engineering disciplines, including mechanical design, aerodynamics, fluid dynamics and biomedical engineering. This edition includes updated material on the hydrodynamic aspects of tribology as well as new advances in the field of biotribology, with a focus throughout on the engineering ap

  15. Attenuation of the gamma rays in tissues

    International Nuclear Information System (INIS)

    Arcos P, A.; Rodriguez N, S.; Pinedo S, A.; Amador V, P.; Chacon R, A.; Vega C, H.R.

    2005-01-01

    The mass and lineal attenuation coefficient and of hepatic tissue, muscular, osseous and of brain before gamma rays of 10 -3 to 10 5 MeV were calculated. For the case of the osseous tissue the calculation was made for the cartilage, the cortical tissue and the bone marrow. During the calculations the elementary composition of the tissues of human origin was used. The calculations include by separate the Photoelectric effect, the Compton scattering and the Pair production, as well as the total. For to establish a comparison with the attenuation capacities, the coefficients of the water, the aluminum and the lead also were calculated. The study was complemented measuring the attenuation coefficient of hepatic tissue of bovine before gamma rays of 0.662 MeV of a source of 137 Cs. The measurement was made through of an experiment of photons transmission through samples frozen of hepatic tissue and with a Geiger-Mueller detector. (Author)

  16. Electromagnetic Wave Attenuation in Atmospheric Pressure Plasma

    International Nuclear Information System (INIS)

    Zhang Shu; Hu Xiwei; Liu Minghai; Luo Fang; Feng Zelong

    2007-01-01

    When an electromagnetic (EM) wave propagates in an atmospheric pressure plasma (APP) layer, its attenuation depends on the APP parameters such as the layer width, the electron density and its profile and collision frequency between electrons and neutrals. This paper proposes that a combined parameter-the product of the line average electron density n-bar and width d of the APP layer (i.e., the total number of electrons in a unit volume along the wave propagation path) can play a more explicit and decisive role in the wave attenuation than any of the above individual parameters does. The attenuation of the EM wave via the product of n-bar and d with various collision frequencies between electrons and neutrals is presented

  17. Development of multilayer constructs for tissue engineering

    NARCIS (Netherlands)

    Bettahalli, N. M. S.; Groen, N.; Steg, H.; Unadkat, H.; de Boer, J.; van Blitterswijk, C. A.; Wessling, M.; Stamatialis, D.

    The rapidly developing field of tissue engineering produces living substitutes that restore, maintain or improve the function of tissues or organs. In contrast to standard therapies, the engineered products become integrated within the patient, affording a potentially permanent and specific cure of

  18. Development of multilayer constructs for tissue engineering

    NARCIS (Netherlands)

    Bettahalli Narasimha, M.S.; Groen, N.; Steg, H.; Unadkat, H.V.; de Boer, Jan; van Blitterswijk, Clemens; Wessling, Matthias; Stamatialis, Dimitrios

    2014-01-01

    The rapidly developing field of tissue engineering produces living substitutes that restore, maintain or improve the function of tissues or organs. In contrast to standard therapies, the engineered products become integrated within the patient, affording a potentially permanent and specific cure of

  19. Analysis of Uncertainties in Infrared Camera Measurements of a Turbofan Engine in an Altitude Test Cell

    National Research Council Canada - National Science Library

    Morris, Thomas

    2004-01-01

    ... from the facility structure, hot exhaust gases, and the measurement equipment itself. The atmosphere and a protective ZnSe window that shields the camera from the hot engine exhaust also introduce measurement uncertainty due to attenuation...

  20. Live and Dead Nodes

    DEFF Research Database (Denmark)

    Jørgensen, Sune Lehman; Jackson, A. D.

    2005-01-01

    In this paper, we explore the consequences of a distinction between `live' and `dead' network nodes; `live' nodes are able to acquire new links whereas `dead' nodes are static. We develop an analytically soluble growing network model incorporating this distinction and show that it can provide...

  1. Food Engineering

    NARCIS (Netherlands)

    Boom, R.M.; Janssen, A.E.M.

    2014-01-01

    Food engineering is a rapidly changing discipline. Traditionally, the main focus was on food preservation and stabilization, whereas trends now are on diversity, health, taste, and sustainable production. Next to a general introduction of the definition of food engineering, this article gives a

  2. Fluids engineering

    International Nuclear Information System (INIS)

    Anon.

    1991-01-01

    Fluids engineering has played an important role in many applications, from ancient flood control to the design of high-speed compact turbomachinery. New applications of fluids engineering, such as in high-technology materials processing, biotechnology, and advanced combustion systems, have kept up unwaining interest in the subject. More accurate and sophisticated computational and measurement techniques are also constantly being developed and refined. On a more fundamental level, nonlinear dynamics and chaotic behavior of fluid flow are no longer an intellectual curiosity and fluid engineers are increasingly interested in finding practical applications for these emerging sciences. Applications of fluid technology to new areas, as well as the need to improve the design and to enhance the flexibility and reliability of flow-related machines and devices will continue to spur interest in fluids engineering. The objectives of the present seminar were: to exchange current information on arts, science, and technology of fluids engineering; to promote scientific cooperation between the fluids engineering communities of both nations, and to provide an opportunity for the participants and their colleagues to explore possible joint research programs in topics of high priority and mutual interest to both countries. The Seminar provided an excellent forum for reviewing the current state and future needs of fluids engineering for the two nations. With the Seminar ear-marking the first formal scientific exchange between Korea and the United States in the area of fluids engineering, the scope was deliberately left broad and general

  3. Biomedical Engineering

    CERN Document Server

    Suh, Sang C; Tanik, Murat M

    2011-01-01

    Biomedical Engineering: Health Care Systems, Technology and Techniques is an edited volume with contributions from world experts. It provides readers with unique contributions related to current research and future healthcare systems. Practitioners and researchers focused on computer science, bioinformatics, engineering and medicine will find this book a valuable reference.

  4. Genetic Engineering

    Science.gov (United States)

    Phillips, John

    1973-01-01

    Presents a review of genetic engineering, in which the genotypes of plants and animals (including human genotypes) may be manipulated for the benefit of the human species. Discusses associated problems and solutions and provides an extensive bibliography of literature relating to genetic engineering. (JR)

  5. Corrosion Engineering.

    Science.gov (United States)

    White, Charles V.

    A description is provided for a Corrosion and Corrosion Control course offered in the Continuing Engineering Education Program at the General Motors Institute (GMI). GMI is a small cooperative engineering school of approximately 2,000 students who alternate between six-week periods of academic study and six weeks of related work experience in…

  6. Evaluating Living Standard Indicators

    Directory of Open Access Journals (Sweden)

    Birčiaková Naďa

    2015-09-01

    Full Text Available This paper deals with the evaluation of selected available indicators of living standards, divided into three groups, namely economic, environmental, and social. We have selected six countries of the European Union for analysis: Bulgaria, the Czech Republic, Hungary, Luxembourg, France, and Great Britain. The aim of this paper is to evaluate indicators measuring living standards and suggest the most important factors which should be included in the final measurement. We have tried to determine what factors influence each indicator and what factors affect living standards. We have chosen regression analysis as our main method. From the study of factors, we can deduce their impact on living standards, and thus the value of indicators of living standards. Indicators with a high degree of reliability include the following factors: size and density of population, health care and spending on education. Emissions of carbon dioxide in the atmosphere also have a certain lower degree of reliability.

