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

Science.gov (United States)

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

2009-11-01

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

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

Science.gov (United States)

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

2015-09-01

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

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

NARCIS (Netherlands)

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

1997-01-01

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

Improved vaccine protection against retrovirus infection after co-administration of adenoviral vectors encoding viral antigens and type I interferon subtypes

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Groitl Peter

2011-09-01

Full Text Available Abstract Background Type I interferons (IFNs exhibit direct antiviral effects, but also distinct immunomodulatory properties. In this study, we analyzed type I IFN subtypes for their effect on prophylactic adenovirus-based anti-retroviral vaccination of mice against Friend retrovirus (FV or HIV. Results Mice were vaccinated with adenoviral vectors encoding FV Env and Gag proteins alone or in combination with vectors encoding IFNα1, IFNα2, IFNα4, IFNα5, IFNα6, IFNα9 or IFNβ. Only the co-administration of adenoviral vectors encoding IFNα2, IFNα4, IFNα6 and IFNα9 resulted in strongly improved immune protection of vaccinated mice from subsequent FV challenge infection with high control over FV-induced splenomegaly and reduced viral loads. The level of protection correlated with augmented virus-specific CD4+ T cell responses and enhanced antibody titers. Similar results were obtained when mice were vaccinated against HIV with adenoviral vectors encoding HIV Env and Gag-Pol in combination with various type I IFN encoding vectors. Here mainly CD4+ T cell responses were enhanced by IFNα subtypes. Conclusions Our results indicate that certain IFNα subtypes have the potential to improve the protective effect of adenovirus-based vaccines against retroviruses. This correlated with augmented virus-specific CD4+ T cell and antibody responses. Thus, co-expression of select type I IFNs may be a valuable tool for the development of anti-retroviral vaccines.

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

Science.gov (United States)

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

2003-10-01

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

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

NARCIS (Netherlands)

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

2005-01-01

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

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

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Donna J Palmer

2016-01-01

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

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

Science.gov (United States)

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

2016-04-01

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

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

NARCIS (Netherlands)

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

2003-01-01

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

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

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Teschemacher Anja G

2009-03-01

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

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

DEFF Research Database (Denmark)

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

2014-01-01

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

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

Science.gov (United States)

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

2015-01-01

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

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

Science.gov (United States)

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

2016-01-01

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

Novel recombinant alphaviral and adenoviral vectors for cancer immunotherapy.

Science.gov (United States)

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

2012-06-01

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

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

Science.gov (United States)

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

2006-01-01

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

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

National Research Council Canada - National Science Library

Rogers, Buck

2002-01-01

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

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

NARCIS (Netherlands)

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

1997-01-01

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

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.

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

Science.gov (United States)

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

2005-10-31

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

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

Directory of Open Access Journals (Sweden)

Ando Tomoaki

2005-10-01

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

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

Directory of Open Access Journals (Sweden)

Vijayendra Dasari

2016-01-01

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

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

NARCIS (Netherlands)

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

2006-01-01

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

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

Science.gov (United States)

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

2018-03-01

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

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

Science.gov (United States)

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

2017-12-07

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

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

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Minglong Liu

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

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

International Nuclear Information System (INIS)

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

2012-01-01

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

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

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Zhang, Wenli; Ehrhardt, Anja

2017-10-01

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

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

NARCIS (Netherlands)

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

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

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

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

2011-01-15

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

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

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Daria A Burmistrova

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

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

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Merry ZC Ruan

2016-01-01

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

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

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Chitose Kurihara

2016-12-01

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

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

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

2009-11-12

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

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

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

2017-07-01

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

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

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Maria Abildgaard Steffensen

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

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

International Nuclear Information System (INIS)

Srivastava, Suresh C.

2005-01-01

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

Presumed Acute Adenoviral Dacryoadenitis Associated with ...

African Journals Online (AJOL)

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

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

International Nuclear Information System (INIS)

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

2008-01-01

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

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

DEFF Research Database (Denmark)

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

2009-01-01

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

Use of adenoviral vectors as veterinary vaccines.

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

2005-10-01

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

Vector-borne disease intelligence: Strategies to deal with disease burden and threats

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Marieta eBraks

2014-12-01

Full Text Available Owing to the complex nature of vector-borne diseases, whereby monitoring of human case patients does not suffice, public health authorities experience challenges in surveillance and control of vector-borne diseases. Knowledge on the presence and distribution of vectors and the pathogens they transmit is vital to a risk assessment process to permit effective early warning, surveillance and control of vector-borne diseases. Upon accepting this reality, public health authorities face the phenomenon of an exponential rise in the number of possible surveillance targets and how to decide which are essential. Here, . we propose a comprehensive approach that integrates three surveillance strategies: population-based surveillance, disease-based surveillance and context-based surveillance for EU member states to tailor the best surveillance strategy for control of vector-borne diseases in their geographic region. By classifying the surveillance structure into 5 different contexts, we hope to provide guidance in optimizing surveillance efforts. Contextual surveillance strategies for vector-borne diseases entail combining organization and data collection approaches that result in disease intelligence rather than a preset static structure.

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

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Shailbala Singh

2014-10-01

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

Gene therapy in the inner ear using adenovirus vectors.

Science.gov (United States)

Husseman, Jacob; Raphael, Yehoash

2009-01-01

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

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

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

2015-09-22

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

Dynamic Price Vector Formation Model-Based Automatic Demand Response Strategy for PV-Assisted EV Charging Stations

Energy Technology Data Exchange (ETDEWEB)

Chen, Qifang; Wang, Fei; Hodge, Bri-Mathias; Zhang, Jianhua; Li, Zhigang; Shafie-Khah, Miadreza; Catalao, Joao P. S.

2017-11-01

A real-time price (RTP)-based automatic demand response (ADR) strategy for PV-assisted electric vehicle (EV) Charging Station (PVCS) without vehicle to grid is proposed. The charging process is modeled as a dynamic linear program instead of the normal day-ahead and real-time regulation strategy, to capture the advantages of both global and real-time optimization. Different from conventional price forecasting algorithms, a dynamic price vector formation model is proposed based on a clustering algorithm to form an RTP vector for a particular day. A dynamic feasible energy demand region (DFEDR) model considering grid voltage profiles is designed to calculate the lower and upper bounds. A deduction method is proposed to deal with the unknown information of future intervals, such as the actual stochastic arrival and departure times of EVs, which make the DFEDR model suitable for global optimization. Finally, both the comparative cases articulate the advantages of the developed methods and the validity in reducing electricity costs, mitigating peak charging demand, and improving PV self-consumption of the proposed strategy are verified through simulation scenarios.

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

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Daniel M Appledorn

2010-03-01

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

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

DEFF Research Database (Denmark)

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

2012-01-01

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

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

Science.gov (United States)

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

2013-08-01

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

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

Science.gov (United States)

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

2016-03-23

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

A stable RNA virus-based vector for citrus trees

International Nuclear Information System (INIS)

Folimonov, Alexey S.; Folimonova, Svetlana Y.; Bar-Joseph, Moshe; Dawson, William O.

2007-01-01

Virus-based vectors are important tools in plant molecular biology and plant genomics. A number of vectors based on viruses that infect herbaceous plants are in use for expression or silencing of genes in plants as well as screening unknown sequences for function. Yet there is a need for useful virus-based vectors for woody plants, which demand much greater stability because of the longer time required for systemic infection and analysis. We examined several strategies to develop a Citrus tristeza virus (CTV)-based vector for transient expression of foreign genes in citrus trees using a green fluorescent protein (GFP) as a reporter. These strategies included substitution of the p13 open reading frame (ORF) by the ORF of GFP, construction of a self-processing fusion of GFP in-frame with the major coat protein (CP), or expression of the GFP ORF as an extra gene from a subgenomic (sg) mRNA controlled either by a duplicated CTV CP sgRNA controller element (CE) or an introduced heterologous CE of Beet yellows virus. Engineered vector constructs were examined for replication, encapsidation, GFP expression during multiple passages in protoplasts, and for their ability to infect, move, express GFP, and be maintained in citrus plants. The most successful vectors based on the 'add-a-gene' strategy have been unusually stable, continuing to produce GFP fluorescence after more than 4 years in citrus trees

A universal mini-vector and an annealing of PCR products (APP)-based cloning strategy for convenient molecular biological manipulations.

Science.gov (United States)

Liu, Xia; Li, Tuoping; Hart, Darren J; Gao, Song; Wang, Hongling; Gao, Herui; Xu, Shumin; Zhang, Yifeng; Liu, Yifei; An, Yingfeng

2018-03-18

Currently, the most widely used strategies for molecular cloning are sticky-end ligation-based cloning, TA cloning, blunt-end ligation-based cloning and ligase-independent cloning. In this study we have developed a novel mini-vector pANY1 which can simultaneously meet the requirements of all these cloning strategies. In addition, the selection of appropriate restriction digestion sites is difficult in some cases because of the presence of internal sites. In this study, an annealing of PCR products (APP)-based sticky-end cloning strategy was introduced to avoid this issue. Additionally, false positives occur during molecular cloning, which increases the workload of isolating positive clones. The plasmid pANY1 contains a ccdB cassette between multiple cloning sites, which efficiently avoids these false positives. Therefore, this mini-vector should serve as a useful tool with wide applications in biosciences, agriculture, food technologies, etc. Copyright © 2018 Elsevier Inc. All rights reserved.

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

Directory of Open Access Journals (Sweden)

Anitra L Farrow

2014-08-01

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

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

Directory of Open Access Journals (Sweden)

Korson Mark

2007-04-01

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

Adenoviral Gene Delivery to Primary Human Cutaneous Cells and Burn Wounds

OpenAIRE

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

2006-01-01

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

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.

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

International Nuclear Information System (INIS)

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

2012-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2012-01-15

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

Characterization of infectivity of knob-modified adenoviral vectors in glioma

NARCIS (Netherlands)

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

2008-01-01

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

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

Science.gov (United States)

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.

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

Energy Technology Data Exchange (ETDEWEB)

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

2012-10-25

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

Reactivation of presumed adenoviral keratitis after laser in situ keratomileusis.

Science.gov (United States)

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

2002-04-01

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

[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.

Vaccination strategies for SIR vector-transmitted diseases.

Science.gov (United States)

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

2014-08-01

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

Desingularization strategies for three-dimensional vector fields

CERN Document Server

Torres, Felipe Cano

1987-01-01

For a vector field #3, where Ai are series in X, the algebraic multiplicity measures the singularity at the origin. In this research monograph several strategies are given to make the algebraic multiplicity of a three-dimensional vector field decrease, by means of permissible blowing-ups of the ambient space, i.e. transformations of the type xi=x'ix1, 2s. A logarithmic point of view is taken, marking the exceptional divisor of each blowing-up and by considering only the vector fields which are tangent to this divisor, instead of the whole tangent sheaf. The first part of the book is devoted to the logarithmic background and to the permissible blowing-ups. The main part corresponds to the control of the algorithms for the desingularization strategies by means of numerical invariants inspired by Hironaka's characteristic polygon. Only basic knowledge of local algebra and algebraic geometry is assumed of the reader. The pathologies we find in the reduction of vector fields are analogous to pathologies in the pro...

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

Directory of Open Access Journals (Sweden)

Alnawaz Rehemtulla

2002-01-01

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

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...

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

NARCIS (Netherlands)

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

2005-01-01

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

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

Directory of Open Access Journals (Sweden)

Gauldie Jack

2010-12-01

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

Space Vector Pulse Width Modulation Strategy for Single-Phase Three-Level CIC T-source Inverter

DEFF Research Database (Denmark)

Shults, Tatiana E.; Husev, Oleksandr O.; Blaabjerg, Frede

2016-01-01

This paper presents a novel space vector pulse-width modulation strategy for a single-phase three-level buck-boost inverter based on an impedance-source network. The case study system is based on T-source inverter with continuous input current. To demonstrate the improved performance of the inver......This paper presents a novel space vector pulse-width modulation strategy for a single-phase three-level buck-boost inverter based on an impedance-source network. The case study system is based on T-source inverter with continuous input current. To demonstrate the improved performance...... of the inverter, the strategy was compared the traditional pulse-width modulation. It is shown that the approach proposed has fewer switching states and does not suffer from neutral point misbalance....

Parameter Improved Particle Swarm Optimization Based Direct-Current Vector Control Strategy for Solar PV System

Directory of Open Access Journals (Sweden)

NAMMALVAR, P.

2018-02-01

Full Text Available This paper projects Parameter Improved Particle Swarm Optimization (PIPSO based direct current vector control technology for the integration of photovoltaic array in an AC micro-grid to enhance the system performance and stability. A photovoltaic system incorporated with AC micro-grid is taken as the pursuit of research study. The test system features two power converters namely, PV side converter which consists of DC-DC boost converter with Perturbation and Observe (P&O MPPT control to reap most extreme power from the PV array, and grid side converter which consists of Grid Side-Voltage Source Converter (GS-VSC with proposed direct current vector control strategy. The gain of the proposed controller is chosen from a set of three values obtained using apriori test and tuned through the PIPSO algorithm so that the Integral of Time multiplied Absolute Error (ITAE between the actual and the desired DC link capacitor voltage reaches a minimum and allows the system to extract maximum power from PV system, whereas the existing d-q control strategy is found to perform slowly to control the DC link voltage under varying solar insolation and load fluctuations. From simulation results, it is evident that the proposed optimal control technique provides robust control and improved efficiency.

Molecular epidemiology of adenoviral keratoconjunctivitis in Saudi Arabia.

Science.gov (United States)

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

2010-10-24

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

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

International Nuclear Information System (INIS)

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

2002-01-01

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

High stability vector-based direct power control for DFIG-based wind turbine

DEFF Research Database (Denmark)

Zhu, Rongwu; Chen, Zhe; Wu, Xiaojie

2015-01-01

This paper proposes an improved vector-based direct power control (DPC) strategy for the doubly-fed induction generator (DFIG)-based wind energy conversion system. Based on the small signal model, the proposed DPC improves the stability of the DFIG, and avoids the DFIG operating in the marginal...

Future prospects for the development of cost-effective Adenovirus vaccines

DEFF Research Database (Denmark)

Fougeroux, Cyrielle; Holst, Peter J

2017-01-01

-vectored vaccine technology with a focus on adenoviral-based vaccines. Adenovirus (Ad) vaccines have proven to be efficient in military vaccinations against Ad4 and Ad7 and as highly efficient vectored vaccines against rabies. The question of how other adenovirus-based vaccines can become as efficient...... as the rabies vaccine is the underlying theme in this review. Here, we will first give an overview of the basic properties of vectored vaccines, followed by an introduction to the characteristics of adenoviral vectors and previously tested modifications of the vector backbone and expression cassettes...

Construction and applications of exon-trapping gene-targeting vectors with a novel strategy for negative selection.

Science.gov (United States)

Saito, Shinta; Ura, Kiyoe; Kodama, Miho; Adachi, Noritaka

2015-06-30

Targeted gene modification by homologous recombination provides a powerful tool for studying gene function in cells and animals. In higher eukaryotes, non-homologous integration of targeting vectors occurs several orders of magnitude more frequently than does targeted integration, making the gene-targeting technology highly inefficient. For this reason, negative-selection strategies have been employed to reduce the number of drug-resistant clones associated with non-homologous vector integration, particularly when artificial nucleases to introduce a DNA break at the target site are unavailable or undesirable. As such, an exon-trap strategy using a promoterless drug-resistance marker gene provides an effective way to counterselect non-homologous integrants. However, constructing exon-trapping targeting vectors has been a time-consuming and complicated process. By virtue of highly efficient att-mediated recombination, we successfully developed a simple and rapid method to construct plasmid-based vectors that allow for exon-trapping gene targeting. These exon-trap vectors were useful in obtaining correctly targeted clones in mouse embryonic stem cells and human HT1080 cells. Most importantly, with the use of a conditionally cytotoxic gene, we further developed a novel strategy for negative selection, thereby enhancing the efficiency of counterselection for non-homologous integration of exon-trap vectors. Our methods will greatly facilitate exon-trapping gene-targeting technologies in mammalian cells, particularly when combined with the novel negative selection strategy.

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

Energy Technology Data Exchange (ETDEWEB)

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

2002-07-01

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

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

International Nuclear Information System (INIS)

Campos, Samuel K.; Barry, Michael A.

2006-01-01

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

Malaria vector control: current and future strategies

NARCIS (Netherlands)

Takken, W.; Knols, B.G.J.

2009-01-01

The recently announced call for malaria eradication represents a new page in the history of this disease. This has been triggered by remarkable reductions in malaria resulting from combined application of effective drugs and vector control. However, this strategy is threatened by development of

Novel Strategy to Control Transgene Expression Mediated by a Sendai Virus-Based Vector Using a Nonstructural C Protein and Endogenous MicroRNAs.

Directory of Open Access Journals (Sweden)

Masayuki Sano

Full Text Available Tissue-specific control of gene expression is an invaluable tool for studying various biological processes and medical applications. Efficient regulatory systems have been utilized to control transgene expression in various types of DNA viral or integrating viral vectors. However, existing regulatory systems are difficult to transfer into negative-strand RNA virus vector platforms because of significant differences in their transcriptional machineries. In this study, we developed a novel strategy for regulating transgene expression mediated by a cytoplasmic RNA vector based on a replication-defective and persistent Sendai virus (SeVdp. Because of the capacity of Sendai virus (SeV nonstructural C proteins to specifically inhibit viral RNA synthesis, overexpression of C protein significantly reduced transgene expression mediated by SeVdp vectors. We found that SeV C overexpression concomitantly reduced SeVdp mRNA levels and genomic RNA synthesis. To control C expression, target sequences for an endogenous microRNA were incorporated into the 3' untranslated region of the C genes. Incorporation of target sequences for miR-21 into the SeVdp vector restored transgene expression in HeLa cells by decreasing C expression. Furthermore, the SeVdp vector containing target sequences for let-7a enabled cell-specific control of transgene expression in human fibroblasts and induced pluripotent stem cells. Our findings demonstrate that SeV C can be used as an effective regulator for controlling transgene expression. This strategy will contribute to efficient and less toxic SeVdp-mediated gene transfer in various biological applications.

A Wavelet Kernel-Based Primal Twin Support Vector Machine for Economic Development Prediction

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Fang Su

2013-01-01

Full Text Available Economic development forecasting allows planners to choose the right strategies for the future. This study is to propose economic development prediction method based on the wavelet kernel-based primal twin support vector machine algorithm. As gross domestic product (GDP is an important indicator to measure economic development, economic development prediction means GDP prediction in this study. The wavelet kernel-based primal twin support vector machine algorithm can solve two smaller sized quadratic programming problems instead of solving a large one as in the traditional support vector machine algorithm. Economic development data of Anhui province from 1992 to 2009 are used to study the prediction performance of the wavelet kernel-based primal twin support vector machine algorithm. The comparison of mean error of economic development prediction between wavelet kernel-based primal twin support vector machine and traditional support vector machine models trained by the training samples with the 3–5 dimensional input vectors, respectively, is given in this paper. The testing results show that the economic development prediction accuracy of the wavelet kernel-based primal twin support vector machine model is better than that of traditional support vector machine.

Link-Based Similarity Measures Using Reachability Vectors

Directory of Open Access Journals (Sweden)

Seok-Ho Yoon

2014-01-01

Full Text Available We present a novel approach for computing link-based similarities among objects accurately by utilizing the link information pertaining to the objects involved. We discuss the problems with previous link-based similarity measures and propose a novel approach for computing link based similarities that does not suffer from these problems. In the proposed approach each target object is represented by a vector. Each element of the vector corresponds to all the objects in the given data, and the value of each element denotes the weight for the corresponding object. As for this weight value, we propose to utilize the probability of reaching from the target object to the specific object, computed using the “Random Walk with Restart” strategy. Then, we define the similarity between two objects as the cosine similarity of the two vectors. In this paper, we provide examples to show that our approach does not suffer from the aforementioned problems. We also evaluate the performance of the proposed methods in comparison with existing link-based measures, qualitatively and quantitatively, with respect to two kinds of data sets, scientific papers and Web documents. Our experimental results indicate that the proposed methods significantly outperform the existing measures.

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

Science.gov (United States)

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

2014-01-01

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

Multi-mode energy management strategy for fuel cell electric vehicles based on driving pattern identification using learning vector quantization neural network algorithm

Science.gov (United States)

Song, Ke; Li, Feiqiang; Hu, Xiao; He, Lin; Niu, Wenxu; Lu, Sihao; Zhang, Tong

2018-06-01

The development of fuel cell electric vehicles can to a certain extent alleviate worldwide energy and environmental issues. While a single energy management strategy cannot meet the complex road conditions of an actual vehicle, this article proposes a multi-mode energy management strategy for electric vehicles with a fuel cell range extender based on driving condition recognition technology, which contains a patterns recognizer and a multi-mode energy management controller. This paper introduces a learning vector quantization (LVQ) neural network to design the driving patterns recognizer according to a vehicle's driving information. This multi-mode strategy can automatically switch to the genetic algorithm optimized thermostat strategy under specific driving conditions in the light of the differences in condition recognition results. Simulation experiments were carried out based on the model's validity verification using a dynamometer test bench. Simulation results show that the proposed strategy can obtain better economic performance than the single-mode thermostat strategy under dynamic driving conditions.

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

International Nuclear Information System (INIS)

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

2004-01-01

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

A sight on the current nanoparticle-based gene delivery vectors

Science.gov (United States)

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

2014-05-01

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

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

Directory of Open Access Journals (Sweden)

Pavlo L Kovalenko

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

Targeting of non-dominant antigens as a vaccine strategy to broaden T-cell responses during chronic viral infection

DEFF Research Database (Denmark)

Holst, Peter Johannes; Jensen, Benjamin Anderschou Holbech; Ragonnaud, Emeline

2015-01-01

In this study, we compared adenoviral vaccine vectors with the capacity to induce equally potent immune responses against non-dominant and immunodominant epitopes of murine lymphocytic choriomeningitis virus (LCMV). Our results demonstrate that vaccination targeting non-dominant epitopes facilita......In this study, we compared adenoviral vaccine vectors with the capacity to induce equally potent immune responses against non-dominant and immunodominant epitopes of murine lymphocytic choriomeningitis virus (LCMV). Our results demonstrate that vaccination targeting non-dominant epitopes...... was lost over time in T cells specific for the dominant T cell epitopes, and these cells were fully capable of expanding in response to a new viral challenge. Overall, our data suggests a potential for broadening of the antiviral CD8+ T-cell response by selecting non-dominant antigens to be targeted...

Showing the Way: Oncolytic Adenoviruses as Chaperones of Immunostimulatory Adjuncts

Directory of Open Access Journals (Sweden)

Jing Li Huang

2016-09-01

Full Text Available Oncolytic adenoviruses (OAds are increasingly recognized as vectors for immunotherapy in the treatment of various solid tumors. The myriads of advantages of using adenovirus include targeted specificity upon infection and selective replication, which lead to localized viral burst, exponential spread of OAds, and antitumor effect. OAds can also induce a strong immune reaction due to the massive release of tumor antigens upon cytolysis and the presence of viral antigens. This review will highlight recent advances in adenoviral vectors expressing immunostimulatory effectors, such as GM-CSF (granulocyte macrophage colony-stimulating factor, interferon-α, interleukin-12, and CD40L. We will also discuss the combination of OAds with other immunotherapeutic strategies and describe the current understanding of how adenoviral vectors interact with the immune system to eliminate cancer cells.

Showing the Way: Oncolytic Adenoviruses as Chaperones of Immunostimulatory Adjuncts.

Science.gov (United States)

Huang, Jing Li; LaRocca, Christopher J; Yamamoto, Masato

2016-09-19

Oncolytic adenoviruses (OAds) are increasingly recognized as vectors for immunotherapy in the treatment of various solid tumors. The myriads of advantages of using adenovirus include targeted specificity upon infection and selective replication, which lead to localized viral burst, exponential spread of OAds, and antitumor effect. OAds can also induce a strong immune reaction due to the massive release of tumor antigens upon cytolysis and the presence of viral antigens. This review will highlight recent advances in adenoviral vectors expressing immunostimulatory effectors, such as GM-CSF (granulocyte macrophage colony-stimulating factor), interferon-α, interleukin-12, and CD40L. We will also discuss the combination of OAds with other immunotherapeutic strategies and describe the current understanding of how adenoviral vectors interact with the immune system to eliminate cancer cells.

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.

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

Science.gov (United States)

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

2014-01-01

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

An adaptive radiotherapy planning strategy for bladder cancer using deformation vector fields

International Nuclear Information System (INIS)

Vestergaard, Anne; Kallehauge, Jesper Folsted; Petersen, Jørgen Breede Baltzer; Høyer, Morten; Søndergaard, Jimmi; Muren, Ludvig Paul

2014-01-01

Purpose: Adaptive radiotherapy (ART) has considerable potential in treatment of bladder cancer due to large inter-fractional changes in shape and size of the target. The aim of this study was to compare our clinically applied method for plan library creation that involves manual bladder delineations (Clin-ART) with a method using the deformation vector fields (DVFs) resulting from intensity-based deformable image registrations (DVF-based ART). Materials and methods: The study included thirteen patients with urinary bladder cancer who had daily cone beam CTs (CBCTs) acquired for set-up. In both ART strategies investigated, three plan selection volumes were generated using the CBCTs from the first four fractions; in Clin-ART boolean combinations of delineated bladders were used, while the DVF-based strategy applied combinations of the mean and standard deviation of patient-specific DVFs. The volume ratios (VRs) of the course-averaged PTV for the two ART strategies relative the non-adaptive PTV were calculated. Results: Both Clin-ART and DVF-based ART considerably reduced the course-averaged PTV, compared to non-adaptive RT. The VR for DVF-based ART was lower than for Clin-ART (0.65 vs. 0.73; p < 0.01). Conclusions: DVF-based ART for bladder irradiation has a considerable normal tissue sparing potential surpassing our already highly conformal clinically applied ART strategy

An adaptive radiotherapy planning strategy for bladder cancer using deformation vector fields.

Science.gov (United States)

Vestergaard, Anne; Kallehauge, Jesper Folsted; Petersen, Jørgen Breede Baltzer; Høyer, Morten; Søndergaard, Jimmi; Muren, Ludvig Paul

2014-09-01

Adaptive radiotherapy (ART) has considerable potential in treatment of bladder cancer due to large inter-fractional changes in shape and size of the target. The aim of this study was to compare our clinically applied method for plan library creation that involves manual bladder delineations (Clin-ART) with a method using the deformation vector fields (DVFs) resulting from intensity-based deformable image registrations (DVF-based ART). The study included thirteen patients with urinary bladder cancer who had daily cone beam CTs (CBCTs) acquired for set-up. In both ART strategies investigated, three plan selection volumes were generated using the CBCTs from the first four fractions; in Clin-ART boolean combinations of delineated bladders were used, while the DVF-based strategy applied combinations of the mean and standard deviation of patient-specific DVFs. The volume ratios (VRs) of the course-averaged PTV for the two ART strategies relative the non-adaptive PTV were calculated. Both Clin-ART and DVF-based ART considerably reduced the course-averaged PTV, compared to non-adaptive RT. The VR for DVF-based ART was lower than for Clin-ART (0.65 vs. 0.73; p<0.01). DVF-based ART for bladder irradiation has a considerable normal tissue sparing potential surpassing our already highly conformal clinically applied ART strategy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

International Nuclear Information System (INIS)

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

2004-01-01

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

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

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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

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

NARCIS (Netherlands)

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

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

Gene therapy strategy to reduced bone marrow aplasia: evaluation in cynomolgus macaque exposed to a gamma total body irradiation

International Nuclear Information System (INIS)

Becard, N.

2003-01-01

The aim of this work was to assess whether direct intra-marrow injection of an adeno-viral vector expressing human IL-1α gene stimulates hematopoiesis in healthy non-irradiated and gamma irradiated cynomolgus macaques. In the first hand, we have evaluated the feasibility of this gene therapy strategy in two healthy non-irradiated macaques. In this work, we have observed an increase of neutrophil, monocyte and platelets in the two animals treated with the therapeutic construct. This effect was associated with no abnormal clinical side effect. On the other hand, we have evaluated this strategy in non-human primate exposed to a sublethal gamma irradiation. Two of three animals treated by the therapeutic construct reduced significantly the neutropenia, thrombocytopenia and anemia radio-induced. In conclusion, this gene therapy strategy gave a similar clinical benefit comparatively to systemic administration of huIL-1α but without severe side effect. (author) [fr

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

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Wan L

2016-12-01

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

Space vector modulation strategy for neutral-point voltage balancing in three-level inverter systems

DEFF Research Database (Denmark)

Choi, Uimin; Lee, Kyo Beum

2013-01-01

This study proposes a space vector modulation (SVM) strategy to balance the neutral-point voltage of three-level inverter systems. The proposed method is implemented by combining conventional symmetric SVM with nearest three-vector (NTV) modulation. The conventional SVM is converted to NTV...... modulation by properly adding or subtracting a minimum gate-on time. In addition, using this method, the switching frequency is reduced and a decrease of switching loss would be yielded. The neutral-point voltage is balanced by the proposed SVM strategy without additional hardware or complex calculations....... Simulation and experimental results are shown to verify the validity and feasibility of the proposed SVM strategy....

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.

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

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Priyanka Sharma

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

Gene delivery to pancreatic exocrine cells in vivo and in vitro

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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.

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

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Philipp Christian Seppelt

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

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

International Nuclear Information System (INIS)

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

1983-01-01

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

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

Science.gov (United States)

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

1998-11-20

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

Genetic manipulation of endosymbionts to control vector and vector borne diseases

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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

Genetic induction of the gastrin releasing peptide receptor on tumor cells for radiolabeled peptide binding

International Nuclear Information System (INIS)

Raben, David; Stackhouse, Murray; Buchsbaum, Donald J.; Mikheeva, Galeena; Khazaeli, M.B.; McLean, Stephanie; Kirkman, Richard; Krasnykh, Victor; Curiel, David T.

1996-01-01

Purpose/Objective: To improve upon existing radioimmunotherapy (RAIT) approaches, we have devised a strategy to genetically induce high levels of new membrane-associated receptors on human cancer cells targetable by radiolabeled peptides. In this context, we report successful adenoviral-mediated transduction of tumor cells to express the murine gastrin releasing peptide receptor (mGRPr) as demonstrated by 125 I-labeled bombesin binding. Materials and Methods: To demonstrate the feasibility of our strategy and to provide rapid proof of principle, we constructed a plasmid encoding the mGRPr gene. We cloned the mGRPr gene into the adenoviral shuttle vector pACMVpLpARS+ (F. Graham). We then utilized the methodology of adenovirus-polylysine-mediated transfection (AdpLmGRPr) to accomplish transient gene expression of mGRPr in two human cancer cell lines including A427 non-small cell lung cancer cells and HeLa cervical cancer cells. Murine GRPr expression was then measured by a live-cell binding assay using 125 I-labeled bombesin. In order to develop this strategy further, it was necessary to construct a vector that would be more efficient for in vivo transduction. In this regard, we constructed a recombinant adenoviral vector (AdCMVGRPr) encoding the mGRPr under the control of the CMV promoter based on in vivo homologous recombination methods. The recombinant shuttle vector containing mGRPr was co-transfected with the adenoviral rescue plasmid pJM17 into the E1A trans complementing cell line 293 allowing for derivation of replication-incompetent, recombinant adenoviral vector. Individual plaques were isolated and subjected to two further rounds of plaque purification. The identity of the virus was confirmed at each step by PCR employing primers for mGRPr. The absence of wild-type adenovirus was confirmed by PCR using primers to the adenoviral E1A gene. SKOV3.ip1 human ovarian cancer cells and MDA-MB-231 human breast cancer cells were transduced in vitro with AdCMVGRPr at

A Subdivision-Based Representation for Vector Image Editing.

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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.

Enhancement of the priming efficacy of DNA vaccines encoding dendritic cell-targeted antigens by synergistic toll-like receptor ligands

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Kornbluth Richard S

2009-08-01

Full Text Available Abstract Background Targeting of protein antigens to dendritic cells (DC via the DEC205 receptor enhances presentation of antigen-derived peptides on MHC-I and MHC-II molecules and, in the presence of costimulatory signals, antigen-specific immune responses. The immunogenicity and efficacy of DNA vaccination can also be enhanced by fusing the encoded antigen to single chain antibodies directed against DEC205. To further improve this strategy, we evaluated different toll-like receptor ligands (TLR and CD40 ligands (CD40L as adjuvants for DNA vaccines encoding a DEC205-single-chain antibody fused to the ovalbumin model antigen or HIV-1 Gag and assessed the priming efficacy of DNA in a DNA prime adenoviral vector boost immunization regimen. Results Mice were primed with the adjuvanted DEC-205 targeted DNA vaccines and boosted with adenoviral vectors encoding the same antigens. CD8+ T cell responses were determined after the adenoviral booster immunization, to determine how well the different DNA immunization regimens prime for the adenoviral boost. In the absence of adjuvants, targeting of DNA-encoded ovalbumin to DCs suppressed CD8+ T-cell responses after the adenoviral booster immunization. CD8+ T-cell responses to the DEC205 targeted DNA vaccines increased only slightly by adding either the TLR-9 ligand CpG, the TLR-3 ligand Poly I:C, or CD40 ligand expression plasmids. However, the combination of both TLR-ligands led to a strong enhancement of CD8+ T-cell responses compared to a non-targeted DNA vaccine. This finding was confirmed using HIV Gag as antigen. Conclusion Although DNA prime adenoviral vector boost immunizations belong to the strongest inducers of cytotoxic T cell responses in different animal models and humans, the CD8+ T cell responses can be further improved by targeting the DNA encoded antigen to DEC205 in the presence of synergistic TLR ligands CpG and Poly I:C.

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

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

2018-01-01

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

An Improved Ensemble of Random Vector Functional Link Networks Based on Particle Swarm Optimization with Double Optimization Strategy.

