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Sample records for raav pseudotyped vectors

  1. Molecular design for recombinant adeno-associated virus (rAAV) vector production.

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    Aponte-Ubillus, Juan Jose; Barajas, Daniel; Peltier, Joseph; Bardliving, Cameron; Shamlou, Parviz; Gold, Daniel

    2018-02-01

    Recombinant adeno-associated virus (rAAV) vectors are increasingly popular tools for gene therapy applications. Their non-pathogenic status, low inflammatory potential, availability of viral serotypes with different tissue tropisms, and prospective long-lasting gene expression are important attributes that make rAAVs safe and efficient therapeutic options. Over the last three decades, several groups have engineered recombinant AAV-producing platforms, yielding high titers of transducing vector particles. Current specific productivity yields from different platforms range from 10 3 to 10 5 vector genomes (vg) per cell, and there is an ongoing effort to improve vector yields in order to satisfy high product demands required for clinical trials and future commercialization.Crucial aspects of vector production include the molecular design of the rAAV-producing host cell line along with the design of AAV genes, promoters, and regulatory elements. Appropriately, configuring and balancing the expression of these elements not only contributes toward high productivity, it also improves process robustness and product quality. In this mini-review, the rational design of rAAV-producing expression systems is discussed, with special attention to molecular strategies that contribute to high-yielding, biomanufacturing-amenable rAAV production processes. Details on molecular optimization from four rAAV expression systems are covered: adenovirus, herpesvirus, and baculovirus complementation systems, as well as a recently explored yeast expression system.

  2. An efficient rHSV-based complementation system for the production of multiple rAAV vector serotypes.

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    Kang, W; Wang, L; Harrell, H; Liu, J; Thomas, D L; Mayfield, T L; Scotti, M M; Ye, G J; Veres, G; Knop, D R

    2009-02-01

    Recombinant herpes simplex virus type 1 (rHSV)-assisted recombinant adeno-associated virus (rAAV) vector production provides a highly efficient and scalable method for manufacture of clinical grade rAAV vectors. Here, we present an rHSV co-infection system for rAAV production, which uses two ICP27-deficient rHSV constructs, one bearing the rep2 and cap (1, 2 or 9) genes of rAAV, and the second bearing an AAV2 ITR-gene of interest (GOI) cassette. The optimum rAAV production parameters were defined by producing rAAV2/GFP in HEK293 cells, yielding greater than 9000 infectious particles per cell with a 14:1 DNase resistance particle to infectious particle (DRP/ip) ratio. The optimized co-infection parameters were then used to generate large-scale stocks of rAAV1/AAT, which encode the human alpha-1-antitrypsin (hAAT) protein, and purified by column chromatography. The purified vector was extensively characterized by rAAV- and rHSV-specific assays and compared to transfection-made vector for in vivo efficacy in mice through intramuscular injection. The co-infection method was also used to produce rAAV9/AAT for comparison to rAAV1/AAT in vivo. Intramuscular administration of 1 x 10(11) DRP per animal of rHSV-produced rAAV1/AAT and rAAV9/AAT resulted in hAAT protein expression of 5.4 x 10(4) and 9.4 x 10(5) ng ml(-1) serum respectively, the latter being clinically relevant.

  3. Pseudotyped Lentiviral Vectors for Retrograde Gene Delivery into Target Brain Regions

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    Kenta Kobayashi

    2017-08-01

    Full Text Available Gene transfer through retrograde axonal transport of viral vectors offers a substantial advantage for analyzing roles of specific neuronal pathways or cell types forming complex neural networks. This genetic approach may also be useful in gene therapy trials by enabling delivery of transgenes into a target brain region distant from the injection site of the vectors. Pseudotyping of a lentiviral vector based on human immunodeficiency virus type 1 (HIV-1 with various fusion envelope glycoproteins composed of different combinations of rabies virus glycoprotein (RV-G and vesicular stomatitis virus glycoprotein (VSV-G enhances the efficiency of retrograde gene transfer in both rodent and nonhuman primate brains. The most recently developed lentiviral vector is a pseudotype with fusion glycoprotein type E (FuG-E, which demonstrates highly efficient retrograde gene transfer in the brain. The FuG-E–pseudotyped vector permits powerful experimental strategies for more precisely investigating the mechanisms underlying various brain functions. It also contributes to the development of new gene therapy approaches for neurodegenerative disorders, such as Parkinson’s disease, by delivering genes required for survival and protection into specific neuronal populations. In this review article, we report the properties of the FuG-E–pseudotyped vector, and we describe the application of the vector to neural circuit analysis and the potential use of the FuG-E vector in gene therapy for Parkinson’s disease.

  4. Supramolecular polypseudorotaxane gels for controlled delivery of rAAV vectors in human mesenchymal stem cells for regenerative medicine.

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    Rey-Rico, Ana; Babicz, Heiko; Madry, Henning; Concheiro, Angel; Alvarez-Lorenzo, Carmen; Cucchiarini, Magali

    2017-10-15

    The aim of this work was to investigate, for the first time, the possibility of using supramolecular polypseudorotaxane gels as scaffolds that can durably deliver rAAV vectors for applications in cartilage regeneration. Dispersions of Pluronic ® F68 (PF68) or Tetronic ® 908 (T908) containing either hyaluronic acid (HA) or chondroitin sulfate (CS) were prepared in PBS. Then, alpha-cyclodextrin (αCD) was added to some dispersions to form polypseudorotaxane gels. Polysaccharides and αCD reinforced the viscoelasticity of the gels, which could withstand autoclaving without changes. In vitro release of rAAV vectors and subsequent transduction of human mesenchymal stem cells (hMSCs) by rAAV vectors from the release medium and from gels in direct contact with the cells were investigated. Compared with free vectors, the gels provided higher levels of transgene expression. CS (or HA)/PF68/αCD gels rapidly released rAAV vectors while CS (or HA)/T908/αCD gels provided sustained release probably due to different interactions with the viral vectors. Incorporation of αCD into CS (or HA)/PF68 gels resulted on higher rAAV concentrations and sustained levels of transgene expression over time. HA increased the bioactivity and cytocompatibility of the gels, especially those based on T908. Overall, combining rAAV gene transfer with polypseudorotaxane gels may provide new, promising tools for human tissue engineering and regenerative medicine strategies. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Longevity of rAAV vector and plasmid DNA in blood after intramuscular injection in nonhuman primates: implications for gene doping.

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    Ni, W; Le Guiner, C; Gernoux, G; Penaud-Budloo, M; Moullier, P; Snyder, R O

    2011-07-01

    Legitimate uses of gene transfer technology can benefit from sensitive detection methods to determine vector biodistribution in pre-clinical studies and in human clinical trials, and similar methods can detect illegitimate gene transfer to provide sports-governing bodies with the ability to maintain fairness. Real-time PCR assays were developed to detect a performance-enhancing transgene (erythropoietin, EPO) and backbone sequences in the presence of endogenous cellular sequences. In addition to developing real-time PCR assays, the steps involved in DNA extraction, storage and transport were investigated. By real-time PCR, the vector transgene is distinguishable from the genomic DNA sequence because of the absence of introns, and the vector backbone can be identified by heterologous gene expression control elements. After performance of the assays was optimized, cynomolgus macaques received a single dose by intramuscular (IM) injection of plasmid DNA, a recombinant adeno-associated viral vector serotype 1 (rAAV1) or a rAAV8 vector expressing cynomolgus macaque EPO. Macaques received a high plasmid dose intended to achieve a significant, but not life-threatening, increase in hematocrit. rAAV vectors were used at low doses to achieve a small increase in hematocrit and to determine the limit of sensitivity for detecting rAAV sequences by single-step PCR. DNA extracted from white blood cells (WBCs) was tested to determine whether WBCs can be collaterally transfected by plasmid or transduced by rAAV vectors in this context, and can be used as a surrogate marker for gene doping. We demonstrate that IM injection of a conventional plasmid and rAAV vectors results in the presence of DNA that can be detected at high levels in blood before rapid elimination, and that rAAV genomes can persist for several months in WBCs.

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

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

    2014-01-01

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

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

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

    2014-10-01

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

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

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    Andrea L H Arnett

    2011-11-01

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

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

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    Mayumi Oakland

    2013-01-01

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

  10. Improved Coinfection with Amphotropic Pseudotyped Retroviral Vectors

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    Yuehong Wu

    2009-01-01

    Full Text Available Amphotropic pseudotyped retroviral vectors have typically been used to infect target cells without prior concentration. Although this can yield high rates of infection, higher rates may be needed where highly efficient coinfection of two or more vectors is needed. In this investigation we used amphotropic retroviral vectors produced by the Plat-A cell line and studied coinfection rates using green and red fluorescent proteins (EGFP and dsRed2. Target cells were primary human fibroblasts (PHF and 3T3 cells. Unconcentrated vector preparations produced a coinfection rate of ∼4% (defined as cells that are both red and green as a percentage of all cells infected. Optimized spinoculation, comprising centrifugation at 1200 g for 2 hours at 15∘C, increased the coinfection rate to ∼10%. Concentration by centrifugation at 10,000 g or by flocculation using Polybrene increased the coinfection rate to ∼25%. Combining the two processes, concentration by Polybrene flocculation and optimized spinoculation, increased the coinfection rate to 35% (3T3 or >50% (PHF. Improved coinfection should be valuable in protocols that require high transduction by combinations of two or more retroviral vectors.

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

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    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.

  12. rAAV Vectors as Safe and Efficient Tools for the Stable Delivery of Genes to Primary Human Chondrosarcoma Cells In Vitro and In Situ

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    Henning Madry

    2012-01-01

    Full Text Available Treatment of chondrosarcoma remains a major challenge in orthopaedic oncology. Gene transfer strategies based on recombinant adenoassociated viral (rAAV vectors may provide powerful tools to develop new, efficient therapeutic options against these tumors. In the present study, we tested the hypothesis that rAAV is adapted for a stable and safe delivery of foreign sequences in human chondrosarcoma tissue by transducing primary human chondrosarcoma cells in vitro and in situ with different reporter genes (E. coli lacZ, firefly luc, Discosoma sp. RFP. The effects of rAAV administration upon cell survival and metabolic activities were also evaluated to monitor possibly detrimental effects of the gene transfer method. Remarkably, we provide evidence that efficient and prolonged expression of transgene sequences via rAAV can be safely achieved in all the systems investigated, demonstrating the potential of the approach of direct application of therapeutic gene vectors as a means to treat chondrosarcoma.

  13. The upstream enhancer elements of the G6PC promoter are critical for optimal G6PC expression in murine glycogen storage disease type Ia.

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    Lee, Young Mok; Pan, Chi-Jiunn; Koeberl, Dwight D; Mansfield, Brian C; Chou, Janice Y

    2013-11-01

    Glycogen storage disease type-Ia (GSD-Ia) patients deficient in glucose-6-phosphatase-α (G6Pase-α or G6PC) manifest impaired glucose homeostasis characterized by fasting hypoglycemia, growth retardation, hepatomegaly, nephromegaly, hyperlipidemia, hyperuricemia, and lactic acidemia. Two efficacious recombinant adeno-associated virus pseudotype 2/8 (rAAV8) vectors expressing human G6Pase-α have been independently developed. One is a single-stranded vector containing a 2864-bp of the G6PC promoter/enhancer (rAAV8-GPE) and the other is a double-stranded vector containing a shorter 382-bp minimal G6PC promoter/enhancer (rAAV8-miGPE). To identify the best construct, a direct comparison of the rAAV8-GPE and the rAAV8-miGPE vectors was initiated to determine the best vector to take forward into clinical trials. We show that the rAAV8-GPE vector directed significantly higher levels of hepatic G6Pase-α expression, achieved greater reduction in hepatic glycogen accumulation, and led to a better toleration of fasting in GSD-Ia mice than the rAAV8-miGPE vector. Our results indicated that additional control elements in the rAAV8-GPE vector outweigh the gains from the double-stranded rAAV8-miGPE transduction efficiency, and that the rAAV8-GPE vector is the current choice for clinical translation in human GSD-Ia. © 2013.

  14. Effective genetic modification and differentiation of hMSCs upon controlled release of rAAV vectors using alginate/poloxamer composite systems.

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    Díaz-Rodríguez, P; Rey-Rico, A; Madry, H; Landin, M; Cucchiarini, M

    2015-12-30

    Viral vectors are common tools in gene therapy to deliver foreign therapeutic sequences in a specific target population via their natural cellular entry mechanisms. Incorporating such vectors in implantable systems may provide strong alternatives to conventional gene transfer procedures. The goal of the present study was to generate different hydrogel structures based on alginate (AlgPH155) and poloxamer PF127 as new systems to encapsulate and release recombinant adeno-associated viral (rAAV) vectors. Inclusion of rAAV in such polymeric capsules revealed an influence of the hydrogel composition and crosslinking temperature upon the vector release profiles, with alginate (AlgPH155) structures showing the fastest release profiles early on while over time vector release was more effective from AlgPH155+PF127 [H] capsules crosslinked at a high temperature (50°C). Systems prepared at room temperature (AlgPH155+PF127 [C]) allowed instead to achieve a more controlled release profile. When tested for their ability to target human mesenchymal stem cells, the different systems led to high transduction efficiencies over time and to gene expression levels in the range of those achieved upon direct vector application, especially when using AlgPH155+PF127 [H]. No detrimental effects were reported on either cell viability or on the potential for chondrogenic differentiation. Inclusion of PF127 in the capsules was also capable of delaying undesirable hypertrophic cell differentiation. These findings are of promising value for the further development of viral vector controlled release strategies. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Novel strategy for generation and titration of recombinant adeno-associated virus vectors.

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    Shiau, Ai-Li; Liu, Pu-Ste; Wu, Chao-Liang

    2005-01-01

    Recombinant adeno-associated virus (rAAV) vectors have many advantages for gene therapeutic applications compared with other vector systems. Several methods that use plasmids or helper viruses have been reported for the generation of rAAV vectors. Unfortunately, the preparation of large-scale rAAV stocks is labor-intensive. Moreover, the biological titration of rAAV is still difficult, which may limit its preclinical and clinical applications. For this study, we developed a novel strategy to generate and biologically titrate rAAV vectors. A recombinant pseudorabies virus (PrV) with defects in its gD, gE, and thymidine kinase genes was engineered to express the AAV rep and cap genes, yielding PS virus, which served as a packaging and helper virus for the generation of rAAV vectors. PS virus was useful not only for generating high-titer rAAV vectors by cotransfection with an rAAV vector plasmid, but also for amplifying rAAV stocks. Notably, the biological titration of rAAV vectors was also feasible when cells were coinfected with rAAV and PS virus. Based on this strategy, we produced an rAAV that expresses prothymosin alpha (ProT). Expression of the ProT protein in vitro and in vivo mediated by rAAV/ProT gene transfer was detected by immunohistochemistry and a bioassay. Taken together, our results demonstrate that the PrV vector-based system is useful for generating rAAV vectors carrying various transgenes.

  16. Unrestricted Hepatocyte Transduction with Adeno-Associated Virus Serotype 8 Vectors in Mice

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    Nakai, Hiroyuki; Fuess, Sally; Storm, Theresa A.; Muramatsu, Shin-ichi; Nara, Yuko; Kay, Mark A.

    2005-01-01

    Recombinant adeno-associated virus (rAAV) vectors can mediate long-term stable transduction in various target tissues. However, with rAAV serotype 2 (rAAV2) vectors, liver transduction is confined to only a small portion of hepatocytes even after administration of extremely high vector doses. In order to investigate whether rAAV vectors of other serotypes exhibit similar restricted liver transduction, we performed a dose-response study by injecting mice with β-galactosidase-expressing rAAV1 and rAAV8 vectors via the portal vein. The rAAV1 vector showed a blunted dose-response similar to that of rAAV2 at high doses, while the rAAV8 vector dose-response remained unchanged at any dose and ultimately could transduce all the hepatocytes at a dose of 7.2 × 1012 vector genomes/mouse without toxicity. This indicates that all hepatocytes have the ability to process incoming single-stranded vector genomes into duplex DNA. A single tail vein injection of the rAAV8 vector was as efficient as portal vein injection at any dose. In addition, intravascular administration of the rAAV8 vector at a high dose transduced all the skeletal muscles throughout the body, including the diaphragm, the entire cardiac muscle, and substantial numbers of cells in the pancreas, smooth muscles, and brain. Thus, rAAV8 is a robust vector for gene transfer to the liver and provides a promising research tool for delivering genes to various target organs. In addition, the rAAV8 vector may offer a potential therapeutic agent for various diseases affecting nonhepatic tissues, but great caution is required for vector spillover and tight control of tissue-specific gene expression. PMID:15596817

  17. Efficient transduction of equine adipose-derived mesenchymal stem cells by VSV-G pseudotyped lentiviral vectors.

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    Petersen, Gayle F; Hilbert, Bryan; Trope, Gareth; Kalle, Wouter; Strappe, Padraig

    2014-12-01

    Equine adipose-derived mesenchymal stem cells (EADMSC) provide a unique cell-based approach for treatment of a variety of equine musculoskeletal injuries, via regeneration of diseased or damaged tissue, or the secretion of immunomodulatory molecules. These capabilities can be further enhanced by genetic modification using lentiviral vectors, which provide a safe and efficient method of gene delivery. We investigated the suitability of lentiviral vector technology for gene delivery into EADMSC, using GFP expressing lentiviral vectors pseudotyped with the G glycoprotein from the vesicular stomatitis virus (V-GFP) or, for the first time, the baculovirus gp64 envelope protein (G-GFP). In this study, we produced similarly high titre V-GFP and G-GFP lentiviral vectors. Flow cytometric analysis showed efficient transduction using V-GFP; however G-GFP exhibited a poor ability to transduce EADMSC. Transduction resulted in sustained GFP expression over four passages, with minimal effects on cell viability and doubling time, and an unaltered chondrogenic differentiation potential. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Cell-cell transmission of VSV-G pseudotyped lentivector particles.

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    Amy M Skinner

    Full Text Available Many replicating viruses, including HIV-1 and HTLV-1, are efficiently transmitted from the cell surface of actively infected cells upon contact with bystander cells. In a previous study, we reported the prolonged cell surface retention of VSV-G replication-deficient pseudotyped lentivector prior to endocytic entry. However, the competing kinetics of cell surface versus dissociation, neutralization or direct transfer to other cells have received comparatively little attention. Here we demonstrate that the relative efficiency of cell-cell surface transmission can outpace "cell-free" transduction at limiting vector input. This coincides with the prolonged half-life of cell bound vector but occurs, unlike HTLV-1, without evidence for particle aggregation. These studies suggest that cell-surface attachment stabilizes particles and alters neutralization kinetics. Our experiments provide novel insight into the underexplored cell-cell transmission of pseudotyped particles.

  19. Comparison of Serum rAAV Serotype-Specific Antibodies in Patients with Duchenne Muscular Dystrophy, Becker Muscular Dystrophy, Inclusion Body Myositis, or GNE Myopathy.

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    Zygmunt, Deborah A; Crowe, Kelly E; Flanigan, Kevin M; Martin, Paul T

    2017-09-01

    Recombinant adeno-associated virus (rAAV) is a commonly used gene therapy vector for the delivery of therapeutic transgenes in a variety of human diseases, but pre-existing serum antibodies to viral capsid proteins can greatly inhibit rAAV transduction of tissues. Serum was assayed from patients with Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), inclusion body myositis (IBM), and GNE myopathy (GNE). These were compared to serum from otherwise normal human subjects to determine the extent of pre-existing serum antibodies to rAAVrh74, rAAV1, rAAV2, rAAV6, rAAV8, and rAAV9. In almost all cases, patients with measurable titers to one rAAV serotype showed titers to all other serotypes tested, with average titers to rAAV2 being highest in all instances. Twenty-six percent of all young normal subjects (18 years old). Fifty percent of all IBM and GNE patients also had antibody titers to all rAAV serotypes, while only 18% of DMD and 0% of BMD patients did. In addition, serum-naïve macaques treated systemically with rAAVrh74 could develop cross-reactive antibodies to all other serotypes tested at 24 weeks post treatment. These data demonstrate that most DMD and BMD patients should be amenable to vascular rAAV-mediated treatment without the concern of treatment blockage by pre-existing serum rAAV antibodies, and that serum antibodies to rAAVrh74 are no more common than those for rAAV6, rAAV8, or rAAV9.

  20. High-titer recombinant adeno-associated virus production utilizing a recombinant herpes simplex virus type I vector expressing AAV-2 Rep and Cap.

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    Conway, J E; Rhys, C M; Zolotukhin, I; Zolotukhin, S; Muzyczka, N; Hayward, G S; Byrne, B J

    1999-06-01

    Recombinant adeno-associated virus type 2 (rAAV) vectors have recently been used to achieve long-term, high level transduction in vivo. Further development of rAAV vectors for clinical use requires significant technological improvements in large-scale vector production. In order to facilitate the production of rAAV vectors, a recombinant herpes simplex virus type I vector (rHSV-1) which does not produce ICP27, has been engineered to express the AAV-2 rep and cap genes. The optimal dose of this vector, d27.1-rc, for AAV production has been determined and results in a yield of 380 expression units (EU) of AAV-GFP produced from 293 cells following transfection with AAV-GFP plasmid DNA. In addition, d27.1-rc was also efficient at producing rAAV from cell lines that have an integrated AAV-GFP provirus. Up to 480 EU/cell of AAV-GFP could be produced from the cell line GFP-92, a proviral, 293 derived cell line. Effective amplification of rAAV vectors introduced into 293 cells by infection was also demonstrated. Passage of rAAV with d27. 1-rc results in up to 200-fold amplification of AAV-GFP with each passage after coinfection of the vectors. Efficient, large-scale production (>109 cells) of AAV-GFP from a proviral cell line was also achieved and these stocks were free of replication-competent AAV. The described rHSV-1 vector provides a novel, simple and flexible way to introduce the AAV-2 rep and cap genes and helper virus functions required to produce high-titer rAAV preparations from any rAAV proviral construct. The efficiency and potential for scalable delivery of d27.1-rc to producer cell cultures should facilitate the production of sufficient quantities of rAAV vectors for clinical application.

  1. A novel and highly efficient production system for recombinant adeno-associated virus vector.

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    Wu, Zhijian; Wu, Xiaobing; Cao, Hui; Dong, Xiaoyan; Wang, Hong; Hou, Yunde

    2002-02-01

    Recombinant adeno-associated virus (rAAV) has proven to be a promising gene delivery vector for human gene therapy. However, its application has been limited by difficulty in obtaining enough quantities of high-titer vector stocks. In this paper, a novel and highly efficient production system for rAAV is described. A recombinant herpes simplex virus type 1 (rHSV-1) designated HSV1-rc/DeltaUL2, which expressed adeno-associated virus type2 (AAV-2) Rep and Cap proteins, was constructed previously. The data confirmed that its functions were to support rAAV replication and packaging, and the generated rAAV was infectious. Meanwhile, an rAAV proviral cell line designated BHK/SG2, which carried the green fluorescent protein (GFP) gene expression cassette, was established by transfecting BHK-21 cells with rAAV vector plasmid pSNAV-2-GFP. Infecting BHK/SG2 with HSV1-rc/DeltaUL2 at an MOI of 0.1 resulted in the optimal yields of rAAV, reaching 250 transducing unit (TU) or 4.28x10(4) particles per cell. Therefore, compared with the conventional transfection method, the yield of rAAV using this "one proviral cell line, one helper virus" strategy was increased by two orders of magnitude. Large-scale production of rAAV can be easily achieved using this strategy and might meet the demands for clinical trials of rAAV-mediated gene therapy.

  2. 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.

  3. 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.

  4. Murine Leukemia Virus (MLV)-based Coronavirus Spike-pseudotyped Particle Production and Infection

    Science.gov (United States)

    Millet, Jean Kaoru; Whittaker, Gary R.

    2016-01-01

    Viral pseudotyped particles (pp) are enveloped virus particles, typically derived from retroviruses or rhabdoviruses, that harbor heterologous envelope glycoproteins on their surface and a genome lacking essential genes. These synthetic viral particles are safer surrogates of native viruses and acquire the tropism and host entry pathway characteristics governed by the heterologous envelope glycoprotein used. They have proven to be very useful tools used in research with many applications, such as enabling the study of entry pathways of enveloped viruses and to generate effective gene-delivery vectors. The basis for their generation lies in the capacity of some viruses, such as murine leukemia virus (MLV), to incorporate envelope glycoproteins of other viruses into a pseudotyped virus particle. These can be engineered to contain reporter genes such as luciferase, enabling quantification of virus entry events upon pseudotyped particle infection with susceptible cells. Here, we detail a protocol enabling generation of MLV-based pseudotyped particles, using the Middle East respiratory syndrome coronavirus (MERS-CoV) spike (S) as an example of a heterologous envelope glycoprotein to be incorporated. We also describe how these particles are used to infect susceptible cells and to perform a quantitative infectivity readout by a luciferase assay. PMID:28018942

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

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    Akikazu Ishihara

    2012-01-01

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

  6. Development and applications of VSV vectors based on cell tropism

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    Hideki eTani

    2012-01-01

    Full Text Available Viral vectors have been available in various fields such as medical and biological research or gene therapy applications. Targeting vectors pseudotyped with distinct viral envelope proteins that influence cell tropism and transfection efficiency is a useful tool not only for examining entry mechanisms or cell tropisms but also for vaccine vector development. Vesicular stomatitis virus (VSV is an excellent candidate for development as a pseudotype vector. A recombinant VSV lacking its own envelope (G gene has been used to produce a pseudotype or recombinant VSV possessing the envelope proteins of heterologous viruses. These viruses possess a reporter gene instead of a VSV G gene in their genome, and therefore it is easy to evaluate their infectivity in the study of viral entry, including identification of viral receptors. Furthermore, advantage can be taken of a property of the pseudotype VSV, which is competence for single-round infection, in handling many different viruses that are either difficult to amplify in cultured cells or animals or that require specialized containment facilities. Here we describe procedures for producing pseudotype or recombinant VSVs and a few of the more prominent examples from among envelope viruses, such as hepatitis C virus, Japanese encephalitis virus, baculovirus, and hemorrhagic fever viruses.

  7. Intrathecal long-term gene expression by self-complementary adeno-associated virus type 1 suitable for chronic pain studies in rats

    Directory of Open Access Journals (Sweden)

    Janssen William GM

    2006-01-01

    Full Text Available Abstract Background Intrathecal (IT gene transfer is an attractive approach for targeting spinal mechanisms of nociception but the duration of gene expression achieved by reported methods is short (up to two weeks impairing their utility in the chronic pain setting. The overall goal of this study was to develop IT gene transfer yielding true long-term transgene expression defined as ≥ 3 mo following a single vector administration. We defined "IT" administration as atraumatic injection into the lumbar cerebrospinal fluid (CSF modeling a lumbar puncture. Our studies focused on recombinant adeno-associated virus (rAAV, one of the most promising vector types for clinical use. Results Conventional single stranded rAAV2 vectors performed poorly after IT delivery in rats. Pseudotyping of rAAV with capsids of serotypes 1, 3, and 5 was tested alone or in combination with a modification of the inverted terminal repeat. The former alters vector tropism and the latter allows packaging of self-complementary rAAV (sc-rAAV vectors. Combining both types of modification led to the identification of sc-rAAV2/l as a vector that performed superiorly in the IT space. IT delivery of 3 × 10e9 sc-rAAV2/l particles per animal led to stable expression of enhanced green fluorescent protein (EGFP for ≥ 3 mo detectable by Western blotting, quantitative PCR, and in a blinded study by confocal microscopy. Expression was strongest in the cauda equina and the lower sections of the spinal cord and only minimal in the forebrain. Microscopic examination of the SC fixed in situ with intact nerve roots and meninges revealed strong EGFP fluorescence in the nerve roots. Conclusion sc-rAAVl mediates stable IT transgene expression for ≥ 3 mo. Our findings support the underlying hypothesis that IT target cells for gene transfer lack the machinery for efficient conversion of the single-stranded rAAV genome into double-stranded DNA and favor uptake of serotype 1 vectors over 2

  8. Process optimization of large-scale production of recombinant adeno-associated vectors using dielectric spectroscopy.

    Science.gov (United States)

    Negrete, Alejandro; Esteban, Geoffrey; Kotin, Robert M

    2007-09-01

    A well-characterized manufacturing process for the large-scale production of recombinant adeno-associated vectors (rAAV) for gene therapy applications is required to meet current and future demands for pre-clinical and clinical studies and potential commercialization. Economic considerations argue in favor of suspension culture-based production. Currently, the only feasible method for large-scale rAAV production utilizes baculovirus expression vectors and insect cells in suspension cultures. To maximize yields and achieve reproducibility between batches, online monitoring of various metabolic and physical parameters is useful for characterizing early stages of baculovirus-infected insect cells. In this study, rAAVs were produced at 40-l scale yielding ~1 x 10(15) particles. During the process, dielectric spectroscopy was performed by real time scanning in radio frequencies between 300 kHz and 10 MHz. The corresponding permittivity values were correlated with the rAAV production. Both infected and uninfected reached a maximum value; however, only infected cell cultures permittivity profile reached a second maximum value. This effect was correlated with the optimal harvest time for rAAV production. Analysis of rAAV indicated the harvesting time around 48 h post-infection (hpi), and 72 hpi produced similar quantities of biologically active rAAV. Thus, if operated continuously, the 24-h reduction in the production process of rAAV gives sufficient time for additional 18 runs a year corresponding to an extra production of ~2 x 10(16) particles. As part of large-scale optimization studies, this new finding will facilitate the bioprocessing scale-up of rAAV and other bioproducts.

  9. Production of recombinant AAV vectors encoding insulin-like growth factor I is enhanced by interaction among AAV rep regulatory sequences

    Directory of Open Access Journals (Sweden)

    Dilley Robert

    2009-01-01

    Full Text Available Abstract Background Adeno-associated virus (AAV vectors are promising tools for gene therapy. Currently, their potential is limited by difficulties in producing high vector yields with which to generate transgene protein product. AAV vector production depends in part upon the replication (Rep proteins required for viral replication. We tested the hypothesis that mutations in the start codon and upstream regulatory elements of Rep78/68 in AAV helper plasmids can regulate recombinant AAV (rAAV vector production. We further tested whether the resulting rAAV vector preparation augments the production of the potentially therapeutic transgene, insulin-like growth factor I (IGF-I. Results We constructed a series of AAV helper plasmids containing different Rep78/68 start codon in combination with different gene regulatory sequences. rAAV vectors carrying the human IGF-I gene were prepared with these vectors and the vector preparations used to transduce HT1080 target cells. We found that the substitution of ATG by ACG in the Rep78/68 start codon in an AAV helper plasmid (pAAV-RC eliminated Rep78/68 translation, rAAV and IGF-I production. Replacement of the heterologous sequence upstream of Rep78/68 in pAAV-RC with the AAV2 endogenous p5 promoter restored translational activity to the ACG mutant, and restored rAAV and IGF-I production. Insertion of the AAV2 p19 promoter sequence into pAAV-RC in front of the heterologous sequence also enabled ACG to function as a start codon for Rep78/68 translation. The data further indicate that the function of the AAV helper construct (pAAV-RC, that is in current widespread use for rAAV production, may be improved by replacement of its AAV2 unrelated heterologous sequence with the native AAV2 p5 promoter. Conclusion Taken together, the data demonstrate an interplay between the start codon and upstream regulatory sequences in the regulation of Rep78/68 and indicate that selective mutations in Rep78/68 regulatory elements

  10. Methods of treating Parkinson's disease using viral vectors

    Energy Technology Data Exchange (ETDEWEB)

    Bankiewicz, Krystof; Cunningham, Janet

    2016-11-15

    Methods of delivering viral vectors, particularly recombinant adeno-associated virus (rAAV) virions, to the central nervous system (CNS) using convection enhanced delivery (CED) are provided. The rAAV virions include a nucleic acid sequence encoding a therapeutic polypeptide. The methods can be used for treating CNS disorders such as for treating Parkinson's Disease.

  11. Complement inhibition enables tumor delivery of LCMV glycoprotein pseudotyped viruses in the presence of antiviral antibodies

    Directory of Open Access Journals (Sweden)

    Laura Evgin

    2016-01-01

    Full Text Available The systemic delivery of therapeutic viruses, such as oncolytic viruses or vaccines, is limited by the generation of neutralizing antibodies. While pseudotyping of rhabdoviruses with the lymphocytic choriomeningitis virus glycoprotein has previously allowed for multiple rounds of delivery in mice, this strategy has not translated to other animal models. For the first time, we provide experimental evidence that antibodies generated against the lymphocytic choriomeningitis virus glycoprotein mediate robust complement-dependent viral neutralization via activation of the classical pathway. We show that this phenotype can be capitalized upon to deliver maraba virus pseudotyped with the lymphocytic choriomeningitis virus glycoprotein in a Fischer rat model in the face of neutralizing antibody through the use of complement modulators. This finding changes the understanding of the humoral immune response to arenaviruses, and also describes methodology to deliver viral vectors to their therapeutic sites of action without the interference of neutralizing antibody.

  12. Deletion of the B-B' and C-C' regions of inverted terminal repeats reduces rAAV productivity but increases transgene expression.

    Science.gov (United States)

    Zhou, Qingzhang; Tian, Wenhong; Liu, Chunguo; Lian, Zhonghui; Dong, Xiaoyan; Wu, Xiaobing

    2017-07-14

    Inverted terminal repeats (ITRs) of the adeno-associated virus (AAV) are essential for rescue, replication, packaging, and integration of the viral genome. While ITR mutations have been identified in previous reports, we designed a new truncated ITR lacking the B-B' and C-C' regions named as ITRΔBC and investigated its effects on viral genome replication, packaging, and expression of recombinant AAV (rAAV). The packaging ability was compared between ITRΔBC rAAV and wild-type (wt) ITR rAAV. Our results showed the productivity of ITRΔBC rAAV was reduced 4-fold, which is consistent with the 8-fold decrease in the replication of viral genomic DNA of ITRΔBC rAAV compared with wt ITR rAAV. Surprisingly, transgene expression was significantly higher for ITRΔBC rAAV. A preliminary exploration of the underlying mechanisms was carried out by inhibiting and degrading the ataxia telangiectasia mutated (ATM) protein and the Mre11 complex (MRN), respectively, since the rAAV expression was inhibited by the ATM and/or MRN through cis interaction or binding with wt ITRs. We demonstrated that the inhibitory effects were weakened on ITRΔBC rAAV expression. This study suggests deletion in ITR can affect the transgene expression of AAV, which provides a new way to improve the AAV expression through ITRs modification.

  13. Neutralization epitopes on HIV pseudotyped with HTLV-I: Conservation of carbohydrate Epitopes

    DEFF Research Database (Denmark)

    Sørensen, A M; Nielsen, C; Arendrup, M

    1994-01-01

    One mechanism for expanding the cellular tropism of human immunodeficiency virus (HIV) in vitro is through formation of phenotypically mixed particles (pseudotypes) with human T lymphotropic virus type I (HTLV-I). In this study we found that pseudotypes allow penetration of HIV particles into CD4......-negative cells, previously nonsusceptible to HIV infection. The infection of CD4-negative cells with pseudotypes could be blocked with anti-HTLV-I serum but failed to be significantly inhibited with anti-HIV serum or a V3-neutralizing anti-gp120 monoclonal antibody. This may represent a possibility...... by cell-free pseudotypes in CD4-negative cells. We suggest that although viral cofactors might expand the tropism of HIV in vivo, HIV and HTLV-I seem to induce common carbohydrate neutralization epitopes....

  14. Neutralization epitopes on HIV pseudotyped with HTLV-I: conservation of carbohydrate epitopes

    DEFF Research Database (Denmark)

    Sørensen, A M; Nielsen, C; Arendrup, M

    1994-01-01

    One mechanism for expanding the cellular tropism of human immunodeficiency virus (HIV) in vitro is through formation of phenotypically mixed particles (pseudotypes) with human T lymphotropic virus type I (HTLV-I). In this study we found that pseudotypes allow penetration of HIV particles into CD4......-negative cells, previously nonsusceptible to HIV infection. The infection of CD4-negative cells with pseudotypes could be blocked with anti-HTLV-I serum but failed to be significantly inhibited with anti-HIV serum or a V3-neutralizing anti-gp120 monoclonal antibody. This may represent a possibility...... by cell-free pseudotypes in CD4-negative cells. We suggest that although viral cofactors might expand the tropism of HIV in vivo, HIV and HTLV-I seem to induce common carbohydrate neutralization epitopes....

  15. Delivery and evaluation of recombinant adeno-associated viral vectors in the equine distal extremity for the treatment of laminitis.

    Science.gov (United States)

    Mason, J B; Gurda, B L; Van Wettere, A; Engiles, J B; Wilson, J M; Richardson, D W

    2017-01-01

    Our long-term aim is to develop a gene therapy approach for the prevention of laminitis in the contralateral foot of horses with major musculoskeletal injuries and non-weightbearing lameness. The goal of this study was to develop a practical method to efficiently deliver therapeutic proteins deep within the equine foot. Randomised in vivo experiment. We used recombinant adeno-associated viral vectors (rAAVs) to deliver marker genes using regional limb perfusion through the palmar digital artery of the horse. Vector serotypes rAAV2/1, 2/8 and 2/9 all successfully transduced equine foot tissues and displayed similar levels and patterns of transduction. The regional distribution of transduction within the foot decreased with decreasing vector dose. The highest transduction values were seen in the sole and coronary regions and the lowest transduction values were detected in the dorsal hoof-wall region. The use of a surfactant-enriched vector diluent increased regional distribution of the vector and improved the transduction in the hoof-wall region. The hoof-wall region of the foot, which exhibited the lowest levels of transduction using saline as the vector diluent, displayed a dramatic increase in transduction when surfactant was included in the vector diluent (9- to 81-fold increase). In transduced tissues, no significant difference was observed between promoters (chicken β-actin vs. cytomegalovirus) for gene expression. All horses tested for vector-neutralising antibodies were positive for serotype-specific neutralising antibodies to rAAV2/5. The current experiments demonstrate that transgenes can be successfully delivered to the equine distal extremity using rAAV vectors and that serotypes 2/8, 2/9 and 2/1 can successfully transduce tissues of the equine foot. When the vector was diluted with surfactant-containing saline, the level of transduction increased dramatically. The increased level of transduction due to the addition of surfactant also improved the

  16. Sindbis Virus-Pseudotyped Lentiviral Vectors Carrying VEGFR2-Specific Nanobody for Potential Transductional Targeting of Tumor Vasculature.

    Science.gov (United States)

    Ahani, Roshank; Roohvand, Farzin; Cohan, Reza Ahangari; Etemadzadeh, Mohammad Hossein; Mohajel, Nasir; Behdani, Mahdi; Shahosseini, Zahra; Madani, Navid; Azadmanesh, Kayhan

    2016-11-01

    Introduction of selectivity/specificity into viral-based gene delivery systems, such as lentiviral vectors (LVs), is crucial in their systemic administration for cancer gene therapy. The pivotal role of tumor-associated endothelial cells (TAECs) in tumor angiogenesis and overexpression of vascular endothelial growth factor receptor-2 (VEGFR2 or KDR) in TAECs makes them a potent target in cancer treatment. Herein, we report the development of VEGFR2-targeted LVs pseudotyped with chimeric sindbis virus E2 glycoprotein (cSVE2s). For this purpose, either sequence of a VEGFR2-specific nanobody or its natural ligand (VEGF 121 ) was inserted into the binding site of sindbis virus E2 glycoprotein. In silico modeling data suggested that the inserted targeting motifs were exposed in the context of cSVE2s. Western blot analysis of LVs indicated the incorporation of cSVE2s into viral particles. Capture ELISA demonstrated the specificity/functionality of the incorporated cSVE2s. Transduction of 293/KDR (expressing VEGFR2) or 293T cells (negative control) by constructed LVs followed by fluorescent microscopy and flow cytometric analyses indicated selective transduction of 293/KDR cells (30 %) by both targeting motifs compared to 293T control cells (1-2 %). These results implied similar targeting properties of VEGFR2-specific nanobody compared to the VEGF 121 and indicated the potential for transductional targeting of tumor vasculature by the nanobody displaying LVs.

  17. An adeno-associated viral vector transduces the rat hypothalamus and amygdala more efficient than a lentiviral vector

    Directory of Open Access Journals (Sweden)

    Vreugdenhil Erno

    2010-07-01

    Full Text Available Abstract Background This study compared the transduction efficiencies of an adeno-associated viral (AAV vector, which was pseudotyped with an AAV1 capsid and encoded the green fluorescent protein (GFP, with a lentiviral (LV vector, which was pseudotyped with a VSV-G envelop and encoded the discosoma red fluorescent protein (dsRed, to investigate which viral vector transduced the lateral hypothalamus or the amygdala more efficiently. The LV-dsRed and AAV1-GFP vector were mixed and injected into the lateral hypothalamus or into the amygdala of adult rats. The titers that were injected were 1 × 108 or 1 × 109 genomic copies of AAV1-GFP and 1 × 105 transducing units of LV-dsRed. Results Immunostaining for GFP and dsRed showed that AAV1-GFP transduced significantly more cells than LV-dsRed in both the lateral hypothalamus and the amygdala. In addition, the number of LV particles that were injected can not easily be increased, while the number of AAV1 particles can be increased easily with a factor 100 to 1000. Both viral vectors appear to predominantly transduce neurons. Conclusions This study showed that AAV1 vectors are better tools to overexpress or knockdown genes in the lateral hypothalamus and amygdala of adult rats, since more cells can be transduced with AAV1 than with LV vectors and the titer of AAV1 vectors can easily be increased to transduce the area of interest.

  18. Differential diagnosis of feline leukemia virus subgroups using pseudotype viruses expressing green fluorescent protein.

    Science.gov (United States)

    Nakamura, Megumi; Sato, Eiji; Miura, Tomoyuki; Baba, Kenji; Shimoda, Tetsuya; Miyazawa, Takayuki

    2010-06-01

    Feline leukemia virus (FeLV) is classified into three receptor interference subgroups, A, B and C. In this study, to differentiate FeLV subgroups, we developed a simple assay system using pseudotype viruses expressing green fluorescent protein (GFP). We prepared gfp pseudotype viruses, named gfp(FeLV-A), gfp(FeLV-B) and gfp(FeLV-C) harboring envelopes of FeLV-A, B and C, respectively. The gfp pseudotype viruses completely interfered with the same subgroups of FeLV reference strains on FEA cells (a feline embryonic fibroblast cell line). We also confirmed that the pseudotype viruses could differentiate FeLV subgroups in field isolates. The assay will be useful for differential diagnosis of FeLV subgroups in veterinary diagnostic laboratories in the future.

  19. Lentiviral Vector Gene Transfer to Porcine Airways

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    Patrick L Sinn

    2012-01-01

    Full Text Available In this study, we investigated lentiviral vector development and transduction efficiencies in well-differentiated primary cultures of pig airway epithelia (PAE and wild-type pigs in vivo. We noted gene transfer efficiencies similar to that observed for human airway epithelia (HAE. Interestingly, feline immunodeficiency virus (FIV-based vectors transduced immortalized pig cells as well as pig primary cells more efficiently than HIV-1–based vectors. PAE express TRIM5α, a well-characterized species-specific lentiviral restriction factor. We contrasted the restrictive properties of porcine TRIM5α against FIV- and HIV-based vectors using gain and loss of function approaches. We observed no effect on HIV-1 or FIV conferred transgene expression in response to porcine TRIM5α overexpression or knockdown. To evaluate the ability of GP64-FIV to transduce porcine airways in vivo, we delivered vector expressing mCherry to the tracheal lobe of the lung and the ethmoid sinus of 4-week-old pigs. One week later, epithelial cells expressing mCherry were readily detected. Our findings indicate that pseudotyped FIV vectors confer similar tropisms in porcine epithelia as observed in human HAE and provide further support for the selection of GP64 as an appropriate envelope pseudotype for future preclinical gene therapy studies in the porcine model of cystic fibrosis (CF.

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

    LENUS (Irish Health Repository)

    Flotte, Terence R

    2011-10-01

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

  1. Remodelling of human osteoarthritic cartilage by FGF-2, alone or combined with Sox9 via rAAV gene transfer.

    Science.gov (United States)

    Cucchiarini, Magali; Terwilliger, Ernest F; Kohn, Dieter; Madry, Henning

    2009-08-01

    Compensating for the loss of extracellular cartilage matrix, as well as counteracting the alterations of the chondrocyte phenotype in osteoarthritis are of key importance to develop effective therapeutic strategies against this disorder. In the present study, we analysed the benefits of applying a potent gene combination to remodel human osteoarthritic (OA) cartilage. We employed the promising recombinant adeno-associated virus (rAAV) vector to deliver the mitogenic fibroblast growth factor 2 (FGF-2) factor, alone or simultaneously with the transcription factor Sox9 as a key activator of matrix synthesis, to human normal and OA articular chondrocytes. We evaluated the effects of single (FGF-2) or combined (FGF-2/SOX9) transgene expression upon the regenerative activities of chondrocytes in three dimensional cultures in vitro and in cartilage explants in situ. Single overexpression of FGF-2 enhanced the survival and proliferation of both normal and OA chondrocytes, without stimulating the matrix synthetic processes in the increased pools of cells. The mitogenic properties of FGF-2 were maintained when SOX9 was co-overexpressed and concomitant with an increase in the production of proteoglycans and type-II collagen, suggesting that the transcription factor was capable of counterbalancing the effects of FGF-2 on matrix accumulation. Also important, expression of type-X collagen, a marker of hypertrophy strongly decreased following treatment by the candidate vectors. Most remarkably, the levels of activities achieved in co-treated human OA cartilage were similar to or higher than those observed in normal cartilage. The present findings show that combined expression of candidate factors in OA cartilage can re-establish key features of normal cartilage and prevent the pathological shift of metabolic homeostasis. These data provide further motivation to develop coupled gene transfer approaches via rAAV for the treatment of human OA.

