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Sample records for vectors immunizations result

  1. Adenovirus Vector-Derived VA-RNA-Mediated Innate Immune Responses

    Directory of Open Access Journals (Sweden)

    Hiroyuki Mizuguchi

    2011-07-01

    Full Text Available The major limitation of the clinical use of replication-incompetent adenovirus (Ad vectors is the interference by innate immune responses, including induction of inflammatory cytokines and interferons (IFN, following in vivo application of Ad vectors. Ad vector-induced production of inflammatory cytokines and IFNs also results in severe organ damage and efficient induction of acquired immune responses against Ad proteins and transgene products. Ad vector-induced innate immune responses are triggered by the recognition of Ad components by pattern recognition receptors (PRRs. In order to reduce the side effects by Ad vector-induced innate immune responses and to develop safer Ad vectors, it is crucial to clarify which PRRs and which Ad components are involved in Ad vector-induced innate immune responses. Our group previously demonstrated that myeloid differentiating factor 88 (MyD88 and toll-like receptor 9 (TLR9 play crucial roles in the Ad vector-induced inflammatory cytokine production in mouse bone marrow-derived dendritic cells. Furthermore, our group recently found that virus associated-RNAs (VA-RNAs, which are about 160 nucleotide-long non-coding small RNAs encoded in the Ad genome, are involved in IFN production through the IFN-β promoter stimulator-1 (IPS-1-mediated signaling pathway following Ad vector transduction. The aim of this review is to highlight the Ad vector-induced innate immune responses following transduction, especially VA-RNA-mediated innate immune responses. Our findings on the mechanism of Ad vector-induced innate immune responses should make an important contribution to the development of safer Ad vectors, such as an Ad vector lacking expression of VA-RNAs.

  2. Adenoviral vector immunity: its implications and circumvention strategies.

    Science.gov (United States)

    Ahi, Yadvinder S; Bangari, Dinesh S; Mittal, Suresh K

    2011-08-01

    Adenoviral (Ad) vectors have emerged as a promising gene delivery platform for a variety of therapeutic and vaccine purposes during last two decades. However, the presence of preexisting Ad immunity and the rapid development of Ad vector immunity still pose significant challenges to the clinical use of these vectors. Innate inflammatory response following Ad vector administration may lead to systemic toxicity, drastically limit vector transduction efficiency and significantly abbreviate the duration of transgene expression. Currently, a number of approaches are being extensively pursued to overcome these drawbacks by strategies that target either the host or the Ad vector. In addition, significant progress has been made in the development of novel Ad vectors based on less prevalent human Ad serotypes and nonhuman Ad. This review provides an update on our current understanding of immune responses to Ad vectors and delineates various approaches for eluding Ad vector immunity. Approaches targeting the host and those targeting the vector are discussed in light of their promises and limitations.

  3. Hexon-chimaeric adenovirus serotype 5 vectors circumvent pre-existing anti-vector immunity

    NARCIS (Netherlands)

    Roberts, Diane M.; Nanda, Anjali; Havenga, Menzo J. E.; Abbink, Peter; Lynch, Diana M.; Ewald, Bonnie A.; Liu, Jinyan; Thorner, Anna R.; Swanson, Patricia E.; Gorgone, Darci A.; Lifton, Michelle A.; Lemckert, Angelique A. C.; Holterman, Lennart; Chen, Bing; Dilraj, Athmanundh; Carville, Angela; Mansfield, Keith G.; Goudsmit, Jaap; Barouch, Dan H.

    2006-01-01

    A common viral immune evasion strategy involves mutating viral surface proteins in order to evade host neutralizing antibodies. Such immune evasion tactics have not previously been intentionally applied to the development of novel viral gene delivery vectors that overcome the critical problem of

  4. Circumventing antivector immunity: potential use of nonhuman adenoviral vectors.

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    Lopez-Gordo, Estrella; Podgorski, Iva I; Downes, Nicholas; Alemany, Ramon

    2014-04-01

    Adenoviruses are efficient gene delivery vectors based on their ability to transduce a wide variety of cell types and drive high-level transient transgene expression. While there have been advances in modifying human adenoviral (HAdV) vectors to increase their safety profile, there are still pitfalls that need to be further addressed. Preexisting humoral and cellular immunity against common HAdV serotypes limits the efficacy of gene transfer and duration of transgene expression. As an alternative, nonhuman AdV (NHAdV) vectors can circumvent neutralizing antibodies against HAdVs in immunized mice and monkeys and in human sera, suggesting that NHAdV vectors could circumvent preexisting humoral immunity against HAdVs in a clinical setting. Consequently, there has been an increased interest in developing NHAdV vectors for gene delivery in humans. In this review, we outline the recent advances and limitations of HAdV vectors for gene therapy and describe examples of NHAdV vectors focusing on their immunogenicity, tropism, and potential as effective gene therapy vehicles.

  5. Experimental and Field Results Regarding Immunity Induced by a Recombinant Turkey Herpesvirus H5 Vector Vaccine Against H5N1 and Other H5 Highly Pathogenic Avian Influenza Virus Challenges.

    Science.gov (United States)

    Gardin, Yannick; Palya, Vilmos; Dorsey, Kristi Moore; El-Attrache, John; Bonfante, Francesco; Wit, Sjaak de; Kapczynski, Darrell; Kilany, Walid Hamdy; Rauw, Fabienne; Steensels, Mieke; Soejoedono, Retno D

    2016-05-01

    Vaccination against H5N1 highly pathogenic avian influenza (AI) virus (HPAIV) is one of the possible complementary means available for affected countries to control AI when the disease has become, or with a high risk of becoming, endemic. Efficacy of the vaccination against AI relies essentially, but not exclusively, on the capacity of the vaccine to induce immunity against the targeted virus (which is prone to undergo antigenic variations), as well as its capacity to overcome interference with maternal immunity transmitted by immunized breeding hens to their progeny. This property of the vaccine is a prerequisite for its administration at the hatchery, which assures higher and more reliable vaccine coverage of the populations than vaccination at the farm. A recombinant vector vaccine (Vectormune® AI), based on turkey herpesvirus expressing the hemagglutinin gene of an H5N1 HPAIV as an insert, has been used in several experiments conducted in different research laboratories, as well as in controlled field trials. The results have demonstrated a high degree of homologous and cross protection against different genetic clades of the H5N1 HPAIV. Furthermore, vaccine-induced immunity was not impaired by the presence of passive immunity, but on the contrary, cumulated with it for improved early protection. The demonstrated levels of protection against the different challenge viruses exhibited variations in terms of postchallenge mortality, as well as challenge virus shedding. The data presented here highlight the advantages of this vaccine as a useful and reliable tool to complement biosecurity and sanitary policies for better controlling the disease due to HPAIV of H5 subtypes, when the vaccination is applied as a control measure.

  6. Arthropod Innate Immune Systems and Vector-Borne Diseases

    OpenAIRE

    Baxter, Richard H. G.; Contet, Alicia; Krueger, Kathryn

    2017-01-01

    Arthropods, especially ticks and mosquitoes, are the vectors for a number of parasitic and viral human diseases, including malaria, sleeping sickness, Dengue, and Zika, yet arthropods show tremendous individual variation in their capacity to transmit disease. A key factor in this capacity is the group of genetically encoded immune factors that counteract infection by the pathogen. Arthropod-specific pattern recognition receptors and protease cascades detect and respond to infection. Proteins ...

  7. Arthropod Innate Immune Systems and Vector-Borne Diseases.

    Science.gov (United States)

    Baxter, Richard H G; Contet, Alicia; Krueger, Kathryn

    2017-02-21

    Arthropods, especially ticks and mosquitoes, are the vectors for a number of parasitic and viral human diseases, including malaria, sleeping sickness, Dengue, and Zika, yet arthropods show tremendous individual variation in their capacity to transmit disease. A key factor in this capacity is the group of genetically encoded immune factors that counteract infection by the pathogen. Arthropod-specific pattern recognition receptors and protease cascades detect and respond to infection. Proteins such as antimicrobial peptides, thioester-containing proteins, and transglutaminases effect responses such as lysis, phagocytosis, melanization, and agglutination. Effector responses are initiated by damage signals such as reactive oxygen species signaling from epithelial cells and recognized by cell surface receptors on hemocytes. Antiviral immunity is primarily mediated by siRNA pathways but coupled with interferon-like signaling, antimicrobial peptides, and thioester-containing proteins. Molecular mechanisms of immunity are closely linked to related traits of longevity and fertility, and arthropods have the capacity for innate immunological memory. Advances in understanding vector immunity can be leveraged to develop novel control strategies for reducing the rate of transmission of both ancient and emerging threats to global health.

  8. A paramyxovirus-vectored intranasal vaccine against Ebola virus is immunogenic in vector-immune animals.

    Science.gov (United States)

    Yang, Lijuan; Sanchez, Anthony; Ward, Jerrold M; Murphy, Brian R; Collins, Peter L; Bukreyev, Alexander

    2008-08-01

    Ebola virus (EBOV) causes outbreaks of a highly lethal hemorrhagic fever in humans. The virus can be transmitted by direct contact as well as by aerosol and is considered a potential bioweapon. Because direct immunization of the respiratory tract should be particularly effective against infection of mucosal surfaces, we previously developed an intranasal vaccine based on replication-competent human parainfluenza virus type 3 (HPIV3) expressing EBOV glycoprotein GP (HPIV3/EboGP) and showed that it is immunogenic and protective against a high dose parenteral EBOV challenge. However, because the adult human population has considerable immunity to HPIV3, which is a common human pathogen, replication and immunogenicity of the vaccine in this population might be greatly restricted. Indeed, in the present study, replication of the vaccine in the respiratory tract of HPIV3-immune guinea pigs was found to be restricted to undetectable levels. This restriction appeared to be based on both neutralizing antibodies and cellular or other components of the immunity to HPIV3. Surprisingly, even though replication of HPIV3/EboGP was highly restricted in HPIV3-immune animals, it induced a high level of EBOV-specific antibodies that nearly equaled that obtained in HPIV3-naive animals. We also show that the previously demonstrated presence of functional GP in the vector particle was not associated with increased replication in the respiratory tract nor with spread beyond the respiratory tract of HPIV3-naive guinea pigs, indicating that expression and functional incorporation of the attachment/penetration glycoprotein of this systemic virus did not mediate a change in tissue tropism.

  9. Microneedle-mediated immunization of an adenovirus-based malaria vaccine enhances antigen-specific antibody immunity and reduces anti-vector responses compared to the intradermal route

    OpenAIRE

    Carey, John B.; Vrdoljak, Anto; O'Mahony, Conor; Hill, Adrian V. S.; Draper, Simon J.; Moore, Anne C.

    2014-01-01

    Substantial effort has been placed in developing efficacious recombinant attenuated adenovirus-based vaccines. However induction of immunity to the vector is a significant obstacle to its repeated use. Here we demonstrate that skin-based delivery of an adenovirus-based malaria vaccine, HAdV5-PyMSP142, to mice using silicon microneedles induces equivalent or enhanced antibody responses to the encoded antigen, however it results in decreased anti-vector responses, compared to intradermal delive...

  10. Microneedle-mediated immunization of an adenovirus-based malaria vaccine enhances antigen-specific antibody immunity and reduces anti-vector responses compared to the intradermal route.

    Science.gov (United States)

    Carey, John B; Vrdoljak, Anto; O'Mahony, Conor; Hill, Adrian V S; Draper, Simon J; Moore, Anne C

    2014-08-21

    Substantial effort has been placed in developing efficacious recombinant attenuated adenovirus-based vaccines. However induction of immunity to the vector is a significant obstacle to its repeated use. Here we demonstrate that skin-based delivery of an adenovirus-based malaria vaccine, HAdV5-PyMSP1₄₂, to mice using silicon microneedles induces equivalent or enhanced antibody responses to the encoded antigen, however it results in decreased anti-vector responses, compared to intradermal delivery. Microneedle-mediated vaccine priming and resultant induction of low anti-vector antibody titres permitted repeated use of the same adenovirus vaccine vector. This resulted in significantly increased antigen-specific antibody responses in these mice compared to ID-treated mice. Boosting with a heterologous vaccine; MVA-PyMSP1₄₂ also resulted in significantly greater antibody responses in mice primed with HAdV5-PyMSP1₄₂ using MN compared to the ID route. The highest protection against blood-stage malaria challenge was observed when a heterologous route of immunization (MN/ID) was used. Therefore, microneedle-mediated immunization has potential to both overcome some of the logistic obstacles surrounding needle-and-syringe-based immunization as well as to facilitate the repeated use of the same adenovirus vaccine thereby potentially reducing manufacturing costs of multiple vaccines. This could have important benefits in the clinical ease of use of adenovirus-based immunization strategies.

  11. Microneedle-mediated immunization of an adenovirus-based malaria vaccine enhances antigen-specific antibody immunity and reduces anti-vector responses compared to the intradermal route

    Science.gov (United States)

    Carey, John B.; Vrdoljak, Anto; O'Mahony, Conor; Hill, Adrian V. S.; Draper, Simon J.; Moore, Anne C.

    2014-01-01

    Substantial effort has been placed in developing efficacious recombinant attenuated adenovirus-based vaccines. However induction of immunity to the vector is a significant obstacle to its repeated use. Here we demonstrate that skin-based delivery of an adenovirus-based malaria vaccine, HAdV5-PyMSP142, to mice using silicon microneedles induces equivalent or enhanced antibody responses to the encoded antigen, however it results in decreased anti-vector responses, compared to intradermal delivery. Microneedle-mediated vaccine priming and resultant induction of low anti-vector antibody titres permitted repeated use of the same adenovirus vaccine vector. This resulted in significantly increased antigen-specific antibody responses in these mice compared to ID-treated mice. Boosting with a heterologous vaccine; MVA-PyMSP142 also resulted in significantly greater antibody responses in mice primed with HAdV5-PyMSP142 using MN compared to the ID route. The highest protection against blood-stage malaria challenge was observed when a heterologous route of immunization (MN/ID) was used. Therefore, microneedle-mediated immunization has potential to both overcome some of the logistic obstacles surrounding needle-and-syringe-based immunization as well as to facilitate the repeated use of the same adenovirus vaccine thereby potentially reducing manufacturing costs of multiple vaccines. This could have important benefits in the clinical ease of use of adenovirus-based immunization strategies. PMID:25142082

  12. Immune modulation by genetic modification of dendritic cells with lentiviral vectors.

    Science.gov (United States)

    Liechtenstein, Therese; Perez-Janices, Noemi; Bricogne, Christopher; Lanna, Alessio; Dufait, Inès; Goyvaerts, Cleo; Laranga, Roberta; Padella, Antonella; Arce, Frederick; Baratchian, Mehdi; Ramirez, Natalia; Lopez, Natalia; Kochan, Grazyna; Blanco-Luquin, Idoia; Guerrero-Setas, David; Breckpot, Karine; Escors, David

    2013-09-01

    Our work over the past eight years has focused on the use of HIV-1 lentiviral vectors (lentivectors) for the genetic modification of dendritic cells (DCs) to control their functions in immune modulation. DCs are key professional antigen presenting cells which regulate the activity of most effector immune cells, including T, B and NK cells. Their genetic modification provides the means for the development of targeted therapies towards cancer and autoimmune disease. We have been modulating with lentivectors the activity of intracellular signalling pathways and co-stimulation during antigen presentation to T cells, to fine-tune the type and strength of the immune response. In the course of our research, we have found unexpected results such as the surprising immunosuppressive role of anti-viral signalling pathways, and the close link between negative co-stimulation in the immunological synapse and T cell receptor trafficking. Here we review our major findings and put them into context with other published work. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Transit through the flea vector induces a pretransmission innate immunity resistance phenotype in Yersinia pestis.

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    Viveka Vadyvaloo

    2010-02-01

    Full Text Available Yersinia pestis, the agent of plague, is transmitted to mammals by infected fleas. Y. pestis exhibits a distinct life stage in the flea, where it grows in the form of a cohesive biofilm that promotes transmission. After transmission, the temperature shift to 37 degrees C induces many known virulence factors of Y. pestis that confer resistance to innate immunity. These factors are not produced in the low-temperature environment of the flea, however, suggesting that Y. pestis is vulnerable to the initial encounter with innate immune cells at the flea bite site. In this study, we used whole-genome microarrays to compare the Y. pestis in vivo transcriptome in infective fleas to in vitro transcriptomes in temperature-matched biofilm and planktonic cultures, and to the previously characterized in vivo gene expression profile in the rat bubo. In addition to genes involved in metabolic adaptation to the flea gut and biofilm formation, several genes with known or predicted roles in resistance to innate immunity and pathogenicity in the mammal were upregulated in the flea. Y. pestis from infected fleas were more resistant to phagocytosis by macrophages than in vitro-grown bacteria, in part attributable to a cluster of insecticidal-like toxin genes that were highly expressed only in the flea. Our results suggest that transit through the flea vector induces a phenotype that enhances survival and dissemination of Y. pestis after transmission to the mammalian host.

  14. Introduction of optical reporter gene into cancer and immune cells using lentiviral vector

    International Nuclear Information System (INIS)

    Min, Jung Joon; Le, Uyenchi N.; Moon, Sung Min; Heo, Young Jun; Song, Ho Chun; Bom, Hee Seung; Kim, Yeon Soo

    2004-01-01

    For some applications such as gene therapy or reporter gene imaging, a gene has to be introduced into the organism of interest. Adenoviral vectors are capable of transducing both replicating and non-dividing cells. The adenoviral vectors do not integrate their DNA into host DNA, but do lead to an immune response. Lentiviruses belong to the retrovirus family and are capable of infecting both dividing and non-dividing cells. The human immunodeficiency virus (HIV) is an example of a lentavirus. A disabled HIV virus has been developed and could be used for in vivo gene delivery. A portion of the viral genome which encodes for accessory proteins canbe deleted without affecting production of the vector and efficiency of infection. Lentiviral delivery into various rodent tissues shows sustained expression of the transgene of up to six months. Furthermore, there seems to be little or no immune response with these vectors. These lentiviral vectors hold significant promise for in vivo gene delivery. We constructed lentiviral vector encoding firefly luciferase (Fluc) and eGFP. Fluc-eGFP fusion gene was inserted into multiple cloning sites of pLentiM1.3 vector. Reporter gene (Fluc-eGFP) was designed to be driven by murine CMV promoter with enhanced efficacy of transgene expression as compared to human CMV promoter. We transfected pLenti1.3-Fluc into human cervix cancer cell line (HeLa) and murine T lymphocytes. We also constructed adenovirus encoding Fluc and transfected to HeLa and T cells. This LentiM1.3-Fluc was transfected into HeLa cells and murine T lymphocytes in vitro, showing consistent expression of eGFP under the fluorescence microscopy from the 2nd day of transfection. Firefly luciferase reporter gene was not expressed in immune cells when it is mediated by adenovirus. Lentivirus was validated as a useful vector for both immune and cancer cells

  15. Meta-analysis of the Effects of Insect Vector Saliva on Host Immune Responses and Infection of Vector-Transmitted Pathogens: A Focus on Leishmaniasis

    OpenAIRE

    Ockenfels, Brittany; Michael, Edwin; McDowell, Mary Ann

    2014-01-01

    A meta-analysis of the effects of vector saliva on the immune response and progression of vector-transmitted disease, specifically with regard to pathology, infection level, and host cytokine levels was conducted. Infection in the absence or presence of saliva in naïve mice was compared. In addition, infection in mice pre-exposed to uninfected vector saliva was compared to infection in unexposed mice. To control for differences in vector and pathogen species, mouse strain, and experimental de...

  16. Meta-analysis of the effects of insect vector saliva on host immune responses and infection of vector-transmitted pathogens: a focus on leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Brittany Ockenfels

    2014-10-01

    Full Text Available A meta-analysis of the effects of vector saliva on the immune response and progression of vector-transmitted disease, specifically with regard to pathology, infection level, and host cytokine levels was conducted. Infection in the absence or presence of saliva in naïve mice was compared. In addition, infection in mice pre-exposed to uninfected vector saliva was compared to infection in unexposed mice. To control for differences in vector and pathogen species, mouse strain, and experimental design, a random effects model was used to compare the ratio of the natural log of the experimental to the control means of the studies. Saliva was demonstrated to enhance pathology, infection level, and the production of Th2 cytokines (IL-4 and IL-10 in naïve mice. This effect was observed across vector/pathogen pairings, whether natural or unnatural, and with single salivary proteins used as a proxy for whole saliva. Saliva pre-exposure was determined to result in less severe leishmaniasis pathology when compared with unexposed mice infected either in the presence or absence of sand fly saliva. The results of further analyses were not significant, but demonstrated trends toward protection and IFN-γ elevation for pre-exposed mice.

  17. Meta-analysis of the effects of insect vector saliva on host immune responses and infection of vector-transmitted pathogens: a focus on leishmaniasis.

    Science.gov (United States)

    Ockenfels, Brittany; Michael, Edwin; McDowell, Mary Ann

    2014-10-01

    A meta-analysis of the effects of vector saliva on the immune response and progression of vector-transmitted disease, specifically with regard to pathology, infection level, and host cytokine levels was conducted. Infection in the absence or presence of saliva in naïve mice was compared. In addition, infection in mice pre-exposed to uninfected vector saliva was compared to infection in unexposed mice. To control for differences in vector and pathogen species, mouse strain, and experimental design, a random effects model was used to compare the ratio of the natural log of the experimental to the control means of the studies. Saliva was demonstrated to enhance pathology, infection level, and the production of Th2 cytokines (IL-4 and IL-10) in naïve mice. This effect was observed across vector/pathogen pairings, whether natural or unnatural, and with single salivary proteins used as a proxy for whole saliva. Saliva pre-exposure was determined to result in less severe leishmaniasis pathology when compared with unexposed mice infected either in the presence or absence of sand fly saliva. The results of further analyses were not significant, but demonstrated trends toward protection and IFN-γ elevation for pre-exposed mice.

  18. Regulation of the Immune Response to α-Gal and Vector-borne Diseases.

    Science.gov (United States)

    Cabezas-Cruz, Alejandro; Mateos-Hernández, Lourdes; Pérez-Cruz, Magdiel; Valdés, James J; Mera, Isabel G Fernández de; Villar, Margarita; de la Fuente, José

    2015-10-01

    Vector-borne diseases (VBD) challenge our understanding of emerging diseases. Recently, arthropod vectors have been involved in emerging anaphylactic diseases. In particular, the immunoglobulin E (IgE) antibody response to the carbohydrate Galα1-3Galβ1-(3)4GlcNAc-R (α-gal) following a tick bite was associated with allergies to red meat, cetuximab, and gelatin. By contrast, an anti-α-gal IgM antibody response was shown to protect against mosquito-borne malaria. Herein, we highlight the interplay between the gut microbiota, vectors, transmitted pathogens, and the regulation of the immune response as a model to understand the protective or allergic effect of α-gal. Establishing the source of α-gal in arthropod vectors and the immune response to vector bites and transmitted pathogens will be essential for diagnosing, treating, and ultimately preventing these emerging anaphylactic and other vector-borne diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Immunization with Hexon modified adenoviral vectors integrated with gp83 epitope provides protection against Trypanosoma cruzi infection.

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    Anitra L Farrow

    2014-08-01

    Full Text Available Trypanosoma cruzi is the causative agent of Chagas disease. Chagas disease is an endemic infection that affects over 8 million people throughout Latin America and now has become a global challenge. The current pharmacological treatment of patients is unsuccessful in most cases, highly toxic, and no vaccines are available. The results of inadequate treatment could lead to heart failure resulting in death. Therefore, a vaccine that elicits neutralizing antibodies mediated by cell-mediated immune responses and protection against Chagas disease is necessary.The "antigen capsid-incorporation" strategy is based upon the display of the T. cruzi epitope as an integral component of the adenovirus' capsid rather than an encoded transgene. This strategy is predicted to induce a robust humoral immune response to the presented antigen, similar to the response provoked by native Ad capsid proteins. The antigen chosen was T. cruzi gp83, a ligand that is used by T. cruzi to attach to host cells to initiate infection. The gp83 epitope, recognized by the neutralizing MAb 4A4, along with His6 were incorporated into the Ad serotype 5 (Ad5 vector to generate the vector Ad5-HVR1-gp83-18 (Ad5-gp83. This vector was evaluated by molecular and immunological analyses. Vectors were injected to elicit immune responses against gp83 in mouse models. Our findings indicate that mice immunized with the vector Ad5-gp83 and challenged with a lethal dose of T. cruzi trypomastigotes confer strong immunoprotection with significant reduction in parasitemia levels, increased survival rate and induction of neutralizing antibodies.This data demonstrates that immunization with adenovirus containing capsid-incorporated T. cruzi antigen elicits a significant anti-gp83-specific response in two different mouse models, and protection against T. cruzi infection by eliciting neutralizing antibodies mediated by cell-mediated immune responses, as evidenced by the production of several Ig isotypes

  20. An adenovirus vectored mucosal adjuvant augments protection of mice immunized intranasally with an adenovirus-vectored foot-and-mouth disease virus subunit vaccine.

    Science.gov (United States)

    Alejo, Diana M; Moraes, Mauro P; Liao, Xiaofen; Dias, Camila C; Tulman, Edan R; Diaz-San Segundo, Fayna; Rood, Debra; Grubman, Marvin J; Silbart, Lawrence K

    2013-04-26

    Foot-and-mouth disease virus (FMDV) is a highly contagious pathogen that causes severe morbidity and economic losses to the livestock industry in many countries. The oral and respiratory mucosae are the main ports of entry of FMDV, so the stimulation of local immunity in these tissues may help prevent initial infection and viral spread. E. coli heat-labile enterotoxin (LT) has been described as one of the few molecules that have adjuvant activity at mucosal surfaces. The objective of this study was to evaluate the efficacy of replication-defective adenovirus 5 (Ad5) vectors encoding either of two LT-based mucosal adjuvants, LTB or LTR72. These vectored adjuvants were delivered intranasally to mice concurrent with an Ad5-FMDV vaccine (Ad5-A24) to assess their ability to augment mucosal and systemic humoral immune responses to Ad5-A24 and protection against FMDV. Mice receiving Ad5-A24 plus Ad5-LTR72 had higher levels of mucosal and systemic neutralizing antibodies than those receiving Ad5-A24 alone or Ad5-A24 plus Ad5-LTB. The vaccine plus Ad5-LTR72 group also demonstrated 100% survival after intradermal challenge with a lethal dose of homologous FMDV serotype A24. These results suggest that Ad5-LTR72 could be used as an important tool to enhance mucosal and systemic immunity against FMDV and potentially other pathogens with a common route of entry. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Humoral Immunity to Primary Smallpox Vaccination: Impact of Childhood versus Adult Immunization on Vaccinia Vector Vaccine Development in Military Populations.

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    Bonnie M Slike

    Full Text Available Modified Vaccinia virus has been shown to be a safe and immunogenic vector platform for delivery of HIV vaccines. Use of this vector is of particular importance to the military, with the implementation of a large scale smallpox vaccination campaign in 2002 in active duty and key civilian personnel in response to potential bioterrorist activities. Humoral immunity to smallpox vaccination was previously shown to be long lasting (up to 75 years and protective. However, using vaccinia-vectored vaccine delivery for other diseases on a background of anti-vector antibodies (i.e. pre-existing immunity may limit their use as a vaccine platform, especially in the military. In this pilot study, we examined the durability of vaccinia antibody responses in adult primary vaccinees in a healthy military population using a standard ELISA assay and a novel dendritic cell neutralization assay. We found binding and neutralizing antibody (NAb responses to vaccinia waned after 5-10 years in a group of 475 active duty military, born after 1972, who were vaccinated as adults with Dryvax®. These responses decreased from a geometric mean titer (GMT of 250 to baseline (30 years with a GMT of 210 (range 112-3234. This data suggests limited durability of antibody responses in adult vaccinees compared to those vaccinated in childhood and further that adult vaccinia recipients may benefit similarly from receipt of a vaccinia based vaccine as those who are vaccinia naïve. Our findings may have implications for the smallpox vaccination schedule and support the ongoing development of this promising viral vector in a military vaccination program.

  2. Alphavirus Replicon DNA Vectors Expressing Ebola GP and VP40 Antigens Induce Humoral and Cellular Immune Responses in Mice

    Directory of Open Access Journals (Sweden)

    Shoufeng Ren

    2018-01-01

    Full Text Available Ebola virus (EBOV causes severe hemorrhagic fevers in humans, and no approved therapeutics or vaccine is currently available. Glycoprotein (GP is the major protective antigen of EBOV, and can generate virus-like particles (VLPs by co-expression with matrix protein (VP40. In this study, we constructed a recombinant Alphavirus Semliki Forest virus (SFV replicon vector DREP to express EBOV GP and matrix viral protein (VP40. EBOV VLPs were successfully generated and achieved budding from 293 cells after co-transfection with DREP-based GP and VP40 vectors (DREP-GP+DREP-VP40. Vaccination of BALB/c mice with DREP-GP, DREP-VP40, or DREP-GP+DREP-VP40 vectors, followed by immediate electroporation resulted in a mixed IgG subclass production, which recognized EBOV GP and/or VP40 proteins. This vaccination regimen also led to the generation of both Th1 and Th2 cellular immune responses in mice. Notably, vaccination with DREP-GP and DREP-VP40, which produces both GP and VP40 antigens, induced a significantly higher level of anti-GP IgG2a antibody and increased IFN-γ secreting CD8+ T-cell responses relative to vaccination with DREP-GP or DREP-VP40 vector alone. Our study indicates that co-expression of GP and VP40 antigens based on the SFV replicon vector generates EBOV VLPs in vitro, and vaccination with recombinant DREP vectors containing GP and VP40 antigens induces Ebola antigen-specific humoral and cellular immune responses in mice. This novel approach provides a simple and efficient vaccine platform for Ebola disease prevention.

  3. NYVAC vector modified by C7L viral gene insertion improves T cell immune responses and effectiveness against leishmaniasis.

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    Sánchez-Sampedro, L; Mejías-Pérez, E; S Sorzano, Carlos Óscar; Nájera, J L; Esteban, M

    2016-07-15

    The NYVAC poxvirus vector is used as vaccine candidate for HIV and other diseases, although there is only limited experimental information on its immunogenicity and effectiveness for use against human pathogens. Here we defined the selective advantage of NYVAC vectors in a mouse model by comparing the immune responses and protection induced by vectors that express the LACK (Leishmania-activated C-kinase antigen), alone or with insertion of the viral host range gene C7L that allows the virus to replicate in human cells. Using DNA prime/virus boost protocols, we show that replication-competent NYVAC-LACK that expresses C7L (NYVAC-LACK-C7L) induced higher-magnitude polyfunctional CD8(+) and CD4(+) primary adaptive and effector memory T cell responses (IFNγ, TNFα, IL-2, CD107a) to LACK antigen than non-replicating NYVAC-LACK. Compared to NYVAC-LACK, the NYVAC-LACK-C7L-induced CD8(+) T cell population also showed higher proliferation when stimulated with LACK antigen. After a challenge by subcutaneous Leishmania major metacyclic promastigotes, NYVAC-LACK-C7L-vaccinated mouse groups showed greater protection than the NYVAC-LACK-vaccinated group. Our results indicate that the type and potency of immune responses induced by LACK-expressing NYVAC vectors is improved by insertion of the C7L gene, and that a replication-competent vector as a vaccine renders greater protection against a human pathogen than a non-replicating vector. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. New gorilla adenovirus vaccine vectors induce potent immune responses and protection in a mouse malaria model.

    Science.gov (United States)

    Limbach, Keith; Stefaniak, Maureen; Chen, Ping; Patterson, Noelle B; Liao, Grant; Weng, Shaojie; Krepkiy, Svetlana; Ekberg, Greg; Torano, Holly; Ettyreddy, Damodar; Gowda, Kalpana; Sonawane, Sharvari; Belmonte, Arnel; Abot, Esteban; Sedegah, Martha; Hollingdale, Michael R; Moormann, Ann; Vulule, John; Villasante, Eileen; Richie, Thomas L; Brough, Douglas E; Bruder, Joseph T

    2017-07-03

    A DNA-human Ad5 (HuAd5) prime-boost malaria vaccine has been shown to protect volunteers against a controlled human malaria infection. The potency of this vaccine, however, appeared to be affected by the presence of pre-existing immunity against the HuAd5 vector. Since HuAd5 seroprevalence is very high in malaria-endemic areas of the world, HuAd5 may not be the most appropriate malaria vaccine vector. This report describes the evaluation of the seroprevalence, immunogenicity and efficacy of three newly identified gorilla adenoviruses, GC44, GC45 and GC46, as potential malaria vaccine vectors. The seroprevalence of GC44, GC45 and GC46 is very low, and the three vectors are not efficiently neutralized by human sera from Kenya and Ghana, two countries where malaria is endemic. In mice, a single administration of GC44, GC45 and GC46 vectors expressing a murine malaria gene, Plasmodium yoelii circumsporozoite protein (PyCSP), induced robust PyCSP-specific T cell and antibody responses that were at least as high as a comparable HuAd5-PyCSP vector. Efficacy studies in a murine malaria model indicated that a prime-boost regimen with DNA-PyCSP and GC-PyCSP vectors can protect mice against a malaria challenge. Moreover, these studies indicated that a DNA-GC46-PyCSP vaccine regimen was significantly more efficacious than a DNA-HuAd5-PyCSP regimen. These data suggest that these gorilla-based adenovectors have key performance characteristics for an effective malaria vaccine. The superior performance of GC46 over HuAd5 highlights its potential for clinical development.

  5. Diagnosing tuberculosis with a novel support vector machine-based artificial immune recognition system.

    Science.gov (United States)

    Saybani, Mahmoud Reza; Shamshirband, Shahaboddin; Golzari Hormozi, Shahram; Wah, Teh Ying; Aghabozorgi, Saeed; Pourhoseingholi, Mohamad Amin; Olariu, Teodora

    2015-04-01

    Tuberculosis (TB) is a major global health problem, which has been ranked as the second leading cause of death from an infectious disease worldwide. Diagnosis based on cultured specimens is the reference standard, however results take weeks to process. Scientists are looking for early detection strategies, which remain the cornerstone of tuberculosis control. Consequently there is a need to develop an expert system that helps medical professionals to accurately and quickly diagnose the disease. Artificial Immune Recognition System (AIRS) has been used successfully for diagnosing various diseases. However, little effort has been undertaken to improve its classification accuracy. In order to increase the classification accuracy of AIRS, this study introduces a new hybrid system that incorporates a support vector machine into AIRS for diagnosing tuberculosis. Patient epacris reports obtained from the Pasteur laboratory of Iran were used as the benchmark data set, with the sample size of 175 (114 positive samples for TB and 60 samples in the negative group). The strategy of this study was to ensure representativeness, thus it was important to have an adequate number of instances for both TB and non-TB cases. The classification performance was measured through 10-fold cross-validation, Root Mean Squared Error (RMSE), sensitivity and specificity, Youden's Index, and Area Under the Curve (AUC). Statistical analysis was done using the Waikato Environment for Knowledge Analysis (WEKA), a machine learning program for windows. With an accuracy of 100%, sensitivity of 100%, specificity of 100%, Youden's Index of 1, Area Under the Curve of 1, and RMSE of 0, the proposed method was able to successfully classify tuberculosis patients. There have been many researches that aimed at diagnosing tuberculosis faster and more accurately. Our results described a model for diagnosing tuberculosis with 100% sensitivity and 100% specificity. This model can be used as an additional tool for

  6. Protective efficacy of a single immunization with capripoxvirus-vectored recombinant peste des petits ruminants vaccines in presence of pre-existing immunity.

    Science.gov (United States)

    Caufour, Philippe; Rufael, Tesfaye; Lamien, Charles Euloge; Lancelot, Renaud; Kidane, Menbere; Awel, Dino; Sertse, Tefera; Kwiatek, Olivier; Libeau, Geneviève; Sahle, Mesfin; Diallo, Adama; Albina, Emmanuel

    2014-06-24

    Sheeppox, goatpox and peste des petits ruminants (PPR) are highly contagious ruminant diseases widely distributed in Africa, the Middle East and Asia. Capripoxvirus (CPV)-vectored recombinant PPR vaccines (rCPV-PPR vaccines), which have been developed and shown to protect against both Capripox (CP) and PPR, would be critical tools in the control of these important diseases. In most parts of the world, these disease distributions overlap each other leaving concerns about the potential impact that pre-existing immunity against either disease may have on the protective efficacy of these bivalent rCPV-PPR vaccines. Currently, this question has not been indisputably addressed. Therefore, we undertook this study, under experimental conditions designed for the context of mass vaccination campaigns of small ruminants, using the two CPV recombinants (Kenya sheep-1 (KS-1) strain-based constructs) developed previously in our laboratory. Pre-existing immunity was first induced by immunization either with an attenuated CPV vaccine strain (KS-1) or the attenuated PPRV vaccine strain (Nigeria 75/1) and animals were thereafter inoculated once subcutaneously with a mixture of CPV recombinants expressing either the hemagglutinin (H) or the fusion (F) protein gene of PPRV (10(3) TCID50/animal of each). Finally, these animals were challenged with a virulent CPV strain followed by a virulent PPRV strain 3 weeks later. Our study demonstrated full protection against CP for vaccinated animals with prior exposure to PPRV and a partial protection against PPR for vaccinated animals with prior exposure to CPV. The latter animals exhibited a mild clinical form of PPR and did not show any post-challenge anamnestic neutralizing antibody response against PPRV. The implications of these results are discussed herein and suggestions made for future research regarding the development of CPV-vectored vaccines. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Vectors

    DEFF Research Database (Denmark)

    Boeriis, Morten; van Leeuwen, Theo

    2017-01-01

    should be taken into account in discussing ‘reactions’, which Kress and van Leeuwen link only to eyeline vectors. Finally, the question can be raised as to whether actions are always realized by vectors. Drawing on a re-reading of Rudolf Arnheim’s account of vectors, these issues are outlined......This article revisits the concept of vectors, which, in Kress and van Leeuwen’s Reading Images (2006), plays a crucial role in distinguishing between ‘narrative’, action-oriented processes and ‘conceptual’, state-oriented processes. The use of this concept in image analysis has usually focused...

  8. A viral vectored prime-boost immunization regime targeting the malaria Pfs25 antigen induces transmission-blocking activity.

    Directory of Open Access Journals (Sweden)

    Anna L Goodman

    Full Text Available The ookinete surface protein Pfs25 is a macrogamete-to-ookinete/ookinete stage antigen of Plasmodium falciparum, capable of exerting high-level anti-malarial transmission-blocking activity following immunization with recombinant protein-in-adjuvant formulations. Here, this antigen was expressed in recombinant chimpanzee adenovirus 63 (ChAd63, human adenovirus serotype 5 (AdHu5 and modified vaccinia virus Ankara (MVA viral vectored vaccines. Two immunizations were administered to mice in a heterologous prime-boost regime. Immunization of mice with AdHu5 Pfs25 at week 0 and MVA Pfs25 at week 10 (Ad-MVA Pfs25 resulted in high anti-Pfs25 IgG titers, consisting of predominantly isotypes IgG1 and IgG2a. A single priming immunization with ChAd63 Pfs25 was as effective as AdHu5 Pfs25 with respect to ELISA titers at 8 weeks post-immunization. Sera from Ad-MVA Pfs25 immunized mice inhibited the transmission of P. falciparum to the mosquito both ex vivo and in vivo. In a standard membrane-feeding assay using NF54 strain P. falciparum, oocyst intensity in Anopheles stephensi mosquitoes was significantly reduced in an IgG concentration-dependent manner when compared to control feeds (96% reduction of intensity, 78% reduction in prevalence at a 1 in 5 dilution of sera. In addition, an in vivo transmission-blocking effect was also demonstrated by direct feeding of immunized mice infected with Pfs25DR3, a chimeric P. berghei line expressing Pfs25 in place of endogenous Pbs25. In this assay the density of Pfs25DR3 oocysts was significantly reduced when mosquitoes were fed on vaccinated as compared to control mice (67% reduction of intensity, 28% reduction in prevalence and specific IgG titer correlated with efficacy. These data confirm the utility of the adenovirus-MVA vaccine platform for the induction of antibodies with transmission-blocking activity, and support the continued development of this alternative approach to transmission-blocking malaria subunit

  9. A new adenovirus based vaccine vector expressing an Eimeria tenella derived TLR agonist improves cellular immune responses to an antigenic target.

    Directory of Open Access Journals (Sweden)

    Daniel M Appledorn

    2010-03-01

    Full Text Available Adenoviral based vectors remain promising vaccine platforms for use against numerous pathogens, including HIV. Recent vaccine trials utilizing Adenovirus based vaccines expressing HIV antigens confirmed induction of cellular immune responses, but these responses failed to prevent HIV infections in vaccinees. This illustrates the need to develop vaccine formulations capable of generating more potent T-cell responses to HIV antigens, such as HIV-Gag, since robust immune responses to this antigen correlate with improved outcomes in long-term non-progressor HIV infected individuals.In this study we designed a novel vaccine strategy utilizing an Ad-based vector expressing a potent TLR agonist derived from Eimeria tenella as an adjuvant to improve immune responses from a [E1-]Ad-based HIV-Gag vaccine. Our results confirm that expression of rEA elicits significantly increased TLR mediated innate immune responses as measured by the influx of plasma cytokines and chemokines, and activation of innate immune responding cells. Furthermore, our data show that the quantity and quality of HIV-Gag specific CD8(+ and CD8(- T-cell responses were significantly improved when coupled with rEA expression. These responses also correlated with a significantly increased number of HIV-Gag derived epitopes being recognized by host T cells. Finally, functional assays confirmed that rEA expression significantly improved antigen specific CTL responses, in vivo. Moreover, we show that these improved responses were dependent upon improved TLR pathway interactions.The data presented in this study illustrate the potential utility of Ad-based vectors expressing TLR agonists to improve clinical outcomes dependent upon induction of robust, antigen specific immune responses.

  10. An adenoviral vector expressing lipoprotein A, a major antigen of Mycoplasma mycoides subspecies mycoides, elicits robust immune responses in mice.

    Science.gov (United States)

    Carozza, Marlène; Rodrigues, Valérie; Unterfinger, Yves; Galea, Sandra; Coulpier, Muriel; Klonjkowski, Bernard; Thiaucourt, François; Totté, Philippe; Richardson, Jennifer

    2015-01-01

    Contagious bovine pleuropneumonia (CBPP), caused by Mycoplasma mycoides subsp. mycoides small colony type (MmmSC), is a devastating respiratory disease of cattle. In sub-Saharan Africa, where CBPP is enzootic, live attenuated vaccines are deployed but afford only short-lived protection. In cattle, recovery from experimental MmmSC infection has been associated with the presence of CD4(+) T lymphocytes that secrete interferon gamma in response to MmmSC, and in particular to the lipoprotein A (LppA) antigen. In an effort to develop a better vaccine against CBPP, a viral vector (Ad5-LppA) that expressed LppA was generated from human adenovirus type 5. The LppA-specific immune responses elicited by the Ad5-LppA vector were evaluated in mice, and compared to those elicited by recombinant LppA formulated with a potent adjuvant. Notably, a single administration of Ad5-LppA, but not recombinant protein, sufficed to elicit a robust LppA-specific humoral response. After a booster administration, both vector and recombinant protein elicited strong LppA-specific humoral and cell-mediated responses. Ex vivo stimulation of splenocytes induced extensive proliferation of CD4(+) T cells for mice immunized with vector or protein, and secretion of T helper 1-associated and proinflammatory cytokines for mice immunized with Ad5-LppA. Our study - by demonstrating the potential of a viral-vectored prototypic vaccine to elicit prompt and robust immune responses against a major antigen of MmmSC - represents a first step in developing a recombinant vaccine against CBPP. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. A novel alphavirus replicon-vectored vaccine delivered by adenovirus induces sterile immunity against classical swine fever.

    Science.gov (United States)

    Sun, Yuan; Li, Hong-Yu; Tian, Da-Yong; Han, Qiu-Ying; Zhang, Xin; Li, Na; Qiu, Hua-Ji

    2011-10-26

    Low efficacy of gene-based vaccines due to inefficient gene delivery and expression has been major bottleneck of their applications. Efforts have been made to improve the efficacy, such as gene gun and electroporation, but the strategies are difficult to put into practical use. In this study, we developed and evaluated an adenovirus-delivered, alphavirus replicon-vectored vaccine (chimeric vector-based vaccine) expressing the E2 gene of classical swine fever virus (CSFV) (rAdV-SFV-E2). Rabbits immunized with rAdV-SFV-E2 developed CSFV-specific antibodies as early as 9 days and as long as 189 days and completely protected from challenge with C-strain. Pigs immunized with rAdV-SFV-E2 (n=5) developed robust humoral and cell-mediated responses to CSFV and were completely protected from subsequent lethal CSFV infection clinically and virologically. The level of immunity and protection induced by rAdV-SFV-E2 was comparable to that provided by the currently used live attenuated vaccine, C-strain. In contrast, both the conventional alphavirus replicon-vectored vaccine pSFV1CS-E2 and conventional adenovirus-vectored vaccine rAdV-E2 provided incomplete protection. The chimeric vector-based vaccine represents the first gene-based vaccine that is able to confer sterile immunity and complete protection against CSFV. The new-concept vaccination strategy may also be valuable in vaccine development against other pathogens. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Heat Shock Protein 70 Enhances Mucosal Immunity against Human Norovirus When Coexpressed from a Vesicular Stomatitis Virus Vector

    Science.gov (United States)

    Ma, Yuanmei; Duan, Yue; Wei, Yongwei; Liang, Xueya; Niewiesk, Stefan; Oglesbee, Michael

    2014-01-01

    ABSTRACT Human norovirus (NoV) accounts for 95% of nonbacterial gastroenteritis worldwide. Currently, there is no vaccine available to combat human NoV as it is not cultivable and lacks a small-animal model. Recently, we demonstrated that recombinant vesicular stomatitis virus (rVSV) expressing human NoV capsid protein (rVSV-VP1) induced strong immunities in mice (Y. Ma and J. Li, J. Virol. 85:2942–2952, 2011). To further improve the safety and efficacy of the vaccine candidate, heat shock protein 70 (HSP70) was inserted into the rVSV-VP1 backbone vector. A second construct was generated in which the firefly luciferase (Luc) gene was inserted in place of HSP70 as a control for the double insertion. The resultant recombinant viruses (rVSV-HSP70-VP1 and rVSV-Luc-VP1) were significantly more attenuated in cell culture and viral spread in mice than rVSV-VP1. At the inoculation dose of 1.0 × 106 PFU, rVSV-HSP70-VP1 triggered significantly higher vaginal IgA than rVSV-VP1 and significantly higher fecal and vaginal IgA responses than rVSV-Luc-VP1, although serum IgG and T cell responses were similar. At the inoculation dose of 5.0 × 106 PFU, rVSV-HSP70-VP1 stimulated significantly higher T cell, fecal, and vaginal IgA responses than rVSV-VP1. Fecal and vaginal IgA responses were also significantly increased when combined vaccination of rVSV-VP1 and rVSV-HSP70 was used. Collectively, these data indicate that (i) insertion of an additional gene (HSP70 or Luc) into the rVSV-VP1 backbone further attenuates the VSV-based vaccine in vitro and in vivo, thus improving the safety of the vaccine candidate, and (ii) HSP70 enhances the human NoV-specific mucosal and T cell immunities triggered by a VSV-based human NoV vaccine. IMPORTANCE Human norovirus (NoV) is responsible for more than 95% of acute nonbacterial gastroenteritis worldwide. Currently, there is no vaccine for this virus. Development of a live attenuated vaccine for human NoV has not been possible because it is

  13. Control of SIV infection and subsequent induction of pandemic H1N1 immunity in rhesus macaques using an Ad5 [E1-, E2b-] vector platform.

    Science.gov (United States)

    Gabitzsch, Elizabeth S; Balint-Junior, Joseph P; Xu, Younong; Balcaitis, Stephanie; Sanders-Beer, Brigitte; Karl, Julie; Weinhold, Kent J; Paessler, Slobodan; Jones, Frank R

    2012-11-26

    Anti-vector immunity mitigates immune responses induced by recombinant adenovirus vector vaccines, limiting their prime-boost capabilities. We have developed a novel gene delivery and expression platform (Ad5 [E1-, E2b-]) that induces immune responses despite pre-existing and/or developed concomitant Ad5 immunity. In the present study, we evaluated if this new Ad5 platform could overcome the adverse condition of pre-existing Ad5 immunity to induce effective immune responses in prime-boost immunization regimens against two different infectious diseases in the same animal. Ad5 immune rhesus macaques (RM) were immunized multiple times with the Ad5 [E1-, E2b-] platform expressing antigens from simian immunodeficiency virus (SIV). Immunized RM developed cell-mediated immunity against SIV antigens Gag, Pol, Nef and Env as well as antibody against Env. Vaccinated and vector control RMs were challenged intra-rectally with homologous SIVmac239. During a 7-week follow-up, there was perturbation of SIV load in some immunized RM. At 7 weeks post-challenge, eight immunized animals (53%) did not have detectable SIV, compared to two RM controls (13%) (Pnow hyper immune to Ad5, were then vaccinated with the same Ad5 [E1-, E2b-] platform expressing H1N1 influenza hemagglutinin (HA). Thirty days post Ad5 [E1-, E2b-]-HA vaccination, significant levels of influenza neutralizing antibody were induced in all animals that increased after an Ad5 [E1-, E2b-]-HA homologous boost. These data demonstrate the versatility of this new vector platform to immunize against two separate disease targets in the same animal despite the presence of immunity against the delivery platform, permitting homologous repeat immunizations with an Ad5 gene delivery platform. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Pre-existing vector immunity does not prevent replication deficient adenovirus from inducing efficient CD8 T-cell memory and recall responses.

    Directory of Open Access Journals (Sweden)

    Maria Abildgaard Steffensen

    Full Text Available Adenoviral vectors have shown a great potential for vaccine development due to their inherent ability to induce potent and protective CD8 T-cell responses. However, a critical issue regarding the use of these vectors is the existence of inhibitory immunity against the most commonly used Ad5 vector in a large part of the human population. We have recently developed an improved adenoviral vaccine vector system in which the vector expresses the transgene tethered to the MHC class II associated invariant chain (Ii. To further evaluate the potential of this system, the concept of pre-existing inhibitory immunity to adenoviral vectors was revisited to investigate whether the inhibition previously seen with the Ad5 vector also applied to the optimized vector system. We found this to be the case, and antibodies dominated as the mechanism underlying inhibitory vector immunity. However, presence of CD8 T cells directed against epitopes in the adenoviral vector seemed to correlate with repression of the induced response in re-vaccinated B-cell deficient mice. More importantly, despite a repressed primary effector CD8 T-cell response in Ad5-immune animals subjected to vaccination, memory T cells were generated that provided the foundation for an efficient recall response and protection upon subsequent viral challenge. Furthermore, the transgene specific response could be efficiently boosted by homologous re-immunization. Taken together, these studies indicate that adenoviral vectors can be used to induce efficient CD8 T-cell memory even in individuals with pre-existing vector immunity.

  15. Pre-existing vector immunity does not prevent replication deficient adenovirus from inducing efficient CD8 T-cell memory and recall responses

    DEFF Research Database (Denmark)

    Steffensen, Maria Abildgaard; Jensen, Benjamin Anderschou Holbech; Holst, Peter Johannes

    2012-01-01

    directed against epitopes in the adenoviral vector seemed to correlate with repression of the induced response in re-vaccinated B-cell deficient mice. More importantly, despite a repressed primary effector CD8 T-cell response in Ad5-immune animals subjected to vaccination, memory T cells were generated...... that provided the foundation for an efficient recall response and protection upon subsequent viral challenge. Furthermore, the transgene specific response could be efficiently boosted by homologous re-immunization. Taken together, these studies indicate that adenoviral vectors can be used to induce efficient CD......8 T-cell memory even in individuals with pre-existing vector immunity....

  16. Alternate adenovirus type-pairs for a possible circumvention of host immune response to recombinant adenovirus vectors.

    Science.gov (United States)

    Nász, I; Adám, E; Lengyel, A

    2001-01-01

    With the help of monoclonal antibodies the existence of at least 18 different earlier not known intertype (IT) specific epitopes were demonstrated in different numbers and combinations on the hexons of different adenovirus serotypes. The IT specific epitopes play an important role in the experimental gene therapy and in the recombinant adenovirus vaccination because of the harmful immune response of the recipient organisms directed against the many different epitopes of the adenovirus vector. For the elimination of harmful effect the authors suggest the use of multiple vectors, each prepared from different adenovirus serotypes showing the loosest antigenic relationship to each other. The vectors would be used sequentially when second or multiple administration is needed. For this purpose the authors determined and described 31 such adenovirus type-pairs, which are probably the best alternates for sequential use in experimental gene therapy.

  17. Increased tumor localization and reduced immune response to adenoviral vector formulated with the liposome DDAB/DOPE.

    Science.gov (United States)

    Steel, Jason C; Cavanagh, Heather M A; Burton, Mark A; Abu-Asab, Mones S; Tsokos, Maria; Morris, John C; Kalle, Wouter H J

    2007-04-01

    We aimed to increase the efficiency of adenoviral vectors by limiting adenoviral spread from the target site and reducing unwanted host immune responses to the vector. We complexed adenoviral vectors with DDAB-DOPE liposomes to form adenovirus-liposomal (AL) complexes. AL complexes were delivered by intratumoral injection in an immunocompetent subcutaneous rat tumor model and the immunogenicity of the AL complexes and the expression efficiency in the tumor and other organs was examined. Animals treated with the AL complexes had significantly lower levels of beta-galactosidase expression in systemic tissues compared to animals treated with the naked adenovirus (NA) (P<0.05). The tumor to non-tumor ratio of beta-galactosidase marker expression was significantly higher for the AL complex treated animals. NA induced significantly higher titers of adenoviral-specific antibodies compared to the AL complexes (P<0.05). The AL complexes provided protection (immunoshielding) to the adenovirus from neutralizing antibody. Forty-seven percent more beta-galactosidase expression was detected following intratumoral injection with AL complexes compared to the NA in animals pre-immunized with adenovirus. Complexing of adenovirus with liposomes provides a simple method to enhance tumor localization of the vector, decrease the immunogenicity of adenovirus, and provide protection of the virus from pre-existing neutralizing antibodies.

  18. Intranasal boosting with an adenovirus-vectored vaccine markedly enhances protection by parenteral Mycobacterium bovis BCG immunization against pulmonary tuberculosis.

    Science.gov (United States)

    Santosuosso, Michael; McCormick, Sarah; Zhang, Xizhong; Zganiacz, Anna; Xing, Zhou

    2006-08-01

    Parenterally administered Mycobacterium bovis BCG vaccine confers only limited immune protection from pulmonary tuberculosis in humans. There is a need for developing effective boosting vaccination strategies. We examined a heterologous prime-boost regimen utilizing BCG as a prime vaccine and our recently described adenoviral vector expressing Ag85A (AdAg85A) as a boost vaccine. Since we recently demonstrated that a single intranasal but not intramuscular immunization with AdAg85A was able to induce potent protection from pulmonary Mycobacterium tuberculosis challenge in a mouse model, we compared the protective effects of parenteral and mucosal booster immunizations following subcutaneous BCG priming. Protection by BCG prime immunization was not effectively boosted by subcutaneous BCG or intramuscular AdAg85A. In contrast, protection by BCG priming was remarkably boosted by intranasal AdAg85A. Such enhanced protection by intranasal AdAg85A was correlated to the numbers of gamma interferon-positive CD4 and CD8 T cells residing in the airway lumen of the lung. Our study demonstrates that intranasal administration of AdAg85A represents an effective way to boost immune protection by parenteral BCG vaccination.

  19. A nonproliferating parvovirus vaccine vector elicits sustained, protective humoral immunity following a single intravenous or intranasal inoculation.

    Science.gov (United States)

    Palmer, Gene A; Brogdon, Jennifer L; Constant, Stephanie L; Tattersall, Peter

    2004-02-01

    An ideal vaccine delivery system would elicit persistent protection following a single administration, preferably by a noninvasive route, and be safe even in the face of immunosuppression, either inherited or acquired, of the recipient. We have exploited the unique life cycle of the autonomous parvoviruses to develop a nonproliferating vaccine platform that appears to both induce priming and continually boost a protective immune response following a single inoculation. A crippled parvovirus vector was constructed, based on a chimera between minute virus of mice (MVM) and LuIII, which expresses Borrelia burgdorferi outer surface protein A (OspA) instead of its coat protein. The vector was packaged into an MVM lymphotropic capsid and inoculated into naive C3H/HeNcr mice. Vaccination with a single vector dose, either intravenously or intranasally, elicited high-titer anti-OspA-specific antibody that provided protection from live spirochete challenge and was sustained over the lifetime of the animal. Both humoral and cell-mediated Th(1) immunity was induced, as shown by anti-OspA immunoglobulin G2a antibody and preferential gamma interferon production by OspA-specific CD4(+) T cells.

  20. Human Ebola virus infection results in substantial immune activation.

    Science.gov (United States)

    McElroy, Anita K; Akondy, Rama S; Davis, Carl W; Ellebedy, Ali H; Mehta, Aneesh K; Kraft, Colleen S; Lyon, G Marshall; Ribner, Bruce S; Varkey, Jay; Sidney, John; Sette, Alessandro; Campbell, Shelley; Ströher, Ute; Damon, Inger; Nichol, Stuart T; Spiropoulou, Christina F; Ahmed, Rafi

    2015-04-14

    Four Ebola patients received care at Emory University Hospital, presenting a unique opportunity to examine the cellular immune responses during acute Ebola virus infection. We found striking activation of both B and T cells in all four patients. Plasmablast frequencies were 10-50% of B cells, compared with less than 1% in healthy individuals. Many of these proliferating plasmablasts were IgG-positive, and this finding coincided with the presence of Ebola virus-specific IgG in the serum. Activated CD4 T cells ranged from 5 to 30%, compared with 1-2% in healthy controls. The most pronounced responses were seen in CD8 T cells, with over 50% of the CD8 T cells expressing markers of activation and proliferation. Taken together, these results suggest that all four patients developed robust immune responses during the acute phase of Ebola virus infection, a finding that would not have been predicted based on our current assumptions about the highly immunosuppressive nature of Ebola virus. Also, quite surprisingly, we found sustained immune activation after the virus was cleared from the plasma, observed most strikingly in the persistence of activated CD8 T cells, even 1 mo after the patients' discharge from the hospital. These results suggest continued antigen stimulation after resolution of the disease. From these convalescent time points, we identified CD4 and CD8 T-cell responses to several Ebola virus proteins, most notably the viral nucleoprotein. Knowledge of the viral proteins targeted by T cells during natural infection should be useful in designing vaccines against Ebola virus.

  1. Immune responses to rAAV6: The influence of canine parvovirus vaccination and neonatal administration of viral vector

    Directory of Open Access Journals (Sweden)

    Andrea L H Arnett

    2011-11-01

    Full Text Available Recombinant adeno-associated viral (rAAV vectors promote long-term gene transfer in many animal species. Significant effort has focused on the evaluation of rAAV delivery and the immune response in both murine and canine models of neuromuscular disease. However, canines provided for research purposes are routinely vaccinated against canine parvovirus (CPV. rAAV and CPV possess significant homology and are both parvoviruses. Thus, any immune response generated to CPV vaccination has the potential to cross-react with rAAV vectors. In this study, we investigated the immune response to rAAV6 delivery in a cohort of CPV-vaccinated canines and evaluated multiple vaccination regimens in a mouse model of CPV-vaccination. We show that CPV-vaccination stimulates production of neutralizing antibodies with minimal cross-reactivity to rAAV6. In addition, no significant differences were observed in the magnitude of the rAAV6-directed immune response between CPV-vaccinated animals and controls. Moreover, CPV-vaccination did not inhibit rAAV6-mediated transduction. We also evaluated the immune response to early rAAV6-vaccination in neonatal mice. The influence of maternal hormones and cytokines leads to a relatively permissive state in the neonate. We hypothesized that immaturity of the immune system would permit induction of tolerance to rAAV6 when delivered during the neonatal period. Mice were vaccinated with rAAV6 at 1 or 5 days of age, and subsequently challenged with rAAV6 exposure during adulthood via two sequential IM injections, one month apart. All vaccinated animals generated a significant neutralizing antibody response to rAAV6-vaccination that was enhanced following IM injection in adulthood. Taken together, these data demonstrate that the immune response raised against rAAV6 is distinct from that which is elicited by the standard parvoviral vaccines and is sufficient to prevent stable tolerization in neonatal mice.

  2. [Immunization with Bifidobacterium bifidum-vectored OprI vaccine of Pseudomonas aeruginosa enhances inhibitory effect on P. aeruginosa in mice].

    Science.gov (United States)

    Liu, Xiao; Li, Wengui

    2017-08-01

    Objective To study the pulmonary bacterial loads, splenocyte proliferation, distributions of T cell subsets and cell apoptosis in mice immunized with Bifidobacterium bifidum-vectored OprI (Bb-OprI) vaccine of Pseudomonas aeruginosa and challenged with P. aeruginosa PA01 strain. Methods BALB/c mice were immunized with 5×10 9 CFUs of vaccine by intragastric administration, 3 times a week for 3 weeks, and challenged intranasally with 5×10 6 CFUs of PA01 strain at the fourth week after the first immunization. At the second week after the challenge, all mice were sacrificed to separate their lungs and spleens, and the pulmonary bacterial loads were counted. The proliferation of the splenocytes was determined by MTT assay. The splenic CD4 + , CD8 + T cell subsets and the apoptotic rate of splenocytes were detected by flow cytometry. Results The number of pulmonary bacterial colonies in the mice immunized with the vaccine and challenged with PA01 strain decreased, while the proliferation of splenocytes and the proportion of CD4 + T cells markedly increased, and the apoptosis of splenocytes was notably reduced. Conclusion The intragastric vaccination of recombinant Bb-OprI vaccine can increase the proportion of CD4 + T cells and enhance the inhibitory effect on P. aeruginosa.

  3. A prime-boost vaccination strategy using attenuated Salmonella typhimurium and a replication-deficient recombinant adenovirus vector elicits protective immunity against human respiratory syncytial virus.

    Science.gov (United States)

    Fu, Yuan-Hui; He, Jin-Sheng; Wang, Xiao-Bo; Zheng, Xian-Xian; Wu, Qiang; Xie, Can; Zhang, Mei; Wei, Wei; Tang, Qian; Song, Jing-Dong; Qu, Jian-Guo; Hong, Tao

    2010-04-23

    Human respiratory syncytial virus (RSV), for which no clinically approved vaccine is available yet, is globally a serious pediatric pathogen of the lower respiratory tract. Several approaches have been used to develop vaccines against RSV, but none of these have been approved for use in humans. An efficient vaccine-enhancing strategy for RSV is still urgently needed. We found previously that oral SL7207/pcDNA3.1/F and intranasal FGAd/F were able to induce an effective protective immune response against RSV. The heterologous prime-boost immunization regime has been reported recently to be an efficient vaccine-enhancing strategy. Therefore, we investigated the ability of an oral SL7207/pcDNA3.1/F prime and intranasal (i.n.) FGAd/F boost regimen to generate immune responses to RSV. The SL7207/pcDNA3.1/F prime-FGAd/F boost regimen generated stronger RSV-specific humoral and mucosal immune responses in BALB/c mice than the oral SL7207/pcDNA3.1/F regimen alone, and stronger specific cellular immune responses than the i.n. FGAd/F regimen alone. Histopathological analysis showed an increased efficacy against RSV challenge by the heterologous prime-boost regimen. These results suggest that such a heterologous prime-boost strategy can enhance the efficacy of either the SL7207 or the FGAd vector regimen in generating immune responses in BALB/c mice. 2010 Elsevier Inc. All rights reserved.

  4. Regulation of anti-Plasmodium immunity by a LITAF-like transcription factor in the malaria vector Anopheles gambiae.

    Directory of Open Access Journals (Sweden)

    Ryan C Smith

    Full Text Available The mosquito is the obligate vector for malaria transmission. To complete its development within the mosquito, the malaria parasite Plasmodium must overcome the protective action of the mosquito innate immune system. Here we report on the involvement of the Anopheles gambiae orthologue of a conserved component of the vertebrate immune system, LPS-induced TNFα transcription factor (LITAF, and its role in mosquito anti-Plasmodium immunity. An. gambiae LITAF-like 3 (LL3 expression is up-regulated in response to midgut invasion by both rodent and human malaria parasites. Silencing of LL3 expression greatly increases parasite survival, indicating that LL3 is part of an anti-Plasmodium defense mechanism. Electrophoretic mobility shift assays identified specific LL3 DNA-binding motifs within the promoter of SRPN6, a gene that also mediates mosquito defense against Plasmodium. Further experiments indicated that these motifs play a direct role in LL3 regulation of SRPN6 expression. We conclude that LL3 is a transcription factor capable of modulating SRPN6 expression as part of the mosquito anti-Plasmodium immune response.

  5. Data access performance through parallelization and vectored access. Some results

    International Nuclear Information System (INIS)

    Furano, F; Hanushevsky, A

    2008-01-01

    High Energy Physics data processing and analysis applications typically deal with the problem of accessing and processing data at high speed. Recent studies, development and test work have shown that the latencies due to data access can often be hidden by parallelizing them with the data processing, thus giving the ability to have applications which process remote data with a high level of efficiency. Techniques and algorithms able to reach this result have been implemented in the client side of the Scalla/xrootd system, and in this contribution we describe the results of some tests done in order to compare their performance and characteristics. These techniques, if used together with multiple streams data access, can also be effective in allowing to efficiently and transparently deal with data repositories accessible via a Wide Area Network

  6. Three results on the PageRank vector: eigenstructure, sensitivity, and the derivative

    OpenAIRE

    Gleich, David; Glynn, Peter; Golub, Gene; Greif, Chen

    2007-01-01

    The three results on the PageRank vector are preliminary but shed light on the eigenstructure of a PageRank modified Markov chain and what happens when changing the teleportation parameter in the PageRank model. Computations with the derivative of the PageRank vector with respect to the teleportation parameter show predictive ability and identify an interesting set of pages from Wikipedia.

  7. Poly-functional and long-lasting anticancer immune response elicited by a safe attenuated Pseudomonas aeruginosa vector for antigens delivery

    Directory of Open Access Journals (Sweden)

    Xavier Chauchet

    2016-01-01

    Full Text Available Live-attenuated bacterial vectors for antigens delivery have aroused growing interest in the field of cancer immunotherapy. Their potency to stimulate innate immunity and to promote intracellular antigen delivery into antigen-presenting cells could be exploited to elicit a strong and specific cellular immune response against tumor cells. We previously described genetically-modified and attenuated Pseudomonas aeruginosa vectors able to deliver in vivo protein antigens into antigen-presenting cells, through Type 3 secretion system of the bacteria. Using this approach, we managed to protect immunized mice against aggressive B16 melanoma development in both a prophylactic and therapeutic setting. In this study, we further investigated the antigen-specific CD8+ T cell response, in terms of phenotypic and functional aspects, obtained after immunizations with a killed but metabolically active P. aeruginosa attenuated vector. We demonstrated that P. aeruginosa vaccine induces a highly functional pool of antigen-specific CD8+ T cell able to infiltrate the tumor. Furthermore, multiple immunizations allowed the development of a long-lasting immune response, represented by a pool of predominantly effector memory cells which protected mice against late tumor challenge. Overall, killed but metabolically active P. aeruginosa vector is a safe and promising approach for active and specific antitumor immunotherapy.

  8. Immune Protection of Nonhuman Primates against Ebola Virus with Single Low-Dose Adenovirus Vectors Encoding Modified GPs

    Science.gov (United States)

    Geisbert, Joan B; Shedlock, Devon J; Xu, Ling; Lamoreaux, Laurie; Custers, Jerome H. H. V; Popernack, Paul M; Yang, Zhi-Yong; Pau, Maria G; Roederer, Mario; Koup, Richard A; Goudsmit, Jaap; Jahrling, Peter B; Nabel, Gary J

    2006-01-01

    Background Ebola virus causes a hemorrhagic fever syndrome that is associated with high mortality in humans. In the absence of effective therapies for Ebola virus infection, the development of a vaccine becomes an important strategy to contain outbreaks. Immunization with DNA and/or replication-defective adenoviral vectors (rAd) encoding the Ebola glycoprotein (GP) and nucleoprotein (NP) has been previously shown to confer specific protective immunity in nonhuman primates. GP can exert cytopathic effects on transfected cells in vitro, and multiple GP forms have been identified in nature, raising the question of which would be optimal for a human vaccine. Methods and Findings To address this question, we have explored the efficacy of mutant GPs from multiple Ebola virus strains with reduced in vitro cytopathicity and analyzed their protective effects in the primate challenge model, with or without NP. Deletion of the GP transmembrane domain eliminated in vitro cytopathicity but reduced its protective efficacy by at least one order of magnitude. In contrast, a point mutation was identified that abolished this cytopathicity but retained immunogenicity and conferred immune protection in the absence of NP. The minimal effective rAd dose was established at 1010 particles, two logs lower than that used previously. Conclusions Expression of specific GPs alone vectored by rAd are sufficient to confer protection against lethal challenge in a relevant nonhuman primate model. Elimination of NP from the vaccine and dose reductions to 1010 rAd particles do not diminish protection and simplify the vaccine, providing the basis for selection of a human vaccine candidate. PMID:16683867

  9. Immune protection of nonhuman primates against Ebola virus with single low-dose adenovirus vectors encoding modified GPs.

