WorldWideScience

Sample records for adenoviral vector safety

  1. Genetically engineering adenoviral vectors for gene therapy.

    Science.gov (United States)

    Coughlan, Lynda

    2014-01-01

    Adenoviral (Ad) vectors are commonly used for various gene therapy applications. Significant advances in the genetic engineering of Ad vectors in recent years has highlighted their potential for the treatment of metastatic disease. There are several methods to genetically modify the Ad genome to incorporate retargeting peptides which will redirect the natural tropism of the viruses, including homologous recombination in bacteria or yeast. However, homologous recombination in yeast is highly efficient and can be achieved without the need for extensive cloning strategies. In addition, the method does not rely on the presence of unique restriction sites within the Ad genome and the reagents required for this method are widely available and inexpensive. Large plasmids containing the entire adenoviral genome (~36 kbp) can be modified within Saccharomyces cerevisiae yeast and genomes easily rescued in Escherichia coli hosts for analysis or amplification. A method for two-step homologous recombination in yeast is described in this chapter.

  2. Endothelial Cell-Targeted Adenoviral Vector for Suppressing Breast Malignancies

    National Research Council Canada - National Science Library

    Huang, Shuang

    2004-01-01

    .... Our proposal is designed to develop an endothelial cell-targeted adenoviral vector and to use the targeted vector to express high levels of anticancer therapeutic genes in the sites of angiogenenic...

  3. Biological activity and safety of adenoviral vector-expressed wild-type p53 after intratumoral injection in melanoma and breast cancer patients with p53-overexpressing tumors

    NARCIS (Netherlands)

    Dummer, R; Bergh, J; Karlsson, Y; Horovitz, JA; Mulder, NH; Huinin, DT; Burg, G; Hofbauer, G; Osanto, S

    p53 mutations are common genetic alterations in human cancer. Gene transfer of a wild-type (wt) p53 gene reverses the loss of normal p53 function in vitro and in vivo. A phase I dose escalation study of single intratumoral (i.t.) injection of a replication-defective adenoviral expression vector

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

    Science.gov (United States)

    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. Targeted cancer gene therapy : the flexibility of adenoviral gene therapy vectors

    NARCIS (Netherlands)

    Rots, MG; Curiel, DT; Gerritsen, WR; Haisma, HJ

    2003-01-01

    Recombinant adenoviral vectors are promising reagents for therapeutic interventions in humans, including gene therapy for biologically complex diseases like cancer and cardiovascular diseases. In this regard, the major advantage of adenoviral vectors is their superior in vivo gene transfer

  6. Adenoviral vectors as genome editing tools : repairing defective DMD alleles

    NARCIS (Netherlands)

    Maggio, Ignazio

    2016-01-01

    Adenoviral vectors (AdVs) constitute powerful gene delivery vehicles. However, so far, their potential for genome editing has not been extensively investigated. By tailoring AdVs as carriers of designer nucleases and donor DNA sequences, the research presented in this thesis expands the utility of

  7. Modification of liposomal concentration in liposome/adenoviral complexes allows significant protection of adenoviral vectors from neutralising antibody, in vitro.

    Science.gov (United States)

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

    2005-06-01

    Adenoviral vectors have been commonly used in gene therapy protocols, however 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 efficacy of complexing liposomes to adenovirus for the protection of the adenovirus from neutralising antibodies in an in vitro setting. Dimethyldioctadecylammonium bromide (DDAB)-dioleoyl-l-phosphatidylethanolamine (DOPE) liposomes were bound at varying concentrations to adenovirus to form AL complexes and tested these complexes' ability to prevent adenoviral neutralisation. It is shown that by increasing the concentration of liposomes in the adenoviral-liposome (AL) complexes we can increase the level of immuno-shielding afforded the adenovirus. It is also shown that the increase in liposomal concentration may lead to drawbacks such as increased cytotoxicity and reductions in expression levels.

  8. 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.

  9. 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.

  10. An Adenoviral Vector Based Vaccine for Rhodococcus equi.

    Directory of Open Access Journals (Sweden)

    Carla Giles

    Full Text Available Rhodococcus equi is a respiratory pathogen which primarily infects foals and is endemic on farms around the world with 50% mortality and 80% morbidity in affected foals. Unless detected early and treated appropriately the disease can be fatal. Currently, there is no vaccine available to prevent this disease. For decades researchers have endeavoured to develop an effective vaccine to no avail. In this study a novel human adenoviral vector vaccine for R. equi was developed and tested in the mouse model. This vaccine generated a strong antibody and cytokine response and clearance of R. equi was demonstrated following challenge. These results show that this vaccine could potentially be developed further for use as a vaccine to prevent R. equi disease in foals.

  11. Fetal muscle gene transfer is not enhanced by an RGD capsid modification to high-capacity adenoviral vectors.

    Science.gov (United States)

    Bilbao, R; Reay, D P; Hughes, T; Biermann, V; Volpers, C; Goldberg, L; Bergelson, J; Kochanek, S; Clemens, P R

    2003-10-01

    High levels of alpha(v) integrin expression by fetal muscle suggested that vector re-targeting to integrins could enhance adenoviral vector-mediated transduction, thereby increasing safety and efficacy of muscle gene transfer in utero. High-capacity adenoviral (HC-Ad) vectors modified by an Arg-Gly-Asp (RGD) peptide motif in the HI loop of the adenoviral fiber (RGD-HC-Ad) have demonstrated efficient gene transfer through binding to alpha(v) integrins. To test integrin targeting of HC-Ad vectors for fetal muscle gene transfer, we compared unmodified and RGD-modified HC-Ad vectors. In vivo, unmodified HC-Ad vector transduced fetal mouse muscle with four-fold higher efficiency compared to RGD-HC-Ad vector. Confirming that the difference was due to muscle cell autonomous factors and not mechanical barriers, transduction of primary myogenic cells isolated from murine fetal muscle in vitro demonstrated a three-fold better transduction by HC-Ad vector than by RGD-HC-Ad vector. We hypothesized that the high expression level of coxsackievirus and adenovirus receptor (CAR), demonstrated in fetal muscle cells both in vitro and in vivo, was the crucial variable influencing the relative transduction efficiencies of HC-Ad and RGD-HC-Ad vectors. To explore this further, we studied transduction by HC-Ad and RGD-HC-Ad vectors in paired cell lines that expressed alpha(v) integrins and differed only by the presence or absence of CAR expression. The results increase our understanding of factors that will be important for retargeting HC-Ad vectors to enhance gene transfer to fetal muscle.

  12. Quantification of residual host cell DNA in adenoviral vectors produced on PER.C6 cells

    NARCIS (Netherlands)

    Gijsbers, Linda; Koel, Björn; Weggeman, Miranda; Goudsmit, Jaap; Havenga, Menzo; Marzio, Giuseppe

    2005-01-01

    Recombinant adenoviral vectors for gene therapy and vaccination are routinely prepared on cultures of immortalized cells, allowing the production of vector batches of high titer and consistent quality. Quantification of residual DNA from the producing cell line is part of the purity tests for

  13. Targeted Adenoviral Vector Demonstrates Enhanced Efficacy for In Vivo Gene Therapy of Uterine Leiomyoma.

    Science.gov (United States)

    Abdelaziz, Mohamed; Sherif, Lotfy; ElKhiary, Mostafa; Nair, Sanjeeta; Shalaby, Shahinaz; Mohamed, Sara; Eziba, Noura; El-Lakany, Mohamed; Curiel, David; Ismail, Nahed; Diamond, Michael P; Al-Hendy, Ayman

    2016-04-01

    Gene therapy is a potentially effective non-surgical approach for the treatment of uterine leiomyoma. We demonstrated that targeted adenovirus vector, Ad-SSTR-RGD-TK/GCV, was highly effective in selectively inducing apoptosis and inhibiting proliferation of human leiomyoma cells in vitro while sparing normal myometrial cells. An in-vivo study, to compare efficacy and safety of modified adenovirus vector Ad-SSTR-RGD-TK/GCV versus untargeted vector for treatment of leiomyoma. Female nude mice were implanted with rat leiomyoma cells subcutaneously. Then mice were randomized into three groups. Group 1 received Ad-LacZ (marker gene), Group 2 received untargeted Ad-TK, and Group 3 received the targeted Ad-SSTR-RGD-TK. Tumors were measured weekly for 4 weeks. Then mice were sacrificed and tissue samples were collected. Evaluation of markers of apoptosis, proliferation, extracellular matrix, and angiogenesis was performed using Western Blot & Immunohistochemistry. Statistical analysis was done using ANOVA. Dissemination of adenovirus was assessed by PCR. In comparison with the untargeted vector, the targeted adenoviral vector significantly shrank leiomyoma size (P leiomyoma lesions with both targeted and untargeted adenovirus. Targeted adenovirus, effectively reduces tumor size in leiomyoma without dissemination to other organs. Further evaluation of this localized targeted strategy for gene therapy is needed in appropriate preclinical humanoid animal models in preparation for a future pilot human trial. © The Author(s) 2016.

  14. Suppression of inflammation by dexamethasone prolongs adenoviral vector-mediated transgene expression in the facial nucleus of the rat

    NARCIS (Netherlands)

    Hermens, W.T.J.M.C.; Verhaagen, J

    1998-01-01

    Adenoviral vector directed gene transfer to rat facial motoneurons occurs efficiently following intra-parenchymal injection of relatively high dosages (> or =10(7) pfu per injection) of a prototype first generation adenoviral vector. However, high level of transgene expression, as observed during

  15. Transient gene transfer to neurons and glia : analysis of adenoviral vector performance in the CNS and PNS

    NARCIS (Netherlands)

    Hermens, W.T.J.M.C.; Giger, Roman J; Holtmaat, Anthony J D G; Dijkhuizen, Paul A; Houweling, D A; Verhaagen, J

    In this paper a detailed protocol is presented for neuroscientists planning to start work on first generation recombinant adenoviral vectors as gene transfer agents for the nervous system. The performance of a prototype adenoviral vector encoding the bacterial lacZ gene as a reporter was studied,

  16. Efficient adenoviral vector directed expression of a foreign gene to neurons and sustentacular cells in the mouse olfactory neuroepithelium

    NARCIS (Netherlands)

    Gispen, W.H.; Holtmaat, A.J.G.D.; Hermens, W.T.J.M.C.; Oestreicher, A.B.; Kaplitt, M.G.; Verhaagen, J.

    1996-01-01

    Replication deficient recombinant adenoviral vectors are efficient gene transfer agents for postmitotic cells, including neurons and glial cells. In this paper we have examined the effectiveness of adenoviral vector-mediated gene transfer to the olfactory epithelium of adult mice. We show that

  17. Efficient adenoviral vector-directed expression of a foreign gene to neurons and sustentacular cells in the mouse olfactory neuroepithelium

    NARCIS (Netherlands)

    Holtmaat, Anthony J D G; Hermens, W.T.J.M.C.; Oestreicher, A B; Gispen, Willem Hendrik; Kaplitt, M G; Verhaagen, J

    1996-01-01

    Replication deficient recombinant adenoviral vectors are efficient gene transfer agents for postmitotic cells, including neurons and glial cells. In this paper we have examined the effectiveness of adenoviral vector-mediated gene transfer to the olfactory epithelium of adult mice. We show that

  18. Adenoviral vector-mediated gene transfer and neurotransplantation : possibilities and limitations in grafting of the fetal rat suprachiasmatic nucleus

    NARCIS (Netherlands)

    van Esseveldt, K E; Liu, R.; Hermens, W.T.J.M.C.; Verhaagen, J; Boer, G J

    Several studies have reported on the use of primary neural cells transduced by adenoviral vectors as donor cells in neurotransplantation. In the present investigation, we examined whether adenoviral vector-mediated gene transfer could be used to introduce and express a foreign gene in solid neural

  19. Safety and immunogenicity of an HIV adenoviral vector boost after DNA plasmid vaccine prime by route of administration: a randomized clinical trial.

    Directory of Open Access Journals (Sweden)

    Beryl A Koblin

    Full Text Available In the development of HIV vaccines, improving immunogenicity while maintaining safety is critical. Route of administration can be an important factor.This multicenter, open-label, randomized trial, HVTN 069, compared routes of administration on safety and immunogenicity of a DNA vaccine prime given intramuscularly at 0, 1 and 2 months and a recombinant replication-defective adenovirus type 5 (rAd5 vaccine boost given at 6 months by intramuscular (IM, intradermal (ID, or subcutaneous (SC route. Randomization was computer-generated by a central data management center; participants and staff were not blinded to group assignment. The outcomes were vaccine reactogenicity and humoral and cellular immunogenicity. Ninety healthy, HIV-1 uninfected adults in the US and Peru, aged 18-50 were enrolled and randomized. Due to the results of the Step Study, injections with rAd5 vaccine were halted; thus 61 received the booster dose of rAd5 vaccine (IM: 20; ID:21; SC:20. After the rAd5 boost, significant differences by study arm were found in severity of headache, pain and erythema/induration. Immune responses (binding and neutralizing antibodies, IFN-γ ELISpot HIV-specific responses and CD4+ and CD8+ T-cell responses by ICS at four weeks after the rAd5 booster were not significantly different by administration route of the rAd5 vaccine boost (Binding antibody responses: IM: 66.7%; ID: 70.0%; SC: 77.8%; neutralizing antibody responses: IM: 11.1%; ID: 0.0%; SC 16.7%; ELISpot responses: IM: 46.7%; ID: 35.3%; SC: 44.4%; CD4+ T-cell responses: IM: 29.4%; ID: 20.0%; SC: 35.3%; CD8+ T-cell responses: IM: 29.4%; ID: 16.7%; SC: 50.0%.This study was limited by the reduced sample size. The higher frequency of local reactions after ID and SC administration and the lack of sufficient evidence to show that there were any differences in immunogenicity by route of administration do not support changing route of administration for the rAd5 boost.ClinicalTrials.gov NCT00384787.

  20. Efficient Gene Delivery to Pig Airway Epithelia and Submucosal Glands Using Helper-Dependent Adenoviral Vectors

    Directory of Open Access Journals (Sweden)

    Huibi Cao

    2013-01-01

    Full Text Available Airway gene delivery is a promising strategy to treat patients with life-threatening lung diseases such as cystic fibrosis (CF. However, this strategy has to be evaluated in large animal preclinical studies in order to translate it to human applications. Because of anatomic and physiological similarities between the human and pig lungs, we utilized pig as a large animal model to examine the safety and efficiency of airway gene delivery with helper-dependent adenoviral vectors. Helper-dependent vectors carrying human CFTR or reporter gene LacZ were aerosolized intratracheally into pigs under bronchoscopic guidance. We found that the LacZ reporter and hCFTR transgene products were efficiently expressed in lung airway epithelial cells. The transgene vectors with this delivery can also reach to submucosal glands. Moreover, the hCFTR transgene protein localized to the apical membrane of both ciliated and nonciliated epithelial cells, mirroring the location of wild-type CF transmembrane conductance regulator (CFTR. Aerosol delivery procedure was well tolerated by pigs without showing systemic toxicity based on the limited number of pigs tested. These results provide important insights into developing clinical strategies for human CF lung gene therapy.

  1. Gene Therapy with Helper-Dependent Adenoviral Vectors: Current Advances and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Philip Ng

    2010-09-01

    Full Text Available Recombinant Adenoviral vectors represent one of the best gene transfer platforms due to their ability to efficiently transduce a wide range of quiescent and proliferating cell types from various tissues and species. The activation of an adaptive immune response against the transduced cells is one of the major drawbacks of first generation Adenovirus vectors and has been overcome by the latest generation of recombinant Adenovirus, the Helper-Dependent Adenoviral (HDAd vectors. HDAds have innovative features including the complete absence of viral coding sequences and the ability to mediate high level transgene expression with negligible chronic toxicity. This review summarizes the many aspects of HDAd biology and structure with a major focus on in vivo gene therapy application and with an emphasis on the unsolved issues that these vectors still presents toward clinical application.

  2. Efficient gene transfer into lymphoma cells using adenoviral vectors combined with lipofection.

    Science.gov (United States)

    Buttgereit, P; Weineck, S; Röpke, G; Märten, A; Brand, K; Heinicke, T; Caselmann, W H; Huhn, D; Schmidt-Wolf, I G

    2000-08-01

    Tumor cells, such as lymphoma cells, are possible targets for gene therapy. In general, gene therapeutic approaches require efficient gene transfer to host cells and sufficient transgene expression. However, lymphoma cells previously have been demonstrated to be resistant to most of the currently available gene transfer methods. The aim of this study was to analyze various methods for transfection of lymphoma cells and to improve the efficiency of gene delivery. In accordance with previously published reports, lymphoma cells were demonstrated to be resistant to lipofection and electroporation. In contrast, we present an improved adenoviral protocol leading to highly efficient gene transfer to lymphoma cell lines derived from B cells as well as primary lymphoma cells being achieved with an adenoviral vector system encoding the beta-galactosidase protein. At a multiplicity of infection of 200, up to 100% of Daudi cells and Raji cells and 70% of OCI-Ly8-LAM53 cells could be transfected. Even at high adenoviral concentrations, no marked toxicity was observed, and the growth characteristics of the lymphoma cell lines were not impaired. The transfection rates in primary cells derived from six patients with non-Hodgkin's lymphoma were 30-65%, respectively. Transfection efficiency could be further increased by addition of cationic liposomes to adenoviral gene transfer. Furthermore, we examined the expression of the Coxsackie-adenoviral receptor (CAR) and the integrin receptors on the lymphoma cell surface. Flow cytometric analysis showed that 88% of Daudi cells, 69% of Raji cells, and 6% of OCI-Ly8-LAM53 cells expressed CAR on the cell surface. According to our data, adenoviral infection of lymphoma cells seems to be mediated by CAR. In contrast, integrin receptors are unlikely to play a major role, because lymphoma cells were negative for alphavbeta3-integrins and negative for alphavbeta5-integrins. In conclusion, this study demonstrates that B-lymphoma cell lines and

  3. Advances and Future Challenges in Recombinant Adenoviral Vectored H5N1 Influenza Vaccines

    Directory of Open Access Journals (Sweden)

    Jianfeng Zhang

    2012-11-01

    Full Text Available The emergence of a highly pathogenic avian influenza virus H5N1 has increased the potential for a new pandemic to occur. This event highlights the necessity for developing a new generation of influenza vaccines to counteract influenza disease. These vaccines must be manufactured for mass immunization of humans in a timely manner. Poultry should be included in this policy, since persistent infected flocks are the major source of avian influenza for human infections. Recombinant adenoviral vectored H5N1 vaccines are an attractive alternative to the currently licensed influenza vaccines. This class of vaccines induces a broadly protective immunity against antigenically distinct H5N1, can be manufactured rapidly, and may allow mass immunization of human and poultry. Recombinant adenoviral vectors derived from both human and non-human adenoviruses are currently being investigated and appear promising both in nonclinical and clinical studies. This review will highlight the current status of various adenoviral vectored H5N1 vaccines and will outline novel approaches for the future.

  4. 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.

  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. Purification of adenoviral vectors by combined anion exchange and gel filtration chromatography.

    Science.gov (United States)

    Eglon, Marc N; Duffy, Aoife M; O'Brien, Timothy; Strappe, Padraig M

    2009-11-01

    Adenoviral vectors are used extensively in human gene therapy trials and in vaccine development. Large-scale GMP production requires a downstream purification process, and liquid chromatography is emerging as the most powerful mode of purification, enabling the production of vectors at a clinically relevant scale and quality. The present study describes the development of a two-step high-performance liquid chromatography (HPLC) process combining anion exchange (AIEX) and gel filtration (GF) in comparison with the caesium chloride density gradient method. HEK-293 cells were cultured in ten-layer CellStacks() and infected with 10 pfu/cell of adenoviral vector expressing green fluorescent protein (Ad5-GFP). Cell-bound virus was harvested and benzonase added to digest DNA, crude lysate was clarified by centrifugation and filtration prior to HPLC. Chromatography fractions were added to HEK-293 cells and GFP expression measured using a fluorescent plate reader. Using AIEX then GF resulted in an adenoviral vector with purity comparable to Ad5-GFP purified by CsCl, whereas the reverse process (GF-AIEX) showed a reduced purity by electrophoresis and required further buffer exchange of the product. The optimal process (AIEX-GF) resulted in a vector yield of 2.3 x 10(7) pfu/cm(2) of cell culture harvested compared to 3.3 x 10(7) pfu/cm(2) for CsCl. The process recovery for the HPLC process was 36% compared to 27.5% for CsCl and total virion to infectious particle ratios of 18 and 11, respectively, were measured. We present a simple two-step chromatography process that is capable of producing high-quality adenovirus at a titre suitable for scale-up and clinical translation.

  7. Adenoviral vector-mediated gene expression in the nervous system of immunocompetent Wistar and T cell-deficient nude rats : preferential survival of transduced astroglial cells in nude rats

    NARCIS (Netherlands)

    Hermens, W.T.J.M.C.; Verhaagen, J

    1997-01-01

    In the present paper, we examined the effect of the adenoviral vector dosage, the role of T cells, and the influence of the presence of replication-competent adenovirus (RCA) in adenoviral vector stocks, on the efficacy of adenoviral vector-directed transgene expression in the facial nucleus of

  8. Reversal of experimental colitis disease activity in mice following administration of an adenoviral IL-10 vector.

    Science.gov (United States)

    Sasaki, Makoto; Mathis, J Michael; Jennings, Merilyn H; Jordan, Paul; Wang, Yuping; Ando, Tomoaki; Joh, Takashi; Alexander, J Steven

    2005-10-31

    Genetic deficiency in the expression of interleukin-10 (IL-10) is associated with the onset and progression of experimental inflammatory bowel disease (IBD). The clinical significance of IL-10 expression is supported by studies showing that immune-augmentation of IL-10 prevents inflammation and mucosal damage in animal models of colitis and in human colitis. Interleukin-10 (IL-10), an endogenous anti-inflammatory and immunomodulating cytokine, has been shown to prevent some inflammation and injury in animal and clinical studies, but the efficacy of IL-10 treatment remains unsatisfactory. We found that intra-peritoneal administration of adenoviral IL-10 to mice significantly reversed colitis induced by administration of 3% DSS (dextran sulfate), a common model of colitis. Adenoviral IL-10 (Ad-IL10) transfected mice developed high levels of IL-10 (394 +/- 136 pg/ml) within the peritoneal cavity where the adenovirus was expressed. Importantly, when given on day 4 (after the induction of colitis w/DSS), Ad-IL10 significantly reduced disease activity and weight loss and completely prevented histopathologic injury to the colon at day 10. Mechanistically, compared to Ad-null and DSS treated mice, Ad-IL10 and DSS-treated mice were able to suppress the expression of MAdCAM-1, an endothelial adhesion molecule associated with IBD. Our results suggest that Ad-IL10 (adenoviral IL-10) gene therapy of the intestine or peritoneum may be useful in the clinical treatment of IBD, since we demonstrated that this vector can reverse the course of an existing gut inflammation and markers of inflammation.

  9. Reversal of experimental colitis disease activity in mice following administration of an adenoviral IL-10 vector

    Directory of Open Access Journals (Sweden)

    Ando Tomoaki

    2005-10-01

    Full Text Available Abstract Genetic deficiency in the expression of interleukin-10 (IL-10 is associated with the onset and progression of experimental inflammatory bowel disease (IBD. The clinical significance of IL-10 expression is supported by studies showing that immune-augmentation of IL-10 prevents inflammation and mucosal damage in animal models of colitis and in human colitis. Interleukin-10 (IL-10, an endogenous anti-inflammatory and immunomodulating cytokine, has been shown to prevent some inflammation and injury in animal and clinical studies, but the efficacy of IL-10 treatment remains unsatisfactory. We found that intra-peritoneal administration of adenoviral IL-10 to mice significantly reversed colitis induced by administration of 3% DSS (dextran sulfate, a common model of colitis. Adenoviral IL-10 (Ad-IL10 transfected mice developed high levels of IL-10 (394 +/- 136 pg/ml within the peritoneal cavity where the adenovirus was expressed. Importantly, when given on day 4 (after the induction of colitis w/DSS, Ad-IL10 significantly reduced disease activity and weight loss and completely prevented histopathologic injury to the colon at day 10. Mechanistically, compared to Ad-null and DSS treated mice, Ad-IL10 and DSS-treated mice were able to suppress the expression of MAdCAM-1, an endothelial adhesion molecule associated with IBD. Our results suggest that Ad-IL10 (adenoviral IL-10 gene therapy of the intestine or peritoneum may be useful in the clinical treatment of IBD, since we demonstrated that this vector can reverse the course of an existing gut inflammation and markers of inflammation.

  10. A Genetically Modified Adenoviral Vector with a Phage Display-Derived Peptide Incorporated into Fiber Fibritin Chimera Prolongs Survival in Experimental Glioma.

    Science.gov (United States)

    Kim, Julius W; Kane, J Robert; Young, Jacob S; Chang, Alan L; Kanojia, Deepak; Morshed, Ramin A; Miska, Jason; Ahmed, Atique U; Balyasnikova, Irina V; Han, Yu; Zhang, Lingjiao; Curiel, David T; Lesniak, Maciej S

    2015-09-01

    The dismal clinical context of advanced-grade glioma demands the development of novel therapeutic strategies with direct patient impact. Adenovirus-mediated virotherapy represents a potentially effective approach for glioma therapy. In this research, we generated a novel glioma-specific adenovirus by instituting more advanced genetic modifications that can maximize the efficiency and safety of therapeutic adenoviral vectors. In this regard, a glioma-specific targeted fiber was developed through the incorporation of previously published glioma-specific, phage-panned peptide (VWT peptide) on a fiber fibritin-based chimeric fiber, designated as "GliomaFF." We showed that the entry of this virus was highly restricted to glioma cells, supporting the specificity imparted by the phage-panned peptide. In addition, the stability of the targeting moiety presented by fiber fibritin structure permitted greatly enhanced infectivity. Furthermore, the replication of this virus was restricted in glioma cells by controlling expression of the E1 gene under the activity of the tumor-specific survivin promoter. Using this approach, we were able to explore the combinatorial efficacy of various adenoviral modifications that could amplify the specificity, infectivity, and exclusive replication of this therapeutic adenovirus in glioma. Finally, virotherapy with this modified virus resulted in up to 70% extended survival in an in vivo murine glioma model. These data demonstrate that this novel adenoviral vector is a safe and efficient treatment for this difficult malignancy.

  11. 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.

  12. CRISPR/Cas9 delivery with one single adenoviral vector devoid of all viral genes.

    Science.gov (United States)

    Ehrke-Schulz, Eric; Schiwon, Maren; Leitner, Theo; Dávid, Stephan; Bergmann, Thorsten; Liu, Jing; Ehrhardt, Anja

    2017-12-07

    The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 system revolutionized the field of gene editing but viral delivery of the CRISPR/Cas9 system has not been fully explored. Here we adapted clinically relevant high-capacity adenoviral vectors (HCAdV) devoid of all viral genes for the delivery of the CRISPR/Cas9 machinery using a single viral vector. We present a platform enabling fast transfer of the Cas9 gene and gRNA expression units into the HCAdV genome including the option to choose between constitutive or inducible Cas9 expression and gRNA multiplexing. Efficacy and versatility of this pipeline was exemplified by producing different CRISPR/Cas9-HCAdV targeting the human papillomavirus (HPV) 18 oncogene E6, the dystrophin gene causing Duchenne muscular dystrophy (DMD) and the HIV co-receptor C-C chemokine receptor type 5 (CCR5). All CRISPR/Cas9-HCAdV proved to be efficient to deliver the respective CRISPR/Cas9 expression units and to introduce the desired DNA double strand breaks at their intended target sites in immortalized and primary cells.

  13. Tropism-Modification Strategies for Targeted Gene Delivery Using Adenoviral Vectors

    Directory of Open Access Journals (Sweden)

    Andrew H. Baker

    2010-10-01

    Full Text Available Achieving high efficiency, targeted gene delivery with adenoviral vectors is a long-standing goal in the field of clinical gene therapy. To achieve this, platform vectors must combine efficient retargeting strategies with detargeting modifications to ablate native receptor binding (i.e. CAR/integrins/heparan sulfate proteoglycans and “bridging” interactions. “Bridging” interactions refer to coagulation factor binding, namely coagulation factor X (FX, which bridges hepatocyte transduction in vivo through engagement with surface expressed heparan sulfate proteoglycans (HSPGs. These interactions can contribute to the off-target sequestration of Ad5 in the liver and its characteristic dose-limiting hepatotoxicity, thereby significantly limiting the in vivo targeting efficiency and clinical potential of Ad5-based therapeutics. To date, various approaches to retargeting adenoviruses (Ad have been described. These include genetic modification strategies to incorporate peptide ligands (within fiber knob domain, fiber shaft, penton base, pIX or hexon, pseudotyping of capsid proteins to include whole fiber substitutions or fiber knob chimeras, pseudotyping with non-human Ad species or with capsid proteins derived from other viral families, hexon hypervariable region (HVR substitutions and adapter-based conjugation/crosslinking of scFv, growth factors or monoclonal antibodies directed against surface-expressed target antigens. In order to maximize retargeting, strategies which permit detargeting from undesirable interactions between the Ad capsid and components of the circulatory system (e.g. coagulation factors, erythrocytes, pre-existing neutralizing antibodies, can be employed simultaneously. Detargeting can be achieved by genetic ablation of native receptor-binding determinants, ablation of “bridging interactions” such as those which occur between the hexon of Ad5 and coagulation factor X (FX, or alternatively, through the use of polymer

  14. Treatment of osteoarthritis using a helper-dependent adenoviral vector retargeted to chondrocytes

    Directory of Open Access Journals (Sweden)

    Merry ZC Ruan

    2016-01-01

    Full Text Available Osteoarthritis (OA is a joint disease characterized by degeneration of the articular cartilage, subchondral bone remodeling, and secondary inflammation. It is among the top three causes of chronic disability, and currently there are no treatment options to prevent disease progression. The localized nature of OA makes it an ideal candidate for gene and cell therapy. However, gene and cell therapy of OA is impeded by inefficient gene transduction of chondrocytes. In this study, we developed a broadly applicable system that retargets cell surface receptors by conjugating antibodies to the capsid of helper-dependent adenoviral vectors (HDVs. Specifically, we applied this system to retarget chondrocytes by conjugating an HDV to an α-10 integrin monoclonal antibody (a10mab. We show that a10mab-conjugated HDV (a10mabHDV-infected chondrocytes efficiently in vitro and in vivo while detargeting other cell types. The therapeutic index of an intra-articular injection of 10mabHDV-expressing proteoglycan 4 (PRG4 into a murine model of post-traumatic OA was 10-fold higher than with standard HDV. Moreover, we show that PRG4 overexpression from articular, superficial zone chondrocytes is effective for chondroprotection in postinjury OA and that α-10 integrin is an effective protein for chondrocyte targeting.

  15. Factors involved in the maturation of murine dendritic cells transduced with adenoviral vector variants

    International Nuclear Information System (INIS)

    Kanagawa, Naoko; Koretomo, Ryosuke; Murakami, Sayaka; Sakurai, Fuminori; Mizuguchi, Hiroyuki; Nakagawa, Shinsaku; Fujita, Takuya; Yamamoto, Akira; Okada, Naoki

    2008-01-01

    Adenoviral vector (Ad)-mediated gene transfer is an attractive method for manipulating the immunostimulatory properties of dendritic cells (DCs) for cancer immunotherapy. DCs treated with Ad have phenotype alterations (maturation) that facilitate T cell sensitization. We investigated the mechanisms of DC maturation with Ad transduction. Expression levels of a maturation marker (CD40) on DCs treated with conventional Ad, fiber-modified Ads (AdRGD, AdF35, AdF35ΔRGD), or a different serotype Ad (Ad35) were correlated with their transduction efficacy. The α v -integrin directional Ad, AdRGD, exhibited the most potent ability to enhance both foreign gene expression and CD40 expression, and induced secretion of interleukin-12, tumor necrosis factor-α, and interferon-α in DCs. The presence of a foreign gene expression cassette in AdRGD was not necessary for DC maturation. Maturation of DCs treated with AdRGD was suppressed by destruction of the Ad genome, inhibition of endocytosis, or endosome acidification, whereas proteasome inhibition increased CD40 expression levels on DCs. Moreover, inhibition of α v -integrin signal transduction and blockade of cytokine secretion affected the maturation of DCs treated with AdRGD only slightly or not at all, respectively. Thus, our data provide evidence that Ad-induced DC maturation is due to Ad invasion of the DCs, followed by nuclear transport of the Ad genome, and not to the expression of foreign genes

  16. 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.

  17. Toxicity and biodistribution of a first-generation recombinant adenoviral vector, in the presence of hydroxychloroquine, following retroductal delivery to a single rat submandibular gland

    NARCIS (Netherlands)

    Zheng, C.; Voutetakis, A.; Kok, M. R.; Goldsmith, C. M.; Smith, G. B. J.; Elmore, S.; Nyska, A.; Vallant, M.; Irwin, R. D.; Baum, B. J.

    2006-01-01

    We examined the toxicity and biodistribution associated with a single administration of a first-generation, serotype 5, adenoviral vector encoding human growth hormone (hGH; AdCMVhGH) to a single rat submandibular gland in the presence of hydroxychloroquine (HCQ). Previously, we showed that hGH is

  18. Induction of Human Somatostatin Receptor Subtype 2 on Breast Tumors with an Adenoviral Vector for Their Treatment and Detection with a Radiolabeled Peptide

    National Research Council Canada - National Science Library

    Rogers, Buck

    2002-01-01

    .... An adenoviral vector encoding the human somatostatin receptor subtype 2 (AdSSTr2) has been produced. The MDA- MB-468 and BT-474 human breast cancer cells were infected with AdSSTr2 and harvested 48 h later for membrane preparations...

  19. Adenoviral vector-mediated expression of B-50/GAP-43 induces alterations in the membrane organization of olfactory axon terminals in vivo

    NARCIS (Netherlands)

    Holtmaat, Anthony J D G; Hermens, W.T.J.M.C.; Sonnemans, M.A.F.; Giger, Roman J; Van Leeuwen, F W; Kaplitt, M G; Oestreicher, A B; Gispen, Willem Hendrik; Verhaagen, J

    1997-01-01

    B-50/GAP-43 is an intraneuronal membrane-associated growth cone protein with an important role in axonal growth and regeneration. By using adenoviral vector-directed expression of B-50/GAP-43 we studied the morphogenic action of B-50/GAP-43 in mature primary olfactory neurons that have established

  20. 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.

  1. Homology Requirements for Efficient, Footprintless Gene Editing at the CFTR Locus in Human iPSCs with Helper-dependent Adenoviral Vectors

    Directory of Open Access Journals (Sweden)

    Donna J Palmer

    2016-01-01

    Full Text Available Helper-dependent adenoviral vectors mediate high efficiency gene editing in induced pluripotent stem cells without needing a designer nuclease thereby avoiding off-target cleavage. Because of their large cloning capacity of 37 kb, helper-dependent adenoviral vectors with long homology arms are used for gene editing. However, this makes vector construction and recombinant analysis difficult. Conversely, insufficient homology may compromise targeting efficiency. Thus, we investigated the effect of homology length on helper-dependent adenoviral vector targeting efficiency at the cystic fibrosis transmembrane conductance regulator locus in induced pluripotent stem cells and found a positive correlation. With 23.8 and 21.4 kb of homology, the frequencies of targeted recombinants were 50–64.6% after positive selection for vector integration, and 97.4–100% after negative selection against random integrations. With 14.8 kb, the frequencies were 26.9–57.1% after positive selection and 87.5–100% after negative selection. With 9.6 kb, the frequencies were 21.4 and 75% after positive and negative selection, respectively. With only 5.6 kb, the frequencies were 5.6–16.7% after positive selection and 50% after negative selection, but these were more than high enough for efficient identification and isolation of targeted clones. Furthermore, we demonstrate helper-dependent adenoviral vector-mediated footprintless correction of cystic fibrosis transmembrane conductance regulator mutations through piggyBac excision of the selectable marker. However, low frequencies (≤ 1 × 10−3 necessitated negative selection for piggyBac-excision product isolation.

  2. Characterization of infectivity of knob-modified adenoviral vectors in glioma

    NARCIS (Netherlands)

    C.P.L. Paul (C. P L); M. Everts (M.); J.N. Glasgow (J.); P. Dent (P.); P.B. Fisher (P.); I.V. Ulasov (I.); M.S. Lesniak (M.); M.A. Stoff-Khalili (M.); J.C. Roth (J.); M. Preuss (Michael); C.M.F. Dirven (Clemens); M.L.M. Lamfers (Martine); T. Siegal (Tali); Z.B. Zhu (Z.); R.E. Curiel (Rafael E.)

    2008-01-01

    textabstractMalignant glioma continues to be a major target for gene therapy and virotherapy due to its aggressive growth and the current lack of effective treatment. However, these approaches have been hampered by inefficient infection of glioma cells by viral vectors, particularly vectors derived

  3. Prophylactic and therapeutic adenoviral vector-based multivirus-specific T-cell immunotherapy for transplant patients

    Directory of Open Access Journals (Sweden)

    Vijayendra Dasari

    2016-01-01

    Full Text Available Viral infections including cytomegalovirus, Epstein-Barr virus, adenovirus, and BK virus are a common and predictable problem in transplant recipients. While cellular immune therapies have been successfully used to tackle infectious complications in transplant recipients, manufacturing immunotherapies to address the multitude of possible pathogens can be technically challenging and labor-intensive. Here we describe a novel adenoviral antigen presentation platform (Ad-MvP as a tool for rapid generation of multivirus-specific T-cells in a single step. Ad-MvP encodes 32 CD8+ T-cell epitopes from cytomegalovirus, Epstein-Barr virus, adenovirus, and BK virus as a contiguous polyepitope. We demonstrate that Ad-MvP vector can be successfully used for rapid in vitro expansion of multivirus-specific T-cells from transplant recipients and in vivo priming of antiviral T-cell immunity. Most importantly, using an in vivo murine model of Epstein-Barr virus-induced lymphoma, we also show that adoptive immunotherapy with Ad-MvP expanded autologous and allogeneic multivirus-specific T-cells is highly effective in controlling Epstein-Barr virus tumor outgrowth and improving overall survival. We propose that Ad-MvP has wide ranging therapeutic applications in greatly facilitating in vivo priming of antiviral T-cells, the generation of third-party T-cell banks as “off-the-shelf” therapeutics as well as autologous T-cell therapies for transplant patients.

  4. Human CD46-transgenic mice in studies involving replication-incompetent adenoviral type 35 vectors

    NARCIS (Netherlands)

    Verhaagh, S.; Jong, E. de; Goudsmit, J.; Lecollinet, S.; Gillissen, G.; Vries, M. de; Leuven, K. van; Que, I.; Ouwehand, K.; Mintardjo, R.; Weverling, G.J.; Radošević, K.; Richardson, J.; Eloit, M.; Lowik, C.; Quax, P.; Havenga, M.

    2006-01-01

    Wild-type strains of mice do not express CD46, a high-affinity receptor for human group B adenoviruses including type 35. Therefore, studies performed to date in mice using replication-incompetent Ad35 (rAd35) vaccine carriers may underestimate potency or result in altered vector distribution. Here,

  5. Radiation-Induced Upregulation of Gene Expression From Adenoviral Vectors Mediated by DNA Damage Repair and Regulation

    International Nuclear Information System (INIS)

    Nokisalmi, Petri; Rajecki, Maria; Pesonen, Sari; Escutenaire, Sophie; Soliymani, Rabah; Tenhunen, Mikko; Ahtiainen, Laura; Hemminki, Akseli

    2012-01-01

    Purpose: In the present study, we evaluated the combination of replication-deficient adenoviruses and radiotherapy in vitro. The purpose of the present study was to analyze the mechanism of radiation-mediated upregulation of adenoviral transgene expression. Methods and Materials: Adenoviral transgene expression (luciferase or green fluorescent protein) was studied with and without radiation in three cell lines: breast cancer M4A4-LM3, prostate cancer PC-3MM2, and lung cancer LNM35/enhanced green fluorescent protein. The effect of the radiation dose, modification of the viral capsid, and five different transgene promoters were studied. The cellular responses were studied using mass spectrometry and immunofluorescence analysis. Double strand break repair was modulated by inhibitors of heat shock protein 90, topoisomerase-I, and DNA protein kinase, and transgene expression was measured. Results: We found that a wide range of radiation doses increased adenoviral transgene expression regardless of the cell line, transgene, promoter, or viral capsid modification. Treatment with adenovirus, radiation, and double strand break repair inhibitors resulted in persistence of double strand breaks and subsequent increases in adenovirus transgene expression. Conclusions: Radiation-induced enhancement of adenoviral transgene expression is linked to DNA damage recognition and repair. Radiation induces a global cellular response that results in increased production of RNA and proteins, including adenoviral transgene products. This study provides a mechanistic rationale for combining radiation with adenoviral gene delivery.

  6. Hexon-modified recombinant E1-deleted adenoviral vectors as bivalent vaccine carriers for Coxsackievirus A16 and Enterovirus 71.

    Science.gov (United States)

    Zhang, Chao; Yang, Yong; Chi, Yudan; Yin, Jieyun; Yan, Lijun; Ku, Zhiqiang; Liu, Qingwei; Huang, Zhong; Zhou, Dongming

    2015-09-22

    Hand, foot and mouth disease (HFMD) is a major public health concern in Asia; more efficient vaccines against HFMD are urgently required. Adenoviral (Ad) capsids have been used widely for the presentation of foreign antigens to induce specific immune responses in the host. Here, we describe a novel bivalent vaccine for HFMD based on the hexon-modified, E1-deleted chimpanzee adenovirus serotype 68 (AdC68). The novel vaccine candidate was generated by incorporating the neutralising epitope of Coxsackievirus A16 (CA16), PEP71, into hypervariable region 1 (HVR1), and a shortened neutralising epitope of Enterovirus 71 (EV71), sSP70, into HVR2 of the AdC68 hexon. In order to enhance the immunogenicity of EV71, VP1 of EV71 was cloned into the E1-region of the AdC68 vectors. The results demonstrated that these two epitopes were well presented on the virion surface and had high affinity towards specific antibodies, and VP1 of EV71 was also significantly expressed. In pre-clinical mouse models, the hexon-modified AdC68 elicited neutralising antibodies against both CA16 and EV71, which conferred protection to suckling mice against a lethal challenge of CA16 and EV71. In summary, this study demonstrates that the hexon-modified AdC68 may represent a promising bivalent vaccine carrier against EV71 and CA16 and an epitope-display platform for other pathogens. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Ex vivo adenoviral vector-mediated neurotrophin gene transfer to olfactory ensheathing glia : effects on rubrospinal tract regeneration, lesion size, and functional recovery after implantation in the injured rat spinal cord

    NARCIS (Netherlands)

    Ruitenberg, Marc J; Plant, Giles W; Hamers, Frank P T; Wortel, Joke; Blits, Bas; Dijkhuizen, Paul A; Gispen, Willem Hendrik; Boer, Gerard J; Verhaagen, J.

    2003-01-01

    The present study uniquely combines olfactory ensheathing glia (OEG) implantation with ex vivo adenoviral (AdV) vector-based neurotrophin gene therapy in an attempt to enhance regeneration after cervical spinal cord injury. Primary OEG were transduced with AdV vectors encoding rat brain-derived

  8. Construction and Antiapoptosis Activities of Recombinant Adenoviral Expression Vector Carrying EBV Latent Membrane Protein 2A

    Directory of Open Access Journals (Sweden)

    Xishuang Liu

    2011-01-01

    Full Text Available To evaluate the possible effects of LMP2A (EBV latent membrane protein 2A on human gastric cancer cell line SGC-7901, LMP2A coding gene was subcloned into shuttle plasmid pAdTrackCMV to form transfer plasmid pAdTrackCMV-2A, which was linearized with PmeI and cotransformed into E.coli BJ5183 with adenovirus genomic plasmid of pAdeasy-1. The identified recombinant adenovirus plasmid DNA was digested with PacI and transfected into 293 cells to package recombinant adenovirus particles named vAd-2A. Then the expression and antiapoptosis activities of LMP2A on SGC-7901 infected with vAd-2A were analyzed. The vAd-2A was successfully constructed and identified by PCR, restriction digestion, and sequencing. LMP2A expression in SGC was identified by strong green fluorescence expression with fluorescence microscopic photograph and Southern blotting. The growth of LMP2A expressing SGC cells was apparently improved. Both cyclin E expression and S phase ratio in LMP2A expressing SGC cells were upregulated by cell cycle analysis and confocal microscopic analysis respectively. The replication-deficient recombinant adenovirus vector can express LMP2A antigen in SGC cells and inhibit their apoptosis. The results indicate that LMP2A might play an important role in pathogenesis of EBV-associated gastric cancer (EBVaGC. This study establishes a foundation for further study on EBVaGC and its gene therapy.

  9. An easy method for preparation of Cre-loxP regulated fluorescent adenoviral expression vectors and its application for direct reprogramming into hepatocytes

    Directory of Open Access Journals (Sweden)

    Chitose Kurihara

    2016-12-01

    Full Text Available The recombinant adenoviral gene expression system is a powerful tool for gene delivery. However, it is difficult to obtain high titers of infectious virus, principally due to the toxicity of the expressed gene which affects on virus replication in the host HEK293 cells. To avoid these problems, we generated a Cre-loxP-regulated fluorescent universal vector (termed pAxCALRL. This vector produces recombinant adenoviruses that express the red fluorescent protein (RFP instead of the inserted gene during proliferation, which limits toxicity and can be used to monitor viral replication. Expression of the gene of interest is induced by co-infection with an adenovirus that expresses Cre-recombinase (AxCANCre. Recombinant adenovirus produced by this system that express Hnf4α and Foxa2 were used to reprogram mouse embryo fibroblast (MEF into induced-hepatocyte-like cells (iHep following several rounds of infection, demonstrating the efficacy of this new system.

  10. Adenoviral vectors for highly selective gene expression in central serotonergic neurons reveal quantal characteristics of serotonin release in the rat brain

    Directory of Open Access Journals (Sweden)

    Teschemacher Anja G

    2009-03-01

    Full Text Available Abstract Background 5-hydroxytryptamine (5 HT, serotonin is one of the key neuromodulators in mammalian brain, but many fundamental properties of serotonergic neurones and 5 HT release remain unknown. The objective of this study was to generate an adenoviral vector system for selective targeting of serotonergic neurones and apply it to study quantal characteristics of 5 HT release in the rat brain. Results We have generated adenoviral vectors which incorporate a 3.6 kb fragment of the rat tryptophan hydroxylase-2 (TPH-2 gene which selectively (97% co-localisation with TPH-2 target raphe serotonergic neurones. In order to enhance the level of expression a two-step transcriptional amplification strategy was employed. This allowed direct visualization of serotonergic neurones by EGFP fluorescence. Using these vectors we have performed initial characterization of EGFP-expressing serotonergic neurones in rat organotypic brain slice cultures. Fluorescent serotonergic neurones were identified and studied using patch clamp and confocal Ca2+ imaging and had features consistent with those previously reported using post-hoc identification approaches. Fine processes of serotonergic neurones could also be visualized in un-fixed tissue and morphometric analysis suggested two putative types of axonal varicosities. We used micro-amperometry to analyse the quantal characteristics of 5 HT release and found that central 5 HT exocytosis occurs predominantly in quanta of ~28000 molecules from varicosities and ~34000 molecules from cell bodies. In addition, in somata, we observed a minority of large release events discharging on average ~800000 molecules. Conclusion For the first time quantal release of 5 HT from somato-dendritic compartments and axonal varicosities in mammalian brain has been demonstrated directly and characterised. Release from somato-dendritic and axonal compartments might have different physiological functions. Novel vectors generated in this

  11. Heterologous prime-boost regimens with a recombinant chimpanzee adenoviral vector and adjuvanted F4 protein elicit polyfunctional HIV-1-specific T-Cell responses in macaques.