  2. Empty virions in AAV8 vector preparations reduce transduction efficiency and may cause total viral particle dose-limiting side effects

    Directory of Open Access Journals (Sweden)

    Kai Gao

    2014-01-01

    Full Text Available Empty virions are inadvertent by-products of recombinant adeno-associated virus (rAAV packaging process, resulting in vector lots with mixtures of full and empty virions at variable ratios. Impact of empty virions on the efficiency and side effects of rAAV transduction has not been well characterized. Here, we generated partially and completely empty AAV8 virions, fully packaged rAAV8 lots, and mixtures of empty and fully packaged virions with variable ratios of empty virions. The aforementioned dosing formulations of rAAV8 expressing either cellular (EGFP (enhanced green fluorescent protein or nuclear-targeted (n LacZ or secreted (human α1-antitrypsin (hA1AT reporter genes were intravenously injected into two different mouse strains, followed by analyses of transgene expressions and serum alanine aminotransferase (ALT levels at different time points. We found that addition of empty particles to the fixed doses of rAAV8 preparations repressed liver transduction up to 64% (serum hA1AT and 44% (nLacZ in C57BL/6 mice, respectively. The similar trend in inhibiting EGFP expression together with concurrent elevations of serum ALT levels were observed in the BALB/c mice, indicating that empty particles may also exacerbate side effects of rAAV8 EGFP transduction. Our results suggest that removal of empty particles from rAAV preparations may improve efficacy and safety of AAV in clinical applications.

  3. Effective in vivo and ex vivo gene transfer to intestinal mucosa by VSV-G-pseudotyped lentiviral vectors

    Directory of Open Access Journals (Sweden)

    Kasahara Noriyuki

    2010-05-01

    Full Text Available Abstract Background Gene transfer to the gastrointestinal (GI mucosa is a therapeutic strategy which could prove particularly advantageous for treatment of various hereditary and acquired intestinal disorders, including inflammatory bowel disease (IBD, GI infections, and cancer. Methods We evaluated vesicular stomatitis virus glycoprotein envelope (VSV-G-pseudotyped lentiviral vectors (LV for efficacy of gene transfer to both murine rectosigmoid colon in vivo and human colon explants ex vivo. LV encoding beta-galactosidase (LV-β-Gal or firefly-luciferase (LV-fLuc reporter genes were administered by intrarectal instillation in mice, or applied topically for ex vivo transduction of human colorectal explant tissues from normal individuals. Macroscopic and histological evaluations were performed to assess any tissue damage or inflammation. Transduction efficiency and systemic biodistribution were evaluated by real-time quantitative PCR. LV-fLuc expression was evaluated by ex vivo bioluminescence imaging. LV-β-Gal expression and identity of transduced cell types were examined by histochemical and immunofluorescence staining. Results Imaging studies showed positive fLuc signals in murine distal colon; β-Gal-positive cells were found in both murine and human intestinal tissue. In the murine model, β-Gal-positive epithelial and lamina propria cells were found to express cytokeratin, CD45, and CD4. LV-transduced β-Gal-positive cells were also seen in human colorectal explants, consisting mainly of CD45, CD4, and CD11c-positive cells confined to the LP. Conclusions We have demonstrated the feasibility of LV-mediated gene transfer into colonic mucosa. We also identified differential patterns of mucosal gene transfer dependent on whether murine or human tissue was used. Within the limitations of the study, the LV did not appear to induce mucosal damage and were not distributed beyond the distal colon.

  4. RD-MolPack technology for the constitutive production of self-inactivating lentiviral vectors pseudotyped with the nontoxic RD114-TR envelope.

    Science.gov (United States)

    Marin, Virna; Stornaiuolo, Anna; Piovan, Claudia; Corna, Stefano; Bossi, Sergio; Pema, Monika; Giuliani, Erica; Scavullo, Cinzia; Zucchelli, Eleonora; Bordignon, Claudio; Rizzardi, Gian Paolo; Bovolenta, Chiara

    2016-01-01

    To date, gene therapy with transiently derived lentivectors has been very successful to cure rare infant genetic diseases. However, transient manufacturing is unfeasible to treat adult malignancies because large vector lots are required. By contrast, stable manufacturing is the best option for high-incidence diseases since it reduces the production cost, which is the major current limitation to scale up the transient methods. We have previously developed the proprietary RD2-MolPack technology for the stable production of second-generation lentivectors, based on the RD114-TR envelope. Of note, opposite to vesicular stomatitis virus glycoprotein (VSV-G) envelope, RD114-TR does not need inducible expression thanks to lack of toxicity. Here, we present the construction of RD2- and RD3-MolPack cells for the production of self-inactivating lentivectors expressing green fluorescent protein (GFP) as a proof-of-concept of the feasibility and safety of this technology before its later therapeutic exploitation. We report that human T lymphocytes transduced with self-inactivating lentivectors derived from RD3-MolPack cells or with self-inactivating VSV-G pseudotyped lentivectors derived from transient transfection show identical T-cell memory differentiation phenotype and comparable transduction efficiency in all T-cell subsets. RD-MolPack technology represents, therefore, a straightforward tool to simplify and standardize lentivector manufacturing to engineer T-cells for frontline immunotherapy applications.

  5. Adeno-associated viral vector serotypes 1 and 5 targeted to the neonatal rat and pig striatum induce widespread transgene expression in the forebrain

    DEFF Research Database (Denmark)

    Kornum, Birgitte R; Stott, Simon R W; Mattsson, Bengt

    2010-01-01

    Viral vector-mediated gene transfer has emerged as a powerful means to target transgene expression in the central nervous system. Here we characterized the efficacy of serotypes 1 and 5 recombinant adeno-associated virus (rAAV) vectors encoding green fluorescent protein (GFP) after stereotaxic...

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

    Science.gov (United States)

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

    2016-09-16

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

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

    Directory of Open Access Journals (Sweden)

    Sarah Moeschler

    2016-09-01

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

  8. Smart and Controllable rAAV Gene Delivery Carriers in Progenitor Cells for Human Musculoskeletal Regenerative Medicine with a Focus on the Articular Cartilage.

    Science.gov (United States)

    Rey-Rico, Ana; Cucchiarini, Magali

    2017-01-01

    Cell therapy using mesenchymal stem cells (MSCs) is a powerful tool for the treatment of various diseases and injuries. Still, important limitations including the large amounts of cells required for application in vivo and the age-related decline in lifespan, proliferation, and potency may hinder the use of MSCs in patients. In this regard, gene therapy may offer strong approaches to optimize the use of MSCs for regenerative medicine. Diverse nonviral and viral gene vehicles have been manipulated to genetically modify MSCs, among which the highly effective and relatively safe recombinant adeno-associated viral (rAAV) vectors that emerged as the preferred gene delivery system to treat human disorders. Yet, clinical adaptation of such gene vehicles may be limited by several hurdles, including the possibility of dissemination to nontarget sites and the presence of immune and toxic responses in the host organism that may impair their therapeutic actions. The use of smart biomaterials acting as interfaces to enhance the temporal and spatial presentation of therapeutic agents in the target place and/or acting as scaffolding for MSC growth is an innovative, valuable approach to overcome these shortcomings that else restrain the efficacy of such potent cell populations. Here, we provide an overview on the most recent tissue engineering approaches based on the use of biomaterials acting as vehicles for rAAV vectors to target MSCs directly in the recipient (in vivo strategy) or as supportive matrices for rAAV-modified MSCs for indirect cell reimplantation (ex vivo strategy) as means to activate the reparative processes in tissues of the musculoskeletal system. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Recombinant adeno-associated virus type 2 replication and packaging is entirely supported by a herpes simplex virus type 1 amplicon expressing Rep and Cap.

    Science.gov (United States)

    Conway, J E; Zolotukhin, S; Muzyczka, N; Hayward, G S; Byrne, B J

    1997-11-01

    Recombinant adeno-associated virus (AAV) type 2 (rAAV) vectors have recently been shown to have great utility as gene transfer agents both in vitro and in vivo. One of the problems associated with the use of rAAV vectors has been the difficulty of large-scale vector production. Low-efficiency plasmid transfection of the rAAV vector and complementing AAV type 2 (AAV-2) functions (rep and cap) followed by superinfection with adenovirus has been the standard approach to rAAV production. The objectives of this study were to demonstrate the ability of a recombinant herpes simplex virus type 1 (HSV-1) amplicon expressing AAV-2 Rep and Cap to support replication and packaging of rAAV vectors. HSV-1 amplicon vectors were constructed which contain the AAV-2 rep and cap genes under control of their native promoters (p5, p19, and p40). An HSV-1 amplicon vector, HSV-RC/KOS or HSV-RC/d27, was generated by supplying helper functions with either wild-type HSV-1 (KOS strain) or the ICP27-deleted mutant of HSV-1, d27-1, respectively. Replication of the amplicon stocks is not inhibited by the presence of AAV-2 Rep proteins, which highlights important differences between HSV-1 and adenovirus replication and the mechanism of providing helper function for productive AAV infection. Coinfection of rAAV and HSV-RC/KOS resulted in the replication and amplification of rAAV genomes. Similarly, rescue and replication of rAAV genomes occurred when rAAV vector plasmids were transfected into cells followed by HSV-RC/KOS infection and when two rAAV proviral cell lines were infected with HSV-RC/KOS or HSV-RC/d27. Production of infectious rAAV by rescue from two rAAV proviral cell lines has also been achieved with HSV-RC/KOS and HSV-RC/d27. The particle titer of rAAV produced with HSV-RC/d27 is equal to that achieved by supplying rep and cap by transfection followed by adenovirus superinfection. Importantly, no detectable wild-type AAV-2 is generated with this approach. These results demonstrate

  10. Adeno-associated viral vector serotypes 1 and 5 targeted to the neonatal rat and pig striatum induce widespread transgene expression in the forebrain

    DEFF Research Database (Denmark)

    Kornum, Birgitte R; Stott, Simon R W; Mattsson, Bengt

    2010-01-01

    . Our results show that striatal delivery of rAAV5 vectors in the neonatal brain represents a useful tool to express genes of interest both in the basal ganglia and the neocortex. Furthermore, we apply, for the first time, viral vector-mediated gene transfer to the pig brain providing the opportunity...

  11. Restoration of central nervous system alpha-N-acetylglucosaminidase activity and therapeutic benefits in mucopolysaccharidosis IIIB mice by a single intracisternal recombinant adeno-associated viral type 2 vector delivery.

    Science.gov (United States)

    Fu, Haiyan; DiRosario, Julianne; Kang, Lu; Muenzer, Joseph; McCarty, Douglas M

    2010-07-01

    Finding efficient central nervous system (CNS) delivery approaches has been the major challenge facing therapeutic development for treating diseases with global neurological manifestation, such as mucopolysaccharidosis (MPS) IIIB, a lysosomal storage disease, caused by autosomal recessive defect of alpha-N-acetylglucosaminidase (NaGlu). Previously, we developed an approach, intracisternal (i.c.) injection, to deliver recombinant adeno-associated viral (rAAV) vector to the CNS of mice, leading to a widespread periventricular distribution of transduction. In the present study, we delivered rAAV2 vector expressing human NaGlu into the CNS of MPS IIIB mice by an i.c. injection approach, to test its therapeutic efficacy and feasibility for treating the neurological manifestation of the disease. We demonstrated significant functional neurological benefits of a single i.c. vector infusion in adult MPS IIIB mice. The treatment slowed the disease progression by mediating widespread recombinant NaGlu expression in the CNS, resulting in the reduction of brain lysosomal storage pathology, significantly improved cognitive function and prolonged survival. However, persisting motor function deficits suggested that pathology in areas outside the CNS contributes to the MPS IIIB behavioral phenotype. The therapeutic benefit of i.c. rAAV2 delivery was dose-dependent and could be attribute solely to the CNS transduction because the procedure did not lead to detectable transduction in somatic tissues. A single IC rAAV2 gene delivery is functionally beneficial for treating the CNS disease of MPS IIIB in mice. It is immediately clinically translatable, with the potential of improving the quality of life for patients with MPS IIIB.

  12. Analysis of proteins of mouse sarcoma pseudotype viruses: type-specific radioimmunoassays for ecotropic virus p30's

    International Nuclear Information System (INIS)

    Kennel, S.J.; Tennant, R.W.

    1979-01-01

    Murine sarcoma virus pseudotypes were prepared by infection of nonproducer cells (A1-2), which were transformed by the Gazdar strain of mouse sarcoma virus, with Gross (N-tropic), WN1802B (B-tropic), or Moloney (NB-tropic) viruses. The respective host range pseudotype sarcoma viruses were defined by the tritration characteristics on cells with the appropriate Fv-1 genotype. Proteins from virus progeny were analyzed by sodium dodecyl sulfate--polyacrylamide gel electrophoresis. Bands present in both the 65,000- and the 10,000- to 20,000-molecular-weight regions of the gel distinguished the pseudotype viruses from their respective helpers. Furthermore, two protein bands were noted in the p30 region of murine sarcoma virus (Gross), one corresponding to Gross virus p30, and another of slightly slower mobility. However, since the mobility of the putative sarcoma p30 is nearly indentical to that of WN1802B, its presence could not be established by sodium dodecyl sulfate--polyacrylamide gel electrophoresis. Type-specific radioimmunossays for Gross virus p30 and for WN1802B p30 were applied for analysis of pseudotype preparations, and among several ecotropic viruses tested, only the homologous virus scored in the respective assay. By use of these assays, pseudotype viruses were found to contain only 8 to 48% helper-specific p30's; the remainder is presumably derived from the sarcoma virus

  13. A Functional Henipavirus Envelope Glycoprotein Pseudotyped Lentivirus Assay System

    Directory of Open Access Journals (Sweden)

    Broder Christopher C

    2010-11-01

    Full Text Available Abstract Background Hendra virus (HeV and Nipah virus (NiV are newly emerged zoonotic paramyxoviruses discovered during outbreaks in Queensland, Australia in 1994 and peninsular Malaysia in 1998/9 respectively and classified within the new Henipavirus genus. Both viruses can infect a broad range of mammalian species causing severe and often-lethal disease in humans and animals, and repeated outbreaks continue to occur. Extensive laboratory studies on the host cell infection stage of HeV and NiV and the roles of their envelope glycoproteins have been hampered by their highly pathogenic nature and restriction to biosafety level-4 (BSL-4 containment. To circumvent this problem, we have developed a henipavirus envelope glycoprotein pseudotyped lentivirus assay system using either a luciferase gene or green fluorescent protein (GFP gene encoding human immunodeficiency virus type-1 (HIV-1 genome in conjunction with the HeV and NiV fusion (F and attachment (G glycoproteins. Results Functional retrovirus particles pseudotyped with henipavirus F and G glycoproteins displayed proper target cell tropism and entry and infection was dependent on the presence of the HeV and NiV receptors ephrinB2 or B3 on target cells. The functional specificity of the assay was confirmed by the lack of reporter-gene signals when particles bearing either only the F or only G glycoprotein were prepared and assayed. Virus entry could be specifically blocked when infection was carried out in the presence of a fusion inhibiting C-terminal heptad (HR-2 peptide, a well-characterized, cross-reactive, neutralizing human mAb specific for the henipavirus G glycoprotein, and soluble ephrinB2 and B3 receptors. In addition, the utility of the assay was also demonstrated by an examination of the influence of the cytoplasmic tail of F in its fusion activity and incorporation into pseudotyped virus particles by generating and testing a panel of truncation mutants of NiV and HeV F

  14. Characterization of Ebola Virus Entry by Using Pseudotyped Viruses: Identification of Receptor-Deficient Cell Lines

    OpenAIRE

    Wool-Lewis, Rouven J.; Bates, Paul

    1998-01-01

    Studies analyzing Ebola virus replication have been severely hampered by the extreme pathogenicity of this virus. To permit analysis of the host range and function of the Ebola virus glycoprotein (Ebo-GP), we have developed a system for pseudotyping these glycoproteins into murine leukemia virus (MLV). This pseudotyped virus, MLV(Ebola), can be readily concentrated to titers which exceed 5 × 106 infectious units/ml and is effectively neutralized by antibodies specific for Ebo-GP. Analysis of ...

  15. Immunogenicity and efficacy of immunodeficiency virus-like particles pseudotyped with the G protein of vesicular stomatitis virus

    International Nuclear Information System (INIS)

    Kuate, Seraphin; Stahl-Hennig, Christiane; Stoiber, Heribert; Nchinda, Godwin; Floto, Anja; Franz, Monika; Sauermann, Ulrike; Bredl, Simon; Deml, Ludwig; Ignatius, Ralf; Norley, Steve; Racz, Paul; Tenner-Racz, Klara; Steinman, Ralph M.; Wagner, Ralf; Uberla, Klaus

    2006-01-01

    Vaccination with exogenous antigens such as recombinant viral proteins, immunodeficiency virus-derived whole inactivated virus particles, or virus-like particles (VLP) has generally failed to provide sufficient protection in animal models for AIDS. Pseudotyping VLPs with the vesicular stomatitis virus G protein (VSV-G), which is known to mediate entry into dendritic cells, might allow more efficient stimulation of immune responses. Therefore, we pseudotyped noninfectious immunodeficiency virus-like particles with VSV-G and carried out a preliminary screen of their immunogenicity and vaccination efficacy. Incorporation of VSV-G into HIV-1 VLPs led to hundred-fold higher antibody titers to HIV-1 Gag and enhancement of T cell responses in mice. Repeated vaccination of rhesus monkeys for 65 weeks with VSV-G pseudotyped simian immunodeficiency virus (SIV)-like particles (VLP[G]) provided initial evidence for efficient suppression of viral load after mucosal challenge with the SIVmac239 virus. Challenge of monkeys after a 28 week vaccination regimen with VLP[G] led to a reduction in peak viremia, but persistent suppression of viral load was not achieved. Due to limitations in the number of animals available for this study, improved efficacy of VSV-G pseudotyped VLPs in nonhuman primates could not be demonstrated. However, mouse experiments revealed that pseudotyping of VLPs with fusion-competent VSV-G clearly improves their immunogenicity. Additional strategies, particularly adjuvants, should be considered to provide greater protection against a challenge with pathogenic immunodeficiency virus

  16. Disruption of Microtubules Post-Virus Entry Enhances Adeno-Associated Virus Vector Transduction

    Science.gov (United States)

    Xiao, Ping-Jie; Mitchell, Angela M.; Huang, Lu; Li, Chengwen; Samulski, R. Jude

    2016-01-01

    Perinuclear retention of viral particles is a poorly understood phenomenon observed during many virus infections. In this study, we investigated whether perinuclear accumulation acts as a barrier to limit recombinant adeno-associated virus (rAAV) transduction. After nocodazole treatment to disrupt microtubules at microtubule-organization center (MT-MTOC) after virus entry, we observed higher rAAV transduction. To elucidate the role of MT-MTOC in rAAV infection and study its underlying mechanisms, we demonstrated that rAAV's perinuclear localization was retained by MT-MTOC with fluorescent analysis, and enhanced rAAV transduction from MT-MTOC disruption was dependent on the rAAV capsid's nuclear import signals. Interestingly, after knocking down RhoA or inhibiting its downstream effectors (ROCK and Actin), MT-MTOC disruption failed to increase rAAV transduction or nuclear entry. These data suggest that enhancement of rAAV transduction is the result of increased trafficking to the nucleus via the RhoA-ROCK-Actin pathway. Ten-fold higher rAAV transduction was also observed by disrupting MT-MTOC in brain, liver, and tumor in vivo. In summary, this study indicates that virus perinuclear accumulation at MT-MTOC is a barrier-limiting parameter for effective rAAV transduction and defines a novel defense mechanism by which host cells restrain viral invasion. PMID:26942476

  17. Genetic modification of lymphocytes by retrovirus-based vectors.

    Science.gov (United States)

    Suerth, Julia D; Schambach, Axel; Baum, Christopher

    2012-10-01

    The genetic modification of lymphocytes is an important topic in the emerging field of gene therapy. Many clinical trials targeting immunodeficiency syndromes or cancer have shown therapeutic benefit; further applications address inflammatory and infectious disorders. Retroviral vector development requires a detailed understanding of the interactions with the host. Most researchers have used simple gammaretroviral vectors to modify lymphocytes, either directly or via hematopoietic stem and progenitor cells. Lentiviral, spumaviral (foamyviral) and alpharetroviral vectors were designed to reduce the necessity for cell stimulation and to utilize potentially safer integration properties. Novel surface modifications (pseudotyping) and transgenes, built using synthetic components, expand the retroviral toolbox, altogether promising increased specificity and potency. Product consistency will be an important criterion for routine clinical use. Copyright © 2012. Published by Elsevier Ltd.

  18. Characterization of Ebola virus entry by using pseudotyped viruses: identification of receptor-deficient cell lines.

    Science.gov (United States)

    Wool-Lewis, R J; Bates, P

    1998-04-01

    Studies analyzing Ebola virus replication have been severely hampered by the extreme pathogenicity of this virus. To permit analysis of the host range and function of the Ebola virus glycoprotein (Ebo-GP), we have developed a system for pseudotyping these glycoproteins into murine leukemia virus (MLV). This pseudotyped virus, MLV(Ebola), can be readily concentrated to titers which exceed 5 x 10(6) infectious units/ml and is effectively neutralized by antibodies specific for Ebo-GP. Analysis of MLV(Ebola) infection revealed that the host range conferred by Ebo-GP is very broad, extending to cells of a variety of species. Notably, all lymphoid cell lines tested were completely resistant to infection; we speculate that this is due to the absence of a cellular receptor for Ebo-GP on B and T cells. The generation of high-titer MLV(Ebola) pseudotypes will be useful for the analysis of immune responses to Ebola virus infection, development of neutralizing antibodies, analysis of glycoprotein function, and isolation of the cellular receptor(s) for the Ebola virus.

  19. Viral vectors for cystic fibrosis gene therapy: What does the future hold?

    Directory of Open Access Journals (Sweden)

    Uta Griesenbach

    2010-12-01

    Full Text Available Uta Griesenbach1, Makoto Inoue2, Mamoru Hasegawa2, Eric WFW Alton11Department of Gene Therapy, Imperial College London, UK; The UK Cystic Fibrosis Gene Therapy Consortium; 2DNAVEC Corporation, Tsukuba, JapanAbstract: Gene transfer to the airway epithelium has been more difficult than originally anticipated, largely because of significant extra- and intracellular barriers in the lung. In general, viral vectors are more adapted to overcoming these barriers than nonviral gene transfer agents and are, therefore, more efficient in transferring genes into recipient cells. Viral vectors derived from adenovirus, adeno-associated virus, and Sendai virus, which all have a natural tropism for the airway epithelium, have been evaluated for cystic fibrosis (CF gene therapy. Although these vectors transduce airway epithelial cells efficiently, gene expression is transient and repeated administration is inefficient. They are, therefore, unlikely to be suitable for CF gene therapy. More recently, lentiviruses (LV have been assessed for lung gene transfer. In contrast to retroviruses, they transduce nondividing cells and randomly integrate into the genome. However, LVs do not have a natural tropism for the lung, and a significant amount of effort has been put into pseudotyping these vectors with proteins suitable for airway gene transfer. Several studies have shown that LV-mediated transduction leads to persistent gene expression (for the lifetime of the animal in the airways and, importantly, repeated administration is feasible. Thus, appropriately pseudotyped LV vectors are promising candidates for CF gene therapy. Here, we will review preclinical and clinical research related to viral CF gene therapy.Keywords: cystic fibrosis, gene therapy, adenovirus, AAV, lentivirus, Sendai virus

  20. Characterization of retrovirus-based reporter viruses pseudotyped with the precursor membrane and envelope glycoproteins of four serotypes of dengue viruses

    International Nuclear Information System (INIS)

    Hu, H.-P.; Hsieh, S.-C.; King, C.-C.; Wang, W.-K.

    2007-01-01

    In this study, we successfully established retrovirus-based reporter viruses pseudotyped with the precursor membrane and envelope (PrM/E) proteins of each of the four serotypes of dengue viruses, which caused the most important arboviral diseases in this century. Co-sedimentation of the dengue E protein and HIV-1 core proteins by sucrose gradient analysis of the pseudotype reporter virus of dengue virus type 2, D2(HIVluc), and detection of HIV-1 core proteins by immunoprecipitation with anti-E monoclonal antibody suggested that dengue viral proteins were incorporated into the pseudotype viral particles. The infectivity in target cells, as assessed by the luciferase activity, can be inhibited by the lysosomotropic agents, suggesting a pH-dependent mechanism of entry. Amino acid substitutions of the leucine at position 107, a critical residue at the fusion loop of E protein, with lysine resulted in severe impairment in infectivity, suggesting that entry of the pseudotype reporter virus is mediated through the fusogenic properties of E protein. With more and more dengue viral sequences available from different outbreaks worldwide, this sensitive and convenient tool has the potential to facilitate molecular characterization of the PrM/E proteins of dengue field isolates

  1. Single residue AAV capsid mutation improves transduction of photoreceptors in the Abca4-/- mouse and bipolar cells in the rd1 mouse and human retina ex vivo.

    Science.gov (United States)

    De Silva, Samantha R; Charbel Issa, Peter; Singh, Mandeep S; Lipinski, Daniel M; Barnea-Cramer, Alona O; Walker, Nathan J; Barnard, Alun R; Hankins, Mark W; MacLaren, Robert E

    2016-11-01

    Gene therapy using adeno-associated viral (AAV) vectors for the treatment of retinal degenerations has shown safety and efficacy in clinical trials. However, very high levels of vector expression may be necessary for the treatment of conditions such as Stargardt disease where a dual vector approach is potentially needed, or in optogenetic strategies for end-stage degeneration in order to achieve maximal light sensitivity. In this study, we assessed two vectors with single capsid mutations, rAAV2/2(Y444F) and rAAV2/8(Y733F) in their ability to transduce retina in the Abca4 -/- and rd1 mouse models of retinal degeneration. We noted significantly increased photoreceptor transduction using rAAV2/8(Y733F) in the Abca4 -/- mouse, in contrast to previous work where vectors tested in this model have shown low levels of photoreceptor transduction. Bipolar cell transduction was achieved following subretinal delivery of both vectors in the rd1 mouse, and via intravitreal delivery of rAAV2/2(Y444F). The successful use of rAAV2/8(Y733F) to target bipolar cells was further validated on human tissue using an ex vivo culture system of retinal explants. Capsid mutant AAV vectors transduce human retinal cells and may be particularly suited to treat retinal degenerations in which high levels of transgene expression are required.

  2. Adeno-Associated Virus-Mediated Correction of a Canine Model of Glycogen Storage Disease Type Ia

    Science.gov (United States)

    Weinstein, David A.; Correia, Catherine E.; Conlon, Thomas; Specht, Andrew; Verstegen, John; Onclin-Verstegen, Karine; Campbell-Thompson, Martha; Dhaliwal, Gurmeet; Mirian, Layla; Cossette, Holly; Falk, Darin J.; Germain, Sean; Clement, Nathalie; Porvasnik, Stacy; Fiske, Laurie; Struck, Maggie; Ramirez, Harvey E.; Jordan, Juan; Andrutis, Karl; Chou, Janice Y.; Byrne, Barry J.

    2010-01-01

    Abstract Glycogen storage disease type Ia (GSDIa; von Gierke disease; MIM 232200) is caused by a deficiency in glucose-6-phosphatase-α. Patients with GSDIa are unable to maintain glucose homeostasis and suffer from severe hypoglycemia, hepatomegaly, hyperlipidemia, hyperuricemia, and lactic acidosis. The canine model of GSDIa is naturally occurring and recapitulates almost all aspects of the human form of disease. We investigated the potential of recombinant adeno-associated virus (rAAV) vector-based therapy to treat the canine model of GSDIa. After delivery of a therapeutic rAAV2/8 vector to a 1-day-old GSDIa dog, improvement was noted as early as 2 weeks posttreatment. Correction was transient, however, and by 2 months posttreatment the rAAV2/8-treated dog could no longer sustain normal blood glucose levels after 1 hr of fasting. The same animal was then dosed with a therapeutic rAAV2/1 vector delivered via the portal vein. Two months after rAAV2/1 dosing, both blood glucose and lactate levels were normal at 4 hr postfasting. With more prolonged fasting, the dog still maintained near-normal glucose concentrations, but lactate levels were elevated by 9 hr, indicating that partial correction was achieved. Dietary glucose supplementation was discontinued starting 1 month after rAAV2/1 delivery and the dog continues to thrive with minimal laboratory abnormalities at 23 months of age (18 months after rAAV2/1 treatment). These results demonstrate that delivery of rAAV vectors can mediate significant correction of the GSDIa phenotype and that gene transfer may be a promising alternative therapy for this disease and other genetic diseases of the liver. PMID:20163245

  3. Factors influencing recombinant adeno-associated virus production.

    Science.gov (United States)

    Salvetti, A; Orève, S; Chadeuf, G; Favre, D; Cherel, Y; Champion-Arnaud, P; David-Ameline, J; Moullier, P

    1998-03-20

    Recombinant adeno-associated virus (rAAV) is produced by transfecting cells with two constructs: the rAAV vector plasmid and the rep-cap plasmid. After subsequent adenoviral infection, needed for rAAV replication and assembly, the virus is purified from total cell lysates through CsCl gradients. Because this is a long and complex procedure, the precise titration of rAAV stocks, as well as the measure of the level of contamination with adenovirus and rep-positive AAV, are essential to evaluate the transduction efficiency of these vectors in vitro and in vivo. Our vector core is in charge of producing rAAV for outside investigators as part of a national network promoted by the Association Française contre les Myopathies/Généthon. We report here the characterization of 18 large-scale rAAV stocks produced during the past year. Three major improvements were introduced and combined in the rAAV production procedure: (i) the titration and characterization of rAAV stocks using a stable rep-cap HeLa cell line in a modified Replication Center Assay (RCA); (ii) the use of different rep-cap constructs to provide AAV regulatory and structural proteins; (iii) the use of an adenoviral plasmid to provide helper functions needed for rAAV replication and assembly. Our results indicate that: (i) rAAV yields ranged between 10(11) to 5 x 10(12) total particles; (ii) the physical particle to infectious particle (measured by RCA) ratios were consistently below 50 when using a rep-cap plasmid harboring an ITR-deleted AAV genome; the physical particle to transducing particle ratios ranged between 400 and 600; (iii) the use of an adenoviral plasmid instead of an infectious virion did not affect the particles or the infectious particles yields nor the above ratio. Most of large-scale rAAV stocks (7/9) produced using this plasmid were free of detectable infectious adenovirus as determined by RCA; (iv) all the rAAV stocks were contaminated with rep-positive AAV as detected by RCA. In summary

  4. Transcriptome Profiling of Neovascularized Corneas Reveals miR-204 as a Multi-target Biotherapy Deliverable by rAAVs

    Directory of Open Access Journals (Sweden)

    Yi Lu

    2018-03-01

    Full Text Available Corneal neovascularization (NV is the major sight-threatening pathology caused by angiogenic stimuli. Current drugs that directly target pro-angiogenic factors to inhibit or reverse the disease require multiple rounds of administration and have limited efficacies. Here, we identify potential anti-angiogenic corneal microRNAs (miRNAs and demonstrate a framework that employs discovered miRNAs as biotherapies deliverable by recombinant adeno-associated viruses (rAAVs. By querying differentially expressed miRNAs in neovascularized mouse corneas induced by alkali burn, we have revealed 39 miRNAs that are predicted to target more than 5,500 differentially expressed corneal mRNAs. Among these, we selected miR-204 and assessed its efficacy and therapeutic benefit for treating injured corneas. Our results show that delivery of miR-204 by rAAV normalizes multiple novel target genes and biological pathways to attenuate vascularization of injured mouse cornea. Importantly, this gene therapy treatment alternative is efficacious and safe for mitigating corneal NV. Overall, our work demonstrates the discovery of potential therapeutic miRNAs in corneal disorders and their translation into viable treatment alternatives.

  5. 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

  6. Magnetic concentration of a retroviral vector using magnetite cationic liposomes.

    Science.gov (United States)

    Ito, Akira; Takahashi, Tetsuya; Kameyama, Yujiro; Kawabe, Yoshinori; Kamihira, Masamichi

    2009-03-01

    For tissue engineering purposes, retroviral vectors represent an efficient method of delivering exogenous genes such as growth factors to injured tissues because gene-transduced cells can produce stable and constant levels of the gene product. However, retroviral vector technology suffers from low yields. In the present study, we used magnetite nanoparticles and magnetic force to concentrate the retroviral vectors to enhance the transduction efficiency and to enable their magnetic manipulation. Magnetite nanoparticles modified with cationic liposomes were added to a solution containing a retroviral vector pseudotyped with vesicular stomatitis virus glycoprotein. The magnetic particles that captured the viral vectors were collected using a magnetic force and seeded into mouse neuroblastoma Neuro2a cells. The viral titer was up to 55 times greater (up to 3 x 10(8) infectious units/mL). Additionally, the magnetically labeled retroviral vectors can be directed to the desired regions for infection by applying magnetic fields, and micro-patterns of gene-transduced cell regions could be created on a cellular monolayer using micro-patterned magnetic concentrators. These results suggest that this technique provides a promising approach to capturing and concentrating viral vectors, thus achieving high transduction efficiency and the ability to deliver genes to a specific injured site by applying a magnetic field.

  7. Long-Term Efficacy Following Readministration of an Adeno-Associated Virus Vector in Dogs with Glycogen Storage Disease Type Ia

    Science.gov (United States)

    Demaster, Amanda; Luo, Xiaoyan; Curtis, Sarah; Williams, Kyha D.; Landau, Dustin J.; Drake, Elizabeth J.; Kozink, Daniel M.; Bird, Andrew; Crane, Bayley; Sun, Francis; Pinto, Carlos R.; Brown, Talmage T.; Kemper, Alex R.

    2012-01-01

    Abstract Glycogen storage disease type Ia (GSD-Ia) is the inherited deficiency of glucose-6-phosphatase (G6Pase), primarily found in liver and kidney, which causes life-threatening hypoglycemia. Dogs with GSD-Ia were treated with double-stranded adeno-associated virus (AAV) vectors encoding human G6Pase. Administration of an AAV9 pseudotyped (AAV2/9) vector to seven consecutive GSD-Ia neonates prevented hypoglycemia during fasting for up to 8 hr; however, efficacy eventually waned between 2 and 30 months of age, and readministration of a new pseudotype was eventually required to maintain control of hypoglycemia. Three of these dogs succumbed to acute hypoglycemia between 7 and 9 weeks of age; however, this demise could have been prevented by earlier readministration an AAV vector, as demonstrated by successful prevention of mortality of three dogs treated earlier in life. Over the course of this study, six out of nine dogs survived after readministration of an AAV vector. Of these, each dog required readministration on average every 9 months. However, two were not retreated until >34 months of age, while one with preexisting antibodies was re-treated three times in 10 months. Glycogen content was normalized in the liver following vector administration, and G6Pase activity was increased in the liver of vector-treated dogs in comparison with GSD-Ia dogs that received only with dietary treatment. G6Pase activity reached approximately 40% of normal in two female dogs following AAV2/9 vector administration. Elevated aspartate transaminase in absence of inflammation indicated that hepatocellular turnover in the liver might drive the loss of vector genomes. Survival was prolonged for up to 60 months in dogs treated by readministration, and all dogs treated by readministration continue to thrive despite the demonstrated risk for recurrent hypoglycemia and mortality from waning efficacy of the AAV2/9 vector. These preclinical data support the further translation of AAV

  8. Cre Activated and Inactivated Recombinant Adeno-Associated Viral Vectors for Neuronal Anatomical Tracing or Activity Manipulation.

    Science.gov (United States)

    Saunders, Arpiar; Sabatini, Bernardo L

    2015-07-01

    Recombinant adeno-associated viruses (rAAVs) transcriptionally activated by Cre recombinase (Cre-On) are powerful tools for determining the anatomy and function of genetically defined neuronal types in transgenic Cre driver mice. Here we describe how rAAVs transcriptionally inactivated by Cre (Cre-Off) can be used in conjunction with Cre-On rAAVs or genomic Cre-reporter alleles to study brain circuits. Intracranial injection of Cre-On/Cre-Off rAAVs into spatially intermingled Cre(+) and Cre(-) neurons allows these populations to be differentially labeled or manipulated within individual animals. This comparison helps define the unique properties of Cre(+) neurons, highlighting the specialized role they play in their constituent brain circuits. This protocol touches on the conceptual and experimental background of Cre-Off rAAV systems, including caveats and methods of validation. Copyright © 2015 John Wiley & Sons, Inc.

  9. Toward exascale production of recombinant adeno-associated virus for gene transfer applications.

    Science.gov (United States)

    Cecchini, S; Negrete, A; Kotin, R M

    2008-06-01

    To gain acceptance as a medical treatment, adeno-associated virus (AAV) vectors require a scalable and economical production method. Recent developments indicate that recombinant AAV (rAAV) production in insect cells is compatible with current good manufacturing practice production on an industrial scale. This platform can fully support development of rAAV therapeutics from tissue culture to small animal models, to large animal models, to toxicology studies, to Phase I clinical trials and beyond. Efforts to characterize, optimize and develop insect cell-based rAAV production have culminated in successful bioreactor-scale production of rAAV, with total yields potentially capable of approaching the exa-(10(18)) scale. These advances in large-scale AAV production will allow us to address specific catastrophic, intractable human diseases such as Duchenne muscular dystrophy, for which large amounts of recombinant vector are essential for successful outcome.

  10. Stable producer cell lines for adeno-associated virus (AAV) assembly.

    Science.gov (United States)

    Chadeuf, Gilliane; Salvetti, Anna

    2010-10-01

    Stable producer cell lines containing both the rep and cap genes and recombinant adeno-associated virus (rAAV) vectors can be infected with a helper virus to provide reliable and efficient production of rAAV stocks. However, the development of these cell lines is time-consuming. The procedure described here is therefore recommended only for studies requiring the production of high amounts of rAAV, such as preclinical studies performed in large animals.

  11. Enhanced immunosurveillance for animal morbilliviruses using vesicular stomatitis virus (VSV) pseudotypes.

    Science.gov (United States)

    Logan, Nicola; Dundon, William G; Diallo, Adama; Baron, Michael D; James Nyarobi, M; Cleaveland, Sarah; Keyyu, Julius; Fyumagwa, Robert; Hosie, Margaret J; Willett, Brian J

    2016-11-11

    The measurement of virus-specific neutralising antibodies represents the "gold-standard" for diagnostic serology. For animal morbilliviruses, such as peste des petits ruminants (PPRV) or rinderpest virus (RPV), live virus-based neutralisation tests require high-level biocontainment to prevent the accidental escape of the infectious agents. In this study, we describe the adaptation of a replication-defective vesicular stomatitis virus (VSVΔG) based pseudotyping system for the measurement of neutralising antibodies against animal morbilliviruses. By expressing the haemagglutinin (H) and fusion (F) proteins of PPRV on VSVΔG pseudotypes bearing a luciferase marker gene, neutralising antibody titres could be measured rapidly and with high sensitivity. Serological responses against the four distinct lineages of PPRV could be measured simultaneously and cross-neutralising responses against other morbilliviruses compared. Using this approach, we observed that titres of neutralising antibodies induced by vaccination with live attenuated PPRV were lower than those induced by wild type virus infection and the level of cross-lineage neutralisation varied between vaccinates. By comparing neutralising responses from animals infected with either PPRV or RPV, we found that responses were highest against the homologous virus, indicating that retrospective analyses of serum samples could be used to confirm the nature of the original pathogen to which an animal had been exposed. Accordingly, when screening sera from domestic livestock and wild ruminants in Tanzania, we detected evidence of cross-species infection with PPRV, canine distemper virus (CDV) and a RPV-related bovine morbillivirus, suggesting that exposure to animal morbilliviruses may be more widespread than indicated previously using existing diagnostic techniques. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Hepatitis C virus quasispecies and pseudotype analysis from acute infection to chronicity in HIV-1 co-infected individuals.

    Science.gov (United States)

    Ferns, R Bridget; Tarr, Alexander W; Hue, Stephane; Urbanowicz, Richard A; McClure, C Patrick; Gilson, Richard; Ball, Jonathan K; Nastouli, Eleni; Garson, Jeremy A; Pillay, Deenan

    2016-05-01

    HIV-1 infected patients who acquire HCV infection have higher rates of chronicity and liver disease progression than patients with HCV mono-infection. Understanding early events in this pathogenic process is important. We applied single genome sequencing of the E1 to NS3 regions and viral pseudotype neutralization assays to explore the consequences of viral quasispecies evolution from pre-seroconversion to chronicity in four co-infected individuals (mean follow up 566 days). We observed that one to three founder viruses were transmitted. Relatively low viral sequence diversity, possibly related to an impaired immune response, due to HIV infection was observed in three patients. However, the fourth patient, after an early purifying selection displayed increasing E2 sequence evolution, possibly related to being on suppressive antiretroviral therapy. Viral pseudotypes generated from HCV variants showed relative resistance to neutralization by autologous plasma but not to plasma collected from later time points, confirming ongoing virus escape from antibody neutralization. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Novel recombinant adeno-associated viruses for Cre activated and inactivated transgene expression in neurons

    Science.gov (United States)

    Saunders, Arpiar; Johnson, Caroline A.; Sabatini, Bernardo L.

    2012-01-01

    Understanding the organization of the nervous system requires methods for dissecting the contributions of each component cell type to circuit function. One widely used approach combines genetic targeting of Cre recombinase to specific cell populations with infection of recombinant adeno-associated viruses (rAAVs) whose transgene expression is activated by Cre (“Cre-On”). Distinguishing how the Cre-expressing neurons differ functionally from neighboring Cre-negative neurons requires rAAVs that are inactivated by Cre (“Cre-Off”) and can be used in tandem with Cre-On viruses. Here we introduce two rAAV vectors that are inactivated by Cre and carry different fluorophore and optogenetic constructs. We demonstrate single and dual rAAV systems to achieve Cre-On and Cre-Off expression in spatially-intermingled cell populations of the striatum. Using these systems, we uncovered cryptic genomic interactions that occur between multiple Cre-sensitive rAAVs or between Cre-sensitive rAAVs and somatic Cre-conditional alleles and devised methods to avoid these interactions. Our data highlight both important experimental caveats associated with Cre-dependent rAAV use as well as opportunities for the development of improved rAAVs for gene delivery. PMID:22866029

  14. Pharmacology of Recombinant Adeno-associated Virus Production

    Directory of Open Access Journals (Sweden)

    Magalie Penaud-Budloo

    2018-03-01

    Full Text Available Recombinant adeno-associated viral (rAAV vectors have been used in more than 150 clinical trials with a good safety profile and significant clinical benefit in many genetic diseases. In addition, due to their ability to infect non-dividing and dividing cells and to serve as efficient substrate for homologous recombination, rAAVs are being used as a tool for gene-editing approaches. However, manufacturing of these vectors at high quantities and fulfilling current good manufacturing practices (GMP is still a challenge, and several technological platforms are competing for this niche. Herein, we will describe the most commonly used upstream methods to produce rAAVs, paying particular attention to the starting materials (input used in each platform and which related impurities can be expected in final products (output. The most commonly found impurities in rAAV stocks include defective particles (i.e., AAV capsids that do contain the therapeutic gene or are not infectious, residual proteins from host cells and helper viruses (adenovirus, herpes simplex virus, or baculoviruses, and illegitimate DNA from plasmids, cells, or helper viruses that may be encapsidated into rAAV particles. Given the role that impurities may play in immunotoxicity, this article reviews the impurities inherently associated with each manufacturing platform.

  15. Resting lymphocyte transduction with measles virus glycoprotein pseudotyped lentiviral vectors relies on CD46 and SLAM

    International Nuclear Information System (INIS)

    Zhou Qi; Schneider, Irene C.; Gallet, Manuela; Kneissl, Sabrina; Buchholz, Christian J.

    2011-01-01

    The measles virus (MV) glycoproteins hemagglutinin (H) and fusion (F) were recently shown to mediate transduction of resting lymphocytes by lentiviral vectors. MV vaccine strains use CD46 or signaling lymphocyte activation molecule (SLAM) as receptor for cell entry. A panel of H protein mutants derived from vaccine strain or wild-type MVs that lost or gained CD46 or SLAM receptor usage were investigated for their ability to mediate gene transfer into unstimulated T lymphocytes. The results demonstrate that CD46 is sufficient for efficient vector particle association with unstimulated lymphocytes. For stable gene transfer into these cells, however, both MV receptors were found to be essential.