    Directory of Open Access Journals (Sweden)

    Nancy J Sullivan

    2006-06-01

    Full Text Available Ebola virus causes a hemorrhagic fever syndrome that is associated with high mortality in humans. In the absence of effective therapies for Ebola virus infection, the development of a vaccine becomes an important strategy to contain outbreaks. Immunization with DNA and/or replication-defective adenoviral vectors (rAd encoding the Ebola glycoprotein (GP and nucleoprotein (NP has been previously shown to confer specific protective immunity in nonhuman primates. GP can exert cytopathic effects on transfected cells in vitro, and multiple GP forms have been identified in nature, raising the question of which would be optimal for a human vaccine.To address this question, we have explored the efficacy of mutant GPs from multiple Ebola virus strains with reduced in vitro cytopathicity and analyzed their protective effects in the primate challenge model, with or without NP. Deletion of the GP transmembrane domain eliminated in vitro cytopathicity but reduced its protective efficacy by at least one order of magnitude. In contrast, a point mutation was identified that abolished this cytopathicity but retained immunogenicity and conferred immune protection in the absence of NP. The minimal effective rAd dose was established at 10(10 particles, two logs lower than that used previously.Expression of specific GPs alone vectored by rAd are sufficient to confer protection against lethal challenge in a relevant nonhuman primate model. Elimination of NP from the vaccine and dose reductions to 10(10 rAd particles do not diminish protection and simplify the vaccine, providing the basis for selection of a human vaccine candidate.

  10. Role of mammalian immune responses in vector-enhanced orbiviral transmission

    Science.gov (United States)

    Culicoides sonorensis biting midges are vectors of several emerging and re-emerging orbiviruses including bluetongue, epizootic hemorrhagic disease, and African horse sickness viruses. They feed primarily on domestic sheep and cattle, but opportunistically feed on a variety of wildlife and on humans...

  11. Control of vector-borne infectious diseases by human immunity against α-Gal

    Czech Academy of Sciences Publication Activity Database

    Cabezas-Cruz, A.; Valdés, James J.; de la Fuente, J.

    2016-01-01

    Roč. 15, č. 8 (2016), s. 953-955 ISSN 1476-0584 EU Projects: European Commission(XE) 278976 - ANTIGONE Institutional support: RVO:60077344 Keywords : microbiota * probiotics * vaccine * α-Gal * vector-borne diseases Subject RIV: FN - Epidemiology, Contagious Diseases ; Clinical Immunology Impact factor: 3.555, year: 2016

  12. Targeting the Immune System to Fight Cancer Using Chemical Receptor Homing Vectors Carrying Polyinosine/Cytosine (PolyIC)

    International Nuclear Information System (INIS)

    Levitzki, Alexander

    2012-01-01

    Cancer researchers have been looking for ways to harness the immune system and to reinstate immune surveillance, to kill cancer cells without collateral damage. Here we scan current approaches to targeting the immune system against cancer, and emphasize our own approach. We are using chemical vectors attached to a specific ligand, to introduce synthetic dsRNA, polyinosine/cytosine (polyIC), into tumors. The ligand binds to a receptor protein that is overexpressed on the surface of the tumor cells. Upon ligand binding, the receptor complex is internalized, introducing the polyIC into the cell. In this fashion a large amount of synthetic dsRNA can be internalized, leading to the activation of dsRNA-binding proteins, such as dsRNA dependent protein kinase (PKR), Toll-like receptor 3 (TLR3), retinoic acid-inducible gene I (RIG-1), and melanoma differentiation-associated gene 5 (MDA5). The simultaneous activation of these signaling proteins leads to the rapid demise of the targeted cell and to cytokine secretion. The cytokines lead to a strong bystander effect and to the recruitment of immune cells that converge upon the targeted cells. The bystander effects lead to the destruction of neighboring tumor cells not targeted themselves by the vector. Normal cells, being more robust than tumor cells, survive. This strategy has several advantages: (1) recruitment of the immune system is localized to the tumor. (2) The response is rapid, leading to fast tumor eradication. (3) The bystander effects lead to the eradication of tumor cells not harboring the target. (4) The multiplicity of pro-death signaling pathways elicited by PolyIC minimizes the likelihood of the emergence of resistance. In this chapter we focus on EGFR as the targeted receptor, which is overexpressed in many tumors. In principle, the strategy can be extended to other tumors that overexpress a protein that can be internalized by a ligand, which can be a small molecule, a single chain antibody, or an affibody.

  13. Targeting the immune system to fight cancer using chemical receptor homing vectors carrying Poly Inosine/Cytosine (PolyIC

    Directory of Open Access Journals (Sweden)

    Alexander eLevitzki

    2012-02-01

    Full Text Available Cancer researchers have been looking for ways to harness the immune system and to reinstate immune surveillance, to kill cancer cells without collateral damage. Here we scan current approaches to targeting the immune system against cancer, and emphasize our own approach. We are using chemical vectors attached to a specific ligand, to introduce synthetic dsRNA, poly Inosine/Cytosine (polyIC, into tumors. The ligand binds to a receptor protein that is overexpressed on the surface of the tumor cells. Upon ligand binding, the receptor complex is internalized, introducing the polyIC into the cell. In this fashion a large amount of synthetic dsRNA can be internalized, leading to the activation of dsRNA binding proteins, such as dsRNA dependent protein kinase (PKR, Toll-3 receptor (TLR3, retinoic acid–inducible gene I (RIG-1 and melanoma differentiation–associated gene 5 (MDA5. The simultaneous activation of these signaling proteins leads to the rapid demise of the targeted cell and to cytokine secretion. The cytokines lead to a strong bystander effect and to the recruitment of immune cells that converge upon the targeted cells. The bystander effects lead to the destruction of neighboring tumor cells not targeted themselves by the vector. Normal cells, being more robust than tumor cells, survive. This strategy has several advantages: (1 Recruitment of the immune system is localized to the tumor. (2 The response is rapid, leading to fast tumor eradication. (3 The bystander effects lead to the eradication of tumor cells not harboring the target. (4 The multiplicity of pro-death signaling pathways elicited by PolyIC minimizes the likelihood of the emergence of resistance. In this chapter we focus on EGFR as the targeted receptor, which is overexpressed in many tumors. In principle, the strategy can be extended to other tumors that overexpress a protein that can be internalized by a ligand, which be a small molecule, a single chain antibody or an

  14. PSMA-targeted polyinosine/polycytosine vector induces prostate tumor regression and invokes an antitumor immune response in mice.

    Science.gov (United States)

    Langut, Yael; Talhami, Alaa; Mamidi, Samarasimhareddy; Shir, Alexei; Zigler, Maya; Joubran, Salim; Sagalov, Anna; Flashner-Abramson, Efrat; Edinger, Nufar; Klein, Shoshana; Levitzki, Alexander

    2017-12-26

    There is an urgent need for an effective treatment for metastatic prostate cancer (PC). Prostate tumors invariably overexpress prostate surface membrane antigen (PSMA). We designed a nonviral vector, PEI-PEG-DUPA (PPD), comprising polyethylenimine-polyethyleneglycol (PEI-PEG) tethered to the PSMA ligand, 2-[3-(1, 3-dicarboxy propyl)ureido] pentanedioic acid (DUPA), to treat PC. The purpose of PEI is to bind polyinosinic/polycytosinic acid (polyIC) and allow endosomal release, while DUPA targets PC cells. PolyIC activates multiple pathways that lead to tumor cell death and to the activation of bystander effects that harness the immune system against the tumor, attacking nontargeted neighboring tumor cells and reducing the probability of acquired resistance and disease recurrence. Targeting polyIC directly to tumor cells avoids the toxicity associated with systemic delivery. PPD selectively delivered polyIC into PSMA-overexpressing PC cells, inducing apoptosis, cytokine secretion, and the recruitment of human peripheral blood mononuclear cells (PBMCs). PSMA-overexpressing tumors in nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice with partially reconstituted immune systems were significantly shrunken following PPD/polyIC treatment, in all cases. Half of the tumors showed complete regression. PPD/polyIC invokes antitumor immunity, but unlike many immunotherapies does not need to be personalized for each patient. The potent antitumor effects of PPD/polyIC should spur its development for clinical use.

  15. Elimination of contaminating cap genes in AAV vector virions reduces immune responses and improves transgene expression in a canine gene therapy model.

    Science.gov (United States)

    Wang, Z; Halbert, C L; Lee, D; Butts, T; Tapscott, S J; Storb, R; Miller, A D

    2014-04-01

    Animal and human gene therapy studies utilizing AAV vectors have shown that immune responses to AAV capsid proteins can severely limit transgene expression. The main source of capsid antigen is that associated with the AAV vectors, which can be reduced by stringent vector purification. A second source of AAV capsid proteins is that expressed from cap genes aberrantly packaged into AAV virions during vector production. This antigen source can be eliminated by the use of a cap gene that is too large to be incorporated into an AAV capsid, such as a cap gene containing a large intron (captron gene). Here, we investigated the effects of elimination of cap gene transfer and of vector purification by CsCl gradient centrifugation on AAV vector immunogenicity and expression following intramuscular injection in dogs. We found that both approaches reduced vector immunogenicity and that combining the two produced the lowest immune responses and highest transgene expression. This combined approach enabled the use of a relatively mild immunosuppressive regimen to promote robust micro-dystrophin gene expression in Duchenne muscular dystrophy-affected dogs. Our study shows the importance of minimizing AAV cap gene impurities and indicates that this improvement in AAV vector production may benefit human applications.

  16. Induction of Robust Immune Responses in Swine by Using a Cocktail of Adenovirus-Vectored African Swine Fever Virus Antigens.

    Science.gov (United States)

    Lokhandwala, Shehnaz; Waghela, Suryakant D; Bray, Jocelyn; Martin, Cameron L; Sangewar, Neha; Charendoff, Chloe; Shetti, Rashmi; Ashley, Clay; Chen, Chang-Hsin; Berghman, Luc R; Mwangi, Duncan; Dominowski, Paul J; Foss, Dennis L; Rai, Sharath; Vora, Shaunak; Gabbert, Lindsay; Burrage, Thomas G; Brake, David; Neilan, John; Mwangi, Waithaka

    2016-11-01

    The African swine fever virus (ASFV) causes a fatal hemorrhagic disease in domestic swine, and at present no treatment or vaccine is available. Natural and gene-deleted, live attenuated strains protect against closely related virulent strains; however, they are yet to be deployed and evaluated in the field to rule out chronic persistence and a potential for reversion to virulence. Previous studies suggest that antibodies play a role in protection, but induction of cytotoxic T lymphocytes (CTLs) could be the key to complete protection. Hence, generation of an efficacious subunit vaccine depends on identification of CTL targets along with a suitable delivery method that will elicit effector CTLs capable of eliminating ASFV-infected host cells and confer long-term protection. To this end, we evaluated the safety and immunogenicity of an adenovirus-vectored ASFV (Ad-ASFV) multiantigen cocktail formulated in two different adjuvants and at two immunizing doses in swine. Immunization with the cocktail rapidly induced unprecedented ASFV antigen-specific antibody and cellular immune responses against all of the antigens. The robust antibody responses underwent rapid isotype switching within 1 week postpriming, steadily increased over a 2-month period, and underwent rapid recall upon boost. Importantly, the primed antibodies strongly recognized the parental ASFV (Georgia 2007/1) by indirect fluorescence antibody (IFA) assay and Western blotting. Significant antigen-specific gamma interferon-positive (IFN-γ + ) responses were detected postpriming and postboosting. Furthermore, this study is the first to demonstrate induction of ASFV antigen-specific CTL responses in commercial swine using Ad-ASFV multiantigens. The relevance of the induced immune responses in regard to protection needs to be evaluated in a challenge study. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  17. Induction of Immune Tolerance to Foreign Protein via Adeno-Associated Viral Vector Gene Transfer in Mid-Gestation Fetal Sheep

    Science.gov (United States)

    Davey, Marcus G.; Riley, John S.; Andrews, Abigail; Tyminski, Alec; Limberis, Maria; Pogoriler, Jennifer E.; Partridge, Emily; Olive, Aliza; Hedrick, Holly L.; Flake, Alan W.; Peranteau, William H.

    2017-01-01

    A major limitation to adeno-associated virus (AAV) gene therapy is the generation of host immune responses to viral vector antigens and the transgene product. The ability to induce immune tolerance to foreign protein has the potential to overcome this host immunity. Acquisition and maintenance of tolerance to viral vector antigens and transgene products may also permit repeat administration thereby enhancing therapeutic efficacy. In utero gene transfer (IUGT) takes advantage of the immunologic immaturity of the fetus to induce immune tolerance to foreign antigens. In this large animal study, in utero administration of AAV6.2, AAV8 and AAV9 expressing green fluorescent protein (GFP) to ~60 day fetal sheep (term: ~150 days) was performed. Transgene expression and postnatal immune tolerance to GFP and viral antigens were assessed. We demonstrate 1) hepatic expression of GFP 1 month following in utero administration of AAV6.2.GFP and AAV8.GFP, 2) in utero recipients of either AAV6.2.GFP or AAV8.GFP fail to mount an anti-GFP antibody response following postnatal GFP challenge and lack inflammatory cellular infiltrates at the intramuscular site of immunization, 3) a serotype specific anti-AAV neutralizing antibody response is elicited following postnatal challenge of in utero recipients of AAV6.2 or AAV8 with the corresponding AAV serotype, and 4) durable hepatic GFP expression was observed up to 6 months after birth in recipients of AAV8.GFP but expression was lost between 1 and 6 months of age in recipients of AAV6.2.GFP. The current study demonstrates, in a preclinical large animal model, the potential of IUGT to achieve host immune tolerance to the viral vector transgene product but also suggests that a single exposure to the vector capsid proteins at the time of IUGT is inadequate to induce tolerance to viral vector antigens. PMID:28141818

  18. Preliminary Experimental Results for Indirect Vector-Control of Induction Motor Drives with Forced Dynamics

    Directory of Open Access Journals (Sweden)

    Jan Vittek

    2003-01-01

    Full Text Available The contribution presents an extension of indirect vector control of electric drives employing induction motors to 'Forced Dynamic Control'. This method of control offers an accurate realisation of dynamic response profiles, which can be selected by the user. The developed system can be integrated into a drive with a shaft position encoder or a shaft sensoriess drive, in which only the stator currents are measured. The applied stator voltages are determined by a computed inverter switching algorithm. Simulation results and preliminary experimental results for indirect vector control of an idle running induction motor indicate good agreement with the theoretical predictions.

  19. Vaccine platforms combining circumsporozoite protein and potent immune modulators, rEA or EAT-2, paradoxically result in opposing immune responses.

    Directory of Open Access Journals (Sweden)

    Nathaniel J Schuldt

    Full Text Available Malaria greatly impacts the health and wellbeing of over half of the world's population. Promising malaria vaccine candidates have attempted to induce adaptive immune responses to Circumsporozoite (CS protein. Despite the inclusion of potent adjuvants, these vaccines have limited protective efficacy. Conventional recombinant adenovirus (rAd based vaccines expressing CS protein can induce CS protein specific immune responses, but these are essentially equivalent to those generated after use of the CS protein subunit based vaccines. In this study we combined the use of rAds expressing CS protein along with rAds expressing novel innate immune response modulating proteins in an attempt to significantly improve the induction of CS protein specific cell mediated immune (CMI responses.BALB/cJ mice were co-vaccinated with a rAd vectors expressing CS protein simultaneous with a rAd expressing either TLR agonist (rEA or SLAM receptors adaptor protein (EAT-2. Paradoxically, expression of the TLR agonist uncovered a potent immunosuppressive activity inherent to the combined expression of the CS protein and rEA. Fortunately, use of the rAd vaccine expressing EAT-2 circumvented CS protein's suppressive activity, and generated a fivefold increase in the number of CS protein responsive, IFNγ secreting splenocytes, as well as increased the breadth of T cells responsive to peptides present in the CS protein. These improvements were positively correlated with the induction of a fourfold improvement in CS protein specific CTL functional activity in vivo.Our results emphasize the need for caution when incorporating CS protein into malaria vaccine platforms expressing or containing other immunostimulatory compounds, as the immunological outcomes may be unanticipated and/or counter-productive. However, expressing the SLAM receptors derived signaling adaptor EAT-2 at the same time of vaccination with CS protein can overcome these concerns, as well as significantly

  20. Heterologous prime-boost immunization of Newcastle disease virus vectored vaccines protected broiler chickens against highly pathogenic avian influenza and Newcastle disease viruses.

    Science.gov (United States)

    Kim, Shin-Hee; Samal, Siba K

    2017-07-24

    Avian Influenza virus (AIV) is an important pathogen for both human and animal health. There is a great need to develop a safe and effective vaccine for AI infections in the field. Live-attenuated Newcastle disease virus (NDV) vectored AI vaccines have shown to be effective, but preexisting antibodies to the vaccine vector can affect the protective efficacy of the vaccine in the field. To improve the efficacy of AI vaccine, we generated a novel vectored vaccine by using a chimeric NDV vector that is serologically distant from NDV. In this study, the protective efficacy of our vaccines was evaluated by using H5N1 highly pathogenic avian influenza virus (HPAIV) strain A/Vietnam/1203/2004, a prototype strain for vaccine development. The vaccine viruses were three chimeric NDVs expressing the hemagglutinin (HA) protein in combination with the neuraminidase (NA) protein, matrix 1 protein, or nonstructural 1 protein. Comparison of their protective efficacy between a single and prime-boost immunizations indicated that prime immunization of 1-day-old SPF chicks with our vaccine viruses followed by boosting with the conventional NDV vector strain LaSota expressing the HA protein provided complete protection of chickens against mortality, clinical signs and virus shedding. Further verification of our heterologous prime-boost immunization using commercial broiler chickens suggested that a sequential immunization of chickens with chimeric NDV vector expressing the HA and NA proteins following the boost with NDV vector expressing the HA protein can be a promising strategy for the field vaccination against HPAIVs and against highly virulent NDVs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Improving immunization in Afghanistan: results from a cross-sectional community-based survey to assess routine immunization coverage

    Directory of Open Access Journals (Sweden)

    Raveesha R. Mugali

    2017-04-01

    Full Text Available Abstract Background Despite progress in recent years, Afghanistan is lagging behind in realizing the full potential of immunization. The country is still endemic for polio transmission and measles outbreaks continue to occur. In spite of significant reductions over the past decade, the mortality rate of children under 5 years of age continues to remain high at 91 per 1000 live births. Methods The study was a descriptive community-based cross sectional household survey. The survey aimed to estimate the levels of immunization coverage at national and province levels. Specific objectives are to: establish valid baseline information to monitor progress of the immunization program; identify reasons why children are not immunized; and make recommendations to enhance access and quality of immunization services in Afghanistan. The survey was carried out in all 34 provinces of the country, with a sample of 6125 mothers of children aged 12–23 months. Results Nationally, 51% of children participating in the survey received all doses of each antigen irrespective of the recommended date of immunization or recommended interval between doses. About 31% of children were found to be partially vaccinated. Reasons for partial vaccination included: place to vaccinate child too far (23%, not aware of the need of vaccination (17%, no faith in vaccination (16%, mother was too busy (15%, and fear of side effects (11%. Conclusion The innovative mechanism of contracting out delivery of primary health care services in Afghanistan, including immunization, to non-governmental organizations is showing some positive results in quickly increasing coverage of essential interventions, including routine immunization. Much ground still needs to be covered with proper planning and management of resources in order to improve the immunization coverage in Afghanistan and increase survival and health status of its children.

  2. Fast Blood Vector Velocity Imaging: Simulations and Preliminary In Vivo Results

    DEFF Research Database (Denmark)

    Udesen, Jesper; Gran, Fredrik; Hansen, Kristoffer Lindskov

    2007-01-01

    for each pulse emission. 2) The transmitted pulse consists of a 13 bit Barker code which is transmitted simultaneously from each transducer element. 3) The 2-D vector velocity of the blood is found using 2-D speckle tracking between segments in consecutive speckle images. III Results: The method was tested...

  3. Immunization

    Science.gov (United States)

    ... a lot worse. Some are even life-threatening. Immunization shots, or vaccinations, are essential. They protect against ... B, polio, tetanus, diphtheria, and pertussis (whooping cough). Immunizations are important for adults as well as children. ...

  4. Immune Response to Recombinant Adenovirus in Humans: Capsid Components from Viral Input Are Targets for Vector-Specific Cytotoxic T Lymphocytes

    Science.gov (United States)

    Molinier-Frenkel, Valérie; Gahery-Segard, Hanne; Mehtali, Majid; Le Boulaire, Christophe; Ribault, Sébastien; Boulanger, Pierre; Tursz, Thomas; Guillet, Jean-Gérard; Farace, Françoise

    2000-01-01

    We previously demonstrated that a single injection of 109 PFU of recombinant adenovirus into patients induces strong vector-specific immune responses (H. Gahéry-Ségard, V. Molinier-Frenkel, C. Le Boulaire, P. Saulnier, P. Opolon, R. Lengagne, E. Gautier, A. Le Cesne, L. Zitvogel, A. Venet, C. Schatz, M. Courtney, T. Le Chevalier, T. Tursz, J.-G. Guillet, and F. Farace, J. Clin. Investig. 100:2218–2226, 1997). In the present study we analyzed the mechanism of vector recognition by cytotoxic T lymphocytes (CTL). CD8+ CTL lines were derived from two patients and maintained in long-term cultures. Target cell infections with E1-deleted and E1-plus E2-deleted adenoviruses, as well as transcription-blocking experiments with actinomycin D, revealed that host T-cell recognition did not require viral gene transcription. Target cells treated with brefeldin A were not lysed, indicating that viral input protein-derived peptides are associated with HLA class I molecules. Using recombinant capsid component-loaded targets, we observed that the three major proteins could be recognized. These results raise the question of the use of multideleted adenoviruses for gene therapy in the quest to diminish antivector CTL responses. PMID:10906225

  5. Immune responses of a native and an invasive bird to Buggy Creek Virus (Togaviridae: Alphavirus and its arthropod vector, the swallow bug (Oeciacus vicarius.

    Directory of Open Access Journals (Sweden)

    Carol A Fassbinder-Orth

    Full Text Available Invasive species often display different patterns of parasite burden and virulence compared to their native counterparts. These differences may be the result of variability in host-parasite co-evolutionary relationships, the occurrence of novel host-parasite encounters, or possibly innate differences in physiological responses to infection between invasive and native hosts. Here we examine the adaptive, humoral immune responses of a resistant, native bird and a susceptible, invasive bird to an arbovirus (Buggy Creek virus; Togaviridae: Alphavirus and its ectoparasitic arthropod vector (the swallow bug; Oeciacus vicarius. Swallow bugs parasitize the native, colonially nesting cliff swallow (Petrochelidon pyrrhonota and the introduced house sparrow (Passer domesticus that occupies nests in cliff swallow colonies. We measured levels of BCRV-specific and swallow bug-specific IgY levels before nesting (prior to swallow bug exposure and after nesting (after swallow bug exposure in house sparrows and cliff swallows in western Nebraska. Levels of BCRV-specific IgY increased significantly following nesting in the house sparrow but not in the cliff swallow. Additionally, house sparrows displayed consistently higher levels of swallow bug-specific antibodies both before and after nesting compared to cliff swallows. The higher levels of BCRV and swallow bug specific antibodies detected in house sparrows may be reflective of significant differences in both antiviral and anti-ectoparasite immune responses that exist between these two avian species. To our knowledge, this is the first study to compare the macro- and microparasite-specific immune responses of an invasive and a native avian host exposed to the same parasites.

  6. Mucosal delivery of a vectored RSV vaccine is safe and elicits protective immunity in rodents and nonhuman primates

    Directory of Open Access Journals (Sweden)

    Angiolo Pierantoni

    Full Text Available Respiratory Syncytial Virus (RSV is a leading cause of severe respiratory disease in infants and the elderly. No vaccine is presently available to address this major unmet medical need. We generated a new genetic vaccine based on chimpanzee Adenovirus (PanAd3-RSV and Modified Vaccinia Ankara RSV (MVA-RSV encoding the F, N, and M2-1 proteins of RSV, for the induction of neutralizing antibodies and broad cellular immunity. Because RSV infection is restricted to the respiratory tract, we compared intranasal (IN and intramuscular (M administration for safety, immunogenicity, and efficacy in different species. A single IN or IM vaccination completely protected BALB/c mice and cotton rats against RSV replication in the lungs. However, only IN administration could prevent infection in the upper respiratory tract. IM vaccination with MVA-RSV also protected cotton rats from lower respiratory tract infection in the absence of detectable neutralizing antibodies. Heterologous prime boost with PanAd3-RSV and MVA-RSV elicited high neutralizing antibody titers and broad T-cell responses in nonhuman primates. In addition, animals primed in the nose developed mucosal IgA against the F protein. In conclusion, we have shown that our vectored RSV vaccine induces potent cellular and humoral responses in a primate model, providing strong support for clinical testing.

  7. Gene therapy for adenosine deaminase-deficient severe combined immune deficiency: clinical comparison of retroviral vectors and treatment plans.

    Science.gov (United States)

    Candotti, Fabio; Shaw, Kit L; Muul, Linda; Carbonaro, Denise; Sokolic, Robert; Choi, Christopher; Schurman, Shepherd H; Garabedian, Elizabeth; Kesserwan, Chimene; Jagadeesh, G Jayashree; Fu, Pei-Yu; Gschweng, Eric; Cooper, Aaron; Tisdale, John F; Weinberg, Kenneth I; Crooks, Gay M; Kapoor, Neena; Shah, Ami; Abdel-Azim, Hisham; Yu, Xiao-Jin; Smogorzewska, Monika; Wayne, Alan S; Rosenblatt, Howard M; Davis, Carla M; Hanson, Celine; Rishi, Radha G; Wang, Xiaoyan; Gjertson, David; Yang, Otto O; Balamurugan, Arumugam; Bauer, Gerhard; Ireland, Joanna A; Engel, Barbara C; Podsakoff, Gregory M; Hershfield, Michael S; Blaese, R Michael; Parkman, Robertson; Kohn, Donald B

    2012-11-01

    We conducted a gene therapy trial in 10 patients with adenosine deaminase (ADA)-deficient severe combined immunodeficiency using 2 slightly different retroviral vectors for the transduction of patients' bone marrow CD34(+) cells. Four subjects were treated without pretransplantation cytoreduction and remained on ADA enzyme-replacement therapy (ERT) throughout the procedure. Only transient (months), low-level (< 0.01%) gene marking was observed in PBMCs of 2 older subjects (15 and 20 years of age), whereas some gene marking of PBMC has persisted for the past 9 years in 2 younger subjects (4 and 6 years). Six additional subjects were treated using the same gene transfer protocol, but after withdrawal of ERT and administration of low-dose busulfan (65-90 mg/m(2)). Three of these remain well, off ERT (5, 4, and 3 years postprocedure), with gene marking in PBMC of 1%-10%, and ADA enzyme expression in PBMC near or in the normal range. Two subjects were restarted on ERT because of poor gene marking and immune recovery, and one had a subsequent allogeneic hematopoietic stem cell transplantation. These studies directly demonstrate the importance of providing nonmyeloablative pretransplantation conditioning to achieve therapeutic benefits with gene therapy for ADA-deficient severe combined immunodeficiency.

  8. Gene therapy for adenosine deaminase–deficient severe combined immune deficiency: clinical comparison of retroviral vectors and treatment plans

    Science.gov (United States)

    Candotti, Fabio; Shaw, Kit L.; Muul, Linda; Carbonaro, Denise; Sokolic, Robert; Choi, Christopher; Schurman, Shepherd H.; Garabedian, Elizabeth; Kesserwan, Chimene; Jagadeesh, G. Jayashree; Fu, Pei-Yu; Gschweng, Eric; Cooper, Aaron; Tisdale, John F.; Weinberg, Kenneth I.; Crooks, Gay M.; Kapoor, Neena; Shah, Ami; Abdel-Azim, Hisham; Yu, Xiao-Jin; Smogorzewska, Monika; Wayne, Alan S.; Rosenblatt, Howard M.; Davis, Carla M.; Hanson, Celine; Rishi, Radha G.; Wang, Xiaoyan; Gjertson, David; Yang, Otto O.; Balamurugan, Arumugam; Bauer, Gerhard; Ireland, Joanna A.; Engel, Barbara C.; Podsakoff, Gregory M.; Hershfield, Michael S.; Blaese, R. Michael; Parkman, Robertson

    2012-01-01

    We conducted a gene therapy trial in 10 patients with adenosine deaminase (ADA)–deficient severe combined immunodeficiency using 2 slightly different retroviral vectors for the transduction of patients' bone marrow CD34+ cells. Four subjects were treated without pretransplantation cytoreduction and remained on ADA enzyme-replacement therapy (ERT) throughout the procedure. Only transient (months), low-level (< 0.01%) gene marking was observed in PBMCs of 2 older subjects (15 and 20 years of age), whereas some gene marking of PBMC has persisted for the past 9 years in 2 younger subjects (4 and 6 years). Six additional subjects were treated using the same gene transfer protocol, but after withdrawal of ERT and administration of low-dose busulfan (65-90 mg/m2). Three of these remain well, off ERT (5, 4, and 3 years postprocedure), with gene marking in PBMC of 1%-10%, and ADA enzyme expression in PBMC near or in the normal range. Two subjects were restarted on ERT because of poor gene marking and immune recovery, and one had a subsequent allogeneic hematopoietic stem cell transplantation. These studies directly demonstrate the importance of providing nonmyeloablative pretransplantation conditioning to achieve therapeutic benefits with gene therapy for ADA-deficient severe combined immunodeficiency. PMID:22968453

  9. Results and future prospects of exclusive vector meson production with pPb collisions at CMS

    CERN Document Server

    Chudasama, Ruchi

    2017-01-01

    Exclusive photoproduction of vector mesons (Upsilon and Rho0) is studied with the large photon flux available in ultra-peripheral pPb collisions at sqrt(sNN) =5.02 TeV with CMS experiment. It provides a clean probe of the gluon distribution at small values of parton fractional momenta $x$ at centralrapidities ($y < 2.5$). The cross sections are measured as a function of the photon-proton centre-of-mass energy, extending the energy range explored by H1 and ZEUS Experiments at HERA. In addition, the differential cross sections (dsigma/dt), where $\\abs{t} \\approx p^2_T$ is the squared transverse momentum of produced vector mesons, are measured and the slope parameters are obtained. The results are compared to previous measurements and to theoretical predictions. Finally, prospect for further measurements of vector meson production that can be performed using the 2016 pPb collision data at 8 TeV to be collected at the end of the year are presented.

  10. Transcriptomic profiling of diverse Aedes aegypti strains reveals increased basal-level immune activation in dengue virus-refractory populations and identifies novel virus-vector molecular interactions.

    Directory of Open Access Journals (Sweden)

    Shuzhen Sim

    Full Text Available Genetic variation among Aedes aegypti populations can greatly influence their vector competence for human pathogens such as the dengue virus (DENV. While intra-species transcriptome differences remain relatively unstudied when compared to coding sequence polymorphisms, they also affect numerous aspects of mosquito biology. Comparative molecular profiling of mosquito strain transcriptomes can therefore provide valuable insight into the regulation of vector competence. We established a panel of A. aegypti strains with varying levels of susceptibility to DENV, comprising both laboratory-maintained strains and field-derived colonies collected from geographically distinct dengue-endemic regions spanning South America, the Caribbean, and Southeast Asia. A comparative genome-wide gene expression microarray-based analysis revealed higher basal levels of numerous immunity-related gene transcripts in DENV-refractory mosquito strains than in susceptible strains, and RNA interference assays further showed different degrees of immune pathway contribution to refractoriness in different strains. By correlating transcript abundance patterns with DENV susceptibility across our panel, we also identified new candidate modulators of DENV infection in the mosquito, and we provide functional evidence for two potential DENV host factors and one potential restriction factor. Our comparative transcriptome dataset thus not only provides valuable information about immune gene regulation and usage in natural refractoriness of mosquito populations to dengue virus but also allows us to identify new molecular interactions between the virus and its mosquito vector.

  11. Incorporating double copies of a chromatin insulator into lentiviral vectors results in less viral integrants

    DEFF Research Database (Denmark)

    Nielsen, Troels T; Jakobsson, Johan; Rosenqvist, Nina

    2009-01-01

    BACKGROUND: Lentiviral vectors hold great promise as gene transfer vectors in gene therapeutic settings. However, problems related to the risk of insertional mutagenesis, transgene silencing and positional effects have stalled the use of such vectors in the clinic. Chromatin insulators are boundary...

  12. Ability of herpes simplex virus vectors to boost immune responses to DNA vectors and to protect against challenge by simian immunodeficiency virus

    International Nuclear Information System (INIS)

    Kaur, Amitinder; Sanford, Hannah B.; Garry, Deirdre; Lang, Sabine; Klumpp, Sherry A.; Watanabe, Daisuke; Bronson, Roderick T.; Lifson, Jeffrey D.; Rosati, Margherita; Pavlakis, George N.; Felber, Barbara K.; Knipe, David M.; Desrosiers, Ronald C.

    2007-01-01

    The immunogenicity and protective capacity of replication-defective herpes simplex virus (HSV) vector-based vaccines were examined in rhesus macaques. Three macaques were inoculated with recombinant HSV vectors expressing Gag, Env, and a Tat-Rev-Nef fusion protein of simian immunodeficiency virus (SIV). Three other macaques were primed with recombinant DNA vectors expressing Gag, Env, and a Pol-Tat-Nef-Vif fusion protein prior to boosting with the HSV vectors. Robust anti-Gag and anti-Env cellular responses were detected in all six macaques. Following intravenous challenge with wild-type, cloned SIV239, peak and 12-week plasma viremia levels were significantly lower in vaccinated compared to control macaques. Plasma SIV RNA in vaccinated macaques was inversely correlated with anti-Rev ELISPOT responses on the day of challenge (P value < 0.05), anti-Tat ELISPOT responses at 2 weeks post challenge (P value < 0.05) and peak neutralizing antibody titers pre-challenge (P value 0.06). These findings support continued study of recombinant herpesviruses as a vaccine approach for AIDS

  13. A novel non-toxic combined CTA1-DD and ISCOMS adjuvant vector for effective mucosal immunization against influenza virus.

    Science.gov (United States)

    Eliasson, Dubravka Grdic; Helgeby, Anja; Schön, Karin; Nygren, Caroline; El-Bakkouri, Karim; Fiers, Walter; Saelens, Xavier; Lövgren, Karin Bengtsson; Nyström, Ida; Lycke, Nils Y

    2011-05-23

    Here we demonstrate that by using non-toxic fractions of saponin combined with CTA1-DD we can achieve a safe and above all highly efficacious mucosal adjuvant vector. We optimized the construction, tested the requirements for function and evaluated proof-of-concept in an influenza A virus challenge model. We demonstrated that the CTA1-3M2e-DD/ISCOMS vector provided 100% protection against mortality and greatly reduced morbidity in the mouse model. The immunogenicity of the vector was superior to other vaccine formulations using the ISCOM or CTA1-DD adjuvants alone. The versatility of the vector was best exemplified by the many options to insert, incorporate or admix vaccine antigens with the vector. Furthermore, the CTA1-3M2e-DD/ISCOMS could be kept 1 year at 4°C or as a freeze-dried powder without affecting immunogenicity or adjuvanticity of the vector. Strong serum IgG and mucosal IgA responses were elicited and CD4 T cell responses were greatly enhanced after intranasal administration of the combined vector. Together these findings hold promise for the combined vector as a mucosal vaccine against influenza virus infections including pandemic influenza. The CTA1-DD/ISCOMS technology represents a breakthrough in mucosal vaccine vector design which successfully combines immunomodulation and targeting in a safe and stable particulate formation. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Experimental Results for Direction of Arrival Estimation with a Single Acoustic Vector Sensor in Shallow Water

    Directory of Open Access Journals (Sweden)

    Alper Bereketli

    2015-01-01

    Full Text Available We study the performances of several computationally efficient and simple techniques for estimating direction of arrival (DOA of an underwater acoustic source using a single acoustic vector sensor (AVS in shallow water. Underwater AVS is a compact device, which consists of one hydrophone and three accelerometers in a packaged form, measuring scalar pressure and three-dimensional acceleration simultaneously at a single position. A very controlled experimental setup is prepared to test how well-known techniques, namely, arctan-based, intensity-based, time domain beamforming, and frequency domain beamforming methods, perform in estimating DOA of a source in different circumstances. Experimental results reveal that for almost all cases beamforming techniques perform best. Moreover, arctan-based method, which is the simplest of all, provides satisfactory results for practical purposes.

  15. About vectors

    CERN Document Server

    Hoffmann, Banesh

    1975-01-01

    From his unusual beginning in ""Defining a vector"" to his final comments on ""What then is a vector?"" author Banesh Hoffmann has written a book that is provocative and unconventional. In his emphasis on the unresolved issue of defining a vector, Hoffmann mixes pure and applied mathematics without using calculus. The result is a treatment that can serve as a supplement and corrective to textbooks, as well as collateral reading in all courses that deal with vectors. Major topics include vectors and the parallelogram law; algebraic notation and basic ideas; vector algebra; scalars and scalar p

  16. Protective immunity against tularemia provided by an adenovirus-vectored vaccine expressing Tul4 of Francisella tularensis.

    Science.gov (United States)

    Kaur, Ravinder; Chen, Shan; Arévalo, Maria T; Xu, Qingfu; Chen, Yanping; Zeng, Mingtao

    2012-03-01

    Francisella tularensis, a category A bioterrorism agent, is a highly infectious organism that is passed on via skin contact and inhalation routes. A live attenuated vaccine strain (LVS) has been developed, but it has not been licensed for public use by the FDA due to safety concerns. Thus, there exists a need for a safer and improved vaccine. In this study, we have constructed a replication-incompetent adenovirus, Ad/opt-Tul4, carrying a codon-optimized gene for expression of a membrane protein, Tul4, of F. tularensis LVS. Its ability to protect against lethal challenge and its immunogenicity were evaluated in a murine model. An intramuscular injection of a single dose (1 × 10(7) PFU) of Ad/opt-Tul4 elicited a robust Tul4-specific antibody response. Assays suggest a Th1-driven response. A single dose elicited 20% protection against challenge with 100 × 50% lethal dose (LD(50)) F. tularensis LVS; two additional booster shots resulted in 60% protection. In comparison, three doses of 5 μg recombinant Tul4 protein did not elicit significant protection against challenge. Therefore, the Ad/opt-Tul4 vaccine was more effective than the protein vaccine, and protection was dose dependent. Compared to LVS, the protection rate is lower, but an adenovirus-vectored vaccine may be more attractive due to its enhanced safety profile and mucosal route of delivery. Furthermore, simple genetic modification of the vaccine may potentially produce antibodies protective against a fully virulent strain of F. tularensis. Our data support the development and further research of an adenovirus-vectored vaccine against Tul4 of F. tularensis LVS.

  17. Regularity results for the minimum time function with Hörmander vector fields

    Science.gov (United States)

    Albano, Paolo; Cannarsa, Piermarco; Scarinci, Teresa

    2018-03-01

    In a bounded domain of Rn with boundary given by a smooth (n - 1)-dimensional manifold, we consider the homogeneous Dirichlet problem for the eikonal equation associated with a family of smooth vector fields {X1 , … ,XN } subject to Hörmander's bracket generating condition. We investigate the regularity of the viscosity solution T of such problem. Due to the presence of characteristic boundary points, singular trajectories may occur. First, we characterize these trajectories as the closed set of all points at which the solution loses point-wise Lipschitz continuity. Then, we prove that the local Lipschitz continuity of T, the local semiconcavity of T, and the absence of singular trajectories are equivalent properties. Finally, we show that the last condition is satisfied whenever the characteristic set of {X1 , … ,XN } is a symplectic manifold. We apply our results to several examples.

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

    Science.gov (United States)

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

    2010-09-01

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

  19. Initial Results from the Vector Electric Field Investigation on the C/NOFS Satellite

    Science.gov (United States)

    Pfaff, R.; Rowland, D.; Acuna, M.; Le, G.; Farrell, W.; Holzworth, R.; Wilson, G.; Burke, W.; Freudenreich, H.; Bromund, K.; hide

    2009-01-01

    Initial results are presented from the Vector Electric Field Investigation (VEFI) on the Air Force Communication/Navigation Outage Forecasting System (C/NOFS) satellite, a mission designed to understand, model, and forecast the presence of equatorial ionospheric irregularities. The VEFI instrument includes a vector DC electric field detector, a fixed-bias Langmuir probe operating in the ion saturation regime, a flux gate magnetometer, an optical lightning detector, and associated electronics including a burst memory. The DC electric field detector has revealed zonal and meridional electric fields that undergo a diurnal variation, typically displaying eastward and outward-directed fields during the day and westward and downward-directed fields at night. In general, the measured DC electric field amplitudes are in the 0.5-2 mV/m range, corresponding to I3 x B drifts of the order of 30-150 m/s. What is surprising is the high degree of large-scale (10's to 100's of km) structure in the DC electric field, particularly at night, regardless of whether well-defined spread-F plasma density depletions are present. The spread-F density depletions and corresponding electric fields that have been detected thus far have displayed a preponderance to appear between midnight and dawn. Associated with the narrow plasma depletions that are detected are broad spectra of electric field and plasma density irregularities for which a full vector set of measurements is available for detailed study. On some occasions, localized regions of low frequency (field broadband irregularities have been detected, suggestive of filamentary currents, although there is no one-to-one correspondence of these waves with the observed plasma density depletions, at least within the data examined thus far. Finally, the data set includes a wide range of ELF/VLF/HF waves corresponding to a variety of plasma waves, in particular banded ELF hiss, whistlers, and lower hybrid wave turbulence triggered by lightning

  20. Phase 2 clinical trial of a recombinant adeno-associated viral vector expressing α1-antitrypsin: interim results.

    LENUS (Irish Health Repository)

    Flotte, Terence R

    2011-10-01

    Recombinant adeno-associated virus (rAAV) vectors offer promise for the gene therapy of α(1)-antitrypsin (AAT) deficiency. In our prior trial, an rAAV vector expressing human AAT (rAAV1-CB-hAAT) provided sustained, vector-derived AAT expression for >1 year. In the current phase 2 clinical trial, this same vector, produced by a herpes simplex virus complementation method, was administered to nine AAT-deficient individuals by intramuscular injection at doses of 6.0×10(11), 1.9×10(12), and 6.0×10(12) vector genomes\\/kg (n=3 subjects\\/dose). Vector-derived expression of normal (M-type) AAT in serum was dose dependent, peaked on day 30, and persisted for at least 90 days. Vector administration was well tolerated, with only mild injection site reactions and no serious adverse events. Serum creatine kinase was transiently elevated on day 30 in five of six subjects in the two higher dose groups and normalized by day 45. As expected, all subjects developed anti-AAV antibodies and interferon-γ enzyme-linked immunospot responses to AAV peptides, and no subjects developed antibodies to AAT. One subject in the mid-dose group developed T cell responses to a single AAT peptide unassociated with any clinical effects. Muscle biopsies obtained on day 90 showed strong immunostaining for AAT and moderate to marked inflammatory cell infiltrates composed primarily of CD3-reactive T lymphocytes that were primarily of the CD8(+) subtype. These results support the feasibility and safety of AAV gene therapy for AAT deficiency, and indicate that serum levels of vector-derived normal human AAT >20 μg\\/ml can be achieved. However, further improvements in the design or delivery of rAAV-AAT vectors will be required to achieve therapeutic target serum AAT concentrations.

  1. Allergies and Asthma: Do Atopic Disorders Result from Inadequate Immune Homeostasis arising from Infant Gut Dysbiosis?

    Science.gov (United States)

    Johnson, Christine C; Ownby, Dennis R

    2016-01-01

    Our global hypothesis is that atopic conditions and asthma develop because an individual's immune system is not able to appropriately resolve inflammation resulting from allergen exposures. We propose that the failure to appropriately down-regulate inflammation and produce a toleragenic state results primarily from less robust immune homeostatic processes rather than from a tendency to over-respond to allergenic stimuli. An individual with lower immune homeostatic capacity is unable to rapidly and completely terminate, on average over time, immune responses to innocuous allergens, increasing risk of allergic disease. A lack of robust homeostasis also increases the risk of other inflammatory conditions, such as prolonged respiratory viral infections and obesity, leading to the common co-occurrence of these conditions. Further, we posit that the development of vigorous immune homeostatic mechanisms is an evolutionary adaptation strongly influenced by both 1) exposure to a diverse maternal microbiota through the prenatal period, labor and delivery, and, 2) an orderly assemblage process of the infant's gut microbiota ecosystem shaped by breastfeeding and early exposure to a wide variety of ingested foods and environmental microbes. This early succession of microbial communities together with early allergen exposures orchestrate the development of an immune system with a robust ability to optimally control inflammatory responses and a lowered risk for atopic disorders.

  2. Mucosal immunization with recombinant adenoviral vectors expressing murine gammaherpesvirus-68 genes M2 and M3 can reduce latent viral load.

    Science.gov (United States)

    Hoegh-Petersen, Mette; Thomsen, Allan R; Christensen, Jan P; Holst, Peter J

    2009-11-12

    Gammaherpesviruses establish life-long latent infections in their hosts. If the host becomes immunosuppressed, these viruses may reactivate and cause severe disease, and even in immunocompetent individuals the gammaherpesviruses are presumed to have an oncogenic potential. Murine gammaherpesvirus-68 (MHV-68) is a member of the Gammaherpesvirinae subfamily and represents a useful murine model for this category of infections, in which new vaccination strategies may initially be evaluated. Two attenuated variants of MHV-68 have successfully been used as vaccines, but the oncogenic potential of the gammaherpesvirinae speaks against using a similar approach in humans. DNA immunization with plasmids encoding the MHV-68 genes M2 or M3 caused a reduction in either acute or early latent viral load, respectively, but neither immunization had an effect at times later than 14 days post-infection. Adenovirus-based vaccines are substantially more immunogenic than DNA vaccines and can be applied to induce mucosal immunity. Here we show that a significant reduction of the late viral load in the spleens, at 60 days post-infection, was achieved when immunizing mice both intranasally and subcutaneously with adenoviral vectors encoding both M2 and M3. Additionally we show that M3 immunization prevented the usual development of virus-induced splenomegaly at 2-3 weeks post-infection. This is the first time that immunization with a non-replicating vaccine has lead to a significantly reduced viral load at time points beyond 14 days post-infection, and thus demonstrates that a non-replicating vaccine may successfully be employed to reduce the viral burden during chronic gammaherpesvirus infection.

  3. Is Declining malaria vector population in Africa a result of intervention Measures or sampling tools inefficiency?

    Directory of Open Access Journals (Sweden)

    Eliningaya Kweka

    2013-01-01

    Full Text Available Recent entomological surveys have shown a declining trend of malaria vector population in sub-Saharan Africa and the observation have beenassociated with the scale-up and intensive use of malaria intervention measures such as insecticides treated nets and insecticide residual sprays.However, little is known on the contribution of the mosquito sampling tools inefficiency on the declining trends of malaria vector population. Inthis commentary paper, we explore the possibility of contribution of mosquito sampling tools’ inefficiency to the observed declining trends ofmalaria vector population in Africa.

  4. Recent results of hadronic decays of J/psi into vector-tensor from MARK III

    International Nuclear Information System (INIS)

    Becker, J.J.; Blaylock, G.T.; Bolton, T.; Brown, J.S.

    1987-02-01

    From a data sample of 5.8 x 10 6 J/psi's collected by the MARK III detector at the storage ring SPEAR at SLAC, two-body decay modes of the J/psi into a vector and a tensor meson have been measured. From the studies of the tensor meson, recoiling against the ideally mixed and well understood vector mesons, quark correlations are established and compared with the theoretical expectations of the J/psi decays and the SU(3) predictions. The beginnings of a similar systematic study of the two-body vector scalar decays are also presented

  5. Multiagent vaccines vectored by Venezuelan equine encephalitis virus replicon elicits immune responses to Marburg virus and protection against anthrax and botulinum neurotoxin in mice.

    Science.gov (United States)

    Lee, John S; Groebner, Jennifer L; Hadjipanayis, Angela G; Negley, Diane L; Schmaljohn, Alan L; Welkos, Susan L; Smith, Leonard A; Smith, Jonathan F

    2006-11-17

    The development of multiagent vaccines offers the advantage of eliciting protection against multiple diseases with minimal inoculations over a shorter time span. We report here the results of using formulations of individual Venezuelan equine encephalitis (VEE) virus replicon-vectored vaccines against a bacterial disease, anthrax; a viral disease, Marburg fever; and against a toxin-mediated disease, botulism. The individual VEE replicon particles (VRP) expressed mature 83-kDa protective antigen (MAT-PA) from Bacillus anthracis, the glycoprotein (GP) from Marburg virus (MBGV), or the H(C) fragment from botulinum neurotoxin (BoNT H(C)). CBA/J mice inoculated with a mixture of VRP expressing BoNT H(C) serotype C (BoNT/C H(C)) and MAT-PA were 80% protected from a B. anthracis (Sterne strain) challenge and then 100% protected from a sequential BoNT/C challenge. Swiss mice inoculated with individual VRP or with mixtures of VRP vaccines expressing BoNT H(C) serotype A (BoNT/A H(C)), MAT-PA, and MBGV-GP produced antibody responses specific to the corresponding replicon-expressed protein. Combination of the different VRP vaccines did not diminish the antibody responses measured for Swiss mice inoculated with formulations of two or three VRP vaccines as compared to mice that received only one VRP vaccine. Swiss mice inoculated with VRP expressing BoNT/A H(C) alone or in combination with VRP expressing MAT-PA and MBGV GP, were completely protected from a BoNT/A challenge. These studies demonstrate the utility of combining individual VRP vaccines into multiagent formulations for eliciting protective immune responses to various types of diseases.

  6. Web-based public health geographic information systems for resources-constrained environment using scalable vector graphics technology: a proof of concept applied to the expanded program on immunization data

    Directory of Open Access Journals (Sweden)

    Kamadjeu Raoul

    2006-06-01

    Full Text Available Abstract Background Geographic Information Systems (GIS are powerful communication tools for public health. However, using GIS requires considerable skill and, for this reason, is sometimes limited to experts. Web-based GIS has emerged as a solution to allow a wider audience to have access to geospatial information. Unfortunately the cost of implementing proprietary solutions may be a limiting factor in the adoption of a public health GIS in a resource-constrained environment. Scalable Vector Graphics (SVG is used to define vector-based graphics for the internet using XML (eXtensible Markup Language; it is an open, platform-independent standard maintained by the World Wide Web Consortium (W3C since 2003. In this paper, we summarize our methodology and demonstrate the potential of this free and open standard to contribute to the dissemination of Expanded Program on Immunization (EPI information by providing interactive maps to a wider audience through the Internet. Results We used SVG to develop a database driven web-based GIS applied to EPI data from three countries of WHO AFRO (World Health Organization – African Region. The system generates interactive district-level country immunization coverage maps and graphs. The approach we describe can be expanded to cover other public health GIS demanding activities, including the design of disease atlases in a resources-constrained environment. Conclusion Our system contributes to accumulating evidence demonstrating the potential of SVG technology to develop web-based public health GIS in resources-constrained settings.

  7. Adenoviral vector-mediated GM-CSF gene transfer improves anti-mycobacterial immunity in mice - role of regulatory T cells.

    Science.gov (United States)

    Singpiel, Alena; Kramer, Julia; Maus, Regina; Stolper, Jennifer; Bittersohl, Lara Friederike; Gauldie, Jack; Kolb, Martin; Welte, Tobias; Sparwasser, Tim; Maus, Ulrich A

    2018-03-01

    Granulocyte macrophage-colony stimulating factor (GM-CSF) is a hematopoietic growth factor involved in differentiation, survival and activation of myeloid and non-myeloid cells with important implications for lung antibacterial immunity. Here we examined the effect of pulmonary adenoviral vector-mediated delivery of GM-CSF (AdGM-CSF) on anti-mycobacterial immunity in M. bovis BCG infected mice. Exposure of M. bovis BCG infected mice to AdGM-CSF either applied on 6h, or 6h and 7days post-infection substantially increased alveolar recruitment of iNOS and IL-12 expressing macrophages, and significantly increased accumulation of IFNγ pos T cells and particularly regulatory T cells (Tregs). This was accompanied by significantly reduced mycobacterial loads in the lungs of mice. Importantly, diphtheria toxin-induced depletion of Tregs did not influence mycobacterial loads, but accentuated immunopathology in AdGM-CSF-exposed mice infected with M. bovis BCG. Together, the data demonstrate that AdGM-CSF therapy improves lung protective immunity against M. bovis BCG infection in mice independent of co-recruited Tregs, which however critically contribute to limit lung immunopathology in BCG-infected mice. These data may be relevant to the development of immunomodulatory strategies to limit immunopathology-based lung injury in tuberculosis in humans. Copyright © 2017 Elsevier GmbH. All rights reserved.

  8. Automotive RF immunity test set-up analysis : why test results can't compare

    NARCIS (Netherlands)

    Coenen, Mart; Pues, H.; Bousquet, T.

    2011-01-01

    Though the automotive RF emission and RF immunity requirements are highly justifiable, the application of those requirements in an non-intended manner leads to false conclusions and unnecessary redesigns for the electronics involved. When the test results become too dependent upon the test set-up

  9. Immune responses to transgene and retroviral vector in patients treated with ex vivo-engineered T cells

    NARCIS (Netherlands)

    Lamers, C.H.; Willemsen, R.; Elzakker, P. van; Steenbergen-Langeveld, S. van; Broertjes, M.; Oosterwijk-Wakka, J.C.; Oosterwijk, E.; Sleijfer, S.; Debets, R.; Gratama, J.W.

    2011-01-01

    Adoptive transfer of immune effector cells that are gene modified by retroviral transduction to express tumor-specific receptors constitutes an attractive approach to treat cancer. In patients with metastatic renal cell carcinoma, we performed a study with autologous T cells genetically retargeted

  10. Immune protection of nonhuman primates against Ebola virus with single low-dose adenovirus vectors encoding modified GPs

    NARCIS (Netherlands)

    Sullivan, Nancy J.; Geisbert, Thomas W.; Geisbert, Joan B.; Shedlock, Devon J.; Xu, Ling; Lamoreaux, Laurie; Custers, Jerome H. H. V.; Popernack, Paul M.; Yang, Zhi-Yong; Pau, Maria G.; Roederer, Mario; Koup, Richard A.; Goudsmit, Jaap; Jahrling, Peter B.; Nabel, Gary J.

    2006-01-01

    BACKGROUND: Ebola virus causes a hemorrhagic fever syndrome that is associated with high mortality in humans. In the absence of effective therapies for Ebola virus infection, the development of a vaccine becomes an important strategy to contain outbreaks. Immunization with DNA and/or

  11. Breadth of T cell responses after immunization with adenovirus vectors encoding ancestral antigens or polyvalent papillomavirus antigens

    DEFF Research Database (Denmark)

    Ragonnaud, Emeline; Pedersen, Anders Gorm; Holst, Peter Johannes

    2017-01-01

    to the other PV proteins. The PV sequences were fused to a T cell adjuvant, the murine invariant chain and encoded in a recombinant adenoviral vector which was administered to naïve outbred mice. By measuring T cell responses induced by these different vaccines and towards peptide pools representing 3...... circulating strains and a putative ancestor of oncogenic HPVs, we showed that the ancestral vaccine antigen has to be approximately 90% identical to the circulating PVs before a marked drop of ~90% mean CD8+ T cell responses ensues. Interestingly, the combination of two or three type-specific PV vaccines did...

  12. Intradermal Immunization of Leishmania donovani Centrin Knock-Out Parasites in Combination with Salivary Protein LJM19 from Sand Fly Vector Induces a Durable Protective Immune Response in Hamsters.

    Directory of Open Access Journals (Sweden)

    Jacqueline Araújo Fiuza

    2016-01-01

    Full Text Available Visceral leishmaniasis (VL is a neglected tropical disease and is fatal if untreated. There is no vaccine available against leishmaniasis. The majority of patients with cutaneous leishmaniasis (CL or VL develop a long-term protective immunity after cure from infection, which indicates that development of an effective vaccine against leishmaniasis is possible. Such protection may also be achieved by immunization with live attenuated parasites that do not cause disease. We have previously reported a protective response in mice, hamsters and dogs with Leishmania donovani centrin gene knock-out parasites (LdCen-/-, a live attenuated parasite with a cell division specific centrin1 gene deletion. In this study we have explored the effects of salivary protein LJM19 as an adjuvant and intradermal (ID route of immunization on the efficacy of LdCen-/- parasites as a vaccine against virulent L. donovani.To explore the potential of a combination of LdCen-/- parasites and salivary protein LJM19 as vaccine antigens, LdCen-/- ID immunization followed by ID challenge with virulent L. donovani were performed in hamsters in a 9-month follow up study. We determined parasite burden (serial dilution, antibody production (ELISA and cytokine expression (qPCR in these animals. Compared to controls, animals immunized with LdCen-/- + LJM19 induced a strong antibody response, a reduction in spleen and liver parasite burden and a higher expression of pro-inflammatory cytokines after immunization and one month post-challenge. Additionally, a low parasite load in lymph nodes, spleen and liver, and a non-inflamed spleen was observed in immunized animals 9 months after the challenge infection.Our results demonstrate that an ID vaccination using LdCen-/-parasites in combination with sand fly salivary protein LJM19 has the capability to confer long lasting protection against visceral leishmaniasis that is comparable to intravenous or intracardial immunization.

  13. Chimeric avian paramyxovirus-based vector immunization against highly pathogenic avian influenza followed by conventional Newcastle disease vaccination eliminates lack of protection from virulent ND virus

    Directory of Open Access Journals (Sweden)

    C. Steglich

    2014-01-01

    Full Text Available Recently, we described a chimeric, hemagglutinin of highly pathogenic avian influenza virus (HPAIV H5 expressing Newcastle disease virus (NDV-based vector vaccine (chNDVFHNPMV8H5 in which NDV envelope glycoproteins were replaced by those of avian paramyxovirus-8 (APMV-8. This chimeric vaccine induced solid protection against lethal HPAIV H5N1 even in chickens with maternal antibodies against NDV (MDA+. However, due to the absence of the major NDV immunogens it failed to induce protection against Newcastle disease (ND. Here, we report on protection of MDA+ chickens against HPAI H5N1 and ND, by vaccination with chNDVFHNPMV8H5 either on day 1 or day seven after hatch, and subsequent immunization with live attenuated NDV seven days later. Vaccination was well tolerated and three weeks after immunization, challenge infections with highly pathogenic NDV as well as HPAIV H5N1 were carried out. All animals remained healthy without exhibiting any clinical signs, whereas non-vaccinated animals showed morbidity and mortality. Therefore, vaccination with chNDVFHNPMV8H5 can be followed by NDV vaccination to protect chickens from HPAIV as well as NDV, indicating that the antibody response against chNDVFHNPMV8H5 does not interfere with live ND vaccination.

  14. Efficacy of genital T cell responses to herpes simplex virus type 2 resulting from immunization of the nasal mucosa

    International Nuclear Information System (INIS)

    Milligan, Gregg N.; Dudley-McClain, Kristen L.; Chu Chinfun; Young, Christal G.

    2004-01-01

    Intravaginal (ivag) or intranasal (i.n.) immunization of C57BL/6J (B6) mice with a thymidine kinase-deficient strain (tk-) of herpes simplex virus type 2 (HSV-2) resulted in comparable protection of the genital epithelium and sensory ganglia against HSV-2 challenge. In contrast, protection of these sites was much reduced in i.n.-immunized compared to ivag-immunized B cell-deficient μMT mice. Fewer HSV-specific T cells were detected in the genital epithelium of i.n.-immunized compared to ivag-immunized μMT mice after HSV-2 challenge. Passive transfer of HSV-specific serum to immune μMT mice restored protection of these sites against HSV-2 challenge. These results suggest that protection of genital and neuronal sites may be conferred by i.n. immunization but may be more dependent on antibody-dependent mechanisms than the protection resulting from genital immunization. These results have implications for immunization strategies to elicit high levels of cell-mediated protection of the genital tract and sensory ganglia

  15. Viral vector-based influenza vaccines

    Science.gov (United States)

    de Vries, Rory D.; Rimmelzwaan, Guus F.

    2016-01-01

    ABSTRACT Antigenic drift of seasonal influenza viruses and the occasional introduction of influenza viruses of novel subtypes into the human population complicate the timely production of effective vaccines that antigenically match the virus strains that cause epidemic or pandemic outbreaks. The development of game-changing vaccines that induce broadly protective immunity against a wide variety of influenza viruses is an unmet need, in which recombinant viral vectors may provide. Use of viral vectors allows the delivery of any influenza virus antigen, or derivative thereof, to the immune system, resulting in the optimal induction of virus-specific B- and T-cell responses against this antigen of choice. This systematic review discusses results obtained with vectored influenza virus vaccines and advantages and disadvantages of the currently available viral vectors. PMID:27455345

  16. Prime-booster vaccination of cattle with an influenza viral vector Brucella abortus vaccine induces a long-term protective immune response against Brucella abortus infection.

    Science.gov (United States)

    Tabynov, Kaissar; Yespembetov, Bolat; Ryskeldinova, Sholpan; Zinina, Nadezhda; Kydyrbayev, Zhailaubay; Kozhamkulov, Yerken; Inkarbekov, Dulat; Sansyzbay, Abylai

    2016-01-20

    This study analyzed the duration of the antigen-specific humoral and T-cell immune responses and protectiveness of a recently-developed influenza viral vector Brucella abortus (Flu-BA) vaccine expressing Brucella proteins Omp16 and L7/L12 and containing the adjuvant Montadine Gel01 in cattle. At 1 month post-booster vaccination (BV), both humoral (up to 3 months post-BV; GMT IgG ELISA titer 214±55 to 857±136, with a prevalence of IgG2a over IgG1 isotype antibodies) and T-cell immune responses were observed in vaccinated heifers (n=35) compared to control animals (n=35, injected with adjuvant/PBS only). A pronounced T-cell immune response was induced and maintained for 12 months post-BV, as indicated by the lymphocyte stimulation index (2.7±0.4 to 10.1±0.9 cpm) and production of IFN-γ (13.7±1.7 to 40.0±3.0 ng/ml) at 3, 6, 9, and 12 months post-BV. Prime-boost vaccination provided significant protection against B. abortus infection at 3, 6, 9 and 12 months (study duration) post-BV (7 heifers per time point; alpha=0.03-0.01 vs. control group). Between 57.1 and 71.4% of vaccinated animals showed no signs of B. abortus infection (or Brucella isolation) at 3, 6, 9 and 12 months post-BV; the severity of infection, as indicated by the index of infection (P=0.0003 to Brucella colonization (P=0.03 to abortus infection was also observed among pregnant vaccinated heifers (alpha=0.03), as well as their fetuses and calves (alpha=0.01), for 12 months post-BV. Additionally, 71.4% of vaccinated heifers calved successfully whereas all pregnant control animals aborted (alpha=0.01). Prime-boost vaccination of cattle with Flu-BA induces an antigen-specific humoral and pronounced T cell immune response and most importantly provides good protectiveness, even in pregnant heifers, for at least 12 months post-BV. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Heterologous Two-Dose Vaccination with Simian Adenovirus and Poxvirus Vectors Elicits Long-Lasting Cellular Immunity to Influenza Virus A in Healthy Adults

    Directory of Open Access Journals (Sweden)

    L. Coughlan

    2018-03-01

    Full Text Available Background: T-cell responses against highly conserved influenza antigens have been previously associated with protection. However, these immune responses are poorly maintained following recovery from influenza infection and are not boosted by inactivated influenza vaccines. We have previously demonstrated the safety and immunogenicity of two viral vectored vaccines, modified vaccinia virus Ankara (MVA and the chimpanzee adenovirus ChAdOx1 expressing conserved influenza virus antigens, nucleoprotein (NP and matrix protein-1 (M1. We now report on the safety and long-term immunogenicity of multiple combination regimes of these vaccines in young and older adults. Methods: We conducted a Phase I open-label, randomized, multi-center study in 49 subjects aged 18–46 years and 24 subjects aged 50 years or over. Following vaccination, adverse events were recorded and the kinetics of the T cell response determined at multiple time points for up to 18 months. Findings: Both vaccines were well tolerated. A two dose heterologous vaccination regimen significantly increased the magnitude of pre-existing T-cell responses to NP and M1 after both doses in young and older adults. The fold-increase and peak immune responses after a single MVA-NP + M1 vaccination was significantly higher compared to ChAdOx1 NP + M1. In a mixed regression model, T-cell responses over 18 months were significantly higher following the two dose vaccination regimen of MVA/ChAdOx1 NP + M1. Interpretation: A two dose heterologous vaccination regimen of MVA/ChAdOx1 NP + M1 was safe and immunogenic in young and older adults, offering a promising vaccination strategy for inducing long-term broadly cross-reactive protection against influenza A. Funding Source: Medical Research Council UK, NIHR BMRC Oxford. Keywords: Influenza, T-cell responses, Influenza vaccines, Viral vectors, Adults, Older adults

  18. Biomarkers of Eating Disorders Using Support Vector Machine Analysis of Structural Neuroimaging Data: Preliminary Results

    Directory of Open Access Journals (Sweden)

    Antonio Cerasa

    2015-01-01

    Full Text Available Presently, there are no valid biomarkers to identify individuals with eating disorders (ED. The aim of this work was to assess the feasibility of a machine learning method for extracting reliable neuroimaging features allowing individual categorization of patients with ED. Support Vector Machine (SVM technique, combined with a pattern recognition method, was employed utilizing structural magnetic resonance images. Seventeen females with ED (six with diagnosis of anorexia nervosa and 11 with bulimia nervosa were compared against 17 body mass index-matched healthy controls (HC. Machine learning allowed individual diagnosis of ED versus HC with an Accuracy ≥ 0.80. Voxel-based pattern recognition analysis demonstrated that voxels influencing the classification Accuracy involved the occipital cortex, the posterior cerebellar lobule, precuneus, sensorimotor/premotor cortices, and the medial prefrontal cortex, all critical regions known to be strongly involved in the pathophysiological mechanisms of ED. Although these findings should be considered preliminary given the small size investigated, SVM analysis highlights the role of well-known brain regions as possible biomarkers to distinguish ED from HC at an individual level, thus encouraging the translational implementation of this new multivariate approach in the clinical practice.

  19. Biomarkers of Eating Disorders Using Support Vector Machine Analysis of Structural Neuroimaging Data: Preliminary Results

    Science.gov (United States)

    Cerasa, Antonio; Castiglioni, Isabella; Salvatore, Christian; Funaro, Angela; Martino, Iolanda; Alfano, Stefania; Donzuso, Giulia; Perrotta, Paolo; Gioia, Maria Cecilia; Gilardi, Maria Carla; Quattrone, Aldo

    2015-01-01

    Presently, there are no valid biomarkers to identify individuals with eating disorders (ED). The aim of this work was to assess the feasibility of a machine learning method for extracting reliable neuroimaging features allowing individual categorization of patients with ED. Support Vector Machine (SVM) technique, combined with a pattern recognition method, was employed utilizing structural magnetic resonance images. Seventeen females with ED (six with diagnosis of anorexia nervosa and 11 with bulimia nervosa) were compared against 17 body mass index-matched healthy controls (HC). Machine learning allowed individual diagnosis of ED versus HC with an Accuracy ≥ 0.80. Voxel-based pattern recognition analysis demonstrated that voxels influencing the classification Accuracy involved the occipital cortex, the posterior cerebellar lobule, precuneus, sensorimotor/premotor cortices, and the medial prefrontal cortex, all critical regions known to be strongly involved in the pathophysiological mechanisms of ED. Although these findings should be considered preliminary given the small size investigated, SVM analysis highlights the role of well-known brain regions as possible biomarkers to distinguish ED from HC at an individual level, thus encouraging the translational implementation of this new multivariate approach in the clinical practice. PMID:26648660

  20. Extended partially conserved axial-vector current hypothesis and model-dependent results

    International Nuclear Information System (INIS)

    Dominguez, C.A.

    1977-01-01

    The corrections to Goldberger-Treiman relations for ΔS = 0 and vertical-bardeltaSvertical-bar = 1 β decays (Δ/sub π/and Δ/sub K/, respectively) are estimated from a Veneziano-type model for three-point functions. The effect of unitarizing the model is also discussed, and it turns out that Δ/sub π/and Δ/sub K/ are almost insensitive to a variation in the widths of the pseudoscalar-meson daughters. Moreover, the predictions for Δ/sub π/and Δ/sub K/ are in close agreement with experiment. Finally, on-mass-shell extrapolation factors for chiral anomalies in eta → γγ and eta → π + π - γ are also derived, and agreement with experiment is found without the need for invoking eta-eta' mixing. In summary, the model discussed here seems to be a suitable implementation of the recently proposed extended partially conserved axial-vector current hypothesis

  1. Cost-effectiveness of rotavirus immunization in Vietnam: Results and challenges

    NARCIS (Netherlands)

    Tu, H.A.T.; Rozenbaum, M.; Coyte, P.C.; Li, S.C.; Postma, M.J.