Science.gov (United States)

Ling, Qing-Hua; Song, Yu-Qing; Han, Fei; Yang, Dan; Huang, De-Shuang

2016-01-01

For ensemble learning, how to select and combine the candidate classifiers are two key issues which influence the performance of the ensemble system dramatically. Random vector functional link networks (RVFL) without direct input-to-output links is one of suitable base-classifiers for ensemble systems because of its fast learning speed, simple structure and good generalization performance. In this paper, to obtain a more compact ensemble system with improved convergence performance, an improved ensemble of RVFL based on attractive and repulsive particle swarm optimization (ARPSO) with double optimization strategy is proposed. In the proposed method, ARPSO is applied to select and combine the candidate RVFL. As for using ARPSO to select the optimal base RVFL, ARPSO considers both the convergence accuracy on the validation data and the diversity of the candidate ensemble system to build the RVFL ensembles. In the process of combining RVFL, the ensemble weights corresponding to the base RVFL are initialized by the minimum norm least-square method and then further optimized by ARPSO. Finally, a few redundant RVFL is pruned, and thus the more compact ensemble of RVFL is obtained. Moreover, in this paper, theoretical analysis and justification on how to prune the base classifiers on classification problem is presented, and a simple and practically feasible strategy for pruning redundant base classifiers on both classification and regression problems is proposed. Since the double optimization is performed on the basis of the single optimization, the ensemble of RVFL built by the proposed method outperforms that built by some single optimization methods. Experiment results on function approximation and classification problems verify that the proposed method could improve its convergence accuracy as well as reduce the complexity of the ensemble system.

Web-based GIS: the vector-borne disease airline importation risk (VBD-AIR) tool.

Science.gov (United States)

Huang, Zhuojie; Das, Anirrudha; Qiu, Youliang; Tatem, Andrew J

2012-08-14

Over the past century, the size and complexity of the air travel network has increased dramatically. Nowadays, there are 29.6 million scheduled flights per year and around 2.7 billion passengers are transported annually. The rapid expansion of the network increasingly connects regions of endemic vector-borne disease with the rest of the world, resulting in challenges to health systems worldwide in terms of vector-borne pathogen importation and disease vector invasion events. Here we describe the development of a user-friendly Web-based GIS tool: the Vector-Borne Disease Airline Importation Risk Tool (VBD-AIR), to help better define the roles of airports and airlines in the transmission and spread of vector-borne diseases. Spatial datasets on modeled global disease and vector distributions, as well as climatic and air network traffic data were assembled. These were combined to derive relative risk metrics via air travel for imported infections, imported vectors and onward transmission, and incorporated into a three-tier server architecture in a Model-View-Controller framework with distributed GIS components. A user-friendly web-portal was built that enables dynamic querying of the spatial databases to provide relevant information. The VBD-AIR tool constructed enables the user to explore the interrelationships among modeled global distributions of vector-borne infectious diseases (malaria. dengue, yellow fever and chikungunya) and international air service routes to quantify seasonally changing risks of vector and vector-borne disease importation and spread by air travel, forming an evidence base to help plan mitigation strategies. The VBD-AIR tool is available at http://www.vbd-air.com. VBD-AIR supports a data flow that generates analytical results from disparate but complementary datasets into an organized cartographical presentation on a web map for the assessment of vector-borne disease movements on the air travel network. The framework built provides a flexible

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

NARCIS (Netherlands)

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

2006-01-01

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

Predictive control strategies for wind turbine system based on permanent magnet synchronous generator.

Science.gov (United States)

Maaoui-Ben Hassine, Ikram; Naouar, Mohamed Wissem; Mrabet-Bellaaj, Najiba

2016-05-01

In this paper, Model Predictive Control and Dead-beat predictive control strategies are proposed for the control of a PMSG based wind energy system. The proposed MPC considers the model of the converter-based system to forecast the possible future behavior of the controlled variables. It allows selecting the voltage vector to be applied that leads to a minimum error by minimizing a predefined cost function. The main features of the MPC are low current THD and robustness against parameters variations. The Dead-beat predictive control is based on the system model to compute the optimum voltage vector that ensures zero-steady state error. The optimum voltage vector is then applied through Space Vector Modulation (SVM) technique. The main advantages of the Dead-beat predictive control are low current THD and constant switching frequency. The proposed control techniques are presented and detailed for the control of back-to-back converter in a wind turbine system based on PMSG. Simulation results (under Matlab-Simulink software environment tool) and experimental results (under developed prototyping platform) are presented in order to show the performances of the considered control strategies. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

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

DEFF Research Database (Denmark)

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

2013-01-01

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

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

Science.gov (United States)

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

2013-01-01

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

A unified triangle carrier based PWM strategy for three-phase N-level diode clamped inverters

DEFF Research Database (Denmark)

Li, Kai; Xie, Chuan; Wei, Min

2017-01-01

The triangle carrier based pulse width modulation (TCB-PWM) can be functionally equivalent to space vector base PWM (SVB-PWM). For multi-level inverter, it is very difficult to realize the SVB-PWM because its vector space is very complex. In this paper, a unified TCB-PWM strategy for three-phase ...

A simple and robust vector-based shRNA expression system used for RNA interference.

Science.gov (United States)

Wang, Xue-jun; Li, Ying; Huang, Hai; Zhang, Xiu-juan; Xie, Pei-wen; Hu, Wei; Li, Dan-dan; Wang, Sheng-qi

2013-01-01

RNA interference (RNAi) mediated by small interfering RNAs (siRNAs) or short hairpin RNAs (shRNAs) has become a powerful genetic tool for conducting functional studies. Previously, vector-based shRNA-expression strategies capable of inducing RNAi in viable cells have been developed, however, these vector systems have some disadvantages, either because they were error-prone or cost prohibitive. In this report we described the development of a simple, robust shRNA expression system utilizing 1 long oligonucleotide or 2 short oligonucleotides for half the cost of conventional shRNA construction methods and with a >95% cloning success rate. The shRNA loop sequence and stem structure were also compared and carefully selected for better RNAi efficiency. Furthermore, an easier strategy was developed based on isocaudomers which permit rapid combination of the most efficient promoter-shRNA cassettes. Finally, using this method, the conservative target sites for hepatitis B virus (HBV) knockdown were systemically screened and HBV antigen expression shown to be successfully suppressed in the presence of connected multiple shRNAs both in vitro and in vivo. This novel design describes an inexpensive and effective way to clone and express single or multiple shRNAs from the same vector with the capacity for potent and effective silencing of target genes.

Instruction-Based Clinical Eye-Tracking Study on the Visual Interpretation of Divergence: How Do Students Look at Vector Field Plots?

Science.gov (United States)

Klein, P.; Viiri, J.; Mozaffari, S.; Dengel, A.; Kuhn, J.

2018-01-01

Relating mathematical concepts to graphical representations is a challenging task for students. In this paper, we introduce two visual strategies to qualitatively interpret the divergence of graphical vector field representations. One strategy is based on the graphical interpretation of partial derivatives, while the other is based on the flux…

The effect of vector control strategy against Dengue transmission between mosquitoes and humans

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Chen-Xia Yang

2017-03-01

Full Text Available With the consideration of mechanism of prevention and control for the spread of dengue fever, a mathematical model of dengue fever dynamical transmission between mosquitoes and humans, incorporating a vector control strategy of impulsive culling of mosquitoes, is proposed in this paper. By using the comparison principle, Floquet theorem and some of analytical methods, we obtain the basic reproductive number $\\mathcal{R}_0$ for this infectious disease, which illustrates the stability of the disease-free periodic solution and the uniform persistence of the disease. Further, the explicit conditions determining the backward or forward bifurcation are obtained and the culling rate $\\phi$ is a major effect on the occurrence of backward bifurcation. Finally, numerical simulations are given to verify the correctness of theoretical results and the most efficiency of vector control strategy.

Instruction-based clinical eye-tracking study on the visual interpretation of divergence: How do students look at vector field plots?

Science.gov (United States)

Klein, P.; Viiri, J.; Mozaffari, S.; Dengel, A.; Kuhn, J.

2018-06-01

Relating mathematical concepts to graphical representations is a challenging task for students. In this paper, we introduce two visual strategies to qualitatively interpret the divergence of graphical vector field representations. One strategy is based on the graphical interpretation of partial derivatives, while the other is based on the flux concept. We test the effectiveness of both strategies in an instruction-based eye-tracking study with N =41 physics majors. We found that students' performance improved when both strategies were introduced (74% correct) instead of only one strategy (64% correct), and students performed best when they were free to choose between the two strategies (88% correct). This finding supports the idea of introducing multiple representations of a physical concept to foster student understanding. Relevant eye-tracking measures demonstrate that both strategies imply different visual processing of the vector field plots, therefore reflecting conceptual differences between the strategies. Advanced analysis methods further reveal significant differences in eye movements between the best and worst performing students. For instance, the best students performed predominantly horizontal and vertical saccades, indicating correct interpretation of partial derivatives. They also focused on smaller regions when they balanced positive and negative flux. This mixed-method research leads to new insights into student visual processing of vector field representations, highlights the advantages and limitations of eye-tracking methodologies in this context, and discusses implications for teaching and for future research. The introduction of saccadic direction analysis expands traditional methods, and shows the potential to discover new insights into student understanding and learning difficulties.

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

International Nuclear Information System (INIS)

Stillman, B.W.; Tamanoi, F.

1983-01-01

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

Great Ellipse Route Planning Based on Space Vector

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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.

Gene Therapy Vectors with Enhanced Transfection Based on Hydrogels Modified with Affinity Peptides

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Shepard, Jaclyn A.; Wesson, Paul J.; Wang, Christine E.; Stevans, Alyson C.; Holland, Samantha J.; Shikanov, Ariella; Grzybowski, Bartosz A.; Shea, Lonnie D.

2011-01-01

Regenerative strategies for damaged tissue aim to present biochemical cues that recruit and direct progenitor cell migration and differentiation. Hydrogels capable of localized gene delivery are being developed to provide a support for tissue growth, and as a versatile method to induce the expression of inductive proteins; however, the duration, level, and localization of expression isoften insufficient for regeneration. We thus investigated the modification of hydrogels with affinity peptides to enhance vector retention and increase transfection within the matrix. PEG hydrogels were modified with lysine-based repeats (K4, K8), which retained approximately 25% more vector than control peptides. Transfection increased 5- to 15-fold with K8 and K4 respectively, over the RDG control peptide. K8- and K4-modified hydrogels bound similar quantities of vector, yet the vector dissociation rate was reduced for K8, suggesting excessive binding that limited transfection. These hydrogels were subsequently applied to an in vitro co-culture model to induce NGF expression and promote neurite outgrowth. K4-modified hydrogels promoted maximal neurite outgrowth, likely due to retention of both the vector and the NGF. Thus, hydrogels modified with affinity peptides enhanced vector retention and increased gene delivery, and these hydrogels may provide a versatile scaffold for numerous regenerative medicine applications. PMID:21514659

Active-Flux-Based, V/f-with-Stabilizing-Loops Versus Sensorless Vector Control of IPMSM Drives

DEFF Research Database (Denmark)

Moldovan, Ana; Blaabjerg, Frede; Boldea, Ion

2011-01-01

. By this control strategy, a fast dynamic speed response, without steady state error and without speed or current regulators, for all AC machines is obtained. The second control method is a sensorless vector control strategy which also has been implemented and tested, just for comparison.......This paper proposes two control methods for Interior Permanent Magnet Synchronous Motor (IPMSM) Drives. The first one is a V/f control with two stabilizing loops: one loop based on active flux balance for voltage magnitude correction and a second, based on speed error, with voltage phase correction...

A simple and robust vector-based shRNA expression system used for RNA interference.

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Xue-jun Wang

Full Text Available BACKGROUND: RNA interference (RNAi mediated by small interfering RNAs (siRNAs or short hairpin RNAs (shRNAs has become a powerful genetic tool for conducting functional studies. Previously, vector-based shRNA-expression strategies capable of inducing RNAi in viable cells have been developed, however, these vector systems have some disadvantages, either because they were error-prone or cost prohibitive. RESULTS: In this report we described the development of a simple, robust shRNA expression system utilizing 1 long oligonucleotide or 2 short oligonucleotides for half the cost of conventional shRNA construction methods and with a >95% cloning success rate. The shRNA loop sequence and stem structure were also compared and carefully selected for better RNAi efficiency. Furthermore, an easier strategy was developed based on isocaudomers which permit rapid combination of the most efficient promoter-shRNA cassettes. Finally, using this method, the conservative target sites for hepatitis B virus (HBV knockdown were systemically screened and HBV antigen expression shown to be successfully suppressed in the presence of connected multiple shRNAs both in vitro and in vivo. CONCLUSION: This novel design describes an inexpensive and effective way to clone and express single or multiple shRNAs from the same vector with the capacity for potent and effective silencing of target genes.

An Autonomous Star Identification Algorithm Based on One-Dimensional Vector Pattern for Star Sensors.

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Luo, Liyan; Xu, Luping; Zhang, Hua

2015-07-07

In order to enhance the robustness and accelerate the recognition speed of star identification, an autonomous star identification algorithm for star sensors is proposed based on the one-dimensional vector pattern (one_DVP). In the proposed algorithm, the space geometry information of the observed stars is used to form the one-dimensional vector pattern of the observed star. The one-dimensional vector pattern of the same observed star remains unchanged when the stellar image rotates, so the problem of star identification is simplified as the comparison of the two feature vectors. The one-dimensional vector pattern is adopted to build the feature vector of the star pattern, which makes it possible to identify the observed stars robustly. The characteristics of the feature vector and the proposed search strategy for the matching pattern make it possible to achieve the recognition result as quickly as possible. The simulation results demonstrate that the proposed algorithm can effectively accelerate the star identification. Moreover, the recognition accuracy and robustness by the proposed algorithm are better than those by the pyramid algorithm, the modified grid algorithm, and the LPT algorithm. The theoretical analysis and experimental results show that the proposed algorithm outperforms the other three star identification algorithms.

Modelling strategies to break transmission of lymphatic filariasis--aggregation, adherence and vector competence greatly alter elimination.

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Irvine, M A; Reimer, L J; Njenga, S M; Gunawardena, S; Kelly-Hope, L; Bockarie, M; Hollingsworth, T D

2015-10-22

With ambitious targets to eliminate lymphatic filariasis over the coming years, there is a need to identify optimal strategies to achieve them in areas with different baseline prevalence and stages of control. Modelling can assist in identifying what data should be collected and what strategies are best for which scenarios. We develop a new individual-based, stochastic mathematical model of the transmission of lymphatic filariasis. We validate the model by fitting to a first time point and predicting future timepoints from surveillance data in Kenya and Sri Lanka, which have different vectors and different stages of the control programme. We then simulate different treatment scenarios in low, medium and high transmission settings, comparing once yearly mass drug administration (MDA) with more frequent MDA and higher coverage. We investigate the potential impact that vector control, systematic non-compliance and different levels of aggregation have on the dynamics of transmission and control. In all settings, increasing coverage from 65 to 80 % has a similar impact on control to treating twice a year at 65 % coverage, for fewer drug treatments being distributed. Vector control has a large impact, even at moderate levels. The extent of aggregation of parasite loads amongst a small portion of the population, which has been estimated to be highly variable in different settings, can undermine the success of a programme, particularly if high risk sub-communities are not accessing interventions. Even moderate levels of vector control have a large impact both on the reduction in prevalence and the maintenance of gains made during MDA, even when parasite loads are highly aggregated, and use of vector control is at moderate levels. For the same prevalence, differences in aggregation and adherence can result in very different dynamics. The novel analysis of a small amount of surveillance data and resulting simulations highlight the need for more individual level data to be

Local Patch Vectors Encoded by Fisher Vectors for Image Classification

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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.

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

International Nuclear Information System (INIS)

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

1999-01-01

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

Multigenic lentiviral vectors for combined and tissue-specific expression of miRNA- and protein-based antiangiogenic factors

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Anne Louise Askou

Full Text Available Lentivirus-based gene delivery vectors carrying multiple gene cassettes are powerful tools in gene transfer studies and gene therapy, allowing coexpression of multiple therapeutic factors and, if desired, fluorescent reporters. Current strategies to express transgenes and microRNA (miRNA clusters from a single vector have certain limitations that affect transgene expression levels and/or vector titers. In this study, we describe a novel vector design that facilitates combined expression of therapeutic RNA- and protein-based antiangiogenic factors as well as a fluorescent reporter from back-to-back RNApolII-driven expression cassettes. This configuration allows effective production of intron-embedded miRNAs that are released upon transduction of target cells. Exploiting such multigenic lentiviral vectors, we demonstrate robust miRNA-directed downregulation of vascular endothelial growth factor (VEGF expression, leading to reduced angiogenesis, and parallel impairment of angiogenic pathways by codelivering the gene encoding pigment epithelium-derived factor (PEDF. Notably, subretinal injections of lentiviral vectors reveal efficient retinal pigment epithelium-specific gene expression driven by the VMD2 promoter, verifying that multigenic lentiviral vectors can be produced with high titers sufficient for in vivo applications. Altogether, our results suggest the potential applicability of combined miRNA- and protein-encoding lentiviral vectors in antiangiogenic gene therapy, including new combination therapies for amelioration of age-related macular degeneration.

Treatment for Retinopathy of Prematurity in an Infant with Adenoviral Conjunctivitis

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Murat Gunay

2015-01-01

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

Delivery of viral vectors to tumor cells: extracellular transport, systemic distribution, and strategies for improvement.

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Wang, Yong; Yuan, Fan

2006-01-01

It is a challenge to deliver therapeutic genes to tumor cells using viral vectors because (i) the size of these vectors are close to or larger than the space between fibers in extracellular matrix and (ii) viral proteins are potentially toxic in normal tissues. In general, gene delivery is hindered by various physiological barriers to virus transport from the site of injection to the nucleus of tumor cells and is limited by normal tissue tolerance of toxicity determined by local concentrations of transgene products and viral proteins. To illustrate the obstacles encountered in the delivery and yet limit the scope of discussion, this review focuses only on extracellular transport in solid tumors and distribution of viral vectors in normal organs after they are injected intravenously or intratumorally. This review also discusses current strategies for improving intratumoral transport and specificity of viral vectors.

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

DEFF Research Database (Denmark)

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

2017-01-01

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

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

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Kim SY

2017-10-01

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

Disturbance observer based current controller for vector controlled IM drives

DEFF Research Database (Denmark)

Teodorescu, Remus; Dal, Mehmet

2008-01-01

induction motor (IM) drives. The control design, based on synchronously rotating d-q frame model of the machine, has a simple structure that combines the proportional portion of a conventional PI control and output of the observer. The observer is predicted to estimate the disturbances caused by parameters...... coupling effects and increase robustness against parameters change without requiring any other compensation strategies. The experimental implementation results are provided to demonstrate validity and performance of the proposed control scheme.......In order to increase the accuracy of the current control loop, usually, well known parameter compensation and/or cross decoupling techniques are employed for advanced ac drives. In this paper, instead of using these techniques an observer-based current controller is proposed for vector controlled...

Construction of permanently inducible miRNA-based expression vectors using site-specific recombinases

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Garwick-Coppens Sara E

2011-11-01

Full Text Available Abstract Background RNA interference (RNAi is a conserved gene silencing mechanism mediated by small inhibitory microRNAs (miRNAs. Promoter-driven miRNA expression vectors have emerged as important tools for delivering natural or artificially designed miRNAs to eukaryotic cells and organisms. Such systems can be used to query the normal or pathogenic functions of natural miRNAs or messenger RNAs, or to therapeutically silence disease genes. Results As with any molecular cloning procedure, building miRNA-based expression constructs requires a time investment and some molecular biology skills. To improve efficiency and accelerate the construction process, we developed a method to rapidly generate miRNA expression vectors using recombinases instead of more traditional cut-and-paste molecular cloning techniques. In addition to streamlining the construction process, our cloning strategy provides vectors with added versatility. In our system, miRNAs can be constitutively expressed from the U6 promoter, or inducibly expressed by Cre recombinase. We also engineered a built-in mechanism to destroy the vector with Flp recombinase, if desired. Finally, to further simplify the construction process, we developed a software package that automates the prediction and design of optimal miRNA sequences using our system. Conclusions We designed and tested a modular system to rapidly clone miRNA expression cassettes. Our strategy reduces the hands-on time required to successfully generate effective constructs, and can be implemented in labs with minimal molecular cloning expertise. This versatile system provides options that permit constitutive or inducible miRNA expression, depending upon the needs of the end user. As such, it has utility for basic or translational applications.

A Plasmodium Promiscuous T Cell Epitope Delivered within the Ad5 Hexon Protein Enhances the Protective Efficacy of a Protein Based Malaria Vaccine.

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Jairo Andres Fonseca

Full Text Available A malaria vaccine is a public health priority. In order to produce an effective vaccine, a multistage approach targeting both the blood and the liver stage infection is desirable. The vaccine candidates also need to induce balanced immune responses including antibodies, CD4+ and CD8+ T cells. Protein-based subunit vaccines like RTS,S are able to induce strong antibody response but poor cellular reactivity. Adenoviral vectors have been effective inducing protective CD8+ T cell responses in several models including malaria; nonetheless this vaccine platform exhibits a limited induction of humoral immune responses. Two approaches have been used to improve the humoral immunogenicity of recombinant adenovirus vectors, the use of heterologous prime-boost regimens with recombinant proteins or the genetic modification of the hypervariable regions (HVR of the capsid protein hexon to express B cell epitopes of interest. In this study, we describe the development of capsid modified Ad5 vectors that express a promiscuous Plasmodium yoelii T helper epitope denominated PyT53 within the hexon HVR2 region. Several regimens were tested in mice to determine the relevance of the hexon modification in enhancing protective immune responses induced by the previously described protein-based multi-stage experimental vaccine PyCMP. A heterologous prime-boost immunization regime that combines a hexon modified vector with transgenic expression of PyCMP followed by protein immunizations resulted in the induction of robust antibody and cellular immune responses in comparison to a similar regimen that includes a vector with unmodified hexon. These differences in immunogenicity translated into a better protective efficacy against both the hepatic and red blood cell stages of P. yoelii. To our knowledge, this is the first time that a hexon modification is used to deliver a promiscuous T cell epitope. Our data support the use of such modification to enhance the immunogenicity

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

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Xianqi Zhao

2015-06-01

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

Determinants of Health Service Responsiveness in Community-Based Vector Surveillance for Chagas Disease in Guatemala, El Salvador, and Honduras

Science.gov (United States)

Hashimoto, Ken; Zúniga, Concepción; Romero, Eduardo; Morales, Zoraida; Maguire, James H.

2015-01-01

Background Central American countries face a major challenge in the control of Triatoma dimidiata, a widespread vector of Chagas disease that cannot be eliminated. The key to maintaining the risk of transmission of Trypanosoma cruzi at lowest levels is to sustain surveillance throughout endemic areas. Guatemala, El Salvador, and Honduras integrated community-based vector surveillance into local health systems. Community participation was effective in detection of the vector, but some health services had difficulty sustaining their response to reports of vectors from the population. To date, no research has investigated how best to maintain and reinforce health service responsiveness, especially in resource-limited settings. Methodology/Principal Findings We reviewed surveillance and response records of 12 health centers in Guatemala, El Salvador, and Honduras from 2008 to 2012 and analyzed the data in relation to the volume of reports of vector infestation, local geography, demography, human resources, managerial approach, and results of interviews with health workers. Health service responsiveness was defined as the percentage of households that reported vector infestation for which the local health service provided indoor residual spraying of insecticide or educational advice. Eight potential determinants of responsiveness were evaluated by linear and mixed-effects multi-linear regression. Health service responsiveness (overall 77.4%) was significantly associated with quarterly monitoring by departmental health offices. Other potential determinants of responsiveness were not found to be significant, partly because of short- and long-term strategies, such as temporary adjustments in manpower and redistribution of tasks among local participants in the effort. Conclusions/Significance Consistent monitoring within the local health system contributes to sustainability of health service responsiveness in community-based vector surveillance of Chagas disease. Even with

Determinants of Health Service Responsiveness in Community-Based Vector Surveillance for Chagas Disease in Guatemala, El Salvador, and Honduras.

Science.gov (United States)

Hashimoto, Ken; Zúniga, Concepción; Romero, Eduardo; Morales, Zoraida; Maguire, James H

2015-01-01

Central American countries face a major challenge in the control of Triatoma dimidiata, a widespread vector of Chagas disease that cannot be eliminated. The key to maintaining the risk of transmission of Trypanosoma cruzi at lowest levels is to sustain surveillance throughout endemic areas. Guatemala, El Salvador, and Honduras integrated community-based vector surveillance into local health systems. Community participation was effective in detection of the vector, but some health services had difficulty sustaining their response to reports of vectors from the population. To date, no research has investigated how best to maintain and reinforce health service responsiveness, especially in resource-limited settings. We reviewed surveillance and response records of 12 health centers in Guatemala, El Salvador, and Honduras from 2008 to 2012 and analyzed the data in relation to the volume of reports of vector infestation, local geography, demography, human resources, managerial approach, and results of interviews with health workers. Health service responsiveness was defined as the percentage of households that reported vector infestation for which the local health service provided indoor residual spraying of insecticide or educational advice. Eight potential determinants of responsiveness were evaluated by linear and mixed-effects multi-linear regression. Health service responsiveness (overall 77.4%) was significantly associated with quarterly monitoring by departmental health offices. Other potential determinants of responsiveness were not found to be significant, partly because of short- and long-term strategies, such as temporary adjustments in manpower and redistribution of tasks among local participants in the effort. Consistent monitoring within the local health system contributes to sustainability of health service responsiveness in community-based vector surveillance of Chagas disease. Even with limited resources, countries can improve health service

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

Vision-Based Perception and Classification of Mosquitoes Using Support Vector Machine

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Masataka Fuchida

2017-01-01

Full Text Available The need for a novel automated mosquito perception and classification method is becoming increasingly essential in recent years, with steeply increasing number of mosquito-borne diseases and associated casualties. There exist remote sensing and GIS-based methods for mapping potential mosquito inhabitants and locations that are prone to mosquito-borne diseases, but these methods generally do not account for species-wise identification of mosquitoes in closed-perimeter regions. Traditional methods for mosquito classification involve highly manual processes requiring tedious sample collection and supervised laboratory analysis. In this research work, we present the design and experimental validation of an automated vision-based mosquito classification module that can deploy in closed-perimeter mosquito inhabitants. The module is capable of identifying mosquitoes from other bugs such as bees and flies by extracting the morphological features, followed by support vector machine-based classification. In addition, this paper presents the results of three variants of support vector machine classifier in the context of mosquito classification problem. This vision-based approach to the mosquito classification problem presents an efficient alternative to the conventional methods for mosquito surveillance, mapping and sample image collection. Experimental results involving classification between mosquitoes and a predefined set of other bugs using multiple classification strategies demonstrate the efficacy and validity of the proposed approach with a maximum recall of 98%.

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

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

2006-01-01

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

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

Directory of Open Access Journals (Sweden)

Wenli Zhang

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

Optimizing torque vectoring strategies for an electric vehicle concept

NARCIS (Netherlands)

van Boekel, J.J.P.; Besselink, I.J.M.; Nijmeijer, H.; Rauh, J.; Knorr, S.; Durnberger, J.

2013-01-01

As part of the internship project carried out at Daimler AG, this report describes the application and optimization of torque vectoring on a research vehicle based on the Mercedes- Benz SLS AMG E-CELL. A concise introduction is given regarding the MATLAB scripts and Simulink models that were used

Application of eco-friendly tools and eco-bio-social strategies to control dengue vectors in urban and peri-urban settings in Thailand.

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Kittayapong, Pattamaporn; Thongyuan, Suporn; Olanratmanee, Phanthip; Aumchareoun, Worawit; Koyadun, Surachart; Kittayapong, Rungrith; Butraporn, Piyarat

2012-12-01

Dengue is considered one of the most important vector-borne diseases in Thailand. Its incidence is increasing despite routine implementation of national dengue control programmes. This study, conducted during 2010, aimed to demonstrate an application of integrated, community-based, eco-bio-social strategies in combination with locally-produced eco-friendly vector control tools in the dengue control programme, emphasizing urban and peri-urban settings in eastern Thailand. Three different community settings were selected and were randomly assigned to intervention and control clusters. Key community leaders and relevant governmental authorities were approached to participate in this intervention programme. Ecohealth volunteers were identified and trained in each study community. They were selected among active community health volunteers and were trained by public health experts to conduct vector control activities in their own communities using environmental management in combination with eco-friendly vector control tools. These trained ecohealth volunteers carried out outreach health education and vector control during household visits. Management of public spaces and public properties, especially solid waste management, was efficiently carried out by local municipalities. Significant reduction in the pupae per person index in the intervention clusters when compared to the control ones was used as a proxy to determine the impact of this programme. Our community-based dengue vector control programme demonstrated a significant reduction in the pupae per person index during entomological surveys which were conducted at two-month intervals from May 2010 for the total of six months in the intervention and control clusters. The programme also raised awareness in applying eco-friendly vector control approaches and increased intersectoral and household participation in dengue control activities. An eco-friendly dengue vector control programme was successfully implemented in

Application of eco-friendly tools and eco-bio-social strategies to control dengue vectors in urban and peri-urban settings in Thailand

Science.gov (United States)

Kittayapong, Pattamaporn; Thongyuan, Suporn; Olanratmanee, Phanthip; Aumchareoun, Worawit; Koyadun, Surachart; Kittayapong, Rungrith; Butraporn, Piyarat

2012-01-01

Background Dengue is considered one of the most important vector-borne diseases in Thailand. Its incidence is increasing despite routine implementation of national dengue control programmes. This study, conducted during 2010, aimed to demonstrate an application of integrated, community-based, eco-bio-social strategies in combination with locally-produced eco-friendly vector control tools in the dengue control programme, emphasizing urban and peri-urban settings in eastern Thailand. Methodology Three different community settings were selected and were randomly assigned to intervention and control clusters. Key community leaders and relevant governmental authorities were approached to participate in this intervention programme. Ecohealth volunteers were identified and trained in each study community. They were selected among active community health volunteers and were trained by public health experts to conduct vector control activities in their own communities using environmental management in combination with eco-friendly vector control tools. These trained ecohealth volunteers carried out outreach health education and vector control during household visits. Management of public spaces and public properties, especially solid waste management, was efficiently carried out by local municipalities. Significant reduction in the pupae per person index in the intervention clusters when compared to the control ones was used as a proxy to determine the impact of this programme. Results Our community-based dengue vector control programme demonstrated a significant reduction in the pupae per person index during entomological surveys which were conducted at two-month intervals from May 2010 for the total of six months in the intervention and control clusters. The programme also raised awareness in applying eco-friendly vector control approaches and increased intersectoral and household participation in dengue control activities. Conclusion An eco-friendly dengue vector control

Comparison of four support-vector based function approximators

NARCIS (Netherlands)

de Kruif, B.J.; de Vries, Theodorus J.A.

2004-01-01

One of the uses of the support vector machine (SVM), as introduced in V.N. Vapnik (2000), is as a function approximator. The SVM and approximators based on it, approximate a relation in data by applying interpolation between so-called support vectors, being a limited number of samples that have been

Advances in Viral Vector-Based TRAIL Gene Therapy for Cancer

International Nuclear Information System (INIS)

Norian, Lyse A.; James, Britnie R.; Griffith, Thomas S.

2011-01-01

Numerous biologic approaches are being investigated as anti-cancer therapies in an attempt to induce tumor regression while circumventing the toxic side effects associated with standard chemo- or radiotherapies. Among these, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has shown particular promise in pre-clinical and early clinical trials, due to its preferential ability to induce apoptotic cell death in cancer cells and its minimal toxicity. One limitation of TRAIL use is the fact that many tumor types display an inherent resistance to TRAIL-induced apoptosis. To circumvent this problem, researchers have explored a number of strategies to optimize TRAIL delivery and to improve its efficacy via co-administration with other anti-cancer agents. In this review, we will focus on TRAIL-based gene therapy approaches for the treatment of malignancies. We will discuss the main viral vectors that are being used for TRAIL gene therapy and the strategies that are currently being attempted to improve the efficacy of TRAIL as an anti-cancer therapeutic

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...

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

Science.gov (United States)

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

2012-02-10

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

Efficient Vector-Based Forwarding for Underwater Sensor Networks

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Peng Xie

2010-01-01

Full Text Available Underwater Sensor Networks (UWSNs are significantly different from terrestrial sensor networks in the following aspects: low bandwidth, high latency, node mobility, high error probability, and 3-dimensional space. These new features bring many challenges to the network protocol design of UWSNs. In this paper, we tackle one fundamental problem in UWSNs: robust, scalable, and energy efficient routing. We propose vector-based forwarding (VBF, a geographic routing protocol. In VBF, the forwarding path is guided by a vector from the source to the target, no state information is required on the sensor nodes, and only a small fraction of the nodes is involved in routing. To improve the robustness, packets are forwarded in redundant and interleaved paths. Further, a localized and distributed self-adaptation algorithm allows the nodes to reduce energy consumption by discarding redundant packets. VBF performs well in dense networks. For sparse networks, we propose a hop-by-hop vector-based forwarding (HH-VBF protocol, which adapts the vector-based approach at every hop. We evaluate the performance of VBF and HH-VBF through extensive simulations. The simulation results show that VBF achieves high packet delivery ratio and energy efficiency in dense networks and HH-VBF has high packet delivery ratio even in sparse networks.

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

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

2004-11-01

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

Biological Control Strategies for Mosquito Vectors of Arboviruses.

Science.gov (United States)

Huang, Yan-Jang S; Higgs, Stephen; Vanlandingham, Dana L

2017-02-10

Historically, biological control utilizes predatory species and pathogenic microorganisms to reduce the population of mosquitoes as disease vectors. This is particularly important for the control of mosquito-borne arboviruses, which normally do not have specific antiviral therapies available. Although development of resistance is likely, the advantages of biological control are that the resources used are typically biodegradable and ecologically friendly. Over the past decade, the advancement of molecular biology has enabled optimization by the manipulation of genetic materials associated with biological control agents. Two significant advancements are the discovery of cytoplasmic incompatibility induced by Wolbachia bacteria, which has enhanced replacement programs, and the introduction of dominant lethal genes into local mosquito populations through the release of genetically modified mosquitoes. As various arboviruses continue to be significant public health threats, biological control strategies have evolved to be more diverse and become critical tools to reduce the disease burden of arboviruses.

Vector control programs in Saint Johns County, Florida and Guayas, Ecuador: successes and barriers to integrated vector management.