  16. Cell-type-specific gene delivery into neuronal cells in vitro and in vivo

    International Nuclear Information System (INIS)

    Parveen, Zahida; Mukhtar, Muhammad; Rafi, Mohammed; Wenger, David A.; Siddiqui, Khwaja M.; Siler, Catherine A.; Dietzschold, Bernhard; Pomerantz, Roger J.; Schnell, Matthias J.; Dornburg, Ralph

    2003-01-01

    The avian retroviruses reticuloendotheliosis virus strain A (REV-A) and spleen necrosis virus (SNV) are not naturally infectious in human cells. However, REV-A-derived viral vectors efficiently infect human cells when they are pseudotyped with envelope proteins displaying targeting ligands specific for human cell-surface receptors. Here we report that vectors containing the gag region of REV-A and pol of SNV can be pseudotyped with the envelope protein of vesicular stomatitis virus (VSV) and the glycoproteins of different rabies virus (RV) strains. Vectors pseudotyped with the envelope protein of the highly neurotropic RV strain CVS-N2c facilitated cell type-specific gene delivery into mouse and human neurons, but did not infect other human cell types. Moreover, when such vector particles were injected into the brain of newborn mice, only neuronal cells were infected in vivo. Cell-type-specific gene delivery into neurons may present quite specific gene therapy approaches for many degenerative diseases of the brain

  17. Design of a titering assay for lentiviral vectors utilizing direct extraction of DNA from transduced cells in microtiter plates

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    Michele E Murphy

    2016-01-01

    Full Text Available Using lentiviral vector products in clinical applications requires an accurate method for measuring transduction titer. For vectors lacking a marker gene, quantitative polymerase chain reaction is used to evaluate the number of vector DNA copies in transduced target cells, from which a transduction titer is calculated. Immune Design previously described an integration-deficient lentiviral vector pseudotyped with a modified Sindbis virus envelope for use in cancer immunotherapy (VP02, of the ZVex platform. Standard protocols for titering integration-competent lentiviral vectors employ commercial spin columns to purify vector DNA from transduced cells, but such columns are not optimized for isolation of extrachromosomal (nonintegrated DNA. Here, we describe a 96-well transduction titer assay in which DNA extraction is performed in situ in the transduction plate, yielding quantitative recovery of extrachromosomal DNA. Vector titers measured by this method were higher than when commercial spin columns were used for DNA isolation. Evaluation of the method's specificity, linear range, and precision demonstrate that it is suitable for use as a lot release assay to support clinical trials with VP02. Finally, the method is compatible with titering both integrating and nonintegrating lentiviral vectors, suggesting that it may be used to evaluate the transduction titer for any lentiviral vector.

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

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    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.

  19. Differentiated neuroprogenitor cells incubated with human or canine adenovirus, or lentiviral vectors have distinct transcriptome profiles.

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    Stefania Piersanti

    Full Text Available Several studies have demonstrated the potential for vector-mediated gene transfer to the brain. Helper-dependent (HD human (HAd and canine (CAV-2 adenovirus, and VSV-G-pseudotyped self-inactivating HIV-1 vectors (LV effectively transduce human brain cells and their toxicity has been partly analysed. However, their effect on the brain homeostasis is far from fully defined, especially because of the complexity of the central nervous system (CNS. With the goal of dissecting the toxicogenomic signatures of the three vectors for human neurons, we transduced a bona fide human neuronal system with HD-HAd, HD-CAV-2 and LV. We analysed the transcriptional response of more than 47,000 transcripts using gene chips. Chip data showed that HD-CAV-2 and LV vectors activated the innate arm of the immune response, including Toll-like receptors and hyaluronan circuits. LV vector also induced an IFN response. Moreover, HD-CAV-2 and LV vectors affected DNA damage pathways--but in opposite directions--suggesting a differential response of the p53 and ATM pathways to the vector genomes. As a general response to the vectors, human neurons activated pro-survival genes and neuron morphogenesis, presumably with the goal of re-establishing homeostasis. These data are complementary to in vivo studies on brain vector toxicity and allow a better understanding of the impact of viral vectors on human neurons, and mechanistic approaches to improve the therapeutic impact of brain-directed gene transfer.

  20. Long-term gene therapy causes transgene-specific changes in the morphology of regenerating retinal ganglion cells.

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    Jennifer Rodger

    Full Text Available Recombinant adeno-associated viral (rAAV vectors can be used to introduce neurotrophic genes into injured CNS neurons, promoting survival and axonal regeneration. Gene therapy holds much promise for the treatment of neurotrauma and neurodegenerative diseases; however, neurotrophic factors are known to alter dendritic architecture, and thus we set out to determine whether such transgenes also change the morphology of transduced neurons. We compared changes in dendritic morphology of regenerating adult rat retinal ganglion cells (RGCs after long-term transduction with rAAV2 encoding: (i green fluorescent protein (GFP, or (ii bi-cistronic vectors encoding GFP and ciliary neurotrophic factor (CNTF, brain-derived neurotrophic factor (BDNF or growth-associated protein-43 (GAP43. To enhance regeneration, rats received an autologous peripheral nerve graft onto the cut optic nerve of each rAAV2 injected eye. After 5-8 months, RGCs with regenerated axons were retrogradely labeled with fluorogold (FG. Live retinal wholemounts were prepared and GFP positive (transduced or GFP negative (non-transduced RGCs injected iontophoretically with 2% lucifer yellow. Dendritic morphology was analyzed using Neurolucida software. Significant changes in dendritic architecture were found, in both transduced and non-transduced populations. Multivariate analysis revealed that transgenic BDNF increased dendritic field area whereas GAP43 increased dendritic complexity. CNTF decreased complexity but only in a subset of RGCs. Sholl analysis showed changes in dendritic branching in rAAV2-BDNF-GFP and rAAV2-CNTF-GFP groups and the proportion of FG positive RGCs with aberrant morphology tripled in these groups compared to controls. RGCs in all transgene groups displayed abnormal stratification. Thus in addition to promoting cell survival and axonal regeneration, vector-mediated expression of neurotrophic factors has measurable, gene-specific effects on the morphology of injured

  1. Assessment of tropism and effectiveness of new primate-derived hybrid recombinant AAV serotypes in the mouse and primate retina.

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    Peter Charbel Issa

    Full Text Available Adeno-associated viral vectors (AAV have been shown to be safe in the treatment of retinal degenerations in clinical trials. Thus, improving the efficiency of viral gene delivery has become increasingly important to increase the success of clinical trials. In this study, structural domains of different rAAV serotypes isolated from primate brain were combined to create novel hybrid recombinant AAV serotypes, rAAV2/rec2 and rAAV2/rec3. The efficacy of these novel serotypes were assessed in wild type mice and in two models of retinal degeneration (the Abca4(-/- mouse which is a model for Stargardt disease and in the Pde6b(rd1/rd1 mouse in vivo, in primate tissue ex-vivo, and in the human-derived SH-SY5Y cell line, using an identical AAV2 expression cassette. We show that these novel hybrid serotypes can transduce retinal tissue in mice and primates efficiently, although no more than AAV2/2 and rAAV2/5 serotypes. Transduction efficiency appeared lower in the Abca4(-/- mouse compared to wild type with all vectors tested, suggesting an effect of specific retinal diseases on the efficiency of gene delivery. Shuffling of AAV capsid domains may have clinical applications for patients who develop T-cell immune responses following AAV gene therapy, as specific peptide antigen sequences could be substituted using this technique prior to vector re-treatments.

  2. Assessment of tropism and effectiveness of new primate-derived hybrid recombinant AAV serotypes in the mouse and primate retina.

    Science.gov (United States)

    Charbel Issa, Peter; De Silva, Samantha R; Lipinski, Daniel M; Singh, Mandeep S; Mouravlev, Alexandre; You, Qisheng; Barnard, Alun R; Hankins, Mark W; During, Matthew J; Maclaren, Robert E

    2013-01-01

    Adeno-associated viral vectors (AAV) have been shown to be safe in the treatment of retinal degenerations in clinical trials. Thus, improving the efficiency of viral gene delivery has become increasingly important to increase the success of clinical trials. In this study, structural domains of different rAAV serotypes isolated from primate brain were combined to create novel hybrid recombinant AAV serotypes, rAAV2/rec2 and rAAV2/rec3. The efficacy of these novel serotypes were assessed in wild type mice and in two models of retinal degeneration (the Abca4(-/-) mouse which is a model for Stargardt disease and in the Pde6b(rd1/rd1) mouse) in vivo, in primate tissue ex-vivo, and in the human-derived SH-SY5Y cell line, using an identical AAV2 expression cassette. We show that these novel hybrid serotypes can transduce retinal tissue in mice and primates efficiently, although no more than AAV2/2 and rAAV2/5 serotypes. Transduction efficiency appeared lower in the Abca4(-/-) mouse compared to wild type with all vectors tested, suggesting an effect of specific retinal diseases on the efficiency of gene delivery. Shuffling of AAV capsid domains may have clinical applications for patients who develop T-cell immune responses following AAV gene therapy, as specific peptide antigen sequences could be substituted using this technique prior to vector re-treatments.

  3. Molecular evidence of inefficient transduction of proliferating human B lymphocytes by VSV-pseudotyped HIV-1-derived lentivectors

    International Nuclear Information System (INIS)

    Serafini, M.; Naldini, L.; Introna, M.

    2004-01-01

    Lentiviral vectors are attractive tools to transduce dividing and nondividing cells. Human tonsillar B lymphocytes have been purified and induced to proliferate by the addition of anti-CD40 + IL-4 or anti-CD40 + anti-μ signals and transduced at high MOI with a VSV pseudotyped lentivector carrying the eGFP gene under the control of the PGK promoter. Parallel cultures of PHA-stimulated T lymphocytes containing a comparable amount of cycling cells during the infection reached over 70% eGFP transduction. By contrast, only less than 3% B lymphocytes became eGFP positive after 7 days from transduction. Molecular analysis of the viral life cycle shows that cytoplasmic retrotranscribed cDNA and nuclear 2LTR circles are detectable at lower levels and for a shorter period of time in proliferating B cells with respect to proliferating T lymphocytes. Moreover, FACS-sorted eGFP-positive and negative B cell populations were both positive for the presence of retrotranscribed cDNA and 2LTR circles nuclear forms. By contrast, nested Alu-LTR PCR allowed us to detect an integrated provirus in FACS-sorted eGFP-positive cells only. Together with the demonstration that infection in saturation conditions led to an increase in the percentage of transduced cells (reaching 9%), these findings suggest that in proliferating B lymphocytes, lentiviral transduction is an inefficient process blocked at the early steps of the viral life cycle possibly involving partially saturable restriction factors

  4. Convection Enhanced Delivery of Recombinant Adeno-associated Virus into the Mouse Brain.

    Science.gov (United States)

    Nash, Kevin R; Gordon, Marcia N

    2016-01-01

    Recombinant adeno-associated virus (rAAV) has become an extremely useful tool for the study of gene over expression or knockdown in the central nervous system of experimental animals. One disadvantage of intracranial injections of rAAV vectors into the brain parenchyma has been restricted distribution to relatively small volumes of the brain. Convection enhanced delivery (CED) is a method for delivery of clinically relevant amounts of therapeutic agents to large areas of the brain in a direct intracranial injection procedure. CED uses bulk flow to increase the hydrostatic pressure and thus improve volume distribution. The CED method has shown robust gene transfer and increased distribution within the CNS and can be successfully used for different serotypes of rAAV for increased transduction of the mouse CNS. This chapter details the surgical injection of rAAV by CED into a mouse brain.

  5. A pseudotype baculovirus expressing the capsid protein of foot-and-mouth disease virus and a T-Cell immunogen shows enhanced immunogenicity in mice

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    Liu Xiangtao

    2011-02-01

    Full Text Available Abstract Background Foot-and-mouth disease (FMD is a highly contagious disease of livestock which causes severe economic loss in cloven-hoofed animals. Vaccination is still a major strategy in developing countries to control FMD. Currently, inactivated vaccine of FMDV has been used in many countries with limited success and safety concerns. Development of a novel effective vaccine is must. Methods In the present study, two recombinant pseudotype baculoviruses, one expressing the capsid of foot-and-mouth disease virus (FMDV under the control of a cytomegalovirus immediate early enhancer/promoter (CMV-IE, and the other the caspid plus a T-cell immunogen coding region under a CAG promoter were constructed, and their expression was characterized in mammalian cells. In addition, their immunogenicity in a mouse model was investigated. The humoral and cell-mediated immune responses induced by pseudotype baculovirus were compared with those of inactivated vaccine. Results Indirect immunofluorescence assay (IFA and indirect sandwich-ELISA (IS-ELISA showed both recombinant baculoviruses (with or without T-cell epitopes were transduced efficiently and expressed target proteins in BHK-21 cells. In mice, intramuscular inoculation of recombinants with 1 × 109 or 1 × 1010 PFU/mouse induced the production of FMDV-specific neutralizing antibodies and gamma interferon (IFN-γ. Furthermore, recombinant baculovirus with T-cell epitopes had better immunogenicity than the recombinant without T-cell epitopes as demonstrated by significantly enhanced IFN-γ production (P P Conclusions These results indicate that pseudotype baculovirus-mediated gene delivery could be a alternative strategy to develop a new generation of vaccines against FMDV infection.

  6. AAV-Mediated Gene Targeting Is Significantly Enhanced by Transient Inhibition of Nonhomologous End Joining or the Proteasome In Vivo

    Science.gov (United States)

    Paulk, Nicole K.; Loza, Laura Marquez; Finegold, Milton J.

    2012-01-01

    Abstract Recombinant adeno-associated virus (rAAV) vectors have clear potential for use in gene targeting but low correction efficiencies remain the primary drawback. One approach to enhancing efficiency is a block of undesired repair pathways like nonhomologous end joining (NHEJ) to promote the use of homologous recombination. The natural product vanillin acts as a potent inhibitor of NHEJ by inhibiting DNA-dependent protein kinase (DNA-PK). Using a homology containing rAAV vector, we previously demonstrated in vivo gene repair frequencies of up to 0.1% in a model of liver disease hereditary tyrosinemia type I. To increase targeting frequencies, we administered vanillin in combination with rAAV. Gene targeting frequencies increased up to 10-fold over AAV alone, approaching 1%. Fah−/−Ku70−/− double knockout mice also had increased gene repair frequencies, genetically confirming the beneficial effects of blocking NHEJ. A second strategy, transient proteasomal inhibition, also increased gene-targeting frequencies but was not additive to NHEJ inhibition. This study establishes the benefit of transient NHEJ inhibition with vanillin, or proteasome blockage with bortezomib, for increasing hepatic gene targeting with rAAV. Functional metabolic correction of a clinically relevant disease model was demonstrated and provided evidence for the feasibility of gene targeting as a therapeutic strategy. PMID:22486314

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

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    Strasak Alexander

    2009-06-01

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

  8. Induction of immunity to antigens expressed by recombinant adeno-associated virus depends on the route of administration.

    Science.gov (United States)

    Brockstedt, D G; Podsakoff, G M; Fong, L; Kurtzman, G; Mueller-Ruchholtz, W; Engleman, E G

    1999-07-01

    Recombinant adeno-associated virus (rAAV) is a replication-defective parvovirus which is being explored as a vector for gene therapy because of its broad host range, excellent safety profile, and durable transgene expression in infected hosts. rAAV has also been reported by several groups to induce little or no immune response to its encoded transgene products. In this study we examined the immunogenicity of rAAV by studying the immune response of C57BL/6 mice to a single dose of rAAV-encoding ovalbumin (AAV-Ova) administered by a variety of routes. Mice injected with AAV-Ova intraperitoneally (ip), intravenously, or subcutaneously developed potent ovalbumin-specific cytotoxic T lymphocytes (CTL) as well as anti-ovalbumin antibodies and antibodies to AAV. In contrast, mice injected with AAV-Ova intramuscularly developed a humoral response to the virus and the transgene but minimal ovalbumin-specific CTLs. The induced CTL response after ip administration of AAV-Ova protected mice against a subsequent tumor challenge with an ovalbumin-transfected B16 melanoma cell line. Studies of the mechanism by which AAV-Ova induces CTL confirmed that the virus delivers the transgene product into the classical MHC class I pathway of antigen processing. Mice that previously had been exposed to rAAV vectors failed to develop ovalbumin-specific CTL following administration of AAV-Ova. Analysis of these mice revealed the presence of circulating anti-AAV antibodies that blocked rAAV transduction in vitro and inhibited CTL induction in vivo. These results suggest a possible role for rAAV in the immunotherapy of malignancies and viral infections, although induced antibody responses to AAV may limit its ability to be administered for repeated vaccinations. Copyright 1999 Academic Press.

  9. Gene delivery to pancreatic exocrine cells in vivo and in vitro

    Directory of Open Access Journals (Sweden)

    Houbracken Isabelle

    2012-10-01

    Full Text Available Abstract Background Effective gene transfer to the pancreas or to pancreatic cells has remained elusive although it is essential for studies of genetic lineage tracing and modulation of gene expression. Different transduction methods and viral vectors were tested in vitro and in vivo, in rat and mouse pancreas. Results For in vitro transfection/transduction of rat exocrine cells lipofection reagents, adenoviral vectors, and Mokola- and VSV-G pseudotyped lentiviral vectors were used. For in vivo transduction of mouse and rat pancreas adenoviral vectors and VSV-G lentiviral vectors were injected into the parenchymal tissue. Both lipofection of rat exocrine cell cultures and transduction with Mokola pseudotyped lentiviral vectors were inefficient and resulted in less than 4% EGFP expressing cells. Adenoviral transduction was highly efficient but its usefulness for gene delivery to rat exocrine cells in vitro was hampered by a drastic increase in cell death. In vitro transduction of rat exocrine cells was most optimal with VSV-G pseudotyped lentiviral vectors, with stable transgene expression, no significant effect on cell survival and about 40% transduced cells. In vivo, pancreatic cells could not be transduced by intra-parenchymal administration of lentiviral vectors in mouse and rat pancreas. However, a high efficiency could be obtained by adenoviral vectors, resulting in transient transduction of mainly exocrine acinar cells. Injection in immune-deficient animals diminished leukocyte infiltration and prolonged transgene expression. Conclusions In summary, our study remarkably demonstrates that transduction of pancreatic exocrine cells requires lentiviral vectors in vitro but adenoviral vectors in vivo.

  10. The impact of envelope glycoprotein cleavage on the antigenicity, infectivity, and neutralization sensitivity of Env-pseudotyped human immunodeficiency virus type 1 particles

    International Nuclear Information System (INIS)

    Herrera, Carolina; Klasse, Per Johan; Michael, Elizabeth; Kake, Shivani; Barnes, Kelly; Kibler, Christopher W.; Campbell-Gardener, Lila; Si, Zhihai; Sodroski, Joseph; Moore, John P.; Beddows, Simon

    2005-01-01

    Endoproteolytic processing of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoproteins is an obligate part of the biosynthetic pathway that generates functional, fusion-competent Env complexes, which are then incorporated into infectious virions. We have examined the influence of cleavage on Env-specific antibody reactivity, Env incorporation into pseudovirions, and the infectivity and neutralization sensitivity of Env-pseudotyped viruses. To do so, we have used both incompletely processed wild-type (Wt) Env and engineered, cleavage-defective Env mutants. We find that there is no simple association between antibody reactivity to cell surface-expressed Env, and the ability of the same antibody to neutralize virus pseudotyped with the same Env proteins. One explanation for the absence of such an association is the diverse array of Env species present on the surface of transiently transfected cells. We also confirm that cleavage-defective mutants are antigenically different from Wt Env. These findings have implications for the use of Env binding assays as predictors of neutralizing activity, and for the development of cleavage-defective Env trimers for use as subunit immunogens

  11. Hepatorenal correction in murine glycogen storage disease type I with a double-stranded adeno-associated virus vector.

    LENUS (Irish Health Repository)

    Luo, Xiaoyan

    2011-11-01

    Glycogen storage disease type Ia (GSD-Ia) is caused by the deficiency of glucose-6-phosphatase (G6Pase). Long-term complications of GSD-Ia include life-threatening hypoglycemia and proteinuria progressing to renal failure. A double-stranded (ds) adeno-associated virus serotype 2 (AAV2) vector encoding human G6Pase was pseudotyped with four serotypes, AAV2, AAV7, AAV8, and AAV9, and we evaluated efficacy in 12-day-old G6pase (-\\/-) mice. Hypoglycemia during fasting (plasma glucose <100 mg\\/dl) was prevented for >6 months by the dsAAV2\\/7, dsAAV2\\/8, and dsAAV2\\/9 vectors. Prolonged fasting for 8 hours revealed normalization of blood glucose following dsAAV2\\/9 vector administration at the higher dose. The glycogen content of kidney was reduced by >65% with both the dsAAV2\\/7 and dsAAV2\\/9 vectors, and renal glycogen content was stably reduced between 7 and 12 months of age for the dsAAV2\\/9 vector-treated mice. Every vector-treated group had significantly reduced glycogen content in the liver, in comparison with untreated G6pase (-\\/-) mice. G6Pase was expressed in many renal epithelial cells of with the dsAAV2\\/9 vector for up to 12 months. Albuminuria and renal fibrosis were reduced by the dsAAV2\\/9 vector. Hepatorenal correction in G6pase (-\\/-) mice demonstrates the potential of AAV vectors for the correction of inherited diseases of metabolism.

  12. Positron Emission Tomography Imaging Demonstrates Correlation between Behavioral Recovery and Correction of Dopamine Neurotransmission after Gene Therapy

    International Nuclear Information System (INIS)

    Leriche, L.; Besret, L.; Gregoire, M.C.; Deglon, N.; Hantraye, Ph.; Leriche, L.; Besret, L.; Gregoire, M.C.; Deglon, N.; Hantraye, Ph.; Bjorklund, T.; Breysse, N.; Carlsson, T.; Kirik, D.; Dolle, F.; Mandel, R.J.; Kirik, D.

    2009-01-01

    In vivo gene transfer using viral vectors is an emerging therapy for neuro-degenerative diseases with a clinical impact recently demonstrated in Parkinson's disease patients. Recombinant adeno-associated viral (rAAV) vectors, in particular, provide an excellent tool for long-term expression of therapeutic genes in the brain. Here we used the [ 11 C]raclopride [(S)-(-)-3, 5-dichloro-N-((1-ethyl-2-pyrrolidinyl)methyl)-2-hydroxy- 6-methoxybenzamide] micro-positron emission tomography (PET) technique to demonstrate that delivery of the tyrosine hydroxylase (TH) and GTP-cyclohydrolase 1 (GCH1) enzymes using an rAAV5 vector normalizes the increased [ 11 C]raclopride binding in hemi-parkinsonian rats. Importantly, we show in vivo by micro-PET imaging and postmortem by classical binding assays performed in the very same animals that the changes in [ 11 C]raclopride after viral vector-based enzyme replacement therapy is attributable to a decrease in the affinity of the tracer binding to the D2 receptors, providing evidence for reconstitution of a functional pool of endogenous dopamine in the striatum. Moreover, the extent of the normalization in this non-invasive imaging measure was highly correlated with the functional recovery in motor behavior. The PET imaging protocol used in this study is fully adaptable to humans and thus can serve as an in vivo imaging technique to follow TH+GCH1 gene therapy in PD patients and provide an additional objective measure to a potential clinical trial using rAAV vectors to deliver L-3, 4-dihydroxyphenylalanine in the brain. (authors)

  13. Construction of adeno-associated virus packaging plasmids and cells that directly select for AAV helper functions.

    Science.gov (United States)

    Whiteway, Alistair; Deru, Wale; Prentice, H Grant; Anderson, Robert

    2003-12-01

    Recombinant adeno-associated virus type 2 (rAAV) has promise for use as a gene therapy vector. Potential problems in the production of rAAV stocks are both the limited amount of recombinant virus that is produced by traditional methods and the possibility of wild-type replication competent adeno-associated virus (wtAAV) contamination. The presence of these contaminants is largely dependent upon the helper plasmid used. Whilst wtAAV is not a pathogen, the presence of these contaminants is undesirable as they may affect experiments concerning the biology of rAAV. Additionally as protocols using rAAV with altered tropism are becoming more prevalent, it is important that no recombination be permitted that may cause the creation of a replication competent AAV with modified (targeting) capsids. Many experimental protocols require the generation of large amounts of high titre rAAV stocks. We describe the production of several AAV helper plasmids and cell lines designed to achieve this goal. These plasmids possess split AAV rep and cap genes to eliminate the production of wtAAV and they possess a selection mechanism which is operatively linked to expression from the AAV cap gene. This allows positive selection of those cells expressing the highest level of the structural capsid proteins and therefore those cells which yield the highest amount of rAAV.

  14. Recombinant AAV-mediated BEST1 transfer to the retinal pigment epithelium: analysis of serotype-dependent retinal effects.

    Directory of Open Access Journals (Sweden)

    Karina E Guziewicz

    Full Text Available Mutations in the BEST1 gene constitute an underlying cause of juvenile macular dystrophies, a group of retinal disorders commonly referred to as bestrophinopathies and usually diagnosed in early childhood or adolescence. The disease primarily affects macular and paramacular regions of the eye leading to major declines in central vision later in life. Currently, there is no cure or surgical management for BEST1-associated disorders. The recently characterized human disease counterpart, canine multifocal retinopathy (cmr, recapitulates a full spectrum of clinical and molecular features observed in human bestrophinopathies and offers a valuable model system for development and testing of therapeutic strategies. In this study, the specificity, efficiency and safety of rAAV-mediated transgene expression driven by the human VMD2 promoter were assessed in wild-type canine retinae. While the subretinal delivery of rAAV2/1 vector serotype was associated with cone damage in the retina when BEST1 and GFP were co-expressed, the rAAV2/2 vector serotype carrying either GFP reporter or BEST1 transgene under control of human VMD2 promoter was safe, and enabled specific transduction of the RPE cell monolayer that was stable for up to 6 months post injection. These encouraging studies with the rAAV2/2 vector lay the groundwork for development of gene augmentation therapy for human bestrophinopathies.

  15. 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

  16. Gene delivery to skeletal muscle results in sustained expression and systemic delivery of a therapeutic protein.

    Science.gov (United States)

    Kessler, P D; Podsakoff, G M; Chen, X; McQuiston, S A; Colosi, P C; Matelis, L A; Kurtzman, G J; Byrne, B J

    1996-11-26

    Somatic gene therapy has been proposed as a means to achieve systemic delivery of therapeutic proteins. However, there is limited evidence that current methods of gene delivery can practically achieve this goal. In this study, we demonstrate that, following a single intramuscular administration of a recombinant adeno-associated virus (rAAV) vector containing the beta-galactosidase (AAV-lacZ) gene into adult BALB/c mice, protein expression was detected in myofibers for at least 32 weeks. A single intramuscular administration of an AAV vector containing a gene for human erythropoietin (AAV-Epo) into mice resulted in dose-dependent secretion of erythropoietin and corresponding increases in red blood cell production that persisted for up to 40 weeks. Primary human myotubes transduced in vitro with the AAV-Epo vector also showed dose-dependent production of Epo. These results demonstrate that rAAV vectors are able to transduce skeletal muscle and are capable of achieving sustained expression and systemic delivery of a therapeutic protein following a single intramuscular administration. Gene therapy using AAV vectors may provide a practical strategy for the treatment of inherited and acquired protein deficiencies.

  17. Gene delivery to skeletal muscle results in sustained expression and systemic delivery of a therapeutic protein

    Science.gov (United States)

    Kessler, Paul D.; Podsakoff, Gregory M.; Chen, Xiaojuan; McQuiston, Susan A.; Colosi, Peter C.; Matelis, Laura A.; Kurtzman, Gary J.; Byrne, Barry J.

    1996-01-01

    Somatic gene therapy has been proposed as a means to achieve systemic delivery of therapeutic proteins. However, there is limited evidence that current methods of gene delivery can practically achieve this goal. In this study, we demonstrate that, following a single intramuscular administration of a recombinant adeno-associated virus (rAAV) vector containing the β-galactosidase (AAV-lacZ) gene into adult BALB/c mice, protein expression was detected in myofibers for at least 32 weeks. A single intramuscular administration of an AAV vector containing a gene for human erythropoietin (AAV-Epo) into mice resulted in dose-dependent secretion of erythropoietin and corresponding increases in red blood cell production that persisted for up to 40 weeks. Primary human myotubes transduced in vitro with the AAV-Epo vector also showed dose-dependent production of Epo. These results demonstrate that rAAV vectors are able to transduce skeletal muscle and are capable of achieving sustained expression and systemic delivery of a therapeutic protein following a single intramuscular administration. Gene therapy using AAV vectors may provide a practical strategy for the treatment of inherited and acquired protein deficiencies. PMID:8943064

  18. Tailored HIV-1 vectors for genetic modification of primary human dendritic cells and monocytes.

    Science.gov (United States)

    Durand, Stéphanie; Nguyen, Xuan-Nhi; Turpin, Jocelyn; Cordeil, Stephanie; Nazaret, Nicolas; Croze, Séverine; Mahieux, Renaud; Lachuer, Joël; Legras-Lachuer, Catherine; Cimarelli, Andrea

    2013-01-01

    Monocyte-derived dendritic cells (MDDCs) play a key role in the regulation of the immune system and are the target of numerous gene therapy applications. The genetic modification of MDDCs is possible with human immunodeficiency virus type 1 (HIV-1)-derived lentiviral vectors (LVs) but requires high viral doses to bypass their natural resistance to viral infection, and this in turn affects their physiological properties. To date, a single viral protein is able to counter this restrictive phenotype, Vpx, a protein derived from members of the HIV-2/simian immunodeficiency virus SM lineage that counters at least two restriction factors present in myeloid cells. By tagging Vpx with a short heterologous membrane-targeting domain, we have obtained HIV-1 LVs incorporating high levels of this protein (HIV-1-Src-Vpx). These vectors efficiently transduce differentiated MDDCs and monocytes either as previously purified populations or as populations within unsorted peripheral blood mononuclear cells (PBMCs). In addition, these vectors can be efficiently pseudotyped with receptor-specific envelopes, further restricting their cellular tropism almost uniquely to MDDCs. Compared to conventional HIV-1 LVs, these novel vectors allow for an efficient genetic modification of MDDCs and, more importantly, do not cause their maturation or affect their survival, which are unwanted side effects of the transduction process. This study describes HIV-1-Src-Vpx LVs as a novel potent tool for the genetic modification of differentiated MDDCs and of circulating monocyte precursors with strong potential for a wide range of gene therapy applications.

  19. Anxiolytic-like effects after vector-mediated overexpression of neuropeptide Y in the amygdala and hippocampus of mice

    DEFF Research Database (Denmark)

    Christiansen, Søren Hofman Oliveira; Olesen, Mikkel Vestergaard; Gøtzsche, Casper René

    2014-01-01

    , injections of rAAV-NPY caused significant anxiolytic-like effect in the open field, elevated plus maze, and light-dark transition tests. In the hippocampus, rAAV-NPY treatment was associated with anxiolytic-like effect only in the elevated plus maze. No additive effect was observed after combined r....... Using a recombinant adeno-associated viral (rAAV) vector, we addressed this idea by testing effects on anxiolytic- and depression-like behaviours in adult mice after overexpression of NPY transgene in the amygdala and/or hippocampus, two brain regions implicated in emotional behaviours. In the amygdala......AAV-NPY injection into both the amygdala and hippocampus where anxiolytic-like effect was found in the elevated plus maze and light-dark transition tests. Antidepressant-like effects were not detected in any of the rAAV-NPY injected groups. Immobility was even increased in the tail suspension and forced swim tests...

  20. Inhibition of HIV-1 lentiviral particles infectivity by Gynostemma ...

    African Journals Online (AJOL)

    These claims motivated the study in which the inhibition of viral vector infectivity of HeLa cells was assessed flow cytometrically by measuring the expression of green fluorescent protein (GFP) transgene incorporated in the lentiviral vector construct. An infectious VSV-G-pseudotyped, human immunodeficiency virus type ...

  1. Detection of exogenous gene doping of IGF-I by a real-time quantitative PCR assay.

    Science.gov (United States)

    Zhang, Jin-Ju; Xu, Jing-Feng; Shen, Yong-Wei; Ma, Shi-Jiao; Zhang, Ting-Ting; Meng, Qing-Lin; Lan, Wen-Jun; Zhang, Chun; Liu, Xiao-Mei

    2017-07-01

    Gene doping can be easily concealed since its product is similar to endogenous protein, making its effective detection very challenging. In this study, we selected insulin-like growth factor I (IGF-I) exogenous gene for gene doping detection. First, the synthetic IGF-I gene was subcloned to recombinant adeno-associated virus (rAAV) plasmid to produce recombinant rAAV2/IGF-I-GFP vectors. Second, in an animal model, rAAV2/IGF-I-GFP vectors were injected into the thigh muscle tissue of mice, and then muscle and blood specimens were sampled at different time points for total DNA isolation. Finally, real-time quantitative PCR was employed to detect the exogenous gene doping of IGF-I. In view of the characteristics of endogenous IGF-I gene sequences, a TaqMan probe was designed at the junction of exons 2 and 3 of IGF-I gene to distinguish it from the exogenous IGF-I gene. In addition, an internal reference control plasmid and its probe were used in PCR to rule out false-positive results through comparison of their threshold cycle (Ct) values. Thus, an accurate exogenous IGF-I gene detection approach was developed in this study. © 2016 International Union of Biochemistry and Molecular Biology, Inc.

  2. Efficient photoreceptor-targeted gene expression in vivo by recombinant adeno-associated virus.

    Science.gov (United States)

    Flannery, J G; Zolotukhin, S; Vaquero, M I; LaVail, M M; Muzyczka, N; Hauswirth, W W

    1997-06-24

    We describe a general approach for achieving efficient and cell type-specific expression of exogenous genes in photoreceptor cells of the mammalian retina. Recombinant adeno-associated virus (rAAV) vectors were used to transfer the bacterial lacZ gene or a synthetic green fluorescent protein gene (gfp) to mouse or rat retinas after injection into the subretinal space. Using a proximal murine rod opsin promoter (+86 to -385) to drive expression, reporter gene product was found exclusively in photoreceptors, not in any other retinal cell type or in the adjacent retinal pigment epithelium. GFP-expressing photoreceptors typically encompassed 10-20% of the total retinal area after a single 2-microl injection. Photoreceptors were transduced with nearly 100% efficiency in the region directly surrounding the injection site. We estimate approximately 2.5 million photoreceptors were transduced as a result of the single subretinal inoculation. This level of gene transfer and expression suggests the feasibility of genetic therapy for retinal disease. The gfp-containing rAAV stock was substantially free of both adenovirus and wild-type AAV, as judged by plaque assay and infectious center assay, respectively. Thus, highly purified, helper virus-free rAAV vectors can achieve high-frequency tissue-specific transduction of terminally differentiated, postmitotic photoreceptor cells.

  3. Large-scale manufacture and characterization of a lentiviral vector produced for clinical ex vivo gene therapy application.

    Science.gov (United States)

    Merten, Otto-Wilhelm; Charrier, Sabine; Laroudie, Nicolas; Fauchille, Sylvain; Dugué, Céline; Jenny, Christine; Audit, Muriel; Zanta-Boussif, Maria-Antonietta; Chautard, Hélène; Radrizzani, Marina; Vallanti, Giuliana; Naldini, Luigi; Noguiez-Hellin, Patricia; Galy, Anne

    2011-03-01

    From the perspective of a pilot clinical gene therapy trial for Wiskott-Aldrich syndrome (WAS), we implemented a process to produce a lentiviral vector under good manufacturing practices (GMP). The process is based on the transient transfection of 293T cells in Cell Factory stacks, scaled up to harvest 50 liters of viral stock per batch, followed by purification of the vesicular stomatitis virus glycoprotein-pseudotyped particles through several membrane-based and chromatographic steps. The process leads to a 200-fold volume concentration and an approximately 3-log reduction in protein and DNA contaminants. An average yield of 13% of infectious particles was obtained in six full-scale preparations. The final product contained low levels of contaminants such as simian virus 40 large T antigen or E1A sequences originating from producer cells. Titers as high as 2 × 10(9) infectious particles per milliliter were obtained, generating up to 6 × 10(11) infectious particles per batch. The purified WAS vector was biologically active, efficiently expressing the genetic insert in WAS protein-deficient B cell lines and transducing CD34(+) cells. The vector introduced 0.3-1 vector copy per cell on average in CD34(+) cells when used at the concentration of 10(8) infectious particles per milliliter, which is comparable to preclinical preparations. There was no evidence of cellular toxicity. These results show the implementation of large-scale GMP production, purification, and control of advanced HIV-1-derived lentiviral technology. Results obtained with the WAS vector provide the initial manufacturing and quality control benchmarking that should be helpful to further development and clinical applications.

  4. Overexpression of the steroidogenic enzyme cytochrome P450 side chain cleavage in the ventral tegmental area increases 3α,5α-THP and reduces long-term operant ethanol self-administration.

    Science.gov (United States)

    Cook, Jason B; Werner, David F; Maldonado-Devincci, Antoniette M; Leonard, Maggie N; Fisher, Kristen R; O'Buckley, Todd K; Porcu, Patrizia; McCown, Thomas J; Besheer, Joyce; Hodge, Clyde W; Morrow, A Leslie

    2014-04-23

    Neuroactive steroids are endogenous neuromodulators capable of altering neuronal activity and behavior. In rodents, systemic administration of endogenous or synthetic neuroactive steroids reduces ethanol self-administration. We hypothesized this effect arises from actions within mesolimbic brain regions that we targeted by viral gene delivery. Cytochrome P450 side chain cleavage (P450scc) converts cholesterol to pregnenolone, the rate-limiting enzymatic reaction in neurosteroidogenesis. Therefore, we constructed a recombinant adeno-associated serotype 2 viral vector (rAAV2), which drives P450scc expression and neuroactive steroid synthesis. The P450scc-expressing vector (rAAV2-P450scc) or control GFP-expressing vector (rAAV2-GFP) were injected bilaterally into the ventral tegmental area (VTA) or nucleus accumbens (NAc) of alcohol preferring (P) rats trained to self-administer ethanol. P450scc overexpression in the VTA significantly reduced ethanol self-administration by 20% over the 3 week test period. P450scc overexpression in the NAc, however, did not alter ethanol self-administration. Locomotor activity was unaltered by vector administration to either region. P450scc overexpression produced a 36% increase in (3α,5α)-3-hydroxypregnan-20-one (3α,5α-THP, allopregnanolone)-positive cells in the VTA, but did not increase 3α,5α-THP immunoreactivity in NAc. These results suggest that P450scc overexpression and the resultant increase of 3α,5α-THP-positive cells in the VTA reduces ethanol reinforcement. 3α,5α-THP is localized to neurons in the VTA, including tyrosine hydroxylase neurons, but not astrocytes. Overall, the results demonstrate that using gene delivery to modulate neuroactive steroids shows promise for examining the neuronal mechanisms of moderate ethanol drinking, which could be extended to other behavioral paradigms and neuropsychiatric pathology.

  5. Chronic Cardiac-Targeted RNA Interference for the Treatment of Heart Failure Restores Cardiac Function and Reduces Pathological Hypertrophy

    Science.gov (United States)

    Suckau, Lennart; Fechner, Henry; Chemaly, Elie; Krohn, Stefanie; Hadri, Lahouaria; Kockskämper, Jens; Westermann, Dirk; Bisping, Egbert; Ly, Hung; Wang, Xiaomin; Kawase, Yoshiaki; Chen, Jiqiu; Liang, Lifan; Sipo, Isaac; Vetter, Roland; Weger, Stefan; Kurreck, Jens; Erdmann, Volker; Tschope, Carsten; Pieske, Burkert; Lebeche, Djamel; Schultheiss, Heinz-Peter; Hajjar, Roger J.; Poller, Wolfgang Ch.

    2009-01-01

    Background RNA interference (RNAi) has the potential to be a novel therapeutic strategy in diverse areas of medicine. We report on targeted RNAi for the treatment of heart failure (HF), an important disorder in humans resulting from multiple etiologies. Successful treatment of HF is demonstrated in a rat model of transaortic banding by RNAi targeting of phospholamban (PLB), a key regulator of cardiac Ca2+ homeostasis. Whereas gene therapy rests on recombinant protein expression as its basic principle, RNAi therapy employs regulatory RNAs to achieve its effect. Methods and Results We describe structural requirements to obtain high RNAi activity from adenoviral (AdV) and adeno-associated virus (AAV9) vectors and show that an AdV short hairpin RNA vector (AdV-shRNA) silenced PLB in cardiomyocytes (NRCMs) and improved hemodynamics in HF rats 1 month after aortic root injection. For simplified long-term therapy we developed a dimeric cardiotropic AAV vector (rAAV9-shPLB) delivering RNAi activity to the heart via intravenous injection. Cardiac PLB protein was reduced to 25% and SERCA2a suppression in the HF groups was rescued. In contrast to traditional vectors rAAV9 shows high affinity for myocardium, but low affinity for liver and other organs. rAAV9-shPLB therapy restored diastolic (LVEDP, dp/dtmin, Tau) and systolic (fractional shortening) functional parameters to normal range. The massive cardiac dilation was normalized and the cardiac hypertrophy, cardiomyocyte diameter and cardiac fibrosis significantly reduced. Importantly, there was no evidence of microRNA deregulation or hepatotoxicity during these RNAi therapies. Conclusion Our data show, for the first time, high efficacy of an RNAi therapeutic strategy in a cardiac disease. PMID:19237664

  6. Phenotypic correction of Fanconi anemia cells in the murine bone marrow after carrier cell mediated delivery of lentiviral vector.

    Science.gov (United States)

    Chakkaramakkil Verghese, Santhosh; Goloviznina, Natalya A; Kurre, Peter

    2016-11-19

    Fanconi anemia (FA) is an autosomal-recessive disorder associated with hematopoietic failure and it is a candidate for hematopoietic stem cell (HSC)-directed gene therapy. However, the characteristically reduced HSC numbers found in FA patients, their ineffective mobilization from the marrow, and re-oxygenation damage during ex vivo manipulation have precluded clinical success using conventional in vitro approaches. We previously demonstrated that lentiviral vector (LV) particles reversibly attach to the cell surface where they gain protection from serum complement neutralization. We reasoned that cellular delivery of LV to the bone marrow niche could avoid detrimental losses during FA HSC mobilization and in vitro modification. Here, we demonstrate that a VSV-G pseudotyped lentivector, carrying the FANCC transgene, can be transmitted from carrier to bystander cells. In cell culture and transplantation models of FA, we further demonstrate that LV carrier cells migrate along SDF-1α gradients and transfer vector particles that stably integrate and phenotypically correct the characteristic DNA alkylator sensitivity in murine and human FA-deficient target bystander cells. Altogether, we demonstrate that cellular homing mechanisms can be harnessed for the functional phenotype correction in murine FA hematopoietic cells.

  7. Phenotypic correction of Fanconi anemia cells in the murine bone marrow after carrier cell mediated delivery of lentiviral vector

    Directory of Open Access Journals (Sweden)

    Santhosh Chakkaramakkil Verghese

    2016-11-01

    Full Text Available Abstract Fanconi anemia (FA is an autosomal-recessive disorder associated with hematopoietic failure and it is a candidate for hematopoietic stem cell (HSC-directed gene therapy. However, the characteristically reduced HSC numbers found in FA patients, their ineffective mobilization from the marrow, and re-oxygenation damage during ex vivo manipulation have precluded clinical success using conventional in vitro approaches. We previously demonstrated that lentiviral vector (LV particles reversibly attach to the cell surface where they gain protection from serum complement neutralization. We reasoned that cellular delivery of LV to the bone marrow niche could avoid detrimental losses during FA HSC mobilization and in vitro modification. Here, we demonstrate that a VSV-G pseudotyped lentivector, carrying the FANCC transgene, can be transmitted from carrier to bystander cells. In cell culture and transplantation models of FA, we further demonstrate that LV carrier cells migrate along SDF-1α gradients and transfer vector particles that stably integrate and phenotypically correct the characteristic DNA alkylator sensitivity in murine and human FA-deficient target bystander cells. Altogether, we demonstrate that cellular homing mechanisms can be harnessed for the functional phenotype correction in murine FA hematopoietic cells.

  8. Alpharetroviral self-inactivating vectors produced by a superinfection-resistant stable packaging cell line allow genetic modification of primary human T lymphocytes.

    Science.gov (United States)

    Labenski, Verena; Suerth, Julia D; Barczak, Elke; Heckl, Dirk; Levy, Camille; Bernadin, Ornellie; Charpentier, Emmanuelle; Williams, David A; Fehse, Boris; Verhoeyen, Els; Schambach, Axel

    2016-08-01

    Primary human T lymphocytes represent an important cell population for adoptive immunotherapies, including chimeric-antigen and T-cell receptor applications, as they have the capability to eliminate non-self, virus-infected and tumor cells. Given the increasing numbers of clinical immunotherapy applications, the development of an optimal vector platform for genetic T lymphocyte engineering, which allows cost-effective high-quality vector productions, remains a critical goal. Alpharetroviral self-inactivating vectors (ARV) have several advantages compared to other vector platforms, including a more random genomic integration pattern and reduced likelihood for inducing aberrant splicing of integrated proviruses. We developed an ARV platform for the transduction of primary human T lymphocytes. We demonstrated functional transgene transfer using the clinically relevant herpes-simplex-virus thymidine kinase variant TK.007. Proof-of-concept of alpharetroviral-mediated T-lymphocyte engineering was shown in vitro and in a humanized transplantation model in vivo. Furthermore, we established a stable, human alpharetroviral packaging cell line in which we deleted the entry receptor (SLC1A5) for RD114/TR-pseudotyped ARVs to prevent superinfection and enhance genomic integrity of the packaging cell line and viral particles. We showed that superinfection can be entirely prevented, while maintaining high recombinant virus titers. Taken together, this resulted in an improved production platform representing an economic strategy for translating the promising features of ARVs for therapeutic T-lymphocyte engineering. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Peripheral blood aspirates overexpressing IGF-I via rAAV gene transfer undergo enhanced chondrogenic differentiation processes.