    2011-01-01

    OBJECTIVES: To assess the cost-effectiveness of universal rotavirus immunization, explicitly the use of Rotateq® and affordability of implementing rotavirus immunization based on the Global Alliance for Vaccines and Immunization (GAVI)-subsidized vaccine price in the context of Vietnamese health

  2. Genetic Passive Immunization with Adenoviral Vector Expressing Chimeric Nanobody-Fc Molecules as Therapy for Genital Infection Caused by Mycoplasma hominis.

    Directory of Open Access Journals (Sweden)

    Daria A Burmistrova

    Full Text Available Developing pathogen-specific recombinant antibody fragments (especially nanobodies is a very promising strategy for the treatment of infectious disease. Nanobodies have great potential for gene therapy application due to their single-gene nature. Historically, Mycoplasma hominis has not been considered pathogenic bacteria due to the lack of acute infection and partially due to multiple studies demonstrating high frequency of isolation of M. hominis samples from asymptomatic patients. However, recent studies on the role of latent M. hominis infection in oncologic transformation, especially prostate cancer, and reports that M. hominis infects Trichomonas and confers antibiotic resistance to Trichomonas, have generated new interest in this field. In the present study we have generated specific nanobody against M. hominis (aMh, for which the identified target is the ABC-transporter substrate-binding protein. aMh exhibits specific antibacterial action against M. hominis. In an attempt to improve the therapeutic properties, we have developed the adenoviral vector-based gene therapy approach for passive immunization with nanobodies against M. hominis. For better penetration into the mucous layer of the genital tract, we fused aMh with the Fc-fragment of IgG. Application of this comprehensive approach with a single systemic administration of recombinant adenovirus expressing aMh-Fc demonstrated both prophylactic and therapeutic effects in a mouse model of genital M. hominis infection.

  3. Transplantation of mouse HSCs genetically modified to express a CD4-restricted TCR results in long-term immunity that destroys tumors and initiates spontaneous autoimmunity.

    Science.gov (United States)

    Ha, Sung P; Klemen, Nicholas D; Kinnebrew, Garrett H; Brandmaier, Andrew G; Marsh, Jon; Hangoc, Giao; Palmer, Douglas C; Restifo, Nicholas P; Cornetta, Kenneth; Broxmeyer, Hal E; Touloukian, Christopher E

    2010-12-01

    The development of effective cancer immunotherapies has been consistently hampered by several factors, including an inability to instigate long-term effective functional antitumor immunity. This is particularly true for immunotherapies that focus on the adoptive transfer of activated or genetically modified mature CD8+ T cells. In this study, we sought to alter and enhance long-term host immunity by genetically modifying, then transplanting, mouse HSCs. We first cloned a previously identified tumor-reactive HLA-DR4-restricted CD4+ TCR specific for the melanocyte differentiation antigen tyrosinase-related protein 1 (Tyrp1), then constructed both a high-expression lentivirus vector and a TCR-transgenic mouse expressing the genes encoding this TCR. Using these tools, we demonstrated that both mouse and human HSCs established durable, high-efficiency TCR gene transfer following long-term transplantation into lethally irradiated mice transgenic for HLA-DR4. Recipients of genetically modified mouse HSCs developed spontaneous autoimmune vitiligo that was associated with the presence of a Th1-polarized memory effector CD4+ T cell population that expressed the Tyrp1-specific TCR. Most importantly, large numbers of CD4+ T cells expressing the Tyrp1-specific TCR were detected in secondary HLA-DR4-transgenic transplant recipients, and these mice were able to destroy subcutaneously administered melanoma cells without the aid of vaccination, immune modulation, or cytokine administration. These results demonstrate the creation of what we believe to be a novel translational model of durable lentiviral gene transfer that results in long-term effective immunity.

  4. Pathogen-induced maternal effects result in enhanced immune responsiveness across generations.

    Science.gov (United States)

    Rosengaus, Rebeca B; Hays, Nicole; Biro, Colette; Kemos, James; Zaman, Muizz; Murray, Joseph; Gezahegn, Bruck; Smith, Wendy

    2017-05-01

    Parental investment theory postulates that adults can accurately perceive cues from their surroundings, anticipate the needs of future offspring based on those cues, and selectively allocate nongenetic resources to their progeny. Such context-dependent parental contributions can result in phenotypically variable offspring. Consistent with these predictions, we show that bacterially exposed Manduca sexta mothers oviposited significantly more variable embryos (as measured by mass, volume, hatching time, and hatching success) relative to naïve and control mothers. By using an in vivo "clearance of infection" assay, we also show that challenged larvae born to heat-killed- or live- Serratia -injected mothers, supported lower microbial loads and cleared the infection faster than progeny of control mothers. Our data support the notion that mothers can anticipate the future pathogenic risks and immunological needs of their unborn offspring, providing progeny with enhanced immune protection likely through transgenerational immune priming. Although the inclusion of live Serratia into oocytes does not appear to be the mechanism by which mothers confer protection to their young, other mechanisms, including epigenetic modifications in the progeny due to maternal pathogenic stress, may be at play. The adaptive nature of maternal effects in the face of pathogenic stress provides insights into parental investment, resource allocation, and life-history theories and highlights the significant role that pathogen-induced maternal effects play as generators and modulators of evolutionary change.

  5. Equivalent Vectors

    Science.gov (United States)

    Levine, Robert

    2004-01-01

    The cross-product is a mathematical operation that is performed between two 3-dimensional vectors. The result is a vector that is orthogonal or perpendicular to both of them. Learning about this for the first time while taking Calculus-III, the class was taught that if AxB = AxC, it does not necessarily follow that B = C. This seemed baffling. The…

  6. Development of a novel, guinea pig-specific IFN-γ ELISPOT assay and characterization of guinea pig cytomegalovirus GP83-specific cellular immune responses following immunization with a modified vaccinia virus Ankara (MVA)-vectored GP83 vaccine.

    Science.gov (United States)

    Gillis, Peter A; Hernandez-Alvarado, Nelmary; Gnanandarajah, Josephine S; Wussow, Felix; Diamond, Don J; Schleiss, Mark R

    2014-06-30

    The guinea pig (Cavia porcellus) provides a useful animal model for studying the pathogenesis of many infectious diseases, and for preclinical evaluation of vaccines. However, guinea pig models are limited by the lack of immunological reagents required for characterization and quantification of antigen-specific T cell responses. To address this deficiency, an enzyme-linked immunospot (ELISPOT) assay for guinea pig interferon (IFN)-γ was developed to measure antigen/epitope-specific T cell responses to guinea pig cytomegalovirus (GPCMV) vaccines. Using splenocytes harvested from animals vaccinated with a modified vaccinia virus Ankara (MVA) vector encoding the GPCMV GP83 (homolog of human CMV pp65 [gpUL83]) protein, we were able to enumerate and map antigen-specific responses, both in vaccinated as well as GPCMV-infected animals, using a panel of GP83-specific peptides. Several potential immunodominant GP83-specific peptides were identified, including one epitope, LGIVHFFDN, that was noted in all guinea pigs that had a detectable CD8+ response to GP83. Development of a guinea pig IFN-γ ELISPOT should be useful in characterization of additional T cell-specific responses to GPCMV, as well as other pathogens. This information in turn can help focus future experimental evaluation of immunization strategies, both for GPCMV as well as for other vaccine-preventable illnesses studied in the guinea pig model. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Prospective study of probiotic supplementation results in immune stimulation and improvement of upper respiratory infection rate

    Directory of Open Access Journals (Sweden)

    Hong Zhang

    2018-06-01

    Full Text Available The human gut microbiota is an important environmental factor for human health with evolutionarily conserved roles in immunity, metabolism, development, and behavior of the host. Probiotic organisms are claimed to offer several functional properties including stimulation of immune system. The purpose of this study is to investigate the effects of a probiotic supplementation on adult volunteers who have contracted the common cold four or more times in the past year. This study is a single center, double-blind, randomized, controlled, prospective trial. Subjects received a probiotic drink containing Lactobacillus paracasei (at least 3 × 107 colony forming units (CFU ml−1, Lactobacillus casei 431® (at least 3 × 107 CFU ml−1 and Lactobacillus fermentium PCC® (at least 3 × 106 CFU ml−1 or an identical placebo without probiotics for a 12-week study period. The consumption of probiotics significantly reduced the incidence of upper respiratory infection (p < 0.023 and flu-like symptoms with an oral temperature higher than 38 °C (p < 0.034 as compared to the placebo group. Subjects that consumed probiotics demonstrated a significantly higher level of IFN-γ in the serum (p < 0.001 and sIgA in the gut (p < 0.010 as compared to the placebo group and a significant higher level of serum IFN-γ (p < 0.001 and gut sIgA (p < 0.001 as compared to their baseline test results. In contrast, there were no significant differences in the serum IL-4, IL-10, IgA, IgG or IgM between the probiotics and the placebo groups. Results of this study demonstrated that probiotics were safe and effective for fighting the common cold and influenza-like respiratory infections by boosting the immune system. Keywords: Probiotics, Upper respiratory infections, Human microbiota, IFN-γ, sIgA

  8. On the resultant property of the Fisher information matrix of a vector ARMA process

    NARCIS (Netherlands)

    Klein, A.; Mélard, G.; Spreij, P.

    2004-01-01

    A matrix is called a multiple resultant matrix associated to two matrix polynomials when it becomes singular if and only if the two matrix polynomials have at least one common eigenvalue. In this paper a new multiple resultant matrix is introduced. It concerns the Fisher information matrix (FIM) of

  9. Hyperpigmentation Results in Aberrant Immune Development in Silky Fowl (Gallus gallus domesticus Brisson.

    Directory of Open Access Journals (Sweden)

    Deping Han

    Full Text Available The Silky Fowl (SF is known for its special phenotypes and atypical distribution of melanocytes among internal organs. Although the genes associated with melanocyte migration have been investigated substantially, there is little information on the postnatal distribution of melanocytes in inner organs and the effect of hyperpigmentation on the development of SF. Here, we analyzed melanocyte distribution in 26 tissues or organs on postnatal day 1 and weeks 2, 3, 4, 6, 10, and 23. Except for the liver, pancreas, pituitary gland, and adrenal gland, melanocytes were distributed throughout the body, primarily around blood vessels. Interaction between melanocytes and the tissue cells was observed, and melanin was transported by filopodia delivery through engulfed and internalized membrane-encapsulated melanosomes. SFs less than 10 weeks old have lower indices of spleen, thymus, and bursa of Fabricius than White Leghorns (WLs. The expression levels of interferon-γ and interlukin-4 genes in the spleen, and serum antibody levels against H5N1 and infectious bursal disease virus were lower in SF than in WL. We also found immune organ developmental difference between Black-boned and non-Black- boned chickens from SFs and WLs hybrid F2 population. However, degeneration of the thymus and bursa of Fabricius occurred later in SF than in WL after sexual maturity. Analysis of apoptotic cells and apoptosis-associated Bax and Bcl-2 proteins indicated that apoptosis is involved in degeneration of the thymus and bursa of Fabricius. Therefore, these results suggest that hyperpigmentation in SF may have a close relationship with immune development in SF, which can provide an important animal model to investigate the roles of melanocyte.

  10. Long-lived tissue resident HIV-1 specific memory CD8+ T cells are generated by skin immunization with live virus vectored microneedle arrays.

    Science.gov (United States)

    Zaric, Marija; Becker, Pablo Daniel; Hervouet, Catherine; Kalcheva, Petya; Ibarzo Yus, Barbara; Cocita, Clement; O'Neill, Lauren Alexandra; Kwon, Sung-Yun; Klavinskis, Linda Sylvia

    2017-12-28

    The generation of tissue resident memory (T RM ) cells at the body surfaces to provide a front line defence against invading pathogens represents an important goal in vaccine development for a wide variety of pathogens. It has been widely assumed that local vaccine delivery to the mucosae is necessary to achieve that aim. Here we characterise a novel micro-needle array (MA) delivery system fabricated to deliver a live recombinant human adenovirus type 5 vaccine vector (AdHu5) encoding HIV-1 gag. We demonstrate rapid dissolution kinetics of the microneedles in skin. Moreover, a consequence of MA vaccine cargo release was the generation of long-lived antigen-specific CD8 + T cells that accumulate in mucosal tissues, including the female genital and respiratory tract. The memory CD8 + T cell population maintained in the peripheral mucosal tissues was attributable to a MA delivered AdHu5 vaccine instructing CD8 + T cell expression of CXCR3 + , CD103 +, CD49a + , CD69 + , CD127 + homing, retention and survival markers. Furthermore, memory CD8 + T cells generated by MA immunization significantly expanded upon locally administered antigenic challenge and showed a predominant poly-functional profile producing high levels of IFNγ and Granzyme B. These data demonstrate that skin vaccine delivery using microneedle technology induces mobilization of long lived, poly-functional CD8 + T cells to peripheral tissues, phenotypically displaying hallmarks of residency and yields new insights into how to design and deliver effective vaccine candidates with properties to exert local immunosurveillance at the mucosal surfaces. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  11. Raster images vectorization system

    OpenAIRE

    Genytė, Jurgita

    2006-01-01

    The problem of raster images vectorization was analyzed and researched in this work. Existing vectorization systems are quite expensive, the results are inaccurate, and the manual vectorization of a large number of drafts is impossible. That‘s why our goal was to design and develop a new raster images vectorization system using our suggested automatic vectorization algorithm and the way to record results in a new universal vectorial file format. The work consists of these main parts: analysis...

  12. Novel influenza virus vectors expressing Brucella L7/L12 or Omp16 proteins in cattle induced a strong T-cell immune response, as well as high protectiveness against B. abortus infection.

    Science.gov (United States)

    Tabynov, Kaissar; Kydyrbayev, Zhailaubay; Ryskeldinova, Sholpan; Yespembetov, Bolat; Zinina, Nadezhda; Assanzhanova, Nurika; Kozhamkulov, Yerken; Inkarbekov, Dulat; Gotskina, Tatyana; Sansyzbay, Abylai

    2014-04-11

    This paper presents the results of a study of the immunogenicity and protectiveness of new candidate vector vaccine against Brucella abortus - a bivalent vaccine formulation consisting of a mixture of recombinant influenza A subtype H5N1 or H1N1 (viral constructs vaccine formulation) viruses expressing Brucella ribosomal protein L7/L12 and Omp16, in cattle. To increase the effectiveness of the candidate vaccine, adjuvants such as Montanide Gel01 or chitosan were included in its composition. Immunization of cattle (heifers aged 1-1.5 years, 5 animals per group) with the viral constructs vaccine formulation only, or its combination with adjuvants Montanide Gel01 or chitosan, was conducted via the conjunctival method using cross prime (influenza virus subtype H5N1) and booster (influenza virus subtype H1N1) vaccination schedules at an interval of 28 days. Vaccine candidates were evaluated in comparison with the positive (B. abortus S19) and negative (PBS) controls. The viral constructs vaccine formulations, particularly in combination with Montanide Gel01 adjuvant promoted formation of IgG antibodies (with a predominance of antibodies of isotype IgG2a) against Brucella L7/L12 and Omp16 proteins in ELISA. Moreover, these vaccines in cattle induced a strong antigen-specific T-cell immune response, as indicated by a high number of CD4(+) and CD8(+) cells, as well as the concentration of IFN-γ, and most importantly provided a high level of protectiveness comparable to the commercial B. abortus S19 vaccine and superior to the B. abortus S19 vaccine in combination with Montanide Gel01 adjuvant. Based on these findings, we recommended the bivalent vaccine formulation containing the adjuvant Montanide Gel01 for practical use in cattle. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Atopic dermatitis results in intrinsic barrier and immune abnormalities: Implications for contact dermatitis

    Science.gov (United States)

    Gittler, Julia K.; Krueger, James G.; Guttman-Yassky, Emma

    2014-01-01

    Atopic dermatitis (AD), as well as irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD), are common skin diseases. These diseases are characterized by skin inflammation mediated by activated innate immunity or acquired immune mechanisms. Although AD, ICD, and ACD can be encountered in pure forms by allergists and dermatologists, patients with AD often present with increased frequency of ICD and ACD. Although a disturbed barrier alone could potentiate immune reactivity in patients with AD through increased antigen penetration, additional immune mechanisms might explain the increased susceptibility of atopic patients to ICD and ACD. This review discusses cellular pathways associated with increased skin inflammation in all 3 conditions and presents mechanisms that might contribute to the increased rate of ICD and ACD in patients with AD. PMID:22939651

  14. Vector geometry

    CERN Document Server

    Robinson, Gilbert de B

    2011-01-01

    This brief undergraduate-level text by a prominent Cambridge-educated mathematician explores the relationship between algebra and geometry. An elementary course in plane geometry is the sole requirement for Gilbert de B. Robinson's text, which is the result of several years of teaching and learning the most effective methods from discussions with students. Topics include lines and planes, determinants and linear equations, matrices, groups and linear transformations, and vectors and vector spaces. Additional subjects range from conics and quadrics to homogeneous coordinates and projective geom

  15. Intestinal epithelial cell-specific RARα depletion results in aberrant epithelial cell homeostasis and underdeveloped immune system.

    Science.gov (United States)

    Jijon, H B; Suarez-Lopez, L; Diaz, O E; Das, S; De Calisto, J; Yaffe, M B; Pittet, M J; Mora, J R; Belkaid, Y; Xavier, R J; Villablanca, E J

    2018-05-01

    Retinoic acid (RA), a dietary vitamin A metabolite, is crucial in maintaining intestinal homeostasis. RA acts on intestinal leukocytes to modulate their lineage commitment and function. Although the role of RA has been characterized in immune cells, whether intestinal epithelial cells (IECs) rely on RA signaling to exert their immune-regulatory function has not been examined. Here we demonstrate that lack of RA receptor α (RARα) signaling in IECs results in deregulated epithelial lineage specification, leading to increased numbers of goblet cells and Paneth cells. Mechanistically, lack of RARα resulted in increased KLF4 + goblet cell precursors in the distal bowel, whereas RA treatment inhibited klf4 expression and goblet cell differentiation in zebrafish. These changes in secretory cells are associated with increased Reg3g, reduced luminal bacterial detection, and an underdeveloped intestinal immune system, as evidenced by an almost complete absence of lymphoid follicles and gut resident mononuclear phagocytes. This underdeveloped intestinal immune system shows a decreased ability to clear infection with Citrobacter rodentium. Collectively, our findings indicate that epithelial cell-intrinsic RARα signaling is critical to the global development of the intestinal immune system.

  16. A representation result for hysteresis operators with vector valued inputs and its application to models for magnetic materials

    Energy Technology Data Exchange (ETDEWEB)

    Klein, Olaf, E-mail: Olaf.Klein@wias-berlin.de

    2014-02-15

    In this work, hysteresis operators mapping continuous vector-valued input functions being piecewise monotaffine, i.e. being piecewise the composition of a monotone with an affine function, to vector-valued output functions are considered. It is shown that the operator can be generated by a unique defined function on the convexity triple free strings. A formulation of a congruence property for periodic inputs is presented and reformulated as a condition for the generating string function.

  17. Mechanical disruption of tumors by iron particles and magnetic field application results in increased anti-tumor immune responses.

    Directory of Open Access Journals (Sweden)

    Myriam N Bouchlaka

    Full Text Available The primary tumor represents a potential source of antigens for priming immune responses for disseminated disease. Current means of debulking tumors involves the use of cytoreductive conditioning that impairs immune cells or removal by surgery. We hypothesized that activation of the immune system could occur through the localized release of tumor antigens and induction of tumor death due to physical disruption of tumor architecture and destruction of the primary tumor in situ. This was accomplished by intratumor injection of magneto-rheological fluid (MRF consisting of iron microparticles, in Balb/c mice bearing orthotopic 4T1 breast cancer, followed by local application of a magnetic field resulting in immediate coalescence of the particles, tumor cell death, slower growth of primary tumors as well as decreased tumor progression in distant sites and metastatic spread. This treatment was associated with increased activation of DCs in the draining lymph nodes and recruitment of both DCs and CD8(+T cells to the tumor. The particles remained within the tumor and no toxicities were observed. The immune induction observed was significantly greater compared to cryoablation. Further anti-tumor effects were observed when MRF/magnet therapy was combined with systemic low dose immunotherapy. Thus, mechanical disruption of the primary tumor with MRF/magnetic field application represents a novel means to induce systemic immune activation in cancer.

  18. Inflammation and Immune Response of Intra-Articular Serotype 2 Adeno-Associated Virus or Adenovirus Vectors in a Large Animal Model

    Directory of Open Access Journals (Sweden)

    Akikazu Ishihara

    2012-01-01

    Full Text Available Intra-articular gene therapy has potential for the treatment of osteoarthritis and rheumatoid arthritis. To quantify in vitro relative gene transduction, equine chondrocytes and synovial cells were treated with adenovirus vectors (Ad, serotype 2 adeno-associated virus vectors (rAAV2, or self-complementary (sc AAV2 vectors carrying green fluorescent protein (GFP. Using 6 horses, bilateral metacarpophalangeal joints were injected with Ad, rAAV2, or scAAV2 vectors carrying GFP genes to assess the in vivo joint inflammation and neutralizing antibody (NAb titer in serum and joint fluid. In vitro, the greater transduction efficiency and sustained gene expression were achieved by scAAV2 compared to rAAV2 in equine chondrocytes and synovial cells. In vivo, AAV2 demonstrated less joint inflammation than Ad, but similar NAb titer. The scAAV2 vectors can induce superior gene transduction than rAAV2 in articular cells, and both rAAV2 and scAAV2 vectors were showed to be safer for intra-articular use than Ad vectors.

  19. Too little but not too late: results of a literature review to improve routine immunization programs in developing countries.

    Science.gov (United States)

    Ryman, Tove K; Dietz, Vance; Cairns, K Lisa

    2008-06-21

    Globally, immunization services have been the center of renewed interest with increased funding to improve services, acceleration of the introduction of new vaccines, and the development of a health systems approach to improve vaccine delivery. Much of the credit for the increased attention is due to the work of the GAVI Alliance and to new funding streams. If routine immunization programs are to take full advantage of the newly available resources, managers need to understand the range of proven strategies and approaches to deliver vaccines to reduce the incidence of diseases. In this paper, we present strategies that may be used at the sub-national level to improve routine immunization programs. We conducted a systematic review of studies and projects reported in the published and gray literature. Each paper that met our inclusion criteria was rated based on methodological rigor and data were systematically abstracted. Routine-immunization - specific papers with a methodological rigor rating of greater than 60% and with conclusive results were reported. Greater than 11,000 papers were identified, of which 60 met our inclusion criteria and 25 papers were reported. Papers were grouped into four strategy approaches: bringing immunizations closer to communities (n = 11), using information dissemination to increase demand for vaccination (n = 3), changing practices in fixed sites (n = 4), and using innovative management practices (n = 7). Immunization programs are at a historical crossroads in terms of developing new funding streams, introducing new vaccines, and responding to the global interest in the health systems approach to improving immunization delivery. However, to complement this, actual service delivery needs to be strengthened and program managers must be aware of proven strategies. Much was learned from the 25 papers, such as the use of non-health workers to provide numerous services at the community level. However it was startling to see how few papers

  20. A low-cost repellent for malaria vectors in the Americas: results of two field trials in Guatemala and Peru

    Directory of Open Access Journals (Sweden)

    Sihuincha Moisés

    2007-08-01

    Full Text Available Abstract Background The cost of mosquito repellents in Latin America has discouraged their wider use among the poor. To address this problem, a low-cost repellent was developed that reduces the level of expensive repellent actives by combining them with inexpensive fixatives that appear to slow repellent evaporation. The chosen actives were a mixture of para-menthane-diol (PMD and lemongrass oil (LG. Methods To test the efficacy of the repellent, field trials were staged in Guatemala and Peru. Repellent efficacy was determined by human-landing catches on volunteers who wore the experimental repellents, control, or 15% DEET. The studies were conducted using a balanced Latin Square design with volunteers, treatments, and locations rotated each night. Results In Guatemala, collections were performed for two hours, commencing three hours after repellent application. The repellent provided >98% protection for five hours after application, with a biting pressure of >100 landings per person/hour. The 15% DEET control provided lower protection at 92% (p 46 landings per person/hour. The 20% DEET control provided significantly lower protection at 64% (p Conclusion In both locations, the PMD/LG repellent provided excellent protection up to six hours after application against a wide range of disease vectors including Anopheles darlingi. The addition of fixatives to the repellent extended its longevity while enhancing efficacy and significantly reducing its cost to malaria-endemic communities.

  1. Immunization with a Novel Human type 5 Adenovirus-Vectored Vaccine Expressing the Premembrane and Envelope Proteins of Zika Virus Provides Consistent and Sterilizing Protection in Multiple Immunocompetent and Immunocompromised Animal Models.

    Science.gov (United States)

    Guo, Qiang; Chan, Jasper Fuk-Woo; Poon, Vincent Kwok-Man; Wu, Shipo; Chan, Chris Chung-Sing; Hou, Lihua; Yip, Cyril Chik-Yan; Ren, Changpeng; Cai, Jian-Piao; Zhao, Mengsu; Zhang, Anna Jinxia; Song, Xiaohong; Chan, Kwok-Hung; Wang, Busen; Kok, Kin-Hang; Wen, Yanbo; Yuen, Kwok-Yung; Chen, Wei

    2018-03-29

    Zika virus (ZIKV) infection may be associated with severe complications and disseminated via both vector-borne and non-vector-borne routes. Adenovirus-vectored vaccines represent a favorable controlling measure for the ZIKV epidemic as they have been shown to be safe, immunogenic, and rapidly generable for other emerging viral infections. Evaluations of two previously reported adenovirus-vectored ZIKV vaccines were performed using non-lethal animal models and/or non-epidemic ZIKV strain. We constructed and evaluated two human adenovirus-5-vectored vaccines containing the ZIKV premembrane-envelope(Ad5-Sig-prM-Env) and envelope(Ad5-Env) proteins, respectively, in multiple non-lethal and lethal animal models using epidemic ZIKV strains. Both vaccines elicited robust humoral and cellular immune responses in immunocompetent BALB/c mice. Dexamethasone-immunosuppressed mice vaccinated with either vaccine demonstrated robust and durable antibody responses and significantly lower blood/tissue viral loads than controls(Panimal models, Ad5-Sig-prM-Env-vaccinated mice had significantly(P<0.05) higher titers of anti-ZIKV-specific neutralizing antibody titers and lower(undetectable) viral loads than Ad5-Env-vaccinated mice. The close correlation between the neutralizing antibody titer and viral load helped to explain the better protective effect of Ad5-Sig-prM-Env than Ad5-Env. Anamnestic response was absent in Ad5-Sig-prM-Env-vaccinated A129 mice. Ad5-Sig-prM-Env provided sterilizing protection against ZIKV infection in mice.

  2. Convexity and Marginal Vectors

    NARCIS (Netherlands)

    van Velzen, S.; Hamers, H.J.M.; Norde, H.W.

    2002-01-01

    In this paper we construct sets of marginal vectors of a TU game with the property that if the marginal vectors from these sets are core elements, then the game is convex.This approach leads to new upperbounds on the number of marginal vectors needed to characterize convexity.An other result is that

  3. Custodial vector model

    DEFF Research Database (Denmark)

    Becciolini, Diego; Franzosi, Diogo Buarque; Foadi, Roshan

    2015-01-01

    We analyze the Large Hadron Collider (LHC) phenomenology of heavy vector resonances with a $SU(2)_L\\times SU(2)_R$ spectral global symmetry. This symmetry partially protects the electroweak S-parameter from large contributions of the vector resonances. The resulting custodial vector model spectrum...

  4. Mucosal immunization with recombinant adenoviral vectors expressing murine gammaherpesvirus-68 genes M2 and M3 can reduce latent viral load

    DEFF Research Database (Denmark)

    Hoegh-Petersen, Mette; Thomsen, Allan R; Christensen, Jan P

    2009-01-01

    -68 (MHV-68) is a member of the Gammaherpesvirinae subfamily and represents a useful murine model for this category of infections, in which new vaccination strategies may initially be evaluated. Two attenuated variants of MHV-68 have successfully been used as vaccines, but the oncogenic potential...... of the gammaherpesvirinae speaks against using a similar approach in humans. DNA immunization with plasmids encoding the MHV-68 genes M2 or M3 caused a reduction in either acute or early latent viral load, respectively, but neither immunization had an effect at times later than 14 days post-infection. Adenovirus......-based vaccines are substantially more immunogenic than DNA vaccines and can be applied to induce mucosal immunity. Here we show that a significant reduction of the late viral load in the spleens, at 60 days post-infection, was achieved when immunizing mice both intranasally and subcutaneously with adenoviral...

  5. Lentiviral vectors in cancer immunotherapy.

    Science.gov (United States)

    Oldham, Robyn Aa; Berinstein, Elliot M; Medin, Jeffrey A

    2015-01-01

    Basic science advances in cancer immunotherapy have resulted in various treatments that have recently shown success in the clinic. Many of these therapies require the insertion of genes into cells to directly kill them or to redirect the host's cells to induce potent immune responses. Other analogous therapies work by modifying effector cells for improved targeting and enhanced killing of tumor cells. Initial studies done using γ-retroviruses were promising, but safety concerns centered on the potential for insertional mutagenesis have highlighted the desire to develop other options for gene delivery. Lentiviral vectors (LVs) have been identified as potentially more effective and safer alternative delivery vehicles. LVs are now in use in clinical trials for many different types of inherited and acquired disorders, including cancer. This review will discuss current knowledge of LVs and the applications of this viral vector-based delivery vehicle to cancer immunotherapy.

  6. Investigating the Potential Range Expansion of the Vector Mosquito Aedes aegypti in Mexico with NASA Earth Science Remote Sensing Results

    Science.gov (United States)

    Crosson, W. L.; Eisen, L.; Estes, M. G.; Estes, S. M.; Hayden, M.; Lozano-Fuentes, S.; Monaghan, A. J.; Moreno Madriñán, M. J.; Ochoa, C.; Quattrochi, D.; Tapia, B.; Welsh-Rodriguez, C. M.

    2012-12-01

    In tropical and sub-tropical regions, the mosquito Aedes aegypti is the major vector for the virus causing dengue, a serious public health issue in these areas. Through ongoing NSF- and NASA-funded studies, field surveys of Aedes aegypti and an integrated modeling approach are being used to improve our understanding of the potential range of the mosquito to expand toward heavily populated high elevation areas such as Mexico City under various climate change and socio-economic scenarios. This work serves three primary objectives: (1) Employ NASA remotely-sensed data to supplement the environmental monitoring and modeling component of the project. These data -- for example, surface temperature, precipitation, vegetation indices, soil moisture and elevation -- are critical for understanding the habitat necessary for mosquito survival and abundance; (2) Implement training sessions to instruct scientists and students from Mexico and the U.S. on how to use remote sensing and implement the NASA SERVIR Regional Visualization and Monitoring System; (3) Employ the SERVIR framework to optimize the dissemination of key project results in order to increase their societal relevance and benefits in developing climate adaptation strategies. Field surveys of larval, pupal and adult Aedes aegypti, as well as detailed physical and social household characteristics, were conducted in the summers of 2011and 2012 at geographic scales from the household to the community along a transect from sea level to 2400 m ASL. These data are being used in models to estimate Aedes aegypti habitat suitability. In 2011, Aedes aegypti were identified at an elevation of over 2150 m in Puebla, the highest elevation at which this species has been observed.

  7. Web-based public health geographic information systems for resources-constrained environment using scalable vector graphics technology: a proof of concept applied to the expanded program on immunization data.

    Science.gov (United States)

    Kamadjeu, Raoul; Tolentino, Herman

    2006-06-03

    Geographic Information Systems (GIS) are powerful communication tools for public health. However, using GIS requires considerable skill and, for this reason, is sometimes limited to experts. Web-based GIS has emerged as a solution to allow a wider audience to have access to geospatial information. Unfortunately the cost of implementing proprietary solutions may be a limiting factor in the adoption of a public health GIS in a resource-constrained environment. Scalable Vector Graphics (SVG) is used to define vector-based graphics for the internet using XML (eXtensible Markup Language); it is an open, platform-independent standard maintained by the World Wide Web Consortium (W3C) since 2003. In this paper, we summarize our methodology and demonstrate the potential of this free and open standard to contribute to the dissemination of Expanded Program on Immunization (EPI) information by providing interactive maps to a wider audience through the Internet. We used SVG to develop a database driven web-based GIS applied to EPI data from three countries of WHO AFRO (World Health Organization - African Region). The system generates interactive district-level country immunization coverage maps and graphs. The approach we describe can be expanded to cover other public health GIS demanding activities, including the design of disease atlases in a resources-constrained environment. Our system contributes to accumulating evidence demonstrating the potential of SVG technology to develop web-based public health GIS in resources-constrained settings.

  8. Deletion of A44L, A46R and C12L Vaccinia Virus Genes from the MVA Genome Improved the Vector Immunogenicity by Modifying the Innate Immune Response Generating Enhanced and Optimized Specific T-Cell Responses

    Directory of Open Access Journals (Sweden)

    María Pía Holgado

    2016-05-01

    Full Text Available MVA is an attenuated vector that still retains immunomodulatory genes. We have previously reported its optimization after deleting the C12L gene, coding for the IL-18 binding-protein. Here, we analyzed the immunogenicity of MVA vectors harboring the simultaneous deletion of A44L, related to steroid synthesis and A46R, a TLR-signaling inhibitor (MVAΔA44L-A46R; or also including a deletion of C12L (MVAΔC12L/ΔA44L-A46R. The absence of biological activities of the deleted genes in the MVA vectors was demonstrated. Adaptive T-cell responses against VACV epitopes, evaluated in spleen and draining lymph-nodes of C57Bl/6 mice at acute/memory phases, were of higher magnitude in those animals that received deleted MVAs compared to MVAwt. MVAΔC12L/ΔA44L-A46R generated cellular specific memory responses of higher quality characterized by bifunctionality (CD107a/b+/IFN-γ+ and proliferation capacity. Deletion of selected genes from MVA generated innate immune responses with higher levels of determining cytokines related to T-cell response generation, such as IL-12, IFN-γ, as well as IL-1β and IFN-β. This study describes for the first time that simultaneous deletion of the A44L, A46R and C12L genes from MVA improved its immunogenicity by enhancing the host adaptive and innate immune responses, suggesting that this approach comprises an appropriate strategy to increase the MVA vaccine potential.

  9. Induction of complex immune responses and strong protection against retrovirus challenge by adenovirus-based immunization depends on the order of vaccine delivery.

    Science.gov (United States)

    Kaulfuß, Meike; Wensing, Ina; Windmann, Sonja; Hrycak, Camilla Patrizia; Bayer, Wibke

    2017-02-06

    In the Friend retrovirus mouse model we developed potent adenovirus-based vaccines that were designed to induce either strong Friend virus GagL 85-93 -specific CD8 + T cell or antibody responses, respectively. To optimize the immunization outcome we evaluated vaccination strategies using combinations of these vaccines. While the vaccines on their own confer strong protection from a subsequent Friend virus challenge, the simple combination of the vaccines for the establishment of an optimized immunization protocol did not result in a further improvement of vaccine effectivity. We demonstrate that the co-immunization with GagL 85-93 /leader-gag encoding vectors together with envelope-encoding vectors abrogates the induction of GagL 85-93 -specific CD8 + T cells, and in successive immunization protocols the immunization with the GagL 85-93 /leader-gag encoding vector had to precede the immunization with an envelope encoding vector for the efficient induction of GagL 85-93 -specific CD8 + T cells. Importantly, the antibody response to envelope was in fact enhanced when the mice were adenovirus-experienced from a prior immunization, highlighting the expedience of this approach. To circumvent the immunosuppressive effect of envelope on immune responses to simultaneously or subsequently administered immunogens, we developed a two immunizations-based vaccination protocol that induces strong immune responses and confers robust protection of highly Friend virus-susceptible mice from a lethal Friend virus challenge.

  10. Augmentation of alphavirus vector-induced human papilloma virus-specific immune and anti-tumour responses by co-expression of interleukin-12

    NARCIS (Netherlands)

    Riezebos-Brilman, Annelies; Regts, Joke; Chen, Margaret; Wilschut, Jan; Daemen, Toos

    2009-01-01

    To enhance the efficacy of a therapeutic immunisition strategy against human papillomavirus-induced cervical cancer we evaluated the adjuvant effect of interleukin-12 (IL12) expressed by a Semliki Forest virus vector (SFV) in mice. Depending on the dose and schedule. SFV-IL12 Stimulated

  11. Evaluation of the Impact of an Innovative Immunization Practice Model Designed to Improve Population Health: Results of the Project IMPACT Immunizations Pilot.

    Science.gov (United States)

    Bluml, Benjamin M; Brock, Kelly A; Hamstra, Scott; Tonrey, Lisa

    2018-02-01

    The goal of the initiative was to evaluate the impact of an innovative practice model on identification of unmet vaccination needs and vaccination rates. This was accomplished through a prospective, multisite, observational study in 8 community pharmacy practices with adults receiving an influenza vaccine with a documented vaccination forecast review from October 22, 2015 through March 22, 2016. When patients presented for influenza vaccinations, pharmacists utilized immunization information systems (IIS) data at the point of care to identify unmet vaccination needs, educate patients, and improve vaccination rates. The main outcome measures were the number of vaccination forecast reviews, patients educated, unmet vaccination needs identified and resolved, and vaccines administered. Pharmacists reviewed vaccination forecasts generated by clinical decision-support technology based on patient information documented in the IIS for 1080 patients receiving influenza vaccinations. The vaccination forecasts predicted there were 1566 additional vaccinations due at the time patients were receiving the influenza vaccine. Pharmacist assessments identified 36 contraindications and 196 potential duplications, leaving a net of 1334 unmet vaccination needs eligible for vaccination. In all, 447 of the 1334 unmet vaccinations needs were resolved during the 6-month study period, and the remainder of patients received information about their vaccination needs and recommendations to follow up for their vaccinations. Integration of streamlined principle-centered processes of care in immunization practices that allow pharmacists to utilize actionable point-of-care data resulted in identification of unmet vaccination needs, education of patients about their vaccination needs, a 41.4% increase in the number of vaccines administered, and significant improvements in routinely recommended adult vaccination rates.

  12. Enhancement of Mucosal Immunogenicity of Viral Vectored Vaccines by the NKT Cell Agonist Alpha-Galactosylceramide as Adjuvant

    Directory of Open Access Journals (Sweden)

    Shailbala Singh

    2014-10-01

    Full Text Available Gene-based vaccination strategies, specifically viral vectors encoding vaccine immunogens are effective at priming strong immune responses. Mucosal routes offer practical advantages for vaccination by ease of needle-free administration, and immunogen delivery at readily accessible oral/nasal sites to efficiently induce immunity at distant gut and genital tissues. However, since mucosal tissues are inherently tolerant for induction of immune responses, incorporation of adjuvants for optimal mucosal vaccination strategies is important. We report here the effectiveness of alpha-galactosylceramide (α-GalCer, a synthetic glycolipid agonist of natural killer T (NKT cells, as an adjuvant for enhancing immunogenicity of vaccine antigens delivered using viral vectors by mucosal routes in murine and nonhuman primate models. Significant improvement in adaptive immune responses in systemic and mucosal tissues was observed by including α-GalCer adjuvant for intranasal immunization of mice with vesicular stomatitis virus vector encoding the model antigen ovalbumin and adenoviral vectors expressing HIV env and Gag antigens. Activation of NKT cells in systemic and mucosal tissues along with significant increases in adaptive immune responses were observed in rhesus macaques immunized by intranasal and sublingual routes with protein or adenovirus vectored antigens when combined with α-GalCer adjuvant. These results support the utility of α-GalCer adjuvant for enhancing immunogenicity of mucosal vaccines delivered using viral vectors.

  13. Vector analysis

    CERN Document Server

    Newell, Homer E

    2006-01-01

    When employed with skill and understanding, vector analysis can be a practical and powerful tool. This text develops the algebra and calculus of vectors in a manner useful to physicists and engineers. Numerous exercises (with answers) not only provide practice in manipulation but also help establish students' physical and geometric intuition in regard to vectors and vector concepts.Part I, the basic portion of the text, consists of a thorough treatment of vector algebra and the vector calculus. Part II presents the illustrative matter, demonstrating applications to kinematics, mechanics, and e

  14. Influence of tularemia live vaccine immunization on the immediate and end-results of combined treatment of patients with endometrial carcinoma

    International Nuclear Information System (INIS)

    Adamyan, R.T.; Movsesyan, M.A.

    1999-01-01

    Early and delayed results of the combined treatment (surgery + remote gamma therapy) of patients with corpus uteri carcinoma preliminary immunized with tularemia live vaccine (TLV). It is shown that the immunization of almost all indices of delayed treatment results ay all disease stages [ru

  15. Long-term results of splenectomy in adult chronic immune thrombocytopenia.

    Science.gov (United States)

    Guan, Yue; Wang, Shixuan; Xue, Feng; Liu, Xiaofan; Zhang, Lei; Li, Huiyuan; Yang, Renchi

    2017-03-01

    We performed this study in adult patients with chronic primary immune thrombocytopenia to explore the long-term efficacy and safety of splenectomy. Data of 174 patients who underwent splenectomy in our hospital from 1994 to 2014 were analyzed. After splenectomy, 126 (72.4%) patients achieved a complete response (CR) and 28 (16.1%) achieved a response (R). Thirty-two (20.8%) responders relapsed with a median time of 24 months. Compared with non-responders and recurrent patients, the stable responders were younger and had higher preoperation and postoperation peak platelet count, later peak platelet count emergence time, and more megakaryocytes. Corticosteroid-dependent patients were more likely to response to splenectomy than those refractory to corticosteroid. We performed a relapse-free survival analysis among the 154 responders. In univariate analyses, corticosteroid dependent and time from diagnosis to splenectomy ≤24 months showed predictive value to persistent response. But only corticosteroid dependent was a significant predictor in multivariate analysis. The 30-d complication rate after the surgery was 25.9%. There were five (2.9%) patients experienced thrombosis and three (1.7%) refractory patients died during follow-up. Splenectomy was a safe treatment with a cure rate of 58.0%. Corticosteroid dependent showed predictive value to persistent response. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Monitoring Results in Routine Immunization: Development of Routine Immunization Dashboard in Selected African Countries in the Context of the Polio Eradication Endgame Strategic Plan.

    Science.gov (United States)

    Poy, Alain; van den Ent, Maya M V X; Sosler, Stephen; Hinman, Alan R; Brown, Sidney; Sodha, Samir; Ehlman, Daniel C; Wallace, Aaron S; Mihigo, Richard

    2017-07-01

    To monitor immunization-system strengthening in the Polio Eradication Endgame Strategic Plan 2013-2018 (PEESP), the Global Polio Eradication Initiative identified 1 indicator: 10% annual improvement in third dose of diphtheria- tetanus-pertussis-containing vaccine (DTP3) coverage in polio high-risk districts of 10 polio focus countries. A multiagency team, including staff from the African Region, developed a comprehensive list of outcome and process indicators measuring various aspects of the performance of an immunization system. The development and implementation of the dashboard to assess immunization system performance allowed national program managers to monitor the key immunization indicators and stratify by high-risk and non-high-risk districts. Although only a single outcome indicator goal (at least 10% annual increase in DTP3 coverage achieved in 80% of high-risk districts) initially existed in the endgame strategy, we successfully added additional outcome indicators (eg, decreasing the number of DTP3-unvaccinated children) as well as program process indicators focusing on cold chain, stock availability, and vaccination sessions to better describe progress on the pathway to raising immunization coverage. When measuring progress toward improving immunization systems, it is helpful to use a comprehensive approach that allows for measuring multiple dimensions of the system. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  17. Effects of Vector Backbone and Pseudotype on Lentiviral Vector-mediated Gene Transfer: Studies in Infant ADA-Deficient Mice and Rhesus Monkeys

    Science.gov (United States)

    Carbonaro Sarracino, Denise; Tarantal, Alice F; Lee, C Chang I.; Martinez, Michele; Jin, Xiangyang; Wang, Xiaoyan; Hardee, Cinnamon L; Geiger, Sabine; Kahl, Christoph A; Kohn, Donald B

    2014-01-01

    Systemic delivery of a lentiviral vector carrying a therapeutic gene represents a new treatment for monogenic disease. Previously, we have shown that transfer of the adenosine deaminase (ADA) cDNA in vivo rescues the lethal phenotype and reconstitutes immune function in ADA-deficient mice. In order to translate this approach to ADA-deficient severe combined immune deficiency patients, neonatal ADA-deficient mice and newborn rhesus monkeys were treated with species-matched and mismatched vectors and pseudotypes. We compared gene delivery by the HIV-1-based vector to murine γ-retroviral vectors pseudotyped with vesicular stomatitis virus-glycoprotein or murine retroviral envelopes in ADA-deficient mice. The vesicular stomatitis virus-glycoprotein pseudotyped lentiviral vectors had the highest titer and resulted in the highest vector copy number in multiple tissues, particularly liver and lung. In monkeys, HIV-1 or simian immunodeficiency virus vectors resulted in similar biodistribution in most tissues including bone marrow, spleen, liver, and lung. Simian immunodeficiency virus pseudotyped with the gibbon ape leukemia virus envelope produced 10- to 30-fold lower titers than the vesicular stomatitis virus-glycoprotein pseudotype, but had a similar tissue biodistribution and similar copy number in blood cells. The relative copy numbers achieved in mice and monkeys were similar when adjusted to the administered dose per kg. These results suggest that this approach can be scaled-up to clinical levels for treatment of ADA-deficient severe combined immune deficiency subjects with suboptimal hematopoietic stem cell transplantation options. PMID:24925206

  18. Effects of vector backbone and pseudotype on lentiviral vector-mediated gene transfer: studies in infant ADA-deficient mice and rhesus monkeys.

    Science.gov (United States)

    Carbonaro Sarracino, Denise; Tarantal, Alice F; Lee, C Chang I; Martinez, Michele; Jin, Xiangyang; Wang, Xiaoyan; Hardee, Cinnamon L; Geiger, Sabine; Kahl, Christoph A; Kohn, Donald B

    2014-10-01

    Systemic delivery of a lentiviral vector carrying a therapeutic gene represents a new treatment for monogenic disease. Previously, we have shown that transfer of the adenosine deaminase (ADA) cDNA in vivo rescues the lethal phenotype and reconstitutes immune function in ADA-deficient mice. In order to translate this approach to ADA-deficient severe combined immune deficiency patients, neonatal ADA-deficient mice and newborn rhesus monkeys were treated with species-matched and mismatched vectors and pseudotypes. We compared gene delivery by the HIV-1-based vector to murine γ-retroviral vectors pseudotyped with vesicular stomatitis virus-glycoprotein or murine retroviral envelopes in ADA-deficient mice. The vesicular stomatitis virus-glycoprotein pseudotyped lentiviral vectors had the highest titer and resulted in the highest vector copy number in multiple tissues, particularly liver and lung. In monkeys, HIV-1 or simian immunodeficiency virus vectors resulted in similar biodistribution in most tissues including bone marrow, spleen, liver, and lung. Simian immunodeficiency virus pseudotyped with the gibbon ape leukemia virus envelope produced 10- to 30-fold lower titers than the vesicular stomatitis virus-glycoprotein pseudotype, but had a similar tissue biodistribution and similar copy number in blood cells. The relative copy numbers achieved in mice and monkeys were similar when adjusted to the administered dose per kg. These results suggest that this approach can be scaled-up to clinical levels for treatment of ADA-deficient severe combined immune deficiency subjects with suboptimal hematopoietic stem cell transplantation options.

  19. HPV Vaccination among Adolescent Males: Results from the National Immunization Survey-Teen

    Science.gov (United States)

    Reiter, Paul L.; Gilkey, Melissa B.; Brewer, Noel T.

    2013-01-01

    US guidelines provided a permissive recommendation forHPV vaccine for males in 2009, with an updated recommendation for routine vaccination in 2011. Dataon vaccine uptake among males, however, remain sparse. We analyzed 2010–2011 data (collected mostlyprior to the recommendation for routine vaccination) from the National Immunization Survey-Teen for a nationally representative sample of adolescent males ages 13–17 (n=22,365). We examined HPV vaccine initiation( receipt of at least one doseba sed on healthcare provider records) as the primary outcome. Analyses used weighted logistic regression. HPV vaccine initiation increased from 1.4% in 2010 to 8.3% in 2011. Parents who reported receiving a healthcare provider recommendation to get their sons HPV vaccine were much more likely to have vaccinated sons (OR=19.02, 95% CI: 14.36–25.19). Initiation was also higher among sons who were Hispanic (OR=1.83, 95% CI: 1.24–2.71) or who were eligible for the Vaccines for Children program (OR=1.53, 95% CI: 1.01–2.31). Only31.0% of parents with unvaccinated sons indicatedtheir sons were “somewhat likely” or “very likely” to receive HPV vaccine in the next year. The most common main reasons for parents not intending to vaccinate were believing vaccination is not needed or not necessary (24.5%), not having received a provider recommendation (22.1%), and lack of knowledge (15.9%). HPV vaccination is low among adolescent males in the US, and provider recommendation for vaccination is likely keyto improv ingvaccine uptake. Given the updated recommendation for routine vaccination and the changes in health insurance coverage that are likely to follow, continued efforts are needed to monitor HPV vaccination among males. PMID:23602667

  20. A rapid Q-PCR titration protocol for adenovirus and helper-dependent adenovirus vectors that produces biologically relevant results

    Science.gov (United States)

    Gallaher, Sean D.; Berk, Arnold J.

    2013-01-01

    Adenoviruses are employed in the study of cellular processes and as expression vectors used in gene therapy. The success and reproducibility of these studies is dependent in part on having accurate and meaningful titers of replication competent and helper-dependent adenovirus stocks, which is problematic due to the use of varied and divergent titration protocols. Physical titration methods, which quantify the total number of viral particles, are used by many, but are poor at estimating activity. Biological titration methods, such as plaque assays, are more biologically relevant, but are time consuming and not applicable to helper-dependent gene therapy vectors. To address this, a protocol was developed called “infectious genome titration” in which viral DNA is isolated from the nuclei of cells ~3 h post-infection, and then quantified by Q-PCR. This approach ensures that only biologically active virions are counted as part of the titer determination. This approach is rapid, robust, sensitive, reproducible, and applicable to all forms of adenovirus. Unlike other Q-PCR-based methods, titers determined by this protocol are well correlated with biological activity. PMID:23624118

  1. A fusion protein of HCMV IE1 exon4 and IE2 exon5 stimulates potent cellular immunity in an MVA vaccine vector

    International Nuclear Information System (INIS)

    Wang, Z.; Zhou, W.; Srivastava, T.; La Rosa, C.; Mandarino, A.; Forman, S.J.; Zaia, J.A.; Britt, W.J.; Diamond, D.J.

    2008-01-01

    A therapeutic CMV vaccine incorporating an antigenic repertoire capable of eliciting a cellular immune response has yet to be successfully implemented for patients who already have acquired an infection. To address this problem, we have developed a vaccine candidate derived from modified vaccinia Ankara (MVA) that expresses three immunodominant antigens (pp65, IE1, IE2) from CMV. The novelty of this vaccine is the fusion of two adjacent exons from the immediate-early region of CMV, their successful expression in MVA, and robust immunogenicity in both primary and memory response models. Evaluation of the immunogenicity of the viral vaccine in mouse models shows that it can stimulate primary immunity against all three antigens in both the CD4 + and CD8 + T cell subsets. Evaluation of human PBMC from healthy CMV-positive donors or patients within 6 months of receiving hematopoietic cell transplant shows robust stimulation of existing CMV-specific CD4 + and CD8 + T cell subsets

  2. Long-lived tissue resident HIV-1 specific memory CD8+ T cells are generated by skin immunization with live virus vectored microneedle arrays

    OpenAIRE

    Zaric, Marija; Becker, Pablo Daniel; Hervouet, Catherine; Kalcheva, Petya; Ibarzo Yus, Barbara; Cocita, Clement; O'Neill, Lauren Alexandra; Kwon, Sung-Yun; Klavinskis, Linda Sylvia

    2017-01-01

    The generation of tissue resident memory (TRM) cells at the body surfaces to provide a front line defence against invading pathogens represents an important goal in vaccine development for a wide variety of pathogens. It has been widely assumed that local vaccine delivery to the mucosae is necessary to achieve that aim. Here we characterise a novel micro-needle array (MA) delivery system fabricated to deliver a live recombinant human adenovirus type 5 vaccine vector (AdHu5) encoding HIV-1 gag...

  3. Elementary vectors

    CERN Document Server

    Wolstenholme, E Œ

    1978-01-01

    Elementary Vectors, Third Edition serves as an introductory course in vector analysis and is intended to present the theoretical and application aspects of vectors. The book covers topics that rigorously explain and provide definitions, principles, equations, and methods in vector analysis. Applications of vector methods to simple kinematical and dynamical problems; central forces and orbits; and solutions to geometrical problems are discussed as well. This edition of the text also provides an appendix, intended for students, which the author hopes to bridge the gap between theory and appl

  4. HIV-1 Adaptation to Antigen Processing Results in Population-Level Immune Evasion and Affects Subtype Diversification

    DEFF Research Database (Denmark)

    Tenzer, Stefan; Crawford, Hayley; Pymm, Phillip

    2014-01-01

    these regions encode epitopes presented by ~30 more common HLA variants. By combining epitope processing and computational analyses of the two HIV subtypes responsible for ~60% of worldwide infections, we identified a hitherto unrecognized adaptation to the antigen-processing machinery through substitutions...... of intrapatient adaptations, is predictable, facilitates viral subtype diversification, and increases global HIV diversity. Because low epitope abundance is associated with infrequent and weak T cell responses, this most likely results in both population-level immune evasion and inadequate responses in most...

  5. Replacing a native Wolbachia with a novel strain results in an increase in endosymbiont load and resistance to dengue virus in a mosquito vector.

    Directory of Open Access Journals (Sweden)

    Guowu Bian

    Full Text Available Wolbachia is a maternally transmitted endosymbiotic bacterium that is estimated to infect up to 65% of insect species. The ability of Wolbachia to both induce pathogen interference and spread into mosquito vector populations makes it possible to develop Wolbachia as a biological control agent for vector-borne disease control. Although Wolbachia induces resistance to dengue virus (DENV, filarial worms, and Plasmodium in mosquitoes, species like Aedes polynesiensis and Aedes albopictus, which carry native Wolbachia infections, are able to transmit dengue and filariasis. In a previous study, the native wPolA in Ae. polynesiensis was replaced with wAlbB from Ae. albopictus, and resulted in the generation of the transinfected "MTB" strain with low susceptibility for filarial worms. In this study, we compare the dynamics of DENV serotype 2 (DENV-2 within the wild type "APM" strain and the MTB strain of Ae. polynesiensis by measuring viral infection in the mosquito whole body, midgut, head, and saliva at different time points post infection. The results show that wAlbB can induce a strong resistance to DENV-2 in the MTB mosquito. Evidence also supports that this resistance is related to a dramatic increase in Wolbachia density in the MTB's somatic tissues, including the midgut and salivary gland. Our results suggests that replacement of a native Wolbachia with a novel infection could serve as a strategy for developing a Wolbachia-based approach to target naturally infected insects for vector-borne disease control.

  6. Vector Fields on Product Manifolds

    OpenAIRE

    Kurz, Stefan

    2011-01-01

    This short report establishes some basic properties of smooth vector fields on product manifolds. The main results are: (i) On a product manifold there always exists a direct sum decomposition into horizontal and vertical vector fields. (ii) Horizontal and vertical vector fields are naturally isomorphic to smooth families of vector fields defined on the factors. Vector fields are regarded as derivations of the algebra of smooth functions.

  7. ARGINASE 2 DEFICIENCY RESULTS IN SPONTANEOUS STEATOHEPATITIS: A NOVEL LINK BETWEEN INNATE IMMUNE ACTIVATION AND HEPATIC DE NOVO LIPOGENESIS

    Science.gov (United States)

    Navarro, Laura A.; Wree, Alexander; Povero, Davide; Berk, Michael P.; Eguchi, Akiko; Ghosh, Sudakshina; Papouchado, Bettina G.; Erzurum, Serpil C.; Feldstein, Ariel E.

    2016-01-01

    BACKGROUND & AIMS Innate immune activation has been postulated as a central mechanism for disease progression from hepatic steatosis to steatohepatitis in obesity-related fatty liver disease. Arginase 2 competes with inducible nitric oxide synthase (iNOS) for its substrate and the balance between these two enzymes plays a crucial role in regulating immune responses and macrophage activation. Our aim was to test the hypothesis that arginase 2 deficiency in mice favors progression from isolated hepatic steatosis, induced by high fat feeding to steatohepatitis. METHODS Arginase 2-knockout (Arg2−/−) mice were studied for changes in liver histology and metabolic phenotype at baseline and after a short term course (7 week) feeding with a high fat (HFAT) diet. In additional experiments, Arg2−/− mice received tail vein injections of liposome-encapsulated clodronate (CLOD) over a three-week period to selectively deplete liver macrophages. RESULTS Unexpectedly, Arg2−/− mice showed profound changes in their livers at baseline characterized by significant steatosis as demonstrated with histological and biochemical analysis. These changes were independent of systemic metabolic parameters and associated with marked increase mRNA levels of genes involved in hepatic de novo lipogenesis. Liver injury and inflammation were present with elevated serum ALT, marked infiltration of F4/80 positive cells, and increased mRNA levels of inflammatory genes. HFAT feeding exacerbated these changes. Macrophage depletion after CLOD injection significantly attenuated lipid deposition and normalized lipogenic mRNA profile of livers from Arg2−/− mice. CONCLUSIONS This study identifies arginase 2 as novel link between innate immune responses, hepatic lipid deposition, and liver injury. PMID:25234945

  8. Custodial vector model

    Science.gov (United States)

    Becciolini, Diego; Franzosi, Diogo Buarque; Foadi, Roshan; Frandsen, Mads T.; Hapola, Tuomas; Sannino, Francesco

    2015-07-01

    We analyze the Large Hadron Collider (LHC) phenomenology of heavy vector resonances with a S U (2 )L×S U (2 )R spectral global symmetry. This symmetry partially protects the electroweak S parameter from large contributions of the vector resonances. The resulting custodial vector model spectrum and interactions with the standard model fields lead to distinct signatures at the LHC in the diboson, dilepton, and associated Higgs channels.

  9. Implicit Real Vector Automata

    Directory of Open Access Journals (Sweden)

    Jean-François Degbomont

    2010-10-01

    Full Text Available This paper addresses the symbolic representation of non-convex real polyhedra, i.e., sets of real vectors satisfying arbitrary Boolean combinations of linear constraints. We develop an original data structure for representing such sets, based on an implicit and concise encoding of a known structure, the Real Vector Automaton. The resulting formalism provides a canonical representation of polyhedra, is closed under Boolean operators, and admits an efficient decision procedure for testing the membership of a vector.

  10. A low-cost repellent for malaria vectors in the Americas: results of two field trials in Guatemala and Peru.

    Science.gov (United States)

    Moore, Sarah J; Darling, Samuel T; Sihuincha, Moisés; Padilla, Norma; Devine, Gregor J

    2007-08-01

    The cost of mosquito repellents in Latin America has discouraged their wider use among the poor. To address this problem, a low-cost repellent was developed that reduces the level of expensive repellent actives by combining them with inexpensive fixatives that appear to slow repellent evaporation. The chosen actives were a mixture of para-menthane-diol (PMD) and lemongrass oil (LG). To test the efficacy of the repellent, field trials were staged in Guatemala and Peru. Repellent efficacy was determined by human-landing catches on volunteers who wore the experimental repellents, control, or 15% DEET. The studies were conducted using a balanced Latin Square design with volunteers, treatments, and locations rotated each night. In Guatemala, collections were performed for two hours, commencing three hours after repellent application. The repellent provided >98% protection for five hours after application, with a biting pressure of >100 landings per person/hour. The 15% DEET control provided lower protection at 92% (p 46 landings per person/hour. The 20% DEET control provided significantly lower protection at 64% (p < 0.0001). In both locations, the PMD/LG repellent provided excellent protection up to six hours after application against a wide range of disease vectors including Anopheles darlingi. The addition of fixatives to the repellent extended its longevity while enhancing efficacy and significantly reducing its cost to malaria-endemic communities.

  11. Immune System

    Science.gov (United States)

    A properly functioning immune system is essential to good health. It defends the body against infectious agents and in some cases tumor cells. Individuals with immune deficiencies resulting from genetic defects, diseases (e.g., AIDS, leukemia), or drug therapies are more suscepti...

  12. Vector analysis

    CERN Document Server

    Brand, Louis

    2006-01-01

    The use of vectors not only simplifies treatments of differential geometry, mechanics, hydrodynamics, and electrodynamics, but also makes mathematical and physical concepts more tangible and easy to grasp. This text for undergraduates was designed as a short introductory course to give students the tools of vector algebra and calculus, as well as a brief glimpse into these subjects' manifold applications. The applications are developed to the extent that the uses of the potential function, both scalar and vector, are fully illustrated. Moreover, the basic postulates of vector analysis are brou

  13. Determination of the components of three dimensional vector and tensor anisotropy of cosmic radiation with application to the results of the Musala experiment

    International Nuclear Information System (INIS)

    Somogyi, A.J.

    1976-09-01

    The paper proves that it is possible to interpret the experimental results of the Musala experiment as being consequences of a vector anisotropy with maximum in the direction of the galactic centre and a tensor anisotropy with principal axes in the physically plausible directions of the galactic arm, the normal direction of the galactic plane and the direction perpendicular them, respectively. It is underlined that the interpretation is not the only possible one and, in addition to this, statistical errors are rather large. The results favour the galactic origin of the particles concerned (E=6x10 13 eV). (Sz.N.Z.)

  14. Immunization with a dicistronic plasmid expressing a truncated form of bovine herpesvirus-1 glycoprotein D and the amino-terminal subunit of glycoprotein B results in reduced gB-specific immune responses

    International Nuclear Information System (INIS)

    Manoj, Sharmila; Babiuk, Lorne A.; Drunen Littel van-Hurk, Sylvia van den

    2003-01-01

    As an approach to create a divalent DNA vaccine, a truncated secreted version of bovine herpesvirus-1 (BHV-1) glycoprotein D (tgD) and the amino-terminal subunit of glycoprotein B (gBb) were expressed from a dicistronic plasmid, designated pSLIAtgD-IRES-gBb. Intradermal immunization of mice with pSLIAtgD-IRES-gBb or a mixture of plasmids encoding tgD (pSLIAtgD) and gBb (pSLIAgBb) by needle injection or gene gun elicited strong tgD-specific immune responses. However, a significant reduction in gBb-specific immune responses was observed upon immunization of mice with pSLIAtgD-IRES-gBb or a mixture of pSLIAtgD and pSLIAgBb in comparison to immunization with pSLIAgBb alone. This reduction in gBb-specific immune responses induced by pSLIAtgD-IRES-gBb was due to production of low amounts of gBb from pSLIAtgD-IRES-gBb, inefficient processing and transport of gBb, and possibly competition for antigen-presenting cells by tgD and gBb. These results indicate that, although divalent plasmids may be used to express different antigens, the efficacy of vaccination with such plasmids may be influenced by the plasmid design and the characteristics of the expressed antigens

  15. [Results of acyclovir treatment of chickenpox and herpes zoster in children with immune tolerance].

    Science.gov (United States)

    Jankowska, H; Szczepańska-Putz, M; Wojnarowski, M

    Acyclovir was used for the treatment of Varicella-zoster virus infections in 53 children (10 neonates and 43 children aged between 2 an 15 years) with immunological system deficiency hospitalized at the Department of the Infectious Diseases of Childhood in the Medical Academy in Warszawa. The obtained results of therapy were favourable except one fatal case of the child with visceral dissemination of the virus prior to acyclovir treatment. Compared with other antiviral agents used by the authors previously, acyclovir proved to be the most effective.

  16. Results from a survey of national immunization programmes on home-based vaccination record practices in 2013

    OpenAIRE

    Young, Stacy L.; Gacic-Dobo, Marta; Brown, David W.

    2015-01-01

    Background Data on home-based records (HBRs) practices within national immunization programmes are non-existent, making it difficult to determine whether current efforts of immunization programmes related to basic recording of immunization services are appropriately focused. Methods During January 2014, WHO and the United Nations Children's Fund sent a one-page questionnaire to 195 countries to obtain information on HBRs including type of record used, number of records printed, whether record...

  17. Vector velocimeter

    DEFF Research Database (Denmark)

    2012-01-01

    The present invention relates to a compact, reliable and low-cost vector velocimeter for example for determining velocities of particles suspended in a gas or fluid flow, or for determining velocity, displacement, rotation, or vibration of a solid surface, the vector velocimeter comprising a laser...

  18. Simian virus 40 vectors for pulmonary gene therapy

    Directory of Open Access Journals (Sweden)

    Oppenheim Ariella

    2007-10-01

    Full Text Available Abstract Background Sepsis remains the leading cause of death in critically ill patients. One of the primary organs affected by sepsis is the lung, presenting as the Acute Respiratory Distress Syndrome (ARDS. Organ damage in sepsis involves an alteration in gene expression, making gene transfer a potential therapeutic modality. This work examines the feasibility of applying simian virus 40 (SV40 vectors for pulmonary gene therapy. Methods Sepsis-induced ARDS was established by cecal ligation double puncture (2CLP. SV40 vectors carrying the luciferase reporter gene (SV/luc were administered intratracheally immediately after sepsis induction. Sham operated (SO as well as 2CLP rats given intratracheal PBS or adenovirus expressing luciferase served as controls. Luc transduction was evaluated by in vivo light detection, immunoassay and luciferase mRNA detection by RT-PCR in tissue harvested from septic rats. Vector abundance and distribution into alveolar cells was evaluated using immunostaining for the SV40 VP1 capsid protein as well as by double staining for VP1 and for the surfactant protein C (proSP-C. Immunostaining for T-lymphocytes was used to evaluate the cellular immune response induced by the vector. Results Luc expression measured by in vivo light detection correlated with immunoassay from lung tissue harvested from the same rats. Moreover, our results showed vector presence in type II alveolar cells. The vector did not induce significant cellular immune response. Conclusion In the present study we have demonstrated efficient uptake and expression of an SV40 vector in the lungs of animals with sepsis-induced ARDS. These vectors appear to be capable of in vivo transduction of alveolar type II cells and may thus become a future therapeutic tool.

  19. Enhancing poxvirus vectors vaccine immunogenicity.

    Science.gov (United States)

    García-Arriaza, Juan; Esteban, Mariano

    2014-01-01

    Attenuated recombinant poxvirus vectors expressing heterologous antigens from pathogens are currently at various stages in clinical trials with the aim to establish their efficacy. This is because these vectors have shown excellent safety profiles, significant immunogenicity against foreign expressed antigens and are able to induce protective immune responses. In view of the limited efficacy triggered by some poxvirus strains used in clinical trials (i.e, ALVAC in the RV144 phase III clinical trial for HIV), and of the restrictive replication capacity of the highly attenuated vectors like MVA and NYVAC, there is a consensus that further improvements of these vectors should be pursuit. In this review we considered several strategies that are currently being implemented, as well as new approaches, to improve the immunogenicity of the poxvirus vectors. This includes heterologous prime/boost protocols, use of co-stimulatory molecules, deletion of viral immunomodulatory genes still present in the poxvirus genome, enhancing virus promoter strength, enhancing vector replication capacity, optimizing expression of foreign heterologous sequences, and the combined use of adjuvants. An optimized poxvirus vector triggering long-lasting immunity with a high protective efficacy against a selective disease should be sought.

  20. Late effects of atomic bomb radiation on human immune responses, (10); Results on studies of immune responses to EB-virus

    Energy Technology Data Exchange (ETDEWEB)

    Kusunoki, Yoichiro; Kyoizumi, Seishi; Ozaki, Kyoko; Saito, Mayumi; Cologne, J.B.; Akiyama, Mitoshi (Radiation Effects Research Foundation, Hiroshima (Japan))

    1992-12-01

    Anti-Epstein-Barr (EV) virus antibody titers were measured in age- and sex-matched three groups of each 124 A-bomb survivors who had exposed to <0.01 Gy, 0.01-1 Gy, or >1 Gy. These serum samples showed positive antibodies against viral capsid antigens (VCA). Antibody titers to anti-VCA-IgM or anti-EA-IgG were significantly higher in the groups of 0.01-1 Gy and >1 Gy than in the group of <0.01 Gy, reflecting decreased immune response ability for EV virus. When precursor frequency of cytotoxic cells against autologous EB virus LCL was determined in 68 other A-bomb survivors, no definitive influence of A-bombing was observed. However, serological study revealed that there was inverse correlation between precursor frequency and anti-EA-IgG antibody titer. These findings suggest that the immune response ability for EB virus may have been damaged and that biological reactivity of EB virus may occur frequently in A-bomb survivors. (N.K.).

  1. Cloning vector

    Science.gov (United States)

    Guilfoyle, Richard A.; Smith, Lloyd M.

    1994-01-01

    A vector comprising a filamentous phage sequence containing a first copy of filamentous phage gene X and other sequences necessary for the phage to propagate is disclosed. The vector also contains a second copy of filamentous phage gene X downstream from a promoter capable of promoting transcription in a bacterial host. In a preferred form of the present invention, the filamentous phage is M13 and the vector additionally includes a restriction endonuclease site located in such a manner as to substantially inactivate the second gene X when a DNA sequence is inserted into the restriction site.