    Science.gov (United States)

    Lorin, Clarisse; Vanloubbeeck, Yannick; Baudart, Sébastien; Ska, Michaël; Bayat, Babak; Brauers, Geoffroy; Clarinval, Géraldine; Donner, Marie-Noëlle; Marchand, Martine; Koutsoukos, Marguerite; Mettens, Pascal; Cohen, Joe; Voss, Gerald

    2015-01-01

    HIV-1-specific CD4+ and CD8+ T lymphocytes are important for HIV-1 replication control. F4/AS01 consists of F4 recombinant fusion protein (containing clade B Gag/p24, Pol/RT, Nef and Gag/p17) formulated in AS01 Adjuvant System, and was shown to induce F4-specific polyfunctional CD4+ T-cell responses in humans. While replication-incompetent recombinant HIV-1/SIV antigen-expressing human adenoviral vectors can elicit high-frequency antigen-specific CD8+ T-cell responses, their use is hampered by widespread pre-existing immunity to human serotypes. Non-human adenovirus serotypes associated with lower prevalence may offer an alternative strategy. We evaluated the immunogenicity of AdC7-GRN ('A'), a recombinant chimpanzee adenovirus type 7 vector expressing clade B Gag, RT and Nef, and F4/AS01 ('P'), when delivered intramuscularly in homologous (PP or AA) and heterologous (AAPP or PPAA) prime-boost regimens, in macaques and mice. Vaccine-induced HIV-1-antigen-specific T cells in peripheral blood (macaques), liver, spleen, and intestinal and genital mucosa (mice) were characterized by intracellular cytokine staining. Vaccine-specific IgG antibodies (macaques) were detected using ELISA. In macaques, only the heterologous prime-boost regimens induced polyfunctional, persistent and balanced CD4+ and CD8+ T-cell responses specific to each HIV-1 vaccine antigen. AdC7-GRN priming increased the polyfunctionality of F4/AS01-induced CD4+ T cells. Approximately 50% of AdC7-GRN-induced memory CD8+ T cells exhibited an effector-memory phenotype. HIV-1-specific antibodies were detected with each regimen. In mice, antigen-specific CD4+ and CD8+ T-cell responses were detected in the mucosal and systemic anatomical compartments assessed. When administered in heterologous prime-boost regimens, AdC7-GRN and F4/AS01 candidate vaccines acted complementarily in inducing potent and persistent peripheral blood HIV-1-specific CD4+ and CD8+ T-cell responses and antibodies in macaques. Besides

  12. Priming of CD8 T Cells by Adenoviral Vectors Is Critically Dependent on B7 and Dendritic Cells but Only Partially Dependent on CD28 Ligation on CD8 T Cells

    DEFF Research Database (Denmark)

    Nielsen, Karen N; Steffensen, Maria A; Christensen, Jan P

    2014-01-01

    expression resulted in a delayed primary response, whereas memory CD8 T cells generated in CD28-deficient mice appeared almost normal in terms of both phenotype and effector cytokine profile, but they exhibited a significantly reduced proliferative capacity upon secondary challenge while retaining immediate...... in vivo effector capabilities: in vivo cytotoxicity and short-term in vivo protective capacity. Overall, our data point to an absolute requirement for professional APCs and the expression of the costimulatory molecules CD80/86 for efficient CD8 T cell priming by adenoviral vectors. Additionally, our......Adenoviral vectors have long been forerunners in the development of effective CD8 T cell-based vaccines; therefore, it is imperative that we understand the factors controlling the induction of robust and long-lasting transgene-specific immune responses by these vectors. In this study, we...

  13. Development of Novel Adenoviral Vectors to Overcome Challenges Observed With HAdV-5–based Constructs

    Science.gov (United States)

    Alonso-Padilla, Julio; Papp, Tibor; Kaján, Győző L; Benkő, Mária; Havenga, Menzo; Lemckert, Angelique; Harrach, Balázs; Baker, Andrew H

    2016-01-01

    Recombinant vectors based on human adenovirus serotype 5 (HAdV-5) have been extensively studied in preclinical models and clinical trials over the past two decades. However, the thorough understanding of the HAdV-5 interaction with human subjects has uncovered major concerns about its product applicability. High vector-associated toxicity and widespread preexisting immunity have been shown to significantly impede the effectiveness of HAdV-5–mediated gene transfer. It is therefore that the in-depth knowledge attained working on HAdV-5 is currently being used to develop alternative vectors. Here, we provide a comprehensive overview of data obtained in recent years disqualifying the HAdV-5 vector for systemic gene delivery as well as novel strategies being pursued to overcome the limitations observed with particular emphasis on the ongoing vectorization efforts to obtain vectors based on alternative serotypes. PMID:26478249

  14. Electric cell-substrate impedance sensing (ECIS) based real-time measurement of titer dependent cytotoxicity induced by adenoviral vectors in an IPI-2I cell culture model.

    Science.gov (United States)

    Müller, Jakob; Thirion, Christian; Pfaffl, Michael W

    2011-01-15

    Recombinant viral vectors are widespread tools for transfer of genetic material in various modern biotechnological applications like for example RNA interference (RNAi). However, an accurate and reproducible titer assignment represents the basic step for most downstream applications regarding a precise multiplicity of infection (MOI) adjustment. As necessary scaffold for the studies described in this work we introduce a quantitative real-time PCR (qPCR) based approach for viral particle measurement. Still an implicated problem concerning physiological effects is that the appliance of viral vectors is often attended by toxic effects on the individual target. To determine the critical viral dose leading to cell death we developed an electric cell-substrate impedance sensing (ECIS) based assay. With ECIS technology the impedance change of a current flow through the cell culture medium in an array plate is measured in a non-invasive manner, visualizing effects like cell attachment, cell-cell contacts or proliferation. Here we describe the potential of this online measurement technique in an in vitro model using the porcine ileal epithelial cell line IPI-2I in combination with an adenoviral transfection vector (Ad5-derivate). This approach shows a clear dose-depending toxic effect, as the amount of applied virus highly correlates (p<0.001) with the level of cell death. Thus this assay offers the possibility to discriminate the minimal non-toxic dose of the individual transfection method. In addition this work suggests that the ECIS-device bears the feasibility to transfer this assay to multiple other cytotoxicological questions. Copyright © 2010 Elsevier B.V. All rights reserved.

  15. 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.

  16. 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.

  17. Post-spinal cord injury astrocyte-mediated functional recovery in rats after intraspinal injection of the recombinant adenoviral vectors Ad5-VEGF and Ad5-ANG.

    Science.gov (United States)

    Povysheva, Tatyana; Shmarov, Maksim; Logunov, Denis; Naroditsky, Boris; Shulman, Ilya; Ogurcov, Sergey; Kolesnikov, Pavel; Islamov, Rustem; Chelyshev, Yuri

    2017-07-01

    OBJECTIVE The most actively explored therapeutic strategy for overcoming spinal cord injury (SCI) is the delivery of genes encoding molecules that stimulate regeneration. In a mouse model of amyotrophic lateral sclerosis and in preliminary clinical trials in patients with amyotrophic lateral sclerosis, the combined administration of recombinant adenoviral vectors (Ad5-VEGF+Ad5-ANG) encoding the neurotrophic/angiogenic factors vascular endothelial growth factor ( VEGF) and angiogenin ( ANG) was found to slow the development of neurological deficits. These results suggest that there may be positive effects of this combination of genes in posttraumatic spinal cord regeneration. The objective of the present study was to determine the effects of Ad5-VEGF+Ad5-ANG combination therapy on motor function recovery and reactivity of astrocytes in a rat model of SCI. METHODS Spinal cord injury was induced in adult Wistar rats by the weight-drop method. Rats (n = 51) were divided into 2 groups: the experimental group (Ad5-VEGF+Ad5-ANG) and the control group (Ad5-GFP [green fluorescent protein]). Recovery of motor function was assessed using the Basso, Beattie, and Bresnahan scale. The duration and intensity of infectivity and gene expression from the injected vectors were assessed by immunofluorescent detection of GFP. Reactivity of glial cells was assessed by changes in the number of immunopositive cells expressing glial fibrillary acidic protein (GFAP), S100β, aquaporin 4 (AQP4), oligodendrocyte transcription factor 2, and chondroitin sulfate proteoglycan 4. The level of S100β mRNA expression in the spinal cord was estimated by real-time polymerase chain reaction. RESULTS Partial recovery of motor function was observed 30 days after surgery in both groups. However, Basso, Beattie, and Bresnahan scores were 35.9% higher in the Ad5-VEGF+Ad5-ANG group compared with the control group. Specific GFP signal was observed at distances of up to 5 mm in the rostral and caudal

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    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. 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.

  1. Regulation of epithelial differentiation in rat intestine by intraluminal delivery of an adenoviral vector or silencing RNA coding for Schlafen 3.

    Directory of Open Access Journals (Sweden)

    Pavlo L Kovalenko

    Full Text Available Although we stimulate enterocytic proliferation to ameliorate short gut syndrome or mucosal atrophy, less effort has been directed at enterocytic differentiation. Schlafen 3 (Slfn3 is a poorly understood protein induced during IEC-6 enterocytic differentiation. We hypothesized that exogenous manipulation of Slfn3 would regulate enterocytic differentiation in vivo. Adenoviral vector coding for Slfn3 cDNA (Ad-GFP-Slfn3 or silencing RNA for Slfn3 (siSlfn3 was introduced intraluminally into rat intestine. We assessed Slfn3, villin, sucrase-isomaltase (SI, Dpp4, and Glut2 by qRT-PCR, Western blot, and immunohistochemistry. We also studied Slfn3 and these differentiation markers in atrophic defunctionalized jejunal mucosa and the crypt-villus axis of normal jejunum. Ad-GFP-Slfn3 but not Ad-GFP increased Slfn3, villin and Dpp4 expression in human Caco-2 intestinal epithelial cells. Injecting Ad-GFP-Slfn3 into rat jejunum in vivo increased mucosal Slfn3 mRNA three days later vs. intraluminal Ad-GFP. This Slfn3 overexpression was associated with increases in all four differentiation markers. Injecting siSlfn3 into rat jejunum in vivo substantially reduced Slfn3 and all four intestinal mucosal differentiation markers three days later, as well as Dpp4 specific activity. Endogenous Slfn3 was reduced in atrophic mucosa from a blind-end Roux-en-Y anastomosis in parallel with differentiation marker expression together with AKT and p38 signaling. Slfn3 was more highly expressed in the villi than the crypts, paralleling Glut2, SI and Dpp4. Slfn3 is a key intracellular regulator of rat enterocytic differentiation. Understanding how Slfn3 works may identify targets to promote enterocytic differentiation and maintain mucosal function in vivo, facilitating enteral nutrition and improving survival in patients with mucosal atrophy or short gut syndrome.

  2. Adenoviral vectors expressing fusogenic membrane glycoproteins activated via matrix metalloproteinase cleavable linkers have significant antitumor potential in the gene therapy of gliomas.

    Science.gov (United States)

    Allen, Cory; McDonald, Cari; Giannini, Caterina; Peng, Kah Whye; Rosales, Gabriela; Russell, Stephen J; Galanis, Evanthia

    2004-11-01

    Fusogenic membrane glycoproteins (FMG) such as the gibbon ape leukemia virus envelope (GALV) glycoprotein are potent therapeutic transgenes with potential utility in the gene therapy of gliomas. Transfection of glioma cell lines with FMG expression constructs results in fusion with massive syncytia formation followed by cytotoxic cell death. Nevertheless, ubiquitous expression of the GALV receptor, Pit-1, makes targeting desirable in order to increase the specificity of the observed cytopathic effect. Here we report on use of matrix metalloproteinase (MMP)-cleavable linkers to target the cytotoxicity of FMG-expressing adenoviral vectors against gliomas. Replication-defective adenoviruses (Ad) were constructed expressing the hyperfusogenic version of the GALV glycoprotein linked to a blocking ligand (C-terminal extracellular domain of CD40 ligand) through either an MMP-cleavable linker (AdM40) or a non-cleavable linker (AdN40). Both viruses also co-expressed the green fluorescent protein (GFP) via an internal ribosomal entry site. The glioma cell lines U87, U118, and U251 characterized by zymography and MMP-2 activity assay as high, medium and low MMP expressors, respectively, the MMP-poor cell lines TE671 and normal human astrocytes were infected with AdM40 and AdN40 at different multiplicities of infection (MOIs) from 1-30. Fusion was quantitated by counting both number and size of syncytia. Infection of these cell lines with AdN40 did not result in fusion or cytotoxic cell death, despite the presence of infection, as demonstrated by GFP positivity, therefore indicating that the displayed CD40 ligand blocked GALV-induced fusion. Fusion was restored after infection of glioma cells with AdM40 at an MOI as low as 1 to an extent dependent on MMP expression and coxsackie adenovirus receptor (CAR) expression in the specific cell line. Western immunoblotting demonstrated the presence of the cleaved CD40 ligand in the supernatant of fused glioma cells. Use of the MMP

  3. Integration profile and safety of an adenovirus hybrid-vector utilizing hyperactive sleeping beauty transposase for somatic integration.

    Directory of Open Access Journals (Sweden)

    Wenli Zhang

    Full Text Available We recently developed adenovirus/transposase hybrid-vectors utilizing the previously described hyperactive Sleeping Beauty (SB transposase HSB5 for somatic integration and we could show stabilized transgene expression in mice and a canine model for hemophilia B. However, the safety profile of these hybrid-vectors with respect to vector dose and genotoxicity remains to be investigated. Herein, we evaluated this hybrid-vector system in C57Bl/6 mice with escalating vector dose settings. We found that in all mice which received the hyperactive SB transposase, transgene expression levels were stabilized in a dose-dependent manner and that the highest vector dose was accompanied by fatalities in mice. To analyze potential genotoxic side-effects due to somatic integration into host chromosomes, we performed a genome-wide integration site analysis using linker-mediated PCR (LM-PCR and linear amplification-mediated PCR (LAM-PCR. Analysis of genomic DNA samples obtained from HSB5 treated female and male mice revealed a total of 1327 unique transposition events. Overall the chromosomal distribution pattern was close-to-random and we observed a random integration profile with respect to integration into gene and non-gene areas. Notably, when using the LM-PCR protocol, 27 extra-chromosomal integration events were identified, most likely caused by transposon excision and subsequent transposition into the delivered adenoviral vector genome. In total, this study provides a careful evaluation of the safety profile of adenovirus/Sleeping Beauty transposase hybrid-vectors. The obtained information will be useful when designing future preclinical studies utilizing hybrid-vectors in small and large animal models.

  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. Efficient delivery and stable gene expression in a hematopoietic cell line using a chimeric serotype 35 fiber pseudotyped helper-dependent adenoviral vector

    International Nuclear Information System (INIS)

    Balamotis, Michael Andrew; Huang, Katie; Mitani, Kohnosuke

    2004-01-01

    Certain human cell populations have remained difficult to infect with human adenovirus (Ad) serotype 5 because of their lack of coxsackievirus B-adenovirus receptor (CAR). Native adenovirus fiber compositions, although diverse, cannot infect all tissue types. Recently, a chimeric Ad5/35 fiber was created, which displays an altered tropism from Ad5. We incorporated this chimeric fiber into a helper-dependent (HD) adenovirus vector system and compared HD to E1-deleted (E1Δ) vectors by transgene expression, cell transduction efficiency, and cytotoxicity. K562 cells were infected ∼50 times more efficiently with the chimeric Ad5/35 fiber compared with the Ad5 fiber. Short-term transgene expression was sustained longer from HD Ad5/35 than E1Δ Ad5/35 vector after in vitro infection of actively dividing K562 cells. Rapid loss of transgene expression from E1Δ Ad5/35 infection was not due to the loss of vector genomes, as determined by quantitative real-time PCR (QRT-PCR), or cytotoxicity, but rather through a putative silencing mechanism

  6. E1(-)E4(+) adenoviral gene transfer vectors function as a "pro-life" signal to promote survival of primary human endothelial cells.

    Science.gov (United States)

    Ramalingam, R; Rafii, S; Worgall, S; Brough, D E; Crystal, R G

    1999-05-01

    Although endothelial cells are quiescent and long-lived in vivo, when they are removed from blood vessels and cultured in vitro they die within days to weeks. In studies of the interaction of E1(-)E4(+) replication-deficient adenovirus (Ad) vectors and human endothelium, the cells remained quiescent and were viable for prolonged periods. Evaluation of these cultures showed that E1(-)E4(+) Ad vectors provide an "antiapoptotic" signal that, in association with an increase in the ratio of Bcl2 to Bax levels, induces the endothelial cells to enter a state of "suspended animation," remaining viable for at least 30 days, even in the absence of serum and growth factors. Although the mechanisms initiating these events are unclear, the antiapoptoic signal requires the presence of E4 genes in the vector genome, suggesting that one or more E4 open reading frames of subgroup C Ad initiate a "pro-life" program that modifies cultured endothelial cells to survive for prolonged periods.

  7. Vectorization of the KENO V.a criticality safety code

    International Nuclear Information System (INIS)

    Hollenbach, D.F.; Dodds, H.L.; Petrie, L.M.

    1991-01-01

    The development of the vector processor, which is used in the current generation of supercomputers and is beginning to be used in workstations, provides the potential for dramatic speed-up for codes that are able to process data as vectors. Unfortunately, the stochastic nature of Monte Carlo codes prevents the old scalar version of these codes from taking advantage of the vector processors. New Monte Carlo algorithms that process all the histories undergoing the same event as a batch are required. Recently, new vectorized Monte Carlo codes have been developed that show significant speed-ups when compared to the scalar version of themselves or equivalent codes. This paper discusses the vectorization of an already existing and widely used criticality safety code, KENO V.a All the changes made to KENO V.a are transparent to the user making it possible to upgrade from the standard scalar version of KENO V.a to the vectorized version without learning a new code

  8. Comparison of Human Sodium/Iodide Symporter (hNIS) Gene Expressions between Lentiviral and Adenoviral Vectors in Rat Mesenchymal Stem Cells

    Energy Technology Data Exchange (ETDEWEB)

    Park, So Yeon; Lee, Won Woo; Kim, Hyun Joo; Chung, June Key; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Sung Jin; Lee, Heui Ran [Medical Research Center, Seoul National University, Seoul (Korea, Republic of)

    2008-10-15

    Quantitative comparison of transgene expression within stem cells between lentivirus and adenovirusmediated delivery systems has not been reported. Here, we evaluated the human sodium iodide symporter (hNIS) gene expression in rat mesenchymal stem cell (rMSC) transduced by lentivirus or adenovirus, and compared the hNIS expression quantitatively between the two delivery systems. Lentiviral-mediated hNIS expressing rMSC (lenti-hNIS-rMSC) was constructed by cloning hNIS gene into pLenti6/UbC/V5-DEST (Invitrogen) to obtain pLenti-hNIS, transducing rMSC with the pLenti-hNIS, and selecting with blasticidin for 3 weeks. Recombinant adenovirus expressing hNIS gene (Rad-hNIS) was produced by homologous recombination and transduction efficiency of Rad-hNIS into rMSC evaluated by Rad-GFP was 19.1{+-}4.7%, 54.0{+-}6.4%, 85.7{+-}8.7%, and 98.4{+-}1.3% at MOI 1, 5, 20, and 100, respectively. The hNIS expressions in lenti-hNIS-rMSC or adeno-hNIS-rMSC were assessed by immunocytochemistry, western blot, and I-125 uptake. Immunocytochemistry and western blot analyses revealed that hNIS expressions in lenti-hNIS-rMSC were greater than those in adeno-hNIS-rMSC at MOI 20 but lower than at MOI 50. However in vitro I-125 uptake test demonstrated that iodide uptake in lenti-hNIS-rMSC (29,704{+-}6,659 picomole/10{sup 6} cells) was greater than that in adeno-hNIS-rMSC at MOI 100 (6,168{+-}2,134 picomole/10{sup 6} cells). Despite lower amount of expressed protein, hNIS function in rMSC was greater by lentivirus than by adenovirus mediated expression. Stem cell tracking using hNIS as a reporter gene should be conducted in consideration of relative vector efficiency for transgene expression.

  9. Comparison of Human Sodium/Iodide Symporter (hNIS) Gene Expressions between Lentiviral and Adenoviral Vectors in Rat Mesenchymal Stem Cells

    International Nuclear Information System (INIS)

    Park, So Yeon; Lee, Won Woo; Kim, Hyun Joo; Chung, June Key; Kim, Sang Eun; Kim, Sung Jin; Lee, Heui Ran

    2008-01-01

    Quantitative comparison of transgene expression within stem cells between lentivirus and adenovirusmediated delivery systems has not been reported. Here, we evaluated the human sodium iodide symporter (hNIS) gene expression in rat mesenchymal stem cell (rMSC) transduced by lentivirus or adenovirus, and compared the hNIS expression quantitatively between the two delivery systems. Lentiviral-mediated hNIS expressing rMSC (lenti-hNIS-rMSC) was constructed by cloning hNIS gene into pLenti6/UbC/V5-DEST (Invitrogen) to obtain pLenti-hNIS, transducing rMSC with the pLenti-hNIS, and selecting with blasticidin for 3 weeks. Recombinant adenovirus expressing hNIS gene (Rad-hNIS) was produced by homologous recombination and transduction efficiency of Rad-hNIS into rMSC evaluated by Rad-GFP was 19.1±4.7%, 54.0±6.4%, 85.7±8.7%, and 98.4±1.3% at MOI 1, 5, 20, and 100, respectively. The hNIS expressions in lenti-hNIS-rMSC or adeno-hNIS-rMSC were assessed by immunocytochemistry, western blot, and I-125 uptake. Immunocytochemistry and western blot analyses revealed that hNIS expressions in lenti-hNIS-rMSC were greater than those in adeno-hNIS-rMSC at MOI 20 but lower than at MOI 50. However in vitro I-125 uptake test demonstrated that iodide uptake in lenti-hNIS-rMSC (29,704±6,659 picomole/10 6 cells) was greater than that in adeno-hNIS-rMSC at MOI 100 (6,168±2,134 picomole/10 6 cells). Despite lower amount of expressed protein, hNIS function in rMSC was greater by lentivirus than by adenovirus mediated expression. Stem cell tracking using hNIS as a reporter gene should be conducted in consideration of relative vector efficiency for transgene expression

  10. 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.

  11. 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.

  12. Adenoviral gene delivery to primary human cutaneous cells and burn wounds.

    Science.gov (United States)

    Hirsch, Tobias; von Peter, Sebastian; Dubin, Grzegorz; Mittler, Dominik; Jacobsen, Frank; Lehnhardt, Markus; Eriksson, Elof; Steinau, Hans-Ulrich; Steinstraesser, Lars

    2006-01-01

    The adenoviral transfer of therapeutic genes into epidermal and dermal cells is an interesting approach to treat skin diseases and to promote wound healing. The aim of this study was to assess the in vitro and in vivo transfection efficacy in skin and burn wounds after adenoviral gene delivery. Primary keratinocytes (HKC), fibroblasts (HFB), and HaCaT cells were transfected using different concentrations of an adenoviral construct (eGFP). Transfection efficiency and cytotoxicity was determined up to 30 days. Expression was quantified by FACS analysis and fluorimeter. Cytotoxicity was measured using the trypan blue exclusion method. 45 male Sprague Dawley rats received 2x10(8) pfu of Ad5-CMV-LacZ or carrier control intradermally into either superficial partial thickness scald burn or unburned skin. Animals were euthanized after 48 h, 7 or 14 days posttreatment. Transgene expression was assessed using immunohistochemistry and bioluminescent assays. The highest transfection rate was observed 48 h posttransfection: 79% for HKC, 70% for HFB, and 48% for HaCaT. The eGFP expression was detectable in all groups over 30 days (P>0.05). Cytotoxic effects of the adenoviral vector were observed for HFB after 10 days and HaCaT after 30 days. Reporter gene expression in vivo was significantly higher in burned skin compared with unburned skin (P=0,004). Gene expression decreases from 2 to 7 days with no significant expression after 14 days. This study demonstrates that effective adenoviral-mediated gene transfer of epidermal primary cells and cell-lines is feasible. Ex vivo gene transfer in epithelial cells might have promise for the use in severely burned patients who receive autologous keratinocyte sheets. Transient cutaneous gene delivery in burn wounds using adenoviral vectors causes significant concentrations in the wound tissue for at least 1 week. Based on these findings, we hypothesize that transient cutaneous adenoviral gene delivery of wound healing promoting factors has

  13. Presumed Acute Adenoviral Dacryoadenitis Associated with ...

    African Journals Online (AJOL)

    of serum adenoviral antibodies IgM and presence of inclusion bodies in conjunctival smear. Epidemic keratoconjunctivitis is caused by adenovirus serovars. 8, 19, and 37.[7] Serological typing and polymerase chain reaction for adenoviral were not available in smear in both eyes. A computerized tomography scan of.

  14. Preclinical safety, toxicology, and biodistribution study of adenoviral gene therapy with sVEGFR-2 and sVEGFR-3 combined with chemotherapy for ovarian cancer.

    Science.gov (United States)

    Tuppurainen, Laura; Sallinen, Hanna; Kokki, Emmi; Koponen, Jonna; Anttila, Maarit; Pulkkinen, Kati; Heikura, Tommi; Toivanen, Pyry; Hämäläinen, Kirsi; Kosma, Veli-Matti; Heinonen, Seppo; Alitalo, Kari; Ylä-Herttuala, Seppo

    2013-03-01

    Abstract Antiangiogenic and antilymphangiogenic gene therapy with soluble vascular endothelial growth factor receptor-2 (VEGFR-2) and soluble VEGFR-3 in combination with chemotherapy is a potential new treatment for ovarian carcinoma. We evaluated the safety, toxicology, and biodistribution of intravenous AdsVEGFR-2 and AdsVEGFR-3 combined with chemotherapy in healthy rats (n=90) before entering a clinical setting. The study groups were: AdLacZ and AdLacZ with chemotherapy as control groups, low dose AdsVEGFR-2 and AdsVEGFR-3, high dose AdsVEGFR-2 and AdsVEGFR-3, combination of low dose AdsVEGFR-2 and AdsVEGFR-3 with chemotherapy, combination of high dose AdsVEGFR-2 and AdVEGFR-3 with chemotherapy, and chemotherapy only. The follow-up time was 4 weeks. Safety and toxicology were assessed by monitoring the clinical status of the animals and by histological, hematological, and clinical chemistry parameters. For the biodistribution studies, quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used. Low dose (2×10(10) vp) AdsVEGFR-2 and AdsVEGFR-3 gene therapy was well tolerated, even when gene therapy was combined with chemotherapy. Notably, only transient elevation of liver enzymes and mild regenerative changes were seen in liver after the gene transfer in the groups that received high doses (2×10(11) vp) of AdsVEGFR-2 and AdsVEGFR-3 with or without chemotherapy. No life-threatening adverse effects were noticed in any of the treatment groups. The highest protein concentration of soluble VEGFR-2 (sVEGFR-2) in circulation was seen 1 week after the gene transfer. The combination of chemotherapy to gene therapy seemed to prolong the time of detectable transgene protein at least 1 week in the circulation. The expression of AdsVEGFR-2 and AdsVEGFR-3 transgenes was mainly seen in the liver and spleen as detected by qRT-PCR. According to these results, AdsVEGFR-2 and AdsVEGFR-3 gene therapy combined with

  15. 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...

  16. Vaccination with an adenoviral vector encoding the tumor antigen directly linked to invariant chain induces potent CD4(+) T-cell-independent CD8(+) T-cell-mediated tumor control

    DEFF Research Database (Denmark)

    Sorensen, Maria R; Holst, Peter J; Pircher, Hanspeter

    2009-01-01

    of the vaccine antigen to invariant chain (Ii). To evaluate this strategy we used a mouse model, in which an immunodominant epitope (GP33) of the LCMV glycoprotein (GP) represents the tumor-associated neoantigen. Prophylactic vaccination of C57BL/6 mice with a replication-deficient human adenovirus 5 vector...... encoding GP linked to Ii (Ad-Ii-GP) resulted in complete protection against GP33-expressing B16.F10 tumors. Therapeutic vaccination with Ad-Ii-GP delayed tumor growth by more than 2 wk compared with sham vaccination. Notably, therapeutic vaccination with the linked vaccine was significantly better than...... the tumor degradation. Finally, Ad-Ii-GP but not Ad-GP vaccination can break the immunological non-reactivity in GP transgenic mice indicating that our vaccine strategy will prove efficient also against endogenous tumor antigens....

  17. Usefulness of intra-arterial embolization method using gelfoam particles in effective gene transduction of adenoviral vector for liver-directed gene therapy: an preliminary animal study in dogs

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jin Hwa; Park, Byeong Ho; Kim, Chan Sung [Dong-A University College of Medicine, Pusan (Korea, Republic of)

    2003-02-01

    Liver-directed gene therapy is being actively pursued and developed as a method of treating various liver diseases. A number of aspects, including gene intervention, an efficient gene delivery system, and stable transgene expression are key to the success of the chosen strategy, and to overcome problems in these areas, several tactics can be used. In this study, we assess the utility of transarterial embolization using gelfoam particles soaked in an adenovirus vector as a gene-delivery method. Using the angiographic approach, three dogs each weighing 9.5-11kg were superselectively catheterized at the left hepatic artery using a 3-F microcatheter and the coaxial method. Two of the dogs were embolized at the left hepatic artery using 3x2x2-mm and 2x1x1-mm gelfoam particles soaked in 2x10{sup 11} particles/kg of recombinant adv. CMV.LacZ(LacZ-adv). The left hepatic artery of the remaining animal, used as a control, was infused with the same dose of lacZ-adv in the same way as before but without embolization of the left hepatic artery. Three days after embolization or the infusion of LacZ-adv, the dogs were sacrificed prior to harvest of the entire liver for the evaluation of gene transduction. X-gal staining of the liver tissue obtained was positive for hepatocytes, but the pattern and degree of gene transduction differed according to gelfoam particle size. Where this was 3x2x2 mm, gene transduction along the liver hilum varied, but where 2x1x1-mm particles were used, transduction was more even. No pathologic hepatic tissue injury or inflammation was apparent, and control liver tissue was not stained by X-gal. Serum SGOT and SGPT levels were slightly higher one day after the procedure, but had normalized by day 3. Intrahepatic transarterial embolization using gelfoam particles soaked in LacZ-adv appears to be a good method for effective liver-targed gene therapy.

  18. Usefulness of intra-arterial embolization method using gelfoam particles in effective gene transduction of adenoviral vector for liver-directed gene therapy: an preliminary animal study in dogs

    International Nuclear Information System (INIS)

    Lee, Jin Hwa; Park, Byeong Ho; Kim, Chan Sung

    2003-01-01

    Liver-directed gene therapy is being actively pursued and developed as a method of treating various liver diseases. A number of aspects, including gene intervention, an efficient gene delivery system, and stable transgene expression are key to the success of the chosen strategy, and to overcome problems in these areas, several tactics can be used. In this study, we assess the utility of transarterial embolization using gelfoam particles soaked in an adenovirus vector as a gene-delivery method. Using the angiographic approach, three dogs each weighing 9.5-11kg were superselectively catheterized at the left hepatic artery using a 3-F microcatheter and the coaxial method. Two of the dogs were embolized at the left hepatic artery using 3x2x2-mm and 2x1x1-mm gelfoam particles soaked in 2x10 11 particles/kg of recombinant adv. CMV.LacZ(LacZ-adv). The left hepatic artery of the remaining animal, used as a control, was infused with the same dose of lacZ-adv in the same way as before but without embolization of the left hepatic artery. Three days after embolization or the infusion of LacZ-adv, the dogs were sacrificed prior to harvest of the entire liver for the evaluation of gene transduction. X-gal staining of the liver tissue obtained was positive for hepatocytes, but the pattern and degree of gene transduction differed according to gelfoam particle size. Where this was 3x2x2 mm, gene transduction along the liver hilum varied, but where 2x1x1-mm particles were used, transduction was more even. No pathologic hepatic tissue injury or inflammation was apparent, and control liver tissue was not stained by X-gal. Serum SGOT and SGPT levels were slightly higher one day after the procedure, but had normalized by day 3. Intrahepatic transarterial embolization using gelfoam particles soaked in LacZ-adv appears to be a good method for effective liver-targed gene therapy

  19. Safety mechanism assisted by the repressor of tetracycline (SMART) vaccinia virus vectors for vaccines and therapeutics.

    Science.gov (United States)

    Grigg, Patricia; Titong, Allison; Jones, Leslie A; Yilma, Tilahun D; Verardi, Paulo H

    2013-09-17

    Replication-competent viruses, such as Vaccinia virus (VACV), are powerful tools for the development of oncolytic viral therapies and elicit superior immune responses when used as vaccine and immunotherapeutic vectors. However, severe complications from uncontrolled viral replication can occur, particularly in immunocompromised individuals or in those with other predisposing conditions. VACVs constitutively expressing interferon-γ (IFN-γ) replicate in cell culture indistinguishably from control viruses; however, they replicate in vivo to low or undetectable levels, and are rapidly cleared even in immunodeficient animals. In an effort to develop safe and highly effective replication-competent VACV vectors, we established a system to inducibly express IFN-γ. Our SMART (safety mechanism assisted by the repressor of tetracycline) vectors are designed to express the tetracycline repressor under a constitutive VACV promoter and IFN-γ under engineered tetracycline-inducible promoters. Immunodeficient SCID mice inoculated with VACVs not expressing IFN-γ demonstrated severe weight loss, whereas those given VACVs expressing IFN-γ under constitutive VACV promoters showed no signs of infection. Most importantly, mice inoculated with a VACV expressing the IFN-γ gene under an inducible promoter remained healthy in the presence of doxycycline, but exhibited severe weight loss in the absence of doxycycline. In this study, we developed a safety mechanism for VACV based on the conditional expression of IFN-γ under a tightly controlled tetracycline-inducible VACV promoter for use in vaccines and oncolytic cancer therapies.

  20. Safety profile, efficacy, and biodistribution of a bicistronic high-capacity adenovirus vector encoding a combined immunostimulation and cytotoxic gene therapy as a prelude to a phase I clinical trial for glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Puntel, Mariana [Department of Neurosurgery, The University of Michigan School of Medicine, MSRB II, RM 4570C, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5689 (United States); Department of Cell and Developmental Biology, The University of Michigan School of Medicine, MSRB II, RM 4570C, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5689 (United States); Gene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048 (United States); Ghulam, Muhammad A.K.M. [Gene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048 (United States); Farrokhi, Catherine [Department of Psychiatry and Behavioral Neurosciences, Cedars Sinai Medical Center, Los Angeles, CA 90048 (United States); VanderVeen, Nathan; Paran, Christopher; Appelhans, Ashley [Department of Neurosurgery, The University of Michigan School of Medicine, MSRB II, RM 4570C, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5689 (United States); Department of Cell and Developmental Biology, The University of Michigan School of Medicine, MSRB II, RM 4570C, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5689 (United States); Kroeger, Kurt M.; Salem, Alireza [Gene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048 (United States); Lacayo, Liliana [Department of Psychiatry and Behavioral Neurosciences, Cedars Sinai Medical Center, Los Angeles, CA 90048 (United States); Pechnick, Robert N. [Department of Psychiatry and Behavioral Neurosciences, Cedars Sinai Medical Center, Los Angeles, CA 90048 (United States); Department of Psychiatry and Behavioral Neurosciences, David Geffen School of Medicine, University of California, Los Angeles, CA (United States); Kelson, Kyle R.; Kaur, Sukhpreet; Kennedy, Sean [Gene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048 (United States); Palmer, Donna; Ng, Philip [Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030 (United States); and others

    2013-05-01

    Adenoviral vectors (Ads) are promising gene delivery vehicles due to their high transduction efficiency; however, their clinical usefulness has been hampered by their immunogenicity and the presence of anti-Ad immunity in humans. We reported the efficacy of a gene therapy approach for glioma consisting of intratumoral injection of Ads encoding conditionally cytotoxic herpes simplex type 1 thymidine kinase (Ad-TK) and the immunostimulatory cytokine fms-like tyrosine kinase ligand 3 (Ad-Flt3L). Herein, we report the biodistribution, efficacy, and neurological and systemic effects of a bicistronic high-capacity Ad, i.e., HC-Ad-TK/TetOn-Flt3L. HC-Ads elicit sustained transgene expression, even in the presence of anti-Ad immunity, and can encode large therapeutic cassettes, including regulatory elements to enable turning gene expression “on” or “off” according to clinical need. The inclusion of two therapeutic transgenes within a single vector enables a reduction of the total vector load without adversely impacting efficacy. Because clinically the vectors will be delivered into the surgical cavity, normal regions of the brain parenchyma are likely to be transduced. Thus, we assessed any potential toxicities elicited by escalating doses of HC-Ad-TK/TetOn-Flt3L (1 × 10{sup 8}, 1 × 10{sup 9}, or 1 × 10{sup 10} viral particles [vp]) delivered into the rat brain parenchyma. We assessed neuropathology, biodistribution, transgene expression, systemic toxicity, and behavioral impact at acute and chronic time points. The results indicate that doses up to 1 × 10{sup 9} vp of HC-Ad-TK/TetOn-Flt3L can be safely delivered into the normal rat brain and underpin further developments for its implementation in a phase I clinical trial for glioma. - Highlights: ► High capacity Ad vectors elicit sustained therapeutic gene expression in the brain. ► HC-Ad-TK/TetOn-Flt3L encodes two therapeutic genes and a transcriptional switch. ► We performed a dose escalation study at

  1. Safety of the novel influenza viral vector Brucella abortus vaccine in pregnant heifers

    Directory of Open Access Journals (Sweden)

    Kaissar Tabynov

    2016-01-01

    Full Text Available ABSTRACT: The present study provides the first information about the safety of a new influenza viral vector vaccine expressing the Brucella ribosomal protein L7/L12 or Omp16 containing the adjuvant Montanide Gel01 in pregnant heifers. Immunization of pregnant heifers was conducted via the conjunctival (n=10 or subcutaneous (n=10 route using cross prime and booster vaccination schedules at an interval of 28 days. The vector vaccine was evaluated in comparison with positive control groups vaccinated with B. abortus S19 (n=10 or B. abortus RB51 (n=10 and a negative (PBS+Montanide Gel01; n=10 control group. Clinical studies, thermometry, assessment of local reactogenicity and observation of abortion showed that the vector vaccine via the conjunctival or subcutaneous route was completely safe for pregnant heifers compared to the commercial vaccines B. abortus S19 or B. abortus RB51. The only single adverse event was the formation of infiltration at the site of subcutaneous injection; this reaction was not observed for the conjunctival route.

  2. Eliminating HIV-1 Packaging Sequences from Lentiviral Vector Proviruses Enhances Safety and Expedites Gene Transfer for Gene Therapy.

    Science.gov (United States)

    Vink, Conrad A; Counsell, John R; Perocheau, Dany P; Karda, Rajvinder; Buckley, Suzanne M K; Brugman, Martijn H; Galla, Melanie; Schambach, Axel; McKay, Tristan R; Waddington, Simon N; Howe, Steven J

    2017-08-02

    Lentiviral vector genomic RNA requires sequences that partially overlap wild-type HIV-1 gag and env genes for packaging into vector particles. These HIV-1 packaging sequences constitute 19.6% of the wild-type HIV-1 genome and contain functional cis elements that potentially compromise clinical safety. Here, we describe the development of a novel lentiviral vector (LTR1) with a unique genomic structure designed to prevent transfer of HIV-1 packaging sequences to patient cells, thus reducing the total HIV-1 content to just 4.8% of the wild-type genome. This has been achieved by reconfiguring the vector to mediate reverse-transcription with a single strand transfer, instead of the usual two, and in which HIV-1 packaging sequences are not copied. We show that LTR1 vectors offer improved safety in their resistance to remobilization in HIV-1 particles and reduced frequency of splicing into human genes. Following intravenous luciferase vector administration to neonatal mice, LTR1 sustained a higher level of liver transgene expression than an equivalent dose of a standard lentivirus. LTR1 vectors produce reverse-transcription products earlier and start to express transgenes significantly quicker than standard lentiviruses after transduction. Finally, we show that LTR1 is an effective lentiviral gene therapy vector as demonstrated by correction of a mouse hemophilia B model. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  3. Impact of intravenous infusion time on AAV8 vector pharmacokinetics, safety, and liver transduction in cynomolgus macaques

    Directory of Open Access Journals (Sweden)

    Jenny A Greig

    2016-01-01

    Full Text Available Systemically delivered adeno-associated viral (AAV vectors are now in early-phase clinical trials for a variety of diseases. While there is a general consensus on inclusion and exclusion criteria for each of these trials, the conditions under which vectors are infused vary significantly. In this study, we evaluated the impact of intravenous infusion rate of AAV8 vector in cynomolgus macaques on transgene expression, vector clearance from the circulation, and potential activation of the innate immune system. The dose of AAV8 vector in terms of genome copies per kilogram body weight and its concentration were fixed, while the rate of infusion varied to deliver the entire dose over different time periods, including 1, 10, or 90 minutes. Analyses during the in-life phase of the experiment included sequential evaluation of whole blood for vector genomes and appearance of proinflammatory cytokines. Liver tissues were analyzed at the time of necropsy for enhanced green fluorescent protein (eGFP expression and vector genomes. The data were remarkable with a relative absence of any statistically significant effect of infusion time on vector transduction, safety, and clearance. However, some interesting and unexpected trends did emerge.

  4. Adenoviral hemorrhagic disease in California mule deer, 1990-2014.

    Science.gov (United States)

    Woods, Leslie W; Schumaker, Brant A; Pesavento, Patricia A; Crossley, Beate M; Swift, Pamela K

    2018-03-01

    We reviewed case records from the California Animal Health and Food Safety (CAHFS) laboratory and the California Department of Fish and Wildlife (CDFW) spanning 25 years (1990-2014) for all deer accessions submitted to CAHFS for pathology and/or histopathology, with and without a diagnosis of adenoviral hemorrhagic disease (AHD), in order to determine the prevalence of AHD in California. We also examined spatial and temporal distribution, age, and mule deer subspecies in deer that died from AHD. Of 483 deer submitted to CAHFS for diagnostic testing in 1990-2014, 17.2% were diagnosed with confirmed AHD, and 26.5% were confirmed plus suspected cases of AHD. Columbian black-tailed deer ( Odocoileus hemionus columbianus), particularly fawns and juveniles, were most frequently affected. Deer adenovirus ( Odocoileus adenovirus 1; OdAdV-1) was detected by immunohistochemistry in archived CDFW formalin-fixed, paraffin-embedded tissues from deer that died in mortality events in 1981, 1983, and 1986-1987. OdAdV-1 is a common cause of hemorrhagic disease mortality events in California deer, and mortality as a result of AHD is documented as early as 1981.

  5. Safety and optimization aspects of radioactive waste long-term storage at the ''Vector'' site

    International Nuclear Information System (INIS)

    Tokarevs'kij, O.V.; Kondrat'jev, S.M.; Aleksjejeva, Z.M.; Ribalka, N.V.

    2015-01-01

    The paper analyzes links between the final disposal option and needs for long-term storage of radioactive waste taking into proposals on possible changes in radwaste classification as regards disposal. It considers the conceptual approach to design facilities for long-term storage of long-lived radioactive waste at the Vector site and approaches to apply requirements of regulatory documents, radiation safety principles and criteria for long-term storage of radwaste and safety assessment.

  6. Reactivation of presumed adenoviral keratitis after laser in situ keratomileusis.

    Science.gov (United States)

    Safak, Nilgün; Bilgihan, Kamil; Gürelik, Gökhan; Ozdek, Sengül; Hasanreisoğlu, Berati

    2002-04-01

    We report a patient with reactivation of presumed adenoviral keratoconjunctivitis after laser in situ keratomileusis (LASIK) to correct high myopia. The preoperative refraction was -13.00 diopters (D) in the right eye and -14.00 D in the left eye, and the best corrected visual acuity was 20/20 in both eyes. On the first postoperative day, mild conjunctival hyperemia and multiple subepithelial infiltrations localized in the flap zone consistent with adenoviral keratoconjunctivitis were seen. After prompt treatment, the lesions resolved. As a consequence, LASIK successfully corrected the high myopia. Adenoviral keratoconjunctivitis can be reactivated after LASIK, unlike after photorefractive keratectomy, despite the absence of symptomatic and clinical findings before the procedure.

  7. A criticality safety analysis code using a vectorized Monte Carlo method on the HITAC S-810 supercomputer

    International Nuclear Information System (INIS)

    Morimoto, Y.; Maruyama, H.

    1987-01-01

    A vectorized Monte Carlo criticality safety analysis code has been developed on the vector supercomputer HITAC S-810. In this code, a multi-particle tracking algorithm was adopted for effective utilization of the vector processor. A flight analysis with pseudo-scattering was developed to reduce the computational time needed for flight analysis, which represents the bulk of computational time. This new algorithm realized a speed-up of factor 1.5 over the conventional flight analysis. The code also adopted the multigroup cross section constants library of the Bodarenko type with 190 groups, with 132 groups being for fast and epithermal regions and 58 groups being for the thermal region. Evaluation work showed that this code reproduce the experimental results to an accuracy of about 1 % for the effective neutron multiplication factor. (author)

  8. Radiolabeled adenoviral sub-unit proteins for molecular imaging and therapeutic applications in oncology

    International Nuclear Information System (INIS)

    Srivastava, Suresh C.

    2005-01-01

    Full text: Our group has initiated investigations on the use of radiolabeled adenoviral (Ad) sub-unit proteins for delivering suitable radionuclides into tumor cells for molecular imaging as well as for combined gene/radionuclide therapy of cancer. A number of issues involved in developing combined gene/radionuclide delivery into tumors mediated by Ad vectors have been identified and are being addressed. Whereas current clinical trials of gene therapy using Ad vectors involve non-systemic delivery of therapeutic genes, the delivery of radionuclides preferably would involve systemic (i.v.) administration. The distribution and delivery of Ad sub-unit proteins following i.v. administration is not understood and must be studied and optimized. In addition, retention of the selective binding and internalization into tumor cells of the radiolabeled viral vectors remains an unmet challenge. We used the intact adenovirus (Ad, ∼80 nm diameter), native adenoviral fiber protein (AdFP, 180 kD trimer, purified from infected human cultured cells) and the adenoviral fiber 'knob' protein (recombinant AdFKP, 60 kD, synthesized in E. Coli), all of which interact with the in-vivo cellular receptor, coxsackie and adenovirus receptor (CAR) through the knob domain of the adenovirus fiber protein. Our initial studies were aimed at optimizing the labeling conditions using I-131 and In-111 to maintain CAR binding activity of the radiolabeled preparations. The CAR-binding was retained as determined using reaction with biotinylated CAR followed by chemiluminescence detection. The biodistribution results in mice and rats following i.v. administration (autoradiography, tissue counting) showed that all three vectors localized preferentially in CAR-expressing organs (liver, lung, heart, kidney), as expected. The CAR-binding of Ad-2 wild serotype was better (∼8 x stronger) than Ad-12, in particular following radiolabeling. Based on the above results, we further focused on the recombinant knob

  9. Application of a support vector machine algorithm to the safety precaution technique of medium-low pressure gas regulators

    Science.gov (United States)

    Hao, Xuejun; An, Xaioran; Wu, Bo; He, Shaoping

    2018-02-01

    In the gas pipeline system, safe operation of a gas regulator determines the stability of the fuel gas supply, and the medium-low pressure gas regulator of the safety precaution system is not perfect at the present stage in the Beijing Gas Group; therefore, safety precaution technique optimization has important social and economic significance. In this paper, according to the running status of the medium-low pressure gas regulator in the SCADA system, a new method for gas regulator safety precaution based on the support vector machine (SVM) is presented. This method takes the gas regulator outlet pressure data as input variables of the SVM model, the fault categories and degree as output variables, which will effectively enhance the precaution accuracy as well as save significant manpower and material resources.

  10. Vectors for Inhaled Gene Therapy in Lung Cancer. Application for Nano Oncology and Safety of Bio Nanotechnology

    Science.gov (United States)

    Zarogouldis, Paul; Karamanos, Nikos K.; Porpodis, Konstantinos; Domvri, Kalliopi; Huang, Haidong; Hohenforst-Schimdt, Wolfgang; Goldberg, Eugene P.; Zarogoulidis, Konstantinos

    2012-01-01

    Novel aerosol therapeutic modalities have been investigated for lung cancer. Inhaled gene therapy has presented safety and effectiveness previously in cystic fibrosis. However, safety concerns have been raised regarding the safety of non-viral vectors for inhaled gene therapy in lung cancer, and therefore small steps have been made towards this multifunctional treatment modality. During the last decade, numerous new nanocomplexes have been created and investigated as a safe gene delivery nano-vehicle. These formulations are multifunctional; they can be used as either local therapy or carrier for an effective inhaled gene therapy for lung cancer. Herein, we present current and future perspectives of nanocomplexes for inhaled gene therapy treatment in lung cancer. PMID:23109824

  11. Adenoviral Gene Delivery to Primary Human Cutaneous Cells and Burn Wounds

    OpenAIRE

    Hirsch, Tobias; von Peter, Sebastian; Dubin, Grzegorz; Mittler, Dominik; Jacobsen, Frank; Lehnhardt, Markus; Eriksson, Elof; Steinau, Hans-Ulrich; Steinstraesser, Lars

    2006-01-01

    The adenoviral transfer of therapeutic genes into epidermal and dermal cells is an interesting approach to treat skin diseases and to promote wound healing. The aim of this study was to assess the in vitro and in vivo transfection efficacy in skin and burn wounds after adenoviral gene delivery. Primary keratinocytes (HKC), fibroblasts (HFB), and HaCaT cells were transfected using different concentrations of an adenoviral construct (eGFP). Transfection efficiency and cytotoxicity was determine...