Science.gov (United States)

Naranjo, Diana P; Qualls, Whitney A; Jurado, Hugo; Perez, Juan C; Xue, Rui-De; Gomez, Eduardo; Beier, John C

2014-07-02

Vector-borne diseases (VBDs) and mosquito control programs (MCPs) diverge in settings and countries, and lead control specialists need to be aware of the most effective control strategies. Integrated Vector Management (IVM) strategies, once implemented in MCPs, aim to reduce cost and optimize protection of the populations against VBDs. This study presents a strengths, weaknesses, opportunities, and threats (SWOT) analysis to compare IVM strategies used by MCPs in Saint Johns County, Florida and Guayas, Ecuador. This research evaluates MCPs strategies to improve vector control activities. Methods included descriptive findings of the MCP operations. Information was obtained from vector control specialists, directors, and residents through field trips, surveys, and questionnaires. Evaluations of the strategies and assets of the control programs where obtained through SWOT analysis and within an IVM approach. Organizationally, the Floridian MCP is a tax-based District able to make decisions independently from county government officials, with the oversight of an elected board of commissioners. The Guayas program is directed by the country government and assessed by non-governmental organizations like the World health Organization. Operationally, the Floridian MCP conducts entomological surveillance and the Ecuadorian MCP focuses on epidemiological monitoring of human disease cases. Strengths of both MCPs were their community participation and educational programs. Weaknesses for both MCPs included limitations in budgets and technical capabilities. Opportunities, for both MCPs, are additional funding and partnerships with private, non-governmental, and governmental organizations. Threats experienced by both MCPs included political constraints and changes in the social and ecological environment that affect mosquito densities and control efforts. IVM pillars for policy making were used to compare the information among the programs. Differences included how the Ecuadorian

Vector control programs in Saint Johns County, Florida and Guayas, Ecuador: successes and barriers to integrated vector management

Science.gov (United States)

2014-01-01

Background Vector-borne diseases (VBDs) and mosquito control programs (MCPs) diverge in settings and countries, and lead control specialists need to be aware of the most effective control strategies. Integrated Vector Management (IVM) strategies, once implemented in MCPs, aim to reduce cost and optimize protection of the populations against VBDs. This study presents a strengths, weaknesses, opportunities, and threats (SWOT) analysis to compare IVM strategies used by MCPs in Saint Johns County, Florida and Guayas, Ecuador. This research evaluates MCPs strategies to improve vector control activities. Methods Methods included descriptive findings of the MCP operations. Information was obtained from vector control specialists, directors, and residents through field trips, surveys, and questionnaires. Evaluations of the strategies and assets of the control programs where obtained through SWOT analysis and within an IVM approach. Results Organizationally, the Floridian MCP is a tax-based District able to make decisions independently from county government officials, with the oversight of an elected board of commissioners. The Guayas program is directed by the country government and assessed by non-governmental organizations like the World health Organization. Operationally, the Floridian MCP conducts entomological surveillance and the Ecuadorian MCP focuses on epidemiological monitoring of human disease cases. Strengths of both MCPs were their community participation and educational programs. Weaknesses for both MCPs included limitations in budgets and technical capabilities. Opportunities, for both MCPs, are additional funding and partnerships with private, non-governmental, and governmental organizations. Threats experienced by both MCPs included political constraints and changes in the social and ecological environment that affect mosquito densities and control efforts. IVM pillars for policy making were used to compare the information among the programs. Differences

A reduce and replace strategy for suppressing vector-borne diseases: insights from a stochastic, spatial model.

Directory of Open Access Journals (Sweden)

Kenichi W Okamoto

Full Text Available Two basic strategies have been proposed for using transgenic Aedes aegypti mosquitoes to decrease dengue virus transmission: population reduction and population replacement. Here we model releases of a strain of Ae. aegypti carrying both a gene causing conditional adult female mortality and a gene blocking virus transmission into a wild population to assess whether such releases could reduce the number of competent vectors. We find this "reduce and replace" strategy can decrease the frequency of competent vectors below 50% two years after releases end. Therefore, this combined approach appears preferable to releasing a strain carrying only a female-killing gene, which is likely to merely result in temporary population suppression. However, the fixation of anti-pathogen genes in the population is unlikely. Genetic drift at small population sizes and the spatially heterogeneous nature of the population recovery after releases end prevent complete replacement of the competent vector population. Furthermore, releasing more individuals can be counter-productive in the face of immigration by wild-type mosquitoes, as greater population reduction amplifies the impact wild-type migrants have on the long-term frequency of the anti-pathogen gene. We expect the results presented here to give pause to expectations for driving an anti-pathogen construct to fixation by relying on releasing individuals carrying this two-gene construct. Nevertheless, in some dengue-endemic environments, a spatially heterogeneous decrease in competent vectors may still facilitate decreasing disease incidence.

Chikungunya Virus Vaccines: Viral Vector-Based Approaches.

Science.gov (United States)

Ramsauer, Katrin; Tangy, Frédéric

2016-12-15

In 2013, a major chikungunya virus (CHIKV) epidemic reached the Americas. In the past 2 years, >1.7 million people have been infected. In light of the current epidemic, with millions of people in North and South America at risk, efforts to rapidly develop effective vaccines have increased. Here, we focus on CHIKV vaccines that use viral-vector technologies. This group of vaccine candidates shares an ability to potently induce humoral and cellular immune responses by use of highly attenuated and safe vaccine backbones. So far, well-described vectors such as modified vaccinia virus Ankara, complex adenovirus, vesicular stomatitis virus, alphavirus-based chimeras, and measles vaccine Schwarz strain (MV/Schw) have been described as potential vaccines. We summarize here the recent data on these experimental vaccines, with a focus on the preclinical and clinical activities on the MV/Schw-based candidate, which is the first CHIKV-vectored vaccine that has completed a clinical trial. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Rule-Based Design of Plant Expression Vectors Using GenoCAD.

Science.gov (United States)

Coll, Anna; Wilson, Mandy L; Gruden, Kristina; Peccoud, Jean

2015-01-01

Plant synthetic biology requires software tools to assist on the design of complex multi-genic expression plasmids. Here a vector design strategy to express genes in plants is formalized and implemented as a grammar in GenoCAD, a Computer-Aided Design software for synthetic biology. It includes a library of plant biological parts organized in structural categories and a set of rules describing how to assemble these parts into large constructs. Rules developed here are organized and divided into three main subsections according to the aim of the final construct: protein localization studies, promoter analysis and protein-protein interaction experiments. The GenoCAD plant grammar guides the user through the design while allowing users to customize vectors according to their needs. Therefore the plant grammar implemented in GenoCAD will help plant biologists take advantage of methods from synthetic biology to design expression vectors supporting their research projects.

Intelligent fault recognition strategy based on adaptive optimized multiple centers

Science.gov (United States)

Zheng, Bo; Li, Yan-Feng; Huang, Hong-Zhong

2018-06-01

For the recognition principle based optimized single center, one important issue is that the data with nonlinear separatrix cannot be recognized accurately. In order to solve this problem, a novel recognition strategy based on adaptive optimized multiple centers is proposed in this paper. This strategy recognizes the data sets with nonlinear separatrix by the multiple centers. Meanwhile, the priority levels are introduced into the multi-objective optimization, including recognition accuracy, the quantity of optimized centers, and distance relationship. According to the characteristics of various data, the priority levels are adjusted to ensure the quantity of optimized centers adaptively and to keep the original accuracy. The proposed method is compared with other methods, including support vector machine (SVM), neural network, and Bayesian classifier. The results demonstrate that the proposed strategy has the same or even better recognition ability on different distribution characteristics of data.

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.

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

Science.gov (United States)

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

2006-08-01

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

Efficient Strategy to Generate a Vectored Duck Enteritis Virus Delivering Envelope of Duck Tembusu Virus

Directory of Open Access Journals (Sweden)

Zhong Zou

2014-06-01

Full Text Available Duck Tembusu virus (DTMUV is a recently emerging pathogenic flavivirus that has resulted in a huge economic loss in the duck industry. However, no vaccine is currently available to control this pathogen. Consequently, a practical strategy to construct a vaccine against this pathogen should be determined. In this study, duck enteritis virus (DEV was examined as a candidate vaccine vector to deliver the envelope (E of DTMUV. A modified mini-F vector was inserted into the SORF3 and US2 gene junctions of the attenuated DEV vaccine strain C-KCE genome to generate an infectious bacterial artificial chromosome (BAC of C-KCE (vBAC-C-KCE. The envelope (E gene of DTMUV was inserted into the C-KCE genome through the mating-assisted genetically integrated cloning (MAGIC strategy, resulting in the recombinant vector, pBAC-C-KCE-E. A bivalent vaccine C-KCE-E was generated by eliminating the BAC backbone. Immunofluorescence and western blot analysis results indicated that the E proteins were vigorously expressed in C-KCE-E-infected chicken embryo fibroblasts (CEFs. Duck experiments demonstrated that the insertion of the E gene did not alter the protective efficacy of C-KCE. Moreover, C-KCE-E-immunized ducks induced neutralization antibodies against DTMUV. These results demonstrated, for the first time, that recombinant C-KCE-E can serve as a potential bivalent vaccine against DEV and DTMUV.

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

Directory of Open Access Journals (Sweden)

Nancy J Sullivan

2006-06-01

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

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

Science.gov (United States)

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

2006-01-01

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

Automated Vectorization of Decision-Based Algorithms

Science.gov (United States)

James, Mark

2006-01-01

Virtually all existing vectorization algorithms are designed to only analyze the numeric properties of an algorithm and distribute those elements across multiple processors. This advances the state of the practice because it is the only known system, at the time of this reporting, that takes high-level statements and analyzes them for their decision properties and converts them to a form that allows them to automatically be executed in parallel. The software takes a high-level source program that describes a complex decision- based condition and rewrites it as a disjunctive set of component Boolean relations that can then be executed in parallel. This is important because parallel architectures are becoming more commonplace in conventional systems and they have always been present in NASA flight systems. This technology allows one to take existing condition-based code and automatically vectorize it so it naturally decomposes across parallel architectures.

A novel gene therapy-based approach that selectively targets hypoxic regions within solid tumors

International Nuclear Information System (INIS)

Dougherty, S.T.; Dougherty, G.J.; Davis, P.D.

2003-01-01

There is compelling evidence that malignant cells present within the hypoxic regions that are commonly found within solid tumors contribute significantly to local recurrence following radiation therapy. We describe now a novel strategy designed to target such cells that exploits the differential production within hypoxic regions of the pro-angiogenic cytokine vascular endothelial cell growth factor (VEGF). Specifically, we have generated cDNA constructs that encode two distinct chimeric cell surface proteins that incorporate, respectively, the extracellular domains of the VEGF receptors Flk-1 or Flt-1, fused in frame to the membrane spanning and cytoplasmic domains of the pro-apoptotic protein Fas. Both chimeric proteins (Flk/Fas and Flt/Fas) appear stable and can be readily detected on the surface of transfected cells by Western blot and/or FACS analysis. Importantly, tumor cells expressing the chimeric proteins were rapidly killed in a dose-dependent fashion upon the addition of exogenous recombinant VEGF. Adenoviral vectors encoding Flk/Fas have been generated and shown to induce tumor cells to undergo apoptosis upon transfer to hypoxic conditions in vitro. This activity is dependent upon the endogenous production of VEGF. Studies are currently underway to test the ability of adenoviral Flk/Fas (Ad.Flk/Fas) to reduce tumor recurrence in vivo when used as an adjuvant therapy in conjunction with clinically relevant doses of ionizing radiation

Biological Control Strategies for Mosquito Vectors of Arboviruses

Directory of Open Access Journals (Sweden)

Yan-Jang S. Huang

2017-02-01

Full Text Available Historically, biological control utilizes predatory species and pathogenic microorganisms to reduce the population of mosquitoes as disease vectors. This is particularly important for the control of mosquito-borne arboviruses, which normally do not have specific antiviral therapies available. Although development of resistance is likely, the advantages of biological control are that the resources used are typically biodegradable and ecologically friendly. Over the past decade, the advancement of molecular biology has enabled optimization by the manipulation of genetic materials associated with biological control agents. Two significant advancements are the discovery of cytoplasmic incompatibility induced by Wolbachia bacteria, which has enhanced replacement programs, and the introduction of dominant lethal genes into local mosquito populations through the release of genetically modified mosquitoes. As various arboviruses continue to be significant public health threats, biological control strategies have evolved to be more diverse and become critical tools to reduce the disease burden of arboviruses.

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

Science.gov (United States)

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

2015-01-01

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

An Engineered Virus Library as a Resource for the Spectrum-wide Exploration of Virus and Vector Diversity

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Wenli Zhang

2017-05-01

Full Text Available Adenoviruses (Ads are large human-pathogenic double-stranded DNA (dsDNA viruses presenting an enormous natural diversity associated with a broad variety of diseases. However, only a small fraction of adenoviruses has been explored in basic virology and biomedical research, highlighting the need to develop robust and adaptable methodologies and resources. We developed a method for high-throughput direct cloning and engineering of adenoviral genomes from different sources utilizing advanced linear-linear homologous recombination (LLHR and linear-circular homologous recombination (LCHR. We describe 34 cloned adenoviral genomes originating from clinical samples, which were characterized by next-generation sequencing (NGS. We anticipate that this recombineering strategy and the engineered adenovirus library will provide an approach to study basic and clinical virology. High-throughput screening (HTS of the reporter-tagged Ad library in a panel of cell lines including osteosarcoma disease-specific cell lines revealed alternative virus types with enhanced transduction and oncolysis efficiencies. This highlights the usefulness of this resource.

Support vector machines optimization based theory, algorithms, and extensions

CERN Document Server

Deng, Naiyang; Zhang, Chunhua

2013-01-01

Support Vector Machines: Optimization Based Theory, Algorithms, and Extensions presents an accessible treatment of the two main components of support vector machines (SVMs)-classification problems and regression problems. The book emphasizes the close connection between optimization theory and SVMs since optimization is one of the pillars on which SVMs are built.The authors share insight on many of their research achievements. They give a precise interpretation of statistical leaning theory for C-support vector classification. They also discuss regularized twi

Traditional and robust vector selection methods for use with similarity based models

International Nuclear Information System (INIS)

Hines, J. W.; Garvey, D. R.

2006-01-01

Vector selection, or instance selection as it is often called in the data mining literature, performs a critical task in the development of nonparametric, similarity based models. Nonparametric, similarity based modeling (SBM) is a form of 'lazy learning' which constructs a local model 'on the fly' by comparing a query vector to historical, training vectors. For large training sets the creation of local models may become cumbersome, since each training vector must be compared to the query vector. To alleviate this computational burden, varying forms of training vector sampling may be employed with the goal of selecting a subset of the training data such that the samples are representative of the underlying process. This paper describes one such SBM, namely auto-associative kernel regression (AAKR), and presents five traditional vector selection methods and one robust vector selection method that may be used to select prototype vectors from a larger data set in model training. The five traditional vector selection methods considered are min-max, vector ordering, combination min-max and vector ordering, fuzzy c-means clustering, and Adeli-Hung clustering. Each method is described in detail and compared using artificially generated data and data collected from the steam system of an operating nuclear power plant. (authors)

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

International Nuclear Information System (INIS)

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

2008-01-01

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

Heading-vector navigation based on head-direction cells and path integration.

Science.gov (United States)

Kubie, John L; Fenton, André A

2009-05-01

Insect navigation is guided by heading vectors that are computed by path integration. Mammalian navigation models, on the other hand, are typically based on map-like place representations provided by hippocampal place cells. Such models compute optimal routes as a continuous series of locations that connect the current location to a goal. We propose a "heading-vector" model in which head-direction cells or their derivatives serve both as key elements in constructing the optimal route and as the straight-line guidance during route execution. The model is based on a memory structure termed the "shortcut matrix," which is constructed during the initial exploration of an environment when a set of shortcut vectors between sequential pairs of visited waypoint locations is stored. A mechanism is proposed for calculating and storing these vectors that relies on a hypothesized cell type termed an "accumulating head-direction cell." Following exploration, shortcut vectors connecting all pairs of waypoint locations are computed by vector arithmetic and stored in the shortcut matrix. On re-entry, when local view or place representations query the shortcut matrix with a current waypoint and goal, a shortcut trajectory is retrieved. Since the trajectory direction is in head-direction compass coordinates, navigation is accomplished by tracking the firing of head-direction cells that are tuned to the heading angle. Section 1 of the manuscript describes the properties of accumulating head-direction cells. It then shows how accumulating head-direction cells can store local vectors and perform vector arithmetic to perform path-integration-based homing. Section 2 describes the construction and use of the shortcut matrix for computing direct paths between any pair of locations that have been registered in the shortcut matrix. In the discussion, we analyze the advantages of heading-based navigation over map-based navigation. Finally, we survey behavioral evidence that nonhippocampal

A fluorescent cassette-based strategy for engineering multiple domain fusion proteins

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Khorchid Ahmad

2003-07-01

Full Text Available Abstract Background The engineering of fusion proteins has become increasingly important and most recently has formed the basis of many biosensors, protein purification systems, and classes of new drugs. Currently, most fusion proteins consist of three or fewer domains, however, more sophisticated designs could easily involve three or more domains. Using traditional subcloning strategies, this requires micromanagement of restriction enzymes sites that results in complex workaround solutions, if any at all. Results Therefore, to aid in the efficient construction of fusion proteins involving multiple domains, we have created a new expression vector that allows us to rapidly generate a library of cassettes. Cassettes have a standard vector structure based on four specific restriction endonuclease sites and using a subtle property of blunt or compatible cohesive end restriction enzymes, they can be fused in any order and number of times. Furthermore, the insertion of PCR products into our expression vector or the recombination of cassettes can be dramatically simplified by screening for the presence or absence of fluorescence. Conclusions Finally, the utility of this new strategy was demonstrated by the creation of basic cassettes for protein targeting to subcellular organelles and for protein purification using multiple affinity tags.

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

International Nuclear Information System (INIS)

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

2009-01-01

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

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

Strategies to obtain multiple recombinant modified vaccinia Ankara vectors. Applications to influenza vaccines.

Science.gov (United States)

Barbieri, Andrea; Panigada, Maddalena; Soprana, Elisa; Di Mario, Giuseppina; Gubinelli, Francesco; Bernasconi, Valentina; Recagni, Marta; Donatelli, Isabella; Castrucci, Maria R; Siccardi, Antonio G

2018-01-01

As a vaccination vector, MVA has been widely investigated both in animal models and humans. The construction of recombinant MVA (rMVA) relies on homologous recombination between an acceptor virus and a donor plasmid in infected/transfected permissive cells. Our construction strategy "Red-to-Green gene swapping" - based on the exchange of two fluorescent markers within the flanking regions of MVA deletion ΔIII, coupled to fluorescence activated cell sorting - is here extended to a second insertion site, within the flanking regions of MVA deletion ΔVI. Exploiting this strategy, both double and triple rMVA were constructed, expressing as transgenes the influenza A proteins HA, NP, M1, and PB1. Upon validation of the harbored transgenes co-expression, double and triple recombinants rMVA(ΔIII)-NP-P2A-M1 and rMVA(ΔIII)-NP-P2A-M1-(ΔVI)-PB1 were assayed for in vivo immunogenicity and protection against lethal challenge. In vivo responses were identical to those obtained with the reported combinations of single recombinants, supporting the feasibility and reliability of the present improvement and the extension of Red-to-Green gene swapping to insertion sites other than ΔIII. Copyright © 2017 Elsevier B.V. All rights reserved.

Wolbachia strain wPip yields a pattern of cytoplasmic incompatibility enhancing a Wolbachia-based suppression strategy against the disease vector Aedes albopictus

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Calvitti Maurizio

2012-11-01

Full Text Available Abstract Background Cytoplasmic incompatibility (CI is induced in nature by Wolbachia bacteria, resulting in conditional male sterility. Previous research demonstrated that the two Wolbachia strains (wAlbA and wAlbB that naturally co-infect the disease vector mosquito Aedes albopictus (Asian tiger mosquito can be replaced with the wPip Wolbachia strain from Culex pipiens. Since Wolbachia-based vector control strategies depend upon the strength and consistency of CI, a greater understanding is needed on the CI relationships between wPip, wAlbA and wAlbB Wolbachia in Ae. albopictus. Methods This work consisted of a collaborative series of crosses carried out in Italy and in US to study the CI relationships between the “wPip” infected Ae. albopictus strain (ARwP and the superinfected SR strain. The Ae. albopictus strains used in Italian tests are the wPip infected ARwP strain (ARwPIT, the superinfected SR strain and the aposymbiotic AR strain. To understand the observed pattern of CI, crossing experiments carried out in USA focused on the study of the CI relationships between ARwP (ARwPUS and artificially-generated single infected lines, in specific HTA and HTB, harbouring only wAlbA and wAlbB Wolbachia respectively. Results The paper reports an unusual pattern of CI observed in crossing experiments between ARwP and SR lines. Specifically, ARwP males are able to induce full sterility in wild type females throughout most of their lifetime, while crosses between SR males and ARwP females become partially fertile with male aging. We demonstrated that the observed decrease in CI penetrance with SR male age, is related to the previously described decrease in Wolbachia density, in particular of the wAlbA strain, occurring in aged superinfected males. Conclusions The results here reported support the use of the ARwP Ae. albopictus line as source of “ready-made sterile males”, as an alternative to gamma radiation sterilized males, for autocidal

Coal demand prediction based on a support vector machine model

Energy Technology Data Exchange (ETDEWEB)

Jia, Cun-liang; Wu, Hai-shan; Gong, Dun-wei [China University of Mining & Technology, Xuzhou (China). School of Information and Electronic Engineering

2007-01-15

A forecasting model for coal demand of China using a support vector regression was constructed. With the selected embedding dimension, the output vectors and input vectors were constructed based on the coal demand of China from 1980 to 2002. After compared with lineal kernel and Sigmoid kernel, a radial basis function(RBF) was adopted as the kernel function. By analyzing the relationship between the error margin of prediction and the model parameters, the proper parameters were chosen. The support vector machines (SVM) model with multi-input and single output was proposed. Compared the predictor based on RBF neural networks with test datasets, the results show that the SVM predictor has higher precision and greater generalization ability. In the end, the coal demand from 2003 to 2006 is accurately forecasted. l0 refs., 2 figs., 4 tabs.

Consolidating strategic planning and operational frameworks for integrated vector management in Eritrea.

Science.gov (United States)

Chanda, Emmanuel; Ameneshewa, Birkinesh; Mihreteab, Selam; Berhane, Araia; Zehaie, Assefash; Ghebrat, Yohannes; Usman, Abdulmumini

2015-12-02

Contemporary malaria vector control relies on the use of insecticide-based, indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs). However, malaria-endemic countries, including Eritrea, have struggled to effectively deploy these tools due technical and operational challenges, including the selection of insecticide resistance in malaria vectors. This manuscript outlines the processes undertaken in consolidating strategic planning and operational frameworks for vector control to expedite malaria elimination in Eritrea. The effort to strengthen strategic frameworks for vector control in Eritrea was the 'case' for this study. The integrated vector management (IVM) strategy was developed in 2010 but was not well executed, resulting in a rise in malaria transmission, prompting a process to redefine and relaunch the IVM strategy with integration of other vector borne diseases (VBDs) as the focus. The information sources for this study included all available data and accessible archived documentary records on malaria vector control in Eritrea. Structured literature searches of published, peer-reviewed sources using online, scientific, bibliographic databases, Google Scholar, PubMed and WHO, and a combination of search terms were utilized to gather data. The literature was reviewed and adapted to the local context and translated into the consolidated strategic framework. In Eritrea, communities are grappling with the challenge of VBDs posing public health concerns, including malaria. The global fund financed the scale-up of IRS and LLIN programmes in 2014. Eritrea is transitioning towards malaria elimination and strategic frameworks for vector control have been consolidated by: developing an integrated vector management (IVM) strategy (2015-2019); updating IRS and larval source management (LSM) guidelines; developing training manuals for IRS and LSM; training of national staff in malaria entomology and vector control, including insecticide resistance

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

DEFF Research Database (Denmark)

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

2009-01-01

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

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

Science.gov (United States)

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

2017-03-01

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

RNA interference-based therapeutics for human immunodeficiency virus HIV-1 treatment: synthetic siRNA or vector-based shRNA?

Science.gov (United States)

Subramanya, Sandesh; Kim, Sang-Soo; Manjunath, N; Shankar, Premlata

2010-02-01

Despite the clinical benefits of highly active antiretroviral therapy (HAART), the prospect of life-long antiretroviral treatment poses significant problems, which has spurred interest in developing new drugs and strategies to treat HIV infection and eliminate persistent viral reservoirs. RNAi has emerged as a therapeutic possibility for HIV. We discuss progress in overcoming hurdles to translating transient and stable RNAi enabling technologies to clinical application for HIV; covering the past 2 - 3 years. HIV inhibition can be achieved by transfection of chemically or enzymatically synthesized siRNAs or by DNA-based vector systems expressing short hairpin RNAs (shRNAs) that are processed intracellularly into siRNA. We compare these approaches, focusing on technical and safety issues that will guide the choice of strategy for clinical use. Introduction of synthetic siRNA into cells or its stable endogenous production using vector-driven shRNA have been shown to suppress HIV replication in vitro and, in some instances, in vivo. Each method has advantages and limitations in terms of ease of delivery, duration of silencing, emergence of escape mutants and potential toxicity. Both appear to have potential as future therapeutics for HIV, once the technical and safety issues of each approach are overcome.

A Support Vector Learning-Based Particle Filter Scheme for Target Localization in Communication-Constrained Underwater Acoustic Sensor Networks.

Science.gov (United States)

Li, Xinbin; Zhang, Chenglin; Yan, Lei; Han, Song; Guan, Xinping

2017-12-21

Target localization, which aims to estimate the location of an unknown target, is one of the key issues in applications of underwater acoustic sensor networks (UASNs). However, the constrained property of an underwater environment, such as restricted communication capacity of sensor nodes and sensing noises, makes target localization a challenging problem. This paper relies on fractional sensor nodes to formulate a support vector learning-based particle filter algorithm for the localization problem in communication-constrained underwater acoustic sensor networks. A node-selection strategy is exploited to pick fractional sensor nodes with short-distance pattern to participate in the sensing process at each time frame. Subsequently, we propose a least-square support vector regression (LSSVR)-based observation function, through which an iterative regression strategy is used to deal with the distorted data caused by sensing noises, to improve the observation accuracy. At the same time, we integrate the observation to formulate the likelihood function, which effectively update the weights of particles. Thus, the particle effectiveness is enhanced to avoid "particle degeneracy" problem and improve localization accuracy. In order to validate the performance of the proposed localization algorithm, two different noise scenarios are investigated. The simulation results show that the proposed localization algorithm can efficiently improve the localization accuracy. In addition, the node-selection strategy can effectively select the subset of sensor nodes to improve the communication efficiency of the sensor network.

Multiscale Distance Coherence Vector Algorithm for Content-Based Image Retrieval

Science.gov (United States)

Jiexian, Zeng; Xiupeng, Liu

2014-01-01

Multiscale distance coherence vector algorithm for content-based image retrieval (CBIR) is proposed due to the same descriptor with different shapes and the shortcomings of antinoise performance of the distance coherence vector algorithm. By this algorithm, the image contour curve is evolved by Gaussian function first, and then the distance coherence vector is, respectively, extracted from the contour of the original image and evolved images. Multiscale distance coherence vector was obtained by reasonable weight distribution of the distance coherence vectors of evolved images contour. This algorithm not only is invariable to translation, rotation, and scaling transformation but also has good performance of antinoise. The experiment results show us that the algorithm has a higher recall rate and precision rate for the retrieval of images polluted by noise. PMID:24883416

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

OpenAIRE

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

2008-01-01

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

A Novel CSR-Based Sparse Matrix-Vector Multiplication on GPUs

Directory of Open Access Journals (Sweden)

Guixia He

2016-01-01

Full Text Available Sparse matrix-vector multiplication (SpMV is an important operation in scientific computations. Compressed sparse row (CSR is the most frequently used format to store sparse matrices. However, CSR-based SpMVs on graphic processing units (GPUs, for example, CSR-scalar and CSR-vector, usually have poor performance due to irregular memory access patterns. This motivates us to propose a perfect CSR-based SpMV on the GPU that is called PCSR. PCSR involves two kernels and accesses CSR arrays in a fully coalesced manner by introducing a middle array, which greatly alleviates the deficiencies of CSR-scalar (rare coalescing and CSR-vector (partial coalescing. Test results on a single C2050 GPU show that PCSR fully outperforms CSR-scalar, CSR-vector, and CSRMV and HYBMV in the vendor-tuned CUSPARSE library and is comparable with a most recently proposed CSR-based algorithm, CSR-Adaptive. Furthermore, we extend PCSR on a single GPU to multiple GPUs. Experimental results on four C2050 GPUs show that no matter whether the communication between GPUs is considered or not PCSR on multiple GPUs achieves good performance and has high parallel efficiency.

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

Digital video steganalysis using motion vector recovery-based features.

Science.gov (United States)

Deng, Yu; Wu, Yunjie; Zhou, Linna

2012-07-10

As a novel digital video steganography, the motion vector (MV)-based steganographic algorithm leverages the MVs as the information carriers to hide the secret messages. The existing steganalyzers based on the statistical characteristics of the spatial/frequency coefficients of the video frames cannot attack the MV-based steganography. In order to detect the presence of information hidden in the MVs of video streams, we design a novel MV recovery algorithm and propose the calibration distance histogram-based statistical features for steganalysis. The support vector machine (SVM) is trained with the proposed features and used as the steganalyzer. Experimental results demonstrate that the proposed steganalyzer can effectively detect the presence of hidden messages and outperform others by the significant improvements in detection accuracy even with low embedding rates.

Therapeutic Endoscopic Ultrasonography: Intratumoral Injection for Pancreatic Adenocarcinoma

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Lawrence A. Shirley

2013-01-01

Full Text Available Pancreatic adenocarcinoma is an aggressive disease that has poor outcomes despite maximal traditional therapies. Thus, treatment of this cancer demands innovative strategies to be used in addition to standing therapies in order to provide new avenues of care. Here, we describe the technique of using endoscopic ultrasound in order to directly inject both novel and conventional therapies into pancreatic tumors. We detail the rationale behind this strategy and the many benefits it provides. We then describe our technique in detail, including our experience injecting the AdV-tk adenoviral vector to create an in situ vaccine effect.

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

Efficient gene transfer into nondividing cells by adeno-associated virus-based vectors.

Science.gov (United States)

Podsakoff, G; Wong, K K; Chatterjee, S

1994-09-01

Gene transfer vectors based on adeno-associated virus (AAV) are emerging as highly promising for use in human gene therapy by virtue of their characteristics of wide host range, high transduction efficiencies, and lack of cytopathogenicity. To better define the biology of AAV-mediated gene transfer, we tested the ability of an AAV vector to efficiently introduce transgenes into nonproliferating cell populations. Cells were induced into a nonproliferative state by treatment with the DNA synthesis inhibitors fluorodeoxyuridine and aphidicolin or by contact inhibition induced by confluence and serum starvation. Cells in logarithmic growth or DNA synthesis arrest were transduced with vCWR:beta gal, an AAV-based vector encoding beta-galactosidase under Rous sarcoma virus long terminal repeat promoter control. Under each condition tested, vCWR:beta Gal expression in nondividing cells was at least equivalent to that in actively proliferating cells, suggesting that mechanisms for virus attachment, nuclear transport, virion uncoating, and perhaps some limited second-strand synthesis of AAV vectors were present in nondividing cells. Southern hybridization analysis of vector sequences from cells transduced while in DNA synthetic arrest and expanded after release of the block confirmed ultimate integration of the vector genome into cellular chromosomal DNA. These findings may provide the basis for the use of AAV-based vectors for gene transfer into quiescent cell populations such as totipotent hematopoietic stem cells.

LandSat-Based Land Use-Land Cover (Vector)

Data.gov (United States)

Minnesota Department of Natural Resources — Vector-based land cover data set derived from classified 30 meter resolution Thematic Mapper satellite imagery. Classification is divided into 16 classes with source...

Expression of Separate Proteins in the Same Plant Leaves and Cells Using Two Independent Virus-Based Gene Vectors

Directory of Open Access Journals (Sweden)

Maria R. Mendoza

2017-11-01

Full Text Available Plant viral vectors enable the expression of proteins at high levels in a relatively short time. For many purposes (e.g., cell biological interaction studies it may be desirable to express more than one protein in a single cell but that is often not feasible when using a single virus vector. Such a co-expression strategy requires the simultaneous delivery by two compatible and non-competitive viruses that can co-exist to each express a separate protein. Here, we report on the use of two agro-launchable coat-protein gene substitution GFP-expressing virus vector systems based on Tomato bushy stunt virus (TBSV referred to as TG, and Tobacco mosaic virus (TMV annotated as TRBO-G. TG expressed GFP in Nicotiana benthamiana, tomato, lettuce and cowpea, whereas expression from TRBO-G was detected only in the first two species. Upon co-infiltration of the two vectors co-expression was monitored by: molecular detection of the two slightly differently sized GFPs, suppressor-complementation assays, and using TG in combination with TRBO-RFP. All the results revealed that in N. benthamiana and tomato the TBSV and TMV vectors accumulated and expressed proteins in the same plants, the same leaves, and in the same cells. Therefore, co-expression by these two vectors provides a platform for fast and high level expression of proteins to study their cell biology or other properties.

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

Directory of Open Access Journals (Sweden)

Angela Cassese

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

Integrated vector management for malaria control

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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

A Core Set Based Large Vector-Angular Region and Margin Approach for Novelty Detection

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Jiusheng Chen

2016-01-01

Full Text Available A large vector-angular region and margin (LARM approach is presented for novelty detection based on imbalanced data. The key idea is to construct the largest vector-angular region in the feature space to separate normal training patterns; meanwhile, maximize the vector-angular margin between the surface of this optimal vector-angular region and abnormal training patterns. In order to improve the generalization performance of LARM, the vector-angular distribution is optimized by maximizing the vector-angular mean and minimizing the vector-angular variance, which separates the normal and abnormal examples well. However, the inherent computation of quadratic programming (QP solver takes O(n3 training time and at least O(n2 space, which might be computational prohibitive for large scale problems. By (1+ε  and  (1-ε-approximation algorithm, the core set based LARM algorithm is proposed for fast training LARM problem. Experimental results based on imbalanced datasets have validated the favorable efficiency of the proposed approach in novelty detection.