  2. Cloning vector

    Science.gov (United States)

    Guilfoyle, R.A.; Smith, L.M.

    1994-12-27

    A vector comprising a filamentous phage sequence containing a first copy of filamentous phage gene X and other sequences necessary for the phage to propagate is disclosed. The vector also contains a second copy of filamentous phage gene X downstream from a promoter capable of promoting transcription in a bacterial host. In a preferred form of the present invention, the filamentous phage is M13 and the vector additionally includes a restriction endonuclease site located in such a manner as to substantially inactivate the second gene X when a DNA sequence is inserted into the restriction site. 2 figures.

  3. Immunity booster

    International Nuclear Information System (INIS)

    Stefanescu, Ioan; Titescu, Gheorghe; Tamaian, Radu; Haulica, Ion; Bild, Walther

    2002-01-01

    The immunity booster is, according to its patent description, microbiologically pure water with an D/(D+H) isotopic concentration of 100 ppm, with physical-chemical characteristics similar to those of distilled water. It is obtained by sterilization of a mixture of deuterium depleted water, with a 25 ppm isotopic concentration, with distilled water in a volume ratio of 4:6. Unlike natural immunity boosters (bacterial agents as Bacillus Chalmette-Guerin, Corynebacterium parvum; lipopolysaccharides; human immunoglobulin) or synthetical products (levamysol; isoprinosyne with immunostimulating action), which cause hypersensitivity and shocks, thrill, fever, sickness and the immunity complex disease, the water of 100 ppm D/(D + H) isotopic concentration is a toxicity free product. The testing for immune reaction of the immunity booster led to the following results: - an increase of cell action capacity in the first immunity shielding stage (macrophages), as evidenced by stimulation of a number of essential characterizing parameters, as well as of the phagocytosis capacity, bactericide capacity, and opsonic capacity of serum; - an increase of the number of leucocyte particularly of the granulocyte in peripheral blood, produced especially when medullar toxic agents like caryolysine are used; - it hinders the effect of lowering the number of erythrocytes in peripheral blood produced by experimentally induced chronic inflammation; - an increase of nonspecific immunity defence capacity against specific bacterial aggression of both Gram-positive bacteria (Streptococcus pneumoniae 558 ) and of the Gram-negative ones (Klebsiella pneumoniae 507 ); - an increase of immunity - stimulating activity (proinflamatory), like that of levamisole as evidenced by the test of stimulation of experimentally induced inflammation by means of carrageenan. The following advantages of the immunity booster are stressed: - it is toxicity free and side effect free; - can be orally administrated as

  4. Escaping deleterious immune response in their hosts: lessons from trypanosomatids

    Directory of Open Access Journals (Sweden)

    Anne eGeiger

    2016-05-01

    Full Text Available The Trypanosomatidae family includes the genera Trypanosoma and Leishmania, protozoan parasites displaying complex digenetic life cycles requiring a vertebrate host and an insect vector. Trypanosoma brucei gambiense, T. cruzi and Leishmania spp are important human pathogens causing Human African Trypanosomiasis (HAT or Sleeping Sickness, Chagas’ disease, and various clinical forms of Leishmaniasis, respectively. They are transmitted to humans by tsetse flies, triatomine bugs or sandflies and affect millions of people worldwide.In humans, extracellular African trypanosomes (T. brucei evade the hosts’ immune defences, allowing their transmission to the next host, via the tsetse vector. By contrast, T. cruzi and Leishmania sp. have developed a complex intracellular lifestyle, also preventing several mechanisms to circumvent the host’s immune response.This review seeks to set out the immune evasion strategies developed by the different trypanosomatids resulting from parasite-host interactions and, will focus on: clinical and epidemiological importance of diseases; life cycles: parasites-hosts-vectors; innate immunity: key steps for trypanosomatids in invading hosts; deregulation of antigen presenting cells; disruption of efficient specific immunity; and the immune responses used for parasite proliferation.

  5. Escaping Deleterious Immune Response in Their Hosts: Lessons from Trypanosomatids

    Science.gov (United States)

    Geiger, Anne; Bossard, Géraldine; Sereno, Denis; Pissarra, Joana; Lemesre, Jean-Loup; Vincendeau, Philippe; Holzmuller, Philippe

    2016-01-01

    The Trypanosomatidae family includes the genera Trypanosoma and Leishmania, protozoan parasites displaying complex digenetic life cycles requiring a vertebrate host and an insect vector. Trypanosoma brucei gambiense, Trypanosoma cruzi, and Leishmania spp. are important human pathogens causing human African trypanosomiasis (HAT or sleeping sickness), Chagas’ disease, and various clinical forms of Leishmaniasis, respectively. They are transmitted to humans by tsetse flies, triatomine bugs, or sandflies, and affect millions of people worldwide. In humans, extracellular African trypanosomes (T. brucei) evade the hosts’ immune defenses, allowing their transmission to the next host, via the tsetse vector. By contrast, T. cruzi and Leishmania sp. have developed a complex intracellular lifestyle, also preventing several mechanisms to circumvent the host’s immune response. This review seeks to set out the immune evasion strategies developed by the different trypanosomatids resulting from parasite–host interactions and will focus on: clinical and epidemiological importance of diseases; life cycles: parasites–hosts–vectors; innate immunity: key steps for trypanosomatids in invading hosts; deregulation of antigen-presenting cells; disruption of efficient specific immunity; and the immune responses used for parasite proliferation. PMID:27303406

  6. Fractal vector optical fields.

    Science.gov (United States)

    Pan, Yue; Gao, Xu-Zhen; Cai, Meng-Qiang; Zhang, Guan-Lin; Li, Yongnan; Tu, Chenghou; Wang, Hui-Tian

    2016-07-15

    We introduce the concept of a fractal, which provides an alternative approach for flexibly engineering the optical fields and their focal fields. We propose, design, and create a new family of optical fields-fractal vector optical fields, which build a bridge between the fractal and vector optical fields. The fractal vector optical fields have polarization states exhibiting fractal geometry, and may also involve the phase and/or amplitude simultaneously. The results reveal that the focal fields exhibit self-similarity, and the hierarchy of the fractal has the "weeding" role. The fractal can be used to engineer the focal field.

  7. NSTX Disruption Simulations of Detailed Divertor and Passive Plate Models by Vector Potential Transfer from OPERA Global Analysis Results

    International Nuclear Information System (INIS)

    Titus, P.H.; Avasaralla, S.; Brooks, A.; Hatcher, R.

    2010-01-01

    The National Spherical Torus Experiment (NSTX) project is planning upgrades to the toroidal field, plasma current and pulse length. This involves the replacement of the center-stack, including the inner legs of the TF, OH, and inner PF coils. A second neutral beam will also be added. The increased performance of the upgrade requires qualification of the remaining components including the vessel, passive plates, and divertor for higher disruption loads. The hardware needing qualification is more complex than is typically accessible by large scale electromagnetic (EM) simulations of the plasma disruptions. The usual method is to include simplified representations of components in the large EM models and attempt to extract forces to apply to more detailed models. This paper describes a more efficient approach of combining comprehensive modeling of the plasma and tokamak conducting structures, using the 2D OPERA code, with much more detailed treatment of individual components using ANSYS electromagnetic (EM) and mechanical analysis. This capture local eddy currents and resulting loads in complex details, and allows efficient non-linear, and dynamic structural analyses.

  8. NSTX Disruption Simulations of Detailed Divertor and Passive Plate Models by Vector Potential Transfer from OPERA Global Analysis Results

    Energy Technology Data Exchange (ETDEWEB)

    P. H. Titus, S. Avasaralla, A.Brooks, R. Hatcher

    2010-09-22

    The National Spherical Torus Experiment (NSTX) project is planning upgrades to the toroidal field, plasma current and pulse length. This involves the replacement of the center-stack, including the inner legs of the TF, OH, and inner PF coils. A second neutral beam will also be added. The increased performance of the upgrade requires qualification of the remaining components including the vessel, passive plates, and divertor for higher disruption loads. The hardware needing qualification is more complex than is typically accessible by large scale electromagnetic (EM) simulations of the plasma disruptions. The usual method is to include simplified representations of components in the large EM models and attempt to extract forces to apply to more detailed models. This paper describes a more efficient approach of combining comprehensive modeling of the plasma and tokamak conducting structures, using the 2D OPERA code, with much more detailed treatment of individual components using ANSYS electromagnetic (EM) and mechanical analysis. This capture local eddy currents and resulting loads in complex details, and allows efficient non-linear, and dynamic structural analyses.

  9. Improved results for the 2H(d, n)3He transverse vector polarization-transfer coefficient Kyy'(0o) at low energies

    International Nuclear Information System (INIS)

    Roper, C.D.; Dunham, J.D.; Clegg, T.B.; Mendez, A.J.; Tornow, W.; Walter, R.L.

    2010-01-01

    Measurements of the 2 H(d, n) 3 He transverse vector polarization-transfer coefficient K y y' at 0 o . are reported for 29 outgoing neutron energies between 3.94 and 8.47 MeV. Our new results determine K y y' (0 o ) more accurately than previous data, especially for neutron energies below 5 MeV. Low-energy data for this reaction are important both as a high-intensity source of highly polarized neutrons for nuclear physics studies with polarized neutron beams, and as a test of the emerging theoretical descriptions of the four-body system, where recently substantial progress has been made. (author)

  10. Improved Results for the H-2(d, n)(3) He Transverse Vector Polarization- Transfer Coefficient K-y(y)' (0 degrees) at Low Energies

    International Nuclear Information System (INIS)

    Roper, C.D.; Clegg, T.; Dunham, J.D.; Mendez, Anthony J. II; Tornow, W.; Walter, R.L.

    2010-01-01

    Measurements of the H-2(d, n)(3) He transverse vector polarization-transfer coefficient K-y(y)' at 0 degrees. are reported for 29 outgoing neutron energies between 3.94 and 8.47MeV. Our new results determine K-y(y)' (0 degrees) more accurately than previous data, especially for neutron energies below 5MeV. Low-energy data for this reaction are important both as a high-intensity source of highly polarized neutrons for nuclear physics studies with polarized neutron beams, and as a test of the emerging theoretical descriptions of the four-body system, where recently substantial progress has been made.

  11. Meeting Postpartum Women’s Family Planning Needs Through Integrated Family Planning and Immunization Services: Results of a Cluster-Randomized Controlled Trial in Rwanda

    Science.gov (United States)

    Dulli, Lisa S; Eichleay, Marga; Rademacher, Kate; Sortijas, Steve; Nsengiyumva, Théophile

    2016-01-01

    ABSTRACT Objective The primary objective of this study was to test the effectiveness of integrating family planning service components into infant immunization services to increase modern contraceptive method use among postpartum women. Methods The study was a separate sample, parallel, cluster-randomized controlled trial. Fourteen randomly selected primary health facilities were equally allocated to intervention (integrated family planning and immunization services at the same time and location) and control groups (standard immunization services only). At baseline (May–June 2010), we interviewed postpartum women attending immunization services for their infant aged 6 to 12 months using a structured questionnaire. A separate sample of postpartum women was interviewed 16 months later after implementation of the experimental health service intervention. We used linear mixed regression models to test the study hypothesis that postpartum women attending immunization services for their infants aged 6–12 months in the intervention facilities will be more likely to use a modern contraceptive method than postpartum women attending immunization services for their infants aged 6–12 months in control group facilities. Results We interviewed and analyzed data for 825 women from the intervention group and 829 women from the control group. Results showed the intervention had a statistically significant, positive effect on modern contraceptive method use among intervention group participants compared with control group participants (regression coefficient, 0.15; 90% confidence interval [CI], 0.04 to 0.26). Although we conducted a 1-sided significance test, this effect was also significant at the 2-sided test with alpha = .05. Among those women who did not initiate a contraceptive method, awaiting the return of menses was the most common reason cited for non-use of a method. Women in both study groups overwhelmingly supported the concept of integrating family planning

  12. Vaccination strategies for SIR vector-transmitted diseases.

    Science.gov (United States)

    Cruz-Pacheco, Gustavo; Esteva, Lourdes; Vargas, Cristobal

    2014-08-01

    Vector-borne diseases are one of the major public health problems in the world with the fastest spreading rate. Control measures have been focused on vector control, with poor results in most cases. Vaccines should help to reduce the diseases incidence, but vaccination strategies should also be defined. In this work, we propose a vector-transmitted SIR disease model with age-structured population subject to a vaccination program. We find an expression for the age-dependent basic reproductive number R(0), and we show that the disease-free equilibrium is locally stable for R(0) ≤ 1, and a unique endemic equilibrium exists for R(0) > 1. We apply the theoretical results to public data to evaluate vaccination strategies, immunization levels, and optimal age of vaccination for dengue disease.

  13. Childhood immunization

    Science.gov (United States)

    Romain, Sandra; Schillaci, Michael A.

    2009-01-01

    ABSTRACT OBJECTIVE To examine childhood immunization levels relative to the number of family physicians, pediatricians, and public health nurses in Ontario. DESIGN Retrospective comparative analysis of publicly available data on immunization coverage levels and the relative number of family physicians, pediatricians, and public health nurses. SETTING Ontario. PARTICIPANTS Seven-year-old children, family physicians, pediatricians, and public health nurses in Ontario. MAIN OUTCOME MEASURES The association between immunization coverage levels and the relative number of family physicians, pediatricians, and public health nurses. RESULTS We found correlations between immunization coverage levels and the relative number (ie, per 1000 Ontario residents) of family physicians (ρ = 0.60) and pediatricians (ρ = 0.70) and a lower correlation with the relative number of public health nurses (ρ = 0.40), although none of these correlations was significant. A comparison of temporal trends illustrated that variation in the relative number of family physicians and pediatricians in Ontario was associated with similar variation in immunization coverage levels. CONCLUSION Increasing the number of family physicians and pediatricians might help to boost access to immunizations and perhaps other components of cost-saving childhood preventive care. PMID:19910599

  14. Health-related quality of life of immune thrombocytopenic purpura patients: results from a web-based survey.

    Science.gov (United States)

    Snyder, Claire F; Mathias, Susan D; Cella, David; Isitt, John J; Wu, Albert W; Young, Joan

    2008-10-01

    To assess the health-related quality of life (HRQOL) of immune thrombocytopenic purpura (ITP) patients. This was a cross-sectional, descriptive study comparing ITP patients' HRQOL to age and gender matched controls. ITP patients from the Platelet Disorder Support Association were recruited until 1000 surveys had been completed. Controls were randomly sampled from the Harris Interactive Online Panel. ITP patients and controls completed a one-time web-based survey, including a comprehensive HRQOL assessment. ITP patients completed the SF-36, the EQ-5D, and the ITP-Patient Assessment Questionnaire (ITP-PAQ). Controls completed the SF-36 and EQ-5D only. ITP patients' SF-36 and EQ-5D scores were compared to controls in unadjusted and adjusted analyses. Associations between splenectomy status, duration of illness, and platelet count with ITP patients' HRQOL scores were also examined. This analysis included 1002 ITP patients and 1031 controls. ITP patients scored worse on seven of eight SF-36 domains and the Physical and Mental Summary scores (all p PAQ scales: Bother, Psychological, Fear, Social Activity, and Work (all p PAQ scales. Lower platelet count was consistently associated with worse ITP-PAQ scores and had weaker associations with SF-36 and EQ-5D scores. ITP was associated with consistent and statistically significant deficits on generic HRQOL measures. The ITP-PAQ demonstrated differences based on disease severity and treatments. The self-selection bias in the two samples limits the generalizability of the results to all patients with ITP. Further research is needed in more generalizable samples.

  15. Thrombopoietin receptor agonists for preparing adult patients with immune thrombocytopenia to splenectomy: results of a retrospective, observational GIMEMA study.

    Science.gov (United States)

    Zaja, Francesco; Barcellini, Wilma; Cantoni, Silvia; Carpenedo, Monica; Caparrotti, Giuseppe; Carrai, Valentina; Di Renzo, Nicola; Santoro, Cristina; Di Nicola, Massimo; Veneri, Dino; Simonetti, Federico; Liberati, Anna M; Ferla, Valeria; Paoloni, Francesca; Crea, Enrico; Volpetti, Stefano; Tuniz, Enrica; Fanin, Renato

    2016-05-01

    In patients with immune thrombocytopenia (ITP) refractory to corticosteroids and intravenous immunoglobulins (IVIG), splenectomy may result at higher risk of peri-operative complications and, for this reason, potentially contraindicated. The thrombopoietin receptor agonists (TPO-RAs) romiplostim and eltrombopag have shown high therapeutic activity in primary ITP, but data of efficacy and safety regarding their use in preparation for splenectomy are missing. Thirty-one adult patients, median age 50 years, with corticosteroids and/or IVIG refractory persistent and chronic ITP who were treated with TPO-RAs (romiplostim= 24; eltrombopag= 7) with the aim to increase platelet count and allow a safer execution of splenectomy were retrospectively evaluated. Twenty-four patients (77%) responded to the use of TPO-RAs with a median platelet count that increased from 11 × 10(9) /L before starting TPO-RAs to 114 × 10(9) /L pre-splenectomy, but a concomitant treatment with corticosteroids and/or IVIG was required in 19 patients. Twenty-nine patients underwent splenectomy while two patients who responded to TPO-RAs subsequently refused surgery. Post-splenectomy complications were characterized by two Grade 3 thrombotic events (1 portal vein thrombosis in the patient with previous history of HCV hepatitis and 1 pulmonary embolism), with a platelet count at the time of thrombosis of 260 and 167 × 10(9) /L, respectively and one Grade 3 infectious event. TPO-RAs may represent a therapeutic option to improve platelet count and reduce the risk of peri-operative complications in ITP candidates to splenectomy. An increased risk of post-splenectomy thromboembolic events cannot be ruled out and thromboprophylaxis with low-molecular weight heparin is generally recommended. © 2016 Wiley Periodicals, Inc.

  16. Hierarchal scalar and vector tetrahedra

    International Nuclear Information System (INIS)

    Webb, J.P.; Forghani, B.

    1993-01-01

    A new set of scalar and vector tetrahedral finite elements are presented. The elements are hierarchal, allowing mixing of polynomial orders; scalar orders up to 3 and vector orders up to 2 are defined. The vector elements impose tangential continuity on the field but not normal continuity, making them suitable for representing the vector electric or magnetic field. Further, the scalar and vector elements are such that they can easily be used in the same mesh, a requirement of many quasi-static formulations. Results are presented for two 50 Hz problems: the Bath Cube, and TEAM Problem 7

  17. VECTOR INTEGRATION

    NARCIS (Netherlands)

    Thomas, E. G. F.

    2012-01-01

    This paper deals with the theory of integration of scalar functions with respect to a measure with values in a, not necessarily locally convex, topological vector space. It focuses on the extension of such integrals from bounded measurable functions to the class of integrable functions, proving

  18. Defective pulmonary innate immune responses post-stem cell transplantation; review and results from one model system

    Directory of Open Access Journals (Sweden)

    Racquel eDomingo-Gonzalez

    2013-05-01

    Full Text Available Infectious pulmonary complications limit the success of hematopoietic stem cell transplantation (HSCT as a therapy for malignant and nonmalignant disorders. Susceptibility to pathogens in both autologous and allogeneic HSCT recipients persists despite successful immune reconstitution. As studying the causal effects of these immune defects in the human population can be limiting, a bone marrow transplant (BMT mouse model can be used to understand the defect in mounting a productive innate immune response post-transplantation. When syngeneic BMT is performed, this system allows the study of BMT-induced alterations in innate immune cell function that are independent of the confounding effects of immunosuppressive therapy and graft-versus-host disease. Studies from several laboratories, including our own show that pulmonary susceptibility to bacterial infections post-BMT are largely due to alterations in the lung alveolar macrophages. Changes in these cells post-BMT include cytokine and eicosanoid dysregulations, scavenger receptor alterations, changes in micro RNA profiles, and alterations in intracellular signaling molecules that limit bacterial phagocytosis and killing. The changes that occur highlight mechanisms that promote susceptibility to infections commonly afflicting HSCT recipients and provide insight into therapeutic targets that may improve patient outcomes post-HSCT.

  19. Maternal immune activation results in complex microglial transcriptome signature in the adult offspring that is reversed by minocycline treatment

    NARCIS (Netherlands)

    Mattei, D.; Ivanov, A.; Ferrai, C.; Jordan, P.; Guneykaya, D.; Buonfiglioli, A.; Schaafsma, W.; Przanowski, P.; Deuther-Conrad, W.; Brust, P.; Hesse, S.; Patt, M.; Sabri, O.; Ross, T. L.; Eggen, B. J. L.; Boddeke, E. W. G. M.; Kaminska, B.; Beule, D.; Pombo, A.; Kettenmann, H.; Wolf, S. A.

    2017-01-01

    Maternal immune activation (MIA) during pregnancy has been linked to an increased risk of developing psychiatric pathologies in later life. This link may be bridged by a defective microglial phenotype in the offspring induced by MIA, as microglia have key roles in the development and maintenance of

  20. E-cigarette use results in suppression of immune and inflammatory-response genes in nasal epithelial cells similar to cigarette smoke.

    Science.gov (United States)

    Martin, Elizabeth M; Clapp, Phillip W; Rebuli, Meghan E; Pawlak, Erica A; Glista-Baker, Ellen; Benowitz, Neal L; Fry, Rebecca C; Jaspers, Ilona

    2016-07-01

    Exposure to cigarette smoke is known to result in impaired host defense responses and immune suppressive effects. However, the effects of new and emerging tobacco products, such as e-cigarettes, on the immune status of the respiratory epithelium are largely unknown. We conducted a clinical study collecting superficial nasal scrape biopsies, nasal lavage, urine, and serum from nonsmokers, cigarette smokers, and e-cigarette users and assessed them for changes in immune gene expression profiles. Smoking status was determined based on a smoking history and a 3- to 4-wk smoking diary and confirmed using serum cotinine and urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) levels. Total RNA from nasal scrape biopsies was analyzed using the nCounter Human Immunology v2 Expression panel. Smoking cigarettes or vaping e-cigarettes resulted in decreased expression of immune-related genes. All genes with decreased expression in cigarette smokers (n = 53) were also decreased in e-cigarette smokers. Additionally, vaping e-cigarettes was associated with suppression of a large number of unique genes (n = 305). Furthermore, the e-cigarette users showed a greater suppression of genes common with those changed in cigarette smokers. This was particularly apparent for suppressed expression of transcription factors, such as EGR1, which was functionally associated with decreased expression of 5 target genes in cigarette smokers and 18 target genes in e-cigarette users. Taken together, these data indicate that vaping e-cigarettes is associated with decreased expression of a large number of immune-related genes, which are consistent with immune suppression at the level of the nasal mucosa. Copyright © 2016 the American Physiological Society.

  1. Procedure for Selection of Suitable Resources in Interactions in Complex Dynamic Systems Using Artificial Immunity

    Directory of Open Access Journals (Sweden)

    Naors Y. anadalsaleem

    2017-03-01

    Full Text Available The dynamic optimization procedure for -dimensional vector function of a system, the state of which is interpreted as adaptable immune cell, is considered Using the results of the theory of artificial immune systems. The procedures for estimate of monitoring results are discussed. The procedure for assessing the entropy is recommended as a general recursive estimation algorithm. The results are focused on solving the optimization problems of cognitive selection of suitable physical resources, what expands the scope of Electromagnetic compatibility.

  2. Specific prebiotics modulate gut microbiota and immune activation in HAART-naive HIV-infected adults : results of the "COPA" pilot randomized trial

    NARCIS (Netherlands)

    Gori, A.; Rizzardini, G.; van't Land, B.; Amor, K. B.; van Schaik, J.; Torti, C.; Quirino, T.; Tincati, C.; Bandera, A.; Knol, J.; Benlhassan-Chahour, K.; Trabattoni, D.; Bray, D.; Vriesema, A.; Welling, G.; Garssen, J.; Clerici, M.

    Intestinal mucosal immune system is an early target for human immunodeficiency virus type 1 (HIV-1) infection, resulting in CD4(+) T-cell depletion, deterioration of gut lining, and fecal microbiota composition. We evaluated the effects of a prebiotic oligosaccharide mixture in highly active

  3. Chikungunya Virus–Vector Interactions

    Directory of Open Access Journals (Sweden)

    Lark L. Coffey

    2014-11-01

    Full Text Available Chikungunya virus (CHIKV is a mosquito-borne alphavirus that causes chikungunya fever, a severe, debilitating disease that often produces chronic arthralgia. Since 2004, CHIKV has emerged in Africa, Indian Ocean islands, Asia, Europe, and the Americas, causing millions of human infections. Central to understanding CHIKV emergence is knowledge of the natural ecology of transmission and vector infection dynamics. This review presents current understanding of CHIKV infection dynamics in mosquito vectors and its relationship to human disease emergence. The following topics are reviewed: CHIKV infection and vector life history traits including transmission cycles, genetic origins, distribution, emergence and spread, dispersal, vector competence, vector immunity and microbial interactions, and co-infection by CHIKV and other arboviruses. The genetics of vector susceptibility and host range changes, population heterogeneity and selection for the fittest viral genomes, dual host cycling and its impact on CHIKV adaptation, viral bottlenecks and intrahost diversity, and adaptive constraints on CHIKV evolution are also discussed. The potential for CHIKV re-emergence and expansion into new areas and prospects for prevention via vector control are also briefly reviewed.

  4. Malaria transmission model for different levels of acquired immunity and temperature-dependent parameters (vector Modelo de transmissão de malária em diferentes níveis de imunidade e de parâmetros temperatura-dependentes (vetor

    Directory of Open Access Journals (Sweden)

    Hyun M Yang

    2000-06-01

    Full Text Available OBJECTIVE: Describe the overall transmission of malaria through a compartmental model, considering the human host and mosquito vector. METHODS: A mathematical model was developed based on the following parameters: human host immunity, assuming the existence of acquired immunity and immunological memory, which boosts the protective response upon reinfection; mosquito vector, taking into account that the average period of development from egg to adult mosquito and the extrinsic incubation period of parasites (transformation of infected but non-infectious mosquitoes into infectious mosquitoes are dependent on the ambient temperature. RESULTS: The steady state equilibrium values obtained with the model allowed the calculation of the basic reproduction ratio in terms of the model's parameters. CONCLUSIONS: The model allowed the calculation of the basic reproduction ratio, one of the most important epidemiological variables.OBJETIVO: Propõe-se um modelo compartimental para descrever a transmissão de malária, levando em consideração duas populações envolvidas: o hospedeiro humano e o vetor mosquito. MÉTODOS: Desenvolveu-se um modelo matemático baseado nas seguintes características: em relação ao hospedeiro humano, assumiu-se a existência de imunidade adquirida e de memória imunológica que, em uma reinfecção, leva ao reforço da resposta imune; em relação ao vetor mosquito, levou-se em consideração que o período médio de desenvolvimento desde ovo até mosquito adulto e o período de incubação extrínseco de parasitas (transformação de mosquitos infectados mas não-infecciosos em mosquitos infecciosos são dependentes de temperatura ambiente. RESULTADOS: Foram obtidos os valores do equilíbrio no estado estacionário do modelo proposto. Da análise da estabilidade dos pontos de equilíbrio, foi determinada a razão de reprodutibilidade basal. CONCLUSÕES: Foi obtida uma variável epidemiológica importante, a razão de

  5. Getting genetic access to natural adenovirus genomes to explore vector diversity.

    Science.gov (United States)

    Zhang, Wenli; Ehrhardt, Anja

    2017-10-01

    Recombinant vectors based on the human adenovirus type 5 (HAdV5) have been developed and extensively used in preclinical and clinical studies for over 30 years. However, certain restrictions of HAdV5-based vectors have limited their clinical applications because they are rather inefficient in specifically transducing cells of therapeutic interest that lack the coxsackievirus and adenovirus receptor (CAR). Moreover, enhanced vector-associated toxicity and widespread preexisting immunity have been shown to significantly hamper the effectiveness of HAdV-5-mediated gene transfer. However, evolution of adenoviruses in the natural host is driving the generation of novel types with altered virulence, enhanced transmission, and altered tissue tropism. As a consequence, an increasing number of alternative adenovirus types were identified, which may represent a valuable resource for the development of novel vector types. Thus, researchers are focusing on the other naturally occurring adenovirus types, which are structurally similar but functionally different from HAdV5. To this end, several strategies have been devised for getting genetic access to adenovirus genomes, resulting in a new panel of adenoviral vectors. Importantly, these vectors were shown to have a host range different from HAdV5 and to escape the anti-HAdV5 immune response, thus underlining the great potential of this approach. In summary, this review provides a state-of-the-art overview of one essential step in adenoviral vector development.

  6. An introduction to vectors, vector operators and vector analysis

    CERN Document Server

    Joag, Pramod S

    2016-01-01

    Ideal for undergraduate and graduate students of science and engineering, this book covers fundamental concepts of vectors and their applications in a single volume. The first unit deals with basic formulation, both conceptual and theoretical. It discusses applications of algebraic operations, Levi-Civita notation, and curvilinear coordinate systems like spherical polar and parabolic systems and structures, and analytical geometry of curves and surfaces. The second unit delves into the algebra of operators and their types and also explains the equivalence between the algebra of vector operators and the algebra of matrices. Formulation of eigen vectors and eigen values of a linear vector operator are elaborated using vector algebra. The third unit deals with vector analysis, discussing vector valued functions of a scalar variable and functions of vector argument (both scalar valued and vector valued), thus covering both the scalar vector fields and vector integration.

  7. Loss of population levels of immunity to malaria as a result of exposure-reducing interventions: consequences for interpretation of disease trends.

    Directory of Open Access Journals (Sweden)

    Azra C Ghani

    Full Text Available BACKGROUND: The persistence of malaria as an endemic infection and one of the major causes of childhood death in most parts of Africa has lead to a radical new call for a global effort towards eradication. With the deployment of a highly effective vaccine still some years away, there has been an increased focus on interventions which reduce exposure to infection in the individual and -by reducing onward transmission-at the population level. The development of appropriate monitoring of these interventions requires an understanding of the timescales of their effect. METHODS & FINDINGS: Using a mathematical model for malaria transmission which incorporates the acquisition and loss of both clinical and parasite immunity, we explore the impact of the trade-off between reduction in exposure and decreased development of immunity on the dynamics of disease following a transmission-reducing intervention such as insecticide-treated nets. Our model predicts that initially rapid reductions in clinical disease incidence will be observed as transmission is reduced in a highly immune population. However, these benefits in the first 5-10 years after the intervention may be offset by a greater burden of disease decades later as immunity at the population level is gradually lost. The negative impact of having fewer immune individuals in the population can be counterbalanced either by the implementation of highly-effective transmission-reducing interventions (such as the combined use of insecticide-treated nets and insecticide residual sprays for an indefinite period or the concurrent use of a pre-erythrocytic stage vaccine or prophylactic therapy in children to protect those at risk from disease as immunity is lost in the population. CONCLUSIONS: Effective interventions will result in rapid decreases in clinical disease across all transmission settings while population-level immunity is maintained but may subsequently result in increases in clinical disease many

  8. Vector financial rogue waves

    International Nuclear Information System (INIS)

    Yan, Zhenya

    2011-01-01

    The coupled nonlinear volatility and option pricing model presented recently by Ivancevic is investigated, which generates a leverage effect, i.e., stock volatility is (negatively) correlated to stock returns, and can be regarded as a coupled nonlinear wave alternative of the Black–Scholes option pricing model. In this Letter, we analytically propose vector financial rogue waves of the coupled nonlinear volatility and option pricing model without an embedded w-learning. Moreover, we exhibit their dynamical behaviors for chosen different parameters. The vector financial rogue wave (rogon) solutions may be used to describe the possible physical mechanisms for the rogue wave phenomena and to further excite the possibility of relative researches and potential applications of vector rogue waves in the financial markets and other related fields. -- Highlights: ► We investigate the coupled nonlinear volatility and option pricing model. ► We analytically present vector financial rogue waves. ► The vector financial rogue waves may be used to describe the extreme events in financial markets. ► This results may excite the relative researches and potential applications of vector rogue waves.

  9. Immunization of Mastomys coucha with Brugia malayi recombinant trehalose-6-phosphate phosphatase results in significant protection against homologous challenge infection.

    Directory of Open Access Journals (Sweden)

    Susheela Kushwaha

    Full Text Available Development of a vaccine to prevent or reduce parasite development in lymphatic filariasis would be a complementary approach to existing chemotherapeutic tools. Trehalose-6-phosphate phosphatase of Brugia malayi (Bm-TPP represents an attractive vaccine target due to its absence in mammals, prevalence in the major life stages of the parasite and immunoreactivity with human bancroftian antibodies, especially from endemic normal subjects. We have recently reported on the cloning, expression, purification and biochemical characterization of this vital enzyme of B. malayi. In the present study, immunoprophylactic evaluation of Bm-TPP was carried out against B. malayi larval challenge in a susceptible host Mastomys coucha and the protective ability of the recombinant protein was evaluated by observing the adverse effects on microfilarial density and adult worm establishment. Immunization caused 78.4% decrease in microfilaremia and 71.04% reduction in the adult worm establishment along with sterilization of 70.06% of the recovered live females. The recombinant protein elicited a mixed Th1/Th2 type of protective immune response as evidenced by the generation of both pro- and anti-inflammatory cytokines IL-2, IFN-γ, TNF-α, IL-4 and an increased production of antibody isotypes IgG1, IgG2a, IgG2b and IgA. Thus immunization with Bm-TPP conferred considerable protection against B. malayi establishment by engendering a long-lasting effective immune response and therefore emerges as a potential vaccine candidate against lymphatic filariasis (LF.

  10. Lack of Proinflammatory Cytokine Interleukin-6 or Tumor Necrosis Factor Receptor-1 Results in a Failure of the Innate Immune Response after Bacterial Meningitis

    Directory of Open Access Journals (Sweden)

    Lea-Jessica Albrecht

    2016-01-01

    Full Text Available The most frequent pathogen that causes bacterial meningitis is the Gram-positive bacterium Streptococcus pneumoniae. By entering the brain, host cells will be activated and proinflammatory cytokines like interleukin-6 (IL-6 and tumor necrosis factor-α (TNF-α are released. The goal of the current study was to examine the interaction between IL-6 and TNFR1 as receptor for TNF-α and the innate immune response in vivo in a model of Streptococcus pneumoniae-induced meningitis. For the experiments IL-6−/−, TNFR1−/−, and TNFR1-IL-6−/− KO mice were used. Our results revealed higher mortality rates and bacterial burden after infection in TNFR1−/−, IL-6−/−, and TNFR1-IL-6−/− mice and a decreased immune response including lower neutrophil infiltration in the meninges of TNFR1−/− and TNFR1-IL-6−/− mice in contrast to IL-6−/− and wild type mice. Furthermore, the increased mortality of TNFR1−/− and TNFR1-IL-6−/− mice correlated with decreased glial cell activation compared to IL-6−/− or wild type mice after pneumococcal meningitis. Altogether, the results show the importance of TNFR1 and IL-6 in the regulation of the innate immune response. The lack of TNFR1 and IL-6 results in higher mortality by weakened immune defence, whereas the lack of TNFR1 results in more severe impairment of the innate immune response than the lack of IL-6 alone.

  11. RESULTS OF THE IMMUNIZATION ACCORDING TO THE NATIONAL CALENDAR ASSOCIATED WITH VACCINATION AGAINST INFLUENZA IN CHILDREN WITH SOMATIC DISORDERS AND IMMUNODEFICIENCY

    Directory of Open Access Journals (Sweden)

    S. M. Kharit

    2014-01-01

    Full Text Available Aim: to study safety and immunological efficacy of vaccination against influenza in separate and associated immunization according to the National Calendar. Patients and methods: 100 children with various disorders as well as children with HIV subjected to revaccination against diphtheria, tetanus, measles, parotiditis and rubella, were included into the study. Children were divided into 5 groups of 20 persons each: groups of separate or associated vaccination. In order to assess safety of vaccination children were observed for 30 days after vaccination. In order to analyze immunologic efficacy participants were taken serum tests before and on the 30th day after vaccination. Results: the study demonstrated high safety of the vaccine against influenza. Mild and moderate topical and general reactions were observed in isolated instances and did not differ in comparison groups. Simultaneous vaccination against influenza with immunization against diphtheria, parotiditis and rubella did not influence synthesis of antibodies, while synthesis of antibodies against measles was decreased; immunization against diphtheria and measles when associated with vaccination against influenza depressed synthesis of antibodies against A/H3N2 influenza. Conclusions: vaccine against influenza has low reactivity, high safety and can be used in association with immunization according to the National calendar in independence to somatic disorders of patients. 

  12. Vector-vector production in photon-photon interactions

    International Nuclear Information System (INIS)

    Ronan, M.T.

    1988-01-01

    Measurements of exclusive untagged /rho/ 0 /rho/ 0 , /rho//phi/, K/sup *//bar K//sup */, and /rho/ω production and tagged /rho/ 0 /rho/ 0 production in photon-photon interactions by the TPC/Two-Gamma experiment are reviewed. Comparisons to the results of other experiments and to models of vector-vector production are made. Fits to the data following a four quark model prescription for vector meson pair production are also presented. 10 refs., 9 figs

  13. Results from a survey of national immunization programmes on home-based vaccination record practices in 2013.

    Science.gov (United States)

    Young, Stacy L; Gacic-Dobo, Marta; Brown, David W

    2015-07-01

    Data on home-based records (HBRs) practices within national immunization programmes are non-existent, making it difficult to determine whether current efforts of immunization programmes related to basic recording of immunization services are appropriately focused. During January 2014, WHO and the United Nations Children's Fund sent a one-page questionnaire to 195 countries to obtain information on HBRs including type of record used, number of records printed, whether records were provided free-of-charge or required by schools, whether there was a stock-out and the duration of any stock-outs that occurred, as well as the total expenditure for printing HBRs during 2013. A total of 140 countries returned a completed HBR questionnaire. Two countries were excluded from analysis because they did not use a HBR during 2013. HBR types varied across countries (vaccination only cards, 32/138 [23.1%]; vaccination plus growth monitoring records, 31/138 [22.4%]; child health books, 48/138 [34.7%]; combination of these, 27/138 [19.5%] countries). HBRs were provided free-of-charge in 124/138 (89.8%) respondent countries. HBRs were required for school entry in 62/138 (44.9%) countries. Nearly a quarter of countries reported HBR stock-outs during 2013. Computed printing cost per record was work remains to improve forecasting where appropriate, to prevent HBR stock-outs, to identify and improve sustainable financing options and to explore viable market shaping opportunities. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.

  14. Immune System and Disorders

    Science.gov (United States)

    Your immune system is a complex network of cells, tissues, and organs that work together to defend against germs. It ... t, to find and destroy them. If your immune system cannot do its job, the results can be ...

  15. Duality in vector optimization

    CERN Document Server

    Bot, Radu Ioan

    2009-01-01

    This book presents fundamentals and comprehensive results regarding duality for scalar, vector and set-valued optimization problems in a general setting. After a preliminary chapter dedicated to convex analysis and minimality notions of sets with respect to partial orderings induced by convex cones a chapter on scalar conjugate duality follows. Then investigations on vector duality based on scalar conjugacy are made. Weak, strong and converse duality statements are delivered and connections to classical results from the literature are emphasized. One chapter is exclusively consecrated to the s

  16. Circumvention of Immunity to the Adenovirus Major Coat Protein Hexon

    Science.gov (United States)

    Roy, Soumitra; Shirley, Pamela S.; McClelland, Alan; Kaleko, Michael

    1998-01-01

    Immunity to adenoviruses is an important hurdle to be overcome for successful gene therapy. The presence of antibodies to the capsid proteins prevents efficacious adenovirus vector administration in vivo. We tested whether immunity to a particular serotype of adenovirus (Ad5) may be overcome with a vector that encodes the hexon sequences from a different adenovirus serotype (Ad12). We successfully constructed an adenovirus vector with a chimeric Ad5-Ad12 hexon which was not neutralized by plasma from C57BL/6 mice immunized with Ad5. The vector was also capable of transducing the livers of C57BL/6 mice previously immunized with Ad5. PMID:9658137

  17. An economic evaluation of vector control in the age of a dengue vaccine.

    Science.gov (United States)

    Fitzpatrick, Christopher; Haines, Alexander; Bangert, Mathieu; Farlow, Andrew; Hemingway, Janet; Velayudhan, Raman

    2017-08-01

    cost immunization strategy, our results suggest that sustained vector control will continue to play an important role in mitigating the impact of environmental change and urbanization on human health. If additional benefits for the control of other Aedes borne diseases, such as Chikungunya, yellow fever and Zika fever are taken into account, the investment case is even stronger. High-burden endemic countries should proceed to map populations to be covered by sustained vector control.

  18. An economic evaluation of vector control in the age of a dengue vaccine.

    Directory of Open Access Journals (Sweden)

    Christopher Fitzpatrick

    2017-08-01

    and low cost immunization strategy, our results suggest that sustained vector control will continue to play an important role in mitigating the impact of environmental change and urbanization on human health. If additional benefits for the control of other Aedes borne diseases, such as Chikungunya, yellow fever and Zika fever are taken into account, the investment case is even stronger. High-burden endemic countries should proceed to map populations to be covered by sustained vector control.

  19. Recombinant vaccines against T. gondii: comparison between homologous and heterologous vaccination protocols using two viral vectors expressing SAG1.

    Science.gov (United States)

    Mendes, Érica Araújo; Fonseca, Flavio G; Casério, Bárbara M; Colina, Janaína P; Gazzinelli, Ricardo Tostes; Caetano, Braulia C

    2013-01-01

    The use of recombinant viral vectors expressing T. gondii antigens is a safe and efficient approach to induce immune response against the parasite and a valuable tool for vaccine development. We have previously protected mice from toxoplasmosis by immunizing the animals with an adenovirus expressing the protein SAG1 (AdSAG1) of T. gondii. We are now looking for ways to improve the vaccination strategy and enhance protection. One limitation of homologous vaccinations (sequential doses of the same vector) is induction of anti-vector immune response that blocks cell transduction, restricts transgene expression and, consequently, compromises the overall outcome of vaccination. One way to avert the effects of anti-vector response is to use different viruses in prime and boost (heterologous vaccination). Bearing this in mind, we generated a modified Vaccinia Virus Ankara encoding SAG1 (MVASAG1), to be tested as boost agent after prime with AdSAG1. Although minor differences were observed in the magnitude of the anti-SAG1 immune response induced by each vaccination protocol, the heterologous immunization with AdSAG1 followed by MVASAG1 resulted in improved capacity to control brain cyst formation in a model of chronic toxoplasmosis in C57BL/6 mice.

  20. Recombinant vaccines against T. gondii: comparison between homologous and heterologous vaccination protocols using two viral vectors expressing SAG1.

    Directory of Open Access Journals (Sweden)

    Érica Araújo Mendes

    Full Text Available The use of recombinant viral vectors expressing T. gondii antigens is a safe and efficient approach to induce immune response against the parasite and a valuable tool for vaccine development. We have previously protected mice from toxoplasmosis by immunizing the animals with an adenovirus expressing the protein SAG1 (AdSAG1 of T. gondii. We are now looking for ways to improve the vaccination strategy and enhance protection. One limitation of homologous vaccinations (sequential doses of the same vector is induction of anti-vector immune response that blocks cell transduction, restricts transgene expression and, consequently, compromises the overall outcome of vaccination. One way to avert the effects of anti-vector response is to use different viruses in prime and boost (heterologous vaccination. Bearing this in mind, we generated a modified Vaccinia Virus Ankara encoding SAG1 (MVASAG1, to be tested as boost agent after prime with AdSAG1. Although minor differences were observed in the magnitude of the anti-SAG1 immune response induced by each vaccination protocol, the heterologous immunization with AdSAG1 followed by MVASAG1 resulted in improved capacity to control brain cyst formation in a model of chronic toxoplasmosis in C57BL/6 mice.

  1. Immune system simulation online

    DEFF Research Database (Denmark)

    Rapin, Nicolas; Lund, Ole; Castiglione, Filippo

    2011-01-01

    MOTIVATION: The recognition of antigenic peptides is a major event of an immune response. In current mesoscopic-scale simulators of the immune system, this crucial step has been modeled in a very approximated way. RESULTS: We have equipped an agent-based model of the immune system with immuno...

  2. Vector optimization set-valued and variational analysis

    CERN Document Server

    Chen, Guang-ya; Yang, Xiaogi

    2005-01-01

    This book is devoted to vector or multiple criteria approaches in optimization. Topics covered include: vector optimization, vector variational inequalities, vector variational principles, vector minmax inequalities and vector equilibrium problems. In particular, problems with variable ordering relations and set-valued mappings are treated. The nonlinear scalarization method is extensively used throughout the book to deal with various vector-related problems. The results presented are original and should be interesting to researchers and graduates in applied mathematics and operations research

  3. Immunity by equilibrium.

    Science.gov (United States)

    Eberl, Gérard

    2016-08-01

    The classical model of immunity posits that the immune system reacts to pathogens and injury and restores homeostasis. Indeed, a century of research has uncovered the means and mechanisms by which the immune system recognizes danger and regulates its own activity. However, this classical model does not fully explain complex phenomena, such as tolerance, allergy, the increased prevalence of inflammatory pathologies in industrialized nations and immunity to multiple infections. In this Essay, I propose a model of immunity that is based on equilibrium, in which the healthy immune system is always active and in a state of dynamic equilibrium between antagonistic types of response. This equilibrium is regulated both by the internal milieu and by the microbial environment. As a result, alteration of the internal milieu or microbial environment leads to immune disequilibrium, which determines tolerance, protective immunity and inflammatory pathology.

  4. Mosquito-Disseminated Insecticide for Citywide Vector Control and Its Potential to Block Arbovirus Epidemics: Entomological Observations and Modeling Results from Amazonian Brazil.

    Directory of Open Access Journals (Sweden)

    Fernando Abad-Franch

    2017-01-01

    Full Text Available Mosquito-borne viruses threaten public health worldwide. When the ratio of competent vectors to susceptible humans is low enough, the virus's basic reproductive number (R0 falls below 1.0 (each case generating, on average, <1.0 additional case and the infection fades out from the population. Conventional mosquito control tactics, however, seldom yield R0 < 1.0. A promising alternative uses mosquitoes to disseminate a potent growth-regulator larvicide, pyriproxyfen (PPF, to aquatic larval habitats; this kills most mosquito juveniles and substantially reduces adult mosquito emergence. We tested mosquito-disseminated PPF in Manacapuru, a 60,000-inhabitant city (~650 ha in Amazonian Brazil.We sampled juvenile mosquitoes monthly in 100 dwellings over four periods in February 2014-January 2016: 12 baseline months, 5 mo of citywide PPF dissemination, 3 mo of focal PPF dissemination around Aedes-infested dwellings, and 3 mo after dissemination ended. We caught 19,434 juvenile mosquitoes (66% Aedes albopictus, 28% Ae. aegypti in 8,271 trap-months. Using generalized linear mixed models, we estimated intervention effects on juvenile catch and adult emergence while adjusting for dwelling-level clustering, unequal sampling effort, and weather-related confounders. Following PPF dissemination, Aedes juvenile catch decreased by 79%-92% and juvenile mortality increased from 2%-7% to 80%-90%. Mean adult Aedes emergence fell from 1,077 per month (range 653-1,635 at baseline to 50.4 per month during PPF dissemination (range 2-117. Female Aedes emergence dropped by 96%-98%, such that the number of females emerging per person decreased to 0.06 females per person-month (range 0.002-0.129. Deterministic models predict, under plausible biological-epidemiological scenarios, that the R0 of typical Aedes-borne viruses would fall from 3-45 at baseline to 0.004-0.06 during PPF dissemination. The main limitations of our study were that it was a before-after trial lacking

  5. Microsphere-liposome complexes protect adenoviral vectors from neutralising antibody without losses in transfection efficiency, in-vitro.

    Science.gov (United States)

    Steel, Jason C; Cavanagh, Heather M A; Burton, Mark A; Kalle, Wouter H J

    2004-11-01

    Adenoviral vectors have been commonly used in gene therapy protocols but the success of their use is often limited by the induction of host immunity to the vector. Following exposure to the adenoviral vector, adenoviral-specific neutralising antibodies are produced, which limits further administration. This study examines the effectiveness of a novel combination of microspheres and liposomes for the shielding of adenovirus from neutralising antibodies in an in-vitro setting. We show that liposomes are effective in the protection of adenovirus from neutralising antibody and that the conjugation of these complexes to microspheres augments the level of protection. This study further reveals that previously neutralised adenovirus may still be transported into the cell via liposome-cell interactions and is still capable of expressing its genes, making this vector an effective tool for circumvention of the humoral immune response. We also looked at possible side effects of using the complexes, namely increases in cytotoxicity and reductions in transfection efficiency. Our results showed that varying the liposome:adenovirus ratio can reduce the cytotoxicity of the vector as well as increase the transfection efficiency. In addition, in cell lines that are adenoviral competent, transfection efficiencies on par with uncomplexed adenoviral vectors were achievable with the combination vector.

  6. Effects of elevated parameters of subclinical ketosis on the immune system of dairy cows: in vivo and in vitro results.

    Science.gov (United States)

    Schulz, Kirsten; Frahm, Jana; Kersten, Susanne; Meyer, Ulrich; Reiche, Dania; Sauerwein, Helga; Dänicke, Sven

    2015-01-01

    Using an established model in which subclinical ketosis is induced, the response of differential blood counts and levels of various haematological variables, including the inflammatory marker haptoglobin (Hp), were tested over the last six weeks of parturition until the 56th day post-partum in cows with lower or higher body condition scores (LBC and HBC, respectively; n = 9/group). Animals in the HBC group evidenced subclinical ketosis whereas LBC animals were metabolically healthy. For in vitro examination with ß-hydroxybutyrate (BHB) as a further stimulus, peripheral blood mononuclear cell (PBMC) counts of cows with and without subclinical ketosis (n = 5/group) were observed. Counts of leucocytes, granulocytes and lymphocytes (LY) peaked at day 1 post-partum in HBC cows, with a more marked increase in heifers. In subclinical ketosis LY count increased again, with significantly higher values in the HBC group. The red blood cell (RBC) profile was affected by parity (counts were higher in heifers). Hp showed a positive linear correlation with BHB and non-esterified fatty acids (NEFA; R(2) = 0.41). PBMC from cows that were not pre-stressed with subclinical ketosis were more sensitive to increasing levels of BHB in vitro, as evidenced by both their higher proliferative capability and increased release of nitric oxide (NO). In summary, cows with subclinical ketosis showed a heightened immune response compared with metabolically healthy individuals, based on increased LY counts, increasing stimulative properties of PBMC and a relationship between Hp and typically increased values of BHB and NEFA. Concentrations of BHB in vivo during subclinical ketosis did not alter the proliferative capability of bovine PBMC in vitro, which was first significantly decreased at a dosage of 5 mM BHB.

  7. Production and purification of non replicative canine adenovirus type 2 derived vectors.

    Science.gov (United States)

    Szelechowski, Marion; Bergeron, Corinne; Gonzalez-Dunia, Daniel; Klonjkowski, Bernard

    2013-12-03

    Adenovirus (Ad) derived vectors have been widely used for short or long-term gene transfer, both for gene therapy and vaccine applications. Because of the frequent pre-existing immunity against the classically used human adenovirus type 5, canine adenovirus type 2 (CAV2) has been proposed as an alternative vector for human gene transfer. The well-characterized biology of CAV2, together with its ease of genetic manipulation, offer major advantages, notably for gene transfer into the central nervous system, or for inducing a wide range of protective immune responses, from humoral to cellular immunity. Nowadays, CAV2 represents one of the most appealing nonhuman adenovirus for use as a vaccine vector. This protocol describes a simple method to construct, produce and titer recombinant CAV2 vectors. After cloning the expression cassette of the gene of interest into a shuttle plasmid, the recombinant genomic plasmid is obtained by homologous recombination in the E. coli BJ5183 bacterial strain. The resulting genomic plasmid is then transfected into canine kidney cells expressing the complementing CAV2-E1 genes (DK-E1). A viral amplification enables the production of a large viral stock, which is purified by ultracentrifugation through cesium chloride gradients and desalted by dialysis. The resulting viral suspension routinely has a titer of over 10(10) infectious particles per ml and can be directly administrated in vivo.

  8. The elimination of the onchocerciasis vector from the island of Bioko as a result of larviciding by the WHO African Programme for Onchocerciasis Control.

    Science.gov (United States)

    Traoré, S; Wilson, M D; Sima, A; Barro, T; Diallo, A; Aké, A; Coulibaly, S; Cheke, R A; Meyer, R R F; Mas, J; McCall, P J; Post, R J; Zouré, H; Noma, M; Yaméogo, L; Sékétéli, A V; Amazigo, U V

    2009-09-01

    The island of Bioko is part of the Republic of Equatorial Guinea and is the only island in the World to have endemic onchocerciasis. The disease is hyperendemic and shows a forest-type epidemiology with low levels of blindness and high levels of skin disease, and the whole population of 68,000 is estimated to be at risk. Control of onchocerciasis began in 1990 using ivermectin and this yielded significant clinical benefits but transmission was not interrupted. Feasibility and preparatory studies carried out between 1995 and 2002 confirmed the probable isolation of the vector on the island, the high vectorial efficiency of the Bioko form of Simulium yahense, the seasonality of river flow, blackfly breeding and biting densities, and the distribution of the vector breeding sites. It was proposed that larviciding should be carried out from January to April, when most of the island's rivers were dry or too low to support Simulium damnosum s.l., and that most rivers would not need to be treated above 500 m altitude because they were too small to support the breeding of S. damnosum s.l. Larviciding (with temephos) would need to be carried out by helicopter (because of problems of access by land), supplemented by ground-based delivery. Insecticide susceptibility trials showed that the Bioko form was highly susceptible to temephos, and insecticide carry was tested in the rivers by assessing the length of river in which S. damnosum s.l. larvae were killed below a temephos dosing point. Regular fly catching points were established in 1999 to provide pre-control biting densities, and to act as monitoring points for control efforts. An environmental impact assessment concluded that the proposed control programme could be expected to do little damage, and a large-scale larviciding trial using ground-based applications of temephos (Abate 20EC) throughout the northern (accessible) part of the island was carried out for five weeks from 12 February 2001. Following this, a first

  9. Early ART Results in Greater Immune Reconstitution Benefits in HIV-Infected Infants: Working with Data Missingness in a Longitudinal Dataset.

    Directory of Open Access Journals (Sweden)

    Livio Azzoni

    Full Text Available Early initiation of anti-retroviral treatment (ART decreases mortality as compared to deferred treatment, but whether it preserves immune cells from early loss or promotes their recovery remains undefined. Determination of complex immunological endpoints in infants is often marred by missing data due to missed visits and/or inadequate sampling. Specialized methods are required to address missingness and facilitate data analysis.We characterized the changes in cellular and humoral immune parameters over the first year of life in 66 HIV-infected infants (0-1 year of age enrolled in the CHER study starting therapy within 12 weeks of birth (n = 42 or upon disease progression (n = 24. A convenience cohort of 23 uninfected infants aged 0-6 months born to mothers with HIV-1 infection was used as controls. Flow cytometry and ELISA were used to evaluate changes in natural killer (NK cells, plasmacytoid dendritic cells (pDC, and CD4+ or CD8+ T-cell frequencies. Data missingness was assessed using Little's test. Complete datasets for analysis were created using Multiple Imputation (MI or Bayesian modeling and multivariate analysis was conducted on the imputed datasets.HIV-1-infected infants had greater frequency of CD4+ T cells with naïve phenotype, as well as higher serum IL-7 levels than HIV exposed/uninfected infants. The elevated data missingness was completely at random, allowing the use of both MI and Bayesian modeling. Both methods indicate that early ART initiation results in higher CD4+ T cell frequency, lower expression of CD95 in CD8+ T cell, and preservation of naïve T cell subsets. In contrast, innate immune effectors appeared to be similar independently of the timing of ART initiation.Early ART initiation in infants with perinatal HIV infection reduces immune activation and preserves an early expansion of naïve T-cells with undiminished innate cell numbers, giving greater immune reconstitution than achieved with deferred ART. Both

  10. Assessment of Lactobacillus gasseri as a candidate oral vaccine vector.

    Science.gov (United States)

    Stoeker, Laura; Nordone, Shila; Gunderson, Sara; Zhang, Lin; Kajikawa, Akinobu; LaVoy, Alora; Miller, Michael; Klaenhammer, Todd R; Dean, Gregg A

    2011-11-01

    Lactobacillus species are commensal bacteria that have long been recognized as probiotic microbes and are generally regarded as safe (GRAS) for human consumption. We have investigated the use of L. gasseri as a vaccine vector for oral immunization against mucosal pathogens. Recent research has shown that the immune response to different lactobacilli can vary widely depending on the species or subspecies of Lactobacillus being studied. While some lactobacilli seem to induce oral tolerance, others induce an adaptive immune response. This study characterized the systemic and mucosal immune response to wild-type and genetically modified L. gasseri. L. gasseri primarily activates TLR2/6, with additional activation through the TLR2 homodimer. To expand the Toll-like receptor (TLR) activation profile of L. gasseri and the immunogenicity of the vector, a plasmid containing fliC, the gene encoding bacterial flagellin, was introduced which resulted in the strong activation of TLR5. The treatment of human myeloid dendritic cells with recombinant lactobacilli expressing flagellin triggered phenotypic maturation and the release of proinflammatory cytokines. In contrast, bacterial treatment also resulted in a statistically significant increase in IL-10 production. In vivo studies established that treatment with L. gasseri led to a diversification of B-cell populations in the lamina propria of the murine colon. Furthermore, treatment with genetically modified L. gasseri led to a significant decrease in the percentage of FoxP3(+) colonic lymphocytes. Taken together, these data clarify the interaction of L. gasseri with the host immune system and support further investigation of the in vivo immunogenicity of L. gasseri expressing both flagellin and candidate vaccine antigens.

  11. Adult Immunization

    Directory of Open Access Journals (Sweden)

    Omer Coskun

    2008-04-01

    Full Text Available Despite the many advances in modern medicine, each year thousands of people in the world die from diseases that are easily prevented by safe and effective vaccines. Few measures in preventive medicine are of such proven value and as easy to implement as routine immunization against infectious diseases. Prevention of infection by immunization is a lifelong process. There are a number of vaccines that all adults (¡I18 years require. There are also other vaccines that need to be tailored to meet individual variations in risk resulting from occupation, foreign travel, underlying illness, lifestyle and age. In this study, we tried to review this important subject. [TAF Prev Med Bull 2008; 7(2.000: 159-166

  12. Construction and evaluation of novel rhesus monkey adenovirus vaccine vectors.

    Science.gov (United States)

    Abbink, Peter; Maxfield, Lori F; Ng'ang'a, David; Borducchi, Erica N; Iampietro, M Justin; Bricault, Christine A; Teigler, Jeffrey E; Blackmore, Stephen; Parenteau, Lily; Wagh, Kshitij; Handley, Scott A; Zhao, Guoyan; Virgin, Herbert W; Korber, Bette; Barouch, Dan H

    2015-02-01

    Adenovirus vectors are widely used as vaccine candidates for a variety of pathogens, including HIV-1. To date, human and chimpanzee adenoviruses have been explored in detail as vaccine vectors. The phylogeny of human and chimpanzee adenoviruses is overlapping, and preexisting humoral and cellular immunity to both are exhibited in human populations worldwide. More distantly related adenoviruses may therefore offer advantages as vaccine vectors. Here we describe the primary isolation and vectorization of three novel adenoviruses from rhesus monkeys. The seroprevalence of these novel rhesus monkey adenovirus vectors was extremely low in sub-Saharan Africa human populations, and these vectors proved to have immunogenicity comparable to that of human and chimpanzee adenovirus vaccine vectors in mice. These rhesus monkey adenoviruses phylogenetically clustered with the poorly described adenovirus species G and robustly stimulated innate immune responses. These novel adenoviruses represent a new class of candidate vaccine vectors. Although there have been substantial efforts in the development of vaccine vectors from human and chimpanzee adenoviruses, far less is known about rhesus monkey adenoviruses. In this report, we describe the isolation and vectorization of three novel rhesus monkey adenoviruses. These vectors exhibit virologic and immunologic characteristics that make them attractive as potential candidate vaccine vectors for both HIV-1 and other pathogens. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  13. Recent advances in genetic modification of adenovirus vectors for cancer treatment.

    Science.gov (United States)

    Yamamoto, Yuki; Nagasato, Masaki; Yoshida, Teruhiko; Aoki, Kazunori

    2017-05-01

    Adenoviruses are widely used to deliver genes to a variety of cell types and have been used in a number of clinical trials for gene therapy and oncolytic virotherapy. However, several concerns must be addressed for the clinical use of adenovirus vectors. Selective delivery of a therapeutic gene by adenovirus vectors to target cancer is precluded by the widespread distribution of the primary cellular receptors. The systemic administration of adenoviruses results in hepatic tropism independent of the primary receptors. Adenoviruses induce strong innate and acquired immunity in vivo. Furthermore, several modifications to these vectors are necessary to enhance their oncolytic activity and ensure patient safety. As such, the adenovirus genome has been engineered to overcome these problems. The first part of the present review outlines recent progress in the genetic modification of adenovirus vectors for cancer treatment. In addition, several groups have recently developed cancer-targeting adenovirus vectors by using libraries that display random peptides on a fiber knob. Pancreatic cancer-targeting sequences have been isolated, and these oncolytic vectors have been shown by our group to be associated with a higher gene transduction efficiency and more potent oncolytic activity in cell lines, murine models, and surgical specimens of pancreatic cancer. In the second part of this review, we explain that combining cancer-targeting strategies can be a promising approach to increase the clinical usefulness of oncolytic adenovirus vectors. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  14. Immune sensitization to methylene diphenyl diisocyanate (MDI resulting from skin exposure: albumin as a carrier protein connecting skin exposure to subsequent respiratory responses

    Directory of Open Access Journals (Sweden)

    Redlich Carrie A

    2011-03-01

    Full Text Available Abstract Background Methylene diphenyl diisocyanate (MDI, a reactive chemical used for commercial polyurethane production, is a well-recognized cause of occupational asthma. The major focus of disease prevention efforts to date has been respiratory tract exposure; however, skin exposure may also be an important route for inducing immune sensitization, which may promote subsequent airway inflammatory responses. We developed a murine model to investigate pathogenic mechanisms by which MDI skin exposure might promote subsequent immune responses, including respiratory tract inflammation. Methods Mice exposed via the skin to varying doses (0.1-10% w/v of MDI diluted in acetone/olive oil were subsequently evaluated for MDI immune sensitization. Serum levels of MDI-specific IgG and IgE were measured by enzyme-linked immunosorbant assay (ELISA, while respiratory tract inflammation, induced by intranasal delivery of MDI-mouse albumin conjugates, was evaluated based on bronchoalveolar lavage (BAL. Autologous serum IgG from "skin only" exposed mice was used to detect and guide the purification/identification of skin proteins antigenically modified by MDI exposure in vivo. Results Skin exposure to MDI resulted in specific antibody production and promoted subsequent respiratory tract inflammation in animals challenged intranasally with MDI-mouse albumin conjugates. The degree of (secondary respiratory tract inflammation and eosinophilia depended upon the (primary skin exposure dose, and was maximal in mice exposed to 1% MDI, but paradoxically limited in mice receiving 10-fold higher doses (e.g. 10% MDI. The major antigenically-modified protein at the local MDI skin exposure site was identified as albumin, and demonstrated biophysical changes consistent with MDI conjugation. Conclusions MDI skin exposure can induce MDI-specific immune sensitivity and promote subsequent respiratory tract inflammatory responses and thus, may play an important role in MDI asthma

  15. Trial watch: Naked and vectored DNA-based anticancer vaccines.

    Science.gov (United States)

    Bloy, Norma; Buqué, Aitziber; Aranda, Fernando; Castoldi, Francesca; Eggermont, Alexander; Cremer, Isabelle; Sautès-Fridman, Catherine; Fucikova, Jitka; Galon, Jérôme; Spisek, Radek; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2015-05-01

    One type of anticancer vaccine relies on the administration of DNA constructs encoding one or multiple tumor-associated antigens (TAAs). The ultimate objective of these preparations, which can be naked or vectored by non-pathogenic viruses, bacteria or yeast cells, is to drive the synthesis of TAAs in the context of an immunostimulatory milieu, resulting in the (re-)elicitation of a tumor-targeting immune response. In spite of encouraging preclinical results, the clinical efficacy of DNA-based vaccines employed as standalone immunotherapeutic interventions in cancer patients appears to be limited. Thus, efforts are currently being devoted to the development of combinatorial regimens that allow DNA-based anticancer vaccines to elicit clinically relevant immune responses. Here, we discuss recent advances in the preclinical and clinical development of this therapeutic paradigm.

  16. Imbalanced immune homeostasis in immune thrombocytopenia.

    Science.gov (United States)

    Yazdanbakhsh, Karina

    2016-04-01

    Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder resulting from low platelet counts caused by inadequate production as well as increased destruction by autoimmune mechanisms. As with other autoimmune disorders, chronic ITP is characterized by perturbations of immune homeostasis with hyperactivated effector cells as well as defective regulatory arm of the adaptive immune system, which will be reviewed here. Interestingly, some ITP treatments are associated with restoring the regulatory imbalance, although it remains unclear whether the immune system is redirected to a state of tolerance once treatment is discontinued. Understanding the mechanisms that result in breakdown of immune homeostasis in ITP will help to identify novel pathways for restoring tolerance and inhibiting effector cell responses. This information can then be translated into developing therapies for averting autoimmunity not only in ITP but also many autoimmune disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. A nano particle vector comprised of poly lactic-co-glycolic acid and monophosphoryl lipid A and recombinant Mycobacterium avium subsp paratuberculosis peptides stimulate a pro-immune profile in bovine macrophages

    Science.gov (United States)

    Current research and development of antigens for vaccination often center on purified recombinant proteins, viral vectored subunits, and synthetic peptides, most of which suffer from poor immunogenicity and are subject to degradation. For these reasons, efficient delivery systems and potent immunost...

  18. Vector Fields and Flows on Differentiable Stacks

    DEFF Research Database (Denmark)

    A. Hepworth, Richard

    2009-01-01

    This paper introduces the notions of vector field and flow on a general differentiable stack. Our main theorem states that the flow of a vector field on a compact proper differentiable stack exists and is unique up to a uniquely determined 2-cell. This extends the usual result on the existence...... of vector fields....

  19. Modeling vector nonlinear time series using POLYMARS

    NARCIS (Netherlands)

    de Gooijer, J.G.; Ray, B.K.

    2003-01-01

    A modified multivariate adaptive regression splines method for modeling vector nonlinear time series is investigated. The method results in models that can capture certain types of vector self-exciting threshold autoregressive behavior, as well as provide good predictions for more general vector

  20. Development of oral CTL vaccine using a CTP-integrated Sabin 1 poliovirus-based vector system.

    Science.gov (United States)

    Han, Seung-Soo; Lee, Jinjoo; Jung, Yideul; Kang, Myeong-Ho; Hong, Jung-Hyub; Cha, Min-Suk; Park, Yu-Jin; Lee, Ezra; Yoon, Cheol-Hee; Bae, Yong-Soo

    2015-09-11

    We developed a CTL vaccine vector by modification of the RPS-Vax system, a mucosal vaccine vector derived from a poliovirus Sabin 1 strain, and generated an oral CTL vaccine against HIV-1. A DNA fragment encoding a cytoplasmic transduction peptide (CTP) was integrated into the RPS-Vax system to generate RPS-CTP, a CTL vaccine vector. An HIV-1 p24 cDNA fragment was introduced into the RPS-CTP vector system and a recombinant poliovirus (rec-PV) named vRPS-CTP/p24 was produced. vRPS-CTP/p24 was genetically stable and efficiently induced Th1 immunity and p24-specific CTLs in immunized poliovirus receptor-transgenic (PVR-Tg) mice. In challenge experiments, PVR-Tg mice that were pre-immunized orally with vRPS-CTP/p24 were resistant to challenge with a lethal dose of p24-expressing recombinant vaccinia virus (rMVA-p24). These results suggested that the RPS-CTP vector system had potential for developing oral CTL vaccines against infectious diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Stable piecewise polynomial vector fields

    Directory of Open Access Journals (Sweden)

    Claudio Pessoa

    2012-09-01

    Full Text Available Let $N={y>0}$ and $S={y<0}$ be the semi-planes of $mathbb{R}^2$ having as common boundary the line $D={y=0}$. Let $X$ and $Y$ be polynomial vector fields defined in $N$ and $S$, respectively, leading to a discontinuous piecewise polynomial vector field $Z=(X,Y$. This work pursues the stability and the transition analysis of solutions of $Z$ between $N$ and $S$, started by Filippov (1988 and Kozlova (1984 and reformulated by Sotomayor-Teixeira (1995 in terms of the regularization method. This method consists in analyzing a one parameter family of continuous vector fields $Z_{epsilon}$, defined by averaging $X$ and $Y$. This family approaches $Z$ when the parameter goes to zero. The results of Sotomayor-Teixeira and Sotomayor-Machado (2002 providing conditions on $(X,Y$ for the regularized vector fields to be structurally stable on planar compact connected regions are extended to discontinuous piecewise polynomial vector fields on $mathbb{R}^2$. Pertinent genericity results for vector fields satisfying the above stability conditions are also extended to the present case. A procedure for the study of discontinuous piecewise vector fields at infinity through a compactification is proposed here.