  7. Living with others

    DEFF Research Database (Denmark)

    Zabiliute, Emilija

    Living with Others’ is an ethnographic study of everyday lives and health-seeking practices among urban poor living in a settlement in the margins of Delhi, India.By exploring subjectivities, lived experiences of poverty, and relations through a prism ofhealth, the inquiry aims to move beyond...... the explorations of precarity embedded in political economies and urban governance that dominate discussions on urban poor neighbourhoods in India.Empirically, the study draws on long-term ethnographic fieldwork and interviews among urban poor,mostly women;and formal and informal health practitioners, abundant...... in the area. Among these are governmental interventions,run under a maternal health developmental programme, National Rural Health Mission.The study argues that the vulnerabilities characterisingthe lives of the urban poor unfold and are negotiated through relations with kin, neighbours, and political patrons...

  8. Engineering surveying

    CERN Document Server

    Schofield, W

    2001-01-01

    The aim of Engineering Surveying has always been to impart and develop a clear understanding of the basic topics of the subject. The author has fully revised the book to make it the most up-to-date and relevant textbook available on the subject.The book also contains the latest information on trigonometric levelling, total stations and one-person measuring systems. A new chapter on satellites ensures a firm grasp of this vitally important topic.The text covers engineering surveying modules for civil engineering students on degree courses and forms a reference for the engineering surveying module in land surveying courses. It will also prove to be a valuable reference for practitioners.* Simple clear introduction to surveying for engineers* Explains key techniques and methods* Details reading systems and satellite position fixing

  9. Emotional engineering

    CERN Document Server

    In an age of increasing complexity, diversification and change, customers expect services that cater to their needs and to their tastes. Emotional Engineering vol 2. describes how their expectations can be satisfied and managed throughout the product life cycle, if producers focus their attention more on emotion. Emotional engineering provides the means to integrate products to create a new social framework and develops services beyond product realization to create of value across a full lifetime.  14 chapters cover a wide range of topics that can be applied to product, process and industry development, with special attention paid to the increasing importance of sensing in the age of extensive and frequent changes, including: • Multisensory stimulation and user experience  • Physiological measurement • Tactile sensation • Emotional quality management • Mental model • Kansei engineering.   Emotional Engineering vol 2 builds on Dr Fukuda’s previous book, Emotional Engineering, and provides read...

  10. Engineering Sustainability: A Technical Approach to Sustainability

    OpenAIRE

    Rosen, Marc A.

    2012-01-01

    Sustainability is a critically important goal for human activity and development. Sustainability in the area of engineering is of great importance to any plans for overall sustainability given 1) the pervasiveness of engineering activities in societies, 2) their importance in economic development and living standards, and 3) the significant impacts that engineering processes and systems have had, and continue to have, on the environment. Many factors that need to be considered and appropriate...

  11. Storage of long lived solid waste

    International Nuclear Information System (INIS)

    Ozarde, P.D.; Agarwal, K.; Gupta, R.K.; Gandhi, K.G.

    2009-01-01

    Long lived solid waste, generated during the fuel cycle mainly includes high level vitrified waste product, high level cladding hulls and low and intermediate level alpha wastes. These wastes require storage in specially designed engineered facilities before final disposal into deep geological repository. Since high-level vitrified waste contain heat generating radionuclides, the facility for their storage is designed for continuous cooling. High level cladding hulls undergo volume reduction by compaction and will be subsequently stored. (author)

  12. Silicone cushions for engineering applications

    International Nuclear Information System (INIS)

    Anon.

    1984-01-01

    When a complex system composed of materials of very different properties is subjected to varying temperature, differential thermal expansion and contraction will produce intolerable stresses unless the parts are separated by suitable cushions. In addition to accommodating differential thermal expansion and contraction, these cushions must absorb shock and vibration, take up dimensional tolerances in the parts, and distribute and attenuate applied loads. We are studying cellular silicone cushions, starting with raw materials and polymer manufacture, to analysis of mechanical and chemical properties, through short- and long-term life testing, in order to tailor cushions to various specific engineering requirements

  13. The news Engine

    DEFF Research Database (Denmark)

    Andersson, Ralf

    for ideas etc. Reporters have limitedpossibilities for making own stories and less time for research - each live reportercovers 5-7 stories during a day. People : In a survey, most reporters replied that the new workflow was afundamental change of their work and had major impact on their identity......The News Engine How a new experiment in newsrooms can change process, product and people.   By Ralf Andersson   In fall 2012, the news department of the Danish Broadcasting Corporation,decided to implement a new workflow called ”The News Engine” - in order to workfaster, more freely, flexible...... and with fewer resources. This was done to raisethe productivity. The fundamental principle was that all stories should fit all platforms(content sharing) - and that no one did their own story anymore. DR News introduced 8-10 mobile live teams who are responsible for doinginterviews, record pictures and sound...

  14. GPR measurements of attenuation in concrete

    Energy Technology Data Exchange (ETDEWEB)

    Eisenmann, David, E-mail: djeisen@cnde.iastate.edu; Margetan, Frank J., E-mail: djeisen@cnde.iastate.edu; Pavel, Brittney, E-mail: djeisen@cnde.iastate.edu [Center for Nondestructive Evaluation, Iowa State University, 1915 Scholl Road, Ames, IA 50011-3042 (United States)

    2015-03-31

    Ground-penetrating radar (GPR) signals from concrete structures are affected by several phenomenon, including: (1) transmission and reflection coefficients at interfaces; (2) the radiation patterns of the antenna(s) being used; and (3) the material properties of concrete and any embedded objects. In this paper we investigate different schemes for determining the electromagnetic (EM) attenuation of concrete from measured signals obtained using commercially-available GPR equipment. We adapt procedures commonly used in ultrasonic inspections where one compares the relative strengths of two or more signals having different travel paths through the material of interest. After correcting for beam spread (i.e., diffraction), interface phenomena, and equipment amplification settings, any remaining signal differences are assumed to be due to attenuation thus allowing the attenuation coefficient (say, in dB of loss per inch of travel) to be estimated. We begin with a brief overview of our approach, and then discuss how diffraction corrections were determined for our two 1.6 GHz GPR antennas. We then present results of attenuation measurements for two types of concrete using both pulse/echo and pitch/catch measurement setups.

  15. Mirtazapine attenuates cocaine seeking in rats.

    Science.gov (United States)

    Barbosa-Méndez, Susana; Leff, Phillipe; Arías-Caballero, Adriana; Hernández-Miramontes, Ricardo; Heinze, Gerardo; Salazar-Juárez, Alberto

    2017-09-01

    Relapse to cocaine use is a major problem in the clinical treatment of cocaine addiction. Antidepressants have been studied for their therapeutic potential to treat cocaine use disorder. Research has suggested that antidepressants attenuate both drug craving and the re-acquisition of drug-seeking and drug-taking behaviors. This study examined the efficacy of mirtazapine, an antidepressant/anxiolytic, in decreasing cocaine seeking in rats. We used the cocaine self-administration paradigm to assess the effects of mirtazapine on rats trained to self-administer cocaine or food under a fixed-ratio schedule. Mirtazapine (30 mg/kg, i.p.) was administered during extinction. Mirtazapine significantly attenuated non-reinforced lever-press responses during extinction. Moreover, the mirtazapine dosed for 30 days during extinction produced sustained attenuation of lever-press responses during re-acquisition of cocaine self-administration, without changing food-seeking behavior. Our results showed that mirtazapine attenuated the re-acquisition of cocaine-seeking responses. Our study pointed to the efficacy of mirtazapine in reducing the risk of drug relapse during abstinence, suggesting for its potential use as a novel pharmacological agent to treat drug abuse. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Controlled Attenuation Parameter And Alcoholic Hepatic Steatosis

    DEFF Research Database (Denmark)

    Thiele, Maja; Rausch, Vanessa; Fluhr, Gabriele

    2018-01-01

    BACKGROUND AND AIMS: Controlled attenuation parameter (CAP) is a novel non-invasive measure of hepatic steatosis, but has not been evaluated in alcoholic liver disease. We therefore aimed to validate CAP for assessment of biopsy-verified alcoholic steatosis and to study the effect of alcohol deto...