Dual delivery systems based on polyamine analog BENSpm as prodrug and gene delivery vectors

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Zhu, Yu

Combination drug and gene therapy shows promise in cancer treatment. However, the success of such strategy requires careful selection of the therapeutic agents, as well as development of efficient delivery vectors. BENSpm (N 1, N11-bisethylnorspermine), a polyamine analogue targeting the intracellular polyamine pathway, draws our special attention because of the following reasons: (1) polyamine pathway is frequently dysregulated in cancer; (2) BENSpm exhibits multiple functions to interfere with the polyamine pathway, such as to up-regulate polyamine metabolism enzymes and down-regulate polyamine biosynthesis enzymes. Therefore BENSpm depletes all natural polyamines and leads to apoptosis and cell growth inhibition in a wide range of cancers; (3) preclinical studies proved that BENSpm can act synergistically with various chemotherapy agents, making it a promising candidate in combination therapy; (4) multiple positive charges in BENSpm enable it as a suitable building block for cationic polymers, which can be further applied to gene delivery. In this dissertation, our goal was to design dual-function delivery vector based on BENSpm that can function as a gene delivery vector and, after intracellular degradation, as an active anticancer agent targeting dysregulated polyamine metabolism. We first demonstrated strong synergism between BENSpm and a potential therapeutic gene product TRAIL. Strong synergism was obtained in both estrogen-dependent MCF-7 breast cancer cells and triple-negative MDA-MB-231 breast cancer cells. Significant dose reduction of TRAIL in combination with BENSpm in MDA-MB-231 cells, together with the fact that BENSpm rendered MCF-7 cells more sensitive to TRAIL treatment verified our rationale of designing BENSpm-based delivery platform. This was expected to be beneficial for overcoming drug resistance in chemotherapy, as well as boosting the therapeutic effect of therapeutic genes. We first designed a lipid-based BENSpm dual vector (Lipo

A Kalman Filter for SINS Self-Alignment Based on Vector Observation.

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Xu, Xiang; Xu, Xiaosu; Zhang, Tao; Li, Yao; Tong, Jinwu

2017-01-29

In this paper, a self-alignment method for strapdown inertial navigation systems based on the q -method is studied. In addition, an improved method based on integrating gravitational apparent motion to form apparent velocity is designed, which can reduce the random noises of the observation vectors. For further analysis, a novel self-alignment method using a Kalman filter based on adaptive filter technology is proposed, which transforms the self-alignment procedure into an attitude estimation using the observation vectors. In the proposed method, a linear psuedo-measurement equation is adopted by employing the transfer method between the quaternion and the observation vectors. Analysis and simulation indicate that the accuracy of the self-alignment is improved. Meanwhile, to improve the convergence rate of the proposed method, a new method based on parameter recognition and a reconstruction algorithm for apparent gravitation is devised, which can reduce the influence of the random noises of the observation vectors. Simulations and turntable tests are carried out, and the results indicate that the proposed method can acquire sound alignment results with lower standard variances, and can obtain higher alignment accuracy and a faster convergence rate.

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-11-01

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

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

International Nuclear Information System (INIS)

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

2014-01-01

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

Declining Prevalence of Disease Vectors Under Climate Change

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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.

A Replication-Defective Human Type 5 Adenovirus-Based Trivalent Vaccine Confers Complete Protection against Plague in Mice and Nonhuman Primates.

Science.gov (United States)

Sha, Jian; Kirtley, Michelle L; Klages, Curtis; Erova, Tatiana E; Telepnev, Maxim; Ponnusamy, Duraisamy; Fitts, Eric C; Baze, Wallace B; Sivasubramani, Satheesh K; Lawrence, William S; Patrikeev, Igor; Peel, Jennifer E; Andersson, Jourdan A; Kozlova, Elena V; Tiner, Bethany L; Peterson, Johnny W; McWilliams, David; Patel, Snehal; Rothe, Eric; Motin, Vladimir L; Chopra, Ashok K

2016-07-01

Currently, no plague vaccine exists in the United States for human use. The capsular antigen (Caf1 or F1) and two type 3 secretion system (T3SS) components, the low-calcium-response V antigen (LcrV) and the needle protein YscF, represent protective antigens of Yersinia pestis We used a replication-defective human type 5 adenovirus (Ad5) vector and constructed recombinant monovalent and trivalent vaccines (rAd5-LcrV and rAd5-YFV) that expressed either the codon-optimized lcrV or the fusion gene designated YFV (consisting of ycsF, caf1, and lcrV). Immunization of mice with the trivalent rAd5-YFV vaccine by either the intramuscular (i.m.) or the intranasal (i.n.) route provided protection superior to that with the monovalent rAd5-LcrV vaccine against bubonic and pneumonic plague when animals were challenged with Y. pestis CO92. Preexisting adenoviral immunity did not diminish the protective response, and the protection was always higher when mice were administered one i.n. dose of the trivalent vaccine (priming) followed by a single i.m. booster dose of the purified YFV antigen. Immunization of cynomolgus macaques with the trivalent rAd5-YFV vaccine by the prime-boost strategy provided 100% protection against a stringent aerosol challenge dose of CO92 to animals that had preexisting adenoviral immunity. The vaccinated and challenged macaques had no signs of disease, and the invading pathogen rapidly cleared with no histopathological lesions. This is the first report showing the efficacy of an adenovirus-vectored trivalent vaccine against pneumonic plague in mouse and nonhuman primate (NHP) models. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Herpes simplex virus type 1-derived recombinant and amplicon vectors.

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Fraefel, Cornel; Marconi, Peggy; Epstein, Alberto L

2011-01-01

Herpes simplex virus type 1 (HSV-1) is a human pathogen whose lifestyle is based on a long-term dual interaction with the infected host, being able to establish both lytic and latent infections. The virus genome is a 153 kbp double-stranded DNA molecule encoding more than 80 genes. The interest of HSV-1 as gene transfer vector stems from its ability to infect many different cell types, both quiescent and proliferating cells, the very high packaging capacity of the virus capsid, the outstanding neurotropic adaptations that this virus has evolved, and the fact that it never integrates into the cellular chromosomes, thus avoiding the risk of insertional mutagenesis. Two types of vectors can be derived from HSV-1, recombinant vectors and amplicon vectors, and different methodologies have been developed to prepare large stocks of each type of vector. This chapter summarizes (1) the two approaches most commonly used to prepare recombinant vectors through homologous recombination, either in eukaryotic cells or in bacteria, and (2) the two methodologies currently used to generate helper-free amplicon vectors, either using a bacterial artificial chromosome (BAC)-based approach or a Cre/loxP site-specific recombination strategy.

Product Quality Modelling Based on Incremental Support Vector Machine

International Nuclear Information System (INIS)

Wang, J; Zhang, W; Qin, B; Shi, W

2012-01-01

Incremental Support vector machine (ISVM) is a new learning method developed in recent years based on the foundations of statistical learning theory. It is suitable for the problem of sequentially arriving field data and has been widely used for product quality prediction and production process optimization. However, the traditional ISVM learning does not consider the quality of the incremental data which may contain noise and redundant data; it will affect the learning speed and accuracy to a great extent. In order to improve SVM training speed and accuracy, a modified incremental support vector machine (MISVM) is proposed in this paper. Firstly, the margin vectors are extracted according to the Karush-Kuhn-Tucker (KKT) condition; then the distance from the margin vectors to the final decision hyperplane is calculated to evaluate the importance of margin vectors, where the margin vectors are removed while their distance exceed the specified value; finally, the original SVs and remaining margin vectors are used to update the SVM. The proposed MISVM can not only eliminate the unimportant samples such as noise samples, but also can preserve the important samples. The MISVM has been experimented on two public data and one field data of zinc coating weight in strip hot-dip galvanizing, and the results shows that the proposed method can improve the prediction accuracy and the training speed effectively. Furthermore, it can provide the necessary decision supports and analysis tools for auto control of product quality, and also can extend to other process industries, such as chemical process and manufacturing process.

Modelling spread of Bluetongue and other vector borne diseases in Denmark and evaluation of intervention strategies

DEFF Research Database (Denmark)

Græsbøll, Kaare

that describes spread of disease using vectors or hosts as agents of the spread. The model is run with bluetongue as the primary case study, and it is demonstrated how an epidemic outbreak of bluetongue 8 in Denmark is sensitive to the use of pasture, climate, vaccination, vector abundance, and flying parameters......The main outcome of this PhD project is a generic model for non-contagious infectious vector-borne disease spread by one vector species between up to two species of hosts distributed on farms and pasture. The model features a within-herd model of disease, combined with a triple movement kernel....... In constructing a more process oriented agent-based approach to spread modeling new parameters describing vector behavior were introduced. When these vector flying parameters have been quantified by experiments, this model can be implemented on areas naïve to the modeled disease with a high predictive power...

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

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

2004-11-01

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

Correlation-based motion vector processing with adaptive interpolation scheme for motion-compensated frame interpolation.

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Huang, Ai-Mei; Nguyen, Truong

2009-04-01

In this paper, we address the problems of unreliable motion vectors that cause visual artifacts but cannot be detected by high residual energy or bidirectional prediction difference in motion-compensated frame interpolation. A correlation-based motion vector processing method is proposed to detect and correct those unreliable motion vectors by explicitly considering motion vector correlation in the motion vector reliability classification, motion vector correction, and frame interpolation stages. Since our method gradually corrects unreliable motion vectors based on their reliability, we can effectively discover the areas where no motion is reliable to be used, such as occlusions and deformed structures. We also propose an adaptive frame interpolation scheme for the occlusion areas based on the analysis of their surrounding motion distribution. As a result, the interpolated frames using the proposed scheme have clearer structure edges and ghost artifacts are also greatly reduced. Experimental results show that our interpolated results have better visual quality than other methods. In addition, the proposed scheme is robust even for those video sequences that contain multiple and fast motions.

Spatially explicit multi-criteria decision analysis for managing vector-borne diseases

Science.gov (United States)

2011-01-01

The complex epidemiology of vector-borne diseases creates significant challenges in the design and delivery of prevention and control strategies, especially in light of rapid social and environmental changes. Spatial models for predicting disease risk based on environmental factors such as climate and landscape have been developed for a number of important vector-borne diseases. The resulting risk maps have proven value for highlighting areas for targeting public health programs. However, these methods generally only offer technical information on the spatial distribution of disease risk itself, which may be incomplete for making decisions in a complex situation. In prioritizing surveillance and intervention strategies, decision-makers often also need to consider spatially explicit information on other important dimensions, such as the regional specificity of public acceptance, population vulnerability, resource availability, intervention effectiveness, and land use. There is a need for a unified strategy for supporting public health decision making that integrates available data for assessing spatially explicit disease risk, with other criteria, to implement effective prevention and control strategies. Multi-criteria decision analysis (MCDA) is a decision support tool that allows for the consideration of diverse quantitative and qualitative criteria using both data-driven and qualitative indicators for evaluating alternative strategies with transparency and stakeholder participation. Here we propose a MCDA-based approach to the development of geospatial models and spatially explicit decision support tools for the management of vector-borne diseases. We describe the conceptual framework that MCDA offers as well as technical considerations, approaches to implementation and expected outcomes. We conclude that MCDA is a powerful tool that offers tremendous potential for use in public health decision-making in general and vector-borne disease management in particular

Spatially explicit multi-criteria decision analysis for managing vector-borne diseases

Directory of Open Access Journals (Sweden)

Hongoh Valerie

2011-12-01

Full Text Available Abstract The complex epidemiology of vector-borne diseases creates significant challenges in the design and delivery of prevention and control strategies, especially in light of rapid social and environmental changes. Spatial models for predicting disease risk based on environmental factors such as climate and landscape have been developed for a number of important vector-borne diseases. The resulting risk maps have proven value for highlighting areas for targeting public health programs. However, these methods generally only offer technical information on the spatial distribution of disease risk itself, which may be incomplete for making decisions in a complex situation. In prioritizing surveillance and intervention strategies, decision-makers often also need to consider spatially explicit information on other important dimensions, such as the regional specificity of public acceptance, population vulnerability, resource availability, intervention effectiveness, and land use. There is a need for a unified strategy for supporting public health decision making that integrates available data for assessing spatially explicit disease risk, with other criteria, to implement effective prevention and control strategies. Multi-criteria decision analysis (MCDA is a decision support tool that allows for the consideration of diverse quantitative and qualitative criteria using both data-driven and qualitative indicators for evaluating alternative strategies with transparency and stakeholder participation. Here we propose a MCDA-based approach to the development of geospatial models and spatially explicit decision support tools for the management of vector-borne diseases. We describe the conceptual framework that MCDA offers as well as technical considerations, approaches to implementation and expected outcomes. We conclude that MCDA is a powerful tool that offers tremendous potential for use in public health decision-making in general and vector

Conservative rigid body dynamics by convected base vectors with implicit constraints

DEFF Research Database (Denmark)

Krenk, Steen; Nielsen, Martin Bjerre

2014-01-01

of differential equations without additional algebraic constraints on the base vectors. A discretized form of the equations of motion is obtained by starting from a finite time increment of the Hamiltonian, and retracing the steps of the continuous formulation in discrete form in terms of increments and mean...... of the base vectors. Orthogonality and unit length of the base vectors are imposed by constraining the equivalent Green strain components, and the kinetic energy is represented corresponding to rigid body motion. The equations of motion are obtained via Hamilton’s equations including the zero...... values over each integration time increment. In this discrete form the Lagrange multipliers are given in terms of a representative value within the integration time interval, and the equations of motion are recast into a conservative mean-value and finite difference format. The Lagrange multipliers...

Classification of e-government documents based on cooperative expression of word vectors

Science.gov (United States)

Fu, Qianqian; Liu, Hao; Wei, Zhiqiang

2017-03-01

The effective document classification is a powerful technique to deal with the huge amount of e-government documents automatically instead of accomplishing them manually. The word-to-vector (word2vec) model, which converts semantic word into low-dimensional vectors, could be successfully employed to classify the e-government documents. In this paper, we propose the cooperative expressions of word vector (Co-word-vector), whose multi-granularity of integration explores the possibility of modeling documents in the semantic space. Meanwhile, we also aim to improve the weighted continuous bag of words model based on word2vec model and distributed representation of topic-words based on LDA model. Furthermore, combining the two levels of word representation, performance result shows that our proposed method on the e-government document classification outperform than the traditional method.

Biosensor method and system based on feature vector extraction

Science.gov (United States)

Greenbaum, Elias [Knoxville, TN; Rodriguez, Jr., Miguel; Qi, Hairong [Knoxville, TN; Wang, Xiaoling [San Jose, CA

2012-04-17

A method of biosensor-based detection of toxins comprises the steps of providing at least one time-dependent control signal generated by a biosensor in a gas or liquid medium, and obtaining a time-dependent biosensor signal from the biosensor in the gas or liquid medium to be monitored or analyzed for the presence of one or more toxins selected from chemical, biological or radiological agents. The time-dependent biosensor signal is processed to obtain a plurality of feature vectors using at least one of amplitude statistics and a time-frequency analysis. At least one parameter relating to toxicity of the gas or liquid medium is then determined from the feature vectors based on reference to the control signal.

Impact of Education Campaign on Community-Based Vector Control in Hastening the Process of Elimination of Lymphatic Filariasis in Tamil Nadu, South India

Science.gov (United States)

Nandha, B.; Krishnamoorthy, K.

2012-01-01

Globally mosquito-borne lymphatic filariasis (LF) is targeted for elimination by 2020. Towards this goal, the scope of community-based vector control as a supplementary strategy to mass drug administration (MDA) was assessed through an intensive education campaign and evaluated using pre- and post-educational surveys in an intervention and…

An episomal vector-based CRISPR/Cas9 system for highly efficient gene knockout in human pluripotent stem cells.

Science.gov (United States)

Xie, Yifang; Wang, Daqi; Lan, Feng; Wei, Gang; Ni, Ting; Chai, Renjie; Liu, Dong; Hu, Shijun; Li, Mingqing; Li, Dajin; Wang, Hongyan; Wang, Yongming

2017-05-24

Human pluripotent stem cells (hPSCs) represent a unique opportunity for understanding the molecular mechanisms underlying complex traits and diseases. CRISPR/Cas9 is a powerful tool to introduce genetic mutations into the hPSCs for loss-of-function studies. Here, we developed an episomal vector-based CRISPR/Cas9 system, which we called epiCRISPR, for highly efficient gene knockout in hPSCs. The epiCRISPR system enables generation of up to 100% Insertion/Deletion (indel) rates. In addition, the epiCRISPR system enables efficient double-gene knockout and genomic deletion. To minimize off-target cleavage, we combined the episomal vector technology with double-nicking strategy and recent developed high fidelity Cas9. Thus the epiCRISPR system offers a highly efficient platform for genetic analysis in hPSCs.

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

Science.gov (United States)

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

1999-05-01

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

Dengue knowledge, attitudes and practices and their impact on community-based vector control in rural Cambodia

Science.gov (United States)

Doum, Dyna; Keo, Vanney; Sokha, Ly; Sam, BunLeng; Chan, Vibol; Alexander, Neal; Bradley, John; Liverani, Marco; Prasetyo, Didot Budi; Rachmat, Agus; Lopes, Sergio; Hii, Jeffrey; Rithea, Leang; Shafique, Muhammad; Hustedt, John

2018-01-01

Background Globally there are an estimated 390 million dengue infections per year, of which 96 million are clinically apparent. In Cambodia, estimates suggest as many as 185,850 cases annually. The World Health Organization global strategy for dengue prevention aims to reduce mortality rates by 50% and morbidity by 25% by 2020. The adoption of integrated vector management approach using community-based methods tailored to the local context is one of the recommended strategies to achieve these objectives. Understanding local knowledge, attitudes and practices is therefore essential to designing suitable strategies to fit each local context. Methods and findings A Knowledge, Attitudes and Practices survey in 600 randomly chosen households was administered in 30 villages in Kampong Cham which is one of the most populated provinces of Cambodia. KAP surveys were administered to a sub-sample of households where an entomology survey was conducted (1200 households), during which Aedes larval/pupae and adult female Aedes mosquito densities were recorded. Participants had high levels of knowledge regarding the transmission of dengue, Aedes breeding, and biting prevention methods; the majority of participants believed they were at risk and that dengue transmission is preventable. However, self-reported vector control practices did not match observed practices recorded in our surveys. No correlation was found between knowledge and observed practices either. Conclusion An education campaign regarding dengue prevention in this setting with high knowledge levels is unlikely to have any significant effect on practices unless it is incorporated in a more comprehensive strategy for behavioural change, such a COMBI method, which includes behavioural models as well as communication and marketing theory and practice. Trial registration ISRCTN85307778. PMID:29451879

Dengue knowledge, attitudes and practices and their impact on community-based vector control in rural Cambodia.

Science.gov (United States)

Kumaran, Emmanuelle; Doum, Dyna; Keo, Vanney; Sokha, Ly; Sam, BunLeng; Chan, Vibol; Alexander, Neal; Bradley, John; Liverani, Marco; Prasetyo, Didot Budi; Rachmat, Agus; Lopes, Sergio; Hii, Jeffrey; Rithea, Leang; Shafique, Muhammad; Hustedt, John

2018-02-01

Globally there are an estimated 390 million dengue infections per year, of which 96 million are clinically apparent. In Cambodia, estimates suggest as many as 185,850 cases annually. The World Health Organization global strategy for dengue prevention aims to reduce mortality rates by 50% and morbidity by 25% by 2020. The adoption of integrated vector management approach using community-based methods tailored to the local context is one of the recommended strategies to achieve these objectives. Understanding local knowledge, attitudes and practices is therefore essential to designing suitable strategies to fit each local context. A Knowledge, Attitudes and Practices survey in 600 randomly chosen households was administered in 30 villages in Kampong Cham which is one of the most populated provinces of Cambodia. KAP surveys were administered to a sub-sample of households where an entomology survey was conducted (1200 households), during which Aedes larval/pupae and adult female Aedes mosquito densities were recorded. Participants had high levels of knowledge regarding the transmission of dengue, Aedes breeding, and biting prevention methods; the majority of participants believed they were at risk and that dengue transmission is preventable. However, self-reported vector control practices did not match observed practices recorded in our surveys. No correlation was found between knowledge and observed practices either. An education campaign regarding dengue prevention in this setting with high knowledge levels is unlikely to have any significant effect on practices unless it is incorporated in a more comprehensive strategy for behavioural change, such a COMBI method, which includes behavioural models as well as communication and marketing theory and practice. ISRCTN85307778.

Vestibular regeneration--experimental models and clinical implications.

Science.gov (United States)

Albu, Silviu; Muresanu, Dafin F

2012-09-01

Therapies aimed at the protection and/or regeneration of inner ear hair cells are of great interest, given the significant monetary and quality of life impact of balance disorders. Different viral vectors have been shown to transfect various cell types in the inner ear. The past decade has provided tremendous advances in the use of adenoviral vectors to achieve targeted treatment delivery. Several routes of delivery have been identified to introduce vectors into the inner ear while minimizing injury to surrounding structures. Recently, the transcription factor Atoh1 was determined to play a critical role in hair cell differentiation. Adenoviral-mediated overexpression of Atoh1 in culture and in vivo has demonstrated the ability to regenerate vestibular hair cells by causing transdifferentiation of neighbouring epithelial-supporting cells. Functional recovery of the vestibular system has also been documented following adenoviral-induced Atoh1 overexpression. Experiments demonstrating gene transfer in human vestibular epithelial cells reveal that the human inner ear is a suitable target for gene therapy. © 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Operational scale entomological intervention for malaria control: strategies, achievements and challenges in Zambia

Directory of Open Access Journals (Sweden)

Chanda Emmanuel

2013-01-01

Full Text Available Abstract Background While consensus on malaria vector control policy and strategy has stimulated unprecedented political-will, backed by international funding organizations and donors, vector control interventions are expansively being implemented based on assumptions with unequaled successes. This manuscript reports on the strategies, achievements and challenges of the past and contemporary malaria vector control efforts in Zambia. Case description All available information and accessible archived documentary records on malaria vector control in Zambia were reviewed. Retrospective analysis of routine surveillance data from the Health Management Information System (HMIS, data from population-based household surveys and various operations research reports was conducted to assess the status in implementing policies and strategies. Discussion and evaluation Empirical evidence is critical for informing policy decisions and tailoring interventions to local settings. Thus, the World Health Organization (WHO encourages the adoption of the integrated vector management (IVM strategy which is a rational decision making process for optimal use of available resources. One of the key features of IVM is capacity building at the operational level to plan, implement, monitor and evaluate vector control and its epidemiological and entomological impact. In Zambia, great progress has been made in implementing WHO-recommended vector control policies and strategies within the context of the IVM Global Strategic framework with strong adherence to its five key attributes. Conclusions The country has solid, consistent and coordinated policies, strategies and guidelines for malaria vector control. The Zambian experience demonstrates the significance of a coordinated multi-pronged IVM approach effectively operationalized within the context of a national health system.

An Effective NoSQL-Based Vector Map Tile Management Approach

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Lin Wan

2016-11-01

Full Text Available Within a digital map service environment, the rapid growth of Spatial Big-Data is driving new requirements for effective mechanisms for massive online vector map tile processing. The emergence of Not Only SQL (NoSQL databases has resulted in a new data storage and management model for scalable spatial data deployments and fast tracking. They better suit the scenario of high-volume, low-latency network map services than traditional standalone high-performance computer (HPC or relational databases. In this paper, we propose a flexible storage framework that provides feasible methods for tiled map data parallel clipping and retrieval operations within a distributed NoSQL database environment. We illustrate the parallel vector tile generation and querying algorithms with the MapReduce programming model. Three different processing approaches, including local caching, distributed file storage, and the NoSQL-based method, are compared by analyzing the concurrent load and calculation time. An online geological vector tile map service prototype was developed to embed our processing framework in the China Geological Survey Information Grid. Experimental results show that our NoSQL-based parallel tile management framework can support applications that process huge volumes of vector tile data and improve performance of the tiled map service.

A decentralized receptance-based damage detection strategy for wireless smart sensors

International Nuclear Information System (INIS)

Jang, Shinae; Spencer Jr, Billie F; Sim, Sung-Han

2012-01-01

Various structural health monitoring strategies have been proposed recently that can be implemented in the decentralized computing environment intrinsic to wireless smart sensor networks (WSSN). Many are based on changes in the experimentally determined flexibility matrix for the structure under consideration. However, the flexibility matrix contains only static information; much richer information is available by considering the dynamic flexibility, or receptance, of the structure. Recently, the stochastic dynamic damage locating vector (SDDLV) method was proposed based on changes of dynamic flexibility matrices employing centrally collected output-only measurements. This paper investigates the potential of the SDDLV method for implementation on a network of wireless smart sensors, where a decentralized, hierarchical, in-network processing approach is used to address issues of scalability of the SDDLV algorithm. Two approaches to aggregate results are proposed that provide robust estimates of damage locations. The efficacy of the developed strategy is first verified using wired sensors emulating a wireless sensor network. Subsequently, the decentralized damage detection strategy is implemented on MEMSIC’s Imote2 smart sensor platform and validated experimentally on a laboratory scale truss bridge. (paper)

A heterologous prime-boosting strategy with replicating Vaccinia virus vectors and plant-produced HIV-1 Gag/dgp41 virus-like particles

Energy Technology Data Exchange (ETDEWEB)

Meador, Lydia R. [Ira A. Fulton School of Engineering, Arizona State University, Tempe, AZ (United States); Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ (United States); Kessans, Sarah A. [Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ (United States); School of Life Sciences, Arizona State University, Tempe, AZ (United States); Kilbourne, Jacquelyn; Kibler, Karen V. [Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ (United States); Pantaleo, Giuseppe [Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne (Switzerland); Swiss Vaccine Research Institute, Lausanne (Switzerland); Roderiguez, Mariano Esteban [Department of Molecular and Cellular Biology, Centro Nacional de Biotecnologia – CSIC, Madrid (Spain); Blattman, Joseph N. [Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ (United States); School of Life Sciences, Arizona State University, Tempe, AZ (United States); Jacobs, Bertram L., E-mail: bjacobs@asu.edu [Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ (United States); School of Life Sciences, Arizona State University, Tempe, AZ (United States); Mor, Tsafrir S., E-mail: tsafrir.mor@asu.edu [Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ (United States); School of Life Sciences, Arizona State University, Tempe, AZ (United States)

2017-07-15

Showing modest efficacy, the RV144 HIV-1 vaccine clinical trial utilized a non-replicating canarypox viral vector and a soluble gp120 protein boost. Here we built upon the RV144 strategy by developing a novel combination of a replicating, but highly-attenuated Vaccinia virus vector, NYVAC-KC, and plant-produced HIV-1 virus-like particles (VLPs). Both components contained the full-length Gag and a membrane anchored truncated gp41 presenting the membrane proximal external region with its conserved broadly neutralizing epitopes in the pre-fusion conformation. We tested different prime/boost combinations of these components in mice and showed that the group primed with NYVAC-KC and boosted with both the viral vectors and plant-produced VLPs have the most robust Gag-specific CD8 T cell responses, at 12.7% of CD8 T cells expressing IFN-γ in response to stimulation with five Gag epitopes. The same immunization group elicited the best systemic and mucosal antibody responses to Gag and dgp41 with a bias towards IgG1. - Highlights: • We devised a prime/boost anti HIV-1 vaccination strategy modeled after RV144. • We used plant-derived virus-like particles (VLPs) consisting of Gag and dgp41. • We used attenuated, replicating vaccinia virus vectors expressing the same antigens. • The immunogens elicited strong cellular and humoral immune responses.

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

Peptide-mediated vectorization of metal complexes: conjugation strategies and biomedical applications.

Science.gov (United States)

Soler, Marta; Feliu, Lidia; Planas, Marta; Ribas, Xavi; Costas, Miquel

2016-08-16

The rich chemical and structural versatility of transition metal complexes provides numerous novel paths to be pursued in the design of molecules that exert particular chemical or physicochemical effects that could operate over specific biological targets. However, the poor cell permeability of metallodrugs represents an important barrier for their therapeutic use. The conjugation between metal complexes and a functional peptide vector can be regarded as a versatile and potential strategy to improve their bioavailability and accumulation inside cells, and the site selectivity of their effect. This perspective lies in reviewing the recent advances in the design of metallopeptide conjugates for biomedical applications. Additionally, we highlight the studies where this approach has been directed towards the incorporation of redox active metal centers into living organisms for modulating the cellular redox balance, as a tool with application in anticancer therapy.

Insecticide resistance in Bemisia tabaci Gennadius (Homoptera: Aleyrodidae) and Anopheles gambiae Giles (Diptera: Culicidae) could compromise the sustainability of malaria vector control strategies in West Africa.

Science.gov (United States)

Gnankiné, Olivier; Bassolé, Imael H N; Chandre, Fabrice; Glitho, Isabelle; Akogbeto, Martin; Dabiré, Roch K; Martin, Thibaud

2013-10-01

Insecticides from the organophosphate (OP) and pyrethroid (PY) chemical families, have respectively, been in use for 50 and 30 years in West Africa, mainly against agricultural pests, but also against vectors of human disease. The selection pressure, with practically the same molecules year after year (mainly on cotton), has caused insecticide resistance in pest populations such as Bemisia tabaci, vector of harmful phytoviruses on vegetables. The evolution toward insecticide resistance in malaria vectors such as Anopheles gambiae sensus lato (s.l.) is probably related to the current use of these insecticides in agriculture. Thus, successful pest and vector control in West Africa requires an investigation of insect susceptibility, in relation to the identification of species and sub species, such as molecular forms or biotypes. Identification of knock down resistance (kdr) and acetylcholinesterase gene (Ace1) mutations modifying insecticide targets in individual insects and measure of enzymes activity typically involved in insecticide metabolism (oxidase, esterase and glutathion-S-transferase) are indispensable in understanding the mechanisms of resistance. Insecticide resistance is a good example in which genotype-phenotype links have been made successfully. Insecticides used in agriculture continue to select new resistant populations of B. tabaci that could be from different biotype vectors of plant viruses. As well, the evolution of insecticide resistance in An. gambiae threatens the management of malaria vectors in West Africa. It raises the question of priority in the use of insecticides in health and/or agriculture, and more generally, the question of sustainability of crop protection and vector control strategies in the region. Here, we review the susceptibility tests, biochemical and molecular assays data for B. tabaci, a major pest in cotton and vegetable crops, and An. gambiae, main vector of malaria. The data reviewed was collected in Benin and Burkina

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

Science.gov (United States)

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

2014-08-21

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

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

Science.gov (United States)

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

2014-01-01

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

Direct-current vector control of three-phase grid-connected rectifier-inverter

Energy Technology Data Exchange (ETDEWEB)

Li, Shuhui; Haskew, Timothy A.; Hong, Yang-Ki; Xu, Ling [Department of Electrical and Computer Engineering, University of Alabama, Tuscaloosa, AL 35475 (United States)

2011-02-15

The three-phase grid-connected converter is widely used in renewable and electric power system applications. Traditionally, control of the three-phase grid-connected converter is based on the standard decoupled d-q vector control mechanism. Nevertheless, the study of this paper shows that there is a limitation in the conventional standard vector control method. Some of the limitations have also been found recently by other researchers. To overcome the shortage of the conventional vector control technique, this paper proposes a new direct-current d-q vector control mechanism in a nested-loop control structure, based on which an optimal control strategy is developed in a nonlinear programming formulation. The behaviors of both the conventional and proposed control methods are compared and evaluated in simulation and laboratory hardware experiment environments, both of which demonstrates that the proposed approach is effective for grid-connected power converter control in a wide system conditions while the conventional standard vector control approach may behave improperly especially when the converter operates beyond its PWM saturation limit. (author)

Biological Control of Mosquito Vectors: Past, Present, and Future

Directory of Open Access Journals (Sweden)

Giovanni Benelli

2016-10-01

Full Text Available Mosquitoes represent the major arthropod vectors of human disease worldwide transmitting malaria, lymphatic filariasis, and arboviruses such as dengue virus and Zika virus. Unfortunately, no treatment (in the form of vaccines or drugs is available for most of these diseases andvectorcontrolisstillthemainformofprevention. Thelimitationsoftraditionalinsecticide-based strategies, particularly the development of insecticide resistance, have resulted in significant efforts to develop alternative eco-friendly methods. Biocontrol strategies aim to be sustainable and target a range of different mosquito species to reduce the current reliance on insecticide-based mosquito control. In thisreview, weoutline non-insecticide basedstrategiesthat havebeenimplemented orare currently being tested. We also highlight the use of mosquito behavioural knowledge that can be exploited for control strategies.

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

Science.gov (United States)

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

2018-01-01

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

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...

Strategies for the AFM-based manipulation of silver nanowires on a flat surface

Science.gov (United States)

Liu, Hong-Zhi; Wu, Sen; Zhang, Jun-Ming; Bai, Hui-Tian; Jin, Fan; Pang, Hai; Hu, Xiao-Dong

2017-09-01

Silver nanowires (Ag NWs) are a promising material for building various sensors and devices at the nanoscale. However, the fast and precise placement of individual Ag NWs is still a challenge today. Atomic force microscopy (AFM) has been widely used to manipulate nanoparticles, yet this technology encounters many difficulties when being applied to the movement of Ag NWs as well as other soft one-dimensional (1D) materials, since the samples are easily distorted or even broken due to friction and adhesion on the substrate. In this paper, two novel manipulation strategies based on the parallel pushing method are presented. This method applies a group of short parallel pushing vectors (PPVs) to the Ag NW along its longitudinal direction. Identical and proportional vectors are respectively proposed to translate and rotate the Ag NWs with a straight-line configuration. The rotation strategy is also applied to straighten flexed Ag NWs. The finite element method simulation is introduced to analyse the behaviour of the Ag NWs as well as to optimize the parameter setting of the PPVs. Experiments are carried out to confirm the efficiency of the presented strategies. By comprehensive application of the new strategies, four Ag NWs are continuously assembled in a rectangular pattern. This study improves the controllability of the position and configuration of Ag NWs on a flat substrate. It also indicates the practicability of automatic nanofabrication using common AFMs.