  2. Retroviruses as tools to study the immune system.

    Science.gov (United States)

    Lois, C; Refaeli, Y; Qin, X F; Van Parijs, L

    2001-08-01

    Retrovirus-based vectors provide an efficient means to introduce and express genes in cells of the immune system and have become a popular tool to study immune function. They are easy to manipulate and provide stable, long-term gene expression because they integrate into the genome. Current retroviral vectors do have limitations that affect their usefulness in certain applications. However, recent advances suggest a number of ways in which these vectors might be improved to extend their utility in immunological research.

  3. Role of complement and antibodies in controlling infection with pathogenic simian immunodeficiency virus (SIV in macaques vaccinated with replication-deficient viral vectors

    Directory of Open Access Journals (Sweden)

    Strasak Alexander

    2009-06-01

    Full Text Available Abstract Background We investigated the interplay between complement and antibodies upon priming with single-cycle replicating viral vectors (SCIV encoding SIV antigens combined with Adeno5-SIV or SCIV pseudotyped with murine leukemia virus envelope boosting strategies. The vaccine was applied via spray-immunization to the tonsils of rhesus macaques and compared with systemic regimens. Results Independent of the application regimen or route, viral loads were significantly reduced after challenge with SIVmac239 (p Conclusion The heterologous prime-boost strategy with replication-deficient viral vectors administered exclusively via the tonsils did not induce any neutralizing antibodies before challenge. However, after challenge, comparable SIV-specific humoral immune responses were observed in all vaccinated animals. Immunization with single cycle immunodeficiency viruses mounts humoral immune responses comparable to live-attenuated immunodeficiency virus vaccines.

  4. First clinical results of minimally invasive vector lumbar interbody fusion (MIS-VLIF) in spondylodiscitis and concomitant osteoporosis: a technical note.

    Science.gov (United States)

    Rieger, Bernhard; Jiang, Hongzhen; Ruess, Daniel; Reinshagen, Clemens; Molcanyi, Marek; Zivcak, Jozef; Tong, Huaiyu; Schackert, Gabriele

    2017-12-01

    First description of MIS-VLIF, a minimally invasive lumbar stabilization, to evaluate its safety and feasibility in patients suffering from weak bony conditions (lumbar spondylodiscitis and/or osteoporosis). After informed consent, 12 patients suffering from lumbar spondylodiscitis underwent single level MIS-VLIF. Eight of them had a manifest osteoporosis, either. Pre- and postoperative clinical status was documented using numeric rating scale (NRS) for leg and back pain. In all cases, the optimal height for the cage was preoperatively determined using software-based range of motion and sagittal balance analysis. CT scans were obtained to evaluate correct placement of the construct and to verify fusion after 6 months. Since 2013, 12 patients with lumbar pyogenic spondylodiscitis underwent MIS-VLIF. Mean surgery time was 169 ± 28 min and average blood loss was less than 400 ml. Postoperative CT scans showed correct placement of the implants. Eleven patients showed considerable postoperative improvement in clinical scores. In one patient, we observed screw loosening. After documented bony fusion in the CT scan, the fixation system was removed in two cases to achieve lower material load. The load-bearing trajectories (vectors) of MIS-VLIF are different from those of conventional coaxial pedicle screw implantation. The dorsally converging construct combines the heads of the dorsoventral pedicle screws with laminar pedicle screws following cortical bone structures within a small approach. In case of lumbar spondylodiscitis and/or osteoporosis, MIS-VLIF relies on cortical bony structures for all screw vectors and the construct does not depend on conventional coaxial pedicle screws in the presence of inflamed, weak, cancellous or osteoporotic bone. MIS-VLIF allows full 360° lumbar fusion including cage implantation via a small, unilateral dorsal midline approach.

  5. Childhood Immunization

    Science.gov (United States)

    ... lowest levels in history, thanks to years of immunization. Children must get at least some vaccines before ... child provide protection for many years, adults need immunizations too. Centers for Disease Control and Prevention

  6. Immunizations - diabetes

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000331.htm Immunizations - diabetes To use the sharing features on this page, please enable JavaScript. Immunizations (vaccines or vaccinations) help protect you from some ...

  7. Mosquito Vectors and the Globalization of Plasmodium falciparum Malaria.

    Science.gov (United States)

    Molina-Cruz, Alvaro; Zilversmit, Martine M; Neafsey, Daniel E; Hartl, Daniel L; Barillas-Mury, Carolina

    2016-11-23

    Plasmodium falciparum malaria remains a devastating public health problem. Recent discoveries have shed light on the origin and evolution of Plasmodium parasites and their interactions with their vertebrate and mosquito hosts. P. falciparum malaria originated in Africa from a single horizontal transfer between an infected gorilla and a human, and became global as the result of human migration. Today, P. falciparum malaria is transmitted worldwide by more than 70 different anopheline mosquito species. Recent studies indicate that the mosquito immune system can be a barrier to malaria transmission and that the P. falciparum Pfs47 gene allows the parasite to evade mosquito immune detection. Here, we review the origin and globalization of P. falciparum and integrate this history with analysis of the biology, evolution, and dispersal of the main mosquito vectors. This new perspective broadens our understanding of P. falciparum population structure and the dispersal of important parasite genetic traits.

  8. Preexisting Salmonella-specific immunity interferes with the subsequent development of immune responses against the Salmonella strains delivering H9N2 hemagglutinin.

    Science.gov (United States)

    Hajam, Irshad Ahmed; Lee, John Hwa

    2017-06-01

    Recombinant Salmonella strains expressing foreign heterologous antigens have been extensively studied as promising live vaccine delivery vehicles. In this study, we constructed attenuated smooth (S-HA) and rough (R-HA) Salmonella strains expressing hemagglutinin (HA) of H9N2, a low pathogenic avian influenza A virus. We then investigated the HA-specific immune responses following oral immunization with either S-HA or R-HA strain in chicken model. We further examined the effects of the preexisting anti-Salmonella immunity on the subsequent elicitation of the HA and the Salmonella ompA specific immune responses. Our results showed that primary immunization with either the S-HA or the R-HA strain elicited comparable HA-specific immune responses and the responses were significantly (pSalmonella vector control. When chickens were pre-immunized with the smooth Salmonella carrier alone and then vaccinated with either S-HA or R-HA strain 3, 6 and 9 weeks later, respectively, significant reductions were seen for HA-specific immune responses at week 6, a point which corresponded to the peak of the primary Salmonella-specific antibody responses. No reductions were seen at week 3 and 9, albeit, the HA-specific immune responses were boosted at week 9, a point which corresponded to the lowest primary Salmonella-specific antibody responses. The ompA recall responses remain refractory at week 3 and 6 following deliberate immunization with the carrier strain, but were significantly (pSalmonella immunity inhibits antigen-specific immune responses and this effect could be avoided by carefully selecting the time point when carrier-specific immune responses are relatively low. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Probing deformed orbitals with vector A( vector e, e' N)B reactions

    International Nuclear Information System (INIS)

    Garrido, E.; Caballero, J.A.; Moya de Guerra, E.; Sarriguren, P.; Udias, J.M.

    1995-01-01

    We present results for response functions and asymmetries in the nuclear reactions 37 vector Ar( vector e, e' n) 36 Ar and 37 vector K( vector e,e' p) 36 Ar at quasifree kinematics. We compare PWIA results obtained using deformed HF wave functions with PWIA and DWIA results obtained assuming a spherical mean field. We show that the complex structure of the deformed orbitals can be probed by coincidence measurements with polarized beam and targets. ((orig.))

  10. Immunization Coverage

    Science.gov (United States)

    ... room/fact-sheets/detail/immunization-coverage","@context":"http://schema.org","@type":"Article"}; العربية 中文 français русский español ... Plan Global Health Observatory (GHO) data - Immunization More information on vaccines and immunization News 1 in 10 ...

  11. Evolution and Function of Thioester-Containing Proteins and the Complement System in the Innate Immune Response

    Directory of Open Access Journals (Sweden)

    Upasana Shokal

    2017-06-01

    Full Text Available The innate immune response is evolutionary conserved among organisms. The complement system forms an important and efficient immune defense mechanism. It consists of plasma proteins that participate in microbial detection, which ultimately results in the production of various molecules with antimicrobial activity. Thioester-containing proteins (TEPs are a superfamily of secreted effector proteins. In vertebrates, certain TEPs act in the innate immune response by promoting recruitment of immune cells, phagocytosis, and direct lysis of microbial invaders. Insects are excellent models for dissecting the molecular basis of innate immune recognition and response to a wide range of microbial infections. Impressive progress in recent years has generated crucial information on the role of TEPs in the antibacterial and antiparasite response of the tractable model insect Drosophila melanogaster and the mosquito malaria vector Anopheles gambiae. This knowledge is critical for better understanding the evolution of TEPs and their involvement in the regulation of the host innate immune system.

  12. A live oral Lawsonia intracellularis vaccine does not result in protective immunity comparable to that of a virulent strain

    DEFF Research Database (Denmark)

    Hvass, Henriette Cordes; Riber, Ulla; Ståhl, Marie

    in subclinical disease. Both groups were treated with antibiotics from day 21 to 26 and challenged at day 49 with the virulent strain. A control group (CC) only received challenge. We here report on clinical outcome, L. intracellularis infection of the intestines and immunological responses. While Re-I pigs had...... in both Vac and Re-I groups after primary inoculation/vaccination compared to the CC group. After challenge, however Vac and CC levels were high and Re-I levels low, indicating that Re-I pigs were protected from disease whereas vaccinated pigs were not. These results show that the vaccination does...

  13. Kochen-Specker vectors

    International Nuclear Information System (INIS)

    Pavicic, Mladen; Merlet, Jean-Pierre; McKay, Brendan; Megill, Norman D

    2005-01-01

    We give a constructive and exhaustive definition of Kochen-Specker (KS) vectors in a Hilbert space of any dimension as well as of all the remaining vectors of the space. KS vectors are elements of any set of orthonormal states, i.e., vectors in an n-dimensional Hilbert space, H n , n≥3, to which it is impossible to assign 1s and 0s in such a way that no two mutually orthogonal vectors from the set are both assigned 1 and that not all mutually orthogonal vectors are assigned 0. Our constructive definition of such KS vectors is based on algorithms that generate MMP diagrams corresponding to blocks of orthogonal vectors in R n , on algorithms that single out those diagrams on which algebraic (0)-(1) states cannot be defined, and on algorithms that solve nonlinear equations describing the orthogonalities of the vectors by means of statistically polynomially complex interval analysis and self-teaching programs. The algorithms are limited neither by the number of dimensions nor by the number of vectors. To demonstrate the power of the algorithms, all four-dimensional KS vector systems containing up to 24 vectors were generated and described, all three-dimensional vector systems containing up to 30 vectors were scanned, and several general properties of KS vectors were found

  14. Vector analysis of low to moderate astigmatism with small incision lenticule extraction (SMILE): results of a 1-year follow-up.

    Science.gov (United States)

    Zhang, Jiamei; Wang, Yan; Wu, Wenjing; Xu, Lulu; Li, Xiaojing; Dou, Rui

    2015-01-24

    To evaluate the refractive outcomes for the correction of low to moderate astigmatism up to 1 year following small incision lenticule extraction (SMILE) surgery. This retrospective study enrolled 98 eyes from 98 patients who underwent SMILE surgery for the correction of myopia and astigmatism. Only right eyes were included in this study to avoid the bias of orientation errors. The vector method was used to analyze the outcomes of astigmatism at 1 month, 6 months and 12 months after the procedure, including the double-angle plots, correction index (CI), index of success (IOS), angle of error (AofE) and magnitude of error (MofE). The effectiveness, safety, stability and predictability were also investigated during the 12-month follow-up. The preoperative cylinder ranged from -2.75 D to -0.25 D (average of -0.90±0.68 D), and the mean postoperative cylinder values were -0.24±0.29 D, -0.24±0.29 D, and -0.20±0.27 D at 1 month, 6 months, and 12 months, respectively. The mean astigmatism in vector form was -0.14 D×27.19° at 1 month, -0.13 D×27.29° at 6 months, and -0.10 D×28.63° at 12 months after surgery. The CI was 1.00±0.32 and IOS was 0.29±0.44 at the 12-month follow-up. Significant negative correlations were found between the CI and absolute target induced astigmatism (TIA) value, and positive correlations were found between the IOS and absolute AofE value (Psafe in correcting low to moderate astigmatism, and stable refractive outcomes were observed at the long-term follow-up. The undercorrection of astigmatism could possibly be influenced by attempted astigmatism correction preoperatively, the axis rotation during the surgery or wound healing postoperatively. This study suggested that nomograms should be adjusted in correcting astigmatism with SMILE surgery.

  15. Immune Modulation of NYVAC-Based HIV Vaccines by Combined Deletion of Viral Genes that Act on Several Signalling Pathways

    Directory of Open Access Journals (Sweden)

    Carmen Elena Gómez

    2017-12-01

    Full Text Available An HIV-1 vaccine continues to be a major target to halt the AIDS pandemic. The limited efficacy of the RV144 phase III clinical trial with the canarypox virus-based vector ALVAC and a gp120 protein component led to the conclusion that improved immune responses to HIV antigens are needed for a more effective vaccine. In non-human primates, the New York vaccinia virus (NYVAC poxvirus vector has a broader immunogenicity profile than ALVAC and has been tested in clinical trials. We therefore analysed the HIV immune advantage of NYVAC after removing viral genes that act on several signalling pathways (Toll-like receptors—TLR—interferon, cytokines/chemokines, as well as genes of unknown immune function. We generated a series of NYVAC deletion mutants and studied immune behaviour (T and B cell to HIV antigens and to the NYVAC vector in mice. Our results showed that combined deletion of selected vaccinia virus (VACV genes is a valuable strategy for improving the immunogenicity of NYVAC-based vaccine candidates. These immune responses were differentially modulated, positive or negative, depending on the combination of gene deletions. The deletions also led to enhanced antigen- or vector-specific cellular and humoral responses. These findings will facilitate the development of optimal NYVAC-based vaccines for HIV and other diseases.

  16. Vectorization of phase space Monte Carlo code in FACOM vector processor VP-200

    International Nuclear Information System (INIS)

    Miura, Kenichi

    1986-01-01

    This paper describes the vectorization techniques for Monte Carlo codes in Fujitsu's Vector Processor System. The phase space Monte Carlo code FOWL is selected as a benchmark, and scalar and vector performances are compared. The vectorized kernel Monte Carlo routine which contains heavily nested IF tests runs up to 7.9 times faster in vector mode than in scalar mode. The overall performance improvement of the vectorized FOWL code over the original scalar code reaches 3.3. The results of this study strongly indicate that supercomputer can be a powerful tool for Monte Carlo simulations in high energy physics. (Auth.)

  17. Immunizing Children

    Directory of Open Access Journals (Sweden)

    Geraldine Jody Macdonald

    2014-11-01

    Full Text Available This article addresses the complex contexts within which Canadian health professionals engage in immunizing children and focuses on the Canadian practice guidelines and current scientific evidence that direct Canadian health professional competencies. The article begins by presenting two current global vaccine initiatives and links these to immunization in Canada. A selected literature review identifies current best immunization practices. With the purpose of promoting quality improvement, three key Canadian immunization competencies for health professional are highlighted: communication with parents, including those who are experiencing vaccine hesitancy; administration of immunizing agents; and documentation of immunizations. Health professionals are encouraged to reflect on immunization competencies and ensure evidence-based practices underpin vaccine delivery in their primary care settings.

  18. High HPV-51 prevalence in invasive cervical cancers: results of a pre-immunization survey in North Sardinia, Italy.

    Directory of Open Access Journals (Sweden)

    Andrea Piana

    Full Text Available BACKGROUND: Human Papilloma virus (HPV is recognized as the etiological agent of benign and malignant ano-genital lesions. The most prevalent genotypes associated with cervical carcinoma are HPV-16 and -18 worldwide. However, recent studies have emphasized the role of other genotypes, such as HPV-51, in the pathogenesis of cervical dysplasia. The aim of the study was to estimate the burden of HPV-51 infection in invasive cervical malignant lesions in Northern Sardinia, Italy. METHODS/PRINCIPAL FINDINGS: An observational, retrospective, prevalence, mono-center study was carried out to evaluate the presence of HPV genotypes in tissues biopsies of cervical lesions (CIN-1, CIN-2, CIN-3 and invasive carcinoma gathered from 1996 to 2009. Biological samples were collected from women admitted consecutively to a tertiary university hospital situated in Sassari, Italy. Molecular methods were used to identify 28 oncogenic HPV types. A total of 155 formalin-fixed and paraffin-embedded cervical tissue samples were analyzed. Approximately half of the cervical lesions were classified as invasive carcinoma. HPV-DNA was detected in 71% of the samples, with a higher frequency (100% in those categorized as invasive neoplasia. Mono- or co-infections were demonstrated in 45.8% and 25.8% of the cervical samples, respectively. Overall, the most prevalent HPV types were -16 (49% and -51 (19.4%, with an increased frequency of detection associated with the severity of the cervical lesions. CONCLUSIONS/SIGNIFICANCE: This survey highlights for the first time the relevant role of HPV-51 infection in the pathogenesis of invasive cervical cancer prior to the introduction of a vaccination program. Although a selection bias could have influenced the results, other recent studies have described the impact of HPV-51. This remarkable epidemiological element should be carefully evaluated, particularly in the view of opting for preventive vaccines, whose cross-protection patterns

  19. Vector regression introduced

    Directory of Open Access Journals (Sweden)

    Mok Tik

    2014-06-01

    Full Text Available This study formulates regression of vector data that will enable statistical analysis of various geodetic phenomena such as, polar motion, ocean currents, typhoon/hurricane tracking, crustal deformations, and precursory earthquake signals. The observed vector variable of an event (dependent vector variable is expressed as a function of a number of hypothesized phenomena realized also as vector variables (independent vector variables and/or scalar variables that are likely to impact the dependent vector variable. The proposed representation has the unique property of solving the coefficients of independent vector variables (explanatory variables also as vectors, hence it supersedes multivariate multiple regression models, in which the unknown coefficients are scalar quantities. For the solution, complex numbers are used to rep- resent vector information, and the method of least squares is deployed to estimate the vector model parameters after transforming the complex vector regression model into a real vector regression model through isomorphism. Various operational statistics for testing the predictive significance of the estimated vector parameter coefficients are also derived. A simple numerical example demonstrates the use of the proposed vector regression analysis in modeling typhoon paths.

  20. Multiscale vector fields for image pattern recognition

    Science.gov (United States)

    Low, Kah-Chan; Coggins, James M.

    1990-01-01

    A uniform processing framework for low-level vision computing in which a bank of spatial filters maps the image intensity structure at each pixel into an abstract feature space is proposed. Some properties of the filters and the feature space are described. Local orientation is measured by a vector sum in the feature space as follows: each filter's preferred orientation along with the strength of the filter's output determine the orientation and the length of a vector in the feature space; the vectors for all filters are summed to yield a resultant vector for a particular pixel and scale. The orientation of the resultant vector indicates the local orientation, and the magnitude of the vector indicates the strength of the local orientation preference. Limitations of the vector sum method are discussed. Investigations show that the processing framework provides a useful, redundant representation of image structure across orientation and scale.

  1. Antibody study in canine distemper virus nucleocapsid protein gene-immunized mice.

    Science.gov (United States)

    Yuan, B; Li, X Y; Zhu, T; Yuan, L; Hu, J P; Chen, J; Gao, W; Ren, W Z

    2015-04-10

    The gene for the nucleocapsid (N) protein of canine distemper virus was cloned into the pMD-18T vector, and positive recombinant plasmids were obtained by enzyme digestion and sequencing. After digestion by both EcoRI and KpnI, the plasmid was directionally cloned into the eukaryotic expression vector pcDNA; the positive clone pcDNA-N was screened by electrophoresis and then transfected into COS-7 cells. Immunofluorescence analysis results showed that the canine distemper virus N protein was expressed in the cytoplasm of transfected COS-7 cells. After emulsification in Freund's adjuvant, the recombinant plasmid pcDNA-N was injected into the abdominal cavity of 8-week-old BABL/c mice, with the pcDNA original vector used as a negative control. Mice were immunized 3 times every 2 weeks. The blood of immunized mice was drawn 2 weeks after completing the immunizations to measure titer levels. The antibody titer in the pcDNA-N test was 10(1.62 ± 0.164), while in the control group this value was 10(0.52 ± 0.56), indicating that specific humoral immunity was induced in canine distemper virus nucleocapsid protein-immunized mice.

  2. An Update on Canine Adenovirus Type 2 and Its Vectors

    Science.gov (United States)

    Bru, Thierry; Salinas, Sara; Kremer, Eric J.

    2010-01-01

    Adenovirus vectors have significant potential for long- or short-term gene transfer. Preclinical and clinical studies using human derived adenoviruses (HAd) have demonstrated the feasibility of flexible hybrid vector designs, robust expression and induction of protective immunity. However, clinical use of HAd vectors can, under some conditions, be limited by pre-existing vector immunity. Pre-existing humoral and cellular anti-capsid immunity limits the efficacy and duration of transgene expression and is poorly circumvented by injections of larger doses and immuno-suppressing drugs. This review updates canine adenovirus serotype 2 (CAV-2, also known as CAdV-2) biology and gives an overview of the generation of early region 1 (E1)-deleted to helper-dependent (HD) CAV-2 vectors. We also summarize the essential characteristics concerning their interaction with the anti-HAd memory immune responses in humans, the preferential transduction of neurons, and its high level of retrograde axonal transport in the central and peripheral nervous system. CAV-2 vectors are particularly interesting tools to study the pathophysiology and potential treatment of neurodegenerative diseases, as anti-tumoral and anti-viral vaccines, tracer of synaptic junctions, oncolytic virus and as a platform to generate chimeric vectors. PMID:21994722

  3. Reciprocal Regulation of NF-kB (Relish) and Subolesin in the Tick Vector, Ixodes scapularis

    Science.gov (United States)

    Galindo, Ruth C.; Kocan, Katherine M.; Blouin, Edmour F.; Mitra, Ruchira; Alberdi, Pilar; Villar, Margarita; de la Fuente, José

    2013-01-01

    Background Tick Subolesin and its ortholog in insects and vertebrates, Akirin, have been suggested to play a role in the immune response through regulation of nuclear factor-kappa B (NF-kB)-dependent and independent gene expression via interaction with intermediate proteins that interact with NF-kB and other regulatory proteins, bind DNA or remodel chromatin to regulate gene expression. The objective of this study was to characterize the structure and regulation of subolesin in Ixodes scapularis. I. scapularis is a vector of emerging pathogens such as Borrelia burgdorferi, Anaplasma phagocytophilum and Babesia microti that cause in humans Lyme disease, anaplasmosis and babesiosis, respectively. The genome of I. scapularis was recently sequenced, and this tick serves as a model organism for the study of vector-host-pathogen interactions. However, basic biological questions such as gene organization and regulation are largely unknown in ticks and other arthropod vectors. Principal Findings The results presented here provide evidence that subolesin/akirin are evolutionarily conserved at several levels (primary sequence, gene organization and function), thus supporting their crucial biological function in metazoans. These results showed that NF-kB (Relish) is involved in the regulation of subolesin expression in ticks, suggesting that as in other organisms, different NF-kB integral subunits and/or unknown interacting proteins regulate the specificity of the NF-kB-mediated gene expression. These results suggested a regulatory network involving cross-regulation between NF-kB (Relish) and Subolesin and Subolesin auto-regulation with possible implications in tick immune response to bacterial infection. Significance These results advance our understanding of gene organization and regulation in I. scapularis and have important implications for arthropod vectors genetics and immunology highlighting the possible role of NF-kB and Subolesin/Akirin in vector

  4. 3D vector flow imaging

    DEFF Research Database (Denmark)

    Pihl, Michael Johannes

    The main purpose of this PhD project is to develop an ultrasonic method for 3D vector flow imaging. The motivation is to advance the field of velocity estimation in ultrasound, which plays an important role in the clinic. The velocity of blood has components in all three spatial dimensions, yet...... are (vx, vy, vz) = (-0.03, 95, 1.0) ± (9, 6, 1) cm/s compared with the expected (0, 96, 0) cm/s. Afterwards, 3D vector flow images from a cross-sectional plane of the vessel are presented. The out of plane velocities exhibit the expected 2D circular-symmetric parabolic shape. The experimental results...... verify that the 3D TO method estimates the complete 3D velocity vectors, and that the method is suitable for 3D vector flow imaging....

  5. A prospective study of long-term results and the red blood cell immune adherence function following 131I treatment of Graves' disease

    International Nuclear Information System (INIS)

    Sun Zengjun; Ma Yuqin; Liu Junqing; Zhang Xia

    2003-01-01

    Objective: To observe the long-term curative effect and red blood cell immune function in patients with Graves' Disease (GD) after radioactive iodine ( 131 I) treatment. Methods: To observe the hyperthyroid symptoms, physical signs and to measure the concentration of FT3, FT4, FSH by radioimmunoassay, the percent of RBC-C 3b R-YR(%), RBC-IC-YR(%). Results: Patients with GD treated by 131 I after three month, these hyperthyroid symptoms, Physical signs are alleviated and even vanished in patients who were treated by 131 I after 1.5 years, RBC-C 3b R-YR(%) are normal in all patients, but RBC-IC-YR(%) are higher than before treatment with 131 I, then become lower after three months, treatment by 131 I but they were higher than those in normal group, when treated with 131 I after 1.5 years, RBC-IC-YR(%) are normal, the relationship between RBC-C 3b R-YR(%) and RBC-IC-YR(%) are positively interacted. Conclusion: The 131 I treatment produces a good rapid curative effect for GD patients, the disorder state of the red cell immune adherence system is rapidly corrected and this effect is unidirectional. So RBC-C 3b R-YR(%), RBC-IC-YR(%) are the useful predictors of GD remission and their relationship, RBC-IC-YR(%) are helpful in explaining the mechanism of radioactive iodine therapy and are the predictors of GD remission after 131 I treatment

  6. Induction of antitumor immunity through xenoplacental immunization

    Directory of Open Access Journals (Sweden)

    Agadjanyan Michael G

    2006-05-01

    Full Text Available Abstract Historically cancer vaccines have yielded suboptimal clinical results. We have developed a novel strategy for eliciting antitumor immunity based upon homology between neoplastic tissue and the developing placenta. Placenta formation shares several key processes with neoplasia, namely: angiogenesis, activation of matrix metalloproteases, and active suppression of immune function. Immune responses against xenoantigens are well known to break self-tolerance. Utilizing xenogeneic placental protein extracts as a vaccine, we have successfully induced anti-tumor immunity against B16 melanoma in C57/BL6 mice, whereas control xenogeneic extracts and B16 tumor extracts where ineffective, or actually promoted tumor growth, respectively. Furthermore, dendritic cells were able to prime tumor immunity when pulsed with the placental xenoantigens. While vaccination-induced tumor regression was abolished in mice depleted of CD4 T cells, both CD4 and CD8 cells were needed to adoptively transfer immunity to naïve mice. Supporting the role of CD8 cells in controlling tumor growth are findings that only freshly isolated CD8 cells from immunized mice were capable of inducing tumor cell caspases-3 activation ex vivo. These data suggest feasibility of using xenogeneic placental preparations as a multivalent vaccine potently targeting not just tumor antigens, but processes that are essential for tumor maintenance of malignant potential.

  7. U.S. Immunization program adult immunization activities and resources

    Science.gov (United States)

    Woods, LaDora O.; Bridges, Carolyn B.; Graitcer, Samuel B.; Lamont, Brock

    2016-01-01

    ABSTRACT Adults are recommended to receive vaccines based on their age, medical conditions, prior vaccinations, occupation and lifestyle. However, adult immunization coverage is low in the United States and lags substantially below Healthy People 2020 goals. To assess activities and resources designated for adult immunization programs by state and local health department immunization programs in the United States, we analyzed 2012 and 2013 data from the Centers for Disease Control and Prevention's (CDC) Program Annual Reports and Progress Assessments (PAPA) survey of CDC-funded immunization programs. Fifty-six of 64 funded US immunization programs' responses were included in the analysis. Eighty-two percent of (n = 46) programs reported having a designated adult immunization coordinator in 2012 and 73% (n = 41) in 2013. Of the 46 coordinators reported in 2012, 30% (n = 14) spent more than 50% of their time on adult immunization activities, and only 24% (n = 10) of the 41 adult coordinators in 2013 spent more than 50% of their time on adult immunization activities. In 2012, 23% (n = 13) of the 56 programs had a separate immunization coalition for adults and 68% (n = 38) included adult issues in their overall immunization program coalition. In 2013, 25% (n = 14) had a separate adult immunization coalition while 57% (n = 32) incorporated adult immunizations into their overall immunization program coalition. The results indicate substantial variation across the US in public health infrastructure to support adult immunizations. Continued assessment of adult immunization resources and activities will be important in improving adult immunization coverage levels though program support. With many programs having limited resources dedicated to improving adult immunization rates in the in US, efforts by the health departments to collaborate with providers and other partners in their jurisdictions to increase awareness, increase the use of proven strategies to improve

  8. Vector manifestation and violation of vector dominance in hot matter

    International Nuclear Information System (INIS)

    Harada, Masayasu; Sasaki, Chihiro

    2004-01-01

    We show the details of the calculation of the hadronic thermal corrections to the two-point functions in the effective field theory of QCD for pions and vector mesons based on the hidden local symmetry (HLS) in hot matter using the background field gauge. We study the temperature dependence of the pion velocity in the low-temperature region determined from the hadronic thermal corrections, and show that, due to the presence of the dynamical vector meson, the pion velocity is smaller than the speed of the light already at one-loop level, in contrast to the result obtained in the ordinary chiral perturbation theory including only the pion at one-loop. Including the intrinsic temperature dependences of the parameters of the HLS Lagrangian determined from the underlying QCD through the Wilsonian matching, we show how the vector manifestation (VM), in which the massless vector meson becomes the chiral partner of pion, is realized at the critical temperature. We present a new prediction of the VM on the direct photon-π-π coupling which measures the validity of the vector dominance (VD) of the electromagnetic form factor of the pion: we find that the VD is largely violated at the critical temperature, which indicates that the assumption of the VD made in several analyses on the dilepton spectra in hot matter may need to be weakened for consistently including the effect of the dropping mass of the vector meson

  9. Vector independent transmission of the vector-borne bluetongue virus.

    Science.gov (United States)

    van der Sluijs, Mirjam Tineke Willemijn; de Smit, Abraham J; Moormann, Rob J M

    2016-01-01

    Bluetongue is an economically important disease of ruminants. The causative agent, Bluetongue virus (BTV), is mainly transmitted by insect vectors. This review focuses on vector-free BTV transmission, and its epizootic and economic consequences. Vector-free transmission can either be vertical, from dam to fetus, or horizontal via direct contract. For several BTV-serotypes, vertical (transplacental) transmission has been described, resulting in severe congenital malformations. Transplacental transmission had been mainly associated with live vaccine strains. Yet, the European BTV-8 strain demonstrated a high incidence of transplacental transmission in natural circumstances. The relevance of transplacental transmission for the epizootiology is considered limited, especially in enzootic areas. However, transplacental transmission can have a substantial economic impact due to the loss of progeny. Inactivated vaccines have demonstrated to prevent transplacental transmission. Vector-free horizontal transmission has also been demonstrated. Since direct horizontal transmission requires close contact of animals, it is considered only relevant for within-farm spreading of BTV. The genetic determinants which enable vector-free transmission are present in virus strains circulating in the field. More research into the genetic changes which enable vector-free transmission is essential to better evaluate the risks associated with outbreaks of new BTV serotypes and to design more appropriate control measures.

  10. Cell-mediated immune responses in rainbow trout after DNA immunization against the viral hemorrhagic septicemia virus

    DEFF Research Database (Denmark)

    Utke, Katrin; Kock, Holger; Schuetze, Heike

    2008-01-01

    injection site rather than to injection sites of heterologous vaccines, suggesting the antigen specificity of homing. By demonstrating CMC responses to distinct viral proteins and homing in rainbow trout, these results substantially contribute to the understanding of the teleost immune system.......To identify viral proteins that induce cell-mediated cytotoxicity (CMC) against viral hemorrhagic septicemia virus (VHSV)-infected cells, rainbow trout were immunized with DNA vectors encoding the glycoprotein G or the nucleocapsid protein N of VHSV. The G protein was a more potent trigger...... of cytotoxic cells than the N protein. Peripheral blood leukocytes (PBL) isolated from trout immunized against the G protein killed both VHSV-infected MHC class I matched (RTG-2) and VHSV-infected xenogeneic (EPC) target cells, suggesting the involvement of both cytotoxic T lymphocytes (CTL) and NK cells...

  11. VectorBase

    Data.gov (United States)

    U.S. Department of Health & Human Services — VectorBase is a Bioinformatics Resource Center for invertebrate vectors. It is one of four Bioinformatics Resource Centers funded by NIAID to provide web-based...

  12. Generalization of concurrence vectors

    International Nuclear Information System (INIS)

    Yu Changshui; Song Heshan

    2004-01-01

    In this Letter, based on the generalization of concurrence vectors for bipartite pure state with respect to employing tensor product of generators of the corresponding rotation groups, we generalize concurrence vectors to the case of mixed states; a new criterion of separability of multipartite pure states is given out, for which we define a concurrence vector; we generalize the vector to the case of multipartite mixed state and give out a good measure of free entanglement

  13. Vector Network Coding

    OpenAIRE

    Ebrahimi, Javad; Fragouli, Christina

    2010-01-01

    We develop new algebraic algorithms for scalar and vector network coding. In vector network coding, the source multicasts information by transmitting vectors of length L, while intermediate nodes process and combine their incoming packets by multiplying them with L X L coding matrices that play a similar role as coding coefficients in scalar coding. Our algorithms for scalar network jointly optimize the employed field size while selecting the coding coefficients. Similarly, for vector co...

  14. Vector Network Coding Algorithms

    OpenAIRE

    Ebrahimi, Javad; Fragouli, Christina

    2010-01-01

    We develop new algebraic algorithms for scalar and vector network coding. In vector network coding, the source multicasts information by transmitting vectors of length L, while intermediate nodes process and combine their incoming packets by multiplying them with L x L coding matrices that play a similar role as coding c in scalar coding. Our algorithms for scalar network jointly optimize the employed field size while selecting the coding coefficients. Similarly, for vector coding, our algori...

  15. Vectoring of parallel synthetic jets

    Science.gov (United States)

    Berk, Tim; Ganapathisubramani, Bharathram; Gomit, Guillaume

    2015-11-01

    A pair of parallel synthetic jets can be vectored by applying a phase difference between the two driving signals. The resulting jet can be merged or bifurcated and either vectored towards the actuator leading in phase or the actuator lagging in phase. In the present study, the influence of phase difference and Strouhal number on the vectoring behaviour is examined experimentally. Phase-locked vorticity fields, measured using Particle Image Velocimetry (PIV), are used to track vortex pairs. The physical mechanisms that explain the diversity in vectoring behaviour are observed based on the vortex trajectories. For a fixed phase difference, the vectoring behaviour is shown to be primarily influenced by pinch-off time of vortex rings generated by the synthetic jets. Beyond a certain formation number, the pinch-off timescale becomes invariant. In this region, the vectoring behaviour is determined by the distance between subsequent vortex rings. We acknowledge the financial support from the European Research Council (ERC grant agreement no. 277472).

  16. Immune System and Kidney Transplantation.

    Science.gov (United States)

    Shrestha, Badri Man

    2017-01-01

    The immune system recognises a transplanted kidney as foreign body and mounts immune response through cellular and humoral mechanisms leading to acute or chronic rejection, which ultimately results in graft loss. Over the last five decades, there have been significant advances in the understanding of the immune responses to transplanted organs in both experimental and clinical transplant settings. Modulation of the immune response by using immunosuppressive agents has led to successful outcomes after kidney transplantation. The paper provides an overview of the general organisation and function of human immune system, immune response to kidney transplantation, and the current practice of immunosuppressive therapy in kidney transplantation in the United Kingdom.

  17. Immunogenicity of ORFV-based vectors expressing the rabies virus glycoprotein in livestock species.

    Science.gov (United States)

    Martins, Mathias; Joshi, Lok R; Rodrigues, Fernando S; Anziliero, Deniz; Frandoloso, Rafael; Kutish, Gerald F; Rock, Daniel L; Weiblen, Rudi; Flores, Eduardo F; Diel, Diego G

    2017-11-01

    The parapoxvirus Orf virus (ORFV) encodes several immunomodulatory proteins (IMPs) that modulate host-innate and pro-inflammatory responses and has been proposed as a vaccine delivery vector for use in animal species. Here we describe the construction and characterization of two recombinant ORFV vectors expressing the rabies virus (RABV) glycoprotein (G). The RABV-G gene was inserted in the ORFV024 or ORFV121 gene loci, which encode for IMPs that are unique to parapoxviruses and inhibit activation of the NF-κB signaling pathway. The immunogenicity of the resultant recombinant viruses (ORFV ∆024 RABV-G or ORFV ∆121 RABV-G, respectively) was evaluated in pigs and cattle. Immunization of the target species with ORFV ∆024 RABV-G and ORFV ∆121 RABV-G elicited robust neutralizing antibody responses against RABV. Notably, neutralizing antibody titers induced in ORFV ∆121 RABV-G-immunized pigs and cattle were significantly higher than those detected in ORFV ∆024 RABV-G-immunized animals, indicating a higher immunogenicity of ORFV Δ121 -based vectors in these animal species. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Synergistic immune responses induced by endogenous retrovirus and herpesvirus antigens result in increased production of inflammatory cytokines in multiple sclerosis patients

    DEFF Research Database (Denmark)

    Brudek, T; Christensen, T; Hansen, H J

    2008-01-01

    Human endogenous retroviruses (HERV) and herpesviruses are increasingly associated with the pathogenesis of the neurological inflammatory disease multiple sclerosis (MS). Herpesviruses are capable of HERV activation and simultaneous presence of HERV and herpesvirus antigens have a synergistic...... effect on cell-mediated immune responses, which tend to be higher in MS patients in comparison with healthy individuals. Here, we investigate whether these synergistic immune responses are reflected in changes in the production of proinflammatory cytokines. Using enzyme-linked immunosorbent assays...

  19. Transcriptome of the Plant Virus Vector Graminella nigrifrons, and the Molecular Interactions of Maize fine streak rhabdovirus Transmission

    Science.gov (United States)

    Chen, Yuting; Cassone, Bryan J.; Bai, Xiaodong; Redinbaugh, Margaret G.; Michel, Andrew P.

    2012-01-01

    Background Leafhoppers (Hemiptera: Cicadellidae) are plant-phloem feeders that are known for their ability to vector plant pathogens. The black-faced leafhopper (Graminella nigrifrons) has been identified as the only known vector for the Maize fine streak virus (MFSV), an emerging plant pathogen in the Rhabdoviridae. Within G. nigrifrons populations, individuals can be experimentally separated into three classes based on their capacity for viral transmission: transmitters, acquirers and non-acquirers. Understanding the molecular interactions between vector and virus can reveal important insights in virus immune defense and vector transmission. Results RNA sequencing (RNA-Seq) was performed to characterize the transcriptome of G. nigrifrons. A total of 38,240 ESTs of a minimum 100 bp were generated from two separate cDNA libraries consisting of virus transmitters and acquirers. More than 60% of known D. melanogaster, A. gambiae, T. castaneum immune response genes mapped to our G. nigrifrons EST database. Real time quantitative PCR (RT-qPCR) showed significant down-regulation of three genes for peptidoglycan recognition proteins (PGRP – SB1, SD, and LC) in G. nigrifrons transmitters versus control leafhoppers. Conclusions Our study is the first to characterize the transcriptome of a leafhopper vector species. Significant sequence similarity in immune defense genes existed between G. nigrifrons and other well characterized insects. The down-regulation of PGRPs in MFSV transmitters suggested a possible role in rhabdovirus transmission. The results provide a framework for future studies aimed at elucidating the molecular mechanisms of plant virus vector competence. PMID:22808205

  20. Transcriptome of the plant virus vector Graminella nigrifrons, and the molecular interactions of maize fine streak rhabdovirus transmission.

    Directory of Open Access Journals (Sweden)

    Yuting Chen

    Full Text Available BACKGROUND: Leafhoppers (HEmiptera: Cicadellidae are plant-phloem feeders that are known for their ability to vector plant pathogens. The black-faced leafhopper (Graminella nigrifrons has been identified as the only known vector for the Maize fine streak virus (MFSV, an emerging plant pathogen in the Rhabdoviridae. Within G. nigrifrons populations, individuals can be experimentally separated into three classes based on their capacity for viral transmission: transmitters, acquirers and non-acquirers. Understanding the molecular interactions between vector and virus can reveal important insights in virus immune defense and vector transmission. RESULTS: RNA sequencing (RNA-Seq was performed to characterize the transcriptome of G. nigrifrons. A total of 38,240 ESTs of a minimum 100 bp were generated from two separate cDNA libraries consisting of virus transmitters and acquirers. More than 60% of known D. melanogaster, A. gambiae, T. castaneum immune response genes mapped to our G. nigrifrons EST database. Real time quantitative PCR (RT-qPCR showed significant down-regulation of three genes for peptidoglycan recognition proteins (PGRP - SB1, SD, and LC in G. nigrifrons transmitters versus control leafhoppers. CONCLUSIONS: Our study is the first to characterize the transcriptome of a leafhopper vector species. Significant sequence similarity in immune defense genes existed between G. nigrifrons and other well characterized insects. The down-regulation of PGRPs in MFSV transmitters suggested a possible role in rhabdovirus transmission. The results provide a framework for future studies aimed at elucidating the molecular mechanisms of plant virus vector competence.

  1. Rotations with Rodrigues' vector

    International Nuclear Information System (INIS)

    Pina, E

    2011-01-01

    The rotational dynamics was studied from the point of view of Rodrigues' vector. This vector is defined here by its connection with other forms of parametrization of the rotation matrix. The rotation matrix was expressed in terms of this vector. The angular velocity was computed using the components of Rodrigues' vector as coordinates. It appears to be a fundamental matrix that is used to express the components of the angular velocity, the rotation matrix and the angular momentum vector. The Hamiltonian formalism of rotational dynamics in terms of this vector uses the same matrix. The quantization of the rotational dynamics is performed with simple rules if one uses Rodrigues' vector and similar formal expressions for the quantum operators that mimic the Hamiltonian classical dynamics.

  2. Vertical vector face lift.

    Science.gov (United States)

    Somoano, Brian; Chan, Joanna; Morganroth, Greg

    2011-01-01

    Facial rejuvenation using local anesthesia has evolved in the past decade as a safer option for patients seeking fewer complications and minimal downtime. Mini- and short-scar face lifts using more conservative incision lengths and extent of undermining can be effective in the younger patient with lower face laxity and minimal loose, elastotic neck skin. By incorporating both an anterior and posterior approach and using an incision length between the mini and more traditional face lift, the Vertical Vector Face Lift can achieve longer-lasting and natural results with lesser cost and risk. Submentoplasty and liposuction of the neck and jawline, fundamental components of the vertical vector face lift, act synergistically with superficial musculoaponeurotic system plication to reestablish a more youthful, sculpted cervicomental angle, even in patients with prominent jowls. Dramatic results can be achieved in the right patient by combining with other procedures such as injectable fillers, chin implants, laser resurfacing, or upper and lower blepharoplasties. © 2011 Wiley Periodicals, Inc.

  3. Platelet turnover and kinetics in immune thrombocytopenic purpura: results with autologous 111In-labeled platelets and homologous 51Cr-labeled platelets differ

    International Nuclear Information System (INIS)

    Heyns A du, P.; Badenhorst, P.N.; Loetter, M.G.P.; Pieters, H.; Wessels, P.; Kotze, H.F.

    1986-01-01

    Mean platelet survival and turnover were simultaneously determined with autologous 111In-labeled platelets (111In-AP) and homologous 51Cr-labeled platelets (51Cr-HP) in ten patients with chronic immune thrombocytopenic purpura (ITP). In vivo redistribution of the 111In-AP was quantitated with a scintillation camera and computer-assisted image analysis. The patients were divided into two groups: those with splenic platelet sequestration (spleen-liver 111In activity ratio greater than 1.4), and those with diffuse sequestration in the reticuloendothelial system. The latter patients had more severe ITP reflected by pronounced thrombocytopenia, decreased platelet turnover, and prominent early hepatic platelet sequestration. Mean platelet life span estimated with 51Cr-HP was consistently shorter than that of 111In-AP. Platelet turnover determined with 51Cr-HP was thus over-estimated. The difference in results with the two isotope labels was apparently due to greater in vivo elution of 51Cr. Although the limitations of the techniques should be taken into account, these findings indicate that platelet turnover is not always normal or increased in ITP, but is low in severe disease. We suggest that this may be ascribed to damage to megakaryocytes by antiplatelet antibody. The physical characteristics in 111In clearly make this radionuclide superior to 51Cr for the study of platelet kinetics in ITP

  4. Immunogenicity in African Green Monkeys of M Protein Mutant Vesicular Stomatitis Virus Vectors and Contribution of Vector-Encoded Flagellin

    Directory of Open Access Journals (Sweden)

    Marlena M. Westcott

    2018-03-01

    Full Text Available Recombinant vesicular stomatitis virus (VSV is a promising platform for vaccine development. M51R VSV, an attenuated, M protein mutant strain, is an effective inducer of Type I interferon and dendritic cell (DC maturation, which are desirable properties to exploit for vaccine design. We have previously evaluated M51R VSV (M51R and M51R VSV that produces flagellin (M51R-F as vaccine vectors using murine models, and found that flagellin enhanced DC activation and VSV-specific antibody production after low-dose vaccination. In this report, the immunogenicity of M51R vectors and the adjuvant effect of virus-produced flagellin were evaluated in nonhuman primates following high-dose (108 pfu and low-dose (105 pfu vaccination. A single intramuscular vaccination of African green monkeys with M51R or M51R-F induced VSV-specific, dose-dependent humoral immune responses. Flagellin induced a significant increase in antibody production (IgM, IgG and neutralizing antibody at the low vaccination dose. A VSV-specific cellular response was detected at 6 weeks post-vaccination, but was neither dose-dependent nor enhanced by flagellin; similar numbers of VSV-specific, IFNγ-producing cells were detected in lymph node and spleen of all animals. These results indicate that virus-directed, intracellular flagellin production may improve VSV-based vaccines encoding heterologous antigens by lowering the dose required to achieve humoral immunity.

  5. Virus-Vectored Influenza Virus Vaccines

    Science.gov (United States)

    Tripp, Ralph A.; Tompkins, S. Mark

    2014-01-01

    Despite the availability of an inactivated vaccine that has been licensed for >50 years, the influenza virus continues to cause morbidity and mortality worldwide. Constant evolution of circulating influenza virus strains and the emergence of new strains diminishes the effectiveness of annual vaccines that rely on a match with circulating influenza strains. Thus, there is a continued need for new, efficacious vaccines conferring cross-clade protection to avoid the need for biannual reformulation of seasonal influenza vaccines. Recombinant virus-vectored vaccines are an appealing alternative to classical inactivated vaccines because virus vectors enable native expression of influenza antigens, even from virulent influenza viruses, while expressed in the context of the vector that can improve immunogenicity. In addition, a vectored vaccine often enables delivery of the vaccine to sites of inductive immunity such as the respiratory tract enabling protection from influenza virus infection. Moreover, the ability to readily manipulate virus vectors to produce novel influenza vaccines may provide the quickest path toward a universal vaccine protecting against all influenza viruses. This review will discuss experimental virus-vectored vaccines for use in humans, comparing them to licensed vaccines and the hurdles faced for licensure of these next-generation influenza virus vaccines. PMID:25105278

  6. Investigation of Optimal Integrated Circuit Raster Image Vectorization Method

    Directory of Open Access Journals (Sweden)

    Leonas Jasevičius

    2011-03-01

    Full Text Available Visual analysis of integrated circuit layer requires raster image vectorization stage to extract layer topology data to CAD tools. In this paper vectorization problems of raster IC layer images are presented. Various line extraction from raster images algorithms and their properties are discussed. Optimal raster image vectorization method was developed which allows utilization of common vectorization algorithms to achieve the best possible extracted vector data match with perfect manual vectorization results. To develop the optimal method, vectorized data quality dependence on initial raster image skeleton filter selection was assessed.Article in Lithuanian

  7. Tumor regression induced by intratumor therapy with a disabled infectious single cycle (DISC) herpes simplex virus (HSV) vector, DISC/HSV/murine granulocyte-macrophage colony-stimulating factor, correlates with antigen-specific adaptive immunity.

    Science.gov (United States)

    Ali, Selman A; Lynam, June; McLean, Cornelia S; Entwisle, Claire; Loudon, Peter; Rojas, José M; McArdle, Stephanie E B; Li, Geng; Mian, Shahid; Rees, Robert C

    2002-04-01

    Direct intratumor injection of a disabled infectious single cycle HSV-2 virus encoding the murine GM-CSF gene (DISC/mGM-CSF) into established murine colon carcinoma CT26 tumors induced a significant delay in tumor growth and complete tumor regression in up to 70% of animals. Pre-existing immunity to HSV did not reduce the therapeutic efficacy of DISC/mGM-CSF, and, when administered in combination with syngeneic dendritic cells, further decreased tumor growth and increased the incidence of complete tumor regression. Direct intratumor injection of DISC/mGM-CSF also inhibited the growth of CT26 tumor cells implanted on the contralateral flank or seeded into the lungs following i.v. injection of tumor cells (experimental lung metastasis). Proliferation of splenocytes in response to Con A was impaired in progressor and tumor-bearer, but not regressor, mice. A potent tumor-specific CTL response was generated from splenocytes of all mice with regressing, but not progressing tumors following in vitro peptide stimulation; this response was specific for the gp70 AH-1 peptide SPSYVYHQF and correlated with IFN-gamma, but not IL-4 cytokine production. Depletion of CD8(+) T cells from regressor splenocytes before in vitro stimulation with the relevant peptide abolished their cytolytic activity, while depletion of CD4(+) T cells only partially inhibited CTL generation. Tumor regression induced by DISC/mGM-CSF virus immunotherapy provides a unique model for evaluating the immune mechanism(s) involved in tumor rejection, upon which tumor immunotherapy regimes may be based.

  8. Decays of the vector glueball

    Science.gov (United States)

    Giacosa, Francesco; Sammet, Julia; Janowski, Stanislaus

    2017-06-01

    We calculate two- and three-body decays of the (lightest) vector glueball into (pseudo)scalar, (axial-)vector, as well as pseudovector and excited vector mesons in the framework of a model of QCD. While absolute values of widths cannot be predicted because the corresponding coupling constants are unknown, some interesting branching ratios can be evaluated by setting the mass of the yet hypothetical vector glueball to 3.8 GeV as predicted by quenched lattice QCD. We find that the decay mode ω π π should be one of the largest (both through the decay chain O →b1π →ω π π and through the direct coupling O →ω π π ). Similarly, the (direct and indirect) decay into π K K*(892 ) is sizable. Moreover, the decays into ρ π and K*(892 )K are, although subleading, possible and could play a role in explaining the ρ π puzzle of the charmonium state ψ (2 S ) thanks to a (small) mixing with the vector glueball. The vector glueball can be directly formed at the ongoing BESIII experiment as well as at the future PANDA experiment at the FAIR facility. If the width is sufficiently small (≲100 MeV ) it should not escape future detection. It should be stressed that the employed model is based on some inputs and simplifying assumptions: the value of glueball mass (at present, the quenched lattice value is used), the lack of mixing of the glueball with other quarkonium states, and the use of few interaction terms. It then represents a first step toward the identification of the main decay channels of the vector glueball, but shall be improved when corresponding experimental candidates and/or new lattice results will be available.

  9. Maternal immunity enhances systemic recall immune responses upon oral immunization of piglets with F4 fimbriae.

    Science.gov (United States)

    Nguyen, Ut V; Melkebeek, Vesna; Devriendt, Bert; Goetstouwers, Tiphanie; Van Poucke, Mario; Peelman, Luc; Goddeeris, Bruno M; Cox, Eric

    2015-06-23

    F4 enterotoxigenic Escherichia coli (ETEC) cause diarrhoea and mortality in piglets leading to severe economic losses. Oral immunization of piglets with F4 fimbriae induces a protective intestinal immune response evidenced by an F4-specific serum and intestinal IgA response. However, successful oral immunization of pigs with F4 fimbriae in the presence of maternal immunity has not been demonstrated yet. In the present study we aimed to evaluate the effect of maternal immunity on the induction of a systemic immune response upon oral immunization of piglets. Whereas F4-specific IgG and IgA could be induced by oral immunization of pigs without maternal antibodies and by intramuscular immunization of pigs with maternal antibodies, no such response was seen in the orally immunized animals with maternal antibodies. Since maternal antibodies can mask an antibody response, we also looked by ELIspot assays for circulating F4-specific antibody secreting cells (ASCs). Enumerating the F4-specific ASCs within the circulating peripheral blood mononuclear cells, and the number of F4-specific IgA ASCs within the circulating IgA(+) B-cells revealed an F4-specific immune response in the orally immunized animals with maternal antibodies. Interestingly, results suggest a more robust IgA booster response by oral immunization of pigs with than without maternal antibodies. These results demonstrate that oral immunization of piglets with F4-specific maternal antibodies is feasible and that these maternal antibodies seem to enhance the secondary systemic immune response. Furthermore, our ELIspot assay on enriched IgA(+) B-cells could be used as a screening procedure to optimize mucosal immunization protocols in pigs with maternal immunity.

  10. Artificial immune kernel clustering network for unsupervised image segmentation

    Institute of Scientific and Technical Information of China (English)

    Wenlong Huang; Licheng Jiao

    2008-01-01

    An immune kernel clustering network (IKCN) is proposed based on the combination of the artificial immune network and the support vector domain description (SVDD) for the unsupervised image segmentation. In the network, a new antibody neighborhood and an adaptive learning coefficient, which is inspired by the long-term memory in cerebral cortices are presented. Starting from IKCN algorithm, we divide the image feature sets into subsets by the antibodies, and then map each subset into a high dimensional feature space by a mercer kernel, where each antibody neighborhood is represented as a support vector hypersphere. The clustering results of the local support vector hyperspheres are combined to yield a global clustering solution by the minimal spanning tree (MST), where a predefined number of clustering is not needed. We compare the proposed methods with two common clustering algorithms for the artificial synthetic data set and several image data sets, including the synthetic texture images and the SAR images, and encouraging experimental results are obtained.

  11. Axial vector mass spectrum and mixing angles

    International Nuclear Information System (INIS)

    Caffarelli, R.V.; Kang, K.

    1976-01-01

    Spectral sum rules of the axial-vector current and axial-vector current-pseudoscalar field are used to study the axial-vector mass spectrum and mixing angles, as well as the decay constants and mixing angles of the pseudoscalar mesons. In general, the result is quite persuasive for the existence of the Jsup(PC) = 1 ++ multiplet in which one has a canonical D-E mixing. (Auth.)

  12. B-cell depletion is protective against anti-AAV capsid immune response: a human subject case study

    Directory of Open Access Journals (Sweden)

    M Corti

    2014-01-01

    Full Text Available Gene therapy strategies for congenital myopathies may require repeat administration of adeno-associated viral (AAV vectors due to aspects of the clinical application, such as: (i administration of doses below therapeutic efficacy in patients enrolled in early phase clinical trials; (ii progressive reduction of the therapeutic gene expression over time as a result of increasing muscle mass in patients treated at a young age; and (iii a possibly faster depletion of pathogenic myofibers in this patient population. Immune response triggered by the first vector administration, and to subsequent doses, represents a major obstacle for successful gene transfer in young patients. Anti-capsid and anti-transgene product related humoral and cell-mediated responses have been previously observed in all preclinical models and human subjects who received gene therapy or enzyme replacement therapy (ERT for congenital myopathies. Immune responses may result in reduced efficacy of the gene transfer over time and/or may preclude for the possibility of re-administration of the same vector. In this study, we evaluated the immune response of a Pompe patient dosed with an AAV1-GAA vector after receiving Rituximab and Sirolimus to modulate reactions against ERT. A key finding of this single subject case report is the observation that B-cell ablation with rituximab prior to AAV vector exposure results in non-responsiveness to both capsid and transgene, therefore allowing the possibility of repeat administration in the future. This observation is significant for future gene therapy studies and establishes a clinically relevant approach to blocking immune responses to AAV vectors.

  13. Local Patch Vectors Encoded by Fisher Vectors for Image Classification

    Directory of Open Access Journals (Sweden)

    Shuangshuang Chen

    2018-02-01

    Full Text Available The objective of this work is image classification, whose purpose is to group images into corresponding semantic categories. Four contributions are made as follows: (i For computational simplicity and efficiency, we directly adopt raw image patch vectors as local descriptors encoded by Fisher vector (FV subsequently; (ii For obtaining representative local features within the FV encoding framework, we compare and analyze three typical sampling strategies: random sampling, saliency-based sampling and dense sampling; (iii In order to embed both global and local spatial information into local features, we construct an improved spatial geometry structure which shows good performance; (iv For reducing the storage and CPU costs of high dimensional vectors, we adopt a new feature selection method based on supervised mutual information (MI, which chooses features by an importance sorting algorithm. We report experimental results on dataset STL-10. It shows very promising performance with this simple and efficient framework compared to conventional methods.

  14. Artificial immune pattern recognition for damage detection in structural health monitoring sensor networks

    Science.gov (United States)

    Chen, Bo; Zang, Chuanzhi

    2009-03-01

    This paper presents an artificial immune pattern recognition (AIPR) approach for the damage detection and classification in structures. An AIPR-based Structure Damage Classifier (AIPR-SDC) has been developed by mimicking immune recognition and learning mechanisms. The structure damage patterns are represented by feature vectors that are extracted from the structure's dynamic response measurements. The training process is designed based on the clonal selection principle in the immune system. The selective and adaptive features of the clonal selection algorithm allow the classifier to generate recognition feature vectors that are able to match the training data. In addition, the immune learning algorithm can learn and remember various data patterns by generating a set of memory cells that contains representative feature vectors for each class (pattern). The performance of the presented structure damage classifier has been validated using a benchmark structure proposed by the IASC-ASCE (International Association for Structural Control - American Society of Civil Engineers) Structural Health Monitoring Task Group. The validation results show a better classification success rate comparing to some of other classification algorithms.

  15. Use of adenoviral vectors as veterinary vaccines.

    Science.gov (United States)

    Ferreira, T B; Alves, P M; Aunins, J G; Carrondo, M J T

    2005-10-01

    Vaccines are the most effective and inexpensive prophylactic tool in veterinary medicine. Ideally, vaccines should induce a lifelong protective immunity against the target pathogen while not causing clinical or pathological signs of diseases in the vaccinated animals. However, such ideal vaccines are rare in the veterinary field. Many vaccines are either of limited effectiveness or have harmful side effects. In addition, there are still severe diseases with no effective vaccines. A very important criterion for an ideal vaccine in veterinary medicine is low cost; this is especially important in developing countries and even more so for poultry vaccination, where vaccines must sell for a few cents a dose. Traditional approaches include inactivated vaccines, attenuated live vaccines and subunit vaccines. Recently, genetic engineering has been applied to design new, improved vaccines. Adenovirus vectors are highly efficient for gene transfer in a broad spectrum of cell types and species. Moreover, adenoviruses often induce humoral, mucosal and cellular immune responses to antigens encoded by the inserted foreign genes. Thus, adenoviruses have become a vector of choice for delivery and expression of foreign proteins for vaccination. Consequently, the market requirements for adenovirus vaccines are increasing, creating a need for production methodologies of concentrated vectors with warranted purity and efficacy. This review summarizes recent developments and approaches of adenovirus production and purification as the application of these vectors, including successes and failures in clinical applications to date.

  16. Cationic lipid-formulated DNA vaccine against hepatitis B virus: immunogenicity of MIDGE-Th1 vectors encoding small and large surface antigen in comparison to a licensed protein vaccine.

    Directory of Open Access Journals (Sweden)

    Anne Endmann

    Full Text Available Currently marketed vaccines against hepatitis B virus (HBV based on the small (S hepatitis B surface antigen (HBsAg fail to induce a protective immune response in about 10% of vaccinees. DNA vaccination and the inclusion of PreS1 and PreS2 domains of HBsAg have been reported to represent feasible strategies to improve the efficacy of HBV vaccines. Here, we evaluated the immunogenicity of SAINT-18-formulated MIDGE-Th1 vectors encoding the S or the large (L protein of HBsAg in mice and pigs. In both animal models, vectors encoding the secretion-competent S protein induced stronger humoral responses than vectors encoding the L protein, which was shown to be retained mainly intracellularly despite the presence of a heterologous secretion signal. In pigs, SAINT-18-formulated MIDGE-Th1 vectors encoding the S protein elicited an immune response of the same magnitude as the licensed protein vaccine Engerix-B, with S protein-specific antibody levels significantly higher than those considered protective in humans, and lasting for at least six months after the third immunization. Thus, our results provide not only the proof of concept for the SAINT-18-formulated MIDGE-Th1 vector approach but also confirm that with a cationic-lipid formulation, a DNA vaccine at a relatively low dose can elicit an immune response similar to a human dose of an aluminum hydroxide-adjuvanted protein vaccine in large animals.

  17. Vector mesons on the light front

    International Nuclear Information System (INIS)

    Naito, K.; Maedan, S.; Itakura, K.

    2004-01-01

    We apply the light-front quantization to the Nambu-Jona-Lasinio model with the vector interaction, and compute vector meson's mass and light-cone wavefunction in the large N limit. Following the same procedure as in the previous analyses for scalar and pseudo-scalar mesons, we derive the bound-state equations of a qq-bar system in the vector channel. We include the lowest order effects of the vector interaction. The resulting transverse and longitudinal components of the bound-state equation look different from each other. But eventually after imposing an appropriate cutoff, one finds these two are identical, giving the same mass and the same (spin-independent) light-cone wavefunction. Mass of the vector meson decreases as one increases the strength of the vector interaction

  18. Supergravity inspired vector curvaton

    International Nuclear Information System (INIS)

    Dimopoulos, Konstantinos

    2007-01-01

    It is investigated whether a massive Abelian vector field, whose gauge kinetic function is growing during inflation, can be responsible for the generation of the curvature perturbation in the Universe. Particle production is studied and it is shown that the vector field can obtain a scale-invariant superhorizon spectrum of perturbations with a reasonable choice of kinetic function. After inflation the vector field begins coherent oscillations, during which it corresponds to pressureless isotropic matter. When the vector field dominates the Universe, its perturbations give rise to the observed curvature perturbation following the curvaton scenario. It is found that this is possible if, after the end of inflation, the mass of the vector field increases at a phase transition at temperature of order 1 TeV or lower. Inhomogeneous reheating, whereby the vector field modulates the decay rate of the inflaton, is also studied

  19. Innate immunity

    African Journals Online (AJOL)

    Ronnie Anderson is Director of the Medical Research Council Unit for Inflammation and Immunity. ... field have included macrophage, T cell, cytokine and cytokine activated killer cell interactions .... monocytes, mast cells, lymphocytes, eccrine.

  20. Vector Differential Calculus

    OpenAIRE

    HITZER, Eckhard MS

    2002-01-01

    This paper treats the fundamentals of the vector differential calculus part of universal geometric calculus. Geometric calculus simplifies and unifies the structure and notation of mathematics for all of science and engineering, and for technological applications. In order to make the treatment self-contained, I first compile all important geometric algebra relationships,which are necesssary for vector differential calculus. Then differentiation by vectors is introduced and a host of major ve...

  1. Vector Boson Scattering at High Mass

    CERN Document Server

    Sherwood, P

    2009-01-01

    In the absence of a light Higgs boson, the mechanism of electroweak symmetry breaking will be best studied in processes of vector boson scattering at high mass. Various models predict resonances in this channel. Here, we investigate W W scalar and vector resonances, W Z vector resonances and a Z Z scalar resonance over a range of diboson centre-of-mass energies. Particular attention is paid to the application reconstruction of dijet pairs with low opening angle resulting from the decay of highly boosted vector bosons.

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

    Science.gov (United States)

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

    2013-08-01

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

  3. Vectorized Monte Carlo

    International Nuclear Information System (INIS)

    Brown, F.B.

    1981-01-01

    Examination of the global algorithms and local kernels of conventional general-purpose Monte Carlo codes shows that multigroup Monte Carlo methods have sufficient structure to permit efficient vectorization. A structured multigroup Monte Carlo algorithm for vector computers is developed in which many particle events are treated at once on a cell-by-cell basis. Vectorization of kernels for tracking and variance reduction is described, and a new method for discrete sampling is developed to facilitate the vectorization of collision analysis. To demonstrate the potential of the new method, a vectorized Monte Carlo code for multigroup radiation transport analysis was developed. This code incorporates many features of conventional general-purpose production codes, including general geometry, splitting and Russian roulette, survival biasing, variance estimation via batching, a number of cutoffs, and generalized tallies of collision, tracklength, and surface crossing estimators with response functions. Predictions of vectorized performance characteristics for the CYBER-205 were made using emulated coding and a dynamic model of vector instruction timing. Computation rates were examined for a variety of test problems to determine sensitivities to batch size and vector lengths. Significant speedups are predicted for even a few hundred particles per batch, and asymptotic speedups by about 40 over equivalent Amdahl 470V/8 scalar codes arepredicted for a few thousand particles per batch. The principal conclusion is that vectorization of a general-purpose multigroup Monte Carlo code is well worth the significant effort required for stylized coding and major algorithmic changes

  4. Vectors and their applications

    CERN Document Server

    Pettofrezzo, Anthony J

    2005-01-01

    Geared toward undergraduate students, this text illustrates the use of vectors as a mathematical tool in plane synthetic geometry, plane and spherical trigonometry, and analytic geometry of two- and three-dimensional space. Its rigorous development includes a complete treatment of the algebra of vectors in the first two chapters.Among the text's outstanding features are numbered definitions and theorems in the development of vector algebra, which appear in italics for easy reference. Most of the theorems include proofs, and coordinate position vectors receive an in-depth treatment. Key concept

  5. Symbolic computer vector analysis

    Science.gov (United States)

    Stoutemyer, D. R.

    1977-01-01

    A MACSYMA program is described which performs symbolic vector algebra and vector calculus. The program can combine and simplify symbolic expressions including dot products and cross products, together with the gradient, divergence, curl, and Laplacian operators. The distribution of these operators over sums or products is under user control, as are various other expansions, including expansion into components in any specific orthogonal coordinate system. There is also a capability for deriving the scalar or vector potential of a vector field. Examples include derivation of the partial differential equations describing fluid flow and magnetohydrodynamics, for 12 different classic orthogonal curvilinear coordinate systems.

  6. Effects of FVIII immunity on hepatocyte and hematopoietic stem cell–directed gene therapy of murine hemophilia A

    Directory of Open Access Journals (Sweden)

    Allison M Lytle

    2016-01-01

    Full Text Available Immune responses to coagulation factors VIII (FVIII and IX (FIX represent primary obstacles to hemophilia treatment. Previously, we showed that hematopoietic stem cell (HSC retroviral gene therapy induces immune nonresponsiveness to FVIII in both naive and preimmunized murine hemophilia A settings. Liver-directed adeno-associated viral (AAV-FIX vector gene transfer achieved similar results in preclinical hemophilia B models. However, as clinical immune responses to FVIII and FIX differ, we investigated the ability of liver-directed AAV-FVIII gene therapy to affect FVIII immunity in hemophilia A mice. Both FVIII naive and preimmunized mice were administered recombinant AAV8 encoding a liver-directed bioengineered FVIII expression cassette. Naive animals receiving high or mid-doses subsequently achieved near normal FVIII activity levels. However, challenge with adjuvant-free recombinant FVIII induced loss of FVIII activity and anti-FVIII antibodies in mid-dose, but not high-dose AAV or HSC lentiviral (LV vector gene therapy cohorts. Furthermore, unlike what was shown previously for FIX gene transfer, AAV-FVIII administration to hemophilia A inhibitor mice conferred no effect on anti-FVIII antibody or inhibitory titers. These data suggest that functional differences exist in the immune modulation achieved to FVIII or FIX in hemophilia mice by gene therapy approaches incorporating liver-directed AAV vectors or HSC-directed LV.