  17. Heat-accelerated radioinactivation of attenuated poliovirus

    International Nuclear Information System (INIS)

    Dugan, V.L.; Trujillo, R.

    1975-01-01

    Attenuated poliovirus is inactivated in a synergistic manner when exposed simultaneously to heat and ionizing radiation. The synergistic response is observed in both the thermally labile and stable forms of the virus. A three-term kinetic model may be used to describe the inactivation response of the virus in a thermal and/or ionizing radiation environment. (orig.) [de

  18. Ultrasonic attenuation in rare-earth monoarsenides

    Indian Academy of Sciences (India)

    2015-11-27

    Home; Journals; Pramana – Journal of Physics; Volume 86; Issue 6. Ultrasonic attenuation in rare-earth monoarsenides .... Proceedings of the International Workshop/Conference on Computational Condensed Matter Physics and Materials Science (IWCCMP-2015). Posted on November 27, 2015. Guest Editors: Anurag ...

  19. GPR measurements of attenuation in concrete

    Science.gov (United States)

    Eisenmann, David; Margetan, Frank J.; Pavel, Brittney

    2015-03-01

    Ground-penetrating radar (GPR) signals from concrete structures are affected by several phenomenon, including: (1) transmission and reflection coefficients at interfaces; (2) the radiation patterns of the antenna(s) being used; and (3) the material properties of concrete and any embedded objects. In this paper we investigate different schemes for determining the electromagnetic (EM) attenuation of concrete from measured signals obtained using commercially-available GPR equipment. We adapt procedures commonly used in ultrasonic inspections where one compares the relative strengths of two or more signals having different travel paths through the material of interest. After correcting for beam spread (i.e., diffraction), interface phenomena, and equipment amplification settings, any remaining signal differences are assumed to be due to attenuation thus allowing the attenuation coefficient (say, in dB of loss per inch of travel) to be estimated. We begin with a brief overview of our approach, and then discuss how diffraction corrections were determined for our two 1.6 GHz GPR antennas. We then present results of attenuation measurements for two types of concrete using both pulse/echo and pitch/catch measurement setups.

  20. GPR measurements of attenuation in concrete

    International Nuclear Information System (INIS)

    Eisenmann, David; Margetan, Frank J.; Pavel, Brittney

    2015-01-01

    Ground-penetrating radar (GPR) signals from concrete structures are affected by several phenomenon, including: (1) transmission and reflection coefficients at interfaces; (2) the radiation patterns of the antenna(s) being used; and (3) the material properties of concrete and any embedded objects. In this paper we investigate different schemes for determining the electromagnetic (EM) attenuation of concrete from measured signals obtained using commercially-available GPR equipment. We adapt procedures commonly used in ultrasonic inspections where one compares the relative strengths of two or more signals having different travel paths through the material of interest. After correcting for beam spread (i.e., diffraction), interface phenomena, and equipment amplification settings, any remaining signal differences are assumed to be due to attenuation thus allowing the attenuation coefficient (say, in dB of loss per inch of travel) to be estimated. We begin with a brief overview of our approach, and then discuss how diffraction corrections were determined for our two 1.6 GHz GPR antennas. We then present results of attenuation measurements for two types of concrete using both pulse/echo and pitch/catch measurement setups

  1. Anethum Graveolens Linn (Umbelliferae) Extract Attenuates Stress ...

    African Journals Online (AJOL)

    Anethum Graveolens Linn (Umbelliferae) Extract Attenuates Stress-induced Urinary Biochemical Changes and Improves Cognition in Scopolamineinduced Amnesic Rats. ... Conclusion: The aqueous extract of A. graveolens exhibited significant anti-stress, antioxidant and memory enhancing activities. The study provides a ...

  2. Electron attenuation characteristics of LiF

    Energy Technology Data Exchange (ETDEWEB)

    Paliwal, B R [Wisconsin Univ., Madison (USA). Div. of Clinical Oncology; Almond, P R

    1976-08-01

    The results of a study, indicating the exponential nature of the attenuation of electrons in LiF, are reported. This conclusion holds good not only for the monoenergetic electrons obtained from several pure ..beta.. emitters but also for the high energy electron beams delivered by radiotherapy facilities.

  3. Microwave attenuation with composite of copper microwires

    International Nuclear Information System (INIS)

    Gorriti, A.G.; Marin, P.; Cortina, D.; Hernando, A.

    2010-01-01

    It is shown that copper microwires composite media attenuates microwave reflection of metallic surfaces. We show how the distance to the metallic surface, as well as the length and volume fraction of microwires, determine the frequency of maximum absorption and the return loss level. Furthermore, we were able to fit the experimental results with a theoretical model based on Maxwell-Garnett mixing formula.

  4. Microwave attenuation with composite of copper microwires

    Energy Technology Data Exchange (ETDEWEB)

    Gorriti, A.G.; Marin, P. [Instituto de Magnetismo Aplicado, (UCM-ADIF-CSIC) and Departamento de Fisica de Materiales (UCM). P.O. Box 155, Las Rozas, Madrid 28230 (Spain); Cortina, D. [Micromag S.L., Las Rozas, Madrid 28230 (Spain); Hernando, A., E-mail: antonio.hernando@adif.e [Instituto de Magnetismo Aplicado, (UCM-ADIF-CSIC) and Departamento de Fisica de Materiales (UCM). P.O. Box 155, Las Rozas, Madrid 28230 (Spain); Micromag S.L., Las Rozas, Madrid 28230 (Spain)

    2010-05-15

    It is shown that copper microwires composite media attenuates microwave reflection of metallic surfaces. We show how the distance to the metallic surface, as well as the length and volume fraction of microwires, determine the frequency of maximum absorption and the return loss level. Furthermore, we were able to fit the experimental results with a theoretical model based on Maxwell-Garnett mixing formula.

  5. Touch Attenuates Infants' Physiological Reactivity to Stress

    Science.gov (United States)

    Feldman, Ruth; Singer, Magi; Zagoory, Orna

    2010-01-01

    Animal studies demonstrate that maternal touch and contact regulate infant stress, and handling during periods of maternal deprivation attenuates the stress response. To measure the effects of touch on infant stress reactivity during simulated maternal deprivation, 53 dyads were tested in two paradigms: still-face (SF) and still-face with maternal…

  6. Increased tissue oxygenation explains the attenuation of hyperemia upon repetitive pneumatic compression of the lower leg.

    Science.gov (United States)

    Messere, Alessandro; Ceravolo, Gianluca; Franco, Walter; Maffiodo, Daniela; Ferraresi, Carlo; Roatta, Silvestro

    2017-12-01

    The rapid hyperemia evoked by muscle compression is short lived and was recently shown to undergo a rapid decrease even in spite of continuing mechanical stimulation. The present study aims at investigating the mechanisms underlying this attenuation, which include local metabolic mechanisms, desensitization of mechanosensitive pathways, and reduced efficacy of the muscle pump. In 10 healthy subjects, short sequences of mechanical compressions ( n = 3-6; 150 mmHg) of the lower leg were delivered at different interstimulus intervals (ranging from 20 to 160 s) through a customized pneumatic device. Hemodynamic monitoring included near-infrared spectroscopy, detecting tissue oxygenation and blood volume in calf muscles, and simultaneous echo-Doppler measurement of arterial (superficial femoral artery) and venous (femoral vein) blood flow. The results indicate that 1 ) a long-lasting (>100 s) increase in local tissue oxygenation follows compression-induced hyperemia, 2 ) compression-induced hyperemia exhibits different patterns of attenuation depending on the interstimulus interval, 3 ) the amplitude of the hyperemia is not correlated with the amount of blood volume displaced by the compression, and 4 ) the extent of attenuation negatively correlates with tissue oxygenation ( r  = -0,78, P < 0.05). Increased tissue oxygenation appears to be the key factor for the attenuation of hyperemia upon repetitive compressive stimulation. Tissue oxygenation monitoring is suggested as a useful integration in medical treatments aimed at improving local circulation by repetitive tissue compression. NEW & NOTEWORTHY This study shows that 1 ) the hyperemia induced by muscle compression produces a long-lasting increase in tissue oxygenation, 2 ) the hyperemia produced by subsequent muscle compressions exhibits different patterns of attenuation at different interstimulus intervals, and 3 ) the extent of attenuation of the compression-induced hyperemia is proportional to the level of

  7. Analysis of biological samples by x-ray attenuation measurements

    International Nuclear Information System (INIS)

    Cesareo, R.