Strategies to generate high-titer, high-potency recombinant AAV3 serotype vectors

Directory of Open Access Journals (Sweden)

Chen Ling

2016-01-01

Full Text Available Although recombinant adeno-associated virus serotype 3 (AAV3 vectors were largely ignored previously, owing to their poor transduction efficiency in most cells and tissues examined, our initial observation of the selective tropism of AAV3 serotype vectors for human liver cancer cell lines and primary human hepatocytes has led to renewed interest in this serotype. AAV3 vectors and their variants have recently proven to be extremely efficient in targeting human and nonhuman primate hepatocytes in vitro as well as in vivo. In the present studies, we wished to evaluate the relative contributions of the cis-acting inverted terminal repeats (ITRs from AAV3 (ITR3, as well as the trans-acting Rep proteins from AAV3 (Rep3 in the AAV3 vector production and transduction. To this end, we utilized two helper plasmids: pAAVr2c3, which carries rep2 and cap3 genes, and pAAVr3c3, which carries rep3 and cap3 genes. The combined use of AAV3 ITRs, AAV3 Rep proteins, and AAV3 capsids led to the production of recombinant vectors, AAV3-Rep3/ITR3, with up to approximately two to fourfold higher titers than AAV3-Rep2/ITR2 vectors produced using AAV2 ITRs, AAV2 Rep proteins, and AAV3 capsids. We also observed that the transduction efficiency of Rep3/ITR3 AAV3 vectors was approximately fourfold higher than that of Rep2/ITR2 AAV3 vectors in human hepatocellular carcinoma cell lines in vitro. The transduction efficiency of Rep3/ITR3 vectors was increased by ∼10-fold, when AAV3 capsids containing mutations in two surface-exposed residues (serine 663 and threonine 492 were used to generate a S663V+T492V double-mutant AAV3 vector. The Rep3/ITR3 AAV3 vectors also transduced human liver tumors in vivo approximately twofold more efficiently than those generated with Rep2/ITR2. Our data suggest that the transduction efficiency of AAV3 vectors can be significantly improved both using homologous Rep proteins and ITRs as well as by capsid optimization. Thus, the combined use of

A support vector density-based importance sampling for reliability assessment

International Nuclear Information System (INIS)

Dai, Hongzhe; Zhang, Hao; Wang, Wei

2012-01-01

An importance sampling method based on the adaptive Markov chain simulation and support vector density estimation is developed in this paper for efficient structural reliability assessment. The methodology involves the generation of samples that can adaptively populate the important region by the adaptive Metropolis algorithm, and the construction of importance sampling density by support vector density. The use of the adaptive Metropolis algorithm may effectively improve the convergence and stability of the classical Markov chain simulation. The support vector density can approximate the sampling density with fewer samples in comparison to the conventional kernel density estimation. The proposed importance sampling method can effectively reduce the number of structural analysis required for achieving a given accuracy. Examples involving both numerical and practical structural problems are given to illustrate the application and efficiency of the proposed methodology.

Virus immobilization on biomaterial scaffolds through biotin-avidin interaction for improving bone regeneration.

Science.gov (United States)

Hu, Wei-Wen; Wang, Zhuo; Krebsbach, Paul H

2016-02-01

To spatially control therapeutic gene delivery for potential tissue engineering applications, a biotin-avidin interaction strategy was applied to immobilize viral vectors on biomaterial scaffolds. Both adenoviral vectors and gelatin sponges were biotinylated and avidin was applied to link them in a virus-biotin-avidin-biotin-material (VBABM) arrangement. The tethered viral particles were stably maintained within scaffolds and SEM images illustrated that viral particles were evenly distributed in three-dimensional (3D) gelatin sponges. An in vivo study demonstrated that transgene expression was restricted to the implant sites only and transduction efficiency was improved using this conjugation method. For an orthotopic bone regeneration model, adenovirus encoding BMP-2 (AdBMP2) was immobilized to gelatin sponges before implanting into critical-sized bone defects in rat calvaria. Compared to gelatin sponges with AdBMP2 loaded in a freely suspended form, the VBABM method enhanced gene transfer and bone regeneration was significantly improved. These results suggest that biotin-avidin immobilization of viral vectors to biomaterial scaffolds may be an effective strategy to facilitate tissue regeneration. Copyright © 2013 John Wiley & Sons, Ltd.

The Potential Use of Wolbachia-Based Mosquito Biocontrol Strategies for Japanese Encephalitis.

Directory of Open Access Journals (Sweden)

Claire L Jeffries

lines. The successful establishment of Wolbachia in wild Aedes aegypti populations has recently been demonstrated, and open releases in dengue-endemic countries are ongoing. This review outlines the current control methods for JEV in addition to highlighting the potential use of Wolbachia-based biocontrol strategies to impact transmission. JEV and dengue virus are both members of the Flavivirus genus, and the successful establishment of Drosophila Wolbachia strains in Cx. Tritaeniorhynchus, as the principal vector of JEV, is predicted to significantly impact JEV transmission.

Virus Database and Online Inquiry System Based on Natural Vectors.

Science.gov (United States)

Dong, Rui; Zheng, Hui; Tian, Kun; Yau, Shek-Chung; Mao, Weiguang; Yu, Wenping; Yin, Changchuan; Yu, Chenglong; He, Rong Lucy; Yang, Jie; Yau, Stephen St

2017-01-01

We construct a virus database called VirusDB (http://yaulab.math.tsinghua.edu.cn/VirusDB/) and an online inquiry system to serve people who are interested in viral classification and prediction. The database stores all viral genomes, their corresponding natural vectors, and the classification information of the single/multiple-segmented viral reference sequences downloaded from National Center for Biotechnology Information. The online inquiry system serves the purpose of computing natural vectors and their distances based on submitted genomes, providing an online interface for accessing and using the database for viral classification and prediction, and back-end processes for automatic and manual updating of database content to synchronize with GenBank. Submitted genomes data in FASTA format will be carried out and the prediction results with 5 closest neighbors and their classifications will be returned by email. Considering the one-to-one correspondence between sequence and natural vector, time efficiency, and high accuracy, natural vector is a significant advance compared with alignment methods, which makes VirusDB a useful database in further research.

Citrus tristeza virus-based RNAi in citrus plants induces gene silencing in Diaphorina citri, a phloem-sap sucking insect vector of citrus greening disease (Huanglongbing).

Science.gov (United States)

Hajeri, Subhas; Killiny, Nabil; El-Mohtar, Choaa; Dawson, William O; Gowda, Siddarame

2014-04-20

A transient expression vector based on Citrus tristeza virus (CTV) is unusually stable. Because of its stability it is being considered for use in the field to control Huanglongbing (HLB), which is caused by Candidatus Liberibacter asiaticus (CLas) and vectored by Asian citrus psyllid, Diaphorina citri. In the absence of effective control strategies for CLas, emphasis has been on control of D. citri. Coincident cohabitation in phloem tissue by CLas, D. citri and CTV was exploited to develop a novel method to mitigate HLB through RNA interference (RNAi). Since CTV has three RNA silencing suppressors, it was not known if CTV-based vector could induce RNAi in citrus. Yet, expression of sequences targeting citrus phytoene desaturase gene by CTV-RNAi resulted in photo-bleaching phenotype. CTV-RNAi vector, engineered with truncated abnormal wing disc (Awd) gene of D. citri, induced altered Awd expression when silencing triggers ingested by feeding D. citri nymphs. Decreased Awd in nymphs resulted in malformed-wing phenotype in adults and increased adult mortality. This impaired ability of D. citri to fly would potentially limit the successful vectoring of CLas bacteria between citrus trees in the grove. CTV-RNAi vector would be relevant for fast-track screening of candidate sequences for RNAi-mediated pest control. Copyright © 2014. Published by Elsevier B.V.

An Improved Single-Step Cloning Strategy Simplifies the Agrobacterium tumefaciens-Mediated Transformation (ATMT)-Based Gene-Disruption Method for Verticillium dahliae.

Science.gov (United States)

Wang, Sheng; Xing, Haiying; Hua, Chenlei; Guo, Hui-Shan; Zhang, Jie

2016-06-01

The soilborne fungal pathogen Verticillium dahliae infects a broad range of plant species to cause severe diseases. The availability of Verticillium genome sequences has provided opportunities for large-scale investigations of individual gene function in Verticillium strains using Agrobacterium tumefaciens-mediated transformation (ATMT)-based gene-disruption strategies. Traditional ATMT vectors require multiple cloning steps and elaborate characterization procedures to achieve successful gene replacement; thus, these vectors are not suitable for high-throughput ATMT-based gene deletion. Several advancements have been made that either involve simplification of the steps required for gene-deletion vector construction or increase the efficiency of the technique for rapid recombinant characterization. However, an ATMT binary vector that is both simple and efficient is still lacking. Here, we generated a USER-ATMT dual-selection (DS) binary vector, which combines both the advantages of the USER single-step cloning technique and the efficiency of the herpes simplex virus thymidine kinase negative-selection marker. Highly efficient deletion of three different genes in V. dahliae using the USER-ATMT-DS vector enabled verification that this newly-generated vector not only facilitates the cloning process but also simplifies the subsequent identification of fungal homologous recombinants. The results suggest that the USER-ATMT-DS vector is applicable for efficient gene deletion and suitable for large-scale gene deletion in V. dahliae.

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

Science.gov (United States)

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

2018-03-01

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

Design of a nonlinear backstepping control strategy of grid interconnected wind power system based PMSG

Science.gov (United States)

Errami, Y.; Obbadi, A.; Sahnoun, S.; Benhmida, M.; Ouassaid, M.; Maaroufi, M.

2016-07-01

This paper presents nonlinear backstepping control for Wind Power Generation System (WPGS) based Permanent Magnet Synchronous Generator (PMSG) and connected to utility grid. The block diagram of the WPGS with PMSG and the grid side back-to-back converter is established with the dq frame of axes. This control scheme emphasises the regulation of the dc-link voltage and the control of the power factor at changing wind speed. Besides, in the proposed control strategy of WPGS, Maximum Power Point Tracking (MPPT) technique and pitch control are provided. The stability of the regulators is assured by employing Lyapunov analysis. The proposed control strategy for the system has been validated by MATLAB simulations under varying wind velocity and the grid fault condition. In addition, a comparison of simulation results based on the proposed Backstepping strategy and conventional Vector Control is provided.

SAM: Support Vector Machine Based Active Queue Management

International Nuclear Information System (INIS)

Shah, M.S.

2014-01-01

Recent years have seen an increasing interest in the design of AQM (Active Queue Management) controllers. The purpose of these controllers is to manage the network congestion under varying loads, link delays and bandwidth. In this paper, a new AQM controller is proposed which is trained by using the SVM (Support Vector Machine) with the RBF (Radial Basis Function) kernal. The proposed controller is called the support vector based AQM (SAM) controller. The performance of the proposed controller has been compared with three conventional AQM controllers, namely the Random Early Detection, Blue and Proportional Plus Integral Controller. The preliminary simulation studies show that the performance of the proposed controller is comparable to the conventional controllers. However, the proposed controller is more efficient in controlling the queue size than the conventional controllers. (author)

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.

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.

A Statistical Parameter Analysis and SVM Based Fault Diagnosis Strategy for Dynamically Tuned Gyroscopes

Institute of Scientific and Technical Information of China (English)

无

2007-01-01

Gyro's fault diagnosis plays a critical role in inertia navigation systems for higher reliability and precision. A new fault diagnosis strategy based on the statistical parameter analysis (SPA) and support vector machine(SVM) classification model was proposed for dynamically tuned gyroscopes (DTG). The SPA, a kind of time domain analysis approach, was introduced to compute a set of statistical parameters of vibration signal as the state features of DTG, with which the SVM model, a novel learning machine based on statistical learning theory (SLT), was applied and constructed to train and identify the working state of DTG. The experimental results verify that the proposed diagnostic strategy can simply and effectively extract the state features of DTG, and it outperforms the radial-basis function (RBF) neural network based diagnostic method and can more reliably and accurately diagnose the working state of DTG.

Availability of thermodynamic system with multiple performance parameters based on vector-universal generating function

International Nuclear Information System (INIS)

Cai Qi; Shang Yanlong; Chen Lisheng; Zhao Yuguang

2013-01-01

Vector-universal generating function was presented to analyze the availability of thermodynamic system with multiple performance parameters. Vector-universal generating function of component's performance was defined, the arithmetic model based on vector-universal generating function was derived for the thermodynamic system, and the calculation method was given for state probability of multi-state component. With the stochastic simulation of the degeneration trend of the multiple factors, the system availability with multiple performance parameters was obtained under composite factors. It is shown by an example that the results of the availability obtained by the binary availability analysis method are somewhat conservative, and the results considering parameter failure based on vector-universal generating function reflect the operation characteristics of the thermodynamic system better. (authors)

Point-based warping with optimized weighting factors of displacement vectors

Science.gov (United States)

Pielot, Ranier; Scholz, Michael; Obermayer, Klaus; Gundelfinger, Eckart D.; Hess, Andreas

2000-06-01

The accurate comparison of inter-individual 3D image brain datasets requires non-affine transformation techniques (warping) to reduce geometric variations. Constrained by the biological prerequisites we use in this study a landmark-based warping method with weighted sums of displacement vectors, which is enhanced by an optimization process. Furthermore, we investigate fast automatic procedures for determining landmarks to improve the practicability of 3D warping. This combined approach was tested on 3D autoradiographs of Gerbil brains. The autoradiographs were obtained after injecting a non-metabolized radioactive glucose derivative into the Gerbil thereby visualizing neuronal activity in the brain. Afterwards the brain was processed with standard autoradiographical methods. The landmark-generator computes corresponding reference points simultaneously within a given number of datasets by Monte-Carlo-techniques. The warping function is a distance weighted exponential function with a landmark- specific weighting factor. These weighting factors are optimized by a computational evolution strategy. The warping quality is quantified by several coefficients (correlation coefficient, overlap-index, and registration error). The described approach combines a highly suitable procedure to automatically detect landmarks in autoradiographical brain images and an enhanced point-based warping technique, optimizing the local weighting factors. This optimization process significantly improves the similarity between the warped and the target dataset.

Vector for IS element entrapment and functional characterization based on turning on expression of distal promoterless genes.

Science.gov (United States)

Szeverényi, I; Hodel, A; Arber, W; Olasz, F

1996-09-26

We constructed and characterized a novel trap vector for rapid isolation of insertion sequences. The strategy used for the isolation of IS elements is based on the ability of many IS elements to turn on the expression of otherwise silent genes distal to some sites of insertion. The simple transposition of an IS element can sometimes cause the constitutive expression of promoterless antibiotic resistance genes resulting in selectable phenotypes. The trap vector pAW1326 is based on a pBR322 replicon, it carries ampicillin and streptomycin resistance genes, and also silenced genes that confer chloramphenicol and kanamycin resistance once activated. The trap vector pAW1326 proved to be efficient and 85 percent of all isolated mutations were insertions. The majority of IS elements resident in the studied Escherichia coli strains tested became trapped, namely IS2, IS3, IS5, IS150, IS186 and Tn1000. We also encountered an insertion sequence, called IS10L/R-2, which is a hybrid of the two IS variants IS10L and IS10R. IS10L/R-2 is absent from most E. coli strains, but it is detectable in some strains such as JM109 which had been submitted to Tn10 mutagenesis. The distribution of the insertion sequences within the trap region was not random. Rather, the integration of chromosomal mobile genetic elements into the offered target sequence occurred in element-specific clusters. This is explained both by the target specificity and by the specific requirements for the activation of gene transcription by the DNA rearrangement. The employed trap vector pAW1326 proved to be useful for the isolation of mobile genetic elements, for a demonstration of their transposition activity as well as for the further characterization of some of the functional parameters of transposition.

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

Science.gov (United States)

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

2018-06-01

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

2D Vector Field Simplification Based on Robustness

KAUST Repository

Skraba, Primoz

2014-03-01

Vector field simplification aims to reduce the complexity of the flow by removing features in order of their relevance and importance, to reveal prominent behavior and obtain a compact representation for interpretation. Most existing simplification techniques based on the topological skeleton successively remove pairs of critical points connected by separatrices, using distance or area-based relevance measures. These methods rely on the stable extraction of the topological skeleton, which can be difficult due to instability in numerical integration, especially when processing highly rotational flows. These geometric metrics do not consider the flow magnitude, an important physical property of the flow. In this paper, we propose a novel simplification scheme derived from the recently introduced topological notion of robustness, which provides a complementary view on flow structure compared to the traditional topological-skeleton-based approaches. Robustness enables the pruning of sets of critical points according to a quantitative measure of their stability, that is, the minimum amount of vector field perturbation required to remove them. This leads to a hierarchical simplification scheme that encodes flow magnitude in its perturbation metric. Our novel simplification algorithm is based on degree theory, has fewer boundary restrictions, and so can handle more general cases. Finally, we provide an implementation under the piecewise-linear setting and apply it to both synthetic and real-world datasets. © 2014 IEEE.

Recombinant fibromodulin has therapeutic effects on diabetic nephropathy by down-regulating transforming growth factor-β1 in streptozotocin-induced diabetic rat model

Directory of Open Access Journals (Sweden)

Maryam Foroutan Jazi

2016-03-01

Conclusion:Intraperitoneal injection of adenoviral vectors expressing fibromodulin  reduced TGF-β1 level in diabetic rat models. The molecular mechanisms involved in this process require further study.

Risk based surveillance for vector borne diseases

DEFF Research Database (Denmark)

Bødker, Rene

of samples and hence early detection of outbreaks. Models for vector borne diseases in Denmark have demonstrated dramatic variation in outbreak risk during the season and between years. The Danish VetMap project aims to make these risk based surveillance estimates available on the veterinarians smart phones...... in Northern Europe. This model approach may be used as a basis for risk based surveillance. In risk based surveillance limited resources for surveillance are targeted at geographical areas most at risk and only when the risk is high. This makes risk based surveillance a cost effective alternative...... sample to a diagnostic laboratory. Risk based surveillance models may reduce this delay. An important feature of risk based surveillance models is their ability to continuously communicate the level of risk to veterinarians and hence increase awareness when risk is high. This is essential for submission...

Robustness-Based Simplification of 2D Steady and Unsteady Vector Fields

KAUST Repository

Skraba, Primoz

2015-08-01

© 2015 IEEE. Vector field simplification aims to reduce the complexity of the flow by removing features in order of their relevance and importance, to reveal prominent behavior and obtain a compact representation for interpretation. Most existing simplification techniques based on the topological skeleton successively remove pairs of critical points connected by separatrices, using distance or area-based relevance measures. These methods rely on the stable extraction of the topological skeleton, which can be difficult due to instability in numerical integration, especially when processing highly rotational flows. In this paper, we propose a novel simplification scheme derived from the recently introduced topological notion of robustness which enables the pruning of sets of critical points according to a quantitative measure of their stability, that is, the minimum amount of vector field perturbation required to remove them. This leads to a hierarchical simplification scheme that encodes flow magnitude in its perturbation metric. Our novel simplification algorithm is based on degree theory and has minimal boundary restrictions. Finally, we provide an implementation under the piecewise-linear setting and apply it to both synthetic and real-world datasets. We show local and complete hierarchical simplifications for steady as well as unsteady vector fields.

Robustness-Based Simplification of 2D Steady and Unsteady Vector Fields.

Science.gov (United States)

Skraba, Primoz; Bei Wang; Guoning Chen; Rosen, Paul

2015-08-01

Vector field simplification aims to reduce the complexity of the flow by removing features in order of their relevance and importance, to reveal prominent behavior and obtain a compact representation for interpretation. Most existing simplification techniques based on the topological skeleton successively remove pairs of critical points connected by separatrices, using distance or area-based relevance measures. These methods rely on the stable extraction of the topological skeleton, which can be difficult due to instability in numerical integration, especially when processing highly rotational flows. In this paper, we propose a novel simplification scheme derived from the recently introduced topological notion of robustness which enables the pruning of sets of critical points according to a quantitative measure of their stability, that is, the minimum amount of vector field perturbation required to remove them. This leads to a hierarchical simplification scheme that encodes flow magnitude in its perturbation metric. Our novel simplification algorithm is based on degree theory and has minimal boundary restrictions. Finally, we provide an implementation under the piecewise-linear setting and apply it to both synthetic and real-world datasets. We show local and complete hierarchical simplifications for steady as well as unsteady vector fields.

Robustness-Based Simplification of 2D Steady and Unsteady Vector Fields

KAUST Repository

Skraba, Primoz; Wang, Bei; Chen, Guoning; Rosen, Paul

2015-01-01

© 2015 IEEE. Vector field simplification aims to reduce the complexity of the flow by removing features in order of their relevance and importance, to reveal prominent behavior and obtain a compact representation for interpretation. Most existing simplification techniques based on the topological skeleton successively remove pairs of critical points connected by separatrices, using distance or area-based relevance measures. These methods rely on the stable extraction of the topological skeleton, which can be difficult due to instability in numerical integration, especially when processing highly rotational flows. In this paper, we propose a novel simplification scheme derived from the recently introduced topological notion of robustness which enables the pruning of sets of critical points according to a quantitative measure of their stability, that is, the minimum amount of vector field perturbation required to remove them. This leads to a hierarchical simplification scheme that encodes flow magnitude in its perturbation metric. Our novel simplification algorithm is based on degree theory and has minimal boundary restrictions. Finally, we provide an implementation under the piecewise-linear setting and apply it to both synthetic and real-world datasets. We show local and complete hierarchical simplifications for steady as well as unsteady vector fields.

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

Science.gov (United States)

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

2011-10-26

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

Track Circuit Fault Diagnosis Method based on Least Squares Support Vector

Science.gov (United States)

Cao, Yan; Sun, Fengru

2018-01-01

In order to improve the troubleshooting efficiency and accuracy of the track circuit, track circuit fault diagnosis method was researched. Firstly, the least squares support vector machine was applied to design the multi-fault classifier of the track circuit, and then the measured track data as training samples was used to verify the feasibility of the methods. Finally, the results based on BP neural network fault diagnosis methods and the methods used in this paper were compared. Results shows that the track fault classifier based on least squares support vector machine can effectively achieve the five track circuit fault diagnosis with less computing time.

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

Science.gov (United States)

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

2016-01-01

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

Integrated Strategies for the Control and Prevention of Dengue Vectors with Particular Reference to Aedes aegypti

Directory of Open Access Journals (Sweden)

Asghar Abbas

2014-01-01

Full Text Available Dengue fever (DF is one of the most threatening vector borne diseases, affecting both humans and animals, causing severe epidemics and has brought the world to take serious steps for its control and prevention. DF is a viral disease transmitted by Aedes mosquitoes. Unfortunately, due to unavailability of vaccine and lack of effective treatment, emphasis is given on its vector control. The only option left for its eradication is to restrict mosquito breeding. This can be achieved by chemical, biological and environment management methods. Use of botanicals is also an alternate and probably most effective approach for controlling DF vector. Community based eradication campaigns including educating people about its prevention and control meseaures and personal prophylaxis also play a vital role to prevent its occurrence. Likewise, use of nanotechnology and micro-emulsion, use of pheromones, insect sterilization techniques has also shown promising results in vector control. Utilization of only one method cannot control this dangerous disease but combination of all above interventions, discussed in the present paper, may prevent the DF vector and ultimately might help in the eradication programs of this disease.

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...

Multiple image encryption scheme based on pixel exchange operation and vector decomposition

Science.gov (United States)

Xiong, Y.; Quan, C.; Tay, C. J.

2018-02-01

We propose a new multiple image encryption scheme based on a pixel exchange operation and a basic vector decomposition in Fourier domain. In this algorithm, original images are imported via a pixel exchange operator, from which scrambled images and pixel position matrices are obtained. Scrambled images encrypted into phase information are imported using the proposed algorithm and phase keys are obtained from the difference between scrambled images and synthesized vectors in a charge-coupled device (CCD) plane. The final synthesized vector is used as an input in a random phase encoding (DRPE) scheme. In the proposed encryption scheme, pixel position matrices and phase keys serve as additional private keys to enhance the security of the cryptosystem which is based on a 4-f system. Numerical simulations are presented to demonstrate the feasibility and robustness of the proposed encryption scheme.

Fuzzy-based multi-kernel spherical support vector machine for ...

Indian Academy of Sciences (India)

In the proposed classifier, we design a new multi-kernel function based on the fuzzy triangular membership function. Finally, a newly developed multi-kernel function is incorporated into the spherical support vector machine to enhance the performance significantly. The experimental results are evaluated and performance is ...

Vector control of wind turbine on the basis of the fuzzy selective neural net*

Science.gov (United States)

Engel, E. A.; Kovalev, I. V.; Engel, N. E.

2016-04-01

An article describes vector control of wind turbine based on fuzzy selective neural net. Based on the wind turbine system’s state, the fuzzy selective neural net tracks an maximum power point under random perturbations. Numerical simulations are accomplished to clarify the applicability and advantages of the proposed vector wind turbine’s control on the basis of the fuzzy selective neuronet. The simulation results show that the proposed intelligent control of wind turbine achieves real-time control speed and competitive performance, as compared to a classical control model with PID controllers based on traditional maximum torque control strategy.

Optimal vaccination strategies against vector-borne diseases

DEFF Research Database (Denmark)

Græsbøll, Kaare; Enøe, Claes; Bødker, Rene

2014-01-01

Using a process oriented semi-agent based model, we simulated the spread of Bluetongue virus by Culicoides, biting midges, between cattle in Denmark. We evaluated the minimum vaccination cover and minimum cost for eight different preventive vaccination strategies in Denmark. The simulation model ...... results when index cases were in the vaccinated areas. However, given that the long-range spread of midge borne disease is still poorly quantified, more robust national vaccination schemes seem preferable....

Prediction of Banking Systemic Risk Based on Support Vector Machine

Directory of Open Access Journals (Sweden)

Shouwei Li

2013-01-01

Full Text Available Banking systemic risk is a complex nonlinear phenomenon and has shed light on the importance of safeguarding financial stability by recent financial crisis. According to the complex nonlinear characteristics of banking systemic risk, in this paper we apply support vector machine (SVM to the prediction of banking systemic risk in an attempt to suggest a new model with better explanatory power and stability. We conduct a case study of an SVM-based prediction model for Chinese banking systemic risk and find the experiment results showing that support vector machine is an efficient method in such case.

A new generation of pPRIG-based retroviral vectors

Directory of Open Access Journals (Sweden)

Boulukos Kim E

2007-11-01

Full Text Available Abstract Background Retroviral vectors are valuable tools for gene transfer. Particularly convenient are IRES-containing retroviral vectors expressing both the protein of interest and a marker protein from a single bicistronic mRNA. This coupled expression increases the relevance of tracking and/or selection of transduced cells based on the detection of a marker protein. pAP2 is a retroviral vector containing eGFP downstream of a modified IRES element of EMCV origin, and a CMV enhancer-promoter instead of the U3 region of the 5'LTR, which increases its efficiency in transient transfection. However, pAP2 contains a limited multicloning site (MCS and shows weak eGFP expression, which previously led us to engineer an improved version, termed pPRIG, harboring: i the wild-type ECMV IRES sequence, thereby restoring its full activity; ii an optimized MCS flanked by T7 and SP6 sequences; and iii a HA tag encoding sequence 5' of the MCS (pPRIG HAa/b/c. Results The convenience of pPRIG makes it a good basic vector to generate additional derivatives for an extended range of use. Here we present several novel pPRIG-based vectors (collectively referred to as PRIGs in which : i the HA tag sequence was inserted in the three reading frames 3' of the MCS (3'HA PRIGs; ii a functional domain (ER, VP16 or KRAB was inserted either 5' or 3' of the MCS (« modular » PRIGs; iii eGFP was replaced by either eCFP, eYFP, mCherry or puro-R (« single color/resistance » PRIGs; and iv mCherry, eYFP or eGFP was inserted 5' of the MCS of the IRES-eGFP, IRES-eCFP or IRES-Puro-R containing PRIGs, respectively (« dual color/selection » PRIGs. Additionally, some of these PRIGs were also constructed in a pMigR MSCV background which has been widely used in pluripotent cells. Conclusion These novel vectors allow for straightforward detection of any expressed protein (3'HA PRIGs, for functional studies of chimeric proteins (« modular » PRIGs, for multiple transductions and

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.

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.

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

NARCIS (Netherlands)

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

2006-01-01

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

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

Directory of Open Access Journals (Sweden)

Roland Zahn

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

Yellow fever vectors' surveillance in three satellite communities of ...

African Journals Online (AJOL)

Outbreaks of yellow fever have continued to occur in various parts of Nigeria. ... easily render themselves to vector and environmental management strategies. ... vectors, while locally adapted CDC (Centre for Disease Control) ovitraps were ...

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

Accelerometer and Camera-Based Strategy for Improved Human Fall Detection

KAUST Repository

Zerrouki, Nabil; Harrou, Fouzi; Sun, Ying; Houacine, Amrane

2016-01-01

In this paper, we address the problem of detecting human falls using anomaly detection. Detection and classification of falls are based on accelerometric data and variations in human silhouette shape. First, we use the exponentially weighted moving average (EWMA) monitoring scheme to detect a potential fall in the accelerometric data. We used an EWMA to identify features that correspond with a particular type of fall allowing us to classify falls. Only features corresponding with detected falls were used in the classification phase. A benefit of using a subset of the original data to design classification models minimizes training time and simplifies models. Based on features corresponding to detected falls, we used the support vector machine (SVM) algorithm to distinguish between true falls and fall-like events. We apply this strategy to the publicly available fall detection databases from the university of Rzeszow’s. Results indicated that our strategy accurately detected and classified fall events, suggesting its potential application to early alert mechanisms in the event of fall situations and its capability for classification of detected falls. Comparison of the classification results using the EWMA-based SVM classifier method with those achieved using three commonly used machine learning classifiers, neural network, K-nearest neighbor and naïve Bayes, proved our model superior.

Accelerometer and Camera-Based Strategy for Improved Human Fall Detection

KAUST Repository

Zerrouki, Nabil

2016-10-29

In this paper, we address the problem of detecting human falls using anomaly detection. Detection and classification of falls are based on accelerometric data and variations in human silhouette shape. First, we use the exponentially weighted moving average (EWMA) monitoring scheme to detect a potential fall in the accelerometric data. We used an EWMA to identify features that correspond with a particular type of fall allowing us to classify falls. Only features corresponding with detected falls were used in the classification phase. A benefit of using a subset of the original data to design classification models minimizes training time and simplifies models. Based on features corresponding to detected falls, we used the support vector machine (SVM) algorithm to distinguish between true falls and fall-like events. We apply this strategy to the publicly available fall detection databases from the university of Rzeszow’s. Results indicated that our strategy accurately detected and classified fall events, suggesting its potential application to early alert mechanisms in the event of fall situations and its capability for classification of detected falls. Comparison of the classification results using the EWMA-based SVM classifier method with those achieved using three commonly used machine learning classifiers, neural network, K-nearest neighbor and naïve Bayes, proved our model superior.

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

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

Science.gov (United States)

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

2012-01-01

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

Vector-borne disease risk indexes in spatially structured populations.

Directory of Open Access Journals (Sweden)

Jorge Velázquez-Castro

2018-02-01

Full Text Available There are economic and physical limitations when applying prevention and control strategies for urban vector borne diseases. Consequently, there are increasing concerns and interest in designing efficient strategies and regulations that health agencies can follow in order to reduce the imminent impact of viruses like Dengue, Zika and Chikungunya. That includes fumigation, abatization, reducing the hatcheries, picking up trash, information campaigns. A basic question that arise when designing control strategies is about which and where these ones should focus. In other words, one would like to know whether preventing the contagion or decrease vector population, and in which area of the city, is more efficient. In this work, we propose risk indexes based on the idea of secondary cases from patch to patch. Thus, they take into account human mobility and indicate which patch has more chance to be a corridor for the spread of the disease and which is more vulnerable, i.e. more likely to have cases?. They can also indicate the neighborhood where hatchery control will reduce more the number of potential cases. In order to illustrate the usefulness of these indexes, we run a set of numerical simulations in a mathematical model that takes into account the urban mobility and the differences in population density among the areas of a city. If we label by i a particular neighborhood, the transmission risk index (TRi measures the potential secondary cases caused by a host in that neighborhood. The vector transmission risk index (VTRi measures the potential secondary cases caused by a vector. Finally, the vulnerability risk index (VRi measures the potential secondary cases in the neighborhood. Transmission indexes can be used to give geographical priority to some neighborhoods when applying prevention and control measures. On the other hand, the vulnerability index can be useful to implement monitoring campaigns or public health investment.

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...

Efficient gene transfer into nondividing cells by adeno-associated virus-based vectors.

OpenAIRE

Podsakoff, G; Wong, K K; Chatterjee, S

1994-01-01

Gene transfer vectors based on adeno-associated virus (AAV) are emerging as highly promising for use in human gene therapy by virtue of their characteristics of wide host range, high transduction efficiencies, and lack of cytopathogenicity. To better define the biology of AAV-mediated gene transfer, we tested the ability of an AAV vector to efficiently introduce transgenes into nonproliferating cell populations. Cells were induced into a nonproliferative state by treatment with the DNA synthe...

DSP Based Direct Torque Control of Permanent Magnet Synchronous Motor (PMSM) using Space Vector Modulation (DTC-SVM)

DEFF Research Database (Denmark)

Swierczynski, Dariusz; Kazmierkowski, Marian P.; Blaabjerg, Frede

2002-01-01

DSP Based Direct Torque Control of Permanent Magnet Synchronous Motor (PMSM) using Space Vector Modulation (DTC-SVM)......DSP Based Direct Torque Control of Permanent Magnet Synchronous Motor (PMSM) using Space Vector Modulation (DTC-SVM)...

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.

PGMA-Based Cationic Nanoparticles with Polyhydric Iodine Units for Advanced Gene Vectors.

Science.gov (United States)

Sun, Yue; Hu, Hao; Yu, Bingran; Xu, Fu-Jian

2016-11-16

It is crucial for successful gene delivery to develop safe, effective, and multifunctional polycations. Iodine-based small molecules are widely used as contrast agents for CT imaging. Herein, a series of star-like poly(glycidyl methacrylate) (PGMA)-based cationic vectors (II-PGEA/II) with abundant flanking polyhydric iodine units are prepared for multifunctional gene delivery systems. The proposed II-PGEA/II star vector is composed of one iohexol intermediate (II) core and five ethanolamine (EA) and II-difunctionalized PGMA arms. The amphipathic II-PGEA/II vectors readily self-assemble into well-defined cationic nanoparticles, where massive hydroxyl groups can establish a hydration shell to stabilize the nanoparticles. The II introduction improves cell viabilities of polycations. Moreover, by controlling the suitable amount of introduced II units, the resultant II-PGEA/II nanoparticles can produce fairly good transfection performances in different cell lines. Particularly, the II-PGEA/II nanoparticles induce much better in vitro CT imaging abilities in tumor cells than iohexol (one commonly used commercial CT contrast agent). The present design of amphipathic PGMA-based nanoparticles with CT contrast agents would provide useful information for the development of new multifunctional gene delivery systems.