  7. Effects of FVIII immunity on hepatocyte and hematopoietic stem cell–directed gene therapy of murine hemophilia A

    Science.gov (United States)

    Lytle, Allison M; Brown, Harrison C; Paik, Na Yoon; Knight, Kristopher A; Wright, J Fraser; Spencer, H Trent; Doering, Christopher B

    2016-01-01

    Immune responses to coagulation factors VIII (FVIII) and IX (FIX) represent primary obstacles to hemophilia treatment. Previously, we showed that hematopoietic stem cell (HSC) retroviral gene therapy induces immune nonresponsiveness to FVIII in both naive and preimmunized murine hemophilia A settings. Liver-directed adeno-associated viral (AAV)-FIX vector gene transfer achieved similar results in preclinical hemophilia B models. However, as clinical immune responses to FVIII and FIX differ, we investigated the ability of liver-directed AAV-FVIII gene therapy to affect FVIII immunity in hemophilia A mice. Both FVIII naive and preimmunized mice were administered recombinant AAV8 encoding a liver-directed bioengineered FVIII expression cassette. Naive animals receiving high or mid-doses subsequently achieved near normal FVIII activity levels. However, challenge with adjuvant-free recombinant FVIII induced loss of FVIII activity and anti-FVIII antibodies in mid-dose, but not high-dose AAV or HSC lentiviral (LV) vector gene therapy cohorts. Furthermore, unlike what was shown previously for FIX gene transfer, AAV-FVIII administration to hemophilia A inhibitor mice conferred no effect on anti-FVIII antibody or inhibitory titers. These data suggest that functional differences exist in the immune modulation achieved to FVIII or FIX in hemophilia mice by gene therapy approaches incorporating liver-directed AAV vectors or HSC-directed LV. PMID:26909355

  8. Topological vector spaces and distributions

    CERN Document Server

    Horvath, John

    2012-01-01

    ""The most readable introduction to the theory of vector spaces available in English and possibly any other language.""-J. L. B. Cooper, MathSciNet ReviewMathematically rigorous but user-friendly, this classic treatise discusses major modern contributions to the field of topological vector spaces. The self-contained treatment includes complete proofs for all necessary results from algebra and topology. Suitable for undergraduate mathematics majors with a background in advanced calculus, this volume will also assist professional mathematicians, physicists, and engineers.The precise exposition o

  9. Generation of arbitrary vector beams

    Science.gov (United States)

    Perez-Garcia, Benjamin; López-Mariscal, Carlos; Hernandez-Aranda, Raul I.; Gutiérrez-Vega, Julio C.

    2017-08-01

    Optical vector beams arise from point to point spatial variations of the electric component of an electromagnetic field over the transverse plane. In this work, we present a novel experimental technique to generate arbitrary vec- tor beams, and provide sufficient evidence to validate their state of polarization. This technique takes advantage of the capability of a Spatial Light Modulator to simultaneously generate two components of an electromagnetic field by halving the screen of the device and subsequently recombining them in a Sagnac interferometer. Our experimental results show the versatility and robustness of this technique for the generation of vector beams.

  10. results

    Directory of Open Access Journals (Sweden)

    Salabura Piotr

    2017-01-01

    Full Text Available HADES experiment at GSI is the only high precision experiment probing nuclear matter in the beam energy range of a few AGeV. Pion, proton and ion beams are used to study rare dielectron and strangeness probes to diagnose properties of strongly interacting matter in this energy regime. Selected results from p + A and A + A collisions are presented and discussed.

  11. Vector competence of Aedes aegypti mosquitoes for filarial nematodes is affected by age and nutrient limitation.

    Science.gov (United States)

    Ariani, Cristina V; Juneja, Punita; Smith, Sophia; Tinsley, Matthew C; Jiggins, Francis M

    2015-01-01

    Mosquitoes are one of the most important vectors of human disease. The ability of mosquitoes to transmit disease is dependent on the age structure of the population, as mosquitoes must survive long enough for the parasites to complete their development and infect another human. Age could have additional effects due to mortality rates and vector competence changing as mosquitoes senesce, but these are comparatively poorly understood. We have investigated these factors using the mosquito Aedes aegypti and the filarial nematode Brugia malayi. Rather than observing any effects of immune senescence, we found that older mosquitoes were more resistant, but this only occurred if they had previously been maintained on a nutrient-poor diet of fructose. Constant blood feeding reversed this decline in vector competence, meaning that the number of parasites remained relatively unchanged as mosquitoes aged. Old females that had been maintained on fructose also experienced a sharp spike in mortality after an infected blood meal ("refeeding syndrome") and few survived long enough for the parasite to develop. Again, this effect was prevented by frequent blood meals. Our results indicate that old mosquitoes may be inefficient vectors due to low vector competence and high mortality, but that frequent blood meals can prevent these effects of age. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Immunization of chickens with a recombinant Ascaridia galli protein results in parasite-specific IgG with no protective effect against infection

    DEFF Research Database (Denmark)

    Fink, Dorte Rosenbek; Schou, T. W.; Norup, L. R.

    2012-01-01

    adjuvants together with a recombinant A. galli antigen. The adjuvants were CAF01, Emulsigen, and STV, and the antigen was Ag-NPA-1, a lipid-binding protein from the nematode polyprotein allergen/antigen family. Three immunizations were given i.m. with three-week intervals. A fourth group of 10 chickens...

  13. Zinc Signals and Immunity.

    Science.gov (United States)

    Maywald, Martina; Wessels, Inga; Rink, Lothar

    2017-10-24

    Zinc homeostasis is crucial for an adequate function of the immune system. Zinc deficiency as well as zinc excess result in severe disturbances in immune cell numbers and activities, which can result in increased susceptibility to infections and development of especially inflammatory diseases. This review focuses on the role of zinc in regulating intracellular signaling pathways in innate as well as adaptive immune cells. Main underlying molecular mechanisms and targets affected by altered zinc homeostasis, including kinases, caspases, phosphatases, and phosphodiesterases, will be highlighted in this article. In addition, the interplay of zinc homeostasis and the redox metabolism in affecting intracellular signaling will be emphasized. Key signaling pathways will be described in detail for the different cell types of the immune system. In this, effects of fast zinc flux, taking place within a few seconds to minutes will be distinguish from slower types of zinc signals, also designated as "zinc waves", and late homeostatic zinc signals regarding prolonged changes in intracellular zinc.

  14. Distribution amplitudes of vector mesons

    Energy Technology Data Exchange (ETDEWEB)

    Braun, V.M. [Regensburg Univ. (Germany). Inst. fuer Theoretische Physik; Broemmel, D. [Deutsches Elektronen-Synchrotron, Hamburg (Germany); Goeckeler, M. [Regensburg Univ. (DE). Inst. fuer Theoretische Physik] (and others)

    2007-11-15

    Results are presented for the lowest moment of the distribution amplitude for the K{sup *} vector meson. Both longitudinal and transverse moments are investigated. We use two flavours of O(a) improved Wilson fermions, together with a non-perturbative renormalisation of the matrix element. (orig.)

  15. Chemoselective ligation and antigen vectorization.

    Science.gov (United States)

    Gras-Masse, H

    2001-01-01

    The interest in cocktail-lipopeptide vaccines has now been confirmed by phase I clinical trials: highly diversified B-, T-helper or cytotoxic T-cell epitopes can be combined with a lipophilic vector for the induction of B- and T-cell responses of predetermined specificity. With the goal of producing an improved vaccine that should ideally induce a multispecific response in non-selected populations, increasing the diversity of the immunizing mixture represents one of the most obvious strategies.The selective delivery of antigens to professional antigen-presenting cells represents another promising approach for the improvement of vaccine efficacy. In this context, the mannose-receptor represents an attractive entry point for the targeting to dendritic cells of antigens linked to clustered glycosides or glycomimetics. In all cases, highly complex but fully characterized molecules must be produced. To develop a modular and flexible strategy which could be generally applicable to a large set of peptide antigens, we elected to explore the potentialities of chemoselective ligation methods. The hydrazone bond was found particularly reliable and fully compatible with sulphide ligation. Hydrazone/thioether orthogonal ligation systems could be developed to account for the nature of the antigens and the solubility of the vector systems. Copyright 2001 The International Association for Biologicals.

  16. Covariant Lyapunov vectors

    International Nuclear Information System (INIS)

    Ginelli, Francesco; Politi, Antonio; Chaté, Hugues; Livi, Roberto

    2013-01-01

    Recent years have witnessed a growing interest in covariant Lyapunov vectors (CLVs) which span local intrinsic directions in the phase space of chaotic systems. Here, we review the basic results of ergodic theory, with a specific reference to the implications of Oseledets’ theorem for the properties of the CLVs. We then present a detailed description of a ‘dynamical’ algorithm to compute the CLVs and show that it generically converges exponentially in time. We also discuss its numerical performance and compare it with other algorithms presented in the literature. We finally illustrate how CLVs can be used to quantify deviations from hyperbolicity with reference to a dissipative system (a chain of Hénon maps) and a Hamiltonian model (a Fermi–Pasta–Ulam chain). This article is part of a special issue of Journal of Physics A: Mathematical and Theoretical devoted to ‘Lyapunov analysis: from dynamical systems theory to applications’. (paper)

  17. Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial.

    Science.gov (United States)

    Henao-Restrepo, Ana Maria; Longini, Ira M; Egger, Matthias; Dean, Natalie E; Edmunds, W John; Camacho, Anton; Carroll, Miles W; Doumbia, Moussa; Draguez, Bertrand; Duraffour, Sophie; Enwere, Godwin; Grais, Rebecca; Gunther, Stephan; Hossmann, Stefanie; Kondé, Mandy Kader; Kone, Souleymane; Kuisma, Eeva; Levine, Myron M; Mandal, Sema; Norheim, Gunnstein; Riveros, Ximena; Soumah, Aboubacar; Trelle, Sven; Vicari, Andrea S; Watson, Conall H; Kéïta, Sakoba; Kieny, Marie Paule; Røttingen, John-Arne

    2015-08-29

    A recombinant, replication-competent vesicular stomatitis virus-based vaccine expressing a surface glycoprotein of Zaire Ebolavirus (rVSV-ZEBOV) is a promising Ebola vaccine candidate. We report the results of an interim analysis of a trial of rVSV-ZEBOV in Guinea, west Africa. For this open-label, cluster-randomised ring vaccination trial, suspected cases of Ebola virus disease in Basse-Guinée (Guinea, west Africa) were independently ascertained by Ebola response teams as part of a national surveillance system. After laboratory confirmation of a new case, clusters of all contacts and contacts of contacts were defined and randomly allocated 1:1 to immediate vaccination or delayed (21 days later) vaccination with rVSV-ZEBOV (one dose of 2 × 10(7) plaque-forming units, administered intramuscularly in the deltoid muscle). Adults (age ≥18 years) who were not pregnant or breastfeeding were eligible for vaccination. Block randomisation was used, with randomly varying blocks, stratified by location (urban vs rural) and size of rings (≤20 vs >20 individuals). The study is open label and masking of participants and field teams to the time of vaccination is not possible, but Ebola response teams and laboratory workers were unaware of allocation to immediate or delayed vaccination. Taking into account the incubation period of the virus of about 10 days, the prespecified primary outcome was laboratory-confirmed Ebola virus disease with onset of symptoms at least 10 days after randomisation. The primary analysis was per protocol and compared the incidence of Ebola virus disease in eligible and vaccinated individuals in immediate vaccination clusters with the incidence in eligible individuals in delayed vaccination clusters. This trial is registered with the Pan African Clinical Trials Registry, number PACTR201503001057193. Between April 1, 2015, and July 20, 2015, 90 clusters, with a total population of 7651 people were included in the planned interim analysis. 48 of

  18. Immunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley fever vaccine in mice.

    Science.gov (United States)

    Warimwe, George M; Lorenzo, Gema; Lopez-Gil, Elena; Reyes-Sandoval, Arturo; Cottingham, Matthew G; Spencer, Alexandra J; Collins, Katharine A; Dicks, Matthew D J; Milicic, Anita; Lall, Amar; Furze, Julie; Turner, Alison V; Hill, Adrian V S; Brun, Alejandro; Gilbert, Sarah C

    2013-12-05

    Rift Valley Fever (RVF) is a viral zoonosis that historically affects livestock production and human health in sub-Saharan Africa, though epizootics have also occurred in the Arabian Peninsula. Whilst an effective live-attenuated vaccine is available for livestock, there is currently no licensed human RVF vaccine. Replication-deficient chimpanzee adenovirus (ChAd) vectors are an ideal platform for development of a human RVF vaccine, given the low prevalence of neutralizing antibodies against them in the human population, and their excellent safety and immunogenicity profile in human clinical trials of vaccines against a wide range of pathogens. Here, in BALB/c mice, we evaluated the immunogenicity and efficacy of a replication-deficient chimpanzee adenovirus vector, ChAdOx1, encoding the RVF virus envelope glycoproteins, Gn and Gc, which are targets of virus neutralizing antibodies. The ChAdOx1-GnGc vaccine was assessed in comparison to a replication-deficient human adenovirus type 5 vector encoding Gn and Gc (HAdV5-GnGc), a strategy previously shown to confer protective immunity against RVF in mice. A single immunization with either of the vaccines conferred protection against RVF virus challenge eight weeks post-immunization. Both vaccines elicited RVF virus neutralizing antibody and a robust CD8+ T cell response. Together the results support further development of RVF vaccines based on replication-deficient adenovirus vectors, with ChAdOx1-GnGc being a potential candidate for use in future human clinical trials.

  19. Application of Vectors to Relative Velocity

    Science.gov (United States)

    Tin-Lam, Toh

    2004-01-01

    The topic 'relative velocity' has recently been introduced into the Cambridge Ordinary Level Additional Mathematics syllabus under the application of Vectors. In this note, the results of relative velocity and the 'reduction to rest' technique of teaching relative velocity are derived mathematically from vector algebra, in the hope of providing…

  20. Vector-Vector Scattering on the Lattice

    Science.gov (United States)

    Romero-López, Fernando; Urbach, Carsten; Rusetsky, Akaki

    2018-03-01

    In this work we present an extension of the LüScher formalism to include the interaction of particles with spin, focusing on the scattering of two vector particles. The derived formalism will be applied to Scalar QED in the Higgs Phase, where the U(1) gauge boson acquires mass.

  1. Selection vector filter framework

    Science.gov (United States)

    Lukac, Rastislav; Plataniotis, Konstantinos N.; Smolka, Bogdan; Venetsanopoulos, Anastasios N.

    2003-10-01

    We provide a unified framework of nonlinear vector techniques outputting the lowest ranked vector. The proposed framework constitutes a generalized filter class for multichannel signal processing. A new class of nonlinear selection filters are based on the robust order-statistic theory and the minimization of the weighted distance function to other input samples. The proposed method can be designed to perform a variety of filtering operations including previously developed filtering techniques such as vector median, basic vector directional filter, directional distance filter, weighted vector median filters and weighted directional filters. A wide range of filtering operations is guaranteed by the filter structure with two independent weight vectors for angular and distance domains of the vector space. In order to adapt the filter parameters to varying signal and noise statistics, we provide also the generalized optimization algorithms taking the advantage of the weighted median filters and the relationship between standard median filter and vector median filter. Thus, we can deal with both statistical and deterministic aspects of the filter design process. It will be shown that the proposed method holds the required properties such as the capability of modelling the underlying system in the application at hand, the robustness with respect to errors in the model of underlying system, the availability of the training procedure and finally, the simplicity of filter representation, analysis, design and implementation. Simulation studies also indicate that the new filters are computationally attractive and have excellent performance in environments corrupted by bit errors and impulsive noise.

  2. Brane vector phenomenology

    International Nuclear Information System (INIS)

    Clark, T.E.; Love, S.T.; Nitta, Muneto; Veldhuis, T. ter; Xiong, C.

    2009-01-01

    Local oscillations of the brane world are manifested as massive vector fields. Their coupling to the Standard Model can be obtained using the method of nonlinear realizations of the spontaneously broken higher-dimensional space-time symmetries, and to an extent, are model independent. Phenomenological limits on these vector field parameters are obtained using LEP collider data and dark matter constraints

  3. Cancer-Targeted Oncolytic Adenoviruses for Modulation of the Immune System.

    Science.gov (United States)

    Cerullo, Vincenzo; Capasso, Cristian; Vaha-Koskela, Markus; Hemminki, Otto; Hemminki, Akseli

    2018-01-01

    Adenovirus is one of the most commonly used vectors for gene therapy and it is the first approved virus-derived drug for treatment of cancer. As an oncolytic agent, it can induce lysis of infected cells, but it can also engage the immune system, promoting activation and maturation of antigen- presenting cells (APCs). In essence, oncolysis combined with the associated immunostimulatory actions result in a "personalized in situ vaccine" for each patient. In order to take full advantage of these features, we should try to understand how adenovirus interacts with the immune system, what are the receptors involved in triggering subsequent signals and which kind of responses they elicit. Tackling these questions will give us further insight in how to manipulate adenovirus-mediated immune responses for enhancement of anti-tumor efficacy. In this review, we first highlight how oncolytic adenovirus interacts with the innate immune system and its receptors such as Toll-like receptors, nucleotide-binding and oligomerization domain (NOD)- like receptors and other immune sensors. Then we describe the effect of these interactions on the adaptive immune system and its cells, especially B and T lymphocytes. Finally, we summarize the most significant preclinical and clinical results in the field of gene therapy where researchers have engineered adenovirus to manipulate the host immune system by expressing cytokines and signalingmediators. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Complex Polynomial Vector Fields

    DEFF Research Database (Denmark)

    The two branches of dynamical systems, continuous and discrete, correspond to the study of differential equations (vector fields) and iteration of mappings respectively. In holomorphic dynamics, the systems studied are restricted to those described by holomorphic (complex analytic) functions...... or meromorphic (allowing poles as singularities) functions. There already exists a well-developed theory for iterative holomorphic dynamical systems, and successful relations found between iteration theory and flows of vector fields have been one of the main motivations for the recent interest in holomorphic...... vector fields. Since the class of complex polynomial vector fields in the plane is natural to consider, it is remarkable that its study has only begun very recently. There are numerous fundamental questions that are still open, both in the general classification of these vector fields, the decomposition...

  5. Complex Polynomial Vector Fields

    DEFF Research Database (Denmark)

    Dias, Kealey

    vector fields. Since the class of complex polynomial vector fields in the plane is natural to consider, it is remarkable that its study has only begun very recently. There are numerous fundamental questions that are still open, both in the general classification of these vector fields, the decomposition...... of parameter spaces into structurally stable domains, and a description of the bifurcations. For this reason, the talk will focus on these questions for complex polynomial vector fields.......The two branches of dynamical systems, continuous and discrete, correspond to the study of differential equations (vector fields) and iteration of mappings respectively. In holomorphic dynamics, the systems studied are restricted to those described by holomorphic (complex analytic) functions...

  6. Existence and Stability of Solutions for Implicit Multivalued Vector Equilibrium Problems

    Directory of Open Access Journals (Sweden)

    Li Qiuying

    2011-01-01

    Full Text Available A class of implicit multivalued vector equilibrium problems is studied. By using the generalized Fan-Browder fixed point theorem, some existence results of solutions for the implicit multivalued vector equilibrium problems are obtained under some suitable assumptions. Moreover, a stability result of solutions for the implicit multivalued vector equilibrium problems is derived. These results extend and unify some recent results for implicit vector equilibrium problems, multivalued vector variational inequality problems, and vector variational inequality problems.

  7. Dynamics of adaptive and innate immunity in patients treated during primary human immunodeficiency virus infection: results from Maraviroc in HIV Acute Infection (MAIN) randomized clinical trial.

    Science.gov (United States)

    Ripa, M; Pogliaghi, M; Chiappetta, S; Galli, L; Pensieroso, S; Cavarelli, M; Scarlatti, G; De Biasi, S; Cossarizza, A; De Battista, D; Malnati, M; Lazzarin, A; Nozza, S; Tambussi, G

    2015-09-01

    We evaluated the dynamics of innate and adaptive immunity in patients treated with combined antiretroviral therapy (cART) during primary human immunodeficiency virus infection (PHI), enrolled in a prospective randomized trial (MAIN, EUDRACT 2008-007004-29). After 48 weeks of cART, we documented a reduction in activated B cells and CD8(+) T cells. Natural killer cell and dendritic cell frequencies were measured and a decrease in CD16(+) CD56(dim) with a reciprocal rise in CD56(high) natural killer cells and an increase in myeloid and plasmacytoid dendritic cells were recorded. In conclusion, 48 weeks of cART during PHI showed significant benefits for both innate and adaptive immunity. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  8. Acute exposure to space flight results in evidence of reduced lymph Transport, tissue fluid Shifts, and immune alterations in the rat gastrointestinal system

    Science.gov (United States)

    Cromer, W. E.; Zawieja, D. C.

    2018-05-01

    Space flight causes a number of alterations in physiological systems, changes in the immunological status of subjects, and altered interactions of the host to environmental stimuli. We studied the effect of space flight on the lymphatic system of the gastrointestinal tract which is responsible for lipid transport and immune surveillance which includes the host interaction with the gut microbiome. We found that there were signs of tissue damage present in the space flown animals that was lacking in ground controls (epithelial damage, crypt morphological changes, etc.). Additionally, morphology of the lymphatic vessels in the tissue suggested a collapsed state at time of harvest and there was a profound change in the retention of lipid in the villi of the ileum. Contrary to our assumptions there was a reduction in tissue fluid volume likely associated with other fluid shifts described. The reduction of tissue fluid volume in the colon and ileum is a likely contributing factor to the state of the lymphatic vessels and lipid transport issues observed. There were also associated changes in the number of MHC-II+ immune cells in the colon tissue, which along with reduced lymphatic competence would favor immune dysfunction in the tissue. These findings help expand our understanding of the effects of space flight on various organ systems. It also points out potential issues that have not been closely examined and have to potential for the need of countermeasure development.

  9. Immunization alters body odor.

    Science.gov (United States)

    Kimball, Bruce A; Opiekun, Maryanne; Yamazaki, Kunio; Beauchamp, Gary K

    2014-04-10

    Infections have been shown to alter body odor. Because immune activation accompanies both infection and immunization, we tested the hypothesis that classical immunization might similarly result in the alteration of body odors detectable by trained biosensor mice. Using a Y-maze, we trained biosensor mice to distinguish between urine odors from rabies-vaccinated (RV) and unvaccinated control mice. RV-trained mice generalized this training to mice immunized with the equine West Nile virus (WNV) vaccine compared with urine of corresponding controls. These results suggest that there are similarities between body odors of mice immunized with these two vaccines. This conclusion was reinforced when mice could not be trained to directly discriminate between urine odors of RV- versus WNV-treated mice. Next, we trained biosensor mice to discriminate the urine odors of mice treated with lipopolysaccharide (LPS; a general elicitor of innate immunological responses) from the urine of control mice. These LPS-trained biosensors could distinguish between the odors of LPS-treated mouse urine and RV-treated mouse urine. Finally, biosensor mice trained to distinguish between the odors of RV-treated mouse urine and control mouse urine did not generalize this training to discriminate between the odors of LPS-treated mouse urine and control mouse urine. From these experiments, we conclude that: (1) immunization alters urine odor in similar ways for RV and WNV immunizations; and (2) immune activation with LPS also alters urine odor but in ways different from those of RV and WNV. Published by Elsevier Inc.

  10. Immune dysfunction in cirrhosis

    Science.gov (United States)

    Sipeki, Nora; Antal-Szalmas, Peter; Lakatos, Peter L; Papp, Maria

    2014-01-01

    Innate and adaptive immune dysfunction, also referred to as cirrhosis-associated immune dysfunction syndrome, is a major component of cirrhosis, and plays a pivotal role in the pathogenesis of both the acute and chronic worsening of liver function. During the evolution of the disease, acute decompensation events associated with organ failure(s), so-called acute-on chronic liver failure, and chronic decompensation with progression of liver fibrosis and also development of disease specific complications, comprise distinct clinical entities with different immunopathology mechanisms. Enhanced bacterial translocation associated with systemic endotoxemia and increased occurrence of systemic bacterial infections have substantial impacts on both clinical situations. Acute and chronic exposure to bacteria and/or their products, however, can result in variable clinical consequences. The immune status of patients is not constant during the illness; consequently, alterations of the balance between pro- and anti-inflammatory processes result in very different dynamic courses. In this review we give a detailed overview of acquired immune dysfunction and its consequences for cirrhosis. We demonstrate the substantial influence of inherited innate immune dysfunction on acute and chronic inflammatory processes in cirrhosis caused by the pre-existing acquired immune dysfunction with limited compensatory mechanisms. Moreover, we highlight the current facts and future perspectives of how the assessment of immune dysfunction can assist clinicians in everyday practical decision-making when establishing treatment and care strategies for the patients with end-stage liver disease. Early and efficient recognition of inappropriate performance of the immune system is essential for overcoming complications, delaying progression and reducing mortality. PMID:24627592

  11. Arkansas community pharmacists' opinions on providing immunizations.

    Science.gov (United States)

    Pace, Anne C; Flowers, Schwanda K; Hastings, Jan K

    2010-10-01

    To determine community pharmacists' attitudes and knowledge on providing immunizations including perceived barriers to immunizing. The study also examined the percentage of Arkansas pharmacists providing immunizations and the utilization of student pharmacists. Survey. Arkansas community pharmacies from February to March 2009. Community pharmacists. Mailed survey. Perceived barriers to providing immunizations, pharmacists' attitudes regarding immunizations, number of immunization-certified pharmacists, immunization administration rates within the last year, and senior student pharmacists utilization. A total of 350 surveys were mailed, and 129 were returned. In all, 79% of the respondents believed administering immunizations has advanced or significantly advanced the profession. Being certified and attitude toward providing immunizations were correlated; 37% of the respondents held certification to immunize, of which 77% reported immunizing within the last year. Commonly reported barriers included time (76%) followed by reimbursement and legal liability. Only half the respondents realized fourth year student pharmacists could immunize and only 33% of certified pharmacists utilized student pharmacists to immunize. Pharmacists perceive many barriers to providing immunizations. Training student pharmacists to give immunizations may not result in them providing immunizations upon graduation. Additional education on overcoming potential barriers and using senior student pharmacists to administer immunizations is needed.

  12. Assessment of Lactobacillus gasseri as a Candidate Oral Vaccine Vector

    Science.gov (United States)

    Stoeker, Laura; Nordone, Shila; Gunderson, Sara; Zhang, Lin; Kajikawa, Akinobu; LaVoy, Alora; Miller, Michael; Klaenhammer, Todd R.; Dean, Gregg A.

    2011-01-01

    Lactobacillus species are commensal bacteria that have long been recognized as probiotic microbes and are generally regarded as safe (GRAS) for human consumption. We have investigated the use of L. gasseri as a vaccine vector for oral immunization against mucosal pathogens. Recent research has shown that the immune response to different lactobacilli can vary widely depending on the species or subspecies of Lactobacillus being studied. While some lactobacilli seem to induce oral tolerance, others induce an adaptive immune response. This study characterized the systemic and mucosal immune response to wild-type and genetically modified L. gasseri. L. gasseri primarily activates TLR2/6, with additional activation through the TLR2 homodimer. To expand the Toll-like receptor (TLR) activation profile of L. gasseri and the immunogenicity of the vector, a plasmid containing fliC, the gene encoding bacterial flagellin, was introduced which resulted in the strong activation of TLR5. The treatment of human myeloid dendritic cells with recombinant lactobacilli expressing flagellin triggered phenotypic maturation and the release of proinflammatory cytokines. In contrast, bacterial treatment also resulted in a statistically significant increase in IL-10 production. In vivo studies established that treatment with L. gasseri led to a diversification of B-cell populations in the lamina propria of the murine colon. Furthermore, treatment with genetically modified L. gasseri led to a significant decrease in the percentage of FoxP3+ colonic lymphocytes. Taken together, these data clarify the interaction of L. gasseri with the host immune system and support further investigation of the in vivo immunogenicity of L. gasseri expressing both flagellin and candidate vaccine antigens. PMID:21900526

  13. Successful vectorization - reactor physics Monte Carlo code

    International Nuclear Information System (INIS)

    Martin, W.R.

    1989-01-01

    Most particle transport Monte Carlo codes in use today are based on the ''history-based'' algorithm, wherein one particle history at a time is simulated. Unfortunately, the ''history-based'' approach (present in all Monte Carlo codes until recent years) is inherently scalar and cannot be vectorized. In particular, the history-based algorithm cannot take advantage of vector architectures, which characterize the largest and fastest computers at the current time, vector supercomputers such as the Cray X/MP or IBM 3090/600. However, substantial progress has been made in recent years in developing and implementing a vectorized Monte Carlo algorithm. This algorithm follows portions of many particle histories at the same time and forms the basis for all successful vectorized Monte Carlo codes that are in use today. This paper describes the basic vectorized algorithm along with descriptions of several variations that have been developed by different researchers for specific applications. These applications have been mainly in the areas of neutron transport in nuclear reactor and shielding analysis and photon transport in fusion plasmas. The relative merits of the various approach schemes will be discussed and the present status of known vectorization efforts will be summarized along with available timing results, including results from the successful vectorization of 3-D general geometry, continuous energy Monte Carlo. (orig.)

  14. Ad Hoc on-Demand Distance Vector (AODV Routing Protocol Performance Evaluation on Hybrid Ad Hoc Network: Comparison of Result of Ns-2 Simulation and Implementation on Testbed using PDA

    Directory of Open Access Journals (Sweden)

    Riri Sari

    2010-10-01

    Full Text Available In Mobile Ad hoc NETwork (MANET, node supplemented with wireless equipment has the capacity to manage and organise autonomously, without the presence of network infrastructures. Hybrid ad hoc network, enable several nodes to move freely (mobile to create instant communication. Independent from infrastructure. They could access the Local Area Network (LAN or the Internet. Functionalities of ad hoc network very much dependent on the routing protocol that determines the routing around node. Ad hoc On-demand Distance Vector (AODV is one of routing protocols in ad hoc network which has a reactive characteristic. This protocol is the most common protocol being researched and used. In this Research, AODV protocol investigation was conducted by developing a testbed using Personal Computer, several Laptops (the Linux Red Hat operation system 9.0 and Fedora Core 2, and Personal Digital Assistant (PDA. This research also made a complete package by mean of cross compilation for PDA iPAQ. In general, results obtained from the simulation of AODV protocol using Network Simulator NS-2 are packet delivery ratio 99.89%, end-to-end delay of 0.14 seconds and routing overhead of 1,756.61 byte per second. Afterwards results from simulation were compared to results from testbed. Results obtained from testbed are as follows: the packet delivery ratio is 99.57%, the end-to-end delay is 1.004 seconds and the routing overhead is 1,360.36 byte per second.

  15. Vectorization, parallelization and porting of nuclear codes (vectorization and parallelization). Progress report fiscal 1998

    International Nuclear Information System (INIS)

    Ishizuki, Shigeru; Kawai, Wataru; Nemoto, Toshiyuki; Ogasawara, Shinobu; Kume, Etsuo; Adachi, Masaaki; Kawasaki, Nobuo; Yatake, Yo-ichi

    2000-03-01

    Several computer codes in the nuclear field have been vectorized, parallelized and transported on the FUJITSU VPP500 system, the AP3000 system and the Paragon system at Center for Promotion of Computational Science and Engineering in Japan Atomic Energy Research Institute. We dealt with 12 codes in fiscal 1998. These results are reported in 3 parts, i.e., the vectorization and parallelization on vector processors part, the parallelization on scalar processors part and the porting part. In this report, we describe the vectorization and parallelization on vector processors. In this vectorization and parallelization on vector processors part, the vectorization of General Tokamak Circuit Simulation Program code GTCSP, the vectorization and parallelization of Molecular Dynamics NTV (n-particle, Temperature and Velocity) Simulation code MSP2, Eddy Current Analysis code EDDYCAL, Thermal Analysis Code for Test of Passive Cooling System by HENDEL T2 code THANPACST2 and MHD Equilibrium code SELENEJ on the VPP500 are described. In the parallelization on scalar processors part, the parallelization of Monte Carlo N-Particle Transport code MCNP4B2, Plasma Hydrodynamics code using Cubic Interpolated Propagation Method PHCIP and Vectorized Monte Carlo code (continuous energy model / multi-group model) MVP/GMVP on the Paragon are described. In the porting part, the porting of Monte Carlo N-Particle Transport code MCNP4B2 and Reactor Safety Analysis code RELAP5 on the AP3000 are described. (author)

  16. Immune System

    Science.gov (United States)

    ... of the Immune System Print en español El sistema inmunitario Whether you're stomping through the showers ... of Use Notice of Nondiscrimination Visit the Nemours Web site. Note: All information on TeensHealth® is for ...

  17. Immunizing Adults

    Centers for Disease Control (CDC) Podcasts

    Vaccines aren’t just for kids; adults also need to get immunized. Overall, far too many people 19 years and older aren’t getting the vaccines they need and remain unprotected. In this podcast, Dr. Walter Williams discuss the importance of adults being fully vaccinated.

  18. Immune mediated liver failure.

    Science.gov (United States)

    Wang, Xiaojing; Ning, Qin

    2014-01-01

    Liver failure is a clinical syndrome of various etiologies, manifesting as jaundice, encephalopathy, coagulopathy and circulatory dysfunction, which result in subsequent multiorgan failure. Clinically, liver failure is classified into four categories: acute, subacute, acute-on-chronic and chronic liver failure. Massive hepatocyte death is considered to be the core event in the development of liver failure, which occurs when the extent of hepatocyte death is beyond the liver regenerative capacity. Direct damage and immune-mediated liver injury are two major factors involved in this process. Increasing evidence has suggested the essential role of immune-mediated liver injury in the pathogenesis of liver failure. Here, we review the evolved concepts concerning the mechanisms of immune-mediated liver injury in liver failure from human and animal studies. Both innate and adaptive immunity, especially the interaction of various immune cells and molecules as well as death receptor signaling system are discussed. In addition, we highlight the concept of "immune coagulation", which has been shown to be related to the disease progression and liver injury exacerbation in HBV related acute-on-chronic liver failure.

  19. Mammalian Gut Immunity

    Science.gov (United States)

    Chassaing, Benoit; Kumar, Manish; Baker, Mark T.; Singh, Vishal; Vijay-Kumar, Matam

    2016-01-01

    The mammalian intestinal tract is the largest immune organ in the body and comprises cells from non-hemopoietic (epithelia, Paneth cells, goblet cells) and hemopoietic (macrophages, dendritic cells, T-cells) origin, and is also a dwelling for trillions of microbes collectively known as the microbiota. The homeostasis of this large microbial biomass is prerequisite to maintain host health by maximizing beneficial symbiotic relationships and minimizing the risks of living in such close proximity. Both microbiota and host immune system communicate with each other to mutually maintain homeostasis in what could be called a “love–hate relationship.” Further, the host innate and adaptive immune arms of the immune system cooperate and compensate each other to maintain the equilibrium of a highly complex gut ecosystem in a stable and stringent fashion. Any imbalance due to innate or adaptive immune deficiency or aberrant immune response may lead to dysbiosis and low-grade to robust gut inflammation, finally resulting in metabolic diseases. PMID:25163502

  20. Immunization in pregnancy.

    Science.gov (United States)

    Gruslin, Andrée; Steben, Marc; Halperin, Scott; Money, Deborah M; Yudin, Mark H

    2009-11-01

    To review the evidence and provide recommendations on immunization in pregnancy. Outcomes evaluated include effectiveness of immunization, risks and benefits for mother and fetus. The Medline and Cochrane databases were searched for articles published up to June 2008 on the topic of immunization in pregnancy. The evidence obtained was reviewed and evaluated by the Infectious Diseases Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) under the leadership of the principal authors, and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care. Implementation of the recommendations in this guideline should result in more appropriate immunization of pregnant and breastfeeding women, decreased risk of contraindicated immunization, and better disease prevention. The quality of evidence reported in this document has been assessed using the evaluation of evidence criteria in the Report of the Canadian Task Force on Preventive Health Care (Table 1). (1) All women of childbearing age should be evaluated for the possibility of pregnancy before immunization. (III-A). (2) Health care providers should obtain a relevant immunization history from all women accessing prenatal care. (III-A). (3) In general, live and/or live-attenuated virus vaccines should not be administered during pregnancy, as there is a, largely theoretical, risk to the fetus. (II-3B). (4) Women who have inadvertently received immunization with live or live-attenuated vaccines during pregnancy should not be counselled to terminate the pregnancy because of a teratogenic risk. (II-2A). (5) Non-pregnant women immunized with a live or live-attenuated vaccine should be counselled to delay pregnancy for at least four weeks. (III-B). (6) Inactivated viral vaccines, bacterial vaccines, and toxoids can be used safely in pregnancy. (II-1A). (7) Women who are breastfeeding can still be immunized (passive-active immunization, live or killed

  1. Vaccines (immunizations) - overview

    Science.gov (United States)

    Vaccinations; Immunizations; Immunize; Vaccine shots; Prevention - vaccine ... of the vaccine. VACCINE SCHEDULE The recommended vaccination (immunization) schedule is updated every 12 months by the ...

  2. Vector Boson Scattering at High Mass

    CERN Document Server

    The ATLAS collaboration

    2009-01-01

    In the absence of a light Higgs boson, the mechanism of electroweak symmetry breaking will be best studied in processes of vector boson scattering at high mass. Various models predict resonances in this channel. Here, we investigate $WW $scalar and vector resonances, $WZ$ vector resonances and a $ZZ$ scalar resonance over a range of diboson centre-of-mass energies. Particular attention is paid to the application of forward jet tagging and to the reconstruction of dijet pairs with low opening angle resulting from the decay of highly boosted vector bosons. The performances of different jet algorithms are compared. We find that resonances in vector boson scattering can be discovered with a few tens of inverse femtobarns of integrated luminosity.

  3. Multi-task Vector Field Learning.

    Science.gov (United States)

    Lin, Binbin; Yang, Sen; Zhang, Chiyuan; Ye, Jieping; He, Xiaofei

    2012-01-01

    Multi-task learning (MTL) aims to improve generalization performance by learning multiple related tasks simultaneously and identifying the shared information among tasks. Most of existing MTL methods focus on learning linear models under the supervised setting. We propose a novel semi-supervised and nonlinear approach for MTL using vector fields. A vector field is a smooth mapping from the manifold to the tangent spaces which can be viewed as a directional derivative of functions on the manifold. We argue that vector fields provide a natural way to exploit the geometric structure of data as well as the shared differential structure of tasks, both of which are crucial for semi-supervised multi-task learning. In this paper, we develop multi-task vector field learning (MTVFL) which learns the predictor functions and the vector fields simultaneously. MTVFL has the following key properties. (1) The vector fields MTVFL learns are close to the gradient fields of the predictor functions. (2) Within each task, the vector field is required to be as parallel as possible which is expected to span a low dimensional subspace. (3) The vector fields from all tasks share a low dimensional subspace. We formalize our idea in a regularization framework and also provide a convex relaxation method to solve the original non-convex problem. The experimental results on synthetic and real data demonstrate the effectiveness of our proposed approach.

  4. Clifford Fourier transform on vector fields.

    Science.gov (United States)

    Ebling, Julia; Scheuermann, Gerik

    2005-01-01

    Image processing and computer vision have robust methods for feature extraction and the computation of derivatives of scalar fields. Furthermore, interpolation and the effects of applying a filter can be analyzed in detail and can be advantages when applying these methods to vector fields to obtain a solid theoretical basis for feature extraction. We recently introduced the Clifford convolution, which is an extension of the classical convolution on scalar fields and provides a unified notation for the convolution of scalar and vector fields. It has attractive geometric properties that allow pattern matching on vector fields. In image processing, the convolution and the Fourier transform operators are closely related by the convolution theorem and, in this paper, we extend the Fourier transform to include general elements of Clifford Algebra, called multivectors, including scalars and vectors. The resulting convolution and derivative theorems are extensions of those for convolution and the Fourier transform on scalar fields. The Clifford Fourier transform allows a frequency analysis of vector fields and the behavior of vector-valued filters. In frequency space, vectors are transformed into general multivectors of the Clifford Algebra. Many basic vector-valued patterns, such as source, sink, saddle points, and potential vortices, can be described by a few multivectors in frequency space.

  5. SOME ISSUES OF DIAGNOSTICS IN IMMUNE PATHOLOGY

    Directory of Open Access Journals (Sweden)

    I. A. Tousankina

    2010-01-01

    Full Text Available Present lecture contains an author's opinion concerning diagnostic issues in immunopathology, including primary and secondary immune deficiencies, immune-dependent states that are based on immunopathological syndromes. Original formulations are suggested for some key categories of clinical immunology, physical, instrumental and laboratory diagnostics of immune deficiencies and immune-dependent diseases. The results of original long-term observations, as well as data on Sverdlovsk Regional Register of primary immune deficiencies are presented in the work.

  6. Cytomegalovirus vector expressing RAE-1γ induces enhanced anti-tumor capacity of murine CD8+ T cells.

    Science.gov (United States)

    Tršan, Tihana; Vuković, Kristina; Filipović, Petra; Brizić, Ana Lesac; Lemmermann, Niels A W; Schober, Kilian; Busch, Dirk H; Britt, William J; Messerle, Martin; Krmpotić, Astrid; Jonjić, Stipan

    2017-08-01

    Designing CD8 + T-cell vaccines, which would provide protection against tumors is still considered a great challenge in immunotherapy. Here we show the robust potential of cytomegalovirus (CMV) vector expressing the NKG2D ligand RAE-1γ as CD8 + T cell-based vaccine against malignant tumors. Immunization with the CMV vector expressing RAE-1γ, delayed tumor growth or even provided complete protection against tumor challenge in both prophylactic and therapeutic settings. Moreover, a potent tumor control in mice vaccinated with this vector can be further enhanced by blocking the immune checkpoints TIGIT and PD-1. CMV vector expressing RAE-1γ potentiated expansion of KLRG1 + CD8 + T cells with enhanced effector properties. This vaccination was even more efficient in neonatal mice, resulting in the expansion and long-term maintenance of epitope-specific CD8 + T cells conferring robust resistance against tumor challenge. Our data show that immunomodulation of CD8 + T-cell responses promoted by herpesvirus expressing a ligand for NKG2D receptor can provide a powerful platform for the prevention and treatment of CD8 + T-cell sensitive tumors. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Adaptation in the innate immune system and heterologous innate immunity.

    Science.gov (United States)

    Martin, Stefan F

    2014-11-01

    The innate immune system recognizes deviation from homeostasis caused by infectious or non-infectious assaults. The threshold for its activation seems to be established by a calibration process that includes sensing of microbial molecular patterns from commensal bacteria and of endogenous signals. It is becoming increasingly clear that adaptive features, a hallmark of the adaptive immune system, can also be identified in the innate immune system. Such adaptations can result in the manifestation of a primed state of immune and tissue cells with a decreased activation threshold. This keeps the system poised to react quickly. Moreover, the fact that the innate immune system recognizes a wide variety of danger signals via pattern recognition receptors that often activate the same signaling pathways allows for heterologous innate immune stimulation. This implies that, for example, the innate immune response to an infection can be modified by co-infections or other innate stimuli. This "design feature" of the innate immune system has many implications for our understanding of individual susceptibility to diseases or responsiveness to therapies and vaccinations. In this article, adaptive features of the innate immune system as well as heterologous innate immunity and their implications are discussed.

  8. Noncausal Bayesian Vector Autoregression

    DEFF Research Database (Denmark)

    Lanne, Markku; Luoto, Jani

    We propose a Bayesian inferential procedure for the noncausal vector autoregressive (VAR) model that is capable of capturing nonlinearities and incorporating effects of missing variables. In particular, we devise a fast and reliable posterior simulator that yields the predictive distribution...

  9. Understanding Vector Fields.

    Science.gov (United States)

    Curjel, C. R.

    1990-01-01

    Presented are activities that help students understand the idea of a vector field. Included are definitions, flow lines, tangential and normal components along curves, flux and work, field conservation, and differential equations. (KR)

  10. GAP Land Cover - Vector

    Data.gov (United States)

    Minnesota Department of Natural Resources — This vector dataset is a detailed (1-acre minimum), hierarchically organized vegetation cover map produced by computer classification of combined two-season pairs of...

  11. Sesquilinear uniform vector integral

    Indian Academy of Sciences (India)

    theory, together with his integral, dominate contemporary mathematics. ... directions belonging to Bartle and Dinculeanu (see [1], [6], [7] and [2]). ... in this manner, namely he integrated vector functions with respect to measures of bounded.

  12. Tagged Vector Contour (TVC)

    Data.gov (United States)

    Kansas Data Access and Support Center — The Kansas Tagged Vector Contour (TVC) dataset consists of digitized contours from the 7.5 minute topographic quadrangle maps. Coverage for the state is incomplete....

  13. Vector hysteresis models

    Czech Academy of Sciences Publication Activity Database

    Krejčí, Pavel

    1991-01-01

    Roč. 2, - (1991), s. 281-292 ISSN 0956-7925 Keywords : vector hysteresis operator * hysteresis potential * differential inequality Subject RIV: BA - General Mathematics http://www.math.cas.cz/~krejci/b15p.pdf

  14. Support vector machines applications

    CERN Document Server

    Guo, Guodong

    2014-01-01

    Support vector machines (SVM) have both a solid mathematical background and good performance in practical applications. This book focuses on the recent advances and applications of the SVM in different areas, such as image processing, medical practice, computer vision, pattern recognition, machine learning, applied statistics, business intelligence, and artificial intelligence. The aim of this book is to create a comprehensive source on support vector machine applications, especially some recent advances.

  15. Exotic composite vector boson

    International Nuclear Information System (INIS)

    Akama, K.; Hattori, T.; Yasue, M.

    1991-01-01

    An exotic composite vector boson V is introduced in two dynamical models of composite quarks, leptons, W, and Z. One is based on four-Fermi interactions, in which composite vector bosons are regarded as fermion-antifermion bound states and the other is based on the confining SU(2) L gauge model, in which they are given by scalar-antiscalar bound states. Both approaches describe the same effective interactions for the sector of composite quarks, leptons, W, Z, γ, and V

  16. Vector borne diseases

    OpenAIRE

    Melillo Fenech, Tanya

    2010-01-01

    A vector-borne disease is one in which the pathogenic microorganism is transmitted from an infected individual to another individual by an arthropod or other agent. The transmission depends upon the attributes and requirements of at least three different Iiving organisms : the pathologic agent which is either a virus, protozoa, bacteria or helminth (worm); the vector, which is commonly an arthropod such as ticks or mosquitoes; and the human host.

  17. Intrapulmonary Versus Nasal Transduction of Murine Airways With GP64-pseudotyped Viral Vectors

    Directory of Open Access Journals (Sweden)

    Mayumi Oakland

    2013-01-01

    Full Text Available Persistent viral vector-mediated transgene expression in the airways requires delivery to cells with progenitor capacity and avoidance of immune responses. Previously, we observed that GP64-pseudotyped feline immunodeficiency virus (FIV-mediated gene transfer was more efficient in the nasal airways than the large airways of the murine lung. We hypothesized that in vivo gene transfer was limited by immunological and physiological barriers in the murine intrapulmonary airways. Here, we systematically investigate multiple potential barriers to lentiviral gene transfer in the airways of mice. We show that GP64-FIV vector transduced primary cultures of well-differentiated murine nasal epithelia with greater efficiency than primary cultures of murine tracheal epithelia. We further demonstrate that neutrophils, type I interferon (IFN responses, as well as T and B lymphocytes are not the major factors limiting the transduction of murine conducting airways. In addition, we observed better transduction of GP64-pseudotyped vesicular stomatitis virus (VSV in the nasal epithelia compared with the intrapulmonary airways in mice. VSVG glycoprotein pseudotyped VSV transduced intrapulmonary epithelia with similar efficiency as nasal epithelia. Our results suggest that the differential transduction efficiency of nasal versus intrapulmonary airways by FIV vector is not a result of immunological barriers or surface area, but rather differential expression of cellular factors specific for FIV vector transduction.

  18. Robust and accurate vectorization of line drawings.

    Science.gov (United States)

    Hilaire, Xavier; Tombre, Karl

    2006-06-01

    This paper presents a method for vectorizing the graphical parts of paper-based line drawings. The method consists of separating the input binary image into layers of homogeneous thickness, skeletonizing each layer, segmenting the skeleton by a method based on random sampling, and simplifying the result. The segmentation method is robust with a best bound of 50 percent noise reached for indefinitely long primitives. Accurate estimation of the recognized vector's parameters is enabled by explicitly computing their feasibility domains. Theoretical performance analysis and expression of the complexity of the segmentation method are derived. Experimental results and comparisons with other vectorization systems are also provided.

  19. Vector fields satisfying the barycenter property

    Directory of Open Access Journals (Sweden)

    Lee Manseob

    2018-04-01

    Full Text Available We show that if a vector field X has the C1 robustly barycenter property then it does not have singularities and it is Axiom A without cycles. Moreover, if a generic C1-vector field has the barycenter property then it does not have singularities and it is Axiom A without cycles. Moreover, we apply the results to the divergence free vector fields. It is an extension of the results of the barycenter property for generic diffeomorphisms and volume preserving diffeomorphisms [1].

  20. Highly evolvable malaria vectors : The genomes of 16 Anopheles mosquitoes

    NARCIS (Netherlands)

    Neafsey, D. E.; Waterhouse, R. M.; Abai, M. R.; Aganezov, S. S.; Alekseyev, M. A.; Allen, J. E.; Amon, J.; Arca, B.; Arensburger, P.; Artemov, G.; Assour, L. A.; Basseri, H.; Berlin, A.; Birren, B. W.; Blandin, S. A.; Brockman, A. I.; Burkot, T. R.; Burt, A.; Chan, C. S.; Chauve, C.; Chiu, J. C.; Christensen, M.; Costantini, C.; Davidson, V. L. M.; Deligianni, E.; Dottorini, T.; Dritsou, V.; Gabriel, S. B.; Guelbeogo, W. M.; Hall, A. B.; Han, M. V.; Hlaing, T.; Hughes, D. S. T.; Jenkins, A. M.; Jiang, X.; Jungreis, I.; Kakani, E. G.; Kamali, M.; Kemppainen, P.; Kennedy, R. C.; Kirmitzoglou, I. K.; Koekemoer, L. L.; Laban, N.; Langridge, N.; Lawniczak, M. K. N.; Lirakis, M.; Lobo, N. F.; Lowy, E.; Maccallum, R. M.; Mao, C.; Maslen, G.; Mbogo, C.; Mccarthy, J.; Michel, K.; Mitchell, S. N.; Moore, W.; Murphy, K. A.; Naumenko, A. N.; Nolan, T.; Novoa, E. M.; O'loughlin, S.; Oringanje, C.; Oshaghi, M. A.; Pakpour, N.; Papathanos, P. A.; Peery, A. N.; Povelones, M.; Prakash, A.; Price, D. P.; Rajaraman, A.; Reimer, L. J.; Rinker, D. C.; Rokas, A.; Russell, T. L.; Sagnon, N.; Sharakhova, M. V.; Shea, T.; Simao, F. A.; Simard, F.; Slotman, M. A.; Somboon, P.; Stegniy, V.; Struchiner, C. J.; Thomas, G. W. C.; Tojo, M.; Topalis, P.; Tubio, J. M. C.; Unger, M. F.; Vontas, J.; Walton, C.; Wilding, C. S.; Willis, J. H.; Wu, Y.-c.; Yan, G.; Zdobnov, E. M.; Zhou, X.; Catteruccia, F.; Christophides, G. K.; Collins, F. H.; Cornman, R. S.; Crisanti, A.; Donnelly, M. J.; Emrich, S. J.; Fontaine, M. C.; Gelbart, W.; Hahn, M. W.; Hansen, I. A.; Howell, P. I.; Kafatos, F. C.; Kellis, M.; Lawson, D.; Louis, C.; Luckhart, S.; Muskavitch, M. A. T.; Ribeiro, J. M.; Riehle, M. A.; Sharakhov, I. V.; Tu, Z.; Zwiebel, L. J.; Besansky, N. J.

    2015-01-01

    Variation in vectorial capacity for human malaria among Anopheles mosquito species is determined by many factors, including behavior, immunity, and life history. To investigate the genomic basis of vectorial capacity and explore new avenues for vector control, we sequenced the genomes of 16

  1. Subcutaneous or oral immunization of mice with Lactococcus lactis expressing F4 fimbrial adhesin FaeG.

    Science.gov (United States)

    Liu, Shujie; Li, Yongming; Xu, Ziwei; Wang, Yicheng

    2013-01-01

    Enterotoxigenic Escherichia coli (ETEC) is one of the most common causes of diarrhea in neonatal and postweaning piglets. Fimbrial adhesion of ETEC has been considered an important colonization factor with antigenicity. To safely and effectively deliver the F4 (K88) fimbrial adhesin FaeG to the immune system, we have previously constructed the secretory expression vector pNZ8112-faeG, and FaeG was produced in cytoplasmic form in Lactococcus lactis. In this work, BALB/c mice were immunized with recombinant L. lactis to further determine the immunogenicity of recombinant FaeG (rFaeG) via the subcutaneous or oral route. Subcutaneous immunization in mice with recombinant L. lactis induced a significant increase in the F4-specific serum IgG titer and the number of antibody-secreting cells (ASCs) in the spleen. Oral immunization of mice with recombinant L. lactis induced mucosal and systemic F4-specific immune responses and increased the number of ASCs in the spleen, mesenteric lymph nodes and Peyer's patches. High-dose (2.8 × 10(11) CFU) recombinant strains and adjuvant cholera toxin B subunit enhanced specific mucosal immune responses. The results suggest the feasibility of delivering rFaeG expressed in L. lactis to the immune system in order to induce an F4-specific immune response.

  2. n-Characteristic Vector Fields of Contact Manifoldss

    OpenAIRE

    Hassanzadeh, Babak

    2017-01-01

    In present paper we define and study $n$-characteristic vector fields. We present definition of Tanaka-Webster connection, then use it for studying the behavior of $n$-characteristic vector fields. Also we show some results about of these vector fields by Tanaka-Webster connection.

  3. Direct and indirect immunosuppression by a malaria parasite in its mosquito vector

    NARCIS (Netherlands)

    Boëte, C.H.J.J.; Paul, R.E.L.; Koëlla, J.C.

    2004-01-01

    Malaria parasites develop as oocysts within the haemocoel of their mosquito vector during a period that is longer than the average lifespan of many of their vectors. How can they escape from the mosquito's immune responses during their long development? Whereas older oocysts might camouflage

  4. Skin Immunization Obviates Alcohol-Related Immune Dysfunction

    Directory of Open Access Journals (Sweden)

    Rhonda M. Brand

    2015-11-01

    Full Text Available Alcoholics suffer from immune dysfunction that can impede vaccine efficacy. If ethanol (EtOH-induced immune impairment is in part a result of direct exposure of immune cells to EtOH, then reduced levels of exposure could result in less immune dysfunction. As alcohol ingestion results in lower alcohol levels in skin than blood, we hypothesized that the skin immune network may be relatively preserved, enabling skin-targeted immunizations to obviate the immune inhibitory effects of alcohol consumption on conventional vaccines. We employed the two most common chronic EtOH mouse feeding models, the liver-damaging Lieber-DeCarli (LD and liver-sparing Meadows-Cook (MC diets, to examine the roles of EtOH and/or EtOH-induced liver dysfunction on alcohol related immunosuppression. Pair-fed mice were immunized against the model antigen ovalbumin (OVA by DNA immunization or against flu by administering the protein-based influenza vaccine either systemically (IV, IM, directly to liver (hydrodynamic, or cutaneously (biolistic, ID. We measured resulting tissue EtOH levels, liver stress, regulatory T cell (Treg, and myeloid-derived suppressor cell (MDSC populations. We compared immune responsiveness by measuring delayed-type hypersensitivity (DTH, antigen-specific cytotoxic T lymphocyte (CTL, and antibody induction as a function of delivery route and feeding model. We found that, as expected, and independent of the feeding model, EtOH ingestion inhibits DTH, CTL lysis, and antigen-specific total IgG induced by traditional systemic vaccines. On the other hand, skin-targeted vaccines were equally immunogenic in alcohol-exposed and non-exposed subjects, suggesting that cutaneous immunization may result in more efficacious vaccination in alcohol-ingesting subjects.

  5. Vector optimization theory, applications, and extensions

    CERN Document Server

    Jahn, Johannes

    2011-01-01

    This new edition of a key monograph has fresh sections on the work of Edgeworth and Pareto in its presentation in a general setting of the fundamentals and important results of vector optimization. It examines background material, applications and theories.

  6. Filoviral Immune Evasion Mechanisms

    Directory of Open Access Journals (Sweden)

    Christopher F. Basler

    2011-09-01

    Full Text Available The Filoviridae family of viruses, which includes the genera Ebolavirus (EBOV and Marburgvirus (MARV, causes severe and often times lethal hemorrhagic fever in humans. Filoviral infections are associated with ineffective innate antiviral responses as a result of virally encoded immune antagonists, which render the host incapable of mounting effective innate or adaptive immune responses. The Type I interferon (IFN response is critical for establishing an antiviral state in the host cell and subsequent activation of the adaptive immune responses. Several filoviral encoded components target Type I IFN responses, and this innate immune suppression is important for viral replication and pathogenesis. For example, EBOV VP35 inhibits the phosphorylation of IRF-3/7 by the TBK-1/IKKε kinases in addition to sequestering viral RNA from detection by RIG-I like receptors. MARV VP40 inhibits STAT1/2 phosphorylation by inhibiting the JAK family kinases. EBOV VP24 inhibits nuclear translocation of activated STAT1 by karyopherin-α. The examples also represent distinct mechanisms utilized by filoviral proteins in order to counter immune responses, which results in limited IFN-α/β production and downstream signaling.

  7. The Insect Microbiome Modulates Vector Competence for Arboviruses

    Directory of Open Access Journals (Sweden)

    Natapong Jupatanakul

    2014-11-01

    Full Text Available Diseases caused by arthropod-borne viruses (arboviruses, such as Dengue, West Nile, and Chikungunya, constitute a major global health burden and are increasing in incidence and geographic range. The natural microbiota of insect vectors influences various aspects of host biology, such as nutrition, reproduction, metabolism, and immunity, and recent studies have highlighted the ability of insect-associated bacteria to reduce vector competence for arboviruses and other pathogens. This reduction can occur through mechanisms, such as immune response activation, resource competition, or the production of anti-viral molecules. Studying the interactions between insect vectors and their microbiota is an important step toward developing alternative strategies for arbovirus transmission control.

  8. A comparison of foamy and lentiviral vector genotoxicity in SCID-repopulating cells shows foamy vectors are less prone to clonal dominance

    Directory of Open Access Journals (Sweden)

    Elizabeth M Everson

    2016-01-01

    Full Text Available Hematopoietic stem cell (HSC gene therapy using retroviral vectors has immense potential, but vector-mediated genotoxicity limits use in the clinic. Lentiviral vectors are less genotoxic than gammaretroviral vectors and have become the vector of choice in clinical trials. Foamy retroviral vectors have a promising integration profile and are less prone to read-through transcription than gammaretroviral or lentiviral vectors. Here, we directly compared the safety and efficacy of foamy vectors to lentiviral vectors in human CD34+ repopulating cells in immunodeficient mice. To increase their genotoxic potential, foamy and lentiviral vectors with identical transgene cassettes with a known genotoxic spleen focus forming virus promoter were used. Both vectors resulted in efficient marking in vivo and a total of 825 foamy and 460 lentiviral vector unique integration sites were recovered in repopulating cells 19 weeks after transplantation. Foamy vector proviruses were observed less often near RefSeq gene and proto-oncogene transcription start sites than lentiviral vectors. The foamy vector group were also more polyclonal with fewer dominant clones (two out of six mice than the lentiviral vector group (eight out of eight mice, and only lentiviral vectors had integrants near known proto-oncogenes in dominant clones. Our data further support the relative safety of foamy vectors for HSC gene therapy.

  9. Immunizations for Preterm Babies

    Science.gov (United States)

    ... Issues Health Issues Health Issues Conditions Injuries & Emergencies Vaccine Preventable Diseases ... Children > Safety & Prevention > Immunizations > Immunizations For Preterm Babies Safety & ...

  10. Weakened Immune Systems

    Science.gov (United States)

    ... Issues Health Issues Health Issues Conditions Injuries & Emergencies Vaccine Preventable Diseases ... Children > Safety & Prevention > Immunizations > Weakened Immune Systems Safety & Prevention ...

  11. Immunizations: Active vs. Passive

    Science.gov (United States)

    ... Issues Health Issues Health Issues Conditions Injuries & Emergencies Vaccine Preventable Diseases ... Children > Safety & Prevention > Immunizations > Immunizations: Active vs. Passive Safety & ...

  12. Innate immunity is not related to the sex of adult Tree Swallows during the nestling period

    Science.gov (United States)

    Houdek, Bradley J.; Lombardo, Michael P.; Thorpe, Patrick A.; Hahn, D. Caldwell

    2011-01-01

    Evolutionary theory predicts that exposure to more diverse pathogens will result in the evolution of a more robust immune response. We predicted that during the breeding season the innate immune function of female Tree Swallows (Tachycineta bicolor) should be more effective than that of males because (1) the transmission of sexually transmitted microbes during copulation puts females at greater risk because ejaculates move from males to females, (2) females copulate with multiple males, exposing them to the potentially pathogenic microbes in semen, and (3) females spend more time in the nest than do males so may be more exposed to nest microbes and ectoparasites that can be vectors of bacterial and viral pathogens. In addition, elevated testosterone in males may suppress immune function. We tested our prediction during the 2009 breeding season with microbicidal assays in vitro to assess the ability of the innate immune system to kill Escherichia coli. The sexes did not differ in the ability of their whole blood to kill E. coli. We also found no significant relationships between the ability of whole blood to kill E. coli and the reproductive performance or the physical condition of males or females. These results indicate that during the nestling period there are no sexual differences in this component of the innate immune system. In addition, they suggest that there is little association between this component of innate immunity and the reproductive performance and physical condition during the nestling period of adult Tree Swallows.

  13. Validation of SplitVectors Encoding for Quantitative Visualization of Large-Magnitude-Range Vector Fields.

    Science.gov (United States)

    Henan Zhao; Bryant, Garnett W; Griffin, Wesley; Terrill, Judith E; Jian Chen

    2017-06-01

    We designed and evaluated SplitVectors, a new vector field display approach to help scientists perform new discrimination tasks on large-magnitude-range scientific data shown in three-dimensional (3D) visualization environments. SplitVectors uses scientific notation to display vector magnitude, thus improving legibility. We present an empirical study comparing the SplitVectors approach with three other approaches - direct linear representation, logarithmic, and text display commonly used in scientific visualizations. Twenty participants performed three domain analysis tasks: reading numerical values (a discrimination task), finding the ratio between values (a discrimination task), and finding the larger of two vectors (a pattern detection task). Participants used both mono and stereo conditions. Our results suggest the following: (1) SplitVectors improve accuracy by about 10 times compared to linear mapping and by four times to logarithmic in discrimination tasks; (2) SplitVectors have no significant differences from the textual display approach, but reduce cluttering in the scene; (3) SplitVectors and textual display are less sensitive to data scale than linear and logarithmic approaches; (4) using logarithmic can be problematic as participants' confidence was as high as directly reading from the textual display, but their accuracy was poor; and (5) Stereoscopy improved performance, especially in more challenging discrimination tasks.

  14. Novel recombinant alphaviral and adenoviral vectors for cancer immunotherapy.

    Science.gov (United States)

    Osada, Takuya; Morse, Michael A; Hobeika, Amy; Lyerly, H Kim

    2012-06-01

    Although cellular immunotherapy based on autolgous dendritic cells (DCs) targeting antigens expressed by metastatic cancer has demonstrated clinical efficacy, the logistical challenges in generating an individualized cell product create an imperative to develop alternatives to DC-based cancer vaccines. Particularly attractive alternatives include in situ delivery of antigen and activation signals to resident antigen-presenting cells (APCs), which can be achieved by novel fusion molecules targeting the mannose receptor and by recombinant viral vectors expressing the antigen of interest and capable of infecting DCs. A particular challenge in the use of viral vectors is the well-appreciated clinical obstacles to their efficacy, specifically vector-specific neutralizing immune responses. Because heterologous prime and boost strategies have been demonstrated to be particularly potent, we developed two novel recombinant vectors based on alphaviral replicon particles and a next-generation adenovirus encoding an antigen commonly overexpressed in many human cancers, carcinoembryonic antigen (CEA). The rationale for developing these vectors, their unique characteristics, the preclinical studies and early clinical experience with each, and opportunities to enhance their effectiveness will be reviewed. The potential of each of these potent recombinant vectors to efficiently generate clinically active anti-tumor immune response alone, or in combination, will be discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Test of Understanding of Vectors: A Reliable Multiple-Choice Vector Concept Test

    Science.gov (United States)

    Barniol, Pablo; Zavala, Genaro

    2014-01-01

    In this article we discuss the findings of our research on students' understanding of vector concepts in problems without physical context. First, we develop a complete taxonomy of the most frequent errors made by university students when learning vector concepts. This study is based on the results of several test administrations of open-ended…

  16. Vectorization in quantum chemistry

    International Nuclear Information System (INIS)

    Saunders, V.R.

    1987-01-01

    It is argued that the optimal vectorization algorithm for many steps (and sub-steps) in a typical ab initio calculation of molecular electronic structure is quite strongly dependent on the target vector machine. Details such as the availability (or lack) of a given vector construct in the hardware, vector startup times and asymptotic rates must all be considered when selecting the optimal algorithm. Illustrations are drawn from: gaussian integral evaluation, fock matrix construction, 4-index transformation of molecular integrals, direct-CI methods, the matrix multiply operation. A cross comparison of practical implementations on the CDC Cyber 205, the Cray-IS and Cray-XMP machines is presented. To achieve portability while remaining optimal on a wide range of machines it is necessary to code all available algorithms in a machine independent manner, and to select the appropriate algorithm using a procedure which is based on machine dependent parameters. Most such parameters concern the timing of certain vector loop kernals, which can usually be derived from a 'bench-marking' routine executed prior to the calculation proper

  17. Transgene Expression and Host Cell Responses to Replication-Defective, Single-Cycle, and Replication-Competent Adenovirus Vectors

    Directory of Open Access Journals (Sweden)

    Catherine M. Crosby

    2017-02-01

    immunodeficient mice, SC-Ad drove stronger luciferase expression than RC- or RD-Ad. These data demonstrate better transgene expression by SC- and RC-Ad in vitro and in vivo than RD-Ad. This higher expression by the replicating vectors results in a peak of expression within 1 to 2 days followed by cell death of infected cells and release of transgene products. While SC- and RC-Ad expression were similar in mice and in Syrian hamsters, RC-Ad provoked much stronger ISG induction which may explain in part SC-Ad′s ability to generate stronger and more persistent immune responses than RC-Ad in Ad permissive hamsters.

  18. Travel and disease vector ticks.

    Science.gov (United States)

    McGarry, John W

    2011-03-01

    There are approximately twenty species of hard (ixodid) ticks worldwide that frequently affect human populations, many of which are associated with serious, sometimes fatal disease(s). When a tick travel souvenir is presented in the clinic, the risk must be immediately assessed by identifying the tick in question, ascertaining its disease vector status and determining if there has been the opportunity for the transfer of potential pathogens. This short review on identification of disease vector ticks and aspects of blood feeding and disease transmission includes the results of an examination of 59 specimens removed from UK domestic travellers and international travellers between 2002 and 2010. Sixteen tick species belonging to six genera were recorded and almost all showed evidence of blood feeding, which appears to contradict the view that because of their size, adult ticks are found early and therefore present an insignificant risk. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Declining Prevalence of Disease Vectors Under Climate Change

    Science.gov (United States)

    Escobar, Luis E.; Romero-Alvarez, Daniel; Leon, Renato; Lepe-Lopez, Manuel A.; Craft, Meggan E.; Borbor-Cordova, Mercy J.; Svenning, Jens-Christian

    2016-12-01

    More than half of the world population is at risk of vector-borne diseases including dengue fever, chikungunya, zika, yellow fever, leishmaniasis, chagas disease, and malaria, with highest incidences in tropical regions. In Ecuador, vector-borne diseases are present from coastal and Amazonian regions to the Andes Mountains; however, a detailed characterization of the distribution of their vectors has never been carried out. We estimate the distribution of 14 vectors of the above vector-borne diseases under present-day and future climates. Our results consistently suggest that climate warming is likely threatening some vector species with extinction, locally or completely. These results suggest that climate change could reduce the burden of specific vector species. Other vector species are likely to shift and constrain their geographic range to the highlands in Ecuador potentially affecting novel areas and populations. These forecasts show the need for development of early prevention strategies for vector species currently absent in areas projected as suitable under future climate conditions. Informed interventions could reduce the risk of human exposure to vector species with distributional shifts, in response to current and future climate changes. Based on the mixed effects of future climate on human exposure to disease vectors, we argue that research on vector-borne diseases should be cross-scale and include climatic, demographic, and landscape factors, as well as forces facilitating disease transmission at fine scales.

  20. Comparative evaluation of three capripoxvirus-vectored peste des petits ruminants vaccines.

    Science.gov (United States)

    Fakri, F; Bamouh, Z; Ghzal, F; Baha, W; Tadlaoui, K; Fihri, O Fassi; Chen, W; Bu, Z; Elharrak, M

    2018-01-15

    Sheep and goat pox (SGP) with peste des petits ruminants (PPR) are transboundary viral diseases of small ruminants that cause huge economic losses. Recombinant vaccines that can protect from both infections have been reported as a promising solution for the future. SGP was used as a vector to express two structural proteins hemagglutinin or the fusion protein of PPRV. We compared immunity conferred by recombinant capripoxvirus vaccines expressing H or F or both HF. Safety and efficacy were evaluated in goats and sheep. Two vaccine doses were tested in sheep, 10 4.5 TCDI50 in 1ml dose was retained for the further experiment. Results showed that the recombinant HF confers an earlier and stronger immunity against both SGP and PPR. This recombinant vaccine protect also against the disease in exposed and unexposed sheep. The potential Differentiating Infected from Vaccinated Animals of recombinant vaccines is of great advantage in any eradication program. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Quercetin, Inflammation and Immunity

    Directory of Open Access Journals (Sweden)

    Yao Li

    2016-03-01

    Full Text Available In vitro and some animal models have shown that quercetin, a polyphenol derived from plants, has a wide range of biological actions including anti-carcinogenic, anti-inflammatory and antiviral activities; as well as attenuating lipid peroxidation, platelet aggregation and capillary permeability. This review focuses on the physicochemical properties, dietary sources, absorption, bioavailability and metabolism of quercetin, especially main effects of quercetin on inflammation and immune function. According to the results obtained both in vitro and in vivo, good perspectives have been opened for quercetin. Nevertheless, further studies are needed to better characterize the mechanisms of action underlying the beneficial effects of quercetin on inflammation and immunity.