  12. Molecular epidemiology of adenoviral keratoconjunctivitis in Saudi Arabia.

    Science.gov (United States)

    Tabbara, Khalid F; Omar, Nazri; Hammouda, Ehab; Akanuma, Masataka; Ohguchi, Takeshi; Ariga, Toshihide; Tagawa, Yoshitsugu; Kitaichi, Nobuyoshi; Ishida, Susumu; Aoki, Koki; Ishiko, Hiroaki; Ohno, Shigeaki

    2010-10-24

    Adenoviral keratoconjunctivitis is a major cause of ocular morbidity and may lead to visual loss. Adenovirus types 8, 19, and 37 may cause epidemic keratoconjunctivitis. The main objective of this study was to determine the types of adenoviruses causing keratoconjunctivitis in Saudi Arabia. We conducted a non-interventional observational clinical study. Seventy three eyes from 65 patients who presented to The Eye Center in Riyadh, Saudi Arabia with clinical features of acute adenoviral keratoconjunctivitis were included. Each patient underwent complete clinical examination and features such as membranous reaction, conjunctival hemorrhage, subepithelial corneal infiltrates, and preauricular lymph node enlargement were recorded. Conjunctival swabs were obtained from patients with presumed acute viral conjunctivitis. Immunochromatography (IC) and restriction fragment length polymorphism polymerase chain reaction (PCR-RFLP) were performed on the conjunctival swabs obtained from each eye. Serotype identification was performed using direct sequencing technique. Forty-nine (67.1%) were adenovirus type 8, 8 (11.0%) were adenovirus type 3, 6 (8.2%) type 37, 5 (6.8%) were adenovirus type 4, and 2 (2.3%) type 19. The remaining 5 were types 14, 19, and 22. The prevalence of membranous conjunctivitis was highest (83%) among eyes with adenovirus type 37 while subepithelial corneal opacities were most commonly seen among eyes with adenovirus type 8 (47%). Immunochromatography tests were positive for adenovirus in 48 (65.7%) out of 73 eyes. This study determined the types of adenoviruses causing keratoconjunctivitis at one center in Saudi Arabia. Direct sequencing techniques is an efficient, accurate, and rapid means of diagnosing adenoviral keratoconjunctivitis. The most common causes of adenoviral keratoconjunctivitis in Saudi Arabia were adenovirus types 8, 3, and 37. Membranous conjunctivitis and subepithelial opacities had the highest frequency of adenovirus types 37 and 8

  13. Lipofectamine and related cationic lipids strongly improve adenoviral infection efficiency of primitive human hematopoietic cells.

    Science.gov (United States)

    Byk, T; Haddada, H; Vainchenker, W; Louache, F

    1998-11-20

    Adenoviral vectors have the potential to infect a large number of cell types including quiescent cells. Their use in hematopoietic cells is limited by the episomal form of their DNA, leading to transgene loss in the progeny cells. However, the use of this vector may be interesting for short-term in vitro modifications of primitive human hematopoietic cells. Therefore, we have investigated the ability of adenovirus to transduce cord blood CD34+ cells. Several promoters were tested using the lacZ reporter gene. The PGK and CMV promoters induced transgene expression in 18-25% of the cells, whereas the HTLV-I and especially the RSV promoter were almost inactive. To improve infection efficiency, adenovirus was complexed with cationic lipids. Lipofectamine, Cellfectin, and RPR120535b, but not Lipofectin, Lipofectace, or DOTAP, markedly improved transgene expression in CD34+ cells (from 19 to 35%). Lipofectamine strongly enhanced infection efficiency of the poorly infectable primitive CD34+CD38low cells (from 11 to 28%) whereas the more mature CD34+CD38+ cells were only slightly affected (from 24 to 31%). Lipofectamine tripled the infection of CFU-GMs and LTC-ICs derived from the CD34+CD38low cell fraction (from 4 to 12% and from 5 to 16%, respectively) and doubled that of BFU-Es (from 13 to 26%). We conclude that cationic lipids can markedly increase the efficiency of adenovirus-mediated gene transfer into primitive hematopoietic cells.

  14. Gene therapy for barrett's esophagus: adenoviral gene transfer in different intestinal models

    NARCIS (Netherlands)

    Marsman, Willem A.; Buskens, Christianne J.; Wesseling, John G.; van Lanschot, J. Jan B.; Bosma, Piter J.

    2005-01-01

    Adenoviral gene therapy could potentially be used for treatment of patients with a Barrett's esophagus. In order to study the feasibility of this approach it is important to study adenoviral intestinal transduction both in vitro and in vivo. In the present study, we used differentiating Caco-2

  15. Novel approach to abuse the hyperactive K-Ras pathway for adenoviral gene therapy of colorectal cancer

    International Nuclear Information System (INIS)

    Naumov, Inna; Kazanov, Dina; Lisiansky, Victoria; Starr, Alex; Aroch, Ilan; Shapira, Shiran; Kraus, Sarah; Arber, Nadir

    2012-01-01

    Background: Functional activation of oncogenic K-Ras signaling pathway plays an important role in the early events of colorectal carcinogenesis (CRC). K-Ras proto-oncogene is involved in 35–40% of CRC cases. Mutations in the Ras gene trigger the transduction of proliferative and anti-apoptotic signals, even in the absence of extra cellular stimuli. The objective of the current study was to use a gene-targeting approach to kill human CRC cells selectively harboring mutated K-Ras. Results: A recombinant adenovirus that carries a lethal gene, PUMA, under the control of a Ras responsive promoter (Ad-Py4-SV40-PUMA) was used selectively to target CRC cells (HCT116, SW480, DLD1 and RIE-Ras) that possess a hyperactive Ras pathway while using HT29 and RIE cells as a control that harbors wild type Ras and exhibit very low Ras activity. Control vector, without the Ras responsive promoter elements was used to assess the specificity of our “gene therapy” approach. Both adenoviral vectors were assed in vitro and in xenograft model in vivo. Ad-Py4-SV40-PUMA showed high potency to induce ∼ 50% apoptosis in vitro, to abolish completely tumor formation by infecting cells with the Ad-Py4-SV40-PUMA prior xenografting them in nude mice and high ability to suppress by ∼ 35% tumor progression in vivo in already established tumors. Conclusions: Selective targeting of CRC cells with the activated Ras pathway may be a novel and effective therapy in CRC. The high potency of this adenoviral vector may help to overcome an undetectable micro metastasis that is the major hurdle in challenging with CRC.

  16. Novel approach to abuse the hyperactive K-Ras pathway for adenoviral gene therapy of colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Naumov, Inna [Integrated Cancer Prevention Center, Tel Aviv (Israel); Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Kazanov, Dina [Integrated Cancer Prevention Center, Tel Aviv (Israel); Lisiansky, Victoria [Integrated Cancer Prevention Center, Tel Aviv (Israel); Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Starr, Alex [Lung and Allergy Institute, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Aroch, Ilan; Shapira, Shiran; Kraus, Sarah [Integrated Cancer Prevention Center, Tel Aviv (Israel); Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Arber, Nadir, E-mail: narber@post.tau.ac.il [Integrated Cancer Prevention Center, Tel Aviv (Israel); Department of Gastroenterology, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel)

    2012-01-15

    Background: Functional activation of oncogenic K-Ras signaling pathway plays an important role in the early events of colorectal carcinogenesis (CRC). K-Ras proto-oncogene is involved in 35-40% of CRC cases. Mutations in the Ras gene trigger the transduction of proliferative and anti-apoptotic signals, even in the absence of extra cellular stimuli. The objective of the current study was to use a gene-targeting approach to kill human CRC cells selectively harboring mutated K-Ras. Results: A recombinant adenovirus that carries a lethal gene, PUMA, under the control of a Ras responsive promoter (Ad-Py4-SV40-PUMA) was used selectively to target CRC cells (HCT116, SW480, DLD1 and RIE-Ras) that possess a hyperactive Ras pathway while using HT29 and RIE cells as a control that harbors wild type Ras and exhibit very low Ras activity. Control vector, without the Ras responsive promoter elements was used to assess the specificity of our 'gene therapy' approach. Both adenoviral vectors were assed in vitro and in xenograft model in vivo. Ad-Py4-SV40-PUMA showed high potency to induce {approx} 50% apoptosis in vitro, to abolish completely tumor formation by infecting cells with the Ad-Py4-SV40-PUMA prior xenografting them in nude mice and high ability to suppress by {approx} 35% tumor progression in vivo in already established tumors. Conclusions: Selective targeting of CRC cells with the activated Ras pathway may be a novel and effective therapy in CRC. The high potency of this adenoviral vector may help to overcome an undetectable micro metastasis that is the major hurdle in challenging with CRC.

  17. Gene therapy in the inner ear using adenovirus vectors.

    Science.gov (United States)

    Husseman, Jacob; Raphael, Yehoash

    2009-01-01

    Therapies for the protection and regeneration of auditory hair cells are of great interest given the significant monetary and lifestyle impact of hearing loss. The past decade has seen tremendous advances in the use of adenoviral vectors to achieve these aims. Preliminary data demonstrated the functional capacity of this technique as adenoviral-induced expression of neurotrophic and growth factors protected hair cells and spiral ganglion neurons from ototoxic insults. Subsequent efforts confirmed the feasibility of adenoviral transfection of cells in the auditory neuroepithelium via cochleostomy into the scala media. Most recently, efforts have focused on regeneration of depleted hair cells. Mammalian hearing loss is generally considered a permanent insult as the auditory epithelium lacks a basal layer capable of producing new hair cells. Recently, the transcription factor Atoh1 has been found to play a critical role in hair cell differentiation. Adenoviral-mediated overexpression of Atoh1 in culture and in vivo have shown the ability to regenerate auditory and vestibular hair cells by causing transdifferentiation of neighboring epithelial-supporting cells. Functional recovery of both the auditory and vestibular systems has been documented following adenoviral induced Atoh1 overexpression. Copyright (c) 2009 S. Karger AG, Basel.

  18. OCCUPATIONAL SAFETY AND HEALTH– VECTOR OF CORPORATE SOCIAL RESPONSIBILITY IN ROMANIAN COMPANIES

    Directory of Open Access Journals (Sweden)

    Geanina Constanța SPĂTARU (PRAVĂȚ

    2015-11-01

    The purpose of this article is to investigate the local reports of the corporate social responsibility of the companies that function in Romania, through their own web page and to make an analysis of the occupational safety and health component as presented in the CSR reports of these companies.

  19. Preclinical correction of human Fanconi anemia complementation group A bone marrow cells using a safety-modified lentiviral vector.

    Science.gov (United States)

    Becker, P S; Taylor, J A; Trobridge, G D; Zhao, X; Beard, B C; Chien, S; Adair, J; Kohn, D B; Wagner, J E; Shimamura, A; Kiem, H-P

    2010-10-01

    One of the major hurdles for the development of gene therapy for Fanconi anemia (FA) is the increased sensitivity of FA stem cells to free radical-induced DNA damage during ex vivo culture and manipulation. To minimize this damage, we have developed a brief transduction procedure for lentivirus vector-mediated transduction of hematopoietic progenitor cells from patients with Fanconi anemia complementation group A (FANCA). The lentiviral vector FancA-sW contains the phosphoglycerate kinase promoter, the FANCA cDNA, and a synthetic, safety-modified woodchuck post transcriptional regulatory element (sW). Bone marrow mononuclear cells or purified CD34(+) cells from patients with FANCA were transduced in an overnight culture on recombinant fibronectin peptide CH-296, in low (5%) oxygen, with the reducing agent, N-acetyl-L-cysteine (NAC), and a combination of growth factors, granulocyte colony-stimulating factor (G-CSF), Flt3 ligand, stem cell factor, and thrombopoietin. Transduced cells plated in methylcellulose in hypoxia with NAC showed increased colony formation compared with 21% oxygen without NAC (Pgene-corrected cells in patients with FANCA.

  20. Molecular Imaging of Gene Expression and Efficacy following Adenoviral-Mediated Brain Tumor Gene Therapy

    Directory of Open Access Journals (Sweden)

    Alnawaz Rehemtulla

    2002-01-01

    Full Text Available Cancer gene therapy is an active area of research relying upon the transfer and subsequent expression of a therapeutic transgene into tumor cells in order to provide for therapeutic selectivity. Noninvasive assessment of therapeutic response and correlation of the location, magnitude, and duration of transgene expression in vivo would be particularly useful in the development of cancer gene therapy protocols by facilitating optimization of gene transfer protocols, vector development, and prodrug dosing schedules. In this study, we developed an adenoviral vector containing both the therapeutic transgene yeast cytosine deaminase (yCD along with an optical reporter gene (luciferase. Following intratumoral injection of the vector into orthotopic 9L gliomas, anatomical and diffusion-weighted MR images were obtained over time in order to provide for quantitative assessment of overall therapeutic efficacy and spatial heterogeneity of cell kill, respectively. In addition, bioluminescence images were acquired to assess the duration and magnitude of gene expression. MR images revealed significant reduction in tumor growth rates associated with yCD/5-fluorocytosine (5FC gene therapy. Significant increases in mean tumor diffusion values were also observed during treatment with 5FC. Moreover, spatial heterogeneity in tumor diffusion changes were also observed revealing that diffusion magnetic resonance imaging could detect regional therapeutic effects due to the nonuniform delivery and/or expression of the therapeutic yCD transgene within the tumor mass. In addition, in vivo bioluminescence imaging detected luciferase gene expression, which was found to decrease over time during administration of the prodrug providing a noninvasive surrogate marker for monitoring gene expression. These results demonstrate the efficacy of the yCD/5FC strategy for the treatment of brain tumors and reveal the feasibility of using multimodality molecular and functional imaging

  1. Imaging expression of adenoviral HSV1-tk suicide gene transfer using the nucleoside analogue FIRU

    International Nuclear Information System (INIS)

    Nanda, Dharmin; Jong, Marion de; Bakker, Willem; Bijster, Magda; Cox, Peter; Vogels, Ronald; Havenga, Menzo; Driesse, Maarten; Avezaat, Cees; Morin, Kevin; Naimi, Ebrahim; Knaus, Edward; Wiebe, Leonard; Smitt, Peter Sillevis

    2002-01-01

    Substrates for monitoring HSV1-tk gene expression include uracil and acycloguanosine derivatives.The most commonly used uracil derivative to monitor HSV1-tk gene transfer is 1-(2-fluoro-2-deoxy-β-D-arabinofuranosyl)-5-[*I]iodouracil (fialuridine; I*-FIAU), where the asterisk denotes any of the radioactive iodine isotopes that can be used. We have previously studied other nucleosides with imaging properties as good as or better than FIAU, including 1-(2-fluoro-2-deoxy-β-D-ribofuranosyl)-5-[*I]iodouracil (FIRU). The first aim of this study was to extend the biodistribution data of 123 I-labelled FIRU. Secondly, we assessed the feasibility of detecting differences in HSV1-tk gene expression levels following adenoviral gene transfer in vivo with 123 I-FIRU. 9L rat gliosarcoma cells were stably transfected with the HSV1-tk gene (9L-tk+). 123 I-FIRU was prepared by radioiodination of 1-(2-fluoro-2-deoxy-β-D-ribofuranosyl)-5-tributylstannyl uracil (FTMRSU; precursor compound) and purified using an activated Sep-Pak column. Incubation of 9L-tk+ cells and the parental 9L cells with 123 I-FIRU resulted in a 100-fold higher accumulation of radioactivity in the 9L-tk+ cells after an optimum incubation time of 4 h. NIH-bg-nu-xid mice were then inoculated subcutaneously with HSV1-tk (-) 9L cells or HSV1-tk (+) 9L-tk+ cells into both flanks. Biodistribution studies and gamma camera imaging were performed at 15 min and 1, 2, 4 and 24 h p.i. At 15 min, the tumour/muscle, tumour/blood and tumour/brain ratios were 5.2, 1.0 and 30.3 respectively. Rapid renal clearance of the tracer from the body resulted in increasing tumour/muscle, tumour/blood and tumour/brain ratios, reaching values of 32.2, 12.5 and 171.6 at 4 h p.i. A maximum specific activity of 22%ID/g tissue was reached in the 9L-tk+ tumours 4 h after 123 I-FIRU injection. Two Ad5-based adenoviral vectors containing the HSV1-tk gene were constructed: a replication-incompetent vector with the transgene in the former E1

  2. Imaging expression of adenoviral HSV1-tk suicide gene transfer using the nucleoside analogue FIRU

    Energy Technology Data Exchange (ETDEWEB)

    Nanda, Dharmin [Department of Neurology, Daniel den Hoed Cancer Centre, University Hospital Rotterdam (Netherlands); Department of Neurosurgery, University Hospital Rotterdam (Netherlands); Jong, Marion de; Bakker, Willem; Bijster, Magda; Cox, Peter [Department of Nuclear Medicine, University Hospital Rotterdam (Netherlands); Vogels, Ronald; Havenga, Menzo [Crucell Holland BV, Leiden (Netherlands); Driesse, Maarten; Avezaat, Cees [Department of Neurosurgery, University Hospital Rotterdam (Netherlands); Morin, Kevin; Naimi, Ebrahim; Knaus, Edward; Wiebe, Leonard [Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton (Canada); Smitt, Peter Sillevis [Department of Neurology, Daniel den Hoed Cancer Centre, University Hospital Rotterdam (Netherlands)

    2002-07-01

    Substrates for monitoring HSV1-tk gene expression include uracil and acycloguanosine derivatives.The most commonly used uracil derivative to monitor HSV1-tk gene transfer is 1-(2-fluoro-2-deoxy-{beta}-D-arabinofuranosyl)-5-[*I]iodouracil (fialuridine; I*-FIAU), where the asterisk denotes any of the radioactive iodine isotopes that can be used. We have previously studied other nucleosides with imaging properties as good as or better than FIAU, including 1-(2-fluoro-2-deoxy-{beta}-D-ribofuranosyl)-5-[*I]iodouracil (FIRU). The first aim of this study was to extend the biodistribution data of {sup 123}I-labelled FIRU. Secondly, we assessed the feasibility of detecting differences in HSV1-tk gene expression levels following adenoviral gene transfer in vivo with {sup 123}I-FIRU. 9L rat gliosarcoma cells were stably transfected with the HSV1-tk gene (9L-tk+). {sup 123}I-FIRU was prepared by radioiodination of 1-(2-fluoro-2-deoxy-{beta}-D-ribofuranosyl)-5-tributylstannyl uracil (FTMRSU; precursor compound) and purified using an activated Sep-Pak column. Incubation of 9L-tk+ cells and the parental 9L cells with {sup 123}I-FIRU resulted in a 100-fold higher accumulation of radioactivity in the 9L-tk+ cells after an optimum incubation time of 4 h. NIH-bg-nu-xid mice were then inoculated subcutaneously with HSV1-tk (-) 9L cells or HSV1-tk (+) 9L-tk+ cells into both flanks. Biodistribution studies and gamma camera imaging were performed at 15 min and 1, 2, 4 and 24 h p.i. At 15 min, the tumour/muscle, tumour/blood and tumour/brain ratios were 5.2, 1.0 and 30.3 respectively. Rapid renal clearance of the tracer from the body resulted in increasing tumour/muscle, tumour/blood and tumour/brain ratios, reaching values of 32.2, 12.5 and 171.6 at 4 h p.i. A maximum specific activity of 22%ID/g tissue was reached in the 9L-tk+ tumours 4 h after {sup 123}I-FIRU injection. Two Ad5-based adenoviral vectors containing the HSV1-tk gene were constructed: a replication-incompetent vector with

  3. Health professional networks as a vector for improving healthcare quality and safety: a systematic review.

    Science.gov (United States)

    Cunningham, Frances C; Ranmuthugala, Geetha; Plumb, Jennifer; Georgiou, Andrew; Westbrook, Johanna I; Braithwaite, Jeffrey

    2012-03-01

    While there is a considerable corpus of theoretical and empirical literature on networks within and outside of the health sector, multiple research questions are yet to be answered. To conduct a systematic review of studies of professionals' network structures, identifying factors associated with network effectiveness and sustainability, particularly in relation to quality of care and patient safety. The authors searched MEDLINE, CINAHL, EMBASE, Web of Science and Business Source Premier from January 1995 to December 2009. A majority of the 26 unique studies identified used social network analysis to examine structural relationships in networks: structural relationships within and between networks, health professionals and their social context, health collaboratives and partnerships, and knowledge sharing networks. Key aspects of networks explored were administrative and clinical exchanges, network performance, integration, stability and influences on the quality of healthcare. More recent studies show that cohesive and collaborative health professional networks can facilitate the coordination of care and contribute to improving quality and safety of care. Structural network vulnerabilities include cliques, professional and gender homophily, and over-reliance on central agencies or individuals. Effective professional networks employ natural structural network features (eg, bridges, brokers, density, centrality, degrees of separation, social capital, trust) in producing collaboratively oriented healthcare. This requires efficient transmission of information and social and professional interaction within and across networks. For those using networks to improve care, recurring success factors are understanding your network's characteristics, attending to its functioning and investing time in facilitating its improvement. Despite this, there is no guarantee that time spent on networks will necessarily improve patient care.

  4. Unique Safety Issues Associated with Virus Vectored Vaccines: Potential for and Theoretical Consequences of Recombination with Wild Type Virus Strains

    Science.gov (United States)

    Condit, Richard C.; Williamson, Anna-Lise; Sheets, Rebecca; Seligman, Stephen J.; Monath, Thomas P.; Excler, Jean-Louis; Gurwith, Marc; Bok, Karin; Robertson, James S.; Kim, Denny; Hendry, Michael; Singh, Vidisha; Mac, Lisa M.; Chen, Robert T.

    2016-01-01

    In 2003 and 2013, the World Health Organization convened informal consultations on characterization and quality aspects of vaccines based on live virus vectors. In the resulting reports, one of several issues raised for future study was the potential for recombination of virus-vectored vaccines with wild type pathogenic virus strains. This paper presents an assessment of this issue formulated by the Brighton Collaboration. To provide an appropriate context for understanding the potential for recombination of virus-vectored vaccines, we review briefly the current status of virus vectored vaccines, mechanisms of recombination between viruses, experience with recombination involving live attenuated vaccines in the field, and concerns raised previously in the literature regarding recombination of virus-vectored vaccines with wild type virus strains. We then present a discussion of the major variables that could influence recombination between a virus-vectored vaccine and circulating wild type virus and the consequences of such recombination, including intrinsic recombination properties of the parent virus used as a vector; sequence relatedness of vector and wild virus; virus host range, pathogenesis and transmission; replication competency of vector in target host; mechanism of vector attenuation; additional factors potentially affecting virulence; and circulation of multiple recombinant vectors in the same target population. Finally, we present some guiding principles for vector design and testing intended to anticipate and mitigate the potential for and consequences of recombination of virus-vectored vaccines with wild type pathogenic virus strains. PMID:27346303

  5. 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....

  6. 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.

  7. Construction of adenoviral vectors expressing F and G glycoproteins of human respiratory syncytial virus (HRSV Construção de vetores adenovirais expressando as glicoproteínas F e G de vírus respiratório sincicial humano (HRSV

    Directory of Open Access Journals (Sweden)

    Ithana Monteiro Kosaka

    2004-06-01

    Full Text Available Human Respiratory Syncytial Virus (HRSV was first characterized in 1957 and has since been recognized as the most common viral cause of severe respiratory tract infection in young infants worldwide. Despite many years of research there is still no effective treatment or any immediate prospect of a vaccine. The HRSV genome is composed of single stranded negative sense RNA and the virion consists of a nucleocapsid packaged within a lipid envelope. The envelope contains spike-like projections, each being a homo-oligomer of one of three transmembrane viral envelope proteins: the attachment protein G, the fusion protein F involved in viral penetration and the small hydrofobic protein SH. The aim of this work was to construct two recombinant replication-defective adenoviruses carrying separately F and G genes from HRSV. This system was chosen because adenovirus delivers genes into target cells with high efficiency in a variety of cell lines and can be used in vitro and in vivo. In order to obtain the recombinant viruses, we did RT-PCR of RNA extracted from the HRSV A2 strain, the genes F and G were cloned in to pAdeno-X vectors. pAdeno-F and pAdeno-G were transfected in HEK-293 cells for the production of recombinant viruses, that expressed efficiently these two proteins and provide us the means for doing functional assays and immunization tests.O Vírus Sincicial Respiratório Humano (HRSV foi isolado e caracterizado pela primeira vez em 1957 e é considerado como o patógeno viral mais freqüente do trato respiratório de bebês e crianças. Apesar de muitos anos de pesquisa, não há ainda um tratamento específico ou uma vacina licenciada. Seu genoma é composto por uma fita simples de RNA polaridade negativa e o vírion consiste em um nucleocapsídeo empacotado por um envelope lipídico. O envelope contém projeções, chamadas espículas, constituídas de homoligômeros de uma das 3 glicoproteínas de membrana: a proteína de ligação G

  8. Adenoviral-mediated correction of methylmalonyl-CoA mutase deficiency in murine fibroblasts and human hepatocytes

    Directory of Open Access Journals (Sweden)

    Korson Mark

    2007-04-01

    Full Text Available Abstract Background Methylmalonic acidemia (MMA, a common organic aciduria, is caused by deficiency of the mitochondrial localized, 5'deoxyadenosylcobalamin dependent enzyme, methylmalonyl-CoA mutase (MUT. Liver transplantation in the absence of gross hepatic dysfunction provides supportive therapy and metabolic stability in severely affected patients, which invites the concept of using cell and gene delivery as future treatments for this condition. Methods To assess the effectiveness of gene delivery to restore the defective metabolism in this disorder, adenoviral correction experiments were performed using murine Mut embryonic fibroblasts and primary human methylmalonyl-CoA mutase deficient hepatocytes derived from a patient who harbored two early truncating mutations, E224X and R228X, in the MUT gene. Enzymatic and expression studies were used to assess the extent of functional correction. Results Primary hepatocytes, isolated from the native liver after removal subsequent to a combined liver-kidney transplantation procedure, or Mut murine fibroblasts were infected with a second generation recombinant adenoviral vector that expressed the murine methylmalonyl-CoA mutase as well as eGFP from distinct promoters. After transduction, [1-14C] propionate macromolecular incorporation studies and Western analysis demonstrated complete correction of the enzymatic defect in both cell types. Viral reconstitution of enzymatic expression in the human methylmalonyl-CoA mutase deficient hepatocytes exceeded that seen in fibroblasts or control hepatocytes. Conclusion These experiments provide proof of principle for viral correction in methylmalonic acidemia and suggest that hepatocyte-directed gene delivery will be an effective therapeutic treatment strategy in both murine models and in human patients. Primary hepatocytes from a liver that was unsuitable for transplantation provided an important resource for these studies.

  9. Coating with spermine-pullulan polymer enhances adenoviral transduction of mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Wan L

    2016-12-01

    coating could enhance adenoviral transduction of MSCs without detectable cytotoxicity or effects on differentiation. Our results argue in favor of the potentiality of the SP-coated Adv as a prototype vector for efficient and safe transduction of MSCs. Keywords: mesenchymal stem cells, adenovirus vectors, spermine-pullulan, polymer, gene transduction

  10. Radiosensitization effect of recombinant adenoviral-mediated PUMA gene on pancreatic carcinoma cells

    International Nuclear Information System (INIS)

    Zhu Dongming; Zhang Kejun; Li Dechun; Zhu Xuefeng; Yang Yong

    2009-01-01

    Objective: To study the effect of PUMA gene mediated by recombinant adenovirus vector combined with radiation on the pancreatic carcinoma. Methods: The PANC-1 cells were infected with Ad- PUMA (MOI=10, 50 and 100, respectively) for 48 h. The expression of PUMA mRNA and protein was detected by RT-PCR and Western blot, respectively. PANC-1 cells were divided into 4 groups: control group, transfection group, irradiation group and combined treatment group. The cell growth inhibition rate and apoptotic rate of PANC-1 cells were assessed by MTT assay and flow cytometry. Human pancreatic carcinomas were transplanted subcutaneously in nude mice, which were randomized into 4 groups: control group, transfection group, irradiation group and combined treatment group. Tumor growth rate and apoptotic index at different time points were recorded in 35 days. Results: The expression of PUMA mRNA and protein was increased with the increase of MOI of Ad-PUMA, which was does-dependant (MOI=10, mRNA=0.46± 0.02, protein=0.75± 0.09; MOI=50, mRNA=1.12±0.09, protein=1.01±0.18; MOI=100, mRNA=1.50±0.08, protein= 1.80±0.15; P 3 , (39.5±9.23)mm 3 , (33.6±10.3)mm 3 and (52.0±11.43)mm 3 , respectively, P<0.05]. And the apoptotic index was increased in the same manner (AI=0.43±0.05, 0.29±0.10, 0.24±0.05 and 0.00±0.00, respectively, P<0.05). Conclusions: Recombinant adenoviral-mediated PUMA gene combined with irradiation could increase the cell-killing effect on pancreatic carcinoma. It is better than that of either one kind of therapy. (authors)

  11. Loss of Endothelial Barrier in Marfan Mice (mgR/mgR Results in Severe Inflammation after Adenoviral Gene Therapy.

    Directory of Open Access Journals (Sweden)

    Philipp Christian Seppelt

    Full Text Available Marfan syndrome is an autosomal dominant inherited disorder of connective tissue. The vascular complications of Marfan syndrome have the biggest impact on life expectancy. The aorta of Marfan patients reveals degradation of elastin layers caused by increased proteolytic activity of matrix metalloproteinases (MMPs. In this study we performed adenoviral gene transfer of human tissue inhibitor of matrix metalloproteinases-1 (hTIMP-1 in aortic grafts of fibrillin-1 deficient Marfan mice (mgR/mgR in order to reduce elastolysis.We performed heterotopic infrarenal transplantation of the thoracic aorta in female mice (n = 7 per group. Before implantation, mgR/mgR and wild-type aortas (WT, C57BL/6 were transduced ex vivo with an adenoviral vector coding for human TIMP-1 (Ad.hTIMP-1 or β-galactosidase (Ad.β-Gal. As control mgR/mgR and wild-type aortas received no gene therapy. Thirty days after surgery, overexpression of the transgene was assessed by immunohistochemistry (IHC and collagen in situ zymography. Histologic staining was performed to investigate inflammation, the neointimal index (NI, and elastin breaks. Endothelial barrier function of native not virus-exposed aortas was evaluated by perfusion of fluorescent albumin and examinations of virus-exposed tissue were performed by transmission electron microscopy (TEM.IHC and ISZ revealed sufficient expression of the transgene. Severe cellular inflammation and intima hyperplasia were seen only in adenovirus treated mgR/mgR aortas (Ad.β-Gal, Ad.hTIMP-1 NI: 0.23; 0.43, but not in native and Ad.hTIMP-1 treated WT (NI: 0.01; 0.00. Compared to native mgR/mgR and Ad.hTIMP-1 treated WT aorta, the NI is highly significant greater in Ad.hTIMP-1 transduced mgR/mgR aorta (p = 0.001; p = 0.001. As expected, untreated Marfan grafts showed significant more elastolysis compared to WT (p = 0.001. However, elastolysis in Marfan aortas was not reduced by adenoviral overexpression of hTIMP-1 (compared to untreated

  12. Reversal of experimental colitis disease activity in mice following administration of an adenoviral IL-10 vector

    OpenAIRE

    Sasaki, Makoto; Mathis, J Michael; Jennings, Merilyn H; Jordan, Paul; Wang, Yuping; Ando, Tomoaki; Joh, Takashi; Alexander, J Steven

    2005-01-01

    Abstract Genetic deficiency in the expression of interleukin-10 (IL-10) is associated with the onset and progression of experimental inflammatory bowel disease (IBD). The clinical significance of IL-10 expression is supported by studies showing that immune-augmentation of IL-10 prevents inflammation and mucosal damage in animal models of colitis and in human colitis. Interleukin-10 (IL-10), an endogenous anti-inflammatory and immunomodulating cytokine, has been shown to prevent some inflammat...

  13. Adenoviral protein V promotes a process of viral assembly through nucleophosmin 1

    Energy Technology Data Exchange (ETDEWEB)

    Ugai, Hideyo; Dobbins, George C.; Wang, Minghui [Division of Human Gene Therapy, Departments of Medicine, Obstetrics and Gynecology, Pathology, and Surgery, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Le, Long P. [Massachusetts General Hospital, Pathology Service, 55 Fruit St.-GRJ 249, Boston, MA 02114 (United States); Matthews, David A. [School of Cellular and Molecular Medicine, Medical Sciences Building, University of Bristol, Bristol BS8 1TD (United Kingdom); Curiel, David T., E-mail: dcuriel@radonc.wustl.edu [Division of Human Gene Therapy, Departments of Medicine, Obstetrics and Gynecology, Pathology, and Surgery, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); The Gene Therapy Center, University of Alabama at Birmingham, Birmingham, AL 35294 (United States)

    2012-10-25

    Adenoviral infection induces nucleoplasmic redistribution of a nucleolar nucleophosmin 1/NPM1/B23.1. NPM1 is preferentially localized in the nucleoli of normal cells, whereas it is also present at the nuclear matrix in cancer cells. However, the biological roles of NPM1 during infection are unknown. Here, by analyzing a pV-deletion mutant, Ad5-dV/TSB, we demonstrate that pV promotes the NPM1 translocation from the nucleoli to the nucleoplasm in normal cells, and the NPM1 translocation is correlated with adenoviral replication. Lack of pV causes a dramatic reduction of adenoviral replication in normal cells, but not cancer cells, and Ad5-dV/TSB was defective in viral assembly in normal cells. NPM1 knockdown inhibits adenoviral replication, suggesting an involvement of NPM1 in adenoviral biology. Further, we show that NPM1 interacts with empty adenovirus particles which are an intermediate during virion maturation by immunoelectron microscopy. Collectively, these data implicate that pV participates in a process of viral assembly through NPM1.

  14. Good Laboratory Practice Preclinical Safety Studies for GSK2696273 (MLV Vector-Based Ex Vivo Gene Therapy for Adenosine Deaminase Deficiency Severe Combined Immunodeficiency) in NSG Mice.

    Science.gov (United States)

    Carriglio, Nicola; Klapwijk, Jan; Hernandez, Raisa Jofra; Vezzoli, Michela; Chanut, Franck; Lowe, Rhiannon; Draghici, Elena; Nord, Melanie; Albertini, Paola; Cristofori, Patrizia; Richards, Jane; Staton, Hazel; Appleby, Jonathan; Aiuti, Alessandro; Sauer, Aisha V

    2017-03-01

    GSK2696273 (autologous CD34+ cells transduced with retroviral vector that encodes for the human adenosine deaminase [ADA] enzyme) is a gamma-retroviral ex vivo gene therapy of bone marrow-derived CD34+ cells for the treatment of adenosine deaminase deficiency severe combined immunodeficiency (ADA-SCID). ADA-SCID is a severe monogenic disease characterized by immunologic and nonimmunologic symptoms. Bone-marrow transplant from a matched related donor is the treatment of choice, but it is available for only a small proportion of patients. Ex vivo gene therapy of patient bone-marrow CD34+ cells is an alternative treatment. In order to prepare for a marketing authorization application in the European Union, preclinical safety studies in mice were requested by the European Medicines Agency (EMA). A pilot study and a main biodistribution study were performed according to Good Laboratory Practice (GLP) at the San Raffaele Telethon Institute for Gene Therapy test facility. In the main study, human umbilical cord blood (UCB)-derived CD34+ cells were transduced with gamma-retroviral vector used in the production of GSK2696273. Groups of 10 male and 10 female NOD-SCID gamma (NSG) mice were injected intravenously with a single dose of transduced- or mock-transduced UCB CD34+ cells, and they were observed for 4 months. Engraftment and multilineage differentiation of blood cells was observed in the majority of animals in both groups. There was no significant difference in the level of chimerism between the two groups. In the gene therapy group, vector was detectable in lymphohemopoietic and nonlymphohemopoietic tissues, consistent with the presence of gene-modified human hematopoietic donor cells. Given the absence of relevant safety concerns in the data, the nonclinical studies and the clinical experience with GSK2696273 supported a successful application for market authorization in the European Union for the treatment of ADA-SCID patients, for whom no suitable human leukocyte

  15. Safety and Immunogenicity of a Recombinant Adenovirus Serotype 35-Vectored HIV-1 Vaccine in Adenovirus Serotype 5 Seronegative and Seropositive Individuals.

    Science.gov (United States)

    Fuchs, Jonathan D; Bart, Pierre-Alexandre; Frahm, Nicole; Morgan, Cecilia; Gilbert, Peter B; Kochar, Nidhi; DeRosa, Stephen C; Tomaras, Georgia D; Wagner, Theresa M; Baden, Lindsey R; Koblin, Beryl A; Rouphael, Nadine G; Kalams, Spyros A; Keefer, Michael C; Goepfert, Paul A; Sobieszczyk, Magdalena E; Mayer, Kenneth H; Swann, Edith; Liao, Hua-Xin; Haynes, Barton F; Graham, Barney S; McElrath, M Juliana

    2015-05-01

    Recombinant adenovirus serotype 5 (rAd5)-vectored HIV-1 vaccines have not prevented HIV-1 infection or disease and pre-existing Ad5 neutralizing antibodies may limit the clinical utility of Ad5 vectors globally. Using a rare Ad serotype vector, such as Ad35, may circumvent these issues, but there are few data on the safety and immunogenicity of rAd35 directly compared to rAd5 following human vaccination. HVTN 077 randomized 192 healthy, HIV-uninfected participants into one of four HIV-1 vaccine/placebo groups: rAd35/rAd5, DNA/rAd5, and DNA/rAd35 in Ad5-seronegative persons; and DNA/rAd35 in Ad5-seropositive persons. All vaccines encoded the HIV-1 EnvA antigen. Antibody and T-cell responses were measured 4 weeks post boost immunization. All vaccines were generally well tolerated and similarly immunogenic. As compared to rAd5, rAd35 was equally potent in boosting HIV-1-specific humoral and cellular immunity and responses were not significantly attenuated in those with baseline Ad5 seropositivity. Like DNA, rAd35 efficiently primed rAd5 boosting. All vaccine regimens tested elicited cross-clade antibody responses, including Env V1/V2-specific IgG responses. Vaccine antigen delivery by rAd35 is well-tolerated and immunogenic as a prime to rAd5 immunization and as a boost to prior DNA immunization with the homologous insert. Further development of rAd35-vectored prime-boost vaccine regimens is warranted.

  16. Adenoviral transfer of the heme oxygenase-1 gene protects striatal astrocytes from heme-mediated oxidative injury.

    Science.gov (United States)

    Teng, Zhi-Ping; Chen, Jing; Chau, Lee-Young; Galunic, Nicholas; Regan, Raymond F

    2004-11-01

    Heme oxygenase-1 (HO-1) is induced in the CNS after hemorrhage, and may have an effect on injury to surrounding tissue. Hemin, the preferred substrate of HO, is a neurotoxin that is present in intracranial hematomas. In a prior study, we observed that HO inhibitors increased the vulnerability of cultured cortical astrocytes to heme-mediated oxidative injury. To investigate the effect of HO more specifically, we used an adenoviral vector encoding the human HO-1 gene to specifically increase HO-1 expression. Incubation with 100 MOI of the HO-1 adenovirus (Adv-HHO-1) for 24 h increased both HO-1 protein and HO activity; a control adenovirus lacking the HO-1 gene had no effect. Using a DNA probe that was specific for human HO-1, 80.5 +/- 7.2% of astrocytes were observed to be infected by in situ hybridization. The cell death produced by 30-60 microM hemin was significantly reduced by pretreatment with 100 MOI Adv-HHO-1, as assessed by LDH release, propidium iodide exclusion, and MTT reduction assay. The threefold increase in cell protein oxidation produced by hemin was also attenuated in cultures pretreated with Adv-HHO-1. These results support the hypothesis that HO-1 protects astrocytes from heme-mediated oxidative injury. Specifically increasing astrocytic HO-1 by gene transfer may have a beneficial effect on hemorrhagic CNS injury.

  17. Micro-computed tomography of pulmonary fibrosis in mice induced by adenoviral gene transfer of biologically active transforming growth factor-β1

    Directory of Open Access Journals (Sweden)

    Gauldie Jack

    2010-12-01

    Full Text Available Abstract Background Micro-computed tomography (micro-CT is a novel tool for monitoring acute and chronic disease states in small laboratory animals. Its value for assessing progressive lung fibrosis in mice has not been reported so far. Here we examined the importance of in vivo micro-CT as non-invasive tool to assess progression of pulmonary fibrosis in mice over time. Methods Pulmonary fibrosis was induced in mice by intratracheal delivery of an adenoviral gene vector encoding biologically active TGF-ß1 (AdTGF-ß1. Respiratory gated and ungated micro-CT scans were performed at 1, 2, 3, and 4 weeks post pulmonary adenoviral gene or control vector delivery, and were then correlated with respective histopathology-based Ashcroft scoring of pulmonary fibrosis in mice. Visual assessment of image quality and consolidation was performed by 3 observers and a semi-automated quantification algorithm was applied to quantify aerated pulmonary volume as an inverse surrogate marker for pulmonary fibrosis. Results We found a significant correlation between classical Ashcroft scoring and micro-CT assessment using both visual assessment and the semi-automated quantification algorithm. Pulmonary fibrosis could be clearly detected in micro-CT, image quality values were higher for respiratory gated exams, although differences were not significant. For assessment of fibrosis no significant difference between respiratory gated and ungated exams was observed. Conclusions Together, we show that micro-CT is a powerful tool to assess pulmonary fibrosis in mice, using both visual assessment and semi-automated quantification algorithms. These data may be important in view of pre-clinical pharmacologic interventions for the treatment of lung fibrosis in small laboratory animals.

  18. Adenoviral DNA replication: DNA sequences and enzymes required for initiation in vitro

    International Nuclear Information System (INIS)

    Stillman, B.W.; Tamanoi, F.

    1983-01-01

    In this paper evidence is provided that the 140,000-dalton DNA polymerase is encoded by the adenoviral genome and is required for the initiation of DNA replication in vitro. The DNA sequences in the template DNA that are required for the initiation of replication have also been identified, using both plasmid DNAs and synthetic oligodeoxyribonucleotides. 48 references, 7 figures, 1 table

  19. Ovarian cancer targeted adenoviral-mediated mda-7/IL-24 gene therapy

    NARCIS (Netherlands)

    Mahasreshti, PJ; Kataram, M; Wu, HJ; Yalavarthy, LP; Carey, D; Dent, P; Chada, S; Alvarez, RD; Haisma, HJ; Fisher, PB; Curiel, DT

    Objective. We have previously shown that adenoviral-mediated melanoma differentiation-associated gene-7 (Ad.mda-7) therapy induces apoptosis in ovarian cancer cells. However, the apoptosis induction was low and directly correlated with infectivity of Ad.mda-7. The objective of this study was to

  20. The effects of combining ionizing radiation and adenoviral p53 therapy in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Li Jianhua; Lax, Stuart A.; Kim, John; Klamut, Henry; Liu Feifei

    1999-01-01

    Purpose: Nasopharyngeal carcinoma (NPC) is a malignant disease of the head/neck region, with a 5-year survival level of approximately 65%. To explore gene therapy as a novel approach which might improve outcome, we have shown previously that introduction of human recombinant wild-type p53 mediated by the adenoviral vector (Ad5CMV-p53) was cytotoxic in two human nasopharyngeal carcinoma (NPC) cell lines (CNE-1 and CNE-2Z). The current work was designed to determine whether this strategy, combined with ionizing radiation (XRT), was more effective than either treatment alone. Methods and Materials: CNE-1, CNE-2Z, and a normal human nasopharyngeal fibroblast strain, KS1, were infected with 2- and 6-plaque-forming units (pfu)/cell of Ad5CMV-p53, respectively. These doses were iso-effective for β-galactosidase activity in the CNE-1 and CNE-2Z cells. XRT was administered 24 h post-infection, and Western blot analyses were conducted for p53, p21 WAF1/CIP1 , bax, and bcl-2 2 days after XRT. Cell survival was assessed using a clonogenic assay. Presence of DNA ladders reflecting apoptosis was detected using DNA agarose gel electrophoresis, and cell cycle was analyzed using flow cytometry. Results: The combination of Ad5CMV-p53 plus XRT (2, 4, and 6 Gy) resulted in an approximately 1-log greater level of cytotoxicity compared to that observed with XRT alone for both NPC cell lines. The two modalities appear to be interacting in a synergistic manner in cancer cells, but not in KS1 fibroblasts. XRT alone stimulated minimal p53 expression in control cells; Ad5CMV-p53 alone induced significant recombinant p53 expression, which was not further enhanced by the addition of XRT. Similar observations were made for p21 WAF1/CIP1 expression. No changes were observed for bax or bcl-2 expression with any of these treatments. Apoptosis was induced following 4 Gy of XRT alone, but was observed after only 2 Gy when combined with Ad5CMV-p53. Cell cycle analysis indicated that Ad5CMV-p53

  1. Preclinical assessment of viral vectored and protein vaccines targeting the Duffy-binding protein region II of Plasmodium vivax

    Directory of Open Access Journals (Sweden)

    Simone C de Cassan

    2015-07-01

    Full Text Available Malaria vaccine development has largely focused on Plasmodium falciparum; however a reawakening to the importance of P. vivax has spurred efforts to develop vaccines against this difficult to treat and at times severe form of relapsing malaria, which constitutes a significant proportion of human malaria cases worldwide. The almost complete dependence of P. vivax red blood cell invasion on the interaction of the P. vivax Duffy-binding protein region II (PvDBP_RII with the human Duffy antigen receptor for chemokines (DARC, makes this antigen an attractive vaccine candidate against blood-stage P. vivax. Here, we generated both preclinical and clinically-compatible adenoviral and poxviral vectored vaccine candidates expressing the Salvador I allele of PvDBP_RII – including human adenovirus serotype 5 (HAdV5, chimpanzee adenovirus serotype 63 (ChAd63 and modified vaccinia virus Ankara (MVA vectors. We report on the antibody and T cell immunogenicity of these vaccines in mice or rabbits, either used alone in a viral vectored prime-boost regime, or in ‘mixed-modality’ adenovirus prime – protein-in-adjuvant boost regimes (using a recombinant protein PvDBP_RII protein antigen formulated in Montanide®ISA720 or Abisco®100 adjuvants. Antibodies induced by these regimes were found to bind to native parasite antigen from P. vivax infected Thai patients and were capable of inhibiting the binding of PvDBP_RII to its receptor DARC using an in vitro binding inhibition assay. In recent years, recombinant ChAd63 and MVA vectors have been quickly translated into human clinical trials for numerous antigens from P. falciparum as well as a growing number of other pathogens. The vectors reported here are immunogenic in small animals, elicit antibodies against PvDBP_RII and have recently entered clinical trials which will provide the first assessment of the safety and immunogenicity of the PvDBP_RII antigen in humans.

  2. Safety issues in construction of facilities for long-term storage of radioactive waste at vector site

    Energy Technology Data Exchange (ETDEWEB)

    Tokarevskyi, O.; Alekseeva, Z.; Kondratiev, S. [State Scientific and Technical Center for Nuclear and Radiation Safety, Kyiv (Ukraine); Rybalka, N. [State Nuclear Regulatory Inspectorate of Ukraine, Kyiv (Ukraine)

    2013-07-01

    In Ukraine, it is planned to create a number of near-surface facilities for disposal of short-lived RW and long-term (up to 100 years) storage of long-lived RW at the Vector site in the Chernobyl exclusion zone. The expected streams of long-lived RW are analyzed in the paper. According to the analysis of RW streams, in particular, issues are considered on development of RW acceptance criteria, admissible radiological impacts during preparation of RW for long-term storage, reliability of barriers (RW packages, modules and structures, etc.) during long-term storage of RW. (orig.)