    1988-01-01

    Over the last few years there has been an increasing interest in X-ray attenuation measurements, mainly due to the enormous development of computer assisted tomography (CAT). With CAT, analytical information concerning the density and the mean atomic number distributions in a sample is deduced from a large number of attenuation measurements. Particular transmission methods developed, based on the differential attenuation method are discussed. The theoretical background for attenuation of radiation and for differential attenuation of radiation is given. Details about the generation of monoenergetic X-rays are discussed. Applications of attenuation measurements in the field of Medicine are presented

  8. Radioactive nuclides in the living environment

    International Nuclear Information System (INIS)

    Ueno, Kaoru; Hoshi, Michio.

    1993-09-01

    There are several radioactive nuclides in the living environment, such as those existing since the creation of the earth, those coming from experimental nuclear explosions, and radiations of the cosmic rays. A lesson on these radioactive nuclides was considered useful for understanding the place of nuclear technology, and have been made on the title of 'Radioactive Nuclides in the Living Environment' in the general course of the Nuclear Engineering School of Japan Atomic Energy Research Institute. When the curriculum of the general course was modified in 1993, the lesson was left in a changed form. Thus, the textbook of the lesson is presented in this report. The contents are natural and artificial radioactive nuclides in the living environment and where they have come from etc. (author)

  9. Interventions in everyday lives

    DEFF Research Database (Denmark)

    Dreier, Ole

    2015-01-01

    The purpose of psychotherapy is to help clients address and overcome problems troubling them in their everyday lives. Therapy can therefore only work if clients include it in their ongoing lives to deal with their problems. Detailed, systematic research is needed on how clients do so...... clients change their everyday lives to overcome their troubles. They also highlight what it involves for clients to accomplish this. It is concluded that we need more research on how to understand intervention; on the interaction between interventions and clients’ conduct of their everyday life...

  10. Digital Living at Home

    DEFF Research Database (Denmark)

    Andersen, Pernille Viktoria Kathja; Christiansen, Ellen Tove

    2013-01-01

    of these user voices has directed us towards a ‘home-keeping’ design discourse, which opens new horizons for design of digital home control systems by allowing users to perform as self-determined controllers and groomers of their habitat. The paper concludes by outlining the implications of a ‘home......Does living with digital technology inevitably lead to digital living? Users talking about a digital home control system, they have had in their homes for eight years, indicate that there is more to living with digital technology than a functional-operational grip on regulation. Our analysis......-keeping’ design discourse....

  11. Glycosylation Engineering

    DEFF Research Database (Denmark)

    Clausen, Henrik; Wandall, Hans H.; Steentoft, Catharina

    2017-01-01

    Knowledge of the cellular pathways of glycosylation across phylogeny provides opportunities for designing glycans via genetic engineering in a wide variety of cell types including bacteria, fungi, plant cells, and mammalian cells. The commercial demand for glycosylation engineering is broad......, including production of biological therapeutics with defined glycosylation (Chapter 57). This chapter describes how knowledge of glycan structures and their metabolism (Parts I–III of this book) has led to the current state of glycosylation engineering in different cell types. Perspectives for rapid...

  12. Engineering mathematics

    CERN Document Server

    Bird, John

    2014-01-01

    A practical introduction to the core mathematics required for engineering study and practiceNow in its seventh edition, Engineering Mathematics is an established textbook that has helped thousands of students to succeed in their exams.John Bird's approach is based on worked examples and interactive problems. This makes it ideal for students from a wide range of academic backgrounds as the student can work through the material at their own pace. Mathematical theories are explained in a straightforward manner, being supported by practical engineering examples and applications in order to ensure

  13. Engineering mathematics

    CERN Document Server

    Stroud, K A

    2013-01-01

    A groundbreaking and comprehensive reference that's been a bestseller since it first debuted in 1970, the new seventh edition of Engineering Mathematics has been thoroughly revised and expanded. Providing a broad mathematical survey, this innovative volume covers a full range of topics from the very basic to the advanced. Whether you're an engineer looking for a useful on-the-job reference or want to improve your mathematical skills, or you are a student who needs an in-depth self-study guide, Engineering Mathematics is sure to come in handy time and time again.

  14. Active inference, sensory attenuation and illusions.

    Science.gov (United States)

    Brown, Harriet; Adams, Rick A; Parees, Isabel; Edwards, Mark; Friston, Karl

    2013-11-01

    Active inference provides a simple and neurobiologically plausible account of how action and perception are coupled in producing (Bayes) optimal behaviour. This can be seen most easily as minimising prediction error: we can either change our predictions to explain sensory input through perception. Alternatively, we can actively change sensory input to fulfil our predictions. In active inference, this action is mediated by classical reflex arcs that minimise proprioceptive prediction error created by descending proprioceptive predictions. However, this creates a conflict between action and perception; in that, self-generated movements require predictions to override the sensory evidence that one is not actually moving. However, ignoring sensory evidence means that externally generated sensations will not be perceived. Conversely, attending to (proprioceptive and somatosensory) sensations enables the detection of externally generated events but precludes generation of actions. This conflict can be resolved by attenuating the precision of sensory evidence during movement or, equivalently, attending away from the consequences of self-made acts. We propose that this Bayes optimal withdrawal of precise sensory evidence during movement is the cause of psychophysical sensory attenuation. Furthermore, it explains the force-matching illusion and reproduces empirical results almost exactly. Finally, if attenuation is removed, the force-matching illusion disappears and false (delusional) inferences about agency emerge. This is important, given the negative correlation between sensory attenuation and delusional beliefs in normal subjects--and the reduction in the magnitude of the illusion in schizophrenia. Active inference therefore links the neuromodulatory optimisation of precision to sensory attenuation and illusory phenomena during the attribution of agency in normal subjects. It also provides a functional account of deficits in syndromes characterised by false inference

  15. Replacement of the Ectodomains of the Hemagglutinin-Neuraminidase and Fusion Glycoproteins of Recombinant Parainfluenza Virus Type 3 (PIV3) with Their Counterparts from PIV2 Yields Attenuated PIV2 Vaccine Candidates

    OpenAIRE

    Tao, Tao; Skiadopoulos, Mario H.; Davoodi, Fatemeh; Riggs, Jeffrey M.; Collins, Peter L.; Murphy, Brian R.

    2000-01-01

    We sought to develop a live attenuated parainfluenza virus type 2 (PIV2) vaccine strain for use in infants and young children, using reverse genetic techniques that previously were used to rapidly produce a live attenuated PIV1 vaccine candidate. The PIV1 vaccine candidate, designated rPIV3-1cp45, was generated by substituting the full-length HN and F proteins of PIV1 for those of PIV3 in the attenuated cp45 PIV3 vaccine candidate (T. Tao et al., J. Virol. 72:2955–2961, 1998; M. H. Skiadopoul...

  16. Living with COPD: Nutrition

    Science.gov (United States)

    ... Diseases > Lung Disease Lookup > COPD > Living With COPD Nutrition and COPD Most people are surprised to learn ... asking your doctor or visiting the Academy of Nutrition and Dietetics at EatRight.org . Be sure to ...