  2. An antivector vaccine protects against a lethal vector-borne pathogen.

    Directory of Open Access Journals (Sweden)

    Milan Labuda

    2006-04-01

    Full Text Available Vaccines that target blood-feeding disease vectors, such as mosquitoes and ticks, have the potential to protect against the many diseases caused by vector-borne pathogens. We tested the ability of an anti-tick vaccine derived from a tick cement protein (64TRP of Rhipicephalus appendiculatus to protect mice against tick-borne encephalitis virus (TBEV transmitted by infected Ixodes ricinus ticks. The vaccine has a "dual action" in immunized animals: when infested with ticks, the inflammatory and immune responses first disrupt the skin feeding site, resulting in impaired blood feeding, and then specific anti-64TRP antibodies cross-react with midgut antigenic epitopes, causing rupture of the tick midgut and death of engorged ticks. Three parameters were measured: "transmission," number of uninfected nymphal ticks that became infected when cofeeding with an infected adult female tick; "support," number of mice supporting virus transmission from the infected tick to cofeeding uninfected nymphs; and "survival," number of mice that survived infection by tick bite and subsequent challenge by intraperitoneal inoculation of a lethal dose of TBEV. We show that one dose of the 64TRP vaccine protects mice against lethal challenge by infected ticks; control animals developed a fatal viral encephalitis. The protective effect of the 64TRP vaccine was comparable to that of a single dose of a commercial TBEV vaccine, while the transmission-blocking effect of 64TRP was better than that of the antiviral vaccine in reducing the number of animals supporting virus transmission. By contrast, the commercial antitick vaccine (TickGARD that targets only the tick's midgut showed transmission-blocking activity but was not protective. The 64TRP vaccine demonstrates the potential to control vector-borne disease by interfering with pathogen transmission, apparently by mediating a local cutaneous inflammatory immune response at the tick-feeding site.

  3. Anopheles gambiae antiviral immune response to systemic O'nyong-nyong infection.

    Directory of Open Access Journals (Sweden)

    Joanna Waldock

    Full Text Available Mosquito-borne viral diseases cause significant burden in much of the developing world. Although host-virus interactions have been studied extensively in the vertebrate host, little is known about mosquito responses to viral infection. In contrast to mosquitoes of the Aedes and Culex genera, Anopheles gambiae, the principal vector of human malaria, naturally transmits very few arboviruses, the most important of which is O'nyong-nyong virus (ONNV. Here we have investigated the A. gambiae immune response to systemic ONNV infection using forward and reverse genetic approaches.We have used DNA microarrays to profile the transcriptional response of A. gambiae inoculated with ONNV and investigate the antiviral function of candidate genes through RNAi gene silencing assays. Our results demonstrate that A. gambiae responses to systemic viral infection involve genes covering all aspects of innate immunity including pathogen recognition, modulation of immune signalling, complement-mediated lysis/opsonisation and other immune effector mechanisms. Patterns of transcriptional regulation and co-infections of A. gambiae with ONNV and the rodent malaria parasite Plasmodium berghei suggest that hemolymph immune responses to viral infection are diverted away from melanisation. We show that four viral responsive genes encoding two putative recognition receptors, a galectin and an MD2-like receptor, and two effector lysozymes, function in limiting viral load.This study is the first step in elucidating the antiviral mechanisms of A. gambiae mosquitoes, and has revealed interesting differences between A. gambiae and other invertebrates. Our data suggest that mechanisms employed by A. gambiae are distinct from described invertebrate antiviral immunity to date, and involve the complement-like branch of the humoral immune response, supressing the melanisation response that is prominent in anti-parasitic immunity. The antiviral immune response in A. gambiae is thus

  4. Bunyavirus-Vector Interactions

    Directory of Open Access Journals (Sweden)

    Kate McElroy Horne

    2014-11-01

    Full Text Available The Bunyaviridae family is comprised of more than 350 viruses, of which many within the Hantavirus, Orthobunyavirus, Nairovirus, Tospovirus, and Phlebovirus genera are significant human or agricultural pathogens. The viruses within the Orthobunyavirus, Nairovirus, and Phlebovirus genera are transmitted by hematophagous arthropods, such as mosquitoes, midges, flies, and ticks, and their associated arthropods not only serve as vectors but also as virus reservoirs in many cases. This review presents an overview of several important emerging or re-emerging bunyaviruses and describes what is known about bunyavirus-vector interactions based on epidemiological, ultrastructural, and genetic studies of members of this virus family.

  5. Sums and Gaussian vectors

    CERN Document Server

    Yurinsky, Vadim Vladimirovich

    1995-01-01

    Surveys the methods currently applied to study sums of infinite-dimensional independent random vectors in situations where their distributions resemble Gaussian laws. Covers probabilities of large deviations, Chebyshev-type inequalities for seminorms of sums, a method of constructing Edgeworth-type expansions, estimates of characteristic functions for random vectors obtained by smooth mappings of infinite-dimensional sums to Euclidean spaces. A self-contained exposition of the modern research apparatus around CLT, the book is accessible to new graduate students, and can be a useful reference for researchers and teachers of the subject.

  6. Multithreading in vector processors

    Science.gov (United States)

    Evangelinos, Constantinos; Kim, Changhoan; Nair, Ravi

    2018-01-16

    In one embodiment, a system includes a processor having a vector processing mode and a multithreading mode. The processor is configured to operate on one thread per cycle in the multithreading mode. The processor includes a program counter register having a plurality of program counters, and the program counter register is vectorized. Each program counter in the program counter register represents a distinct corresponding thread of a plurality of threads. The processor is configured to execute the plurality of threads by activating the plurality of program counters in a round robin cycle.

  7. Matrix vector analysis

    CERN Document Server

    Eisenman, Richard L

    2005-01-01

    This outstanding text and reference applies matrix ideas to vector methods, using physical ideas to illustrate and motivate mathematical concepts but employing a mathematical continuity of development rather than a physical approach. The author, who taught at the U.S. Air Force Academy, dispenses with the artificial barrier between vectors and matrices--and more generally, between pure and applied mathematics.Motivated examples introduce each idea, with interpretations of physical, algebraic, and geometric contexts, in addition to generalizations to theorems that reflect the essential structur

  8. Free topological vector spaces

    OpenAIRE

    Gabriyelyan, Saak S.; Morris, Sidney A.

    2016-01-01

    We define and study the free topological vector space $\\mathbb{V}(X)$ over a Tychonoff space $X$. We prove that $\\mathbb{V}(X)$ is a $k_\\omega$-space if and only if $X$ is a $k_\\omega$-space. If $X$ is infinite, then $\\mathbb{V}(X)$ contains a closed vector subspace which is topologically isomorphic to $\\mathbb{V}(\\mathbb{N})$. It is proved that if $X$ is a $k$-space, then $\\mathbb{V}(X)$ is locally convex if and only if $X$ is discrete and countable. If $X$ is a metrizable space it is shown ...

  9. Scalar-vector bootstrap

    Energy Technology Data Exchange (ETDEWEB)

    Rejon-Barrera, Fernando [Institute for Theoretical Physics, University of Amsterdam,Science Park 904, Postbus 94485, 1090 GL, Amsterdam (Netherlands); Robbins, Daniel [Department of Physics, Texas A& M University,TAMU 4242, College Station, TX 77843 (United States)

    2016-01-22

    We work out all of the details required for implementation of the conformal bootstrap program applied to the four-point function of two scalars and two vectors in an abstract conformal field theory in arbitrary dimension. This includes a review of which tensor structures make appearances, a construction of the projectors onto the required mixed symmetry representations, and a computation of the conformal blocks for all possible operators which can be exchanged. These blocks are presented as differential operators acting upon the previously known scalar conformal blocks. Finally, we set up the bootstrap equations which implement crossing symmetry. Special attention is given to the case of conserved vectors, where several simplifications occur.

  10. Spin information from vector-meson decay in photoproduction

    International Nuclear Information System (INIS)

    Kloet, W.M.; Chiang, W.; Tabakin, F.

    1998-01-01

    For the photoproduction of vector mesons, all single and double spin observables involving vector-meson two-body decays are defined consistently in the γN center-of-mass frame. These definitions yield a procedure for extracting physically meaningful single and double spin observables that are subject to known rules concerning their angle and energy evolution. As part of this analysis, we show that measuring the two-meson decay of a photo produced ρ or φ does not determine the vector meson's vector polarization, but only its tensor polarization. The vector meson decay into lepton pairs is also insensitive to the vector meson's vector polarization, unless one measures the spin of one of the leptons. Similar results are found for all double spin observables which involve observation of vector-meson decay. To access the vector meson's vector polarization, one therefore needs to either measure the spin of the decay leptons, make an analysis of the background interference effects, or relate the vector meson's vector polarization to other accessible spin observables. copyright 1998 The American Physical Society

  11. Measurement of Charmless B to Vector-Vector decays at BaBar

    International Nuclear Information System (INIS)

    Olaiya, Emmanuel

    2011-01-01

    The authors present results of B → vector-vector (VV) and B → vector-axial vector (VA) decays B 0 → φX(X = φ,ρ + or ρ 0 ), B + → φK (*)+ , B 0 → K*K*, B 0 → ρ + b 1 - and B + → K* 0 α 1 + . The largest dataset used for these results is based on 465 x 10 6 Υ(4S) → B(bar B) decays, collected with the BABAR detector at the PEP-II B meson factory located at the Stanford Linear Accelerator Center (SLAC). Using larger datasets, the BABAR experiment has provided more precise B → VV measurements, further supporting the smaller than expected longitudinal polarization fraction of B → φK*. Additional B meson to vector-vector and vector-axial vector decays have also been studied with a view to shedding light on the polarization anomaly. Taking into account the available errors, we find no disagreement between theory and experiment for these additional decays.

  12. Maxwell's Multipole Vectors and the CMB

    OpenAIRE

    Weeks, Jeffrey R.

    2004-01-01

    The recently re-discovered multipole vector approach to understanding the harmonic decomposition of the cosmic microwave background traces its roots to Maxwell's Treatise on Electricity and Magnetism. Taking Maxwell's directional derivative approach as a starting point, the present article develops a fast algorithm for computing multipole vectors, with an exposition that is both simpler and better motivated than in the author's previous work. Tests show the resulting algorithm, coded up as a ...

  13. Search for vector-like quarks

    CERN Document Server

    Varnes, Erich; The ATLAS collaboration

    2017-01-01

    Vector like quarks appear in many theories beyond the Standard Model as a way to cancel the mass divergence for the Higgs boson. The current status of the ATLAS searches for the production of vector like quarks will be reviewed for proton-proton collisions at 13 TeV. This presentation will address the analysis techniques, in particular the selection criteria, the background modeling and the related experimental uncertainties. The phenomenological implications of the obtained results will also be discussed.

  14. Speech Data Compression using Vector Quantization

    OpenAIRE

    H. B. Kekre; Tanuja K. Sarode

    2008-01-01

    Mostly transforms are used for speech data compressions which are lossy algorithms. Such algorithms are tolerable for speech data compression since the loss in quality is not perceived by the human ear. However the vector quantization (VQ) has a potential to give more data compression maintaining the same quality. In this paper we propose speech data compression algorithm using vector quantization technique. We have used VQ algorithms LBG, KPE and FCG. The results table s...

  15. HIV-derived vectors for gene therapy targeting dendritic cells.

    Science.gov (United States)

    Rossetti, Maura; Cavarelli, Mariangela; Gregori, Silvia; Scarlatti, Gabriella

    2013-01-01

    Human immunodeficiency virus type 1 (HIV-1)-derived lentiviral vectors (LV) have the potential to mediate stable therapeutic gene transfer. However, similarly to other viral vectors, their benefit is compromised by the induction of an immune response toward transgene-expressing cells that closely mimics antiviral immunity. LV share with the parental HIV the ability to activate dendritic cells (DC), while lack the peculiar ability of subverting DC functions, which is responsible for HIV immune escape. Understanding the interaction between LV and DC, with plasmacytoid and myeloid DC playing fundamental and distinct roles, has paved the way to novel approaches aimed at regulating transgene-specific immune responses. Thanks to the ability to target either DC subsets LV might be a powerful tool to induce immunity (i.e., gene therapy of cancer), cell death (i.e., in HIV/AIDS infection), or tolerance (i.e., gene therapy strategies for monogenic diseases). In this chapter, similarities and differences between the LV-mediated and HIV-mediated induction of immune responses, with specific focus on their interactions with DC, are discussed.

  16. Nutritional components regulate the gut immune system and its association with intestinal immune disease development.

    Science.gov (United States)

    Lamichhane, Aayam; Kiyono, Hiroshi; Kunisawa, Jun

    2013-12-01

    The gut is equipped with a unique immune system for maintaining immunological homeostasis, and its functional immune disruption can result in the development of immune diseases such as food allergy and intestinal inflammation. Accumulating evidence has demonstrated that nutritional components play an important role in the regulation of gut immune responses and also in the development of intestinal immune diseases. In this review, we focus on the immunological functions of lipids, vitamins, and nucleotides in the regulation of the intestinal immune system and as potential targets for the control of intestinal immune diseases. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  17. Rethinking vector immunology: the role of environmental temperature in shaping resistance

    OpenAIRE

    Murdock, Courtney C.; Paaijmans, Krijn P.; Cox-Foster, Diana; Read, Andrew F.; Thomas, Matthew B.

    2012-01-01

    Recent ecological research has revealed that environmental factors can strongly affect insect immunity and influence the outcome of host–parasite interactions. To date, however, most studies examining immune function in mosquitoes have ignored environmental variability. We argue that one such environmental variable, temperature, influences both vector immunity and the parasite itself. As temperatures in the field can vary greatly from the ambient temperature in the laboratory, it will be esse...

  18. Integrated Circuit Immunity

    Science.gov (United States)

    Sketoe, J. G.; Clark, Anthony

    2000-01-01

    This paper presents a DOD E3 program overview on integrated circuit immunity. The topics include: 1) EMI Immunity Testing; 2) Threshold Definition; 3) Bias Tee Function; 4) Bias Tee Calibration Set-Up; 5) EDM Test Figure; 6) EMI Immunity Levels; 7) NAND vs. and Gate Immunity; 8) TTL vs. LS Immunity Levels; 9) TP vs. OC Immunity Levels; 10) 7805 Volt Reg Immunity; and 11) Seventies Chip Set. This paper is presented in viewgraph form.

  19. Immunization of mice with the nef gene from Human Immunodeficiency Virus type 1: Study of immunological memory and long-term toxicology

    Directory of Open Access Journals (Sweden)

    Engström Gunnel

    2007-07-01

    Full Text Available Abstract Background The human immunodeficiency virus type 1 (HIV-1 regulatory protein, Nef, is an attractive vaccine target because it is involved in viral pathogenesis, is expressed early in the viral life cycle and harbors many T and B cell epitopes. Several clinical trials include gene-based vaccines encoding this protein. However, Nef has been shown to transform certain cell types in vitro. Based on these findings we performed a long-term toxicity and immunogenicity study of Nef, encoded either by Modified Vaccinia virus Ankara or by plasmid DNA. BALB/c mice were primed twice with either DNA or MVA encoding Nef and received a homologous or heterologous boost ten months later. In the meantime, the Nef-specific immune responses were monitored and at the time of sacrifice an extensive toxicological evaluation was performed, where presence of tumors and other pathological changes were assessed. Results The toxicological evaluation showed that immunization with MVAnef is safe and does not cause cellular transformation or other toxicity in somatic organs. Both DNAnef and MVAnef immunized animals developed potent Nef-specific cellular responses that declined to undetectable levels over time, and could readily be boosted after almost one year. This is of particular interest since it shows that plasmid DNA vaccine can also be used as a potent late booster of primed immune responses. We observed qualitative differences between the T cell responses induced by the two different vectors: DNA-encoded nef induced long-lasting CD8+ T cell memory responses, whereas MVA-encoded nef induced CD4+ T cell memory responses. In terms of the humoral immune responses, we show that two injections of MVAnef induce significant anti-Nef titers, while repeated injections of DNAnef do not. A single boost with MVAnef could enhance the antibody response following DNAnef prime to the same level as that observed in animals immunized repeatedly with MVAnef. We also demonstrate

  20. Logarithmic bred vectors in spatiotemporal chaos: structure and growth.

    Science.gov (United States)

    Hallerberg, Sarah; Pazó, Diego; López, Juan M; Rodríguez, Miguel A

    2010-06-01

    Bred vectors are a type of finite perturbation used in prediction studies of atmospheric models that exhibit spatially extended chaos. We study the structure, spatial correlations, and the growth rates of logarithmic bred vectors (which are constructed by using a given norm). We find that, after a suitable transformation, logarithmic bred vectors are roughly piecewise copies of the leading Lyapunov vector. This fact allows us to deduce a scaling law for the bred vector growth rate as a function of its amplitude. In addition, we relate growth rates with the spectrum of Lyapunov exponents corresponding to the most expanding directions. We illustrate our results with simulations of the Lorenz 1996 model.

  1. Triviality and Split of Vector Bundles on Rationally Connected Varieties

    OpenAIRE

    Pan, Xuanyu

    2013-01-01

    In this paper, we give a simple proof of a triviality criterion due to I.Biswas and J.Pedro and P.Dos Santos. We also prove a vector bundle on a homogenous space is trivial if and only if the restrictions of the vector bundle to Schubert lines are trivial. Using this result and Chern classes of vector bundles, we give a general criterion of a uniform vector bundle on a homogenous space to be splitting. As an application, we prove a uniform vector bundle on classical Grassmannians and quadrics...

  2. Epidemic spreading and global stability of an SIS model with an infective vector on complex networks

    Science.gov (United States)

    Kang, Huiyan; Fu, Xinchu

    2015-10-01

    In this paper, we present a new SIS model with delay on scale-free networks. The model is suitable to describe some epidemics which are not only transmitted by a vector but also spread between individuals by direct contacts. In view of the biological relevance and real spreading process, we introduce a delay to denote average incubation period of disease in a vector. By mathematical analysis, we obtain the epidemic threshold and prove the global stability of equilibria. The simulation shows the delay will effect the epidemic spreading. Finally, we investigate and compare two major immunization strategies, uniform immunization and targeted immunization.

  3. Estimation of vector velocity

    DEFF Research Database (Denmark)

    2000-01-01

    Using a pulsed ultrasound field, the two-dimensional velocity vector can be determined with the invention. The method uses a transversally modulated ultrasound field for probing the moving medium under investigation. A modified autocorrelation approach is used in the velocity estimation. The new...

  4. Production of lentiviral vectors

    Directory of Open Access Journals (Sweden)

    Otto-Wilhelm Merten

    2016-01-01

    Full Text Available Lentiviral vectors (LV have seen considerably increase in use as gene therapy vectors for the treatment of acquired and inherited diseases. This review presents the state of the art of the production of these vectors with particular emphasis on their large-scale production for clinical purposes. In contrast to oncoretroviral vectors, which are produced using stable producer cell lines, clinical-grade LV are in most of the cases produced by transient transfection of 293 or 293T cells grown in cell factories. However, more recent developments, also, tend to use hollow fiber reactor, suspension culture processes, and the implementation of stable producer cell lines. As is customary for the biotech industry, rather sophisticated downstream processing protocols have been established to remove any undesirable process-derived contaminant, such as plasmid or host cell DNA or host cell proteins. This review compares published large-scale production and purification processes of LV and presents their process performances. Furthermore, developments in the domain of stable cell lines and their way to the use of production vehicles of clinical material will be presented.

  5. Orthogonalisation of Vectors

    Indian Academy of Sciences (India)

    The Gram-Schmidt process is one of the first things one learns in a course ... We might want to stay as close to the experimental data as possible when converting these vectors to orthonormal ones demanded by the model. The process of finding the closest or- thonormal .... is obtained by writing the matrix A = [aI, an], then.

  6. From vectors to mnesors

    OpenAIRE

    Champenois, Gilles

    2007-01-01

    The mnesor theory is the adaptation of vectors to artificial intelligence. The scalar field is replaced by a lattice. Addition becomes idempotent and multiplication is interpreted as a selection operation. We also show that mnesors can be the foundation for a linear calculus.

  7. Calculus with vectors

    CERN Document Server

    Treiman, Jay S

    2014-01-01

    Calculus with Vectors grew out of a strong need for a beginning calculus textbook for undergraduates who intend to pursue careers in STEM. fields. The approach introduces vector-valued functions from the start, emphasizing the connections between one-variable and multi-variable calculus. The text includes early vectors and early transcendentals and includes a rigorous but informal approach to vectors. Examples and focused applications are well presented along with an abundance of motivating exercises. All three-dimensional graphs have rotatable versions included as extra source materials and may be freely downloaded and manipulated with Maple Player; a free Maple Player App is available for the iPad on iTunes. The approaches taken to topics such as the derivation of the derivatives of sine and cosine, the approach to limits, and the use of "tables" of integration have been modified from the standards seen in other textbooks in order to maximize the ease with which students may comprehend the material. Additio...

  8. On vector equilibrium problem

    Indian Academy of Sciences (India)

    [G] Giannessi F, Theorems of alternative, quadratic programs and complementarity problems, in: Variational Inequalities and Complementarity Problems (eds) R W Cottle, F Giannessi and J L Lions (New York: Wiley) (1980) pp. 151±186. [K1] Kazmi K R, Existence of solutions for vector optimization, Appl. Math. Lett. 9 (1996).

  9. Vector-borne Infections

    Centers for Disease Control (CDC) Podcasts

    2011-04-18

    This podcast discusses emerging vector-borne pathogens, their role as prominent contributors to emerging infectious diseases, how they're spread, and the ineffectiveness of mosquito control methods.  Created: 4/18/2011 by National Center for Emerging Zoonotic and Infectious Diseases (NCEZID).   Date Released: 4/27/2011.

  10. Non-coaxial superposition of vector vortex beams.

    Science.gov (United States)

    Aadhi, A; Vaity, Pravin; Chithrabhanu, P; Reddy, Salla Gangi; Prabakar, Shashi; Singh, R P

    2016-02-10

    Vector vortex beams are classified into four types depending upon spatial variation in their polarization vector. We have generated all four of these types of vector vortex beams by using a modified polarization Sagnac interferometer with a vortex lens. Further, we have studied the non-coaxial superposition of two vector vortex beams. It is observed that the superposition of two vector vortex beams with same polarization singularity leads to a beam with another kind of polarization singularity in their interaction region. The results may be of importance in ultrahigh security of the polarization-encrypted data that utilizes vector vortex beams and multiple optical trapping with non-coaxial superposition of vector vortex beams. We verified our experimental results with theory.

  11. Immune Evasion, Immunopathology and the Regulation of the Immune System

    Directory of Open Access Journals (Sweden)

    Bruno Faivre

    2013-02-01

    Full Text Available Costs and benefits of the immune response have attracted considerable attention in the last years among evolutionary biologists. Given the cost of parasitism, natural selection should favor individuals with the most effective immune defenses. Nevertheless, there exists huge variation in the expression of immune effectors among individuals. To explain this apparent paradox, it has been suggested that an over-reactive immune system might be too costly, both in terms of metabolic resources and risks of immune-mediated diseases, setting a limit to the investment into immune defenses. Here, we argue that this view neglects one important aspect of the interaction: the role played by evolving pathogens. We suggest that taking into account the co-evolutionary interactions between the host immune system and the parasitic strategies to overcome the immune response might provide a better picture of the selective pressures that shape the evolution of immune functioning. Integrating parasitic strategies of host exploitation can also contribute to understand the seemingly contradictory results that infection can enhance, but also protect from, autoimmune diseases. In the last decades, the incidence of autoimmune disorders has dramatically increased in wealthy countries of the northern hemisphere with a concomitant decrease of most parasitic infections. Experimental work on model organisms has shown that this pattern may be due to the protective role of certain parasites (i.e., helminths that rely on the immunosuppression of hosts for their persistence. Interestingly, although parasite-induced immunosuppression can protect against autoimmunity, it can obviously favor the spread of other infections. Therefore, we need to think about the evolution of the immune system using a multidimensional trade-off involving immunoprotection, immunopathology and the parasitic strategies to escape the immune response.

  12. Vector-transmitted disease vaccines: targeting salivary proteins in transmission (SPIT).

    Science.gov (United States)

    McDowell, Mary Ann

    2015-08-01

    More than half the population of the world is at risk for morbidity and mortality from vector-transmitted diseases, and emerging vector-transmitted infections are threatening new populations. Rising insecticide resistance and lack of efficacious vaccines highlight the need for novel control measures. One such approach is targeting the vector-host interface by incorporating vector salivary proteins in anti-pathogen vaccines. Debate remains about whether vector saliva exposure exacerbates or protects against more severe clinical manifestations, induces immunity through natural exposure or extends to all vector species and associated pathogens. Nevertheless, exploiting this unique biology holds promise as a viable strategy for the development of vaccines against vector-transmitted diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Weaving Knotted Vector Fields with Tunable Helicity.

    Science.gov (United States)

    Kedia, Hridesh; Foster, David; Dennis, Mark R; Irvine, William T M

    2016-12-30

    We present a general construction of divergence-free knotted vector fields from complex scalar fields, whose closed field lines encode many kinds of knots and links, including torus knots, their cables, the figure-8 knot, and its generalizations. As finite-energy physical fields, they represent initial states for fields such as the magnetic field in a plasma, or the vorticity field in a fluid. We give a systematic procedure for calculating the vector potential, starting from complex scalar functions with knotted zero filaments, thus enabling an explicit computation of the helicity of these knotted fields. The construction can be used to generate isolated knotted flux tubes, filled by knots encoded in the lines of the vector field. Lastly, we give examples of manifestly knotted vector fields with vanishing helicity. Our results provide building blocks for analytical models and simulations alike.

  14. Properties of vector and axial-vector mesons from a generalized Nambu-Jona-Lasinio model

    International Nuclear Information System (INIS)

    Bernard, V.; Meissner, U.G.; Massachusetts Inst. of Tech., Cambridge; Massachusetts Inst. of Tech., Cambridge

    1988-01-01

    We construct a generalized Nambu-Jona-Lasinio lagrangian including scalar, pseudoscalar, vector and axial-vector mesons. We specialize to the two-flavor case. The properties of the structured vacuum as well as meson masses and coupling constants are calculated giving an overall agreement within 20% of the experimental data. We investigate the meson properties at finite density. In contrast to the mass of the scalar σ-meson, which decreases sharply with increasing density, the vector meson masses are almost independent of density. Furthermore, the vector-meson-quark coupling constants are also stable against density changes. We point out that these results imply a softening of the nuclear equation of state at high densities. Furthermore, we discuss the breakdown of the KFSR relation on the quark level as well as other deviations from phenomenological concepts such as universality and vector meson dominance. (orig.)

  15. Effects of in ovo administration of betaine and choline on hatchability results, growth and carcass characteristics and immune response of broiler chickens

    Directory of Open Access Journals (Sweden)

    Jafar Gholami

    2015-05-01

    Full Text Available The effect of in ovo administration of different levels of betaine and choline on egg hatchability, immune response, growth and carcass traits of broiler chickens was studied. Four thousand hatching eggs from Ross 308 broiler breeder layers, weighed individually, were incubated for 21 days in a commercial hatchery. At 12th day of incubation, 3456 fertilized eggs were randomly divided into 8 experimental groups of 3 replicates each (144 eggs per replicate: negative control (NC – not injected; positive control (PC – injected with 0.5 mL deionized water; Bet 0.25 – injected with 0.5 mL deionized water+0.25 mg soluble betaine; Bet 0.375 – injected with 0.5 mL deionized water+0.375 mg soluble betaine; Bet 0.50 – injected with 0.5 mL deionized water+0.50 mg soluble betaine; Chol 0.25 – injected with 0.5 mL deionized water+0.25 mg soluble choline; Chol 0.375 – injected with 0.5 mL deionized water+0.375 mg soluble choline; Chol 0.50 – injected with 0.5 mL deionized water+0.50 mg soluble choline. Among the hatched chickens, 360 males were randomly chosen (45 for each group and were grown up to 42nd day of age. The embryo mortality, pecked eggs, infected eggs and hatchability percentages were similar among the experimental groups. The betaine and choline treatments improved hatching weight and final weight of chickens, while reduced feed conversion ratio and abdominal fat percentage. No effect on carcass yield, and breast muscle, leg and wings percentages, as well as on immunoglobulin M (IgM, G (IgG, and total antibody (IgT titers was observed. The treatments had little effect on internal organs.

  16. Heavy Scalar, Vector, and Axial-Vector Mesons in Hot and Dense Nuclear Medium

    Directory of Open Access Journals (Sweden)

    Arvind Kumar

    2014-01-01

    Full Text Available In this work we shall investigate the mass modifications of scalar mesons (D0; B0, vector mesons (D*; B*, and axial-vector mesons (D1; B1 at finite density and temperature of the nuclear medium. The above mesons are modified in the nuclear medium through the modification of quark and gluon condensates. We will find the medium modification of quark and gluon condensates within chiral SU(3 model through the medium modification of scalar-isoscalar fields σ and ζ at finite density and temperature. These medium modified quark and gluon condensates will further be used through QCD sum rules for the evaluation of in-medium properties of the above mentioned scalar, vector, and axial vector mesons. We will also discuss the effects of density and temperature of the nuclear medium on the scattering lengths of the above scalar, vector, and axial-vector mesons. The study of the medium modifications of the above mesons may be helpful for understanding their production rates in heavy-ion collision experiments. The results of present investigations of medium modifications of scalar, vector, and axial-vector mesons at finite density and temperature can be verified in the compressed baryonic matter (CBM experiment of FAIR facility at GSI, Germany.

  17. Vectorization, parallelization and porting of nuclear codes. Vectorization and parallelization. Progress report fiscal 1999

    Energy Technology Data Exchange (ETDEWEB)

    Adachi, Masaaki; Ogasawara, Shinobu; Kume, Etsuo [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Ishizuki, Shigeru; Nemoto, Toshiyuki; Kawasaki, Nobuo; Kawai, Wataru [Fujitsu Ltd., Tokyo (Japan); Yatake, Yo-ichi [Hitachi Ltd., Tokyo (Japan)

    2001-02-01

    Several computer codes in the nuclear field have been vectorized, parallelized and trans-ported on the FUJITSU VPP500 system, the AP3000 system, the SX-4 system and the Paragon system at Center for Promotion of Computational Science and Engineering in Japan Atomic Energy Research Institute. We dealt with 18 codes in fiscal 1999. These results are reported in 3 parts, i.e., the vectorization and the parallelization part on vector processors, the parallelization part on scalar processors and the porting part. In this report, we describe the vectorization and parallelization on vector processors. In this vectorization and parallelization on vector processors part, the vectorization of Relativistic Molecular Orbital Calculation code RSCAT, a microscopic transport code for high energy nuclear collisions code JAM, three-dimensional non-steady thermal-fluid analysis code STREAM, Relativistic Density Functional Theory code RDFT and High Speed Three-Dimensional Nodal Diffusion code MOSRA-Light on the VPP500 system and the SX-4 system are described. (author)

  18. Efficient Strategy to Generate a Vectored Duck Enteritis Virus Delivering Envelope of Duck Tembusu Virus

    Directory of Open Access Journals (Sweden)

    Zhong Zou

    2014-06-01

    Full Text Available Duck Tembusu virus (DTMUV is a recently emerging pathogenic flavivirus that has resulted in a huge economic loss in the duck industry. However, no vaccine is currently available to control this pathogen. Consequently, a practical strategy to construct a vaccine against this pathogen should be determined. In this study, duck enteritis virus (DEV was examined as a candidate vaccine vector to deliver the envelope (E of DTMUV. A modified mini-F vector was inserted into the SORF3 and US2 gene junctions of the attenuated DEV vaccine strain C-KCE genome to generate an infectious bacterial artificial chromosome (BAC of C-KCE (vBAC-C-KCE. The envelope (E gene of DTMUV was inserted into the C-KCE genome through the mating-assisted genetically integrated cloning (MAGIC strategy, resulting in the recombinant vector, pBAC-C-KCE-E. A bivalent vaccine C-KCE-E was generated by eliminating the BAC backbone. Immunofluorescence and western blot analysis results indicated that the E proteins were vigorously expressed in C-KCE-E-infected chicken embryo fibroblasts (CEFs. Duck experiments demonstrated that the insertion of the E gene did not alter the protective efficacy of C-KCE. Moreover, C-KCE-E-immunized ducks induced neutralization antibodies against DTMUV. These results demonstrated, for the first time, that recombinant C-KCE-E can serve as a potential bivalent vaccine against DEV and DTMUV.

  19. Vaccine efficacy against malaria by the combination of porcine parvovirus-like particles and vaccinia virus vectors expressing CS of Plasmodium.

    Directory of Open Access Journals (Sweden)

    Dolores Rodríguez

    Full Text Available With the aim to develop an efficient and cost-effective approach to control malaria, we have generated porcine parvovirus-like particles (PPV-VLPs carrying the CD8(+ T cell epitope (SYVPSAEQI of the circumsporozoite (CS protein from Plasmodium yoelii fused to the PPV VP2 capsid protein (PPV-PYCS, and tested in prime/boost protocols with poxvirus vectors for efficacy in a rodent malaria model. As a proof-of concept, we have characterized the anti-CS CD8(+ T cell response elicited by these hybrid PPV-VLPs in BALB/c mice after immunizations with the protein PPV-PYCS administered alone or in combination with recombinant vaccinia virus (VACV vectors from the Western Reserve (WR and modified virus Ankara (MVA strains expressing the entire P. yoelii CS protein. The results of different immunization protocols showed that the combination of PPV-PYCS prime/poxvirus boost was highly immunogenic, inducing specific CD8+ T cell responses to CS resulting in 95% reduction in liver stage parasites two days following sporozoite challenge. In contrast, neither the administration of PPV-PYCS alone nor the immunization with the vectors given in the order poxvirus/VLPs was as effective. The immune profile induced by VLPs/MVA boost was associated with polyfunctional and effector memory CD8+ T cell responses. These findings highlight the use of recombinant parvovirus PPV-PYCS particles as priming agents and poxvirus vectors, like MVA, as booster to enhance specific CD8+ T cell responses to Plasmodium antigens and to control infection. These observations are relevant in the design of T cell-inducing vaccines against malaria.

  20. Vaccine efficacy against malaria by the combination of porcine parvovirus-like particles and vaccinia virus vectors expressing CS of Plasmodium.

    Science.gov (United States)

    Rodríguez, Dolores; González-Aseguinolaza, Gloria; Rodríguez, Juan R; Vijayan, Aneesh; Gherardi, Magdalena; Rueda, Paloma; Casal, J Ignacio; Esteban, Mariano

    2012-01-01

    With the aim to develop an efficient and cost-effective approach to control malaria, we have generated porcine parvovirus-like particles (PPV-VLPs) carrying the CD8(+) T cell epitope (SYVPSAEQI) of the circumsporozoite (CS) protein from Plasmodium yoelii fused to the PPV VP2 capsid protein (PPV-PYCS), and tested in prime/boost protocols with poxvirus vectors for efficacy in a rodent malaria model. As a proof-of concept, we have characterized the anti-CS CD8(+) T cell response elicited by these hybrid PPV-VLPs in BALB/c mice after immunizations with the protein PPV-PYCS administered alone or in combination with recombinant vaccinia virus (VACV) vectors from the Western Reserve (WR) and modified virus Ankara (MVA) strains expressing the entire P. yoelii CS protein. The results of different immunization protocols showed that the combination of PPV-PYCS prime/poxvirus boost was highly immunogenic, inducing specific CD8+ T cell responses to CS resulting in 95% reduction in liver stage parasites two days following sporozoite challenge. In contrast, neither the administration of PPV-PYCS alone nor the immunization with the vectors given in the order poxvirus/VLPs was as effective. The immune profile induced by VLPs/MVA boost was associated with polyfunctional and effector memory CD8+ T cell responses. These findings highlight the use of recombinant parvovirus PPV-PYCS particles as priming agents and poxvirus vectors, like MVA, as booster to enhance specific CD8+ T cell responses to Plasmodium antigens and to control infection. These observations are relevant in the design of T cell-inducing vaccines against malaria.

  1. The Concordance of Parent and Child Immunization.

    Science.gov (United States)

    Robison, Steve G; Osborn, Andrew W

    2017-05-01

    A substantial body of work has related survey-based parental vaccine hesitancy to noncompliant childhood immunization. However little attention has been paid to the connection between parents' own immunization behavior and the immunizations their children receive. Using the Oregon ALERT Immunization Information System, we identified adult caregiver-child pairs for children between 9 months and 17 years of age. The likelihood of adult-child concordance of influenza immunization per influenza season from 2010-2011 through 2014-2015 was assessed. The utility of adult immunization as a predictor was also assessed for other, noninfluenza recommended immunizations for children and adolescents. A total of 450 687 matched adult caregiver-child pairs were included in the study. The children of immunizing adults were 2.77 times more likely to also be immunized for seasonal influenza across all seasons (95% confidence interval, 2.74-2.79), with similar results applying within each season. Adult immunization status was also significantly associated with the likelihood of children and adolescents getting other noninfluenza immunizations, such as the human papillomavirus vaccine (HPV). When adults improved their own behavior from nonimmunizing to immunizing across influenza seasons, their children if not immunized in the previous season were 5.44 times (95% confidence interval, 5.35-5.53) more likely to become immunized for influenza. Children's likelihood of following immunization recommendations is associated with the immunization behavior of their parents. Encouraging parental immunization is a potential tool for increasing children's immunization rates. Copyright © 2017 by the American Academy of Pediatrics.

  2. Sculpting humoral immunity through dengue vaccination to enhance protective immunity

    Directory of Open Access Journals (Sweden)

    Wayne eCrill

    2012-11-01

    Full Text Available Dengue viruses (DENV are the most important mosquito transmitted viral pathogens infecting humans. DENV infection produces a spectrum of disease, most commonly causing a self-limiting flu-like illness known as dengue fever; yet with increased frequency, manifesting as life-threatening dengue hemorrhagic fever (DHF. Waning cross-protective immunity from any of the four dengue serotypes may enhance subsequent infection with another heterologous serotype to increase the probability of DHF. Decades of effort to develop dengue vaccines are reaching the finishing line with multiple candidates in clinical trials. Nevertheless, concerns remain that imbalanced immunity, due to the prolonged prime-boost schedules currently used in clinical trials, could leave some vaccinees temporarily unprotected or with increased susceptibility to enhanced disease. Here we develop a DENV serotype 1 (DENV-1 DNA vaccine with the immunodominant cross-reactive B cell epitopes associated with immune enhancement removed. We compare wild-type (WT with this cross-reactivity reduced (CRR vaccine and demonstrate that both vaccines are equally protective against lethal homologous DENV-1 challenge. Under conditions mimicking natural exposure prior to acquiring protective immunity, WT vaccinated mice enhanced a normally sub-lethal heterologous DENV-2 infection resulting in DHF-like disease and 95% mortality in AG129 mice. However, CRR vaccinated mice exhibited redirected serotype-specific and protective immunity, and significantly reduced morbidity and mortality not differing from naïve mice. Thus, we demonstrate in an in vivo DENV disease model, that non-protective vaccine-induced immunity can prime vaccinees for enhanced DHF-like disease and that CRR DNA immunization significantly reduces this potential vaccine safety concern. The sculpting of immune memory by the modified vaccine and resulting redirection of humoral immunity provide insight into DENV vaccine induced immune

  3. Gaussian statistics for palaeomagnetic vectors

    Science.gov (United States)

    Love, J.J.; Constable, C.G.

    2003-01-01

    With the aim of treating the statistics of palaeomagnetic directions and intensities jointly and consistently, we represent the mean and the variance of palaeomagnetic vectors, at a particular site and of a particular polarity, by a probability density function in a Cartesian three-space of orthogonal magnetic-field components consisting of a single (unimoda) non-zero mean, spherically-symmetrical (isotropic) Gaussian function. For palaeomagnetic data of mixed polarities, we consider a bimodal distribution consisting of a pair of such symmetrical Gaussian functions, with equal, but opposite, means and equal variances. For both the Gaussian and bi-Gaussian distributions, and in the spherical three-space of intensity, inclination, and declination, we obtain analytical expressions for the marginal density functions, the cumulative distributions, and the expected values and variances for each spherical coordinate (including the angle with respect to the axis of symmetry of the distributions). The mathematical expressions for the intensity and off-axis angle are closed-form and especially manageable, with the intensity distribution being Rayleigh-Rician. In the limit of small relative vectorial dispersion, the Gaussian (bi-Gaussian) directional distribution approaches a Fisher (Bingham) distribution and the intensity distribution approaches a normal distribution. In the opposite limit of large relative vectorial dispersion, the directional distributions approach a spherically-uniform distribution and the intensity distribution approaches a Maxwell distribution. We quantify biases in estimating the properties of the vector field resulting from the use of simple arithmetic averages, such as estimates of the intensity or the inclination of the mean vector, or the variances of these quantities. With the statistical framework developed here and using the maximum-likelihood method, which gives unbiased estimates in the limit of large data numbers, we demonstrate how to

  4. Gaussian statistics for palaeomagnetic vectors

    Science.gov (United States)

    Love, J. J.; Constable, C. G.

    2003-03-01

    With the aim of treating the statistics of palaeomagnetic directions and intensities jointly and consistently, we represent the mean and the variance of palaeomagnetic vectors, at a particular site and of a particular polarity, by a probability density function in a Cartesian three-space of orthogonal magnetic-field components consisting of a single (unimodal) non-zero mean, spherically-symmetrical (isotropic) Gaussian function. For palaeomagnetic data of mixed polarities, we consider a bimodal distribution consisting of a pair of such symmetrical Gaussian functions, with equal, but opposite, means and equal variances. For both the Gaussian and bi-Gaussian distributions, and in the spherical three-space of intensity, inclination, and declination, we obtain analytical expressions for the marginal density functions, the cumulative distributions, and the expected values and variances for each spherical coordinate (including the angle with respect to the axis of symmetry of the distributions). The mathematical expressions for the intensity and off-axis angle are closed-form and especially manageable, with the intensity distribution being Rayleigh-Rician. In the limit of small relative vectorial dispersion, the Gaussian (bi-Gaussian) directional distribution approaches a Fisher (Bingham) distribution and the intensity distribution approaches a normal distribution. In the opposite limit of large relative vectorial dispersion, the directional distributions approach a spherically-uniform distribution and the intensity distribution approaches a Maxwell distribution. We quantify biases in estimating the properties of the vector field resulting from the use of simple arithmetic averages, such as estimates of the intensity or the inclination of the mean vector, or the variances of these quantities. With the statistical framework developed here and using the maximum-likelihood method, which gives unbiased estimates in the limit of large data numbers, we demonstrate how to

  5. Induction of protective immunity in swine by recombinant bamboo mosaic virus expressing foot-and-mouth disease virus epitopes

    Directory of Open Access Journals (Sweden)

    Lin Na-Sheng

    2007-09-01

    Full Text Available Abstract Background Plant viruses can be employed as versatile vectors for the production of vaccines by expressing immunogenic epitopes on the surface of chimeric viral particles. Although several viruses, including tobacco mosaic virus, potato virus X and cowpea mosaic virus, have been developed as vectors, we aimed to develop a new viral vaccine delivery system, a bamboo mosaic virus (BaMV, that would carry larger transgene loads, and generate better immunity in the target animals with fewer adverse environmental effects. Methods We engineered the BaMV as a vaccine vector expressing the antigenic epitope(s of the capsid protein VP1 of foot-and-mouth disease virus (FMDV. The recombinant BaMV plasmid (pBVP1 was constructed by replacing DNA encoding the 35 N-terminal amino acid residues of the BaMV coat protein with that encoding 37 amino acid residues (T128-N164 of FMDV VP1. Results The pBVP1 was able to infect host plants and to generate a chimeric virion BVP1 expressing VP1 epitopes in its coat protein. Inoculation of swine with BVP1 virions resulted in the production of anti-FMDV neutralizing antibodies. Real-time PCR analysis of peripheral blood mononuclear cells from the BVP1-immunized swine revealed that they produced VP1-specific IFN-γ. Furthermore, all BVP1-immunized swine were protected against FMDV challenge. Conclusion Chimeric BaMV virions that express partial sequence of FMDV VP1 can effectively induce not only humoral and cell-mediated immune responses but also full protection against FMDV in target animals. This BaMV-based vector technology may be applied to other vaccines that require correct expression of antigens on chimeric viral particles.

  6. Search Results | Page 2 | IDRC - International Development ...

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

    2014-01-01

    Results 11 - 20 of 103 ... Ecological, biological and social dimensions of dengue vector breeding in five urban settings ... dengue vector densities to prevent transmission are in demand by vector control programs. Published date. January 1, 2014.

  7. Effective SIMD Vectorization for Intel Xeon Phi Coprocessors

    Directory of Open Access Journals (Sweden)

    Xinmin Tian

    2015-01-01

    Full Text Available Efficiently exploiting SIMD vector units is one of the most important aspects in achieving high performance of the application code running on Intel Xeon Phi coprocessors. In this paper, we present several effective SIMD vectorization techniques such as less-than-full-vector loop vectorization, Intel MIC specific alignment optimization, and small matrix transpose/multiplication 2D vectorization implemented in the Intel C/C++ and Fortran production compilers for Intel Xeon Phi coprocessors. A set of workloads from several application domains is employed to conduct the performance study of our SIMD vectorization techniques. The performance results show that we achieved up to 12.5x performance gain on the Intel Xeon Phi coprocessor. We also demonstrate a 2000x performance speedup from the seamless integration of SIMD vectorization and parallelization.

  8. Vector grammars and PN machines

    Institute of Scientific and Technical Information of China (English)

    蒋昌俊

    1996-01-01

    The concept of vector grammars under the string semantic is introduced.The dass of vector grammars is given,which is similar to the dass of Chomsky grammars.The regular vector grammar is divided further.The strong and weak relation between the vector grammar and scalar grammar is discussed,so the spectrum system graph of scalar and vector grammars is made.The equivalent relation between the regular vector grammar and Petri nets (also called PN machine) is pointed.The hybrid PN machine is introduced,and its language is proved equivalent to the language of the context-free vector grammar.So the perfect relation structure between vector grammars and PN machines is formed.

  9. immune response can measuring immunity to hiv during ...

    African Journals Online (AJOL)

    2005-11-01

    Nov 1, 2005 ... inhibitors (PIs), have resulted in significant suppression of viral replication. ... thymus, with the potential for immune reconstitution when ..... HIV-exposed but uninfected Gambian women [published erratum appears in. Nat Med ...

  10. Immunization with a DNA vaccine encoding Toxoplasma gondii Superoxide dismutase (TgSOD) induces partial immune protection against acute toxoplasmosis in BALB/c mice.

    Science.gov (United States)

    Liu, Yuan; Cao, Aiping; Li, Yawen; Li, Xun; Cong, Hua; He, Shenyi; Zhou, Huaiyu

    2017-06-07

    Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite that infects all warm-blooded animals including humans and causes toxoplasmosis. An effective vaccine could be an ideal choice for preventing and controlling toxoplasmosis. T. gondii Superoxide dismutase (TgSOD) might participate in affecting the intracellular growth of both bradyzoite and tachyzoite forms. In the present study, the TgSOD gene was used to construct a DNA vaccine (pEGFP-SOD). TgSOD gene was amplified and inserted into eukaryotic vector pEGFP-C1 and formed the DNA vaccine pEGFP-SOD. Then the BALB/c mice were immunized intramuscularly with the DNA vaccine and those injected with pEGFP-C1, PBS or nothing were treated as controls. Four weeks after the last immunization, all mouse groups followed by challenging intraperitoneally with tachyzoites of T. gondii ME49 strain. Results showed higher levels of total IgG, IgG2α in the sera and interferon gamma (IFN-γ) in the splenocytes from pEGFP-SOD inoculated mice than those unvaccinated, or inoculated with either empty plasmid vector or PBS. The proportions of CD4 + T cells and CD8 + T cells in the spleen from pEGFP-SOD inoculated mice were significantly (p < 0.05) increased compared to control groups. In addition, the survival time of mice immunized with pEGFP-SOD was significantly prolonged as compared to the controls (p < 0.05) although all the mice died. The present study revealed that the DNA vaccine triggered strong humoral and cellular immune responses, and aroused partial protective immunity against acute T. gondii infection in BALB/c mice. The collective data suggests the SOD may be a potential vaccine candidate for further development.

  11. SOME ISSUES OF DIAGNOSTICS IN IMMUNE PATHOLOGY

    OpenAIRE

    I. A. Tousankina

    2010-01-01

    Present lecture contains an author's opinion concerning diagnostic issues in immunopathology, including primary and secondary immune deficiencies, immune-dependent states that are based on immunopathological syndromes. Original formulations are suggested for some key categories of clinical immunology, physical, instrumental and laboratory diagnostics of immune deficiencies and immune-dependent diseases. The results of original long-term observations, as well as data on Sverdlovsk Regional Reg...

  12. [Orthogonal Vector Projection Algorithm for Spectral Unmixing].

    Science.gov (United States)

    Song, Mei-ping; Xu, Xing-wei; Chang, Chein-I; An, Ju-bai; Yao, Li

    2015-12-01

    Spectrum unmixing is an important part of hyperspectral technologies, which is essential for material quantity analysis in hyperspectral imagery. Most linear unmixing algorithms require computations of matrix multiplication and matrix inversion or matrix determination. These are difficult for programming, especially hard for realization on hardware. At the same time, the computation costs of the algorithms increase significantly as the number of endmembers grows. Here, based on the traditional algorithm Orthogonal Subspace Projection, a new method called. Orthogonal Vector Projection is prompted using orthogonal principle. It simplifies this process by avoiding matrix multiplication and inversion. It firstly computes the final orthogonal vector via Gram-Schmidt process for each endmember spectrum. And then, these orthogonal vectors are used as projection vector for the pixel signature. The unconstrained abundance can be obtained directly by projecting the signature to the projection vectors, and computing the ratio of projected vector length and orthogonal vector length. Compared to the Orthogonal Subspace Projection and Least Squares Error algorithms, this method does not need matrix inversion, which is much computation costing and hard to implement on hardware. It just completes the orthogonalization process by repeated vector operations, easy for application on both parallel computation and hardware. The reasonability of the algorithm is proved by its relationship with Orthogonal Sub-space Projection and Least Squares Error algorithms. And its computational complexity is also compared with the other two algorithms', which is the lowest one. At last, the experimental results on synthetic image and real image are also provided, giving another evidence for effectiveness of the method.

  13. Amyloid and immune homeostasis.

    Science.gov (United States)

    Wang, Ying-Hui; Zhang, Yu-Gen

    2018-03-01

    Extracellular amyloid deposition defines a range of amyloidosis and amyloid-related disease. Addition to primary and secondary amyloidosis, amyloid-related disease can be observed in different tissue/organ that sharing the common pathogenesis based on the formation of amyloid deposition. Currently, both Alzheimer's disease and type 2 diabetes can be diagnosed with certainly only based on the autopsy results, by which amyloidosis of the associative tissue/organ is observed. Intriguingly, since it demonstrated that amyloid deposits trigger inflammatory reaction through the activation of cascaded immune response, wherein several lines of evidence implies a protective role of amyloid in preventing autoimmunity. Furthermore, attempts for preventing amyloid formation and/or removing amyloid deposits from the brain have caused meningoencephalitis and consequent deaths among the subjects. Hence, it is important to note that amyloid positively participates in maintaining immune homeostasis and contributes to irreversible inflammatory response. In this review, we will focus on the interactive relationship between amyloid and the immune system, discussing the potential functional roles of amyloid in immune tolerance and homeostasis. Copyright © 2017 Elsevier GmbH. All rights reserved.

  14. Lymphoma: Immune Evasion Strategies

    International Nuclear Information System (INIS)

    Upadhyay, Ranjan; Hammerich, Linda; Peng, Paul; Brown, Brian; Merad, Miriam; Brody, Joshua D.

    2015-01-01

    While the cellular origin of lymphoma is often characterized by chromosomal translocations and other genetic aberrations, its growth and development into a malignant neoplasm is highly dependent upon its ability to escape natural host defenses. Neoplastic cells interact with a variety of non-malignant cells in the tumor milieu to create an immunosuppressive microenvironment. The resulting functional impairment and dysregulation of tumor-associated immune cells not only allows for passive growth of the malignancy but may even provide active growth signals upon which the tumor subsequently becomes dependent. In the past decade, the success of immune checkpoint blockade and adoptive cell transfer for relapsed or refractory lymphomas has validated immunotherapy as a possible treatment cornerstone. Here, we review the mechanisms by which lymphomas have been found to evade and even reprogram the immune system, including alterations in surface molecules, recruitment of immunosuppressive subpopulations, and secretion of anti-inflammatory factors. A fundamental understanding of the immune evasion strategies utilized by lymphomas may lead to better prognostic markers and guide the development of targeted interventions that are both safer and more effective than current standards of care

  15. Lymphoma: Immune Evasion Strategies

    Energy Technology Data Exchange (ETDEWEB)

    Upadhyay, Ranjan; Hammerich, Linda; Peng, Paul [Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Brown, Brian [Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Merad, Miriam [Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Brody, Joshua D., E-mail: joshua.brody@mssm.edu [Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States)

    2015-04-30

    While the cellular origin of lymphoma is often characterized by chromosomal translocations and other genetic aberrations, its growth and development into a malignant neoplasm is highly dependent upon its ability to escape natural host defenses. Neoplastic cells interact with a variety of non-malignant cells in the tumor milieu to create an immunosuppressive microenvironment. The resulting functional impairment and dysregulation of tumor-associated immune cells not only allows for passive growth of the malignancy but may even provide active growth signals upon which the tumor subsequently becomes dependent. In the past decade, the success of immune checkpoint blockade and adoptive cell transfer for relapsed or refractory lymphomas has validated immunotherapy as a possible treatment cornerstone. Here, we review the mechanisms by which lymphomas have been found to evade and even reprogram the immune system, including alterations in surface molecules, recruitment of immunosuppressive subpopulations, and secretion of anti-inflammatory factors. A fundamental understanding of the immune evasion strategies utilized by lymphomas may lead to better prognostic markers and guide the development of targeted interventions that are both safer and more effective than current standards of care.

  16. How random is a random vector?

    Science.gov (United States)

    Eliazar, Iddo

    2015-12-01

    Over 80 years ago Samuel Wilks proposed that the "generalized variance" of a random vector is the determinant of its covariance matrix. To date, the notion and use of the generalized variance is confined only to very specific niches in statistics. In this paper we establish that the "Wilks standard deviation" -the square root of the generalized variance-is indeed the standard deviation of a random vector. We further establish that the "uncorrelation index" -a derivative of the Wilks standard deviation-is a measure of the overall correlation between the components of a random vector. Both the Wilks standard deviation and the uncorrelation index are, respectively, special cases of two general notions that we introduce: "randomness measures" and "independence indices" of random vectors. In turn, these general notions give rise to "randomness diagrams"-tangible planar visualizations that answer the question: How random is a random vector? The notion of "independence indices" yields a novel measure of correlation for Lévy laws. In general, the concepts and results presented in this paper are applicable to any field of science and engineering with random-vectors empirical data.

  17. How random is a random vector?

    International Nuclear Information System (INIS)

    Eliazar, Iddo

    2015-01-01

    Over 80 years ago Samuel Wilks proposed that the “generalized variance” of a random vector is the determinant of its covariance matrix. To date, the notion and use of the generalized variance is confined only to very specific niches in statistics. In this paper we establish that the “Wilks standard deviation” –the square root of the generalized variance–is indeed the standard deviation of a random vector. We further establish that the “uncorrelation index” –a derivative of the Wilks standard deviation–is a measure of the overall correlation between the components of a random vector. Both the Wilks standard deviation and the uncorrelation index are, respectively, special cases of two general notions that we introduce: “randomness measures” and “independence indices” of random vectors. In turn, these general notions give rise to “randomness diagrams”—tangible planar visualizations that answer the question: How random is a random vector? The notion of “independence indices” yields a novel measure of correlation for Lévy laws. In general, the concepts and results presented in this paper are applicable to any field of science and engineering with random-vectors empirical data.

  18. Feature Vector Construction Method for IRIS Recognition

    Science.gov (United States)

    Odinokikh, G.; Fartukov, A.; Korobkin, M.; Yoo, J.

    2017-05-01

    One of the basic stages of iris recognition pipeline is iris feature vector construction procedure. The procedure represents the extraction of iris texture information relevant to its subsequent comparison. Thorough investigation of feature vectors obtained from iris showed that not all the vector elements are equally relevant. There are two characteristics which determine the vector element utility: fragility and discriminability. Conventional iris feature extraction methods consider the concept of fragility as the feature vector instability without respect to the nature of such instability appearance. This work separates sources of the instability into natural and encodinginduced which helps deeply investigate each source of instability independently. According to the separation concept, a novel approach of iris feature vector construction is proposed. The approach consists of two steps: iris feature extraction using Gabor filtering with optimal parameters and quantization with separated preliminary optimized fragility thresholds. The proposed method has been tested on two different datasets of iris images captured under changing environmental conditions. The testing results show that the proposed method surpasses all the methods considered as a prior art by recognition accuracy on both datasets.

  19. Immune System Quiz

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Quiz: Immune System KidsHealth / For Kids / Quiz: Immune System Print How much do you know about your immune system? Find out by taking this quiz! About Us ...

  20. Immunization Schedules for Adults

    Science.gov (United States)

    ... ACIP Vaccination Recommendations Why Immunize? Vaccines: The Basics Immunization Schedule for Adults (19 Years of Age and ... diseases that can be prevented by vaccines . 2018 Immunization Schedule Recommended Vaccinations for Adults by Age and ...

  1. Immunizations and African Americans

    Science.gov (United States)

    ... Data > Minority Population Profiles > Black/African American > Immunizations Immunizations and African Americans African American adults are less ... 19 to 35 months had comparable rates of immunization. African American women are as likely to have ...

  2. Instant Childhood Immunization Schedule

    Science.gov (United States)

    ... Recommendations Why Immunize? Vaccines: The Basics Instant Childhood Immunization Schedule Recommend on Facebook Tweet Share Compartir Get ... date. See Disclaimer for additional details. Based on Immunization Schedule for Children 0 through 6 Years of ...

  3. Vehicle Based Vector Sensor

    Science.gov (United States)

    2015-09-28

    buoyant underwater vehicle with an interior space in which a length of said underwater vehicle is equal to one tenth of the acoustic wavelength...underwater vehicle with an interior space in which a length of said underwater vehicle is equal to one tenth of the acoustic wavelength; an...unmanned underwater vehicle that can function as an acoustic vector sensor. (2) Description of the Prior Art [0004] It is known that a propagating

  4. Reciprocity in Vector Acoustics

    Science.gov (United States)

    2017-03-01

    Green’s Theorem to the left hand side of Equation (3.2) converts it to a surface integral that vanishes for the impedance boundary conditions one...There are situations where this assumption does not hold, such as at boundaries between layers or in an inhomogeneous layer , because the density gradient...instead of requiring one model run for each source location. Application of the vector-scalar reciprocity principle is demonstrated with analytic

  5. Tensor Calculus: Unlearning Vector Calculus

    Science.gov (United States)

    Lee, Wha-Suck; Engelbrecht, Johann; Moller, Rita

    2018-01-01

    Tensor calculus is critical in the study of the vector calculus of the surface of a body. Indeed, tensor calculus is a natural step-up for vector calculus. This paper presents some pitfalls of a traditional course in vector calculus in transitioning to tensor calculus. We show how a deeper emphasis on traditional topics such as the Jacobian can…

  6. The most common friend first immunization

    International Nuclear Information System (INIS)

    Nian Fu-Zhong; Hu Cha-Sheng

    2016-01-01

    In this paper, a standard susceptible-infected-recovered-susceptible(SIRS) epidemic model based on the Watts–Strogatz (WS) small-world network model and the Barabsi–Albert (BA) scale-free network model is established, and a new immunization scheme — “the most common friend first immunization” is proposed, in which the most common friend’s node is described as being the first immune on the second layer protection of complex networks. The propagation situations of three different immunization schemes — random immunization, high-risk immunization, and the most common friend first immunization are studied. At the same time, the dynamic behaviors are also studied on the WS small-world and the BA scale-free network. Moreover, the analytic and simulated results indicate that the immune effect of the most common friend first immunization is better than random immunization, but slightly worse than high-risk immunization. However, high-risk immunization still has some limitations. For example, it is difficult to accurately define who a direct neighbor in the life is. Compared with the traditional immunization strategies having some shortcomings, the most common friend first immunization is effective, and it is nicely consistent with the actual situation. (paper)

  7. T cell immunity

    OpenAIRE

    Emel Bülbül Başkan

    2013-01-01

    Since birth, our immune system is constantly bombarded with self-antigens and foreign pathogens. To stay healthy, complex immune strategies have evolved in our immune system to maintain self-tolerance and to defend against foreign pathogens. Effector T cells are the key players in steering the immune responses to execute immune functions. While effector T cells were initially identified to be immune promoting, recent studies unraveled negative regulatory functions of effector T cells...

  8. Improved vaccine protection against retrovirus infection after co-administration of adenoviral vectors encoding viral antigens and type I interferon subtypes

    Directory of Open Access Journals (Sweden)

    Groitl Peter

    2011-09-01

    Full Text Available Abstract Background Type I interferons (IFNs exhibit direct antiviral effects, but also distinct immunomodulatory properties. In this study, we analyzed type I IFN subtypes for their effect on prophylactic adenovirus-based anti-retroviral vaccination of mice against Friend retrovirus (FV or HIV. Results Mice were vaccinated with adenoviral vectors encoding FV Env and Gag proteins alone or in combination with vectors encoding IFNα1, IFNα2, IFNα4, IFNα5, IFNα6, IFNα9 or IFNβ. Only the co-administration of adenoviral vectors encoding IFNα2, IFNα4, IFNα6 and IFNα9 resulted in strongly improved immune protection of vaccinated mice from subsequent FV challenge infection with high control over FV-induced splenomegaly and reduced viral loads. The level of protection correlated with augmented virus-specific CD4+ T cell responses and enhanced antibody titers. Similar results were obtained when mice were vaccinated against HIV with adenoviral vectors encoding HIV Env and Gag-Pol in combination with various type I IFN encoding vectors. Here mainly CD4+ T cell responses were enhanced by IFNα subtypes. Conclusions Our results indicate that certain IFNα subtypes have the potential to improve the protective effect of adenovirus-based vaccines against retroviruses. This correlated with augmented virus-specific CD4+ T cell and antibody responses. Thus, co-expression of select type I IFNs may be a valuable tool for the development of anti-retroviral vaccines.

  9. Immune escape strategies of malaria parasites

    Directory of Open Access Journals (Sweden)

    Pollyanna Stephanie Gomes

    2016-10-01

    Full Text Available Malaria is one of the most life-threatening infectious diseases worldwide. Immunity to malaria is slow and short-lived despite the repeated parasite exposure in endemic areas. Malaria parasites have evolved refined machinery to evade the immune system based on a range of genetic changes that include allelic variation, biomolecular exposure of proteins and intracellular replication. All of these features increase the probability of survival in both mosquitoes and the vertebrate host. Plasmodium species escape from the first immunological trap in its invertebrate vector host, the Anopheles mosquitoes. The parasites have to pass through various immunological barriers within the mosquito such as anti-microbial molecules and the mosquito microbiota in order to achieve successful transmission to the vertebrate host. Within these hosts, Plasmodium species employ various immune evasion strategies during different life cycle stages. Parasite persistence against the vertebrate immune response depends on the balance among virulence factors, pathology, metabolic cost of the host immune response, and the parasites ability to evade the immune response. In this review we discuss the strategies that Plasmodium parasites use to avoid the vertebrate host immune system and how they promote successful infection and transmission.

  10. Immune System Dysfunction in the Elderly.

    Science.gov (United States)

    Fuentes, Eduardo; Fuentes, Manuel; Alarcón, Marcelo; Palomo, Iván

    2017-01-01

    Human aging is characterized by both physical and physiological frailty that profoundly affects the immune system. In this context aging is associated with declines in adaptive and innate immunity established as immunosenescence. Immunosenescence is a new concept that reflects the age-associated restructuring changes of innate and adaptive immune functions. Thus elderly individuals usually present chronic low-level inflammation, higher infection rates and chronic diseases. A study of alterations in the immune system during aging could provide a potentially useful biomarker for the evaluation of immune senescence treatment. The immune system is the result of the interplay between innate and adaptive immunity, yet the impact of aging on this function is unclear. In this article the function of the immune system during aging is explored.

  11. Immunization Action Coalition

    Science.gov (United States)

    ... IAC | Contact | A-Z Index | Donate | Shop | SUBSCRIBE Immunization Action Coalition Favorites ACIP Recommendations Package Inserts Additional Immunization Resources Photos Adult Vaccination Screening Checklists Ask the ...

  12. Chimpanzee Adenovirus Vector Ebola Vaccine.

    Science.gov (United States)

    Ledgerwood, Julie E; DeZure, Adam D; Stanley, Daphne A; Coates, Emily E; Novik, Laura; Enama, Mary E; Berkowitz, Nina M; Hu, Zonghui; Joshi, Gyan; Ploquin, Aurélie; Sitar, Sandra; Gordon, Ingelise J; Plummer, Sarah A; Holman, LaSonji A; Hendel, Cynthia S; Yamshchikov, Galina; Roman, Francois; Nicosia, Alfredo; Colloca, Stefano; Cortese, Riccardo; Bailer, Robert T; Schwartz, Richard M; Roederer, Mario; Mascola, John R; Koup, Richard A; Sullivan, Nancy J; Graham, Barney S

    2017-03-09

    The unprecedented 2014 epidemic of Ebola virus disease (EVD) prompted an international response to accelerate the availability of a preventive vaccine. A replication-defective recombinant chimpanzee adenovirus type 3-vectored ebolavirus vaccine (cAd3-EBO), encoding the glycoprotein from Zaire and Sudan species, that offers protection in the nonhuman primate model, was rapidly advanced into phase 1 clinical evaluation. We conducted a phase 1, dose-escalation, open-label trial of cAd3-EBO. Twenty healthy adults, in sequentially enrolled groups of 10 each, received vaccination intramuscularly in doses of 2×10 10 particle units or 2×10 11 particle units. Primary and secondary end points related to safety and immunogenicity were assessed throughout the first 8 weeks after vaccination; in addition, longer-term vaccine durability was assessed at 48 weeks after vaccination. In this small study, no safety concerns were identified; however, transient fever developed within 1 day after vaccination in two participants who had received the 2×10 11 particle-unit dose. Glycoprotein-specific antibodies were induced in all 20 participants; the titers were of greater magnitude in the group that received the 2×10 11 particle-unit dose than in the group that received the 2×10 10 particle-unit dose (geometric mean titer against the Zaire antigen at week 4, 2037 vs. 331; P=0.001). Glycoprotein-specific T-cell responses were more frequent among those who received the 2×10 11 particle-unit dose than among those who received the 2×10 10 particle-unit dose, with a CD4 response in 10 of 10 participants versus 3 of 10 participants (P=0.004) and a CD8 response in 7 of 10 participants versus 2 of 10 participants (P=0.07) at week 4. Assessment of the durability of the antibody response showed that titers remained high at week 48, with the highest titers in those who received the 2×10 11 particle-unit dose. Reactogenicity and immune responses to cAd3-EBO vaccine were dose-dependent. At

  13. Humoral immune response to AAV

    Directory of Open Access Journals (Sweden)

    Roberto eCalcedo

    2013-10-01

    Full Text Available Adeno-associated virus (AAV is a member of the family parvoviridae that has been widely used as a vector for gene therapy because of its safety profile, its ability to transduce both dividing and non-dividing cells, and its low immunogenicity. AAV has been detected in many different tissues of several animal species but has not been associated with any disease. As a result of natural infections, antibodies to AAV can be found in many animals including humans. It has been shown that pre-existing AAV antibodies can modulate the safety and efficacy of AAV vector-mediated gene therapy by blocking vector transduction or by redirecting distribution of AAV vectors to tissues other than the target organ. This review will summarize antibody responses against natural AAV infections, as well as AAV gene therapy vectors and their impact in the clinical development of AAV vectors for gene therapy. We will also review and discuss the various methods used for AAV antibody detection and strategies to overcome neutralizing antibodies in AAV-mediated gene therapy.

  14. Recombinant Kunjin virus replicon vaccines induce protective T-cell immunity against human papillomavirus 16 E7-expressing tumour

    International Nuclear Information System (INIS)

    Herd, Karen A.; Harvey, Tracey; Khromykh, Alexander A.; Tindle, Robert W.