  3. Preclinical safety and efficacy of an anti–HIV-1 lentiviral vector containing a short hairpin RNA to CCR5 and the C46 fusion inhibitor

    Directory of Open Access Journals (Sweden)

    Orit Wolstein

    2014-01-01

    Full Text Available Gene transfer has therapeutic potential for treating HIV-1 infection by generating cells that are resistant to the virus. We have engineered a novel self-inactivating lentiviral vector, LVsh5/C46, using two viral-entry inhibitors to block early steps of HIV-1 cycle. The LVsh5/C46 vector encodes a short hairpin RNA (shRNA for downregulation of CCR5, in combination with the HIV-1 fusion inhibitor, C46. We demonstrate here the effective delivery of LVsh5/C46 to human T cell lines, peripheral blood mononuclear cells, primary CD4+ T lymphocytes, and CD34+ hematopoietic stem/progenitor cells (HSPC. CCR5-targeted shRNA (sh5 and C46 peptide were stably expressed in the target cells and were able to effectively protect gene-modified cells against infection with CCR5- and CXCR4-tropic strains of HIV-1. LVsh5/C46 treatment was nontoxic as assessed by cell growth and viability, was noninflammatory, and had no adverse effect on HSPC differentiation. LVsh5/C46 could be produced at a scale sufficient for clinical development and resulted in active viral particles with very low mutagenic potential and the absence of replication-competent lentivirus. Based on these in vitro results, plus additional in vivo safety and efficacy data, LVsh5/C46 is now being tested in a phase 1/2 clinical trial for the treatment of HIV-1 disease.

  4. Pre-Clinical Efficacy and Safety of Experimental Vaccines Based on Non-Replicating Vaccinia Vectors against Yellow Fever

    Science.gov (United States)

    Schäfer, Birgit; Holzer, Georg W.; Joachimsthaler, Alexandra; Coulibaly, Sogue; Schwendinger, Michael; Crowe, Brian A.; Kreil, Thomas R.; Barrett, P. Noel; Falkner, Falko G.

    2011-01-01

    Background Currently existing yellow fever (YF) vaccines are based on the live attenuated yellow fever virus 17D strain (YFV-17D). Although, a good safety profile was historically attributed to the 17D vaccine, serious adverse events have been reported, making the development of a safer, more modern vaccine desirable. Methodology/Principal Findings A gene encoding the precursor of the membrane and envelope (prME) protein of the YFV-17D strain was inserted into the non-replicating modified vaccinia virus Ankara and into the D4R-defective vaccinia virus. Candidate vaccines based on the recombinant vaccinia viruses were assessed for immunogenicity and protection in a mouse model and compared to the commercial YFV-17D vaccine. The recombinant live vaccines induced γ-interferon-secreting CD4- and functionally active CD8-T cells, and conferred full protection against lethal challenge already after a single low immunization dose of 105 TCID50. Surprisingly, pre-existing immunity against wild-type vaccinia virus did not negatively influence protection. Unlike the classical 17D vaccine, the vaccinia virus-based vaccines did not cause mortality following intracerebral administration in mice, demonstrating better safety profiles. Conclusions/Significance The non-replicating recombinant YF candidate live vaccines induced a broad immune response after single dose administration, were effective even in the presence of a pre-existing immunity against vaccinia virus and demonstrated an excellent safety profile in mice. PMID:21931732

  5. Pre-clinical efficacy and safety of experimental vaccines based on non-replicating vaccinia vectors against yellow fever.

    Directory of Open Access Journals (Sweden)

    Birgit Schäfer

    Full Text Available BACKGROUND: Currently existing yellow fever (YF vaccines are based on the live attenuated yellow fever virus 17D strain (YFV-17D. Although, a good safety profile was historically attributed to the 17D vaccine, serious adverse events have been reported, making the development of a safer, more modern vaccine desirable. METHODOLOGY/PRINCIPAL FINDINGS: A gene encoding the precursor of the membrane and envelope (prME protein of the YFV-17D strain was inserted into the non-replicating modified vaccinia virus Ankara and into the D4R-defective vaccinia virus. Candidate vaccines based on the recombinant vaccinia viruses were assessed for immunogenicity and protection in a mouse model and compared to the commercial YFV-17D vaccine. The recombinant live vaccines induced γ-interferon-secreting CD4- and functionally active CD8-T cells, and conferred full protection against lethal challenge already after a single low immunization dose of 10(5 TCID(50. Surprisingly, pre-existing immunity against wild-type vaccinia virus did not negatively influence protection. Unlike the classical 17D vaccine, the vaccinia virus-based vaccines did not cause mortality following intracerebral administration in mice, demonstrating better safety profiles. CONCLUSIONS/SIGNIFICANCE: The non-replicating recombinant YF candidate live vaccines induced a broad immune response after single dose administration, were effective even in the presence of a pre-existing immunity against vaccinia virus and demonstrated an excellent safety profile in mice.

  6. Safety

    International Nuclear Information System (INIS)

    1998-01-01

    A brief account of activities carried out by the Nuclear power plants Jaslovske Bohunice in 1997 is presented. These activities are reported under the headings: (1) Nuclear safety; (2) Industrial and health safety; (3) Radiation safety; and Fire protection

  7. Isolation of proteins involved in the replication of adenoviral DNA in vitro

    International Nuclear Information System (INIS)

    Lichy, J.H.; Nagata, K.; Friefeld, B.R.; Enomoto, T.; Field, J.; Guggenheimer, R.A.; Ikeda, J.E.; Horwitz, M.S.; Hurwitz, J.

    1983-01-01

    The simple mechanism of replication of adenoviral DNA has made adenovirus an especially useful model system for studies of eukaryotic replication mechanisms. The availability of this in vitro system that replicates exogenously added Ad DNA-pro has made it possible to characterize the factors involved in replication. The results presented in this paper summarize our further fractionation of the in vitro system. First, the properties of two factors purified from the uninfected nuclear extract are described. Second, the separation of the pTP/Ad Pol complex into subunits and the properties of the isolated subunits are presented. The 140K protein is shown to possess the Ad DNA polymerase activity. The results suggest that the only DNA polymerase required for adenoviral DNA replication in vitro is the 140K Ad DNA polymerase and that this enzyme is probably a viral gene product. 50 references, 10 figures, 3 tables

  8. Down-regulation of viral replication by adenoviral-mediated expression of siRNA against cellular cofactors for hepatitis C virus

    International Nuclear Information System (INIS)

    Zhang Jing; Yamada, Osamu; Sakamoto, Takashi; Yoshida, Hiroshi; Iwai, Takahiro; Matsushita, Yoshihisa; Shimamura, Hideo; Araki, Hiromasa; Shimotohno, Kunitada

    2004-01-01

    Small interfering RNA (siRNA) is currently being evaluated not only as a powerful tool for functional genomics, but also as a potentially promising therapeutic agent for cancer and infectious diseases. Inhibitory effect of siRNA on viral replication has been demonstrated in multiple pathogenic viruses. However, because of the high sequence specificity of siRNA-mediated RNA degradation, antiviral efficacy of siRNA directed to viral genome will be largely limited by emergence of escape variants resistant to siRNA due to high mutation rates of virus, especially RNA viruses such as poliovirus and hepatitis C virus (HCV). To investigate the therapeutic feasibility of siRNAs specific for the putative cellular cofactors for HCV, we constructed adenovirus vectors expressing siRNAs against La, polypyrimidine tract-binding protein (PTB), subunit gamma of human eukaryotic initiation factors 2B (eIF2Bγ), and human VAMP-associated protein of 33 kDa (hVAP-33). Adenoviral-mediated expression of siRNAs markedly diminished expression of the endogenous genes, and silencing of La, PTB, and hVAP-33 by siRNAs substantially blocked HCV replication in Huh-7 cells. Thus, our studies demonstrate the feasibility and potential of adenoviral-delivered siRNAs specific for cellular cofactors in combating HCV infection, which can be used either alone or in combination with siRNA against viral genome to prevent the escape of mutant variants and provide additive or synergistic anti-HCV effects

  9. Treatment for Retinopathy of Prematurity in an Infant with Adenoviral Conjunctivitis

    Directory of Open Access Journals (Sweden)

    Murat Gunay

    2015-01-01

    Full Text Available Retinopathy of prematurity (ROP has been a major problematic disorder during childhood. Laser photocoagulation (LPC has been proven to be effective in most of the ROP cases. Adenoviral conjunctivitis (AVC is responsible for epidemics among adult and pediatric population. It has also been reported to be a cause of outbreaks in neonatal intensive care units (NICU several times. We herein demonstrate a case with AVC who underwent LPC for ROP. And we discuss the treatment methodology in such cases.

  10. When should adenoviral non-gonococcal urethritis be suspected? Two case reports.

    Science.gov (United States)

    Avolio, Manuela; De Rosa, Rita; Modolo, Maria Luisa; Stano, Paola; Camporese, Alessandro

    2014-01-01

    The impact of Adenovirus as agent of non-gonococcal urethritis (NGU) is still poorly documented in the literature. We describe two cases showing that adenoviral infection should be reasonably hypothesized in men with dysuria and scant urethral discharge in addition to meatus inflammation and/or edema (meatitis) or conjunctivitis. Case 1: a 55-year-old man came to our observation in July 2012 referring a 5-day-history of intense dysuria and scant mucoid urethral discharge. Physical examination revealed the urethral discharge referred, but also modest meatitis and an intense conjunctival hyperemia on his right eye. Adenoviral infection was investigated and Adenovirus DNA (type 37) was detected in both the urethral and conjunctival swabs. Case 2: a 43-year-old man with intense dysuria, started 4-5 days earlier, came to our attention with his wife in August 2012. Scant urethral mucoid secretions, severe meatal inflammation of the male patient were revealed during physical examination. His wife instead complained of a 2-day history of intense burning eyes. Adenoviral infection was investigated and Adenovirus DNA (type 37) was positive both in the male urethral swab and in his wife's conjunctival swab. Adenovirus seems to cause a distinct and recognisable clinical syndrome in men presenting with urethritis. Studies on the prevalence and role of Adenovirus as a causative agent of urethritis are limited. Moreover, as rapid advanced molecular microbiology is now available, we believe that extending the search to Adenovirus in sexually active men with dysuria, scant discharge in addition to meatitis or conjunctivitis, should be a useful approach improving our understanding about adenoviral NGU, and especially avoiding or stopping unnecessary empirical antibiotic therapy.

  11. Generation of a functional and durable vascular niche by the adenoviral E4ORF1 gene

    OpenAIRE

    Seandel, Marco; Butler, Jason M.; Kobayashi, Hideki; Hooper, Andrea T.; White, Ian A.; Zhang, Fan; Vertes, Eva L.; Kobayashi, Mariko; Zhang, Yan; Shmelkov, Sergey V.; Hackett, Neil R.; Rabbany, Sina; Boyer, Julie L.; Rafii, Shahin

    2008-01-01

    Vascular cells contribute to organogenesis and tumorigenesis by producing unknown factors. Primary endothelial cells (PECs) provide an instructive platform for identifying factors that support stem cell and tumor homeostasis. However, long-term maintenance of PECs requires stimulation with cytokines and serum, resulting in loss of their angiogenic properties. To circumvent this hurdle, we have discovered that the adenoviral E4ORF1 gene product maintains long-term survival and facilitates orga...

  12. Adenoviral infection in a collection of juvenile inland bearded dragons (Pogona vitticeps).

    Science.gov (United States)

    Doneley, R J T; Buckle, K N; Hulse, L

    2014-01-01

    Juvenile inland bearded dragons (Pogona vitticeps) from a breeding collection in south-east Queensland were presented at age 6-10 weeks with neurological signs, poor growth and occasional deaths. Histopathological examination revealed that six of eight lizards had multifocal non-suppurative hepatitis associated with 5-10 μm diameter, smudgy, basophilic, hyaline intranuclear inclusion bodies that marginated the nuclear chromatin. These histological lesions were considered consistent with adenoviral hepatitis. Infection with adenovirus was confirmed positive in one of the eight dragons by PCR for adenoviral DNA. DNA was extracted from formalin-fixed paraffin-embedded pooled tissues of the juvenile inland bearded dragons and tested using a nested-PCR protocol with primers specific for identification of adenovirus. Sequencing of the one PCR-positive dragon showed 95% nucleotide sequence alignment with agamid atadenovirus 1. Further investigation involved testing the breeding population, including the parents of the affected juveniles. Blood and cloacal samples were collected from the adult population, DNA was extracted and tested by PCR for adenovirus. There was a high percentage of positive results from the samples collected from the breeding population. This is the first reported group outbreak of adenoviral disease in bearded dragons in Australia. © 2014 Australian Veterinary Association.

  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. 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

  15. 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.

  16. Adenoviral short hairpin RNA therapy targeting phosphodiesterase 5a relieves cardiac remodeling and dysfunction following myocardial infarction

    Science.gov (United States)

    Li, Longhu; Haider, Husnain Kh.; Wang, Linlin; Lu, Gang

    2012-01-01

    We previously showed that treatment with tadalafil, a long-acting phosphodiesterase-5a (PDE5a) inhibitor, effectively prevented adverse left ventricular (LV) remodeling of the infarcted heart. We hypothesized that short-hairpin RNA (shRNA) therapy targeting PDE5a would simulate the effects of pharmacological intervention for treatment of postinfarction LV remodeling and dysfunction. Experimental model of myocardial infarction was developed in female mice by permanent ligation of left coronary artery. Immediately after that, an adenoviral vector encoding for shRNA sequence targeting PDE5a (Ad-shPDE5a) was injected intramyocardially, which specifically inhibited PDE5a in the heart. Four weeks later, Ad-shPDE5a treated mice showed significant mitigation of the left ventricle (LV) dilatation and dysfunction as indicated by smaller LV cavity and more preserved ejection fraction and fractional shortening. Infarction size and fibrosis were significantly reduced in Ad-shPDE5a-treated mice. Additionally, more salvaged cardiomyocytes, significantly reduced collagen contents, and higher blood vessel density were observed in Ad-shPDE5a-treated mice. The cytoprotective effects of Ad-shPDE5a were demonstrated in vitro in Ad-shPDE5a transfected cardiomyocytes cultured under oxygen glucose deprivation. Among downstream mediators of PDE5a signaling, cyclic GMP (cGMP) and cGMP-dependent protein kinase G (PKG) were activated with concomitant reduction in caspase-3 activity. However, no significant change in PKA and cAMP activities were observed in Ad-shPDE5a-treated hearts. Inhibition with shRNA improved cardiac remodeling and dysfunction by reducing infarction size and cardiac fibrosis and increased cGMP and PKG activity. These findings suggest that PDE5 inhibition with Ad-shPDE5a is a novel approach for treatment of myocardial infarction. PMID:22447941

  17. Vectorization at the KENO-IV code

    International Nuclear Information System (INIS)

    Asai, K.; Higuchi, K.; Katakura, J.

    1986-01-01

    The multigroup criticality safety code KENO-IV has been vectorized and tested on the FACOM VP-100 vector processor. At first, the vectorized KENO-IV on a scalar processor was slower than the original one by a factor of 1.4 because of the overhead introduced by vectorization. Making modifications of algorithms and techniques for vectorization, the vectorized version has become faster than the original one by a factor of 1.4 on the vector processor. For further speedup of the code, some improvements on compiler and hardware, especially on addition of Monte Carlo pipelines to the vector processor, are discussed

  18. 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

  19. Apparent field safety of a raccoon poxvirus-vectored plague vaccine in free-ranging prairie dogs (Cynomys spp.), Colorado, USA.

    Science.gov (United States)

    Tripp, Daniel W; Rocke, Tonie E; Streich, Sean P; Abbott, Rachel C; Osorio, Jorge E; Miller, Michael W

    2015-04-01

    Prairie dogs (Cynomys spp.) suffer high rates of mortality from plague. An oral sylvatic plague vaccine using the raccoon poxvirus vector (designated RCN-F1/V307) has been developed for prairie dogs. This vaccine is incorporated into palatable bait along with rhodamine B as a biomarker. We conducted trials in August and September 2012 to demonstrate uptake and apparent safety of the RCN-F1/V307 vaccine in two prairie dog species under field conditions. Free-ranging prairie dogs and other associated small rodents readily consumed vaccine-laden baits during field trials with no apparent adverse effects; most sampled prairie dogs (90%) and associated small rodents (78%) had consumed baits. Visual counts of prairie dogs and their burrows revealed no evidence of prairie dog decline after vaccine exposure. No vaccine-related morbidity, mortality, or gross or microscopic lesions were observed. Poxviruses were not isolated from any animal sampled prior to bait distribution or on sites that received placebo baits. We isolated RCN-F1/V307 from 17 prairie dogs and two deer mice (Peromyscus maniculatus) captured on sites where vaccine-laden baits were distributed. Based on these findings, studies examining the utility and effectiveness of oral vaccination to prevent plague-induced mortality in prairie dogs and associated species are underway.

  20. Apparent field safety of a raccoon poxvirus-vectored plague vaccine in free-ranging prairie dogs (Cynomys spp.), Colorado, USA

    Science.gov (United States)

    Tripp, Daniel W.; Rocke, Tonie E.; Streich, Sean P.; Abbott, Rachel C.; Osorio, Jorge E.; Miller, Michael W.

    2015-01-01

    Prairie dogs (Cynomys spp.) suffer high rates of mortality from plague. An oral sylvatic plague vaccine using the raccoon poxvirus vector (designated RCN-F1/V307) has been developed for prairie dogs. This vaccine is incorporated into palatable bait along with rhodamine B as a biomarker. We conducted trials in August and September 2012 to demonstrate uptake and apparent safety of the RCN-F1/V307 vaccine in two prairie dog species under field conditions. Free-ranging prairie dogs and other associated small rodents readily consumed vaccine-laden baits during field trials with no apparent adverse effects; most sampled prairie dogs (90%) and associated small rodents (78%) had consumed baits. Visual counts of prairie dogs and their burrows revealed no evidence of prairie dog decline after vaccine exposure. No vaccine-related morbidity, mortality, or gross or microscopic lesions were observed. Poxviruses were not isolated from any animal sampled prior to bait distribution or on sites that received placebo baits. We isolated RCN-F1/V307 from 17 prairie dogs and two deer mice (Peromyscus maniculatus) captured on sites where vaccine-laden baits were distributed. Based on these findings, studies examining the utility and effectiveness of oral vaccination to prevent plague-induced mortality in prairie dogs and associated species are underway.

  1. SAFETY

    CERN Multimedia

    Niels Dupont

    2013-01-01

    CERN Safety rules and Radiation Protection at CMS The CERN Safety rules are defined by the Occupational Health & Safety and Environmental Protection Unit (HSE Unit), CERN’s institutional authority and central Safety organ attached to the Director General. In particular the Radiation Protection group (DGS-RP1) ensures that personnel on the CERN sites and the public are protected from potentially harmful effects of ionising radiation linked to CERN activities. The RP Group fulfils its mandate in collaboration with the CERN departments owning or operating sources of ionising radiation and having the responsibility for Radiation Safety of these sources. The specific responsibilities concerning "Radiation Safety" and "Radiation Protection" are delegated as follows: Radiation Safety is the responsibility of every CERN Department owning radiation sources or using radiation sources put at its disposition. These Departments are in charge of implementing the requi...

  2. Sensitivity and specificity of the AdenoPlus test for diagnosing adenoviral conjunctivitis.

    Science.gov (United States)

    Sambursky, Robert; Trattler, William; Tauber, Shachar; Starr, Christopher; Friedberg, Murray; Boland, Thomas; McDonald, Marguerite; DellaVecchia, Michael; Luchs, Jodi

    2013-01-01

    To compare the clinical sensitivity and specificity of the AdenoPlus test with those of both viral cell culture (CC) with confirmatory immunofluorescence assay (IFA) and polymerase chain reaction (PCR) at detecting the presence of adenovirus in tear fluid. A prospective, sequential, masked, multicenter clinical trial enrolled 128 patients presenting with a clinical diagnosis of acute viral conjunctivitis from a combination of 8 private ophthalmology practices and academic centers. Patients were tested with AdenoPlus, CC-IFA, and PCR to detect the presence of adenovirus. The sensitivity and specificity of AdenoPlus were assessed for identifying cases of adenoviral conjunctivitis. Of the 128 patients enrolled, 36 patients' results were found to be positive by either CC-IFA or PCR and 29 patients' results were found to be positive by both CC-IFA and PCR. When compared only with CC-IFA, AdenoPlus showed a sensitivity of 90% (28/31) and specificity of 96% (93/97). When compared only with PCR, AdenoPlus showed a sensitivity of 85% (29/34) and specificity of 98% (89/91). When compared with both CC-IFA and PCR, AdenoPlus showed a sensitivity of 93% (27/29) and specificity of 98% (88/90). When compared with PCR, CC-IFA showed a sensitivity of 85% (29/34) and specificity of 99% (90/91). AdenoPlus is sensitive and specific at detecting adenoviral conjunctivitis. An accurate and rapid in-office test can prevent the misdiagnosis of adenoviral conjunctivitis that leads to the spread of disease, unnecessary antibiotic use, and increased health care costs. Additionally, AdenoPlus may help a clinician make a more informed treatment decision regarding the use of novel therapeutics. clinicaltrials.gov Identifier: NCT00921895.

  3. Safety

    International Nuclear Information System (INIS)

    2001-01-01

    This annual report of the Senior Inspector for the Nuclear Safety, analyses the nuclear safety at EDF for the year 1999 and proposes twelve subjects of consideration to progress. Five technical documents are also provided and discussed concerning the nuclear power plants maintenance and safety (thermal fatigue, vibration fatigue, assisted control and instrumentation of the N4 bearing, 1300 MW reactors containment and time of life of power plants). (A.L.B.)

  4. 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

  5. Initial preclinical safety of non-replicating human endogenous retrovirus envelope protein-coated baculovirus vector-based vaccines against human papillomavirus.

    Science.gov (United States)

    Han, Su-Eun; Kim, Mi-Gyeong; Lee, Soondong; Cho, Hee-Jeong; Byun, Youngro; Kim, Sujeong; Kim, Young Bong; Choi, Yongseok; Oh, Yu-Kyoung

    2013-12-01

    Human endogenous retrovirus (HERV) envelope protein-coated, baculovirus vector-based HPV 16 L1 (AcHERV-HPV16L1) is a non-replicating recombinant baculoviral vaccine. Here, we report an initial evaluation of the preclinical safety of AcHERV-HPV16L1 vaccine. In an acute toxicity study, a single administration of AcHERV-HPV16L1 DNA vaccine given intramuscularly (i.m.) to mice at a dose of 1 × 10(8) plaque-forming units (PFU) did not cause significant changes in body weight compared with vehicle-treated controls. It did cause a brief increase in the weights of some organs on day 15 post-treatment, but by day 30, all organ weights were not significantly different from those in the vehicle-treated control group. No hematological changes were observed on day 30 post-treatment. In a range-finding toxicity study with three doses of 1 × 10(7) , 2 × 10(7) and 5 × 10(7) PFU once daily for 5 days, the group treated with 5 × 10(7) PFU showed a transient decrease in the body weights from day 5 to day 15 post-treatment, but recovery to the levels similar to those in the vehicle-treated control group by post-treatment day 20. Organ weights were slightly higher for lymph nodes, spleen, thymus and liver after repeated dosing with 5 × 10(7) PFU on day 15, but had normalized by day 30. Moreover, repeated administration of AcHERV-HPV16L1 did not induce myosin-specific autoantibody in serum, and did not cause immune complex deposition or tissue damage at injection sites. Taken together, these results provide preliminary evidence of the preclinical safety of AcHERV-based HPV16L1 DNA vaccines in mice. Copyright © 2012 John Wiley & Sons, Ltd.

  6. 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...

  7. Adenoviral gene transfer of PLD1-D4 enhances insulin sensitivity in mice by disrupting phospholipase D1 interaction with PED/PEA-15.

    Directory of Open Access Journals (Sweden)

    Angela Cassese

    Full Text Available Over-expression of phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes (PED/PEA-15 causes insulin resistance by interacting with the D4 domain of phospholipase D1 (PLD1. Indeed, the disruption of this association restores insulin sensitivity in cultured cells over-expressing PED/PEA-15. Whether the displacement of PLD1 from PED/PEA-15 improves insulin sensitivity in vivo has not been explored yet. In this work we show that treatment with a recombinant adenoviral vector containing the human D4 cDNA (Ad-D4 restores normal glucose homeostasis in transgenic mice overexpressing PED/PEA-15 (Tg ped/pea-15 by improving both insulin sensitivity and secretion. In skeletal muscle of these mice, D4 over-expression inhibited PED/PEA-15-PLD1 interaction, decreased Protein Kinase C alpha activation and restored insulin induced Protein Kinase C zeta activation, leading to amelioration of insulin-dependent glucose uptake. Interestingly, Ad-D4 administration improved insulin sensitivity also in high-fat diet treated obese C57Bl/6 mice. We conclude that PED/PEA-15-PLD1 interaction may represent a novel target for interventions aiming at improving glucose tolerance.

  8. 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.

  9. 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.

  10. Scenarios of radiological impacts in the long-term safety analysis of radioactive waste disposal at the Vector Site located in the Chernobyl exclusion zone

    Energy Technology Data Exchange (ETDEWEB)

    Rybalka, N.; Mykolaichuk, O. [State Nuclear Regulatory Inspectorate of Ukraine, Kyiv (Ukraine); Alekseeva, Z.; Kondratiev, S.; Nikolaev, E. [State Scientific and Technical Center for Nuclear and Radiation Safety, Kyiv (Ukraine)

    2013-07-01

    In Ukraine, at the Vector site in the Chernobyl exclusion zone, it is planned to dispose of large amounts of radioactive wastes, including those of Chernobyl origin, containing transuranium elements. The paper analyzes the main possible scenarios of radiological impacts of the Vector site for a long-term period after expiration of its active administrative control taking into account location of the Vector site in the exclusion zone. In the paper, assessment of total activities that can be disposed of on site is demonstrated, based on non-exceeding of admissible radiological impacts. (orig.)

  11. Effective single chain antibody (scFv) concentrations in vivo via adenoviral vector mediated expression of secretory scFv

    NARCIS (Netherlands)

    Arafat, WO; Gomez-Navarro, J; Buchsbaum, DJ; Xiang, J; Casado, E; Barker, SD; Mahasreshti, PJ; Haisma, HJ; Barnes, MN; Siegal, GP; Alvarez, RD; Hemminki, A; Nettelbeck, DM; Curiel, DT

    Single chain antibodies (scFv) represent powerful interventional agents for the achievement of targeted therapeutics. The practical utility of these agents have been limited, however, by difficulties related to production of recombinant scFv and the achievement of effective and sustained levels of

  12. Immunization With AFP + GM CSF Plasmid Prime and AFP Adenoviral Vector Boost in Patients With Hepatocellular Carcinoma

    Science.gov (United States)

    2015-12-01

    Hepatocellular Carcinoma; Hepatoma; Liver Cancer, Adult; Liver Cell Carcinoma; Liver Cell Carcinoma, Adult; Cancer of Liver; Cancer of the Liver; Cancer, Hepatocellular; Hepatic Cancer; Hepatic Neoplasms; Hepatocellular Cancer; Liver Cancer; Neoplasms, Hepatic; Neoplasms, Liver

  13. Optimization and physicochemical characterization of a cationic lipid-phosphatidylcholine mixed emulsion formulated as a highly efficient vehicle that facilitates adenoviral gene transfer

    Directory of Open Access Journals (Sweden)

    Kim SY

    2017-10-01

    Full Text Available Soo-Yeon Kim,1,2 Sang-Jin Lee,2 Jin-Ki Kim,3 Han-Gon Choi,3 Soo-Jeong Lim1 1Department of Bioscience and Bioengineering, Sejong University, Seoul, Kwangjin-gu, Seoul, 2Immunotherapeutics Branch, Research Institute, National Cancer Center, Ilsandong-gu, Goyang-si, Gyeonggi-do, 3College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, Sangnok-gu, Ansan, Republic of Korea Abstract: Cationic lipid-based nanoparticles enhance viral gene transfer by forming electrostatic complexes with adenoviral vectors. We recently demonstrated the superior complexation capabilities of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP emulsion compared with a liposomal counterpart but the cytotoxicity of DOTAP emulsions remained a challenge. The present study is aimed at formulating an emulsion capable of acting as a highly effective viral gene transfer vehicle with reduced cytotoxicity and to physicochemically characterize the structures of virus-emulsion complexes in comparison with virus–liposome complexes when the only difference between emulsions and liposomes was the presence or absence of inner oil core. The emulsion formulation was performed by 1 reducing the content of DOTAP while increasing the content of zwitterionic lipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC, and 2 optimizing the oil content. The complexation capability of formulated DOTAP:DMPC mixed emulsions was similar to those of emulsions containing DOTAP alone while displaying significantly lower cytotoxicity. The complexation capabilities of the DOTAP:DMPC mixed emulsion were serum-compatible and were monitored in a variety of cell types, whereas its liposomal counterpart was totally ineffective. Characterization by scanning electron microscopy, transmission electron microscopy, atomic force microscopy, and dynamic light scattering studies indicated that the optimized emulsions spontaneously surrounded the virus particles to generate emulsions that

  14. 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…

  15. Isolation, culture and adenoviral transduction of parietal cells from mouse gastric mucosa

    International Nuclear Information System (INIS)

    Gliddon, Briony L; Nguyen, Nhung V; Gunn, Priscilla A; Gleeson, Paul A; Driel, Ian R van

    2008-01-01

    Here we describe a method for the isolation of intact gastric glands from mice and primary culture and transfection of mouse gastric epithelial cells. Collagenase digestion of PBS-perfused mouse stomachs released large intact gastric glands that were plated on a basement membrane matrix. The heterogeneous gland cell cultures typically contain ∼60% parietal cells. Isolated mouse parietal cells remain viable in culture for up to 5 days and react strongly with an antibody specific to the gastric H + /K + ATPase. Isolated intact mouse gastric glands and primary cultures of mouse parietal cells respond to the secretagogue, histamine. Typical morphological changes from a resting to an acid-secreting active parietal cell were observed. In resting cultures of mouse parietal cells, the H + /K + ATPase displayed a cytoplasmic punctate staining pattern consistent with tubulovesicle element structures. Following histamine stimulation, an expansion of internal apical vacuole structures was observed together with a pronounced redistribution of the H + /K + ATPase from the cytoplasm to the apical vacuoles. A reproducible procedure to express genes of interest exogenously in these cultures of mouse parietal cells was also established. This method combines recombinant adenoviral transduction with magnetic field-assisted transfection resulting in ∼30% transduced parietal cells. Adenoviral-transduced parietal cells maintain their ability to undergo agonist-induced activation. This protocol will be useful for the isolation, culture and expression of genes in parietal cells from genetically modified mice and as such will be an invaluable tool for studying the complex exocytic and endocytic trafficking events of the H + /K + ATPase which underpin the regulation of acid secretion

  16. Sidestream smoke exposure increases the susceptibility of airway epithelia to adenoviral infection.

    Directory of Open Access Journals (Sweden)

    Priyanka Sharma

    Full Text Available Although significant epidemiological evidence indicates that cigarette smoke exposure increases the incidence and severity of viral infection, the molecular mechanisms behind the increased susceptibility of the respiratory tract to viral pathogens are unclear. Adenoviruses are non-enveloped DNA viruses and important causative agents of acute respiratory disease. The Coxsackievirus and adenovirus receptor (CAR is the primary receptor for many adenoviruses. We hypothesized that cigarette smoke exposure increases epithelial susceptibility to adenovirus infection by increasing the abundance of apical CAR.Cultured human airway epithelial cells (CaLu-3 were used as a model to investigate the effect of sidestream cigarette smoke (SSS, mainstream cigarette smoke (MSS, or control air exposure on the susceptibility of polarized respiratory epithelia to adenoviral infection. Using a Cultex air-liquid interface exposure system, we have discovered novel differences in epithelial susceptibility between SSS and MSS exposures. SSS exposure upregulates an eight-exon isoform of CAR and increases adenoviral entry from the apical surface whilst MSS exposure is similar to control air exposure. Additionally, the level of cellular glycogen synthase kinase 3β (GSK3β is downregulated by SSS exposure and treatment with a specific GSK3β inhibitor recapitulates the effects of SSS exposure on CAR expression and viral infection.This is the first time that SSS exposure has been shown to directly enhance the susceptibility of a polarized epithelium to infection by a common respiratory viral pathogen. This work provides a novel understanding of the impact of SSS on the burden of respiratory viral infections and may lead to new strategies to alter viral infections. Moreover, since GSK3β inhibitors are under intense clinical investigation as therapeutics for a diverse range of diseases, studies such as these might provide insight to extend the use of clinically relevant

  17. 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

  18. 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

  19. 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

  20. SAFETY

    CERN Multimedia

    M. Plagge, C. Schaefer and N. Dupont

    2013-01-01

    Fire Safety – Essential for a particle detector The CMS detector is a marvel of high technology, one of the most precise particle measurement devices we have built until now. Of course it has to be protected from external and internal incidents like the ones that can occur from fires. Due to the fire load, the permanent availability of oxygen and the presence of various ignition sources mostly based on electricity this has to be addressed. Starting from the beam pipe towards the magnet coil, the detector is protected by flooding it with pure gaseous nitrogen during operation. The outer shell of CMS, namely the yoke and the muon chambers are then covered by an emergency inertion system also based on nitrogen. To ensure maximum fire safety, all materials used comply with the CERN regulations IS 23 and IS 41 with only a few exceptions. Every piece of the 30-tonne polyethylene shielding is high-density material, borated, boxed within steel and coated with intumescent (a paint that creates a thick co...

  1. SAFETY

    CERN Multimedia

    C. Schaefer and N. Dupont

    2013-01-01

      “Safety is the highest priority”: this statement from CERN is endorsed by the CMS management. An interpretation of this statement may bring you to the conclusion that you should stop working in order to avoid risks. If the safety is the priority, work is not! This would be a misunderstanding and misinterpretation. One should understand that “working safely” or “operating safely” is the priority at CERN. CERN personnel are exposed to different hazards on many levels on a daily basis. However, risk analyses and assessments are done in order to limit the number and the gravity of accidents. For example, this process takes place each time you cross the road. The hazard is the moving vehicle, the stake is you and the risk might be the risk of collision between both. The same principle has to be applied during our daily work. In particular, keeping in mind the general principles of prevention defined in the late 1980s. These principles wer...

  2. Comparison of adenovirus fiber, protein IX, and hexon capsomeres as scaffolds for vector purification and cell targeting

    International Nuclear Information System (INIS)

    Campos, Samuel K.; Barry, Michael A.

    2006-01-01

    The direct genetic modification of adenoviral capsid proteins with new ligands is an attractive means to confer targeted tropism to adenoviral vectors. Although several capsid proteins have been reported to tolerate the genetic fusion of foreign peptides and proteins, direct comparison of cell targeting efficiencies through the different capsomeres has been lacking. Likewise, direct comparison of with one or multiple ligands has not been performed due to a lack of capsid-compatible ligands available for retargeting. Here we utilize a panel of metabolically biotinylated Ad vectors to directly compare targeted transduction through the fiber, protein IX, and hexon capsomeres using a variety of biotinylated ligands including antibodies, transferrin, EGF, and cholera toxin B. These results clearly demonstrate that cell targeting with a variety of high affinity receptor-binding ligands is only effective when transduction is redirected through the fiber protein. In contrast, protein IX and hexon-mediated targeting by the same set of ligands failed to mediate robust vector targeting, perhaps due to aberrant trafficking at the cell surface or inside targeted cells. These data suggest that vector targeting by genetic incorporation of high affinity ligands will likely be most efficient through modification of the adenovirus fiber rather than the protein IX and hexon capsomeres. In contrast, single-step monomeric avidin affinity purification of Ad vectors using the metabolic biotinylation system is most effective through capsomeres like protein IX and hexon

  3. Safety

    International Nuclear Information System (INIS)

    Jones, P.M.S.

    1987-01-01

    Aspects of fission reactors are considered - control, heat removal and containment. Brief descriptions of the reactor accidents at the SL-1 reactor (1961), Windscale (1957), Browns Ferry (1975), Three Mile Island (1979) and Chernobyl (1986) are given. The idea of inherently safe reactor designs is discussed. Safety assessment is considered under the headings of preliminary hazard analysis, failure mode analysis, event trees, fault trees, common mode failure and probabalistic risk assessments. These latter can result in a series of risk distributions linked to specific groups of fault sequences and specific consequences. A frequency-consequence diagram is shown. Fatal accident incidence rates in different countries including the United Kingdom for various industries are quoted. The incidence of fatal cancers from occupational exposure to chemicals is tabulated. Human factors and the acceptability of risk are considered. (U.K.)

  4. 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.

  5. Qualitative and quantitative analysis of adenovirus type 5 vector-induced memory CD8 T cells

    DEFF Research Database (Denmark)

    Steffensen, Maria Abildgaard; Holst, Peter Johannes; Steengaard, Sanne Skovvang

    2013-01-01

    infection with lymphocytic choriomeningitis virus. We found that localized immunization with intermediate doses of Ad vector induce a moderate number of functional CD8 T cells, which qualitatively match those found in LCMV-infected mice. Numbers of these cells may be efficiently increased by additional...... adenoviral boosting and, importantly, the generated secondary memory cells cannot be qualitatively differentiated from those induced by primary infection with replicating virus. Quantitatively, DNA priming prior to Ad-vaccination will lead to even higher numbers of memory cells. In this case, the vaccination...

  6. Experimental study on the effects of recombinant adenoviral-mediated mI{kappa}B{alpha} gene combined with irradiation on the treatment of hepatocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kejun, Zhang; Dechun, Li; Dongming, Zhu [The First Affiliated Hospital to Suzhou Univ., Suzhou (China); Caixia, Song

    2007-10-15

    Objective: To explore the effect of recombinant adenovirus vector mediated mutant I{kappa}B{alpha} (mI{kappa}B{alpha}) combined with radiation on the hepatocarcinoma. Methods: Limited dilution method was used to test the virus titer in 293 cells. The HCC9204 cells were infected with MOI 10,20,30 and 50 for 48 h, respectively. The expression of p65 and mI{kappa}B{alpha} protein was analyzed by Western blot. Transfected HCC9204 cells and controls were treated with 4 Gy {gamma} rays. The inhibition rate of HCC9204 cells was examined by MTT. Rat models of HCC9204 was constructed. AdmI{kappa}B{alpha} plasmids were injected into tumor tissue and the tumors were administered with 6 Gy {gamma} irradiation 48 hours later. Tumor growth at different time points was recorded during 28 days. Results: The titer of AdmI{kappa}B{alpha} is 1.252 x 10{sup 9} pfu/ml. The expression of mI{kappa}B{alpha} protein was increased with titer of AdmI{kappa}B{alpha}, and p65 protein began to decrease when MOI was 10, and reached the lowest when MOI was 50, they were all dose-dependent. The proliferation of HCC9204 cell lines were suppressed, as was more significant combined with radiation, and the effect was in a viral dose-dependent manner. From days 7 to 28 after AdmI{kappa}B{alpha} gene and radiotherapy, the tumor growth was significantly slower than after irradiation or gene therapy alone. Conclusions: Recombinant adenoviral-mediated mI{kappa}B{alpha} gene, combined with irradiation, can increase the cell-killing effect. It is better than that of either one alone. (authors)

  7. Experimental study on the effects of recombinant adenoviral-mediated mIκBα gene combined with irradiation on the treatment of hepatocarcinoma

    International Nuclear Information System (INIS)

    Zhang Kejun; Li Dechun; Zhu Dongming; Song Caixia

    2007-01-01

    Objective: To explore the effect of recombinant adenovirus vector mediated mutant IκBα (mIκBα) combined with radiation on the hepatocarcinoma. Methods: Limited dilution method was used to test the virus titer in 293 cells. The HCC9204 cells were infected with MOI 10,20,30 and 50 for 48 h, respectively. The expression of p65 and mIκBα protein was analyzed by Western blot. Transfected HCC9204 cells and controls were treated with 4 Gy γ rays. The inhibition rate of HCC9204 cells was examined by MTT. Rat models of HCC9204 was constructed. AdmIκBα plasmids were injected into tumor tissue and the tumors were administered with 6 Gy γ irradiation 48 hours later. Tumor growth at different time points was recorded during 28 days. Results: The titer of AdmIκBΑ is 1.252 x 10 9 pfu/ml. The expression of mIκBα protein was increased with titer of AdmIκBα, and p65 protein began to decrease when MOI was 10, and reached the lowest when MOI was 50, they were all dose-dependent. The proliferation of HCC9204 cell lines were suppressed, as was more significant combined with radiation, and the effect was in a viral dose-dependent manner. From days 7 to 28 after AdmIκBα gene and radiotherapy, the tumor growth was significantly slower than after irradiation or gene therapy alone. Conclusions: Recombinant adenoviral-mediated mIκBα gene, combined with irradiation, can increase the cell-killing effect. It is better than that of either one alone. (authors)

  8. Detection and phylogenetic analysis of a new adenoviral polymerase gene in reptiles in Korea.

    Science.gov (United States)

    Bak, Eun-Jung; Jho, Yeonsook; Woo, Gye-Hyeong

    2018-06-01

    Over a period of 7 years (2004-2011), samples from 34 diseased reptiles provided by local governments, zoos, and pet shops were tested for viral infection. Animals were diagnosed based on clinical signs, including loss of appetite, diarrhea, rhinorrhea, and unexpected sudden death. Most of the exotic animals had gastrointestinal problems, such as mucosal redness and ulcers, while the native animals had no clinical symptoms. Viral sequences were found in seven animals. Retroviral genes were amplified from samples from five Burmese pythons (Python molurus bivittatus), an adenovirus was detected in a panther chameleon (Furcifer pardalis), and an adenovirus and a paramyxovirus were detected in a tropical girdled lizard (Cordylus tropidosternum). Phylogenetic analysis of retroviruses and paramyxoviruses showed the highest sequence identity to both a Python molurus endogenous retrovirus and a Python curtus endogenous retrovirus and to a lizard isolate, respectively. Partial sequencing of an adenoviral DNA polymerase gene from the lizard isolate suggested that the corresponding virus was a novel isolate different from the reference strain (accession no. AY576677.1). The virus was not isolated but was detected, using molecular genetic techniques, in a lizard raised in a pet shop. This animal was also coinfected with a paramyxovirus.

  9. 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.

  10. Vectorization of KENO IV code and an estimate of vector-parallel processing

    International Nuclear Information System (INIS)

    Asai, Kiyoshi; Higuchi, Kenji; Katakura, Jun-ichi; Kurita, Yutaka.

    1986-10-01

    The multi-group criticality safety code KENO IV has been vectorized and tested on FACOM VP-100 vector processor. At first the vectorized KENO IV on a scalar processor became slower than the original one by a factor of 1.4 because of the overhead introduced by the vectorization. Making modifications of algorithms and techniques for vectorization, the vectorized version has become faster than the original one by a factor of 1.4 and 3.0 on the vector processor for sample problems of complex and simple geometries, respectively. For further speedup of the code, some improvements on compiler and hardware, especially on addition of Monte Carlo pipelines to the vector processor, are discussed. Finally a pipelined parallel processor system is proposed and its performance is estimated. (author)

  11. Safety and tolerability of conserved region vaccines vectored by plasmid DNA, simian adenovirus and modified vaccinia virus ankara administered to human immunodeficiency virus type 1-uninfected adults in a randomized, single-blind phase I trial.

    Directory of Open Access Journals (Sweden)

    Emma-Jo Hayton

    Full Text Available HIV-1 vaccine development has advanced slowly due to viral antigenic diversity, poor immunogenicity and recently, safety concerns associated with human adenovirus serotype-5 vectors. To tackle HIV-1 variation, we designed a unique T-cell immunogen HIVconsv from functionally conserved regions of the HIV-1 proteome, which were presented to the immune system using a heterologous prime-boost combination of plasmid DNA, a non-replicating simian (chimpanzee adenovirus ChAdV-63 and a non-replicating poxvirus, modified vaccinia virus Ankara. A block-randomized, single-blind, placebo-controlled phase I trial HIV-CORE 002 administered for the first time candidate HIV-1- vaccines or placebo to 32 healthy HIV-1/2-uninfected adults in Oxford, UK and elicited high frequencies of HIV-1-specific T cells capable of inhibiting HIV-1 replication in vitro. Here, detail safety and tolerability of these vaccines are reported.Local and systemic reactogenicity data were collected using structured interviews and study-specific diary cards. Data on all other adverse events were collected using open questions. Serum neutralizing antibody titres to ChAdV-63 were determined before and after vaccination.Two volunteers withdrew for vaccine-unrelated reasons. No vaccine-related serious adverse events or reactions occurred during 190 person-months of follow-up. Local and systemic events after vaccination occurred in 27/32 individuals and most were mild (severity grade 1 and predominantly transient (<48 hours. Myalgia and flu-like symptoms were more strongly associated with MVA than ChAdV63 or DNA vectors and more common in vaccine recipients than in placebo. There were no intercurrent HIV-1 infections during follow-up. 2/24 volunteers had low ChAdV-63-neutralizing titres at baseline and 7 increased their titres to over 200 with a median (range of 633 (231-1533 post-vaccination, which is of no safety concern.These data demonstrate safety and good tolerability of the pSG2

  12. 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...

  13. Bioengineering a non-genotoxic vector for genetic modification of mesenchymal stem cells.

    Science.gov (United States)

    Chen, Xuguang; Nomani, Alireza; Patel, Niket; Nouri, Faranak S; Hatefi, Arash

    2018-01-01

    Vectors used for stem cell transfection must be non-genotoxic, in addition to possessing high efficiency, because they could potentially transform normal stem cells into cancer-initiating cells. The objective of this research was to bioengineer an efficient vector that can be used for genetic modification of stem cells without any negative somatic or genetic impact. Two types of multifunctional vectors, namely targeted and non-targeted were genetically engineered and purified from E. coli. The targeted vectors were designed to enter stem cells via overexpressed receptors. The non-targeted vectors were equipped with MPG and Pep1 cell penetrating peptides. A series of commercial synthetic non-viral vectors and an adenoviral vector were used as controls. All vectors were evaluated for their efficiency and impact on metabolic activity, cell membrane integrity, chromosomal aberrations (micronuclei formation), gene dysregulation, and differentiation ability of stem cells. The results of this study showed that the bioengineered vector utilizing VEGFR-1 receptors for cellular entry could transfect mesenchymal stem cells with high efficiency without inducing genotoxicity, negative impact on gene function, or ability to differentiate. Overall, the vectors that utilized receptors as ports for cellular entry (viral and non-viral) showed considerably better somato- and genosafety profiles in comparison to those that entered through electrostatic interaction with cellular membrane. The genetically engineered vector in this study demonstrated that it can be safely and efficiently used to genetically modify stem cells with potential applications in tissue engineering and cancer therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Generation of a functional and durable vascular niche by the adenoviral E4ORF1 gene.

    Science.gov (United States)

    Seandel, Marco; Butler, Jason M; Kobayashi, Hideki; Hooper, Andrea T; White, Ian A; Zhang, Fan; Vertes, Eva L; Kobayashi, Mariko; Zhang, Yan; Shmelkov, Sergey V; Hackett, Neil R; Rabbany, Sina; Boyer, Julie L; Rafii, Shahin

    2008-12-09

    Vascular cells contribute to organogenesis and tumorigenesis by producing unknown factors. Primary endothelial cells (PECs) provide an instructive platform for identifying factors that support stem cell and tumor homeostasis. However, long-term maintenance of PECs requires stimulation with cytokines and serum, resulting in loss of their angiogenic properties. To circumvent this hurdle, we have discovered that the adenoviral E4ORF1 gene product maintains long-term survival and facilitates organ-specific purification of PECs, while preserving their vascular repertoire for months, in serum/cytokine-free cultures. Lentiviral introduction of E4ORF1 into human PECs (E4ORF1(+) ECs) increased the long-term survival of these cells in serum/cytokine-free conditions, while preserving their in vivo angiogenic potential for tubulogenesis and sprouting. Although E4ORF1, in the absence of mitogenic signals, does not induce proliferation of ECs, stimulation with VEGF-A and/or FGF-2 induced expansion of E4ORF1(+) ECs in a contact-inhibited manner. Indeed, VEGF-A-induced phospho MAPK activation of E4ORF1(+) ECs is comparable with that of naive PECs, suggesting that the VEGF receptors remain functional upon E4ORF1 introduction. E4ORF1(+) ECs inoculated in implanted Matrigel plugs formed functional, patent, humanized microvessels that connected to the murine circulation. E4ORF1(+) ECs also incorporated into neo-vessels of human tumor xenotransplants and supported serum/cytokine-free expansion of leukemic and embryonal carcinoma cells. E4ORF1 augments survival of PECs in part by maintaining FGF-2/FGF-R1 signaling and through tonic Ser-473 phosphorylation of Akt, thereby activating the mTOR and NF-kappaB pathways. Therefore, E4ORF1(+) ECs establish an Akt-dependent durable vascular niche not only for expanding stem and tumor cells but also for interrogating the roles of vascular cells in regulating organ-specific vascularization and tumor neo-angiogenesis.