Cancer gene therapy with targeted adenoviruses.

Science.gov (United States)

Bachtarzi, Houria; Stevenson, Mark; Fisher, Kerry

2008-11-01

Clinical experience with adenovirus vectors has highlighted the need for improved delivery and targeting. This manuscript aims to provide an overview of the techniques currently under development for improving adenovirus delivery to malignant cells in vivo. Primary research articles reporting improvements in adenoviral gene delivery are described. Strategies include genetic modification of viral coat proteins, non-genetic modifications including polymer encapsulation approaches and pharmacological interventions. Reprogramming adenovirus tropism in vitro has been convincingly demonstrated using a range of genetic and physical strategies. These studies have provided new insights into our understanding of virology and the field is progressing. However, there are still some limitations that need special consideration before adenovirus-targeted cancer gene therapy emerges as a routine treatment in the clinical setting.

Learning word vector representations based on acoustic counts

OpenAIRE

Ribeiro, Sam; Watts, Oliver; Yamagishi, Junichi

2017-01-01

This paper presents a simple count-based approach to learning word vector representations by leveraging statistics of cooccurrences between text and speech. This type of representation requires two discrete sequences of units defined across modalities. Two possible methods for the discretization of an acoustic signal are presented, which are then applied to fundamental frequency and energy contours of a transcribed corpus of speech, yielding a sequence of textual objects (e.g. words, syllable...

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.

Development of new USER-based cloning vectors for multiple genes expression in Saccharomyces cerevisiae

DEFF Research Database (Denmark)

Kildegaard, Kanchana Rueksomtawin; Jensen, Niels Bjerg; Maury, Jerome

2013-01-01

auxotrophic and dominant markers for convenience of use. Our vector set also contains both integrating and multicopy vectors for stability of protein expression and high expression level. We will make the new vector system available to the yeast community and provide a comprehensive protocol for cloning...... the production strain with the proper phenotype and product yield. However, the sequential number of metabolic engineering is time-consuming. Furthermore, the number of available selectable markers is also limiting the number of genetic modifications. To overcome these limitations, we have developed a new set...... of shuttle vectors for convenience of use for high-throughput cloning and selectable marker recycling. The new USER-based cloning vectors consist of a unique USER site and a CRE-loxP-mediated marker recycling system. The USER site allows insertion of genes of interest along with a bidirectional promoter...

Control strategy for Single-phase Transformerless Three-leg Unified Power Quality Conditioner Based on Space Vector Modulation

DEFF Research Database (Denmark)

Lu, Yong; Xiao, Guochun; Wang, Xiongfei

2016-01-01

The unified power quality conditioner (UPQC) is known as an effective compensation device to improve PQ for sensitive end-users. This paper investigates the operation and control of a single-phase three-leg UPQC (TL-UPQC), where a novel space vector modulation method is proposed for naturally...

Comparative Visualization of Vector Field Ensembles Based on Longest Common Subsequence

Energy Technology Data Exchange (ETDEWEB)

Liu, Richen; Guo, Hanqi; Zhang, Jiang; Yuan, Xiaoru

2016-04-19

We propose a longest common subsequence (LCS) based approach to compute the distance among vector field ensembles. By measuring how many common blocks the ensemble pathlines passing through, the LCS distance defines the similarity among vector field ensembles by counting the number of sharing domain data blocks. Compared to the traditional methods (e.g. point-wise Euclidean distance or dynamic time warping distance), the proposed approach is robust to outlier, data missing, and sampling rate of pathline timestep. Taking the advantages of smaller and reusable intermediate output, visualization based on the proposed LCS approach revealing temporal trends in the data at low storage cost, and avoiding tracing pathlines repeatedly. Finally, we evaluate our method on both synthetic data and simulation data, which demonstrate the robustness of the proposed approach.

Managing the resilience space of the German energy system - A vector analysis.

Science.gov (United States)

Schlör, Holger; Venghaus, Sandra; Märker, Carolin; Hake, Jürgen-Friedrich

2018-07-15

The UN Sustainable Development Goals formulated in 2016 confirmed the sustainability concept of the Earth Summit of 1992 and supported UNEP's green economy transition concept. The transformation of the energy system (Energiewende) is the keystone of Germany's sustainability strategy and of the German green economy concept. We use ten updated energy-related indicators of the German sustainability strategy to analyse the German energy system. The development of the sustainable indicators is examined in the monitoring process by a vector analysis performed in two-dimensional Euclidean space (Euclidean plane). The aim of the novel vector analysis is to measure the current status of the Energiewende in Germany and thereby provide decision makers with information about the strains for the specific remaining pathway of the single indicators and of the total system in order to meet the sustainability targets of the Energiewende. Within this vector model, three vectors (the normative sustainable development vector, the real development vector, and the green economy vector) define the resilience space of our analysis. The resilience space encloses a number of vectors representing different pathways with different technological and socio-economic strains to achieve a sustainable development of the green economy. In this space, the decision will be made as to whether the government measures will lead to a resilient energy system or whether a readjustment of indicator targets or political measures is necessary. The vector analysis enables us to analyse both the government's ambitiousness, which is expressed in the sustainability target for the indicators at the start of the sustainability strategy representing the starting preference order of the German government (SPO) and, secondly, the current preference order of German society in order to bridge the remaining distance to reach the specific sustainability goals of the strategy summarized in the current preference order (CPO

Onto2Vec: joint vector-based representation of biological entities and their ontology-based annotations

KAUST Repository

Smaili, Fatima Z.; Gao, Xin; Hoehndorf, Robert

2018-01-01

We propose the Onto2Vec method, an approach to learn feature vectors for biological entities based on their annotations to biomedical ontologies. Our method can be applied to a wide range of bioinformatics research problems such as similarity-based prediction of interactions between proteins, classification of interaction types using supervised learning, or clustering.

Onto2Vec: joint vector-based representation of biological entities and their ontology-based annotations

KAUST Repository

Smaili, Fatima Zohra

2018-01-31

We propose the Onto2Vec method, an approach to learn feature vectors for biological entities based on their annotations to biomedical ontologies. Our method can be applied to a wide range of bioinformatics research problems such as similarity-based prediction of interactions between proteins, classification of interaction types using supervised learning, or clustering.

Pseudotyped Lentiviral Vectors for Retrograde Gene Delivery into Target Brain Regions

Directory of Open Access Journals (Sweden)

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.

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

Gene therapy prospects--intranasal delivery of therapeutic genes.

Science.gov (United States)

Podolska, Karolina; Stachurska, Anna; Hajdukiewicz, Karolina; Małecki, Maciej

2012-01-01

Gene therapy is recognized to be a novel method for the treatment of various disorders. Gene therapy strategies involve gene manipulation on broad biological processes responsible for the spreading of diseases. Cancer, monogenic diseases, vascular and infectious diseases are the main targets of gene therapy. In order to obtain valuable experimental and clinical results, sufficient gene transfer methods are required. Therapeutic genes can be administered into target tissues via gene carriers commonly defined as vectors. The retroviral, adenoviral and adeno-associated virus based vectors are most frequently used in the clinic. So far, gene preparations may be administered directly into target organs or by intravenous, intramuscular, intratumor or intranasal injections. It is common knowledge that the number of gene therapy clinical trials has rapidly increased. However, some limitations such as transfection efficiency and stable and long-term gene expression are still not resolved. Consequently, great effort is focused on the evaluation of new strategies of gene delivery. There are many expectations associated with intranasal delivery of gene preparations for the treatment of diseases. Intranasal delivery of therapeutic genes is regarded as one of the most promising forms of pulmonary gene therapy research. Gene therapy based on inhalation of gene preparations offers an alternative way for the treatment of patients suffering from such lung diseases as cystic fibrosis, alpha-1-antitrypsin defect, or cancer. Experimental and first clinical trials based on plasmid vectors or recombinant viruses have revealed that gene preparations can effectively deliver therapeutic or marker genes to the cells of the respiratory tract. The noninvasive intranasal delivery of gene preparations or conventional drugs seems to be very encouraging, although basic scientific research still has to continue.

Support-Vector-based Least Squares for learning non-linear dynamics

NARCIS (Netherlands)

de Kruif, B.J.; de Vries, Theodorus J.A.

2002-01-01

A function approximator is introduced that is based on least squares support vector machines (LSSVM) and on least squares (LS). The potential indicators for the LS method are chosen as the kernel functions of all the training samples similar to LSSVM. By selecting these as indicator functions the

Improved Reliability-Based Optimization with Support Vector Machines and Its Application in Aircraft Wing Design

Directory of Open Access Journals (Sweden)

Yu Wang

2015-01-01

Full Text Available A new reliability-based design optimization (RBDO method based on support vector machines (SVM and the Most Probable Point (MPP is proposed in this work. SVM is used to create a surrogate model of the limit-state function at the MPP with the gradient information in the reliability analysis. This guarantees that the surrogate model not only passes through the MPP but also is tangent to the limit-state function at the MPP. Then, importance sampling (IS is used to calculate the probability of failure based on the surrogate model. This treatment significantly improves the accuracy of reliability analysis. For RBDO, the Sequential Optimization and Reliability Assessment (SORA is employed as well, which decouples deterministic optimization from the reliability analysis. The improved SVM-based reliability analysis is used to amend the error from linear approximation for limit-state function in SORA. A mathematical example and a simplified aircraft wing design demonstrate that the improved SVM-based reliability analysis is more accurate than FORM and needs less training points than the Monte Carlo simulation and that the proposed optimization strategy is efficient.

Research on intrusion detection based on Kohonen network and support vector machine

Science.gov (United States)

Shuai, Chunyan; Yang, Hengcheng; Gong, Zeweiyi

2018-05-01

In view of the problem of low detection accuracy and the long detection time of support vector machine, which directly applied to the network intrusion detection system. Optimization of SVM parameters can greatly improve the detection accuracy, but it can not be applied to high-speed network because of the long detection time. a method based on Kohonen neural network feature selection is proposed to reduce the optimization time of support vector machine parameters. Firstly, this paper is to calculate the weights of the KDD99 network intrusion data by Kohonen network and select feature by weight. Then, after the feature selection is completed, genetic algorithm (GA) and grid search method are used for parameter optimization to find the appropriate parameters and classify them by support vector machines. By comparing experiments, it is concluded that feature selection can reduce the time of parameter optimization, which has little influence on the accuracy of classification. The experiments suggest that the support vector machine can be used in the network intrusion detection system and reduce the missing rate.

Predictions of malaria vector distribution in Belize based on multispectral satellite data.

Science.gov (United States)

Roberts, D R; Paris, J F; Manguin, S; Harbach, R E; Woodruff, R; Rejmankova, E; Polanco, J; Wullschleger, B; Legters, L J

1996-03-01

Use of multispectral satellite data to predict arthropod-borne disease trouble spots is dependent on clear understandings of environmental factors that determine the presence of disease vectors. A blind test of remote sensing-based predictions for the spatial distribution of a malaria vector, Anopheles pseudopunctipennis, was conducted as a follow-up to two years of studies on vector-environmental relationships in Belize. Four of eight sites that were predicted to be high probability locations for presence of An. pseudopunctipennis were positive and all low probability sites (0 of 12) were negative. The absence of An. pseudopunctipennis at four high probability locations probably reflects the low densities that seem to characterize field populations of this species, i.e., the population densities were below the threshold of our sampling effort. Another important malaria vector, An. darlingi, was also present at all high probability sites and absent at all low probability sites. Anopheles darlingi, like An. pseudopunctipennis, is a riverine species. Prior to these collections at ecologically defined locations, this species was last detected in Belize in 1946.

Entropy-Based Video Steganalysis of Motion Vectors

Directory of Open Access Journals (Sweden)

Elaheh Sadat Sadat

2018-04-01

Full Text Available In this paper, a new method is proposed for motion vector steganalysis using the entropy value and its combination with the features of the optimized motion vector. In this method, the entropy of blocks is calculated to determine their texture and the precision of their motion vectors. Then, by using a fuzzy cluster, the blocks are clustered into the blocks with high and low texture, while the membership function of each block to a high texture class indicates the texture of that block. These membership functions are used to weight the effective features that are extracted by reconstructing the motion estimation equations. Characteristics of the results indicate that the use of entropy and the irregularity of each block increases the precision of the final video classification into cover and stego classes.

Effective Clipart Image Vectorization through Direct Optimization of Bezigons.

Science.gov (United States)

Yang, Ming; Chao, Hongyang; Zhang, Chi; Guo, Jun; Yuan, Lu; Sun, Jian

2016-02-01

Bezigons, i.e., closed paths composed of Bézier curves, have been widely employed to describe shapes in image vectorization results. However, most existing vectorization techniques infer the bezigons by simply approximating an intermediate vector representation (such as polygons). Consequently, the resultant bezigons are sometimes imperfect due to accumulated errors, fitting ambiguities, and a lack of curve priors, especially for low-resolution images. In this paper, we describe a novel method for vectorizing clipart images. In contrast to previous methods, we directly optimize the bezigons rather than using other intermediate representations; therefore, the resultant bezigons are not only of higher fidelity compared with the original raster image but also more reasonable because they were traced by a proficient expert. To enable such optimization, we have overcome several challenges and have devised a differentiable data energy as well as several curve-based prior terms. To improve the efficiency of the optimization, we also take advantage of the local control property of bezigons and adopt an overlapped piecewise optimization strategy. The experimental results show that our method outperforms both the current state-of-the-art method and commonly used commercial software in terms of bezigon quality.

Lentiviral Vectors for Cancer Immunotherapy and Clinical Applications

Directory of Open Access Journals (Sweden)

David Escors

2013-07-01

Full Text Available The success of immunotherapy against infectious diseases has shown us the powerful potential that such a treatment offers, and substantial work has been done to apply this strategy in the fight against cancer. Cancer is however a fiercer opponent than pathogen-caused diseases due to natural tolerance towards tumour associated antigens and tumour-induced immunosuppression. Recent gene therapy clinical trials with viral vectors have shown clinical efficacy in the correction of genetic diseases, HIV and cancer. The first successful gene therapy clinical trials were carried out with onco(g-retroviral vectors but oncogenesis by insertional mutagenesis appeared as a serious complication. Lentiviral vectors have emerged as a potentially safer strategy, and recently the first clinical trial of patients with advanced leukemia using lentiviral vectors has proven successful. Additionally, therapeutic lentivectors have shown clinical efficacy for the treatment of HIV, X-linked adrenoleukodystrophy, and b-thalassaemia. This review aims at describing lentivectors and how they can be utilized to boost anti-tumour immune responses by manipulating the effector immune cells.

Lentiviral Vectors for Cancer Immunotherapy and Clinical Applications

Energy Technology Data Exchange (ETDEWEB)

Liechtenstein, Therese, E-mail: t.liechtenstein.12@ucl.ac.uk [University College London, 5 University Street, London, WC1E 6JF (United Kingdom); Perez-Janices, Noemi; Escors, David [University College London, 5 University Street, London, WC1E 6JF (United Kingdom); Navarrabiomed Fundacion Miguel Servet, 3 Irunlarrea St., Hospital Complex of Navarra, 31008 Pamplona, Navarra (Spain)

2013-07-02

The success of immunotherapy against infectious diseases has shown us the powerful potential that such a treatment offers, and substantial work has been done to apply this strategy in the fight against cancer. Cancer is however a fiercer opponent than pathogen-caused diseases due to natural tolerance towards tumour associated antigens and tumour-induced immunosuppression. Recent gene therapy clinical trials with viral vectors have shown clinical efficacy in the correction of genetic diseases, HIV and cancer. The first successful gene therapy clinical trials were carried out with onco(γ-)retroviral vectors but oncogenesis by insertional mutagenesis appeared as a serious complication. Lentiviral vectors have emerged as a potentially safer strategy, and recently the first clinical trial of patients with advanced leukemia using lentiviral vectors has proven successful. Additionally, therapeutic lentivectors have shown clinical efficacy for the treatment of HIV, X-linked adrenoleukodystrophy, and β-thalassaemia. This review aims at describing lentivectors and how they can be utilized to boost anti-tumour immune responses by manipulating the effector immune cells.

Lentiviral Vectors for Cancer Immunotherapy and Clinical Applications

International Nuclear Information System (INIS)

Liechtenstein, Therese; Perez-Janices, Noemi; Escors, David

2013-01-01

The success of immunotherapy against infectious diseases has shown us the powerful potential that such a treatment offers, and substantial work has been done to apply this strategy in the fight against cancer. Cancer is however a fiercer opponent than pathogen-caused diseases due to natural tolerance towards tumour associated antigens and tumour-induced immunosuppression. Recent gene therapy clinical trials with viral vectors have shown clinical efficacy in the correction of genetic diseases, HIV and cancer. The first successful gene therapy clinical trials were carried out with onco(γ-)retroviral vectors but oncogenesis by insertional mutagenesis appeared as a serious complication. Lentiviral vectors have emerged as a potentially safer strategy, and recently the first clinical trial of patients with advanced leukemia using lentiviral vectors has proven successful. Additionally, therapeutic lentivectors have shown clinical efficacy for the treatment of HIV, X-linked adrenoleukodystrophy, and β-thalassaemia. This review aims at describing lentivectors and how they can be utilized to boost anti-tumour immune responses by manipulating the effector immune cells

Slope Deformation Prediction Based on Support Vector Machine

Directory of Open Access Journals (Sweden)

Lei JIA

2013-07-01

Full Text Available This paper principally studies the prediction of slope deformation based on Support Vector Machine (SVM. In the prediction process，explore how to reconstruct the phase space. The geological body’s displacement data obtained from chaotic time series are used as SVM’s training samples. Slope displacement caused by multivariable coupling is predicted by means of single variable. Results show that this model is of high fitting accuracy and generalization, and provides reference for deformation prediction in slope engineering.

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 ...

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

Science.gov (United States)

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

2014-11-01

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

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.

Ecdysone Receptor-based Singular Gene Switches for Regulated Transgene Expression in Cells and Adult Rodent Tissues

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Seoghyun Lee

2016-01-01

Full Text Available Controlled gene expression is an indispensable technique in biomedical research. Here, we report a convenient, straightforward, and reliable way to induce expression of a gene of interest with negligible background expression compared to the most widely used tetracycline (Tet-regulated system. Exploiting a Drosophila ecdysone receptor (EcR-based gene regulatory system, we generated nonviral and adenoviral singular vectors designated as pEUI(+ and pENTR-EUI, respectively, which contain all the required elements to guarantee regulated transgene expression (GAL4-miniVP16-EcR, termed GvEcR hereafter, and 10 tandem repeats of an upstream activation sequence promoter followed by a multiple cloning site. Through the transient and stable transfection of mammalian cell lines with reporter genes, we validated that tebufenozide, an ecdysone agonist, reversibly induced gene expression, in a dose- and time-dependent manner, with negligible background expression. In addition, we created an adenovirus derived from the pENTR-EUI vector that readily infected not only cultured cells but also rodent tissues and was sensitive to tebufenozide treatment for regulated transgene expression. These results suggest that EcR-based singular gene regulatory switches would be convenient tools for the induction of gene expression in cells and tissues in a tightly controlled fashion.

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

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

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Simone C de Cassan

2015-07-01

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

Dual linear structured support vector machine tracking method via scale correlation filter

Science.gov (United States)

Li, Weisheng; Chen, Yanquan; Xiao, Bin; Feng, Chen

2018-01-01

Adaptive tracking-by-detection methods based on structured support vector machine (SVM) performed well on recent visual tracking benchmarks. However, these methods did not adopt an effective strategy of object scale estimation, which limits the overall tracking performance. We present a tracking method based on a dual linear structured support vector machine (DLSSVM) with a discriminative scale correlation filter. The collaborative tracker comprised of a DLSSVM model and a scale correlation filter obtains good results in tracking target position and scale estimation. The fast Fourier transform is applied for detection. Extensive experiments show that our tracking approach outperforms many popular top-ranking trackers. On a benchmark including 100 challenging video sequences, the average precision of the proposed method is 82.8%.

Spatio-temporal Rich Model Based Video Steganalysis on Cross Sections of Motion Vector Planes.

Science.gov (United States)

Tasdemir, Kasim; Kurugollu, Fatih; Sezer, Sakir

2016-05-11

A rich model based motion vector steganalysis benefiting from both temporal and spatial correlations of motion vectors is proposed in this work. The proposed steganalysis method has a substantially superior detection accuracy than the previous methods, even the targeted ones. The improvement in detection accuracy lies in several novel approaches introduced in this work. Firstly, it is shown that there is a strong correlation, not only spatially but also temporally, among neighbouring motion vectors for longer distances. Therefore, temporal motion vector dependency along side the spatial dependency is utilized for rigorous motion vector steganalysis. Secondly, unlike the filters previously used, which were heuristically designed against a specific motion vector steganography, a diverse set of many filters which can capture aberrations introduced by various motion vector steganography methods is used. The variety and also the number of the filter kernels are substantially more than that of used in previous ones. Besides that, filters up to fifth order are employed whereas the previous methods use at most second order filters. As a result of these, the proposed system captures various decorrelations in a wide spatio-temporal range and provides a better cover model. The proposed method is tested against the most prominent motion vector steganalysis and steganography methods. To the best knowledge of the authors, the experiments section has the most comprehensive tests in motion vector steganalysis field including five stego and seven steganalysis methods. Test results show that the proposed method yields around 20% detection accuracy increase in low payloads and 5% in higher payloads.

Space vector-based analysis of overmodulation in triangle ...

Indian Academy of Sciences (India)

methods such as vector control or field oriented control are used for fast dynamic response .... This average voltage vector falls in sector-I as shown in figure 5 for .... The dwell times T1, T2 and Tz can be derived using volt-second balance.

Voltage Stability Control of Electrical Network Using Intelligent Load Shedding Strategy Based on Fuzzy Logic

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Houda Jouini

2010-01-01

Full Text Available As a perspective to ensure the power system stability and to avoid the vulnerability leading to the blackouts, several preventive and curative means are adopted. In order to avoid the voltage collapse, load shedding schemes represent a suitable action to maintain the power system service quality and to control its vulnerability. In this paper, we try to propose an intelligent load shedding strategy as a new approach based on fuzzy controllers. This strategy was founded on the calculation of generated power sensitivity degree related to those injected at different network buses. During the fault phase, fuzzy controller algorithms generate monitor vectors ensuring a precalculated load shedding ratio in the purpose to reestablish the power balance and conduct the network to a new steady state.

Use of a mixture statistical model in studying malaria vectors density.

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Olayidé Boussari

Full Text Available Vector control is a major step in the process of malaria control and elimination. This requires vector counts and appropriate statistical analyses of these counts. However, vector counts are often overdispersed. A non-parametric mixture of Poisson model (NPMP is proposed to allow for overdispersion and better describe vector distribution. Mosquito collections using the Human Landing Catches as well as collection of environmental and climatic data were carried out from January to December 2009 in 28 villages in Southern Benin. A NPMP regression model with "village" as random effect is used to test statistical correlations between malaria vectors density and environmental and climatic factors. Furthermore, the villages were ranked using the latent classes derived from the NPMP model. Based on this classification of the villages, the impacts of four vector control strategies implemented in the villages were compared. Vector counts were highly variable and overdispersed with important proportion of zeros (75%. The NPMP model had a good aptitude to predict the observed values and showed that: i proximity to freshwater body, market gardening, and high levels of rain were associated with high vector density; ii water conveyance, cattle breeding, vegetation index were associated with low vector density. The 28 villages could then be ranked according to the mean vector number as estimated by the random part of the model after adjustment on all covariates. The NPMP model made it possible to describe the distribution of the vector across the study area. The villages were ranked according to the mean vector density after taking into account the most important covariates. This study demonstrates the necessity and possibility of adapting methods of vector counting and sampling to each setting.

Introduction to Vector Field Visualization

Science.gov (United States)

Kao, David; Shen, Han-Wei

2010-01-01

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

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.

Vehicle Based Vector Sensor

Science.gov (United States)

2015-09-28

buoyant underwater vehicle with an interior space in which a length of said underwater vehicle is equal to one tenth of the acoustic wavelength...underwater vehicle with an interior space in which a length of said underwater vehicle is equal to one tenth of the acoustic wavelength; an...unmanned underwater vehicle that can function as an acoustic vector sensor. (2) Description of the Prior Art [0004] It is known that a propagating

Exploring query execution strategies for JIT vectorization and SIMD

NARCIS (Netherlands)

T.K. Gubner (Tim); P.A. Boncz (Peter)

2017-01-01

textabstractThis paper partially explores the design space for efficient query processors on future hardware that is rich in SIMD capabilities. It departs from two well-known approaches: (1) interpreted block-at-a-time execution (a.k.a. "vectorization") and (2) "data-centric" JIT compilation, as in

Intrusive versus domiciliated triatomines and the challenge of adapting vector control practices against Chagas disease

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Etienne Waleckx

2015-05-01

Full Text Available Chagas disease prevention remains mostly based on triatomine vector control to reduce or eliminate house infestation with these bugs. The level of adaptation of triatomines to human housing is a key part of vector competence and needs to be precisely evaluated to allow for the design of effective vector control strategies. In this review, we examine how the domiciliation/intrusion level of different triatomine species/populations has been defined and measured and discuss how these concepts may be improved for a better understanding of their ecology and evolution, as well as for the design of more effective control strategies against a large variety of triatomine species. We suggest that a major limitation of current criteria for classifying triatomines into sylvatic, intrusive, domiciliary and domestic species is that these are essentially qualitative and do not rely on quantitative variables measuring population sustainability and fitness in their different habitats. However, such assessments may be derived from further analysis and modelling of field data. Such approaches can shed new light on the domiciliation process of triatomines and may represent a key tool for decision-making and the design of vector control interventions.

A versatile system for USER cloning-based assembly of expression vectors for mammalian cell engineering.

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Anne Mathilde Lund

Full Text Available A new versatile mammalian vector system for protein production, cell biology analyses, and cell factory engineering was developed. The vector system applies the ligation-free uracil-excision based technique--USER cloning--to rapidly construct mammalian expression vectors of multiple DNA fragments and with maximum flexibility, both for choice of vector backbone and cargo. The vector system includes a set of basic vectors and a toolbox containing a multitude of DNA building blocks including promoters, terminators, selectable marker- and reporter genes, and sequences encoding an internal ribosome entry site, cellular localization signals and epitope- and purification tags. Building blocks in the toolbox can be easily combined as they contain defined and tested Flexible Assembly Sequence Tags, FASTs. USER cloning with FASTs allows rapid swaps of gene, promoter or selection marker in existing plasmids and simple construction of vectors encoding proteins, which are fused to fluorescence-, purification-, localization-, or epitope tags. The mammalian expression vector assembly platform currently allows for the assembly of up to seven fragments in a single cloning step with correct directionality and with a cloning efficiency above 90%. The functionality of basic vectors for FAST assembly was tested and validated by transient expression of fluorescent model proteins in CHO, U-2-OS and HEK293 cell lines. In this test, we included many of the most common vector elements for heterologous gene expression in mammalian cells, in addition the system is fully extendable by other users. The vector system is designed to facilitate high-throughput genome-scale studies of mammalian cells, such as the newly sequenced CHO cell lines, through the ability to rapidly generate high-fidelity assembly of customizable gene expression vectors.

Medical image compression based on vector quantization with variable block sizes in wavelet domain.

Science.gov (United States)

Jiang, Huiyan; Ma, Zhiyuan; Hu, Yang; Yang, Benqiang; Zhang, Libo

2012-01-01

An optimized medical image compression algorithm based on wavelet transform and improved vector quantization is introduced. The goal of the proposed method is to maintain the diagnostic-related information of the medical image at a high compression ratio. Wavelet transformation was first applied to the image. For the lowest-frequency subband of wavelet coefficients, a lossless compression method was exploited; for each of the high-frequency subbands, an optimized vector quantization with variable block size was implemented. In the novel vector quantization method, local fractal dimension (LFD) was used to analyze the local complexity of each wavelet coefficients, subband. Then an optimal quadtree method was employed to partition each wavelet coefficients, subband into several sizes of subblocks. After that, a modified K-means approach which is based on energy function was used in the codebook training phase. At last, vector quantization coding was implemented in different types of sub-blocks. In order to verify the effectiveness of the proposed algorithm, JPEG, JPEG2000, and fractal coding approach were chosen as contrast algorithms. Experimental results show that the proposed method can improve the compression performance and can achieve a balance between the compression ratio and the image visual quality.

Vestibular regeneration ? experimental models and clinical implications

OpenAIRE

Albu, Silviu; Muresanu, Dafin F

2012-01-01

Therapies aimed at the protection and/or regeneration of inner ear hair cells are of great interest, given the significant monetary and quality of life impact of balance disorders. Different viral vectors have been shown to transfect various cell types in the inner ear. The past decade has provided tremendous advances in the use of adenoviral vectors to achieve targeted treatment delivery. Several routes of delivery have been identified to introduce vectors into the inner ear while minimizing...

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)

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

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Xishuang Liu

2011-01-01

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

Early life vaccination

DEFF Research Database (Denmark)

Nazerai, Loulieta; Bassi, Maria Rosaria; Uddbäck, Ida Elin Maria

2016-01-01

Intracellular pathogens represent a serious threat during early life. Importantly, even though the immune system of newborns may be characterized as developmentally immature, with a propensity to develop Th2 immunity, significant CD8+ T-cell responses may still be elicited in the context of optimal...... the first period of life and provide a pertinent alternative in infant vaccinology. To address this, infant mice were vaccinated with three different adenoviral vectors and the CD8+ T-cell response after early life vaccination was explored. We assessed the frequency, polyfunctionality and in vivo...... cytotoxicity of the elicited memory CD8+ T cells, as well as the potential of these cells to respond to secondary infections and confer protection. We further tested the impact of maternal immunity against our replication-deficient adenoviral vector during early life vaccination. Overall, our results indicate...

Modelling and Simulation of SVPWM Based Vector Controlled HVDC Light Systems

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Ajay Kumar MOODADLA

2012-11-01

Full Text Available Recent upgrades in power electronics technology have lead to the improvements of insulated gate bipolar transistor (IGBT based Voltage source converter High voltage direct current (VSC HVDC transmission systems. These are also commercially known as HVDC Light systems, which are popular in renewable, micro grid, and electric power systems. Out of different pulse width modulation (PWM schemes, Space vector PWM (SVPWM control scheme finds growing importance in power system applications because of its better dc bus utilization. In this paper, modelling of the converter is described, and SVPWM scheme is utilized to control the HVDC Light system in order to achieve better DC bus utilization, harmonic reduction, and for reduced power fluctuations. The simulations are carried out in the MATLAB/SIMULINK environment and the results are provided for steady state and dynamic conditions. Finally, the performance of SVPWM based vector controlled HVDC Light transmission system is compared with sinusoidal pulse width modulation (SPWM based HVDC Light system in terms of output voltage and total harmonic distortion (THD.

Retrieving current and wind vectors from ATI SAR data: airborne evidence and inversion strategy

Science.gov (United States)

Martin, Adrien; Gommenginger, Christine; Chapron, Bertrand; Marquez, José; Doody, Sam

2017-04-01

Conventional and along-track interferometric (ATI) Synthetic Aperture Radar (SAR) sense the motion of the ocean surface by measuring the Doppler shift of reflected signals. Together with the water displacement associated with ocean currents, the SAR measurements are also affected by a Wind-wave induced Artefact Surface Velocity (WASV) caused by the velocity of Bragg scatterers and the orbital velocity of ocean surface gravity waves. The WASV has been modelled theoretically in past studies but has been estimated empirically only once using Envisat ASAR. Here we propose, firstly, to evaluate this WASV from airborne ATI SAR data, secondly, to validate the airborne retrieved surface current after correction of the WASV against HF radar measurements and thirdly to examine the best inversion strategy for a an Ocean Surface Current (OSC) satellite mission to retrieve accurately both the ocean surface current vector (OSCV) and the wind vector in the frame of an OSC satellite mission. The airborne ATI SAR data were acquired in the tidally dominated Irish Sea using a Wavemill-type dual-beam SAR interferometer. A comprehensive collection of airborne Wavemill data acquired in a star pattern over a well-instrumented site made it possible to estimate the magnitude and dependence on azimuth and incidence angle of the WASV. The airborne results compare favourably with those reported for Envisat ASAR, empirical model, which has been used to correct for it. Validation of the current retrieval capabilities of the proof-of-concept has been conducted against HF radar giving a precisions typically better than 0.1 m/s for surface current speed and 7° for direction. Comparisons with POLCOMS (1.8 km) indicate that the model reproduces well the overall temporal evolution but does not capture the high spatial variability of ocean surface currents at the maximum ebb flow. Airborne retrieved currents highlight a short-scale spatial variability up to 100m related to bathymetry channels, which

A support vector machine (SVM) based voltage stability classifier

Energy Technology Data Exchange (ETDEWEB)

Dosano, R.D.; Song, H. [Kunsan National Univ., Kunsan, Jeonbuk (Korea, Republic of); Lee, B. [Korea Univ., Seoul (Korea, Republic of)

2007-07-01

Power system stability has become even more complex and critical with the advent of deregulated energy markets and the growing desire to completely employ existing transmission and infrastructure. The economic pressure on electricity markets forces the operation of power systems and components to their limit of capacity and performance. System conditions can be more exposed to instability due to greater uncertainty in day to day system operations and increase in the number of potential components for system disturbances potentially resulting in voltage stability. This paper proposed a support vector machine (SVM) based power system voltage stability classifier using local measurements of voltage and active power of load. It described the procedure for fast classification of long-term voltage stability using the SVM algorithm. The application of the SVM based voltage stability classifier was presented with reference to the choice of input parameters; input data preconditioning; moving window for feature vector; determination of learning samples; and other considerations in SVM applications. The paper presented a case study with numerical examples of an 11-bus test system. The test results for the feasibility study demonstrated that the classifier could offer an excellent performance in classification with time-series measurements in terms of long-term voltage stability. 9 refs., 14 figs.