  17. Living Day by Day

    Science.gov (United States)

    Kaplan, Rachel L.; Khoury, Cynthia El; Field, Emily R. S.; Mokhbat, Jacques

    2016-01-01

    We examined the meaning of living with HIV/AIDS among women in Lebanon. Ten women living with HIV/AIDS (WLWHA) described their experiences via semistructured in-depth interviews. They navigated a process of HIV diagnosis acceptance that incorporated six overlapping elements: receiving the news, accessing care, starting treatment, navigating disclosure decisions, negotiating stigma, and maintaining stability. Through these elements, we provide a framework for understanding three major themes that were constructed during data analysis: Stand by my side: Decisions of disclosure; Being “sick” and feeling “normal”: Interacting with self, others, and society; and Living day by day: focusing on the present. We contribute to the existing literature by providing a theoretical framework for understanding the process of diagnosis and sero-status acceptance among WLWHA. This was the first study of its kind to examine the meaning of living with HIV/AIDS among women in a Middle Eastern country. PMID:28462340

  18. Living Day by Day

    Directory of Open Access Journals (Sweden)

    Rachel L. Kaplan

    2016-05-01

    Full Text Available We examined the meaning of living with HIV/AIDS among women in Lebanon. Ten women living with HIV/AIDS (WLWHA described their experiences via semistructured in-depth interviews. They navigated a process of HIV diagnosis acceptance that incorporated six overlapping elements: receiving the news, accessing care, starting treatment, navigating disclosure decisions, negotiating stigma, and maintaining stability. Through these elements, we provide a framework for understanding three major themes that were constructed during data analysis: Stand by my side: Decisions of disclosure; Being “sick” and feeling “normal”: Interacting with self, others, and society; and Living day by day: focusing on the present. We contribute to the existing literature by providing a theoretical framework for understanding the process of diagnosis and sero-status acceptance among WLWHA. This was the first study of its kind to examine the meaning of living with HIV/AIDS among women in a Middle Eastern country.

  19. Living With Diabetes

    Science.gov (United States)

    ... Problems Diabetes, Sexual, & Bladder Problems Clinical Trials Managing Diabetes You can manage your diabetes and live a ... you have diabetes. How can I manage my diabetes? With the help of your health care team, ...

  20. Thalassemia: Healthy Living

    Science.gov (United States)

    ... Thalassemia” More What can a person living with thalassemia do to stay healthy? A healthy lifestyle is ... disorder”, as well as making healthy choices. Managing Thalassemia Thalassemia is a treatable disorder that can be ...

  1. Writing lives in sport

    DEFF Research Database (Denmark)

    Christensen, Mette Krogh

    dealing with anonymous individuals, whose anonymity results from the confidentiality requirements of a social scientific research methodology, to those leaning more towards the literary-historical traditions of 'conventional' biographical writing. However, these examples are polar extremes and none...... in the academis world of sport studies. It does not set out to be a methodological treatise but through the writing of lives in sports does raise questions of method. Each essay in this collection deals with problems of writing sports-people's lives. These essays could be said to fall along a spectrum from those......Writing lives in sport is a book of stories about sports-persons. The people concerned include sports stars, sports people who are not quite so famous, and relatively unknown physical education teachers and sports scientists.Writing lives in sport raises questions about writing biographies...

  2. Living with Tuberculosis

    Science.gov (United States)

    ... Diseases > Lung Disease Lookup > Tuberculosis (TB) Living With Tuberculosis What to Expect You will need regular checkups ... XML file."); } }); } } --> Blank Section Header Lung Disease Lookup Tuberculosis (TB) Learn About Tuberculosis Tuberculosis Symptoms, Causes & Risk ...

  3. Tips for Daily Living

    Science.gov (United States)

    ... Simple Techniques Can Help Memory after a Stroke Self-Esteem after Stroke Cognitive Challenges After Stroke Depression Trumps ... Living Driving Finding Support You Are Not Alone Online Support Recovery and Support after Stroke Stroke Family ...

  4. Our Urban Living Room

    DEFF Research Database (Denmark)

    Hjortshøj, Rasmus

    2016-01-01

    Our Urban Living Room is an exhibition and a book, created by Cobe. The theme is based on Cobe’s ten years of practice, grounded in social livability and urban democracy, and our aim to create buildings and spaces that invite Copenhageners to use and define them; as an extended living room, where...... the boundaries between private and public space become fluid. Based on specific Cobe projects, Our Urban Living Room tells stories about the architectural development of Copenhagen, while exploring the progression of the Danish Capital - from an industrial city into an urban living room, known as one...... of the world’s most livable places. Photography by Rasmus Hjortshøj....

  5. Harmonic engine

    Science.gov (United States)

    Bennett, Charles L [Livermore, CA

    2009-10-20

    A high efficiency harmonic engine based on a resonantly reciprocating piston expander that extracts work from heat and pressurizes working fluid in a reciprocating piston compressor. The engine preferably includes harmonic oscillator valves capable of oscillating at a resonant frequency for controlling the flow of working fluid into and out of the expander, and also preferably includes a shunt line connecting an expansion chamber of the expander to a buffer chamber of the expander for minimizing pressure variations in the fluidic circuit of the engine. The engine is especially designed to operate with very high temperature input to the expander and very low temperature input to the compressor, to produce very high thermal conversion efficiency.

  6. Engineering personnel

    International Nuclear Information System (INIS)

    Paskievici, W.

    The expansion of nuclear power is taxing human, material, and capital resources in developed and developing countries. This paper explores the human resources as represented by employment, graduation statistics, and educational curricula for nuclear engineers. (E.C.B.)

  7. Green Engineering

    Science.gov (United States)

    Green Engineering is the design, commercialization and use of processes and products that are feasible and economical while reducing the generation of pollution at the source and minimizing the risk to human health and the environment.

  8. Coastal Engineering

    NARCIS (Netherlands)

    Van der Velden, E.T.J.M.

    1989-01-01

    Introduction, waves, sediment transport, littoral transport, lonshore sediment transport, onshore-offshore sediment transport, coastal changes, dune erosion and storm surges, sedimentation in channels and trenches, coastal engineering in practice.

  9. Geoenvironmental engineering

    International Nuclear Information System (INIS)

    Shin, Eun Cheol; Park, Jeong Jun

    2009-08-01

    This book deals with definition of soil and scope of clean-up of soil, trend of geoenvironmental engineering at home and foreign countries, main concern of geoenvironmental engineering in domestic and abroad, design and building of landfills such as summary, trend of landfill policy in Korea, post management of landfill facilities, stabilizing and stability of landfill, research method and soil pollution source, restoration technology of soil pollution like restoration technique of oil pollution with thermal processing.

  10. Microwave engineering

    CERN Document Server

    Pozar, David M

    2012-01-01

    The 4th edition of this classic text provides a thorough coverage of RF and microwave engineering concepts, starting from fundamental principles of electrical engineering, with applications to microwave circuits and devices of practical importance.  Coverage includes microwave network analysis, impedance matching, directional couplers and hybrids, microwave filters, ferrite devices, noise, nonlinear effects, and the design of microwave oscillators, amplifiers, and mixers. Material on microwave and RF systems includes wireless communications, radar, radiometry, and radiation hazards. A large

  11. Reliability Engineering

    International Nuclear Information System (INIS)

    Lee, Sang Yong

    1992-07-01

    This book is about reliability engineering, which describes definition and importance of reliability, development of reliability engineering, failure rate and failure probability density function about types of it, CFR and index distribution, IFR and normal distribution and Weibull distribution, maintainability and movability, reliability test and reliability assumption in index distribution type, normal distribution type and Weibull distribution type, reliability sampling test, reliability of system, design of reliability and functionality failure analysis by FTA.