  15. Generation of a functional and durable vascular niche by the adenoviral E4ORF1 gene

    Science.gov (United States)

    Seandel, Marco; Butler, Jason M.; Kobayashi, Hideki; Hooper, Andrea T.; White, Ian A.; Zhang, Fan; Vertes, Eva L.; Kobayashi, Mariko; Zhang, Yan; Shmelkov, Sergey V.; Hackett, Neil R.; Rabbany, Sina; Boyer, Julie L.; Rafii, Shahin

    2008-01-01

    Vascular cells contribute to organogenesis and tumorigenesis by producing unknown factors. Primary endothelial cells (PECs) provide an instructive platform for identifying factors that support stem cell and tumor homeostasis. However, long-term maintenance of PECs requires stimulation with cytokines and serum, resulting in loss of their angiogenic properties. To circumvent this hurdle, we have discovered that the adenoviral E4ORF1 gene product maintains long-term survival and facilitates organ-specific purification of PECs, while preserving their vascular repertoire for months, in serum/cytokine-free cultures. Lentiviral introduction of E4ORF1 into human PECs (E4ORF1+ ECs) increased the long-term survival of these cells in serum/cytokine-free conditions, while preserving their in vivo angiogenic potential for tubulogenesis and sprouting. Although E4ORF1, in the absence of mitogenic signals, does not induce proliferation of ECs, stimulation with VEGF-A and/or FGF-2 induced expansion of E4ORF1+ ECs in a contact-inhibited manner. Indeed, VEGF-A-induced phospho MAPK activation of E4ORF1+ ECs is comparable with that of naive PECs, suggesting that the VEGF receptors remain functional upon E4ORF1 introduction. E4ORF1+ ECs inoculated in implanted Matrigel plugs formed functional, patent, humanized microvessels that connected to the murine circulation. E4ORF1+ ECs also incorporated into neo-vessels of human tumor xenotransplants and supported serum/cytokine-free expansion of leukemic and embryonal carcinoma cells. E4ORF1 augments survival of PECs in part by maintaining FGF-2/FGF-R1 signaling and through tonic Ser-473 phosphorylation of Akt, thereby activating the mTOR and NF-κB pathways. Therefore, E4ORF1+ ECs establish an Akt-dependent durable vascular niche not only for expanding stem and tumor cells but also for interrogating the roles of vascular cells in regulating organ-specific vascularization and tumor neo-angiogenesis. PMID:19036927

  16. Doxycycline-regulated 3T3-L1 preadipocyte cell line with inducible, stable expression of adenoviral E4orf1 gene: a cell model to study insulin-independent glucose disposal.

    Science.gov (United States)

    Krishnapuram, Rashmi; Dhurandhar, Emily J; Dubuisson, Olga; Hegde, Vijay; Dhurandhar, Nikhil V

    2013-01-01

    Impaired glycemic control and excessive adiposity are major risk factors for Type 2 Diabetes mellitus. In rodent models, Ad36, a human adenovirus, improves glycemic control, independent of dietary fat intake or adiposity. It is impractical to use Ad36 for therapeutic action. Instead, we identified that E4orf1 protein of Ad36, mediates its anti-hyperglycemic action independent of insulin signaling. To further evaluate the therapeutic potential of E4orf1 to improve glycemic control, we established a stable 3T3-L1 cell system in which E4orf1 expression can be regulated. The development and characterization of this cell line is described here. Full-length adenoviral-36 E4orf1 cDNA obtained by PCR was cloned into a tetracycline responsive element containing vector (pTRE-Tight-E4orf1). Upon screening dozens of pTRE-Tight-E4orf1 clones, we identified the one with the highest expression of E4orf1 in response to doxycycline treatment. Furthermore, using this inducible system we characterized the ability of E4orf1 to improve glucose disposal in a time dependent manner. This stable cell line offers a valuable resource to carefully study the novel signaling pathways E4orf1 uses to enhance cellular glucose disposal independent of insulin.

  17. Doxycycline-regulated 3T3-L1 preadipocyte cell line with inducible, stable expression of adenoviral E4orf1 gene: a cell model to study insulin-independent glucose disposal.

    Directory of Open Access Journals (Sweden)

    Rashmi Krishnapuram

    Full Text Available Impaired glycemic control and excessive adiposity are major risk factors for Type 2 Diabetes mellitus. In rodent models, Ad36, a human adenovirus, improves glycemic control, independent of dietary fat intake or adiposity. It is impractical to use Ad36 for therapeutic action. Instead, we identified that E4orf1 protein of Ad36, mediates its anti-hyperglycemic action independent of insulin signaling. To further evaluate the therapeutic potential of E4orf1 to improve glycemic control, we established a stable 3T3-L1 cell system in which E4orf1 expression can be regulated. The development and characterization of this cell line is described here. Full-length adenoviral-36 E4orf1 cDNA obtained by PCR was cloned into a tetracycline responsive element containing vector (pTRE-Tight-E4orf1. Upon screening dozens of pTRE-Tight-E4orf1 clones, we identified the one with the highest expression of E4orf1 in response to doxycycline treatment. Furthermore, using this inducible system we characterized the ability of E4orf1 to improve glucose disposal in a time dependent manner. This stable cell line offers a valuable resource to carefully study the novel signaling pathways E4orf1 uses to enhance cellular glucose disposal independent of insulin.

  18. Adenovirus type 35-vectored tuberculosis vaccine has an acceptable safety and tolerability profile in healthy, BCG-vaccinated, QuantiFERON(®)-TB Gold (+) Kenyan adults without evidence of tuberculosis.

    Science.gov (United States)

    Walsh, Douglas S; Owira, Victorine; Polhemus, Mark; Otieno, Lucas; Andagalu, Ben; Ogutu, Bernhards; Waitumbi, John; Hawkridge, Anthony; Shepherd, Barbara; Pau, Maria Grazia; Sadoff, Jerald; Douoguih, Macaya; McClain, J Bruce

    2016-05-05

    In a Phase 1 trial, we evaluated the safety of AERAS-402, an adenovirus 35-vectored TB vaccine candidate expressing 3 Mycobacterium tuberculosis (Mtb) immunodominant antigens, in subjects with and without latent Mtb infection. HIV-negative, BCG-vaccinated Kenyan adults without evidence of tuberculosis, 10 QuantiFERON(®)-TB Gold In-Tube test (QFT-G)(-) and 10 QFT-G(+), were randomized 4:1 to receive AERAS-402 or placebo as two doses, on Days 0 and 56, with follow up to Day 182. There were no deaths, serious adverse events or withdrawals. For 1 AERAS-402 QFT-G(-) and 1 AERAS-402 QFT-G(+) subject, there were 3 self-limiting severe AEs of injection site pain: 1 after the first vaccination and 1 after each vaccination, respectively. Two additional severe AEs considered vaccine-related were reported after the first vaccination in AERAS-402 QFT-G(+) subjects: elevated blood creatine phosphokinase and neutropenia, the latter slowly improving but remaining abnormal until study end. AERAS-402 was not detected in urine or throat cultures for any subject. In intracellular cytokine staining studies, curtailed by technical issues, we saw modest CD4+ and CD8+ T cell responses to Mtb Ag85A/b peptide pools among both QFT-G(-) and (+) subjects, with trends in the CD4+ T cells suggestive of boosting after the second vaccine dose, slightly more so in QFT-G(+) subjects. CD4+ and CD8+ responses to Mtb antigen TB10.4 were minimal. Increases in Adenovirus 35 neutralizing antibodies from screening to end of study, seen in 50% of AERAS-402 recipients, were mostly minimal. This small study confirms acceptable safety and tolerability profiles for AERAS-402, in line with other Phase 1 studies of AERAS-402, now to include QFT-G(+) subjects. Published by Elsevier Ltd.

  19. 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...

  20. 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

  1. 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.

  2. 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.

  3. Highly efficient retrograde gene transfer into motor neurons by a lentiviral vector pseudotyped with fusion glycoprotein.

    Directory of Open Access Journals (Sweden)

    Miyabi Hirano

    Full Text Available The development of gene therapy techniques to introduce transgenes that promote neuronal survival and protection provides effective therapeutic approaches for neurological and neurodegenerative diseases. Intramuscular injection of adenoviral and adeno-associated viral vectors, as well as lentiviral vectors pseudotyped with rabies virus glycoprotein (RV-G, permits gene delivery into motor neurons in animal models for motor neuron diseases. Recently, we developed a vector with highly efficient retrograde gene transfer (HiRet by pseudotyping a human immunodeficiency virus type 1 (HIV-1-based vector with fusion glycoprotein B type (FuG-B or a variant of FuG-B (FuG-B2, in which the cytoplasmic domain of RV-G was replaced by the corresponding part of vesicular stomatitis virus glycoprotein (VSV-G. We have also developed another vector showing neuron-specific retrograde gene transfer (NeuRet with fusion glycoprotein C type, in which the short C-terminal segment of the extracellular domain and transmembrane/cytoplasmic domains of RV-G was substituted with the corresponding regions of VSV-G. These two vectors afford the high efficiency of retrograde gene transfer into different neuronal populations in the brain. Here we investigated the efficiency of the HiRet (with FuG-B2 and NeuRet vectors for retrograde gene transfer into motor neurons in the spinal cord and hindbrain in mice after intramuscular injection and compared it with the efficiency of the RV-G pseudotype of the HIV-1-based vector. The main highlight of our results is that the HiRet vector shows the most efficient retrograde gene transfer into both spinal cord and hindbrain motor neurons, offering its promising use as a gene therapeutic approach for the treatment of motor neuron diseases.

  4. Adenoviral Mediated Expression of BMP2 by Bone Marrow Stromal Cells Cultured in 3D Copolymer Scaffolds Enhances Bone Formation.

    Science.gov (United States)

    Sharma, Sunita; Sapkota, Dipak; Xue, Ying; Sun, Yang; Finne-Wistrand, Anna; Bruland, Ove; Mustafa, Kamal

    2016-01-01

    Selection of appropriate osteoinductive growth factors, suitable delivery method and proper supportive scaffold are critical for a successful outcome in bone tissue engineering using bone marrow stromal cells (BMSC). This study examined the molecular and functional effect of a combination of adenoviral mediated expression of bone morphogenetic protein-2 (BMP2) in BMSC and recently developed and characterized, biodegradable Poly(L-lactide-co-є-caprolactone){poly(LLA-co-CL)}scaffolds in osteogenic molecular changes and ectopic bone formation by using in vitro and in vivo approaches. Pathway-focused custom PCR array, validation using TaqMan based quantitative RT-PCR (qRT-PCR) and ALP staining showed significant up-regulation of several osteogenic and angiogenic molecules, including ALPL and RUNX2 in ad-BMP2 BMSC group grown in poly(LLA-co-CL) scaffolds both at 3 and 14 days. Micro CT and histological analyses of the subcutaneously implanted scaffolds in NOD/SCID mice revealed significantly increased radiopaque areas, percentage bone volume and formation of vital bone in ad-BMP2 scaffolds as compared to the control groups both at 2 and 8 weeks. The increased bone formation in the ad-BMP2 group in vivo was paralleled at the molecular level with concomitant over-expression of a number of osteogenic and angiogenic genes including ALPL, RUNX2, SPP1, ANGPT1. The increased bone formation in ad-BMP2 explants was not found to be associated with enhanced endochondral activity as evidenced by qRT-PCR (SOX9 and FGF2) and Safranin O staining. Taken together, combination of adenoviral mediated BMP-2 expression in BMSC grown in the newly developed poly(LLA-co-CL) scaffolds induced expression of osteogenic markers and enhanced bone formation in vivo.

  5. First-in-Human Evaluation of the Safety and Immunogenicity of an Intranasally Administered Replication-Competent Sendai Virus–Vectored HIV Type 1 Gag Vaccine: Induction of Potent T-Cell or Antibody Responses in Prime-Boost Regimens

    Science.gov (United States)

    Nyombayire, Julien; Anzala, Omu; Gazzard, Brian; Karita, Etienne; Bergin, Philip; Hayes, Peter; Kopycinski, Jakub; Omosa-Manyonyi, Gloria; Jackson, Akil; Bizimana, Jean; Farah, Bashir; Sayeed, Eddy; Parks, Christopher L.; Inoue, Makoto; Hironaka, Takashi; Hara, Hiroto; Shu, Tsugumine; Matano, Tetsuro; Dally, Len; Barin, Burc; Park, Harriet; Gilmour, Jill; Lombardo, Angela; Excler, Jean-Louis; Fast, Patricia; Laufer, Dagna S.; Cox, Josephine H.

    2017-01-01

    Background. We report the first-in-human safety and immunogenicity assessment of a prototype intranasally administered, replication-competent Sendai virus (SeV)–vectored, human immunodeficiency virus type 1 (HIV-1) vaccine. Methods. Sixty-five HIV-1–uninfected adults in Kenya, Rwanda, and the United Kingdom were assigned to receive 1 of 4 prime-boost regimens (administered at 0 and 4 months, respectively; ratio of vaccine to placebo recipients, 12:4): priming with a lower-dose SeV-Gag given intranasally, followed by boosting with an adenovirus 35–vectored vaccine encoding HIV-1 Gag, reverse transcriptase, integrase, and Nef (Ad35-GRIN) given intramuscularly (SLA); priming with a higher-dose SeV-Gag given intranasally, followed by boosting with Ad35-GRIN given intramuscularly (SHA); priming with Ad35-GRIN given intramuscularly, followed by boosting with a higher-dose SeV-Gag given intranasally (ASH); and priming and boosting with a higher-dose SeV-Gag given intranasally (SHSH). Results. All vaccine regimens were well tolerated. Gag-specific IFN-γ enzyme-linked immunospot–determined response rates and geometric mean responses were higher (96% and 248 spot-forming units, respectively) in groups primed with SeV-Gag and boosted with Ad35-GRIN (SLA and SHA) than those after a single dose of Ad35-GRIN (56% and 54 spot-forming units, respectively) or SeV-Gag (55% and 59 spot-forming units, respectively); responses persisted for ≥8 months after completion of the prime-boost regimen. Functional CD8+ T-cell responses with greater breadth, magnitude, and frequency in a viral inhibition assay were also seen in the SLA and SHA groups after Ad35-GRIN boost, compared with those who received either vaccine alone. SeV-Gag did not boost T-cell counts in the ASH group. In contrast, the highest Gag-specific antibody titers were seen in the ASH group. Mucosal antibody responses were sporadic. Conclusions. SeV-Gag primed functional, durable HIV-specific T

  6. First-in-Human Evaluation of the Safety and Immunogenicity of an Intranasally Administered Replication-Competent Sendai Virus-Vectored HIV Type 1 Gag Vaccine: Induction of Potent T-Cell or Antibody Responses in Prime-Boost Regimens.

    Science.gov (United States)

    Nyombayire, Julien; Anzala, Omu; Gazzard, Brian; Karita, Etienne; Bergin, Philip; Hayes, Peter; Kopycinski, Jakub; Omosa-Manyonyi, Gloria; Jackson, Akil; Bizimana, Jean; Farah, Bashir; Sayeed, Eddy; Parks, Christopher L; Inoue, Makoto; Hironaka, Takashi; Hara, Hiroto; Shu, Tsugumine; Matano, Tetsuro; Dally, Len; Barin, Burc; Park, Harriet; Gilmour, Jill; Lombardo, Angela; Excler, Jean-Louis; Fast, Patricia; Laufer, Dagna S; Cox, Josephine H

    2017-01-01

     We report the first-in-human safety and immunogenicity assessment of a prototype intranasally administered, replication-competent Sendai virus (SeV)-vectored, human immunodeficiency virus type 1 (HIV-1) vaccine.  Sixty-five HIV-1-uninfected adults in Kenya, Rwanda, and the United Kingdom were assigned to receive 1 of 4 prime-boost regimens (administered at 0 and 4 months, respectively; ratio of vaccine to placebo recipients, 12:4): priming with a lower-dose SeV-Gag given intranasally, followed by boosting with an adenovirus 35-vectored vaccine encoding HIV-1 Gag, reverse transcriptase, integrase, and Nef (Ad35-GRIN) given intramuscularly (S L A); priming with a higher-dose SeV-Gag given intranasally, followed by boosting with Ad35-GRIN given intramuscularly (S H A); priming with Ad35-GRIN given intramuscularly, followed by boosting with a higher-dose SeV-Gag given intranasally (AS H ); and priming and boosting with a higher-dose SeV-Gag given intranasally (S H S H ).  All vaccine regimens were well tolerated. Gag-specific IFN-γ enzyme-linked immunospot-determined response rates and geometric mean responses were higher (96% and 248 spot-forming units, respectively) in groups primed with SeV-Gag and boosted with Ad35-GRIN (S L A and S H A) than those after a single dose of Ad35-GRIN (56% and 54 spot-forming units, respectively) or SeV-Gag (55% and 59 spot-forming units, respectively); responses persisted for ≥8 months after completion of the prime-boost regimen. Functional CD8 + T-cell responses with greater breadth, magnitude, and frequency in a viral inhibition assay were also seen in the S L A and S H A groups after Ad35-GRIN boost, compared with those who received either vaccine alone. SeV-Gag did not boost T-cell counts in the AS H group. In contrast, the highest Gag-specific antibody titers were seen in the AS H group. Mucosal antibody responses were sporadic.  SeV-Gag primed functional, durable HIV-specific T-cell responses and boosted antibody

  7. 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)

  8. 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...

  9. 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

  10. 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...

  11. 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...

  12. Safety and immunogenicity of a novel recombinant adenovirus type-5 vector-based Ebola vaccine in healthy adults in China: preliminary report of a randomised, double-blind, placebo-controlled, phase 1 trial.

    Science.gov (United States)

    Zhu, Feng-Cai; Hou, Li-Hua; Li, Jing-Xin; Wu, Shi-Po; Liu, Pei; Zhang, Gui-Rong; Hu, Yue-Mei; Meng, Fan-Yue; Xu, Jun-Jie; Tang, Rong; Zhang, Jin-Long; Wang, Wen-Juan; Duan, Lei; Chu, Kai; Liang, Qi; Hu, Jia-Lei; Luo, Li; Zhu, Tao; Wang, Jun-Zhi; Chen, Wei

    2015-06-06

    Up to now, all tested Ebola virus vaccines have been based on the virus strain from the Zaire outbreak in 1976. We aimed to assess the safety and immunogenicity of a novel recombinant adenovirus type-5 vector-based Ebola vaccine expressing the glycoprotein of the 2014 epidemic strain. We did this randomised, double-blind, placebo-controlled, phase 1 clinical trial at one site in Taizhou County, Jiangsu Province, China. Healthy adults (aged 18-60 years) were sequentially enrolled and randomly assigned (2:1), by computer-generated block randomisation (block size of six), to receive placebo, low-dose adenovirus type-5 vector-based Ebola vaccine, or high-dose vaccine. Randomisation was pre-stratified by dose group. All participants, investigators, and laboratory staff were masked to treatment allocation. The primary safety endpoint was occurrence of solicited adverse reactions within 7 days of vaccination. The primary immunogenicity endpoints were glycoprotein-specific antibody titres and T-cell responses at day 28 after the vaccination. Analysis was by intention to treat. The study is registered with ClinicalTrials.gov, number NCT02326194. Between Dec 28, 2014, and Jan 9, 2015, 120 participants were enrolled and randomly assigned to receive placebo (n=40), low-dose vaccine (n=40), or high-dose vaccine. Participants were followed up for 28 days. Overall, 82 (68%) participants reported at least one solicited adverse reaction within 7 days of vaccination (n=19 in the placebo group vs n=27 in the low-dose group vs n=36 in the high-dose group; p=0·0002). The most common reaction was mild pain at the injection site, which was reported in eight (20%) participants in the placebo group, 14 (35%) participants in the low-dose group, and 29 (73%) participants in the high-dose vaccine group (pvaccine groups at both day 14 (geometric mean titre 421·4 [95% CI 249·7-711·3] and 820·5 [598·9-1124·0], respectively; pday 28 (682·7 [424·3-1098·5] and 1305·7 [970·1-1757·2

  13. 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

  14. 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...

  15. 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.

  16. 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.

  17. 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.

  18. 5-Fluorouracil-related enhancement of adenoviral infection is Coxsackievirus-adenovirus receptor independent and associated with morphological changes in lipid membranes

    Science.gov (United States)

    Cabrele, Chiara; Vogel, Mandy; Piso, Pompiliu; Rentsch, Markus; Schröder, Josef; Jauch, Karl W; Schlitt, Hans J; Beham, Alexander

    2006-01-01

    AIM: To evaluate the mechanism underlying the effects of 5-Fluorouracil (5-FU) on adenoviral infection. METHODS: Low and high Coxsackievirus-Adenovirus Receptor (CAR) expressing human colon carcinoma cell lines were treated with 5-FU and two E1-deleted adenoviral constructs, one transferring GFP (Ad/CMV-GFP) the other bax (Ad/CEA-bax). The number of infected cells were monitored by GFP expression. To evaluate the effects of 5-FU in a receptor free system, Ad/GFP were encapsulated in liposomes and treated with 5-FU. Ad/GFP release was estimated with PCR and infection of 293 cells with the supernatant. Electron microscopy of the Ad5-GFP-liposome complex was made to investigate morphological changes of the liposomes after 5-FU. RESULTS: Infection rates of all cell lines increased from 50% to 98% with emerging 5-FU concentrations. The enhanced viral uptake was independent of the CAR expression. Additionally, 5-FU treated liposomes released 2-2.5 times more adenoviruses. Furthermore, 5-FU-treated liposomes appeared irregular and porous-like. CONCLUSION: adenoviral uptake is enhanced in the presence of 5-FU irrespective of CAR and is associated with morphological changes in membranes making the combination of both a promising option in gene therapy. PMID:16937527

  19. Lentiviral Vector Mediated Claudin1 Silencing Inhibits Epithelial to Mesenchymal Transition in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Xianqi Zhao

    2015-06-01

    Full Text Available Breast cancer has a high incidence and mortality rate worldwide. Several viral vectors including lentiviral, adenoviral and adeno-associated viral vectors have been used in gene therapy for various forms of human cancer, and have shown promising effects in controlling tumor development. Claudin1 (CLDN1 is a member of the tetraspan transmembrane protein family that plays a major role in tight junctions and is associated with tumor metastasis. However, the role of CLDN1 in breast cancer is largely unexplored. In this study, we tested the therapeutic potential of silencing CLDN1 expression in two breast cancer (MDA-MB-231 and MCF7 cell lines using lentiviral vector mediated RNA interference. We found that a CLDN1 short hairpin (shRNA construct efficiently silenced CLDN1 expression in both breast cancer cell lines, and CLDN1 knockdown resulted in reduced cell proliferation, survival, migration and invasion. Furthermore, silencing CLDN1 inhibited epithelial to mesenchymal transition (EMT by upregulating the epithelial cell marker, E-cadherin, and downregulating mesenchymal markers, smooth muscle cell alpha-actin (SMA and Snai2. Our data demonstrated that lentiviral vector mediated CLDN1 RNA interference has great potential in breast cancer gene therapy by inhibiting EMT and controlling tumor cell growth.

  20. Oncolytic Adenovirus: Strategies and Insights for Vector Design and Immuno-Oncolytic Applications

    Directory of Open Access Journals (Sweden)

    Hanni Uusi-Kerttula

    2015-11-01

    Full Text Available Adenoviruses (Ad are commonly used both experimentally and clinically, including oncolytic virotherapy applications. In the clinical area, efficacy is frequently hampered by the high rates of neutralizing immunity, estimated as high as 90% in some populations that promote vector clearance and limit bioavailability for tumor targeting following systemic delivery. Active tumor targeting is also hampered by the ubiquitous nature of the Ad5 receptor, hCAR, as well as the lack of highly tumor-selective targeting ligands and suitable targeting strategies. Furthermore, significant off-target interactions between the viral vector and cellular and proteinaceous components of the bloodstream have been documented that promote uptake into non-target cells and determine dose-limiting toxicities. Novel strategies are therefore needed to overcome the obstacles that prevent efficacious Ad deployment for wider clinical applications. The use of less seroprevalent Ad serotypes, non-human serotypes, capsid pseudotyping, chemical shielding and genetic masking by heterologous peptide incorporation are all potential strategies to achieve efficient vector escape from humoral immune recognition. Conversely, selective vector arming with immunostimulatory agents can be utilized to enhance their oncolytic potential by activation of cancer-specific immune responses against the malignant tissues. This review presents recent advantages and pitfalls occurring in the field of adenoviral oncolytic therapies.

  1. Preparation of a recombinant adenoviral encoding human NIS gene and its specific expression in cardiomyocytes

    International Nuclear Information System (INIS)

    Wang Lihua; Zhang Miao; Guo Rui; Shi Shuo; Li Biao

    2012-01-01

    Objective: To construct a recombinant adenovirus vector containing the human NIS gene with the myosin light chain-2(MLC-2v) gene as the promoter and evaluate its specific expression and feasibility as a reporter gene in cardiomyocytes. Methods: MLC-2v promoter and NIS were subcloned into an adenovirus shuttle vector, and forwarded by homologous recombination in the bacteria BJ5183 containing AdEasy-1 plasmid. Positive recombinant adenovirus vector was selected, packaged and amplified in the HEK293 cells to obtain recombinant adenovirus Ad-MLC-NIS. Ad-cytomegalovirus (CMV)-NIS with cytomegalovirus as the promoter, Ad-MLC without NIS and Ad-NIS without promoter were constructed as the controls. Cardiomyocytes and non-cardiomyocytes were then infected by the adenovirus. The protein expression was tested by Western blot analysis. The function and features of NIS protein were evaluated by dynamic iodide uptake and NaClO 4 iodine uptake inhibition test in vitro. The viability and proliferation of cardiomyocytes after adenovirus transfection and radioiodine incubation were checked by trypan blue staining. Results: Recombinant NIS adenovirus was successfully constructed. Western blot analysis showed that the NIS protein was highly expressed in cardiomyocytes transfected with Ad-MLC-NIS, and all cells transfected with Ad-CMV-NIS. However, in non-cardiomyocytes transfected with Ad-MLC-NIS, little NIS protein was detected. Dynamic iodine uptake tests showed that the peaks of iodide uptake of the three different cell lines (H9C2, A549, U87 cell) transfected with Ad-MLC-NIS were 5844.0, 833.6 and 846.0 counts · min -1 , respectively. The iodide uptake function of H9C2 was inhibited by NaClO 4 . There was almost no change in cell viability and proliferation when the MOI was 100. Conclusions: Ad-MLC-NIS allows myocardial specific expression of an external gene, and the cardiomyocytes with NIS expression are capable of iodine uptake. Further research of NIS as a reporter gene in

  2. Measurement of feline cytokines interleukin-12 and interferon- g produced by heat inducible gene therapy adenoviral vector using real time PCR

    International Nuclear Information System (INIS)

    Siddiqui, F.; Avery, P.R.; Ullrich, R.L.; LaRue, S.M.; Dewhirst, M.W.; Li, C.-Y.

    2003-01-01

    Biologic tumor therapy using Interleukin-12 (IL-12) has shown promise as an adjuvant to radiation therapy. The goals for cancer gene immunotherapy include effective eradication of established tumors and generation of a lasting systemic immune response. Among the cytokines, IL-12 has been found to be most effective gene in eradicating experimental tumors, preventing the development of metastases, and eliciting long-term antitumor immunity. Depending on the tumor model, IL-12 can exert antitumor activities via T cells, NK cells or NKT cells. It induces the production of IFN-g and IFN-inducible protein-10. It is also postulated to have antiangiogenic effects, thus inhibiting tumor formation and metastases. However, its use in clinical trials has been restricted largely owing to its systemic hematologic and hepatotoxicity. We tested the efficacy of adenovirus mediated expression of feline IL-12 gene placed under the control of an inducible promoter, the heat shock proteins (hsp70B). This places gene expression under the control of an external physical agent (hyperthermia), thus offering an 'on-off' switch and potentially reducing systemic toxicity by restricting its expression locally to the tumor. Crandell Feline Kidney (CrFK) cells were infected using the construct and the supernatant was then used to stimulate production of interferon g (IFN-g) in feline peripheral blood mononuclear cells (PBMC). As there is no commercially available ELISA kit currently available to detect or measure feline cytokines, we used real time-PCR to measure cytokine mRNA. These results will be used to initiate a clinical trial in cats with soft tissue sarcomas examining hyperthermia Induced gene therapy in conjunction with radiation therapy. The real time- PCR techniques developed here will be used to quantitatively measure cytokine mRNA levels in the punch biopsy samples obtained from the cats during the clinical trial. Support for this study was in part by NCI grant CA72745

  3. Adenoviral vector-mediated expression of a foreign gene in peripheral nerve tissue bridges implanted in the injured peripheral and central nervous system

    NARCIS (Netherlands)

    Blits, B; Dijkhuizen, Paul A; Carlstedt, Thomas P; Poldervaart, H A; Schiemanck, S; Boer, G J; Verhaagen, J

    1999-01-01

    Axons of the CNS do normally not regenerate after injury, in contrast to axons of the PNS. This is due to a different microenvironment at the site of the lesion as well as a particular intrinsic program of axonal regrowth. Although transplantation of peripheral nerve tissue bridges is perhaps the

  4. Comparison of human sodium iodide symporter (hNIS) gene expression between lentiviral and adenoviral vectors in rat mesenchymal stem cell

    International Nuclear Information System (INIS)

    Park, So Yeon; Lee, Won Woo; Kim, Sung Jin; Lee, Heui Ran; Kim, Hyun Joo; Chung, June Key; Kim, Sang Eun

    2007-01-01

    Quantitative comparison of transgene expression within stem cells between lentivirus and adenovirus-mediated delivery systems has not been done. Here, we evaluated the human sodium iodide symporter (hNIS) gene expression in rat mesenchymal stem cell (rMSC) transduced by lentivirus or adenovirus, and compared the hNIS expression quantitatively between the two delivery systems. Lentiviral-mediated stably hNIS expressing rMSC (lenti-hNIS-rMSC) was constructed by cloning the hNIS gene into pLenti6/UbC/V5-DEST (Invitrogen) to obtain pLenti-hNIS, transducing rMSC with the pLenti-hNIS, and selecting with blasticidin for 3 weeks. Recombinant adenovirus expressing hNIS gene (Rad-hNIS) was produced by homologous recombination and Rad-hNIS transduced rMSC (adeno-hNIS-rMSC) was evaluated for the hNIS expression 48 hours post infection at MOI 1, 5, 20, 50, and 100. The hNIS expression in lenti-hNIS-rMSC or adeno-hNIS-rMSC was assessed by immunocytochemistry, western blot, and I-125 uptake. Immunocytochemistry using mono-clonal anti-hNIS antibody revealed that intensity of hNIS immunoreactivity in lenti-hNIS-rMSC was greater than that in adeno-hNIS-rMSC at MOl 20 but lower than that at MOl 50. Western blot analysis also showed that lenti-hNIS-rMSC was intermediate between adeno-hNIS-rMSCs at MOl 20 and 50 in hNIS expression. However in vitro I-125 uptake test demonstrated that iodide uptake in lenti-hNIS-rMSC (297046659 picomole/106 cells) was greater than that in adeno-hNIS-rMSC at MOI 100 (61682134 picomole/106 cells). These results suggest that lentivirus mediated hNIS expression is greater in terms of hNIS function but lower in terms of hNIS protein amount than adenovirus mediated hNIS expression 48 hours post infection. Stem cell tracking using hNIS as a reporter gene should be conducted in consideration of relative viral efficiency of transgene expression

  5. Generation of neutralizing monoclonal antibodies against a conformational epitope of human adenovirus type 7 (HAdv-7 incorporated in capsid encoded in a HAdv-3-based vector.

    Directory of Open Access Journals (Sweden)

    Minglong Liu

    Full Text Available The generation of monoclonal antibodies (MAbs by epitope-based immunization is difficult because the immunogenicity of simple peptides is poor and T cells must be potently stimulated and immunological memory elicited. A strategy in which antigen is incorporated into the adenoviral capsid protein has been used previously to develop antibody responses against several vaccine targets and may offer a solution to this problem. In this study, we used a similar strategy to develop HAdv-7-neutralizing MAbs using rAdMHE3 virions into which hexon hypervariable region 5 (HVR5 of adenovirus type 7 (HAdv-7 was incorporated. The epitope mutant rAdMHE3 was generated by replacing HVR5 of Ad3EGFP, a recombinant HAdv-3-based vector expressing enhanced green fluorescence protein, with HVR5 of HAdv-7. We immunized BALB/c mice with rAdMHE3 virions and produced 22 different MAbs against them, four of which showed neutralizing activity against HAdv-7 in vitro. Using an indirect enzyme-linked immunosorbent assay (ELISA analysis and an antibody-binding-competition ELISA with Ad3EGFP, HAdv-7, and a series of chimeric adenoviral particles containing epitope mutants, we demonstrated that the four MAbs recognize the neutralization site within HVR5 of the HAdv-7 virion. Using an immunoblotting analysis and ELISA with HAdv-7, recombinant peptides, and a synthetic peptide, we also showed that the neutralizing epitope within HVR5 of the HAdv-7 virion is a conformational epitope. These findings suggest that it is feasible to use a strategy in which antigen is incorporated into the adenoviral capsid protein to generate neutralizing MAbs. This strategy may also be useful for developing therapeutic neutralizing MAbs and designing recombinant vector vaccines against HAdv-7, and in structural analysis of adenoviruses.

  6. 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

  7. 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.

  8. 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...

  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. 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

  11. 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

  12. 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.

  13. Characterization of adenoviral transduction profile in prostate cancer cells and normal prostate tissue.

    Science.gov (United States)

    Ai, Jianzhong; Tai, Phillip W L; Lu, Yi; Li, Jia; Ma, Hong; Su, Qin; Wei, Qiang; Li, Hong; Gao, Guangping

    2017-09-01

    Prostate diseases are common in males worldwide with high morbidity. Gene therapy is an attractive therapeutic strategy for prostate diseases, however, it is currently underdeveloped. As well known, adeno virus (Ad) is the most widely used gene therapy vector. The aims of this study are to explore transduction efficiency of Ad in prostate cancer cells and normal prostate tissue, thus further providing guidance for future prostate pathophysiological studies and therapeutic development of prostate diseases. We produced Ad expressing enhanced green fluorescence protein (EGFP), and characterized the transduction efficiency of Ad in both human and mouse prostate cancer cell lines in vitro, as well as prostate tumor xenograft, and wild-type mouse prostate tissue in vivo. Ad transduction efficiency was determined by EGFP fluorescence using microscopy and flow cytometry. Cell type-specific transduction was examined by immunofluorescence staining of cell markers. Our data showed that Ad efficiently transduced human and mouse prostate cancer cells in vitro in a dose dependent manner. Following intratumoral and intraprostate injection, Ad could efficiently transduce prostate tumor xenograft and the major prostatic cell types in vivo, respectively. Our findings suggest that Ad can efficiently transduce prostate tumor cells in vitro as well as xenograft and normal prostate tissue in vivo, and further indicate that Ad could be a potentially powerful toolbox for future gene therapy of prostate diseases. © 2017 Wiley Periodicals, Inc.

  14. Adenoviral transfer of HSP-70 into pulmonary epithelium ameliorates experimental acute respiratory distress syndrome.

    Science.gov (United States)

    Weiss, Yoram G; Maloyan, Alina; Tazelaar, John; Raj, Nichelle; Deutschman, Clifford S

    2002-09-01

    The acute respiratory distress syndrome (ARDS) provokes three pathologic processes: unchecked inflammation, interstitial/alveolar protein accumulation, and destruction of pulmonary epithelial cells. The highly conserved heat shock protein HSP-70 can limit all three responses but is not appropriately expressed in the lungs after cecal ligation and double puncture (2CLP), a clinically relevant model of ARDS. We hypothesize that restoring expression of HSP-70 using adenovirus-mediated gene therapy will limit pulmonary pathology following 2CLP. We administered a vector containing the porcine HSP-70 cDNA driven by a CMV promoter (AdHSP) into the lungs of rats subjected to 2CLP or sham operation. Administration of AdHSP after either sham operation or 2CLP increased HSP-70 protein expression in lung tissue, as determined by immunohistochemistry and Western blot hybridization. Administration of AdHSP significantly attenuated interstitial and alveolar edema and protein exudation and dramatically decreased neutrophil accumulation, relative to a control adenovirus. CLP-associated mortality at 48 hours was reduced by half. Modulation of HSP-70 production reduces pathologic changes and may improve outcome in experimental ARDS.

  15. 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.

  16. 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.

  17. 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

  18. 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...

  19. 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...

  20. Adenoviral gene transfer of angiostatic ATF-BPTI inhibits tumour growth

    International Nuclear Information System (INIS)

    Lefesvre, Pierre; Attema, Joline; Bekkum, Dirk van

    2002-01-01

    The outgrowth of new vessels – angiogenesis – in the tumour mass is considered to be a limiting factor of tumour growth. To inhibit the matrix lysis that is part of the tumour angiogenesis, we employed the chimeric protein mhATF-BPTI, composed of the receptor binding part of the urokinase (ATF) linked to an inhibitor of plasmin (BPTI). For delivery, recombinant adenovirus encoding the transgene of interest was injected intravenously or locally into the tumour. The anti tumour effect of this compound was compared to that of human endostatin and of mhATF alone in two different rat bronchial carcinomas growing either as subcutaneous implants or as metastases. Significant inhibition of the tumour growth and decrease of the number of lung metastasis was achieved when the concentration of mhATF-BPTI at the tumour site was above 400 of ng / g tissue. This concentration could be achieved via production by the liver, only if permissive to the recombinant adenovirus. When the tumour cells could be transduced, local delivery of the vector was enough to obtain a response. In the case of metastasis, the capacity of the lung tissue to concentrate the encoded protein was essential to reach the required therapeutic levels. Further, endostatin or mhATF could not reproduce the effects of mhATF-BPTI, at similar concentrations (mhATF) and even at 10-fold higher concentration (endostatin). The ATF-BPTI was shown to inhibit tumour growth of different rat lung tumours when critical concentration was reached. In these tumour models, endostatin or ATF induce almost no tumour response

  1. Metabolic flux profiling of MDCK cells during growth and canine adenovirus vector production.

    Science.gov (United States)

    Carinhas, Nuno; Pais, Daniel A M; Koshkin, Alexey; Fernandes, Paulo; Coroadinha, Ana S; Carrondo, Manuel J T; Alves, Paula M; Teixeira, Ana P

    2016-03-23

    Canine adenovirus vector type 2 (CAV2) represents an alternative to human adenovirus vectors for certain gene therapy applications, particularly neurodegenerative diseases. However, more efficient production processes, assisted by a greater understanding of the effect of infection on producer cells, are required. Combining [1,2-(13)C]glucose and [U-(13)C]glutamine, we apply for the first time (13)C-Metabolic flux analysis ((13)C-MFA) to study E1-transformed Madin-Darby Canine Kidney (MDCK) cells metabolism during growth and CAV2 production. MDCK cells displayed a marked glycolytic and ammoniagenic metabolism, and (13)C data revealed a large fraction of glutamine-derived labelling in TCA cycle intermediates, emphasizing the role of glutamine anaplerosis. (13)C-MFA demonstrated the importance of pyruvate cycling in balancing glycolytic and TCA cycle activities, as well as occurrence of reductive alphaketoglutarate (AKG) carboxylation. By turn, CAV2 infection significantly upregulated fluxes through most central metabolism, including glycolysis, pentose-phosphate pathway, glutamine anaplerosis and, more prominently, reductive AKG carboxylation and cytosolic acetyl-coenzyme A formation, suggestive of increased lipogenesis. Based on these results, we suggest culture supplementation strategies to stimulate nucleic acid and lipid biosynthesis for improved canine adenoviral vector production.

  2. A rapid generation of adenovirus vector with a genetic modification in hexon protein.

    Science.gov (United States)

    Di, Bingyan; Mao, Qinwen; Zhao, Junli; Li, Xing; Wang, Dongyang; Xia, Haibin

    2012-02-10

    The generation of hexon-modified adenovirus vector has proven difficult. In this paper, we developed a novel method for rapid generation of hexon-modified adenoviral vector via one step ligation in vitro followed by quick white/blue color screening. The new system has the following features. First, eGFP expression driven by the CMV promoter in E1 region functions as a reporter to evaluate the tropism of hexon-modified adenovirus in vitro. Second, it has two unique restriction enzyme sites with sticky ends located in the hexon HVR5 region. Third, a lacZ expression cassette under the control of plac promoter is placed between the two restriction enzyme sites, which allows recombinants to be selected using blue/white screening. To prove the principle of the method, genetically modified adenoviruses were successfully produced by insertion of NGR, RGD or Tat PTD peptide into hexon HVR5. Furthermore, the transduction efficiency of the Tat PTD modified virus was shown to be a significant enhancement in A172 and CHO-K1 cells. In conclusion, the novel system makes the production of truly retargeted vectors more promising, which would be of substantial benefit for cancer gene therapy. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. 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.

  4. Adenoviral overexpression of Lhx2 attenuates cell viability but does not preserve the stem cell like phenotype of hepatic stellate cells

    Energy Technology Data Exchange (ETDEWEB)

    Genz, Berit [Institute for Experimental Surgery, Rostock University Medical Center, Rostock (Germany); Thomas, Maria [Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart (Germany); Pützer, Brigitte M. [Institute of Experimental Gene Therapy and Cancer Research, Rostock University Medical Center, Rostock (Germany); Siatkowski, Marcin; Fuellen, Georg [Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, Rostock (Germany); Vollmar, Brigitte [Institute for Experimental Surgery, Rostock University Medical Center, Rostock (Germany); Abshagen, Kerstin, E-mail: kerstin.abshagen@uni-rostock.de [Institute for Experimental Surgery, Rostock University Medical Center, Rostock (Germany)

    2014-11-01

    Hepatic stellate cells (HSC) are well known initiators of hepatic fibrosis. After liver cell damage, HSC transdifferentiate into proliferative myofibroblasts, representing the major source of extracellular matrix in the fibrotic organ. Recent studies also demonstrate a role of HSC as progenitor or stem cell like cells in liver regeneration. Lhx2 is described as stem cell maintaining factor in different organs and as an inhibitory transcription factor in HSC activation. Here we examined whether a continuous expression of Lhx2 in HSC could attenuate their activation and whether Lhx2 could serve as a potential target for antifibrotic gene therapy. Therefore, we evaluated an adenoviral mediated overexpression of Lhx2 in primary HSC and investigated mRNA expression patterns by qRT-PCR as well as the activation status by different in vitro assays. HSC revealed a marked increase in activation markers like smooth muscle actin alpha (αSMA) and collagen 1α independent from adenoviral transduction. Lhx2 overexpression resulted in attenuated cell viability as shown by a slightly hampered migratory and contractile phenotype of HSC. Expression of stem cell factors or signaling components was also unaffected by Lhx2. Summarizing these results, we found no antifibrotic or stem cell maintaining effect of Lhx2 overexpression in primary HSC. - Highlights: • We performed adenoviral overexpression of Lhx2 in primary hepatic stellate cells. • Hepatic stellate cells expressed stem cell markers during cultivation. • Cell migration and contractility was slightly hampered upon Lhx2 overexpression. • Lhx2 overexpression did not affect stem cell character of hepatic stellate cells.

  5. Adenoviral overexpression of Lhx2 attenuates cell viability but does not preserve the stem cell like phenotype of hepatic stellate cells

    International Nuclear Information System (INIS)

    Genz, Berit; Thomas, Maria; Pützer, Brigitte M.; Siatkowski, Marcin; Fuellen, Georg; Vollmar, Brigitte; Abshagen, Kerstin

    2014-01-01

    Hepatic stellate cells (HSC) are well known initiators of hepatic fibrosis. After liver cell damage, HSC transdifferentiate into proliferative myofibroblasts, representing the major source of extracellular matrix in the fibrotic organ. Recent studies also demonstrate a role of HSC as progenitor or stem cell like cells in liver regeneration. Lhx2 is described as stem cell maintaining factor in different organs and as an inhibitory transcription factor in HSC activation. Here we examined whether a continuous expression of Lhx2 in HSC could attenuate their activation and whether Lhx2 could serve as a potential target for antifibrotic gene therapy. Therefore, we evaluated an adenoviral mediated overexpression of Lhx2 in primary HSC and investigated mRNA expression patterns by qRT-PCR as well as the activation status by different in vitro assays. HSC revealed a marked increase in activation markers like smooth muscle actin alpha (αSMA) and collagen 1α independent from adenoviral transduction. Lhx2 overexpression resulted in attenuated cell viability as shown by a slightly hampered migratory and contractile phenotype of HSC. Expression of stem cell factors or signaling components was also unaffected by Lhx2. Summarizing these results, we found no antifibrotic or stem cell maintaining effect of Lhx2 overexpression in primary HSC. - Highlights: • We performed adenoviral overexpression of Lhx2 in primary hepatic stellate cells. • Hepatic stellate cells expressed stem cell markers during cultivation. • Cell migration and contractility was slightly hampered upon Lhx2 overexpression. • Lhx2 overexpression did not affect stem cell character of hepatic stellate cells

  6. Lysyl Oxidase-Like 1 Protein Deficiency Protects Mice from Adenoviral Transforming Growth Factor-β1-induced Pulmonary Fibrosis.

    Science.gov (United States)

    Bellaye, Pierre-Simon; Shimbori, Chiko; Upagupta, Chandak; Sato, Seidai; Shi, Wei; Gauldie, Jack; Ask, Kjetil; Kolb, Martin

    2018-04-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by excessive deposition of extracellular matrix (ECM) in the lung parenchyma. The abnormal ECM deposition slowly overtakes normal lung tissue, disturbing gas exchange and leading to respiratory failure and death. ECM cross-linking and subsequent stiffening is thought to be a major contributor of disease progression and also promotes the activation of transforming growth factor (TGF)-β1, one of the main profibrotic growth factors. Lysyl oxidase-like (LOXL) 1 belongs to the cross-linking enzyme family and has been shown to be up-regulated in active fibrotic regions of bleomycin-treated mice and patients with IPF. We demonstrate in this study that LOXL1-deficient mice are protected from experimental lung fibrosis induced by overexpression of TGF-β1 using adenoviral (Ad) gene transfer (AdTGF-β1). The lack of LOXL1 prevented accumulation of insoluble cross-linked collagen in the lungs, and therefore limited lung stiffness after AdTGF-β1. In addition, we applied mechanical stretch to lung slices from LOXL1 +/+ and LOXL1 -/- mice treated with AdTGF-β1. Lung stiffness (Young's modulus) of LOXL1 -/- lung slices was significantly lower compared with LOXL1 +/+ lung slices. Moreover, the release of activated TGF-β1 after mechanical stretch was significantly lower in LOXL1 -/- mice compared with LOXL1 +/+ mice after AdTGF-β1. These data support the concept that cross-linking enzyme inhibition represents an interesting therapeutic target for drug development in IPF.

  7. Use of Cre/loxP recombination to swap cell binding motifs on the adenoviral capsid protein IX

    International Nuclear Information System (INIS)

    Poulin, Kathy L.; Tong, Grace; Vorobyova, Olga; Pool, Madeline; Kothary, Rashmi; Parks, Robin J.

    2011-01-01

    We used Cre/loxP recombination to swap targeting ligands present on the adenoviral capsid protein IX (pIX). A loxP-flanked sequence encoding poly-lysine (pK-binds heparan sulfate proteoglycans) was engineered onto the 3'-terminus of pIX, and the resulting fusion protein allowed for routine virus propagation. Growth of this virus on Cre-expressing cells removed the pK coding sequence, generating virus that could only infect through alternative ligands, such as a tyrosine kinase receptor A (TrkA)-binding motif engineered into the capsid fibre protein for enhanced infection of neuronal cells. We used a similar approach to swap the pK motif on pIX for a sequence encoding a single-domain antibody directed towards CD66c for targeted infection of cancer cells; Cre-mediated removal of the pK-coding sequence simultaneously placed the single-domain antibody coding sequence in frame with pIX. Thus, we have developed a simple method to propagate virus lacking native viral tropism but containing cell-specific binding ligands. - Highlights: → We describe a method to grow virus lacking native tropism but containing novel cell-binding ligands. → Cre/loxP recombination was used to modify the adenovirus genome. → A targeting ligand present on capsid protein IX was removed or replaced using recombination. → Cre-loxP was also used to 'swap' the identity of the targeting ligand present on pIX.