    Science.gov (United States)

    Frisch, Janina; Orth, Patrick; Rey-Rico, Ana; Venkatesan, Jagadeesh Kumar; Schmitt, Gertrud; Madry, Henning; Kohn, Dieter; Cucchiarini, Magali

    2017-11-01

    Implantation of peripheral blood aspirates induced towards chondrogenic differentiation upon genetic modification in sites of articular cartilage injury may represent a powerful strategy to enhance cartilage repair. Such a single-step approach may be less invasive than procedures based on the use of isolated or concentrated MSCs, simplifying translational protocols in patients. In this study, we provide evidence showing the feasibility of overexpressing the mitogenic and pro-anabolic insulin-like growth factor I (IGF-I) in human peripheral blood aspirates via rAAV-mediated gene transfer, leading to enhanced proliferative and chondrogenic differentiation (proteoglycans, type-II collagen, SOX9) activities in the samples relative to control (reporter rAAV-lacZ) treatment over extended periods of time (at least 21 days, the longest time-point evaluated). Interestingly, IGF-I gene transfer also triggered hypertrophic, osteo- and adipogenic differentiation processes in the aspirates, suggesting that careful regulation of IGF-I expression may be necessary to contain these events in vivo. Still, the current results demonstrate the potential of targeting human peripheral blood aspirates via therapeutic rAAV transduction as a novel, convenient tool to treat articular cartilage injuries. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  10. Vaccinia virus as a subhelper for AAV replication and packaging

    Directory of Open Access Journals (Sweden)

    Andrea R Moore

    Full Text Available Adeno-associated virus (AAV has been widely used as a gene therapy vector to treat a variety of disorders. While these vectors are increasingly popular and successful in the clinic, there is still much to learn about the viruses. Understanding the biology of these viruses is essential in engineering better vectors and generating vectors more efficiently for large-scale use. AAV requires a helper for production and replication making this aspect of the viral life cycle crucial. Vaccinia virus (VV has been widely cited as a helper virus for AAV. However, to date, there are no detailed analyses of its helper function. Here, the helper role of VV was studied in detail. In contrast to common belief, we demonstrated that VV was not a sufficient helper virus for AAV replication. Vaccinia failed to produce rAAV and activate AAV promoters. While this virus could not support rAAV production, Vaccinia could initiate AAV replication and packaging when AAV promoter activation is not necessary. This activity is due to the ability of Vaccinia-driven Rep78 to transcribe in the cytoplasm and subsequently translate in the nucleus and undergo typical functions in the AAV life cycle. As such, VV is subhelper for AAV compared to complete helper functions of adenovirus.

  11. A reliable and feasible qPCR strategy for titrating AAV vectors.

    Science.gov (United States)

    Wang, Feng; Cui, Xiuling; Wang, Mingxi; Xiao, Weidong; Xu, Ruian

    2013-07-05

    Previous studies have revealed that traditional real-time quantitative PCR (qPCR) underestimates adeno-associated virus (AAV) titer. Because the inverted terminal repeat (ITR) exists in all AAV vectors, the only remaining element from the wild genome could form special configurations to interfere with qPCR titration. To solve this problem, a modified and universal qPCR method was tested and established. In this work, there was a great variation in titration of ssAAV2-EGFP (Enhanced Green Fluorescence Protein) and scAAV2-EGFP genome by traditional qPCR. For ssAAV2-EGFP, the highest titer was found by using the targeting EGFP primers and the lowest titer was measured by those targeting bovine growth hormone polyA element (pBGH) primers. Experimental data were reverse for ssAAV2-EGFP and scAAV2-EGFP. Here we report an improved and universal SmaI qPCR method, based on cleaving all ITRs in AAV2 genome by SmaI with several advantages: (1) impact of all ITRs in ssAAV2 and scAAV2 was dismissed; (2) titers increased remarkably, up to 7-fold, especially for scAAV2; (3) the variation of titers was reduced when different primers were applied. A similar phenomenon was also observed in other ssAAV2 and scAAV2 products when the range of titration was at 3×107 to 7×109 V.G/µl in this study. This modified qPCR strategy can increase rAAV' titer and reduce titration variance, possibly become a universal method for titrating AAV vectors.

  12. Novel cyclo-peptides inhibit Ebola pseudotyped virus entry by targeting primed GP protein.

    Science.gov (United States)

    Li, Quanjie; Ma, Ling; Yi, Dongrong; Wang, Han; Wang, Jing; Zhang, Yongxin; Guo, Ying; Li, Xiaoyu; Zhou, Jinming; Shi, Yi; Gao, George F; Cen, Shan

    2018-07-01

    Ebola virus (EBOV) causes fatal hemorrhagic fever with high death rates in human. Currently, there are no available clinically-approved prophylactic or therapeutic treatments. The recently solved crystal structure of cleavage-primed EBOV glycoprotein (GPcl) in complex with the C domain of endosomal protein Niemann-Pick C1 (NPC1) provides a new target for the development of EBOV entry inhibitors. In this work, a computational approach using docking and molecular dynamic simulations is carried out for the rational design of peptide inhibitors. A novel cyclo-peptide (Pep-3.3) was identified to target at the late stage of EBOV entry and exhibit specific inhibitory activity against EBOV-GP pseudotyped viruses, with 50% inhibitory concentration (IC50) of 5.1 μM. In vitro binding assay and molecular simulations revealed that Pep-3.3 binds to GPcl with a KD value of 69.7 μM, through interacting with predicted residues in the hydrophobic binding pocket of GPcl. Mutation of predicted residues T83 caused resistance to Pep-3.3 inhibition in viral infectivity, providing preliminary support for the model of the peptide binding to GPcl. This study demonstrates the feasibility of inhibiting EBOV entry by targeting GPcl with peptides. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Measles virus envelope pseudotyped lentiviral vectors transduce quiescent human HSCs at an efficiency without precedent.

    Science.gov (United States)

    Lévy, Camille; Amirache, Fouzia; Girard-Gagnepain, Anais; Frecha, Cecilia; Roman-Rodríguez, Francisco J; Bernadin, Ornellie; Costa, Caroline; Nègre, Didier; Gutierrez-Guerrero, Alejandra; Vranckx, Lenard S; Clerc, Isabelle; Taylor, Naomi; Thielecke, Lars; Cornils, Kerstin; Bueren, Juan A; Rio, Paula; Gijsbers, Rik; Cosset, François-Loïc; Verhoeyen, Els

    2017-10-24

    Hematopoietic stem cell (HSC)-based gene therapy trials are now moving toward the use of lentiviral vectors (LVs) with success. However, one challenge in the field remains: efficient transduction of HSCs without compromising their stem cell potential. Here we showed that measles virus glycoprotein-displaying LVs (hemagglutinin and fusion protein LVs [H/F-LVs]) were capable of transducing 100% of early-acting cytokine-stimulated human CD34 + (hCD34 + ) progenitor cells upon a single application. Strikingly, these H/F-LVs also allowed transduction of up to 70% of nonstimulated quiescent hCD34 + cells, whereas conventional vesicular stomatitis virus G (VSV-G)-LVs reached 5% at the most with H/F-LV entry occurring exclusively through the CD46 complement receptor. Importantly, reconstitution of NOD/SCIDγc -/- (NSG) mice with H/F-LV transduced prestimulated or resting hCD34 + cells confirmed these high transduction levels in all myeloid and lymphoid lineages. Remarkably, for resting CD34 + cells, secondary recipients exhibited increasing transduction levels of up to 100%, emphasizing that H/F-LVs efficiently gene-marked HSCs in the resting state. Because H/F-LVs promoted ex vivo gene modification of minimally manipulated CD34 + progenitors that maintained stemness, we assessed their applicability in Fanconi anemia, a bone marrow (BM) failure with chromosomal fragility. Notably, only H/F-LVs efficiently gene-corrected minimally stimulated hCD34 + cells in unfractionated BM from these patients. These H/F-LVs improved HSC gene delivery in the absence of cytokine stimulation while maintaining their stem cell potential. Thus, H/F-LVs will facilitate future clinical applications requiring HSC gene modification, including BM failure syndromes, for which treatment has been very challenging up to now.

  14. Normal-tissue radioprotection by overexpression of the copper-zinc and manganese superoxide dismutase genes

    Energy Technology Data Exchange (ETDEWEB)

    Veldwijk, Marlon R. [Dept. of Radiation Oncology, Univ. Medical Center Mannheim, Univ. of Heidelberg, Mannheim (Germany); Pharmacology of Cancer Treatment (G402), German Cancer Research Center, Heidelberg (Germany); Herskind, Carsten; Wenz, Frederik [Dept. of Radiation Oncology, Univ. Medical Center Mannheim, Univ. of Heidelberg, Mannheim (Germany); Sellner, Leopold; Zeller, W. Jens [Pharmacology of Cancer Treatment (G402), German Cancer Research Center, Heidelberg (Germany); Radujkovic, Aleksandar [Dept. of Internal Medicine V, Univ. of Heidelberg (Germany); Laufs, Stephanie [Dept. of Experimental Surgery, Univ. Medical Center Mannheim, Univ. of Heidelberg, Mannheim (Germany); Molecular Oncology of Solid Tumors (G360), German Cancer Research Center, Heidelberg (Germany); Fruehauf, Stefan [Center for Tumor Diagnostic and Therapy, Paracelsus-Klinik, Osnabrueck (Germany)

    2009-08-15

    Background and Purpose: Protection of normal tissue against radiation-induced damage may increase the therapeutic ratio of radiotherapy. A promising strategy for testing this approach is gene therapy-mediated overexpression of the copper-zinc (CuZnSOD) or manganese superoxide dismutase (MnSOD) using recombinant adeno-associated viral (rAAV2) vectors. The purpose of this study was to test the modulating effects of the SOD genes on human primary lung fibroblasts (HPLF) after irradiation. Material and Methods: HPLF were transduced with rAAV2 vectors containing cDNA for the CuZnSOD, MnSOD or a control gene. The cells were irradiated (1-6 Gy), and gene transfer efficiency, apoptosis, protein expression/activity, and radiosensitivity measured by the colony-forming assay determined. Results: After transduction, 90.0% {+-} 6.4% of the cells expressed the transgene. A significant fivefold overexpression of both SOD was confirmed by an SOD activity assay (control: 21.1 {+-} 12.6, CuZnSOD: 95.1 {+-} 17.1, MnSOD: 108.5 {+-} 36.0 U SOD/mg protein) and immunohistochemistry. CuZnSOD and MnSOD overexpression resulted in a significant radioprotection of HPLF compared to controls (surviving fraction [SF] ratio SOD/control > 1): CuZnSOD: 1.18-fold (95% confidence interval [CI]: 1.06-1.32; p = 0.005), MnSOD: 1.23-fold (95% CI: 1.07-1.43; p = 0.01). Conclusion: Overexpression of CuZnSOD and MnSOD in HPLF mediated an increase in clonogenic survival after irradiation compared to controls. In previous works, a lack of radioprotection in SOD-overexpressing tumor cells was observed. Therefore, the present results suggest that rAAV2 vectors are promising tools for the delivery of radioprotective genes in normal tissue. (orig.)

  15. Validation of an automated system for aliquoting of HIV-1 Env-pseudotyped virus stocks.

    Science.gov (United States)

    Schultz, Anke; Germann, Anja; Fuss, Martina; Sarzotti-Kelsoe, Marcella; Ozaki, Daniel A; Montefiori, David C; Zimmermann, Heiko; von Briesen, Hagen

    2018-01-01

    The standardized assessments of HIV-specific immune responses are of main interest in the preclinical and clinical stage of HIV-1 vaccine development. In this regard, HIV-1 Env-pseudotyped viruses play a central role for the evaluation of neutralizing antibody profiles and are produced according to Good Clinical Laboratory Practice- (GCLP-) compliant manual and automated procedures. To further improve and complete the automated production cycle an automated system for aliquoting HIV-1 pseudovirus stocks has been implemented. The automation platform consists of a modified Tecan-based system including a robot platform for handling racks containing 48 cryovials, a Decapper, a tubing pump and a safety device consisting of ultrasound sensors for online liquid level detection of each individual cryovial. With the aim to aliquot the HIV-1 pseudoviruses in an automated manner under GCLP-compliant conditions a validation plan was developed where the acceptance criteria-accuracy, precision as well as the specificity and robustness-were defined and summarized. By passing the validation experiments described in this article the automated system for aliquoting has been successfully validated. This allows the standardized and operator independent distribution of small-scale and bulk amounts of HIV-1 pseudovirus stocks with a precise and reproducible outcome to support upcoming clinical vaccine trials.

  16. Recombinant AAV-mediated in vivo long-term expression and antitumour activity of an anti-ganglioside GM3(Neu5Gc) antibody.

    Science.gov (United States)

    Piperno, G M; López-Requena, A; Predonzani, A; Dorvignit, D; Labrada, M; Zentilin, L; Burrone, O R; Cesco-Gaspere, M

    2015-12-01

    The ganglioside GM3(Neu5Gc) has gained increasing attention as therapeutic target because of its selective expression in various human tumours, such as melanoma, breast and lung cancer. 14F7 is a mouse IgG1 with specific reactivity to GM3(Neu5Gc)-positive tumours. The therapeutic activity of 14F7 has also been demonstrated in vivo, through its repetitive passive administration in tumour-bearing animals. In this work we used an alternative strategy to deliver recombinant 14F7 in vivo and analysed the therapeutic efficacy of this approach. We engineered a recombinant adeno-associated vector to direct the expression of secretable recombinant 14F7 in BALB/c animals. A single administration of the rAAV induced efficient production and secretion of the antibody in the bloodstream, with an expression level reaching plateau at ∼3 weeks after injection and persisting for almost a year. Strikingly, upon challenge with GM3(Neu5Gc)-positive X63-AG8.653 myeloma cells, tumour development was significantly delayed in animals treated with rAAV-14F7 with respect to animals treated with a control rAAV codifying for an irrelevant antibody. Finally, no significant differences in survival proportion were detected in animals injected with rAAV-14F7 or treated by standard administration of repetitive doses of purified monoclonal antibody 14F7.

  17. Protective CD8+ T-cell responses to cytomegalovirus driven by rAAV/GFP/IE1 loading of dendritic cells

    Directory of Open Access Journals (Sweden)

    Dalle-Donne Isabella

    2008-10-01

    Full Text Available Abstract Background Recent studies demonstrate that recombinant adeno-associated virus (rAAV-based antigen loading of dendritic cells (DCs generates in vitro, significant and rapid cytotoxic T-lymphocyte (CTL responses against viral antigens. Methods We used the rAAV system to induce specific CTLs against CVM antigens for the development of cytomegalovirus HCMV gene therapy. As an extension of the versatility of the rAAV system, we incorporated immediate-early 1 (IE1, expressed in HCMV. Our rAAV vector induced a strong stimulation of CTLs directed against the HCMV antigen IE1. We then investigated the efficiency of the CTLs in killing IE1 targeted cells. Results A significant MHC Class I-restricted, anti-IE1-specific CTL killing was demonstrated against IE1 positive peripheral blood mononuclear cells (PBMC after one, in vitro, stimulation. Conclusion In summary, single PBMC stimulation with rAAV/IE1 pulsed DCs induces strong antigen specific-CTL generation. CTLs were capable to lyse low doses of peptides pulsed into target cells. These data suggest that AAV-based antigen loading of DCs is highly effective for generating human CTL responses against HCMV antigens.

  18. Recombinant adeno-associated virus mediates a high level of gene transfer but less efficient integration in the K562 human hematopoietic cell line.

    Science.gov (United States)

    Malik, P; McQuiston, S A; Yu, X J; Pepper, K A; Krall, W J; Podsakoff, G M; Kurtzman, G J; Kohn, D B

    1997-03-01

    We tested the ability of a recombinant adeno-associated virus (rAAV) vector to express and integrate exogenous DNA into human hematopoietic cells in the absence of selection. We developed an rAAV vector, AAV-tNGFR, carrying a truncated rat nerve growth factor receptor (tNGFR) cDNA as a cell surface reporter under the control of the Moloney murine leukemia virus (MoMuLV) long terminal repeat. An analogous MoMuLV-based retroviral vector (L-tNGFR) was used in parallel, and gene transfer and expression in human hematopoietic cells were assessed by flow cytometry and DNA analyses. Following gene transfer into K562 cells with AAV-tNGFR at a multiplicity of infection (MOI) of 13 infectious units (IU), 26 to 38% of cells expressed tNGFR on the surface early after transduction, but the proportion of tNGFR expressing cells steadily declined to 3.0 to 3.5% over 1 month of culture. At an MOI of 130 IU, nearly all cells expressed tNGFR immediately posttransduction, but the proportion of cells expressing tNGFR declined to 62% over 2 months of culture. The decline in the proportion of AAV-tNGFR-expressing cells was associated with ongoing losses of vector genomes. In contrast, K562 cells transduced with the retroviral vector L-tNGFR expressed tNGFR in a constant fraction. Integration analyses on clones showed that integration occurred at different sites. Integration frequencies were estimated at about 49% at an MOI of 130 and 2% at an MOI of 1.3. Transduction of primary human CD34+ progenitor cells by AAV-tNGFR was less efficient than with K562 cells and showed a declining percentage of cells expressing tNGFR over 2 weeks of culture. Thus, purified rAAV caused very high gene transfer and expression in human hematopoietic cells early after transduction, which steadily declined during cell passage in the absence of selection. Although the efficiency of integration was low, overall integration was markedly improved at a high MOI. While prolonged episomal persistence may be adequate

  19. 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.

  20. Sustained miRNA-mediated knockdown of mutant AAT with simultaneous augmentation of wild-type AAT has minimal effect on global liver miRNA profiles.

    Science.gov (United States)

    Mueller, Christian; Tang, Qiushi; Gruntman, Alisha; Blomenkamp, Keith; Teckman, Jeffery; Song, Lina; Zamore, Phillip D; Flotte, Terence R

    2012-03-01

    α-1 antitrypsin (AAT) deficiency can exhibit two pathologic states: a lung disease that is primarily due to the loss of AAT's antiprotease function, and a liver disease resulting from a toxic gain-of-function of the PiZ-AAT (Z-AAT) mutant protein. We have developed several recombinant adeno-associated virus (rAAV) vectors that incorporate microRNA (miRNA) sequences targeting the AAT gene while also driving the expression of miRNA-resistant wild-type AAT-PiM (M-AAT) gene, thus achieving concomitant Z-AAT knockdown in the liver and increased expression of M-AAT. Transgenic mice expressing the human PiZ allele treated with dual-function rAAV9 vectors showed that serum PiZ was stably and persistently reduced by an average of 80%. Treated animals showed knockdown of Z-AAT in liver and serum with concomitant increased serum M-AAT as determined by allele-specific enzyme-linked immunosorbent assays (ELISAs). In addition, decreased globular accumulation of misfolded Z-AAT in hepatocytes and a reduction in inflammatory infiltrates in the liver was observed. Results from microarray studies demonstrate that endogenous miRNAs were minimally affected by this treatment. These data suggests that miRNA mediated knockdown does not saturate the miRNA pathway as has been seen with viral vector expression of short hairpin RNAs (shRNAs). This safe dual-therapy approach can be applied to other disorders such as amyotrophic lateral sclerosis, Huntington disease, cerebral ataxia, and optic atrophies.

  1. Gene Transfer Corrects Acute GM2 Gangliosidosis—Potential Therapeutic Contribution of Perivascular Enzyme Flow

    Science.gov (United States)

    Cachón-González, M Begoña; Wang, Susan Z; McNair, Rosamund; Bradley, Josephine; Lunn, David; Ziegler, Robin; Cheng, Seng H; Cox, Timothy M

    2012-01-01

    The GM2 gangliosidoses are fatal lysosomal storage diseases principally affecting the brain. Absence of β-hexosaminidase A and B activities in the Sandhoff mouse causes neurological dysfunction and recapitulates the acute Tay–Sachs (TSD) and Sandhoff diseases (SD) in infants. Intracranial coinjection of recombinant adeno-associated viral vectors (rAAV), serotype 2/1, expressing human β-hexosaminidase α (HEXA) and β (HEXB) subunits into 1-month-old Sandhoff mice gave unprecedented survival to 2 years and prevented disease throughout the brain and spinal cord. Classical manifestations of disease, including spasticity—as opposed to tremor-ataxia—were resolved by localized gene transfer to the striatum or cerebellum, respectively. Abundant biosynthesis of β-hexosaminidase isozymes and their global distribution via axonal, perivascular, and cerebrospinal fluid (CSF) spaces, as well as diffusion, account for the sustained phenotypic rescue—long-term protein expression by transduced brain parenchyma, choroid plexus epithelium, and dorsal root ganglia neurons supplies the corrective enzyme. Prolonged survival permitted expression of cryptic disease in organs not accessed by intracranial vector delivery. We contend that infusion of rAAV into CSF space and intraparenchymal administration by convection-enhanced delivery at a few strategic sites will optimally treat neurodegeneration in many diseases affecting the nervous system. PMID:22453766

  2. Long-term effect of gene therapy on Leber's congenital amaurosis.

    Science.gov (United States)

    Bainbridge, James W B; Mehat, Manjit S; Sundaram, Venki; Robbie, Scott J; Barker, Susie E; Ripamonti, Caterina; Georgiadis, Anastasios; Mowat, Freya M; Beattie, Stuart G; Gardner, Peter J; Feathers, Kecia L; Luong, Vy A; Yzer, Suzanne; Balaggan, Kamaljit; Viswanathan, Ananth; de Ravel, Thomy J L; Casteels, Ingele; Holder, Graham E; Tyler, Nick; Fitzke, Fred W; Weleber, Richard G; Nardini, Marko; Moore, Anthony T; Thompson, Debra A; Petersen-Jones, Simon M; Michaelides, Michel; van den Born, L Ingeborgh; Stockman, Andrew; Smith, Alexander J; Rubin, Gary; Ali, Robin R

    2015-05-14

    Mutations in RPE65 cause Leber's congenital amaurosis, a progressive retinal degenerative disease that severely impairs sight in children. Gene therapy can result in modest improvements in night vision, but knowledge of its efficacy in humans is limited. We performed a phase 1-2 open-label trial involving 12 participants to evaluate the safety and efficacy of gene therapy with a recombinant adeno-associated virus 2/2 (rAAV2/2) vector carrying the RPE65 complementary DNA, and measured visual function over the course of 3 years. Four participants were administered a lower dose of the vector, and 8 were administered a higher dose. In a parallel study in dogs, we investigated the relationship among vector dose, visual function, and electroretinography (ERG) findings. Improvements in retinal sensitivity were evident, to varying extents, in six participants for up to 3 years, peaking at 6 to 12 months after treatment and then declining. No associated improvement in retinal function was detected by means of ERG. Three participants had intraocular inflammation, and two had clinically significant deterioration of visual acuity. The reduction in central retinal thickness varied among participants. In dogs, RPE65 gene therapy with the same vector at lower doses improved vision-guided behavior, but only higher doses resulted in improvements in retinal function that were detectable with the use of ERG. Gene therapy with rAAV2/2 RPE65 vector improved retinal sensitivity, albeit modestly and temporarily. Comparison with the results obtained in the dog model indicates that there is a species difference in the amount of RPE65 required to drive the visual cycle and that the demand for RPE65 in affected persons was not met to the extent required for a durable, robust effect. (Funded by the National Institute for Health Research and others; ClinicalTrials.gov number, NCT00643747.).

  3. Efficient transduction of neurons using Ross River glycoprotein-pseudotyped lentiviral vectors

    DEFF Research Database (Denmark)

    Jakobsson, J; Nielsen, T Tolstrup; Staflin, K

    2006-01-01

    , including the possibility to establish stable producer cell lines. After injection of RRV-LV expressing green fluorescent protein into different structures in the rat brain we found efficient transduction of both neurons and glial cells. By using two cell-type-specific promoters, neuron-specific enolase...

  4. Highly efficient transduction of human plasmacytoid dendritic cells without phenotypic and functional maturation

    Directory of Open Access Journals (Sweden)

    Plumas Joel

    2009-01-01

    Full Text Available Abstract Background Gene modified dendritic cells (DC are able to modulate DC functions and induce therapeutic immunity or tolerance in an antigen-specific manner. Among the different DC subsets, plasmacytoid DC (pDC are well known for their ability to recognize and respond to a variety of viruses by secreting high levels of type I interferon. Methods We analyzed here, the transduction efficiency of a pDC cell line, GEN2.2, and of pDC derived from CD34+ progenitors, using lentiviral vectors (LV pseudotyped with different envelope glycoproteins such as the vesicular stomatitis virus envelope (VSVG, the gibbon ape leukaemia virus envelope (GaLV or the feline endogenous virus envelope (RD114. At the same time, we evaluated transgene expression (E-GFP reporter gene under the control of different promoters. Results We found that efficient gene transfer into pDC can be achieved with VSVG-pseudotyped lentiviral vectors (LV under the control of phoshoglycerate kinase (PGK and elongation factor-1 (EF1α promoters (28% to 90% of E-GFP+ cells, respectively in the absence of phenotypic and functional maturation. Surprisingly, promoters (desmin or synthetic C5–12 described as muscle-specific and which drive gene expression in single strand AAV vectors in gene therapy protocols were very highly active in pDC using VSVG-LV. Conclusion Taken together, our results indicate that LV vectors can serve to design pDC-based vaccines in humans, and they are also useful in vitro to evaluate the immunogenicity of the vector preparations, and the specificity and safety of given promoters used in gene therapy protocols.

  5. Use of retroviral-mediated gene transfer to deliver and test function of chimeric antigen receptors in human T-cells

    Directory of Open Access Journals (Sweden)

    Ana C. Parente-Pereira

    2014-07-01

    Full Text Available Chimeric antigen receptors (CARs are genetically delivered fusion molecules that elicit T-cell activation upon binding of a native cell surface molecule. These molecules can be used to generate a large number of memory and effector T-cells that are capable of recognizing and attacking tumor cells. Most commonly, stable CAR expression is achieved in T-cells using retroviral vectors. In the method described here, retroviral vectors are packaged in a two-step procedure. First, H29D human retroviral packaging cells (a derivative of 293 cells are transfected with the vector of interest, which is packaged transiently in vesicular stomatitis virus (VSV G pseudotyped particles. These particles are used to deliver the vector to PG13 cells, which achieve stable packaging of gibbon ape leukaemia virus (GALV-pseudotyped particles that are suitable for infection of human T-cells. The key advantage of the method reported here is that it robustly generates polyclonal PG13 cells that are 100% positive for the vector of interest. This means that efficient gene transfer may be repeatedly achieved without the need to clone individual PG13 cells for experimental pre-clinical testing. To achieve T-cell transduction, cells must first be activated using a non-specific mitogen. Phytohemagglutinin (PHA provides an economic and robust stimulus to achieve this. After 48-72 h, activated T-cells and virus-conditioned medium are mixed in RetroNectin-coated plasticware, which enhances transduction efficiency. Transduced cells are analyzed for gene transfer efficiency by flow cytometry 48 h following transduction and may then be tested in several assays to evaluate CAR function, including target-dependent cytotoxicity, cytokine production and proliferation.

  6. The gene therapy revolution in ophthalmology.

    Science.gov (United States)

    Al-Saikhan, Fahad I

    2013-04-01

    The advances in gene therapy hold significant promise for the treatment of ophthalmic conditions. Several studies using animal models have been published. Animal models on retinitis pigmentosa, Leber's Congenital Amaurosis (LCA), and Stargardt disease have involved the use of adeno-associated virus (AAV) to deliver functional genes into mice and canines. Mice models have been used to show that a mutation in cGMP phosphodiesterase that results in retinitis pigmentosa can be corrected using rAAV vectors. Additionally, rAAV vectors have been successfully used to deliver ribozyme into mice with a subsequent improvement in autosomal dominant retinitis pigmentosa. By using dog models, researchers have made progress in studying X-linked retinitis pigmentosa which results from a RPGR gene mutation. Mouse and canine models have also been used in the study of LCA. The widely studied form of LCA is LCA2, resulting from a mutation in the gene RPE65. Mice and canines that were injected with normal copies of RPE65 gene showed signs such as improved retinal pigment epithelium transduction, visual acuity, and functional recovery. Studies on Stargardt disease have shown that mutations in the ABCA4 gene can be corrected with AAV vectors, or nanoparticles. Gene therapy for the treatment of red-green color blindness was successful in squirrel monkeys. Plans are at an advanced stage to begin clinical trials. Researchers have also proved that CD59 can be used with AMD. Gene therapy is also able to treat primary open angle glaucoma (POAG) in animal models, and studies show it is economically viable.

  7. Replacement of the murine leukemia virus (MLV) envelope gene with a truncated HIV envelope gene in MLV generates a virus with impaired replication capacity

    International Nuclear Information System (INIS)

    Nack, Ursula; Schnierle, Barbara S.

    2003-01-01

    Murine leukemia virus (MLV) capsid particles can be efficiently pseudotyped with a variant of the HIV-1 envelope protein (Env) containing the surface glycoprotein gp120-SU and a carboxyl-terminally truncated transmembrane (TM) protein, with only seven cytoplasmic amino acids. MLV/HIV pseudotyped vector particles acquire the natural host tropism of HIV-1 and their entry is dependent on the presence of CD4 and an appropriate co-receptor on the surface of the target cell. We describe here the construction of chimeric MLV/HIV proviruses containing the truncated HIV envelope gene. The MLV/HIV provirus was generated by direct replacement of the MLV envelope gene with HIV Env coding sequences either with or without the additional inclusion of the woodchuck hepatitis virus posttranscriptional regulatory element (WPRE). Chimeric MLV/HIV particles could be generated from transfected 293T cells and were able to infect CD4/CXCR4-positive target cells. However, the second round of infection of target cells was severely impaired, despite the fact that the WPRE element enhanced the amount of viral mRNA detected. Viral particles released from infected cells showed reduced HIV Env incorporation, indicating that additional factors required for efficient replication of MLV/HIV pseudotyped viruses are missing

  8. “Marker of Self” CD47 on lentiviral vectors decreases macrophage-mediated clearance and increases delivery to SIRPA-expressing lung carcinoma tumors

    Directory of Open Access Journals (Sweden)

    Nisha G Sosale

    2016-01-01

    Full Text Available Lentiviruses infect many cell types and are now widely used for gene delivery in vitro, but in vivo uptake of these foreign vectors by macrophages is a limitation. Lentivectors are produced here from packaging cells that overexpress “Marker of Self” CD47, which inhibits macrophage uptake of cells when prophagocytic factors are also displayed. Single particle analyses show “hCD47-Lenti” display properly oriented human-CD47 for interactions with the macrophage's inhibitory receptor SIRPA. Macrophages derived from human and NOD/SCID/Il2rg−/− (NSG mice show a SIRPA-dependent decrease in transduction, i.e., transgene expression, by hCD47-Lenti compared to control Lenti. Consistent with known “Self” signaling pathways, macrophage transduction by control Lenti is decreased by drug inhibition of Myosin-II to the same levels as hCD47-Lenti. In contrast, human lung carcinoma cells express SIRPA and use it to enhance transduction by hCD47-Lenti- as illustrated by more efficient gene deletion using CRISPR/Cas9. Intravenous injection of hCD47-Lenti into NSG mice shows hCD47 prolongs circulation, unless a blocking anti-SIRPA is preinjected. In vivo transduction of spleen and liver macrophages also decreases for hCD47-Lenti while transduction of lung carcinoma xenografts increases. hCD47 could be useful when macrophage uptake is limiting on other viral vectors that are emerging in cancer treatments (e.g., Measles glycoprotein-pseudotyped lentivectors and also in targeting various SIRPA-expressing tumors such as glioblastomas.

  9. Long-Term Effect of Gene Therapy on Leber's Congenital Amaurosis

    OpenAIRE

    Bainbridge, James W B; Mehat, Manjit S; Sundaram, Venki; Robbie, Scott J; Barker, Susie E; Ripamonti, Caterina; Georgiadis, Anastasios; Mowat, Freya M; Beattie, Stuart G; Gardner, Peter J; Feathers, Kecia L; Luong, Vy A; Yzer, Suzanne; Balaggan, Kamaljit; Viswanathan, Ananth

    2015-01-01

    Background Mutations in RPE65 cause Leber's congenital amaurosis, a progressive retinal degenerative disease that severely impairs sight in children. Gene therapy can result in modest improvements in night vision, but knowledge of its efficacy in humans is limited. Methods We performed a phase 1-2 open-label trial involving 12 participants to evaluate the safety and efficacy of gene therapy with a recombinant adeno-associated virus 2/2 (rAAV2/2) vector carrying the RPE65 complementary DNA, an...

  10. Effect and Mechanism of Mitomycin C Combined with Recombinant Adeno-Associated Virus Type II against Glioma

    Directory of Open Access Journals (Sweden)

    Hong Ma

    2013-12-01

    Full Text Available The effect of chemotherapy drug Mitomycin C (MMC in combination with recombinant adeno-associated virus II (rAAV2 in cancer therapy was investigated, and the mechanism of MMC affecting rAAV2’s bioactivity was also studied. The combination effect was evaluated by the level of GFP and TNF expression in a human glioma cell line, and the mechanism of MMC effects on rAAV mediated gene expression was investigated by AAV transduction related signal molecules. C57 and BALB/c nude mice were injected with rAAV-EGFP or rAAV-TNF alone, or mixed with MMC, to evaluate the effect of MMC on AAV-mediated gene expression and tumor suppression. MMC was shown to improve the infection activity of rAAV2 both in vitro and in vivo. Enhancement was found to be independent of initial rAAV2 receptor binding stage or subsequent second-strand synthesis of target DNA, but was related to cell cycle retardation followed by blocked genome degradation. In vivo injection of MMC combined with rAAV2 into the tumors of the animals resulted in significant suppression of tumor growth. It was thus demonstrated for the first time that MMC could enhance the expression level of the target gene mediated by rAAV2. The combination of rAAV2 and MMC may be a promising strategy in cancer therapy.

  11. A translational approach for limb vascular delivery of the micro-dystrophin gene without high volume or high pressure for treatment of Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Chicoine Louis G

    2007-09-01

    Full Text Available Abstract Background Duchenne muscular dystrophy (DMD is an X-linked recessive disorder with monogenic mutations setting the stage for successful gene therapy treatment. We have completed a study that directly deals with the following key issues that can be directly adapted to a gene therapy clinical trial using rAAV considering the following criteria: 1 A regional vascular delivery approach that will protect the patient from widespread dissemination of virus; 2 an approach to potentially facilitate safe passage of the virus for efficient skeletal muscle transduction; 3 the use of viral doses to accommodate current limitations imposed by vector production methods; 4 and at the same time, achieve a clinically meaningful outcome by transducing multiple muscles in the lower limb to prolong ambulation. Methods The capacity of AAV1, AAV6 or AAV8 to cross the vascular endothelial barrier carrying a micro-dystrophin cDNA was compared under identical conditions with delivery through a catheter placed in the femoral artery of the mdx mouse. Transduction efficiency was assessed by immuno-staining using an antibody (Manex1a that recognizes the N-terminus of micro-dystrophin. The degree of physiologic correction was assessed by measuring tetanic force and protection from eccentric contraction in the extensor digitorum longus muscle (EDL. The vascular delivery paradigm found successful in the mouse was carried to the non-human primate to test its potential translation to boys with DMD. Results Regional vascular delivery resulted in transduction by rAAV8.micro-dystrophin reaching 94.5 ± 0.9 (1 month, 91.3 ± 3.1 (2 months, and 89.6 ± 1.6% (3 months. rAAV6.micro-dystrophin treated animals demonstrated 87.7 ± 6.8 (1 month, 78.9 ± 7.4 (2 months, and 81.2 ± 6.2% (3 months transduction. In striking contrast, rAAV1 demonstrated very low transduction efficiency [0.9 ± 0.3 (1 month, 2.1 ± 0.8 (2 months, and 2.1 ± 0.7% (3 months] by vascular delivery. Micro

  12. Sustained miRNA-mediated Knockdown of Mutant AAT With Simultaneous Augmentation of Wild-type AAT Has Minimal Effect on Global Liver miRNA Profiles

    OpenAIRE

    2013-01-01

    α-1 antitrypsin (AAT) deficiency can exhibit two pathologic states: a lung disease that is primarily due to the loss of AAT's antiprotease function, and a liver disease resulting from a toxic gain-of-function of the PiZ-AAT (Z-AAT) mutant protein. We have developed several recombinant adeno-associated virus (rAAV) vectors that incorporate microRNA (miRNA) sequences targeting the AAT gene while also driving the expression of miRNA-resistant wild-type AAT-PiM (M-AAT) gene, thus achieving concom...

  13. Adeno-associated virus-mediated doxycycline-regulatable TRAIL expression suppresses growth of human breast carcinoma in nude mice

    International Nuclear Information System (INIS)

    Zheng, Liu; Weilun, Zhang; Minghong, Jiang; Yaxi, Zhang; Shilian, Liu; Yanxin, Liu; Dexian, Zheng

    2012-01-01

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) functions as a cytokine to selectively kill various cancer cells without toxicity to most normal cells. Numerous studies have demonstrated the potential use of recombinant soluble TRAIL as a cancer therapeutic agent. We have showed previous administration of a recombinant adeno-associated virus (rAAV) vector expressing soluble TRAIL results in an efficient suppression of human tumor growth in nude mice. In the present study, we introduced Tet-On gene expression system into the rAAV vector to control the soluble TRAIL expression and evaluate the efficiency of the system in cancer gene therapy. Controllability of the Tet-On system was determined by luciferase activity assay, and Western blotting and enzyme-linked immunoabsorbent assay. Cell viability was determined by MTT assay. The breast cancer xenograft animal model was established and recombinant virus was administrated through tail vein injection to evaluate the tumoricidal activity. The expression of soluble TRAIL could be strictly controlled by the Tet-On system in both normal and cancer cells. Transduction of human cancer cell lines with rAAV-TRE-TRAIL&rAAV-Tet-On under the presence of inducer doxycycline resulted in a considerable cell death by apoptosis. Intravenous injection of the recombinant virus efficiently suppressed the growth of human breast carcinoma in nude mice when activated by doxycycline. These data suggest that rAAV-mediated soluble TRAIL expression under the control of the Tet-On system is a promising strategy for breast cancer therapy

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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...

  19. Vector regression introduced

    Directory of Open Access Journals (Sweden)

    Mok Tik

    2014-06-01

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

  20. Neutralizing Activity of Broadly Neutralizing Anti-HIV-1 Antibodies against Clade B Clinical Isolates Produced in Peripheral Blood Mononuclear Cells.

    Science.gov (United States)

    Cohen, Yehuda Z; Lorenzi, Julio C C; Seaman, Michael S; Nogueira, Lilian; Schoofs, Till; Krassnig, Lisa; Butler, Allison; Millard, Katrina; Fitzsimons, Tomas; Daniell, Xiaoju; Dizon, Juan P; Shimeliovich, Irina; Montefiori, David C; Caskey, Marina; Nussenzweig, Michel C

    2018-03-01

    HIV-1 epidemic. Antibodies with exceptional neutralizing activity against HIV-1 may provide several advantages to traditional HIV drugs, including an improved side-effect profile, a reduced dosing frequency, and immune enhancement. The activity of these antibodies has been established in vitro by utilizing HIV-1 Env-pseudotyped viruses derived from circulating viruses but produced in 293T cells by pairing Env proteins with a backbone vector. We tested PBMC-produced circulating viruses against five anti-HIV-1 antibodies currently in clinical development. We found that the activity of these antibodies against PBMC isolates is significantly less than that against 293T Env-pseudotyped viruses. This decline varied among the antibodies tested, with some demonstrating moderate reductions in activity and others showing an almost 100-fold reduction. As the development of these antibodies progresses, it will be critical to determine how the results of different in vitro tests correspond to performance in the clinic. Copyright © 2018 Cohen et al.

  1. 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

  2. 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

  3. High-throughput screening using pseudotyped lentiviral particles: a strategy for the identification of HIV-1 inhibitors in a cell-based assay.

    Science.gov (United States)

    Garcia, Jean-Michel; Gao, Anhui; He, Pei-Lan; Choi, Joyce; Tang, Wei; Bruzzone, Roberto; Schwartz, Olivier; Naya, Hugo; Nan, Fa-Jun; Li, Jia; Altmeyer, Ralf; Zuo, Jian-Ping

    2009-03-01

    Two decades after its discovery the human immunodeficiency virus (HIV) is still spreading worldwide and killing millions. There are 25 drugs formally approved for HIV currently on the market, but side effects as well as the emergence of HIV strains showing single or multiple resistances to current drug-therapy are causes for concern. Furthermore, these drugs target only 4 steps of the viral cycle, hence the urgent need for new drugs and also new targets. In order to tackle this problem, we have devised a cell-based assay using lentiviral particles to look for post-entry inhibitors of HIV-1. We report here the assay development, validation as well as confirmation of the hits using both wild-type and drug-resistant HIV-1 viruses. The screening was performed on an original library, rich in natural compounds and pure molecules from Traditional Chinese Medicine pharmacopoeia, which had never been screened for anti-HIV activity. The identified hits belong to four chemical sub-families that appear to be all non-nucleoside reverse transcriptase inhibitors (NNRTIs). Secondary tests with live viruses showed that there was good agreement with pseudotyped particles, confirming the validity of this approach for high-throughput drug screens. This assay will be a useful tool that can be easily adapted to screen for inhibitors of viral entry.

  4. 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

  5. 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

  6. Adeno-associated virus-mediated doxycycline-regulatable TRAIL expression suppresses growth of human breast carcinoma in nude mice

    Directory of Open Access Journals (Sweden)

    Zheng Liu

    2012-04-01

    Full Text Available Abstract Background Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL functions as a cytokine to selectively kill various cancer cells without toxicity to most normal cells. Numerous studies have demonstrated the potential use of recombinant soluble TRAIL as a cancer therapeutic agent. We have showed previous administration of a recombinant adeno-associated virus (rAAV vector expressing soluble TRAIL results in an efficient suppression of human tumor growth in nude mice. In the present study, we introduced Tet-On gene expression system into the rAAV vector to control the soluble TRAIL expression and evaluate the efficiency of the system in cancer gene therapy. Methods Controllability of the Tet-On system was determined by luciferase activity assay, and Western blotting and enzyme-linked immunoabsorbent assay. Cell viability was determined by MTT assay. The breast cancer xenograft animal model was established and recombinant virus was administrated through tail vein injection to evaluate the tumoricidal activity. Results The expression of soluble TRAIL could be strictly controlled by the Tet-On system in both normal and cancer cells. Transduction of human cancer cell lines with rAAV-TRE-TRAIL&rAAV-Tet-On under the presence of inducer doxycycline resulted in a considerable cell death by apoptosis. Intravenous injection of the recombinant virus efficiently suppressed the growth of human breast carcinoma in nude mice when activated by doxycycline. Conclusion These data suggest that rAAV-mediated soluble TRAIL expression under the control of the Tet-On system is a promising strategy for breast cancer therapy.

  7. 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

  8. Rare Hadronic B Decays to Vector, Axial-Vector and Tensors

    International Nuclear Information System (INIS)

    Gao, Y.Y.

    2011-01-01

    The authors review BABAR measurements of several rare B decays, including vector-axial-vector decays B ± → φK 1 ± (1270), B ± → φ K 1 ± (1400) and B ± → b 1 # -+ρ# ± , vector-vector decays B ± → φK* ± (1410), B 0 → K* 0 (bar K)* 0 , B 0 → K*0K*0 and B 0 → K*+K*-, vector-tensor decays B ± → φK* 2 (1430) ± and φK 2 (1770)/ ± (1820), and vector-scalar decays B ± → φK* 0 (1430) ± . Understanding the observed polarization pattern requires amplitude contributions from an uncertain source.

  9. 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

  10. 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

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

    International Nuclear Information System (INIS)

    Olaiya, Emmanuel

    2011-01-01

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

  12. Viral single-strand DNA induces p53-dependent apoptosis in human embryonic stem cells.

    Science.gov (United States)

    Hirsch, Matthew L; Fagan, B Matthew; Dumitru, Raluca; Bower, Jacquelyn J; Yadav, Swati; Porteus, Matthew H; Pevny, Larysa H; Samulski, R Jude

    2011-01-01

    Human embryonic stem cells (hESCs) are primed for rapid apoptosis following mild forms of genotoxic stress. A natural form of such cellular stress occurs in response to recombinant adeno-associated virus (rAAV) single-strand DNA genomes, which exploit the host DNA damage response for replication and genome persistence. Herein, we discovered a unique DNA damage response induced by rAAV transduction specific to pluripotent hESCs. Within hours following rAAV transduction, host DNA damage signaling was elicited as measured by increased gamma-H2AX, ser15-p53 phosphorylation, and subsequent p53-dependent transcriptional activation. Nucleotide incorporation assays demonstrated that rAAV transduced cells accumulated in early S-phase followed by the induction of apoptosis. This lethal signaling sequalae required p53 in a manner independent of transcriptional induction of Puma, Bax and Bcl-2 and was not evident in cells differentiated towards a neural lineage. Consistent with a lethal DNA damage response induced upon rAAV transduction of hESCs, empty AAV protein capsids demonstrated no toxicity. In contrast, DNA microinjections demonstrated that the minimal AAV origin of replication and, in particular, a 40 nucleotide G-rich tetrad repeat sequence, was sufficient for hESC apoptosis. Our data support a model in which rAAV transduction of hESCs induces a p53-dependent lethal response that is elicited by a telomeric sequence within the AAV origin of replication.

  13. Viral single-strand DNA induces p53-dependent apoptosis in human embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Matthew L Hirsch

    Full Text Available Human embryonic stem cells (hESCs are primed for rapid apoptosis following mild forms of genotoxic stress. A natural form of such cellular stress occurs in response to recombinant adeno-associated virus (rAAV single-strand DNA genomes, which exploit the host DNA damage response for replication and genome persistence. Herein, we discovered a unique DNA damage response induced by rAAV transduction specific to pluripotent hESCs. Within hours following rAAV transduction, host DNA damage signaling was elicited as measured by increased gamma-H2AX, ser15-p53 phosphorylation, and subsequent p53-dependent transcriptional activation. Nucleotide incorporation assays demonstrated that rAAV transduced cells accumulated in early S-phase followed by the induction of apoptosis. This lethal signaling sequalae required p53 in a manner independent of transcriptional induction of Puma, Bax and Bcl-2 and was not evident in cells differentiated towards a neural lineage. Consistent with a lethal DNA damage response induced upon rAAV transduction of hESCs, empty AAV protein capsids demonstrated no toxicity. In contrast, DNA microinjections demonstrated that the minimal AAV origin of replication and, in particular, a 40 nucleotide G-rich tetrad repeat sequence, was sufficient for hESC apoptosis. Our data support a model in which rAAV transduction of hESCs induces a p53-dependent lethal response that is elicited by a telomeric sequence within the AAV origin of replication.