    2004-01-01

    The persistence of the E7 oncoprotein in transformed cells in human papillomavirus (HPV)-associated cervical cancer provides a tumour-specific antigen to which immunotherapeutic strategies may be directed. Self-replicating RNA (replicon) vaccine vectors derived from the flavivirus Kunjin (KUN) have recently been reported to induce T-cell immunity. Here, we report that inclusion of a CTL epitope of HPV16 E7 protein into a polyepitope encoded by a KUN vector induced E7-directed T-cell responses and protected mice against challenge with an E7-expressing epithelial tumour. We found replicon RNA packaged into virus-like particles to be more effective than naked replicon RNA or plasmid DNA constructed to allow replicon RNA transcription in vivo. Protective immunity was induced although the E7 CTL epitope was subdominant in the context of other CTL epitopes in the polyepitope. The results demonstrate the efficacy of the KUN replicon vector system for inducing protective immunity directed towards a virally encoded human tumour-specific antigen, and for inducing multi-epitopic CTL responses

  15. Leishmaniasis vector behaviour in Kenya

    International Nuclear Information System (INIS)

    Mutinga, M.J.

    1980-01-01

    Leishmaniasis in Kenya exists in two forms: cutaneous and visceral. The vectors of visceral leishmaniasis have been the subject of investigation by various researchers since World War II, when the outbreak of the disease was first noticed. The vectors of cutaneous leishmaniasis were first worked on only a decade ago after the discovery of the disease focus in Mt. Elgon. The vector behaviour of these diseases, namely Phlebotomus pedifer, the vector of cutaneous leishmaniasis, and Phlebotomus martini, the vector of visceral leishmaniasis, are discussed in detail. P. pedifer has been found to breed and bite inside caves, whereas P. martini mainly bites inside houses. (author)

  16. Two-host, two-vector basic reproduction ratio (R(0 for bluetongue.

    Directory of Open Access Journals (Sweden)

    Joanne Turner

    Full Text Available Mathematical formulations for the basic reproduction ratio (R(0 exist for several vector-borne diseases. Generally, these are based on models of one-host, one-vector systems or two-host, one-vector systems. For many vector borne diseases, however, two or more vector species often co-occur and, therefore, there is a need for more complex formulations. Here we derive a two-host, two-vector formulation for the R(0 of bluetongue, a vector-borne infection of ruminants that can have serious economic consequences; since 1998 for example, it has led to the deaths of well over 1 million sheep in Europe alone. We illustrate our results by considering the situation in South Africa, where there are two major hosts (sheep, cattle and two vector species with differing ecologies and competencies as vectors, for which good data exist. We investigate the effects on R(0 of differences in vector abundance, vector competence and vector host preference between vector species. Our results indicate that R(0 can be underestimated if we assume that there is only one vector transmitting the infection (when there are in fact two or more and/or vector host preferences are overlooked (unless the preferred host is less beneficial or more abundant. The two-host, one-vector formula provides a good approximation when the level of cross-infection between vector species is very small. As this approaches the level of intraspecies infection, a combination of the two-host, one-vector R(0 for each vector species becomes a better estimate. Otherwise, particularly when the level of cross-infection is high, the two-host, two-vector formula is required for accurate estimation of R(0. Our results are equally relevant to Europe, where at least two vector species, which co-occur in parts of the south, have been implicated in the recent epizootic of bluetongue.

  17. Diagnostics of vector magnetic fields

    Science.gov (United States)

    Stenflo, J. O.

    1985-01-01

    It is shown that the vector magnetic fields derived from observations with a filter magnetograph will be severely distorted if the spatially unresolved magnetic structure is not properly accounted for. Thus the apparent vector field will appear much more horizontal than it really is, but this distortion is strongly dependent on the area factor and the temperature line weakenings. As the available fluxtube models are not sufficiently well determined, it is not possible to correct the filter magnetograph observations for these effects in a reliable way, although a crude correction is of course much better than no correction at all. The solution to this diagnostic problem is to observe simultaneously in suitable combinations of spectral lines, and/or use Stokes line profiles recorded with very high spectral resolution. The diagnostic power of using a Fourier transform spectrometer for polarimetry is shown and some results from I and V spectra are illustrated. The line asymmetries caused by mass motions inside the fluxtubes adds an extra complication to the diagnostic problem, in particular as there are indications that the motions are nonstationary in nature. The temperature structure appears to be a function of fluxtube diameter, as a clear difference between plage and network fluxtubes was revealed. The divergence of the magnetic field with height plays an essential role in the explanation of the Stokes V asymmetries (in combination with the mass motions). A self consistent treatment of the subarcsec field geometry may be required to allow an accurate derivation of the spatially averaged vector magnetic field from spectrally resolved data.

  18. Emerging Cancer Vaccines: The Promise of Genetic Vectors

    International Nuclear Information System (INIS)

    Aurisicchio, Luigi; Ciliberto, Gennaro

    2011-01-01

    Therapeutic vaccination against cancer is an important approach which, when combined with other therapies, can improve long-term control of cancer. In fact, the induction of adaptive immune responses against Tumor Associated Antigens (TAAs) as well as innate immunity are important factors for tumor stabilization/eradication. A variety of immunization technologies have been explored in last decades and are currently under active evaluation, such as cell-based, protein, peptide and heat-shock protein-based cancer vaccines. Genetic vaccines are emerging as promising methodologies to elicit immune responses against a wide variety of antigens, including TAAs. Amongst these, Adenovirus (Ad)-based vectors show excellent immunogenicity profile and have achieved immunological proof of concept in humans. In vivo electroporation of plasmid DNA (DNA-EP) is also a desirable vaccine technology for cancer vaccines, as it is repeatable several times, a parameter required for the long-term maintenance of anti-tumor immunity. Recent findings show that combinations of different modalities of immunization (heterologous prime/boost) are able to induce superior immune reactions as compared to single-modality vaccines. In this review, we will discuss the challenges and requirements of emerging cancer vaccines, particularly focusing on the genetic cancer vaccines currently under active development and the promise shown by Ad and DNA-EP heterologous prime-boost

  19. Reinforcement Learning Based Artificial Immune Classifier

    Directory of Open Access Journals (Sweden)

    Mehmet Karakose

    2013-01-01

    Full Text Available One of the widely used methods for classification that is a decision-making process is artificial immune systems. Artificial immune systems based on natural immunity system can be successfully applied for classification, optimization, recognition, and learning in real-world problems. In this study, a reinforcement learning based artificial immune classifier is proposed as a new approach. This approach uses reinforcement learning to find better antibody with immune operators. The proposed new approach has many contributions according to other methods in the literature such as effectiveness, less memory cell, high accuracy, speed, and data adaptability. The performance of the proposed approach is demonstrated by simulation and experimental results using real data in Matlab and FPGA. Some benchmark data and remote image data are used for experimental results. The comparative results with supervised/unsupervised based artificial immune system, negative selection classifier, and resource limited artificial immune classifier are given to demonstrate the effectiveness of the proposed new method.

  20. Ebola and Immune System

    OpenAIRE

    KOMENAN, Alexis

    2016-01-01

    Ebola hemorrhagic fever is a formidable disease whose surges always result in a high number of victims in sub-Saharan Africa. There is no official treatment against the virus, which makes the task of containment extremely delicate. However, the existence of survivors to the virus demonstrates curable nature of the disease and suggests the existence of favorable factors of immunity. The author examines these factors and their challenges and perspectives in the cure of the disease.

  1. Immune disorders in anorexia

    Directory of Open Access Journals (Sweden)

    Sylwia Małgorzata Słotwińska

    2017-10-01

    Full Text Available Anorexia nervosa is a disease involving eating disorders. It mainly affects young people, especially teenage women. The disease is often latent and occurs in many sub-clinical and partial forms. Approximately from 0.3% to 1% of the population suffers from anorexia. It has been shown that patients with anorexia develop neurotransmitter-related disorders, leading to uncontrolled changes in the immune and endocrine systems. Interactions between cytokines, neuropeptides, and neurotransmitters play an important role in disease development. Significant malnutrition induces disorders and alterations in T-cell populations. The cellular response in patients with anorexia nervosa has been shown to be normal, although opinions on this issue are controversial. Laboratory studies on neutrophils in anorexia patients showed decreased adhesion and reduced bactericidal and cell activities. Despite such unfavourable results, patients with anorexia are resistant to infections, which are very rare in this group. Glutamine improves the performance of the human immune system. The administration of glutamine to anorexia patients, as a supplement to parenteral nutrition, has resulted in significant improvements in immune system parameters. The results of previous studies on the causes and risk factors in the development of anorexia nervosa are still ambiguous. One can hope that the differences and similarities between patients with anorexia nervosa and those with other forms of protein-calorie malnutrition may be helpful in determining the relationship between nutritional status and body defences and susceptibility to infection, and can help to broaden the knowledge about the aetiopathogenesis of anorexia nervosa.

  2. Immune disorders in anorexia.

    Science.gov (United States)

    Słotwińska, Sylwia Małgorzata; Słotwiński, Robert

    2017-01-01

    Anorexia nervosa is a disease involving eating disorders. It mainly affects young people, especially teenage women. The disease is often latent and occurs in many sub-clinical and partial forms. Approximately from 0.3% to 1% of the population suffers from anorexia. It has been shown that patients with anorexia develop neurotransmitter-related disorders, leading to uncontrolled changes in the immune and endocrine systems. Interactions between cytokines, neuropeptides, and neurotransmitters play an important role in disease development. Significant malnutrition induces disorders and alterations in T-cell populations. The cellular response in patients with anorexia nervosa has been shown to be normal, although opinions on this issue are controversial. Laboratory studies on neutrophils in anorexia patients showed decreased adhesion and reduced bactericidal and cell activities. Despite such unfavourable results, patients with anorexia are resistant to infections, which are very rare in this group. Glutamine improves the performance of the human immune system. The administration of glutamine to anorexia patients, as a supplement to parenteral nutrition, has resulted in significant improvements in immune system parameters. The results of previous studies on the causes and risk factors in the development of anorexia nervosa are still ambiguous. One can hope that the differences and similarities between patients with anorexia nervosa and those with other forms of protein-calorie malnutrition may be helpful in determining the relationship between nutritional status and body defences and susceptibility to infection, and can help to broaden the knowledge about the aetiopathogenesis of anorexia nervosa.

  3. Next generation of adeno-associated virus 2 vectors: Point mutations in tyrosines lead to high-efficiency transduction at lower doses

    OpenAIRE

    Zhong, Li; Li, Baozheng; Mah, Cathryn S.; Govindasamy, Lakshmanan; Agbandje-McKenna, Mavis; Cooper, Mario; Herzog, Roland W.; Zolotukhin, Irene; Warrington, Kenneth H.; Weigel-Van Aken, Kirsten A.; Hobbs, Jacqueline A.; Zolotukhin, Sergei; Muzyczka, Nicholas; Srivastava, Arun

    2008-01-01

    Recombinant adeno-associated virus 2 (AAV2) vectors are in use in several Phase I/II clinical trials, but relatively large vector doses are needed to achieve therapeutic benefits. Large vector doses also trigger an immune response as a significant fraction of the vectors fails to traffic efficiently to the nucleus and is targeted for degradation by the host cell proteasome machinery. We have reported that epidermal growth factor receptor protein tyrosine kinase (EGFR-PTK) signaling negatively...

  4. Drought and immunity determine the intensity of West Nile virus epidemics and climate change impacts.

    Science.gov (United States)

    Paull, Sara H; Horton, Daniel E; Ashfaq, Moetasim; Rastogi, Deeksha; Kramer, Laura D; Diffenbaugh, Noah S; Kilpatrick, A Marm

    2017-02-08

    The effect of global climate change on infectious disease remains hotly debated because multiple extrinsic and intrinsic drivers interact to influence transmission dynamics in nonlinear ways. The dominant drivers of widespread pathogens, like West Nile virus, can be challenging to identify due to regional variability in vector and host ecology, with past studies producing disparate findings. Here, we used analyses at national and state scales to examine a suite of climatic and intrinsic drivers of continental-scale West Nile virus epidemics, including an empirically derived mechanistic relationship between temperature and transmission potential that accounts for spatial variability in vectors. We found that drought was the primary climatic driver of increased West Nile virus epidemics, rather than within-season or winter temperatures, or precipitation independently. Local-scale data from one region suggested drought increased epidemics via changes in mosquito infection prevalence rather than mosquito abundance. In addition, human acquired immunity following regional epidemics limited subsequent transmission in many states. We show that over the next 30 years, increased drought severity from climate change could triple West Nile virus cases, but only in regions with low human immunity. These results illustrate how changes in drought severity can alter the transmission dynamics of vector-borne diseases. © 2017 The Author(s).

  5. Vector-borne diseases

    DEFF Research Database (Denmark)

    More, Simon J.; Bicout, Dominique; Bøtner, Anette

    2017-01-01

    After a request from the Europea n Commission, EFSA’s Panel on Animal Health and Welfaresummarised the main characteristics of 36 vector-borne disease s (VBDs) in 36 web-based storymaps.The risk of introduction in the EU through movement of livestock or pets was assessed for eac h of the36 VBDs......-agents for which the rate of introduction wasestimated to be very low, no further asse ssments were made. Due to the uncertainty related to someparameters used for the risk assessment or the instable or unpredictability disease situation in some ofthe source regions, it is recommended to update the assessment when...

  6. Scalar and vector Galileons

    International Nuclear Information System (INIS)

    Rodríguez, Yeinzon; Navarro, Andrés A.

    2017-01-01

    An alternative for the construction of fundamental theories is the introduction of Galileons. These are fields whose action leads to non higher than second-order equations of motion. As this is a necessary but not sufficient condition to make the Hamiltonian bounded from below, as long as the action is not degenerate, the Galileon construction is a way to avoid pathologies both at the classical and quantum levels. Galileon actions are, therefore, of great interest in many branches of physics, specially in high energy physics and cosmology. This proceedings contribution presents the generalities of the construction of both scalar and vector Galileons following two different but complimentary routes. (paper)

  7. Vectors to success

    International Nuclear Information System (INIS)

    Otsason, J.

    1998-01-01

    The Vector Pipeline project linking the Chicago supply hub to markets in eastern Canada, the northeastern U.S. and the Mid-Atlantic states, is described. Subsidiary objectives of the promoters are to match market timing to upstream pipelines and market requirements, and to provide low cost expandability to complement upstream expandability. The presentation includes description of the project, costs, leased facilities, rates and tariffs, right of way considerations, storage facilities and a project schedule. Construction is to begin in March 1999 and the line should be in service in November 1999

  8. Integrating Transgenic Vector Manipulation with Clinical Interventions to Manage Vector-Borne Diseases.

    Directory of Open Access Journals (Sweden)

    Kenichi W Okamoto

    2016-03-01

    Full Text Available Many vector-borne diseases lack effective vaccines and medications, and the limitations of traditional vector control have inspired novel approaches based on using genetic engineering to manipulate vector populations and thereby reduce transmission. Yet both the short- and long-term epidemiological effects of these transgenic strategies are highly uncertain. If neither vaccines, medications, nor transgenic strategies can by themselves suffice for managing vector-borne diseases, integrating these approaches becomes key. Here we develop a framework to evaluate how clinical interventions (i.e., vaccination and medication can be integrated with transgenic vector manipulation strategies to prevent disease invasion and reduce disease incidence. We show that the ability of clinical interventions to accelerate disease suppression can depend on the nature of the transgenic manipulation deployed (e.g., whether vector population reduction or replacement is attempted. We find that making a specific, individual strategy highly effective may not be necessary for attaining public-health objectives, provided suitable combinations can be adopted. However, we show how combining only partially effective antimicrobial drugs or vaccination with transgenic vector manipulations that merely temporarily lower vector competence can amplify disease resurgence following transient suppression. Thus, transgenic vector manipulation that cannot be sustained can have adverse consequences-consequences which ineffective clinical interventions can at best only mitigate, and at worst temporarily exacerbate. This result, which arises from differences between the time scale on which the interventions affect disease dynamics and the time scale of host population dynamics, highlights the importance of accounting for the potential delay in the effects of deploying public health strategies on long-term disease incidence. We find that for systems at the disease-endemic equilibrium, even

  9. Broad patterns in domestic vector-borne Trypanosoma cruzi transmission dynamics: synanthropic animals and vector control.

    Science.gov (United States)

    Peterson, Jennifer K; Bartsch, Sarah M; Lee, Bruce Y; Dobson, Andrew P

    2015-10-22

    Chagas disease (caused by Trypanosoma cruzi) is the most important neglected tropical disease (NTD) in Latin America, infecting an estimated 5.7 million people in the 21 countries where it is endemic. It is one of the NTDs targeted for control and elimination by the 2020 London Declaration goals, with the first goal being to interrupt intra-domiciliary vector-borne T. cruzi transmission. A key question in domestic T. cruzi transmission is the role that synanthropic animals play in T. cruzi transmission to humans. Here, we ask, (1) do synanthropic animals need to be targeted in Chagas disease prevention policies?, and (2) how does the presence of animals affect the efficacy of vector control? We developed a simple mathematical model to simulate domestic vector-borne T. cruzi transmission and to specifically examine the interaction between the presence of synanthropic animals and effects of vector control. We used the model to explore how the interactions between triatomine bugs, humans and animals impact the number and proportion of T. cruzi-infected bugs and humans. We then examined how T. cruzi dynamics change when control measures targeting vector abundance are introduced into the system. We found that the presence of synanthropic animals slows the speed of T. cruzi transmission to humans, and increases the sensitivity of T. cruzi transmission dynamics to vector control measures at comparable triatomine carrying capacities. However, T. cruzi transmission is amplified when triatomine carrying capacity increases with the abundance of syntathoropic hosts. Our results suggest that in domestic T. cruzi transmission scenarios where no vector control measures are in place, a reduction in synanthropic animals may slow T. cruzi transmission to humans, but it would not completely eliminate transmission. To reach the 2020 goal of interrupting intra-domiciliary T. cruzi transmission, it is critical to target vector populations. Additionally, where vector control measures

  10. Immunogenicity of heterologous recombinant adenovirus prime-boost vaccine regimens is enhanced by circumventing vector cross-reactivity

    NARCIS (Netherlands)

    Thorner, Anna R.; Lemckert, Angelique A. C.; Goudsmit, Jaap; Lynch, Diana M.; Ewald, Bonnie A.; Denholtz, Matthew; Havenga, Menzo J. E.; Barouch, Dan H.

    2006-01-01

    The high prevalence of preexisting immunity to adenovirus serotype 5 (Ad5) in human populations has led to the development of recombinant adenovirus (rAd) vectors derived from rare Ad serotypes as vaccine candidates for human immunodeficiency virus type 1 and other pathogens. Vaccine vectors have

  11. [Vector transmitted diseases and climate changes in Europe].

    Science.gov (United States)

    Rossati, Antonella; Bargiacchi, Olivia; Kroumova, Vesselina; Garavelli, Pietro Luigi

    2014-09-01

    The increase in temperatures recorded since the mid-nineteenth century is unprecedented in the history of mankind. The consequences of climate changes are numerous and can affect human health through direct (extreme events, natural disasters) or indirect (alteration of the ecosystem) mechanisms. Climate changes have repercussions on ecosystems, agriculture, social conditions, migration, conflicts and the transmission mode of infectious diseases. Vector-borne diseases are infections transmitted by the bite of infected arthropods such as mosquitoes, ticks, triatomines, sand flies and flies. Epidemiological cornerstones of vector-borne diseases are: the ecology and behaviour of the host, the ecology and behaviour of the vector, and the population's degree of immunity. Mosquito vectors related to human diseases mainly belong to the genus Culex, Aedes and Mansonia. Climate changes in Europe have increased the spread of new vectors, such as Aedes albopictus, and in some situations have made it possible to sustain the autochthonous transmission of some diseases (outbreak of Chukungunya virus in northern Italy in 2007, cases of dengue in the South of France and in Croatia). Despite the eradication of malaria from Europe, anopheline carriers are still present, and they may allow the transmission of the disease if the climatic conditions favour the development of the vectors and their contacts with plasmodium carriers. The tick Ixodes ricinus is a vector whose expansion has been documented both in latitude and in altitude in relation to the temperature increase; at the same time the related main viral and bacterial infections have increased. In northern Italy and Germany, the appearance of Leishmaniasis has been associated to climatic conditions that favour the development of the vector Phlebotomus papatasi and the maturation of the parasite within the vector, although the increase of cases of visceral leishmaniasis is also related to host immune factors, particularly

  12. A Subdivision-Based Representation for Vector Image Editing.

    Science.gov (United States)

    Liao, Zicheng; Hoppe, Hugues; Forsyth, David; Yu, Yizhou

    2012-11-01

    Vector graphics has been employed in a wide variety of applications due to its scalability and editability. Editability is a high priority for artists and designers who wish to produce vector-based graphical content with user interaction. In this paper, we introduce a new vector image representation based on piecewise smooth subdivision surfaces, which is a simple, unified and flexible framework that supports a variety of operations, including shape editing, color editing, image stylization, and vector image processing. These operations effectively create novel vector graphics by reusing and altering existing image vectorization results. Because image vectorization yields an abstraction of the original raster image, controlling the level of detail of this abstraction is highly desirable. To this end, we design a feature-oriented vector image pyramid that offers multiple levels of abstraction simultaneously. Our new vector image representation can be rasterized efficiently using GPU-accelerated subdivision. Experiments indicate that our vector image representation achieves high visual quality and better supports editing operations than existing representations.

  13. Design and Potential of Non-Integrating Lentiviral Vectors

    Directory of Open Access Journals (Sweden)

    Aaron Shaw

    2014-01-01

    Full Text Available Lentiviral vectors have demonstrated promising results in clinical trials that target cells of the hematopoietic system. For these applications, they are the vectors of choice since they provide stable integration into cells that will undergo extensive expansion in vivo. Unfortunately, integration can have unintended consequences including dysregulated cell growth. Therefore, lentiviral vectors that do not integrate are predicted to have a safer profile compared to integrating vectors and should be considered for applications where transient expression is required or for sustained episomal expression such as in quiescent cells. In this review, the system for generating lentiviral vectors will be described and used to illustrate how alterations in the viral integrase or vector Long Terminal Repeats have been used to generate vectors that lack the ability to integrate. In addition to their safety advantages, these non-integrating lentiviral vectors can be used when persistent expression would have adverse consequences. Vectors are currently in development for use in vaccinations, cancer therapy, site-directed gene insertions, gene disruption strategies, and cell reprogramming. Preclinical work will be described that illustrates the potential of this unique vector system in human gene therapy.

  14. Our Immune System

    Science.gov (United States)

    Our Immune System A story for children with primary immunodeficiency diseases Written by Sara LeBien IMMUNE DEFICIENCY FOUNDATION A note ... who are immune deficient to better understand their immune system. What is a “ B-cell, ” a “ T-cell, ” ...

  15. Vector prime/protein boost vaccine that overcomes defects acquired during aging and cancer

    DEFF Research Database (Denmark)

    Tang, Y.; Akbulut, H.; Maynard, J.

    2006-01-01

    We showed that the Ad-sig-TAA/ecdCD40L vaccine induces a tumor suppressive immune response to the hMUC-1 and rH2N tumor-associated self Ags (TAA) and to the Annexin A1 tumor vascular Ag, even in mice in which anergy exists to these Ags. When the TAA/ecdCD40L protein is given s.c. as a boost...... following the Ad-sig-TAA/ecdCD40L vector, the levels of the TAA-specific CD8 T cells and Abs increase dramatically over that seen with vector alone, in young (2-mo-old) as well as old (18-mo-old) mice. The Abs induced against hMUC-1 react with human breast cancer. This vaccine also induces a 4-fold...... decrement of negative regulatory CD4CD25FOXP3-T cells in the tumor tissue of 18-mo-old mice. These results suggest that the Ad-sig-TAA/ecdCD40L vector prime-TAA/ecdCD40L protein boost vaccine platform may be valuable in reducing postsurgery recurrence in a variety of epithelial neoplasms....

  16. Mass Spectrometry Based Proteomic Analysis of Salivary Glands of Urban Malaria Vector Anopheles stephensi

    Directory of Open Access Journals (Sweden)

    Sonam Vijay

    2014-01-01

    Full Text Available Salivary gland proteins of Anopheles mosquitoes offer attractive targets to understand interactions with sporozoites, blood feeding behavior, homeostasis, and immunological evaluation of malaria vectors and parasite interactions. To date limited studies have been carried out to elucidate salivary proteins of An. stephensi salivary glands. The aim of the present study was to provide detailed analytical attributives of functional salivary gland proteins of urban malaria vector An. stephensi. A proteomic approach combining one-dimensional electrophoresis (1DE, ion trap liquid chromatography mass spectrometry (LC/MS/MS, and computational bioinformatic analysis was adopted to provide the first direct insight into identification and functional characterization of known salivary proteins and novel salivary proteins of An. stephensi. Computational studies by online servers, namely, MASCOT and OMSSA algorithms, identified a total of 36 known salivary proteins and 123 novel proteins analysed by LC/MS/MS. This first report describes a baseline proteomic catalogue of 159 salivary proteins belonging to various categories of signal transduction, regulation of blood coagulation cascade, and various immune and energy pathways of An. stephensi sialotranscriptome by mass spectrometry. Our results may serve as basis to provide a putative functional role of proteins in concept of blood feeding, biting behavior, and other aspects of vector-parasite host interactions for parasite development in anopheline mosquitoes.

  17. Design and Construction of a Cloning Vector Containing the hspX Gene of Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Atieh Yaghoubi

    2016-10-01

    Full Text Available Background: Tuberculosis (TB is a major cause of death worldwide. Finding an effective vaccine against TB is the best way to control it. Several vaccines against this disease have been developed but none are completely protective. The aim of this study was to design and construct a cloning vector containing the Mycobacterium tuberculosis (M. tuberculosis heat shock protein X (hspX. Methods: First, an hspX fragment was amplified by PCR and cloned into plasmid pcDNA3.1(+ and recombinant vector was confirmed. Results: A 435 bp hspX fragment was isolated. The fragment was 100% homologous with hspX of M. tuberculosis strain H37Rv in GenBank. Conclusions: In this study, the cloning vector pcDNA3.1(+, containing a 435-bp hspX fragment of M. tuberculosis, was constructed. This could be used as a DNA vaccine to induce immune responses in animal models in future studies.

  18. Vector potential quantization and the photon wave-particle representation

    International Nuclear Information System (INIS)

    Meis, C; Dahoo, P R

    2016-01-01

    The quantization procedure of the vector potential is enhanced at a single photon state revealing the possibility for a simultaneous representation of the wave-particle nature of the photon. Its relationship to the quantum vacuum results naturally. A vector potential amplitude operator is defined showing the parallelism with the Hamiltonian of a massless particle. It is further shown that the quantized vector potential satisfies both the wave propagation equation and a linear time-dependent Schrödinger-like equation. (paper)

  19. Isometric Reflection Vectors and Characterizations of Hilbert Spaces

    Directory of Open Access Journals (Sweden)

    Donghai Ji

    2014-01-01

    Full Text Available A known characterization of Hilbert spaces via isometric reflection vectors is based on the following implication: if the set of isometric reflection vectors in the unit sphere SX of a Banach space X has nonempty interior in SX, then X is a Hilbert space. Applying a recent result based on well-known theorem of Kronecker from number theory, we improve this by substantial reduction of the set of isometric reflection vectors needed in the hypothesis.

  20. Immunity to Fasciola hepatica in the rat

    International Nuclear Information System (INIS)

    Armour, J.; Dargie, J.D.

    1974-01-01

    Experiments were carried out which demonstrated an acquired immunity to Fasciola hapatica in the rat. It was shown that this immunity could be transferred to recipients using either lymphoid cells or serum from infected donor rats. The extent of the protection obtained by cells appeared to be related to the quantity and persistence of the antigenic stimulus in the donor. Likewise, the degree of immunity conferred by immune serum was dependent upon the volume transferred. The significance of these results in relation to the mechanism of immunity to fascioliasis is discussed

  1. Immunity to tumour antigens.

    Science.gov (United States)

    Li, Geng; Ali, Selman A; McArdle, Stephanie E B; Mian, Shahid; Ahmad, Murrium; Miles, Amanda; Rees, Robert C

    2005-01-01

    During the last decade, a large number of human tumour antigens have been identified. These antigens are classified as tumour-specific shared antigens, tissue-specific differentiation antigens, overexpressed antigens, tumour antigens resulting from mutations, viral antigens and fusion proteins. Antigens recognised by effectors of immune system are potential targets for antigen-specific cancer immunotherapy. However, most tumour antigens are self-proteins and are generally of low immunogenicity and the immune response elicited towards these tumour antigens is not always effective. Strategies to induce and enhance the tumour antigen-specific response are needed. This review will summarise the approaches to discovery of tumour antigens, the current status of tumour antigens, and their potential application to cancer treatment.

  2. Application of Vector Triggering Random Decrement

    DEFF Research Database (Denmark)

    Asmussen, J. C.; Ibrahim, S. R.; Brincker, Rune

    result is a Random Decrement function from each measurement. In traditional Random Decrement estimation the triggering condition is a scalar condition, which should only be fulfilled in a single measurement. In vector triggering Random Decrement the triggering condition is a vector condition......This paper deals with applications of the vector triggering Random Decrement technique. This technique is new and developed with the aim of minimizing estimation time and identification errors. The theory behind the technique is discussed in an accompanying paper. The results presented...... in this paper should be regarded as a further documentation of the technique. The key point in Random Decrement estimation is the formulation of a triggering condition. If the triggering condition is fulfilled a time segment from each measurement is picked out and averaged with previous time segments. The final...

  3. Application of Vector Triggering Random Decrement

    DEFF Research Database (Denmark)

    Asmussen, J. C.; Ibrahim, S. R.; Brincker, Rune

    1997-01-01

    result is a Random Decrement function from each measurement. In traditional Random Decrement estimation the triggering condition is a scalar condition, which should only be fulfilled in a single measurement. In vector triggering Random Decrement the triggering condition is a vector condition......This paper deals with applications of the vector triggering Random Decrement technique. This technique is new and developed with the aim of minimizing estimation time and identification errors. The theory behind the technique is discussed in an accompanying paper. The results presented...... in this paper should be regarded as a further documentation of the technique. The key point in Random Decrement estimation is the formulation of a triggering condition. If the triggering condition is fulfilled a time segment from each measurement is picked out and averaged with previous time segments. The final...

  4. Does the delta quench Gamow-Teller strength in (p,n)- and (p vector,p vector')-reactions

    International Nuclear Information System (INIS)

    Osterfeld, F.; Schulte, A.; Udagawa, T.; Yabe, M.

    1986-01-01

    Microscopic analyses of complete forward angle intermediate energy (p,n)-, ( 3 He,t)- and (p vector,p vector')-spin-flip spectra are presented for the reactions 90 Zr(p,n), 90 Zr( 3 He,t) and 90 Zr(p vector,p vector'). It is shown that the whole spectra up to high excitation energies (E X ∝50 MeV) are the result of correlated one-particle-one-hole (1p1h) spin-isospin transitions only. The spectra reflect, therefore, the linear spin-isospin response of the target nucleus to the probing external hadronic fields. Our results suggest that the measured (p,n)-, ( 3 He,t)- and (p vector,p vector')-cross sections are compatible with the transition strength predictions as obtained from random phase approximation (RPA) calculations. This means that the Δ isobar quenching mechanism is likely to be rather small. (orig.)

  5. Vector control in leishmaniasis.

    Science.gov (United States)

    Kishore, K; Kumar, V; Kesari, S; Dinesh, D S; Kumar, A J; Das, P; Bhattacharya, S K

    2006-03-01

    Indoor residual spraying is a simple and cost effective method of controlling endophilic vectors and DDT remains the insecticide of choice for the control of leishmaniasis. However resistance to insecticide is likely to become more widespread in the population especially in those areas in which insecticide has been used for years. In this context use of slow release emulsified suspension (SRES) may be the best substitute. In this review spraying frequencies of DDT and new schedule of spray have been discussed. Role of biological control and environment management in the control of leishmaniasis has been emphasized. Allethrin (coil) 0.1 and 1.6 per cent prallethrin (liquid) have been found to be effective repellents against Phlebotomus argentipes, the vector of Indian kalaazar. Insecticide impregnated bednets is another area which requires further research on priority basis for the control of leishmaniasis. Role of satellite remote sensing for early prediction of disease by identifying the sandflygenic conditions cannot be undermined. In future synthetic pheromons can be exploited in the control of leishmaniasis.

  6. Experimental demonstration of vector E x vector B plasma divertor

    International Nuclear Information System (INIS)

    Strait, E.J.; Kerst, D.W.; Sprott, J.C.

    1977-01-01

    The vector E x vector B drift due to an applied radial electric field in a tokamak with poloidal divertor can speed the flow of plasma out of the scrape-off region, and provide a means of externally controlling the flow rate and thus the width of the density fall-off. An experiment in the Wisconsin levitated toroidal octupole, using vector E x vector B drifts alone, demonstrates divertor-like behavior, including 70% reduction of plasma density near the wall and 40% reduction of plasma flux to the wall, with no adverse effects on confinement of the main plasma

  7. Engineering BioBrick vectors from BioBrick parts

    Directory of Open Access Journals (Sweden)

    Knight Thomas F

    2008-04-01

    Full Text Available Abstract Background The underlying goal of synthetic biology is to make the process of engineering biological systems easier. Recent work has focused on defining and developing standard biological parts. The technical standard that has gained the most traction in the synthetic biology community is the BioBrick standard for physical composition of genetic parts. Parts that conform to the BioBrick assembly standard are BioBrick standard biological parts. To date, over 2,000 BioBrick parts have been contributed to, and are available from, the Registry of Standard Biological Parts. Results Here we extended the same advantages of BioBrick standard biological parts to the plasmid-based vectors that are used to provide and propagate BioBrick parts. We developed a process for engineering BioBrick vectors from BioBrick parts. We designed a new set of BioBrick parts that encode many useful vector functions. We combined the new parts to make a BioBrick base vector that facilitates BioBrick vector construction. We demonstrated the utility of the process by constructing seven new BioBrick vectors. We also successfully used the resulting vectors to assemble and propagate other BioBrick standard biological parts. Conclusion We extended the principles of part reuse and standardization to BioBrick vectors. As a result, myriad new BioBrick vectors can be readily produced from all existing and newly designed BioBrick parts. We invite the synthetic biology community to (1 use the process to make and share new BioBrick vectors; (2 expand the current collection of BioBrick vector parts; and (3 characterize and improve the available collection of BioBrick vector parts.

  8. Lentiviral Vectors for Cancer Immunotherapy and Clinical Applications

    Energy Technology Data Exchange (ETDEWEB)

    Liechtenstein, Therese, E-mail: t.liechtenstein.12@ucl.ac.uk [University College London, 5 University Street, London, WC1E 6JF (United Kingdom); Perez-Janices, Noemi; Escors, David [University College London, 5 University Street, London, WC1E 6JF (United Kingdom); Navarrabiomed Fundacion Miguel Servet, 3 Irunlarrea St., Hospital Complex of Navarra, 31008 Pamplona, Navarra (Spain)

    2013-07-02

    The success of immunotherapy against infectious diseases has shown us the powerful potential that such a treatment offers, and substantial work has been done to apply this strategy in the fight against cancer. Cancer is however a fiercer opponent than pathogen-caused diseases due to natural tolerance towards tumour associated antigens and tumour-induced immunosuppression. Recent gene therapy clinical trials with viral vectors have shown clinical efficacy in the correction of genetic diseases, HIV and cancer. The first successful gene therapy clinical trials were carried out with onco(γ-)retroviral vectors but oncogenesis by insertional mutagenesis appeared as a serious complication. Lentiviral vectors have emerged as a potentially safer strategy, and recently the first clinical trial of patients with advanced leukemia using lentiviral vectors has proven successful. Additionally, therapeutic lentivectors have shown clinical efficacy for the treatment of HIV, X-linked adrenoleukodystrophy, and β-thalassaemia. This review aims at describing lentivectors and how they can be utilized to boost anti-tumour immune responses by manipulating the effector immune cells.

  9. Lentiviral Vectors for Cancer Immunotherapy and Clinical Applications

    International Nuclear Information System (INIS)

    Liechtenstein, Therese; Perez-Janices, Noemi; Escors, David

    2013-01-01

    The success of immunotherapy against infectious diseases has shown us the powerful potential that such a treatment offers, and substantial work has been done to apply this strategy in the fight against cancer. Cancer is however a fiercer opponent than pathogen-caused diseases due to natural tolerance towards tumour associated antigens and tumour-induced immunosuppression. Recent gene therapy clinical trials with viral vectors have shown clinical efficacy in the correction of genetic diseases, HIV and cancer. The first successful gene therapy clinical trials were carried out with onco(γ-)retroviral vectors but oncogenesis by insertional mutagenesis appeared as a serious complication. Lentiviral vectors have emerged as a potentially safer strategy, and recently the first clinical trial of patients with advanced leukemia using lentiviral vectors has proven successful. Additionally, therapeutic lentivectors have shown clinical efficacy for the treatment of HIV, X-linked adrenoleukodystrophy, and β-thalassaemia. This review aims at describing lentivectors and how they can be utilized to boost anti-tumour immune responses by manipulating the effector immune cells

  10. Progress on adenovirus-vectored universal influenza vaccines.

    Science.gov (United States)

    Xiang, Kui; Ying, Guan; Yan, Zhou; Shanshan, Yan; Lei, Zhang; Hongjun, Li; Maosheng, Sun

    2015-01-01

    Influenza virus (IFV) infection causes serious health problems and heavy financial burdens each year worldwide. The classical inactivated influenza virus vaccine (IIVV) and live attenuated influenza vaccine (LAIV) must be updated regularly to match the new strains that evolve due to antigenic drift and antigenic shift. However, with the discovery of broadly neutralizing antibodies that recognize conserved antigens, and the CD8(+) T cell responses targeting viral internal proteins nucleoprotein (NP), matrix protein 1 (M1) and polymerase basic 1 (PB1), it is possible to develop a universal influenza vaccine based on the conserved hemagglutinin (HA) stem, NP, and matrix proteins. Recombinant adenovirus (rAd) is an ideal influenza vaccine vector because it has an ideal stability and safety profile, induces balanced humoral and cell-mediated immune responses due to activation of innate immunity, provides 'self-adjuvanting' activity, can mimic natural IFV infection, and confers seamless protection against mucosal pathogens. Moreover, this vector can be developed as a low-cost, rapid-response vaccine that can be quickly manufactured. Therefore, an adenovirus vector encoding conserved influenza antigens holds promise in the development of a universal influenza vaccine. This review will summarize the progress in adenovirus-vectored universal flu vaccines and discuss future novel approaches.

  11. Lentiviral Vectors for Cancer Immunotherapy and Clinical Applications

    Directory of Open Access Journals (Sweden)

    David Escors

    2013-07-01

    Full Text Available The success of immunotherapy against infectious diseases has shown us the powerful potential that such a treatment offers, and substantial work has been done to apply this strategy in the fight against cancer. Cancer is however a fiercer opponent than pathogen-caused diseases due to natural tolerance towards tumour associated antigens and tumour-induced immunosuppression. Recent gene therapy clinical trials with viral vectors have shown clinical efficacy in the correction of genetic diseases, HIV and cancer. The first successful gene therapy clinical trials were carried out with onco(g-retroviral vectors but oncogenesis by insertional mutagenesis appeared as a serious complication. Lentiviral vectors have emerged as a potentially safer strategy, and recently the first clinical trial of patients with advanced leukemia using lentiviral vectors has proven successful. Additionally, therapeutic lentivectors have shown clinical efficacy for the treatment of HIV, X-linked adrenoleukodystrophy, and b-thalassaemia. This review aims at describing lentivectors and how they can be utilized to boost anti-tumour immune responses by manipulating the effector immune cells.

  12. [Immunology in the medical practice.XXXII. Transplantation of autologous hematopoietic stem cells for treatment of refractory auto-immune diseases; preliminary favorable results with 35 patients].

    Science.gov (United States)

    Vlieger, A M; van den Hoogen, F H; Brinkman, D M; van Laar, J M; Schipperus, M; Kruize, A A; Wulffraat, N M

    2000-08-12

    The objective of this study was to document the experiences in the first Dutch pilot studies of the effect of transplantation of autologous haematopoietic stem cells in patients with therapy-resistant autoimmune disease. The first results in 21 adults and 14 children are promising: remission of the disease was achieved in 13 patients, while in the others a significant reduction of disease activity was seen with a corresponding improvement of the quality of life. Infectious complications were frequently observed. Two children with systemic juvenile idiopathic arthritis developed a fatal infection-associated macrophage activation syndrome. Multicentre randomised studies are necessary to study the effects of autologous stem cell transplantation and modifications such as T-cell depletion.

  13. ON THE ISSUE OF VECTOR CONTROL OF THE ASYNCHRONOUS MOTORS

    Directory of Open Access Journals (Sweden)

    B. I. Firago

    2015-01-01

    Full Text Available The paper considers the issue of one of the widespread types of vector control realization for the asynchronous motors with a short-circuited rotor. Of all more than 20 vector control types known presently, the following are applied most frequently: direct vector control with velocity pickup (VP, direct vector control without VP, indirect vector control with VP and indirect vector control without VP. Despite the fact that the asynchronous-motor indirect vector control without VP is the easiest and most spread, the absence of VP does not allow controlling the motor electromagnetic torque at zero velocity. This is the reason why for electric motor drives of such requirements they utilize the vector control with a velocity transducer. The systems of widest dissemination became the direct and indirect vector control systems with X-axis alignment of the synchronously rotating x–y-coordinate frame along the rotor flux-linkage vector inasmuch as this provides the simplest correlations for controlling variables. Although these two types of vector control are well presented in literature, a number of issues concerning their realization and practical application require further elaboration. These include: the block schemes adequate representation as consisted with the modern realization of vector control and clarification of the analytical expressions for evaluating the regulator parameters.The authors present a technique for evaluating the dynamics of an asynchronous electric motor drive with direct vector control and x-axis alignment along the vector of rotor flux linkage. The article offers a generalized structure of this vector control type with detailed description of its principal blocks: controlling system, frequency converter, and the asynchronous motor.The paper presents a direct vector control simulating model developed in the MatLab environment on the grounds of this structure. The authors illustrate the described technique with the results

  14. Progresses towards safe and efficient gene therapy vectors.

    Science.gov (United States)

    Chira, Sergiu; Jackson, Carlo S; Oprea, Iulian; Ozturk, Ferhat; Pepper, Michael S; Diaconu, Iulia; Braicu, Cornelia; Raduly, Lajos-Zsolt; Calin, George A; Berindan-Neagoe, Ioana

    2015-10-13

    The emergence of genetic engineering at the beginning of the 1970's opened the era of biomedical technologies, which aims to improve human health using genetic manipulation techniques in a clinical context. Gene therapy represents an innovating and appealing strategy for treatment of human diseases, which utilizes vehicles or vectors for delivering therapeutic genes into the patients' body. However, a few past unsuccessful events that negatively marked the beginning of gene therapy resulted in the need for further studies regarding the design and biology of gene therapy vectors, so that this innovating treatment approach can successfully move from bench to bedside. In this paper, we review the major gene delivery vectors and recent improvements made in their design meant to overcome the issues that commonly arise with the use of gene therapy vectors. At the end of the manuscript, we summarized the main advantages and disadvantages of common gene therapy vectors and we discuss possible future directions for potential therapeutic vectors.

  15. Artificial immune system applications in computer security

    CERN Document Server

    Tan, Ying

    2016-01-01

    This book provides state-of-the-art information on the use, design, and development of the Artificial Immune System (AIS) and AIS-based solutions to computer security issues. Artificial Immune System: Applications in Computer Security focuses on the technologies and applications of AIS in malware detection proposed in recent years by the Computational Intelligence Laboratory of Peking University (CIL@PKU). It offers a theoretical perspective as well as practical solutions for readers interested in AIS, machine learning, pattern recognition and computer security. The book begins by introducing the basic concepts, typical algorithms, important features, and some applications of AIS. The second chapter introduces malware and its detection methods, especially for immune-based malware detection approaches. Successive chapters present a variety of advanced detection approaches for malware, including Virus Detection System, K-Nearest Neighbour (KNN), RBF networ s, and Support Vector Machines (SVM), Danger theory, ...

  16. [Escherichia coli heat-labile enterotoxin B subunit enhances the immune response against canine parvovirus VP2 in mice immunized by VP2 DNA vaccine].

    Science.gov (United States)

    Han, Dongmei; Zhong, Fei; Li, Xiujin; Wang, Wei; Wang, Xingxing; Pan, Sumin

    2011-01-01

    To investigate the effect of Escherichia coli heat-labile enterotoxin (LT) B subunit (LTB) gene on canine parvovirus (CPV) VP2 gene vaccine. The LTB gene was amplified by PCR from genomic DNA of E. coli 44815 strain. The VP2-70 fragment (210 bp) encoding major epitope of VP2 (70 amino acids) was amplified by PCR from a plasmid encoding VP2 gene. VP2-70 and LTB genes were inserted into the eukaryotic vector to construct VP2-70 gene,LTB gene and VP2-70-LTB fused gene vectors. The mice were immunized with VP2-70 vector, VP2-70-LTB fused vector, or VP2-70 vector plus LTB vector, respectively. The antibody titers at the different time were measured by using ELISA method. The spleen lymphocyte proliferation activity was analyzed by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The sequence of VP2-70 and LTB genes was identified. The recombinant VP2-70 and LTB proteins could be expressed in HEK293T cells in a secretory manner. The mice immunized with VP2-70 vector, VP2-70-LTB vector or VP2-70 vector plus LTB vector could generate the specific antibody against VP2 protein. The antibody titer immunized with VP2-70-LTB vector reached 1:5120 at 35 d post immunization, significantly higher than that of other two groups (P vaccine in mice.

  17. Video Vectorization via Tetrahedral Remeshing.

    Science.gov (United States)

    Wang, Chuan; Zhu, Jie; Guo, Yanwen; Wang, Wenping

    2017-02-09

    We present a video vectorization method that generates a video in vector representation from an input video in raster representation. A vector-based video representation offers the benefits of vector graphics, such as compactness and scalability. The vector video we generate is represented by a simplified tetrahedral control mesh over the spatial-temporal video volume, with color attributes defined at the mesh vertices. We present novel techniques for simplification and subdivision of a tetrahedral mesh to achieve high simplification ratio while preserving features and ensuring color fidelity. From an input raster video, our method is capable of generating a compact video in vector representation that allows a faithful reconstruction with low reconstruction errors.

  18. Hyperbolic-symmetry vector fields.

    Science.gov (United States)

    Gao, Xu-Zhen; Pan, Yue; Cai, Meng-Qiang; Li, Yongnan; Tu, Chenghou; Wang, Hui-Tian

    2015-12-14

    We present and construct a new kind of orthogonal coordinate system, hyperbolic coordinate system. We present and design a new kind of local linearly polarized vector fields, which is defined as the hyperbolic-symmetry vector fields because the points with the same polarization form a series of hyperbolae. We experimentally demonstrate the generation of such a kind of hyperbolic-symmetry vector optical fields. In particular, we also study the modified hyperbolic-symmetry vector optical fields with the twofold and fourfold symmetric states of polarization when introducing the mirror symmetry. The tight focusing behaviors of these vector fields are also investigated. In addition, we also fabricate micro-structures on the K9 glass surfaces by several tightly focused (modified) hyperbolic-symmetry vector fields patterns, which demonstrate that the simulated tightly focused fields are in good agreement with the fabricated micro-structures.

  19. Extended vector-tensor theories

    Energy Technology Data Exchange (ETDEWEB)

    Kimura, Rampei; Naruko, Atsushi; Yoshida, Daisuke, E-mail: rampei@th.phys.titech.ac.jp, E-mail: naruko@th.phys.titech.ac.jp, E-mail: yoshida@th.phys.titech.ac.jp [Department of Physics, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8551 (Japan)

    2017-01-01

    Recently, several extensions of massive vector theory in curved space-time have been proposed in many literatures. In this paper, we consider the most general vector-tensor theories that contain up to two derivatives with respect to metric and vector field. By imposing a degeneracy condition of the Lagrangian in the context of ADM decomposition of space-time to eliminate an unwanted mode, we construct a new class of massive vector theories where five degrees of freedom can propagate, corresponding to three for massive vector modes and two for massless tensor modes. We find that the generalized Proca and the beyond generalized Proca theories up to the quartic Lagrangian, which should be included in this formulation, are degenerate theories even in curved space-time. Finally, introducing new metric and vector field transformations, we investigate the properties of thus obtained theories under such transformations.

  20. Oral inoculation of young dairy calves with Mycoplasma bovis results in colonization of tonsils, development of otitis media and local immunity.

    Directory of Open Access Journals (Sweden)

    Fiona Maunsell

    Full Text Available Because M. bovis otitis media is an economically important problem, there is a need to understand the pathogenesis of disease, not only to improve our understanding of the factors contributing to the development of this disease but also to inform the development of improved diagnostic tests and therapy. Oral ingestion of M. bovis-contaminated milk is linked, but not definitively proven, to development of otitis media. In the current study, we demonstrate that oral ingestion of M. bovis infected colostrum can result in an ascending infection and development of otitis media. Importantly, M. bovis was found to have a previously unrecognized tendency for colonization of the tonsils of calves, which most likely contributed to the subsequent development of otitis media. In contrast, transtracheal inoculation failed to produce clinically significant upper respiratory tract disease, although did induce lower respiratory tract disease. The upper respiratory tract was the major site of M. bovis-specific B cell and mucosal IgA responses in calves inoculated by the oral route. The oral inoculation route of infection presented here is particularly suited to the study of host-pathogen interactions during initial colonization of the tonsils, expansion of infection and dissemination to the lower respiratory tract and middle ear. In addition, it could be used to investigate potential new preventative or control strategies, especially those aimed at limiting colonization of the tonsils and/or spread to the middle ear.

  1. Optimality Conditions in Vector Optimization

    CERN Document Server

    Jiménez, Manuel Arana; Lizana, Antonio Rufián

    2011-01-01

    Vector optimization is continuously needed in several science fields, particularly in economy, business, engineering, physics and mathematics. The evolution of these fields depends, in part, on the improvements in vector optimization in mathematical programming. The aim of this Ebook is to present the latest developments in vector optimization. The contributions have been written by some of the most eminent researchers in this field of mathematical programming. The Ebook is considered essential for researchers and students in this field.

  2. Symmetric vectors and algebraic classification

    International Nuclear Information System (INIS)

    Leibowitz, E.

    1980-01-01

    The concept of symmetric vector field in Riemannian manifolds, which arises in the study of relativistic cosmological models, is analyzed. Symmetric vectors are tied up with the algebraic properties of the manifold curvature. A procedure for generating a congruence of symmetric fields out of a given pair is outlined. The case of a three-dimensional manifold of constant curvature (''isotropic universe'') is studied in detail, with all its symmetric vector fields being explicitly constructed

  3. Comparative Genomics Reveals the Origins and Diversity of Arthropod Immune Systems.

    Science.gov (United States)

    Palmer, William J; Jiggins, Francis M

    2015-08-01

    Insects are an important model for the study of innate immune systems, but remarkably little is known about the immune system of other arthropod groups despite their importance as disease vectors, pests, and components of biological diversity. Using comparative genomics, we have characterized the immune system of all the major groups of arthropods beyond insects for the first time--studying five chelicerates, a myriapod, and a crustacean. We found clear traces of an ancient origin of innate immunity, with some arthropods having Toll-like receptors and C3-complement factors that are more closely related in sequence or structure to vertebrates than other arthropods. Across the arthropods some components of the immune system, such as the Toll signaling pathway, are highly conserved. However, there is also remarkable diversity. The chelicerates apparently lack the Imd signaling pathway and beta-1,3 glucan binding proteins--a key class of pathogen recognition receptors. Many genes have large copy number variation across species, and this may sometimes be accompanied by changes in function. For example, we find that peptidoglycan recognition proteins have frequently lost their catalytic activity and switch between secreted and intracellular forms. We also find that there has been widespread and extensive duplication of the cellular immune receptor Dscam (Down syndrome cell adhesion molecule), which may be an alternative way to generate the high diversity produced by alternative splicing in insects. In the antiviral short interfering RNAi pathway Argonaute 2 evolves rapidly and is frequently duplicated, with a highly variable copy number. Our results provide a detailed analysis of the immune systems of several important groups of animals for the first time and lay the foundations for functional work on these groups. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  4. [The Importance of Vector Management for Prevention of Hospital Infections].

    Science.gov (United States)

    Çetin, Hüseyin

    2015-09-01

    Many researches show that cockroaches, ants, some other arthropods and also rodents in hospitals, can act as potential vectors of medically important bacteria, fungi and parasites. The results of microbiological studies show that these animals play a significant role in the epidemiology of hospital infections. These vectors may be found inside of the kitchens, patient rooms, toilets, medicine stores, canteen and wards in health care environments. The importance of vector control in order to prevent the spread of nosocomial infections in healthcare facilities was discussed in this paper. This study also gives information on integrated control methods for vectors in hospitals.

  5. Charmless Hadronic B Decays into Vector, Axial Vector and Tensor Final States at BaBar

    International Nuclear Information System (INIS)

    Gandini, Paolo

    2012-01-01

    We present experimental measurements of branching fraction and longitudinal polarization fraction in charmless hadronic B decays into vector, axial vector and tensor final states with the final dataset of BABAR. Measurements of such kind of decays are a powerful tool both to test the Standard Model and search possible sources of new physics. In this document we present a short review of the last experimental results at BABAR concerning charmless quasi two-body decays in final states containing particles with spin 1 or spin 2 and different parities. This kind of decays has received considerable theoretical interest in the last few years and this particular attention has led to interesting experimental results at the current b-factories. In fact, the study of longitudinal polarization fraction f L in charmless B decays to vector vector (VV), vector axial-vector (VA) and axial-vector axial-vector (AA) mesons provides information on the underlying helicity structure of the decay mechanism. Naive helicity conservation arguments predict a dominant longitudinal polarization fraction f L ∼ 1 for both tree and penguin dominated decays and this pattern seems to be confirmed by tree-dominated B → ρρ and B + → (Omega)ρ + decays. Other penguin dominated decays, instead, show a different behavior: the measured value of f L ∼ 0.5 in B → φK* decays is in contrast with naive Standard Model (SM) calculations. Several solutions have been proposed such as the introduction of non-factorizable terms and penguin-annihilation amplitudes, while other explanations invoke new physics. New modes have been investigated to shed more light on the problem.

  6. The immune response to sand fly salivary proteins and its influence on Leishmania immunity

    Directory of Open Access Journals (Sweden)

    Regis eGomes

    2012-05-01

    Full Text Available Leishmaniasis is a vector-borne disease transmitted by bites of phlebotomine sand flies. During Leishmania transmission, sand fly saliva is co-inoculated with parasites into the skin of the mammalian host. Sand fly saliva consists of roughly thirty different salivary proteins, many with known roles linked to blood feeding facilitation. Apart from the anti-hemostatic capacity of saliva, several sand fly salivary proteins have been shown to be immunogenic upon multiple contacts with a mammalian host. Immunization with single immunogenic salivary proteins or exposure to uninfected bites can produce protective immune responses against leishmaniasis. These sand fly salivary proteins induce cellular immune responses and/or antibodies. Antibodies to saliva are not required for protection in a mouse model against leishmaniasis. A strong body of evidence points to the role for saliva-specific T cells producing IFN-γ in the form of a delayed-type hypersensitivity reaction at the bite site as the main protective response. Herein, we review immunity to sand fly salivary proteins in the context of its vector-parasite-host combinations and vaccine potential, as well as some recent advances to shed light on the mechanism of how an immune response to sand fly saliva protects against leishmaniasis.

  7. Vector continued fractions using a generalized inverse

    International Nuclear Information System (INIS)

    Haydock, Roger; Nex, C M M; Wexler, Geoffrey

    2004-01-01

    A real vector space combined with an inverse (involution) for vectors is sufficient to define a vector continued fraction whose parameters consist of vector shifts and changes of scale. The choice of sign for different components of the vector inverse permits construction of vector analogues of the Jacobi continued fraction. These vector Jacobi fractions are related to vector and scalar-valued polynomial functions of the vectors, which satisfy recurrence relations similar to those of orthogonal polynomials. The vector Jacobi fraction has strong convergence properties which are demonstrated analytically, and illustrated numerically

  8. Linear ubiquitination in immunity.

    Science.gov (United States)

    Shimizu, Yutaka; Taraborrelli, Lucia; Walczak, Henning

    2015-07-01

    Linear ubiquitination is a post-translational protein modification recently discovered to be crucial for innate and adaptive immune signaling. The function of linear ubiquitin chains is regulated at multiple levels: generation, recognition, and removal. These chains are generated by the linear ubiquitin chain assembly complex (LUBAC), the only known ubiquitin E3 capable of forming the linear ubiquitin linkage de novo. LUBAC is not only relevant for activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) in various signaling pathways, but importantly, it also regulates cell death downstream of immune receptors capable of inducing this response. Recognition of the linear ubiquitin linkage is specifically mediated by certain ubiquitin receptors, which is crucial for translation into the intended signaling outputs. LUBAC deficiency results in attenuated gene activation and increased cell death, causing pathologic conditions in both, mice, and humans. Removal of ubiquitin chains is mediated by deubiquitinases (DUBs). Two of them, OTULIN and CYLD, are constitutively associated with LUBAC. Here, we review the current knowledge on linear ubiquitination in immune signaling pathways and the biochemical mechanisms as to how linear polyubiquitin exerts its functions distinctly from those of other ubiquitin linkage types. © 2015 The Authors. Immunological Reviews Published by John Wiley & Sons Ltd.

  9. Evaluation of Traditional Medicines III: The Mechanism of Immune ...

    African Journals Online (AJOL)

    These results show that PHELA did not stimulate Th1 cytokines of a normal immune system but stimulated them when the immune system was suppressed by cyclosporine-A. In conclusion, PHELA is an immune-stimulant to a compromised immune system. Key words: PHELA, traditional medicine, cyclosporine-A, cytokines, ...

  10. Evaluation of lung immunity in chimpanzees

    International Nuclear Information System (INIS)

    Bice, D.E.; Harris, D.L.; Muggenburg, B.A.; Bowen, J.A.

    1980-01-01

    The effects of inhaled pollutants on the immune defenses in the lung can be studied in several animal species. To assure that the data obtained can be extrapolated to man, it is essential that the development of lung immunity is similar in the experimental animal selected and in humans. Because of the similarity of immune responses in chimpanzees and in humans, the development of immunity in the chimpanzee after lung immunization was evaluated. The results from the chimpanzees were qualitatively the same as those from previous studies in which single lung lobes of dogs were immunized. It was concluded that immunotoxicology data obtained in dogs can be used to estimate the effects of inhaled pollutants on the immune defense mechanism in the human lung

  11. Vector-Interaction-Enhanced Bag Model

    Science.gov (United States)

    Cierniak, Mateusz; Klähn, Thomas; Fischer, Tobias; Bastian, Niels-Uwe

    2018-02-01

    A commonly applied quark matter model in astrophysics is the thermodynamic bag model (tdBAG). The original MIT bag model approximates the effect of quark confinement, but does not explicitly account for the breaking of chiral symmetry, an important property of Quantum Chromodynamics (QCD). It further ignores vector repulsion. The vector-interaction-enhanced bag model (vBag) improves the tdBAG approach by accounting for both dynamical chiral symmetry breaking and repulsive vector interactions. The latter is of particular importance to studies of dense matter in beta-equilibriumto explain the two solar mass maximum mass constraint for neutron stars. The model is motivated by analyses of QCD based Dyson-Schwinger equations (DSE), assuming a simple quark-quark contact interaction. Here, we focus on the study of hybrid neutron star properties resulting from the application of vBag and will discuss possible extensions.

  12. Axisymmetric thrust-vectoring nozzle performance prediction

    International Nuclear Information System (INIS)

    Wilson, E. A.; Adler, D.; Bar-Yoseph, P.Z

    1998-01-01

    Throat-hinged geometrically variable converging-diverging thrust-vectoring nozzles directly affect the jet flow geometry and rotation angle at the nozzle exit as a function of the nozzle geometry, the nozzle pressure ratio and flight velocity. The consideration of nozzle divergence in the effective-geometric nozzle relation is theoretically considered here for the first time. In this study, an explicit calculation procedure is presented as a function of nozzle geometry at constant nozzle pressure ratio, zero velocity and altitude, and compared with experimental results in a civil thrust-vectoring scenario. This procedure may be used in dynamic thrust-vectoring nozzle design performance predictions or analysis for civil and military nozzles as well as in the definition of initial jet flow conditions in future numerical VSTOL/TV jet performance studies

  13. Reversible Vector Ratchet Effect in Skyrmion Systems

    Science.gov (United States)

    Ma, Xiaoyu; Reichhardt, Charles; Reichhardt, Cynthia

    Magnetic skyrmions are topological non-trivial spin textures found in several magnetic materials. Since their motion can be controlled using ultralow current densities, skyrmions are appealing for potential applications in spintronics as information carriers and processing devices. In this work, we studied the collective transport properties of driven skyrmions based on a particle-like model with molecular dynamics (MD) simulation. Our results show that ac driven skyrmions interacting with an asymmetric substrate provide a realization of a new class of ratchet system, which we call a vector ratchet, that arises due to the effect of the Magnus term on the skyrmion dynamics. In a vector ratchet, the dc motion induced by the ac drive can be described as a vector that can be rotated up to 360 degrees relative to the substrate asymmetry direction. This could represent a new method for controlling skyrmion motion for spintronic applications.

  14. Safety and immunogenicity of adenovirus-vectored near-consensus HIV type 1 clade B gag vaccines in healthy adults.

    Science.gov (United States)

    Harro, Clayton D; Robertson, Michael N; Lally, Michelle A; O'Neill, Lori D; Edupuganti, Srilatha; Goepfert, Paul A; Mulligan, Mark J; Priddy, Frances H; Dubey, Sheri A; Kierstead, Lisa S; Sun, Xiao; Casimiro, Danilo R; DiNubile, Mark J; Shiver, John W; Leavitt, Randi Y; Mehrotra, Devan V

    2009-01-01

    Vaccines inducing pathogen-specific cell-mediated immunity are being developed using attenuated adenoviral (Ad) vectors. We report the results of two independent Phase I trials of similar replication-deficient Ad5 vaccines containing a near-consensus HIV-1 clade B gag transgene. Healthy HIV-uninfected adults were enrolled in two separate, multicenter, dose-escalating, blinded, placebo-controlled studies to assess the safety and immunogenicity of a three-dose homologous regimen of Ad5 and MRKAd5 HIV-1 gag vaccines given on day 1, week 4, and week 26. Adverse events were collected for 29 days following each intradeltoid injection. The primary immunogenicity endpoint was the proportion of subjects with a positive unfractionated Gag-specific IFN-gamma ELISPOT response measured 4 weeks after the last dose (week 30). Analyses were performed after combining data for each dose group from both protocols, stratifying by baseline Ad5 titers. Overall, 252 subjects were randomized to receive either vaccine or placebo, including 229 subjects (91%) who completed the study through week 30. Tolerability and immunogenicity did not appear to differ between the Ad5 and MRKAd5 vaccines. The frequency of injection-site reactions was dose dependent. Systemic adverse events were also dose dependent and more frequent in subjects with baseline Ad5 titers or =200, especially after the first dose. The percent of ELISPOT responders and the ELISPOT geometric means overall were significantly higher for all four vaccine doses studied compared to placebo, and were generally higher in vaccine recipients with baseline Ad5 titers or = 200. Ad5 titers increased after vaccination in a dose-dependent fashion. Both Ad5-vectored HIV-1 vaccines were generally well tolerated and induced cell-mediated immune responses against HIV Gag-peptides in the majority of healthy adults with baseline Ad5 titers vaccine-induced immunity to the Ad5 vector may dampen the CMI response to HIV Gag.

  15. Variable ordering structures in vector optimization

    CERN Document Server

    Eichfelder, Gabriele

    2014-01-01

    This book provides an introduction to vector optimization with variable ordering structures, i.e., to optimization problems with a vector-valued objective function where the elements in the objective space are compared based on a variable ordering structure: instead of a partial ordering defined by a convex cone, we see a whole family of convex cones, one attached to each element of the objective space. The book starts by presenting several applications that have recently sparked new interest in these optimization problems, and goes on to discuss fundamentals and important results on a wide ra

  16. Genetic modification of hematopoietic cells using retroviral and lentiviral vectors: safety considerations for vector design and delivery into target cells.

    Science.gov (United States)

    Dropulic, Boro

    2005-07-01

    The recent development of leukemia in three patients following retroviral vector gene transfer in hematopoietic stem cells, resulting in the death of one patient, has raised safety concerns for the use of integrating gene transfer vectors for human gene therapy. This review discusses these serious adverse events from the perspective of whether restrictions on vector design and vector-modified target cells are warranted at this time. A case is made against presently establishing specific restrictions for vector design and transduced cells; rather, their safety should be ascertained by empiric evaluation in appropriate preclinical models on a case-by-case basis. Such preclinical data, coupled with proper informed patient consent and a risk-benefit ratio analysis, provide the best available prospective evaluation of gene transfer vectors prior to their translation into the clinic.

  17. DNA immunization with a herpes simplex virus 2 bacterial artificial chromosome

    International Nuclear Information System (INIS)

    Meseda, Clement A.; Schmeisser, Falko; Pedersen, Robin; Woerner, Amy; Weir, Jerry P.

    2004-01-01

    Construction of a herpes simplex virus 2 (HSV-2) bacterial artificial chromosome (BAC) is described. BAC vector sequences were inserted into the thymidine kinase gene of HSV-2 by homologous recombination. DNA from cells infected with the resulting recombinant virus was transformed into E. coli, and colonies containing the HSV-2 BAC (HSV2-BAC) were isolated and analyzed for the expected genotype. HSV2-BAC DNA was infectious when transfected back into mammalian cells and the resulting virus was thymidine kinase negative. When used to immunize mice, the HSV2-BAC DNA elicited a strong HSV-2 specific antibody response that was equal to or greater than live virus immunization. Further, HSV2-BAC immunization was protective when animals were challenged with a lethal dose of virus. The utility of the HSV2-BAC for construction of recombinant virus genomes was demonstrated by elimination of the HSV-2 glycoprotein D (gD) gene. A recombinant HSV-2 BAC with the gD gene deleted was isolated and shown to be incapable of producing infectious virus following transfection unless an HSV gD gene was expressed in a complementing cell line. Immunization of mice with the HSV2 gD-BAC also elicited an HSV-2 specific antibody response and was protective. The results demonstrate the feasibility of DNA immunization with HSV-2 bacterial artificial chromosomes for replicating and nonreplicating candidate HSV-2 vaccines, as well as the utility of BAC technology for construction and maintenance of novel HSV-2 vaccines. The results further suggest that such technology will be a powerful tool for dissecting the immune response to HSV-2

  18. Chameleon vector bosons

    International Nuclear Information System (INIS)

    Nelson, Ann E.; Walsh, Jonathan

    2008-01-01

    We show that for a force mediated by a vector particle coupled to a conserved U(1) charge, the apparent range and strength can depend on the size and density of the source, and the proximity to other sources. This chameleon effect is due to screening from a light charged scalar. Such screening can weaken astrophysical constraints on new gauge bosons. As an example we consider the constraints on chameleonic gauged B-L. We show that although Casimir measurements greatly constrain any B-L force much stronger than gravity with range longer than 0.1 μm, there remains an experimental window for a long-range chameleonic B-L force. Such a force could be much stronger than gravity, and long or infinite range in vacuum, but have an effective range near the surface of the earth which is less than a micron.

  19. Architecture and Vector Control

    DEFF Research Database (Denmark)

    von Seidlein, Lorenz; Knols, Bart GJ; Kirby, Matthew

    2012-01-01

    , closing of eaves and insecticide treated bednets. All of these interventions have an effect on the indoor climate. Temperature, humidity and airflow are critical for a comfortable climate. Air-conditioning and fans allow us to control indoor climate, but many people in Africa and Asia who carry the brunt...... of vector-borne diseases have no access to electricity. Many houses in the hot, humid regions of Asia have adapted to the environment, they are built of porous materials and are elevated on stilts features which allow a comfortable climate even in the presence of bednets and screens. In contrast, many...... buildings in Africa and Asia in respect to their indoor climate characteristics and finally, show how state-of-the-art 3D modelling can predict climate characteristics and help to optimize buildings....

  20. Development of immune organs and functioning in humans and test animals: Implications for immune intervention studies.

    Science.gov (United States)

    Kuper, C Frieke; van Bilsen, Jolanda; Cnossen, Hilde; Houben, Geert; Garthoff, Jossie; Wolterbeek, Andre

    2016-09-01

    A healthy immune status is mostly determined during early life stages and many immune-related diseases may find their origin in utero and the first years of life. Therefore, immune health optimization may be most effective during early life. This review is an inventory of immune organ maturation events in relation to developmental timeframes in minipig, rat, mouse and human. It is concluded that time windows of immune organ development in rodents can be translated to human, but minipig reflects the human timeframes better; however the lack of prenatal maternal-fetal immune interaction in minipig may cause less responsiveness to prenatal intervention. It is too early to conclude which immune parameters are most appropriate, because there are not enough comparative immune parameters. Filling these gaps will increase the predictability of results observed in experimental animals, and guide future intervention studies by assessing relevant parameters in the right corresponding developmental time frames. Copyright © 2016 Elsevier Inc. All rights reserved.