  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. The INERIS at the heart of energy transition - INERISmag Nr 35. Clean energy - hydrogen, an energy vector for the future. Storage of electrochemical energy - To assess and to improve the safety of batteries. Methanization - Biogas: an energy which valorises organic wastes

    International Nuclear Information System (INIS)

    2014-11-01

    The first article of this magazine proposes a brief comment on the content of the bill project related to energy transition and green growth, and briefly outlines the role the INERIS is to play in this perspective. The second article addresses the perspectives of development of the use of hydrogen as an energy vector, and evokes the GHRYD project in which the INERIS is involved with GDF Suez, the Dunkirk urban community and other partners, and which is based on the use of a mix of hydrogen, methane and natural gas for mobility and household applications. The third article evokes works and researches undertaken to improve the safety of batteries. The last article briefly evokes INERIS activities on the safety of the methanization process, and in investigating characteristics of bio-wastes and domestic wastes with respect to French and European standards

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. Adenoviral overexpression of Lhx2 attenuates cell viability but does not preserve the stem cell like phenotype of hepatic stellate cells.

    Science.gov (United States)

    Genz, Berit; Thomas, Maria; Pützer, Brigitte M; Siatkowski, Marcin; Fuellen, Georg; Vollmar, Brigitte; Abshagen, Kerstin

    2014-11-01

    Hepatic stellate cells (HSC) are well known initiators of hepatic fibrosis. After liver cell damage, HSC transdifferentiate into proliferative myofibroblasts, representing the major source of extracellular matrix in the fibrotic organ. Recent studies also demonstrate a role of HSC as progenitor or stem cell like cells in liver regeneration. Lhx2 is described as stem cell maintaining factor in different organs and as an inhibitory transcription factor in HSC activation. Here we examined whether a continuous expression of Lhx2 in HSC could attenuate their activation and whether Lhx2 could serve as a potential target for antifibrotic gene therapy. Therefore, we evaluated an adenoviral mediated overexpression of Lhx2 in primary HSC and investigated mRNA expression patterns by qRT-PCR as well as the activation status by different in vitro assays. HSC revealed a marked increase in activation markers like smooth muscle actin alpha (αSMA) and collagen 1α independent from adenoviral transduction. Lhx2 overexpression resulted in attenuated cell viability as shown by a slightly hampered migratory and contractile phenotype of HSC. Expression of stem cell factors or signaling components was also unaffected by Lhx2. Summarizing these results, we found no antifibrotic or stem cell maintaining effect of Lhx2 overexpression in primary HSC. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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

  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. 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...

  11. 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.

  12. 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.

  13. 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.

  14. 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...

  15. 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).

  16. 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.

  17. Dual AAV Vectors for Stargardt Disease.

    Science.gov (United States)

    Trapani, Ivana

    2018-01-01

    Stargardt disease (STGD1), due to mutations in the large ABCA4 gene, is the most common inherited macular degeneration in humans. Attempts at developing gene therapy approaches for treatment of STGD1 are currently ongoing. Among all the vectors available for gene therapy of inherited retinal diseases, those based on adeno-associated viruses (AAV) are the most promising given the efficacy shown in various animal models and their excellent safety profile in humans, as confirmed in many ongoing clinical trials. However, one of the main obstacles for the use of AAV is their limited effective packaging capacity of about 5 kb. Taking advantage of the AAV genome's ability to concatemerize , others and we have recently developed dual AAV vectors to overcome this limit. We tested dual AAV vectors for ABCA4 delivery, and found that they transduce efficiently both mouse and pig photoreceptors , and rescue the Abca4-/- mouse retinal phenotype, indicating their potential for gene therapy of STGD1. This chapter details how we designed dual AAV vectors for the delivery of the ABCA4 gene and describes the techniques that can be explored to evaluate dual AAV transduction efficiency in vitro and in the retina, and their efficacy in the mouse model of STGD1.

  18. Amelioration of carbon tetrachloride-induced cirrhosis and portal hypertension in rat using adenoviral gene transfer of Akt.

    Science.gov (United States)

    Deng, Gang; Huang, Xiang-Jun; Luo, Hong-Wu; Huang, Fei-Zhou; Liu, Xun-Yang; Wang, Yong-Heng

    2013-01-01

    To investigate whether a virus constitutively expressing active Akt is useful to prevent cirrhosis induced by carbon tetrachloride (CCl4). Using cre-loxp technique, we created an Ad-myr-HA-Akt virus, in which Akt is labeled by a HA tag and its expression is driven by myr promoter. Further, through measuring enzyme levels and histological structure, we determined the efficacy of this Ad-myr-HA-Akt virus in inhibiting the development of cirrhosis induced by CCl4 in rats. Lastly, using western blotting, we examined the expression levels and/or phosphorylation status of Akt, apoptotic mediators, endothelial nitric oxide synthase (eNOS), and markers for hepatic stellate cells activation to understand the underlying mechanisms of protective role of this virus. The Ad-myr-HA-Akt virus was confirmed using polymerase chain reaction amplification of inserted Akt gene and sequencing for full length of inserted fragment, which was consistent with the sequence reported in the GenBank. The concentrations of Ad-myr-HA-Akt and adenoviral enhanced green fluorescent protein (Ad-EGFP) virus used in the current study were 5.5 × 10(11) vp/mL. The portal vein diameter, peak velocity of blood flow, portal blood flow and congestion index were significantly increased in untreated, saline and Ad-EGFP cirrhosis groups when compared to normal control after the virus was introduced to animal through tail veil injection. In contrast, these parameters in the Akt cirrhosis group were comparable to normal control group. Compared to the normal control, the liver function (Alanine aminotransferase, Aspartate aminotransferase and Albumin) was significantly impaired in the untreated, saline and Ad-EGFP cirrhosis groups. The Akt cirrhosis group showed significant improvement of liver function when compared to the untreated, saline and Ad-EGFP cirrhosis groups. The Hyp level and portal vein pressure in Akt cirrhosis groups were also significantly lower than other cirrhosis groups. The results of HE and

  19. 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.

  20. Viral Hybrid Vectors for Somatic Integration - Are They the Better Solution?

    Directory of Open Access Journals (Sweden)

    Anja Ehrhardt

    2009-12-01

    Full Text Available The turbulent history of clinical trials in viral gene therapy has taught us important lessons about vector design and safety issues. Much effort was spent on analyzing genotoxicity after somatic integration of therapeutic DNA into the host genome. Based on these findings major improvements in vector design including the development of viral hybrid vectors for somatic integration have been achieved. This review provides a state-of-the-art overview of available hybrid vectors utilizing viruses for high transduction efficiencies in concert with various integration machineries for random and targeted integration patterns. It discusses advantages but also limitations of each vector system.

  1. Comparison of [{sup 18}F]FHBG and [{sup 14}C]FIAU for imaging of HSV1-tk reporter gene expression: adenoviral infection vs stable transfection

    Energy Technology Data Exchange (ETDEWEB)

    Min, Jung-Jun; Iyer, Meera [The Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, UCLA School of Medicine, B3-399A BRI 700 Westwood Plaza, CA 90095-1770, Los Angeles (United States); Gambhir, Sanjiv S. [The Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, UCLA School of Medicine, B3-399A BRI 700 Westwood Plaza, CA 90095-1770, Los Angeles (United States); Department of Radiology, Bio-X Program, Stanford University, Stanford, California (United States)

    2003-11-01

    Earlier studies involving comparison of different reporter probes have shown conflicting results between pyrimidine nucleosides [e.g., 2'-fluoro-2'-deoxy-1-{beta}-d-arabinofuranosyl-5-iodouracil (FIAU)] and acycloguanosine derivatives [e.g., penciclovir (PCV), 9-(4-fluoro-3-hydroxymethylbutyl)guanine (FHBG)]. We hypothesized that this reported discrepancy may be related to how the reporter gene is delivered to the cells - stably transfected vs adenoviral infection. We directly compared the uptake characteristics of [{sup 18}F]FHBG, [{sup 3}H]PCV, and [{sup 14}C]FIAU in cell culture and in vivo using an adenoviral mediated gene transfer model and stably transfected cells. We further compared the uptake of three reporter probes using both HSV1-tk and a mutant HSV1-sr39tk expressing cells to assess the optimal reporter probe/reporter gene combination. [{sup 14}C]FIAU accumulation was greater than that of [{sup 3}H]PCV and [{sup 18}F]FHBG in control cells and in HSV1-tk stably transfected cells (P<0.001). After infection of C6 cells with AdCMV-HSV1-tk (1.5 x 10{sup 8} pfu), [{sup 18}F]FHBG and [{sup 3}H]PCV accumulation was significantly greater than that of [{sup 14}C]FIAU (P<0.01). [{sup 18}F]FHBG and [{sup 3}H]PCV accumulated to a significantly greater extent than [{sup 14}C]FIAU in C6-stb-sr39tk+ and AdCMV-HSV1-sr39tk infected C6 cells (P<0.001). Results from the nude mice supported the results in cell culture. [{sup 14}C]FIAU led to significantly higher %ID/g in C6-stb-tk+ xenografts than [{sup 18}F]FHBG (P<0.05); however, compared with [{sup 14}C]FIAU, [{sup 18}F]FHBG led to as high %ID/g in HSV1-tk expressing hepatocytes and to significantly greater %ID/g in C6-stb-sr39tk+ xenografts and HSV1-sr39tk expressing hepatocytes. Dynamic sequential images showed that [{sup 18}F]FHBG was well retained in HSV1-sr39tk expressing cells (C6-stb-sr39tk+) for at least 4 h after injection, while it was rapidly cleared from HSV1-tk expressing cells (MH3924A

  2. 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

  3. 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

  4. 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…

  5. Playground Safety

    Science.gov (United States)

    ... Prevention Fall Prevention Playground Safety Poisoning Prevention Road Traffic Safety Sports Safety Get Email Updates To receive ... at the Consumer Product Safety Commission’s Playground Safety website . References U.S. Consumer Product Safety Commission. Injuries and ...

  6. 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

  7. 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)

  8. 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...

  9. 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)

  10. 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

  11. Improvement of oncolytic adenovirus vectors through genetic capsid modifications

    NARCIS (Netherlands)

    Vrij, Jeroen de

    2012-01-01

    Recombinant viral vectors hold great promise in the field of cancer gene therapy. While a plethora of viruses is being evaluated as oncolytic agents, human adenoviruses of serotype 5 (HAdV-5) are among the most popular of viruses to be developed. Although clinical studies have demonstrated safety of

  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. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. In-vitro evaluation of ion-exchange microspheres for the sustained release of liposomal-adenoviral conjugates.

    Science.gov (United States)

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

    2004-03-24

    This study looks at the development of a novel combination vector consisting of adenovirus conjugated to liposomes (AL complexes) bound to cation-exchanging microspheres (MAL complexes). With adenovirus having a net negative charge and the liposomes a net positive charge it was possible to modify the net charge of the AL complexes by varying the concentrations of adenovirus to liposomes. The modification of the net charge resulted in altered binding and release characteristics. Of the complexes tested, the 5:1 and 2:1 ratio AL complexes were able to be efficiently bound by the microspheres and exhibited sustained release over 24 h. The 1:1 and 1:2 AL complexes, however, bound poorly to the microspheres and were rapidly released. In addition the MAL complexes also were able to reduce the toxicity of the AL complexes, which was seen with the 10:1 ratio. The AL complexes showed considerably more toxicity alone than in combination with microspheres, highlighting a potential benefit of this vector.

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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....

  5. 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)

  6. 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

  7. Safety and immunogenicity of GamEvac-Combi, a heterologous VSV- and Ad5-vectored Ebola vaccine: An open phase I/II trial in healthy adults in Russia.

    Science.gov (United States)

    Dolzhikova, I V; Zubkova, O V; Tukhvatulin, A I; Dzharullaeva, A S; Tukhvatulina, N M; Shcheblyakov, D V; Shmarov, M M; Tokarskaya, E A; Simakova, Y V; Egorova, D A; Scherbinin, D N; Tutykhina, I L; Lysenko, A A; Kostarnoy, A V; Gancheva, P G; Ozharovskaya, T A; Belugin, B V; Kolobukhina, L V; Pantyukhov, V B; Syromyatnikova, S I; Shatokhina, I V; Sizikova, T V; Rumyantseva, I G; Andrus, A F; Boyarskaya, N V; Voytyuk, A N; Babira, V F; Volchikhina, S V; Kutaev, D A; Bel'skih, A N; Zhdanov, K V; Zakharenko, S M; Borisevich, S V; Logunov, D Y; Naroditsky, B S; Gintsburg, A L

    2017-03-04

    Ebola hemorrhagic fever, also known as Ebola virus disease or EVD, is one of the most dangerous viral diseases in humans and animals. In this open-label, dose-escalation clinical trial, we assessed the safety, side effects, and immunogenicity of a novel, heterologous prime-boost vaccine against Ebola, which was administered in 2 doses to 84 healthy adults of both sexes between 18 and 55 years. The vaccine consists of live-attenuated recombinant vesicular stomatitis virus (VSV) and adenovirus serotype-5 (Ad5) expressing Ebola envelope glycoprotein. The most common adverse event was pain at the injection site, although no serious adverse events were reported. The vaccine did not significantly impact blood, urine, and immune indices. Seroconversion rate was 100 %. Antigen-specific IgG geometric mean titer at day 42 was 3,277 (95 % confidence interval 2,401-4,473) in volunteers immunized at full dose. Neutralizing antibodies were detected in 93.1 % of volunteers immunized at full dose, with geometric mean titer 20. Antigen-specific response in peripheral blood mononuclear cells was also detected in 100 % of participants, as well as in CD4+ and CD8+ T cells in 82.8 % and 58.6 % of participants vaccinated at full dose, respectively. The data indicate that the vaccine is safe and induces strong humoral and cellular immune response in up to 100 % of healthy adult volunteers, and provide a rationale for testing efficacy in Phase III trials. Indeed, the strong immune response to the vaccine may elicit long-term protection. This trial was registered with grls.rosminzdrav.ru (No. 495*), and with zakupki.gov.ru (No. 0373100043215000055).

  8. Simplified Representation of Vector Fields

    NARCIS (Netherlands)

    Telea, Alexandru; Wijk, Jarke J. van

    1999-01-01

    Vector field visualization remains a difficult task. Although many local and global visualization methods for vector fields such as flow data exist, they usually require extensive user experience on setting the visualization parameters in order to produce images communicating the desired insight. We

  9. Estimation of Motion Vector Fields

    DEFF Research Database (Denmark)

    Larsen, Rasmus

    1993-01-01

    This paper presents an approach to the estimation of 2-D motion vector fields from time varying image sequences. We use a piecewise smooth model based on coupled vector/binary Markov random fields. We find the maximum a posteriori solution by simulated annealing. The algorithm generate sample...... fields by means of stochastic relaxation implemented via the Gibbs sampler....

  10. GPU Accelerated Vector Median Filter

    Science.gov (United States)

    Aras, Rifat; Shen, Yuzhong

    2011-01-01

    Noise reduction is an important step for most image processing tasks. For three channel color images, a widely used technique is vector median filter in which color values of pixels are treated as 3-component vectors. Vector median filters are computationally expensive; for a window size of n x n, each of the n(sup 2) vectors has to be compared with other n(sup 2) - 1 vectors in distances. General purpose computation on graphics processing units (GPUs) is the paradigm of utilizing high-performance many-core GPU architectures for computation tasks that are normally handled by CPUs. In this work. NVIDIA's Compute Unified Device Architecture (CUDA) paradigm is used to accelerate vector median filtering. which has to the best of our knowledge never been done before. The performance of GPU accelerated vector median filter is compared to that of the CPU and MPI-based versions for different image and window sizes, Initial findings of the study showed 100x improvement of performance of vector median filter implementation on GPUs over CPU implementations and further speed-up is expected after more extensive optimizations of the GPU algorithm .

  11. Archimedeanization of ordered vector spaces

    OpenAIRE

    Emelyanov, Eduard Yu.

    2014-01-01

    In the case of an ordered vector space with an order unit, the Archimedeanization method has been developed recently by V.I Paulsen and M. Tomforde. We present a general version of the Archimedeanization which covers arbitrary ordered vector spaces.

  12. Vector superconductivity in cosmic strings

    International Nuclear Information System (INIS)

    Dvali, G.R.; Mahajan, S.M.

    1992-03-01

    We argue that in most realistic cases, the usual Witten-type bosonic superconductivity of the cosmic string is automatically (independent of the existence of superconducting currents) accompanied by the condensation of charged gauge vector bosons in the core giving rise to a new vector type superconductivity. The value of the charged vector condensate is related with the charged scalar expectation value, and vanishes only if the latter goes to zero. The mechanism for the proposed vector superconductivity, differing fundamentally from those in the literature, is delineated using the simplest realistic example of the two Higgs doublet standard model interacting with the extra cosmic string. It is shown that for a wide range of parameters, for which the string becomes scalarly superconducting, W boson condensates (the sources of vector superconductivity) are necessarily excited. (author). 14 refs

  13. Efficacy, Safety and Cost of Insecticide Treated Wall Lining, Insecticide Treated Bed Nets and Indoor Wall Wash with Lime for Visceral Leishmaniasis Vector Control in the Indian Sub-continent: A Multi-country Cluster Randomized Controlled Trial

    Science.gov (United States)

    Das, Pradeep; Ghosh, Debashis; Priyanka, Jyoti; Matlashewski, Greg; Kroeger, Axel; Upfill-Brown, Alexander

    2016-01-01

    Background We investigated the efficacy, safety and cost of lime wash of household walls plus treatment of sand fly breeding places with bleach (i.e. environmental management or EM), insecticide impregnated durable wall lining (DWL), and bed net impregnation with slow release insecticide (ITN) for sand fly control in the Indian sub-continent. Methods This multi-country cluster randomized controlled trial had 24 clusters in each three sites with eight clusters per high, medium or low sand fly density stratum. Every cluster included 45–50 households. Five households from each cluster were randomly selected for entomological measurements including sand fly density and mortality at one, three, nine and twelve months post intervention. Household interviews were conducted for socioeconomic information and intervention acceptability assessment. Cost for each intervention was calculated. There was a control group without intervention. Findings Sand fly mortality [mean and 95%CI] ranged from 84% (81%-87%) at one month to 74% (71%-78%) at 12 months for DWL, 75% (71%-79%) at one month to 49% (43%-55%) at twelve months for ITN, and 44% (34%-53%) at one month to 22% (14%-29%) at twelve months for EM. Adjusted intervention effect on sand fly density measured by incidence rate ratio ranged from 0.28 (0.23–0.34) at one month to 0.62 (0.51–0.75) at 12 months for DWL; 0.72 (0.62–0.85) at one month to 1.02 (0.86–1.22) at 12 months for ITN; and 0.89 (0.76–1.03) at one months to 1.49 (1.26–1.74) at 12 months for EM. Household acceptance of EM was 74% compared to 94% for both DWL and ITN. Operational cost per household in USD was about 5, 8, and 2 for EM, DWL and ITN, respectively. Minimal adverse reactions were reported for EM and ITN while 36% of households with DWL reported transient itching. Interpretation DWL is the most effective, durable and acceptable control method followed by ITN. The Visceral Leishmaniasis (VL) Elimination Program in the Indian sub

  14. Emerging vector borne diseases – incidence through vectors

    Directory of Open Access Journals (Sweden)

    Sara eSavic

    2014-12-01

    Full Text Available Vector borne diseases use to be a major public health concern only in tropical and subtropical areas, but today they are an emerging threat for the continental and developed countries also. Nowdays, in intercontinetal countries, there is a struggle with emerging diseases which have found their way to appear through vectors. Vector borne zoonotic diseases occur when vectors, animal hosts, climate conditions, pathogens and susceptible human population exist at the same time, at the same place. Global climate change is predicted to lead to an increase in vector borne infectious diseases and disease outbreaks. It could affect the range and popultion of pathogens, host and vectors, transmission season, etc. Reliable surveilance for diseases that are most likely to emerge is required. Canine vector borne diseases represent a complex group of diseases including anaplasmosis, babesiosis, bartonellosis, borreliosis, dirofilariosis, erlichiosis, leishmaniosis. Some of these diseases cause serious clinical symptoms in dogs and some of them have a zoonotic potential with an effect to public health. It is expected from veterinarians in coordination with medical doctors to play a fudamental role at primeraly prevention and then treatment of vector borne diseases in dogs. The One Health concept has to be integrated into the struggle against emerging diseases.During a four year period, from 2009-2013, a total number of 551 dog samples were analysed for vector borne diseases (borreliosis, babesiosis, erlichiosis, anaplasmosis, dirofilariosis and leishmaniasis in routine laboratory work. The analysis were done by serological tests – ELISA for borreliosis, dirofilariosis and leishmaniasis, modified Knott test for dirofilariosis and blood smear for babesiosis, erlichiosis and anaplasmosis. This number of samples represented 75% of total number of samples that were sent for analysis for different diseases in dogs. Annually, on avarege more then half of the samples

  15. Recent Advances in Non-viral Vectors for Gene Delivery

    Science.gov (United States)

    Guo, Xia; Huang, Leaf

    2011-01-01

    CONSPECTUS Non-viral vectors, typically based on cationic lipids or polymers, are preferred due to safety concerns with viral vectors. So far, non-viral vectors can proficiently transfect cells in culture, but obtaining efficient nanomedicines is far from evident. To overcome the hurdles associated with non-viral vectors is significant for improving delivery efficiency and therapeutic effect of nucleic acid. The drawbacks include the strong interaction of cationic delivery vehicles with blood components, uptake by the reticuloendothelial system (RES), toxicity, targeting ability of the carriers to the cells of interest, and so on. PEGylation is the predominant method used to reduce the binding of plasma proteins with non-viral vectors and minimize the clearance by RES after intravenous administration. The nanoparticles that are not rapidly cleared from the circulation accumulate in the tumors due to the enhanced permeability and retention effect, and the targeting ligands attached to the distal end of the PEGylated components allow binding to the receptors on the target cell surface. Neutral or anionic liposomes have been also developed for systemic delivery of nucleic acids in experimental animal model. Designing and synthesizing novel cationic lipids and polymers, and binding nucleic acid with peptides, targeting ligands, polymers, or environmentally sensitive moieties also attract many attentions for resolving the problems encountered by non-viral vectors. The application of inorganic nanoparticles in nucleic acid delivery is an emerging field, too. Recently, different classes of non-viral vectors appear to be converging and the features of different classes of non-viral vectors could be combined in one strategy. More hurdles associated with efficient nucleic acid delivery therefore might be expected to be overcome. In this account, we will focus on these novel non-viral vectors, which are classified into multifunctional hybrid nucleic acid vectors, novel

  16. 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.

  17. 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.

  18. An anti-VEGF ribozyme embedded within the adenoviral VAI sequence inhibits glioblastoma cell angiogenic potential in vitro.

    Science.gov (United States)

    Ciafrè, Silvia Anna; Niola, Francesco; Wannenes, Francesca; Farace, Maria Giulia

    2004-01-01

    Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis, where it functions as one of the major angiogenic factors sustaining growth and draining catabolites. In this study, we developed an anti-VEGF ribozyme targeted to the 5' part of human VEGF mRNA. We endowed this ribozyme with an additional feature expected to improve its activity in vivo, by cloning it into a VAI transcriptional cassette. VAI is originally part of the adenovirus genome, and is characterized by high transcription rates, good stability due to its strong secondary structure and cytoplasmic localization. Transfection of U87 human glioblastoma cells with plasmid vectors encoding for this ribozyme resulted in a strong (-56%) reduction of VEGF secreted in the extracellular medium, indicating a good biological activity of the ribozyme. Moreover, this reduction in VEGF secretion had the important functional consequence of drastically diminishing the formation of tube-like structures of human umbilical vascular endothelial cells in a Matrigel in vitro angiogenesis assay. In conclusion, our VAI-embedded anti-VEGF ribozyme is a good inhibitor of angiogenesis in vitro, in a glioblastoma cell context. Thus, it may represent a useful tool for future applications in vivo, for antiangiogenic gene therapy of glioblastoma and of highly vascularized tumors. Copyright 2004 S. Karger AG, Basel

  19. Auto Safety

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Auto Safety KidsHealth / For Parents / Auto Safety What's in this ... by teaching some basic rules. Importance of Child Safety Seats Using a child safety seat (car seat) ...

  20. Violation of vector dominance in the vector manifestation

    International Nuclear Information System (INIS)

    Sasaki, Chihiro

    2003-01-01

    The vector manifestation (VM) is a new pattern for realizing the chiral symmetry in QCD. In the VM, the massless vector meson becomes the chiral partner of pion at the critical point, in contrast with the restoration based on the linear sigma model. Including the intrinsic temperature dependences of the parameters of the hidden local symmetry (HLS) Lagrangian determined from the underlying QCD through the Wilsonian matching together with the hadronic thermal corrections, 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 analysis 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. (author)

  1. Emerging Vector-Borne Diseases - Incidence through Vectors.

    Science.gov (United States)

    Savić, Sara; Vidić, Branka; Grgić, Zivoslav; Potkonjak, Aleksandar; Spasojevic, Ljubica

    2014-01-01

    Vector-borne diseases use to be a major public health concern only in tropical and subtropical areas, but today they are an emerging threat for the continental and developed countries also. Nowadays, in intercontinental countries, there is a struggle with emerging diseases, which have found their way to appear through vectors. Vector-borne zoonotic diseases occur when vectors, animal hosts, climate conditions, pathogens, and susceptible human population exist at the same time, at the same place. Global climate change is predicted to lead to an increase in vector-borne infectious diseases and disease outbreaks. It could affect the range and population of pathogens, host and vectors, transmission season, etc. Reliable surveillance for diseases that are most likely to emerge is required. Canine vector-borne diseases represent a complex group of diseases including anaplasmosis, babesiosis, bartonellosis, borreliosis, dirofilariosis, ehrlichiosis, and leishmaniosis. Some of these diseases cause serious clinical symptoms in dogs and some of them have a zoonotic potential with an effect to public health. It is expected from veterinarians in coordination with medical doctors to play a fundamental role at primarily prevention and then treatment of vector-borne diseases in dogs. The One Health concept has to be integrated into the struggle against emerging diseases. During a 4-year period, from 2009 to 2013, a total number of 551 dog samples were analyzed for vector-borne diseases (borreliosis, babesiosis, ehrlichiosis, anaplasmosis, dirofilariosis, and leishmaniasis) in routine laboratory work. The analysis was done by serological tests - ELISA for borreliosis, dirofilariosis, and leishmaniasis, modified Knott test for dirofilariosis, and blood smear for babesiosis, ehrlichiosis, and anaplasmosis. This number of samples represented 75% of total number of samples that were sent for analysis for different diseases in dogs. Annually, on average more then half of the samples

  2. On the Witt vector Frobenius

    DEFF Research Database (Denmark)

    Davis, Christopher James; Kedlaya, Kiran

    2014-01-01

    We study the kernel and cokernel of the Frobenius map on the p-typical Witt vectors of a commutative ring, not necessarily of characteristic p. We give many equivalent conditions to surjectivity of the Frobenius map on both finite and infinite length Witt vectors. In particular, surjectivity...... on finite Witt vectors turns out to be stable under certain integral extensions; this provides a clean formulation of a strong generalization of Faltings’s almost purity theorem from p-adic Hodge theory, incorporating recent improvements by Kedlaya–Liu and by Scholze....

  3. Vector boson scattering at CLIC

    Energy Technology Data Exchange (ETDEWEB)

    Kilian, Wolfgang; Fleper, Christian [Department Physik, Universitaet Siegen, 57068 Siegen (Germany); Reuter, Juergen [DESY Theory Group, 22603 Hamburg (Germany); Sekulla, Marco [Institut fuer Theoretische Physik, Karlsruher Institut fuer Technologie, 76131 Karlsruhe (Germany)

    2016-07-01

    Linear colliders operating in a range of multiple TeV are able to investigate the details of vector boson scattering and electroweak symmetry breaking. We calculate cross sections with the Monte Carlo generator WHIZARD for vector boson scattering processes at the future linear e{sup +} e{sup -} collider CLIC. By finding suitable cuts, the vector boson scattering signal processes are isolated from the background. Finally, we are able to determine exclusion sensitivities on the non-Standard Model parameters of the relevant dimension eight operators.

  4. Vector control of induction machines

    CERN Document Server

    Robyns, Benoit

    2012-01-01

    After a brief introduction to the main law of physics and fundamental concepts inherent in electromechanical conversion, ""Vector Control of Induction Machines"" introduces the standard mathematical models for induction machines - whichever rotor technology is used - as well as several squirrel-cage induction machine vector-control strategies. The use of causal ordering graphs allows systematization of the design stage, as well as standardization of the structure of control devices. ""Vector Control of Induction Machines"" suggests a unique approach aimed at reducing parameter sensitivity for

  5. Vectors of rickettsiae in Africa.

    Science.gov (United States)

    Bitam, Idir

    2012-12-01

    Vector-borne diseases are caused by parasites, bacteria, or viruses transmitted by the bites of hematophagous arthropods. In Africa, there has been a recent emergence of new diseases and the re-emergence of existing diseases, usually with changes in disease epidemiology (e.g., geographical distribution, prevalence, and pathogenicity). In Africa, rickettsioses are recognized as important emerging vector-borne infections in humans. Rickettsial diseases are transmitted by different types of arthropods, ticks, fleas, lice, and mites. This review will examine the roles of these different arthropod vectors and their geographical distributions. Copyright © 2012 Elsevier GmbH. All rights reserved.

  6. Recommendation on vectors and vector-transmitted diseases

    OpenAIRE

    Netherlands Food and Consumer Product Safety Authority

    2009-01-01

    In view of their increasing risk of introduction and their possible implications in causing major disease outbreaks, vectors, as well as vector-transmitted diseases like dengue, West Nile disease, Lyme disease and bluetongue need to be recognised as a threat to public and animal health and to the economy, also in the Netherlands. There has been an increase in the incidence of these diseases in the past two to three decades. Climate changes and changes in the use of land, water managemen...

  7. 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

  8. 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.

  9. Introduction to matrices and vectors

    CERN Document Server

    Schwartz, Jacob T

    2001-01-01

    In this concise undergraduate text, the first three chapters present the basics of matrices - in later chapters the author shows how to use vectors and matrices to solve systems of linear equations. 1961 edition.

  10. GRE Enzymes for Vector Analysis

    Data.gov (United States)

    U.S. Environmental Protection Agency — Microbial enzyme data that were collected during the 2004-2006 EMAP-GRE program. These data were then used by Moorhead et al (2016) in their ecoenzyme vector...

  11. Scanning vector Hall probe microscopy

    International Nuclear Information System (INIS)

    Cambel, V.; Gregusova, D.; Fedor, J.; Kudela, R.; Bending, S.J.

    2004-01-01

    We have developed a scanning vector Hall probe microscope for mapping magnetic field vector over magnetic samples. The microscope is based on a micromachined Hall sensor and the cryostat with scanning system. The vector Hall sensor active area is ∼5x5 μm 2 . It is realized by patterning three Hall probes on the tilted faces of GaAs pyramids. Data from these 'tilted' Hall probes are used to reconstruct the full magnetic field vector. The scanning area of the microscope is 5x5 mm 2 , space resolution 2.5 μm, field resolution ∼1 μT Hz -1/2 at temperatures 10-300 K

  12. 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....

  13. 3-D Vector Flow Imaging

    DEFF Research Database (Denmark)

    Holbek, Simon

    , if this significant reduction in the element count can still provide precise and robust 3-D vector flow estimates in a plane. The study concludes that the RC array is capable of estimating precise 3-D vector flow both in a plane and in a volume, despite the low channel count. However, some inherent new challenges...... ultrasonic vector flow estimation and bring it a step closer to a clinical application. A method for high frame rate 3-D vector flow estimation in a plane using the transverse oscillation method combined with a 1024 channel 2-D matrix array is presented. The proposed method is validated both through phantom...... hampers the task of real-time processing. In a second study, some of the issue with the 2-D matrix array are solved by introducing a 2-D row-column (RC) addressing array with only 62 + 62 elements. It is investigated both through simulations and via experimental setups in various flow conditions...

  14. Transcriptional Silencing of Retroviral Vectors

    DEFF Research Database (Denmark)

    Lund, Anders Henrik; Duch, M.; Pedersen, F.S.

    1996-01-01

    . Extinction of long-term vector expression has been observed after implantation of transduced hematopoietic cells as well as fibroblasts, myoblasts and hepatocytes. Here we review the influence of vector structure, integration site and cell type on transcriptional silencing. While down-regulation of proviral...... transcription is known from a number of cellular and animal models, major insight has been gained from studies in the germ line and embryonal cells of the mouse. Key elements for the transfer and expression of retroviral vectors, such as the viral transcriptional enhancer and the binding site for the t......RNA primer for reverse transcription may have a major influence on transcriptional silencing. Alterations of these elements of the vector backbone as well as the use of internal promoter elements from housekeeping genes may contribute to reduce transcriptional silencing. The use of cell culture and animal...

  15. High Accuracy Vector Helium Magnetometer

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed HAVHM instrument is a laser-pumped helium magnetometer with both triaxial vector and omnidirectional scalar measurement capabilities in a single...

  16. An exotic composite vector boson

    International Nuclear Information System (INIS)

    Akama, Keiichi; Hattori, Takashi; Yasue, Masaki.

    1990-08-01

    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. (author)

  17. 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).

  18. Versatile generation of optical vector fields and vector beams using a non-interferometric approach.

    Science.gov (United States)

    Tripathi, Santosh; Toussaint, Kimani C

    2012-05-07

    We present a versatile, non-interferometric method for generating vector fields and vector beams which can produce all the states of polarization represented on a higher-order Poincaré sphere. The versatility and non-interferometric nature of this method is expected to enable exploration of various exotic properties of vector fields and vector beams. To illustrate this, we study the propagation properties of some vector fields and find that, in general, propagation alters both their intensity and polarization distribution, and more interestingly, converts some vector fields into vector beams. In the article, we also suggest a modified Jones vector formalism to represent vector fields and vector beams.

  19. Status of pesticide management in the practice of vector control: a global survey in countries at risk of malaria or other major vector-borne diseases

    Directory of Open Access Journals (Sweden)

    Tan Soo

    2011-05-01

    Full Text Available Abstract Background It is critical that vector control pesticides are used for their acceptable purpose without causing adverse effects on health and the environment. This paper provides a global overview of the current status of pesticides management in the practice of vector control. Methods A questionnaire was distributed to WHO member states and completed either by the director of the vector-borne disease control programme or by the national manager for vector control. In all, 113 countries responded to the questionnaire (80% response rate, representing 94% of the total population of the countries targeted. Results Major gaps were evident in countries in pesticide procurement practices, training on vector control decision making, certification and quality control of pesticide application, monitoring of worker safety, public awareness programmes, and safe disposal of pesticide-related waste. Nevertheless, basic conditions of policy and coordination have been established in many countries through which the management of vector control pesticides could potentially be improved. Most countries responded that they have adopted relevant recommendations by the WHO. Conclusions Given the deficiencies identified in this first global survey on public health pesticide management and the recent rise in pesticide use for malaria control, the effectiveness and safety of pesticide use are being compromised. This highlights the urgent need for countries to strengthen their capacity on pesticide management and evidence-based decision making within the context of an integrated vector management approach.

  20. Status of pesticide management in the practice of vector control: a global survey in countries at risk of malaria or other major vector-borne diseases.

    Science.gov (United States)

    van den Berg, Henk; Hii, Jeffrey; Soares, Agnes; Mnzava, Abraham; Ameneshewa, Birkinesh; Dash, Aditya P; Ejov, Mikhail; Tan, Soo Hian; Matthews, Graham; Yadav, Rajpal S; Zaim, Morteza

    2011-05-14

    It is critical that vector control pesticides are used for their acceptable purpose without causing adverse effects on health and the environment. This paper provides a global overview of the current status of pesticides management in the practice of vector control. A questionnaire was distributed to WHO member states and completed either by the director of the vector-borne disease control programme or by the national manager for vector control. In all, 113 countries responded to the questionnaire (80% response rate), representing 94% of the total population of the countries targeted. Major gaps were evident in countries in pesticide procurement practices, training on vector control decision making, certification and quality control of pesticide application, monitoring of worker safety, public awareness programmes, and safe disposal of pesticide-related waste. Nevertheless, basic conditions of policy and coordination have been established in many countries through which the management of vector control pesticides could potentially be improved. Most countries responded that they have adopted relevant recommendations by the WHO. Given the deficiencies identified in this first global survey on public health pesticide management and the recent rise in pesticide use for malaria control, the effectiveness and safety of pesticide use are being compromised. This highlights the urgent need for countries to strengthen their capacity on pesticide management and evidence-based decision making within the context of an integrated vector management approach.

  1. Practical utilization of recombinant AAV vector reference standards: focus on vector genomes titration by free ITR qPCR

    Directory of Open Access Journals (Sweden)

    Susan D'Costa

    2016-01-01

    Full Text Available Clinical trials using recombinant adeno-associated virus (rAAV vectors have demonstrated efficacy and a good safety profile. Although the field is advancing quickly, vector analytics and harmonization of dosage units are still a limitation for commercialization. AAV reference standard materials (RSMs can help ensure product safety by controlling the consistency of assays used to characterize rAAV stocks. The most widely utilized unit of vector dosing is based on the encapsidated vector genome. Quantitative polymerase chain reaction (qPCR is now the most common method to titer vector genomes (vg; however, significant inter- and intralaboratory variations have been documented using this technique. Here, RSMs and rAAV stocks were titered on the basis of an inverted terminal repeats (ITRs sequence-specific qPCR and we found an artificial increase in vg titers using a widely utilized approach. The PCR error was introduced by using single-cut linearized plasmid as the standard curve. This bias was eliminated using plasmid standards linearized just outside the ITR region on each end to facilitate the melting of the palindromic ITR sequences during PCR. This new “Free-ITR” qPCR delivers vg titers that are consistent with titers obtained with transgene-specific qPCR and could be used to normalize in-house product-specific AAV vector standards and controls to the rAAV RSMs. The free-ITR method, including well-characterized controls, will help to calibrate doses to compare preclinical and clinical data in the field.

  2. Practical utilization of recombinant AAV vector reference standards: focus on vector genomes titration by free ITR qPCR.

    Science.gov (United States)

    D'Costa, Susan; Blouin, Veronique; Broucque, Frederic; Penaud-Budloo, Magalie; François, Achille; Perez, Irene C; Le Bec, Christine; Moullier, Philippe; Snyder, Richard O; Ayuso, Eduard

    2016-01-01

    Clinical trials using recombinant adeno-associated virus (rAAV) vectors have demonstrated efficacy and a good safety profile. Although the field is advancing quickly, vector analytics and harmonization of dosage units are still a limitation for commercialization. AAV reference standard materials (RSMs) can help ensure product safety by controlling the consistency of assays used to characterize rAAV stocks. The most widely utilized unit of vector dosing is based on the encapsidated vector genome. Quantitative polymerase chain reaction (qPCR) is now the most common method to titer vector genomes (vg); however, significant inter- and intralaboratory variations have been documented using this technique. Here, RSMs and rAAV stocks were titered on the basis of an inverted terminal repeats (ITRs) sequence-specific qPCR and we found an artificial increase in vg titers using a widely utilized approach. The PCR error was introduced by using single-cut linearized plasmid as the standard curve. This bias was eliminated using plasmid standards linearized just outside the ITR region on each end to facilitate the melting of the palindromic ITR sequences during PCR. This new "Free-ITR" qPCR delivers vg titers that are consistent with titers obtained with transgene-specific qPCR and could be used to normalize in-house product-specific AAV vector standards and controls to the rAAV RSMs. The free-ITR method, including well-characterized controls, will help to calibrate doses to compare preclinical and clinical data in the field.

  3. INGN 201: Ad-p53, Ad5CMV-p53, Adenoviral p53, INGN 101, p53 gene therapy--Introgen, RPR/INGN 201.

    Science.gov (United States)

    2003-01-01

    Introgen's adenoviral p53 gene therapy [INGN 201, ADVEXIN] is in clinical development for the treatment of various cancers. The p53 tumour suppressor gene is deleted or mutated in many tumour cells and is one of the most frequently mutated genes in human tumours. INGN 201 has been shown to kill cancer cells directly. In August 2002, Introgen announced plans to file an application for INGN 201 with the European Agency for the Evaluation of Medicinal Products (EMEA) for the treatment of head and neck cancer; the European filing will be submitted simultaneously with the previously scheduled (planned for 2004) submission of a Biologics License Application (BLA) for ADVEXIN to the US FDA. On 20 February 2003, INGN 201 received orphan drug designation from the US FDA for head and neck cancer. INGN 201 is available for licensing although Introgen favours retaining partial or full rights to the therapy in the US. Introgen Therapeutics and its collaborative partner for the p53 programme, Aventis Gencell, have been developing p53 gene therapy products. The agreement was originally signed by Rhône-Poulenc Rorer's Gencell division, which became Aventis Gencell after Rhône-Poulenc Rorer merged with Hoechst Marion Roussel to form Aventis Pharma. According to the original agreement, Introgen was responsible for phase I and preclinical development in North America, while Aventis Gencell was responsible for clinical trials conducted in Europe and for clinical trials in North America beyond phase I. In April 2001, Aventis Gencell and Introgen restructured their existing collaboration agreement for p53 gene therapy products. Aventis Gencell indicated that p53 research had suffered from internal competition for resources and was pulling back from its development agreement with Introgen for p53 gene therapy products. Introgen will assume responsibility for worldwide development of all p53 programmes and will obtain exclusive worldwide commercial rights to p53-based gene therapy

  4. Human Articular Cartilage Progenitor Cells Are Responsive to Mechanical Stimulation and Adenoviral-Mediated Overexpression of Bone-Morphogenetic Protein 2.

    Directory of Open Access Journals (Sweden)

    Alexander J Neumann

    Full Text Available Articular cartilage progenitor cells (ACPCs represent a new and potentially powerful alternative cell source to commonly used cell sources for cartilage repair, such as chondrocytes and bone-marrow derived mesenchymal stem cells (MSCs. This is particularly due to the apparent resistance of ACPCs to hypertrophy. The current study opted to investigate whether human ACPCs (hACPCs are responsive towards mechanical stimulation and/or adenoviral-mediated overexpression of bone morphogenetic protein 2 (BMP-2. hACPCs were cultured in fibrin-polyurethane composite scaffolds. Cells were cultured in a defined chondro-permissive medium, lacking exogenous growth factors. Constructs were cultured, for 7 or 28 days, under free-swelling conditions or with the application of complex mechanical stimulation, using a custom built bioreactor that is able to generate joint-like movements. Outcome parameters were quantification of BMP-2 and transforming growth factor beta 1 (TGF-β1 concentration within the cell culture medium, biochemical and gene expression analyses, histology and immunohistochemistry. The application of mechanical stimulation alone resulted in the initiation of chondrogenesis, demonstrating the cells are mechanoresponsive. This was evidenced by increased GAG production, lack of expression of hypertrophic markers and a promising gene expression profile (significant up-regulation of cartilaginous marker genes, specifically collagen type II, accompanied by no increase in the hypertrophic marker collagen type X or the osteogenic marker alkaline phosphatase. To further investigate the resistance of ACPCs to hypertrophy, overexpression of a factor associated with hypertrophic differentiation, BMP-2, was investigated. A novel, three-dimensional, transduction protocol was used to transduce cells with an adenovirus coding for BMP-2. Over-expression of BMP-2, independent of load, led to an increase in markers associated with hypertropy. Taken together ACPCs

  5. Effect of adenovirus infection on transgene expression under the adenoviral MLP/TPL and the CMVie promoter/enhancer in CHO cells

    Directory of Open Access Journals (Sweden)

    Mohamed A. El-Mogy

    2017-06-01

    Full Text Available The adenovirus major late promoter (MLP and its translational regulator – the tripartite leader (TPL sequence – can actively drive efficient gene expression during adenoviral infection. However, both elements have not been widely tested in transgene expression outside of the adenovirus genome context. In this study, we tested whether the combination of MLP and TPL would enhance transgene expression beyond that of the most widely used promoter in transgene expression in mammalian cells, the cytomegalovirus immediate early (CMVie promoter/enhancer. The activity of these two regulatory elements was compared in Chinese hamster ovary (CHO cells. Although transient expression was significantly higher under the control of the CMVie promoter/enhance compared to the MLP/TPL, this difference was greater at the level of transcription (30 folds than translation (11 folds. Even with adenovirus infection to provide additional elements (in trans, CMVie promoter/enhancer exhibited significantly higher activity relative to MLP/TPL. Interestingly, the CMVie promoter/enhancer was 1.9 folds more active in adenovirus-infected cells than in non-infected cells. Our study shows that the MLP-TPL drives lower transgene expression than the CMVie promoter/enhancer particularly at the transcription level. The data also highlight the utility of the TPL sequence at the translation level and/or possible overwhelming of the cellular translational machinery by the high transcription activity of the CMVie promoter/enhancer. In addition, here we present data that show stimulation of the CMVie promoter/enhancer by adenovirus infection, which may prove interesting in future work to test the combination of CMVie/TPL sequence, and additional adenovirus elements, for transgene expression.

  6. Adenovirally delivered shRNA strongly inhibits Na+-Ca2+ exchanger expression but does not prevent contraction of neonatal cardiomyocytes.

    Science.gov (United States)

    Hurtado, Cecilia; Ander, Bradley P; Maddaford, Thane G; Lukas, Anton; Hryshko, Larry V; Pierce, Grant N

    2005-04-01

    The cardiac Na(+)-Ca(2+) exchanger (NCX1) is the main mechanism for Ca(2+) efflux in the heart and is thought to serve an essential role in cardiac excitation-contraction (E-C) coupling. The demonstration that an NCX1 gene knock-out is embryonic lethal provides further support for this essential role. However, a recent report employing the Cre/loxP technique for cardiac specific knock-out of NCX1 has revealed that cardiac function is remarkably preserved in these mice, which survived to adulthood. This controversy highlights the necessity for further investigation of NCX1 function in the heart. In this study, we report on a novel approach for depletion of NCX1 in postnatal rat myocytes that utilizes RNA interference (RNAi), administered with high efficiency via adenoviral transfection. Depletion of NCX1 was confirmed by immunocytochemical detection, Western blots and radioisotopic assays of Na(+)-Ca(2+) exchange activity. Exchanger expression was inhibited by up to approximately 94%. Surprisingly, spontaneous beating of these cardiomyocytes was still maintained, although at a lower frequency. Electrical stimulation could elicit a normal beating rhythm, although NCX depleted cells exhibited a depressed Ca(2+) transient amplitude, a depressed rate of Ca(2+) rise and decline, elevated diastolic [Ca(2+)], and shorter action potentials. We also observed a compensatory increase in sarcolemmal Ca(2+) pump expression. Our data support an important, though non-essential, role for the NCX1 in E-C coupling in these neonatal heart cells. Furthermore, this approach provides a valuable means for assessing the role of NCX1 and could be utilized to examine other cardiac proteins in physiological and pathological studies.

  7. 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.

  8. Nuclear safety

    International Nuclear Information System (INIS)

    1991-02-01

    This book reviews the accomplishments, operations, and problems faced by the defense Nuclear Facilities Safety Board. Specifically, it discusses the recommendations that the Safety Board made to improve safety and health conditions at the Department of Energy's defense nuclear facilities, problems the Safety Board has encountered in hiring technical staff, and management problems that could affect the Safety Board's independence and credibility

  9. 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.

  10. Learning with LOGO: Logo and Vectors.

    Science.gov (United States)

    Lough, Tom; Tipps, Steve

    1986-01-01

    This is the first of a two-part series on the general concept of vector space. Provides tool procedures to allow investigation of vector properties, vector addition and subtraction, and X and Y components. Lists several sources of additional vector ideas. (JM)

  11. Vectorization, parallelization and porting of nuclear codes on the VPP500 system (vectorization). Progress report fiscal 1996

    Energy Technology Data Exchange (ETDEWEB)

    Nemoto, Toshiyuki; Kawai, Wataru [Fujitsu Ltd., Tokyo (Japan); Kawasaki, Nobuo [and others

    1997-12-01

    Several computer codes in the nuclear field have been vectorized, parallelized and transported on the FUJITSU VPP500 system at Center for Promotion of Computational Science and Engineering in Japan Atomic Energy Research Institute. These results are reported in 3 parts, i.e., the vectorization part, the parallelization part and the porting part. In this report, we describe the vectorization. In this vectorization part, the vectorization of two and three dimensional discrete ordinates simulation code DORT-TORT, gas dynamics analysis code FLOWGR and relativistic Boltzmann-Uehling-Uhlenbeck simulation code RBUU are described. In the parallelization part, the parallelization of 2-Dimensional relativistic electromagnetic particle code EM2D, Cylindrical Direct Numerical Simulation code CYLDNS and molecular dynamics code for simulating radiation damages in diamond crystals DGR are described. And then, in the porting part, the porting of reactor safety analysis code RELAP5/MOD3.2 and RELAP5/MOD3.2.1.2, nuclear data processing system NJOY and 2-D multigroup discrete ordinate transport code TWOTRAN-II are described. And also, a survey for the porting of command-driven interactive data analysis plotting program IPLOT are described. (author)

  12. Elliptic-symmetry vector optical fields.

    Science.gov (United States)

    Pan, Yue; Li, Yongnan; Li, Si-Min; Ren, Zhi-Cheng; Kong, Ling-Jun; Tu, Chenghou; Wang, Hui-Tian

    2014-08-11

    We present in principle and demonstrate experimentally a new kind of vector fields: elliptic-symmetry vector optical fields. This is a significant development in vector fields, as this breaks the cylindrical symmetry and enriches the family of vector fields. Due to the presence of an additional degrees of freedom, which is the interval between the foci in the elliptic coordinate system, the elliptic-symmetry vector fields are more flexible than the cylindrical vector fields for controlling the spatial structure of polarization and for engineering the focusing fields. The elliptic-symmetry vector fields can find many specific applications from optical trapping to optical machining and so on.