  14. 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)

  15. The effect of surface demineralization of cortical bone allograft on the properties of recombinant adeno-associated virus coatings.

    Science.gov (United States)

    Yazici, Cemal; Yanoso, Laura; Xie, Chao; Reynolds, David G; Samulski, R Jude; Samulski, Jade; Yannariello-Brown, Judith; Gertzman, Arthur A; Zhang, Xinping; Awad, Hani A; Schwarz, Edward M

    2008-10-01

    Freeze-dried recombinant adeno-associated virus (rAAV) coated structural allografts have emerged as an approach to engender necrotic cortical bone with host factors that will persist for weeks following surgery to facilitate revascularization, osteointegration, and remodeling. However, one major limitation is the nonporous cortical surface that prohibits uniform distribution of the rAAV coating prior to freeze-drying. To overcome this we have developed a demineralization method to increase surface absorbance while retaining the structural integrity of the allograft. Demineralized bone wafers (DBW) made from human femoral allograft rings demonstrated a significant 21.1% (73.6+/-3.9% versus 52.5+/-2.6%; pcoating versus mineralized controls. Co-incubation of rAAV-luciferase (rAAV-Luc) coated DBW with a monolayer of C3H10T1/2 cells in culture led to peak luciferase levels that were not significantly different from soluble rAAV-Luc controls (p>0.05), although the peaks occurred at 60h and 12h, respectively. To assess the transduction efficiency of rAAV-Luc coated DBW in vivo, we first performed a dose response with allografts containing 10(7), 10(9) or 10(10) particles that were surgically implanted into the quadriceps of mice, and assayed by in vivo bioluminescence imaging (BLI) on days 1, 3, 5, 7, 10, 14, and 21. The results demonstrated a dose response in which the DBW coated with 10(10) rAAV-Luc particles achieved peak gene expression levels on day 3, which persisted until day 21, and was significantly greater than the 10(7) dose throughout this time period (pcoated with 10(10) rAAV-Luc particles failed to demonstrate any significant differences in transduction kinetics or efficiency in vivo. Thus, surface demineralization of human cortical bone allograft increases its absorbance for uniform rAAV coating, without affecting vector transduction efficiency.

  16. 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.

  17. 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

  18. 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...

  19. 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.

  20. 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...

  1. 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...

  2. 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

  3. 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.

  4. 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)

  5. Measurement of K/sub NN/, K/sub LL/ in p vector d → n vector X and p vector 9Be → n vector X at 800 MeV

    International Nuclear Information System (INIS)

    Riley, P.J.; Hollas, C.L.; Newsom, C.R.

    1980-01-01

    The spin transfer parameters, K/sub NN/ and K/sub LL/, have been measured in p vector d → n vector X and p vector 9 Be → n vector X at 0 0 and 800 MeV. The rather large values of K/sub LL/ demonstrate that this transfer mechanism will provide a useful source of polarized neutrons at LAMPF energies

  6. 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...

  7. 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.)

  8. A new system for parallel drug screening against multiple-resistant HIV mutants based on lentiviral self-inactivating (SIN vectors and multi-colour analyses

    Directory of Open Access Journals (Sweden)

    Prokofjeva Maria M

    2013-01-01

    Full Text Available Abstract Background Despite progress in the development of combined antiretroviral therapies (cART, HIV infection remains a significant challenge for human health. Current problems of cART include multi-drug-resistant virus variants, long-term toxicity and enormous treatment costs. Therefore, the identification of novel effective drugs is urgently needed. Methods We developed a straightforward screening approach for simultaneously evaluating the sensitivity of multiple HIV gag-pol mutants to antiviral drugs in one assay. Our technique is based on multi-colour lentiviral self-inactivating (SIN LeGO vector technology. Results We demonstrated the successful use of this approach for screening compounds against up to four HIV gag-pol variants (wild-type and three mutants simultaneously. Importantly, the technique was adapted to Biosafety Level 1 conditions by utilising ecotropic pseudotypes. This allowed upscaling to a large-scale screening protocol exploited by pharmaceutical companies in a successful proof-of-concept experiment. Conclusions The technology developed here facilitates fast screening for anti-HIV activity of individual agents from large compound libraries. Although drugs targeting gag-pol variants were used here, our approach permits screening compounds that target several different, key cellular and viral functions of the HIV life-cycle. The modular principle of the method also allows the easy exchange of various mutations in HIV sequences. In conclusion, the methodology presented here provides a valuable new approach for the identification of novel anti-HIV drugs.

  9. 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.

  10. 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...

  11. 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.

  12. 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.

  13. 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.

  14. Suramin is a potent inhibitor of Chikungunya and Ebola virus cell entry.

    Science.gov (United States)

    Henß, Lisa; Beck, Simon; Weidner, Tatjana; Biedenkopf, Nadine; Sliva, Katja; Weber, Christopher; Becker, Stephan; Schnierle, Barbara S

    2016-08-31

    Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes high fever, rash, and recurrent arthritis in humans. It has efficiently adapted to Aedes albopictus, which also inhabits temperate regions and currently causes large outbreaks in the Caribbean and Latin America. Ebola virus (EBOV) is a member of the filovirus family. It causes the Ebola virus disease (EDV), formerly known as Ebola hemorrhagic fever in humans and has a mortality rate of up to 70 %. The last outbreak in Western Africa was the largest in history and has caused approximately 25,000 cases and 10,000 deaths. For both viral infections no specific treatment or licensed vaccine is currently available. The bis-hexasulfonated naphthylurea, suramin, is used as a treatment for trypanosome-caused African river blindness. As a competitive inhibitor of heparin, suramin has been described to have anti-viral activity. We tested the activity of suramin during CHIKV or Ebola virus infection, using CHIKV and Ebola envelope glycoprotein pseudotyped lentiviral vectors and wild-type CHIKV and Ebola virus. Suramin efficiently inhibited CHIKV and Ebola envelope-mediated gene transfer while vesicular stomatitis virus G protein pseudotyped vectors were only marginally affected. In addition, suramin was able to inhibit wild-type CHIKV and Ebola virus replication in vitro. Inhibition occurred at early time points during CHIKV infection. Suramin, also known as Germanin or Bayer-205, is a market-authorized drug, however shows significant side effects, which probably prevents its use as a CHIKV drug, but due to the high lethality of Ebola virus infections, suramin might be valuable against Ebola infections.

  15. 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.))

  16. Multi-perspective views of students’ difficulties with one-dimensional vector and two-dimensional vector

    Science.gov (United States)

    Fauzi, Ahmad; Ratna Kawuri, Kunthi; Pratiwi, Retno

    2017-01-01

    Researchers of students’ conceptual change usually collects data from written tests and interviews. Moreover, reports of conceptual change often simply refer to changes in concepts, such as on a test, without any identification of the learning processes that have taken place. Research has shown that students have difficulties with vectors in university introductory physics courses and high school physics courses. In this study, we intended to explore students’ understanding of one-dimensional and two-dimensional vector in multi perspective views. In this research, we explore students’ understanding through test perspective and interviews perspective. Our research study adopted the mixed-methodology design. The participants of this research were sixty students of third semester of physics education department. The data of this research were collected by testand interviews. In this study, we divided the students’ understanding of one-dimensional vector and two-dimensional vector in two categories, namely vector skills of the addition of one-dimensionaland two-dimensional vector and the relation between vector skills and conceptual understanding. From the investigation, only 44% of students provided correct answer for vector skills of the addition of one-dimensional and two-dimensional vector and only 27% students provided correct answer for the relation between vector skills and conceptual understanding.

  17. 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.

  18. 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...

  19. Vectorization, parallelization and porting of nuclear codes. Vectorization and parallelization. Progress report fiscal 1999

    Energy Technology Data Exchange (ETDEWEB)

    Adachi, Masaaki; Ogasawara, Shinobu; Kume, Etsuo [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Ishizuki, Shigeru; Nemoto, Toshiyuki; Kawasaki, Nobuo; Kawai, Wataru [Fujitsu Ltd., Tokyo (Japan); Yatake, Yo-ichi [Hitachi Ltd., Tokyo (Japan)

    2001-02-01

    Several computer codes in the nuclear field have been vectorized, parallelized and trans-ported on the FUJITSU VPP500 system, the AP3000 system, the SX-4 system and the Paragon system at Center for Promotion of Computational Science and Engineering in Japan Atomic Energy Research Institute. We dealt with 18 codes in fiscal 1999. These results are reported in 3 parts, i.e., the vectorization and the parallelization part on vector processors, the parallelization part on scalar processors and the porting part. In this report, we describe the vectorization and parallelization on vector processors. In this vectorization and parallelization on vector processors part, the vectorization of Relativistic Molecular Orbital Calculation code RSCAT, a microscopic transport code for high energy nuclear collisions code JAM, three-dimensional non-steady thermal-fluid analysis code STREAM, Relativistic Density Functional Theory code RDFT and High Speed Three-Dimensional Nodal Diffusion code MOSRA-Light on the VPP500 system and the SX-4 system are described. (author)

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  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. 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. 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.

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

    International Nuclear Information System (INIS)

    Harada, Masayasu; Sasaki, Chihiro

    2004-01-01

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

  9. Heavy Scalar, Vector, and Axial-Vector Mesons in Hot and Dense Nuclear Medium

    Directory of Open Access Journals (Sweden)

    Arvind Kumar

    2014-01-01

    Full Text Available In this work we shall investigate the mass modifications of scalar mesons (D0; B0, vector mesons (D*; B*, and axial-vector mesons (D1; B1 at finite density and temperature of the nuclear medium. The above mesons are modified in the nuclear medium through the modification of quark and gluon condensates. We will find the medium modification of quark and gluon condensates within chiral SU(3 model through the medium modification of scalar-isoscalar fields σ and ζ at finite density and temperature. These medium modified quark and gluon condensates will further be used through QCD sum rules for the evaluation of in-medium properties of the above mentioned scalar, vector, and axial vector mesons. We will also discuss the effects of density and temperature of the nuclear medium on the scattering lengths of the above scalar, vector, and axial-vector mesons. The study of the medium modifications of the above mesons may be helpful for understanding their production rates in heavy-ion collision experiments. The results of present investigations of medium modifications of scalar, vector, and axial-vector mesons at finite density and temperature can be verified in the compressed baryonic matter (CBM experiment of FAIR facility at GSI, Germany.

  10. 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.

  11. Light scattering of rectangular slot antennas: parallel magnetic vector vs perpendicular electric vector

    Science.gov (United States)

    Lee, Dukhyung; Kim, Dai-Sik

    2016-01-01

    We study light scattering off rectangular slot nano antennas on a metal film varying incident polarization and incident angle, to examine which field vector of light is more important: electric vector perpendicular to, versus magnetic vector parallel to the long axis of the rectangle. While vector Babinet’s principle would prefer magnetic field along the long axis for optimizing slot antenna function, convention and intuition most often refer to the electric field perpendicular to it. Here, we demonstrate experimentally that in accordance with vector Babinet’s principle, the incident magnetic vector parallel to the long axis is the dominant component, with the perpendicular incident electric field making a small contribution of the factor of 1/|ε|, the reciprocal of the absolute value of the dielectric constant of the metal, owing to the non-perfectness of metals at optical frequencies.

  12. Generalization of concurrence vectors

    International Nuclear Information System (INIS)

    Yu Changshui; Song Heshan

    2004-01-01

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

  13. Vector Network Coding 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...

  14. 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...

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

    Science.gov (United States)

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

    2017-06-01

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

  16. 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)

  17. 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…

  18. 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...

  19. 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

  20. Reciprocity relationships in vector acoustics and their application to vector field calculations.

    Science.gov (United States)

    Deal, Thomas J; Smith, Kevin B

    2017-08-01

    The reciprocity equation commonly stated in underwater acoustics relates pressure fields and monopole sources. It is often used to predict the pressure measured by a hydrophone for multiple source locations by placing a source at the hydrophone location and calculating the field everywhere for that source. A similar equation that governs the orthogonal components of the particle velocity field is needed to enable this computational method to be used for acoustic vector sensors. This paper derives a general reciprocity equation that accounts for both monopole and dipole sources. This vector-scalar reciprocity equation can be used to calculate individual components of the received vector field by altering the source type used in the propagation calculation. This enables a propagation model to calculate the received vector field components for an arbitrary number of source locations with a single model run for each vector field component instead of requiring one model run for each source location. Application of the vector-scalar reciprocity principle is demonstrated with analytic solutions for a range-independent environment and with numerical solutions for a range-dependent environment using a parabolic equation model.

  1. 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

  2. Convexity and Marginal Vectors

    NARCIS (Netherlands)

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

    2002-01-01

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

  3. Integrating Transgenic Vector Manipulation with Clinical Interventions to Manage Vector-Borne Diseases.

    Directory of Open Access Journals (Sweden)

    Kenichi W Okamoto

    2016-03-01

    Full Text Available Many vector-borne diseases lack effective vaccines and medications, and the limitations of traditional vector control have inspired novel approaches based on using genetic engineering to manipulate vector populations and thereby reduce transmission. Yet both the short- and long-term epidemiological effects of these transgenic strategies are highly uncertain. If neither vaccines, medications, nor transgenic strategies can by themselves suffice for managing vector-borne diseases, integrating these approaches becomes key. Here we develop a framework to evaluate how clinical interventions (i.e., vaccination and medication can be integrated with transgenic vector manipulation strategies to prevent disease invasion and reduce disease incidence. We show that the ability of clinical interventions to accelerate disease suppression can depend on the nature of the transgenic manipulation deployed (e.g., whether vector population reduction or replacement is attempted. We find that making a specific, individual strategy highly effective may not be necessary for attaining public-health objectives, provided suitable combinations can be adopted. However, we show how combining only partially effective antimicrobial drugs or vaccination with transgenic vector manipulations that merely temporarily lower vector competence can amplify disease resurgence following transient suppression. Thus, transgenic vector manipulation that cannot be sustained can have adverse consequences-consequences which ineffective clinical interventions can at best only mitigate, and at worst temporarily exacerbate. This result, which arises from differences between the time scale on which the interventions affect disease dynamics and the time scale of host population dynamics, highlights the importance of accounting for the potential delay in the effects of deploying public health strategies on long-term disease incidence. We find that for systems at the disease-endemic equilibrium, even

  4. Complex Polynomial Vector Fields

    DEFF Research Database (Denmark)

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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. Results at 2 Years after Gene Therapy for RPE65-Deficient Leber Congenital Amaurosis and Severe Early-Childhood-Onset Retinal Dystrophy.

    Science.gov (United States)

    Weleber, Richard G; Pennesi, Mark E; Wilson, David J; Kaushal, Shalesh; Erker, Laura R; Jensen, Lauren; McBride, Maureen T; Flotte, Terence R; Humphries, Margaret; Calcedo, Roberto; Hauswirth, William W; Chulay, Jeffrey D; Stout, J Timothy

    2016-07-01

    To provide an initial assessment of the safety of a recombinant adeno-associated virus vector expressing RPE65 (rAAV2-CB-hRPE65) in adults and children with retinal degeneration caused by RPE65 mutations. Nonrandomized, multicenter clinical trial. Eight adults and 4 children, 6 to 39 years of age, with Leber congenital amaurosis (LCA) or severe early-childhood-onset retinal degeneration (SECORD). Patients received a subretinal injection of rAAV2-CB-hRPE65 in the poorer-seeing eye, at either of 2 dose levels, and were followed up for 2 years after treatment. The primary safety measures were ocular and nonocular adverse events. Exploratory efficacy measures included changes in best-corrected visual acuity (BCVA), static perimetry central 30° visual field hill of vision (V30) and total visual field hill of vision (VTOT), kinetic perimetry visual field area, and responses to a quality-of-life questionnaire. All patients tolerated subretinal injections and there were no treatment-related serious adverse events. Common adverse events were those associated with the surgical procedure and included subconjunctival hemorrhage in 8 patients and ocular hyperemia in 5 patients. In the treated eye, BCVA increased in 5 patients, V30 increased in 6 patients, VTOT increased in 5 patients, and kinetic visual field area improved in 3 patients. One subject showed a decrease in BCVA and 2 patients showed a decrease in kinetic visual field area. Treatment with rAAV2-CB-hRPE65 was not associated with serious adverse events, and improvement in 1 or more measures of visual function was observed in 9 of 12 patients. The greatest improvements in visual acuity were observed in younger patients with better baseline visual acuity. Evaluation of more patients and a longer duration of follow-up will be needed to determine the rate of uncommon or rare side effects or safety concerns. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  10. 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

  11. The Cross Product of Two Vectors Is Not Just Another Vector--A Major Misconception Being Perpetuated in Calculus and Vector Analysis Textbooks.

    Science.gov (United States)

    Elk, Seymour B.

    1997-01-01

    Suggests that the cross product of two vectors can be more easily and accurately explained by starting from the perspective of dyadics because then the concept of vector multiplication has a simple geometrical picture that encompasses both the dot and cross products in any number of dimensions in terms of orthogonal unit vector components. (AIM)

  12. Major vectors and vector-borne diseases in small ruminants in Ethiopia: A systematic review.

    Science.gov (United States)

    Asmare, Kassahun; Abayneh, Takele; Sibhat, Berhanu; Shiferaw, Dessie; Szonyi, Barbara; Krontveit, Randi I; Skjerve, Eystein; Wieland, Barbara

    2017-06-01

    Vector-borne diseases are among major health constraints of small ruminant in Ethiopia. While various studies on single vector-borne diseases or presence of vectors have been conducted, no summarized evidence is available on the occurrence of these diseases and the related vectors. This systematic literature review provides a comprehensive summary on major vectors and vector-borne diseases in small ruminants in Ethiopia. Search for published and unpublished literature was conducted between 8th of January and 25th of June 2015. The search was both manual and electronic. The databases used in electronic search were PubMed, Web of Science, CAB Direct and AJOL. For most of the vector-borne diseases, the summary was limited to narrative synthesis due to lack of sufficient data. Meta-analysis was computed for trypanosomosis and dermatophilosis while meta-regression and sensitivity analysis was done only for trypanososmosis due to lack of sufficient reports on dermatophilosis. Owing emphasis to their vector role, ticks and flies were summarized narratively at genera/species level. In line with inclusion criteria, out of 106 initially identified research reports 43 peer-reviewed articles passed the quality assessment. Data on 7 vector-borne diseases were extracted at species and region level from each source. Accordingly, the pooled prevalence estimate of trypanosomosis was 3.7% with 95% confidence interval (CI) 2.8, 4.9), while that of dermatophilosis was 3.1% (95% CI: 1.6, 6.0). The in-between study variance noted for trypanosomosis was statistically significant (pparasitic presence in blood was documented for babesiosis (3.7% in goats); and anaplasmosis (3.9% in sheep). Serological evidence was retrieved for bluetongue ranging from 34.1% to 46.67% in sheep, and coxiellosis was 10.4% in goats. There was also molecular evidence on the presence of theileriosis in sheep (93%, n=160) and goats (1.9%, n=265). Regarding vectors of veterinary importance, 14 species of ticks in

  13. 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 .

  14. Effects of Climate and Climate Change on Vectors and Vector-Borne Diseases: Ticks Are Different.

    Science.gov (United States)

    Ogden, Nick H; Lindsay, L Robbin

    2016-08-01

    There has been considerable debate as to whether global risk from vector-borne diseases will be impacted by climate change. This has focussed on important mosquito-borne diseases that are transmitted by the vectors from infected to uninfected humans. However, this debate has mostly ignored the biological diversity of vectors and vector-borne diseases. Here, we review how climate and climate change may impact those most divergent of arthropod disease vector groups: multivoltine insects and hard-bodied (ixodid) ticks. We contrast features of the life cycles and behaviour of these arthropods, and how weather, climate, and climate change may have very different impacts on the spatiotemporal occurrence and abundance of vectors, and the pathogens they transmit. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

  15. 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

  16. Receptor-Targeted Nipah Virus Glycoproteins Improve Cell-Type Selective Gene Delivery and Reveal a Preference for Membrane-Proximal Cell Attachment.

    Directory of Open Access Journals (Sweden)

    Ruben R Bender

    2016-06-01

    Full Text Available Receptor-targeted lentiviral vectors (LVs can be an effective tool for selective transfer of genes into distinct cell types of choice. Moreover, they can be used to determine the molecular properties that cell surface proteins must fulfill to act as receptors for viral glycoproteins. Here we show that LVs pseudotyped with receptor-targeted Nipah virus (NiV glycoproteins effectively enter into cells when they use cell surface proteins as receptors that bring them closely enough to the cell membrane (less than 100 Å distance. Then, they were flexible in receptor usage as demonstrated by successful targeting of EpCAM, CD20, and CD8, and as selective as LVs pseudotyped with receptor-targeted measles virus (MV glycoproteins, the current standard for cell-type specific gene delivery. Remarkably, NiV-LVs could be produced at up to two orders of magnitude higher titers compared to their MV-based counterparts and were at least 10,000-fold less effectively neutralized than MV glycoprotein pseudotyped LVs by pooled human intravenous immunoglobulin. An important finding for NiV-LVs targeted to Her2/neu was an about 100-fold higher gene transfer activity when particles were targeted to membrane-proximal regions as compared to particles binding to a more membrane-distal epitope. Likewise, the low gene transfer activity mediated by NiV-LV particles bound to the membrane distal domains of CD117 or the glutamate receptor subunit 4 (GluA4 was substantially enhanced by reducing receptor size to below 100 Å. Overall, the data suggest that the NiV glycoproteins are optimally suited for cell-type specific gene delivery with LVs and, in addition, for the first time define which parts of a cell surface protein should be targeted to achieve optimal gene transfer rates with receptor-targeted LVs.

  17. 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.

  18. 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...

  19. Test of understanding of vectors: A reliable multiple-choice vector concept test

    Science.gov (United States)

    Barniol, Pablo; Zavala, Genaro

    2014-06-01

    In this article we discuss the findings of our research on students' understanding of vector concepts in problems without physical context. First, we develop a complete taxonomy of the most frequent errors made by university students when learning vector concepts. This study is based on the results of several test administrations of open-ended problems in which a total of 2067 students participated. Using this taxonomy, we then designed a 20-item multiple-choice test [Test of understanding of vectors (TUV)] and administered it in English to 423 students who were completing the required sequence of introductory physics courses at a large private Mexican university. We evaluated the test's content validity, reliability, and discriminatory power. The results indicate that the TUV is a reliable assessment tool. We also conducted a detailed analysis of the students' understanding of the vector concepts evaluated in the test. The TUV is included in the Supplemental Material as a resource for other researchers studying vector learning, as well as instructors teaching the material.

  20. 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)

  1. 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)

  2. Multidrug resistance and retroviral transduction potential in human small cell lung cancer cell lines

    DEFF Research Database (Denmark)

    Theilade, M D; Gram, G J; Jensen, P B

    1999-01-01

    Multidrug resistance (MDR) remains a major problem in the successful treatment of small cell lung cancer (SCLC). New treatment strategies are needed, such as gene therapy specifically targeting the MDR cells in the tumor. Retroviral LacZ gene-containing vectors that were either pseudotyped...... for the gibbon ape leukemia virus (GALV-1) receptor or had specificity for the amphotropic murine leukemia virus (MLV-A) receptor were used for transduction of five SCLC cell lines differing by a range of MDR mechanisms. Transduction efficiencies in these cell lines were compared by calculating the percentage...... of blue colonies after X-Gal staining of the cells grown in soft agar. All examined SCLC cell lines were transducible with either vector. Transduction efficiencies varied from 5.7% to 33.5% independent of the presence of MDR. These results indicate that MDR does not severely impair transduction of SCLC...

  3. Strangeness Vector and Axial-Vector Form Factors of the Nucleon

    Directory of Open Access Journals (Sweden)

    Pate Stephen

    2014-03-01

    Full Text Available A revised global fit of electroweak ep and vp elastic scattering data has been performed, with the goal of determining the strange quark contribution to the vector and axial-vector form factors of the nucleon in the momentum-transfer range 0 < Q2 < 1 GeV2. The two vector (electric and magnetic form factors GsE(Q2 and GsM(Q2 are strongly constrained by ep elastic scattering data, while the major source of information on the axial-vector form factor GsA(Q2 is vp scattering data. Combining the two kinds of data into a single global fit makes possible additional precision in the determination of these form factors, and provides a unique way to determine the strange quark contribution to the nucleon spin, ΔS , independently of leptonic deep-inelastic scattering. The fit makes use of data from the BNL-E734, SAMPLE, HAPPEx, G0, and PVA4 experiments; we will also compare the result of the fit with recent data from MiniBooNE, and anticipate how this fit can be improved when new data from MicroBooNE become available.

  4. 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.

  5. 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.

  6. 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.

  7. 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...

  8. 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

  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. 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).

  11. Modulation of medial prefrontal cortical activity using in vivo recordings and optogenetics

    Directory of Open Access Journals (Sweden)

    Ji Guangchen

    2012-10-01

    Full Text Available Abstract Background The medial prefrontal cortex (mPFC serves major executive functions. mPFC output to subcortical brain areas such as the amygdala controls emotional processing and plays an important role in fear extinction. Impaired mPFC function correlates with extinction deficits in anxiety disorders such as PTSD and with cognitive decision-making deficits in neuropsychiatric disorders and persistent pain. Controlling mPFC output is a desirable therapeutic goal in neuropsychiatric disorders but functional differences of cell types (pyramidal cells and interneurons and regions (infralimbic and prelimbic represent a challenge. This electrophysiological study used optogenetics for the cell- and region-specific modulation of mPFC pyramidal output in the intact anesthetized animal. Results Extracellular single-unit recordings were made from infralimbic (IL pyramidal cells, IL interneurons and prelimbic (PL pyramidal cells 2–3 weeks after intra-IL injection of a viral vector encoding channel rhodopsin 2 (ChR2 under the control of the CaMKII promoter (rAAV5/CaMKIIa-ChR2(H134R-EYFP or a control vector that lacked the ChR2 sequence (rAAV5/CaMKIIa-EYFP. Optical stimulation with laser-generated blue light pulses delivered through an optical fiber to the IL increased spontaneous and evoked action potential firing of ChR2 expressing IL pyramidal cells but had no effect on IL interneurons that were distinguished from pyramidal cells based on their higher firing rate and shorter spike duration. Optical activation of IL pyramidal cells also inhibited PL pyramidal cells, suggesting that IL output controls PL output. The effects were light intensity-dependent and reversible. Confocal microscopy confirmed ChR2-EYFP or control vector expression in mPFC pyramidal cells but not in GABAergic cells. Conclusions The novelty of our study is the analysis of optogenetic effects on background and evoked activity of defined cell types in different mPFC regions. The

  12. 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

  13. Properties of vector and axial-vector mesons from a generalized Nambu-Jona-Lasinio model

    International Nuclear Information System (INIS)

    Bernard, V.; Meissner, U.G.; Massachusetts Inst. of Tech., Cambridge; Massachusetts Inst. of Tech., Cambridge

    1988-01-01

    We construct a generalized Nambu-Jona-Lasinio lagrangian including scalar, pseudoscalar, vector and axial-vector mesons. We specialize to the two-flavor case. The properties of the structured vacuum as well as meson masses and coupling constants are calculated giving an overall agreement within 20% of the experimental data. We investigate the meson properties at finite density. In contrast to the mass of the scalar σ-meson, which decreases sharply with increasing density, the vector meson masses are almost independent of density. Furthermore, the vector-meson-quark coupling constants are also stable against density changes. We point out that these results imply a softening of the nuclear equation of state at high densities. Furthermore, we discuss the breakdown of the KFSR relation on the quark level as well as other deviations from phenomenological concepts such as universality and vector meson dominance. (orig.)

  14. Vector geometry

    CERN Document Server

    Robinson, Gilbert de B

    2011-01-01

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

  15. Electroproduction and photoproduction of vector mesons and generalized vector meson dominance

    International Nuclear Information System (INIS)

    Fraas, H.; Kuroda, M.

    1977-05-01

    Using generalized vector meson dominance, electro- and photoproduction of vector mesons is studied. The unnatural parity exchange part of ω(1.2) production is estimated to be about one fourth of that of ω-production. The off diagonal transition model suggests the suppression of diffractive rho(1.2) and ω(1.2) production. (orig.) [de

  16. 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)

  17. Quark-gluon plasma tomography by vector mesons

    International Nuclear Information System (INIS)

    Lovas, I.; Schram, Zs.; Csernai, L.P.; Hungarian Academy of Sciences, Budapest; Nyiri, A.

    2001-01-01

    The fireball formed in a heavy ion collision is characterized by the impact parameter vector b-vector, which can be determined from the multiplicity and the angular distribution of the reaction products. By appropriate rotations the b-vector vectors of each collision can be aligned into a fixed direction. Using the measured values of the momentum distributions independent integral equations can be formulated for the unknown emission densities (E M (r-vector)) and for the unknown absorption densities (Δμ(r-vector)) of the different vector mesons. (author)

  18. 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

  19. 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

  20. Distribution of Brugia malayi larvae and DNA in vector and non-vector mosquitoes: implications for molecular diagnostics

    Directory of Open Access Journals (Sweden)

    Christensen Bruce M

    2009-11-01

    Full Text Available Abstract Background The purpose of this study was to extend prior studies of molecular detection of Brugia malayi DNA in vector (Aedes aegypti- Liverpool and non-vector (Culex pipiens mosquitoes at different times after ingestion of infected blood. Results Parasite DNA was detected over a two week time course in 96% of pooled thoraces of vector mosquitoes. In contrast, parasite DNA was detected in only 24% of thorax pools from non-vectors; parasite DNA was detected in 56% of midgut pools and 47% of abdomen pools from non-vectors. Parasite DNA was detected in vectors in the head immediately after the blood meal and after 14 days. Parasite DNA was also detected in feces and excreta of the vector and non-vector mosquitoes which could potentially confound results obtained with field samples. However, co-housing experiments failed to demonstrate transfer of parasite DNA from infected to non-infected mosquitoes. Parasites were also visualized in mosquito tissues by immunohistololgy using an antibody to the recombinant filarial antigen Bm14. Parasite larvae were detected consistently after mf ingestion in Ae. aegypti- Liverpool. Infectious L3s were seen in the head, thorax and abdomen of vector mosquitoes 14 days after Mf ingestion. In contrast, parasites were only detected by histology shortly after the blood meal in Cx. pipiens, and these were not labeled by the antibody. Conclusion This study provides new information on the distribution of filarial parasites and parasite DNA in vector and non-vector mosquitoes. This information should be useful for those involved in designing and interpreting molecular xenomonitoring studies.

  1. Insecticide resistance in disease vectors from Mayotte: an opportunity for integrated vector management.

    Science.gov (United States)

    Pocquet, Nicolas; Darriet, Frédéric; Zumbo, Betty; Milesi, Pascal; Thiria, Julien; Bernard, Vincent; Toty, Céline; Labbé, Pierrick; Chandre, Fabrice

    2014-07-01

    Mayotte, a small island in the Indian Ocean, has been affected for many years by vector-borne diseases. Malaria, Bancroftian filariasis, dengue, chikungunya and Rift Valley fever have circulated or still circulate on the island. They are all transmitted by Culicidae mosquitoes. To limit the impact of these diseases on human health, vector control has been implemented for more than 60 years on Mayotte. In this study, we assessed the resistance levels of four major vector species (Anopheles gambiae, Culex pipiens quinquefasciatus, Aedes aegypti and Aedes albopictus) to two types of insecticides: i) the locally currently-used insecticides (organophosphates, pyrethroids) and ii) alternative molecules that are promising for vector control and come from different insecticide families (bacterial toxins or insect growth regulators). When some resistance was found to one of these insecticides, we characterized the mechanisms involved. Larval and adult bioassays were used to evaluate the level of resistance. When resistance was found, we tested for the presence of metabolic resistance through detoxifying enzyme activity assays, or for target-site mutations through molecular identification of known resistance alleles. Resistance to currently-used insecticides varied greatly between the four vector species. While no resistance to any insecticides was found in the two Aedes species, bioassays confirmed multiple resistance in Cx. p. quinquefasciatus (temephos: ~ 20 fold and deltamethrin: only 10% mortality after 24 hours). In An. gambiae, resistance was scarce: only a moderate resistance to temephos was found (~5 fold). This resistance appears to be due only to carboxyl-esterase overexpression and not to target modification. Finally, and comfortingly, none of the four species showed resistance to any of the new insecticides. The low resistance observed in Mayotte's main disease vectors is particularly interesting, because it leaves a range of tools useable by vector control

  2. 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.

  3. 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…

  4. 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

  5. Does the delta quench Gamow-Teller strength in (p,n)- and (p vector,p vector')-reactions

    International Nuclear Information System (INIS)

    Osterfeld, F.; Schulte, A.; Udagawa, T.; Yabe, M.

    1986-01-01

    Microscopic analyses of complete forward angle intermediate energy (p,n)-, ( 3 He,t)- and (p vector,p vector')-spin-flip spectra are presented for the reactions 90 Zr(p,n), 90 Zr( 3 He,t) and 90 Zr(p vector,p vector'). It is shown that the whole spectra up to high excitation energies (E X ∝50 MeV) are the result of correlated one-particle-one-hole (1p1h) spin-isospin transitions only. The spectra reflect, therefore, the linear spin-isospin response of the target nucleus to the probing external hadronic fields. Our results suggest that the measured (p,n)-, ( 3 He,t)- and (p vector,p vector')-cross sections are compatible with the transition strength predictions as obtained from random phase approximation (RPA) calculations. This means that the Δ isobar quenching mechanism is likely to be rather small. (orig.)

  6. 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.

  7. 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.

  8. Two-hadron saturation for the pseudoscalar-vector-vector correlator and phenomenological applications

    Energy Technology Data Exchange (ETDEWEB)

    Husek, Tomas [Charles University, Faculty of Mathematics and Physics, Institute of Particle and Nuclear Physics, Prague 8 (Czech Republic); Leupold, Stefan [Uppsala Universitet, Institutionen foer Fysik och Astronomi, Box 516, Uppsala (Sweden)

    2015-12-15

    The pseudoscalar-vector-vector correlator is constructed using two meson multiplets in the vector and two in the pseudoscalar channel. The parameters are constrained by the operator product expansion at leading order where two or all three momenta are considered as large. Demanding in addition the Brodsky-Lepage limit one obtains (in the chiral limit) pion-vector-vector (πVV) correlator with only one free parameter. The singly virtual pion transition form factor F{sub π{sup 0}γγ*} and the decay width of ω → π{sup 0}γ are independent of this parameter and can serve as cross-checks of the results. The free parameter is determined from a fit of the ω-π transition form factor F{sub π{sup 0}ωγ*}. The resulting πVV correlator is used to calculate the decay widths ω → π{sup 0}e{sup +}e{sup -} and ω → π{sup 0}μ{sup +}μ{sup -} and finally the widths of the rare decay π{sup 0} → e{sup +}e{sup -} and of the Dalitz decay π{sup 0} → e{sup +}e{sup -}γ. Incorporating radiative QED corrections the calculations of π{sup 0} decays are compared to the KTeV results. We find a deviation of 2 σ or less for the rare pion decay. (orig.)

  9. 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.

  10. 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

  11. Non-coaxial superposition of vector vortex beams.

    Science.gov (United States)

    Aadhi, A; Vaity, Pravin; Chithrabhanu, P; Reddy, Salla Gangi; Prabakar, Shashi; Singh, R P

    2016-02-10

    Vector vortex beams are classified into four types depending upon spatial variation in their polarization vector. We have generated all four of these types of vector vortex beams by using a modified polarization Sagnac interferometer with a vortex lens. Further, we have studied the non-coaxial superposition of two vector vortex beams. It is observed that the superposition of two vector vortex beams with same polarization singularity leads to a beam with another kind of polarization singularity in their interaction region. The results may be of importance in ultrahigh security of the polarization-encrypted data that utilizes vector vortex beams and multiple optical trapping with non-coaxial superposition of vector vortex beams. We verified our experimental results with theory.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Charmless Hadronic B Decays into Vector, Axial Vector and Tensor Final States at BaBar

    International Nuclear Information System (INIS)

    Gandini, Paolo

    2012-01-01

    We present experimental measurements of branching fraction and longitudinal polarization fraction in charmless hadronic B decays into vector, axial vector and tensor final states with the final dataset of BABAR. Measurements of such kind of decays are a powerful tool both to test the Standard Model and search possible sources of new physics. In this document we present a short review of the last experimental results at BABAR concerning charmless quasi two-body decays in final states containing particles with spin 1 or spin 2 and different parities. This kind of decays has received considerable theoretical interest in the last few years and this particular attention has led to interesting experimental results at the current b-factories. In fact, the study of longitudinal polarization fraction f L in charmless B decays to vector vector (VV), vector axial-vector (VA) and axial-vector axial-vector (AA) mesons provides information on the underlying helicity structure of the decay mechanism. Naive helicity conservation arguments predict a dominant longitudinal polarization fraction f L ∼ 1 for both tree and penguin dominated decays and this pattern seems to be confirmed by tree-dominated B → ρρ and B + → (Omega)ρ + decays. Other penguin dominated decays, instead, show a different behavior: the measured value of f L ∼ 0.5 in B → φK* decays is in contrast with naive Standard Model (SM) calculations. Several solutions have been proposed such as the introduction of non-factorizable terms and penguin-annihilation amplitudes, while other explanations invoke new physics. New modes have been investigated to shed more light on the problem.

  17. A stable murine-based RD114 retroviral packaging line efficiently transduces human hematopoietic cells.

    Science.gov (United States)

    Ward, Maureen; Sattler, Rose; Grossman, I Robert; Bell, Anthony J; Skerrett, Donna; Baxi, Laxmi; Bank, Arthur

    2003-11-01

    Several barriers exist to high-efficiency transfer of therapeutic genes into human hematopoietic stem cells (HSCs) using complex oncoretroviral vectors. Human clinical trials to date have used Moloney leukemia virus-based amphotropic and gibbon ape leukemia virus-based envelopes in stable retroviral packaging lines. However, retroviruses pseudotyped with these envelopes have low titers due to the inability to concentrate viral supernatants efficiently by centrifugation without damaging the virus and low transduction efficiencies because of low-level expression of viral target receptors on human HSC. The RD114 envelope from the feline endogenous virus has been shown to transduce human CD34+ cells using transient packaging systems and to be concentrated to high titers by centrifugation. Stable packaging systems have potential advantages over transient systems because greater and more reproducible viral productions can be attained. We have, therefore, constructed and tested a stable RD114-expressing packaging line capable of high-level transduction of human CD34+ cells. Viral particles from this cell line were concentrated up to 100-fold (up to 10(7) viral particles/ml) by ultracentrifugation. Human hematopoietic progenitors from cord blood and sickle cell CD34+ cells were efficiently transduced with a Neo(R)-containing vector after a single exposure to concentrated RD114-pseudotyped virus produced from this cell line. Up to 78% of progenitors from transduced cord blood CD34+ cells and 51% of progenitors from sickle cell CD34+ cells expressed the NeoR gene. We also show transfer of a human beta-globin gene into progenitor cells from CD34+ cells from sickle cell patients with this new RD114 stable packaging system. The results indicate that this packaging line may eventually be useful in human clinical trials of globin gene therapy.

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

    Science.gov (United States)

    Barniol, Pablo; Zavala, Genaro

    2014-01-01

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

  19. 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.

  20. Vector-Vector Scattering on the Lattice

    Science.gov (United States)

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

    2018-03-01

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

  1. Conformal Killing vectors in Robertson-Walker spacetimes

    International Nuclear Information System (INIS)

    Maartens, R.; Maharaj, S.d.

    1986-01-01

    It is well known that Robertson-Walker spacetimes admit a conformal Killingl vector normal to the spacelike homogeneous hypersurfaces. Because these spacetimes are conformally flat, there are a further eight conformal Killing vectors, which are neither normal nor tangent to the homogeneous hypersurfaces. The authors find these further conformal Killing vectors and the Lie algebra of the full G 15 of conformal motions. Conditions on the metric scale factor are determined which reduce some of the conformal Killing vectors to homothetic Killing vectors or Killing vectors, allowing one to regain in a unified way the known special geometries. The non-normal conformal Killing vectors provide a counter-example to show that conformal motions do not, in general, map a fluid flow conformally. These non-normal vectors are also used to find the general solution of the null geodesic equation and photon Liouville equation. (author)

  2. 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.

  3. Broad patterns in domestic vector-borne Trypanosoma cruzi transmission dynamics: synanthropic animals and vector control.

    Science.gov (United States)

    Peterson, Jennifer K; Bartsch, Sarah M; Lee, Bruce Y; Dobson, Andrew P

    2015-10-22

    Chagas disease (caused by Trypanosoma cruzi) is the most important neglected tropical disease (NTD) in Latin America, infecting an estimated 5.7 million people in the 21 countries where it is endemic. It is one of the NTDs targeted for control and elimination by the 2020 London Declaration goals, with the first goal being to interrupt intra-domiciliary vector-borne T. cruzi transmission. A key question in domestic T. cruzi transmission is the role that synanthropic animals play in T. cruzi transmission to humans. Here, we ask, (1) do synanthropic animals need to be targeted in Chagas disease prevention policies?, and (2) how does the presence of animals affect the efficacy of vector control? We developed a simple mathematical model to simulate domestic vector-borne T. cruzi transmission and to specifically examine the interaction between the presence of synanthropic animals and effects of vector control. We used the model to explore how the interactions between triatomine bugs, humans and animals impact the number and proportion of T. cruzi-infected bugs and humans. We then examined how T. cruzi dynamics change when control measures targeting vector abundance are introduced into the system. We found that the presence of synanthropic animals slows the speed of T. cruzi transmission to humans, and increases the sensitivity of T. cruzi transmission dynamics to vector control measures at comparable triatomine carrying capacities. However, T. cruzi transmission is amplified when triatomine carrying capacity increases with the abundance of syntathoropic hosts. Our results suggest that in domestic T. cruzi transmission scenarios where no vector control measures are in place, a reduction in synanthropic animals may slow T. cruzi transmission to humans, but it would not completely eliminate transmission. To reach the 2020 goal of interrupting intra-domiciliary T. cruzi transmission, it is critical to target vector populations. Additionally, where vector control measures

  4. Spin information from vector-meson decay in photoproduction

    International Nuclear Information System (INIS)

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

    1998-01-01

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

  5. [Effects of plant viruses on vector and non-vector herbivorous arthropods and their natural enemies: a mini review].

    Science.gov (United States)

    He, Xiao-Chan; Xu, Hong-Xing; Zhou, Xiao-Jun; Zheng, Xu-Song; Sun, Yu-Jian; Yang, Ya-Jun; Tian, Jun-Ce; Lü, Zhong-Xian

    2014-05-01

    Plant viruses transmitted by arthropods, as an important biotic factor, may not only directly affect the yield and quality of host plants, and development, physiological characteristics and ecological performances of their vector arthropods, but also directly or indirectly affect the non-vector herbivorous arthropods and their natural enemies in the same ecosystem, thereby causing influences to the whole agro-ecosystem. This paper reviewed the progress on the effects of plant viruses on herbivorous arthropods, including vector and non-vector, and their natural enemies, and on their ecological mechanisms to provide a reference for optimizing the management of vector and non-vector arthropod populations and sustainable control of plant viruses in agro-ecosystem.

  6. Virus-Vectored Influenza Virus Vaccines

    Science.gov (United States)

    Tripp, Ralph A.; Tompkins, S. Mark

    2014-01-01

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

  7. 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.

  8. 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

  9. [New strategy for RNA vectorization in mammalian cells. Use of a peptide vector].

    Science.gov (United States)

    Vidal, P; Morris, M C; Chaloin, L; Heitz, F; Divita, G

    1997-04-01

    A major barrier for gene delivery is the low permeability of nucleic acids to cellular membranes. The development of antisenses and gene therapy has focused mainly on improving methods of oligonucleotide or gene delivery to the cell. In this report we described a new strategy for RNA cell delivery, based on a short single peptide. This peptide vector is derived from both the fusion domain of the gp41 protein of HIV and the nuclear localization sequence of the SV40 large T antigen. This peptide vector localizes rapidly to the cytoplasm then to the nucleus of human fibroblasts (HS-68) within a few minutes and exhibits a high affinity for a single-stranded mRNA encoding the p66 subunit of the HIV-1 reverse transcriptase (in a 100 nM range). The peptide/RNA complex formation involves mainly electrostatic interactions between the basic residues of the peptide and the charges on the phosphate group of the RNA. In the presence of the peptide-vector fluorescently-labelled mRNA is delivered into the cytoplasm of mammalian cells (HS68 human fibroblasts) in less than 1 h with a relatively high efficiency (80%). This new concept based on a peptide-derived vector offers several advantages compared to other compounds commonly used in gene delivery. This vector is highly soluble and exhibits no cytotoxicity at the concentrations used for optimal gene delivery. This result clearly supports the fact that this peptide vector is a powerful tool and that it can be used widely, as much for laboratory research as for new applications and development in gene and/or antisense therapy.

  10. Attenuated Vector Tomography -- An Approach to Image Flow Vector Fields with Doppler Ultrasonic Imaging

    International Nuclear Information System (INIS)

    Huang, Qiu; Peng, Qiyu; Huang, Bin; Cheryauka, Arvi; Gullberg, Grant T.