  12. Systems Engineering

    OpenAIRE

    Vaughan, William W.

    2016-01-01

    The term “systems engineering” when entered into the Google search page, produces a significant number of results, evidence that systems engineering is recognized as being important for the success of essentially all products. Since most readers of this item will be rather well versed in documents concerning systems engineering, I have elected to share some of the points made on this subject in a document developed by the European Cooperation for Space Standardization (ECSS), a component of t...

  13. Production of cloned pigs with targeted attenuation of gene expression.

    Directory of Open Access Journals (Sweden)

    Vilceu Bordignon

    Full Text Available The objective of this study was to demonstrate that RNA interference (RNAi and somatic cell nuclear transfer (SCNT technologies can be used to attenuate the expression of specific genes in tissues of swine, a large animal species. Apolipoprotein E (apoE, a secreted glycoprotein known for its major role in lipid and lipoprotein metabolism and transport, was selected as the target gene for this study. Three synthetic small interfering RNAs (siRNA targeting the porcine apoE mRNA were tested in porcine granulosa cells in primary culture and reduced apoE mRNA abundance ranging from 45-82% compared to control cells. The most effective sequence was selected for cloning into a short hairpin RNA (shRNA expression vector under the control of RNA polymerase III (U6 promoter. Stably transfected fetal porcine fibroblast cells were generated and used to produce embryos with in vitro matured porcine oocytes, which were then transferred into the uterus of surrogate gilts. Seven live and one stillborn piglet were born from three gilts that became pregnant. Integration of the shRNA expression vector into the genome of clone piglets was confirmed by PCR and expression of the GFP transgene linked to the expression vector. Analysis showed that apoE protein levels in the liver and plasma of the clone pigs bearing the shRNA expression vector targeting the apoE mRNA was significantly reduced compared to control pigs cloned from non-transfected fibroblasts of the same cell line. These results demonstrate the feasibility of applying RNAi and SCNT technologies for introducing stable genetic modifications in somatic cells for eventual attenuation of gene expression in vivo in large animal species.

  14. Improvement of quantitation in SPECT: Attenuation and scatter correction using non-uniform attenuation data

    International Nuclear Information System (INIS)

    Mukai, T.; Torizuka, K.; Douglass, K.H.; Wagner, H.N.

    1985-01-01

    Quantitative assessment of tracer distribution with single photon emission computed tomography (SPECT) is difficult because of attenuation and scattering of gamma rays within the object. A method considering the source geometry was developed, and effects of attenuation and scatter on SPECT quantitation were studied using phantoms with non-uniform attenuation. The distribution of attenuation coefficients (μ) within the source were obtained by transmission CT. The attenuation correction was performed by an iterative reprojection technique. The scatter correction was done by convolution of the attenuation corrected image and an appropriate filter made by line source studies. The filter characteristics depended on μ and SPEC measurement at each pixel. The SPECT obtained by this method showed the most reasonable results than the images reconstructed by other methods. The scatter correction could compensate completely for a 28% scatter components from a long line source, and a 61% component for thick and extended source. Consideration of source geometries was necessary for effective corrections. The present method is expected to be valuable for the quantitative assessment of regional tracer activity

  15. Live Attenuated Recombinant Vaccine Protects Nonhuman Primates Against Ebola and Marburg Viruses

    National Research Council Canada - National Science Library

    Jones, Steven M; Feldmann, Heinz; Stroher, Ute; Geisbert, Joan B; Fernando, Lisa; Grolla, Allen; Klenk, Hans-Dieter; Sullivan, Nancy J; Volchkov, Viktor E; Fritz, Elizabeth A; Daddario, Kathleen M; Hensley, Lisa E; Jahrling, Peter B; Geisbert, Thomas W

    2005-01-01

    Vaccines and therapies are urgently needed to address public health needs stemming from emerging pathogens and biological threat agents such as the filoviruses Ebola virus (EBOV) and Marburg virus (MARV...

  16. Effect of live attenuated vaccines on the course of experimental allergic encephalomyelitis. A pilot study.

    Science.gov (United States)

    Caspary, E A

    1977-01-01

    The clinical severity of EAE is enhanced by pre-treatment with distemper, measles and BCG vaccine, measles vaccine gives a more severe onset of disease. Rubella vaccine and TAB leads to mild disease which recurs on re-treatment with the appropriate vaccine. These findings and their possible significance in MS are briefly discussed.

  17. Tobacco Smoke Exposure and Altered Nasal Responses to Live Attenuated Influenza Virus

    Science.gov (United States)

    Background: Epidemiologic evidence links tobacco smoke and increased risk for influenza in humans, but the specific host defense pathways involved are unclear. Objective. Develop a model to examine influenza-induced innate immune responses in humans and test the hypothesis that ...

  18. Horizontal transmission of the Leningrad-3 live attenuated mumps vaccine virus.

    Science.gov (United States)

    Atrasheuskaya, A V; Neverov, A A; Rubin, S; Ignatyev, G M

    2006-03-06

    Here we describe symptomatic transmission of the Leningrad-3 mumps vaccine virus from healthy vaccinees to previously vaccinated contacts. Throat swab and serum samples were taken from six symptomatic mumps cases and from 13 family contacts. Assessment of serum IgG and IgM anti-mumps virus antibodies and IgG avidity testing was performed using commercial test kits. Sera neutralizing antibodies were measured by plaque reduction neutralization assay using the L-3 vaccine mumps virus as the target. All six of the symptomatic mumps cases and three contact subjects tested positive for mumps by RT-PCR. The genomic sequences tested (F, SH and HN genes) of all nine of these samples were identical to the L-3 mumps vaccine strain. All 13 contacts were asymptomatic; however clear serological evidence of mumps infection was found in some of them. The likely epidemiological source of the transmitted L-3 mumps virus was children who were recently vaccinated at the schools attended by the six symptomatic mumps patients described here. The L-3 mumps vaccine virus can be shed and transmitted horizontally, even to subjects previously vaccinated with the same virus.

  19. Cross-Protection against Marburg Virus Strains by Using a Live, Attenuated Recombinant Vaccine

    National Research Council Canada - National Science Library

    Daddario-DiCaprio, Kathleen M; Geisbert, Thomas W; Geisbert, Joan B; Stroeher, Ute; Hensley, Lisa E; Grolla, Allen; Fritz, Elizabeth A; Feldmann, Friederike; Feldmann, Heinz; Jones, Steven M

    2006-01-01

    Marburg virus (MARV) has been associated with sporadic episodes of hemorrhagic fever, including a recent highly publicized outbreak in Angola that produced severe disease and significant mortality in infected patients...

  20. Live Probiotic Cultures and the Gastrointestinal Tract: Symbiotic Preservation of Tolerance Whilst Attenuating Pathogenicity.

    Directory of Open Access Journals (Sweden)

    Luis eVitetta

    2014-10-01

    Full Text Available Bacteria comprise the earliest form of independent life on this planet. Bacterial development has included co–operative symbiosis with plants (e.g., Leguminosae family and nitrogen fixing bacteria in soil and animals (e.g., the gut microbiome. A fusion event of two prokaryotes evolutionarily gave rise to the eukaryote cell in which mitochondria may be envisaged as a genetically functional mosaic, a relic from one of the prokaryote cells. The discovery of bacterial inhibitors such chloramphenicol and others has been exploited to highlight mitochondria as arising from a bacterial progenitor. As such the evolution of human life has been complexly connected to bacterial activity. This is embodied, by the appearance of mitochondria in eukaryotes (alphaproteobacteria contribution, a significant endosymbiotic evolutionary event. During the twentieth century there was an increasing dependency on anti–microbials as mainline therapy against bacterial infections. It is only comparatively recently that the essential roles played by the gastrointestinal tract (GIT microbiome in animal health and development has been recognized as opposed to the GIT microbiome being a toxic collection of micro–organisms. It is now well documented that t

  1. Effects of environmental tobacco smoke on nasal responses to live attenuated influenza virus

    Science.gov (United States)

    Background: Published and preliminary data in our laboratory suggest that airborne pollutants including tobacco smoke increase susceptibility of respiratory epithelium to infection with influenza A. However, no studies have specifically looked at the interaction between tobacco s...