Soft sensor development and optimization of the commercial petrochemical plant integrating support vector regression and genetic algorithm

Directory of Open Access Journals (Sweden)

S.K. Lahiri

2009-09-01

Full Text Available Soft sensors have been widely used in the industrial process control to improve the quality of the product and assure safety in the production. The core of a soft sensor is to construct a soft sensing model. This paper introduces support vector regression (SVR, a new powerful machine learning methodbased on a statistical learning theory (SLT into soft sensor modeling and proposes a new soft sensing modeling method based on SVR. This paper presents an artificial intelligence based hybrid soft sensormodeling and optimization strategies, namely support vector regression – genetic algorithm (SVR-GA for modeling and optimization of mono ethylene glycol (MEG quality variable in a commercial glycol plant. In the SVR-GA approach, a support vector regression model is constructed for correlating the process data comprising values of operating and performance variables. Next, model inputs describing the process operating variables are optimized using genetic algorithm with a view to maximize the process performance. The SVR-GA is a new strategy for soft sensor modeling and optimization. The major advantage of the strategies is that modeling and optimization can be conducted exclusively from the historic process data wherein the detailed knowledge of process phenomenology (reaction mechanism, kinetics etc. is not required. Using SVR-GA strategy, a number of sets of optimized operating conditions were found. The optimized solutions, when verified in an actual plant, resulted in a significant improvement in the quality.

A Reactive Power Based Reference Model for Adaptive Control Strategy in a SEIG

Directory of Open Access Journals (Sweden)

M. A. Taghikhani

2018-02-01

Full Text Available In this paper, a new control strategy is proposed for a three-phase squirrel-cage self-excited induction generator (SEIG connected to a variable speed wind turbine in autonomous mode. In order to improve the dynamic performance of the mentioned vector control system, a model reference adaptive controller is used for online rotor time constant estimation. Thus, the main drawbacks of this method, which include the effects of the changes in machine parameters on rotor flux estimation, slip speed, the creation of instability problems and the system leaving vector control mode, are resolved. In this control strategy, a PI controller is used to control the dc voltage and three similar hysteresis current controllers (HCC are used to control the switching of IGBTs. The results of the dynamic simulation indicate the desirable performance of the proposed system.

Energy Based Clutter Filtering for Vector Flow Imaging

DEFF Research Database (Denmark)

Villagómez Hoyos, Carlos Armando; Jensen, Jonas; Ewertsen, Caroline

2017-01-01

for obtaining vector flow measurements, since the spectra overlaps at high beam-to-flow angles. In this work a distinct approach is proposed, where the energy of the velocity spectrum is used to differentiate among the two signals. The energy based method is applied by limiting the amplitude of the velocity...... spectrum function to a predetermined threshold. The effect of the clutter filtering is evaluated on a plane wave (PW) scan sequence in combination with transverse oscillation (TO) and directional beamforming (DB) for velocity estimation. The performance of the filter is assessed by comparison...

Ecology of Anopheles darlingi Root with respect to vector importance: a review

NARCIS (Netherlands)

Hiwat, H.; Bretas, G.

2011-01-01

Anopheles darlingi is one of the most important malaria vectors in the Americas. In this era of new tools and strategies for malaria and vector control it is essential to have knowledge on the ecology and behavior of vectors in order to evaluate appropriateness and impact of control measures. This

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.

A method for attitude measurement of a test vehicle based on the tracking of vectors

International Nuclear Information System (INIS)

Yang, Ning; Yang, Ming; Huo, Ju

2015-01-01

In the vehicle simulation test, in order to improve the measuring precision for the attitude of a test vehicle, a measuring method based on the vectors of light beams is presented, in which light beams are mounted on the test vehicle as the cooperation target, and the attitude of the test vehicle is calculated with the light beams’ vectors in the test vehicle’s coordinate system and the world coordinate system. Meanwhile, in order to expand the measuring range of the attitude parameters, cooperation targets and light beams in each cooperation target are increased. On this basis, the concept of an attitude calculation container is defined, and the selection method for the attitude calculation container that participates in the calculation is given. Simultaneously, the vectors of light beams are tracked so as to ensure the normal calculation of the attitude parameters. The experiments results show that this measuring method based on the tracking of vectors can achieve the high precision and wide range of measurement for the attitude of the test vehicle. (paper)

Oral Modeling of an Adenovirus-Based Quadrivalent Influenza Vaccine in Ferrets and Mice.

Science.gov (United States)

Scallan, Ciaran D; Lindbloom, Jonathan D; Tucker, Sean N

2016-06-01

Oral vaccines delivered as tablets offer a number of advantages over traditional parenteral-based vaccines including the ease of delivery, lack of needles, no need for trained medical personnel, and the ability to formulate into temperature-stable tablets. We have been evaluating an oral vaccine platform based on recombinant adenoviral vectors for the purpose of creating a prophylactic vaccine to prevent influenza, and have demonstrated vaccine efficacy in animal models and substantial immunogenicity in humans. These studies have evaluated monovalent vaccines to date. To protect against the major circulating A and B influenza strains, a multivalent influenza vaccine will be required. In this study, the immunogenicity of orally delivered monovalent, bivalent, trivalent, and quadrivalent vaccines was tested in ferrets and mice. The various vaccine combinations were tested by blending monovalent recombinant adenovirus vaccines, each expressing hemagglutinin from a single strain. Human tablet delivery was modeled in animals by oral gavage in mice and by endoscopic delivery in ferrets. We demonstrated minimal interference between the various vaccine vectors when used in combination and that the oral quadrivalent vaccine compared favorably to an approved trivalent inactivated vaccine. The quadrivalent vaccine presented here produced immune responses that we predict should be capable of providing protection against multiple influenza strains, and the platform should have applications to other multivalent vaccines. Vaxart, Inc.

a Method for the Seamlines Network Automatic Selection Based on Building Vector

Science.gov (United States)

Li, P.; Dong, Y.; Hu, Y.; Li, X.; Tan, P.

2018-04-01

In order to improve the efficiency of large scale orthophoto production of city, this paper presents a method for automatic selection of seamlines network in large scale orthophoto based on the buildings' vector. Firstly, a simple model of the building is built by combining building's vector, height and DEM, and the imaging area of the building on single DOM is obtained. Then, the initial Voronoi network of the measurement area is automatically generated based on the positions of the bottom of all images. Finally, the final seamlines network is obtained by optimizing all nodes and seamlines in the network automatically based on the imaging areas of the buildings. The experimental results show that the proposed method can not only get around the building seamlines network quickly, but also remain the Voronoi network' characteristics of projection distortion minimum theory, which can solve the problem of automatic selection of orthophoto seamlines network in image mosaicking effectively.

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

International Nuclear Information System (INIS)

Zhang Kejun; Li Dechun; Zhu Dongming; Song Caixia

2007-01-01

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

Rigid Body Time Integration by Convected Base Vectors with Implicit Constraints

DEFF Research Database (Denmark)

Krenk, Steen; Nielsen, Martin Bjerre

2013-01-01

of the kinetic energy used in the present formulation is deliberately chosen to correspond to a rigid body rotation, and the orthonormality constraints are introduced via the equivalent Green strain components of the base vectors. The particular form of the extended inertia tensor used here implies a set...

Modeling Malaria Vector Distribution under Climate Change Scenarios in Kenya

Science.gov (United States)

Ngaina, J. N.

2017-12-01

Projecting the distribution of malaria vectors under climate change is essential for planning integrated vector control strategies for sustaining elimination and preventing reintroduction of malaria. However, in Kenya, little knowledge exists on the possible effects of climate change on malaria vectors. Here we assess the potential impact of future climate change on locally dominant Anopheles vectors including Anopheles gambiae, Anopheles arabiensis, Anopheles merus, Anopheles funestus, Anopheles pharoensis and Anopheles nili. Environmental data (Climate, Land cover and elevation) and primary empirical geo-located species-presence data were identified. The principle of maximum entropy (Maxent) was used to model the species' potential distribution area under paleoclimate, current and future climates. The Maxent model was highly accurate with a statistically significant AUC value. Simulation-based estimates suggest that the environmentally suitable area (ESA) for Anopheles gambiae, An. arabiensis, An. funestus and An. pharoensis would increase under all two scenarios for mid-century (2016-2045), but decrease for end century (2071-2100). An increase in ESA of An. Funestus was estimated under medium stabilizing (RCP4.5) and very heavy (RCP8.5) emission scenarios for mid-century. Our findings can be applied in various ways such as the identification of additional localities where Anopheles malaria vectors may already exist, but has not yet been detected and the recognition of localities where it is likely to spread to. Moreover, it will help guide future sampling location decisions, help with the planning of vector control suites nationally and encourage broader research inquiry into vector species niche modeling

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.

A glycolipid adjuvant, 7DW8-5, enhances CD8+ T cell responses induced by an adenovirus-vectored malaria vaccine in non-human primates.

Science.gov (United States)

Padte, Neal N; Boente-Carrera, Mar; Andrews, Chasity D; McManus, Jenny; Grasperge, Brooke F; Gettie, Agegnehu; Coelho-dos-Reis, Jordana G; Li, Xiangming; Wu, Douglass; Bruder, Joseph T; Sedegah, Martha; Patterson, Noelle; Richie, Thomas L; Wong, Chi-Huey; Ho, David D; Vasan, Sandhya; Tsuji, Moriya

2013-01-01

A key strategy to a successful vaccine against malaria is to identify and develop new adjuvants that can enhance T-cell responses and improve protective immunity. Upon co-administration with a rodent malaria vaccine in mice, 7DW8-5, a recently identified novel analog of α-galactosylceramide (α-GalCer), enhances the level of malaria-specific protective immune responses more strongly than the parent compound. In this study, we sought to determine whether 7DW8-5 could provide a similar potent adjuvant effect on a candidate human malaria vaccine in the more relevant non-human primate (NHP) model, prior to committing to clinical development. The candidate human malaria vaccine, AdPfCA (NMRC-M3V-Ad-PfCA), consists of two non-replicating recombinant adenoviral (Ad) vectors, one expressing the circumsporozoite protein (CSP) and another expressing the apical membrane antigen-1 (AMA1) of Plasmodium falciparum. In several phase 1 clinical trials, AdPfCA was well tolerated and demonstrated immunogenicity for both humoral and cell-mediated responses. In the study described herein, 25 rhesus macaques received prime and boost intramuscular (IM) immunizations of AdPfCA alone or with an ascending dose of 7DW8-5. Our results indicate that 7DW8-5 is safe and well-tolerated and provides a significant enhancement (up to 9-fold) in malaria-specific CD8+ T-cell responses after both priming and boosting phases, supporting further clinical development.

A glycolipid adjuvant, 7DW8-5, enhances CD8+ T cell responses induced by an adenovirus-vectored malaria vaccine in non-human primates.

Directory of Open Access Journals (Sweden)

Neal N Padte

Full Text Available A key strategy to a successful vaccine against malaria is to identify and develop new adjuvants that can enhance T-cell responses and improve protective immunity. Upon co-administration with a rodent malaria vaccine in mice, 7DW8-5, a recently identified novel analog of α-galactosylceramide (α-GalCer, enhances the level of malaria-specific protective immune responses more strongly than the parent compound. In this study, we sought to determine whether 7DW8-5 could provide a similar potent adjuvant effect on a candidate human malaria vaccine in the more relevant non-human primate (NHP model, prior to committing to clinical development. The candidate human malaria vaccine, AdPfCA (NMRC-M3V-Ad-PfCA, consists of two non-replicating recombinant adenoviral (Ad vectors, one expressing the circumsporozoite protein (CSP and another expressing the apical membrane antigen-1 (AMA1 of Plasmodium falciparum. In several phase 1 clinical trials, AdPfCA was well tolerated and demonstrated immunogenicity for both humoral and cell-mediated responses. In the study described herein, 25 rhesus macaques received prime and boost intramuscular (IM immunizations of AdPfCA alone or with an ascending dose of 7DW8-5. Our results indicate that 7DW8-5 is safe and well-tolerated and provides a significant enhancement (up to 9-fold in malaria-specific CD8+ T-cell responses after both priming and boosting phases, supporting further clinical development.

Modulation Strategy of a 3 × 5 Modular Multilevel Matrix Converter

Directory of Open Access Journals (Sweden)

Rutian Wang

2018-02-01

Full Text Available In this paper, a modulation strategy of a 3 × 5 modular multilevel matrix converter (M3C is proposed. The circuit of 3 × 5 M3C is firstly introduced. Then, operation rules of 3 × 5 M3C are illustrated, and a connection pattern of branches is determined based on these rules. Different voltage states in the input and output side can be achieved by different connection patterns. These voltage states are represented in the form of vector. It is hard to synthesize five-phase output with the three-level synthesis method. Therefore, the five-level synthesis method is adopted in this paper; i.e., is the branch states have been increased. Ten effective vectors and a zero vector are selected based on the five-level synthesis method. With this modulation strategy, we achieve output line-to-line voltages that are in line with the trend of a sine wave. The segment division and duty cycle calculation are very simple, and the modulation strategy can be implemented easily. The simulation model of 3 × 5 M3C is constructed based on Matlab/Simulink, and the corresponding experimental platform is set up. The results of simulation and experiment show that the proposed method is reasonable and correct.

Medical Image Compression Based on Vector Quantization with Variable Block Sizes in Wavelet Domain

Directory of Open Access Journals (Sweden)

Huiyan Jiang

2012-01-01

Full Text Available An optimized medical image compression algorithm based on wavelet transform and improved vector quantization is introduced. The goal of the proposed method is to maintain the diagnostic-related information of the medical image at a high compression ratio. Wavelet transformation was first applied to the image. For the lowest-frequency subband of wavelet coefficients, a lossless compression method was exploited; for each of the high-frequency subbands, an optimized vector quantization with variable block size was implemented. In the novel vector quantization method, local fractal dimension (LFD was used to analyze the local complexity of each wavelet coefficients, subband. Then an optimal quadtree method was employed to partition each wavelet coefficients, subband into several sizes of subblocks. After that, a modified K-means approach which is based on energy function was used in the codebook training phase. At last, vector quantization coding was implemented in different types of sub-blocks. In order to verify the effectiveness of the proposed algorithm, JPEG, JPEG2000, and fractal coding approach were chosen as contrast algorithms. Experimental results show that the proposed method can improve the compression performance and can achieve a balance between the compression ratio and the image visual quality.

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.

A New Curve Tracing Algorithm Based on Local Feature in the Vectorization of Paper Seismograms

Directory of Open Access Journals (Sweden)

Maofa Wang

2014-02-01

Full Text Available History paper seismograms are very important information for earthquake monitoring and prediction. The vectorization of paper seismograms is an import problem to be resolved. Auto tracing of waveform curves is a key technology for the vectorization of paper seismograms. It can transform an original scanning image into digital waveform data. Accurately tracing out all the key points of each curve in seismograms is the foundation for vectorization of paper seismograms. In the paper, we present a new curve tracing algorithm based on local feature, applying to auto extraction of earthquake waveform in paper seismograms.

Medical Image Compression Based on Vector Quantization with Variable Block Sizes in Wavelet Domain

OpenAIRE

Jiang, Huiyan; Ma, Zhiyuan; Hu, Yang; Yang, Benqiang; Zhang, Libo

2012-01-01

An optimized medical image compression algorithm based on wavelet transform and improved vector quantization is introduced. The goal of the proposed method is to maintain the diagnostic-related information of the medical image at a high compression ratio. Wavelet transformation was first applied to the image. For the lowest-frequency subband of wavelet coefficients, a lossless compression method was exploited; for each of the high-frequency subbands, an optimized vector quantization with vari...

Knock-in Luciferase Reporter Mice for In Vivo Monitoring of CREB Activity.

Directory of Open Access Journals (Sweden)

Dmitry Akhmedov

Full Text Available The cAMP response element binding protein (CREB is induced during fasting in the liver, where it stimulates transcription of rate-limiting gluconeogenic genes to maintain metabolic homeostasis. Adenoviral and transgenic CREB reporters have been used to monitor hepatic CREB activity non-invasively using bioluminescence reporter imaging. However, adenoviral vectors and randomly inserted transgenes have several limitations. To overcome disadvantages of the currently used strategies, we created a ROSA26 knock-in CREB reporter mouse line (ROSA26-CRE-luc. cAMP-inducing ligands stimulate the reporter in primary hepatocytes and myocytes from ROSA26-CRE-luc animals. In vivo, these animals exhibit little hepatic CREB activity in the ad libitum fed state but robust induction after fasting. Strikingly, CREB was markedly stimulated in liver, but not in skeletal muscle, after overnight voluntary wheel-running exercise, uncovering differential regulation of CREB in these tissues under catabolic states. The ROSA26-CRE-luc mouse line is a useful resource to study dynamics of CREB activity longitudinally in vivo and can be used as a source of primary cells for analysis of CREB regulatory pathways ex vivo.

Vector magnetometer based on synchronous manipulation of nitrogen-vacancy centers in all crystal directions

Science.gov (United States)

Zhang, Chen; Yuan, Heng; Zhang, Ning; Xu, Lixia; Zhang, Jixing; Li, Bo; Fang, Jiancheng

2018-04-01

Negatively charged nitrogen vacancy (NV‑) centers in diamond have been extensively studied as high-sensitivity magnetometers, showcasing a wide range of applications. This study experimentally demonstrates a vector magnetometry scheme based on synchronous manipulation of NV‑ center ensembles in all crystal directions using double frequency microwaves (MWs) and multi-coupled-strip-lines (mCSL) waveguide. The application of the mCSL waveguide ensures a high degree of synchrony (99%) for manipulating NV‑ centers in multiple orientations in a large volume. Manipulation with double frequency MWs makes NV‑ centers of all four crystal directions involved, and additionally leads to an enhancement of the manipulation field. In this work, by monitoring the changes in the slope of the resonance line consisting of multi-axes NV‑ centers, measurement of the direction of the external field vector was demonstrated with a sensitivity of {{10}\\prime}/\\sqrt{Hz} . Based on the scheme, the fluorescence signal contrast was improved by four times higher and the sensitivity to the magnetic field strength was improved by two times. The method provides a more practical way of achieving vector sensors based on NV‑ center ensembles in diamond.

Segmentation of Clinical Endoscopic Images Based on the Classification of Topological Vector Features

Directory of Open Access Journals (Sweden)

O. A. Dunaeva

2013-01-01

Full Text Available In this work, we describe a prototype of an automatic segmentation system and annotation of endoscopy images. The used algorithm is based on the classification of vectors of the topological features of the original image. We use the image processing scheme which includes image preprocessing, calculation of vector descriptors defined for every point of the source image and the subsequent classification of descriptors. Image preprocessing includes finding and selecting artifacts and equalizating the image brightness. In this work, we give the detailed algorithm of the construction of topological descriptors and the classifier creating procedure based on mutual sharing the AdaBoost scheme and a naive Bayes classifier. In the final section, we show the results of the classification of real endoscopic images.

Conservative strategy-based ensemble surrogate model for optimal groundwater remediation design at DNAPLs-contaminated sites

Science.gov (United States)

Ouyang, Qi; Lu, Wenxi; Lin, Jin; Deng, Wenbing; Cheng, Weiguo

2017-08-01

The surrogate-based simulation-optimization techniques are frequently used for optimal groundwater remediation design. When this technique is used, surrogate errors caused by surrogate-modeling uncertainty may lead to generation of infeasible designs. In this paper, a conservative strategy that pushes the optimal design into the feasible region was used to address surrogate-modeling uncertainty. In addition, chance-constrained programming (CCP) was adopted to compare with the conservative strategy in addressing this uncertainty. Three methods, multi-gene genetic programming (MGGP), Kriging (KRG) and support vector regression (SVR), were used to construct surrogate models for a time-consuming multi-phase flow model. To improve the performance of the surrogate model, ensemble surrogates were constructed based on combinations of different stand-alone surrogate models. The results show that: (1) the surrogate-modeling uncertainty was successfully addressed by the conservative strategy, which means that this method is promising for addressing surrogate-modeling uncertainty. (2) The ensemble surrogate model that combines MGGP with KRG showed the most favorable performance, which indicates that this ensemble surrogate can utilize both stand-alone surrogate models to improve the performance of the surrogate model.

Optical vector network analyzer based on double-sideband modulation.

Science.gov (United States)

Jun, Wen; Wang, Ling; Yang, Chengwu; Li, Ming; Zhu, Ning Hua; Guo, Jinjin; Xiong, Liangming; Li, Wei

2017-11-01

We report an optical vector network analyzer (OVNA) based on double-sideband (DSB) modulation using a dual-parallel Mach-Zehnder modulator. The device under test (DUT) is measured twice with different modulation schemes. By post-processing the measurement results, the response of the DUT can be obtained accurately. Since DSB modulation is used in our approach, the measurement range is doubled compared with conventional single-sideband (SSB) modulation-based OVNA. Moreover, the measurement accuracy is improved by eliminating the even-order sidebands. The key advantage of the proposed scheme is that the measurement of a DUT with bandpass response can also be simply realized, which is a big challenge for the SSB-based OVNA. The proposed method is theoretically and experimentally demonstrated.

A belief-based evolutionarily stable strategy.

Science.gov (United States)

Deng, Xinyang; Wang, Zhen; Liu, Qi; Deng, Yong; Mahadevan, Sankaran

2014-11-21

As an equilibrium refinement of the Nash equilibrium, evolutionarily stable strategy (ESS) is a key concept in evolutionary game theory and has attracted growing interest. An ESS can be either a pure strategy or a mixed strategy. Even though the randomness is allowed in mixed strategy, the selection probability of pure strategy in a mixed strategy may fluctuate due to the impact of many factors. The fluctuation can lead to more uncertainty. In this paper, such uncertainty involved in mixed strategy has been further taken into consideration: a belief strategy is proposed in terms of Dempster-Shafer evidence theory. Furthermore, based on the proposed belief strategy, a belief-based ESS has been developed. The belief strategy and belief-based ESS can reduce to the mixed strategy and mixed ESS, which provide more realistic and powerful tools to describe interactions among agents. Copyright © 2014 Elsevier Ltd. All rights reserved.

A Novel Approach to Asynchronous MVP Data Interpretation Based on Elliptical-Vectors

Science.gov (United States)

Kruglyakov, M.; Trofimov, I.; Korotaev, S.; Shneyer, V.; Popova, I.; Orekhova, D.; Scshors, Y.; Zhdanov, M. S.

2014-12-01

We suggest a novel approach to asynchronous magnetic-variation profiling (MVP) data interpretation. Standard method in MVP is based on the interpretation of the coefficients of linear relation between vertical and horizontal components of the measured magnetic field.From mathematical point of view this pair of linear coefficients is not a vector which leads to significant difficulties in asynchronous data interpretation. Our approach allows us to actually treat such a pair of complex numbers as a special vector called an ellipse-vector (EV). By choosing the particular definitions of complex length and direction, the basic relation of MVP can be considered as the dot product. This considerably simplifies the interpretation of asynchronous data. The EV is described by four real numbers: the values of major and minor semiaxes, the angular direction of the major semiaxis and the phase. The notation choice is motivated by historical reasons. It is important that different EV's components have different sensitivity with respect to the field sources and the local heterogeneities. Namely, the value of major semiaxis and the angular direction are mostly determined by the field source and the normal cross-section. On the other hand, the value of minor semiaxis and the phase are responsive to local heterogeneities. Since the EV is the general form of complex vector, the traditional Schmucker vectors can be explicitly expressed through its components.The proposed approach was successfully applied to interpretation the results of asynchronous measurements that had been obtained in the Arctic Ocean at the drift stations "North Pole" in 1962-1976.

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.

Surface expression of anti-CD3scfv stimulates locoregional immunotherapy against hepatocellular carcinoma depending on the E1A-engineered human umbilical cord mesenchymal stem cells.

Science.gov (United States)

Zhang, Qing; Yuan, Xiang-Fei; Lu, Yang; Li, Zhen-Zhen; Bao, Shi-Qi; Zhang, Xiao-Long; Yang, Yuan-Yuan; Fan, Dong-Mei; Zhang, Yi-Zhi; Wu, Chen-Xuan; Guo, Hong-Xing; Zhang, Yan-Jun; Ye, Zhou; Xiong, Dong-Sheng

2017-10-01

Tumor antigens is at the core of cancer immunotherapy, however, the ideal antigen selection is difficult especially in poorly immunogenic tumors. In this study, we designed a strategy to modify hepatocellular carcinoma (HCC) cells by surface expressing anti-CD3scfv within the tumor site strictly, which depended on the E1A-engineered human umbilical cord mesenchymal stem cells (HUMSC.E1A) delivery system. Subsequently, membrane-bound anti-CD3scfv actived the lymphocytes which lysed HCC cells bypassing the expression of antigens or MHC restriction. First, we constructed the anti-CD3scfv gene driven by human α-fetoprotein (AFP) promoter into an adenoviral vector and the E1A gene into the lentiviral vector. Our results showed that anti-CD3scfv could specifically express on the surface of HCC cells and activate the lymphocytes to kill target cells effectively in vitro. HUMSC infected by AdCD3scfv followed by LentiR.E1A could support the adenoviral replication and packaging in vitro 36 h after LentiR.E1A infection. Using a subcutaneous HepG2 xenograft model, we confirmed that AdCD3scfv and LentiR.E1A co-transfected HUMSC could migrate selectively to the tumor site and produce considerable adenoviruses. The new generated AdCD3scfv infected and modified tumor cells successfully. Mice injected with the MSC.E1A.AdCD3scfv and lymphocytes significantly inhibited the tumor growth compared with control groups. Furthermore, 5-fluorouracil (5-FU) could sensitize adenovirus infection at low MOI resulting in improved lymphocytes cytotoxicity in vitro and in vivo. In summary, this study provides a promising strategy for solid tumor immunotherapy. © 2017 UICC.

Use of Lanczos vectors in fluid/structure interaction problems

International Nuclear Information System (INIS)

Jeans, R.; Mathews, I.C.

1992-01-01

The goals of any numerical computational technique used for the solution of structural acoustics problems in the exterior infinite domain should be of accuracy with rapid convergence, robustness, and computational efficiency. A computer program has been developed to achieve each of these three goals. Accuracy and robustness in the numerical representation of the integral equations used to represent the infinite fluid was attained through the use of boundary element implementations of the surface Helmholtz integral equations. The computational efficiency was resolved through the use of Lanczos vectors to model the deformation characteristics of the structure. The authors have developed collocation and variational techniques to overcome the difficulties previously encountered in the numerical implementation of the hypersingular integral operator. The Cauchy singularity present in the integral formulation is made numerically amenable through the use of tangential derivatives in both the collocation and variational techniques. The variational approach has the advantage that the resulting added fluid mass term is symmetric and combines efficiently with a finite element approximation of the structural elastic response. Several different strategies making use of the Lanczos vectors have been investigated. The first involved the use of Lanczos vectors solely to characterize the structural response. This reduced form of the structural dynamical matrix was then substituted back into a Burton and Miller formulation of the acoustic problem. The second strategy investigated involved forming the complex Lanzcos vectors of the dynamical matrix formed from the addition of a symmetrical added fluid matrix to the structural mass matrix. The size of resultant matrix equation set solved at each frequency for this strategy is determined by the number of Lanczos vectors used. 19 refs., 10 figs., 2 tabs

Leg-adjustment strategies for stable running in three dimensions

International Nuclear Information System (INIS)

Peuker, Frank; Maufroy, Christophe; Seyfarth, André

2012-01-01

The dynamics of the center of mass (CoM) in the sagittal plane in humans and animals during running is well described by the spring-loaded inverted pendulum (SLIP). With appropriate parameters, SLIP running patterns are stable, and these models can recover from perturbations without the need for corrective strategies, such as the application of additional forces. Rather, it is sufficient to adjust the leg to a fixed angle relative to the ground. In this work, we consider the extension of the SLIP to three dimensions (3D SLIP) and investigate feed-forward strategies for leg adjustment during the flight phase. As in the SLIP model, the leg is placed at a fixed angle. We extend the scope of possible reference axes from only fixed horizontal and vertical axes to include the CoM velocity vector as a movement-related reference, resulting in six leg-adjustment strategies. Only leg-adjustment strategies that include the CoM velocity vector produced stable running and large parameter domains of stability. The ability of the model to recover from perturbations along the direction of motion (directional stability) depended on the strategy for lateral leg adjustment. Specifically, asymptotic and neutral directional stability was observed for strategies based on the global reference axis and the velocity vector, respectively. Additional features of velocity-based leg adjustment are running at arbitrary low speed (kinetic energy) and the emergence of large domains of stable 3D running that are smoothly transferred to 2D SLIP stability and even to 1D SLIP hopping. One of the additional leg-adjustment strategies represented a large convex region of parameters where stable and robust hopping and running patterns exist. Therefore, this strategy is a promising candidate for implementation into engineering applications, such as robots, for instance. In a preliminary comparison, the model predictions were in good agreement with the experimental data, suggesting that the 3D SLIP is an

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.

EVE: Explainable Vector Based Embedding Technique Using Wikipedia

OpenAIRE

Qureshi, M. Atif; Greene, Derek

2017-01-01

We present an unsupervised explainable word embedding technique, called EVE, which is built upon the structure of Wikipedia. The proposed model defines the dimensions of a semantic vector representing a word using human-readable labels, thereby it readily interpretable. Specifically, each vector is constructed using the Wikipedia category graph structure together with the Wikipedia article link structure. To test the effectiveness of the proposed word embedding model, we consider its usefulne...

Consolidating tactical planning and implementation frameworks for integrated vector management in Uganda.

Science.gov (United States)

Okia, Michael; Okui, Peter; Lugemwa, Myers; Govere, John M; Katamba, Vincent; Rwakimari, John B; Mpeka, Betty; Chanda, Emmanuel

2016-04-14

Integrated vector management (IVM) is the recommended approach for controlling some vector-borne diseases (VBD). In the face of current challenges to disease vector control, IVM is vital to achieve national targets set for VBD control. Though global efforts, especially for combating malaria, now focus on elimination and eradication, IVM remains useful for Uganda which is principally still in the control phase of the malaria continuum. This paper outlines the processes undertaken to consolidate tactical planning and implementation frameworks for IVM in Uganda. The Uganda National Malaria Control Programme with its efforts to implement an IVM approach to vector control was the 'case' for this study. Integrated management of malaria vectors in Uganda remained an underdeveloped component of malaria control policy. In 2012, knowledge and perceptions of malaria vector control policy and IVM were assessed, and recommendations for a specific IVM policy were made. In 2014, a thorough vector control needs assessment (VCNA) was conducted according to WHO recommendations. The findings of the VCNA informed the development of the national IVM strategic guidelines. Information sources for this study included all available data and accessible archived documentary records on VBD control in Uganda. The literature was reviewed and adapted to the local context and translated into the consolidated tactical framework. WHO recommends implementation of IVM as the main strategy to vector control and has encouraged member states to adopt the approach. However, many VBD-endemic countries lack IVM policy frameworks to guide implementation of the approach. In Uganda most VBD coexists and could be managed more effectively if done in tandem. In order to successfully control malaria and other VBD and move towards their elimination, the country needs to scale up proven and effective vector control interventions and also learn from the experience of other countries. The IVM strategy is important in

A method of recovering the initial vectors of globally coupled map lattices based on symbolic dynamics

International Nuclear Information System (INIS)

Sun Li-Sha; Kang Xiao-Yun; Zhang Qiong; Lin Lan-Xin

2011-01-01

Based on symbolic dynamics, a novel computationally efficient algorithm is proposed to estimate the unknown initial vectors of globally coupled map lattices (CMLs). It is proved that not all inverse chaotic mapping functions are satisfied for contraction mapping. It is found that the values in phase space do not always converge on their initial values with respect to sufficient backward iteration of the symbolic vectors in terms of global convergence or divergence (CD). Both CD property and the coupling strength are directly related to the mapping function of the existing CML. Furthermore, the CD properties of Logistic, Bernoulli, and Tent chaotic mapping functions are investigated and compared. Various simulation results and the performances of the initial vector estimation with different signal-to-noise ratios (SNRs) are also provided to confirm the proposed algorithm. Finally, based on the spatiotemporal chaotic characteristics of the CML, the conditions of estimating the initial vectors using symbolic dynamics are discussed. The presented method provides both theoretical and experimental results for better understanding and characterizing the behaviours of spatiotemporal chaotic systems. (general)

A method of recovering the initial vectors of globally coupled map lattices based on symbolic dynamics

Science.gov (United States)

Sun, Li-Sha; Kang, Xiao-Yun; Zhang, Qiong; Lin, Lan-Xin

2011-12-01

Based on symbolic dynamics, a novel computationally efficient algorithm is proposed to estimate the unknown initial vectors of globally coupled map lattices (CMLs). It is proved that not all inverse chaotic mapping functions are satisfied for contraction mapping. It is found that the values in phase space do not always converge on their initial values with respect to sufficient backward iteration of the symbolic vectors in terms of global convergence or divergence (CD). Both CD property and the coupling strength are directly related to the mapping function of the existing CML. Furthermore, the CD properties of Logistic, Bernoulli, and Tent chaotic mapping functions are investigated and compared. Various simulation results and the performances of the initial vector estimation with different signal-to-noise ratios (SNRs) are also provided to confirm the proposed algorithm. Finally, based on the spatiotemporal chaotic characteristics of the CML, the conditions of estimating the initial vectors using symbolic dynamics are discussed. The presented method provides both theoretical and experimental results for better understanding and characterizing the behaviours of spatiotemporal chaotic systems.

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.)

Biology, diversity and strategies for the monitoring and control of triatomines--Chagas disease vectors.

Science.gov (United States)

Costa, Jane; Lorenzo, Marcelo

2009-07-01

Despite the relevant achievements in the control of the main Chagas disease vectors Triatoma infestans and Rhodnius prolixus, several factors still promote the risk of infection. The disease is a real threat to the poor rural regions of several countries in Latin America. The current situation in Brazil requires renewed attention due to its high diversity of triatomine species and to the rapid and drastic environmental changes that are occurring. Using the biology, behaviour and diversity of triatomines as a basis for new strategies for monitoring and controlling the vectorial transmission are discussed here. The importance of ongoing long-term monitoring activities for house infestations by T. infestans, Triatoma brasiliensis, Panstrongylus megistus, Triatoma rubrovaria and R. prolixus is also stressed, as well as understanding the invasion by sylvatic species. Moreover, the insecticide resistance is analysed. Strong efforts to sustain and improve surveillance procedures are crucial, especially when the vectorial transmission is considered interrupted in many endemic areas.

A terrestrial lidar-based workflow for determining three-dimensional slip vectors and associated uncertainties

Science.gov (United States)

Gold, Peter O.; Cowgill, Eric; Kreylos, Oliver; Gold, Ryan D.