    2008-01-01

    The measurement of flow obtained using continuous wave Doppler ultrasound is formulated as a directional projection of a flow vector field. When a continuous ultrasound wave bounces against a flowing particle, a signal is backscattered. This signal obtains a Doppler frequency shift proportional to the speed of the particle along the ultrasound beam. This occurs for each particle along the beam, giving rise to a Doppler velocity spectrum. The first moment of the spectrum provides the directional projection of the flow along the ultrasound beam. Signals reflected from points further away from the detector will have lower amplitude than signals reflected from points closer to the detector. The effect is very much akin to that modeled by the attenuated Radon transform in emission computed tomography.A least-squares method was adopted to reconstruct a 2D vector field from directional projection measurements. Attenuated projections of only the longitudinal projections of the vector field were simulated. The components of the vector field were reconstructed using the gradient algorithm to minimize a least-squares criterion. This result was compared with the reconstruction of longitudinal projections of the vector field without attenuation. If attenuation is known, the algorithm was able to accurately reconstruct both components of the full vector field from only one set of directional projection measurements. A better reconstruction was obtained with attenuation than without attenuation implying that attenuation provides important information for the reconstruction of flow vector fields.This confirms previous work where we showed that knowledge of the attenuation distribution helps in the reconstruction of MRI diffusion tensor fields from fewer than the required measurements. In the application of ultrasound the attenuation distribution is obtained with pulse wave transmission computed tomography and flow information is obtained with continuous wave Doppler

  11. 40 CFR 503.33 - Vector attraction reduction.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Vector attraction reduction. 503.33... STANDARDS FOR THE USE OR DISPOSAL OF SEWAGE SLUDGE Pathogens and Vector Attraction Reduction § 503.33 Vector attraction reduction. (a)(1) One of the vector attraction reduction requirements in § 503.33 (b)(1) through...

  12. 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.

  13. 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.

  14. Multineuronal vectorization is more efficient than time-segmental vectorization for information extraction from neuronal activities in the inferior temporal cortex.

    Science.gov (United States)

    Kaneko, Hidekazu; Tamura, Hiroshi; Tate, Shunta; Kawashima, Takahiro; Suzuki, Shinya S; Fujita, Ichiro

    2010-08-01

    In order for patients with disabilities to control assistive devices with their own neural activity, multineuronal spike trains must be efficiently decoded because only limited computational resources can be used to generate prosthetic control signals in portable real-time applications. In this study, we compare the abilities of two vectorizing procedures (multineuronal and time-segmental) to extract information from spike trains during the same total neuron-seconds. In the multineuronal vectorizing procedure, we defined a response vector whose components represented the spike counts of one to five neurons. In the time-segmental vectorizing procedure, a response vector consisted of components representing a neuron's spike counts for one to five time-segment(s) of a response period of 1 s. Spike trains were recorded from neurons in the inferior temporal cortex of monkeys presented with visual stimuli. We examined whether the amount of information of the visual stimuli carried by these neurons differed between the two vectorizing procedures. The amount of information calculated with the multineuronal vectorizing procedure, but not the time-segmental vectorizing procedure, significantly increased with the dimensions of the response vector. We conclude that the multineuronal vectorizing procedure is superior to the time-segmental vectorizing procedure in efficiently extracting information from neuronal signals. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  15. 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.

  16. A Subdivision-Based Representation for Vector Image Editing.

    Science.gov (United States)

    Liao, Zicheng; Hoppe, Hugues; Forsyth, David; Yu, Yizhou

    2012-11-01

    Vector graphics has been employed in a wide variety of applications due to its scalability and editability. Editability is a high priority for artists and designers who wish to produce vector-based graphical content with user interaction. In this paper, we introduce a new vector image representation based on piecewise smooth subdivision surfaces, which is a simple, unified and flexible framework that supports a variety of operations, including shape editing, color editing, image stylization, and vector image processing. These operations effectively create novel vector graphics by reusing and altering existing image vectorization results. Because image vectorization yields an abstraction of the original raster image, controlling the level of detail of this abstraction is highly desirable. To this end, we design a feature-oriented vector image pyramid that offers multiple levels of abstraction simultaneously. Our new vector image representation can be rasterized efficiently using GPU-accelerated subdivision. Experiments indicate that our vector image representation achieves high visual quality and better supports editing operations than existing representations.

  17. 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.

  18. 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.

  19. Inverse Operation of Four-dimensional Vector Matrix

    OpenAIRE

    H J Bao; A J Sang; H X Chen

    2011-01-01

    This is a new series of study to define and prove multidimensional vector matrix mathematics, which includes four-dimensional vector matrix determinant, four-dimensional vector matrix inverse and related properties. There are innovative concepts of multi-dimensional vector matrix mathematics created by authors with numerous applications in engineering, math, video conferencing, 3D TV, and other fields.

  20. Multiscale vector fields for image pattern recognition

    Science.gov (United States)

    Low, Kah-Chan; Coggins, James M.

    1990-01-01

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

  1. 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

  2. Long-term correction of obesity and diabetes in genetically obese mice by a single intramuscular injection of recombinant adeno-associated virus encoding mouse leptin

    Science.gov (United States)

    Murphy, John E.; Zhou, Shangzhen; Giese, Klaus; Williams, Lewis T.; Escobedo, Jaime A.; Dwarki, Varavani J.

    1997-01-01

    The ob/ob mouse is genetically deficient in leptin and exhibits a phenotype that includes obesity and non-insulin-dependent diabetes melitus. This phenotype closely resembles the morbid obesity seen in humans. In this study, we demonstrate that a single intramuscular injection of a recombinant adeno-associated virus (AAV) vector encoding mouse leptin (rAAV-leptin) in ob/ob mice leads to prevention of obesity and diabetes. The treated animals show normalization of metabolic abnormalities including hyperglycemia, insulin resistance, impaired glucose tolerance, and lethargy. The effects of a single injection have lasted through the 6-month course of the study. At all time points measured the circulating levels of leptin in the serum were similar to age-matched control C57 mice. These results demonstrate that maintenance of normal levels of leptin (2–5 ng/ml) in the circulation can prevent both the onset of obesity and associated non-insulin-dependent diabetes. Thus a single injection of a rAAV vector expressing a therapeutic gene can lead to complete and long-term correction of a genetic disorder. Our study demonstrates the long-term correction of a disease caused by a genetic defect and proves the feasibility of using rAAV-based vectors for the treatment of chronic disorders like obesity. PMID:9391128

  3. 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

  4. Integrated optic vector-matrix multiplier

    Science.gov (United States)

    Watts, Michael R [Albuquerque, NM

    2011-09-27

    A vector-matrix multiplier is disclosed which uses N different wavelengths of light that are modulated with amplitudes representing elements of an N.times.1 vector and combined to form an input wavelength-division multiplexed (WDM) light stream. The input WDM light stream is split into N streamlets from which each wavelength of the light is individually coupled out and modulated for a second time using an input signal representing elements of an M.times.N matrix, and is then coupled into an output waveguide for each streamlet to form an output WDM light stream which is detected to generate a product of the vector and matrix. The vector-matrix multiplier can be formed as an integrated optical circuit using either waveguide amplitude modulators or ring resonator amplitude modulators.

  5. 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....

  6. 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

  7. NPY gene transfer in the hippocampus attenuates synaptic plasticity and learning

    DEFF Research Database (Denmark)

    Sørensen, Andreas T; Kanter-Schlifke, Irene; Carli, Mirjana

    2008-01-01

    -mediated mechanisms. In addition, transgene NPY seems to be released during high frequency neuronal activity, leading to decreased glutamate release in excitatory synapses. Importantly, memory consolidation appears to be affected by the treatment. We found that long-term potentiation (LTP) in the CA1 area...... processing. Here we show, by electrophysiological recordings in CA1 of the hippocampal formation of rats, that hippocampal NPY gene transfer into the intact brain does not affect basal synaptic transmission, but slightly alters short-term synaptic plasticity, most likely via NPY Y2 receptor....... Future clinical progress, however, requires more detailed evaluation of possible side effects of this treatment. Until now it has been unknown whether rAAV vector-based NPY overexpression in the hippocampus alters normal synaptic transmission and plasticity, which could disturb learning and memory...

  8. Gauge structure of neutral-vector field theory. [Massive vector fields, massless limits

    Energy Technology Data Exchange (ETDEWEB)

    Kubo, R; Yokoyama, [Hiroshima univ., Takehara (Japan). Research Inst. for Theoretical Physics

    1975-03-01

    General aspects of gauge structure of neutral-vector field theory are investigated from an extended standpoint, where massive vector fields are treated in a form corresponding to the electromagnetic fields in a general gauge formalism reported previously. All results obtained are shown to have unique massless limits. It is shown that a generalized q-number gauge transformation for fields makes the theory invariant in cooperation with a simultaneous transformation for relevant gauge parameters. A method of differentiation with respect to a gauge variable is found to clarify some essential features of the gauge structure. Two possible types of gauge structure also emerge correspondingly to the massless case. A neutral-vector field theory proposed in a preceding paper is included in the present framework as the most preferable case.

  9. 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

  10. Declining Prevalence of Disease Vectors Under Climate Change

    Science.gov (United States)

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

    2016-12-01

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

  11. 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.

  12. 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.

  13. Virtual-vector-based space vector pulse width modulation of the DC-AC multilevel-clamped multilevel converter (MLC2)

    DEFF Research Database (Denmark)

    Rodriguez, Pedro; Busquets-Monge, Sergio; Blaabjerg, Frede

    2011-01-01

    This work presents the development of the space vector pulse width modulation (SVPWM) of a new multi-level converter topology. First, the proposed converter and its natural space vector diagram are presented. Secondly, a modified space vector diagram based on the virtual-vectors technique is show...

  14. 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

  15. 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...

  16. 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 ...

  17. 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....

  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. 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.

  20. How random is a random vector?

    International Nuclear Information System (INIS)

    Eliazar, Iddo

    2015-01-01

    Over 80 years ago Samuel Wilks proposed that the “generalized variance” of a random vector is the determinant of its covariance matrix. To date, the notion and use of the generalized variance is confined only to very specific niches in statistics. In this paper we establish that the “Wilks standard deviation” –the square root of the generalized variance–is indeed the standard deviation of a random vector. We further establish that the “uncorrelation index” –a derivative of the Wilks standard deviation–is a measure of the overall correlation between the components of a random vector. Both the Wilks standard deviation and the uncorrelation index are, respectively, special cases of two general notions that we introduce: “randomness measures” and “independence indices” of random vectors. In turn, these general notions give rise to “randomness diagrams”—tangible planar visualizations that answer the question: How random is a random vector? The notion of “independence indices” yields a novel measure of correlation for Lévy laws. In general, the concepts and results presented in this paper are applicable to any field of science and engineering with random-vectors empirical data.

  1. How random is a random vector?

    Science.gov (United States)

    Eliazar, Iddo

    2015-12-01

    Over 80 years ago Samuel Wilks proposed that the "generalized variance" of a random vector is the determinant of its covariance matrix. To date, the notion and use of the generalized variance is confined only to very specific niches in statistics. In this paper we establish that the "Wilks standard deviation" -the square root of the generalized variance-is indeed the standard deviation of a random vector. We further establish that the "uncorrelation index" -a derivative of the Wilks standard deviation-is a measure of the overall correlation between the components of a random vector. Both the Wilks standard deviation and the uncorrelation index are, respectively, special cases of two general notions that we introduce: "randomness measures" and "independence indices" of random vectors. In turn, these general notions give rise to "randomness diagrams"-tangible planar visualizations that answer the question: How random is a random vector? The notion of "independence indices" yields a novel measure of correlation for Lévy laws. In general, the concepts and results presented in this paper are applicable to any field of science and engineering with random-vectors empirical data.

  2. 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.

  3. 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

  4. 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

  5. Effective SIMD Vectorization for Intel Xeon Phi Coprocessors

    OpenAIRE

    Tian, Xinmin; Saito, Hideki; Preis, Serguei V.; Garcia, Eric N.; Kozhukhov, Sergey S.; Masten, Matt; Cherkasov, Aleksei G.; Panchenko, Nikolay

    2015-01-01

    Efficiently exploiting SIMD vector units is one of the most important aspects in achieving high performance of the application code running on Intel Xeon Phi coprocessors. In this paper, we present several effective SIMD vectorization techniques such as less-than-full-vector loop vectorization, Intel MIC specific alignment optimization, and small matrix transpose/multiplication 2D vectorization implemented in the Intel C/C++ and Fortran production compilers for Intel Xeon Phi coprocessors. A ...

  6. 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.

  7. 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

  8. 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.

  9. Effective SIMD Vectorization for Intel Xeon Phi Coprocessors

    Directory of Open Access Journals (Sweden)

    Xinmin Tian

    2015-01-01

    Full Text Available Efficiently exploiting SIMD vector units is one of the most important aspects in achieving high performance of the application code running on Intel Xeon Phi coprocessors. In this paper, we present several effective SIMD vectorization techniques such as less-than-full-vector loop vectorization, Intel MIC specific alignment optimization, and small matrix transpose/multiplication 2D vectorization implemented in the Intel C/C++ and Fortran production compilers for Intel Xeon Phi coprocessors. A set of workloads from several application domains is employed to conduct the performance study of our SIMD vectorization techniques. The performance results show that we achieved up to 12.5x performance gain on the Intel Xeon Phi coprocessor. We also demonstrate a 2000x performance speedup from the seamless integration of SIMD vectorization and parallelization.

  10. Engineering BioBrick vectors from BioBrick parts

    Directory of Open Access Journals (Sweden)

    Knight Thomas F

    2008-04-01

    Full Text Available Abstract Background The underlying goal of synthetic biology is to make the process of engineering biological systems easier. Recent work has focused on defining and developing standard biological parts. The technical standard that has gained the most traction in the synthetic biology community is the BioBrick standard for physical composition of genetic parts. Parts that conform to the BioBrick assembly standard are BioBrick standard biological parts. To date, over 2,000 BioBrick parts have been contributed to, and are available from, the Registry of Standard Biological Parts. Results Here we extended the same advantages of BioBrick standard biological parts to the plasmid-based vectors that are used to provide and propagate BioBrick parts. We developed a process for engineering BioBrick vectors from BioBrick parts. We designed a new set of BioBrick parts that encode many useful vector functions. We combined the new parts to make a BioBrick base vector that facilitates BioBrick vector construction. We demonstrated the utility of the process by constructing seven new BioBrick vectors. We also successfully used the resulting vectors to assemble and propagate other BioBrick standard biological parts. Conclusion We extended the principles of part reuse and standardization to BioBrick vectors. As a result, myriad new BioBrick vectors can be readily produced from all existing and newly designed BioBrick parts. We invite the synthetic biology community to (1 use the process to make and share new BioBrick vectors; (2 expand the current collection of BioBrick vector parts; and (3 characterize and improve the available collection of BioBrick vector parts.

  11. Bioreactor production of recombinant herpes simplex virus vectors.

    Science.gov (United States)

    Knop, David R; Harrell, Heather

    2007-01-01

    Serotypical application of herpes simplex virus (HSV) vectors to gene therapy (type 1) and prophylactic vaccines (types 1 and 2) has garnered substantial clinical interest recently. HSV vectors and amplicons have also been employed as helper virus constructs for manufacture of the dependovirus adeno-associated virus (AAV). Large quantities of infectious HSV stocks are requisite for these therapeutic applications, requiring a scalable vector manufacturing and processing platform comprised of unit operations which accommodate the fragility of HSV. In this study, production of a replication deficient rHSV-1 vector bearing the rep and cap genes of AAV-2 (denoted rHSV-rep2/cap2) was investigated. Adaptation of rHSV production from T225 flasks to a packed bed, fed-batch bioreactor permitted an 1100-fold increment in total vector production without a decrease in specific vector yield (pfu/cell). The fed-batch bioreactor system afforded a rHSV-rep2/cap2 vector recovery of 2.8 x 10(12) pfu. The recovered vector was concentrated by tangential flow filtration (TFF), permitting vector stocks to be formulated at greater than 1.5 x 10(9) pfu/mL.

  12. Cosmological evolution in vector-tensor theories of gravity

    International Nuclear Information System (INIS)

    Beltran Jimenez, Jose; Maroto, Antonio L.

    2009-01-01

    We present a detailed study of the cosmological evolution in general vector-tensor theories of gravity without potential terms. We consider the evolution of the vector field throughout the expansion history of the Universe and carry out a classification of models according to the behavior of the vector field in each cosmological epoch. We also analyze the case in which the Universe is dominated by the vector field, performing a complete analysis of the system phase map and identifying those attracting solutions which give rise to accelerated expansion. Moreover, we consider the evolution in a universe filled with a pressureless fluid in addition to the vector field and study the existence of attractors in which we can have a transition from matter domination to vector domination with accelerated expansion so that the vector field may play the role of dark energy. We find that the existence of solutions with late-time accelerated expansion is a generic prediction of vector-tensor theories and that such solutions typically lead to the presence of future singularities. Finally, limits from local gravity tests are used to get constraints on the value of the vector field at small (Solar System) scales.

  13. n-Characteristic Vector Fields of Contact Manifoldss

    OpenAIRE

    Hassanzadeh, Babak

    2017-01-01

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

  14. 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.)

  15. A study of biorthogonal multiple vector-valued wavelets

    International Nuclear Information System (INIS)

    Han Jincang; Cheng Zhengxing; Chen Qingjiang

    2009-01-01

    The notion of vector-valued multiresolution analysis is introduced and the concept of biorthogonal multiple vector-valued wavelets which are wavelets for vector fields, is introduced. It is proved that, like in the scalar and multiwavelet case, the existence of a pair of biorthogonal multiple vector-valued scaling functions guarantees the existence of a pair of biorthogonal multiple vector-valued wavelet functions. An algorithm for constructing a class of compactly supported biorthogonal multiple vector-valued wavelets is presented. Their properties are investigated by means of operator theory and algebra theory and time-frequency analysis method. Several biorthogonality formulas regarding these wavelet packets are obtained.

  16. 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...

  17. Black holes in vector-tensor theories

    Energy Technology Data Exchange (ETDEWEB)

    Heisenberg, Lavinia [Institute for Theoretical Studies, ETH Zurich, Clausiusstrasse 47, 8092 Zurich (Switzerland); Kase, Ryotaro; Tsujikawa, Shinji [Department of Physics, Faculty of Science, Tokyo University of Science, 1-3, Kagurazaka, Shinjuku-ku, Tokyo 162-8601 (Japan); Minamitsuji, Masato, E-mail: lavinia.heisenberg@eth-its.ethz.ch, E-mail: r.kase@rs.tus.ac.jp, E-mail: masato.minamitsuji@tecnico.ulisboa.pt, E-mail: shinji@rs.kagu.tus.ac.jp [Centro Multidisciplinar de Astrofisica—CENTRA, Departamento de Fisica, Instituto Superior Tecnico—IST, Universidade de Lisboa—UL, Avenida Rovisco Pais 1, 1049-001 Lisboa (Portugal)

    2017-08-01

    We study static and spherically symmetric black hole (BH) solutions in second-order generalized Proca theories with nonminimal vector field derivative couplings to the Ricci scalar, the Einstein tensor, and the double dual Riemann tensor. We find concrete Lagrangians which give rise to exact BH solutions by imposing two conditions of the two identical metric components and the constant norm of the vector field. These exact solutions are described by either Reissner-Nordström (RN), stealth Schwarzschild, or extremal RN solutions with a non-trivial longitudinal mode of the vector field. We then numerically construct BH solutions without imposing these conditions. For cubic and quartic Lagrangians with power-law couplings which encompass vector Galileons as the specific cases, we show the existence of BH solutions with the difference between two non-trivial metric components. The quintic-order power-law couplings do not give rise to non-trivial BH solutions regular throughout the horizon exterior. The sixth-order and intrinsic vector-mode couplings can lead to BH solutions with a secondary hair. For all the solutions, the vector field is regular at least at the future or past horizon. The deviation from General Relativity induced by the Proca hair can be potentially tested by future measurements of gravitational waves in the nonlinear regime of gravity.

  18. Investigation of Optimal Integrated Circuit Raster Image Vectorization Method

    Directory of Open Access Journals (Sweden)

    Leonas Jasevičius

    2011-03-01

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

  19. Environmental management: a re-emerging vector control strategy.

    Science.gov (United States)

    Ault, S K

    1994-01-01

    Vector control may be accomplished by environmental management (EM), which consists of permanent or long-term modification of the environment, temporary or seasonal manipulation of the environment, and modifying or changing our life styles and practices to reduce human contact with infective vectors. The primary focus of this paper is EM in the control of human malaria, filariasis, arboviruses, Chagas' disease, and schistosomiasis. Modern EM developed as a discipline based primarily in ecologic principles and lessons learned from the adverse environmental impacts of rural development projects. Strategies such as the suppression of vector populations through the provision of safe water supplies, proper sanitation, solid waste management facilities, sewerage and excreta disposal systems, water manipulation in dams and irrigation systems, vector diversion by zooprophylaxis, and vector exclusion by improved housing, are discussed with appropriate examples. Vectors of malaria, filariasis, Chagas' disease, and schistosomiasis have been controlled by drainage or filling aquatic breeding sites, improved housing and sanitation, the use of expanded polystyrene beads, zooprophylaxis, or the provision of household water supplies. Community participation has been effective in the suppression of dengue vectors in Mexico and the Dominican Republic. Alone or combined with other vector control methods, EM has been proven to be a successful approach to vector control in a number of places. The future of EM in vector control looks promising.

  20. TimesVector: a vectorized clustering approach to the analysis of time series transcriptome data from multiple phenotypes.

    Science.gov (United States)

    Jung, Inuk; Jo, Kyuri; Kang, Hyejin; Ahn, Hongryul; Yu, Youngjae; Kim, Sun

    2017-12-01

    Identifying biologically meaningful gene expression patterns from time series gene expression data is important to understand the underlying biological mechanisms. To identify significantly perturbed gene sets between different phenotypes, analysis of time series transcriptome data requires consideration of time and sample dimensions. Thus, the analysis of such time series data seeks to search gene sets that exhibit similar or different expression patterns between two or more sample conditions, constituting the three-dimensional data, i.e. gene-time-condition. Computational complexity for analyzing such data is very high, compared to the already difficult NP-hard two dimensional biclustering algorithms. Because of this challenge, traditional time series clustering algorithms are designed to capture co-expressed genes with similar expression pattern in two sample conditions. We present a triclustering algorithm, TimesVector, specifically designed for clustering three-dimensional time series data to capture distinctively similar or different gene expression patterns between two or more sample conditions. TimesVector identifies clusters with distinctive expression patterns in three steps: (i) dimension reduction and clustering of time-condition concatenated vectors, (ii) post-processing clusters for detecting similar and distinct expression patterns and (iii) rescuing genes from unclassified clusters. Using four sets of time series gene expression data, generated by both microarray and high throughput sequencing platforms, we demonstrated that TimesVector successfully detected biologically meaningful clusters of high quality. TimesVector improved the clustering quality compared to existing triclustering tools and only TimesVector detected clusters with differential expression patterns across conditions successfully. The TimesVector software is available at http://biohealth.snu.ac.kr/software/TimesVector/. sunkim.bioinfo@snu.ac.kr. Supplementary data are available at

  1. 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.

  2. 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

  3. 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.

  4. 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...

  5. 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

  6. How effective is integrated vector management against malaria and lymphatic filariasis where the diseases are transmitted by the same vector?

    OpenAIRE

    Stone, C.; Lindsay, S.W.; Chitnis, N.

    2014-01-01

    Background: The opportunity to integrate vector management across multiple vector-borne diseases is particularly plausible for malaria and lymphatic filariasis (LF) control where both diseases are transmitted by the same vector. To date most examples of integrated control targeting these diseases have been unanticipated consequences of malaria vector control, rather than planned strategies that aim to maximize the efficacy and take the complex ecological and biological interactions between th...

  7. Two-dimensional gauge model with vector U(1) and axial-vector U(1) symmetries

    International Nuclear Information System (INIS)

    Watabiki, Y.

    1989-01-01

    We have succeeded in constructing a two-dimensional gauge model with both vector U(1) and axial-vector U(1) symmetries. This model is exactly solvable. The Schwinger term vanishes in this model as a consequence of the above symmetries, and negative-norm states appear. However, the norms of physical states are always positive semidefinite due to the gauge symmetries

  8. Air travel and vector-borne disease movement.

    Science.gov (United States)

    Tatem, A J; Huang, Z; Das, A; Qi, Q; Roth, J; Qiu, Y

    2012-12-01

    Recent decades have seen substantial expansions in the global air travel network and rapid increases in traffic volumes. The effects of this are well studied in terms of the spread of directly transmitted infections, but the role of air travel in the movement of vector-borne diseases is less well understood. Increasingly however, wider reaching surveillance for vector-borne diseases and our improving abilities to map the distributions of vectors and the diseases they carry, are providing opportunities to better our understanding of the impact of increasing air travel. Here we examine global trends in the continued expansion of air transport and its impact upon epidemiology. Novel malaria and chikungunya examples are presented, detailing how geospatial data in combination with information on air traffic can be used to predict the risks of vector-borne disease importation and establishment. Finally, we describe the development of an online tool, the Vector-Borne Disease Airline Importation Risk (VBD-Air) tool, which brings together spatial data on air traffic and vector-borne disease distributions to quantify the seasonally changing risks for importation to non-endemic regions. Such a framework provides the first steps towards an ultimate goal of adaptive management based on near real time flight data and vector-borne disease surveillance.

  9. 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.

  10. Lyapunov, singular and bred vectors in a multi-scale system: an empirical exploration of vectors related to instabilities

    International Nuclear Information System (INIS)

    Norwood, Adrienne; Kalnay, Eugenia; Ide, Kayo; Yang, Shu-Chih; Wolfe, Christopher

    2013-01-01

    We compute and compare the three types of vectors frequently used to explore the instability properties of dynamical models, namely Lyapunov vectors (LVs), singular vectors (SVs) and bred vectors (BVs) in two systems, using the Wolfe–Samelson (2007 Tellus A 59 355–66) algorithm to compute all of the Lyapunov vectors. The first system is the Lorenz (1963 J. Atmos. Sci. 20 130–41) three-variable model. Although the leading Lyapunov vector, LV1, grows fastest globally, the second Lyapunov vector, LV2, which has zero growth globally, often grows faster than LV1 locally. Whenever this happens, BVs grow closer to LV2, suggesting that in larger atmospheric or oceanic models where several instabilities can grow in different areas of the world, BVs will grow toward the fastest growing local unstable mode. A comparison of their growth rates at different times shows that all three types of dynamical vectors have the ability to predict regime changes and the duration of the new regime based on their growth rates in the last orbit of the old regime, as shown for BVs by Evans et al (2004 Bull. Am. Meteorol. Soc. 520–4). LV1 and BVs have similar predictive skill, LV2 has a tendency to produce false alarms, and even LV3 shows that maximum decay is also associated with regime change. Initial and final SVs grow much faster and are the most accurate predictors of regime change, although the characteristics of the initial SVs are strongly dependent on the length of the optimization window. The second system is the toy ‘ocean-atmosphere’ model developed by Peña and Kalnay (2004 Nonlinear Process. Geophys. 11 319–27) coupling three Lorenz (1963 J. Atmos. Sci. 20 130–41) systems with different time scales, in order to test the effects of fast and slow modes of growth on the dynamical vectors. A fast ‘extratropical atmosphere’ is weakly coupled to a fast ‘tropical atmosphere’ which is, in turn, strongly coupled to a slow ‘ocean’ system, the latter coupling

  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. The charge form factor of the neutron from sup 2 H-vector, (e-vector, e' n)p

    CERN Document Server

    Passchier, I; Szczerba, D; Alarcon, R; Bauer, T S; Boersma, D J; Van der Brand, J F J; Bulten, H J; Ferro-Luzzi, M; Higinbotham, D W; Jager, C W D; Klous, S; Kolster, H; Lang, J; Nikolenko, D M; Nooren, G J; Norum, B E; Poolman, H R; Rachek, Igor A; Simani, M C; Six, E; Vries, H D; Wang, K; Zhou, Z L

    2000-01-01

    We report on the first measurement of spin-correlation parameters in quasifree electron scattering from vector-polarized deuterium. Polarized electrons were injected into an electron storage ring at a beam energy of 720 MeV. A Siberian snake was employed to preserve longitudinal polarization at the interaction point. Vector-polarized deuterium was produced by an atomic beam source and injected into an open-ended cylindrical cell, internal to the electron storage ring. The spin correlation parameter A sup V sub e sub d was measured for the reaction sup 2 H-vector, (e-vector, e'n)p at a four-momentum transfer squared of 0.21 (GeV/c) sup 2 from which a value for the charge form factor of the neutron was extracted.

  13. 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.

  14. 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....

  15. 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.

  16. Integrated vector management for malaria control

    Directory of Open Access Journals (Sweden)

    Impoinvil Daniel E

    2008-12-01

    Full Text Available Abstract Integrated vector management (IVM is defined as "a rational decision-making process for the optimal use of resources for vector control" and includes five key elements: 1 evidence-based decision-making, 2 integrated approaches 3, collaboration within the health sector and with other sectors, 4 advocacy, social mobilization, and legislation, and 5 capacity-building. In 2004, the WHO adopted IVM globally for the control of all vector-borne diseases. Important recent progress has been made in developing and promoting IVM for national malaria control programmes in Africa at a time when successful malaria control programmes are scaling-up with insecticide-treated nets (ITN and/or indoor residual spraying (IRS coverage. While interventions using only ITNs and/or IRS successfully reduce transmission intensity and the burden of malaria in many situations, it is not clear if these interventions alone will achieve those critical low levels that result in malaria elimination. Despite the successful employment of comprehensive integrated malaria control programmes, further strengthening of vector control components through IVM is relevant, especially during the "end-game" where control is successful and further efforts are required to go from low transmission situations to sustained local and country-wide malaria elimination. To meet this need and to ensure sustainability of control efforts, malaria control programmes should strengthen their capacity to use data for decision-making with respect to evaluation of current vector control programmes, employment of additional vector control tools in conjunction with ITN/IRS tactics, case-detection and treatment strategies, and determine how much and what types of vector control and interdisciplinary input are required to achieve malaria elimination. Similarly, on a global scale, there is a need for continued research to identify and evaluate new tools for vector control that can be integrated with

  17. Applications of the conserved vector current theory and the partially conserved axial-vector current theory to nuclear beta-decays

    International Nuclear Information System (INIS)

    Tint, M.

    The contribution of the mesonic exchange effect to the conserved vector current in the first forbidden β-decay of Ra E is estimated under the headings: (1) The conserved vector current. (2) The CVC theory and the first forbidden β-decays. (3) Shell model calculations of some matrix-elements. (4) Direct calculation of the exchange term. Considering the mesonic exchange effect in the axial vector-current of β-decay the partially conserved axial vector current theory and experimental results of the process p + p → d + π + are examined. (U.K.)

  18. Feature Vector Construction Method for IRIS Recognition

    Science.gov (United States)

    Odinokikh, G.; Fartukov, A.; Korobkin, M.; Yoo, J.

    2017-05-01

    One of the basic stages of iris recognition pipeline is iris feature vector construction procedure. The procedure represents the extraction of iris texture information relevant to its subsequent comparison. Thorough investigation of feature vectors obtained from iris showed that not all the vector elements are equally relevant. There are two characteristics which determine the vector element utility: fragility and discriminability. Conventional iris feature extraction methods consider the concept of fragility as the feature vector instability without respect to the nature of such instability appearance. This work separates sources of the instability into natural and encodinginduced which helps deeply investigate each source of instability independently. According to the separation concept, a novel approach of iris feature vector construction is proposed. The approach consists of two steps: iris feature extraction using Gabor filtering with optimal parameters and quantization with separated preliminary optimized fragility thresholds. The proposed method has been tested on two different datasets of iris images captured under changing environmental conditions. The testing results show that the proposed method surpasses all the methods considered as a prior art by recognition accuracy on both datasets.

  19. Vectorization of Monte Carlo particle transport

    International Nuclear Information System (INIS)

    Burns, P.J.; Christon, M.; Schweitzer, R.; Lubeck, O.M.; Wasserman, H.J.; Simmons, M.L.; Pryor, D.V.

    1989-01-01

    This paper reports that fully vectorized versions of the Los Alamos National Laboratory benchmark code Gamteb, a Monte Carlo photon transport algorithm, were developed for the Cyber 205/ETA-10 and Cray X-MP/Y-MP architectures. Single-processor performance measurements of the vector and scalar implementations were modeled in a modified Amdahl's Law that accounts for additional data motion in the vector code. The performance and implementation strategy of the vector codes are related to architectural features of each machine. Speedups between fifteen and eighteen for Cyber 205/ETA-10 architectures, and about nine for CRAY X-MP/Y-MP architectures are observed. The best single processor execution time for the problem was 0.33 seconds on the ETA-10G, and 0.42 seconds on the CRAY Y-MP

  20. 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.

  1. A vector lattice version of Radström's embedding theorem

    African Journals Online (AJOL)

    Radström's embedding theorem for 'near vector spaces', which are essentially vector spaces without additive inverses, is extended to embeddings of 'near vector lattices', which are essentially vector lattices without additive inverses, into vector lattices. If the 'near vector space' is endowed with a metric, properties on the ...

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. [Orthogonal Vector Projection Algorithm for Spectral Unmixing].

    Science.gov (United States)

    Song, Mei-ping; Xu, Xing-wei; Chang, Chein-I; An, Ju-bai; Yao, Li

    2015-12-01

    Spectrum unmixing is an important part of hyperspectral technologies, which is essential for material quantity analysis in hyperspectral imagery. Most linear unmixing algorithms require computations of matrix multiplication and matrix inversion or matrix determination. These are difficult for programming, especially hard for realization on hardware. At the same time, the computation costs of the algorithms increase significantly as the number of endmembers grows. Here, based on the traditional algorithm Orthogonal Subspace Projection, a new method called. Orthogonal Vector Projection is prompted using orthogonal principle. It simplifies this process by avoiding matrix multiplication and inversion. It firstly computes the final orthogonal vector via Gram-Schmidt process for each endmember spectrum. And then, these orthogonal vectors are used as projection vector for the pixel signature. The unconstrained abundance can be obtained directly by projecting the signature to the projection vectors, and computing the ratio of projected vector length and orthogonal vector length. Compared to the Orthogonal Subspace Projection and Least Squares Error algorithms, this method does not need matrix inversion, which is much computation costing and hard to implement on hardware. It just completes the orthogonalization process by repeated vector operations, easy for application on both parallel computation and hardware. The reasonability of the algorithm is proved by its relationship with Orthogonal Sub-space Projection and Least Squares Error algorithms. And its computational complexity is also compared with the other two algorithms', which is the lowest one. At last, the experimental results on synthetic image and real image are also provided, giving another evidence for effectiveness of the method.

  7. Applicability of vector processing to large-scale nuclear codes

    International Nuclear Information System (INIS)

    Ishiguro, Misako; Harada, Hiroo; Matsuura, Toshihiko; Okuda, Motoi; Ohta, Fumio; Umeya, Makoto.

    1982-03-01

    To meet the growing trend of computational requirements in JAERI, introduction of a high-speed computer with vector processing faculty (a vector processor) is desirable in the near future. To make effective use of a vector processor, appropriate optimization of nuclear codes to pipelined-vector architecture is vital, which will pose new problems concerning code development and maintenance. In this report, vector processing efficiency is assessed with respect to large-scale nuclear codes by examining the following items: 1) The present feature of computational load in JAERI is analyzed by compiling the computer utilization statistics. 2) Vector processing efficiency is estimated for the ten heavily-used nuclear codes by analyzing their dynamic behaviors run on a scalar machine. 3) Vector processing efficiency is measured for the other five nuclear codes by using the current vector processors, FACOM 230-75 APU and CRAY-1. 4) Effectiveness of applying a high-speed vector processor to nuclear codes is evaluated by taking account of the characteristics in JAERI jobs. Problems of vector processors are also discussed from the view points of code performance and ease of use. (author)

  8. 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....

  9. 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

  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 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].

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

    Directory of Open Access Journals (Sweden)

    Hiroyuki Mizuguchi

    2011-07-01

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

  13. 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.

  14. Magnetic vector field tag and seal

    Science.gov (United States)

    Johnston, Roger G.; Garcia, Anthony R.

    2004-08-31

    One or more magnets are placed in a container (preferably on objects inside the container) and the magnetic field strength and vector direction are measured with a magnetometer from at least one location near the container to provide the container with a magnetic vector field tag and seal. The location(s) of the magnetometer relative to the container are also noted. If the position of any magnet inside the container changes, then the measured vector fields at the these locations also change, indicating that the tag has been removed, the seal has broken, and therefore that the container and objects inside may have been tampered with. A hollow wheel with magnets inside may also provide a similar magnetic vector field tag and seal. As the wheel turns, the magnets tumble randomly inside, removing the tag and breaking the seal.

  15. Design of 2D time-varying vector fields.

    Science.gov (United States)

    Chen, Guoning; Kwatra, Vivek; Wei, Li-Yi; Hansen, Charles D; Zhang, Eugene

    2012-10-01

    Design of time-varying vector fields, i.e., vector fields that can change over time, has a wide variety of important applications in computer graphics. Existing vector field design techniques do not address time-varying vector fields. In this paper, we present a framework for the design of time-varying vector fields, both for planar domains as well as manifold surfaces. Our system supports the creation and modification of various time-varying vector fields with desired spatial and temporal characteristics through several design metaphors, including streamlines, pathlines, singularity paths, and bifurcations. These design metaphors are integrated into an element-based design to generate the time-varying vector fields via a sequence of basis field summations or spatial constrained optimizations at the sampled times. The key-frame design and field deformation are also introduced to support other user design scenarios. Accordingly, a spatial-temporal constrained optimization and the time-varying transformation are employed to generate the desired fields for these two design scenarios, respectively. We apply the time-varying vector fields generated using our design system to a number of important computer graphics applications that require controllable dynamic effects, such as evolving surface appearance, dynamic scene design, steerable crowd movement, and painterly animation. Many of these are difficult or impossible to achieve via prior simulation-based methods. In these applications, the time-varying vector fields have been applied as either orientation fields or advection fields to control the instantaneous appearance or evolving trajectories of the dynamic effects.

  16. AAV Vectorization of DSB-mediated Gene Editing Technologies.

    Science.gov (United States)

    Moser, Rachel J; Hirsch, Matthew L

    2016-01-01

    Recent work both at the bench and the bedside demonstrate zinc-finger nucleases (ZFNs), CRISPR/Cas9, and other programmable site-specific endonuclease technologies are being successfully utilized within and alongside AAV vectors to induce therapeutically relevant levels of directed gene editing within the human chromosome. Studies from past decades acknowledge that AAV vector genomes are enhanced substrates for homology-directed repair in the presence or absence of targeted DNA damage within the host genome. Additionally, AAV vectors are currently the most efficient format for in vivo gene delivery with no vector related complications in >100 clinical trials for diverse diseases. At the same time, advancements in the design of custom-engineered site-specific endonucleases and the utilization of elucidated endonuclease formats have resulted in efficient and facile genetic engineering for basic science and for clinical therapies. AAV vectors and gene editing technologies are an obvious marriage, using AAV for the delivery of repair substrate and/or a gene encoding a designer endonuclease; however, while efficient delivery and enhanced gene targeting by vector genomes are advantageous, other attributes of AAV vectors are less desirable for gene editing technologies. This review summarizes the various roles that AAV vectors play in gene editing technologies and provides insight into its trending applications for the treatment of genetic diseases.

  17. Leishmania attachment in permissive vectors and the role of sand fly midgut proteins in parasite-vector interaction

    OpenAIRE

    Dostálová, Anna

    2012-01-01

    of PhD. thesis named "Leishmania attachment in permissive vectors and the role of sand fly midgut proteins in parasite-vector interaction", Anna Dostálová, 2011 This thesis focuses on the development of protozoan parasites of the genus Leishmania in their insect vectors, sand flies. It sums up results of three projects I was involved in during my PhD studies. Main emphasis was put on permissive sand fly species that support development of various species of Leishmania. Using a novel method of...

  18. Warps, grids and curvature in triple vector bundles

    Science.gov (United States)

    Flari, Magdalini K.; Mackenzie, Kirill

    2018-06-01

    A triple vector bundle is a cube of vector bundle structures which commute in the (strict) categorical sense. A grid in a triple vector bundle is a collection of sections of each bundle structure with certain linearity properties. A grid provides two routes around each face of the triple vector bundle, and six routes from the base manifold to the total manifold; the warps measure the lack of commutativity of these routes. In this paper we first prove that the sum of the warps in a triple vector bundle is zero. The proof we give is intrinsic and, we believe, clearer than the proof using decompositions given earlier by one of us. We apply this result to the triple tangent bundle T^3M of a manifold and deduce (as earlier) the Jacobi identity. We further apply the result to the triple vector bundle T^2A for a vector bundle A using a connection in A to define a grid in T^2A . In this case the curvature emerges from the warp theorem.

  19. 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.

  20. 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...

  1. 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

  2. Polarization coupling of vector Bessel–Gaussian beams

    International Nuclear Information System (INIS)

    Takeuchi, Ryushi; Kozawa, Yuichi; Sato, Shunichi

    2013-01-01

    We report polarization coupling of radial and azimuthal electric field components of a vector light beam as predicted by the fact that the vector Helmholtz equation is expressed as coupled differential equations in cylindrical coordinates. To clearly observe the polarization variation of a beam as it propagates, higher order transverse modes of a vector Bessel–Gaussian beam were generated by a gain distribution modulation technique, which created a narrow ring-shaped gain region in a Nd:YVO 4 crystal. The polarization coupling was confirmed by the observation that the major polarization component of a vector Bessel–Gaussian beam alternates between radial and azimuthal components along with the propagation. (paper)

  3. 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)

  4. 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

  5. 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.)

  6. Proteasome-independent degradation of HIV-1 in naturally non-permissive human placental trophoblast cells

    Directory of Open Access Journals (Sweden)

    Barré-Sinoussi Françoise

    2009-05-01

    Full Text Available Abstract Background The human placenta-derived cell line BeWo has been demonstrated to be restrictive to cell-free HIV-1 infection. BeWo cells are however permissive to infection by VSV-G pseudotyped HIV-1, which enters cells by a receptor-independent mechanism, and to infection by HIV-1 via a cell-to-cell route. Results Here we analysed viral entry in wild type BeWo (CCR5+, CXCR4+ and BeWo-CD4+ (CD4+, CCR5+, CXCR4+ cells. We report that HIV-1 internalisation is not restricted in either cell line. Levels of internalised p24 antigen between VSV-G HIV-1 pseudotypes and R5 or X4 virions were comparable. We next analysed the fate of internalised virions; X4 and R5 HIV-1 virions were less stable over time in BeWo cells than VSV-G HIV-1 pseudotypes. We then investigated the role of the proteasome in restricting cell-free HIV-1 infection in BeWo cells using proteasome inhibitors. We observed an increase in the levels of VSV-G pseudotyped HIV-1 infection in proteasome-inhibitor treated cells, but the infection by R5-Env or X4-Env pseudotyped virions remains restricted. Conclusion Collectively these results suggest that cell-free HIV-1 infection encounters a surface block leading to a non-productive entry route, which either actively targets incoming virions for non-proteasomal degradation, and impedes their release into the cytoplasm, or causes the inactivation of mechanisms essential for viral replication.

  7. Matrix elements of a hyperbolic vector operator under SO(2,1)

    International Nuclear Information System (INIS)

    Zettili, N.; Boukahil, A.

    2003-01-01

    We deal here with the use of Wigner–Eckart type arguments to calculate the matrix elements of a hyperbolic vector operator V-vector by expressing them in terms of reduced matrix elements. In particular, we focus on calculating the matrix elements of this vector operator within the basis of the hyperbolic angular momentum T-vector whose components T-vector 1 , T-vector 2 , T-vector 3 satisfy an SO(2,1) Lie algebra. We show that the commutation rules between the components of V-vector and T-vector can be inferred from the algebra of ordinary angular momentum. We then show that, by analogy to the Wigner–Eckart theorem, we can calculate the matrix elements of V-vector within a representation where T-vector 2 and T-vector 3 are jointly diagonal. (author)

  8. Vector and Raster Data Storage Based on Morton Code

    Science.gov (United States)

    Zhou, G.; Pan, Q.; Yue, T.; Wang, Q.; Sha, H.; Huang, S.; Liu, X.

    2018-05-01

    Even though geomatique is so developed nowadays, the integration of spatial data in vector and raster formats is still a very tricky problem in geographic information system environment. And there is still not a proper way to solve the problem. This article proposes a method to interpret vector data and raster data. In this paper, we saved the image data and building vector data of Guilin University of Technology to Oracle database. Then we use ADO interface to connect database to Visual C++ and convert row and column numbers of raster data and X Y of vector data to Morton code in Visual C++ environment. This method stores vector and raster data to Oracle Database and uses Morton code instead of row and column and X Y to mark the position information of vector and raster data. Using Morton code to mark geographic information enables storage of data make full use of storage space, simultaneous analysis of vector and raster data more efficient and visualization of vector and raster more intuitive. This method is very helpful for some situations that need to analyse or display vector data and raster data at the same time.

  9. Structuring Stokes correlation functions using vector-vortex beam

    Science.gov (United States)

    Kumar, Vijay; Anwar, Ali; Singh, R. P.

    2018-01-01

    Higher order statistical correlations of the optical vector speckle field, formed due to scattering of a vector-vortex beam, are explored. Here, we report on the experimental construction of the Stokes parameters covariance matrix, consisting of all possible spatial Stokes parameters correlation functions. We also propose and experimentally realize a new Stokes correlation functions called Stokes field auto correlation functions. It is observed that the Stokes correlation functions of the vector-vortex beam will be reflected in the respective Stokes correlation functions of the corresponding vector speckle field. The major advantage of proposing Stokes correlation functions is that the Stokes correlation function can be easily tuned by manipulating the polarization of vector-vortex beam used to generate vector speckle field and to get the phase information directly from the intensity measurements. Moreover, this approach leads to a complete experimental Stokes characterization of a broad range of random fields.

  10. 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

  11. 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.

  12. 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.