  13. A generalized nonlocal vector calculus

    Science.gov (United States)

    Alali, Bacim; Liu, Kuo; Gunzburger, Max

    2015-10-01

    A nonlocal vector calculus was introduced in Du et al. (Math Model Meth Appl Sci 23:493-540, 2013) that has proved useful for the analysis of the peridynamics model of nonlocal mechanics and nonlocal diffusion models. A formulation is developed that provides a more general setting for the nonlocal vector calculus that is independent of particular nonlocal models. It is shown that general nonlocal calculus operators are integral operators with specific integral kernels. General nonlocal calculus properties are developed, including nonlocal integration by parts formula and Green's identities. The nonlocal vector calculus introduced in Du et al. (Math Model Meth Appl Sci 23:493-540, 2013) is shown to be recoverable from the general formulation as a special example. This special nonlocal vector calculus is used to reformulate the peridynamics equation of motion in terms of the nonlocal gradient operator and its adjoint. A new example of nonlocal vector calculus operators is introduced, which shows the potential use of the general formulation for general nonlocal models.

  14. Generalized Selection Weighted Vector Filters

    Directory of Open Access Journals (Sweden)

    Rastislav Lukac

    2004-09-01

    Full Text Available This paper introduces a class of nonlinear multichannel filters capable of removing impulsive noise in color images. The here-proposed generalized selection weighted vector filter class constitutes a powerful filtering framework for multichannel signal processing. Previously defined multichannel filters such as vector median filter, basic vector directional filter, directional-distance filter, weighted vector median filters, and weighted vector directional filters are treated from a global viewpoint using the proposed framework. Robust order-statistic concepts and increased degree of freedom in filter design make the proposed method attractive for a variety of applications. Introduced multichannel sigmoidal adaptation of the filter parameters and its modifications allow to accommodate the filter parameters to varying signal and noise statistics. Simulation studies reported in this paper indicate that the proposed filter class is computationally attractive, yields excellent performance, and is able to preserve fine details and color information while efficiently suppressing impulsive noise. This paper is an extended version of the paper by Lukac et al. presented at the 2003 IEEE-EURASIP Workshop on Nonlinear Signal and Image Processing (NSIP '03 in Grado, Italy.

  15. Drug Safety

    Science.gov (United States)

    ... over-the-counter drug. The FDA evaluates the safety of a drug by looking at Side effects ... clinical trials The FDA also monitors a drug's safety after approval. For you, drug safety means buying ...

  16. Nuclear safety

    International Nuclear Information System (INIS)

    Tarride, Bruno

    2015-10-01

    The author proposes an overview of methods and concepts used in the nuclear industry, at the design level as well as at the exploitation level, to ensure an acceptable safety level, notably in the case of nuclear reactors. He first addresses the general objectives of nuclear safety and the notion of acceptable risk: definition and organisation of nuclear safety (relationships between safety authorities and operators), notion of acceptable risk, deterministic safety approach and main safety principles (safety functions and confinement barriers, concept of defence in depth). Then, the author addresses the safety approach at the design level: studies of operational situations, studies of internal and external aggressions, safety report, design principles for important-for-safety systems (failure criterion, redundancy, failure prevention, safety classification). The next part addresses safety during exploitation and general exploitation rules: definition of the operation domain and of its limits, periodic controls and tests, management in case of incidents, accidents or aggressions

  17. Safety culture

    International Nuclear Information System (INIS)

    Keen, L.J.

    2003-01-01

    Safety culture has become a topic of increasing interest for industry and regulators as issues are raised on safety problems around the world. The keys to safety culture are organizational effectiveness, effective communications, organizational learning, and a culture that encourages the identification and resolution of safety issues. The necessity of a strong safety culture places an onus on all of us to continually question whether the safety measures already in place are sufficient, and are being applied. (author)

  18. Toward lattice fractional vector calculus

    Science.gov (United States)

    Tarasov, Vasily E.

    2014-09-01

    An analog of fractional vector calculus for physical lattice models is suggested. We use an approach based on the models of three-dimensional lattices with long-range inter-particle interactions. The lattice analogs of fractional partial derivatives are represented by kernels of lattice long-range interactions, where the Fourier series transformations of these kernels have a power-law form with respect to wave vector components. In the continuum limit, these lattice partial derivatives give derivatives of non-integer order with respect to coordinates. In the three-dimensional description of the non-local continuum, the fractional differential operators have the form of fractional partial derivatives of the Riesz type. As examples of the applications of the suggested lattice fractional vector calculus, we give lattice models with long-range interactions for the fractional Maxwell equations of non-local continuous media and for the fractional generalization of the Mindlin and Aifantis continuum models of gradient elasticity.

  19. Gauge Theories of Vector Particles

    Science.gov (United States)

    Glashow, S. L.; Gell-Mann, M.

    1961-04-24

    The possibility of generalizing the Yang-Mills trick is examined. Thus we seek theories of vector bosons invariant under continuous groups of coordinate-dependent linear transformations. All such theories may be expressed as superpositions of certain "simple" theories; we show that each "simple theory is associated with a simple Lie algebra. We may introduce mass terms for the vector bosons at the price of destroying the gauge-invariance for coordinate-dependent gauge functions. The theories corresponding to three particular simple Lie algebras - those which admit precisely two commuting quantum numbers - are examined in some detail as examples. One of them might play a role in the physics of the strong interactions if there is an underlying super-symmetry, transcending charge independence, that is badly broken. The intermediate vector boson theory of weak interactions is discussed also. The so-called "schizon" model cannot be made to conform to the requirements of partial gauge-invariance.

  20. Search for intermediate vector bosons

    International Nuclear Information System (INIS)

    Cline, D.B.; Rubbia, C.; van der Meer, S.

    1982-01-01

    Over the past 15 years a new class of unified theories has been developed to describe the forces acting between elementary particles. The most successful of the new theories establishes a link between electromagnetism and the weak force. A crucial prediction of this unified electroweak theory is the existence of three massive particles called intermediate vector bosons. If these intermediate vector bosons exist and if they have properties attributed to them by electroweak theory, they should soon be detected, as the world's first particle accelerator with enough energy to create such particles has recently been completed at the European Organization for Nuclear Research (CERN) in Geneva. The accelerator has been converted to a colliding beam machine in which protons and antiprotons collide head on. According to electroweak theory, intermediate vector bosons can be created in proton-antiproton collisions. (SC)

  1. Search for intermediate vector bosons

    International Nuclear Information System (INIS)

    Klajn, D.B.; Rubbia, K.; Meer, S.

    1983-01-01

    Problem of registration and search for intermediate vector bosons is discussed. According to weak-current theory there are three intermediate vector bosons with +1(W + )-1(W - ) and zero (Z 0 ) electric charges. It was suggested to conduct the investigation into particles in 1976 by cline, Rubbia and Makintair using proton-antiproton beams. Major difficulties of the experiment are related to the necessity of formation of sufficient amount of antiparticles and the method of antiproton beam ''cooling'' for the purpose of reduction of its random movements. The stochastic method was suggested by van der Meer in 1968 as one of possible cooling methods. Several large detectors were designed for searching intermediate vector bosons

  2. Synthetic Aperture Vector Flow Imaging

    DEFF Research Database (Denmark)

    Villagómez Hoyos, Carlos Armando

    The main objective of this project was to continue the development of a synthetic aperture vector flow estimator. This type of estimator is capable of overcoming two of the major limitations in conventional ultrasound systems: 1) the inability to scan large region of interest with high temporal......, this thesis showed that novel information can be obtained with vector velocity methods providing quantitative estimates of blood flow and insight into the complexity of the hemodynamics dynamics. This could give the clinician a new tool in assessment and treatment of a broad range of diseases....

  3. Vector mesons and chiral symmetry

    International Nuclear Information System (INIS)

    Ecker, G.

    1989-01-01

    The ambiguities in the off-shell behaviour of spin-1 exchange can be resolved to O(p 4 ) in the chiral low-energy expansion if the asymptotic behaviour of QCD is properly incorporated. As a consequence, the chiral version of vector (and axial-vector) meson dominance is model independent. Additional high-energy constraints motivated by QCD determine the V,A resonance couplings uniquely. In particular, QCD in its effective chiral realization sucessfully predicts Γ(ρ→2π). 10 refs. (Author)

  4. 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

  5. Learning with Support Vector Machines

    CERN Document Server

    Campbell, Colin

    2010-01-01

    Support Vectors Machines have become a well established tool within machine learning. They work well in practice and have now been used across a wide range of applications from recognizing hand-written digits, to face identification, text categorisation, bioinformatics, and database marketing. In this book we give an introductory overview of this subject. We start with a simple Support Vector Machine for performing binary classification before considering multi-class classification and learning in the presence of noise. We show that this framework can be extended to many other scenarios such a

  6. 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.

  7. 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.

  8. Progress in developing cationic vectors for non-viral systemic gene therapy against cancer.

    Science.gov (United States)

    Morille, Marie; Passirani, Catherine; Vonarbourg, Arnaud; Clavreul, Anne; Benoit, Jean-Pierre

    2008-01-01

    Initially, gene therapy was viewed as an approach for treating hereditary diseases, but its potential role in the treatment of acquired diseases such as cancer is now widely recognized. The understanding of the molecular mechanisms involved in cancer and the development of nucleic acid delivery systems are two concepts that have led to this development. Systemic gene delivery systems are needed for therapeutic application to cells inaccessible by percutaneous injection and for multi-located tumor sites, i.e. metastases. Non-viral vectors based on the use of cationic lipids or polymers appear to have promising potential, given the problems of safety encountered with viral vectors. Using these non-viral vectors, the current challenge is to obtain a similarly effective transfection to viral ones. Based on the advantages and disadvantages of existing vectors and on the hurdles encountered with these carriers, the aim of this review is to describe the "perfect vector" for systemic gene therapy against cancer.

  9. Graphene materials as 2D non-viral gene transfer vector platforms.

    Science.gov (United States)

    Vincent, M; de Lázaro, I; Kostarelos, K

    2017-03-01

    Advances in genomics and gene therapy could offer solutions to many diseases that remain incurable today, however, one of the critical reasons halting clinical progress is due to the difficulty in designing efficient and safe delivery vectors for the appropriate genetic cargo. Safety and large-scale production concerns counter-balance the high gene transfer efficiency achieved with viral vectors, while non-viral strategies have yet to become sufficiently efficient. The extraordinary physicochemical, optical and photothermal properties of graphene-based materials (GBMs) could offer two-dimensional components for the design of nucleic acid carrier systems. We discuss here such properties and their implications for the optimization of gene delivery. While the design of such vectors is still in its infancy, we provide here an exhaustive and up-to-date analysis of the studies that have explored GBMs as gene transfer vectors, focusing on the functionalization strategies followed to improve vector performance and on the biological effects attained.

  10. Widespread and highly persistent gene transfer to the CNS by retrovirus vector in utero: implication for gene therapy to Krabbe disease.

    Science.gov (United States)

    Shen, Jin-Song; Meng, Xing-Li; Yokoo, Takashi; Sakurai, Ken; Watabe, Kazuhiko; Ohashi, Toya; Eto, Yoshikatsu

    2005-05-01

    Brain-directed prenatal gene therapy may benefit some lysosomal storage diseases that affect the central nervous system (CNS) before birth. Our previous study showed that intrauterine introduction of recombinant adenoviruses into cerebral ventricles results in efficient gene transfer to the CNS in the mouse. However, transgene expression decreased with time due to the non-integrative property of adenoviral vectors. In this study, in order to obtain permanent gene transduction, we investigated the feasibility of retrovirus-mediated in utero gene transduction. Concentrated retrovirus encoding the LacZ gene was injected into the cerebral ventricles of the embryos of normal and twitcher mice (a murine model of Krabbe disease) at embryonic day 12. The distribution and maintenance of the transgene expression in the recipient brain were analyzed histochemically, biochemically and by the quantitative polymerase chain reaction method pre- and postnatally. Efficient and highly persistent gene transduction to the brain was achieved both in normal and the twitcher mouse. Transduced neurons, astrocytes and oligodendrocytes were distributed throughout the brain. The transduced LacZ gene, its transcript and protein expression in the brain were maintained for 14 months without decrement. In addition, gene transduction to multiple tissues other than the brain was also detected at low levels. This study suggests that brain-directed in utero gene transfer using retrovirus vector may be beneficial to the treatment of lysosomal storage diseases with severe brain damage early in life, such as Krabbe disease. Copyright (c) 2005 John Wiley & Sons, Ltd.

  11. Enhanced and sustained CD8+ T cell responses with an adenoviral vector-based hepatitis C virus vaccine encoding NS3 linked to the MHC class II chaperone protein invariant chain

    DEFF Research Database (Denmark)

    Mikkelsen, Marianne; Holst, Peter Johannes; Bukh, Jens

    2011-01-01

    memory. Functionally, the AdIiNS3-vaccinated mice had a significantly increased cytotoxic capacity compared with the AdNS3 group. The AdIiNS3-induced CD8(+) T cells protected mice from infection with recombinant vaccinia virus expressing HCV NS3 of heterologous 1b strains, and studies in knockout mice...

  12. Scalar Calibration of Vector Magnetometers

    DEFF Research Database (Denmark)

    Merayo, José M.G.; Brauer, Peter; Primdahl, Fritz

    2000-01-01

    The calibration parameters of a vector magnetometer are estimated only by the use of a scalar reference magnetometer. The method presented in this paper differs from those previously reported in its linearized parametrization. This allows the determination of three offsets or signals in the absence...

  13. Parallel Sparse Matrix - Vector Product

    DEFF Research Database (Denmark)

    Alexandersen, Joe; Lazarov, Boyan Stefanov; Dammann, Bernd

    This technical report contains a case study of a sparse matrix-vector product routine, implemented for parallel execution on a compute cluster with both pure MPI and hybrid MPI-OpenMP solutions. C++ classes for sparse data types were developed and the report shows how these class can be used...

  14. Reference vectors in economic choice

    Directory of Open Access Journals (Sweden)

    Teycir Abdelghani GOUCHA

    2013-07-01

    Full Text Available In this paper the introduction of notion of reference vector paves the way for a combination of classical and social approaches in the framework of referential preferences given by matrix groups. It is shown that individual demand issue from rational decision does not depend on that reference.

  15. The consequences of poor vectorization

    CERN Multimedia

    CERN. Geneva

    2016-01-01

    This talk briefly discusses the vectorization problem and how it impacts scientific and engineering systems. A simple cost model of designing such system in context of different phases of software lifetime is considered. Finally a concept for scalable solution is presented.

  16. The Large Vector Multiplet Action

    OpenAIRE

    Ryb, Itai

    2007-01-01

    We discuss possible actions for the d=2, N=(2,2) large vector multiplet that gauges isometries of generalized Kahler geometries. We explore two scenarios that allow us to write kinetic and superpotential terms for the scalar field-strengths, and write kinetic terms for the spinor invariants that can introduce topological terms for the connections.

  17. Portfolio Analysis for Vector Calculus

    Science.gov (United States)

    Kaplan, Samuel R.

    2015-01-01

    Classic stock portfolio analysis provides an applied context for Lagrange multipliers that undergraduate students appreciate. Although modern methods of portfolio analysis are beyond the scope of vector calculus, classic methods reinforce the utility of this material. This paper discusses how to introduce classic stock portfolio analysis in a…

  18. Vector ecology of equine piroplasmosis

    Science.gov (United States)

    Equine piroplasmosis (EP) is a disease of equidae including horses, donkeys, mules and zebras caused by either of two protozoan parasites, Theileria equi or Babesia caballi. These parasites are biologically transmitted between hosts via tick-vectors and although they have inherent differences, they ...

  19. Vector-meson dominance revisited

    Directory of Open Access Journals (Sweden)

    Terschlüsen Carla

    2012-12-01

    Full Text Available The interaction of mesons with electromagnetism is often well described by the concept of vector-meson dominance (VMD. However, there are also examples where VMD fails. A simple chiral Lagrangian for pions, rho and omega mesons is presented which can account for the respective agreement and disagreement between VMD and phenomenology in the sector of light mesons.

  20. Vector fields on nonorientable surfaces

    Directory of Open Access Journals (Sweden)

    Ilie Barza

    2003-01-01

    X, and the space of vector fields on X are proved by using a symmetrisation process. An example related to the normal derivative on the border of the Möbius strip supports the nontriviality of the concepts introduced in this paper.

  1. 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.)

  2. Listeria monocytogenes as a vector for anti-cancer therapies.

    LENUS (Irish Health Repository)

    Tangney, Mark

    2012-01-31

    The intracellular pathogen Listeria monocytogenes represents a promising therapeutic vector for the delivery of DNA, RNA or protein to cancer cells or to prime immune responses against tumour-specific antigens. A number of biological properties make L. monocytogenes a promising platform for development as a vector for either gene therapy or as an anti-cancer vaccine vector. L. monocytogenes is particularly efficient in mediating internalization into host cells. Once inside cells, the bacterium produces specific virulence factors which lyse the vaculolar membrane and allow escape into the cytoplasm. Once in the cytosol, L. monocytogenes is capable of actin-based motility and cell-to-cell spread without an extracellular phase. The cytoplasmic location of L. monocytogenes is significant as this potentiates entry of antigens into the MHC Class I antigen processing pathway leading to priming of specific CD8(+) T cell responses. The cytoplasmic location is also beneficial for the delivery of DNA (bactofection) by L. monocytogenes whilst cell-to-cell spread may facilitate access of the vector to cells throughout the tumour. Several preclinical studies have demonstrated the ability of L. monocytogenes for intracellular gene or protein delivery in vitro and in vivo, and this vector has also displayed safety and efficacy in clinical trial. Here, we review the features of the L. monocytogenes host-pathogen interaction that make this bacterium such an attractive candidate with which to induce appropriate therapeutic responses. We focus primarily upon work that has led to attenuation of the pathogen, demonstrated DNA, RNA or protein delivery to tumour cells as well as research that shows the efficacy of L. monocytogenes as a vector for tumour-specific vaccine delivery.

  3. Reactor safety

    International Nuclear Information System (INIS)

    Butz, H.P.; Heuser, F.W.; May, H.

    1985-01-01

    The paper comprises an introduction into nuclear physics bases, the safety concept generally speaking, safety devices of pwr type reactors, accident analysis, external influences, probabilistic safety assessment and risk studies. It further describes operational experience, licensing procedures under the Atomic Energy Law, research in reactor safety and the nuclear fuel cycle. (DG) [de

  4. Vectors and Rotations in 3-Dimensions: Vector Algebra for the C++ Programmer

    Science.gov (United States)

    2016-12-01

    release; distribution is unlimited. 1. Introduction This report describes 2 C++ classes: a Vector class for performing vector algebra in 3-dimensional...ARL-TR-7894•DEC 2016 US Army Research Laboratory Vectors and Rotations in 3-Dimensions:Vector Algebra for the C++ Programmer by Richard Saucier...Army Research Laboratory Vectors and Rotations in 3-Dimensions:Vector Algebra for the C++ Programmer by Richard Saucier Survivability/Lethality

  5. Nonseparable closed vector subspaces of separable topological vector spaces

    Czech Academy of Sciences Publication Activity Database

    Kąkol, Jerzy; Leiderman, A. G.; Morris, S. A.

    2017-01-01

    Roč. 182, č. 1 (2017), s. 39-47 ISSN 0026-9255 R&D Projects: GA ČR GF16-34860L Institutional support: RVO:67985840 Keywords : locally convex topological vector space * separable topological space Subject RIV: BA - General Mathematics OBOR OECD: Pure mathematics Impact factor: 0.716, year: 2016 https://link.springer.com/article/10.1007%2Fs00605-016-0876-2

  6. 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.

  7. Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant

    Directory of Open Access Journals (Sweden)

    Muhammad Qamar Saeed

    2014-01-01

    Full Text Available HIV-1 derived vectors are among the most efficient for gene transduction in mammalian tissues. As the parent virus, they carry out vector genome insertion into the host cell chromatin. Consequently, their preferential integration in transcribed genes raises several conceptual and safety issues. To address part of these questions, HIV-derived vectors have been engineered to be nonintegrating. This was mainly achieved by mutating HIV-1 integrase at functional hotspots of the enzyme enabling the development of streamlined nuclear DNA circles functional for transgene expression. Few integrase mutant vectors have been successfully tested so far for gene transfer. They are cleared with time in mitotic cells, but stable within nondividing retina cells or neurons. Here, we compared six HIV vectors carrying different integrases, either wild type or with different mutations (D64V, D167H, Q168A, K186Q+Q214L+Q216L, and RRK262-264AAH shown to modify integrase enzymatic activity, oligomerization, or interaction with key cellular cofactor of HIV DNA integration as LEDGF/p75 or TNPO3. We show that these mutations differently affect the transduction efficiency as well as rates and patterns of integration of HIV-derived vectors suggesting their different processing in the nucleus. Surprisingly and most interestingly, we report that an integrase carrying the D167H substitution improves vector transduction efficiency and integration in both HEK-293T and primary CD34+ cells.

  8. Transversals of Complex Polynomial Vector Fields

    DEFF Research Database (Denmark)

    Dias, Kealey

    Vector fields in the complex plane are defined by assigning the vector determined by the value P(z) to each point z in the complex plane, where P is a polynomial of one complex variable. We consider special families of so-called rotated vector fields that are determined by a polynomial multiplied...... by rotational constants. Transversals are a certain class of curves for such a family of vector fields that represent the bifurcation states for this family of vector fields. More specifically, transversals are curves that coincide with a homoclinic separatrix for some rotation of the vector field. Given...... a concrete polynomial, it seems to take quite a bit of work to prove that it is generic, i.e. structurally stable. This has been done for a special class of degree d polynomial vector fields having simple equilibrium points at the d roots of unity, d odd. In proving that such vector fields are generic...

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

    International Nuclear Information System (INIS)

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

    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 porting. In this porting part, the porting of Monte Carlo N-Particle Transport code MCNP4B2 and Reactor Safety Analysis code RELAP5 on the AP3000 are described. In the 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 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. (author)

  10. 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

  11. 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.

  12. Problems of vector Lagrangians in field theories

    International Nuclear Information System (INIS)

    Krivsky, I.Yu.; Simulik, V.M.

    1997-01-01

    A vector Lagrange approach to the Dirac spinor field and the relationship between the vector Lagrangians for the spinor and electromagnetic fields are considered. A vector Lagrange approach for the system of interacting electromagnetic B=(B μ υ)=(E-bar,H-bar) and spinor Ψ fields is constructed. New Lagrangians (scalar and vector) for electromagnetic field in terms of field strengths are found. The foundations of two new QED models are formulated

  13. 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.

  14. Disease Vector Ecology Profile: Ecuador

    Science.gov (United States)

    1998-12-01

    years occurred in Peru in the northern departments bordering Ecuador in 1992-1994. Sylvatic plague is endemic in the southern provinces of Loja and... Ecuador ) Micrurus bocourti (Pacific lowlands of western Ecuador ) Micrurus catamayensis (Catamayo Valley, Loja Province) Micrurus dumerilii spp...Disease Vector Ecology Profile Ecuador -~· ""’ -.. ~ """ Defense Pest Management Information Analysis Center’ Armed Forces Pest Management

  15. Plebotomine Vectors of Human Disease.

    Science.gov (United States)

    1984-12-30

    incriminated as vectors of Leishmania mexicana among rodents and/or humans from Mexico to the Amazon Basin. Specimens referable to L. olmeca olmeca...in the format similar to that given for the species group baityi included in this report. Additional phlebotomines from Tanzania, Brazil, Peru and...species group baityi included in this report. Additional phlebotomines from Tanzania, Brazil, Peru and Venezuela were slide-mounted and added to the

  16. Characterizing Convexity of Games using Marginal Vectors

    NARCIS (Netherlands)

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

    2003-01-01

    In this paper we study the relation between convexity of TU games and marginal vectors.We show that if specfic marginal vectors are core elements, then the game is convex.We characterize sets of marginal vectors satisfying this property, and we derive the formula for the minimum number of marginal

  17. Herbivore arthropods benefit from vectoring plant viruses

    NARCIS (Netherlands)

    Belliure, B.; Janssen, A.; Maris, P.C.; Peters, D.; Sabelis, M.W.

    2005-01-01

    Plants infected with pathogens often attract the pathogens' vectors, but it is not clear if this is advantageous to the vectors. We therefore quantified the direct and indirect (through the host plant) effects of a pathogen on its vector. A positive direct effect of the plant-pathogenic Tomato

  18. Vector fields and gravity on the lattice

    International Nuclear Information System (INIS)

    Khatsymovsky, V.M.

    1988-01-01

    The problem of discretization of vector field on Regge lattice is considered. Our approach is based on geometrical interpretation of the vector field as the field of infinitesimal coordinate transformation. A discrete version of the vector field action is obtained as a particular case of the continuum action, and it is shown to have the true continuum limit

  19. 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....

  20. Visualizing vector field topology in fluid flows

    Science.gov (United States)

    Helman, James L.; Hesselink, Lambertus

    1991-01-01

    Methods of automating the analysis and display of vector field topology in general and flow topology in particular are discussed. Two-dimensional vector field topology is reviewed as the basis for the examination of topology in three-dimensional separated flows. The use of tangent surfaces and clipping in visualizing vector field topology in fluid flows is addressed.

  1. 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

  2. Construction of expression vectors carrying mouse peroxisomal ...

    African Journals Online (AJOL)

    The aim of this study was to construct expression vectors carrying mouse peroxisomal protein gene (PEP-cDNA) in prokaryotic and mammalian expression vectors in ... pGEX6p2-PEP and pUcD3-FLAG-PEP constructed vectors were transformed into the one shot TOP10 and JM105 bacterial competent cells, respectively.

  3. Extremal vectors and rectifiability | Enflo | Quaestiones Mathematicae

    African Journals Online (AJOL)

    Extremal vectors and rectifiability. ... The concept of extremal vectors of a linear operator with a dense range but not onto on a Hilbert space was introduced by P. Enflo in 1996 as a new approach to study invariant subspaces ... We show that in general curves that map numbers to backward minimal vectors are not rectifiable.

  4. Toward lattice fractional vector calculus

    International Nuclear Information System (INIS)

    Tarasov, Vasily E

    2014-01-01

    An analog of fractional vector calculus for physical lattice models is suggested. We use an approach based on the models of three-dimensional lattices with long-range inter-particle interactions. The lattice analogs of fractional partial derivatives are represented by kernels of lattice long-range interactions, where the Fourier series transformations of these kernels have a power-law form with respect to wave vector components. In the continuum limit, these lattice partial derivatives give derivatives of non-integer order with respect to coordinates. In the three-dimensional description of the non-local continuum, the fractional differential operators have the form of fractional partial derivatives of the Riesz type. As examples of the applications of the suggested lattice fractional vector calculus, we give lattice models with long-range interactions for the fractional Maxwell equations of non-local continuous media and for the fractional generalization of the Mindlin and Aifantis continuum models of gradient elasticity. (papers)

  5. 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

  6. 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

  7. Vaccine Safety

    Science.gov (United States)

    ... During Pregnancy Frequently Asked Questions about Vaccine Recalls Historical Vaccine Safety Concerns FAQs about GBS and Menactra ... CISA Resources for Healthcare Professionals Evaluation Current Studies Historical Background 2001-12 Publications Technical Reports Vaccine Safety ...

  8. SAFETY FIRST

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Ensuring safety while peacefully utilizing nuclear energy is a top priority for China A fter a recent earthquake in Japan caused radioactive leaks at a nuclear power plant in Tokyo, the safety of nuclear energy has again aroused public attention.

  9. ITER safety

    International Nuclear Information System (INIS)

    Raeder, J.; Piet, S.; Buende, R.

    1991-01-01

    As part of the series of publications by the IAEA that summarize the results of the Conceptual Design Activities for the ITER project, this document describes the ITER safety analyses. It contains an assessment of normal operation effluents, accident scenarios, plasma chamber safety, tritium system safety, magnet system safety, external loss of coolant and coolant flow problems, and a waste management assessment, while it describes the implementation of the safety approach for ITER. The document ends with a list of major conclusions, a set of topical remarks on technical safety issues, and recommendations for the Engineering Design Activities, safety considerations for siting ITER, and recommendations with regard to the safety issues for the R and D for ITER. Refs, figs and tabs

  10. Water Safety

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Water Safety KidsHealth / For Parents / Water Safety What's in ... remains your best measure of protection. Making Kids Water Wise It's important to teach your kids proper ...

  11. Problems and worked solutions in vector analysis

    CERN Document Server

    Shorter, LR

    2014-01-01

    ""A handy book like this,"" noted The Mathematical Gazette, ""will fill a great want."" Devoted to fully worked out examples, this unique text constitutes a self-contained introductory course in vector analysis for undergraduate and graduate students of applied mathematics.Opening chapters define vector addition and subtraction, show how to resolve and determine the direction of two or more vectors, and explain systems of coordinates, vector equations of a plane and straight line, relative velocity and acceleration, and infinitely small vectors. The following chapters deal with scalar and vect

  12. Food safety

    Science.gov (United States)

    ... safety URL of this page: //medlineplus.gov/ency/article/002434.htm Food safety To use the sharing features on this page, please enable JavaScript. Food safety refers to the conditions and practices that preserve the quality of food. These practices prevent contamination and foodborne ...

  13. Tomorrow's vector vaccines for small ruminants.

    Science.gov (United States)

    Kyriakis, C S

    2015-12-14

    Inactivated and attenuated vaccines have contributed to the control or even the eradication of significant animal pathogens. However, these traditional vaccine technologies have limitations and disadvantages. Inactivated vaccines lack efficacy against certain pathogens, while attenuated vaccines are not always as safe. New technology vaccines, namely DNA and recombinant viral vector vaccines, are being developed and tested against pathogens of small ruminants. These vaccines induce both humoral and cellular immune responses, are safe to manufacture and use and can be utilized in strategies for differentiation of infected from vaccinated animals. Although there are more strict regulatory requirements for the safety standards of these vaccines, once a vaccine platform is evaluated and established, effective vaccines can be rapidly produced and deployed in the field to prevent spread of emerging pathogens. The present article offers an introduction to these next generation technologies and examples of vaccines that have been tested against important diseases of sheep and goats. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. 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.

  15. Safety handbook

    International Nuclear Information System (INIS)

    1990-01-01

    The purpose of the Australian Nuclear Science and Technology Organization's Safety Handbook is to outline simply the fundamental procedures and safety precautions which provide an appropriate framework for safe working with any potential hazards, such as fire and explosion, welding, cutting, brazing and soldering, compressed gases, cryogenic liquids, chemicals, ionizing radiations, non-ionising radiations, sound and vibration, as well as safety in the office. It also specifies the organisation for safety at the Lucas Heights Research Laboratories and the responsibilities of individuals and committees. It also defines the procedures for the scrutiny and review of all operations and the resultant setting of safety rules for them. ills

  16. Determination of key parameters of vector multifractal vector fields

    Science.gov (United States)

    Schertzer, D. J. M.; Tchiguirinskaia, I.

    2017-12-01

    For too long time, multifractal analyses and simulations have been restricted to scalar-valued fields (Schertzer and Tchiguirinskaia, 2017a,b). For instance, the wind velocity multifractality has been mostly analysed in terms of scalar structure functions and with the scalar energy flux. This restriction has had the unfortunate consequences that multifractals were applicable to their full extent in geophysics, whereas it has inspired them. Indeed a key question in geophysics is the complexity of the interactions between various fields or they components. Nevertheless, sophisticated methods have been developed to determine the key parameters of scalar valued fields. In this communication, we first present the vector extensions of the universal multifractal analysis techniques to multifractals whose generator belong to a Levy-Clifford algebra (Schertzer and Tchiguirinskaia, 2015). We point out further extensions noting the increased complexity. For instance, the (scalar) index of multifractality becomes a matrice. Schertzer, D. and Tchiguirinskaia, I. (2015) `Multifractal vector fields and stochastic Clifford algebra', Chaos: An Interdisciplinary Journal of Nonlinear Science, 25(12), p. 123127. doi: 10.1063/1.4937364. Schertzer, D. and Tchiguirinskaia, I. (2017) `An Introduction to Multifractals and Scale Symmetry Groups', in Ghanbarian, B. and Hunt, A. (eds) Fractals: Concepts and Applications in Geosciences. CRC Press, p. (in press). Schertzer, D. and Tchiguirinskaia, I. (2017b) `Pandora Box of Multifractals: Barely Open ?', in Tsonis, A. A. (ed.) 30 Years of Nonlinear Dynamics in Geophysics. Berlin: Springer, p. (in press).

  17. Safety design

    International Nuclear Information System (INIS)

    Kunitomi, Kazuhiko; Shiozawa, Shusaku

    2004-01-01

    JAERI established the safety design philosophy of the HTTR based on that of current reactors such as LWR in Japan, considering inherent safety features of the HTTR. The strategy of defense in depth was implemented so that the safety engineering functions such as control of reactivity, removal of residual heat and confinement of fission products shall be well performed to ensure safety. However, unlike the LWR, the inherent design features of the high-temperature gas-cooled reactor (HTGR) enables the HTTR meet stringent regulatory criteria without much dependence on active safety systems. On the other hand, the safety in an accident typical to the HTGR such as the depressurization accident initiated by a primary pipe rupture shall be ensured. The safety design philosophy of the HTTR considers these unique features appropriately and is expected to be the basis for future Japanese HTGRs. This paper describes the safety design philosophy and safety evaluation procedure of the HTTR especially focusing on unique considerations to the HTTR. Also, experiences obtained from an HTTR safety review and R and D needs for establishing the safety philosophy for the future HTGRs are reported

  18. Nuclear Safety

    International Nuclear Information System (INIS)

    1978-09-01

    In this short paper it has only been possible to deal in a rather general way with the standards of safety used in the UK nuclear industry. The record of the industry extending over at least twenty years is impressive and, indeed, unique. No other industry has been so painstaking in protection of its workers and in its avoidance of damage to the environment. Headings are: introduction; how a nuclear power station works; radiation and its effects (including reference to ICRP, the UK National Radiological Protection Board, and safety standards); typical radiation doses (natural radiation, therapy, nuclear power programme and other sources); safety of nuclear reactors - design; key questions (matters of concern which arise in the public mind); safety of operators; safety of people in the vicinity of a nuclear power station; safety of the general public; safety bodies. (U.K.)

  19. 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.

  20. Emerging Vector-Borne Diseases.

    Science.gov (United States)

    Huntington, Mark K; Allison, Jay; Nair, Dilip

    2016-10-01

    Several mosquito-borne viral infections have recently emerged in North America; West Nile virus is the most common in the United States. Although West Nile virus generally causes a self-limited, flulike febrile illness, a serious neuroinvasive form may occur. Dengue is the most common vector-borne viral disease worldwide, and it has been a significant public health threat in the United States since 2009. Known as breakbone fever for its severe myalgias and arthralgias, dengue may cause a hemorrhagic syndrome. Chikungunya also causes flulike febrile illness and disabling arthralgias. Although meningoencephalitis may occur with chikungunya, bleeding is uncommon. Symptoms of Zika virus infection are similar to those of dengue, but milder. Zika virus increases the risk of fetal brain abnormalities, including microcephaly, if a pregnant woman is infected. Zika virus is spread through Aedes albopictus mosquito bites, is transmitted sexually, and may rarely spread nonsexually from person to person. Diagnosis of these vectorborne infections is clinical and serologic, and treatment is supportive. Other, well-established vector-borne diseases are also important. Ehrlichiosis is a tick-borne bacterial disease that presents as a nonspecific syndrome of fever, headache, malaise, and myalgias. It is diagnosed via blood smear testing, with confirmatory serology. Ehrlichiosis is treated with doxycycline. Rickettsial infections are transmitted by fleas, mites, and ticks, and severity ranges from mild to life threatening. Rocky Mountain spotted fever, the most significant rickettsial infection, is primarily a clinical diagnosis that presents as fever, headache, myalgias, petechial rash, and tick exposure. Doxycycline is effective for rickettsial infections if administered promptly. Vector avoidance strategies are critical to the prevention of all of these infections.

  1. Bridging the Vector Calculus Gap

    Science.gov (United States)

    Dray, Tevian; Manogue, Corinne

    2003-05-01

    As with Britain and America, mathematicians and physicists are separated from each other by a common language. In a nutshell, mathematics is about functions, but physics is about things. For the last several years, we have led an NSF-supported effort to "bridge the vector calculus gap" between mathematics and physics. The unifying theme we have discovered is to emphasize geometric reasoning, not (just) algebraic computation. In this talk, we will illustrate the language differences between mathematicians and physicists, and how we are trying reconcile them in the classroom. For further information about the project go to: http://www.physics.orst.edu/bridge

  2. Properties of Vector Preisach Models

    Science.gov (United States)

    Kahler, Gary R.; Patel, Umesh D.; Torre, Edward Della

    2004-01-01

    This paper discusses rotational anisotropy and rotational accommodation of magnetic particle tape. These effects have a performance impact during the reading and writing of the recording process. We introduce the reduced vector model as the basis for the computations. Rotational magnetization models must accurately compute the anisotropic characteristics of ellipsoidally magnetizable media. An ellipticity factor is derived for these media that computes the two-dimensional magnetization trajectory for all applied fields. An orientation correction must be applied to the computed rotational magnetization. For isotropic materials, an orientation correction has been developed and presented. For anisotropic materials, an orientation correction is introduced.

  3. Ad35 and ad26 vaccine vectors induce potent and cross-reactive antibody and T-cell responses to multiple filovirus species.

    Directory of Open Access Journals (Sweden)

    Roland Zahn

    Full Text Available Filoviruses cause sporadic but highly lethal outbreaks of hemorrhagic fever in Africa in the human population. Currently, no drug or vaccine is available for treatment or prevention. A previous study with a vaccine candidate based on the low seroprevalent adenoviruses 26 and 35 (Ad26 and Ad35 was shown to provide protection against homologous Ebola Zaire challenge in non human primates (NHP if applied in a prime-boost regimen. Here we have aimed to expand this principle to construct and evaluate Ad26 and Ad35 vectors for development of a vaccine to provide universal filovirus protection against all highly lethal strains that have caused major outbreaks in the past. We have therefore performed a phylogenetic analysis of filovirus glycoproteins to select the glycoproteins from two Ebola species (Ebola Zaire and Ebola Sudan/Gulu,, two Marburg strains (Marburg Angola and Marburg Ravn and added the more distant non-lethal Ebola Ivory Coast species for broadest coverage. Ad26 and Ad35 vectors expressing these five filovirus glycoproteins were evaluated to induce a potent cellular and humoral immune response in mice. All adenoviral vectors induced a humoral immune response after single vaccination in a dose dependent manner that was cross-reactive within the Ebola and Marburg lineages. In addition, both strain-specific as well as cross-reactive T cell responses could be detected. A heterologous Ad26-Ad35 prime-boost regime enhanced mainly the humoral and to a lower extend the cellular immune response against the transgene. Combination of the five selected filovirus glycoproteins in one multivalent vaccine potentially elicits protective immunity in man against all major filovirus strains that have caused lethal outbreaks in the last 20 years.

  4. 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.

  5. A sight on the current nanoparticle-based gene delivery vectors

    Science.gov (United States)

    Dizaj, Solmaz Maleki; Jafari, Samira; Khosroushahi, Ahmad Yari

    2014-05-01

    Nowadays, gene delivery for therapeutic objects is considered one of the most promising strategies to cure both the genetic and acquired diseases of human. The design of efficient gene delivery vectors possessing the high transfection efficiencies and low cytotoxicity is considered the major challenge for delivering a target gene to specific tissues or cells. On this base, the investigations on non-viral gene vectors with the ability to overcome physiological barriers are increasing. Among the non-viral vectors, nanoparticles showed remarkable properties regarding gene delivery such as the ability to target the specific tissue or cells, protect target gene against nuclease degradation, improve DNA stability, and increase the transformation efficiency or safety. This review attempts to represent a current nanoparticle based on its lipid, polymer, hybrid, and inorganic properties. Among them, hybrids, as efficient vectors, are utilized in gene delivery in terms of materials (synthetic or natural), design, and in vitro/ in vivo transformation efficiency.

  6. Estimation of pure autoregressive vector models for revenue series ...

    African Journals Online (AJOL)

    This paper aims at applying multivariate approach to Box and Jenkins univariate time series modeling to three vector series. General Autoregressive Vector Models with time varying coefficients are estimated. The first vector is a response vector, while others are predictor vectors. By matrix expansion each vector, whether ...

  7. Vector-Tensor and Vector-Vector Decay Amplitude Analysis of B0→φK*0

    International Nuclear Information System (INIS)

    Aubert, B.; Bona, M.; Boutigny, D.; Couderc, F.; Karyotakis, Y.; Lees, J. P.; Poireau, V.; Tisserand, V.; Zghiche, A.; Grauges, E.; Palano, A.; Chen, J. C.; Qi, N. D.; Rong, G.; Wang, P.; Zhu, Y. S.; Eigen, G.; Ofte, I.; Stugu, B.; Abrams, G. S.

    2007-01-01

    We perform an amplitude analysis of the decays B 0 →φK 2 * (1430) 0 , φK * (892) 0 , and φ(Kπ) S-wave 0 with a sample of about 384x10 6 BB pairs recorded with the BABAR detector. The fractions of longitudinal polarization f L of the vector-tensor and vector-vector decay modes are measured to be 0.853 -0.069 +0.061 ±0.036 and 0.506±0.040±0.015, respectively. Overall, twelve parameters are measured for the vector-vector decay and seven parameters for the vector-tensor decay, including the branching fractions and parameters sensitive to CP violation

  8. 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.

  9. 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.

  10. 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.)

  11. Safety culture

    International Nuclear Information System (INIS)

    1991-01-01

    The response to a previous publication by the International Nuclear Safety Advisory Group (INSAG), indicated a broad international interest in expansion of the concept of Safety Culture, in such a way that its effectiveness in particular cases may be judged. This report responds to that need. In its manifestation, Safety Culture has two major components: the framework determined by organizational policy and by managerial action, and the response of individuals in working within and benefiting by the framework. 1 fig

  12. Safety; Avertissement

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-07-01

    This annual report of the Senior Inspector for the Nuclear Safety, analyses the nuclear safety at EDF for the year 1999 and proposes twelve subjects of consideration to progress. Five technical documents are also provided and discussed concerning the nuclear power plants maintenance and safety (thermal fatigue, vibration fatigue, assisted control and instrumentation of the N4 bearing, 1300 MW reactors containment and time of life of power plants). (A.L.B.)

  13. On the Vectorization of FIR Filterbanks

    Directory of Open Access Journals (Sweden)

    Barbedo Jayme Garcia Arnal

    2007-01-01

    Full Text Available This paper presents a vectorization technique to implement FIR filterbanks. The word vectorization, in the context of this work, refers to a strategy in which all iterative operations are replaced by equivalent vector and matrix operations. This approach allows that the increasing parallelism of the most recent computer processors and systems be properly explored. The vectorization techniques are applied to two kinds of FIR filterbanks (conventional and recursi ve, and are presented in such a way that they can be easily extended to any kind of FIR filterbanks. The vectorization approach is compared to other kinds of implementation that do not explore the parallelism, and also to a previous FIR filter vectorization approach. The tests were performed in Matlab and , in order to explore different aspects of the proposed technique.

  14. On the Vectorization of FIR Filterbanks

    Directory of Open Access Journals (Sweden)

    Amauri Lopes

    2007-01-01

    Full Text Available This paper presents a vectorization technique to implement FIR filterbanks. The word vectorization, in the context of this work, refers to a strategy in which all iterative operations are replaced by equivalent vector and matrix operations. This approach allows that the increasing parallelism of the most recent computer processors and systems be properly explored. The vectorization techniques are applied to two kinds of FIR filterbanks (conventional and recursi ve, and are presented in such a way that they can be easily extended to any kind of FIR filterbanks. The vectorization approach is compared to other kinds of implementation that do not explore the parallelism, and also to a previous FIR filter vectorization approach. The tests were performed in Matlab and C, in order to explore different aspects of the proposed technique.

  15. 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

  16. Vector assembly of colloids on monolayer substrates

    Science.gov (United States)

    Jiang, Lingxiang; Yang, Shenyu; Tsang, Boyce; Tu, Mei; Granick, Steve

    2017-06-01

    The key to spontaneous and directed assembly is to encode the desired assembly information to building blocks in a programmable and efficient way. In computer graphics, raster graphics encodes images on a single-pixel level, conferring fine details at the expense of large file sizes, whereas vector graphics encrypts shape information into vectors that allow small file sizes and operational transformations. Here, we adapt this raster/vector concept to a 2D colloidal system and realize `vector assembly' by manipulating particles on a colloidal monolayer substrate with optical tweezers. In contrast to raster assembly that assigns optical tweezers to each particle, vector assembly requires a minimal number of optical tweezers that allow operations like chain elongation and shortening. This vector approach enables simple uniform particles to form a vast collection of colloidal arenes and colloidenes, the spontaneous dissociation of which is achieved with precision and stage-by-stage complexity by simply removing the optical tweezers.

  17. Optimized support vector regression for drilling rate of penetration estimation

    Science.gov (United States)

    Bodaghi, Asadollah; Ansari, Hamid Reza; Gholami, Mahsa

    2015-12-01

    In the petroleum industry, drilling optimization involves the selection of operating conditions for achieving the desired depth with the minimum expenditure while requirements of personal safety, environment protection, adequate information of penetrated formations and productivity are fulfilled. Since drilling optimization is highly dependent on the rate of penetration (ROP), estimation of this parameter is of great importance during well planning. In this research, a novel approach called `optimized support vector regression' is employed for making a formulation between input variables and ROP. Algorithms used for optimizing the support vector regression are the genetic algorithm (GA) and the cuckoo search algorithm (CS). Optimization implementation improved the support vector regression performance by virtue of selecting proper values for its parameters. In order to evaluate the ability of optimization algorithms in enhancing SVR performance, their results were compared to the hybrid of pattern search and grid search (HPG) which is conventionally employed for optimizing SVR. The results demonstrated that the CS algorithm achieved further improvement on prediction accuracy of SVR compared to the GA and HPG as well. Moreover, the predictive model derived from back propagation neural network (BPNN), which is the traditional approach for estimating ROP, is selected for comparisons with CSSVR. The comparative results revealed the superiority of CSSVR. This study inferred that CSSVR is a viable option for precise estimation of ROP.

  18. Non-Replicating Adenovirus-Vectored Anthrax Vaccine

    International Nuclear Information System (INIS)

    Van Kampen, K. R.; Zhang, J.; Jex, E.; Tang, D. C.

    2007-01-01

    As bioterrorism is emerging as a national threat, it is urgent to develop a new generation of anthrax vaccines that can be rapidly produced and mass administered in an emergency setting. We have demonstrated that protective immunity against anthrax spores could be elicited in mice by intranasal administration of a non-replicating human adenovirus serotype 5 (Ad5)-derived vector encoding Bacillus anthracis protective antigen (PA) in a single-dose regimen. The potency of an Ad5 vector encoding PA was remarkably enhanced by codon optimization of the PA gene to match the tRNA pool found in human cells. This nasal vaccine can be mass-administered by non-medical personnel during a bioterrorist attack. In addition, replication-competent adenovirus (RCA)-free Ad5-vectored anthrax vaccines can be mass produced in PER.C6 cells in serum-free wave bioreactors and purified by column chromatography to meet a surge in demand. The non-replicating nature of this new generation of anthrax vaccine ensures an excellent safety profile for vaccines and the environment.(author)

  19. Avipoxviruses: infection biology and their use as vaccine vectors.

    Science.gov (United States)

    Weli, Simon C; Tryland, Morten

    2011-02-03

    Avipoxviruses (APVs) belong to the Chordopoxvirinae subfamily of the Poxviridae family. APVs are distributed worldwide and cause disease in domestic, pet and wild birds of many species. APVs are transmitted by aerosols and biting insects, particularly mosquitoes and arthropods and are usually named after the bird species from which they were originally isolated. The virus species Fowlpox virus (FWPV) causes disease in poultry and associated mortality is usually low, but in flocks under stress (other diseases, high production) mortality can reach up to 50%. APVs are also major players in viral vaccine vector development for diseases in human and veterinary medicine. Abortive infection in mammalian cells (no production of progeny viruses) and their ability to accommodate multiple gene inserts are some of the characteristics that make APVs promising vaccine vectors. Although abortive infection in mammalian cells conceivably represents a major vaccine bio-safety advantage, molecular mechanisms restricting APVs to certain hosts are not yet fully understood. This review summarizes the current knowledge relating to APVs, including classification, morphogenesis, host-virus interactions, diagnostics and disease, and also highlights the use of APVs as recombinant vaccine vectors.