2012-01-01

Three-dimensional (3D) slip vectors recorded by displaced landforms are difficult to constrain across complex fault zones, and the uncertainties associated with such measurements become increasingly challenging to assess as landforms degrade over time. We approach this problem from a remote sensing perspective by using terrestrial laser scanning (TLS) and 3D structural analysis. We have developed an integrated TLS data collection and point-based analysis workflow that incorporates accurate assessments of aleatoric and epistemic uncertainties using experimental surveys, Monte Carlo simulations, and iterative site reconstructions. Our scanning workflow and equipment requirements are optimized for single-operator surveying, and our data analysis process is largely completed using new point-based computing tools in an immersive 3D virtual reality environment. In a case study, we measured slip vector orientations at two sites along the rupture trace of the 1954 Dixie Valley earthquake (central Nevada, United States), yielding measurements that are the first direct constraints on the 3D slip vector for this event. These observations are consistent with a previous approximation of net extension direction for this event. We find that errors introduced by variables in our survey method result in <2.5 cm of variability in components of displacement, and are eclipsed by the 10–60 cm epistemic errors introduced by reconstructing the field sites to their pre-erosion geometries. Although the higher resolution TLS data sets enabled visualization and data interactivity critical for reconstructing the 3D slip vector and for assessing uncertainties, dense topographic constraints alone were not sufficient to significantly narrow the wide (<26°) range of allowable slip vector orientations that resulted from accounting for epistemic uncertainties.

Effects of infection with recombinant adenovirus on human vascular endothelial and smooth muscle cells

NARCIS (Netherlands)

Quax, P.H.A.; Lamfers, M.L.M.; Grimbergen, J.M.; Teeling, J.; Hoeben, R.C.; Nieuw Amerongen, G.P. van; Hinsbergh, V.W.M. van

1996-01-01

The plasminogen activation (PA) system is involved in vascular remodelling. Modulating its activity in vascular cells might be a way to interfere in processes such as angiogenesis and restenosis. Adenoviral vectors have become a favourable tool for direct gene transfer into vascular cells. In the

MHC class II-associated invariant chain linkage of antigen dramatically improves cell-mediated immunity induced by adenovirus vaccines

DEFF Research Database (Denmark)

Holst, Peter Johannes; Mandrup Jensen, Camilla Maria; Orskov, Cathrine

2008-01-01

The ideal vaccine induces a potent protective immune response, which should be rapidly induced, long-standing, and of broad specificity. Recombinant adenoviral vectors induce potent Ab and CD8+ T cell responses against transgenic Ags within weeks of administration, and they are among the most...

RNA Interference in Insect Vectors for Plant Viruses

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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.

Spatial pattern evolution of Aedes aegypti breeding sites in an Argentinean city without a dengue vector control programme

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Manuel O. Espinosa

2016-11-01

Full Text Available The main objective of this study was to obtain and analyse the space-time dynamics of Aedes aegypti breeding sites in Clorinda City, Formosa Province, Argentina coupled with landscape analysis using the maximum entropy approach in order to generate a dengue vector niche model. In urban areas, without vector control activities, 12 entomologic (larval samplings were performed during three years (October 2011 to October 2014. The entomologic surveillance area represented 16,511 houses. Predictive models for Aedes distribution were developed using vector breeding abundance data, density analysis, clustering and geoprocessing techniques coupled with Earth observation satellite data. The spatial analysis showed a vector spatial distribution pattern with clusters of high density in the central region of Clorinda with a well-defined high-risk area in the western part of the city. It also showed a differential temporal behaviour among different areas, which could have implications for risk models and control strategies at the urban scale. The niche model obtained for Ae. aegypti, based on only one year of field data, showed that 85.8% of the distribution of breeding sites is explained by the percentage of water supply (48.2%, urban distribution (33.2%, and the percentage of urban coverage (4.4%. The consequences for the development of control strategies are discussed with reference to the results obtained using distribution maps based on environmental variables.

Spatial pattern evolution of Aedes aegypti breeding sites in an Argentinean city without a dengue vector control programme.

Science.gov (United States)

Espinosa, Manuel O; Polop, Francisco; Rotela, Camilo H; Abril, Marcelo; Scavuzzo, Carlos M

2016-11-21

The main objective of this study was to obtain and analyse the space-time dynamics of Aedes aegypti breeding sites in Clorinda City, Formosa Province, Argentina coupled with landscape analysis using the maximum entropy approach in order to generate a dengue vector niche model. In urban areas, without vector control activities, 12 entomologic (larval) samplings were performed during three years (October 2011 to October 2014). The entomologic surveillance area represented 16,511 houses. Predictive models for Aedes distribution were developed using vector breeding abundance data, density analysis, clustering and geoprocessing techniques coupled with Earth observation satellite data. The spatial analysis showed a vector spatial distribution pattern with clusters of high density in the central region of Clorinda with a well-defined high-risk area in the western part of the city. It also showed a differential temporal behaviour among different areas, which could have implications for risk models and control strategies at the urban scale. The niche model obtained for Ae. aegypti, based on only one year of field data, showed that 85.8% of the distribution of breeding sites is explained by the percentage of water supply (48.2%), urban distribution (33.2%), and the percentage of urban coverage (4.4%). The consequences for the development of control strategies are discussed with reference to the results obtained using distribution maps based on environmental variables.

Integrated vector management: The Zambian experience

Directory of Open Access Journals (Sweden)

Katebe Cecilia

2008-08-01

Full Text Available Abstract Background The Zambian Malaria Control Programme with the Roll Back Malaria (RBM partners have developed the current National Malaria Strategic Plan (NMSP 2006–2011 which focuses on prevention based on the Integrated Vector Management (IVM strategy. The introduction and implementation of an IVM strategy was planned in accordance with the World Health Organization (WHO steps towards IVM implementation namely Introduction Phase, Consolidation Phase and Expansion Phase. Achievements IVM has created commitment for Legal and Regulatory policy review, monitoring, Research and a strong stewardship by the chemical suppliers. It has also leveraged additional resources, improved inter-sectoral collaboration, capacity building and enhanced community participation which facilitated a steady scaling up in coverage and utilisation of key preventive interventions. Thus, markedly reducing malaria incidence and case fatalities in the country. Conclusion Zambia has successfully introduced, consolidated and expanded IVM activities. Resulting in increased coverage and utilization of interventions and markedly reducing malaria-related morbidity and mortality while ensuring a better protection of the environment.

Integrated vector management: the Zambian experience.

Science.gov (United States)

Chanda, Emmanuel; Masaninga, Fred; Coleman, Michael; Sikaala, Chadwick; Katebe, Cecilia; Macdonald, Michael; Baboo, Kumar S; Govere, John; Manga, Lucien

2008-08-27

The Zambian Malaria Control Programme with the Roll Back Malaria (RBM) partners have developed the current National Malaria Strategic Plan (NMSP 2006-2011) which focuses on prevention based on the Integrated Vector Management (IVM) strategy. The introduction and implementation of an IVM strategy was planned in accordance with the World Health Organization (WHO) steps towards IVM implementation namely Introduction Phase, Consolidation Phase and Expansion Phase. IVM has created commitment for Legal and Regulatory policy review, monitoring, Research and a strong stewardship by the chemical suppliers. It has also leveraged additional resources, improved inter-sectoral collaboration, capacity building and enhanced community participation which facilitated a steady scaling up in coverage and utilisation of key preventive interventions. Thus, markedly reducing malaria incidence and case fatalities in the country. Zambia has successfully introduced, consolidated and expanded IVM activities. Resulting in increased coverage and utilization of interventions and markedly reducing malaria-related morbidity and mortality while ensuring a better protection of the environment.

The Insect Microbiome Modulates Vector Competence for Arboviruses

Directory of Open Access Journals (Sweden)

Natapong Jupatanakul

2014-11-01

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

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…

Novel deadbeat power control strategy for grid connected systems

Directory of Open Access Journals (Sweden)

Yousry Atia

2015-09-01

Full Text Available This paper introduces a novel approach for power control of three phase voltage source inverter (VSI in grid connected distribution generation system. In this approach, the control of active and reactive power is based on deadbeat control strategy. First, the difference between the reference and actual currents are introduced in different approach. Then current to power substitutions are carried out to obtain direct relationship between the required inverter voltage and instantaneous power errors. There is no need for coordinate transformation or PLL, where the required inverter voltage vector calculations carried out in α–β stationary reference frame. The proposed technique introduces two cross coupling components in the control function. Including these two components, the controller can achieve nearly zero steady-state tracking error of the controlled variables. To obtain fixed switching frequency operations, space vector modulation (SVM is used to synthesize the required inverter voltage vector and to generate the switching pulses for the VSI. The proposed strategy has the simplicity of the direct power control (DPC technique and doesn’t require any current control loops. The proposed strategy is experimentally implemented using fixed-point microcontroller. Simulation and experimental results are presented to confirm the superiority of the proposed strategy.

Wide-angle full-vector beam propagation method based on an alternating direction implicit preconditioner

Science.gov (United States)

Chui, Siu Lit; Lu, Ya Yan

2004-03-01

Wide-angle full-vector beam propagation methods (BPMs) for three-dimensional wave-guiding structures can be derived on the basis of rational approximants of a square root operator or its exponential (i.e., the one-way propagator). While the less accurate BPM based on the slowly varying envelope approximation can be efficiently solved by the alternating direction implicit (ADI) method, the wide-angle variants involve linear systems that are more difficult to handle. We present an efficient solver for these linear systems that is based on a Krylov subspace method with an ADI preconditioner. The resulting wide-angle full-vector BPM is used to simulate the propagation of wave fields in a Y branch and a taper.

Improvement in vehicle agility and stability by G-Vectoring control

Science.gov (United States)

Yamakado, Makoto; Takahashi, Jyunya; Saito, Shinjiro; Yokoyama, Atsushi; Abe, Masato

2010-12-01

We extracted a trade-off strategy between longitudinal traction/braking force and cornering force by using jerk information through observing an expert driver's voluntary braking and turning action. Using the expert driver's strategy, we developed a new control concept, called 'G-Vectoring control', which is an automatic longitudinal acceleration control (No DYC) in accordance with the vehicle's lateral jerk caused by the driver's steering manoeuvres. With the control, the direction of synthetic acceleration (G) changes seamlessly (i.e. vectoring). The improvements in vehicle agility and stability were evaluated by theoretical analysis and through computer simulation. We then introduced a 'G-Vectoring' equipped test vehicle realised by brake-by-wire technology and executed a detailed examination on a test track. We have confirmed that the vehicle motion in view of both handling and ride quality has improved dramatically.

Near State Vector Selection-Based Model Predictive Control with Common Mode Voltage Mitigation for a Three-Phase Four-Leg Inverter

Directory of Open Access Journals (Sweden)

Abdul Mannan Dadu

2017-12-01

Full Text Available A high computational burden is required in conventional model predictive control, as all of the voltage vectors of a power inverter are used to predict the future behavior of the system. Apart from that, the common mode voltage (CMV of a three-phase four-leg inverter utilizes up to half of the DC-link voltage due to the use of all of the available voltage vectors. Thus, this paper proposes a near state vector selection-based model predictive control (NSV-MPC scheme to mitigate the CMV and reduce computational burden. In the proposed technique, only six active voltage vectors are used in the predictive model, and the vectors are selected based on the position of the future reference vector. In every sampling period, the position of the reference current is used to detect the voltage vectors surrounding the reference voltage vector. Besides the six active vectors, one of the zero vectors is also used. The proposed technique is compared with the conventional control scheme in terms of execution time, CMV variation, and load current ripple in both simulation and an experimental setup. The LabVIEW Field programmable gate array rapid prototyping controller is used to validate the proposed control scheme experimentally, and demonstrate that the CMV can be bounded within one-fourth of the DC-link voltage.

Helper-dependent adenovirus achieve more efficient and persistent liver transgene expression in non-human primates under immunosuppression.

Science.gov (United States)

Unzu, C; Melero, I; Hervás-Stubbs, S; Sampedro, A; Mancheño, U; Morales-Kastresana, A; Serrano-Mendioroz, I; de Salamanca, R E; Benito, A; Fontanellas, A

2015-11-01

Helper-dependent adenoviral (HDA) vectors constitute excellent gene therapy tools for metabolic liver diseases. We have previously shown that an HDA vector encoding human porphobilinogen deaminase (PBGD) corrects acute intermittent porphyria mice. Now, six non-human primates were injected in the left hepatic lobe with the PBGD-encoding HDA vector to study levels and persistence of transgene expression. Intrahepatic administration of 5 × 10(12) viral particles kg(-1) (10(10) infective units kg(-1)) of HDA only resulted in transient (≈14 weeks) transgene expression in one out of three individuals. In contrast, a more prolonged 90-day immunosuppressive regimen (tacrolimus, mycophenolate, rituximab and steroids) extended meaningful transgene expression for over 76 weeks in two out of two cases. Transgene expression under immunosuppression (IS) reached maximum levels 6 weeks after HDA administration and gradually declined reaching a stable plateau within the therapeutic range for acute porphyria. The non-injected liver lobes also expressed the transgene because of vector circulation. IS controlled anticapsid T-cell responses and decreased the induction of neutralizing antibodies. Re-administration of HDA-hPBGD at week +78 achieved therapeutically meaningful transgene expression only in those animals receiving IS again at the time of this second vector exposure. Overall, immunity against adenoviral capsids poses serious hurdles for long-term HDA-mediated liver transduction, which can be partially circumvented by pharmacological IS.

Controlling Aedes aegypti population as DHF vector with radiation based-sterile insect technique in Banjarnegara Regency, Central Java

International Nuclear Information System (INIS)

Siti Nurhayati; Bambang Yunianto; Tri Ramadhani; Bina Ikawati; Budi Santoso; Ali Rahayu

2013-01-01

The control program of dengue hemorrhagic fever (DHF) in Indonesia is still a problem due to the incomplete integrated handling. Sterile insect technique (SIT) for Aedes aegypti as DHF vector was considered as a potential strategy for controlling the DHF. A preliminary survey was carried out to determine the characteristic of A aegypti population in the study site before the implementation of SIT. The implementation of radiation based-SIT was carried out in Krandegan and Kutabanjar Villages of Banjarnegara Regency, Central Java which involved 99 houses. One hundred gamma rays irradiated male mosquitoes were released to each house up to five times. The eggs, larvae and adult mosquitoes were collected using ovitrap and weekly observed. The initial population density of A. aegypti in the studied area was obtained to be 6 mosquitoes per house with the mean index of house was 15.86% and the mean sterility of sterilized mosquitoes was 79.16%. The SIT effectively reduced A. aegypti population after the fifth release of irradiated mosquitoes into the houses. It can be assumed that the SIT was effective in controlling DHF vector in the studied area, nevertheless, it will be more effective if it is combined with other handling techniques. (author)

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.

Parameter Selection Method for Support Vector Regression Based on Adaptive Fusion of the Mixed Kernel Function

Directory of Open Access Journals (Sweden)

Hailun Wang

2017-01-01

Full Text Available Support vector regression algorithm is widely used in fault diagnosis of rolling bearing. A new model parameter selection method for support vector regression based on adaptive fusion of the mixed kernel function is proposed in this paper. We choose the mixed kernel function as the kernel function of support vector regression. The mixed kernel function of the fusion coefficients, kernel function parameters, and regression parameters are combined together as the parameters of the state vector. Thus, the model selection problem is transformed into a nonlinear system state estimation problem. We use a 5th-degree cubature Kalman filter to estimate the parameters. In this way, we realize the adaptive selection of mixed kernel function weighted coefficients and the kernel parameters, the regression parameters. Compared with a single kernel function, unscented Kalman filter (UKF support vector regression algorithms, and genetic algorithms, the decision regression function obtained by the proposed method has better generalization ability and higher prediction accuracy.

Adeno-associated viral vector-induced overexpression of neuropeptide Y Y2 receptors in the hippocampus suppresses seizures

DEFF Research Database (Denmark)

Woldbye, David Paul Drucker; Ängehagen, Mikael; Gøtzsche, Casper René

2010-01-01

Gene therapy using recombinant adeno-associated viral vectors overexpressing neuropeptide Y in the hippocampus exerts seizure-suppressant effects in rodent epilepsy models and is currently considered for clinical application in patients with intractable mesial temporal lobe epilepsy. Seizure...... recombinant adeno-associated viral vectors. In two temporal lobe epilepsy models, electrical kindling and kainate-induced seizures, vector-based transduction of Y2 receptor complementary DNA in the hippocampus of adult rats exerted seizure-suppressant effects. Simultaneous overexpression of Y2...... and neuropeptide Y had a more pronounced seizure-suppressant effect. These results demonstrate that overexpression of Y2 receptors (alone or in combination with neuropeptide Y) could be an alternative strategy for epilepsy treatment....

Clinical validation of coronal and sagittal spinal curve measurements based on three-dimensional vertebra vector parameters.

Science.gov (United States)

Somoskeöy, Szabolcs; Tunyogi-Csapó, Miklós; Bogyó, Csaba; Illés, Tamás

2012-10-01

For many decades, visualization and evaluation of three-dimensional (3D) spinal deformities have only been possible by two-dimensional (2D) radiodiagnostic methods, and as a result, characterization and classification were based on 2D terminologies. Recent developments in medical digital imaging and 3D visualization techniques including surface 3D reconstructions opened a chance for a long-sought change in this field. Supported by a 3D Terminology on Spinal Deformities of the Scoliosis Research Society, an approach for 3D measurements and a new 3D classification of scoliosis yielded several compelling concepts on 3D visualization and new proposals for 3D classification in recent years. More recently, a new proposal for visualization and complete 3D evaluation of the spine by 3D vertebra vectors has been introduced by our workgroup, a concept, based on EOS 2D/3D, a groundbreaking new ultralow radiation dose integrated orthopedic imaging device with sterEOS 3D spine reconstruction software. Comparison of accuracy, correlation of measurement values, intraobserver and interrater reliability of methods by conventional manual 2D and vertebra vector-based 3D measurements in a routine clinical setting. Retrospective, nonrandomized study of diagnostic X-ray images created as part of a routine clinical protocol of eligible patients examined at our clinic during a 30-month period between July 2007 and December 2009. In total, 201 individuals (170 females, 31 males; mean age, 19.88 years) including 10 healthy athletes with normal spine and patients with adolescent idiopathic scoliosis (175 cases), adult degenerative scoliosis (11 cases), and Scheuermann hyperkyphosis (5 cases). Overall range of coronal curves was between 2.4 and 117.5°. Analysis of accuracy and reliability of measurements was carried out on a group of all patients and in subgroups based on coronal plane deviation: 0 to 10° (Group 1; n=36), 10 to 25° (Group 2; n=25), 25 to 50° (Group 3; n=69), 50 to 75�

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2003-11-01

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

Output-only modal parameter estimator of linear time-varying structural systems based on vector TAR model and least squares support vector machine

Science.gov (United States)

Zhou, Si-Da; Ma, Yuan-Chen; Liu, Li; Kang, Jie; Ma, Zhi-Sai; Yu, Lei

2018-01-01

Identification of time-varying modal parameters contributes to the structural health monitoring, fault detection, vibration control, etc. of the operational time-varying structural systems. However, it is a challenging task because there is not more information for the identification of the time-varying systems than that of the time-invariant systems. This paper presents a vector time-dependent autoregressive model and least squares support vector machine based modal parameter estimator for linear time-varying structural systems in case of output-only measurements. To reduce the computational cost, a Wendland's compactly supported radial basis function is used to achieve the sparsity of the Gram matrix. A Gamma-test-based non-parametric approach of selecting the regularization factor is adapted for the proposed estimator to replace the time-consuming n-fold cross validation. A series of numerical examples have illustrated the advantages of the proposed modal parameter estimator on the suppression of the overestimate and the short data. A laboratory experiment has further validated the proposed estimator.

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

Science.gov (United States)

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

2013-01-01

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

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

Directory of Open Access Journals (Sweden)

Rashmi Krishnapuram

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

Screw Remaining Life Prediction Based on Quantum Genetic Algorithm and Support Vector Machine

Directory of Open Access Journals (Sweden)

Xiaochen Zhang

2017-01-01

Full Text Available To predict the remaining life of ball screw, a screw remaining life prediction method based on quantum genetic algorithm (QGA and support vector machine (SVM is proposed. A screw accelerated test bench is introduced. Accelerometers are installed to monitor the performance degradation of ball screw. Combined with wavelet packet decomposition and isometric mapping (Isomap, the sensitive feature vectors are obtained and stored in database. Meanwhile, the sensitive feature vectors are randomly chosen from the database and constitute training samples and testing samples. Then the optimal kernel function parameter and penalty factor of SVM are searched with the method of QGA. Finally, the training samples are used to train optimized SVM while testing samples are adopted to test the prediction accuracy of the trained SVM so the screw remaining life prediction model can be got. The experiment results show that the screw remaining life prediction model could effectively predict screw remaining life.

Generation of a Vero-Based Packaging Cell Line to Produce SV40 Gene Delivery Vectors for Use in Clinical Gene Therapy Studies

Directory of Open Access Journals (Sweden)

Miguel G. Toscano

2017-09-01

Full Text Available Replication-defective (RD recombinant simian virus 40 (SV40-based gene delivery vectors hold a great potential for clinical applications because of their presumed non-immunogenicity and capacity to induce immune tolerance to the transgene products in humans. However, the clinical use of SV40 vectors has been hampered by the lack of a packaging cell line that produces replication-competent (RC free SV40 particles in the vector production process. To solve this problem, we have adapted the current SV40 vector genome used for the production of vector particles and generated a novel Vero-based packaging cell line named SuperVero that exclusively expresses the SV40 large T antigen. SuperVero cells produce similar numbers of SV40 vector particles compared to the currently used packaging cell lines, albeit in the absence of contaminating RC SV40 particles. Our unique SV40 vector platform named SVac paves the way to clinically test a whole new generation of SV40-based therapeutics for a broad range of important diseases.

Non-Primate Lentiviral Vectors and Their Applications in Gene Therapy for Ocular Disorders

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Vincenzo Cavalieri

2018-06-01

Full Text Available Lentiviruses have a number of molecular features in common, starting with the ability to integrate their genetic material into the genome of non-dividing infected cells. A peculiar property of non-primate lentiviruses consists in their incapability to infect and induce diseases in humans, thus providing the main rationale for deriving biologically safe lentiviral vectors for gene therapy applications. In this review, we first give an overview of non-primate lentiviruses, highlighting their common and distinctive molecular characteristics together with key concepts in the molecular biology of lentiviruses. We next examine the bioengineering strategies leading to the conversion of lentiviruses into recombinant lentiviral vectors, discussing their potential clinical applications in ophthalmological research. Finally, we highlight the invaluable role of animal organisms, including the emerging zebrafish model, in ocular gene therapy based on non-primate lentiviral vectors and in ophthalmology research and vision science in general.

PB1 as a potential target for increasing the breadth of T-cell mediated immunity to Influenza A

DEFF Research Database (Denmark)

Uddbäck, Ida E M; Steffensen, Maria A; Pedersen, Sara R

2016-01-01

Recently, we showed that combined intranasal and subcutaneous immunization with a non-replicating adenoviral vector expressing NP of influenza A, strain PR8, induced long-standing protection against a range of influenza A viruses. However, H-2(b) mice challenged with an influenza A strain mutated...

Diversity and transmission competence in lymphatic filariasis vectors in West Africa, and the implications for accelerated elimination of Anopheles-transmitted filariasis

Directory of Open Access Journals (Sweden)

de Souza Dziedzom K

2012-11-01

Full Text Available Abstract Lymphatic Filariasis (LF is targeted for elimination by the Global Programme for the Elimination of Lymphatic Filariasis (GPELF. The strategy adopted is based on the density dependent phenomenon of Facilitation, which hypothesizes that in an area where the vector species transmitting Wuchereria bancrofti are Anopheles mosquitoes, it is feasible to eliminate LF using Mass Drug Administration (MDA because of the inability of Anopheles species to transmit low-density microfilaraemia. Even though earlier studies have shown Anopheles species can exhibit the process of Facilitation in West Africa, observations point towards the process of Limitation in certain areas, in which case vector control is recommended. Studies on Anopheles species in West Africa have also shown genetic differentiation, cryptic taxa and speciation, insecticide resistance and the existence of molecular and chromosomal forms, all of which could influence the vectorial capacity of the mosquitoes and ultimately the elimination goal. This paper outlines the uniqueness of LF vectors in West Africa and the challenges it poses to the 2020 elimination goal, based on the current MDA strategies.

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

Energy-efficient multicast traffic grooming strategy based on light-tree splitting for elastic optical networks

Science.gov (United States)

Liu, Huanlin; Yin, Yarui; Chen, Yong

2017-07-01

In order to address the problem of optimizing the spectrum resources and power consumption in elastic optical networks (EONs), we investigate the potential gains by jointly employing the light-tree splitting and traffic grooming for multicast requests. An energy-efficient multicast traffic grooming strategy based on light-tree splitting (EED-MTGS-LS) is proposed in this paper. Firstly, we design a traffic pre-processing mechanism to decide the multicast requests' routing order, which considers the request's bandwidth requirement and physical hops synthetically. Then, by dividing a light-tree to some sub-light-trees and grooming the request to these sub-light-trees, the light-tree sharing ratios of multicast requests can be improved. What's more, a priority scheduling vector is constructed, which aims to improve the success rate of spectrum assignment for grooming requests. Finally, a grooming strategy is designed to optimize the total power consumption by reducing the use of transponders and IP routers during routing. Simulation results show that the proposed strategy can significantly improve the spectrum utilization and save the power consumption.

Hypergraph partitioning implementation for parallelizing matrix-vector multiplication using CUDA GPU-based parallel computing

Science.gov (United States)

Murni, Bustamam, A.; Ernastuti, Handhika, T.; Kerami, D.

2017-07-01

Calculation of the matrix-vector multiplication in the real-world problems often involves large matrix with arbitrary size. Therefore, parallelization is needed to speed up the calculation process that usually takes a long time. Graph partitioning techniques that have been discussed in the previous studies cannot be used to complete the parallelized calculation of matrix-vector multiplication with arbitrary size. This is due to the assumption of graph partitioning techniques that can only solve the square and symmetric matrix. Hypergraph partitioning techniques will overcome the shortcomings of the graph partitioning technique. This paper addresses the efficient parallelization of matrix-vector multiplication through hypergraph partitioning techniques using CUDA GPU-based parallel computing. CUDA (compute unified device architecture) is a parallel computing platform and programming model that was created by NVIDIA and implemented by the GPU (graphics processing unit).

[Construction and expression of a recombinant adenovirus with LZP3].

Science.gov (United States)

Chen, Bang-dang; Zhang, Fu-chun; Sun, Mei-yu; Li, Yi-jie; Ma, Zheng-hai

2007-08-01

To explore a new immunocontraceptive vaccine and construct an attenuated recombinant adenoviral vaccine against Lagurus lagurus zona pellucida 3(LZP3). LZP3 gene was subcloned into the shuttle vector pShuttle-CMV, and then a two-step transformation procedure was employed to construct a recombinant adenoviral plasmid with LZP3, which was digested with Pac I and transfected into HEK293 cells to package recombinant adenovirus particles. Finally, HeLa cells were infected by the recombinant adenovirus. LZP3 gene was detected from the recombinant virus by PCR, and its transcription and expression were analyzed by RT-PCR and Western blot. Recombinant adenovirus vector pAd-LZP3 with LZP3 gene was constructed by homologous recombination in E.coli, and a recombinant adenovirus was obtained by transfecting HEK293 cells with pAd-LZP3. PCR test indicated that LZP3 gene was successfully integrated into the adenoviral genome, and the titer of the recombinant adenovirus reached 1.2x10(10) pfu/L. The transcription and expression of LZP3 gene in the infected HeLa cells were confirmed by RT-PCR and Western blot. The recombinant adenovirus RAd-LZP3 can be successfully expressed in the infected HeLa cells, which lays the foundation for further researches into immunizing animals with RAd-LZP3.

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

The developmental transcriptome of the mosquito Aedes aegypti, an invasive species and major arbovirus vector.

Science.gov (United States)

Akbari, Omar S; Antoshechkin, Igor; Amrhein, Henry; Williams, Brian; Diloreto, Race; Sandler, Jeremy; Hay, Bruce A

2013-09-04

Mosquitoes are vectors of a number of important human and animal diseases. The development of novel vector control strategies requires a thorough understanding of mosquito biology. To facilitate this, we used RNA-seq to identify novel genes and provide the first high-resolution view of the transcriptome throughout development and in response to blood feeding in a mosquito vector of human disease, Aedes aegypti, the primary vector for Dengue and yellow fever. We characterized mRNA expression at 34 distinct time points throughout Aedes development, including adult somatic and germline tissues, by using polyA+ RNA-seq. We identify a total of 14,238 novel new transcribed regions corresponding to 12,597 new loci, as well as many novel transcript isoforms of previously annotated genes. Altogether these results increase the annotated fraction of the transcribed genome into long polyA+ RNAs by more than twofold. We also identified a number of patterns of shared gene expression, as well as genes and/or exons expressed sex-specifically or sex-differentially. Expression profiles of small RNAs in ovaries, early embryos, testes, and adult male and female somatic tissues also were determined, resulting in the identification of 38 new Aedes-specific miRNAs, and ~291,000 small RNA new transcribed regions, many of which are likely to be endogenous small-interfering RNAs and Piwi-interacting RNAs. Genes of potential interest for transgene-based vector control strategies also are highlighted. Our data have been incorporated into a user-friendly genome browser located at www.Aedes.caltech.edu, with relevant links to Vectorbase (www.vectorbase.org).

Improving Dengue Virus Capture Rates in Humans and Vectors in Kamphaeng Phet Province, Thailand, Using an Enhanced Spatiotemporal Surveillance Strategy

Science.gov (United States)

Thomas, Stephen J.; Aldstadt, Jared; Jarman, Richard G.; Buddhari, Darunee; Yoon, In-Kyu; Richardson, Jason H.; Ponlawat, Alongkot; Iamsirithaworn, Sopon; Scott, Thomas W.; Rothman, Alan L.; Gibbons, Robert V.; Lambrechts, Louis; Endy, Timothy P.

2015-01-01

Dengue is of public health importance in tropical and sub-tropical regions. Dengue virus (DENV) transmission dynamics was studied in Kamphaeng Phet Province, Thailand, using an enhanced spatiotemporal surveillance of 93 hospitalized subjects with confirmed dengue (initiates) and associated cluster individuals (associates) with entomologic sampling. A total of 438 associates were enrolled from 208 houses with household members with a history of fever, located within a 200-m radius of an initiate case. Of 409 associates, 86 (21%) had laboratory-confirmed DENV infection. A total of 63 (1.8%) of the 3,565 mosquitoes collected were dengue polymerase chain reaction positive (PCR+). There was a significant relationship between spatial proximity to the initiate case and likelihood of detecting DENV from associate cases and Aedes mosquitoes. The viral detection rate from human hosts and mosquito vectors in this study was higher than previously observed by the study team in the same geographic area using different methodologies. We propose that the sampling strategy used in this study could support surveillance of DENV transmission and vector interactions. PMID:25986580

Anopheles Vectors in Mainland China While Approaching Malaria Elimination.

Science.gov (United States)

Zhang, Shaosen; Guo, Shaohua; Feng, Xinyu; Afelt, Aneta; Frutos, Roger; Zhou, Shuisen; Manguin, Sylvie

2017-11-01

China is approaching malaria elimination; however, well-documented information on malaria vectors is still missing, which could hinder the development of appropriate surveillance strategies and WHO certification. This review summarizes the nationwide distribution of malaria vectors, their bionomic characteristics, control measures, and related studies. After several years of effort, the area of distribution of the principal malaria vectors was reduced, in particular for Anopheles lesteri (synonym: An. anthropophagus) and Anopheles dirus s.l., which nearly disappeared from their former endemic regions. Anopheles sinensis is becoming the predominant species in southwestern China. The bionomic characteristics of these species have changed, and resistance to insecticides was reported. There is a need to update surveillance tools and investigate the role of secondary vectors in malaria transmission. Copyright © 2017 Elsevier Ltd. All rights reserved.

Support vector regression model based predictive control of water level of U-tube steam generators

Energy Technology Data Exchange (ETDEWEB)

Kavaklioglu, Kadir, E-mail: kadir.kavaklioglu@pau.edu.tr

2014-10-15

Highlights: • Water level of U-tube steam generators was controlled in a model predictive fashion. • Models for steam generator water level were built using support vector regression. • Cost function minimization for future optimal controls was performed by using the steepest descent method. • The results indicated the feasibility of the proposed method. - Abstract: A predictive control algorithm using support vector regression based models was proposed for controlling the water level of U-tube steam generators of pressurized water reactors. Steam generator data were obtained using a transfer function model of U-tube steam generators. Support vector regression based models were built using a time series type model structure for five different operating powers. Feedwater flow controls were calculated by minimizing a cost function that includes the level error, the feedwater change and the mismatch between feedwater and steam flow rates. Proposed algorithm was applied for a scenario consisting of a level setpoint change and a steam flow disturbance. The results showed that steam generator level can be controlled at all powers effectively by the proposed method.

A titratable two-step transcriptional amplification strategy for targeted gene therapy based on ligand-induced intramolecular folding of a mutant human estrogen receptor

DEFF Research Database (Denmark)

Chen, Ian Y; Paulmurugan, Ramasamy; Nielsen, Carsten Haagen

2014-01-01

PURPOSE: The efficacy and safety of cardiac gene therapy depend critically on the level and the distribution of therapeutic gene expression following vector administration. We aimed to develop a titratable two-step transcriptional amplification (tTSTA) vector strategy, which allows modulation...... of transcriptionally targeted gene expression in the myocardium. PROCEDURES: We constructed a tTSTA plasmid vector (pcTnT-tTSTA-fluc), which uses the cardiac troponin T (cTnT) promoter to drive the expression of the recombinant transcriptional activator GAL4-mER(LBD)-VP2, whose ability to transactivate the downstream...... induction of myocardial fluc expression. HTV injection of pcTnT-tTSTA-fluc led to negligible long-term hepatic fluc expression, regardless of the raloxifene dose given. CONCLUSIONS: The tTSTA vector strategy can effectively modulate transgene expression in a tissue-specific manner. Further refinement...

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.

GPU Accelerated Vector Median Filter