  13. 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 ...

  14. Design of 2D Time-Varying Vector Fields

    KAUST Repository

    Chen, Guoning

    2012-10-01

    Design of time-varying vector fields, i.e., vector fields that can change over time, has a wide variety of important applications in computer graphics. Existing vector field design techniques do not address time-varying vector fields. In this paper, we present a framework for the design of time-varying vector fields, both for planar domains as well as manifold surfaces. Our system supports the creation and modification of various time-varying vector fields with desired spatial and temporal characteristics through several design metaphors, including streamlines, pathlines, singularity paths, and bifurcations. These design metaphors are integrated into an element-based design to generate the time-varying vector fields via a sequence of basis field summations or spatial constrained optimizations at the sampled times. The key-frame design and field deformation are also introduced to support other user design scenarios. Accordingly, a spatial-temporal constrained optimization and the time-varying transformation are employed to generate the desired fields for these two design scenarios, respectively. We apply the time-varying vector fields generated using our design system to a number of important computer graphics applications that require controllable dynamic effects, such as evolving surface appearance, dynamic scene design, steerable crowd movement, and painterly animation. Many of these are difficult or impossible to achieve via prior simulation-based methods. In these applications, the time-varying vector fields have been applied as either orientation fields or advection fields to control the instantaneous appearance or evolving trajectories of the dynamic effects. © 1995-2012 IEEE.

  15. Design of 2D Time-Varying Vector Fields

    KAUST Repository

    Chen, Guoning; Kwatra, Vivek; Wei, Li-Yi; Hansen, Charles D.; Zhang, Eugene

    2012-01-01

    Design of time-varying vector fields, i.e., vector fields that can change over time, has a wide variety of important applications in computer graphics. Existing vector field design techniques do not address time-varying vector fields. In this paper, we present a framework for the design of time-varying vector fields, both for planar domains as well as manifold surfaces. Our system supports the creation and modification of various time-varying vector fields with desired spatial and temporal characteristics through several design metaphors, including streamlines, pathlines, singularity paths, and bifurcations. These design metaphors are integrated into an element-based design to generate the time-varying vector fields via a sequence of basis field summations or spatial constrained optimizations at the sampled times. The key-frame design and field deformation are also introduced to support other user design scenarios. Accordingly, a spatial-temporal constrained optimization and the time-varying transformation are employed to generate the desired fields for these two design scenarios, respectively. We apply the time-varying vector fields generated using our design system to a number of important computer graphics applications that require controllable dynamic effects, such as evolving surface appearance, dynamic scene design, steerable crowd movement, and painterly animation. Many of these are difficult or impossible to achieve via prior simulation-based methods. In these applications, the time-varying vector fields have been applied as either orientation fields or advection fields to control the instantaneous appearance or evolving trajectories of the dynamic effects. © 1995-2012 IEEE.

  16. Two-host, two-vector basic reproduction ratio (R(0 for bluetongue.

    Directory of Open Access Journals (Sweden)

    Joanne Turner

    Full Text Available Mathematical formulations for the basic reproduction ratio (R(0 exist for several vector-borne diseases. Generally, these are based on models of one-host, one-vector systems or two-host, one-vector systems. For many vector borne diseases, however, two or more vector species often co-occur and, therefore, there is a need for more complex formulations. Here we derive a two-host, two-vector formulation for the R(0 of bluetongue, a vector-borne infection of ruminants that can have serious economic consequences; since 1998 for example, it has led to the deaths of well over 1 million sheep in Europe alone. We illustrate our results by considering the situation in South Africa, where there are two major hosts (sheep, cattle and two vector species with differing ecologies and competencies as vectors, for which good data exist. We investigate the effects on R(0 of differences in vector abundance, vector competence and vector host preference between vector species. Our results indicate that R(0 can be underestimated if we assume that there is only one vector transmitting the infection (when there are in fact two or more and/or vector host preferences are overlooked (unless the preferred host is less beneficial or more abundant. The two-host, one-vector formula provides a good approximation when the level of cross-infection between vector species is very small. As this approaches the level of intraspecies infection, a combination of the two-host, one-vector R(0 for each vector species becomes a better estimate. Otherwise, particularly when the level of cross-infection is high, the two-host, two-vector formula is required for accurate estimation of R(0. Our results are equally relevant to Europe, where at least two vector species, which co-occur in parts of the south, have been implicated in the recent epizootic of bluetongue.

  17. Thresholds and Smooth Transitions in Vector Autoregressive Models

    DEFF Research Database (Denmark)

    Hubrich, Kirstin; Teräsvirta, Timo

    This survey focuses on two families of nonlinear vector time series models, the family of Vector Threshold Regression models and that of Vector Smooth Transition Regression models. These two model classes contain incomplete models in the sense that strongly exogeneous variables are allowed in the...

  18. Examples of in-vivo blood vector velocity estimation

    DEFF Research Database (Denmark)

    Udesen, Jesper; Nielsen, Michael Bachmann; Nielsen, Kristian R.

    2007-01-01

    In this paper examples of in-vivo blood vector velocity images of the carotid artery are presented. The transverse oscillation (TO) method for blood vector velocity estimation has been used to estimate the vector velocities and the method is first evaluated in a circulating flowrig where...

  19. Killing vectors in empty space algebraically special metrics. II

    International Nuclear Information System (INIS)

    Held, A.

    1976-01-01

    Empty space algebraically special metrics possessing an expanding degenerate principal null vector and Killing vectors are investigated. Attention is centered on that class of Killing vector (called nonpreferred) which is necessarily spacelike in the asymptotic region. A detailed analysis of the relationship between the Petrov--Penrose classification and these Killing vectors is carried out

  20. Vectorization of three-dimensional neutron diffusion code CITATION

    International Nuclear Information System (INIS)

    Harada, Hiroo; Ishiguro, Misako

    1985-01-01

    Three-dimensional multi-group neutron diffusion code CITATION has been widely used for reactor criticality calculations. The code is expected to be run at a high speed by using recent vector supercomputers, when it is appropriately vectorized. In this paper, vectorization methods and their effects are described for the CITATION code. Especially, calculation algorithms suited for vectorization of the inner-outer iterative calculations which spend most of the computing time are discussed. The SLOR method, which is used in the original CITATION code, and the SOR method, which is adopted in the revised code, are vectorized by odd-even mesh ordering. The vectorized CITATION code is executed on the FACOM VP-100 and VP-200 computers, and is found to run over six times faster than the original code for a practical-scale problem. The initial value of the relaxation factor and the number of inner-iterations given as input data are also investigated since the computing time depends on these values. (author)

  1. Progresses towards safe and efficient gene therapy vectors.

    Science.gov (United States)

    Chira, Sergiu; Jackson, Carlo S; Oprea, Iulian; Ozturk, Ferhat; Pepper, Michael S; Diaconu, Iulia; Braicu, Cornelia; Raduly, Lajos-Zsolt; Calin, George A; Berindan-Neagoe, Ioana

    2015-10-13

    The emergence of genetic engineering at the beginning of the 1970's opened the era of biomedical technologies, which aims to improve human health using genetic manipulation techniques in a clinical context. Gene therapy represents an innovating and appealing strategy for treatment of human diseases, which utilizes vehicles or vectors for delivering therapeutic genes into the patients' body. However, a few past unsuccessful events that negatively marked the beginning of gene therapy resulted in the need for further studies regarding the design and biology of gene therapy vectors, so that this innovating treatment approach can successfully move from bench to bedside. In this paper, we review the major gene delivery vectors and recent improvements made in their design meant to overcome the issues that commonly arise with the use of gene therapy vectors. At the end of the manuscript, we summarized the main advantages and disadvantages of common gene therapy vectors and we discuss possible future directions for potential therapeutic vectors.

  2. Application of Bred Vectors To Data Assimilation

    Science.gov (United States)

    Corazza, M.; Kalnay, E.; Patil, Dj

    We introduced a statistic, the BV-dimension, to measure the effective local finite-time dimensionality of the atmosphere. We show that this dimension is often quite low, and suggest that this finding has important implications for data assimilation and the accuracy of weather forecasting (Patil et al, 2001). The original database for this study was the forecasts of the NCEP global ensemble forecasting system. The initial differences between the control forecast and the per- turbed forecasts are called bred vectors. The control and perturbed initial conditions valid at time t=n(t are evolved using the forecast model until time t=(n+1) (t. The differences between the perturbed and the control forecasts are scaled down to their initial amplitude, and constitute the bred vectors valid at (n+1) (t. Their growth rate is typically about 1.5/day. The bred vectors are similar by construction to leading Lya- punov vectors except that they have small but finite amplitude, and they are valid at finite times. The original NCEP ensemble data set has 5 independent bred vectors. We define a local bred vector at each grid point by choosing the 5 by 5 grid points centered at the grid point (a region of about 1100km by 1100km), and using the north-south and east- west velocity components at 500mb pressure level to form a 50 dimensional column vector. Since we have k=5 global bred vectors, we also have k local bred vectors at each grid point. We estimate the effective dimensionality of the subspace spanned by the local bred vectors by performing a singular value decomposition (EOF analysis). The k local bred vector columns form a 50xk matrix M. The singular values s(i) of M measure the extent to which the k column unit vectors making up the matrix M point in the direction of v(i). We define the bred vector dimension as BVDIM={Sum[s(i)]}^2/{Sum[s(i)]^2} For example, if 4 out of the 5 vectors lie along v, and one lies along v, the BV- dimension would be BVDIM[sqrt(4), 1, 0

  3. Adeno-associated Virus Serotype 9 - Driven Expression of BAG3 Improves Left Ventricular Function in Murine Hearts with Left Ventricular Dysfunction Secondary to a Myocardial Infarction.

    Science.gov (United States)

    Knezevic, Tijana; Myers, Valerie D; Su, Feifei; Wang, JuFang; Song, Jianliang; Zhang, Xue-Qian; Gao, Erhe; Gao, Guofeng; Muniswamy, Madesh; Gupta, Manish K; Gordon, Jennifer; Weiner, Kristen N; Rabinowitz, Joseph; Ramsey, Frederick V; Tilley, Douglas G; Khalili, Kamel; Cheung, Joseph Y; Feldman, Arthur M

    2016-12-01

    The present study was undertaken to test the hypothesis that gene delivery of BCL2-Associated Athanogene 3 (BAG3) to the heart of mice with left ventricular dysfunction secondary to a myocardial infarction could enhance cardiac performance. BAG3 is a 575 amino acid protein that has pleotropic functions in the cell including pro-autophagy and anti-apoptosis. Mutations in BAG3 have been associated with both skeletal muscle dysfunction and familial dilated cardiomyopathy and BAG3 levels are diminished in non-familial heart failure. Eight-week-old C57/BL6 mice underwent ligation of the left coronary artery (MI) or sham surgery (Sham). Eight weeks later, mice in both groups were randomly assigned to receive either a retro-orbital injection of rAAV9-BAG3 (MI-BAG3 or Sham-BAG3) or rAAV9-GFP (MI-GFP or Sham GFP). Mice were sacrificed at 3 weeks post-injection and myocytes were isolated from the left ventricle. MI-BAG3 mice demonstrated a significantly (p BAG3 injection with further improvement in LVEF, fractional shortening and stroke volume at 3 weeks post-injection without changes in LV mass or LV volume. Injection of rAAV9-BAG3 had no effect on LVEF in Sham mice. The salutary benefits of rAAV9-BAG3 were also observed in myocytes isolated from MI hearts including improved cell shortening (pBAG3 gene therapy may provide a novel therapeutic option for the treatment of heart failure.

  4. Adeno-associated Virus Serotype 9 – Driven Expression of BAG3 Improves Left Ventricular Function in Murine Hearts with Left Ventricular Dysfunction Secondary to a Myocardial Infarction

    Science.gov (United States)

    Knezevic, Tijana; Myers, Valerie D.; Su, Feifei; Wang, JuFang; Song, Jianliang; Zhang, Xue-Qian; Gao, Erhe; Gao, Guofeng; Muniswamy, Madesh; Gupta, Manish K.; Gordon, Jennifer; Weiner, Kristen N.; Rabinowitz, Joseph; Ramsey, Frederick V.; Tilley, Douglas G.; Khalili, Kamel; Cheung, Joseph Y.; Feldman, Arthur M.

    2016-01-01

    Objectives The present study was undertaken to test the hypothesis that gene delivery of BCL2-Associated Athanogene 3 (BAG3) to the heart of mice with left ventricular dysfunction secondary to a myocardial infarction could enhance cardiac performance. Background BAG3 is a 575 amino acid protein that has pleotropic functions in the cell including pro-autophagy and anti-apoptosis. Mutations in BAG3 have been associated with both skeletal muscle dysfunction and familial dilated cardiomyopathy and BAG3 levels are diminished in non-familial heart failure. Methods Eight-week-old C57/BL6 mice underwent ligation of the left coronary artery (MI) or sham surgery (Sham). Eight weeks later, mice in both groups were randomly assigned to receive either a retro-orbital injection of rAAV9-BAG3 (MI-BAG3 or Sham-BAG3) or rAAV9-GFP (MI-GFP or Sham GFP). Mice were sacrificed at 3 weeks post-injection and myocytes were isolated from the left ventricle. Results MI-BAG3 mice demonstrated a significantly (p BAG3 injection with further improvement in LVEF, fractional shortening and stroke volume at 3 weeks post-injection without changes in LV mass or LV volume. Injection of rAAV9-BAG3 had no effect on LVEF in Sham mice. The salutary benefits of rAAV9-BAG3 were also observed in myocytes isolated from MI hearts including improved cell shortening (pBAG3 gene therapy may provide a novel therapeutic option for the treatment of heart failure. PMID:28164169

  5. Vectorization of nuclear codes 90-1

    International Nuclear Information System (INIS)

    Nonomiya, Iwao; Nemoto, Toshiyuki; Ishiguro, Misako; Harada, Hiroo; Hori, Takeo.

    1990-09-01

    The vectorization has been made for four codes: SONATINA-2V HTTR version, TRIDOSE, VIENUS, and SCRYU. SONATINA-2V HTTR version is a code for analyzing the dynamic behavior of fuel blocks in the vertical slice of the HTGR (High Temperature Gas-cooled Reactor) core under seismic perturbation, TRIDOSE is a code for calculating environmental tritium concentration and dose, VIENUS is a code for analyzing visco elastic stress of the fuel block of HTTR (High Temperature gas-cooled Test Reactor), and SCRYU is a thermal-hydraulics code with boundary fitted coordinate system. The total speedup ratio of the vectorized versions to the original scalar ones is 5.2 for SONATINA-2V HTTR version. 5.9 ∼ 6.9 for TRIDOSE, 6.7 for VIENUS, 7.6 for SCRYU, respectively. In this report, we describe outline of codes, techniques used for the vectorization, verification of computed results, and speedup effect on the vectorized codes. (author)

  6. Determination of the ratio of axial-vector-to-vector weak coupling constants for beta decay of triton

    CERN Document Server

    Akulov, Y A

    2002-01-01

    Data on the chemical shifts of half-lives for atomic and molecular tritium were used to determine the ratio of axial-vector-to-vector weak coupling constants for beta decay of triton (G sub A /G sub V) sub t = -1.2646 +- 0.0035

  7. Projected economic losses due to vector and vector-borne parasitic diseases in livestock of India and its significance in implementing the concept of integrated practices for vector management

    Directory of Open Access Journals (Sweden)

    B. W. Narladkar

    2018-02-01

    Full Text Available Broadly, species of arthropods infesting livestock are grouped into flies (biting and non-biting, fleas, lice (biting and sucking, ticks (soft and hard, and mites (burrowing, non-burrowing, and follicular. Among which, biting and non-biting flies and ticks are the potent vectors for many bacterial, viral, rickettsial, and protozoan diseases. Vectors of livestock are having economic significance on three points (1 direct losses from their bite and annoyance, worries, and psychological disturbances produced during the act of biting and feeding, (2 diseases they transmit, and (3 expenditure incurred for their control. Flies such as Culicoides spp. and Musca spp. and various species of hard ticks play important role in disease transmission in addition to their direct effects. For control of vectors, recent concept of integrated pest management (IPM provides the best solution and also addresses the problems related to acaricide resistance and environmental protection from hazardous chemicals. However, to successfully implement the concept of IPM, for each vector species, estimation of two monitory benchmarks, i.e., economic injury level (EIL and economic threshold level (ETL is essential prerequisite. For many vector species and under several circumstances, estimation of EIL and ETL appears to be difficult. Under such scenario, although may not be exact, an approximate estimate can be accrued by taking into account several criteria such as percent prevalence of vectors in a geographical area, percent losses produced, total livestock population, and current prices of livestock products such as milk, meat, and wool. Method for approximate estimation is first time described and elaborated in the present review article.

  8. Projected economic losses due to vector and vector-borne parasitic diseases in livestock of India and its significance in implementing the concept of integrated practices for vector management

    Science.gov (United States)

    Narladkar, B. W.

    2018-01-01

    Broadly, species of arthropods infesting livestock are grouped into flies (biting and non-biting), fleas, lice (biting and sucking), ticks (soft and hard), and mites (burrowing, non-burrowing, and follicular). Among which, biting and non-biting flies and ticks are the potent vectors for many bacterial, viral, rickettsial, and protozoan diseases. Vectors of livestock are having economic significance on three points (1) direct losses from their bite and annoyance, worries, and psychological disturbances produced during the act of biting and feeding, (2) diseases they transmit, and (3) expenditure incurred for their control. Flies such as Culicoides spp. and Musca spp. and various species of hard ticks play important role in disease transmission in addition to their direct effects. For control of vectors, recent concept of integrated pest management (IPM) provides the best solution and also addresses the problems related to acaricide resistance and environmental protection from hazardous chemicals. However, to successfully implement the concept of IPM, for each vector species, estimation of two monitory benchmarks, i.e., economic injury level (EIL) and economic threshold level (ETL) is essential prerequisite. For many vector species and under several circumstances, estimation of EIL and ETL appears to be difficult. Under such scenario, although may not be exact, an approximate estimate can be accrued by taking into account several criteria such as percent prevalence of vectors in a geographical area, percent losses produced, total livestock population, and current prices of livestock products such as milk, meat, and wool. Method for approximate estimation is first time described and elaborated in the present review article. PMID:29657396

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

    Science.gov (United States)

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

    2015-02-01

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

  10. Modified montmorillonite as vector for gene delivery.

    Science.gov (United States)

    Lin, Feng-Huei; Chen, Chia-Hao; Cheng, Winston T K; Kuo, Tzang-Fu

    2006-06-01

    Currently, gene delivery systems can be divided into two parts: viral or non-viral vectors. In general, viral vectors have a higher efficiency on gene delivery. However, they may sometimes provoke mutagenesis and carcinogenesis once re-activating in human body. Lots of non-viral vectors have been developed that tried to solve the problems happened on viral vectors. Unfortunately, most of non-viral vectors showed relatively lower transfection rate. The aim of this study is to develop a non-viral vector for gene delivery system. Montmorillonite (MMT) is one of clay minerals that consist of hydrated aluminum with Si-O tetrahedrons on the bottom of the layer and Al-O(OH)2 octahedrons on the top. The inter-layer space is about 12 A. The room is not enough to accommodate DNA for gene delivery. In the study, the cationic hexadecyltrimethylammonium (HDTMA) will be intercalated into the interlayer of MMT as a layer expander to expand the layer space for DNA accommodation. The optimal condition for the preparation of DNA-HDTMA-MMT is as follows: 1 mg of 1.5CEC HDTMA-MMT was prepared under pH value of 10.7 and with soaking time for 2 h. The DNA molecules can be protected from nuclease degradation, which can be proven by the electrophoresis analysis. DNA was successfully transfected into the nucleus of human dermal fibroblast and expressed enhanced green fluorescent protein (EGFP) gene with green fluorescence emission. The HDTMA-MMT has a great potential as a vector for gene delivery in the future.

  11. Energy-exchange collisions of dark-bright-bright vector solitons.

    Science.gov (United States)

    Radhakrishnan, R; Manikandan, N; Aravinthan, K

    2015-12-01

    We find a dark component guiding the practically interesting bright-bright vector one-soliton to two different parametric domains giving rise to different physical situations by constructing a more general form of three-component dark-bright-bright mixed vector one-soliton solution of the generalized Manakov model with nine free real parameters. Moreover our main investigation of the collision dynamics of such mixed vector solitons by constructing the multisoliton solution of the generalized Manakov model with the help of Hirota technique reveals that the dark-bright-bright vector two-soliton supports energy-exchange collision dynamics. In particular the dark component preserves its initial form and the energy-exchange collision property of the bright-bright vector two-soliton solution of the Manakov model during collision. In addition the interactions between bound state dark-bright-bright vector solitons reveal oscillations in their amplitudes. A similar kind of breathing effect was also experimentally observed in the Bose-Einstein condensates. Some possible ways are theoretically suggested not only to control this breathing effect but also to manage the beating, bouncing, jumping, and attraction effects in the collision dynamics of dark-bright-bright vector solitons. The role of multiple free parameters in our solution is examined to define polarization vector, envelope speed, envelope width, envelope amplitude, grayness, and complex modulation of our solution. It is interesting to note that the polarization vector of our mixed vector one-soliton evolves in sphere or hyperboloid depending upon the initial parametric choices.

  12. Vectorization, parallelization and porting of nuclear codes on the VPP500 system (vectorization). Progress report fiscal 1997

    International Nuclear Information System (INIS)

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

    1999-05-01

    Several computer codes in the nuclear field have been vectorized, parallelized and transported on the FUJITSU VPP500 system and/or the AP3000 system at Center for Promotion of Computational Science and Engineering in Japan Atomic Energy Research Institute. We dealt with 14 codes in fiscal 1997. 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 multidimensional two-fluid model code ACE-3D for evaluation of constitutive equations, statistical decay code SD and three-dimensional thermal analysis code for in-core test section (T2) of HENDEL SSPHEAT are described. In the parallelization part, the parallelization of cylindrical direct numerical simulation code CYLDNS44N, worldwide version of system for prediction of environmental emergency dose information code WSPEEDI, extension of quantum molecular dynamics code EQMD and three-dimensional non-steady compressible fluid dynamics code STREAM are described. In the porting part, the porting of transient reactor analysis code TRAC-BF1 and Monte Carlo radiation transport code MCNP4A on the AP3000 are described. In addition, a modification of program libraries for command-driven interactive data analysis plotting program IPLOT is described. (author)

  13. 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)

  14. 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

  15. ON THE ISSUE OF VECTOR CONTROL OF THE ASYNCHRONOUS MOTORS

    Directory of Open Access Journals (Sweden)

    B. I. Firago

    2015-01-01

    Full Text Available The paper considers the issue of one of the widespread types of vector control realization for the asynchronous motors with a short-circuited rotor. Of all more than 20 vector control types known presently, the following are applied most frequently: direct vector control with velocity pickup (VP, direct vector control without VP, indirect vector control with VP and indirect vector control without VP. Despite the fact that the asynchronous-motor indirect vector control without VP is the easiest and most spread, the absence of VP does not allow controlling the motor electromagnetic torque at zero velocity. This is the reason why for electric motor drives of such requirements they utilize the vector control with a velocity transducer. The systems of widest dissemination became the direct and indirect vector control systems with X-axis alignment of the synchronously rotating x–y-coordinate frame along the rotor flux-linkage vector inasmuch as this provides the simplest correlations for controlling variables. Although these two types of vector control are well presented in literature, a number of issues concerning their realization and practical application require further elaboration. These include: the block schemes adequate representation as consisted with the modern realization of vector control and clarification of the analytical expressions for evaluating the regulator parameters.The authors present a technique for evaluating the dynamics of an asynchronous electric motor drive with direct vector control and x-axis alignment along the vector of rotor flux linkage. The article offers a generalized structure of this vector control type with detailed description of its principal blocks: controlling system, frequency converter, and the asynchronous motor.The paper presents a direct vector control simulating model developed in the MatLab environment on the grounds of this structure. The authors illustrate the described technique with the results

  16. 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...

  17. 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...

  18. Vector-Interaction-Enhanced Bag Model

    Science.gov (United States)

    Cierniak, Mateusz; Klähn, Thomas; Fischer, Tobias; Bastian, Niels-Uwe

    2018-02-01

    A commonly applied quark matter model in astrophysics is the thermodynamic bag model (tdBAG). The original MIT bag model approximates the effect of quark confinement, but does not explicitly account for the breaking of chiral symmetry, an important property of Quantum Chromodynamics (QCD). It further ignores vector repulsion. The vector-interaction-enhanced bag model (vBag) improves the tdBAG approach by accounting for both dynamical chiral symmetry breaking and repulsive vector interactions. The latter is of particular importance to studies of dense matter in beta-equilibriumto explain the two solar mass maximum mass constraint for neutron stars. The model is motivated by analyses of QCD based Dyson-Schwinger equations (DSE), assuming a simple quark-quark contact interaction. Here, we focus on the study of hybrid neutron star properties resulting from the application of vBag and will discuss possible extensions.

  19. 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)

  20. 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…

  1. 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...

  2. A design of a computer complex including vector processors

    International Nuclear Information System (INIS)

    Asai, Kiyoshi

    1982-12-01

    We, members of the Computing Center, Japan Atomic Energy Research Institute have been engaged for these six years in the research of adaptability of vector processing to large-scale nuclear codes. The research has been done in collaboration with researchers and engineers of JAERI and a computer manufacturer. In this research, forty large-scale nuclear codes were investigated from the viewpoint of vectorization. Among them, twenty-six codes were actually vectorized and executed. As the results of the investigation, it is now estimated that about seventy percents of nuclear codes and seventy percents of our total amount of CPU time of JAERI are highly vectorizable. Based on the data obtained by the investigation, (1)currently vectorizable CPU time, (2)necessary number of vector processors, (3)necessary manpower for vectorization of nuclear codes, (4)computing speed, memory size, number of parallel 1/0 paths, size and speed of 1/0 buffer of vector processor suitable for our applications, (5)necessary software and operational policy for use of vector processors are discussed, and finally (6)a computer complex including vector processors is presented in this report. (author)

  3. Bearing estimation with acoustic vector-sensor arrays

    International Nuclear Information System (INIS)

    Hawkes, M.; Nehorai, A.

    1996-01-01

    We consider direction-of-arrival (DOA) estimation using arrays of acoustic vector sensors in free space, and derive expressions for the Cramacute er-Rao bound on the DOA parameters when there is a single source. The vector-sensor array is seen to have improved performance over the traditional scalar-sensor (pressure-sensor) array for two distinct reasons: its elements have an inherent directional sensitivity and the array makes a greater number of measurements. The improvement is greatest for small array apertures and low signal-to-noise ratios. Examination of the conventional beamforming and Capon DOA estimators shows that vector-sensor arrays can completely resolve the bearing, even with a linear array, and can remove the ambiguities associated with spatial undersampling. We also propose and analyze a diversely-oriented array of velocity sensors that possesses some of the advantages of the vector-sensor array without the increase in hardware and computation. In addition, in certain scenarios it can avoid problems with spatially correlated noise that the vector-sensor array may suffer. copyright 1996 American Institute of Physics

  4. Vectoring of parallel synthetic jets: A parametric study

    Science.gov (United States)

    Berk, Tim; Gomit, Guillaume; Ganapathisubramani, Bharathram

    2016-11-01

    The vectoring of a pair of parallel synthetic jets can be described using five dimensionless parameters: the aspect ratio of the slots, the Strouhal number, the Reynolds number, the phase difference between the jets and the spacing between the slots. In the present study, the influence of the latter four on the vectoring behaviour of the jets is examined experimentally using particle image velocimetry. Time-averaged velocity maps are used to study the variations in vectoring behaviour for a parametric sweep of each of the four parameters independently. A topological map is constructed for the full four-dimensional parameter space. The vectoring behaviour is described both qualitatively and quantitatively. A vectoring mechanism is proposed, based on measured vortex positions. We acknowledge the financial support from the European Research Council (ERC Grant Agreement No. 277472).

  5. Line Width Recovery after Vectorization of Engineering Drawings

    Directory of Open Access Journals (Sweden)

    Gramblička Matúš

    2016-12-01

    Full Text Available Vectorization is the conversion process of a raster image representation into a vector representation. The contemporary commercial vectorization software applications do not provide sufficiently high quality outputs for such images as do mechanical engineering drawings. Line width preservation is one of the problems. There are applications which need to know the line width after vectorization because this line attribute carries the important semantic information for the next 3D model generation. This article describes the algorithm that is able to recover line width of individual lines in the vectorized engineering drawings. Two approaches are proposed, one examines the line width at three points, whereas the second uses a variable number of points depending on the line length. The algorithm is tested on real mechanical engineering drawings.

  6. Vector-transmitted disease vaccines: targeting salivary proteins in transmission (SPIT).

    Science.gov (United States)

    McDowell, Mary Ann

    2015-08-01

    More than half the population of the world is at risk for morbidity and mortality from vector-transmitted diseases, and emerging vector-transmitted infections are threatening new populations. Rising insecticide resistance and lack of efficacious vaccines highlight the need for novel control measures. One such approach is targeting the vector-host interface by incorporating vector salivary proteins in anti-pathogen vaccines. Debate remains about whether vector saliva exposure exacerbates or protects against more severe clinical manifestations, induces immunity through natural exposure or extends to all vector species and associated pathogens. Nevertheless, exploiting this unique biology holds promise as a viable strategy for the development of vaccines against vector-transmitted diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. RNA Interference in Insect Vectors for Plant Viruses

    Directory of Open Access Journals (Sweden)

    Surapathrudu Kanakala

    2016-12-01

    Full Text Available Insects and other arthropods are the most important vectors of plant pathogens. The majority of plant pathogens are disseminated by arthropod vectors such as aphids, beetles, leafhoppers, planthoppers, thrips and whiteflies. Transmission of plant pathogens and the challenges in managing insect vectors due to insecticide resistance are factors that contribute to major food losses in agriculture. RNA interference (RNAi was recently suggested as a promising strategy for controlling insect pests, including those that serve as important vectors for plant pathogens. The last decade has witnessed a dramatic increase in the functional analysis of insect genes, especially those whose silencing results in mortality or interference with pathogen transmission. The identification of such candidates poses a major challenge for increasing the role of RNAi in pest control. Another challenge is to understand the RNAi machinery in insect cells and whether components that were identified in other organisms are also present in insect. This review will focus on summarizing success cases in which RNAi was used for silencing genes in insect vector for plant pathogens, and will be particularly helpful for vector biologists.

  8. Current vector control challenges in the fight against malaria.

    Science.gov (United States)

    Benelli, Giovanni; Beier, John C

    2017-10-01

    The effective and eco-friendly control of Anopheles vectors plays a key role in any malaria management program. Integrated Vector Management (IVM) suggests making use of the full range of vector control tools available. The strategies for IVM require novel technologies to control outdoor transmission of malaria. Despite the wide number of promising control tools tested against mosquitoes, current strategies for malaria vector control used in most African countries are not sufficient to achieve successful malaria control. The majority of National Malaria Control Programs in Africa still rely on indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs). These methods reduce malaria incidence but generally have little impact on malaria prevalence. In addition to outdoor transmission, growing levels of insecticide resistance in targeted vectors threaten the efficacy of LLINs and IRS. Larvicidal treatments can be useful, but are not recommended for rural areas. The research needed to improve the quality and delivery of mosquito vector control should focus on (i) optimization of processes and methods for vector control delivery; (ii) monitoring of vector populations and biting activity with reliable techniques; (iii) the development of effective and eco-friendly tools to reduce the burden or locally eliminate malaria and other mosquito-borne diseases; (iv) the careful evaluation of field suitability and efficacy of new mosquito control tools to prove their epidemiological impact; (v) the continuous monitoring of environmental changes which potentially affect malaria vector populations; (vi) the cooperation among different disciplines, with main emphasis on parasitology, tropical medicine, ecology, entomology, and ecotoxicology. A better understanding of behavioral ecology of malaria vectors is required. Key ecological obstacles that limit the effectiveness of vector control include the variation in mosquito behavior, development of insecticide resistance

  9. Vector pulsing soliton of self-induced transparency in waveguide

    International Nuclear Information System (INIS)

    Adamashvili, G.T.

    2015-01-01

    A theory of an optical resonance vector pulsing soliton in waveguide is developed. A thin transition layer containing semiconductor quantum dots forms the boundary between the waveguide and one of the connected media. Analytical and numerical solutions for the optical vector pulsing soliton in waveguide are obtained. The vector pulsing soliton in the presence of excitonic and bi-excitonic excitations is compared with the soliton for waveguide TM-modes with parameters that can be used in modern optical experiments. It is shown that these nonlinear waves have significantly different parameters and shapes. - Highlights: • An optical vector pulsing soliton in a planar waveguide is presented. • Explicit form of the optical vector pulsing soliton are obtained. • The vector pulsing soliton and the soliton have different parameters and profiles

  10. 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

  11. 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.

  12. Characterizing Compromise Stability of Games Using Larginal Vectors

    NARCIS (Netherlands)

    Platz, T.T.; Hamers, H.J.M.; Quant, M.

    2011-01-01

    The core cover of a TU-game is a superset of the core and equals the convex hull of its larginal vectors. A larginal vector corresponds to an order of the players and describes the efficient payoff vector giving the first players in the order their utopia demand as long as it is still possible to

  13. Measurements of the n vector p vector total cross section differences for pure helicity states at 1.20, 2.50 and 3.66 GeV

    International Nuclear Information System (INIS)

    Sharov, V.I.; Zaporozhets, S.A.; Ad''yasevich, B.P.

    1996-01-01

    The quantity Δσ L (n vector p vector), the difference of n vector p vector total cross sections for antiparallel and parallel longitudinal (L) spin states, has been measured for the first time in an energy region of several GeV using a free polarized neutron beam and a polarized proton target. The new data are discussed together with existing results and modern theoretical predictions. This is the first of a planned series of measurements of Δσ L,T (n vector p vector) in this new energy region. 28 refs., 3 figs

  14. Viruses vector control proposal: genus Aedes emphasis

    Directory of Open Access Journals (Sweden)

    Nelson Nogueira Reis

    2017-07-01

    Full Text Available The dengue fever is a major public health problem in the world. In Brazil, in 2015, there were 1,534,932 cases, being 20,320 cases of severe form, and 811 deaths related to this disease. The distribution of Aedes aegypti, the vector, is extensive. Recently, Zika and Chikungunya viruses had arisen, sharing the same vector as dengue and became a huge public health issue. Without specific treatment, it is urgently required as an effective vector control. This article is focused on reviewing vector control strategies, their effectiveness, viability and economical impact. Among all, the Sterile Insect Technique is highlighted as the best option to be adopted in Brazil, once it is largely effectively used in the USA and Mexico for plagues related to agribusiness.

  15. 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.

  16. Tumour necrosis factor-α stimulates HIV-1 replication in single-cycle infection of human term placental villi fragments in a time, viral dose and envelope dependent manner

    Directory of Open Access Journals (Sweden)

    Barré-Sinoussi Françoise

    2006-06-01

    Full Text Available Abstract Background The placenta plays an important role in the control of in utero HIV-1 mother-to-child transmission (MTCT. Proinflammatory cytokines in the placental environment are particularly implicated in this control. We thus investigated the effect of TNF-α on HIV-1 expression in human placental tissues in vitro. Results Human placental chorionic villi fragments were infected with varying doses of luciferase reporter HIV-1 pseudotypes with the R5, X4-Env or the vesicular stomatitis virus protein G (VSV-G. Histocultures were then performed in the presence or absence of recombinant human TNF-α. Luciferase activity was measured at different time points in cell lysates or on whole fragments using ex vivo imaging systems. A significant increase in viral expression was detected in placental fragments infected with 0.2 ng of p24 antigen/fragment (P = 0.002 of VSV-G pseudotyped HIV-1 in the presence of TNF-α seen after 120 hours of culture. A time independent significant increase of viral expression by TNF-α was observed with higher doses of VSV-G pseudotyped HIV-1. When placental fragments were infected with R5-Env pseudotyped HIV-1, a low level of HIV expression at 168 hours of culture was detected for 3 of the 5 placentas tested, with no statistically significant enhancement by TNF-α. Infection with X4-Env pseudotyped HIV-1 did not lead to any detectable luciferase activity at any time point in the absence or in the presence of TNF-α. Conclusion TNF-α in the placental environment increases HIV-1 expression and could facilitate MTCT of HIV-1, particularly in an inflammatory context.

  17. Search for vector-like quarks

    CERN Document Server

    Varnes, Erich; The ATLAS collaboration

    2017-01-01

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

  18. Zoonotic aspects of vector-borne infections.

    Science.gov (United States)

    Failloux, A-B; Moutailler, S

    2015-04-01

    Vector-borne diseases are principally zoonotic diseases transmitted to humans by animals. Pathogens such as bacteria, parasites and viruses are primarily maintained within an enzootic cycle between populations of non-human primates or other mammals and largely non-anthropophilic vectors. This 'wild' cycle sometimes spills over in the form of occasional infections of humans and domestic animals. Lifestyle changes, incursions by humans into natural habitats and changes in agropastoral practices create opportunities that make the borders between wildlife and humans more permeable. Some vector-borne diseases have dispensed with the need for amplification in wild or domestic animals and they can now be directly transmitted to humans. This applies to some viruses (dengue and chikungunya) that have caused major epidemics. Bacteria of the genus Bartonella have reduced their transmission cycle to the minimum, with humans acting as reservoir, amplifier and disseminator. The design of control strategies for vector-borne diseases should be guided by research into emergence mechanisms in order to understand how a wild cycle can produce a pathogen that goes on to cause devastating urban epidemics.

  19. Attenuation of Replication-Competent Adenovirus Serotype 26 Vaccines by Vectorization.

    Science.gov (United States)

    Maxfield, Lori F; Abbink, Peter; Stephenson, Kathryn E; Borducchi, Erica N; Ng'ang'a, David; Kirilova, Marinela M; Paulino, Noelix; Boyd, Michael; Shabram, Paul; Ruan, Qian; Patel, Mayank; Barouch, Dan H

    2015-11-01

    Replication-competent adenovirus (rcAd)-based vaccine vectors may theoretically provide immunological advantages over replication-incompetent Ad vectors, but they also raise additional potential clinical and regulatory issues. We produced replication-competent Ad serotype 26 (rcAd26) vectors by adding the E1 region back into a replication-incompetent Ad26 vector backbone with the E3 or E3/E4 regions deleted. We assessed the effect of vectorization on the replicative capacity of the rcAd26 vaccines. Attenuation occurred in a stepwise fashion, with E3 deletion, E4 deletion, and human immunodeficiency virus type 1 (HIV-1) envelope (Env) gene insertion all contributing to reduced replicative capacity compared to that with the wild-type Ad26 vector. The rcAd26 vector with E3 and E4 deleted and containing the Env transgene exhibited 2.7- to 4.4-log-lower replicative capacity than that of the wild-type Ad26 in vitro. This rcAd26 vector is currently being evaluated in a phase 1 clinical trial. Attenuation as a result of vectorization and transgene insertion has implications for the clinical development of replication-competent vaccine vectors. Copyright © 2015, Maxfield et al.

  20. Interactions between parasites and insects vectors

    Directory of Open Access Journals (Sweden)

    Hilary Hurd

    1994-01-01

    Full Text Available This review stresses the importance of studies that will provide a basic understanding of the pathology of parasite-infected vector insects. This knowledge should be a vital component of the very focussed initiatives currently being funded in the areas of vector control. Vector fecundity reduction is discussed as an example of such pathology. Underlying mechanisms are being investigated in a model system, Hymenolepis diminuta-infected Tenebrio molitor and in Onchocerca-infected blackflies and Plasmodium-infected Anopheles stephensi. In all cases, host vitellogenesis is disrupted by the parasite and, in the tapeworm/beetle model, interaction between the parasite and the endocrine control of the insect's reproductive physiology has been demonstrated.

  1. The optical analogy for vector fields

    Science.gov (United States)

    Parker, E. N. (Editor)

    1991-01-01

    This paper develops the optical analogy for a general vector field. The optical analogy allows the examination of certain aspects of a vector field that are not otherwise readily accessible. In particular, in the cases of a stationary Eulerian flow v of an ideal fluid and a magnetostatic field B, the vectors v and B have surface loci in common with their curls. The intrinsic discontinuities around local maxima in absolute values of v and B take the form of vortex sheets and current sheets, respectively, the former playing a fundamental role in the development of hydrodyamic turbulence and the latter playing a major role in heating the X-ray coronas of stars and galaxies.

  2. 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.

  3. Method of dynamic fuzzy symptom vector in intelligent diagnosis

    International Nuclear Information System (INIS)

    Sun Hongyan; Jiang Xuefeng

    2010-01-01

    Aiming at the requirement of diagnostic symptom real-time updating brought from diagnostic knowledge accumulation and great gap in unit and value of diagnostic symptom in multi parameters intelligent diagnosis, the method of dynamic fuzzy symptom vector is proposed. The concept of dynamic fuzzy symptom vector is defined. Ontology is used to specify the vector elements, and the vector transmission method based on ontology is built. The changing law of symptom value is analyzed and fuzzy normalization method based on fuzzy membership functions is built. An instance proved method of dynamic fussy symptom vector is efficient to solve the problems of symptom updating and unify of symptom value and unit. (authors)

  4. Logarithmic bred vectors in spatiotemporal chaos: structure and growth.

    Science.gov (United States)

    Hallerberg, Sarah; Pazó, Diego; López, Juan M; Rodríguez, Miguel A

    2010-06-01

    Bred vectors are a type of finite perturbation used in prediction studies of atmospheric models that exhibit spatially extended chaos. We study the structure, spatial correlations, and the growth rates of logarithmic bred vectors (which are constructed by using a given norm). We find that, after a suitable transformation, logarithmic bred vectors are roughly piecewise copies of the leading Lyapunov vector. This fact allows us to deduce a scaling law for the bred vector growth rate as a function of its amplitude. In addition, we relate growth rates with the spectrum of Lyapunov exponents corresponding to the most expanding directions. We illustrate our results with simulations of the Lorenz 1996 model.

  5. Topics in the generalized vector dominance model

    International Nuclear Information System (INIS)

    Chavin, S.

    1976-01-01

    Two topics are covered in the generalized vector dominance model. In the first topic a model is constructed for dilepton production in hadron-hadron interactions based on the idea of generalized vector-dominance. It is argued that in the high mass region the generalized vector-dominance model and the Drell-Yan parton model are alternative descriptions of the same underlying physics. In the low mass regions the models differ; the vector-dominance approach predicts a greater production of dileptons. It is found that the high mass vector mesons which are the hallmark of the generalized vector-dominance model make little contribution to the large yield of leptons observed in the transverse-momentum range 1 less than p/sub perpendicular/ less than 6 GeV. The recently measured hadronic parameters lead one to believe that detailed fits to the data are possible under the model. The possibility was expected, and illustrated with a simple model the extreme sensitivity of the large-p/sub perpendicular/ lepton yield to the large-transverse-momentum tail of vector-meson production. The second topic is an attempt to explain the mysterious phenomenon of photon shadowing in nuclei utilizing the contribution of the longitudinally polarized photon. It is argued that if the scalar photon anti-shadows, it could compensate for the transverse photon, which is presumed to shadow. It is found in a very simple model that the scalar photon could indeed anti-shadow. The principal feature of the model is a cancellation of amplitudes. The scheme is consistent with scalar photon-nucleon data as well. The idea is tested with two simple GVDM models and finds that the anti-shadowing contribution of the scalar photon is not sufficient to compensate for the contribution of the transverse photon. It is found doubtful that the scalar photon makes a significant contribution to the total photon-nuclear cross section

  6. Observability of B0 - B vector0 mixing in the e+e- → BB vector X reaction at √s approx. = 15 - 30 GeV

    International Nuclear Information System (INIS)

    Fridman, A.; Schwarz, A.

    1985-01-01

    The possibility of observing mixing in the B 0 B vector B 0 system has been rather widely discussed. In particular theoretical estimates have been made for the case of B 0 B vector 0 production in the e + e - → upsilon (4S) → B 0 B vector 0 reaction. Mixing in this specific channel is expected to appear as a small effect and might thus be hardly measurable. Here the authors will therefore consider the e + e - → BB vector X reaction (X meaning anything well above the BB vector threshold where any combination of BB vector mesons (B/sub u/B vector/sub u/, B/sub u/B vector/sub d/, B/sub u/B vector/sub s/, etc.) can be produced. This reaction might be advantageous as mixing is expected to be almost complete for the B/sub s/ mesons. In this respect the study of mixing effects in the e + e - → BB vector X reaction is complementary to that in the e + e - → upsilon (4S) → B/sub d/ 0 B vector /sub e/ 0 process. In Section B.2 the authors recall briefly the parameters used to describe the BB vector mixing and in Section B.3 they give estimates for the mixing effects which could be observed in the e + e - → BB vector X reaction as well as in the upsilon (4S) decays. The authors have also evaluated the influence of a non-spectator component in the B-decay on the observability of the mixing phenomenon. Finally, in Section B.4 they give estimates for the number of signal and background events which could be observed in an e + e - experiment with an accumulated luminosity of 1000 pb -1 . 33 references, 4 figures

  7. Virus infection of a weed increases vector attraction to and vector fitness on the weed.

    Science.gov (United States)

    Chen, Gong; Pan, Huipeng; Xie, Wen; Wang, Shaoli; Wu, Qingjun; Fang, Yong; Shi, Xiaobin; Zhang, Youjun

    2013-01-01

    Weeds are important in the ecology of field crops, and when crops are harvested, weeds often become the main hosts for plant viruses and their insect vectors. Few studies, however, have examined the relationships between plant viruses, vectors, and weeds. Here, we investigated how infection of the weed Datura stramonium L. by tomato yellow leaf curl virus (TYLCV) affects the host preference and performance of the TYLCV vector, Bemisia tabaci (Gennadius) Q. The results of a choice experiment indicated that B. tabaci Q preferentially settled and oviposited on TYLCV-infected plants rather than on healthy plants. In addition, B. tabaci Q performed better on TYLCV-infected plants than on healthy plants. These results demonstrate that TYLCV is indirectly mutualistic to B. tabaci Q. The mutually beneficial interaction between TYLCV and B. tabaci Q may help explain the concurrent outbreaks of TYLCV and B. tabaci Q in China.