  2. Construction and evaluation of Bordetella pertussis live attenuated vaccine strain BPZE1 producing Fim3.

    NARCIS (Netherlands)

    Debrie, Anne-Sophie; Coutte, Loïc; Raze, Dominique; Mooi, Frits; Alexander, Frances; Gorringe, Andrew; Mielcarek, Nathalie; Locht, Camille

    2018-01-01

    Pertussis or whooping cough is currently the most prevalent vaccine-preventable childhood disease despite >85% global vaccination coverage. In recent years incidence has greatly increased in several high-income countries that have switched from the first-generation, whole-cell vaccine to the newer

  3. Rational design of avian metapneumovirus live attenuated vaccines by inhibiting viral messenger RNA cap methyltransferase

    Science.gov (United States)

    Avian metapneumovirus (aMPV), also known as avian pneumovirus or turkey rhinotracheitis, is a non-segmented negative-sense RNA virus belonging to the family of Paramyxoviridae, the subfamily Pneumovirinae, and the genus Metapneumovirus. aMPV is the causative agent of respiratory tract infection and ...

  4. A recombinant live attenuated tetravalent vaccine for the prevention of dengue.

    Science.gov (United States)

    Guy, Bruno; Noriega, Fernando; Ochiai, R Leon; L'azou, Maïna; Delore, Valentine; Skipetrova, Anna; Verdier, François; Coudeville, Laurent; Savarino, Stephen; Jackson, Nicholas

    2017-07-01

    Dengue is an important and still growing public health problem associated with substantial morbidity, as well as significant social and economic impact. The present review describes the main features and development of the first dengue vaccine (CYD-TDV, Dengvaxia®), which has been licensed by several dengue-endemic countries in Asia and Latin America for use in populations above 9 years of age. Areas covered: The review focuses on the large clinical development of CYD-TDV, which includes in particular two pivotal phase III efficacy trials conducted in Asia and Latin America and supported vaccine licensure. Based on these clinical data, the WHO Strategic Advisory Group of Experts (SAGE) on Immunization recommended considering introduction of the vaccine in geographic settings (national or subnational) with high burden of disease. Long-term safety follow-up studies of the efficacy trials are currently ongoing, and post-licensure studies will evaluate the vaccine effectiveness and safety in 'real-life' following vaccine introduction. Expert commentary: During vaccine development, a number of complexities were tackled, innovation pursued, and risk managed. These aspects, as well as the potential impact of CYD-TDV on public health are also discussed.

  5. aroA-Deficient Salmonella enterica Serovar Typhimurium Is More Than a Metabolically Attenuated Mutant

    Science.gov (United States)

    Frahm, Michael; Kocijancic, Dino; Rohde, Manfred; Eckweiler, Denitsa; Bielecka, Agata; Bueno, Emilio; Cava, Felipe; Abraham, Wolf-Rainer; Curtiss, Roy; Häussler, Susanne; Erhardt, Marc; Weiss, Siegfried

    2016-01-01

    ABSTRACT Recombinant attenuated Salmonella enterica serovar Typhimurium strains are believed to act as powerful live vaccine carriers that are able to elicit protection against various pathogens. Auxotrophic mutations, such as a deletion of aroA, are commonly introduced into such bacteria for attenuation without incapacitating immunostimulation. In this study, we describe the surprising finding that deletion of aroA dramatically increased the virulence of attenuated Salmonella in mouse models. Mutant bacteria lacking aroA elicited increased levels of the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) after systemic application. A detailed genetic and phenotypic characterization in combination with transcriptomic and metabolic profiling demonstrated that ΔaroA mutants display pleiotropic alterations in cellular physiology and lipid and amino acid metabolism, as well as increased sensitivity to penicillin, complement, and phagocytic uptake. In concert with other immunomodulating mutations, deletion of aroA affected flagellin phase variation and gene expression of the virulence-associated genes arnT and ansB. Finally, ΔaroA strains displayed significantly improved tumor therapeutic activity. These results highlight the importance of a functional shikimate pathway to control homeostatic bacterial physiology. They further highlight the great potential of ΔaroA-attenuated Salmonella for the development of vaccines and cancer therapies with important implications for host-pathogen interactions and translational medicine. PMID:27601574

  6. Evaluation of near-surface attenuation of S-waves based on PS logging and vertical array seismic observation

    International Nuclear Information System (INIS)

    Kobayashi, Genyu

    2014-01-01

    As a result of the lessons learned from the experience of Kashiwazaki-Kariwa NPP due to the 2007 Niigata Chuetsu Oki Earthquake, it has become clear that a rational method of near-surface attenuation characteristics covering a depth range from engineering bedrock to seismic bedrock urgently needs to be established. JNES performed PS logging and vertical array seismic ground motion observation at a soil ground site (SODB 1. site), sedimentary rock site, and an igneous rock site (SODB 2. site), and proposed an evaluation method of attenuation characteristics (site characteristics) for the deep underground. (author)

  7. Engineering Enhanced Vaccine Cell Lines To Eradicate Vaccine-Preventable Diseases: the Polio End Game.

    Science.gov (United States)

    van der Sanden, Sabine M G; Wu, Weilin; Dybdahl-Sissoko, Naomi; Weldon, William C; Brooks, Paula; O'Donnell, Jason; Jones, Les P; Brown, Cedric; Tompkins, S Mark; Oberste, M Steven; Karpilow, Jon; Tripp, Ralph A

    2016-02-15

    Vaccine manufacturing costs prevent a significant portion of the world's population from accessing protection from vaccine-preventable diseases. To enhance vaccine production at reduced costs, a genome-wide RNA interference (RNAi) screen was performed to identify gene knockdown events that enhanced poliovirus replication. Primary screen hits were validated in a Vero vaccine manufacturing cell line using attenuated and wild-type poliovirus strains. Multiple single and dual gene silencing events increased poliovirus titers >20-fold and >50-fold, respectively. Host gene knockdown events did not affect virus antigenicity, and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9-mediated knockout of the top candidates dramatically improved viral vaccine strain production. Interestingly, silencing of several genes that enhanced poliovirus replication also enhanced replication of enterovirus 71, a clinically relevant virus to which vaccines are being targeted. The discovery that host gene modulation can markedly increase virus vaccine production dramatically alters mammalian cell-based vaccine manufacturing possibilities and should facilitate polio eradication using the inactivated poliovirus vaccine. Using a genome-wide RNAi screen, a collection of host virus resistance genes was identified that, upon silencing, increased poliovirus and enterovirus 71 production by from 10-fold to >50-fold in a Vero vaccine manufacturing cell line. This report provides novel insights into enterovirus-host interactions and describes an approach to developing the next generation of vaccine manufacturing through engineered vaccine cell lines. The results show that specific gene silencing and knockout events can enhance viral titers of both attenuated (Sabin strain) and wild-type polioviruses, a finding that should greatly facilitate global implementation of inactivated polio vaccine as well as further reduce costs for live-attenuated oral polio vaccines. This work

  8. Hire a Milwaukee Engineer | College of Engineering & Applied Science

    Science.gov (United States)

    Electrical Engineering Instructional Laboratories Student Resources Industrial & Manufacturing Engineering Industrial & Manufacturing Engineering Academic Programs Industrial & Manufacturing Engineering Major Industrial & Manufacturing Engineering Minor Industrial & Manufacturing Engineering

  9. Overview of recent developments in attenuation models

    International Nuclear Information System (INIS)

    Riera, J.D.