  20. Avipoxviruses: infection biology and their use as vaccine vectors

    Directory of Open Access Journals (Sweden)

    Tryland Morten

    2011-02-01

    Full Text Available Abstract Avipoxviruses (APVs belong to the Chordopoxvirinae subfamily of the Poxviridae family. APVs are distributed worldwide and cause disease in domestic, pet and wild birds of many species. APVs are transmitted by aerosols and biting insects, particularly mosquitoes and arthropods and are usually named after the bird species from which they were originally isolated. The virus species Fowlpox virus (FWPV causes disease in poultry and associated mortality is usually low, but in flocks under stress (other diseases, high production mortality can reach up to 50%. APVs are also major players in viral vaccine vector development for diseases in human and veterinary medicine. Abortive infection in mammalian cells (no production of progeny viruses and their ability to accommodate multiple gene inserts are some of the characteristics that make APVs promising vaccine vectors. Although abortive infection in mammalian cells conceivably represents a major vaccine bio-safety advantage, molecular mechanisms restricting APVs to certain hosts are not yet fully understood. This review summarizes the current knowledge relating to APVs, including classification, morphogenesis, host-virus interactions, diagnostics and disease, and also highlights the use of APVs as recombinant vaccine vectors.

  1. Prevention of vector transmitted diseases with clove oil insect repellent.

    Science.gov (United States)

    Shapiro, Rochel

    2012-08-01

    Vector repellent is one element in the prevention of vector-borne diseases. Families that neglect protecting their children against vectors risk their children contracting illnesses such as West Nile virus, eastern equine encephalitis, Lyme disease, malaria, dengue hemorrhagic fever, yellow fever, babesiosis, Crimean-Congo hemorrhagic fever, Rocky Mountain spotted fever, Southern tick-associated rash illness, ehrlichiosis, tick-borne relapsing fever, tularemia, and other insect and arthropod related diseases (CDC, 2011). Identification of families at risk includes screening of the underlying basis for reluctance to apply insect repellent. Nurses and physicians can participate in a positive role by assisting families to determine the proper prophylaxis by recommending insect repellent choices that are economical, safe, and easy to use. A holistic alternative might include the suggestion of clove oil in cases where families might have trepidations regarding the use of DEET on children. This article will explore the safety and effectiveness of clove oil and its use as an insect repellent. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Visit safety

    CERN Document Server

    2012-01-01

    Experiment areas, offices, workshops: it is possible to have co-workers or friends visit these places.     You already know about the official visits service, the VIP office, and professional visits. But do you know about the safety instruction GSI-OHS1, “Visits on the CERN site”? This is a mandatory General Safety Instruction that was created to assist you in ensuring safety for all your visits, whatever their nature—especially those that are non-official. Questions? The HSE Unit will be happy to answer them. Write to safety-general@cern.ch.   The HSE Unit

  3. 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.)

  4. Some remarks on a generalized vector product

    OpenAIRE

    ACOSTA-HUMÁNEZ, PRIMITIVO; ARANDA, MOISÉS; NÚÑEZ, REINALDO

    2011-01-01

    Abstract. In this paper we use a generalized vector product to construct an exterior form ⊥ : , where Finally, for n = k - 1 we introduce the reversing operation to study this generalized vector product over palindromic and antipalindromic vectors. Resumen. En este art&íacute;culo usamos un producto vectorial generalizado para construir una forma exterior ⊥ : , en donde como es natural, Finalmente, para n = k - 1 introducimos la operación reversar para estudiar este producto vectorial gene...

  5. Virtual Vector Machine for Bayesian Online Classification

    OpenAIRE

    Minka, Thomas P.; Xiang, Rongjing; Yuan; Qi

    2012-01-01

    In a typical online learning scenario, a learner is required to process a large data stream using a small memory buffer. Such a requirement is usually in conflict with a learner's primary pursuit of prediction accuracy. To address this dilemma, we introduce a novel Bayesian online classi cation algorithm, called the Virtual Vector Machine. The virtual vector machine allows you to smoothly trade-off prediction accuracy with memory size. The virtual vector machine summarizes the information con...

  6. Genetic manipulation of endosymbionts to control vector and vector borne diseases

    Directory of Open Access Journals (Sweden)

    Jay Prakash Gupta

    Full Text Available Vector borne diseases (VBD are on the rise because of failure of the existing methods of control of vector and vector borne diseases and the climate change. A steep rise of VBDs are due to several factors like selection of insecticide resistant vector population, drug resistant parasite population and lack of effective vaccines against the VBDs. Environmental pollution, public health hazard and insecticide resistant vector population indicate that the insecticides are no longer a sustainable control method of vector and vector-borne diseases. Amongst the various alternative control strategies, symbiont based approach utilizing endosymbionts of arthropod vectors could be explored to control the vector and vector borne diseases. The endosymbiont population of arthropod vectors could be exploited in different ways viz., as a chemotherapeutic target, vaccine target for the control of vectors. Expression of molecules with antiparasitic activity by genetically transformed symbiotic bacteria of disease-transmitting arthropods may serve as a powerful approach to control certain arthropod-borne diseases. Genetic transformation of symbiotic bacteria of the arthropod vector to alter the vector’s ability to transmit pathogen is an alternative means of blocking the transmission of VBDs. In Indian scenario, where dengue, chikungunya, malaria and filariosis are prevalent, paratransgenic based approach can be used effectively. [Vet World 2012; 5(9.000: 571-576

  7. Low-Dose Gene Therapy for Murine PKU Using Episomal Naked DNA Vectors Expressing PAH from Its Endogenous Liver Promoter

    Directory of Open Access Journals (Sweden)

    Hiu Man Grisch-Chan

    2017-06-01

    Full Text Available Limited duration of transgene expression, insertional mutagenesis, and size limitations for transgene cassettes pose challenges and risk factors for many gene therapy vectors. Here, we report on physiological expression of liver phenylalanine hydroxylase (PAH by delivery of naked DNA/minicircle (MC-based vectors for correction of homozygous enu2 mice, a model of human phenylketonuria (PKU. Because MC vectors lack a defined size limit, we constructed a MC vector expressing a codon-optimized murine Pah cDNA that includes a truncated intron and is under the transcriptional control of a 3.6-kb native Pah promoter/enhancer sequence. This vector, delivered via hydrodynamic injection, yielded therapeutic liver PAH activity and sustained correction of blood phenylalanine comparable to viral or synthetic liver promoters. Therapeutic efficacy was seen with vector copy numbers of 95% loss of vector genomes and PAH activity in liver, demonstrating that MC vectors had not integrated into the liver genome. In conclusion, MC vectors, which do not have a defined size-limitation, offer a favorable safety profile for hepatic gene therapy due to their non-integration in combination with native promoters.

  8. Vector (two-dimensional) magnetic phenomena

    International Nuclear Information System (INIS)

    Enokizono, Masato

    2002-01-01

    In this paper, some interesting phenomena were described from the viewpoint of two-dimensional magnetic property, which is reworded with the vector magnetic property. It shows imperfection of conventional magnetic property and some interested phenomena were discovered, too. We found magnetic materials had the strong nonlinearity both magnitude and spatial phase due to the relationship between the magnetic field strength H-vector and the magnetic flux density B-vector. Therefore, magnetic properties should be defined as the vector relationship. Furthermore, the new Barukhausen signal was observed under rotating flux. (Author)

  9. 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.

  10. Vector models in RETRAN-02 MOD 2

    International Nuclear Information System (INIS)

    Kinnersly, S.R.

    1985-06-01

    The vector momentum model in RETRAN-02 allows momentum flux to be modelled in two dimensions. Vector models in RETRAN-2 are described, including both the actual implementation in the code and the specification given in the code manual. The vector momentum model is described in detail. Other models which use vector quantities include models for volume average flow, volume average slip velocity, volume average phase velocities and fill junction flows. Both code implementations and code manual descriptions are described and inconsistencies noted. The differences between the standard RETRA-02 Mod 2 version and the Winfrith version RETN2204 are noted. (U.K.)

  11. Vector Boson Scattering at ATLAS

    CERN Document Server

    Ozcan, V E

    2009-01-01

    While the Higgs model is the best studied scenario of electroweak symmetry breaking, there is no fundamental reason for the physics responsible for the symmetry breaking to be weakly-coupled. Many alternatives exist, predicting highly model-dependent signatures. By measuring the cross-section for the W and Z scattering at the LHC, it will be possible to obtain model-independent evidence for strong symmetry breaking or to constrain these various models. ATLAS Collaboration has recently performed a realistic simulation of this process and its backgrounds, which takes into account the detector effects and has developed new jet-analysis techniques for identifying vector bosons within the immense QCD backgrounds expected at the LHC. These techniques and the prospects for measuring the scattering signal will be presented.

  12. Vector Boson Scattering at ATLAS

    CERN Document Server

    Ozcan, V E

    2008-01-01

    While the Higgs model is the best studied scenario of electroweak symmetry breaking, there is no fundamental reason for the physics responsible for the symmetry breaking to be weakly-coupled. Many alternatives exist, predicting highly model-dependent signatures. By measuring the cross-section for the W and Z scattering at the LHC, it will be possible to obtain model-independent evidence for strong symmetry breaking or to constrain these various models. ATLAS Collaboration has recently performed a realistic simulation of this process and its backgrounds, which takes into account the detector effects and has developed new jet-analysis techniques for identifying vector bosons within the immense QCD backgrounds expected at the LHC. These techniques and the prospects for measuring the scattering signal will be presented.

  13. CERN vector boson hunt successful

    International Nuclear Information System (INIS)

    Robinson, A.L.

    1983-01-01

    UA-1 and UA-2 are code names for two groups of physicists at the European Laboratory for Particle Physics (CERN), together comprising almost 200 researchers. From data collected in two 3-month-long runs last fall and spring, the groups have collected 100 intermediate vector bosons (90 W's and 10 Z 0 's) whose properties so far fit the predictions of the unified quantum field theory of the electromagnetic and weak forces. Although the number of events is short of staggering, the discovery is immensely important. Physicists have been looking for the W for about 50 years. The Z 0 is crucial to the success of the method by which the two forces were melded into one - the electro-weak force

  14. On Weighted Support Vector Regression

    DEFF Research Database (Denmark)

    Han, Xixuan; Clemmensen, Line Katrine Harder

    2014-01-01

    We propose a new type of weighted support vector regression (SVR), motivated by modeling local dependencies in time and space in prediction of house prices. The classic weights of the weighted SVR are added to the slack variables in the objective function (OF‐weights). This procedure directly...... shrinks the coefficient of each observation in the estimated functions; thus, it is widely used for minimizing influence of outliers. We propose to additionally add weights to the slack variables in the constraints (CF‐weights) and call the combination of weights the doubly weighted SVR. We illustrate...... the differences and similarities of the two types of weights by demonstrating the connection between the Least Absolute Shrinkage and Selection Operator (LASSO) and the SVR. We show that an SVR problem can be transformed to a LASSO problem plus a linear constraint and a box constraint. We demonstrate...

  15. Pattern recognition with vector hits

    International Nuclear Information System (INIS)

    Frühwirth, R

    2012-01-01

    Trackers at the future high-luminosity LHC, designed to have triggering capability, will feature layers of stacked modules with a small stack separation. This will allow the reconstruction of track stubs or vector hits with position and direction information, but lacking precise curvature information. This opens up new possibilities for track finding, online and offline. Two track finding methods, the Kalman filter and the convergent Hough transform are studied in this context. Results from a simplified fast simulation are presented. It is shown that the performance of the methods depends to a large extent on the size of the stack separation. We conclude that the detector design and the choice of the track finding algorithm(s) are strongly coupled and should proceed conjointly.

  16. The evaporative vector: Homogeneous systems

    International Nuclear Information System (INIS)

    Klots, C.E.

    1987-05-01

    Molecular beams of van der Waals molecules are the subject of much current research. Among the methods used to form these beams, three-sputtering, laser ablation, and the sonic nozzle expansion of neat gases - yield what are now recognized to be ''warm clusters.'' They contain enough internal energy to undergo a number of first-order processes, in particular that of evaporation. Because of this evaporation and its attendant cooling, the properties of such clusters are time-dependent. The states of matter which can be arrived at via an evaporative vector on a typical laboratory time-scale are discussed. Topics include the (1) temperatures, (2) metastability, (3) phase transitions, (4) kinetic energies of fragmentation, and (5) the expression of magical properties, all for evaporating homogeneous clusters

  17. Introduction to Vector Field Visualization

    Science.gov (United States)

    Kao, David; Shen, Han-Wei

    2010-01-01

    Vector field visualization techniques are essential to help us understand the complex dynamics of flow fields. These can be found in a wide range of applications such as study of flows around an aircraft, the blood flow in our heart chambers, ocean circulation models, and severe weather predictions. The vector fields from these various applications can be visually depicted using a number of techniques such as particle traces and advecting textures. In this tutorial, we present several fundamental algorithms in flow visualization including particle integration, particle tracking in time-dependent flows, and seeding strategies. For flows near surfaces, a wide variety of synthetic texture-based algorithms have been developed to depict near-body flow features. The most common approach is based on the Line Integral Convolution (LIC) algorithm. There also exist extensions of LIC to support more flexible texture generations for 3D flow data. This tutorial reviews these algorithms. Tensor fields are found in several real-world applications and also require the aid of visualization to help users understand their data sets. Examples where one can find tensor fields include mechanics to see how material respond to external forces, civil engineering and geomechanics of roads and bridges, and the study of neural pathway via diffusion tensor imaging. This tutorial will provide an overview of the different tensor field visualization techniques, discuss basic tensor decompositions, and go into detail on glyph based methods, deformation based methods, and streamline based methods. Practical examples will be used when presenting the methods; and applications from some case studies will be used as part of the motivation.

  18. Safety Principles

    Directory of Open Access Journals (Sweden)

    V. A. Grinenko

    2011-06-01

    Full Text Available The offered material in the article is picked up so that the reader could have a complete representation about concept “safety”, intrinsic characteristics and formalization possibilities. Principles and possible strategy of safety are considered. A material of the article is destined for the experts who are taking up the problems of safety.

  19. Safety Systems

    Science.gov (United States)

    Halligan, Tom

    2009-01-01

    Colleges across the country are rising to the task by implementing safety programs, response strategies, and technologies intended to create a secure environment for teachers and students. Whether it is preparing and responding to a natural disaster, health emergency, or act of violence, more schools are making campus safety a top priority. At…

  20. Safety First

    Science.gov (United States)

    Taft, Darryl

    2011-01-01

    Ned Miller does not take security lightly. As director of campus safety and emergency management at the Des Moines Area Community College (DMACC), any threat requires serious consideration. As community college administrators adopt a more proactive approach to campus safety, many institutions are experimenting with emerging technologies, including…

  1. Speculative dynamic vectorization to assist static vectorization in a HW/SW co-designed environment

    OpenAIRE

    Kumar, R.; Martinez, A.; Gonzalez, A.

    2013-01-01

    Compiler based static vectorization is used widely to extract data level parallelism from computation intensive applications. Static vectorization is very effective in vectorizing traditional array based applications. However, compilers inability to reorder ambiguous memory references severely limits vectorization opportunities, especially in pointer rich applications. HW/SW co-designed processors provide an excellent opportunity to optimize the applications at runtime. The availability of dy...

  2. 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.))

  3. Gauge anomaly with vector and axial-vector fields in 6D curved space

    Science.gov (United States)

    Yajima, Satoshi; Eguchi, Kohei; Fukuda, Makoto; Oka, Tomonori

    2018-03-01

    Imposing the conservation equation of the vector current for a fermion of spin 1/2 at the quantum level, a gauge anomaly for the fermion coupling with non-Abelian vector and axial-vector fields in 6D curved space is expressed in tensorial form. The anomaly consists of terms that resemble the chiral U(1) anomaly and the commutator terms that disappear if the axial-vector field is Abelian.

  4. 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

  5. Constraining vectors and axial-vectors in walking technicolour by a holographic principle

    DEFF Research Database (Denmark)

    D. Dietrich, Dennis; Kouvaris, Christoforos

    2008-01-01

    We use a holographic principle to study the low-energy spectrum of walking technicolour models. In particular, we predict the masses of the axial vectors as well as the decay constants of vectors and axial vectors as functions of the mass of the techni-rho. Given that there are very few...

  6. Clustering Categories in Support Vector Machines

    DEFF Research Database (Denmark)

    Carrizosa, Emilio; Nogales-Gómez, Amaya; Morales, Dolores Romero

    2017-01-01

    The support vector machine (SVM) is a state-of-the-art method in supervised classification. In this paper the Cluster Support Vector Machine (CLSVM) methodology is proposed with the aim to increase the sparsity of the SVM classifier in the presence of categorical features, leading to a gain in in...

  7. 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.)

  8. Nonlinear dynamics of a vectored thrust aircraft

    DEFF Research Database (Denmark)

    Sørensen, C.B; Mosekilde, Erik

    1996-01-01

    With realistic relations for the aerodynamic coefficients, numerical simulations are applied to study the longitudional dynamics of a thrust vectored aircraft. As function of the thrust magnitude and the thrust vectoring angle the equilibrium state exhibits two saddle-node bifurcations and three...

  9. 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…

  10. Limit theorems for functionals of Gaussian vectors

    Institute of Scientific and Technical Information of China (English)

    Hongshuai DAI; Guangjun SHEN; Lingtao KONG

    2017-01-01

    Operator self-similar processes,as an extension of self-similar processes,have been studied extensively.In this work,we study limit theorems for functionals of Gaussian vectors.Under some conditions,we determine that the limit of partial sums of functionals of a stationary Gaussian sequence of random vectors is an operator self-similar process.

  11. Chickering's Vectors and the Adult Child Experience.

    Science.gov (United States)

    Sitten, Robin J.

    This document looks at the college student who is an adult child from a dysfunctional family, applying Chickering's seven vectors of college-age student development to that student's experiences at college. Each of Chickering's seven vectors (developing competence, managing emotions, developing autonomy, establishing identity, freeing…

  12. Zika and its vector mosquitoes in Mexico

    Directory of Open Access Journals (Sweden)

    Luis del Carpio-Orantes

    2018-06-01

    Full Text Available In the present study, we carried out a review on the potential vectors of the Zika virus in the Americas, specifically in Mexico. Being vectors of the Culicidae family, they have great predominance in those territories, which could facilitate viral dissemination.

  13. morphological identification of malaria vectors within anopheles

    African Journals Online (AJOL)

    DR. AMIN

    Africa among the human population. Determination of risk of malaria transmission requires quick and accurate methods of identification of Anopheles mosquitoes especially when targeting vector control. (Maxwell, et al., 2003). Anopheles mosquito transmits malaria. The most important vectors of malaria are members of.

  14. Vector fields and differential operators: noncommutative case

    International Nuclear Information System (INIS)

    Borowiec, A.

    1997-01-01

    A notion of Cartan pairs as an analogy of vector fields in the realm of noncommutative geometry has been proposed previously. In this paper an outline is given of the construction of a noncommutative analogy of the algebra of differential operators as well as its (algebraic) Fock space realization. Co-universal vector fields and covariant derivatives will also be discussed

  15. Deep Support Vector Machines for Regression Problems

    NARCIS (Netherlands)

    Wiering, Marco; Schutten, Marten; Millea, Adrian; Meijster, Arnold; Schomaker, Lambertus

    2013-01-01

    In this paper we describe a novel extension of the support vector machine, called the deep support vector machine (DSVM). The original SVM has a single layer with kernel functions and is therefore a shallow model. The DSVM can use an arbitrary number of layers, in which lower-level layers contain

  16. Pair production of intermediate vector bosons

    International Nuclear Information System (INIS)

    Mikaelian, K.O.

    1979-01-01

    The production of intermediate vector boson pairs W + W - , Z 0 Z 0 , W +- Z 0 and W +- γ in pp and p anti p collisions is discussed. The motivation is to detect the self-interactions among the four intermediate vector bosons

  17. Construction of expression vectors carrying mouse peroxisomal ...

    African Journals Online (AJOL)

    PRECIOUS

    2009-11-16

    Nov 16, 2009 ... The aim of this study was to construct expression vectors carrying mouse peroxisomal protein gene. (PEP-cDNA) in prokaryotic and mammalian expression vectors in chimeric cDNA types, encompassing. GST and FLAG with PEP-cDNA. PEP-cDNA was sub-cloned in pGEX6p2 prokaryotic expression ...

  18. 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.

  19. 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.

  20. In Vitro Transduction and Target-Mutagenesis Efficiency of HIV-1 pol Gene Targeting ZFN and CRISPR/Cas9 Delivered by Various Plasmids and/or Vectors: Toward an HIV Cure.

    Science.gov (United States)

    Okee, Moses; Bayiyana, Alice; Musubika, Carol; Joloba, Moses L; Ashaba-Katabazi, Fred; Bagaya, Bernard; Wayengera, Misaki

    2018-01-01

    Efficiency of artificial restriction enzymes toward curing HIV has only been separately examined, using differing delivery vehicles. We compared the in vitro transduction and target-mutagenesis efficiency of consortium plasmid and adenoviral vector delivered HIV-1 pol gene targeting zinc finger nuclease (ZFN) with CRISPR/Cas, Custom-ZFN, CRISPR-Cas-9, and plasmids and vectors (murCTSD_pZFN, pGS-U-gRNA, pCMV-Cas-D01A, Ad5-RGD); cell lines (TZM-bl and ACH-2/J-Lat cells); and the latency reversing agents prostratin, suberoylanilide hydroxamic acid, and phorbol myristate acetate. Cell lines were grown in either Dulbecco's modified Eagle's medium or Roswell Park Memorial Institute with the antibiotics kanamycin, zeocin, and efavirenz. Efficiency was assayed by GFP/luciferase activity and/or validated by yeast MEL1 reporter assay, CEL1 restriction fragment assay, and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Ad5-RGD vectors had better transduction efficiency than murCTSD and pGS-U-gRNA/pCMV-Cas-D01A plasmids. CRISPR/Cas9 exhibited better target-mutagenesis efficiency relative to ZFN (delivered by either plasmid or Ad5 vector) based on gel electrophoresis of pol gene amplicons within ACH-2 and J-Lat cells. Ad-5-RGD vectors enhanced target mutagenesis of ZFN, relative to murCTSD_pZFN plasmids, to levels of CRISPR/Cas9 plasmids. Similar reduction of luciferase activity among TZM-bl treated with Ad5-ZFN vectors relative to CRISPR/Cas-9 and murCTSD_pZFN plasmids was observed on challenge with HIV-1. qRT-PCR of HIV-1 pol gene transcripts affirmed that Ad5 (RGD) vectors enhanced target mutagenesis of ZFN. Whereas CRISPR/Cas-9 may possess inherent superior target-mutagenesis efficiency; the efficiency of ZFN (off-target toxicity withstanding) can be enhanced by altering delivery vehicle from plasmid to Ad5 (RGD) vectors.

  1. Fundamental safety principles. Safety fundamentals

    International Nuclear Information System (INIS)

    2006-01-01

    This publication states the fundamental safety objective and ten associated safety principles, and briefly describes their intent and purpose. The fundamental safety objective - to protect people and the environment from harmful effects of ionizing radiation - applies to all circumstances that give rise to radiation risks. The safety principles are applicable, as relevant, throughout the entire lifetime of all facilities and activities - existing and new - utilized for peaceful purposes, and to protective actions to reduce existing radiation risks. They provide the basis for requirements and measures for the protection of people and the environment against radiation risks and for the safety of facilities and activities that give rise to radiation risks, including, in particular, nuclear installations and uses of radiation and radioactive sources, the transport of radioactive material and the management of radioactive waste

  2. Fundamental safety principles. Safety fundamentals

    International Nuclear Information System (INIS)

    2007-01-01

    This publication states the fundamental safety objective and ten associated safety principles, and briefly describes their intent and purpose. The fundamental safety objective - to protect people and the environment from harmful effects of ionizing radiation - applies to all circumstances that give rise to radiation risks. The safety principles are applicable, as relevant, throughout the entire lifetime of all facilities and activities - existing and new - utilized for peaceful purposes, and to protective actions to reduce existing radiation risks. They provide the basis for requirements and measures for the protection of people and the environment against radiation risks and for the safety of facilities and activities that give rise to radiation risks, including, in particular, nuclear installations and uses of radiation and radioactive sources, the transport of radioactive material and the management of radioactive waste

  3. 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.

  4. Projection correlation between two random vectors.

    Science.gov (United States)

    Zhu, Liping; Xu, Kai; Li, Runze; Zhong, Wei

    2017-12-01

    We propose the use of projection correlation to characterize dependence between two random vectors. Projection correlation has several appealing properties. It equals zero if and only if the two random vectors are independent, it is not sensitive to the dimensions of the two random vectors, it is invariant with respect to the group of orthogonal transformations, and its estimation is free of tuning parameters and does not require moment conditions on the random vectors. We show that the sample estimate of the projection correction is [Formula: see text]-consistent if the two random vectors are independent and root-[Formula: see text]-consistent otherwise. Monte Carlo simulation studies indicate that the projection correlation has higher power than the distance correlation and the ranks of distances in tests of independence, especially when the dimensions are relatively large or the moment conditions required by the distance correlation are violated.

  5. Safety strategy

    International Nuclear Information System (INIS)

    Schultheiss, G.F.

    1980-01-01

    The basis for safety strategy in nuclear industry and especially nuclear power plants is the prevention of radioactivity release inside or outside of the technical installation. Therefore either technical or administrative measures are combined to a general strategy concept. This introduction will explain in more detail the following topics: - basic principles of safety - lines of assurance (LOA) - defense in depth - deterministic and probabilistic methods. This presentation is seen as an introduction to the more detailed discussion following in this course, nevertheless some selected examples will be used to illustrate the aspects of safety strategy development although they might be repeated later on. (orig.)

  6. Safety culture

    International Nuclear Information System (INIS)

    Drukraroff, C.

    2010-01-01

    The concept of Safety Culture was defined after Chernobyl's nuclear accident in 1986. It has not been exempt from discussion interpretations, adding riders, etc..., over the last 24 years because it has to do with human behavior and performance in the organizations. Safety Culture is not an easy task to define, assess and monitor. The proof of it is that today we still discussing and writing about it. How has been the evolution of Safety Culture at the Juzbado Factory since 1985 to today?. What is the strategy that we will be following in the future. (Author)

  7. Radiation safety

    International Nuclear Information System (INIS)

    1996-04-01

    Most of the ionizing radiation that people are exposed to in day-to-day activities comes from natural, rather than manmade, sources. The health effects of radiation - both natural and artificial - are relatively well understood and can be effectively minimized through careful safety measures and practices. The IAEA, together with other international and expert organizations, is helping to promote and institute Basic Safety Standards on an international basis to ensure that radiation sources and radioactive materials are managed for both maximum safety and human benefit

  8. Nuclear Safety

    Energy Technology Data Exchange (ETDEWEB)

    Silver, E G [ed.

    1989-01-01

    This document is a review journal that covers significant developments in the field of nuclear safety. Its scope includes the analysis and control of hazards associated with nuclear energy, operations involving fissionable materials, and the products of nuclear fission and their effects on the environment. Primary emphasis is on safety in reactor design, construction, and operation; however, the safety aspects of the entire fuel cycle, including fuel fabrication, spent-fuel processing, nuclear waste disposal, handling of radioisotopes, and environmental effects of these operations, are also treated.

  9. Recombinant vesicular stomatitis virus vaccine vectors expressing filovirus glycoproteins lack neurovirulence in nonhuman primates.

    Directory of Open Access Journals (Sweden)

    Chad E Mire

    Full Text Available The filoviruses, Marburg virus and Ebola virus, cause severe hemorrhagic fever with high mortality in humans and nonhuman primates. Among the most promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (rVSV that expresses an individual filovirus glycoprotein (GP in place of the VSV glycoprotein (G. The main concern with all replication-competent vaccines, including the rVSV filovirus GP vectors, is their safety. To address this concern, we performed a neurovirulence study using 21 cynomolgus macaques where the vaccines were administered intrathalamically. Seven animals received a rVSV vector expressing the Zaire ebolavirus (ZEBOV GP; seven animals received a rVSV vector expressing the Lake Victoria marburgvirus (MARV GP; three animals received rVSV-wild type (wt vector, and four animals received vehicle control. Two of three animals given rVSV-wt showed severe neurological symptoms whereas animals receiving vehicle control, rVSV-ZEBOV-GP, or rVSV-MARV-GP did not develop these symptoms. Histological analysis revealed major lesions in neural tissues of all three rVSV-wt animals; however, no significant lesions were observed in any animals from the filovirus vaccine or vehicle control groups. These data strongly suggest that rVSV filovirus GP vaccine vectors lack the neurovirulence properties associated with the rVSV-wt parent vector and support their further development as a vaccine platform for human use.

  10. Reactor safety

    International Nuclear Information System (INIS)

    Meneley, D.A.

    The people of Ontario have begun to receive the benefits of a low cost, assured supply of electrical energy from CANDU nuclear stations. This indigenous energy source also has excellent safety characteristics. Safety has been one of the central themes of the CANDU development program from its very beginning. A great deal of work has been done to establish that public risks are small. However, safety design criteria are now undergoing extensive review, with a real prospect of more stringent requirements being applied in the future. Considering the newness of the technology it is not surprising that a consensus does not yet exist; this makes it imperative to discuss the issues. It is time to examine the policies and practice of reactor safety management in Canada to decide whether or not further restrictions are justified in the light of current knowledge

  11. Generation of arbitrary vector fields based on a pair of orthogonal elliptically polarized base vectors.

    Science.gov (United States)

    Xu, Danfeng; Gu, Bing; Rui, Guanghao; Zhan, Qiwen; Cui, Yiping

    2016-02-22

    We present an arbitrary vector field with hybrid polarization based on the combination of a pair of orthogonal elliptically polarized base vectors on the Poincaré sphere. It is shown that the created vector field is only dependent on the latitude angle 2χ but is independent on the longitude angle 2ψ on the Poincaré sphere. By adjusting the latitude angle 2χ, which is related to two identical waveplates in a common path interferometric arrangement, one could obtain arbitrary type of vector fields. Experimentally, we demonstrate the generation of such kind of vector fields and confirm the distribution of state of polarization by the measurement of Stokes parameters. Besides, we investigate the tight focusing properties of these vector fields. It is found that the additional degree of freedom 2χ provided by arbitrary vector field with hybrid polarization allows one to control the spatial structure of polarization and to engineer the focusing field.

  12. Vector 33: A reduce program for vector algebra and calculus in orthogonal curvilinear coordinates

    Science.gov (United States)

    Harper, David

    1989-06-01

    This paper describes a package with enables REDUCE 3.3 to perform algebra and calculus operations upon vectors. Basic algebraic operations between vectors and between scalars and vectors are provided, including scalar (dot) product and vector (cross) product. The vector differential operators curl, divergence, gradient and Laplacian are also defined, and are valid in any orthogonal curvilinear coordinate system. The package is written in RLISP to allow algebra and calculus to be performed using notation identical to that for operations. Scalars and vectors can be mixed quite freely in the same expression. The package will be of interest to mathematicians, engineers and scientists who need to perform vector calculations in orthogonal curvilinear coordinates.

  13. Image Coding Based on Address Vector Quantization.

    Science.gov (United States)

    Feng, Yushu

    Image coding is finding increased application in teleconferencing, archiving, and remote sensing. This thesis investigates the potential of Vector Quantization (VQ), a relatively new source coding technique, for compression of monochromatic and color images. Extensions of the Vector Quantization technique to the Address Vector Quantization method have been investigated. In Vector Quantization, the image data to be encoded are first processed to yield a set of vectors. A codeword from the codebook which best matches the input image vector is then selected. Compression is achieved by replacing the image vector with the index of the code-word which produced the best match, the index is sent to the channel. Reconstruction of the image is done by using a table lookup technique, where the label is simply used as an address for a table containing the representative vectors. A code-book of representative vectors (codewords) is generated using an iterative clustering algorithm such as K-means, or the generalized Lloyd algorithm. A review of different Vector Quantization techniques are given in chapter 1. Chapter 2 gives an overview of codebook design methods including the Kohonen neural network to design codebook. During the encoding process, the correlation of the address is considered and Address Vector Quantization is developed for color image and monochrome image coding. Address VQ which includes static and dynamic processes is introduced in chapter 3. In order to overcome the problems in Hierarchical VQ, Multi-layer Address Vector Quantization is proposed in chapter 4. This approach gives the same performance as that of the normal VQ scheme but the bit rate is about 1/2 to 1/3 as that of the normal VQ method. In chapter 5, a Dynamic Finite State VQ based on a probability transition matrix to select the best subcodebook to encode the image is developed. In chapter 6, a new adaptive vector quantization scheme, suitable for color video coding, called "A Self -Organizing

  14. Safety first!

    CERN Multimedia

    2016-01-01

    Among the many duties I assumed at the beginning of the year was the ultimate responsibility for Safety at CERN: the responsibility for the physical safety of the personnel, the responsibility for the safe operation of the facilities, and the responsibility to ensure that CERN acts in accordance with the highest standards of radiation and environmental protection.   The Safety Policy document drawn up in September 2014 is an excellent basis for the implementation of Safety in all areas of CERN’s work. I am happy to commit during my mandate to help meet its objectives, not least by ensuring the Organization makes available the necessary means to achieve its Safety objectives. One of the main objectives of the HSE (Occupational Health and Safety and Environmental Protection) unit in the coming months is to enhance the measures to minimise CERN’s impact on the environment. I believe CERN should become a role model for an environmentally-aware scientific research laboratory. Risk ...

  15. Radiation safety

    International Nuclear Information System (INIS)

    Jain, Priyanka

    2014-01-01

    The use of radiation sources is a privilege; in order to retain the privilege, all persons who use sources of radiation must follow policies and procedures for their safe and legal use. The purpose of this poster is to describe the policies and procedures of the Radiation Protection Program. Specific conditions of radiation safety require the establishment of peer committees to evaluate proposals for the use of radionuclides, the appointment of a radiation safety officer, and the implementation of a radiation safety program. In addition, the University and Medical Centre administrations have determined that the use of radiation producing machines and non-ionizing radiation sources shall be included in the radiation safety program. These Radiation Safety policies are intended to ensure that such use is in accordance with applicable State and Federal regulations and accepted standards as directed towards the protection of health and the minimization of hazard to life or property. It is the policy that all activities involving ionizing radiation or radiation emitting devices be conducted so as to keep hazards from radiation to a minimum. Persons involved in these activities are expected to comply fully with the Canadian Nuclear Safety Act and all it. The risk of prosecution by the Department of Health and Community Services exists if compliance with all applicable legislation is not fulfilled. (author)

  16. Vector-like quarks: t’ and partners

    International Nuclear Information System (INIS)

    PANIZZI, L.

    2014-01-01

    Vector-like quarks are predicted in various scenarios of new physics, and their peculiar signatures from both pair and single production have been already investigated in detail. However no signals of vector-like quarks have been detected so far, pushing limits on their masses above 600–700GeV, depending on assumptions on their couplings. Experimental searches consider specific final states to pose bounds on the mass of a vector-like quark, usually assuming it is the only particle that contributes to the signal of new physics in that specific final state. However, realistic scenarios predict the existence of multiple vector-like quarks, possibly with similar masses. The reinterpretation of mass bounds from experimental searches is therefore not always straightforward. In this analysis I briefly summarise the constraints on vector-like quarks and their possible signatures at the LHC, focusing in particular on a model-independent description of single production processes for vector-like quark that mix with all generations and on the development of a framework to study scenarios with multiple vector-like quarks.

  17. Correlated Topic Vector for Scene Classification.

    Science.gov (United States)

    Wei, Pengxu; Qin, Fei; Wan, Fang; Zhu, Yi; Jiao, Jianbin; Ye, Qixiang

    2017-07-01

    Scene images usually involve semantic correlations, particularly when considering large-scale image data sets. This paper proposes a novel generative image representation, correlated topic vector, to model such semantic correlations. Oriented from the correlated topic model, correlated topic vector intends to naturally utilize the correlations among topics, which are seldom considered in the conventional feature encoding, e.g., Fisher vector, but do exist in scene images. It is expected that the involvement of correlations can increase the discriminative capability of the learned generative model and consequently improve the recognition accuracy. Incorporated with the Fisher kernel method, correlated topic vector inherits the advantages of Fisher vector. The contributions to the topics of visual words have been further employed by incorporating the Fisher kernel framework to indicate the differences among scenes. Combined with the deep convolutional neural network (CNN) features and Gibbs sampling solution, correlated topic vector shows great potential when processing large-scale and complex scene image data sets. Experiments on two scene image data sets demonstrate that correlated topic vector improves significantly the deep CNN features, and outperforms existing Fisher kernel-based features.

  18. On vector fields having properties of Reeb fields

    OpenAIRE

    Hajduk, Boguslaw; Walczak, Rafal

    2011-01-01

    We study constructions of vector fields with properties which are characteristic to Reeb vector fields of contact forms. In particular, we prove that all closed oriented odd-dimensional manifold have geodesible vector fields.

  19. The standardised freight container: vector of vectors and vector-borne diseases.

    Science.gov (United States)

    Reiter, P

    2010-04-01

    The standardised freight container was one of the most important innovations of the 20th Century. Containerised cargoes travel from their point of origin to their destination by ship, road and rail as part of a single journey, without unpacking. This simple concept is the key element in cheap, rapid transport by land and sea, and has led to a phenomenal growth in global trade. Likewise, containerised air cargo has led to a remarkable increase in the inter-continental transportation of goods, particularly perishable items such as flowers, fresh vegetables and live animals. In both cases, containerisation offers great advantages in speed and security, but reduces the opportunity to inspect cargoes in transit. An inevitable consequence is the globalisation of undesirable species of animals, plants and pathogens. Moreover, cheap passenger flights offer worldwide travel for viral and parasitic pathogens in infected humans. The continued emergence of exotic pests, vectors and pathogens throughout the world is an unavoidable consequence of these advances in transportation technology.

  20. 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.

  1. Interior point decoding for linear vector channels

    International Nuclear Information System (INIS)

    Wadayama, T

    2008-01-01

    In this paper, a novel decoding algorithm for low-density parity-check (LDPC) codes based on convex optimization is presented. The decoding algorithm, called interior point decoding, is designed for linear vector channels. The linear vector channels include many practically important channels such as inter-symbol interference channels and partial response channels. It is shown that the maximum likelihood decoding (MLD) rule for a linear vector channel can be relaxed to a convex optimization problem, which is called a relaxed MLD problem

  2. Higgs decays and brane gravi-vectors

    International Nuclear Information System (INIS)

    Clark, T. E.; Liu Boyang; Love, S. T.; Xiong, C.; Veldhuis, T. ter

    2008-01-01

    Higgs boson decays in flexible brane world models with stable, massive gravi-vectors are considered. Such vectors couple bilinearly to the standard model fields through either the standard model energy-momentum tensor, the weak hypercharge field strength, or the Higgs scalar. The role of the coupling involving the extrinsic curvature is highlighted. It is found that within the presently allowed parameter space, the decay rate of the Higgs into two gravi-vectors (which would appear as an invisible Higgs decay) can be comparable to the rate for any of the standard model decay modes.

  3. Vector analysis for mathematicians, scientists and engineers

    CERN Document Server

    Simons, S

    1970-01-01

    Vector Analysis for Mathematicians, Scientists and Engineers, Second Edition, provides an understanding of the methods of vector algebra and calculus to the extent that the student will readily follow those works which make use of them, and further, will be able to employ them himself in his own branch of science. New concepts and methods introduced are illustrated by examples drawn from fields with which the student is familiar, and a large number of both worked and unworked exercises are provided. The book begins with an introduction to vectors, covering their representation, addition, geome

  4. 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].

  5. Vector Boolean Functions: applications in symmetric cryptography

    OpenAIRE

    Álvarez Cubero, José Antonio

    2015-01-01

    Esta tesis establece los fundamentos teóricos y diseña una colección abierta de clases C++ denominada VBF (Vector Boolean Functions) para analizar funciones booleanas vectoriales (funciones que asocian un vector booleano a otro vector booleano) desde una perspectiva criptográfica. Esta nueva implementación emplea la librería NTL de Victor Shoup, incorporando nuevos módulos que complementan a las funciones de NTL, adecuándolas para el análisis criptográfico. La clase fundamental que representa...

  6. Robust Pseudo-Hierarchical Support Vector Clustering

    DEFF Research Database (Denmark)

    Hansen, Michael Sass; Sjöstrand, Karl; Olafsdóttir, Hildur

    2007-01-01

    Support vector clustering (SVC) has proven an efficient algorithm for clustering of noisy and high-dimensional data sets, with applications within many fields of research. An inherent problem, however, has been setting the parameters of the SVC algorithm. Using the recent emergence of a method...... for calculating the entire regularization path of the support vector domain description, we propose a fast method for robust pseudo-hierarchical support vector clustering (HSVC). The method is demonstrated to work well on generated data, as well as for detecting ischemic segments from multidimensional myocardial...

  7. Interior point decoding for linear vector channels

    Energy Technology Data Exchange (ETDEWEB)

    Wadayama, T [Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya, Aichi, 466-8555 (Japan)], E-mail: wadayama@nitech.ac.jp

    2008-01-15

    In this paper, a novel decoding algorithm for low-density parity-check (LDPC) codes based on convex optimization is presented. The decoding algorithm, called interior point decoding, is designed for linear vector channels. The linear vector channels include many practically important channels such as inter-symbol interference channels and partial response channels. It is shown that the maximum likelihood decoding (MLD) rule for a linear vector channel can be relaxed to a convex optimization problem, which is called a relaxed MLD problem.

  8. Vector properties in molecular photodissociation

    International Nuclear Information System (INIS)

    Underwood, J.

    1999-12-01

    The technique of resonance enhanced multi-photon ionization (REMPI) of atomic and molecular species produced from a photofragmentation event combined with time-of flight (TOF) detection is used to examine scalar and vector properties following photodissociation. This technique is applied to the study of methyl bromide dissociation in a product state specific manner. We report measurements of the angular distributions and kinetic energy releases of the resulting bromine atoms in the ground and first spin-orbit excited state. Additionally we report measurements of the angular distributions and kinetic energy releases of the methyl fragment in the ground vibrational state, and also the excited state with one quanta in the ν 2 vibrational modes. These studies were carried out in the red wing of the absorption band at several wavelengths. For these measurements we were able to resolve the spin orbit state of the partner bromine fragment. From our observations we find new evidence for enhanced nonadiabatic curve crossing active in methyl bromide dissociation in comparison with earlier studies of methyl iodide. The atomic polarization produced following photodissociation of a diatomic molecule was investigated both theoretically and experimentally. We develop theoretical expressions relating the lab frame and molecular frame atomic polarization to the photoexcitation and subsequent dissociation of a diatomic molecule. This treatment includes both incoherent, coherent and non-adiabatic processes which may be active in the photodissociation process. We treat the general case of a polarized diatomic molecule yielding two fragments with non zero angular momentum. Experimentally, an investigation of the polarization of atomic Cl( 2 P 3/2 ) photofragments from the ∼330 nm photolysis of molecular chlorine using the REMPI-TOF technique is reported. We present a theoretical framework in which to treat such experiments allowing the extraction of parameters with direct physical

  9. SAFETY INSTRUCTION AND SAFETY NOTE

    CERN Multimedia

    TIS Secretariat

    2002-01-01

    Please note that the SAFETY INSTRUCTION N0 49 (IS 49) and the SAFETY NOTE N0 28 (NS 28) entitled respectively 'AVOIDING CHEMICAL POLLUTION OF WATER' and 'CERN EXHIBITIONS - FIRE PRECAUTIONS' are available on the web at the following urls: http://edms.cern.ch/document/335814 and http://edms.cern.ch/document/335861 Paper copies can also be obtained from the TIS Divisional Secretariat, email: TIS.Secretariat@cern.ch

  10. System safety education focused on flight safety

    Science.gov (United States)

    Holt, E.

    1971-01-01

    The measures necessary for achieving higher levels of system safety are analyzed with an eye toward maintaining the combat capability of the Air Force. Several education courses were provided for personnel involved in safety management. Data include: (1) Flight Safety Officer Course, (2) Advanced Safety Program Management, (3) Fundamentals of System Safety, and (4) Quantitative Methods of Safety Analysis.

  11. Generalized 2-vector spaces and general linear 2-groups

    OpenAIRE

    Elgueta, Josep

    2008-01-01

    In this paper a notion of {\\it generalized 2-vector space} is introduced which includes Kapranov and Voevodsky 2-vector spaces. Various kinds of generalized 2-vector spaces are considered and examples are given. The existence of non free generalized 2-vector spaces and of generalized 2-vector spaces which are non Karoubian (hence, non abelian) categories is discussed, and it is shown how any generalized 2-vector space can be identified with a full subcategory of an (abelian) functor category ...

  12. Strategic vectors of transformational shifts in the national tourism system of Ukraine

    Directory of Open Access Journals (Sweden)

    Alla OKHRIMENKO

    2017-10-01

    Full Text Available The article determines transformational factors, which influence a national tourism system (NTS of Ukraine and proposes strategical vectors of its development. Research of the NTS as an economic system is a pre-condition for formation of strategic vectors of development. Transformational driving forces principally change scales, components, and proportions between external and internal factors of development of the NTS. Correspondingly, the mentioned processes objectively encourage modernization of the national tourism system and application of innovative managerial methods. The following Strategical vectors of transformational shifts in the NTS were grounded: 1 Safety of tourists and investors; 2 The normative and legislative framework of the NTS development; 3 Development of infrastructure of the NTS component; 4 Human resources development; 5 A marketing policy of the NTS promotion; 6 Ecological and cultural policies. Their implementation will improve efficiency and competitiveness of the NTS and the national economy.

  13. Viral Vectors for Use in the Development of Biodefense Vaccines

    National Research Council Canada - National Science Library

    Lee, John S; Hadjipanayis, Angela G; Parker, Michael D

    2005-01-01

    .... DNA vectors, live-attenuated viruses and bacteria, recombinant proteins combined with adjuvant, and viral- or bacterial-vectored vaccines have been developed as countermeasures against many potential...

  14. Horizontal vectorization of electron repulsion integrals.

    Science.gov (United States)

    Pritchard, Benjamin P; Chow, Edmond

    2016-10-30

    We present an efficient implementation of the Obara-Saika algorithm for the computation of electron repulsion integrals that utilizes vector intrinsics to calculate several primitive integrals concurrently in a SIMD vector. Initial benchmarks display a 2-4 times speedup with AVX instructions over comparable scalar code, depending on the basis set. Speedup over scalar code is found to be sensitive to the level of contraction of the basis set, and is best for (lAlB|lClD) quartets when lD  = 0 or lB=lD=0, which makes such a vectorization scheme particularly suitable for density fitting. The basic Obara-Saika algorithm, how it is vectorized, and the performance bottlenecks are analyzed and discussed. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. 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.

  16. 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

  17. All optical vector magnetometer, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — This Phase I research project will investigate a novel method of operating an atomic magnetometer to simultaneously measure total magnetic fields and vector magnetic...

  18. Fractional Vector Calculus and Fractional Special Function

    OpenAIRE

    Li, Ming-Fan; Ren, Ji-Rong; Zhu, Tao

    2010-01-01

    Fractional vector calculus is discussed in the spherical coordinate framework. A variation of the Legendre equation and fractional Bessel equation are solved by series expansion and numerically. Finally, we generalize the hypergeometric functions.

  19. Meromorphic Vector Fields and Circle Packings

    DEFF Research Database (Denmark)

    Dias, Kealey

    The objective of the Ph.D. project is to initiate a classification of bifurcations of meromorphic vector fields and to clarify their relation to circle packings. Technological applications are to image analysis and to effective grid generation using discrete conformal mappings. 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. Restricting...

  20. 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.