  8. Controllability of linear vector fields on Lie groups

    International Nuclear Information System (INIS)

    Ayala, V.; Tirao, J.

    1994-11-01

    In this paper, we shall deal with a linear control system Σ defined on a Lie group G with Lie algebra g. The dynamic of Σ is determined by the drift vector field which is an element in the normalizer of g in the Lie algebra of all smooth vector field on G and by the control vectors which are elements in g considered as left-invariant vector fields. We characterize the normalizer of g identifying vector fields on G with C ∞ -functions defined on G into g. For this class of control systems we study algebraic conditions for the controllability problem. Indeed, we prove that if the drift vector field has a singularity then the Lie algebra rank condition is necessary for the controllability property, but in general this condition does not determine this property. On the other hand, we show that the rank (ad-rank) condition is sufficient for the controllability of Σ. In particular, we extend the fundamental Kalman's theorem when G is an Abelian connected Lie group. Our work is related with a paper of L. Markus and we also improve his results. (author). 7 refs

  9. Neuron-specific RNA interference using lentiviral vectors

    DEFF Research Database (Denmark)

    Nielsen, Troels Tolstrup; Marion, Ingrid van; Hasholt, Lis

    2009-01-01

    BACKGROUND: Viral vectors have been used in several different settings for the delivery of small hairpin (sh) RNAs. However, most vectors have utilized ubiquitously-expressing polymerase (pol) III promoters to drive expression of the hairpin as a result of the strict requirement for precise...... transcriptional initiation and termination. Recently, pol II promoters have been used to construct vectors for RNA interference (RNAi). By embedding the shRNA into a micro RNA-context (miRNA) the endogenous miRNA processing machinery is exploited to achieve the mature synthetic miRNA (smiRNA), thereby expanding...... the possible promoter choices and eventually allowing cell type specific down-regulation of target genes. METHODS: In the present study, we constructed lentiviral vectors expressing smiRNAs under the control of pol II promoters to knockdown gene expression in cell culture and in the brain. RESULTS: We...

  10. VEST: Abstract vector calculus simplification in Mathematica

    Science.gov (United States)

    Squire, J.; Burby, J.; Qin, H.

    2014-01-01

    We present a new package, VEST (Vector Einstein Summation Tools), that performs abstract vector calculus computations in Mathematica. Through the use of index notation, VEST is able to reduce three-dimensional scalar and vector expressions of a very general type to a well defined standard form. In addition, utilizing properties of the Levi-Civita symbol, the program can derive types of multi-term vector identities that are not recognized by reduction, subsequently applying these to simplify large expressions. In a companion paper Burby et al. (2013) [12], we employ VEST in the automation of the calculation of high-order Lagrangians for the single particle guiding center system in plasma physics, a computation which illustrates its ability to handle very large expressions. VEST has been designed to be simple and intuitive to use, both for basic checking of work and more involved computations.

  11. 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.

  12. The evolution of heart gene delivery vectors

    Science.gov (United States)

    Wasala, Nalinda B.; Shin, Jin-Hong; Duan, Dongsheng

    2012-01-01

    Gene therapy holds promise for treating numerous heart diseases. A key premise for the success of cardiac gene therapy is the development of powerful gene transfer vehicles that can achieve highly efficient and persistent gene transfer specifically in the heart. Other features of an ideal vector include negligible toxicity, minimal immunogenicity and easy manufacturing. Rapid progress in the fields of molecular biology and virology has offered great opportunities to engineer various genetic materials for heart gene delivery. Several nonviral vectors (e.g. naked plasmids, plasmid lipid/polymer complexes and oligonucleotides) have been tested. Commonly used viral vectors include lentivirus, adenovirus and adeno-associated virus. Among these, adeno-associated virus has shown many attractive features for pre-clinical experimentation in animal models of heart diseases. We review the history and evolution of these vectors for heart gene transfer. PMID:21837689

  13. Techniques for vector analyzing power measurements of the 2H(n vector,np)n breakup reaction at low energies

    International Nuclear Information System (INIS)

    Howell, C.R.; Tornow, W.; Pfuetzner, H.G.; Li Anli; Roberts, M.L.; Murphy, K.; Felsher, P.D.; Weisel, G.J.; Naqvi, A.; Walter, R.L.; Lambert, J.M.; Treado, P.A.

    1990-01-01

    Experimental methods to measure the vector analyzing powers over a broad range of kinematic configurations in the n-d breakup reaction have been developed at TUNL. These techniques employ the polarized beam facilities at TUNL and use the 2 H(d vector, n vector) 3 He reaction as a source of low-energy polarized neutrons. Our methods permit measurements to a high statistical accuracy over a large fraction of three-nucleon phase space. The techniques are described and experimental spectra along with kinematic calculations are presented. (orig.)

  14. Data-driven identification of potential Zika virus vectors

    Science.gov (United States)

    Evans, Michelle V; Dallas, Tad A; Han, Barbara A; Murdock, Courtney C; Drake, John M

    2017-01-01

    Zika is an emerging virus whose rapid spread is of great public health concern. Knowledge about transmission remains incomplete, especially concerning potential transmission in geographic areas in which it has not yet been introduced. To identify unknown vectors of Zika, we developed a data-driven model linking vector species and the Zika virus via vector-virus trait combinations that confer a propensity toward associations in an ecological network connecting flaviviruses and their mosquito vectors. Our model predicts that thirty-five species may be able to transmit the virus, seven of which are found in the continental United States, including Culex quinquefasciatus and Cx. pipiens. We suggest that empirical studies prioritize these species to confirm predictions of vector competence, enabling the correct identification of populations at risk for transmission within the United States. DOI: http://dx.doi.org/10.7554/eLife.22053.001 PMID:28244371

  15. 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)

  16. 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)

  17. 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...

  18. 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

  19. Can really the electromagnetic transverse waves with E-vector parallel to B-vector and finite energy exist?

    International Nuclear Information System (INIS)

    Malinowski, S.

    1984-01-01

    It is shown that the total field energy for general solutions of the sourceless Maxwell's equations with E-vector parallel to B-vector is infinite. Moreover the action and/or the ''pseudoscalar charge'' must be infinite too in this case. Therefore the expected similarity to the instanton or meron solutions of nonabelian gauge theories is illusory. 5 refs. (author)

  20. 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.

  1. 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)

  2. 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.

  3. Study of The Vector Product using Three Dimensions Vector Card of Engineering in Pathumwan Institute of Technology

    Science.gov (United States)

    Mueanploy, Wannapa

    2015-06-01

    The objective of this research was to offer the way to improve engineering students in Physics topic of vector product. The sampling of this research was the engineering students at Pathumwan Institute of Technology during the first semester of academic year 2013. 1) Select 120 students by random sampling are asked to fill in a satisfaction questionnaire scale, to select size of three dimensions vector card in order to apply in the classroom. 2) Select 60 students by random sampling to do achievement test and take the test to be used in the classroom. The methods used in analysis of achievement test by the Kuder-Richardson Method (KR- 20). The results show that 12 items of achievement test are appropriate to be applied in the classroom. The achievement test gets Difficulty (P) = 0.40-0.67, Discrimination = 0.33-0.73 and Reliability (r) = 0.70.The experimental in the classroom. 3) Select 60 students by random sampling divide into two groups; group one (the controlled group) with 30 students was chosen to study in the vector product lesson by the regular teaching method. Group two (the experimental group) with 30 students was chosen to learn the vector product lesson with three dimensions vector card. 4) Analyzed data between the controlled group and the experimental group, the result showed that experimental group got higher achievement test than the controlled group significant at .01 level.

  4. Nonperturbative Aspects of Axial Vector Vertex

    Institute of Scientific and Technical Information of China (English)

    ZONG Hong-Shi; CHEN Xiang-Song; WANG Fan; CHANG Chao-Hsi; ZHAO En-Guang

    2002-01-01

    It is shown how the axial vector current of current quarks is related to that of constituent quarks within the framework of the global color symmetry model.Gluon dressing of the axial vector vertex and the quark self-energy functions are described by the inhomogeneous Bethe-Salpeter equation in the ladder approximation and the Schwinger Dyson equation in the rainbow approximation,respectively.

  5. VECTOR BORNE TRANSMISSIBLE ZOONOSES IN MONTENEGRO

    Directory of Open Access Journals (Sweden)

    Gordana Mijovic

    2012-02-01

    Full Text Available Vector borne transmissible zoonoses are becoming more and more important in the group of emerging and re-emerging infections. We present the characteristics and actuality of this group of infectious diseases in Montenegro for the period 1998 - 2011. In examinations, standard epidemiological, clinical, serological, pathohistological diagnostic methods are employed. Natural conditions in Montenegro make it an important endemic area for more vector borne transmissible zoonoses. The changes of ecological characteristics, the vectors and infective agents, present the accidence for expansion and increasing importance of these infections in national pathology. According to the fact that it is an international port of nautical, continental and air traffic, Montenegro has responsibility for control and management of diseases belonging to the group of the travel and tropical diseases.

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

    Directory of Open Access Journals (Sweden)

    Li Qiuying

    2011-01-01

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

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

    OpenAIRE

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

    2014-01-01

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

  8. Urbanization, land tenure security and vector-borne Chagas disease

    Science.gov (United States)

    Levy, Michael Z.; Barbu, Corentin M.; Castillo-Neyra, Ricardo; Quispe-Machaca, Victor R.; Ancca-Juarez, Jenny; Escalante-Mejia, Patricia; Borrini-Mayori, Katty; Niemierko, Malwina; Mabud, Tarub S.; Behrman, Jere R.; Naquira-Velarde, Cesar

    2014-01-01

    Modern cities represent one of the fastest growing ecosystems on the planet. Urbanization occurs in stages; each stage characterized by a distinct habitat that may be more or less susceptible to the establishment of disease vector populations and the transmission of vector-borne pathogens. We performed longitudinal entomological and epidemiological surveys in households along a 1900 × 125 m transect of Arequipa, Peru, a major city of nearly one million inhabitants, in which the transmission of Trypanosoma cruzi, the aetiological agent of Chagas disease, by the insect vector Triatoma infestans, is an ongoing problem. The transect spans a cline of urban development from established communities to land invasions. We find that the vector is tracking the development of the city, and the parasite, in turn, is tracking the dispersal of the vector. New urbanizations are free of vector infestation for decades. T. cruzi transmission is very recent and concentrated in more established communities. The increase in land tenure security during the course of urbanization, if not accompanied by reasonable and enforceable zoning codes, initiates an influx of construction materials, people and animals that creates fertile conditions for epidemics of some vector-borne diseases. PMID:24990681

  9. Sharp Efficiency for Vector Equilibrium Problems on Banach Spaces

    Directory of Open Access Journals (Sweden)

    Si-Huan Li

    2013-01-01

    Full Text Available The concept of sharp efficient solution for vector equilibrium problems on Banach spaces is proposed. Moreover, the Fermat rules for local efficient solutions of vector equilibrium problems are extended to the sharp efficient solutions by means of the Clarke generalized differentiation and the normal cone. As applications, some necessary optimality conditions and sufficient optimality conditions for local sharp efficient solutions of a vector optimization problem with an abstract constraint and a vector variational inequality are obtained, respectively.

  10. Vector Directional Distance Rational Hybrid Filters for Color Image Restoration

    Directory of Open Access Journals (Sweden)

    L. Khriji

    2005-12-01

    Full Text Available A new class of nonlinear filters, called vector-directional distance rational hybrid filters (VDDRHF for multispectral image processing, is introduced and applied to color image-filtering problems. These filters are based on rational functions (RF. The VDDRHF filter is a two-stage filter, which exploits the features of the vector directional distance filter (VDDF, the center weighted vector directional distance filter (CWVDDF and those of the rational operator. The filter output is a result of vector rational function (VRF operating on the output of three sub-functions. Two vector directional distance (VDDF filters and one center weighted vector directional distance filter (CWVDDF are proposed to be used in the first stage due to their desirable properties, such as, noise attenuation, chromaticity retention, and edges and details preservation. Experimental results show that the new VDDRHF outperforms a number of widely known nonlinear filters for multi-spectral image processing such as the vector median filter (VMF, the generalized vector directional filters (GVDF and distance directional filters (DDF with respect to all criteria used.

  11. Great Ellipse Route Planning Based on Space Vector

    Directory of Open Access Journals (Sweden)

    LIU Wenchao

    2015-07-01

    Full Text Available Aiming at the problem of navigation error caused by unified earth model in great circle route planning using sphere model and modern navigation equipment using ellipsoid mode, a method of great ellipse route planning based on space vector is studied. By using space vector algebra method, the vertex of great ellipse is solved directly, and description of great ellipse based on major-axis vector and minor-axis vector is presented. Then calculation formulas of great ellipse azimuth and distance are deduced using two basic vectors. Finally, algorithms of great ellipse route planning are studied, especially equal distance route planning algorithm based on Newton-Raphson(N-R method. Comparative examples show that the difference of route planning between great circle and great ellipse is significant, using algorithms of great ellipse route planning can eliminate the navigation error caused by the great circle route planning, and effectively improve the accuracy of navigation calculation.

  12. 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...

  13. Vector velocity ultrasound—a new ultrasound technique

    DEFF Research Database (Denmark)

    Lönn, Lars; Jensen, Jørgen Arendt; Olesen, Jacob Bjerring

    2018-01-01

    Vector fow techniques, with their many advantages over conventional Doppler techniques, are powerful alternatives for blood fow evaluation. • Vector fow imaging can visualise complex fow; refne the classic fow parameters; and introduce new fow parameters and insonation windows. • These factors...

  14. 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.

  15. [Conflicts and vector-borne diseases

    DEFF Research Database (Denmark)

    Bygbjerg, Ib Christian

    2010-01-01

    Based on literature and personal experiences, vector-borne diseases and conflicts are reviewed. Simple rapid diagnostic tests for three important parasitoses are available. Resort is often made to case definitions and to presumptive treatment. Resistance is an emerging problem. Vaccines are still...... not available for most diseases. Promising preventive methods, including long-lasting impregnated bed-nets and tents, are available. War has been an impetus for disclosing life-cycles of vector-borne diseases and for control methods; peace, reconciliation and poverty reduction are required to achieve lasting...

  16. 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

  17. Isomorphism Theorem on Vector Spaces over a Ring

    Directory of Open Access Journals (Sweden)

    Futa Yuichi

    2017-10-01

    Full Text Available In this article, we formalize in the Mizar system [1, 4] some properties of vector spaces over a ring. We formally prove the first isomorphism theorem of vector spaces over a ring. We also formalize the product space of vector spaces. ℤ-modules are useful for lattice problems such as LLL (Lenstra, Lenstra and Lovász [5] base reduction algorithm and cryptographic systems [6, 2].

  18. RNA Interference in Insect Vectors for Plant Viruses

    OpenAIRE

    Kanakala, Surapathrudu; Ghanim, Murad

    2016-01-01

    Insects and other arthropods are the most important vectors of plant pathogens. The majority of plant pathogens are disseminated by arthropod vectors such as aphids, beetles, leafhoppers, planthoppers, thrips and whiteflies. Transmission of plant pathogens and the challenges in managing insect vectors due to insecticide resistance are factors that contribute to major food losses in agriculture. RNA interference (RNAi) was recently suggested as a promising strategy for controlling insect pests...

  19. Simian virus 40 vectors for pulmonary gene therapy

    Directory of Open Access Journals (Sweden)

    Oppenheim Ariella

    2007-10-01

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

  20. Polarization observables D/sub NN/, P and A for vector pp → vector pπ+n at 800 MeV

    International Nuclear Information System (INIS)

    Bonner, B.E.; McNaughton, M.W.; van Dyck, O.B.

    1983-01-01

    In conjunction with a vector polarization transfer measurement in the vector pp → vector dπ + reaction, we also obtained data on polarization observables for vector pp → vector pπ + n at 800 MeV incident proton energy. Scattered protons were detected in a spectrometer at angles from 5 0 to 11 0 . Pions were detected in coincidence at angles 80 0 to 130 0 . The proton momentum range covered was from 800 to 1300 MeV/c. The prominent peak observed near 1150 MeV/c in the proton spectrum is a reflection of Δ ++ production at center of mass angles from 0 0 to 30 0 . Regions of the spectrum corresponding to Δ ++ production at backward THETA/sub cm/ angles and to the 1 S 0 np final state interaction fall below the momentum acceptance limit for the spectrometer setting used in the present measurements. The events were binned into five proton momentum bins for the determination of the polarization observables D/sub NN/, P, and A

  1. 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

  2. Reducing vector-borne disease by empowering farmers in integrated vector management

    NARCIS (Netherlands)

    Berg, van den H.; Hildebrand, von A.; Ragunathan, V.; Das, P.K.

    2007-01-01

    PROBLEM: Irrigated agriculture exposes rural people to health risks associated with vector-borne diseases and pesticides used in agriculture and for public health protection. Most developing countries lack collaboration between the agricultural and health sectors to jointly address these problems.

  3. Generation of arbitrary vector beams with liquid crystal polarization converters and vector-photoaligned q-plates

    International Nuclear Information System (INIS)

    Chen, Peng; Ji, Wei; Wei, Bing-Yan; Hu, Wei; Lu, Yan-Qing; Chigrinov, Vladimir

    2015-01-01

    Arbitrary vector beams (VBs) are realized by the designed polarization converters and corresponding vector-photoaligned q-plates. The polarization converter is a specific twisted nematic cell with one substrate homogeneously aligned and the other space-variantly aligned. By combining a polarization-sensitive alignment agent with a dynamic micro-lithography system, various categories of liquid crystal polarization converters are demonstrated. Besides, traditional radially/azimuthally polarized light, high-order and multi-ringed VBs, and a VB array with different orders are generated. The obtained converters are further utilized as polarization masks to implement vector-photoaligning. The technique facilitates both the volume duplication of these converters and the generation of another promising optical element, the q-plate, which is suitable for the generation of VBs for coherent lasers. The combination of proposed polarization converters and correspondingly fabricated q-plates would drastically enhance the capability of polarization control and may bring more possibilities for the design of photonic devices

  4. Black hole superradiance signatures of ultralight vectors

    Science.gov (United States)

    Baryakhtar, Masha; Lasenby, Robert; Teo, Mae

    2017-08-01

    The process of superradiance can extract angular momentum and energy from astrophysical black holes (BHs) to populate gravitationally bound states with an exponentially large number of light bosons. We analytically calculate superradiant growth rates for vectors around rotating BHs in the regime where the vector Compton wavelength is much larger than the BH size. Spin-1 bound states have superradiance times as short as a second around stellar BHs, growing up to a thousand times faster than their spin-0 counterparts. The fast rates allow us to use measurements of rapidly spinning BHs in x-ray binaries to exclude a wide range of masses for weakly coupled spin-1 particles, 5 ×10-14-2 ×10-11 eV ; lighter masses in the range 6 ×10-20-2 ×10-17 eV start to be constrained by supermassive BH spin measurements at a lower level of confidence. We also explore routes to detection of new vector particles possible with the advent of gravitational wave (GW) astronomy. The LIGO-Virgo Collaboration could discover hints of a new light vector particle in statistical analyses of masses and spins of merging BHs. Vector annihilations source continuous monochromatic gravitational radiation which could be observed by current GW observatories. At design sensitivity, Advanced LIGO may measure up to thousands of annihilation signals from within the Milky Way, while hundreds of BHs born in binary mergers across the observable Universe may superradiate vector bound states and become new beacons of monochromatic gravitational waves.

  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. Researches on Key Algorithms in Analogue Seismogram Records Vectorization

    Directory of Open Access Journals (Sweden)

    Maofa WANG

    2014-09-01

    Full Text Available History paper seismograms are very important information for earthquake monitoring and prediction, and the vectorization of paper seismograms is a very import problem to be resolved. In our study, a new tracing algorithm for simulated seismogram curves based on visual filed feature is presented. We also give out the technological process to vectorizing simulated seismograms, and an analog seismic record vectorization system has been accomplished independently. Using it, we can precisely and speedy vectorize analog seismic records (need professionals to participate interactively.

  7. Investigation of propagation dynamics of truncated vector vortex beams.

    Science.gov (United States)

    Srinivas, P; Perumangatt, C; Lal, Nijil; Singh, R P; Srinivasan, B

    2018-06-01

    In this Letter, we experimentally investigate the propagation dynamics of truncated vector vortex beams generated using a Sagnac interferometer. Upon focusing, the truncated vector vortex beam is found to regain its original intensity structure within the Rayleigh range. In order to explain such behavior, the propagation dynamics of a truncated vector vortex beam is simulated by decomposing it into the sum of integral charge beams with associated complex weights. We also show that the polarization of the truncated composite vector vortex beam is preserved all along the propagation axis. The experimental observations are consistent with theoretical predictions based on previous literature and are in good agreement with our simulation results. The results hold importance as vector vortex modes are eigenmodes of the optical fiber.

  8. A new mass relation among the hadron vector resonances

    CERN Document Server

    Chizhov, M.V.

    2001-01-01

    We show that the hadron vector resonances are described by fields transforming according to different inequivalent representations of the Lorentz group: (1/2,1/2) and (1,0)+(0,1). The vector representation (1/2,1/2) is well studied and corresponds to the gauge fields. On the other hand, the chiral representations (1,0) and (0,1) are described by the second rank antisymmetric tensor fields, for which interaction theory has not yet been constructed. In the framework of the phenomenological Nambu - Jona-Lasinio approach we have introduced and used all these fields for a description of the vector resonances. A new mass relation between low-lying hadron vector and axial-vector resonances is obtained. This relation is in agreement with the present experimental data.

  9. 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…

  10. 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.

  11. Triviality and Split of Vector Bundles on Rationally Connected Varieties

    OpenAIRE

    Pan, Xuanyu

    2013-01-01

    In this paper, we give a simple proof of a triviality criterion due to I.Biswas and J.Pedro and P.Dos Santos. We also prove a vector bundle on a homogenous space is trivial if and only if the restrictions of the vector bundle to Schubert lines are trivial. Using this result and Chern classes of vector bundles, we give a general criterion of a uniform vector bundle on a homogenous space to be splitting. As an application, we prove a uniform vector bundle on classical Grassmannians and quadrics...

  12. Switching non-local vector median filter

    Science.gov (United States)

    Matsuoka, Jyohei; Koga, Takanori; Suetake, Noriaki; Uchino, Eiji

    2016-04-01

    This paper describes a novel image filtering method that removes random-valued impulse noise superimposed on a natural color image. In impulse noise removal, it is essential to employ a switching-type filtering method, as used in the well-known switching median filter, to preserve the detail of an original image with good quality. In color image filtering, it is generally preferable to deal with the red (R), green (G), and blue (B) components of each pixel of a color image as elements of a vectorized signal, as in the well-known vector median filter, rather than as component-wise signals to prevent a color shift after filtering. By taking these fundamentals into consideration, we propose a switching-type vector median filter with non-local processing that mainly consists of a noise detector and a noise removal filter. Concretely, we propose a noise detector that proactively detects noise-corrupted pixels by focusing attention on the isolation tendencies of pixels of interest not in an input image but in difference images between RGB components. Furthermore, as the noise removal filter, we propose an extended version of the non-local median filter, we proposed previously for grayscale image processing, named the non-local vector median filter, which is designed for color image processing. The proposed method realizes a superior balance between the preservation of detail and impulse noise removal by proactive noise detection and non-local switching vector median filtering, respectively. The effectiveness and validity of the proposed method are verified in a series of experiments using natural color images.

  13. [Vector transmitted diseases and climate changes in Europe].

    Science.gov (United States)

    Rossati, Antonella; Bargiacchi, Olivia; Kroumova, Vesselina; Garavelli, Pietro Luigi

    2014-09-01

    The increase in temperatures recorded since the mid-nineteenth century is unprecedented in the history of mankind. The consequences of climate changes are numerous and can affect human health through direct (extreme events, natural disasters) or indirect (alteration of the ecosystem) mechanisms. Climate changes have repercussions on ecosystems, agriculture, social conditions, migration, conflicts and the transmission mode of infectious diseases. Vector-borne diseases are infections transmitted by the bite of infected arthropods such as mosquitoes, ticks, triatomines, sand flies and flies. Epidemiological cornerstones of vector-borne diseases are: the ecology and behaviour of the host, the ecology and behaviour of the vector, and the population's degree of immunity. Mosquito vectors related to human diseases mainly belong to the genus Culex, Aedes and Mansonia. Climate changes in Europe have increased the spread of new vectors, such as Aedes albopictus, and in some situations have made it possible to sustain the autochthonous transmission of some diseases (outbreak of Chukungunya virus in northern Italy in 2007, cases of dengue in the South of France and in Croatia). Despite the eradication of malaria from Europe, anopheline carriers are still present, and they may allow the transmission of the disease if the climatic conditions favour the development of the vectors and their contacts with plasmodium carriers. The tick Ixodes ricinus is a vector whose expansion has been documented both in latitude and in altitude in relation to the temperature increase; at the same time the related main viral and bacterial infections have increased. In northern Italy and Germany, the appearance of Leishmaniasis has been associated to climatic conditions that favour the development of the vector Phlebotomus papatasi and the maturation of the parasite within the vector, although the increase of cases of visceral leishmaniasis is also related to host immune factors, particularly

  14. 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

  15. 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....

  16. 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

  17. Vaxvec: The first web-based recombinant vaccine vector database and its data analysis

    Science.gov (United States)

    Deng, Shunzhou; Martin, Carly; Patil, Rasika; Zhu, Felix; Zhao, Bin; Xiang, Zuoshuang; He, Yongqun

    2015-01-01

    A recombinant vector vaccine uses an attenuated virus, bacterium, or parasite as the carrier to express a heterologous antigen(s). Many recombinant vaccine vectors and related vaccines have been developed and extensively investigated. To compare and better understand recombinant vectors and vaccines, we have generated Vaxvec (http://www.violinet.org/vaxvec), the first web-based database that stores various recombinant vaccine vectors and those experimentally verified vaccines that use these vectors. Vaxvec has now included 59 vaccine vectors that have been used in 196 recombinant vector vaccines against 66 pathogens and cancers. These vectors are classified to 41 viral vectors, 15 bacterial vectors, 1 parasitic vector, and 1 fungal vector. The most commonly used viral vaccine vectors are double-stranded DNA viruses, including herpesviruses, adenoviruses, and poxviruses. For example, Vaxvec includes 63 poxvirus-based recombinant vaccines for over 20 pathogens and cancers. Vaxvec collects 30 recombinant vector influenza vaccines that use 17 recombinant vectors and were experimentally tested in 7 animal models. In addition, over 60 protective antigens used in recombinant vector vaccines are annotated and analyzed. User-friendly web-interfaces are available for querying various data in Vaxvec. To support data exchange, the information of vaccine vectors, vaccines, and related information is stored in the Vaccine Ontology (VO). Vaxvec is a timely and vital source of vaccine vector database and facilitates efficient vaccine vector research and development. PMID:26403370

  18. Axisymmetric thrust-vectoring nozzle performance prediction

    International Nuclear Information System (INIS)

    Wilson, E. A.; Adler, D.; Bar-Yoseph, P.Z

    1998-01-01

    Throat-hinged geometrically variable converging-diverging thrust-vectoring nozzles directly affect the jet flow geometry and rotation angle at the nozzle exit as a function of the nozzle geometry, the nozzle pressure ratio and flight velocity. The consideration of nozzle divergence in the effective-geometric nozzle relation is theoretically considered here for the first time. In this study, an explicit calculation procedure is presented as a function of nozzle geometry at constant nozzle pressure ratio, zero velocity and altitude, and compared with experimental results in a civil thrust-vectoring scenario. This procedure may be used in dynamic thrust-vectoring nozzle design performance predictions or analysis for civil and military nozzles as well as in the definition of initial jet flow conditions in future numerical VSTOL/TV jet performance studies

  19. Application of Vector Triggering Random Decrement

    DEFF Research Database (Denmark)

    Asmussen, J. C.; Ibrahim, S. R.; Brincker, Rune

    result is a Random Decrement function from each measurement. In traditional Random Decrement estimation the triggering condition is a scalar condition, which should only be fulfilled in a single measurement. In vector triggering Random Decrement the triggering condition is a vector condition......This paper deals with applications of the vector triggering Random Decrement technique. This technique is new and developed with the aim of minimizing estimation time and identification errors. The theory behind the technique is discussed in an accompanying paper. The results presented...... in this paper should be regarded as a further documentation of the technique. The key point in Random Decrement estimation is the formulation of a triggering condition. If the triggering condition is fulfilled a time segment from each measurement is picked out and averaged with previous time segments. The final...

  20. Application of Vector Triggering Random Decrement

    DEFF Research Database (Denmark)

    Asmussen, J. C.; Ibrahim, S. R.; Brincker, Rune

    1997-01-01

    result is a Random Decrement function from each measurement. In traditional Random Decrement estimation the triggering condition is a scalar condition, which should only be fulfilled in a single measurement. In vector triggering Random Decrement the triggering condition is a vector condition......This paper deals with applications of the vector triggering Random Decrement technique. This technique is new and developed with the aim of minimizing estimation time and identification errors. The theory behind the technique is discussed in an accompanying paper. The results presented...... in this paper should be regarded as a further documentation of the technique. The key point in Random Decrement estimation is the formulation of a triggering condition. If the triggering condition is fulfilled a time segment from each measurement is picked out and averaged with previous time segments. The final...

  1. Redshift-space distortions from vector perturbations

    Science.gov (United States)

    Bonvin, Camille; Durrer, Ruth; Khosravi, Nima; Kunz, Martin; Sawicki, Ignacy

    2018-02-01

    We compute a general expression for the contribution of vector perturbations to the redshift space distortion of galaxy surveys. We show that they contribute to the same multipoles of the correlation function as scalar perturbations and should thus in principle be taken into account in data analysis. We derive constraints for next-generation surveys on the amplitude of two sources of vector perturbations, namely non-linear clustering and topological defects. While topological defects leave a very small imprint on redshift space distortions, we show that the multipoles of the correlation function are sensitive to vorticity induced by non-linear clustering. Therefore future redshift surveys such as DESI or the SKA should be capable of measuring such vector modes, especially with the hexadecapole which appears to be the most sensitive to the presence of vorticity.

  2. General projective relativity and the vector-tensor gravitational field

    International Nuclear Information System (INIS)

    Arcidiacono, G.

    1986-01-01

    In the general projective relativity, the induced 4-dimensional metric is symmetric in three cases, and we obtain the vector-tensor, the scalar-tensor, and the scalar-vector-tensor theories of gravitation. In this work we examine the vector-tensor theory, similar to the Veblen's theory, but with a different physical interpretation

  3. VECTORS OF MALARIA AND FILARIASIS IN INDONESIA

    Directory of Open Access Journals (Sweden)

    Hoedojo Hoedojo

    2012-09-01

    Full Text Available Malaria at present is still one of the important mosquito-borne diseases in Indonesia. The disease is widespread all over the country and involves nearly all islands. Sixteen Anopheles species have been reconfirmed as malaria vectors. They were distributed geographi­cally as follows: Coastal areas and lagoons ------------------------------------- An sundaicus and An.subpictus Cultivated ricefields and swampy areas -------------------- An.aconitus, An.barbirostris, An.nigerrimus and An.sinensis Forest inland areas in shaded temporary pools, muddy animal wallows and hoof-prints -------------------------------------------------------- An.balabacensis, An.bancrofti, An.farauti, An.koliensis and An.punctulatus Swamp forest edge in ditches with vegeta- ---------------- An.letifer and An.ludlowae don Hilly areas in seepages, streams and clear moving water ---------------------------------------------- Anflavirostris, An.maculatus and Anminimus.   The species (of most general importance is An.sundaicus, which is restricted by its preference for brackish water and is prevalent in coastal areas of Java. Their types in behaviour of An.sundaicus appear as follows : 1. An.sundaicus in South Coast of Java in general. This species is essentially anthropophilic, exophagic and rests outdoor. It shows susceptible to DDT. 2. An.sundaicus in Cilacap, Central Java. This mosquito is a pure anthropophilic form. It bites man in houses and outdoors, rests indoors and is known resistant to DDT. 3. An.sundaicus in Yogyakarta and Purworejo, Central Java. This mosquito is a strong zoophilic species. It rests and prefers to bite outdoors and shows tolerance to DDT. Human filariasis in Indonesia is the result of infection by three endemic species, namely, Wuchereria bancrofti, Brugia malayi, and Brugia timori.W.bancrofti infection is found in both urban and rural areas. Twenty species of mosquitoes are confirmed as filariasis vectors. The urban type bancroftian filariasis

  4. Transmutations between singular and subsingular vectors of the N = 2 superconformal algebras

    International Nuclear Information System (INIS)

    Doerrzapf, Matthias; Gato-Rivera, Beatriz

    1999-01-01

    We present subsingular vectors of the N = 2 superconformal algebras other than the ones which become singular in chiral Verma modules, reported recently by Gato-Rivera and Rosado. We show that two large classes of singular vectors of the topological algebra become subsingular vectors of the antiperiodic NS algebra under the topological untwistings. These classes consist of BRST-invariant singular vectors with relative charges q = -2, -1 and zero conformal weight, and nolabel singular vectors with q = 0, -1. In turn the resulting NS subsingular vectors are transformed by the spectral flows into subsingular and singular vectors of the periodic R algebra. We write down these singular and subsingular vectors starting from the topological singular vectors at levels 1 and 2

  5. Arterial secondary blood flow patterns visualized with vector flow ultrasound

    DEFF Research Database (Denmark)

    Pedersen, Mads Møller; Pihl, Michael Johannes; Hansen, Jens Munk

    2011-01-01

    This study presents the first quantification and visualisation of secondary flow patterns with vector flow ultrasound. The first commercial implementation of the vector flow method Transverse Oscillation was used to obtain in-vivo, 2D vector fields in real-time. The hypothesis of this study...... was that the rotational direction is constant within each artery. Three data sets of 10 seconds were obtained from three main arteries in healthy volunteers. For each data set the rotational flow patterns were identified during the diastole. Each data set contains a 2D vector field over time and with the vector angles...

  6. Isometric Reflection Vectors and Characterizations of Hilbert Spaces

    Directory of Open Access Journals (Sweden)

    Donghai Ji

    2014-01-01

    Full Text Available A known characterization of Hilbert spaces via isometric reflection vectors is based on the following implication: if the set of isometric reflection vectors in the unit sphere SX of a Banach space X has nonempty interior in SX, then X is a Hilbert space. Applying a recent result based on well-known theorem of Kronecker from number theory, we improve this by substantial reduction of the set of isometric reflection vectors needed in the hypothesis.

  7. A Hybrid Pressure and Vector Sensor Towed Array

    National Research Council Canada - National Science Library

    Huang, Dehua

    2008-01-01

    The invention as disclosed is of a combined acoustic pressure and acoustic vector sensor array, where multiple acoustic pressure sensors are integrated with an acoustic vector sensor in a towed array...

  8. Probabilistic Extraction Of Vectors In PIV

    Science.gov (United States)

    Humphreys, William M., Jr.

    1994-01-01

    Probabilistic technique for extraction of velocity vectors in particle-image velocimetry (PIV) implemented with much less computation. Double-exposure photograph of particles in flow illuminated by sheet of light provides data on velocity field of flow. Photograph converted into video image then digitized and processed by computer into velocity-field data. Velocity vectors in interrogation region chosen from magnitude and angle histograms constructed from centroid map of region.

  9. 40 CFR 503.15 - Operational standards-pathogens and vector attraction reduction.

    Science.gov (United States)

    2010-07-01

    ... vector attraction reduction. 503.15 Section 503.15 Protection of Environment ENVIRONMENTAL PROTECTION... § 503.15 Operational standards—pathogens and vector attraction reduction. (a) Pathogens—sewage sludge... reclamation site. (c) Vector attraction reduction—sewage sludge. (1) One of the vector attraction reduction...

  10. First measurement of the helicity-dependent vector gamma)vector(p)->p eta differential cross-section

    CERN Document Server

    Ahrens, J; Aulenbacher, K; Beck, R; Drechsel, D; Von Harrach, D; Heid, E; Altieri, S; Annand, J R M; Anton, G; Bradtke, C; Görtz, S; Harmsen, J; Braghieri, A; D'Hose, N; Dutz, H; Grabmayr, P; Hansen, K; Hasegawa, S; Hasegawa, T; Helbing, K; Holvoet, H; Van Hoorebeke, L; Horikawa, N; Iwata, T; Jahn, O; Jennewein, P; Kageya, T; Kiel, B; Klein, F; Kondratiev, R; Kossert, K; Krimmer, J; Lang, M; Lannoy, B; Leukel, R; Lisin, V; Matsuda, T; McGeorge, J C; Meier, A; Menze, D; Meyer, Werner T; Michel, T; Naumann, J; Panzeri, A; Pedroni, P; Pinelli, T; Preobrajenski, I; Radtke, E; Reichert, E; Reicherz, G; Rohlof, C; Rosner, G; Ryckbosch, D; Sauer, M C; Schoch, B; Schumacher, M; Seitz, B; Speckner, T; Takabayashi, N; Tamas, G; Thomas, A; Van De Vyver, R; Wakai, A; Weihofen, W; Wissmann, F; Zapadtka, F; Zeitler, G

    2003-01-01

    The helicity dependence of the vector(gamma)vector(p)->p eta reaction has been measured for the first time at a center-of-mass angle theta sup * subeta=70 in the photon energy range from 780 MeV to 790 MeV. The experiment, performed at the Mainz microtron MAMI, used a 4 pi-detector system, a circularly polarized, tagged photon beam, and a longitudinally polarized frozen-spin target. The helicity 3/2 cross-section is found to be small and the results for helicity 1/2 agree with predictions from the MAID analysis. (orig.)

  11. Dynamical creation of complex vector solitons in spinor Bose-Einstein condensates

    International Nuclear Information System (INIS)

    Xiong Bo; Gong Jiangbin

    2010-01-01

    By numerical simulations of the Gross-Pitaevskii mean-field equations, we show that the dynamical creation of stable complex vector solitons in a homogeneous spin-1 Bose-Einstein condensate can be achieved by applying a localized magnetic field for a certain duration, with the initial uniform density prepared differently for the formation of different vector solitons. In particular, it is shown that stable dark-bright-dark vector solitons, dark-bright-bright vector solitons, and other analogous solutions can be dynamically created. It is also found that the peak intensity and the group velocity of the vector solitons thus generated can be tuned by adjusting the applied magnetic field. Extensions of our approach also allow for the creation of vector-soliton chains or the pumping of many vector solitons. The results can be useful for possible vector-soliton-based applications of dilute Bose-Einstein condensates.

  12. 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...

  13. How effective is integrated vector management against malaria and lymphatic filariasis where the diseases are transmitted by the same vector?

    Directory of Open Access Journals (Sweden)

    Christopher M Stone

    2014-12-01

    Full Text Available The opportunity to integrate vector management across multiple vector-borne diseases is particularly plausible for malaria and lymphatic filariasis (LF control where both diseases are transmitted by the same vector. To date most examples of integrated control targeting these diseases have been unanticipated consequences of malaria vector control, rather than planned strategies that aim to maximize the efficacy and take the complex ecological and biological interactions between the two diseases into account.We developed a general model of malaria and LF transmission and derived expressions for the basic reproductive number (R0 for each disease. Transmission of both diseases was most sensitive to vector mortality and biting rate. Simulating different levels of coverage of long lasting-insecticidal nets (LLINs and larval control confirms the effectiveness of these interventions for the control of both diseases. When LF was maintained near the critical density of mosquitoes, minor levels of vector control (8% coverage of LLINs or treatment of 20% of larval sites were sufficient to eliminate the disease. Malaria had a far greater R0 and required a 90% population coverage of LLINs in order to eliminate it. When the mosquito density was doubled, 36% and 58% coverage of LLINs and larval control, respectively, were required for LF elimination; and malaria elimination was possible with a combined coverage of 78% of LLINs and larval control.Despite the low level of vector control required to eliminate LF, simulations suggest that prevalence of LF will decrease at a slower rate than malaria, even at high levels of coverage. If representative of field situations, integrated management should take into account not only how malaria control can facilitate filariasis elimination, but strike a balance between the high levels of coverage of (multiple interventions required for malaria with the long duration predicted to be required for filariasis elimination.

  14. How effective is integrated vector management against malaria and lymphatic filariasis where the diseases are transmitted by the same vector?

    Science.gov (United States)

    Stone, Christopher M; Lindsay, Steve W; Chitnis, Nakul

    2014-12-01

    The opportunity to integrate vector management across multiple vector-borne diseases is particularly plausible for malaria and lymphatic filariasis (LF) control where both diseases are transmitted by the same vector. To date most examples of integrated control targeting these diseases have been unanticipated consequences of malaria vector control, rather than planned strategies that aim to maximize the efficacy and take the complex ecological and biological interactions between the two diseases into account. We developed a general model of malaria and LF transmission and derived expressions for the basic reproductive number (R0) for each disease. Transmission of both diseases was most sensitive to vector mortality and biting rate. Simulating different levels of coverage of long lasting-insecticidal nets (LLINs) and larval control confirms the effectiveness of these interventions for the control of both diseases. When LF was maintained near the critical density of mosquitoes, minor levels of vector control (8% coverage of LLINs or treatment of 20% of larval sites) were sufficient to eliminate the disease. Malaria had a far greater R0 and required a 90% population coverage of LLINs in order to eliminate it. When the mosquito density was doubled, 36% and 58% coverage of LLINs and larval control, respectively, were required for LF elimination; and malaria elimination was possible with a combined coverage of 78% of LLINs and larval control. Despite the low level of vector control required to eliminate LF, simulations suggest that prevalence of LF will decrease at a slower rate than malaria, even at high levels of coverage. If representative of field situations, integrated management should take into account not only how malaria control can facilitate filariasis elimination, but strike a balance between the high levels of coverage of (multiple) interventions required for malaria with the long duration predicted to be required for filariasis elimination.

  15. Unsupervised learning of binary vectors: A Gaussian scenario

    International Nuclear Information System (INIS)

    Copelli, Mauro; Van den Broeck, Christian

    2000-01-01

    We study a model of unsupervised learning where the real-valued data vectors are isotropically distributed, except for a single symmetry-breaking binary direction B(set-membership sign){-1,+1} N , onto which the projections have a Gaussian distribution. We show that a candidate vector J undergoing Gibbs learning in this discrete space, approaches the perfect match J=B exponentially. In addition to the second-order ''retarded learning'' phase transition for unbiased distributions, we show that first-order transitions can also occur. Extending the known result that the center of mass of the Gibbs ensemble has Bayes-optimal performance, we show that taking the sign of the components of this vector (clipping) leads to the vector with optimal performance in the binary space. These upper bounds are shown generally not to be saturated with the technique of transforming the components of a special continuous vector, except in asymptotic limits and in a special linear case. Simulations are presented which are in excellent agreement with the theoretical results. (c) 2000 The American Physical Society

  16. Vector-Parallel processing of the successive overrelaxation method

    International Nuclear Information System (INIS)

    Yokokawa, Mitsuo

    1988-02-01

    Successive overrelaxation method, called SOR method, is one of iterative methods for solving linear system of equations, and it has been calculated in serial with a natural ordering in many nuclear codes. After the appearance of vector processors, this natural SOR method has been changed for the parallel algorithm such as hyperplane or red-black method, in which the calculation order is modified. These methods are suitable for vector processors, and more high-speed calculation can be obtained compared with the natural SOR method on vector processors. In this report, a new scheme named 4-colors SOR method is proposed. We find that the 4-colors SOR method can be executed on vector-parallel processors and it gives the most high-speed calculation among all SOR methods according to results of the vector-parallel execution on the Alliant FX/8 multiprocessor system. It is also shown that the theoretical optimal acceleration parameters are equal among five different ordering SOR methods, and the difference between convergence rates of these SOR methods are examined. (author)

  17. 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.

  18. Construction and decomposition of biorthogonal vector-valued wavelets with compact support

    International Nuclear Information System (INIS)

    Chen Qingjiang; Cao Huaixin; Shi Zhi

    2009-01-01

    In this article, we introduce vector-valued multiresolution analysis and the biorthogonal vector-valued wavelets with four-scale. The existence of a class of biorthogonal vector-valued wavelets with compact support associated with a pair of biorthogonal vector-valued scaling functions with compact support is discussed. A method for designing a class of biorthogonal compactly supported vector-valued wavelets with four-scale is proposed by virtue of multiresolution analysis and matrix theory. The biorthogonality properties concerning vector-valued wavelet packets are characterized with the aid of time-frequency analysis method and operator theory. Three biorthogonality formulas regarding them are presented.

  19. On the calculation of multi-group fission spectrum vectors

    International Nuclear Information System (INIS)

    Mueller, E.Z.

    1984-05-01

    In this report, the problem of calculating fission spectrum vectors in a consistent manner is formulated. The practical implications of using fission spectrum vectors in multi-group transport calculations are also addressed. The significance of the weighting spectra used for the calculation of fission spectrum vectors is illustrated for the case of a simple neutronic assembly

  20. Engineered XcmI cassette-containing vector for PCR-based ...

    Indian Academy of Sciences (India)

    Unknown

    A simple and general method is described to construct a new vector bearing a synthetic XcmI cassette for direct cloning of PCR-amplified genes of interest. Cleavage of the vector with XcmI generates a linearized molecule with a single thymidine (T) overhang at the 3′ ends (T-vector) that facilitates TA cloning of PCR ...