    2001-01-01

    Attenuation equations predict features of the seismic motion, such as the horizontal and vertical peak ground accelerations (PGA), the peak ground velocities (PGV) and the 5% damped spectral acceleration response (SA), in terms of the earthquake magnitude and distance from source to site. Occasionally other factors, like the type of faulting, are considered in the attenuation expressions. An overview of recent developments in this field is presented in the paper, including a discussion of the applicability of various models for short source to site distances. In such a case, i.e. in the neighbourhood of the epicentral region, which is of utmost importance in Nuclear Power Plant applications, the use of two parameters to define the earthquake size is suggested, instead of the single parameter, a magnitude scale. Recent evidence of the importance in such situations of so-called directivity effects, which require a more complete description of the focal mechanism, completes the paper. (author)

  10. P300 is attenuated during dissociative episodes.

    Science.gov (United States)

    Kirino, Eiji

    2006-02-01

    The present study examined the pathophysiology of dissociative phenomena using the P300 component of event-related potentials, quantitative electroencephalography (QEEG), and morphology measures of computed tomography scan. Event-related potentials during an auditory oddball paradigm and QEEG in resting state were recorded. Patients exhibited attenuation of P300 amplitudes compared with controls during dissociative episodes, but exhibited recovery to control levels in remission. Patients had a larger Sylvian fissure-brain ratio than did controls. QEEG findings revealed no significant differences between the patients and controls or between episodes and remission in the patient group. Attenuation of the P300 can be interpreted as the result of a negative feedback loop from the medial temporal lobe to the cortex, which decreases the amount of information flow, allocation of attentional resources, and updating of working memory to avoid both excessive long-term memory system activity in medial temporal lobe and resurgence of affect-laden memories.

  11. Indoor signal attenuation assessment via fuzzy logic

    Directory of Open Access Journals (Sweden)

    Alexandre de Assis Mota

    2011-09-01

    Full Text Available This work focuses on the analysis of signal´s attenuation in indoor environments using a fuzzy logic approach based on the Shadowing Signal Propagation Model (SSPM. The SSPM allows the characterization of the attenuation caused by the environment through the ? parameter present in this model. In addition to this, the Fuzzy Logic provides a form of approximate reasoning that allows the treatment of problems with incomplete, vague and imprecise information. Also, it offers a simple way to obtain a possible solution for a problem using the heuristic knowledge about a particular situation. The results show that the methodology produced satisfactory results, close to the ones yielded by experimental methods.

  12. Attenuation of gamma radiation in concrete shields

    International Nuclear Information System (INIS)

    Azevedo e Souza, A.C. de.

    1978-12-01

    The attenuation characteristics of γ radiation in concrete layers considering their mechanical resistence and densities were determined. A 137 Cs source was used in a 'good geometry' arrangement to eliminate the effects of the buildup factor. The ordinary and the heavy concrete were irradiated and for the latter it was used as additives iron ore and Fe 2 O 3 pellets in various grain sizes. The detection system consisted of a 2' x 2' NaI (Tl) crystal coupled to a photomultiplier tube and the associated electronic equipment. FORTRAN programs were used for determining the absorption coefficients and the attenuation factors. These programs calculate photopeak areas eliminating all contributions due to Compton effect and background. (Author) [pt

  13. Anomalies of ultrasound attenuation in metals under hydrostatic pressure

    International Nuclear Information System (INIS)

    Galkin, A.A.; Datsko, O.I.; Varyukhin, V.N.; Pilipenko, N.P.

    1978-01-01

    Ultrasonic attenuation was measured in polycrystal specimens of molybdenum, chromium and zinc under hydrostatic pressure up to 6 kbar. On the plot of ultrasound attenuation dependence on the pressure in molybdenum the maxima are observed under the pressure of 2 kbar. The anomaly of ultrasound attenuation is shown to connect only with brittle-ductile transtion

  14. Phonic Attenuation due to Screen-Barriers

    Directory of Open Access Journals (Sweden)

    Vasile Bacria

    2011-10-01

    Full Text Available The technique of noise decreasing admits two basic approaches: an active approach and a passive one. In the frame of passive method one can count the employment of screen-barriers. In this paper we present some considerations on sound attenuation due to screen-barriers emphasizing the elements which influence it. The elucidation of these elements is made by measurements. The obtained results can be applied in every other practical situation concerning the protection against noise.

  15. Mid-European seismic attenuation anomaly

    Czech Academy of Sciences Publication Activity Database

    Málek, Jiří; Brokešová, J.; Vackář, Jiří

    2017-01-01

    Roč. 712, AUG 21 (2017), s. 557-577 ISSN 0040-1951 Grant - others:AV ČR(CZ) StrategieAV21/4 Program:StrategieAV Institutional support: RVO:67985891 Keywords : seismic wave attenuation * peak ground motion * H/V ratio Subject RIV: DC - Siesmology, Volcanology, Earth Structure OBOR OECD: Geology Impact factor: 2.693, year: 2016

  16. Attenuation and scatter correction in SPECT

    International Nuclear Information System (INIS)

    Pant, G.S.; Pandey, A.K.

    2000-01-01

    While passing through matter, photons undergo various types of interactions. In the process, some photons are completely absorbed, some are scattered in different directions with or without any change in their energy and some pass through unattenuated. These unattenuated photons carry the information with them. However, the image data gets corrupted with attenuation and scatter processes. This paper deals with the effect of these two processes in nuclear medicine images and suggests the methods to overcome them

  17. Natural attenuation of biogas in landfill covers

    International Nuclear Information System (INIS)

    Cossu, R.; Privato, A.; Raga, R.

    2005-01-01

    In the risk evaluation of uncontrolled biogas emissions from landfills, the process of natural attenuation in landfill covers assumes a very important role. The capacity of biogas oxidation in the cover soils seems to be the most important control to mitigate the biogas emission during the aftercare period when the biogas collection system might fail. In the present paper laboratory experiences on lab columns to study the biogas oxidation are discussed [it

  18. Radiation attenuation gauge with magnetically coupled source

    International Nuclear Information System (INIS)

    Wallace, S.A.

    1978-01-01

    Disclosed is a radiation attenuation gauge for measuring thickness and density of a material which includes, in combination, a source of gamma radiation contained within a housing of magnetic or ferromagnetic material, and a means for measuring the intensity of gamma radiation. The measuring means has an aperture and magnetic means disposed adjacent to the aperture for attracting and holding the housed source in position before the aperture. The material to be measured is placed between the source and the measuring means

  19. Wave attenuation charcteristics of tethered float system

    Digital Repository Service at National Institute of Oceanography (India)

    Vethamony, P.

    incident wave height transmitted wave height G wave number float mass number of rows of floats drag power transmitted wave power incident wave power 111 112 P. Vethamony float radius wave period time velocity and acceleration of fluid... particles, respectively wave attenuation in percentage displacement, velocity and acceleration of float, respectively amplitude of float displacement added mass damping coefficient fluid particle displacement amplitude of fluid particle displacement...

  20. The attenuation of the periodic table

    International Nuclear Information System (INIS)

    Cook, N.D.

    1990-01-01

    Unique among models of nuclear structure, the face-centered-cubic (FCC) lattice model predicts the attenuation of the periodic table at Z < 110 and the impossibility of superheavy nuclei. The total binding energies of superheavy nuclei in the FCC model (109 < Z < 127) were calculated on the basis of parameters obtained from a least-squares best-fit for 914 nuclei (Z < 99). No indication of increased stability is found for any of the transuranic elements